FN Thomson Reuters Web of Science™ VR 1.0 PT S AU Rapisarda, A Melillo, G AF Rapisarda, Annamaria Melillo, Giovanni BE Daar, IO TI Role of the VEGF/VEGFR Axis in Cancer Biology and Therapy SO GUIDANCE MOLECULES IN CANCER AND TUMOR ANGIOGENESIS SE Advances in Cancer Research LA English DT Review; Book Chapter ID ENDOTHELIAL-GROWTH-FACTOR; RENAL-CELL CARCINOMA; TYROSINE KINASE INHIBITOR; BEVACIZUMAB PLUS IRINOTECAN; HYPOXIA-INDUCIBLE FACTOR-1; ANTI-VEGF TREATMENT; ADVANCED BREAST-CANCER; TUMOR-GROWTH; ANTIANGIOGENIC THERAPY; FACTOR RECEPTOR-2 AB New vessel formation (angiogenesis) is an essential physiological process for embryologic development, normal growth, and tissue repair. Angiogenesis is tightly regulated at the molecular level; however, this process is dysregulated in several pathological conditions such as cancer. The imbalance between pro- and antiangiogenic signaling molecules within tumors creates an abnormal vascular network that is characterized by dilated, tortuous, and leaky vessels. The pathoph ysiological consequences of these vascular abnormalities include temporal and spatial heterogeneity in tumor blood flow, oxygenation, and increased tumor interstitial fluid pressure. The resultant microenvironment deeply impacts on tumor progression, and also leads to a reduction in therapy efficacy. The discovery of vascular endothelial growth factor (VEGF) as a major driver of tumor angiogenesis has led to efforts to develop novel therapeutics aimed at inhibiting its activity. Anti-VEGF therapy has become an important option for the management of several human malignancies; however, a significant number of patients do not respond to anti-VEGF therapy when used either as single agent or in combination with chemotherapy. In addition, the benefit of antiangiogenic therapy is relatively short lived and the majority of patients relapse and progress. An increasing amount of reports suggest several potential mechanisms of resistance to antiangiogenic therapy including, but not limited to, tumor hypoxia. This chapter discusses the role of the VEGF axis in tumor biology and highlights the clinical application of anti-VEGF therapies elaborating on pitfalls and strategies to improve clinical outcome. (C) 2012 Elsevier Inc. C1 [Rapisarda, Annamaria] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Frederick, MD USA. [Melillo, Giovanni] Bristol Myers Squibb Co, Discovery Med Oncol, Princeton, NJ USA. RP Rapisarda, A (reprint author), SAIC Frederick Inc, Frederick Natl Lab Canc Res, Frederick, MD USA. FU NCI NIH HHS [N01-CO-12400] NR 162 TC 59 Z9 66 U1 1 U2 25 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-230X BN 978-0-12-386503-8 J9 ADV CANCER RES JI Adv.Cancer Res. PY 2012 VL 114 BP 237 EP 267 DI 10.1016/B978-0-12-386503-8.00006-5 PG 31 WC Oncology SC Oncology GA BBH98 UT WOS:000306934000006 PM 22588059 ER PT J AU Sun, GH Shi, YB AF Sun, Guihong Shi, Yun-Bo TI Thyroid Hormone Regulation of Adult Intestinal Stem Cell Development: Mechanisms and Evolutionary Conservations SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Review DE adult organ-specific stem cell; histone methyltransferase; transcriptional coactivator; thyroid hormone receptor; dedifferentiation; Xenopus laevis; metamorphosis ID ARGININE METHYLTRANSFERASE 1; XENOPUS-LAEVIS; AMPHIBIAN METAMORPHOSIS; POSTEMBRYONIC DEVELOPMENT; VERTEBRATE DEVELOPMENT; GENE-EXPRESSION; TRANSCRIPTIONAL REGULATION; RECEPTOR SUPERFAMILY; CHROMATIN DISRUPTION; TR-ALPHA AB The adult mammalian intestine has long been used as a model to study adult stem cell function and tissue renewal as the intestinal epithelium is constantly undergoing self-renewal throughout adult life. This is accomplished through the proliferation and subsequent differentiation of the adult stem cells located in the crypt. The development of this self-renewal system is, however, poorly understood. A number of studies suggest that the formation/maturation of the adult intestine is conserved in vertebrates and depends on endogenous thyroid hormone (T3). In amphibians such as Xenopus laevis, the process takes place during metamorphosis, which is totally dependent upon T3 and resembles postembryonic development in mammals when T3 levels are also high. During metamorphosis, the larval epithelial cells in the tadpole intestine undergo apoptosis and concurrently, adult epithelial stem/progenitor cells are formed de novo, which subsequently lead to the formation of a trough-crest axis of the epithelial fold in the frog, resembling the crypt-villus axis in the adult mammalian intestine. Here we will review some recent molecular and genetic studies that support the conservation of the development of the adult intestinal stem cells in vertebrates. We will discuss the mechanisms by which T3 regulates this process via its nuclear receptors. C1 [Sun, Guihong] Wuhan Univ, Sch Med, Key Lab Allergy & Immune Related Dis, Wuhan 430072, Peoples R China. [Sun, Guihong] Wuhan Univ, Sch Med, Med Res Ctr, Wuhan 430072, Peoples R China. [Shi, Yun-Bo] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Morphogenesis, PCRM, NIH, Bethesda, MD 20892 USA. RP Shi, YB (reprint author), Wuhan Univ, Sch Med, Key Lab Allergy & Immune Related Dis, Wuhan 430072, Peoples R China. EM ghsunlab@whu.edu.cn; shi@helix.nih.gov FU National Natural Science Foundation of China [30870113]; Intramural Research Program of NICHD, NIH FX This research was supported in part by the National Natural Science Foundation of China No. 30870113 and the Intramural Research Program of NICHD, NIH. NR 70 TC 17 Z9 17 U1 1 U2 10 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2012 VL 8 IS 8 BP 1217 EP 1224 DI 10.7150/ijbs.5109 PG 8 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 023SL UT WOS:000310055600013 PM 23136549 ER PT S AU Gondre-Lewis, MC Park, JJ Loh, YP AF Gondre-Lewis, Marjorie C. Park, Joshua J. Loh, Y. Peng BE Jeon, KW TI Cellular Mechanisms for the Biogenesis and Transport of Synaptic and Dense-Core Vesicles SO INTERNATIONAL REVIEW OF CELL AND MOLECULAR BIOLOGY, VOL 299 SE International Review of Cell and Molecular Biology LA English DT Review; Book Chapter ID REGULATED SECRETORY PATHWAY; PANCREATIC BETA-CELLS; VESICULAR ACETYLCHOLINE TRANSPORTER; FRAGILE-X-SYNDROME; FROG NEUROMUSCULAR-JUNCTION; AMYLOID PRECURSOR PROTEIN; PRESYNAPTIC ACTIVE ZONE; ADP-RIBOSYLATION FACTOR; GTP-BINDING PROTEIN; HIPPOCAMPAL EXCITATORY SYNAPSES AB The release of intercellular messengers from synaptic (SVs) and dense-core vesicles (DCVs) constitutes the primary mechanism for communication between neighboring or distant cells and organs in response to stimuli. Here we review the life span of SVs and DCVs found in the brain, neuroendocrine and exocrine tissues. These vesicles must be formed, trafficked, and their contents secreted; processes which require orchestrated actions of a great repertoire of lipids, proteins, and enzymes. For biogenesis and vesicular budding, lipids that influence curvature and aggregation of cargo are necessary for pinching off of vesicles. Vesicles travel on cytoskeletal filaments powered by motors that control the dynamics: location, speed, and directionality of movement. Regardless of mechanisms of traffic, vesicles arrive at sites of release and are docked for exocytosis, followed by membrane fusion, and release of vesicular content to exert physiological responses. Neurological disorders with pathology involving abnormal vesicular budding, trafficking, or secretion are discussed. C1 [Gondre-Lewis, Marjorie C.] Howard Univ, Dept Anat, Lab Neurodev, Coll Med, Washington, DC 20059 USA. [Park, Joshua J.] Univ Toledo, Dept Neurosci, Sch Med, Toledo, OH 43606 USA. [Loh, Y. Peng] Eunice Kennedy Shiiver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, Program Dev Neurosci, NIH, Bethesda, MD USA. RP Gondre-Lewis, MC (reprint author), Howard Univ, Dept Anat, Lab Neurodev, Coll Med, Washington, DC 20059 USA. FU Intramural NIH HHS NR 460 TC 11 Z9 11 U1 2 U2 18 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1937-6448 BN 978-0-12-394310-1 J9 INT REV CEL MOL BIO JI Int. Rev. Cell Mol. Biol. PY 2012 VL 299 BP 27 EP 115 DI 10.1016/B978-0-12-394310-1.00002-3 PG 89 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BCI79 UT WOS:000310253000002 PM 22959301 ER PT S AU Cohen, S Etingov, I Pante, N AF Cohen, Sarah Etingov, Igor Pante, Nelly BE Jeon, KW TI Effect of Viral Infection on the Nuclear Envelope and Nuclear Pore Complex SO INTERNATIONAL REVIEW OF CELL AND MOLECULAR BIOLOGY, VOL 299 SE International Review of Cell and Molecular Biology LA English DT Review; Book Chapter ID CYCLE-DEPENDENT PHOSPHORYLATION; HERPES-SIMPLEX VIRUS-1; PROTEIN-KINASE-C; NUCLEOCYTOPLASMIC TRANSPORT; ADENOASSOCIATED VIRUS; MESSENGER-RNA; CANINE PARVOVIRUS; MEMBRANE-PROTEIN; LEADER PROTEIN; CELL-CYCLE AB The nuclear envelope (NE) is a vital structure that separates the nucleus from the cytoplasm. Because the NE is such a critical cellular barrier, many viral pathogens have evolved to modulate its permeability. They do this either by breaching the NE or by disrupting the integrity and functionality of the nuclear pore complex (NPC). Viruses modulate NE permeability for different reasons. Some viruses disrupt NE to deliver the viral genome into the nucleus for replication, while others cause NE disruption during nuclear egress of newly assembled capsids. Yet, other viruses modulate NE permeability and affect the compartmentalization of host proteins or block the nuclear transport of host proteins involved in the host antiviral response. Recent scientific advances demonstrated that other viruses use proteins of the NPC for viral assembly or disassembly. Here we review the ways in which various viruses affect NE and NPC during infection. C1 [Cohen, Sarah; Etingov, Igor; Pante, Nelly] Univ British Columbia, Dept Zool, Vancouver, BC, Canada. RP Cohen, S (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. FU Canadian Institutes of Health Research NR 179 TC 9 Z9 9 U1 3 U2 16 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1937-6448 BN 978-0-12-394310-1 J9 INT REV CEL MOL BIO JI Int. Rev. Cell Mol. Biol. PY 2012 VL 299 BP 117 EP 159 DI 10.1016/B978-0-12-394310-1.00003-5 PG 43 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BCI79 UT WOS:000310253000003 PM 22959302 ER PT J AU Tranah, GJ Nalls, MA Katzman, SM Yokoyama, JS Lam, ET Zhao, YQ Mooney, S Thomas, F Newman, AB Liu, YM Cummings, SR Harris, TB Yaffe, K AF Tranah, Gregory J. Nalls, Michael A. Katzman, Shana M. Yokoyama, Jennifer S. Lam, Ernest T. Zhao, Yiqiang Mooney, Sean Thomas, Fridtjof Newman, Anne B. Liu, Yongmei Cummings, Steven R. Harris, Tamara B. Yaffe, Kristine CA Hlth Aging & Body Composition Stud TI Mitochondrial DNA Sequence Variation Associated with Dementia and Cognitive Function in the Elderly SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Cognitive function; dementia; DNA sequencing; mitochondria; mtDNA; oxidative phosphorylation ID GENOME-WIDE ASSOCIATION; ALPHA-KETOGLUTARATE DEHYDROGENASE; CYTOCHROME-C-OXIDASE; HUMAN SUBSTANTIA-NIGRA; ACTIVITY ENERGY-EXPENDITURE; AMYLOID PRECURSOR PROTEIN; AMINO-ACID SUBSTITUTIONS; INDUCED OXIDATIVE STRESS; HUMAN SKELETAL-MUSCLE; ALZHEIMERS-DISEASE AB Mitochondrial dysfunction is a prominent hallmark of Alzheimer's disease (AD). Mitochondrial DNA (mtDNA) damage may be a major cause of abnormal reactive oxidative species production in AD or increased neuronal susceptibility to oxidative injury during aging. The purpose of this study was to assess the influence of mtDNA sequence variation on clinically significant cognitive impairment and dementia risk in the population-based Health, Aging, and Body Composition (Health ABC) Study. We first investigated the role of common mtDNA haplogroups and individual variants on dementia risk and 8-year change on the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) among 1,631 participants of European genetic ancestry. Participants were free of dementia at baseline and incidence was determined in 273 cases from hospital and medication records over 10-12 follow-up years. Participants from haplogroup T had a statistically significant increased risk of developing dementia (OR = 1.86, 95% CI = 1.23, 2.82, p = 0.0008) and haplogroup J participants experienced a statistically significant 8-year decline in 3MS (beta = -0.14, 95% CI = -0.27, -0.03, p = 0.0006), both compared with common haplogroup H. The m. 15244A>G, p.G166G, CytB variant was associated with a significant decline in DSST score (beta = -0.58, 95% CI -0.89, -0.28, p = 0.00019) and the m.14178T>C, p.I166V, ND6 variant was associated with a significant decline in 3MS score (beta = -0.87, 95% CI-1.31, -3.86, p = 0.00012). Finally, we sequenced the complete similar to 16.5 kb mtDNA from 135 Health ABC participants and identified several highly conserved and potentially functional nonsynonymous variants unique to 22 dementia cases and aggregate sequence variation across the hypervariable 2-3 regions that influences 3MS and DSST scores. C1 [Tranah, Gregory J.] UCSF, Calif Pacific Med Ctr, Res Inst, San Francisco Coordinating Ctr, San Francisco, CA 94107 USA. [Nalls, Michael A.] NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA. [Katzman, Shana M.; Zhao, Yiqiang; Mooney, Sean] Buck Inst Res Aging, Novato, CA USA. [Yokoyama, Jennifer S.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Lam, Ernest T.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Thomas, Fridtjof] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. RP Tranah, GJ (reprint author), UCSF, Calif Pacific Med Ctr, Res Inst, San Francisco Coordinating Ctr, 185 Berry St,Lobby 5,Suite 5700, San Francisco, CA 94107 USA. EM gtranah@sfcc-cpmc.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU National Institute on Aging (NIA) [N01 AG62101, N01 AG62103, N01 AG62106, R01 AG028050, R03 AG032498, 1R01 AG032098-01A1]; NINR [R01 NR012459, Z01 AG000951]; NIH [T32 GM007175]; NLM [LM009722]; Intramural Research Program of the NIH, NIA; National Institutes of Health [HHSN268200782096C] FX This research was supported by National Institute on Aging (NIA) Contracts N01 AG62101; N01 AG62103; N01 AG62106; NIA grants R01 AG028050 and R03 AG032498, NINR grant R01 NR012459; and Z01 AG000951. E. T. L. was supported in part by NIH Training Grant T32 GM007175 and Y.Z. by NLM grant LM009722. This research was supported in part by the Intramural Research Program of the NIH, NIA. The genome-wide association study was funded by NIA grant 1R01 AG032098-01A1 to Wake Forest University Health Sciences and genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to Johns Hopkins University, contract number HHSN268200782096C. Data analyses for this study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, Maryland (http://biowulf.nih.gov). NR 170 TC 9 Z9 9 U1 3 U2 15 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2012 VL 32 IS 2 BP 357 EP 372 DI 10.3233/JAD-2012-120466 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 022QY UT WOS:000309977800010 PM 22785396 ER PT S AU Cole, HA Howard, BH Clark, DJ AF Cole, Hope A. Howard, Bruce H. Clark, David J. BE Wu, C Allis, CD TI Genome-Wide Mapping of Nucleosomes in Yeast Using Paired-End Sequencing SO NUCLEOSOMES, HISTONES & CHROMATIN, PT B SE Methods in Enzymology LA English DT Review; Book Chapter ID SACCHAROMYCES-CEREVISIAE; MICROCOCCAL NUCLEASE; HIGH-RESOLUTION; ENTIRE GENE; CHROMATIN; DNA; POSITIONS; ORGANIZATION; ACTIVATION; OCCUPANCY AB The DNA of eukaryotic cells is packaged into chromatin by histone proteins, which play a central role in regulating access to genetic information. The nucleosome core is the basic structural unit of chromatin: it is composed of an octamer of the four major core histones (two molecules each of H2A, H2B, H3, and H4), around which are wrapped similar to 1.75 negative superhelical turns of DNA, a total of 145-147 bp. Nucleosome cores are regularly spaced along the DNA in vivo, separated by linker DNA. Nucleosomes are compact structures capable of blocking access to the DNA that they contain. For example, they may prevent the binding of transcription factors to their cognate sites. It is therefore very important to obtain quantitative information on the positions of nucleosomes with respect to regulatory regions in vivo. The advent of high-throughput sequencing methods has revolutionized this field. We describe the use and advantages of paired-end sequencing to map nucleosomal DNA obtained by micrococcal nuclease digestion of budding yeast nuclei. This approach provides high-quality genome-wide nucleosome occupancy and position maps. C1 [Cole, Hope A.; Howard, Bruce H.; Clark, David J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD USA. RP Clark, DJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD USA. EM clarkda@mail.nih.gov FU Intramural NIH HHS NR 33 TC 11 Z9 11 U1 0 U2 7 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-391938-0 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2012 VL 513 BP 145 EP 168 DI 10.1016/B978-0-12-391938-0.00006-9 PG 24 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BCI73 UT WOS:000310250800007 PM 22929768 ER PT S AU Wei, G Hu, GQ Cui, KR Zhao, KJ AF Wei, Gang Hu, Gangqing Cui, Kairong Zhao, Keji BE Wu, C Allis, CD TI Genome-Wide Mapping of Nucleosome Occupancy, Histone Modifications, and Gene Expression Using Next-Generation Sequencing Technology SO NUCLEOSOMES, HISTONES & CHROMATIN, PT B SE Methods in Enzymology LA English DT Review; Book Chapter ID EMBRYONIC STEM-CELLS; RNA-SEQ DATA; CHIP-SEQ; T-CELLS; LANDSCAPE; ENHANCERS; PACKAGE; DIFFERENTIATION; TRANSCRIPTOME; METHYLATIONS AB Gene transcription can be regulated through alteration of chromatin structure, such as changes in nucleosome positioning and histone-modification patterns. Recent development of techniques based on the next-generation sequencing technology has allowed high-resolution analysis of genome-wide distribution of these chromatin features. In this chapter, we describe in detail the protocols of ChIP-Seq and MNase-Seq, which have been developed to detect the genome-wide profiles of transcription factor binding, histone modifications, and nucleosome occupancy. We also describe RNA-Seq protocols used to map global gene expression profiles. C1 [Wei, Gang; Hu, Gangqing; Cui, Kairong; Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. RP Zhao, KJ (reprint author), NHLBI, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM zhaok@nhlbi.nih.gov RI HU, GANGQING/K-5849-2012 FU Intramural NIH HHS NR 40 TC 16 Z9 16 U1 2 U2 14 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-391938-0 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2012 VL 513 BP 297 EP 313 DI 10.1016/B978-0-12-391938-0.00013-6 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BCI73 UT WOS:000310250800014 PM 22929775 ER PT S AU Mizuguchi, G Wu, WH Alami, S Luk, E AF Mizuguchi, Gaku Wu, Wei-Hua Alami, Samar Luk, Ed BE Wu, C Allis, CD TI Biochemical Assay for Histone H2A.Z Replacement by the Yeast SWR1 Chromatin Remodeling Complex SO NUCLESOMES, HISTONES & CHROMATIN, PT A SE Methods in Enzymology LA English DT Review; Book Chapter ID VARIANT H2A.Z; EUCHROMATIN; NUCLEOSOME AB The evolutionarily conserved histone variant H2A.Z has an important role in the regulation of gene expression and the establishment of a buffer to the spread of silent heterochromatin. Saccharomyces cerevisiae Swr1, a Swi2/Snf2-related ATPase, is the catalytic core of a multisubunit chromatin remodeling enzyme, called the SWR1 complex, that efficiently replaces conventional histone H2A in nucleosomes with histone H2A.Z. Swr1 is required for the deposition of histone H2A.Z at stereotypical promoter locations in vivo, and Swr1 and H2A.Z commonly regulate a subset of yeast genes. Here, we describe an integrated nucleosome assembly histone replacement system whereby histone exchange by chromatin remodeling activities may be analyzed in vitro. The system demonstrates ATP- and SWR1-complex-dependent replacement of histone H2A for histone H2A.Z on a preassembled nucleosome array. This system may also be adapted to analyze dynamic interactions between chromatin remodeling and modifying enzymes, histone chaperones, and nucleosome substrates containing canonical, variant, or covalently modified histones. C1 [Mizuguchi, Gaku] Howard Hughes Med Inst, Ashburn, VA USA. [Wu, Wei-Hua; Alami, Samar; Luk, Ed] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Mizuguchi, G (reprint author), Howard Hughes Med Inst, Janelia Farm Res Campus, Ashburn, VA USA. EM mizuguchim@janelia.hhmi.org OI Luk, Ed/0000-0002-6619-2258 FU Howard Hughes Medical Institute; Intramural NIH HHS NR 21 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-391940-3 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2012 VL 512 BP 275 EP 291 DI 10.1016/B978-0-12-391940-3.00012-3 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BCI45 UT WOS:000310245000012 PM 22910211 ER PT J AU Tozatti, CSS Khodyuk, RGD da Silva, AO dos Santos, ED do Amaral, MS de Lima, DP Hamel, E AF Suniga Tozatti, Camila Santos Diniz Khodyuk, Rejane Goncalves da Silva, Adriano Olimpio dos Santos, Edson dos Anjos do Amaral, Marcos Serrou de Lima, Denis Pires Hamel, Ernest TI SYNTHESIS AND BIOLOGICAL EVALUATION OF BIARYL ANALOGS OF ANTITUBULIN COMPOUNDS SO QUIMICA NOVA LA English DT Article DE methanones; esters; antitubulin ID ANTINEOPLASTIC AGENTS; ANTIMITOTIC AGENTS; ORGANIC-ACIDS; TUBULIN; COMBRETASTATIN; INHIBITION; POLYMERIZATION; SUBSTITUENT; COLCHICINE; PHOSPHATE AB This paper reports the synthesis of methanones and esters bearing different substitution patterns as spacer groups between aromatic rings. This series of compounds can be considered phenstatin analogs. Two of the newly synthesized compounds, 5a and 5c, strongly inhibited tubulin polymerization and the binding of [H-3] colchicine to tubulin, suggesting that, akin to phenstatin and combretastatin A-4, they can bind to tubulin at the colchicine site. C1 [Suniga Tozatti, Camila Santos; Diniz Khodyuk, Rejane Goncalves; da Silva, Adriano Olimpio; dos Santos, Edson dos Anjos; do Amaral, Marcos Serrou; de Lima, Denis Pires] Univ Fed Mato Grosso do Sul, Ctr Ciencias Exatas & Tecnol, BR-79074460 Campo Grande, MS, Brazil. [Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA. RP Tozatti, CSS (reprint author), Univ Fed Mato Grosso do Sul, Ctr Ciencias Exatas & Tecnol, Av Senador Filinto Muller 1555, BR-79074460 Campo Grande, MS, Brazil. EM denis.lima@ufms.br RI Amaral, Marcos/I-6927-2012; dos Santos, Edson/I-6324-2016; de Lima, Denis/I-4607-2013 OI Amaral, Marcos/0000-0001-8101-6933; de Lima, Denis/0000-0002-6023-4867 FU CAPES (Brazil); FUNDECT-MS (Brazil); PROPP-UFMS FX The authors wish to thank CAPES (Brazil) and FUNDECT-MS (Brazil) for scholarship and financial support and PROPP-UFMS for the support and infrastructure provided. NR 21 TC 1 Z9 1 U1 1 U2 6 PU SOC BRASILEIRA QUIMICA PI SAO PAULO PA CAIXA POSTAL 26037, 05599-970 SAO PAULO, BRAZIL SN 0100-4042 J9 QUIM NOVA JI Quim. Nova PY 2012 VL 35 IS 9 BP 1758 EP U65 PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA 019FI UT WOS:000309722200010 PM 23087491 ER PT J AU Hendrix, A Lambein, K Westbroek, W Seabra, MC Cocquyt, V Pauwels, P Bracke, M Gespach, C De Wever, O AF Hendrix, An Lambein, Kathleen Westbroek, Wendy Seabra, Miguel C. Cocquyt, Veronique Pauwels, Patrick Bracke, Marc Gespach, Christian De Wever, Olivier TI An immunohistochemical analysis of Rab27B distribution in fetal and adult tissue SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE development; small GTPase; exocytosis; secretory Rab; Rab27 ID SMALL GTPASE RAB27B; CELLS; EXOCYTOSIS; SECRETION; GRANULES; EXPRESSION; PROTEINS; INVOLVEMENT; MEMBRANE; GROWTH AB Regulated secretory pathways coordinated by small Rab GTPases are critically involved in intercellular communications. Here, we report the expression and localization of Rab27B in developing and differentiated epithelial human tissues by immunohistochemistry. Rab27B is poorly expressed in fetal tissues suggesting that several developmental mechanisms involved in epithelial differentiation and functions are mediated by other secretory Rab GTPases, such as Rab27A or Rab3 family members. In adult tissues, Rab27B is expressed in a wide variety of differentiated secretory epithelial cells, including those lining the salivary gland, gastrointestinal, mammary and prostate tracts. The complex pattern of Rab27B expression indicates that dysregulation of Rab27B-mediated secretion may have profound implications for disease pathology. C1 [Hendrix, An; Bracke, Marc; De Wever, Olivier] Ghent Univ Hosp, Dept Radiat Oncol & Expt Canc Res, Lab Expt Canc Res, B-9000 Ghent, Belgium. [Hendrix, An; Cocquyt, Veronique] Ghent Univ Hosp, Dept Med Oncol, B-9000 Ghent, Belgium. [Lambein, Kathleen; Pauwels, Patrick] Ghent Univ Hosp, Dept Pathol, B-9000 Ghent, Belgium. [Westbroek, Wendy] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. [Seabra, Miguel C.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. [Seabra, Miguel C.] Univ Nova Lisboa, Fac Ciencias Med, CEDOC, P-1200 Lisbon, Portugal. [Seabra, Miguel C.] Inst Gulbenkian Ciencias, Oeiras, Portugal. [Gespach, Christian] Univ Paris 06, Fac Med, INSERM Mol & Clin Oncol U938, Paris, France. [Pauwels, Patrick] Univ Antwerp, Dept Pathol, B-2020 Antwerp, Belgium. RP Hendrix, A (reprint author), Ghent Univ Hosp, Dept Radiat Oncol & Expt Canc Res, Lab Expt Canc Res, De Pintelaan 185, B-9000 Ghent, Belgium. EM an.hendrix@ugent.be RI de wever, olivier/J-3094-2013; Faculdade de Ciencias Medicas, Nova Medical School/K-6209-2013; OI de wever, olivier/0000-0002-5453-760X; Seabra, Miguel/0000-0002-6404-4892 FU Intramural Research Program of the National Human Genome Research Institute; Foundation against Cancer, Spearhead Oncology of Ghent University Hospital; Special Research Fund of Ghent University FX This work was supported by the Intramural Research Program of the National Human Genome Research Institute, Foundation against Cancer, Spearhead Oncology of Ghent University Hospital, and a postdoctoral grant from Special Research Fund of Ghent University (AH). NR 34 TC 4 Z9 4 U1 0 U2 10 PU U B C PRESS PI BILBAO PA UNIV BASQUE COUNTRY, EDITORIAL SERVICES, PO BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PY 2012 VL 56 IS 5 BP 363 EP 368 DI 10.1387/ijdb.120008ah PG 6 WC Developmental Biology SC Developmental Biology GA 020FP UT WOS:000309794700007 PM 22811270 ER PT J AU Gaglio, B Glasgow, RE Bull, SS AF Gaglio, Bridget Glasgow, Russell E. Bull, Sheana S. TI Do Patient Preferences for Health Information Vary by Health Literacy or Numeracy? A Qualitative Assessment SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID DISPARITIES; FRAMEWORK; SEEKING AB Seeking health information can be a complicated process for a patient. Patients must know the topic of interest, where to look or ask, how to assess and comprehend, and how to evaluate the credibility and trustworthiness of the sources. In this study, the authors describe preferences of patients with multiple risk factors for cardiovascular disease with varying health literacy and numeracy abilities for receiving health information. Participants were recruited from 2 health care systems. Health literacy and numeracy were assessed and participants completed an orally administered survey consisting of open-ended questions about obtaining health information and preferences for health information. In-depth interviews were conducted with a subset of participants. A diverse sample of 150 individuals (11.3% Latino, 37.3% African American, 44.7% with income less than $15,000/year) participated. Most participants had adequate functional health literacy, while 65% had low numeracy skills. Regardless of health literacy or numeracy ability, participants overwhelmingly preferred to receive health information during a face-to-face conversation with their health care provider. While individuals with adequate functional health literacy identified a variety of health information sources, actions are needed to ensure multiple modalities are available and are in plain, clear language that reinforces patients' understanding and application of information to health behavior. C1 [Gaglio, Bridget] Kaiser Permanente, Mid Atlantic Permanente Med Grp, Mid Atlantic Permanente Res Inst, Rockville, MD 20852 USA. [Glasgow, Russell E.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA. [Bull, Sheana S.] Univ Colorado, Colorado Sch Publ Hlth, Aurora, CO USA. RP Gaglio, B (reprint author), Kaiser Permanente, Mid Atlantic Permanente Med Grp, Mid Atlantic Permanente Res Inst, 2101 E Jefferson St,3 West, Rockville, MD 20852 USA. EM bridget.gaglio@kp.org NR 20 TC 10 Z9 11 U1 0 U2 15 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2012 VL 17 SU 3 SI SI BP 109 EP 121 DI 10.1080/10810730.2012.712616 PG 13 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 019OV UT WOS:000309750100011 PM 23030565 ER PT J AU Rutten, LJF Davis, T Beckjord, EB Blake, K Moser, RP Hesse, BW AF Rutten, Lila J. Finney Davis, Terisa Beckjord, Ellen Burke Blake, Kelly Moser, Richard P. Hesse, Bradford W. TI Picking Up the Pace: Changes in Method and Frame for the Health Information National Trends Survey (2011-2014) SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID CANCER SCREENING UTILIZATION; SURVEY HINTS; PROVIDER COMMUNICATION; RISK PERCEPTIONS; UNITED-STATES; CARE PROVIDERS; KNOWLEDGE; SEEKING; DISPARITIES; TELEPHONE AB communication and health information technology influence the ways in which health care professionals and the public seek, use, and comprehend health information. The Health Information National Trends Survey (HINTS) program was developed to assess the effect of health communication and health information technology on health-related attitudes, knowledge, and behavior. HINTS has fielded 3 national data collections with the fourth (HINTS 4) currently underway. Throughout this time, the Journal of Health Communication has been a dedicated partner in disseminating research based on HINTS data. Thus, the authors thought it the perfect venue to provide an historical overview of the HINTS program and to introduce the most recent HINTS data collection effort. This commentary describes the rationale for and structure of HINTS 4, summarizes the methodological approach applied in Cycle 1 of HINTS 4, describes the timeline for the HINTS 4 data collection, and identifies priorities for research using HINTS 4 data. C1 [Rutten, Lila J. Finney] NCI, Clin Monitoring Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Davis, Terisa] WESTAT Corp, Rockville, MD 20850 USA. [Beckjord, Ellen Burke] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Blake, Kelly; Moser, Richard P.; Hesse, Bradford W.] NCI, Behav Res Program, Bethesda, MD 20892 USA. RP Rutten, LJF (reprint author), NCI, Clin Monitoring Res Program, SAIC Frederick Inc, 5705 Ind Lane, Frederick, MD 21702 USA. EM finneyl@mail.nih.gov OI Hesse, Bradford/0000-0003-1142-1161 NR 53 TC 18 Z9 18 U1 0 U2 9 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2012 VL 17 IS 8 BP 979 EP 989 DI 10.1080/10810730.2012.700998 PG 11 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 019ON UT WOS:000309749300009 ER PT J AU Moser, RP Beckjord, EB Rutten, LJF Blake, K Hesse, BW AF Moser, Richard P. Beckjord, Ellen Burke Rutten, Lila J. Finney Blake, Kelly Hesse, Bradford W. TI Using Collaborative Web Technology to Construct the Health Information National Trends Survey SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article AB Scientists are taking advantage of web-based technology to work in new collaborative environments, a phenomenon known as Science 2.0. The National Cancer Institute created a web-based tool called HINTS-GEM, which allows a diverse group of stakeholders to collaborate in a virtual environment by providing input on content for the Health Information National Trends Survey (HINTS). This involved stakeholders providing new suggested content and commenting and rating on existing content. HINTS is a nationally representative survey of the US noninstitutionalized adult population. This article describes the conceptual development of HINTS-GEM and provides results of its use by stakeholders in creating an improved survey instrument. C1 [Moser, Richard P.; Blake, Kelly; Hesse, Bradford W.] NCI, Behav Res Program, Bethesda, MD 20892 USA. [Beckjord, Ellen Burke] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Rutten, Lila J. Finney] NCI, Clin Res Directorate CMRP, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Moser, RP (reprint author), 6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. EM moserr@mail.nih.gov OI Hesse, Bradford/0000-0003-1142-1161 FU CCR NIH HHS [HHSN261200800001C]; NCI NIH HHS [HHSN261200800001E, HHSN261200800001E]; PHS HHS [HHSN261200800001E] NR 14 TC 1 Z9 1 U1 0 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2012 VL 17 IS 8 BP 990 EP 1000 DI 10.1080/10810730.2012.700999 PG 11 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 019ON UT WOS:000309749300010 PM 23020764 ER PT S AU Liu, G Wang, ZY Lee, S Ai, H Chen, XY AF Liu, Gang Wang, Zhiyong Lee, Seulki Ai, Hua Chen, Xiaoyuan BE Duzgunes, N TI DESIGN AND FABRICATION OF N-ALKYL-POLYETHYLENIMINE-STABILIZED IRON OXIDE NANOCLUSTERS FOR GENE DELIVERY SO NANOMEDICINE: INFECTIOUS DISEASES, IMMUNOTHERAPY, DIAGNOSTICS, ANTIFIBROTICS, TOXICOLOGY AND GENE MEDICINE SE Methods in Enzymology LA English DT Review; Book Chapter ID IN-VIVO; GOLD NANOPARTICLES; PEI; CELLS; SIRNA AB With the rapid development of nanotechnology, inorganic magnetic nanoparticles, especially iron oxide nanoparticles (IOs), have emerged as great vehicles for biomedical diagnostic and therapeutic applications. In order to rationally design IO-based gene delivery nanovectors, surface modification is essential and determines the loading and release of the gene of interest. Here we highlight the basic concepts and applications of nonviral gene delivery vehicles based on low molecular weight N-alkyl polyethylenimine-stabilized IOs. The experimental protocols related to these topics are described in this chapter. C1 [Wang, Zhiyong; Ai, Hua] Sichuan Univ, Natl Engn Res Ctr Biomat, Chengdu 610064, Peoples R China. [Liu, Gang; Chen, Xiaoyuan] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, Xiamen, Peoples R China. [Liu, Gang; Lee, Seulki; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA. [Liu, Gang] N Sichuan Med Coll, Sichuan Key Lab Med Imaging, Nanchong, Peoples R China. RP Ai, H (reprint author), Sichuan Univ, Natl Engn Res Ctr Biomat, Chengdu 610064, Peoples R China. EM huaai@scu.edu.cn; shawn.chen@nih.gov FU Intramural NIH HHS [Z99 EB999999, ZIA EB000073-03] NR 23 TC 3 Z9 3 U1 0 U2 16 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-391858-1 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2012 VL 509 BP 263 EP 276 DI 10.1016/B978-0-12-391858-1.00009-5 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BBU36 UT WOS:000308198000013 PM 22568910 ER PT S AU Hammersla, AM Rohrbaugh, ML AF Hammersla, A. M. Rohrbaugh, M. L. BE Atala, A TI Intellectual property claims to stem cell technologies: research, clinical testing and product sales SO PROGENITOR AND STEM CELL TECHNOLOGIES AND THERAPIES SE Woodhead Publishing Series in Biomaterials LA English DT Article; Book Chapter DE stem cells; patents; laws; court cases; intellectual property; policy; international patent law ID LANDSCAPE AB This chapter reviews the debates arising in national arenas throughout the industrialized world and among international organizations regarding the use and patentability of stem cells. These debates involve many stakeholders, including researchers, politicians, religious organizations, ethicists, policy makers, patent experts, court systems, patient advocacy groups and governments, leading to an international patchwork of stem cell patent laws. This patchwork of laws, conflicting goals of countries and researchers, and possible patent thickets have to some extent restricted worldwide collaborative research and commercialization of stem cell based therapies. C1 [Hammersla, A. M.; Rohrbaugh, M. L.] NIH, Off Technol Transfer, Rockville, MD 20852 USA. RP Rohrbaugh, ML (reprint author), NIH, Off Technol Transfer, 6011 Execut Blvd,Suite 325,MSC 7660, Rockville, MD 20852 USA. EM rohrbaugh@nih.gov NR 34 TC 0 Z9 1 U1 0 U2 0 PU WOODHEAD PUBL LTD PI CAMBRIDGE PA ABINGTON HALL ABINGTON, CAMBRIDGE CB1 6AH, CAMBS, ENGLAND SN 2049-9485 BN 978-0-85709-607-4; 978-1-84569-984-0 J9 WOODH PUBL SER BIOM PY 2012 VL 38 BP 121 EP 146 D2 10.1533/9780857096074 PG 26 WC Cell & Tissue Engineering; Cell Biology; Engineering, Biomedical SC Cell Biology; Engineering GA BCI09 UT WOS:000310233400008 ER PT J AU Handel, D AF Handel, Dan TI The science of happiness: How our brains make us happy and what we can do to get happier SO AMERICAN JOURNAL OF CLINICAL HYPNOSIS LA English DT Book Review C1 [Handel, Dan] NIH, Bethesda, MD 20892 USA. RP Handel, D (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 1 U2 10 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0002-9157 J9 AM J CLIN HYPN JI Am. J. Clin. Hypn. PY 2012 VL 55 IS 2 BP 195 EP 196 DI 10.1080/00029157.2013.686413 PG 2 WC Psychology, Clinical SC Psychology GA 017ST UT WOS:000309612000011 ER PT J AU Balsam, J Ossandon, M Bruck, HA Rasooly, A AF Balsam, Joshua Ossandon, Miguel Bruck, Hugh Alan Rasooly, Avraham TI Modeling and design of micromachined optical Soller collimators for lensless CCD-based fluorometry SO ANALYST LA English DT Article ID OPTOFLUIDIC MICROSCOPY; CAENORHABDITIS-ELEGANS; CHIP; IMMUNODETECTION; SYSTEM AB To address the needs of medical diagnostics in resource-poor settings, it is necessary to develop low cost, simple and portable Point of Care detectors for integrated medical diagnostics. Previously, we have described a simple lensless fluorometer with sensitivity in the range of current ELISA plate readers. The key to the lensfree fluorometer is the uniform spatial distribution of light, which we achieved using a simple optical collimator based on a "stack of pinholes'' (a stack of black PMMA plates with arrays of pinholes machined via laser) enabling the light to be collimated from the LED light source through the necessary wavelength filters and the assay's microfluidics directly onto the CCD without a lens. In this paper, we describe the optical principle for designing these Soller collimators for lensfree CCD-based fluorometry. The illuminating surface was modeled as a collection of differential areas emitting uniformly and spherically, and the intensity contribution of each emitting area was summed over the detector surface. To compute the final light intensity distribution from such a differential model we derived an integral equation to sum the individual intensity contributions from the two-dimensional emitting surface. The equation is for a single-hole collimator. Light intensity measurements were taken by placing a collimator with a particular aspect ratio (the ratio of hole length to diameter (L/d)) over the CCD image sensor and capturing an image. The resulting image is the 2D light intensity profile generated by the collimator. As the aspect ratio is increased the slope of the light intensity profile increases, corresponding to an increased degree of collimation. To test the model, the measured maximum and mean light intensities were compared with the theoretical predictions generated from the model. There was an agreement between the variation of the mean (R-2 = 0.990) and maximum (R-2 = 0.938) values of light intensities with aspect ratios based modeling. These profile measurements suggest an excellent agreement with the theoretical predictions. The integral equation presented here can be used to perfect the design of the optical Soller collimator. These results may lead to the development of more effective Soller collimators for lensfree CCD-based fluorometry for use in simple low cost lensfree optical detectors with the potential to enhance the accessibility and the quality of health care for underserved populations. C1 [Balsam, Joshua; Bruck, Hugh Alan; Rasooly, Avraham] US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. [Ossandon, Miguel; Rasooly, Avraham] NCI, NIH, Bethesda, MD USA. [Balsam, Joshua] UMCP, College Pk, MD 20742 USA. RP Rasooly, A (reprint author), US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. EM rasoolya@mail.nih.gov NR 22 TC 9 Z9 9 U1 1 U2 8 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0003-2654 J9 ANALYST JI Analyst PY 2012 VL 137 IS 21 BP 5011 EP 5017 DI 10.1039/c2an35729a PG 7 WC Chemistry, Analytical SC Chemistry GA 015EF UT WOS:000309427600018 PM 22973572 ER PT J AU Petry, NM AF Petry, Nancy M. BA Petry, NM BF Petry, NM TI Contingency Management FOR SUBSTANCE ABUSE TREATMENT A Guide to Implementing This Evidence-Based Practice Introduction SO CONTINGENCY MANAGEMENT FOR SUBSTANCE ABUSE TREATMENT: A GUIDE TO IMPLEMENTING THIS EVIDENCE-BASED PRACTICE LA English DT Editorial Material; Book Chapter C1 [Petry, Nancy M.] Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. [Petry, Nancy M.] NIH, Bethesda, MD USA. RP Petry, NM (reprint author), Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-1-13669-945-0 PY 2012 BP 3 EP 7 PG 5 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA BBP65 UT WOS:000307820900002 ER PT J AU Petry, NM AF Petry, Nancy M. BA Petry, NM BF Petry, NM TI Background of Behavioral Therapies and the Evolution of Contingency Management SO CONTINGENCY MANAGEMENT FOR SUBSTANCE ABUSE TREATMENT: A GUIDE TO IMPLEMENTING THIS EVIDENCE-BASED PRACTICE LA English DT Article; Book Chapter C1 [Petry, Nancy M.] Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. [Petry, Nancy M.] NIH, Bethesda, MD USA. RP Petry, NM (reprint author), Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-1-13669-945-0 PY 2012 BP 9 EP 16 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA BBP65 UT WOS:000307820900003 ER PT J AU Petry, NM AF Petry, Nancy M. BA Petry, NM BF Petry, NM TI Contingency Management FOR SUBSTANCE ABUSE TREATMENT A Guide to Implementing This Evidence-Based Practice Author's Note and Preface SO CONTINGENCY MANAGEMENT FOR SUBSTANCE ABUSE TREATMENT: A GUIDE TO IMPLEMENTING THIS EVIDENCE-BASED PRACTICE LA English DT Editorial Material; Book Chapter C1 [Petry, Nancy M.] Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. [Petry, Nancy M.] NIH, Bethesda, MD USA. RP Petry, NM (reprint author), Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-1-13669-945-0 PY 2012 BP XI EP + PG 14 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA BBP65 UT WOS:000307820900001 ER PT J AU Petry, NM AF Petry, Nancy M. BA Petry, NM BF Petry, NM TI Empirical Evidence of the Efficacy of Contingency Management SO CONTINGENCY MANAGEMENT FOR SUBSTANCE ABUSE TREATMENT: A GUIDE TO IMPLEMENTING THIS EVIDENCE-BASED PRACTICE LA English DT Article; Book Chapter C1 [Petry, Nancy M.] Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. [Petry, Nancy M.] NIH, Bethesda, MD USA. RP Petry, NM (reprint author), Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-1-13669-945-0 PY 2012 BP 17 EP 32 PG 16 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA BBP65 UT WOS:000307820900004 ER PT J AU Petry, NM AF Petry, Nancy M. BA Petry, NM BF Petry, NM TI Applications of Contingency Management in Novel Settings and With Special Populations SO CONTINGENCY MANAGEMENT FOR SUBSTANCE ABUSE TREATMENT: A GUIDE TO IMPLEMENTING THIS EVIDENCE-BASED PRACTICE LA English DT Article; Book Chapter C1 [Petry, Nancy M.] Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. [Petry, Nancy M.] NIH, Bethesda, MD USA. RP Petry, NM (reprint author), Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-1-13669-945-0 PY 2012 BP 33 EP 51 PG 19 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA BBP65 UT WOS:000307820900005 ER PT J AU Petry, NM AF Petry, Nancy M. BA Petry, NM BF Petry, NM TI Selecting a Behavior to Reinforce SO CONTINGENCY MANAGEMENT FOR SUBSTANCE ABUSE TREATMENT: A GUIDE TO IMPLEMENTING THIS EVIDENCE-BASED PRACTICE LA English DT Article; Book Chapter C1 [Petry, Nancy M.] Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. [Petry, Nancy M.] NIH, Bethesda, MD USA. RP Petry, NM (reprint author), Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-1-13669-945-0 PY 2012 BP 55 EP 68 PG 14 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA BBP65 UT WOS:000307820900006 ER PT J AU Petry, NM AF Petry, Nancy M. BA Petry, NM BF Petry, NM TI Choosing a Population SO CONTINGENCY MANAGEMENT FOR SUBSTANCE ABUSE TREATMENT: A GUIDE TO IMPLEMENTING THIS EVIDENCE-BASED PRACTICE LA English DT Article; Book Chapter C1 [Petry, Nancy M.] Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. [Petry, Nancy M.] NIH, Bethesda, MD USA. RP Petry, NM (reprint author), Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-1-13669-945-0 PY 2012 BP 69 EP 79 PG 11 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA BBP65 UT WOS:000307820900007 ER PT J AU Petry, NM AF Petry, Nancy M. BA Petry, NM BF Petry, NM TI Determining a Behavior Monitoring Schedule SO CONTINGENCY MANAGEMENT FOR SUBSTANCE ABUSE TREATMENT: A GUIDE TO IMPLEMENTING THIS EVIDENCE-BASED PRACTICE LA English DT Article; Book Chapter C1 [Petry, Nancy M.] Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. [Petry, Nancy M.] NIH, Bethesda, MD USA. RP Petry, NM (reprint author), Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-1-13669-945-0 PY 2012 BP 81 EP 102 PG 22 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA BBP65 UT WOS:000307820900008 ER PT J AU Petry, NM AF Petry, Nancy M. BA Petry, NM BF Petry, NM TI Reinforcers to Use SO CONTINGENCY MANAGEMENT FOR SUBSTANCE ABUSE TREATMENT: A GUIDE TO IMPLEMENTING THIS EVIDENCE-BASED PRACTICE LA English DT Article; Book Chapter C1 [Petry, Nancy M.] Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. [Petry, Nancy M.] NIH, Bethesda, MD USA. RP Petry, NM (reprint author), Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-1-13669-945-0 PY 2012 BP 103 EP 120 PG 18 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA BBP65 UT WOS:000307820900009 ER PT J AU Petry, NM AF Petry, Nancy M. BA Petry, NM BF Petry, NM TI Designing a Reinforcement Schedule SO CONTINGENCY MANAGEMENT FOR SUBSTANCE ABUSE TREATMENT: A GUIDE TO IMPLEMENTING THIS EVIDENCE-BASED PRACTICE LA English DT Article; Book Chapter C1 [Petry, Nancy M.] Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. [Petry, Nancy M.] NIH, Bethesda, MD USA. RP Petry, NM (reprint author), Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-1-13669-945-0 PY 2012 BP 121 EP 138 PG 18 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA BBP65 UT WOS:000307820900010 ER PT J AU Petry, NM AF Petry, Nancy M. BA Petry, NM BF Petry, NM TI Calculating Costs SO CONTINGENCY MANAGEMENT FOR SUBSTANCE ABUSE TREATMENT: A GUIDE TO IMPLEMENTING THIS EVIDENCE-BASED PRACTICE LA English DT Article; Book Chapter C1 [Petry, Nancy M.] Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. [Petry, Nancy M.] NIH, Bethesda, MD USA. RP Petry, NM (reprint author), Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-1-13669-945-0 PY 2012 BP 139 EP 165 PG 27 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA BBP65 UT WOS:000307820900011 ER PT J AU Petry, NM AF Petry, Nancy M. BA Petry, NM BF Petry, NM TI Raising Funds to Support Contingency Management Interventions SO CONTINGENCY MANAGEMENT FOR SUBSTANCE ABUSE TREATMENT: A GUIDE TO IMPLEMENTING THIS EVIDENCE-BASED PRACTICE LA English DT Article; Book Chapter C1 [Petry, Nancy M.] Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. [Petry, Nancy M.] NIH, Bethesda, MD USA. RP Petry, NM (reprint author), Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-1-13669-945-0 PY 2012 BP 167 EP 175 PG 9 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA BBP65 UT WOS:000307820900012 ER PT J AU Petry, NM AF Petry, Nancy M. BA Petry, NM BF Petry, NM TI Getting Started Stocking a Prize Cabinet and Obtaining Other Needed Supplies SO CONTINGENCY MANAGEMENT FOR SUBSTANCE ABUSE TREATMENT: A GUIDE TO IMPLEMENTING THIS EVIDENCE-BASED PRACTICE LA English DT Article; Book Chapter C1 [Petry, Nancy M.] Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. [Petry, Nancy M.] NIH, Bethesda, MD USA. RP Petry, NM (reprint author), Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-1-13669-945-0 PY 2012 BP 179 EP 203 PG 25 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA BBP65 UT WOS:000307820900013 ER PT J AU Petry, NM AF Petry, Nancy M. BA Petry, NM BF Petry, NM TI Implementation Guide for Reinforcing Abstinence Using Prize Contingency Management SO CONTINGENCY MANAGEMENT FOR SUBSTANCE ABUSE TREATMENT: A GUIDE TO IMPLEMENTING THIS EVIDENCE-BASED PRACTICE LA English DT Article; Book Chapter C1 [Petry, Nancy M.] Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. [Petry, Nancy M.] NIH, Bethesda, MD USA. RP Petry, NM (reprint author), Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-1-13669-945-0 PY 2012 BP 205 EP 241 PG 37 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA BBP65 UT WOS:000307820900014 ER PT J AU Petry, NM AF Petry, Nancy M. BA Petry, NM BF Petry, NM TI Implementation Guide for Name-in-the-Hat Prize CM for Reinforcing Group Attendance SO CONTINGENCY MANAGEMENT FOR SUBSTANCE ABUSE TREATMENT: A GUIDE TO IMPLEMENTING THIS EVIDENCE-BASED PRACTICE LA English DT Article; Book Chapter C1 [Petry, Nancy M.] Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. [Petry, Nancy M.] NIH, Bethesda, MD USA. RP Petry, NM (reprint author), Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-1-13669-945-0 PY 2012 BP 243 EP 269 PG 27 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA BBP65 UT WOS:000307820900015 ER PT J AU Petry, NM AF Petry, Nancy M. BA Petry, NM BF Petry, NM TI Monitoring and Supervising Adherence and Competence in Contingency Management Delivery SO CONTINGENCY MANAGEMENT FOR SUBSTANCE ABUSE TREATMENT: A GUIDE TO IMPLEMENTING THIS EVIDENCE-BASED PRACTICE LA English DT Article; Book Chapter C1 [Petry, Nancy M.] Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. [Petry, Nancy M.] NIH, Bethesda, MD USA. RP Petry, NM (reprint author), Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-1-13669-945-0 PY 2012 BP 271 EP 293 PG 23 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA BBP65 UT WOS:000307820900016 ER PT J AU Petry, NM AF Petry, Nancy M. BA Petry, NM BF Petry, NM TI Contingency Management FOR SUBSTANCE ABUSE TREATMENT A Guide to Implementing This Evidence-Based Practice Conclusion SO CONTINGENCY MANAGEMENT FOR SUBSTANCE ABUSE TREATMENT: A GUIDE TO IMPLEMENTING THIS EVIDENCE-BASED PRACTICE LA English DT Editorial Material; Book Chapter C1 [Petry, Nancy M.] Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. [Petry, Nancy M.] NIH, Bethesda, MD USA. RP Petry, NM (reprint author), Univ Connecticut, Ctr Hlth, Calhoun Cardiol Ctr, Storrs, CT 06269 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-1-13669-945-0 PY 2012 BP 297 EP 299 PG 3 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA BBP65 UT WOS:000307820900017 ER PT S AU Celik, H Shaka, AJ AF Celik, Hasan Shaka, Athan J. GP IEEE TI A New Approach For Mixture Separation Using NMR Spectroscopy: Blind Iterative Source Identification SO 2012 38TH ANNUAL NORTHEAST BIOENGINEERING CONFERENCE (NEBEC) SE Annual IEEE Northeast Bioengineering Conference LA English DT Proceedings Paper CT 38th Annual Northeast Bioengineering Conference (NEBEC) CY MAR 16-18, 2012 CL Temple Univ, Philadelphia, PA SP Natl Sci Fdn (NSF), Temple Univ, Coll Engn, Temple Univ, Off Senior Vice Provost Res & Grad Educ, Temple Univ, Dept Bioengn, ACS Synthet Biol, IEEE - EMBS, AIMBE, Spectrum Chem, IEEE HO Temple Univ C1 [Celik, Hasan] NIA, Magnet Resonance Imaging & Spect Sect, NIH, Baltimore, MD 21224 USA. [Shaka, Athan J.] Univ Calif Irvine, Dept Chem, Irvine, CA USA. RP Celik, H (reprint author), NIA, Magnet Resonance Imaging & Spect Sect, NIH, Baltimore, MD 21224 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0277-1063 BN 978-1-4673-1142-7 J9 NORTHEAST BIOENGIN C PY 2012 BP 149 EP + PG 2 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BBY91 UT WOS:000309001200075 ER PT S AU Padalkar, M Spencer, R Pleshko, N AF Padalkar, M. Spencer, R. Pleshko, N. GP IEEE TI Near Infrared Spectroscopic Evaluation of Water in Hyaline Cartilage SO 2012 38TH ANNUAL NORTHEAST BIOENGINEERING CONFERENCE (NEBEC) SE Annual IEEE Northeast Bioengineering Conference LA English DT Proceedings Paper CT 38th Annual Northeast Bioengineering Conference (NEBEC) CY MAR 16-18, 2012 CL Temple Univ, Philadelphia, PA SP Natl Sci Fdn (NSF), Temple Univ, Coll Engn, Temple Univ, Off Senior Vice Provost Res & Grad Educ, Temple Univ, Dept Bioengn, ACS Synthet Biol, IEEE - EMBS, AIMBE, Spectrum Chem, IEEE HO Temple Univ AB Articular cartilage is avascular and has limited capacity for repair. In diseased conditions such as osteoarthritis, there is an increase in water content from the average normal of 60-85% to greater than 90%. As cartilage has very little capability for self-repair, methods of early detection of degeneration are required, and assessment of water could prove to be a useful diagnostic method. Non-destructivenear infrared spectroscopyis extremely sensitive to the chemical composition and molecular structure of tissues and could prove to be a useful method for early diagnosis of cartilage degeneration. The hypothesis that NIR spectra can be used to assess water content in cartilage was investigated in the current study. C1 [Padalkar, M.; Pleshko, N.] Temple Univ, Dept Bioengn, Philadelphia, PA 19122 USA. [Spencer, R.] NIH, NIA, Baltimore, MD 21224 USA. RP Padalkar, M (reprint author), Temple Univ, Dept Bioengn, Philadelphia, PA 19122 USA. FU Intramural Research Program of the NIH (NIA); NIH [AR056145] FX This study was supported in part by the Intramural Research Program of the NIH (NIA), and by NIH AR056145. NR 8 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0277-1063 BN 978-1-4673-1142-7 J9 NORTHEAST BIOENGIN C PY 2012 BP 370 EP + PG 2 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BBY91 UT WOS:000309001200185 ER PT J AU Li, KG Seo, DC Torabi, MR Peng, CYJ Kay, NS Kolbe, LJ AF Li, Kaigang Seo, Dong-Chul Torabi, Mohammad R. Peng, Chao-Ying J. Kay, Noy S. Kolbe, Lloyd J. TI Social-Ecological Factors of Leisure-Time Physical Activity in Black Adults SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Article DE leisure-time physical activity; social-ecological model; self-regulation; African-Americans; structural equation modeling; outcome-expectancy value ID AFRICAN-AMERICAN WOMEN; STRUCTURAL EQUATION ANALYSIS; NUTRITION EXAMINATION SURVEY; ENVIRONMENTAL-INFLUENCES; COGNITIVE DETERMINANTS; EXERCISE BEHAVIOR; HEALTH-PROMOTION; PLANNED BEHAVIOR; NATIONAL-HEALTH; SPORTS-MEDICINE AB Objectives: To develop and test an explicative model of leisure-time physical activity (LTPA), including 6 selected contributory factors: self-efficacy, self-regulation, social support, perceived physical environment, outcome-expectancy value, and policy beliefs. Methods: A social-ecological model of LTPA using the structural equation modeling technique was estimated in a regional, church-going sample of 649 African Americans. Results: The results indicated this model is good fit to the data. LTPA was associated with self-regulation and gender directly (P<.05) and social support, self-efficacy, perceived access to LTPA facilities, and positive outcome-expectancy value indirectly (P<.05). Conclusions: Multitiered interventions considering cultural relevance are recommended to improve LTPA engagement. C1 [Li, Kaigang] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Bethesda, MD USA. [Seo, Dong-Chul; Kay, Noy S.] Indiana Univ, Dept Appl Hlth Sci, Bloomington, IN 47405 USA. [Torabi, Mohammad R.] Indiana Univ, Sch Hlth Phys Educ & Recreat, Bloomington, IN USA. [Peng, Chao-Ying J.] Indiana Univ, Sch Educ, Bloomington, IN 47405 USA. RP Li, KG (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Bethesda, MD USA. EM likaigang@gmail.com RI Seo, Dong-Chul/A-6935-2009 OI Seo, Dong-Chul/0000-0002-1972-6237 NR 55 TC 5 Z9 5 U1 3 U2 21 PU PNG PUBLICATIONS PI OAK RIDGE PA 2205-K OAK RIDGE RD, #115, OAK RIDGE, NC 27310 USA SN 1945-7359 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PY 2012 VL 36 IS 6 BP 797 EP 810 DI 10.5993/AJHB.36.6.7 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 014EN UT WOS:000309358000007 PM 23026038 ER PT J AU Airavaara, M Harvey, BK Voutilainen, MH Shen, H Chou, J Lindholm, P Lindahl, M Tuominen, RK Saarma, M Hoffer, B Wang, Y AF Airavaara, Mikko Harvey, Brandon K. Voutilainen, Merja H. Shen, Hui Chou, Jenny Lindholm, Paivi Lindahl, Maria Tuominen, Raimo K. Saarma, Mart Hoffer, Barry Wang, Yun TI CDNF Protects the Nigrostriatal Dopamine System and Promotes Recovery After MPTP Treatment in Mice SO CELL TRANSPLANTATION LA English DT Article DE Cerebral dopamine neurotrophic factor (CDNF); Mesencephalic astrocyte-derived neurotrophic factor (MANF); 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); Parkinson's disease ID ISCHEMIC BRAIN-INJURY; NEURONS IN-VIVO; NEUROTROPHIC FACTOR; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; TREATED MICE; MOUSE MODEL; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; MANF; INFUSION AB Cerebral dopamine neurotrophic factor (CDNF) is a recently discovered protein, which belongs to the evolutionarily conserved CDNF/MANF family of neurotrophic factors. The degeneration of dopamine neurons following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment is well characterized, and efficacy in this model is considered a standard criterion for development of parkinsonian therapies. MPTP is a neurotoxin, which produces parkinsonian symptoms in humans and in C57/B16 mice. To date, there are no reports about the effects of CDNF on dopamine neuron survival or function in the MPTP rodent model, a critical gap. Therefore, we studied whether CDNF has neuroprotective and neurorestorative properties for the nigrostriatal dopamine system after MPTP injections in C57/B16 mice. We found that bilateral striatal CDNF injections. given 20 h before MPTP, improved horizontal and vertical motor behavior. CDNF pretreatment increased tyrosine hydroxylase (TH) immunoreactivity in the striatum and in the substantia nigra pars reticulata (SNpr), as well as the number of TH-positive cells in substantia nigra pars compacta (SNpc). Posttreatment with CDNF, given I week after MPTP injections, increased horizontal and vertical motor behavior of mice, as well as dopamine fiber densities in the striatum and the number of TH-positive cells in SNpc. CDNF did not alter any of the analyzed dopaminergic biomarkers or locomotor behavior in MPTP-untreated animals. We conclude that striatal CDNF administration is both neuroprotective and neurorestorative for the TH-positive cells in the nigrostriatal dopamine system in the MPTP model, which supports the development of CDNF-based treatment for Parkinson's disease. C1 [Airavaara, Mikko; Harvey, Brandon K.; Shen, Hui; Chou, Jenny; Hoffer, Barry; Wang, Yun] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Voutilainen, Merja H.; Tuominen, Raimo K.] Univ Helsinki, Dept Pharmacol & Toxicol, Fac Pharm, FIN-00170 Helsinki, Finland. [Lindholm, Paivi; Lindahl, Maria; Saarma, Mart] Univ Helsinki, Inst Biotechnol, Helsinki, Finland. RP Wang, Y (reprint author), Natl Inst Drug Abuse, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM ywang@intra.nida.nih.gov RI Voutilainen, Merja/D-9601-2014; OI Airavaara, Mikko/0000-0002-2026-1609 FU IRP of NIDA; IRP of NIH; IRP of DHHS FX This research was supported by the IRP of NIDA, NIH, DHHS. We would like to thank Carl Lupica, Alex Hoffman, and Christopher Richie for their help with the study. The authors declare no conflicts of interest. NR 44 TC 32 Z9 33 U1 1 U2 13 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2012 VL 21 IS 6 BP 1213 EP 1223 DI 10.3727/0963689IIX600948 PG 11 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 009OO UT WOS:000309035300012 PM 21943517 ER PT J AU Soleimanpour, SA Hirshberg, B Bunnell, DJ Sumner, AE Ader, M Remaley, AT Rother, KI Rickels, MR Harlan, DM AF Soleimanpour, Scott A. Hirshberg, Boaz Bunnell, David J. Sumner, Anne E. Ader, Marilyn Remaley, Alan T. Rother, Kristina I. Rickels, Michael R. Harlan, David M. TI Metabolic Function of a Suboptimal Transplanted Islet Mass in Nonhuman Primates on Rapamycin Monotherapy SO CELL TRANSPLANTATION LA English DT Article DE Nonhuman primates; Islet transplantation; Metabolic function ID BETA-CELL FUNCTION; INSULIN SENSITIVITY; PANCREATIC-ISLETS; PORTAL-VEIN; GLUCOSE-TOLERANCE; IN-VIVO; MODEL; SIROLIMUS; RECIPIENTS; IMMUNOSUPPRESSION AB Although islet transplantation may restore insulin independence to individuals with type 1 diabetes mellitus. most have abnormal glucose tolerance. We asked whether the defective glucose tolerance is due to inadequate beta-cell mass or to impaired insulin sensitivity. We performed metabolic studies on four cynornolgus primates before inducing diabetes with streptozotocin (STZ), then again 2-3 weeks after restoring insulin independence via intrahepatic islet transplantation utilizing a calcineurin inhibitor-free immunosuppressive regimen (induction with rabbit antithymocyte globulin and maintenance therapy with rapamycin). Engrafted beta-cell mass was assessed by acute insulin and C-peptide responses to glucose (AIR(glu) and ACR(glu)) and arginine (AIR(arg) and ACR(arg)). Insulin sensitivity (S-1) was determined in naive and transplanted primates from an intravenous glucose tolerance test using the minimal model, alpha-Cell function was determined by the acute glucagon response to arginine (AGR(arg)). Glucose tolerance (K-8) decreased from 4.1 +/- 0.5%/min in naive primates to 1.8 +/- 0.3%/min in transplanted primates (p < 0.01). Following transplantation, AIR(glu) was 28.7 +/- 13.1 mu U/ml compared to 169.9 +/- 43.1 mu U/ml (p < 0.03) in the naive condition, ACR(glu) was 14.5 +/- 6.0 ng/ml compared to 96.5 +/- 17.0 ng/ml naive (p < 0.01), AIR(arg), was 29.1 +/- 13.1 mu U/ml compared to 91.4 +/- 28.2 mu U/ml naive (p < 0.05), and ACR(arg) was 1.11 +/- 0.51 ng/ml compared to 2.79 0.77 ng/ml naive (p < 0.05). S-1 did not differ from naive to posttransplant states. AGR(arg) was reduced in transplanted primates (349 +/- 118 pg/ml) when compared to both naive (827 +/- 354 pg/ml) and post-STZ diabetic primates (1020 +/- 440 pg/ml) (p < 0.01 for both comparisons). These data suggest that impaired glucose tolerance observed in islet transplant recipients is secondary to low functional beta-cell mass and not to insulin resistance shortly after transplant. Furthermore, improved glycemic control achieved via islet transplantation over the diabetic state might be attained, in part, via reduced glucagon secretion. C1 [Soleimanpour, Scott A.] Univ Penn, Sch Med, Inst Diabet Obes & Metab, Translat Res Ctr, Philadelphia, PA 19104 USA. [Soleimanpour, Scott A.; Hirshberg, Boaz; Bunnell, David J.; Harlan, David M.] NIDDK, Islet & Autoimmun Branch, NIH, Bethesda, MD USA. [Sumner, Anne E.; Rother, Kristina I.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD USA. [Ader, Marilyn] Univ So Calif, Dept Physiol & Biophys, Los Angeles, CA 90089 USA. [Remaley, Alan T.] NIH, Dept Lab Med, Bethesda, MD 20892 USA. [Harlan, David M.] Univ Massachusetts, Sch Med, Dept Med, Diabet Div, Worcester, MA USA. RP Soleimanpour, SA (reprint author), Univ Penn, Sch Med, Inst Diabet Obes & Metab, Translat Res Ctr, 3400 Civ Ctr Blvd,Bldg 421,Room 12-165, Philadelphia, PA 19104 USA. EM scott.soleimanpour@uphs.upenn.edu FU HHMI-NIH Research Scholars Program; Benjamin and Mary Siddons Measey Foundation; Charles H. Humpton, Jr. Endowment; Margaret Q. Landenberger Foundation; Schiffrin Family Foundation; intramural program of NIDDK/NIH FX The authors wish to thank Monnie Choongkittaworn and Noelle Patterson for their technical support. We wish to thank Michael Quon and Alan Cherrington for their advice. We wish to acknowledge the excellent husbandry and care provided by the NIH Veterinary Resources Program, building 14D staff The authors also wish to acknowledge support of the HHMI-NIH Research Scholars Program, the Benjamin and Mary Siddons Measey Foundation, the Charles H. Humpton, Jr. Endowment, and the Margaret Q. Landenberger Foundation to S.A.S., and support of the Schiffrin Family Foundation to M.R.R. A.E.S. and K.I.R. were supported by the intramural program of NIDDK/NIH. NR 34 TC 3 Z9 3 U1 0 U2 1 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2012 VL 21 IS 6 BP 1297 EP 1304 DI 10.3727/096368911X603620 PG 8 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 009OO UT WOS:000309035300019 PM 22080915 ER PT J AU Qu, P Boelte, KC Lin, PC AF Qu, Peng Boelte, Kimberly C. Lin, P. Charles TI Negative Regulation of Myeloid-derived Suppressor Cells in Cancer SO IMMUNOLOGICAL INVESTIGATIONS LA English DT Article DE MDSC; Cancer; Inflammation ID TUMOR-BEARING MICE; COLONY-STIMULATING FACTOR; CD8(+) T-CELLS; IMMUNE DYSFUNCTION; ANTITUMOR IMMUNITY; MAMMARY CARCINOMAS; DOWN-REGULATION; ARGINASE-I; INFLAMMATION; EXPANSION AB Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells with suppressive function on immune response. In this review, we discuss recent studies about mechanisms of expansion and suppressive function of MDSCs during inflammation, infection and autoimmune diseases, as well as pro-angiogenic and pro-metastatic functions of these cells in tumor development. Further, we focus on novel studies of MDSCs and therapeutic approaches to eliminate these cells in cancer. C1 [Qu, Peng; Boelte, Kimberly C.; Lin, P. Charles] NCI, NIH, Frederick, MD 21702 USA. RP Lin, PC (reprint author), NCI, NIH, Frederick, MD 21702 USA. EM p.lin@nih.gov NR 107 TC 16 Z9 16 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0882-0139 J9 IMMUNOL INVEST JI Immunol. Invest. PY 2012 VL 41 IS 6-7 BP 562 EP 580 DI 10.3109/08820139.2012.685538 PG 19 WC Immunology SC Immunology GA 015LS UT WOS:000309448100003 PM 23017135 ER PT J AU Haile, LA Greten, TF Korangy, F AF Haile, Lydia A. Greten, Tim F. Korangy, Firouzeh TI Immune Suppression: The Hallmark of Myeloid Derived Suppressor Cells SO IMMUNOLOGICAL INVESTIGATIONS LA English DT Article DE Cancer; Tumor immunology; Tolerance ID TUMOR-BEARING MICE; CD8(+) T-CELLS; HEPATOCELLULAR-CARCINOMA; CANCER-PATIENTS; EXPANSION; MECHANISM; ANTIGEN; TOLERANCE; DYSFUNCTION; POPULATION AB Myeloid derived suppressor cells (MDSC) are heterogeneous cell population consisting of myeloid progenitor cells and immature myeloid cells. These cells have essential immunoregulatory role in tumor bearing hosts and under different inflammatory conditions. No specific marker has been described to identify MDSC, which leaves their suppressor activity as their only hallmark function. In this review, we discuss the current in vivo and in vitro developed assays for elucidation of MDSC function and describe the discrepancies between murine and human MDSC in regard to their suppressor function. We also discuss antigen specificity of MDSC function and approaches to determine the effector function of these cells in vivo. Finally, we summarize different approaches currently being employed to target MDSC with the aim to enhance immune based therapies. C1 [Haile, Lydia A.; Greten, Tim F.; Korangy, Firouzeh] NCI, Gastrointestinal Malignancy Sect, Med Oncol Branch, Bethesda, MD 20892 USA. [Haile, Lydia A.] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, D-3000 Hannover, Germany. RP Korangy, F (reprint author), NCI, Gastrointestinal Malignancy Sect, Med Oncol Branch, Bldg 10,Rm 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM firouzeh.korangy@nih.gov RI Greten, Tim/B-3127-2015 OI Greten, Tim/0000-0002-0806-2535 NR 59 TC 26 Z9 29 U1 0 U2 7 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0882-0139 J9 IMMUNOL INVEST JI Immunol. Invest. PY 2012 VL 41 IS 6-7 BP 581 EP 594 DI 10.3109/08820139.2012.680635 PG 14 WC Immunology SC Immunology GA 015LS UT WOS:000309448100004 PM 23017136 ER PT J AU Resnik, DB AF Resnik, David B. TI Editorial: Plagiarism: Words and Ideas SO ACCOUNTABILITY IN RESEARCH-POLICIES AND QUALITY ASSURANCE LA English DT Editorial Material C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Resnik, DB (reprint author), NIEHS, NIH, Mail Drop CU 03,Box 12233, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov FU Intramural NIH HHS [ZIA ES102646-05, ZIA ES102646-04] NR 7 TC 5 Z9 5 U1 1 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0898-9621 J9 ACCOUNT RES JI Account. Res. PY 2012 VL 19 IS 5 BP 269 EP 272 DI 10.1080/08989621.2012.718677 PG 4 WC Medical Ethics SC Medical Ethics GA 012ZN UT WOS:000309275400001 PM 23009267 ER PT J AU Wang, Z Huang, P Bhirde, A Jin, A Ma, Y Niu, G Neamati, N Chen, XY AF Wang, Zhe Huang, Peng Bhirde, Ashwinkumar Jin, Albert Ma, Ying Niu, Gang Neamati, Nouri Chen, Xiaoyuan TI A nanoscale graphene oxide-peptide biosensor for real-time specific biomarker detection on the cell surface SO CHEMICAL COMMUNICATIONS LA English DT Article ID QUANTUM DOTS; INTEGRIN; NANOPARTICLES; DELIVERY; THERAPY; COMPLEX; PROTEIN; SHEETS; SENSOR AB A nanoscale RGD-pyrene-graphene oxide (GO) biosensor was prepared for real-time in situ detection of a cancer cell surface marker, integrin alpha v beta 3. This nanoscale GO-based biosensor is simple, robust, sensitive and of high selectivity. It can also be adapted to other cancer cell surface marker evaluation systems. C1 [Wang, Zhe; Neamati, Nouri] Univ So Calif, Sch Pharm, Dept Pharmacol & Pharmaceut Sci, Los Angeles, CA 90089 USA. [Wang, Zhe; Huang, Peng; Bhirde, Ashwinkumar; Ma, Ying; Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. [Wang, Zhe; Huang, Peng] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, Xiamen 361005, Peoples R China. [Jin, Albert] Natl Inst Biomed Imaging & Bioengn, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA. RP Neamati, N (reprint author), Univ So Calif, Sch Pharm, Dept Pharmacol & Pharmaceut Sci, 1985 Zonal Ave, Los Angeles, CA 90089 USA. EM neamati@usc.edu; shawn.chen@nih.gov RI Huang, Peng/H-9985-2013; Huang, Peng/R-2480-2016; OI Huang, Peng/0000-0003-3651-7813; Jin, Albert/0000-0003-3826-1081 FU Intramural NIH HHS [ZIA EB000015-05, Z99 EB999999, ZIA EB000073-03]; NCI NIH HHS [R01CA120188] NR 25 TC 46 Z9 48 U1 4 U2 132 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 J9 CHEM COMMUN JI Chem. Commun. PY 2012 VL 48 IS 78 BP 9768 EP 9770 DI 10.1039/c2cc31974h PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 000UM UT WOS:000308414500027 PM 22919703 ER PT J AU Harford, TC Yi, HY Freeman, RC AF Harford, Thomas C. Yi, Hsiao-Ye Freeman, Robert C. TI A Typology of Violence Against Self and Others and Its Associations With Drinking and Other Drug Use Among High School Students in a US General Population Survey SO JOURNAL OF CHILD & ADOLESCENT SUBSTANCE ABUSE LA English DT Article DE aggression; binge drinking; illicit drug use; suicide; violence typology ID ADOLESCENT SUICIDE ATTEMPTS; HEALTH-RISK BEHAVIORS; ALCOHOL-USE; DATING VIOLENCE; ANTISOCIAL-BEHAVIOR; PEER VIOLENCE; UNITED-STATES; USE DISORDERS; SUBSTANCE USE; YOUTH AB This study examines associations between binge drinking and other substance use and perpetration of violence against self and others. Data were pooled from the 2003, 2005, and 2007 Youth Risk Behavior Surveys, yielding a sample of 43,172 U.S. high school students. A typology was constructed to reflect four categories of behaviors: other-directed violence only, self-directed violence only, combined other- and self-directed violence, and no violence. Results from multinomial logistic regressions show that the frequency of binge drinking and other substance use were significant risk factors for each of the violence categories relative to no violence. However, the strengths of these associations varied across the violence categories. C1 [Harford, Thomas C.; Yi, Hsiao-Ye] CSR Inc, Arlington, VA 22201 USA. [Freeman, Robert C.] NIAAA, Bethesda, MD USA. RP Yi, HY (reprint author), CSR Inc, 2107 Wilson Blvd,Suite 1000, Arlington, VA 22201 USA. EM hyi@csrincorporated.com FU NIAAA NIH HHS [HHSN267200800023C] NR 61 TC 6 Z9 6 U1 3 U2 7 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1067-828X J9 J CHILD ADOLES SUBST JI J. Child Adolesc. Subst. Abus. PY 2012 VL 21 IS 4 BP 349 EP 366 DI 10.1080/1067828X.2012.710028 PG 18 WC Substance Abuse SC Substance Abuse GA 008VU UT WOS:000308985500005 PM 26478688 ER PT S AU Hall, KD AF Hall, Kevin D. BE Cousins, RJ TI Modeling Metabolic Adaptations and Energy Regulation in Humans SO ANNUAL REVIEW OF NUTRITION, VOL 32 SE Annual Review of Nutrition LA English DT Review; Book Chapter DE mathematical model; body weight; body composition; obesity; energy balance; macronutrient balance ID RANDOMIZED CONTROLLED-TRIAL; WEIGHT-LOSS MAINTENANCE; DOUBLY LABELED WATER; LOW-CALORIE DIET; FAT-FREE MASS; BODY-WEIGHT; ADAPTIVE THERMOGENESIS; PHYSICAL-ACTIVITY; COMPUTATIONAL MODEL; MATHEMATICAL-MODEL AB Mathematical modeling of human energy regulation and body weight change has recently reached the level of sophistication required for accurate predictions. Mathematical models are beginning to provide a quantitative framework for integrating experimental data in humans and thereby help us better understand the dynamic imbalances of energy and macronutrients that give rise to changes in body weight and composition. This review provides an overview of the various approaches that have been used to model body weight dynamics and energy regulation in humans, highlights several insights that these models have provided, and suggests how mathematical models can serve as a guide for future experimental research. C1 NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. RP Hall, KD (reprint author), NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. EM kevinh@niddk.nih.gov RI Biguzzi, Felipe/E-4724-2015 FU Intramural NIH HHS NR 110 TC 18 Z9 18 U1 3 U2 19 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0199-9885 BN 978-0-8243-2832-0 J9 ANNU REV NUTR JI Annu. Rev. Nutr. PY 2012 VL 32 BP 35 EP 54 DI 10.1146/annurev-nutr-071811-150705 PG 20 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BBR29 UT WOS:000307963100003 PM 22540251 ER PT S AU Davis, CD Tsuji, PA Milner, JA AF Davis, Cindy D. Tsuji, Petra A. Milner, John A. BE Cousins, RJ TI Selenoproteins and Cancer Prevention SO ANNUAL REVIEW OF NUTRITION, VOL 32 SE Annual Review of Nutrition LA English DT Review; Book Chapter DE selenium; glutathione peroxidase; thioredoxin reductase; 15 kDa selenoprotein; genetic polymorphisms ID THIOREDOXIN REDUCTASE 1; GPX1 PRO198LEU POLYMORPHISM; HYDROPEROXIDE GLUTATHIONE-PEROXIDASE; SINGLE-NUCLEOTIDE POLYMORPHISM; SQUAMOUS-CELL CARCINOMA; BREAST-CANCER; PROSTATE-CANCER; LUNG-CANCER; GENE-EXPRESSION; BLADDER-CANCER AB The discovery of multiple selenoproteins has raised tantalizing questions about their role in maintaining normal cellular function. Unfortunately, many of these remain inadequately investigated. While they have a role in maintaining redox balance, other functions are becoming increasingly recognized. As the roles of these selenoproteins are further characterized, a better understanding of the true physiological significance of this trace element will arise. This knowledge will be essential in defining optimum intakes to achieve cellular homeostasis in order to optimize health, including a reduction in cancer, for diverse populations. Human variation in the response to selenium likely reflects significant interactions between the type and amounts of selenium consumed with the genome and a host of environmental factors including the totality of the diet, as discussed in this review. C1 [Tsuji, Petra A.] Towson Univ, Dept Biol Sci, Towson, MD 21252 USA. [Davis, Cindy D.; Milner, John A.] NCI, Nutr Sci Res Grp, Rockville, MD 20892 USA. RP Davis, CD (reprint author), NIH, Off Dietary Supplements, Bldg 10, Rockville, MD 20892 USA. EM davisci@mail.nih.gov; ptsuji@towson.edu; milnerj@mail.nih.gov NR 128 TC 59 Z9 61 U1 2 U2 27 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0199-9885 BN 978-0-8243-2832-0 J9 ANNU REV NUTR JI Annu. Rev. Nutr. PY 2012 VL 32 BP 73 EP + DI 10.1146/annurev-nutr-071811-150740 PG 25 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BBR29 UT WOS:000307963100005 PM 22404120 ER PT S AU Wang, HJ Gao, B Zakhari, S Nagy, LE AF Wang, H. Joe Gao, Bin Zakhari, Samir Nagy, Laura E. BE Cousins, RJ TI Inflammation in Alcoholic Liver Disease SO ANNUAL REVIEW OF NUTRITION, VOL 32 SE Annual Review of Nutrition LA English DT Review; Book Chapter DE ethanol; liver injury; hepatic macrophage; cytokines; complement; inflammasome ID TUMOR-NECROSIS-FACTOR; RAT KUPFFER CELLS; TNF-ALPHA PRODUCTION; INTERCELLULAR-ADHESION MOLECULE-1; DIETARY SATURATED FAT; TOLL-LIKE RECEPTOR-4; SHORT-TERM SURVIVAL; KAPPA-B PATHWAYS; CHRONIC ETHANOL; SIGNAL TRANSDUCER AB Frank Burr Mallory's landmark observation in 1911 on the histopathology of alcoholic liver disease (ALD) was the first identification of a link between inflammation and ALD. In this review, we summarize recent advances regarding the origins and roles of various inflammatory components in ALD. Metabolism of ethanol generates a number of metabolites, including acetate, reactive oxygen species, acetaldehyde, and epigenetic changes, that can induce inflammatory responses. Alcohol and its metabolites can also initiate and aggravate inflammatory conditions by promoting gut leakiness of microbial products, by sensitizing immune cells to stimulation, and by activating innate immune pathways, such as complement. Chronic alcohol consumption also sensitizes non-immune cells, e.g., hepatocytes, to inflammatory signals and impairs their ability to respond to protective signals. Based on these advances, a number of inflammatory targets have been identified with potential for therapeutic intervention in ALD, presenting new opportunities and challenges for translational research. C1 [Wang, H. Joe; Zakhari, Samir] NIAAA, Div Metab & Hlth Effects, Bethesda, MD 20892 USA. [Gao, Bin] NIAAA, Lab Liver Dis, Bethesda, MD 20892 USA. [Nagy, Laura E.] Case Western Reserve Univ, Cleveland Clin, Ctr Liver Dis Res, Cleveland, OH 44106 USA. [Nagy, Laura E.] Case Western Reserve Univ, Dept Nutr, Cleveland, OH 44106 USA. [Nagy, Laura E.] Case Western Reserve Univ, Dept Mol Med, Cleveland, OH 44106 USA. RP Wang, HJ (reprint author), NIAAA, Div Metab & Hlth Effects, Bethesda, MD 20892 USA. EM wangh4@mail.nih.gov; bgao@mail.nih.gov FU Intramural NIH HHS [ZIA AA000368-11, ZIA AA000369-11, Z99 AA999999]; NIAAA NIH HHS [P20 AA017837, R01 AA011876, R01 AA011975, R01 AA016399, R37 AA011876] NR 158 TC 78 Z9 80 U1 4 U2 28 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0199-9885 BN 978-0-8243-2832-0 J9 ANNU REV NUTR JI Annu. Rev. Nutr. PY 2012 VL 32 BP 343 EP + DI 10.1146/annurev-nutr-072610-145138 PG 27 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BBR29 UT WOS:000307963100017 PM 22524187 ER PT J AU Vyas, NS Puri, BK AF Vyas, Nora S. Puri, Basant K. TI Evidence for an Association between Brain-Derived Neurotrophic Factor Val66Met Gene Polymorphism and General Intellectual Ability in Early-Onset Schizophrenia SO ISRAEL JOURNAL OF PSYCHIATRY AND RELATED SCIENCES LA English DT Article ID FAMILY-BASED ASSOCIATION; FACTOR BDNF GENE; COGNITIVE DEFICITS; HIGH-RISK; AFFECTIVE PSYCHOSES; ALZHEIMERS-DISEASE; BIPOLAR DISORDER; SEMANTIC MEMORY; LIFE-SPAN; INTELLIGENCE AB Background: Brain-derived neurotrophic factor (BDNF) plays a crucial role in the survival, development and maintenance of neuronal systems, and the Val66Met polymorphism has been implicated in memory functions. Method: We examined the association of BDNF with general intellectual ability in 161 individuals including 53 early-onset patients with schizophrenia (EOS), 91 healthy biological relatives, and 17 relatives with major depressive disorder (MDD), using the Wechsler Intelligence Scales (WISC). Results: Regardless of diagnosis, individuals with the Met66 allele had a significantly higher performance score than those homozygous for Val66 on vocabulary, block design and object assembly subtests of the WISC. EOS probands showed poor performance on all IQ subtests compared with relatives with and without MDD. Limitations: Relatively smaller sample size of individual genotypes. Conclusions: BDNF genotype may play a role in specific cognitive functions and dimensions of intelligence. The Met allele appears to be associated with superior performance in IQ compared with relatives Val/Val genotype. C1 [Vyas, Nora S.] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. [Vyas, Nora S.] Kings Coll London, Inst Psychiat, SGDP Ctr, London WC2R 2LS, England. [Vyas, Nora S.] Kings Coll London, Dept Psychosis Studies, London WC2R 2LS, England. [Puri, Basant K.] Imperial Coll Healthcare NHS Trust, Hammersmith Hosp, Dept Imaging, London, England. RP Vyas, NS (reprint author), NIMH, Child Psychiat Branch, NIH, Bldg 10,Rm 3N202, Bethesda, MD 20892 USA. EM nora.vyas@nih.gov FU departmental fund at King's College London; Institute of Psychiatry, London, U.K; Fulbright Distinguished Scholar Award; Lindemann Trust Fellowship; US-UK Fulbright Commission FX This work was supported by a departmental fund at King's College London, Institute of Psychiatry, London, U.K. We are grateful to the patients and relatives who participated in the VIPS project. We thank child and adolescent consultant psychiatrists from the adolescent services who referred suitable participants for this study.; Dr. Nora S. Vyas was supported by the Fulbright Distinguished Scholar Award by the US-UK Fulbright Commission and is currently supported by the Lindemann Trust Fellowship. NR 70 TC 0 Z9 0 U1 2 U2 5 PU MEDIAFARM GROUP PI TEL-AVIV PA 23 ZAMENHOFF ST, TEL-AVIV, 64373, ISRAEL SN 0333-7308 J9 ISR J PSYCHIATR REL JI Isr. J. Psychiatr. Relat. Sci. PY 2012 VL 49 IS 2 BP 137 EP 144 PN 2 PG 8 WC Psychiatry SC Psychiatry GA 004RB UT WOS:000308697700008 ER PT J AU Dong, YQ Guha, S Sun, XP Cao, M Wang, XX Zou, SG AF Dong, Yuqing Guha, Sujay Sun, Xiaoping Cao, Min Wang, Xiaoxia Zou, Sige TI Nutraceutical Interventions for Promoting Healthy Aging in Invertebrate Models SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY LA English DT Review ID LIFE-SPAN EXTENSION; BILOBA EXTRACT EGB-761; AMYLOID-BETA AGGREGATION; AMAZONIAN PALM BERRY; OLERACEAE MART. ACAI; TEPHRITID FRUIT-FLY; GREEN TEA CATECHINS; CAENORHABDITIS-ELEGANS; DIETARY-RESTRICTION; DROSOPHILA-MELANOGASTER AB Aging is a complex and inevitable biological process that is associated with numerous chronically debilitating health effects. Development of effective interventions for promoting healthy aging is an active but challenging area of research. Mechanistic studies in various model organisms, noticeably two invertebrates, Caenorhabditis elegans and Drosophila melanogaster, have identified many genes and pathways as well as dietary interventions that modulate lifespan and healthspan. These studies have shed light on some of the mechanisms involved in aging processes and provide valuable guidance for developing efficacious aging interventions. Nutraceuticals made from various plants contain a significant amount of phytochemicals with diverse biological activities. Phytochemicals can modulate many signaling pathways that exert numerous health benefits, such as reducing cancer incidence and inflammation, and promoting healthy aging. In this paper, we outline the current progress in aging intervention studies using nutraceuticals from an evolutionary perspective in invertebrate models. C1 [Dong, Yuqing; Guha, Sujay; Cao, Min; Wang, Xiaoxia] Clemson Univ, Dept Biol Sci, Clemson, SC 29634 USA. [Dong, Yuqing; Cao, Min] Clemson Univ, Inst Engaged Aging, Clemson, SC 29634 USA. [Sun, Xiaoping; Zou, Sige] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA. RP Dong, YQ (reprint author), Clemson Univ, Dept Biol Sci, 132 Long Hall, Clemson, SC 29634 USA. EM ydong@clemson.edu; zous@grc.nia.nih.gov RI Cao, Min/A-3532-2013 FU Creative Inquiry fund at Clemson University; Yamada Research Grant; American Federation of Aging Research (AFAR) grant; Intramural Research Program at National Institute on Aging, NIH FX The authors thank Edward Spangler and Robert Kosinski for critical reading of the paper. They also thank Cole Murbach for editorial assistance. This work was supported by the Creative Inquiry fund at Clemson University and the Yamada Research Grant to Y. Dong and M. Cao, an American Federation of Aging Research (AFAR) grant to Y. Dong and the Intramural Research Program at the National Institute on Aging, NIH to S. Zou. NR 148 TC 8 Z9 9 U1 3 U2 20 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1942-0900 J9 OXID MED CELL LONGEV JI Oxidative Med. Cell. Longev. PY 2012 AR 718491 DI 10.1155/2012/718491 PG 10 WC Cell Biology SC Cell Biology GA 005NQ UT WOS:000308757500001 ER PT J AU Jing, BY Li, ZP Qin, J Zhou, W AF Jing, Bing-Yi Li, Zhouping Qin, Jing Zhou, Wang TI Jackknife empirical likelihood method for case-control studies with gene-environment independence on controls SO STATISTICS AND ITS INTERFACE LA English DT Article DE Case-control study; Gene-environment independence; Jackknife empirical likelihood; Logistic regression; Multiplicative-intercept risk model; U-statistics ID LOGISTIC-REGRESSION; U-STATISTICS; MODELS; DISCRIMINATION; SAMPLE AB In this paper, we propose a jackknife empirical likelihood method to do inference for the interested parameters of the multiplicative-intercept risk models by taking into account the gene-environment independence on controls in case-control studies. It is shown that the proposed statistic is asymptotically chi-squared distributed. Simulation studies investigate the small-sample properties. A real example is also given. C1 [Li, Zhouping] Lanzhou Univ, Sch Math & Stat, Lanzhou 730000, Peoples R China. [Jing, Bing-Yi] Hong Kong Univ Sci & Technol, Dept Math, Kowloon, Hong Kong, Peoples R China. [Qin, Jing] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. [Zhou, Wang] Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117546, Singapore. RP Li, ZP (reprint author), Lanzhou Univ, Sch Math & Stat, Lanzhou 730000, Peoples R China. EM majing@ust.hk; lizhp@lzu.edu.cn; jingqin@niaid.nih.gov; stazw@nus.edu.sg FU HK RGC [HKUST6011/07P, HKUST6015/08P, HKUST6019/10P]; National Nature Science Foundation of China [71071155]; Fundamental Research Funds for the Central Universities; Research Funds of Renmin University of China [10XNL007]; NSFC [71071155]; Fundamental Research Funds for the Central Universities [lzujbky-2011-121]; National University of Singapore [R-155-000-116-112] FX The authors would like to thank the Editor, an Associate Editor and referees for their suggestions and criticisms which helped to improve this paper. Jing's research is partially supported by HK RGC grants HKUST6011/07P and HKUST6015/08P, HKUST6019/10P, the National Nature Science Foundation of China (71071155), the Fundamental Research Funds for the Central Universities, and the Research Funds of Renmin University of China (Grant No. 10XNL007), and in part by NSFC (Grant No. 71071155). Li's research is partially supported by the Fundamental Research Funds for the Central Universities (Grant No. lzujbky-2011-121). Zhou's research is partially supported by a grant R-155-000-116-112 at the National University of Singapore. NR 31 TC 1 Z9 1 U1 1 U2 3 PU INT PRESS BOSTON, INC PI SOMERVILLE PA PO BOX 43502, SOMERVILLE, MA 02143 USA SN 1938-7989 J9 STAT INTERFACE JI Stat. Interface PY 2012 VL 5 IS 3 SI SI BP 293 EP 302 PG 10 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA 008PQ UT WOS:000308969400003 ER PT S AU Blackstone, C AF Blackstone, Craig BE Hyman, SE TI Cellular Pathways of Hereditary Spastic Paraplegia SO ANNUAL REVIEW OF NEUROSCIENCE, VOL 35 SE Annual Review of Neuroscience LA English DT Review; Book Chapter DE spasticity; lipid droplet; BMP; cytokinesis; endosome; endoplasmic reticulum ID RECESSIVE INTELLECTUAL DISABILITY; ENDOPLASMIC-RETICULUM STRESS; MOTOR-NEURON DISEASE; AMYOTROPHIC-LATERAL-SCLEROSIS; PELIZAEUS-MERZBACHER-DISEASE; NEUROPATHY TARGET ESTERASE; FAST AXONAL-TRANSPORT; TUBULAR ER NETWORK; NERVOUS-SYSTEM; ESCRT-III AB Human voluntary movement is controlled by the pyramidal motor system, a long CNS pathway comprising corticospinal and lower motor neurons. Hereditary spastic paraplegias (HSPs) are a large, genetically diverse group of inherited neurologic disorders characterized by a length-dependent distal axonopathy of the corticospinal tracts, resulting in lower limb spasticity and weakness. A range of studies are converging on alterations in the shaping of organelles, particularly the endoplasmic reticulum, as well as intracellular membrane trafficking and distribution as primary defects underlying the HSPs, with clear relevance for other long axonopathies affecting peripheral nerves and lower motor neurons. C1 NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Blackstone, C (reprint author), NINDS, Neurogenet Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM blackstc@ninds.nih.gov FU Intramural NIH HHS NR 145 TC 106 Z9 107 U1 2 U2 16 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0147-006X BN 978-0-8243-2435-3 J9 ANNU REV NEUROSCI JI Annu. Rev. Neurosci. PY 2012 VL 35 BP 25 EP 47 DI 10.1146/annurev-neuro-062111-150400 PG 23 WC Neurosciences SC Neurosciences & Neurology GA BBR21 UT WOS:000307960400003 PM 22540978 ER PT S AU Leopold, DA AF Leopold, David A. BE Hyman, SE TI Primary Visual Cortex: Awareness and Blindsight SO ANNUAL REVIEW OF NEUROSCIENCE, VOL 35 SE Annual Review of Neuroscience LA English DT Review; Book Chapter DE V1; visual perception; blindsight; cortical lesion; consciousness; cerebral cortex; thalamus ID LATERAL GENICULATE-NUCLEUS; RETINAL GANGLION-CELLS; MIDDLE TEMPORAL AREA; REFLECTS PERCEPTUAL SUPPRESSION; MAMMALIAN SUPERIOR COLLICULUS; NEW-WORLD MONKEYS; STRIATE CORTEX; MACAQUE MONKEY; BINOCULAR-RIVALRY; EXTRAGENICULOSTRIATE VISION AB The primary visual cortex (V1) is the principal telencephalic recipient of visual input in humans and monkeys. It is unique among cortical areas in that its destruction results in chronic blindness. However, certain patients with V1 damage, though lacking visual awareness, exhibit visually guided behavior: blindsight. This phenomenon, together with evidence from electrophysiological, neuroimaging, and psychophysical experiments, has led to speculation that V1 activity has a special or direct role in generating conscious perception. To explore this issue, this article reviews experiments that have used two powerful paradigms-stimulus-induced perceptual suppression and chronic V1 ablation-each of which disrupts the ability to perceive salient visual stimuli. Focus is placed on recent neurophysiological, behavioral, and functional imaging studies from the nonhuman primate that shed light on V1's role in conscious awareness. In addition, anatomical pathways that relay visual information to the cortex during normal vision and in blindsight are reviewed. Although the critical role of V1 in primate vision follows naturally from its position as a bottleneck of visual signals, little evidence supports its direct contribution to visual awareness. C1 NIMH, Sect Cognit Neurophysiol & Imaging, Neuropsychol Lab,Dept Hlth & Human Serv, Neurophysiol Imaging Facil,NINDS,NEI,NIH, Bethesda, MD 20892 USA. RP Leopold, DA (reprint author), NIMH, Sect Cognit Neurophysiol & Imaging, Neuropsychol Lab,Dept Hlth & Human Serv, Neurophysiol Imaging Facil,NINDS,NEI,NIH, Bethesda, MD 20892 USA. EM leopoldd@mail.nih.gov OI Leopold, David/0000-0002-1345-6360 FU Intramural NIH HHS [ZIA MH002838-08, ZIA MH002896-05] NR 128 TC 35 Z9 36 U1 8 U2 80 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0147-006X BN 978-0-8243-2435-3 J9 ANNU REV NEUROSCI JI Annu. Rev. Neurosci. PY 2012 VL 35 BP 91 EP 109 DI 10.1146/annurev-neuro-062111-150356 PG 19 WC Neurosciences SC Neurosciences & Neurology GA BBR21 UT WOS:000307960400006 PM 22715879 ER PT S AU Nienborg, H Cohen, MR Cumming, BG AF Nienborg, Hendrikje Cohen, Marlene R. Cumming, Bruce G. BE Hyman, SE TI Decision-Related Activity in Sensory Neurons: Correlations Among Neurons and with Behavior SO ANNUAL REVIEW OF NEUROSCIENCE, VOL 35 SE Annual Review of Neuroscience LA English DT Review; Book Chapter DE choice probability; decision making; noise correlation ID LATERAL INTRAPARIETAL AREA; PRIMARY VISUAL-CORTEX; STEREOSCOPIC DEPTH-PERCEPTION; MIDDLE TEMPORAL AREA; NEURAL ACTIVITY; SPATIAL ATTENTION; PSYCHOPHYSICAL PERFORMANCE; INTERNEURONAL CORRELATIONS; DISPARITY DISCRIMINATION; VENTRAL INTRAPARIETAL AB Neurons in early sensory cortex show weak but systematic correlations with perceptual decisions when trained animals perform at psychophysical threshold. These correlations are observed across repeated presentations of identical stimuli and cannot be explained by variation in external factors. The relationship between the activity of individual sensory neurons and the animal's behavioral choice means that even neurons in early sensory cortex carry information about an upcoming decision. This relationship, termed choice probability, may reflect the effect of fluctuations in neuronal firing rate on the animal's decision, but it can also reflect modulation of sensory responses by cognitive factors, or network properties such as variability that is shared among populations of neurons. Here, we review recent work clarifying the relationship among fluctuations in the responses of individual neurons, correlated variability, and behavior in a variety of tasks and cortical areas. We also discuss the possibility that choice probability may in part reflect the influence of cognitive factors on sensory neurons and explore the situations in which choice probability can be used to make inferences about the role of particular sensory neurons in the decision-making process. C1 [Nienborg, Hendrikje] Werner Reichardt Ctr Integrat Neurosci, D-72076 Tubingen, Germany. [Cohen, Marlene R.] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA 15213 USA. [Cohen, Marlene R.] Univ Pittsburgh, Ctr Neural Basis Cognit, Pittsburgh, PA 15213 USA. [Cumming, Bruce G.] NEI, Lab Sensorimotor Res, NIH, Bethesda, MD 20892 USA. RP Nienborg, H (reprint author), Werner Reichardt Ctr Integrat Neurosci, D-72076 Tubingen, Germany. EM hnienb@gmail.com; cohenm@pitt.edu; bgc@lsr.nei.nih.gov NR 65 TC 68 Z9 68 U1 0 U2 25 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0147-006X BN 978-0-8243-2435-3 J9 ANNU REV NEUROSCI JI Annu. Rev. Neurosci. PY 2012 VL 35 BP 463 EP 483 DI 10.1146/annurev-neuro-062111-150403 PG 21 WC Neurosciences SC Neurosciences & Neurology GA BBR21 UT WOS:000307960400023 PM 22483043 ER PT J AU Traynor, B AF Traynor, Bryan TI Frontotemporal dementia and motor neuron disease SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Meeting Abstract CT 8th International Conference on Frontotemporal Dementias CY SEP 05-07, 2012 CL Manchester, ENGLAND C1 [Traynor, Bryan] NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2012 VL 33 SU 1 BP 6 EP 6 PG 1 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 003LG UT WOS:000308612400012 ER PT J AU Kukull, W Knopman, D Mesulam, M Grossman, M Miller, B Weintraub, S Kramer, J Rankin, K Rosen, H Hillis, A Boeve, B Mendez, M Phelps, C Morris, J AF Kukull, Walter Knopman, David Mesulam, Marsel Grossman, Murray Miller, Bruce Weintraub, Sandra Kramer, Joel Rankin, Katherine Rosen, Howard Hillis, Argye Boeve, Brad Mendez, Mario Phelps, Creighton Morris, John TI Standardized data collection and diagnostic formulation for FTLD Clinical Exam: The FTLD Module. SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Meeting Abstract CT 8th International Conference on Frontotemporal Dementias CY SEP 05-07, 2012 CL Manchester, ENGLAND C1 [Phelps, Creighton] NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2012 VL 33 SU 1 BP 226 EP 227 PG 2 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 003LG UT WOS:000308612400329 ER PT J AU Yusuf, D Butland, SL Swanson, MI Bolotin, E Ticoll, A Cheung, WA Zhang, XYC Dickman, CTD Fulton, DL Lim, JS Schnabl, JM Ramos, OHP Vasseur-Cognet, M de Leeuw, CN Simpson, EM Ryffel, GU Lam, EWF Kist, R Wilson, MSC Marco-Ferreres, R Brosens, JJ Beccari, LL Bovolenta, P Benayoun, BA Monteiro, LJ Schwenen, HDC Grontved, L Wederell, E Mandrup, S Veitia, RA Chakravarthy, H Hoodless, PA Mancarelli, MM Torbett, BE Banham, AH Reddy, SP Cullum, RL Liedtke, M Tschan, MP Vaz, M Rizzino, A Zannini, M Frietze, S Farnham, PJ Eijkelenboom, A Brown, PJ Laperriere, D Leprince, D de Cristofaro, T Prince, KL Putker, M del Peso, L Camenisch, G Wenger, RH Mikula, M Rozendaal, M Mader, S Ostrowski, J Rhodes, SJ Van Rechem, C Boulay, G Olechnowicz, SWZ Breslin, MB Lan, MS Nanan, KK Wegner, M Hou, J Mullen, RD Colvin, SC Noy, PJ Webb, CF Witek, ME Ferrell, S Daniel, JM Park, J Waldman, SA Peet, DJ Taggart, M Jayaraman, PS Karrich, JJ Blom, B Vesuna, F O'Geen, H Sun, YF Gronostajski, RM Woodcroft, MW Hough, MR Chen, E Europe-Finner, GN Karolczak-Bayatti, M Bailey, J Hankinson, O Raman, V LeBrun, DP Biswal, S Harvey, CJ DeBruyne, JP Hogenesch, JB Hevner, RF Heligon, C Luo, XM Blank, MC Millen, KJ Sharlin, DS Forrest, D Dahlman-Wright, K Zhao, CY Mishima, Y Sinha, S Chakrabarti, R Portales-Casamar, E Sladek, FM Bradley, PH Wasserman, WW AF Yusuf, Dimas Butland, Stefanie L. Swanson, Magdalena I. Bolotin, Eugene Ticoll, Amy Cheung, Warren A. Zhang, Xiao Yu Cindy Dickman, Christopher T. D. Fulton, Debra L. Lim, Jonathan S. Schnabl, Jake M. Ramos, Oscar H. P. Vasseur-Cognet, Mireille de Leeuw, Charles N. Simpson, Elizabeth M. Ryffel, Gerhart U. Lam, Eric W-F Kist, Ralf Wilson, Miranda S. C. Marco-Ferreres, Raquel Brosens, Jan J. Beccari, Leonardo L. Bovolenta, Paola Benayoun, Berenice A. Monteiro, Lara J. Schwenen, Helma D. C. Grontved, Lars Wederell, Elizabeth Mandrup, Susanne Veitia, Reiner A. Chakravarthy, Harini Hoodless, Pamela A. Mancarelli, M. Michela Torbett, Bruce E. Banham, Alison H. Reddy, Sekhar P. Cullum, Rebecca L. Liedtke, Michaela Tschan, Mario P. Vaz, Michelle Rizzino, Angie Zannini, Mariastella Frietze, Seth Farnham, Peggy J. Eijkelenboom, Astrid Brown, Philip J. Laperriere, David Leprince, Dominique de Cristofaro, Tiziana Prince, Kelly L. Putker, Marrit del Peso, Luis Camenisch, Gieri Wenger, Roland H. Mikula, Michal Rozendaal, Marieke Mader, Sylvie Ostrowski, Jerzy Rhodes, Simon J. Van Rechem, Capucine Boulay, Gaylor Olechnowicz, Sam W. Z. Breslin, Mary B. Lan, Michael S. Nanan, Kyster K. Wegner, Michael Hou, Juan Mullen, Rachel D. Colvin, Stephanie C. Noy, Peter John Webb, Carol F. Witek, Matthew E. Ferrell, Scott Daniel, Juliet M. Park, Jason Waldman, Scott A. Peet, Daniel J. Taggart, Michael Jayaraman, Padma-Sheela Karrich, Julien J. Blom, Bianca Vesuna, Farhad O'Geen, Henriette Sun, Yunfu Gronostajski, Richard M. Woodcroft, Mark W. Hough, Margaret R. Chen, Edwin Europe-Finner, G. Nicholas Karolczak-Bayatti, Magdalena Bailey, Jarrod Hankinson, Oliver Raman, Venu LeBrun, David P. Biswal, Shyam Harvey, Christopher J. DeBruyne, Jason P. Hogenesch, John B. Hevner, Robert F. Heligon, Christophe Luo, Xin M. Blank, Marissa Cathleen Millen, Kathleen Joyce Sharlin, David S. Forrest, Douglas Dahlman-Wright, Karin Zhao, Chunyan Mishima, Yuriko Sinha, Satrajit Chakrabarti, Rumela Portales-Casamar, Elodie Sladek, Frances M. Bradley, Philip H. Wasserman, Wyeth W. TI The Transcription Factor Encyclopedia SO GENOME BIOLOGY LA English DT Article ID PROTEIN DATA-BANK; MENDELIAN-INHERITANCE; GENE-REGULATION; DATABASE; INFORMATION; ANNOTATION; WIKI; KNOWLEDGEBASE; EVOLUTION; UPDATE AB Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written and vetted by experts in the field. TFe is available at http://www.cisreg.ca/tfe. C1 [Yusuf, Dimas; Butland, Stefanie L.; Zhang, Xiao Yu Cindy; Lim, Jonathan S.; de Leeuw, Charles N.; Simpson, Elizabeth M.; Portales-Casamar, Elodie; Wasserman, Wyeth W.] Univ British Columbia, Dept Med Genet, Ctr Mol Med & Therapeut, Fac Med,Child & Family Res Inst, Vancouver, BC V5Z 4H4, Canada. [Swanson, Magdalena I.] Fraser Hlth Author, Evaluat Serv, Surrey, BC V3R 7P8, Canada. [Swanson, Magdalena I.] Fraser Hlth Author, Res Serv, Surrey, BC V3R 7P8, Canada. [Bolotin, Eugene] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. [Ticoll, Amy; Bradley, Philip H.] Fred Hutchinson Canc Res Ctr, Computat Biol Program, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Cheung, Warren A.] Univ British Columbia, Dept Bioinformat, Ctr Mol Med & Therapeut, Child & Family Res Inst, Vancouver, BC V5Z 4H4, Canada. [Dickman, Christopher T. D.] Univ Western Ontario, Dept Biol, London, ON N6A 5B7, Canada. [Fulton, Debra L.] Univ British Columbia, Genet Program, Ctr Mol Med & Therapeut, Child & Family Res Inst, Vancouver, BC V5Z 4H4, Canada. [Schnabl, Jake M.; Sladek, Frances M.] Univ Calif Riverside, Inst Integrated Genome Biol, Riverside, CA 92521 USA. [Ramos, Oscar H. P.] CEA, SIMOPRO, Lab Life Sci, F-91191 Saclay, Ile De France, France. [Vasseur-Cognet, Mireille] Inst Cochin, Dept Endocrinol Metab & Canc, INSERM, U1016, F-75014 Paris, Ile De France, France. [Ryffel, Gerhart U.] Univ Duisburg Essen, Inst Zellbiol, Univ Klinikum Essen, D-45122 Essen, Nordrhein Westf, Germany. [Lam, Eric W-F; Wilson, Miranda S. C.; Monteiro, Lara J.; Schwenen, Helma D. C.] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, Div Canc, London W12 0NN, England. [Kist, Ralf] Newcastle Univ, Ctr Oral Hlth Res, Sch Dent Sci, Sch Med, Newcastle Upon Tyne NE2 4BW, Tyne & Wear, England. [Marco-Ferreres, Raquel; Bovolenta, Paola] CSIC, Dept Dev & Differentiat, CBMSO, E-28049 Madrid, Spain. [Marco-Ferreres, Raquel; Beccari, Leonardo L.; Bovolenta, Paola] CIBERER, Madrid 28049, Spain. [Brosens, Jan J.] Univ Warwick, Div Reprod Hlth, Warwick Med Sch, Coventry CV2 2DX, W Midlands, England. [Benayoun, Berenice A.] Univ Paris 07, Dept Mol & Cellular Pathol, Inst Jacques Monod, F-75013 Paris, Ile De France, France. [Grontved, Lars; Mandrup, Susanne] Univ So Denmark, Dept Biochem & Mol Biol, DK-5230 Odense, Region Syddanma, Denmark. [Wederell, Elizabeth; Hoodless, Pamela A.; Cullum, Rebecca L.; Hou, Juan] BC Canc Agcy, Prov Hlth Serv Author, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. [Veitia, Reiner A.] Univ Paris 07, Inst Jacques Monod, Mol & Cellular Pathol Program, F-75013 Paris, Ile De France, France. [Chakravarthy, Harini; Rizzino, Angie] Univ Nebraska, Eppley Inst Res Canc & Allied Dis, Univ Nebraska Med Ctr, Omaha, NE 68198 USA. [Mancarelli, M. Michela] Scripps Res Inst, Dept Mol Expt Med, La Jolla, CA 92037 USA. [Torbett, Bruce E.] Scripps Res Inst, Dept Immunol & Microbial Sci MEM 131, La Jolla, CA 92037 USA. [Torbett, Bruce E.] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. [Banham, Alison H.] Univ Oxford, Nuffield Dept Clin Lab Sci, John Radcliffe Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 9DU, Oxon, England. [Reddy, Sekhar P.] Univ Illinois, Dept Pediat, Coll Med, Chicago, IL 60612 USA. [Liedtke, Michaela] Stanford Univ, Sch Med, Dept Med Hematol, Stanford, CA 94305 USA. [Tschan, Mario P.] Univ Bern, Dept Med, CH-3012 Bern, Switzerland. [Vaz, Michelle] Johns Hopkins Univ, Sch Med, Dept Oncol, Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21237 USA. [Zannini, Mariastella; de Cristofaro, Tiziana] CNR Natl Res Council, Inst Expt Endocrinol & Oncol IEOS, I-80131 Naples, Italy. [Frietze, Seth; Farnham, Peggy J.] Univ So Calif, Dept Biochem & Mol Biol, Norris Comprehens Canc Ctr, Los Angeles, CA 90089 USA. [Eijkelenboom, Astrid] Univ Utrecht, Dept Mol Canc Res, Univ Med Ctr Utrecht, NL-3584 CG Utrecht, Netherlands. [Brown, Philip J.] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Lab Sci, Div Med Sci, Oxford OX3 9DU, Oxon, England. [Laperriere, David] Univ Montreal, Mol Targeting Breast Canc Res Unit, Inst Res Immunol & Canc, Montreal, PQ H3T 1J4, Canada. [Leprince, Dominique; Boulay, Gaylor] Inst Pasteur, Ctr Natl Rech Sci CNRS UMR 8161, Inst Biol Lille, F-59021 Lille, Nord Pas De Cal, France. [Prince, Kelly L.; Colvin, Stephanie C.] Indiana Univ Purdue Univ, Dept Cellular & Integrat Physiol, Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Putker, Marrit] Univ Utrecht, Univ Med Ctr Utrecht, Dept Physiol Chem, NL-3584 CG Utrecht, Netherlands. [del Peso, Luis] Univ Autonoma Madrid, Dept Biochem, Sch Med, Madrid 28029, Spain. [Camenisch, Gieri; Wenger, Roland H.] Univ Zurich, Inst Physiol, Zurich Ctr Integrat Human Physiol, CH-8057 Zurich, Switzerland. [Mikula, Michal; Ostrowski, Jerzy] Maria Sklodowska Curie Mem Canc Ctr & Inst Oncol, Dept Oncol Genet, Med Ctr Postgrad Educ, PL-02781 Warsaw, Mazovia, Poland. [Rozendaal, Marieke] Univ Montreal, Dept Biochem, Inst Res Immunol & Canc, Stn Ctr Ville, Montreal, PQ H3C 3J7, Canada. [Mader, Sylvie] Univ Montreal, Dept Biochem, Inst Res Immunol & Canc, Montreal, PQ H3T 1J4, Canada. [Rhodes, Simon J.] Indiana Univ Purdue Univ, Dept Biol, Sch Sci, Indianapolis, IN 46202 USA. [Van Rechem, Capucine] Harvard Univ, Sch Med, Dept Med, Canc Ctr,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Olechnowicz, Sam W. Z.] Univ Adelaide, Dept Biochem, Sch Mol & Biomed Sci, Adelaide, SA 5005, Australia. [Breslin, Mary B.] Louisiana State Univ, Hlth Sci Ctr, Dept Pediat & Biochem & Mol Biol, Res Inst Children,Childrens Hosp New Orleans, New Orleans, LA 70118 USA. [Lan, Michael S.] Louisiana State Univ, Hlth Sci Ctr, Dept Pediat, Res Inst Children,Childrens Hosp New Orleans, New Orleans, LA 70118 USA. [Lan, Michael S.] Louisiana State Univ, Hlth Sci Ctr, Dept Genet, Res Inst Children,Childrens Hosp New Orleans, New Orleans, LA 70118 USA. [Nanan, Kyster K.; LeBrun, David P.] Queens Univ, Dept Pathol & Mol Med, Queens Canc Res Inst, Kingston, ON K7L 3N6, Canada. [Wegner, Michael] Univ Erlangen Nurnberg, Sch Med, Inst Fuer Biochem, Emil Fischer Zentrum, D-91096 Erlangen, Bavaria, Germany. [Mullen, Rachel D.] Indiana Univ Purdue Univ, Dept Mol Biol & Biochem, Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Noy, Peter John] Univ Birmingham, Dept Immun & Infect, Sch Med & Dent Sci, Birmingham B15 2TT, W Midlands, England. [Webb, Carol F.] Oklahoma Med Res Fdn, Immunobiol & Canc Program, Oklahoma City, OK 73104 USA. [Witek, Matthew E.] Jefferson Univ Hosp, Dept Pharmacol & Expt Therapeut, Philadelphia, PA 19107 USA. [Ferrell, Scott] Univ Oklahoma, Dept Microbiol & Immunol, Hlth Sci Ctr, Oklahoma City, OK 73104 USA. [Daniel, Juliet M.] McMaster Univ, Dept Biol, Hamilton, ON L8S 4K1, Canada. [Waldman, Scott A.] Thomas Jefferson Univ, Dept Pharmacol & Expt Therapeut, Jefferson Med Coll, Philadelphia, PA 19107 USA. [Peet, Daniel J.] Univ Adelaide, Discipline Biochem, Sch Mol & Biomed Sci, Adelaide, SA 5005, Australia. [Taggart, Michael; Europe-Finner, G. Nicholas] Newcastle Univ, Inst Cellular Med, Fac Med, Sch Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Jayaraman, Padma-Sheela] Univ Birmingham, Dept Immun & Immunol, Sch Med & Dent Sci, Birmingham B15 2TT, W Midlands, England. [Karrich, Julien J.; Blom, Bianca] Univ Amsterdam, Dept Cell Biol & Histol, Ctr Immunol Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Noord Holland, Netherlands. [Vesuna, Farhad] Johns Hopkins Univ, Div Canc Imaging Res, Dept Radiol, Sch Med, Baltimore, MD 21205 USA. [O'Geen, Henriette] Univ Calif Davis, Genome Ctr, Davis, CA 95616 USA. [Sun, Yunfu] Univ Calif San Diego, San Diego, CA 92093 USA. [Gronostajski, Richard M.] SUNY Buffalo, Ctr Excellence Bioinformat & Life Sci, Dept Biochem, Buffalo, NY 14203 USA. [Gronostajski, Richard M.] SUNY Buffalo, Ctr Excellence Bioinformat & Life Sci, Dev Genom Grp, Buffalo, NY 14203 USA. [Woodcroft, Mark W.] Queens Univ, Dept Pathol & Mol Med, Queens Canc Res Inst, Kingston, ON K7K 4G4, Canada. [Hough, Margaret R.] Univ Toronto, Dept Mol & Cellular Biol, Dept Lab Med & Pathobiol, Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Karolczak-Bayatti, Magdalena] Newcastle Univ, Sch Med, Inst Cellular Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. [Bailey, Jarrod] Newcastle Univ, Sch Med, Inst Cellular Med, Fac Med Sci, Newcastle Upon Tyne NE2 4AA, Tyne & Wear, England. [Hankinson, Oliver] Univ Calif Los Angeles, Dept Pathol & Lab Med, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Biswal, Shyam; Harvey, Christopher J.] Johns Hopkins Univ, Dept Environm Hlth Sci, Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [DeBruyne, Jason P.] Morehouse Sch Med, Dept Pharmacol & Toxicol, Neurosci Inst, Atlanta, GA 30310 USA. [Hogenesch, John B.] Univ Penn, Dept Pharmacol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Hevner, Robert F.] Univ Washington, Dept Neurol Surg, Seattle Childrens Res Inst, Seattle, WA 98101 USA. [Heligon, Christophe] Univ Lausanne, Fac Biol & Med, Ctr Integrated Genom, CH-1015 Lausanne, Vaud, Switzerland. [Luo, Xin M.] Virginia Polytech Inst & State Univ, Dept Biomed Sci & Pathobiol, VA MD Reg Coll Vet Med, Blacksburg, VA 24061 USA. [Millen, Kathleen Joyce; Mishima, Yuriko] Univ Washington, Ctr Integrat Brain Res, Seattle Childrens Res Inst, Seattle, WA 98101 USA. [Blank, Marissa Cathleen] Univ Illinois, Dept Mol Genet & Cell Biol, Chicago, IL 60637 USA. [Sharlin, David S.; Forrest, Douglas] Natl Inst Diabet Digest & Kidney Disorders, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. [Dahlman-Wright, Karin; Zhao, Chunyan] Karolinska Inst, Dept Biosci & Nutr, Novum, SE-14183 Stockholm, Sweden. [Sinha, Satrajit; Chakrabarti, Rumela] SUNY Buffalo, Dept Biochem, Sch Med & Biomed Sci, Buffalo, NY 14203 USA. RP Wasserman, WW (reprint author), Univ British Columbia, Dept Med Genet, Ctr Mol Med & Therapeut, Fac Med,Child & Family Res Inst, 950 W 28th Ave, Vancouver, BC V5Z 4H4, Canada. EM wyeth@cmmt.ubc.ca RI Vesuna, Farhad/G-3179-2010; Mikula, Michal/G-8276-2011; Marco-Ferreres, Raquel/J-7122-2012; Wenger, Roland/B-7953-2009; Kist, Ralf/B-4982-2008; Ramos, Oscar/E-1862-2013; Banham, Alison/B-2966-2009; Benayoun, Berenice/K-7048-2012; del Peso, Luis/K-9391-2014; Zannini, Mariastella/I-1735-2012; Wasserman, Wyeth/I-4866-2015; de Leeuw, Charles/G-2939-2012; Luo, Xin/J-6544-2016; OI Banham, Alison/0000-0002-3197-273X; Vesuna, Farhad/0000-0002-0356-5096; Noy, Peter/0000-0001-6142-8957; Olechnowicz, Sam/0000-0001-7879-7708; Taggart, Michael/0000-0002-9981-2783; Farnham, Peggy/0000-0003-4469-7914; Cheung, Warren/0000-0003-0267-7464; Grontved, Lars/0000-0002-6735-8483; Brosens, Jan/0000-0003-0116-9329; DeBruyne, Jason/0000-0001-9803-9568; Mikula, Michal/0000-0003-3447-7328; Wenger, Roland/0000-0001-7592-4839; Kist, Ralf/0000-0003-3729-5693; Ramos, Oscar/0000-0002-5788-4500; Benayoun, Berenice/0000-0002-7401-4777; del Peso, Luis/0000-0003-4014-5688; de Leeuw, Charles/0000-0001-9413-2095; Luo, Xin/0000-0002-2809-5836; Mandrup, Susanne/0000-0002-0961-5787; Wasserman, Wyeth/0000-0001-6098-6412; Portales-Casamar, Elodie/0000-0002-9998-7858; Tschan, Mario P./0000-0001-5897-3647; Wegner, Michael/0000-0002-4586-3294; Hoodless, Pamela/0000-0003-1371-0725 FU Pleiades Promoter project; Genome Canada; Genome British Columbia; GlaxoSmithKline RD Limited; British Columbia Mental Health and Addiction Services; Child and Family Research Institute; University of British Columbia Institute of Mental Health; University of British Columbia Office of the Vice President Research; National Institutes of Health [R01GM084875, CA45250, 1U54HG004558, GM007377, U01 ES017154, R01 HD42024, 044215, CA75123, CA95026, CA146033, NIH/NIAID R01-AI080564-01, GM079239, HL081205, R01 MH058869, R01GM069417, R01 GM088277-01]; Gene Regulation Bioinformatics Laboratory; Canada Foundation for Innovation (CFI); University of British Columbia Work Study Program; Faculty of Medicine of the University of British Columbia; National Sciences and Engineering Research Council of Canada; Michael Smith Foundation for Health Research (MSFHR); Canadian Institutes of Health Research/MSFHR Strategic Program in Bioinformatics; Canadian Institutes of Health Research (CIHR) Frederick Banting; Charles Best Canada Graduate Scholarship Doctoral Award; MSFHR Graduate Doctoral Scholarship award; CHAARM in Europe; INSERM; EFSD; ANR; CIHR CGS-M Graduate Award; MSFHR Junior Graduate Scholarship; Canadian Institutes of Health Research; Sharon Stewart Trust; Deutsche Forschungsgemeinschaft; Cancer Research UK; Breast Cancer Campaign; Faculty of Medical Sciences, Newcastle University; BBSRC; Novartis; Ministerio de Economia y Competitividad (MEyC) in Spain; CAM; Biomedical Research Unit in Reproductive Health; University Hospitals Coventry; Warwickshire NHS Trust; private foundation Fundaluce; private foundation ONCE; private foundation Retina Espana; AMN; Universite Paris Diderot-Paris 7; Danish Natural Science Research Council; Centre national de la recherche scientifique (CNRS); Universite Paris-Diderot; Association pour la recherche contre le cancer (ARC); Fondation pour la recherche medicale (FRM); Institut Universitaire de France (IUF); MSFHR; Canadian Institutes for Health Research; Leukaemia and Lymphoma Research and Cancer Research UK; National Institutes of Health (NIH) [ES11863, ES018998, HL66109, K08 CA120349, ES11893, HL 66109, F32HD068113, R01DK061436, R01CA28868, T32GM007183, R01NS050386, R01NS044262, R01 DK053892, R21 MH087397]; CIHR; Heart and Stroke Foundation of Canada; National Institute for General Medical Sciences; Nebraska Department of Health; National Cancer Institute; Italian Association for Cancer Research (AIRC); Italian Ministry of Education, University and Research (MIUR-PRIN); Leukaemia and Lymphoma Research; NIH [HD42024, 5RO1 CA097226-03, R01 NS050386]; Spanish Ministry of Science and Innovation; 7th Framework research Program of the European Union; EU FP7; Swiss National Science Foundation [31003A_129962/1]; Ministry of Science and Higher Education [IP 2010 026770, N N401 071439]; Montreal Center for Experimental Therapeutics in Cancer; Canadian Institutes for Health Research [MOP 13-147]; Faculte des Etudes Superieures at Universite de Montreal; Research Institute for Children, Children's Hospital New Orleans, LA; Research Institute at Children's Hospital, New Orleans; Canadian Institutes of Health Research [MOP-84320]; Fonds der Chemischen Industrie; CIHR [MOP-84320, MOP-89806]; Department of Medical and Dental Sciences, University of Birmingham; Oklahoma Center for Adult Stem Cell Research; Natural Sciences and Engineering Research Council of Canada (NSERC) [RGPIN/238700-2010]; Australian Research Council; National Health and Medical Research Council of Australia; Welcome Trust and Breast Cancer Campaign; Dutch Organization for Medical Research (ZonMW); Netherlands organization for health research and development ZonMW [VIDI-917-66-310]; Landsteiner foundation [0608]; National Heart, Lung and Blood Institute (NHLBI) at the National Institutes of Health (NIH); New York State Stem Cell Science (NYSTEM); Cancer Research Society; Dina Gordon-Malkin Ontario Graduate Scholarship in Science and Technology; Medical Research Council (MRC) in the United Kingdom; British Heart Foundation; Wellcome Trust; Action Medical Research; Medical Research Council (MRC) in the United Kingdom [G0800202]; Leukemia and Lymphoma Society of Canada; National Heart, Lung, and Blood Institute Specialized Centers of Clinically Oriented Research [P50HL084945]; Center for Childhood Asthma in the Urban Environment [P50ES015903]; National Institute on Environmental Health Sciences Center [P30 ES003819]; Clinical Innovator Award from the Flight Attendant Medical Research Institute; NIEHS [ES07141]; Swedish Medical Research Council; Swedish Cancer Foundation; Novo Nordisk Foundation; Swedish Cancer Society (Cancerfonden) [CAN 2007/1113]; Fred Hutchinson Cancer Research Center (FHCRC); [T32]; [HL091219]; [R24 EY017540] FX We thank all authors who have made this project possible, especially our alpha and beta testers who have worked closely with us to refine the contents and user interface of this resource. We thank David J Arenillas, and Miroslav Hatas for providing programming assistance and systems administration support. We highlight author Frances M Sladek (University of California, Riverside) for extensive suggestions about the system interface and contents. We thank Frederick Pio (Simon Fraser University) for early assistance with TF structural modeling. TFe was supported by the Pleiades Promoter project, which is funded by Genome Canada, Genome British Columbia, GlaxoSmithKline R&D Limited, the British Columbia Mental Health and Addiction Services, Child and Family Research Institute, the University of British Columbia Institute of Mental Health, and the University of British Columbia Office of the Vice President Research. It is now supported by funding from the National Institutes of Health (grant no. R01GM084875 to WWW). Computer hardware resources utilized in this project were supported by the Gene Regulation Bioinformatics Laboratory funded by the Canada Foundation for Innovation (CFI). We sincerely thank the multitude of funding agencies throughout the world that have turned this project into reality. Here are our funding acknowledgments. DY is supported by funding from the University of British Columbia Work Study Program as well as the Faculty of Medicine of the University of British Columbia. EB is funded by T32 training grant. WAC is funded by the National Sciences and Engineering Research Council of Canada, the Michael Smith Foundation for Health Research (MSFHR) and the Canadian Institutes of Health Research/MSFHR Strategic Program in Bioinformatics. DLF is supported by a Canadian Institutes of Health Research (CIHR) Frederick Banting and Charles Best Canada Graduate Scholarship Doctoral Award and MSFHR Graduate Doctoral Scholarship award. OHPR is funded by CHAARM in Europe. MVC is funded by INSERM, EFSD, and ANR. CNdL is funded by a CIHR CGS-M Graduate Award and a MSFHR Junior Graduate Scholarship. EMS is currently funded by Canadian Institutes of Health Research, Sharon Stewart Trust, and Genome British Columbia. GUR's work is supported by funding from Deutsche Forschungsgemeinschaft. EWFL's work is supported by Cancer Research UK and Breast Cancer Campaign. RK was funded by a research fellowship of the Faculty of Medical Sciences, Newcastle University. MSW is funded by a CASE Studentship from the BBSRC in partnership with Novartis. RMF's work is supported by funding from Ministerio de Economia y Competitividad (MEyC) in Spain, CAM, and private foundations Fundaluce, ONCE, and Retina Espana. JJB is funded by the Biomedical Research Unit in Reproductive Health, University Hospitals Coventry and Warwickshire NHS Trust. LLB's work is supported by funding from Ministerio de Economia y Competitividad (MEyC) in Spain, CAM, and private foundations Fundaluce, ONCE, and Retina Espana. PB's work is supported by funding from Ministerio de Economia y Competitividad (MEyC) in Spain, CAM, and private foundations Fundaluce, ONCE, and Retina Espana. BAB was supported by an AMN and Universite Paris Diderot-Paris 7 PhD fellowship. LG is funded by the Danish Natural Science Research Council. SuM is funded by the Danish Natural Science Research Council.; RAV's laboratory is funded by the Centre national de la recherche scientifique (CNRS), Universite Paris-Diderot, Association pour la recherche contre le cancer (ARC), Fondation pour la recherche medicale (FRM), and Institut Universitaire de France (IUF). PAH is supported by funding from the MSFHR, Genome Canada, Genome British Columbia and Canadian Institutes for Health Research. BET is funded by grants number HL091219 and R24 EY017540. AHB is funded by Leukaemia and Lymphoma Research and Cancer Research UK. SPR is funded by the National Institutes of Health (NIH) grants ES11863, ES018998 and HL66109. RLC is funded by CIHR and the Heart and Stroke Foundation of Canada. ML is funded by the National Institutes of Health (NIH) grant K08 CA120349. MV is funded by the National Institutes of Health (NIH) grants ES11893 and HL 66109. AR is funded by the National Institute for General Medical Sciences, Nebraska Department of Health and the National Cancer Institute. MZ is funded by the Italian Association for Cancer Research (AIRC) and the Italian Ministry of Education, University and Research (MIUR-PRIN). SF is funded by the National Institutes of Health (grants CA45250, 1U54HG004558, GM007377). PJF is funded by the National Institutes of Health (grants CA45250, 1U54HG004558, and U01 ES017154). PJB is funded by Leukaemia and Lymphoma Research. KLP is funded by the National Institutes of Health (NIH) grant F32HD068113, and SJR is funded by NIH grant HD42024. LdP is funded by the Spanish Ministry of Science and Innovation, as well as the 7th Framework research Program of the European Union. RHW is funded by the EU FP7 and the Swiss National Science Foundation (grant 31003A_129962/1). MM is supported by the Ministry of Science and Higher Education (grant IP 2010 026770). MR was supported by studentships from the Faculte des Etudes Superieures at Universite de Montreal and from the Montreal Center for Experimental Therapeutics in Cancer. SyM is funded by the Canadian Institutes for Health Research (grant MOP 13-147) and holds the CIBC Breast Cancer Research Chair at Universite de Montreal. JO is supported by the Ministry of Science and Higher Education (grant N N401 071439) SJR is funded by the National Institutes of Health grant R01 HD42024. MBB is funded by the Research Institute for Children, Children's Hospital New Orleans, LA. MBB performed this work in collaboration with the Diana Helis Henry Medical Research Foundation. MSL is funded by the Research Institute at Children's Hospital, New Orleans, and the National Institutes of Health (NIH) grant R01DK061436. KKN and JMD are funded by Canadian Institutes of Health Research (grant MOP-84320). MW is funded by Deutsche Forschungsgemeinschaft and Fonds der Chemischen Industrie. JH is funded by CIHR (grant MOP-89806). PN is funded by the Department of Medical and Dental Sciences, University of Birmingham. CFW is funded by the National Institutes of Health (grant 044215) and the Oklahoma Center for Adult Stem Cell Research. JMD is supported by funding from the CIHR (grant MOP-84320) and the Natural Sciences and Engineering Research Council of Canada (NSERC grant RGPIN/238700-2010). SW is funded by the National Institutes of Health grants CA75123, CA95026, and CA146033. DJP is funded by Australian Research Council and the National Health and Medical Research Council of Australia PSJ is funded by the Welcome Trust and Breast Cancer Campaign. JJK is funded by the Dutch Organization for Medical Research (ZonMW).; BB is funded by the Netherlands organization for health research and development ZonMW (grant VIDI-917-66-310), the Landsteiner foundation (grant 0608), and the National Institutes of Health (grant NIH/NIAID R01-AI080564-01). RMG is supported by funding from the National Heart, Lung and Blood Institute (NHLBI) at the National Institutes of Health (NIH), and New York State Stem Cell Science (NYSTEM). MWW is a recipient of a Doctoral Award from the Canadian Institutes of Health Research. MRH is funded by the Canadian Institutes of Health Research and the Cancer Research Society. EC is funded by the Dina Gordon-Malkin Ontario Graduate Scholarship in Science and Technology. GNEF have been supported by funding from the Medical Research Council (MRC) in the United Kingdom, the British Heart Foundation, the Wellcome Trust, and Action Medical Research. MKB is funded by the Medical Research Council (MRC) in the United Kingdom, grant G0800202. OH is funded by the National Institutes of Health (NIH) grant R01CA28868. VR is funded by the NIH grant 5RO1 CA097226-03. DPL is funded by the Canadian Institutes of Health Research, Cancer Research Society, and the Leukemia and Lymphoma Society of Canada. SB is funded by the National Institutes of Health grants GM079239 and HL081205, National Heart, Lung, and Blood Institute Specialized Centers of Clinically Oriented Research grant P50HL084945, Center for Childhood Asthma in the Urban Environment grant P50ES015903, National Institute on Environmental Health Sciences Center grant P30 ES003819, and a Clinical Innovator Award from the Flight Attendant Medical Research Institute. CJH is funded by NIEHS grant ES07141. RFH is funded by the National Institutes of Health (grant R01 MH058869). MCB was funded by National Institutes of Health (NIH) training grant T32GM007183 and also by the NIH grant R01 NS050386 (through KJM). KJM is funded by the National Institutes of Health (grants R01NS050386, R01NS044262). KD is funded by the Swedish Medical Research Council, the Swedish Cancer Foundation, and the Novo Nordisk Foundation. CZ's work was supported by grants from the Swedish Cancer Society (Cancerfonden), grant CAN 2007/1113. SS is funded by the National Institutes of Health (grant R01GM069417). FMS is funded by the National Institutes of Health (NIH) grants R01 DK053892 and R21 MH087397. PHB is funded by a new development funding from the Fred Hutchinson Cancer Research Center (FHCRC) and the National Institutes of Health (grant no. R01 GM088277-01). NR 40 TC 34 Z9 34 U1 1 U2 23 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-7596 J9 GENOME BIOL JI Genome Biol. PY 2012 VL 13 IS 3 AR R24 DI 10.1186/gb-2012-13-3-r24 PG 25 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 002PL UT WOS:000308544200009 PM 22458515 ER PT J AU Ebbesson, SOE Lopez-Alvarenga, JC Okin, PM Devereux, RB Tejero, ME Harris, WS Ebbesson, LOE MacCluer, JW Wenger, C Laston, S Fabsitz, RR Kennish, J Howard, WJ Howard, BV Umans, J Comuzzie, AG AF Ebbesson, Sven O. E. Lopez-Alvarenga, Juan C. Okin, Peter M. Devereux, Richard B. Tejero, Maria Elizabeth Harris, William S. Ebbesson, Lars O. E. MacCluer, Jean W. Wenger, Charlotte Laston, Sandra Fabsitz, Richard R. Kennish, John Howard, William J. Howard, Barbara V. Umans, Jason Comuzzie, Anthony G. TI Heart rate is associated with markers of fatty acid desaturation: the GOCADAN study SO INTERNATIONAL JOURNAL OF CIRCUMPOLAR HEALTH LA English DT Article DE Inuit; diet; fatty acid metabolism; CVD risk factors ID CORONARY-ARTERY-DISEASE; MIDDLE-AGED MEN; DIETARY-FAT; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; METABOLIC SYNDROME; ALASKA NATIVES; DEATH; FISH; ATHEROSCLEROSIS AB Objectives: To determine if heart rate (HR) is associated with desaturation indexes as HR is associated with arrhythmia and sudden death. Study design: A community based cross-sectional study of 1214 Alaskan Inuit. Methods: Data of FA concentrations from plasma and red blood cell membranes from those >= 35 years of age (n = 819) were compared to basal HR at the time of examination. Multiple linear regression with backward stepwise selection was employed to analyze the effect of the desaturase indexes on HR, after adjustment for relevant covariates. Results: The Delta(5) desaturase index (Delta(5)-DI) measured in serum has recently been associated with a protective role for cardiovascular disease. This index measured here in plasma and red blood cells showed a negative correlation with HR. The plasma stearoyl-CoA-desaturase (SCD) index, previously determined to be related to cardiovascular disease (CVD) mortality, on the other hand, was positively associated with HR, while the Delta(6) desaturase index (Delta(6)-DI) had no significant effect on HR. Conclusion: Endogenous FA desaturation is associated with HR and thereby, in the case of SCD, possibly with arrhythmia and sudden death, which would at least partially explain the previously observed association between cardiovascular mortality and desaturase activity. C1 [Ebbesson, Sven O. E.] Norton Sound Hlth Corp, GOCADAN Dept, Nome, AK 99762 USA. [Lopez-Alvarenga, Juan C.; Tejero, Maria Elizabeth; MacCluer, Jean W.; Wenger, Charlotte; Laston, Sandra; Comuzzie, Anthony G.] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Okin, Peter M.; Devereux, Richard B.] Weill Cornell Med Coll, Dept Med, Div Cardiol, New York, NY USA. [Harris, William S.] S Dakota Hlth Res Fdn, Sioux Falls, SD USA. [Ebbesson, Lars O. E.] Uni Res AS, Uni Environm, Integrat Fish Biol, Bergen, Norway. [Fabsitz, Richard R.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Kennish, John] Univ Alaska Anchorage, Dept Chem, Anchorage, AK USA. [Howard, William J.; Howard, Barbara V.; Umans, Jason] MedStar Res Inst, Penn Med Lab, Hyattsville, MD USA. RP Ebbesson, SOE (reprint author), Norton Sound Hlth Corp, GOCADAN Dept, POB 966, Nome, AK 99762 USA. EM soebbesson@alaska.edu FU National Center for Research Resources, National Institutes of Health [C06 RR017515]; National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD, USA [RO1-HL64244, U01 HL082458, U01 HL082490, M10RR0047-34 (GCRC)] FX The authors are grateful to the Norton Sound Health Corporation (NSHC) and the participants of villages participating in this study. The study was approved by the Research Ethics Review Board of the NSHC and the Institutional Review Boards of MedStar Research Institute. This investigation was conducted in facilities constructed with support from Research Facilities Improvement Program Grant Number C06 RR017515 from the National Center for Research Resources, National Institutes of Health. The contributions to the work described in this article are as follows: Design of the study: Sven O.E. Ebbesson, Richard B. Devereux, Peter M. Okin, Jean W. MacCluer, Barbara V. Howard, Wm J. Howard, Anthony G. Comuzzie, Richard R. Fabsitz. Collection of the data: Sven O.E. Ebbesson, Peter M. Okin, Sandra Laston, Charlotte Wenger, William S. Harris, John Kennish, Jason Umans. Analysis of data: Juan Carlos Lopez-Alvarenga, M. Elizabeth Tejero, Lars O. E. Ebbesson. Writing of the manuscript: Sven O. E. Ebbesson, Richard B. Devereux.; The study was funded by grants RO1-HL64244, U01 HL082458, U01 HL082490, and M10RR0047-34 (GCRC) from the National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD, USA. NR 28 TC 5 Z9 5 U1 0 U2 4 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 1239-9736 J9 INT J CIRCUMPOL HEAL JI Int. J. Circumpolar Health PY 2012 VL 71 AR 17343 DI 10.3402/ijch.v71i0.17343 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 998GN UT WOS:000308225600003 PM 22456045 ER PT J AU Dickstein, DP Leibenluft, E AF Dickstein, Daniel P. Leibenluft, Ellen TI Beyond Dogma: From Diagnostic Controversies to Data About Pediatric Bipolar Disorder and Children with Chronic Irritability and Mood Dysregulation SO ISRAEL JOURNAL OF PSYCHIATRY AND RELATED SCIENCES LA English DT Article ID EMOTION LABELING DEFICITS; FACE-LIKE STIMULI; SPECTRUM DISORDERS; NATIONAL TRENDS; ADOLESCENT BIPOLARITY; LONGITUDINAL COURSE; ANXIETY DISORDERS; NEURAL CIRCUITRY; CLINICAL-COURSE; MANIA AB From the mid-1990s through the present, studies have demonstrated a significant rise in the numbers of children and adolescents diagnosed with bipolar disorder (BD). Why is this? The present manuscript reviews several possibilities, most notably ambiguity in the diagnostic criteria for mania and how they may apply to children with functionally-impairing irritability. Furthermore, we discuss ongoing phenomenological and affective neuroscience research approaches to address those children most on the fringes of our current psychiatric nosology. In summary, these studies suggest that BD youths may be distinguished on some measures from those with chronic irritability and severe mood dysregulation, although the two groups also have some shared deficits. C1 [Dickstein, Daniel P.] Brown Univ, Pediat Mood Imaging & NeuroDev Program, Bradley Hosp, Alpert Med Sch, E Providence, RI USA. [Leibenluft, Ellen] NIMH, Sect Bipolar Spectrum Disorders, Emot & Dev Branch, Bethesda, MD 20892 USA. RP Dickstein, DP (reprint author), Bradley Hosp, PediMIND Program, 1011 Vet Mem Pkwy, E Providence, RI 02915 USA. EM Daniel_Dickstein@Brown.edu RI Dickstein, Daniel/L-3210-2016 OI Dickstein, Daniel/0000-0003-1647-5329 FU Intramural NIH HHS [Z01 MH002778-09] NR 61 TC 5 Z9 5 U1 7 U2 7 PU MEDIAFARM GROUP PI TEL-AVIV PA 23 ZAMENHOFF ST, TEL-AVIV, 64373, ISRAEL SN 0333-7308 J9 ISR J PSYCHIATR REL JI Isr. J. Psychiatr. Relat. Sci. PY 2012 VL 49 IS 1 BP 52 EP 61 PN 1 PG 10 WC Psychiatry SC Psychiatry GA 004RA UT WOS:000308697600006 PM 22652929 ER PT J AU Schulz, GM Hosey, LA Bradberry, TJ Stager, SV Lee, LC Pawha, R Lyons, KE Metman, LV Braun, AR AF Schulz, Geralyn M. Hosey, Lara A. Bradberry, Trent J. Stager, Sheila V. Lee, Li-Ching Pawha, Rajesh Lyons, Kelly E. Metman, Leo Verhagen Braun, Allen R. TI Selective Left, Right and Bilateral Stimulation of Subthalamic Nuclei in Parkinson's Disease: Differential Effects on Motor, Speech and Language Function SO JOURNAL OF PARKINSONS DISEASE LA English DT Article DE Parkinson's disease; deep brain stimulation; speech; language; lateralization ID DEEP-BRAIN-STIMULATION; QUALITY-OF-LIFE; 5-YEAR FOLLOW-UP; VERBAL FLUENCY; HYPOKINETIC DYSARTHRIA; SYNTAX COMPREHENSION; STN STIMULATION; ORAL CONTROL; DEFICITS; DECLINES AB Deep brain stimulation (DBS) of the subthalamic nucleus improves the motor symptoms of Parkinson's disease, but may produce a worsening of speech and language performance at rates and amplitudes typically selected in clinical practice. The possibility that these dissociated effects might be modulated by selective stimulation of left and right STN has never been systematically investigated. To address this issue, we analyzed motor, speech and language functions of 12 patients implanted with bilateral stimulators configured for optimal motor responses. Behavioral responses were quantified under four stimulator conditions: bilateral DBS, right-only DBS, left-only DBS and no DBS. Under bilateral and left-only DBS conditions, our results exhibited a significant improvement in motor symptoms but worsening of speech and language. These findings contribute to the growing body of literature demonstrating that bilateral STN DBS compromises speech and language function and suggests that these negative effects may be principally due to left-sided stimulation. These findings may have practical clinical consequences, suggesting that clinicians might optimize motor, speech and language functions by carefully adjusting left-and right-sided stimulation parameters. C1 [Schulz, Geralyn M.] George Washington Univ, Dept Speech & Hearing Sci, Washington, DC USA. [Hosey, Lara A.; Bradberry, Trent J.; Braun, Allen R.] Natl Inst Deafness & Other Commun Disorders, Language Sect, Voice Speech & Language Branch, NIH, Bethesda, MD USA. [Bradberry, Trent J.] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. [Stager, Sheila V.] George Washington Univ, Med Ctr, Voice Treatment Ctr, Med Fac Associates, Washington, DC 20037 USA. [Lee, Li-Ching] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Pawha, Rajesh; Lyons, Kelly E.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Metman, Leo Verhagen] Rush Univ, Ctr Med, Dept Neurol Sci, Chicago, IL 60612 USA. RP Schulz, GM (reprint author), Columbian Coll Arts & Sci, 801 22nd St NW,Phillips Hall,Room 213, Washington, DC 20052 USA. EM schulz@gwu.edu OI Schulz, Geralyn/0000-0003-3831-8105; Stager, Sheila/0000-0002-4294-2114 FU Division of Intramural Research at the National Institute on Deafness and other Communication Disorders FX We would like to gratefully acknowledge the clinical staff at the University of Kansas Medical Center for their invaluable help with PD patients that participated in this study. This study was financially supported by the Division of Intramural Research at the National Institute on Deafness and other Communication Disorders. NR 85 TC 11 Z9 11 U1 0 U2 22 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1877-7171 J9 J PARKINSON DIS JI J. Parkinsons Dis. PY 2012 VL 2 IS 1 BP 29 EP 40 DI 10.3233/JPD-2012-11049 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 001UE UT WOS:000308484800005 PM 23939406 ER PT J AU Kepka, DL Coronado, GD Rodriguez, HP Thompson, B AF Kepka, Deanna L. Coronado, Gloria D. Rodriguez, Hector P. Thompson, Beti TI DEVELOPMENT OF A RADIONOVELA TO PROMOTE HPV VACCINE AWARENESS AND KNOWLEDGE AMONG LATINO PARENTS SO PUBLIC HEALTH REPORTS LA English DT Article ID HUMAN-PAPILLOMAVIRUS VACCINE; PREVENTING CERVICAL-CANCER; AFRICAN-AMERICAN WOMEN; HISPANIC WOMEN; ACCEPTABILITY; ATTITUDES; BELIEFS C1 [Kepka, Deanna L.; Coronado, Gloria D.] Univ Washington, Fred Hutchinson Canc Res Ctr, Dept Hlth Serv, Seattle, WA 98195 USA. [Rodriguez, Hector P.] Univ Calif Los Angeles, Dept Hlth Serv, Sch Publ Hlth Los Angeles, Los Angeles, CA 90024 USA. RP Kepka, DL (reprint author), NCI, 6130 Execut Blvd,Room 4017, Bethesda, MD 20892 USA. EM deanna.kepka@nih.gov FU AHRQ HHS [T32 HS013853]; NCI NIH HHS [R25 CA092408, U01 CA114633] NR 30 TC 4 Z9 5 U1 1 U2 5 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1900 M ST NW, STE 710, WASHINGTON, DC 20036 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JAN-FEB PY 2012 VL 127 IS 1 BP 130 EP 138 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 002DF UT WOS:000308510500016 PM 22298937 ER PT J AU Pan, JY Chou, MF Zhang, J Liu, YP AF Pan, J. -Y. Chou, M. -F. Zhang, J. Liu, Y. -P. TI Sleep patterns, insomnia, and daytime sleepiness between Guangdong and Macau Chinese adolescents: a cross-cultural comparison study SO BIOLOGICAL RHYTHM RESEARCH LA English DT Article DE adolescents; cross-cultural differences; sleep patterns; insomnia; daytime sleepiness ID WAKE PATTERNS; CHILDREN; PREVALENCE; HABITS; CONSEQUENCES; EPIDEMIOLOGY; METAANALYSIS; POPULATION; CHILDHOOD; QUALITY AB There was limited data on sleep patterns, insomnia, and daytime sleepiness in both south China adolescents and Macau adolescents. A school-based epidemiologic study (861 from Guangdong site and 618 from Macau) was conducted among high school adolescents from both sites. We found that Macau adolescents had slightly shorter nocturnal sleep duration during weekdays [mean (SD) = 7: 24 (1: 06) vs. 7: 31 (0: 35), p = 0.008] but longer nocturnal sleep duration during weekends [mean (SD) = 9: 56 (1: 40) vs. 8: 48 (1: 23)] than Guangdong adolescents. The rates of overall insomnia were 16.5% and 22.9% for Macau adolescents and Guangdong adolescents respectively (p < 0.001). Macau adolescents had higher scores in modified Epworth Sleepiness Scale than Guangdong adolescents. Multivariate analysis showed that study site was the most robust predictors for most of these variables of interest. Adolescents in Guangdong had shorter sleep duration, increased rates of insomnia, and habitual napping but were less sleepy than adolescents in Macau. C1 [Pan, J. -Y.; Zhang, J.; Liu, Y. -P.] Jinan Univ, Affiliated Hosp 1, Dept Psychiat, Guangzhou, Guangdong, Peoples R China. [Chou, M. -F.] Hlth Bur, Fai Chi Kei Hlth Ctr, Macao, Peoples R China. [Zhang, J.] NIMH, Sect Dev Genet Epidemiol, NIH, Bethesda, MD 20892 USA. RP Pan, JY (reprint author), Jinan Univ, Affiliated Hosp 1, Dept Psychiat, Guangzhou, Guangdong, Peoples R China. EM jiypan@163.com; zhangj10@mail.nih.gov FU Society Development Project of the Department of Science and Technology in Guangdong Province, China [2006B36004002] FX The authors thank the cooperation and participation of all the schools, teachers, and adolescents. The study is supported by a grant from Society Development Project of the Department of Science and Technology in Guangdong Province, China (No. 2006B36004002). NR 41 TC 2 Z9 2 U1 1 U2 11 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0929-1016 J9 BIOL RHYTHM RES JI Biol. Rhythm Res. PY 2012 VL 43 IS 5 BP 527 EP 539 DI 10.1080/09291016.2011.614791 PG 13 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 001ET UT WOS:000308443900007 ER PT J AU Niu, TC Gaff, HD Papelis, YE Hartley, DM AF Niu, Tianchan Gaff, Holly D. Papelis, Yiannis E. Hartley, David M. TI An Epidemiological Model of Rift Valley Fever with Spatial Dynamics SO COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE LA English DT Article ID MOSQUITOS DIPTERA; SENSITIVITY-ANALYSIS; VECTOR COMPETENCE; CULICIDAE; VIRUS; TRANSMISSION; UNCERTAINTY; TUBERCULOSIS; EXAMPLE; TEXAS AB As a category A agent in the Center for Disease Control bioterrorism list, Rift Valley fever (RVF) is considered a major threat to the United States (USA). Should the pathogen be intentionally or unintentionally introduced to the continental USA, there is tremendous potential for economic damages due to loss of livestock, trade restrictions, and subsequent food supply chain disruptions. We have incorporated the effects of space into a mathematical model of RVF in order to study the dynamics of the pathogen spread as affected by the movement of humans, livestock, and mosquitoes. The model accounts for the horizontal transmission of Rift Valley fever virus (RVFV) between two mosquito and one livestock species, and mother-to-offspring transmission of virus in one of the mosquito species. Space effects are introduced by dividing geographic space into smaller patches and considering the patch-to-patch movement of species. For each patch, a system of ordinary differential equations models fractions of populations susceptible to, incubating, infectious with, or immune to RVFV. The main contribution of this work is a methodology for analyzing the likelihood of pathogen establishment should an introduction occur into an area devoid of RVF. Examples are provided for general and specific cases to illustrate the methodology. C1 [Gaff, Holly D.] Old Dominion Univ, Dept Biol Sci, Norfolk, VA 23529 USA. [Niu, Tianchan] Georgetown Univ, Med Ctr, Div Integrated Biodef, ISIS Ctr, Washington, DC 20007 USA. [Niu, Tianchan; Hartley, David M.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Gaff, Holly D.; Papelis, Yiannis E.] Old Dominion Univ, Virginia Modeling Anal & Simulat Ctr, Suffolk, VA 23435 USA. [Hartley, David M.] Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20007 USA. RP Gaff, HD (reprint author), Old Dominion Univ, Dept Biol Sci, Norfolk, VA 23529 USA. EM hgaff@odu.edu RI Barley, Kamal/F-9579-2011; OI , David/0000-0003-2589-2538; Barley, Kamal/0000-0003-1874-9813; Hartley, David/0000-0001-5202-6278 FU Science & Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health; National Center for Foreign Animal and Zoonotic Disease Defense FX The authors (David M. Hartley, Tianchan Niu) are grateful to the Research and Policy for Infectious Disease Dynamics (RAPIDD) program of the Science & Technology Directorate, Department of Homeland Security and Fogarty International Center, National Institutes of Health for support of this work. David M. Hartley, Tianchan Niu, Holly D. Gaff also acknowledge support of this work by the National Center for Foreign Animal and Zoonotic Disease Defense. NR 39 TC 14 Z9 14 U1 2 U2 20 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1748-670X J9 COMPUT MATH METHOD M JI Comput. Math. Method Med. PY 2012 AR 138757 DI 10.1155/2012/138757 PG 12 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 997YZ UT WOS:000308205700001 ER PT J AU Ross, A Friedmann, E Bevans, M Thomas, S AF Ross, Alyson Friedmann, Erika Bevans, Margaret Thomas, Sue TI Frequency of Yoga Practice Predicts Health: Results of a National Survey of Yoga Practitioners SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Article ID FREIBURG MINDFULNESS INVENTORY; MIDDLE-AGED MEN; PHYSICAL-ACTIVITY; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; HATHA YOGA; MORTALITY; RISK; EXERCISE; STRESS AB Background. Yoga shows promise as a therapeutic intervention, but relationships between yoga practice and health are underexplored. Purpose. To examine the relationship between yoga practice and health (subjective well-being, diet, BMI, smoking, alcohol/caffeine consumption, sleep, fatigue, social support, mindfulness, and physical activity). Methods. Cross-sectional, anonymous internet surveys distributed to 4307 randomly selected from 18,160 individuals at 15 US Iyengar yoga studios; 1045 (24.3%) surveys completed. Results. Mean age 51.7 (+/- 11.7) years; 84.2% female. Frequency of home practice favorably predicted (P < .001): mindfulness, subjective well-being, BMI, fruit and vegetable consumption, vegetarian status, sleep, and fatigue. Each component of yoga practice (different categories of physical poses, breath work, meditation, philosophy study) predicted at least 1 health outcome (P < .05). Conclusions. Home practice of yoga predicted health better than years of practice or class frequency. Different physical poses and yoga techniques may have unique health benefits. C1 [Ross, Alyson; Friedmann, Erika; Thomas, Sue] Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA. [Bevans, Margaret] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Ross, A (reprint author), Univ Maryland, Sch Nursing, 655 W Lombard St, Baltimore, MD 21201 USA. EM alyross1@verizon.net OI Friedmann, Erika/0000-0003-2924-0449 NR 68 TC 16 Z9 16 U1 2 U2 26 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1741-427X J9 EVID-BASED COMPL ALT JI Evid.-based Complement Altern. Med. PY 2012 AR 983258 DI 10.1155/2012/983258 PG 10 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 999HJ UT WOS:000308300200001 ER PT J AU Malone, JH Cho, DY Mattiuzzo, NR Artieri, CG Jiang, LC Dale, RK Smith, HE McDaniel, J Munro, S Salit, M Andrews, J Przytycka, TM Oliver, B AF Malone, John H. Cho, Dong-Yeon Mattiuzzo, Nicolas R. Artieri, Carlo G. Jiang, Lichun Dale, Ryan K. Smith, Harold E. McDaniel, Jennifer Munro, Sarah Salit, Marc Andrews, Justen Przytycka, Teresa M. Oliver, Brian TI Mediation of Drosophila autosomal dosage effects and compensation by network interactions SO GENOME BIOLOGY LA English DT Article ID GENE-EXPRESSION; X-CHROMOSOME; MUTUAL INFORMATION; BIASED EXPRESSION; HUMAN GENOME; RNA-SEQ; MELANOGASTER; DATABASE; TRANSCRIPTOME; COLLECTION AB Background: Gene dosage change is a mild perturbation that is a valuable tool for pathway reconstruction in Drosophila. While it is often assumed that reducing gene dose by half leads to two-fold less expression, there is partial autosomal dosage compensation in Drosophila, which may be mediated by feedback or buffering in expression networks. Results: We profiled expression in engineered flies where gene dose was reduced from two to one. While expression of most one-dose genes was reduced, the gene-specific dose responses were heterogeneous. Expression of two-dose genes that are first-degree neighbors of one-dose genes in novel network models also changed and the directionality of change depended on the response of one-dose genes. Conclusions: Our data indicate that expression perturbation propagates in network space. Autosomal compensation, or the lack thereof, is a gene-specific response, largely mediated by interactions with the rest of the transcriptome. C1 [Cho, Dong-Yeon; Przytycka, Teresa M.] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20814 USA. [Malone, John H.; Mattiuzzo, Nicolas R.; Artieri, Carlo G.; Jiang, Lichun; Dale, Ryan K.; Oliver, Brian] NIDDKD, Lab Cellular & Dev Biol, Bethesda, MD USA. [Malone, John H.] Florida State Univ, Dept Biol, Tallahassee, FL 32306 USA. [Artieri, Carlo G.] Stanford Univ, Dept Biol, Stanford, CA 94304 USA. [Jiang, Lichun] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Smith, Harold E.] NIDDKD, Genom Core, Bethesda, MD 20814 USA. [McDaniel, Jennifer; Munro, Sarah; Salit, Marc] Natl Inst Stand & Technol, Biochem Sci Div, Mol Measurement Lab, Gaithersburg, MD 20899 USA. [Andrews, Justen] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA. RP Przytycka, TM (reprint author), NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20814 USA. EM przytyck@ncbi.nlm.nih.gov; oliver@helix.nih.gov OI Dale, Ryan/0000-0003-2664-3744 FU Intramural Research Programs of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Library of Medicine (NLM); National Institute of Standards and Technology (NIST) FX We thank the Drosophila Stock Center (Bloomington, IN, USA) and Steve Russell (Cambridge, UK) for flies and the Spyros Artavanis-Tsakonas lab (Boston, MA, USA) for sharing pre-publication protein-protein interaction data. We thank fellow members of our labs for stimulating discussion, advice, feedback, and encouragement. This research was supported by the Intramural Research Programs of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and National Library of Medicine (NLM), and National Institute of Standards and Technology (NIST). Certain commercial equipment, instruments, or materials are identified in this document. Such identification does not imply recommendation or endorsement by NIH or NIST, nor does it imply that the products identified are necessarily the best available for the purpose. NR 68 TC 41 Z9 41 U1 0 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2012 VL 13 IS 4 AR r28 DI 10.1186/gb-2012-13-4-r28 PG 17 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 002PQ UT WOS:000308544700004 PM 22531030 ER PT J AU Nellaker, C Keane, TM Yalcin, B Wong, K Agam, A Belgard, TG Flint, J Adams, DJ Frankel, WN Ponting, CP AF Nellaker, Christoffer Keane, Thomas M. Yalcin, Binnaz Wong, Kim Agam, Avigail Belgard, T. Grant Flint, Jonathan Adams, David J. Frankel, Wayne N. Ponting, Chris P. TI The genomic landscape shaped by selection on transposable elements across 18 mouse strains SO GENOME BIOLOGY LA English DT Article ID DENSITY GRADIENT CENTRIFUGATION; X-CHROMOSOME INACTIVATION; SHORT-READ; STRUCTURAL VARIATION; RNA-SEQ; ENDOGENOUS RETROVIRUSES; EUKARYOTIC GENOMES; SUBSTITUTION RATES; REPEAT HYPOTHESIS; MAMMALIAN GENOMES AB Background: Transposable element (TE)-derived sequence dominates the landscape of mammalian genomes and can modulate gene function by dysregulating transcription and translation. Our current knowledge of TEs in laboratory mouse strains is limited primarily to those present in the C57BL/6J reference genome, with most mouse TEs being drawn from three distinct classes, namely short interspersed nuclear elements (SINEs), long interspersed nuclear elements (LINEs) and the endogenous retrovirus (ERV) superfamily. Despite their high prevalence, the different genomic and gene properties controlling whether TEs are preferentially purged from, or are retained by, genetic drift or positive selection in mammalian genomes remain poorly defined. Results: Using whole genome sequencing data from 13 classical laboratory and 4 wild-derived mouse inbred strains, we developed a comprehensive catalogue of 103,798 polymorphic TE variants. We employ this extensive data set to characterize TE variants across the Mus lineage, and to infer neutral and selective processes that have acted over 2 million years. Our results indicate that the majority of TE variants are introduced though the male germline and that only a minority of TE variants exert detectable changes in gene expression. However, among genes with differential expression across the strains there are twice as many TE variants identified as being putative causal variants as expected. Conclusions: Most TE variants that cause gene expression changes appear to be purged rapidly by purifying selection. Our findings demonstrate that past TE insertions have often been highly deleterious, and help to prioritize TE variants according to their likely contribution to gene expression or phenotype variation. C1 [Nellaker, Christoffer; Agam, Avigail; Belgard, T. Grant; Ponting, Chris P.] Univ Oxford, Dept Physiol Anat & Genet, MRC Funct Genom Unit, Oxford OX1 3PT, England. [Keane, Thomas M.; Wong, Kim; Adams, David J.; Ponting, Chris P.] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England. [Yalcin, Binnaz; Agam, Avigail; Flint, Jonathan] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Belgard, T. Grant] Univ Calif Los Angeles, Los Angeles, CA 90095 USA. [Belgard, T. Grant] NHGRI, NIH, Bethesda, MD 20892 USA. [Frankel, Wayne N.] Jackson Lab, Bar Harbor, ME 04609 USA. RP Nellaker, C (reprint author), Univ Oxford, Dept Physiol Anat & Genet, MRC Funct Genom Unit, S Parks Rd, Oxford OX1 3PT, England. EM christoffer.nellaker@dpag.ox.ac.uk RI Yalcin, Binnaz/P-5482-2016; OI Yalcin, Binnaz/0000-0002-1924-6807; Nellaker, Christoffer/0000-0002-2887-2068; Flint, Jonathan/0000-0002-9427-4429; Belgard, Tildon/0000-0002-6962-7894; Ponting, Chris/0000-0003-0202-7816; Keane, Thomas/0000-0001-7532-6898 FU Medical Research Council, UK; Wellcome Trust; National Institutes of Health (NIH) [R01 NS031348]; Cancer Research UK; National Human Genome Research Institute; MRC Biomedical Informatics Training Fellowship FX This study was funded by the Medical Research Council, UK and the Wellcome Trust. WNF is funded by National Institutes of Health (NIH) grant R01 NS031348. DJA is funded by Cancer Research UK and the Wellcome Trust. TGB was funded by the Intramural Research Program of the National Human Genome Research Institute. CN is funded by a MRC Biomedical Informatics Training Fellowship. NR 79 TC 30 Z9 32 U1 4 U2 19 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-7596 J9 GENOME BIOL JI Genome Biol. PY 2012 VL 13 IS 6 AR R45 DI 10.1186/gb-2012-13-6-r45 PG 21 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 002QD UT WOS:000308546300005 PM 22703977 ER PT J AU Lee, CJ Ramirez, AS Lewis, N Gray, SW Hornik, RC AF Lee, Chul-joo Ramirez, A. Susana Lewis, Nehama Gray, Stacy W. Hornik, Robert C. TI Looking Beyond the Internet: Examining Socioeconomic Inequalities in Cancer Information Seeking Among Cancer Patients SO HEALTH COMMUNICATION LA English DT Article ID HEALTH INFORMATION; KNOWLEDGE GAP; NEWS; DISPARITIES; BEHAVIORS; COVERAGE; CARE AB The gap in cancer information seeking between high-socioeconomic-status (high-SES) cancer patients and low-SES cancer patients deserves serious attention, considering the importance of information and knowledge in cancer control. We thus explored the association of SES, as measured by education, with cancer patients' overall cancer information seeking, and with seeking from each source (i.e., the Internet, mass media, medical sources, and nonmedical interpersonal sources) and across two topic categories (i.e., treatment, quality of life). We then asked whether the effect of education on treatment information seeking is reduced among those who are particularly motivated to control treatment choices. We conducted a survey with breast, prostate, and colon cancer patients diagnosed in 2005 (n = 2,013), who were randomly drawn from the Pennsylvania Cancer Registry in the fall of 2006. We found that education was more strongly associated with Internet use than with the use of other sources regardless of topics. Also, when information was sought from mass media, education had a greater association with treatment information seeking than with quality-of-life information seeking. Preference for active participation in treatment decision making, however, did not moderate the effect of education on treatment information seeking. The implications of these findings for public health research and cancer patient education were discussed. C1 [Lee, Chul-joo] Ohio State Univ, Sch Commun, Columbus, OH 43210 USA. [Ramirez, A. Susana] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Lewis, Nehama] Florida Int Univ, Dept Psychol, Miami, FL 33199 USA. [Gray, Stacy W.] Harvard Univ, Dana Farber Canc Inst, Cambridge, MA 02138 USA. [Hornik, Robert C.] Univ Penn, Annenberg Sch Commun, Philadelphia, PA 19104 USA. RP Lee, CJ (reprint author), Ohio State Univ, Sch Commun, 3062 Derby Hall,154 N Oval Mall, Columbus, OH 43210 USA. EM lee.4030@osu.edu OI Hornik, Robert/0000-0002-2148-8805 FU NCI NIH HHS [5P50CA095856-05, P50 CA095856] NR 44 TC 9 Z9 9 U1 4 U2 16 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1041-0236 J9 HEALTH COMMUN JI Health Commun. PY 2012 VL 27 IS 8 BP 806 EP 817 DI 10.1080/10410236.2011.647621 PG 12 WC Communication; Health Policy & Services SC Communication; Health Care Sciences & Services GA 994SW UT WOS:000307953200008 PM 22356137 ER PT J AU Jasien, J Daimon, CM Maudsley, S Shapiro, BK Martin, B AF Jasien, Joan Daimon, Caitlin M. Maudsley, Stuart Shapiro, Bruce K. Martin, Bronwen TI Aging and Bone Health in Individuals with Developmental Disabilities SO INTERNATIONAL JOURNAL OF ENDOCRINOLOGY LA English DT Review ID SEVERE CEREBRAL-PALSY; MINERAL DENSITY; MENTAL-RETARDATION; INTELLECTUAL DISABILITY; DOWNS-SYNDROME; RISK-FACTORS; SPASTIC QUADRIPLEGIA; MUSCLE STRENGTH; LIFE EXPECTANCY; OLDER-ADULTS AB Low bone mass density (BMD), a classical age-related health issue and a known health concern for fair skinned, thin, postmenopausal Caucasian women, is found to be common among individuals with developmental/intellectual disabilities (D/IDs). It is the consensus that BMDis decreased in both men and women with D/ID. Maintaining good bone health is important for this population as fractures could potentially go undetected in nonverbal individuals, leading to increased morbidity and a further loss of independence. This paper provides a comprehensive overview of bone health of adults with D/ID, their risk of fractures, and how this compares to the general aging population. We will specifically focus on the bone health of two common developmental disabilities, Down syndrome (DS) and cerebral palsy (CP), and will discuss BMD and fracture rates in these complex populations. Gaining a greater understanding of how bone health is affected in individuals with D/ID could lead to better customized treatments for these specific populations. C1 [Jasien, Joan; Daimon, Caitlin M.; Martin, Bronwen] NIA, Metab Unit, NIH, Baltimore, MD 21224 USA. [Jasien, Joan; Shapiro, Bruce K.] Kennedy Krieger Inst, Dept Neurol & Neurodev, Baltimore, MD 21224 USA. [Maudsley, Stuart] NIA, Receptor Pharmacol Unit, NIH, Baltimore, MD 21224 USA. RP Jasien, J (reprint author), NIA, Metab Unit, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. EM jasien@kennedykrieger.org FU Intramural Research Program of the National Institute on Aging, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. NR 63 TC 6 Z9 6 U1 1 U2 9 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-8337 J9 INT J ENDOCRINOL JI Int. J. Endocrinol. PY 2012 AR 469235 DI 10.1155/2012/469235 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 997VG UT WOS:000308194800001 ER PT J AU Hou, ZC Sterner, KN Romero, R Than, NG Gonzalez, JM Weckle, A Xing, J Benirschke, K Goodman, M Wildman, DE AF Hou, Zhuo-Cheng Sterner, Kirstin N. Romero, Roberto Than, Nandor Gabor Gonzalez, Juan M. Weckle, Amy Xing, Jun Benirschke, Kurt Goodman, Morris Wildman, Derek E. TI Elephant Transcriptome Provides Insights into the Evolution of Eutherian Placentation SO GENOME BIOLOGY AND EVOLUTION LA English DT Article DE comparative transcriptomics; Loxodonta africana; RNA-seq; placenta development ID GROWTH-HORMONE; AFRICAN ELEPHANT; SPIRAL ARTERIES; HUMAN GENOME; MAMMALS; MOUSE; TROPHOBLAST; EXPRESSION; GENES; PREGNANCY AB The chorioallantoic placenta connects mother and fetus in eutherian pregnancies. In order to understand the evolution of the placenta and provide further understanding of placenta biology, we sequenced the transcriptome of a term placenta of an African elephant (Loxodonta africana) and compared these data with RNA sequence and microarray data from other eutherian placentas including human, mouse, and cow. We characterized the composition of 55,910 expressed sequence tag (i.e., cDNA) contigs using our custom annotation pipeline. A Markov algorithm was used to cluster orthologs of human, mouse, cow, and elephant placenta transcripts. We found 2,963 genes are commonly expressed in the placentas of these eutherian mammals. Gene ontology categories previously suggested to be important for placenta function (e.g., estrogen receptor signaling pathway, cell motion and migration, and adherens junctions) were significantly enriched in these eutherian placenta-expressed genes. Genes duplicated in different lineages and also specifically expressed in the placenta contribute to the great diversity observed in mammalian placenta anatomy. We identified 1,365 human lineage-specific, 1,235 mouse lineage-specific, 436 cow lineage-specific, and 904 elephant-specific placenta-expressed (PE) genes. The most enriched clusters of human-specific PE genes are signal/glycoprotein and immunoglobulin, and humans possess a deeply invasive human hemochorial placenta that comes into direct contact with maternal immune cells. Inference of phylogenetically conserved and derived transcripts demonstrates the power of comparative transcriptomics to trace placenta evolution and variation across mammals and identified candidate genes that may be important in the normal function of the human placenta, and their dysfunction may be related to human pregnancy complications. C1 [Hou, Zhuo-Cheng; Romero, Roberto; Than, Nandor Gabor; Gonzalez, Juan M.; Weckle, Amy; Xing, Jun; Wildman, Derek E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Hou, Zhuo-Cheng; Sterner, Kirstin N.; Romero, Roberto; Weckle, Amy; Xing, Jun; Goodman, Morris; Wildman, Derek E.] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48202 USA. [Hou, Zhuo-Cheng] China Agr Univ, Dept Anim Genet, Beijing 100094, Peoples R China. [Gonzalez, Juan M.; Wildman, Derek E.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48202 USA. [Benirschke, Kurt] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. [Goodman, Morris] Wayne State Univ, Sch Med, Dept Anat & Cell Biol, Detroit, MI 48202 USA. RP Romero, R (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. EM prbchiefstaff@med.wayne.edu; wildman@med.wayne.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development/NIH/DHHS; National Science Foundation [BCS0827546] FX We would like to acknowledge our coauthor and friend, distinguished Prof. Morris Goodman (Wayne State University, Detroit, MI), who sadly passed away during the completion of this manuscript. In his long and distinguished career, Dr. Goodman. emphasized the importance of a comparative approach that uses molecular data to study mammalian biology and adaptation in an evolutionary context. It was in this light that we developed this project. We acknowledge the Wayne State University Grid for providing computational resources. The authors would like to acknowledge the Broad Institute as the source of the elephant genome sequence data. This work was supported in part by the Intramural Research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development/NIH/DHHS and the National Science Foundation (BCS0827546). NR 71 TC 9 Z9 9 U1 1 U2 26 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1759-6653 J9 GENOME BIOL EVOL JI Genome Biol. Evol. PY 2012 VL 4 IS 5 BP 713 EP 725 DI 10.1093/gbe/evs045 PG 13 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 993BQ UT WOS:000307829700010 PM 22546564 ER PT J AU Strait, JB Lakatta, EG AF Strait, James B. Lakatta, Edward G. TI Aging-Associated Cardiovascular Changes and Their Relationship to Heart Failure SO HEART FAILURE CLINICS LA English DT Article DE Heart failure; Cardiovascular aging; Cardiac function; Cardiac reserve ID PRESERVED EJECTION FRACTION; SUBCLINICAL ARTERIAL-DISEASE; PULSE-WAVE VELOCITY; AGE-RELATED-CHANGES; ANGIOTENSIN-II; AMBULATORY ELECTROCARDIOGRAPHY; VENTRICULAR-FUNCTION; CARDIAC-ARRHYTHMIAS; MAJOR SHAREHOLDERS; AEROBIC CAPACITY AB Aging represents a convergence of declining cardioprotective systems and increasing disease processes that is fertile ground for the development of heart failure. Fifty percent of all heart failure diagnoses and 90% of all heart failure deaths occur in individuals older than 70. This article discusses the microscopic and macroscopic changes in cardiovascular structure, function, protective systems, and disease associated with aging. In addition to outlining important clinical considerations and conditions in older persons, the link between normal aging and the elevated risk for development of stage B heart failure is explained and potential therapeutic pathways are highlighted. C1 [Strait, James B.] NIA, Cardiovasc Sci Lab, Intramural Res Program, Clin Res Branch,NIH,Harbor Hosp, Baltimore, MD 21225 USA. [Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Intramural Res Program, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. RP Strait, JB (reprint author), NIA, Cardiovasc Sci Lab, Intramural Res Program, Clin Res Branch,NIH,Harbor Hosp, NM-500,3001 S Hanover St, Baltimore, MD 21225 USA. EM Straitj@mail.nih.gov FU Intramural NIH HHS [Z99 AG999999] NR 90 TC 59 Z9 62 U1 2 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7136 J9 HEART FAIL CLIN JI Heart Fail. Clin. PD JAN PY 2012 VL 8 IS 1 BP 143 EP + DI 10.1016/j.hfc.2011.08.011 PG 23 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 988MK UT WOS:000307494900015 PM 22108734 ER PT J AU Balshaw, DM AF Balshaw, David M. TI Engineering Circuits and Systems at the Interface of Environment and Health SO IEEE CIRCUITS AND SYSTEMS MAGAZINE LA English DT Article ID EXPOSURE; DISEASE; EPIDEMIOLOGY AB As people go about their daily routine, they encounter myriad chemicals. Some of these chemicals, oxygen for instance, are absolutely essential for life. Others, environmental pollutants, are potentially harmful and a major factor that contributes to illness. The field of environmental health strives to understand not only what we encounter every day and over our lifespan, but also how our bodies respond to those exposures. The responses can be good (improving health), bad, or indifferent (by far the most common). Environmental health scientists have long studied the effects of environment on health using the tools we have available, steadily improving our ability to make connections and improve health as new technologies emerge. This commentary will lay out a number of challenges in two specific areas where the circuits and systems engineering community can help us address some of our biggest needs: the development of sensor systems for assessing exposures to environmental factors and the development of engineered tissue systems for assessing the biological response to the factors we are exposed to. C1 NIEHS, Ctr Risk & Integrated Sci, Div Extramural Res & Training, Durham, NC 27709 USA. RP Balshaw, DM (reprint author), NIEHS, Ctr Risk & Integrated Sci, Div Extramural Res & Training, MD K3-04,POB 12233, Durham, NC 27709 USA. EM Balshaw@nih.gov NR 18 TC 0 Z9 0 U1 1 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1531-636X J9 IEEE CIRC SYST MAG JI IEEE Circuits Syst. Mag. PY 2012 VL 12 IS 3 BP 30 EP 34 DI 10.1109/MCAS.2012.2205975 PG 5 WC Engineering, Electrical & Electronic SC Engineering GA 995OI UT WOS:000308018800004 ER PT J AU Grundfest, WS Ayers, J Gallagher, S Abu-Taleb, L Watson, JT AF Grundfest, Warren S. Ayers, Jennifer Gallagher, Sean Abu-Taleb, Laith Watson, John T. TI AIMBE's Role in Promoting Biomedical Engineering Input to Public Policy SO IEEE CIRCUITS AND SYSTEMS MAGAZINE LA English DT Letter C1 [Grundfest, Warren S.] Univ Calif Los Angeles, UCLA Sch Engn, Los Angeles, CA 90095 USA. [Grundfest, Warren S.] Univ Calif Los Angeles, UCLA Sch Med, Los Angeles, CA 90095 USA. [Ayers, Jennifer] PLANET, Herndon, VA USA. [Abu-Taleb, Laith] Univ Maryland, Funct Macromol Lab, College Pk, MD 20742 USA. [Watson, John T.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Watson, John T.] NHLBI, NIH, Devices & Technol Branch, Bethesda, MD USA. RP Grundfest, WS (reprint author), Univ Calif Los Angeles, UCLA Sch Engn, 4121H Engr 5,Box 951600, Los Angeles, CA 90095 USA. EM warrenbe@seas.ucla.edu; sgallagher@aimbe.org NR 9 TC 0 Z9 0 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1531-636X J9 IEEE CIRC SYST MAG JI IEEE Circuits Syst. Mag. PY 2012 VL 12 IS 3 BP 36 EP 40 DI 10.1109/MCAS.2012.2205976 PG 5 WC Engineering, Electrical & Electronic SC Engineering GA 995OI UT WOS:000308018800005 ER PT J AU Takacs, S Biessmann, H Reddy, HM Mason, JM Torok, T AF Takacs, Sandor Biessmann, Harald Reddy, Hemakumar M. Mason, James M. Toeroek, Tibor TI Protein Interactions on Telomeric Retrotransposons in Drosophila SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE chromatin; Chromator; prod; putzig; Z4; sumoylation; telomere; Drosophila; retrotransposon ID DISTINCT CHROMATIN DOMAINS; POLYTENE CHROMOSOMES; PROLIFERATION-DISRUPTER; CHROMODOMAIN PROTEIN; CELL-PROLIFERATION; MELANOGASTER; KINASE; HETEROCHROMATIN; ELONGATION; LENGTH AB Telomere length in Drosophila is maintained by targeted transposition of three non-LTR retrotransposons: HeT-A, TART and TAHRE (HTT), but understanding the regulation of this process is hindered by our poor knowledge of HTT associated proteins. We have identified new protein components of the HTT array: Chromator (Chro), the TRF2/DREF complex and the sumoylation machinery. Chro was localized on telomeric HTT arrays by immunostaining, where it may interact with Prod directly, as indicated by yeast two-hybrid interaction, co-IP, and colocalization on polytene chromosomes. The TRF2/DREF complex may promote the open structure of HTT chromatin. The protein interactions controlling HTT chromatin structure and telomere length may be modulated by sumoylation. C1 [Takacs, Sandor; Toeroek, Tibor] Univ Szeged, Dept Genet, H-6701 Szeged, Hungary. [Reddy, Hemakumar M.; Mason, James M.] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. [Biessmann, Harald] Univ Calif Irvine, Ctr Dev Biol, Irvine, CA 92697 USA. RP Torok, T (reprint author), Univ Szeged, Dept Genet, H-6701 Szeged, Hungary. RI Mutra, Hemakumara/D-3876-2014 OI Mutra, Hemakumara/0000-0002-3769-6609 FU NIH; National Institute of Environmental Health Sciences [OTKA T/F 037422]; European Union; European Social Fund; [TAMOP-4.2.2/B-10/1-2010-0012] FX We thank Harald Saumweber, Pavel Georgiev and the Bloomington Drosophila Stock Center for fly stocks, and Harald Saumweber, Jacob Seeler and Imre Boros for antibodies. This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences, OTKA T/F 037422. The publication is supported by the European Union and co-funded by the European Social Fund. Project title: "Broadening the knowledge base and supporting the long term professional sustainability of the Research University Centre of Excellence at the University of Szeged by ensuring the rising generation of excellent scientists." Project number: TAMOP-4.2.2/B-10/1-2010-0012. NR 28 TC 4 Z9 4 U1 0 U2 4 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2012 VL 8 IS 7 BP 1055 EP 1061 DI 10.7150/ijbs.4460 PG 7 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 999XB UT WOS:000308347700014 PM 22949888 ER PT J AU Stranahan, AM Mattson, MP AF Stranahan, Alexis M. Mattson, Mark P. TI Metabolic Reserve as a Determinant of Cognitive Aging SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Review DE Brain-derived neurotrophic factor (BDNF); caloric restriction; diabetes; diet; exercise; insulin; metabolic syndrome; neurodegeneration ID TRANSGENIC MOUSE MODEL; FIBROBLAST-GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; NEUROTROPHIC FACTOR; MESSENGER-RNA; AMYLOID-BETA; HIPPOCAMPAL-NEURONS; VOLUNTARY EXERCISE; MEDITERRANEAN DIET AB Mild cognitive impairment (MCI) and Alzheimer's disease (AD) represent points on a continuum of cognitive performance in aged populations. Cognition may be impaired or preserved in the context of brain aging. One theory to account for memory maintenance in the context of extensive pathology involves 'cognitive reserve', or the ability to compensate for neuropathology through greater recruitment of remaining neurons. In this review, we propose a complementary hypothesis of 'metabolic reserves, where a brain with high metabolic reserve is characterized by the presence of neuronal circuits that respond adaptively to Perturbations in cellular and somatic energy metabolism and thereby protects against declining cognition. Lifestyle determinants of metabolic reserve, such as exercise, reduced caloric intake, and intake of specific dietary components can promote neuroprotection, while pathological states arising from sedentary lifestyles and excessive caloric intake contribute to neuronal endangerment. This bidirectional relationship between metabolism and cognition may be mediated by alterations in central insulin and neurotrophic factor signaling and glucose metabolism, with downstream consequences for accumulation of amyloid-beta and hyperphosphorylated tau. The metabolic reserve hypothesis is supported by epidemiological findings and the spectrum of individual cognitive trajectories during aging, with additional data from animal models identifying potential mechanisms for this relationship. Identification of biomarkers for metabolic reserve could assist in generating a predictive model for the likelihood of cognitive decline with aging. C1 [Stranahan, Alexis M.] Georgia Hlth Sci Univ, Dept Physiol, Augusta, GA 30912 USA. [Mattson, Mark P.] NIA, Cellular & Mol Neurosci Sect, Lab Neurosci, Intramural Res Program,Biomed Res Ctr, Baltimore, MD 21224 USA. RP Stranahan, AM (reprint author), Georgia Hlth Sci Univ, Dept Physiol, 1120,15th St,Room CA3145, Augusta, GA 30912 USA. EM astranahan@georgiahealth.edu FU Georgia Health Sciences University; Intramural Research Program of the National Institute on Aging FX A.M.S. is currently supported by start-up funds from Georgia Health Sciences University and M.P.M. is supported by the Intramural Research Program of the National Institute on Aging. NR 92 TC 13 Z9 14 U1 2 U2 22 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2012 VL 30 SU 2 SI SI BP S5 EP S13 DI 10.3233/JAD-2011-110899 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 994EZ UT WOS:000307915000002 PM 22045480 ER PT J AU Becerra, SP Dass, CR Yabe, T Crawford, SE AF Becerra, S. Patricia Dass, Crispin R. Yabe, Takeshi Crawford, Susan E. TI Pigment Epithelium-Derived Factor: Chemistry, Structure, Biology, and Applications SO JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY LA English DT Editorial Material C1 [Becerra, S. Patricia] NEI, Sect Prot Struct & Funct, Lab Retinal Cell & Mol Biol, Bethesda, MD 20892 USA. [Dass, Crispin R.] Victoria Univ, Sch Biomed Sci, Melbourne, Vic 8001, Australia. [Yabe, Takeshi] Setsunan Univ, Dept Med Pharm, Osaka 5730101, Japan. [Crawford, Susan E.] St Louis Univ, Dept Pathol, St Louis, MO 63104 USA. RP Becerra, SP (reprint author), NEI, Sect Prot Struct & Funct, Lab Retinal Cell & Mol Biol, Bethesda, MD 20892 USA. EM becerrap@nei.nih.gov NR 0 TC 1 Z9 1 U1 1 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1110-7243 J9 J BIOMED BIOTECHNOL JI J. Biomed. Biotechnol. PY 2012 AR 830975 DI 10.1155/2012/830975 PG 2 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 001UZ UT WOS:000308486900001 ER PT J AU Wininger, M AF Wininger, Michael TI A Generalized Strategy for Measuring Performance in the Velocity-Position Phase Plane SO JOURNAL OF MOTOR BEHAVIOR LA English DT Article DE smoothness; jerk; proficiency; performance; measurement ID SENSITIVITY AB Recent work has proposed the reformulation of smoothness measures derived from standard integrated squared jerk, as a function of position, not time. However, its promulgation was in the context of monotonic excursion data extracted from single degree-of-freedom (DOF) movements; the result was a formulation of a phase smoothness measure with limited generalizability. Here, we present a complete methodology for implementing the phase smoothness measure in arbitrary datasets, i.e. for multi-DOF movements with no assumptions of monotonicity in the kinematic profile. Additional suggestions are made for best practices. C1 [Wininger, Michael] VA Connecticut Healthcare Syst, VA Cooperat Studies Program, Coordinating Ctr, West Haven, CT 06516 USA. [Wininger, Michael] Univ Hartford, Prosthet & Orthot Program, Hartford, CT 06117 USA. [Wininger, Michael] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP Wininger, M (reprint author), VA Connecticut Healthcare Syst, VA Cooperat Studies Program, Coordinating Ctr, West Haven, CT 06516 USA. EM michael.wininger@va.gov NR 6 TC 1 Z9 1 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0022-2895 J9 J MOTOR BEHAV JI J. Mot. Behav. PY 2012 VL 44 IS 4 BP 269 EP 273 DI 10.1080/00222895.2012.692407 PG 5 WC Neurosciences; Psychology; Psychology, Experimental; Sport Sciences SC Neurosciences & Neurology; Psychology; Sport Sciences GA 994KK UT WOS:000307929400007 PM 22857393 ER PT J AU Giulianelli, S Vaque, JP Wargon, V Soldati, R Vanzulli, SI Martins, R Zeitlin, E Helguero, L Lamb, C Molinolo, AA Gutkind, JS Lanari, C AF Giulianelli, Sebastian Vaque, Jose P. Wargon, Victoria Soldati, Rocio Vanzulli, Silvia I. Martins, Ruben Zeitlin, Eduardo Helguero, Luisa Lamb, Caroline Molinolo, Alfredo A. Gutkind, J. Silvio Lanari, Claudia TI The role of estrogen receptor alpha in breast cancer cell proliferation mediated by progestins SO MEDICINA-BUENOS AIRES LA Spanish DT Article DE breast cancer; ER alpha; PR; MPA; CCND1/MYC ID PROGESTERONE-RECEPTOR; ACTIVATION; DOMAINS; GENE; ANTIPROGESTIN; PATHWAY; GROWTH AB The role of estrogen receptor alpha in breast cancer cell proliferation mediated by progestins. In C4-HD murine mammary carcinomas and in human breast cancer T47D cells, we showed that medroxyprogesterone acetate (MPA) induces a nuclear physical association between estrogen receptor alpha (ER alpha) and progesterone receptors (PR). The blockade of ER alpha inhibits cell proliferation mediated by progestins. We hypothesized that this nuclear association between ER alpha/PR is necessary to trigger progestin-induced cell proliferation and tumor growth. We demonstrated that fulvestrant (FUL, ICI182.780) induced complete regression of C4-HD tumors growing with progestins. MPA treatment induced an early increase in both CCND1 and MYC expression in T47D cells. The blockade of ER alpha prevented the MPA-dependent transcription of both genes. Specific binding of PR/ER alpha was observed at the same MPA-sensitive regions at the CCND1 and MYC gene promoters after chromatin immunoprecipitation (ChIP) analysis. ICI inhibited binding of ER alpha to both gene regulatory sequences while PR binding was unaffected. The nuclear colocalization between both receptors in T47D cells was confirmed by: confocal microscopy, Duolink assays and co-immunoprecipitation assays. In breast cancer samples we also observed a nuclear interaction between both steroid receptors. Our results indicate that the presence of ER alpha interacting with activated PR at the CCND1 and MYC promoters is required to trigger progestin-induced gene transcription and cell proliferation in breast cancer cells. C1 [Giulianelli, Sebastian; Wargon, Victoria; Soldati, Rocio; Lamb, Caroline; Lanari, Claudia] IByME CONICET, Inst Biol & Med Expt, RA-1428 Buenos Aires, DF, Argentina. [Vaque, Jose P.; Molinolo, Alfredo A.; Gutkind, J. Silvio] NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. [Martins, Ruben; Zeitlin, Eduardo] Policlin Bancaria, Buenos Aires, DF, Argentina. [Helguero, Luisa] Univ Aveiro, P-3800 Aveiro, Portugal. RP Lanari, C (reprint author), IByME CONICET, Inst Biol & Med Expt, Vuelta Obligado 2490, RA-1428 Buenos Aires, DF, Argentina. EM lanari.claudia@gmail.com RI Helguero, Luisa/B-1221-2013; Vaque, Jose/H-8413-2015 OI Helguero, Luisa/0000-0001-8237-2390; Vaque, Jose/0000-0002-3913-2495 NR 15 TC 3 Z9 4 U1 0 U2 3 PU MEDICINA (BUENOS AIRES) PI BUENOS AIRES PA DONATO ALVAREZ 3150, 1427 BUENOS AIRES, ARGENTINA SN 0025-7680 J9 MEDICINA-BUENOS AIRE JI Med.-Buenos Aires PY 2012 VL 72 IS 4 BP 315 EP 320 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 995DF UT WOS:000307987400007 PM 22892083 ER PT J AU Erinosho, TO Oh, AY Moser, RP Davis, KL Nebeling, LC Yaroch, AL AF Erinosho, Temitope O. Oh, April Y. Moser, Richard P. Davis, Kia L. Nebeling, Linda C. Yaroch, Amy L. TI Association Between Perceived Food Environment and Self-Efficacy for Fruit and Vegetable Consumption Among US Adults, 2007 SO PREVENTING CHRONIC DISEASE LA English DT Article AB Consumption of diets high in fruits and vegetables is associated with reduced risk of chronic diseases, and self-efficacy and the food environment influence consumption of fruits and vegetables. We analyzed data from 3,021 non-Hispanic white (n = 2,187) and non-Hispanic black (n = 834) US adults who responded to National Cancer Institute's 2007 Food Attitudes and Behaviors Survey to assesss self-efficacy and perception of the food environment. Adults who perceived that it was easy to obtain fruits and vegetables when they ate out reported greater self-efficacy to consume fruits and vegetables than did participants who did not have this perception (odds ratio [OR] = 1.56, 95% confidence interval [CI], 1.24-1.97). However, adults who perceived that fruits were not available at restaurants where they ate out (OR = 0.65, 95% CI, 0.50-0.86) or that other (ie, non-fast food) restaurants offered enough choices of fruits and vegetables on their menus (OR = 0.76, 95% CI, 0.61-0.97) reported lower self-efficacy to consume fruits and vegetables than did participants who did not have these perceptions. Findings suggest that perceptions about availability of fruits and vegetables in restaurants are important to promote self-efficacy for consuming fruits and vegetables among adults. C1 [Oh, April Y.; Moser, Richard P.; Nebeling, Linda C.] NCI, Rockville, MD USA. [Davis, Kia L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Yaroch, Amy L.] Gretchen Swanson Ctr Nutr, Omaha, NE USA. [Davis, Kia L.] SAIC Frederick Inc, Rockville, MD USA. [Erinosho, Temitope O.] US Natl Canc Inst, Rockville, MD USA. RP Erinosho, TO (reprint author), Univ N Carolina, Dept Nutr, 1700 Martin Luther King Jr Blvd,2nd Fl,CB 7426, Chapel Hill, NC 27599 USA. EM tope_erinosho@unc.edu NR 9 TC 0 Z9 0 U1 1 U2 9 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD JAN PY 2012 VL 9 AR 100291 DI 10.5888/pcd9.100291 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 977GI UT WOS:000306644300010 ER PT J AU Hekler, EB Buman, MP Ahn, D Dunton, G Atienza, AA King, AC AF Hekler, Eric B. Buman, Matthew P. Ahn, David Dunton, Genevieve Atienza, Audie A. King, Abby C. TI Are daily fluctuations in perceived environment associated with walking? SO PSYCHOLOGY & HEALTH LA English DT Article DE exercise; ecological momentary assessment; older adults; perceived built environment; social cognitive theory ID ECOLOGICAL MOMENTARY ASSESSMENT; RANDOMIZED CONTROLLED-TRIAL; PHYSICAL-ACTIVITY; IMPLEMENTATION INTENTIONS; PLANNED BEHAVIOR; OLDER ADULTS; HEALTH; INTERVENTION; EXERCISE; OUTCOMES AB The physical environment is thought to influence walking; however, daily variations in perceived environment have received little attention. The current study sought to examine if key within-person factors (i.e., implementation intentions, social support, affect and self-efficacy) would be associated with walking and if perceived access to supportive environments (e.g., access to nice walking paths) and perceived environmental barriers (e.g., bad weather and safety issues) were uniquely associated with walking after controlling for other constructs. Participants (N = 14, 50.0% men, 78.6% White, M age = 59.4 +/- 6.4) were in the intervention arm of an 8-week controlled trial promoting walking via personal digital assistants. Participants completed electronic surveys twice a day (total entries = 804) in which they reported brisk walking levels and psychosocial and environmental factors. Multilevel modelling was used to examine within-person variations in constructs as determinants of walking. Results suggested that daily variations in implementation intentions, social support and positive affect were positively associated with walking. Further, perceived access to supportive environments, though not perceived environmental barriers, was positively associated with walking after controlling for other constructs (p < 0.05). Future research should explore intervention components that target context-specific information about perceived access to supportive environments as part of a broader perspective on intervention development. C1 [Hekler, Eric B.; Buman, Matthew P.; Ahn, David; King, Abby C.] Stanford Univ, Stanford Prevent Res Ctr, Stanford, CA 94305 USA. [Hekler, Eric B.; Buman, Matthew P.] Arizona State Univ, Sch Nutr & Hlth Promot, Phoenix, AZ USA. [Dunton, Genevieve] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Atienza, Audie A.] NCI, Bethesda, MD 20892 USA. RP Hekler, EB (reprint author), Stanford Univ, Stanford Prevent Res Ctr, Stanford, CA 94305 USA. EM ehekler@asu.edu FU NHLBI NIH HHS [5 T32 HL007034, T32 HL007034] NR 29 TC 13 Z9 13 U1 3 U2 18 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0887-0446 J9 PSYCHOL HEALTH JI Psychol. Health PY 2012 VL 27 IS 9 BP 1009 EP 1020 DI 10.1080/08870446.2011.645213 PG 12 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary SC Public, Environmental & Occupational Health; Psychology GA 994OS UT WOS:000307941100001 PM 22214492 ER PT J AU Williams, RW Noronha, A AF Williams, Robert W. Noronha, Antonio TI A Watershed Year for an Update on the Genetics of Alcoholism SO ALCOHOL RESEARCH-CURRENT REVIEWS LA English DT Editorial Material C1 [Williams, Robert W.] Univ Tennessee, Ctr Hlth Sci, Ctr Integrat & Translat Genom, Memphis, TN 38163 USA. [Noronha, Antonio] NIAAA, Div Neurosci & Behav, Bethesda, MD USA. RP Williams, RW (reprint author), Univ Tennessee, Ctr Hlth Sci, Ctr Integrat & Translat Genom, Memphis, TN 38163 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 J9 ALCOHOL RES-CURR REV JI Alcohol Res.-Curr. Rev. PY 2012 VL 34 IS 3 BP 263 EP 263 PG 1 WC Substance Abuse SC Substance Abuse GA 980CU UT WOS:000306872000002 ER PT J AU Reilly, MT Harris, RA Noronha, A AF Reilly, Matthew T. Harris, R. Adron Noronha, Antonio TI Using Genetically Engineered Animal Models in the Postgenomic Era to Understand Gene Function in Alcoholism SO ALCOHOL RESEARCH-CURRENT REVIEWS LA English DT Review DE Alcoholism; genetic; genetic basis of alcoholism; neuroscience; gene function; genetic engineering; genetic technology; gene knockout technology; gene sequencing; gene functions; phenotype; genome; epigenome; transcriptome; animal studies; knockout mice ID RECEPTOR KNOCKOUT MICE; KINASE-C-EPSILON; GABA(A) RECEPTORS; MOUSE; CONSUMPTION; EXPRESSION; SENSITIVITY AB Over the last 50 years, researchers have made substantial progress in identifying genetic variations that underlie the complex phenotype of alcoholism. Not much is known, however, about how this genetic variation translates into altered biological function. Genetic animal models recapitulating specific characteristics of the human condition have helped elucidate gene function and the genetic basis of disease. In particular, major advances have come from the ability to manipulate genes through a variety of genetic technologies that provide an unprecedented capacity to determine gene function in the living organism and in alcohol-related behaviors. Even newer genetic-engineering technologies have given researchers the ability to control when and where a specific gene or mutation is activated or deleted, allowing investigators to narrow the role of the gene's function to circumscribed neural pathways and across development. These technologies are important for all areas of neuroscience, and several public and private initiatives are making a new generation of genetic-engineering tools available to the scientific community at large. Finally, high-throughput "next-generation sequencing" technologies are set to rapidly increase knowledge of the genome, epigenome, and transcriptome, which, combined with genetically engineered mouse mutants, will enhance insight into biological function. All of these resources will provide deeper insight into the genetic basis of alcoholism. C1 [Reilly, Matthew T.; Noronha, Antonio] NIAAA, Div Neurosci & Behav, Bethesda, MD USA. [Harris, R. Adron] Univ Texas Austin, Waggoner Ctr Alcohol & Addict Res, Austin, TX 78712 USA. RP Reilly, MT (reprint author), NIAAA, Div Neurosci & Behav, Bethesda, MD USA. NR 41 TC 3 Z9 4 U1 0 U2 8 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 J9 ALCOHOL RES-CURR REV JI Alcohol Res.-Curr. Rev. PY 2012 VL 34 IS 3 BP 282 EP 291 PG 10 WC Substance Abuse SC Substance Abuse GA 980CU UT WOS:000306872000006 PM 23134044 ER PT J AU Antoniou, AC Kuchenbaecker, KB Soucy, P Beesley, J Chen, XQ McGuffog, L Lee, A Barrowdale, D Healey, S Sinilnikova, OM Caligo, MA Loman, N Harbst, K Lindblom, A Arver, B Rosenquist, R Karlsson, P Nathanson, K Domchek, S Rebbeck, T Jakubowska, A Lubinski, J Jaworska, K Durda, K Zlowowcka-Perlowska, E Osorio, A Duran, M Andres, R Benitez, J Hamann, U Hogervorst, FB van Os, TA Verhoef, S Meijers-Heijboer, HEJ Wijnen, J Garcia, EBG Ligtenberg, MJ Kriege, M Collee, M Ausems, MGEM Oosterwijk, JC Peock, S Frost, D Ellis, SD Platte, R Fineberg, E Evans, DG Lalloo, F Jacobs, C Eeles, R Adlard, J Davidson, R Cole, T Cook, J Paterson, J Douglas, F Brewer, C Hodgson, S Morrison, PJ Walker, L Rogers, MT Donaldson, A Dorkins, H Godwin, AK Bove, B Stoppa-Lyonnet, D Houdayer, C Buecher, B de Pauw, A Mazoyer, S Calender, A Leone, M Bressac-de Paillerets, B Caron, O Sobol, H Frenay, M Prieur, F Ferrer, SF Mortemousque, I Buys, S Daly, M Miron, A Terry, MB Hopper, JL John, EM Southey, M Goldgar, D Singer, CF Fink-Retter, A Tea, MK Kaulich, DG Hansen, TVO Nielsen, FC Barkardottir, RB Gaudet, M Kirchhoff, T Joseph, V Dutra-Clarke, A Offit, K Piedmonte, M Kirk, J Cohn, D Hurteau, J Byron, J Fiorica, J Toland, AE Montagna, M Oliani, C Imyanitov, E Isaacs, C Tihomirova, L Blanco, I Lazaro, C Teule, A Del Valle, J Gayther, SA Odunsi, K Gross, J Karlan, BY Olah, E Teo, SH Ganz, PA Beattie, MS Dorfling, CM van Rensburg, EJ Diez, O Kwong, A Schmutzler, RK Wappenschmidt, B Engel, C Meindl, A Ditsch, N Arnold, N Heidemann, S Niederacher, D Preisler-Adams, S Gadzicki, D Varon-Mateeva, R Deissler, H Gehrig, A Sutter, C Kast, K Fiebig, B Schafer, D Caldes, T de la Hoya, M Nevanlinna, H Muranen, TA Lesperance, B Spurdle, AB Neuhausen, SL Ding, YC Wang, XS Fredericksen, Z Pankratz, VS Lindor, NM Peterlongo, P Manoukian, S Peissel, B Zaffaroni, D Bonanni, B Bernard, L Dolcetti, R Papi, L Ottini, L Radice, P Greene, MH Loud, JT Andrulis, IL Ozcelik, H Mulligan, AM Glendon, G Thomassen, M Gerdes, AM Jensen, UB Skytte, AB Kruse, TA Chenevix-Trench, G Couch, FJ Simard, J Easton, DF AF Antoniou, Antonis C. Kuchenbaecker, Karoline B. Soucy, Penny Beesley, Jonathan Chen, Xiaoqing McGuffog, Lesley Lee, Andrew Barrowdale, Daniel Healey, Sue Sinilnikova, Olga M. Caligo, Maria A. Loman, Niklas Harbst, Katja Lindblom, Annika Arver, Brita Rosenquist, Richard Karlsson, Per Nathanson, Kate Domchek, Susan Rebbeck, Tim Jakubowska, Anna Lubinski, Jan Jaworska, Katarzyna Durda, Katarzyna Zlowowcka-Perlowska, Elzbieta Osorio, Ana Duran, Mercedes Andres, Raquel Benitez, Javier Hamann, Ute Hogervorst, Frans B. van Os, Theo A. Verhoef, Senno Meijers-Heijboer, Hanne E. J. Wijnen, Juul Garcia, Encarna B. Gomez Ligtenberg, Marjolijn J. Kriege, Mieke Collee, Margriet Ausems, Margreet G. E. M. Oosterwijk, Jan C. Peock, Susan Frost, Debra Ellis, Steve D. Platte, Radka Fineberg, Elena Evans, D. Gareth Lalloo, Fiona Jacobs, Chris Eeles, Ros Adlard, Julian Davidson, Rosemarie Cole, Trevor Cook, Jackie Paterson, Joan Douglas, Fiona Brewer, Carole Hodgson, Shirley Morrison, Patrick J. Walker, Lisa Rogers, Mark T. Donaldson, Alan Dorkins, Huw Godwin, Andrew K. Bove, Betsy Stoppa-Lyonnet, Dominique Houdayer, Claude Buecher, Bruno de Pauw, Antoine Mazoyer, Sylvie Calender, Alain Leone, Melanie Bressac-de Paillerets, Brigitte Caron, Olivier Sobol, Hagay Frenay, Marc Prieur, Fabienne Ferrer, Sandra Fert Mortemousque, Isabelle Buys, Saundra Daly, Mary Miron, Alexander Terry, Mary Beth Hopper, John L. John, Esther M. Southey, Melissa Goldgar, David Singer, Christian F. Fink-Retter, Anneliese Tea, Muy-Kheng Kaulich, Daphne Geschwantler Hansen, Thomas V. O. Nielsen, Finn C. Barkardottir, Rosa B. Gaudet, Mia Kirchhoff, Tomas Joseph, Vijai Dutra-Clarke, Ana Offit, Kenneth Piedmonte, Marion Kirk, Judy Cohn, David Hurteau, Jean Byron, John Fiorica, James Toland, Amanda E. Montagna, Marco Oliani, Cristina Imyanitov, Evgeny Isaacs, Claudine Tihomirova, Laima Blanco, Ignacio Lazaro, Conxi Teule, Alex Del Valle, J. Gayther, Simon A. Odunsi, Kunle Gross, Jenny Karlan, Beth Y. Olah, Edith Teo, Soo-Hwang Ganz, Patricia A. Beattie, Mary S. Dorfling, Cecelia M. van Rensburg, Elizabeth Jansen Diez, Orland Kwong, Ava Schmutzler, Rita K. Wappenschmidt, Barbara Engel, Christoph Meindl, Alfons Ditsch, Nina Arnold, Norbert Heidemann, Simone Niederacher, Dieter Preisler-Adams, Sabine Gadzicki, Dorothea Varon-Mateeva, Raymonda Deissler, Helmut Gehrig, Andrea Sutter, Christian Kast, Karin Fiebig, Britta Schaefer, Dieter Caldes, Trinidad de la Hoya, Miguel Nevanlinna, Heli Muranen, Taru A. Lesperance, Bernard Spurdle, Amanda B. Neuhausen, Susan L. Ding, Yuan C. Wang, Xianshu Fredericksen, Zachary Pankratz, Vernon S. Lindor, Noralane M. Peterlongo, Paolo Manoukian, Siranoush Peissel, Bernard Zaffaroni, Daniela Bonanni, Bernardo Bernard, Loris Dolcetti, Riccardo Papi, Laura Ottini, Laura Radice, Paolo Greene, Mark H. Loud, Jennifer T. Andrulis, Irene L. Ozcelik, Hilmi Mulligan, Anna Marie Glendon, Gord Thomassen, Mads Gerdes, Anne-Marie Jensen, Uffe B. Skytte, Anne-Bine Kruse, Torben A. Chenevix-Trench, Georgia Couch, Fergus J. Simard, Jacques Easton, Douglas F. CA CIMBA Study Collaborator SWE-BRCA Study Collaborator HEBON Study Collaborator EMBRACE Study Collaborator GEMO Study Collaborator KConFab Investigators TI Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers SO BREAST CANCER RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; HORMONE-RELATED PROTEIN; OVARIAN-CANCER; SUSCEPTIBILITY LOCI; MAMMOGRAPHIC DENSITY; GENETIC MODIFIERS; TUMOR SUBTYPES; ALLELES; CONSORTIUM; INVESTIGATORS AB Introduction: Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2). Methods: To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework. Results: Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 x 10(-4)). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 x 10(-5), P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df P = 0.007; rs1292011 2df P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 x 10(-5)) and there was marginal evidence of association with ER- negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049). Conclusions: The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers. C1 [Antoniou, Antonis C.; Kuchenbaecker, Karoline B.; McGuffog, Lesley; Lee, Andrew; Barrowdale, Daniel; Peock, Susan; Frost, Debra; Ellis, Steve D.; Platte, Radka; Fineberg, Elena; Easton, Douglas F.; EMBRACE Study Collaborator] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England. [Soucy, Penny] Ctr Hosp Univ Quebec, Canc Genom Lab, Quebec City, PQ, Canada. [Beesley, Jonathan; Chen, Xiaoqing; Healey, Sue; Spurdle, Amanda B.; Chenevix-Trench, Georgia] Queensland Inst Med Res, Genet & Populat Hlth Div, Brisbane, Qld 4006, Australia. [Sinilnikova, Olga M.] Ctr Hosp Univ Lyon, Ctr Leon Berard, Unite Mixte Genet Constitut Canc Frequents, F-69373 Lyon, France. [Sinilnikova, Olga M.] Univ Lyon 1, INSERM, U1052, Canc Res Ctr Lyon,CNRS,UMR5286, F-69373 Lyon, France. [Caligo, Maria A.] Univ Pisa, Dept Lab Med, Sect Genet Oncol, I-56125 Pisa, Italy. [Caligo, Maria A.] Univ Hosp Pisa, I-56125 Pisa, Italy. [Loman, Niklas; Harbst, Katja; CIMBA Study Collaborator; SWE-BRCA Study Collaborator] Univ Lund Hosp, Dept Oncol, S-22185 Lund, Sweden. [Lindblom, Annika] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden. [Arver, Brita] Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden. [Rosenquist, Richard] Uppsala Univ, Dept Genet & Pathol, Rudbeck Lab, Uppsala, Sweden. [Karlsson, Per] Sahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden. [Nathanson, Kate; Domchek, Susan; Rebbeck, Tim] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Zlowowcka-Perlowska, Elzbieta] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland. [Durda, Katarzyna] Warsaw Med Univ, Postgrad Sch Mol Med, Warsaw, Poland. [Osorio, Ana] Spanish Natl Canc Res Ctr, Human Canc Genet Programme, Human Genet Grp, Madrid, Spain. [Duran, Mercedes] Univ Valladolid IBGM UVA, Inst Biol & Mol Genet, Valladolid, Spain. [Andres, Raquel] Hosp Clin Univ Lozano Blesa, Oncol Unit, Zaragoza, Spain. [Benitez, Javier] Spanish Natl Canc Res Ctr, Genotyping Unit, Human Canc Genet Programme, Madrid, Spain. [Hamann, Ute] Deutsch Krebsforschungszentrum DKFZ, Heidelberg, Germany. [Hogervorst, Frans B.] Netherlands Canc Inst, Family Canc Clin, Amsterdam, Netherlands. [van Os, Theo A.] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands. [Verhoef, Senno] Netherlands Canc Inst, Dept Clin Genet, Amsterdam, Netherlands. [Meijers-Heijboer, Hanne E. J.] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Amsterdam, Netherlands. [Wijnen, Juul; Garcia, Encarna B. Gomez] MUMC, Sch Oncol & Dev Biol, GROM, Maastricht, Netherlands. [Wijnen, Juul; Garcia, Encarna B. Gomez] MUMC, Sch Oncol & Dev Biol, Dept Clin Genet, Maastricht, Netherlands. [Ligtenberg, Marjolijn J.] Radboud Univ Nijmegen, Dept Human Genet, Med Ctr, NL-6525 ED Nijmegen, Netherlands. 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[Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany. [Meindl, Alfons] Tech Univ Munich, Klinikum Rechts Isar, Div Tumor Genet, Dept Obstet & Gynaecol, D-8000 Munich, Germany. [Ditsch, Nina] Univ Munich, Dept Obstet & Gynaecol, D-80539 Munich, Germany. [Arnold, Norbert] Univ Kiel, Univ Hosp Schleswig Holstein, Dept Obstet & Gynaecol, D-24098 Kiel, Germany. [Heidemann, Simone] Univ Kiel, Univ Hosp Schleswig Holstein, Inst Human Genet, D-24098 Kiel, Germany. [Niederacher, Dieter] Univ Dusseldorf, Univ Hosp Dusseldorf, Dept Obstet & Gynaecol, Dusseldorf, Germany. [Preisler-Adams, Sabine] Univ Munster, Inst Human Genet, D-4400 Munster, Germany. [Gadzicki, Dorothea] Hannover Med Sch, Inst Cell & Mol Pathol, D-3000 Hannover, Germany. [Varon-Mateeva, Raymonda] Charite, Inst Human Genet, Campus Virchov Klinikum, Berlin, Germany. [Deissler, Helmut] Univ Hosp Ulm, Dept Obstet & Gynaecol, Ulm, Germany. [Gehrig, Andrea] Univ Wurzburg, Dept Med Genet, Inst Human Genet, Ctr Familial Breast & Ovarian Canc, D-97070 Wurzburg, Germany. [Sutter, Christian] Univ Heidelberg Hosp, Dept Med Genet, Inst Human Genet, Heidelberg, Germany. [Kast, Karin] Tech Univ Dresden, Dept Obstet & Gynaecol, Univ Hosp Carl Gustav Carus, Dresden, Germany. [Fiebig, Britta] Univ Regensburg, Inst Human Genet, D-8400 Regensburg, Germany. [Schaefer, Dieter] Univ Hosp Frankfurt, Inst Human Genet, Frankfurt, Germany. [Schaefer, Dieter; Caldes, Trinidad; de la Hoya, Miguel] Hosp Clin San Carlos, Mol Oncol Lab, Madrid, Spain. [Nevanlinna, Heli; Muranen, Taru A.] Univ Helsinki, Dept Obstet & Gynecol, Helsinki 00029, Finland. [Nevanlinna, Heli; Muranen, Taru A.] Helsinki Univ Cent Hosp, Biomedicum Helsinki, Helsinki 00029, Finland. [Lesperance, Bernard] Univ Montreal, Fac Med Med & Med Specialties, Montreal, PQ, Canada. [Lesperance, Bernard] Hop Sacre Coeur, Hematooncol Serv, Montreal, PQ H4J 1C5, Canada. [KConFab Investigators] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Neuhausen, Susan L.; Ding, Yuan C.] Beckman Res Inst City Hope, Dept Populat Sci, Duarte, CA USA. [Wang, Xianshu] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Fredericksen, Zachary; Pankratz, Vernon S.] Mayo Clin, Dept Med Genet, Rochester, MN USA. [Lindor, Noralane M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Peterlongo, Paolo; Radice, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predicted Med, Unit Mol Bases Genet Risk & Genet Testing, Milan, Italy. [Peterlongo, Paolo; Radice, Paolo] Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy. [Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela] Fdn Ist Nazl Tumori INT, Dept Prevent & Predict Med, Unit Med Genet, Milan, Italy. [Bonanni, Bernardo] Ist Europeo Oncol IEO, Div Canc Prevent & Genet, Milan, Italy. [Bernard, Loris] Ist Europeo Oncol, Dept Expt Oncol, Milan, Italy. [Bernard, Loris] Consortium Genom Technol Cogentech, Milan, Italy. [Dolcetti, Riccardo] IRCCS, Ctr Riferimento Oncol, Canc Bioimmunotherapy Unit, Aviano, PN, Italy. [Papi, Laura] Univ Florence, Dept Clin Physiopathol, Med Genet Unit, Florence, Italy. [Ottini, Laura] Univ Roma La Sapienza, Dept Mol Med, Rome, Italy. [Greene, Mark H.; Loud, Jennifer T.] NCI, Clin Genet Branch, DCEG, Rockville, MD 20852 USA. [Andrulis, Irene L.; Ozcelik, Hilmi] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Andrulis, Irene L.] Univ Toronto, Canc Care Ontario, Dept Mol Genet, Toronto, ON M5S 1A1, Canada. [Andrulis, Irene L.] Univ Toronto, Canc Care Ontario, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A1, Canada. [Mulligan, Anna Marie] St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, Toronto, ON M5B 1W8, Canada. [Mulligan, Anna Marie] St Michaels Hosp, Dept Lab Med, Toronto, ON M5B 1W8, Canada. [Glendon, Gord] Ontario Canc Genet Network, Toronto, ON, Canada. [Thomassen, Mads; Kruse, Torben A.] Odense Univ Hosp, Dept Clin Genet, Odense, Denmark. [Gerdes, Anne-Marie] Rigshosp, Dept Clin Genet, Copenhagen, Denmark. [Gerdes, Anne-Marie] Univ Copenhagen, DK-1168 Copenhagen, Denmark. [Jensen, Uffe B.] Skejby Hosp, Dept Clin Genet, Aarhus, Denmark. [Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Simard, Jacques] Ctr Hosp Univ Quebec, Canc Genom Lab, Quebec City, PQ, Canada. [Simard, Jacques] Univ Laval, Fac Med, Canada Res Chair Oncogenet, Dept Mol Med, Quebec City, PQ G1K 7P4, Canada. RP Antoniou, AC (reprint author), Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England. EM antonis@srl.cam.ac.uk RI del Valle, Jesus/I-2527-2015; Jakubowska, Anna/O-8050-2014; Dolcetti, Riccardo/O-3832-2015; Ligtenberg, Marjolijn/N-9666-2013; Peissel, Bernard/E-8187-2017; Teo, Soo-hwang/H-2353-2014; Arnold, Norbert/E-3012-2010; Osorio, Ana/I-4324-2014; Bernard, Loris/K-5953-2014; montagna, marco/E-2225-2012; Andrulis, Irene/E-7267-2013; Toland, Amanda/E-4202-2011; Joseph, Vijai/J-9158-2013; Radice, Paolo/O-3119-2013; Jansen van Rensburg, Elizabeth (Lizette)/B-9104-2011; Blanco, Ignacio/D-2565-2013; Ditsch, Nina/F-6267-2014; Oosterwijk, Jan C./G-5770-2011 OI del Valle, Jesus/0000-0003-3607-7045; Muranen, Taru/0000-0002-5895-1808; Nevanlinna, Heli/0000-0002-0916-2976; Kirchhoff, Tomas/0000-0002-9055-2364; Jacobs, Chris/0000-0002-9557-9080; Evans, Gareth/0000-0002-8482-5784; Dolcetti, Riccardo/0000-0003-1625-9853; Ligtenberg, Marjolijn/0000-0003-1290-1474; Peissel, Bernard/0000-0001-9233-3571; Eeles, Rosalind/0000-0002-3698-6241; Nathanson, Katherine/0000-0002-6740-0901; Barrowdale, Daniel/0000-0003-1661-3939; Arnold, Norbert/0000-0003-4523-8808; Osorio, Ana/0000-0001-8124-3984; montagna, marco/0000-0002-4929-2150; Joseph, Vijai/0000-0002-7933-151X; Blanco, Ignacio/0000-0002-7414-7481; FU Cancer Research UK [C12292/A11174, C1287/A10118, C1287/A11990, C5047/A8385]; European Community's Seventh Framework Programme [223175, HEALTH-F2-2009-223175]; Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program; Canadian Breast Cancer Research Alliance [019511]; NIH grant [CA128978]; NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]; U.S. Department of Defence Ovarian Cancer Idea award [W81XWH-10-1-0341]; Breast Cancer Research Foundation; Komen Foundation; European Social Fund [2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016]; Cancer Association of South Africa; National Cancer Institute, National Institutes of Health [RFA-CA-06-503]; Breast Cancer Family Registry (BCFR) and Principal Investigators; Cancer Care Ontario [U01 CA69467]; Columbia University [U01 CA69398]; Fox Chase Cancer Center [U01 CA69631]; Huntsman Cancer Institute [U01 CA69446]; Cancer Prevention Institute of California (formerly the Northern California Cancer Center) [U01 CA69417]; University of Melbourne [U01 CA69638]; Research Triangle Institute Informatics Support Center [N02PC45022-46]; Mutua Madrile a Foundation; Red de Investigacion en Cancer [RD06/0020/1160]; Spanish Ministry of Science and Innovation [FIS PI08 1120, SAF201020493]; NEYE foundation; DKFZ; NIHR grant; Familial Cancer Registry; Tissue Culture Shared Registry at Georgetown University (NIH/NCI) [P30-CA051008]; Cancer Genetics Network [HHSN261200744000C]; Swing Fore the Cure; National Cancer Institute; GOG Tissue Bank [CA 27469]; GOG Statistical and Data Center [CA 37517, CA 101165]; GOG's Cancer Prevention and Control Committee; intramural (Clinical Genetics Branch, DCEG) NCI program; extramural (Community Oncology and Prevention Trials Program - COPTRG) NCI program; Instituto de Salud Carlos III [RD06/0020/0021]; Dutch Cancer Society [NKI1998-1854, NKI2004-3088, NKI2007-3756]; ZonMW [91109024]; Helsinki University Central Hospital Research Fund; Academy of Finland [132473]; Finnish Cancer Society; Sigrid Juselius Foundation; Asociacion Espanola Contra el Cancer; Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute; Autonomous Government of Catalonia; Icelandic Association "Walking for Breast Cancer Research"; Landspitali University Hospital Research Fund; Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR); "Ministero della Salute" ("Progetto Tumouri Femminili) [RFPS 2006-5-341353, ACC2/R6.9]; NHMRC; National Breast Cancer Foundation; Cancer Australia [628333]; National Health and Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer Councils of New South Wales, Victoria; Cancer Councils of New South Wales, Tasmania; Cancer Councils of New South Wales, South Australia; Cancer Foundation of Western Australia; NHMRC Senior Research Fellowship; Intramural Research Program of the US National Cancer Institute at the National Institutes of Health; Westat, Inc, Rockville, MD [NO2-CP-11019-50, N02-CP-65504]; Russian Federation for Basic Research [10-04-92601, 10-04-92110, 11-04-00227]; Federal Agency for Science and Innovations [16.512.11.2237]; Royal Society International Joint grant [JP090615]; Ellen Li Charitable Foundation; Norwegian EEA Financial Mechanism [HU0115/NA/2008-3/P-9]; Hungarian Research Grant KTIA-OTKA [CK-80745]; Ohio State University Comprehensive Cancer Center; Cancer Care Ontario; "CIHR Team in Familial Risks of Breast Cancer" program; US National Cancer Institute; National Institutes of Health under RFA [CA-06-503]; Breast Cancer Family Registry (BCFR); Principal Investigators; National Institutes of Health [R01 CA74415]; Morris and Horowitz Families Endowment; CRUK; Eileen Stein Jacoby Fund while at FCCC; University of Kansas Cancer Center; Kansas Bioscience Authority Eminent Scholar Program; American Cancer Society Clinical Research Professorship [SIOP-06-258-COUN]; [SCIIIRETIC RD06/0020/1051]; [PI10/01422]; [PI10/31488]; [2009SGR290]; [U01CA69631]; [5U01CA113916] FX This work was supported by Cancer Research UK grants C12292/A11174 and C1287/A10118. The research leading to these results has received funding from the European Community's Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175), from the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program and by the Canadian Breast Cancer Research Alliance-grant #019511. This research was also supported by NIH grant CA128978, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a U.S. Department of Defence Ovarian Cancer Idea award (W81XWH-10-1-0341) and grants from the Breast Cancer Research Foundation and the Komen Foundation for the Cure. ACA is a CR-UK Senior Cancer Research Fellow, DFE is CR-UK Principal Research Fellow, GCT is a NHMRC Senior Principal Research Fellow, J.S. is Chairholder of the Canada Research Chair in Oncogenetics.; Research and Study Centre and Ramunas Janavicius (Vilnius University Hospital Santariskiu Clinics, Lithuania) for data and DNA samples for BFBOCC. The work was supported in part by a grant from the European Social Fund Nr. 2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016.; BMBSA was supported by grants from the Cancer Association of South Africa (CANSA) to Elizabeth J. van Rensburg.; This work was supported by the National Cancer Institute, National Institutes of Health under RFA-CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Columbia University (U01 CA69398), Fox Chase Cancer Center (U01 CA69631), Huntsman Cancer Institute (U01 CA69446), Cancer Prevention Institute of California (formerly the Northern California Cancer Center) (U01 CA69417), University of Melbourne (U01 CA69638), and Research Triangle Institute Informatics Support Center (RFP No. N02PC45022-46). Samples from the FCCC, HCI and CPIC were processed and distributed by the Coriell Institute for Medical Research. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the BCFR, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government or the BCFR.; The research leading to these results has been partially funded by Mutua Madrile a Foundation, "Red de Investigacion en Cancer RD06/0020/1160" and Spanish Ministry of Science and Innovation (FIS PI08 1120 and SAF201020493).; We would like to thank Bent Ejlertsen for clinical data and acknowledge the NEYE foundation for financial support.; The DKFZ study was supported by the DKFZ.; Epidemiological study of BRCA1 & BRCA2 mutation carriers (EMBRACE) Douglas F. Easton is the PI of the study. EMBRACE Collaborating Centres are: Coordinating Centre, Cambridge: Susan Peock, Debra Frost, Steve D. Ellis, Elena Fineberg, Radka Platte, Clare Oliver. North of Scotland Regional Genetics Service, Aberdeen: Zosia Miedzybrodzka, Helen Gregory. Northern Ireland Regional Genetics Service, Belfast: Patrick Morrison, Lisa Jeffers. West Midlands Regional Clinical Genetics Service, Birmingham: Trevor Cole, Kai-ren Ong, Jonathan Hoffman. South West Regional Genetics Service, Bristol: Alan Donaldson, Margaret James. East Anglian Regional Genetics Service, Cambridge: Joan Paterson, Sarah Downing, Amy Taylor. Medical Genetics Services for Wales, Cardiff: Alexandra Murray, Mark T. Rogers, Emma McCann. St James's Hospital, Dublin and National Centre for Medical Genetics, Dublin: M. John Kennedy, David Barton. South East of Scotland Regional Genetics Service, Edinburgh: Mary Porteous, Sarah Drummond. Peninsula Clinical Genetics Service, Exeter: Carole Brewer, Emma Kivuva, Anne Searle, Selina Goodman, Kathryn Hill. West of Scotland Regional Genetics Service, Glasgow: Rosemarie Davidson, Victoria Murday, Nicola Bradshaw, Lesley Snadden, Mark Longmuir, Catherine Watt, Sarah Gibson, Eshika Haque, Ed Tobias, Alexis Duncan. South East Thames Regional Genetics Service, Guy's Hospital London: Louise Izatt, Chris Jacobs, Caroline Langman. North West Thames Regional Genetics Service, Harrow: Huw Dorkins. Leicestershire Clinical Genetics Service, Leicester: Julian Barwell. Yorkshire Regional Genetics Service, Leeds: Julian Adlard, Gemma Serra-Feliu. Cheshire & Merseyside Clinical Genetics Service, Liverpool: Ian Ellis, Catherine Houghton. Manchester Regional Genetics Service, Manchester: D Gareth Evans, Fiona Lalloo, Jane Taylor. North East Thames Regional Genetics Service, NE Thames, London: Lucy Side, Alison Male, Cheryl Berlin. Nottingham Centre for Medical Genetics, Nottingham: Jacqueline Eason, Rebecca Collier. Northern Clinical Genetics Service, Newcastle: Fiona Douglas, Oonagh Claber, Irene Jobson. Oxford Regional Genetics Service, Oxford: Lisa Walker, Diane McLeod, Dorothy Halliday, Sarah Durell, Barbara Stayner. The Institute of Cancer Research and Royal Marsden NHS Foundation Trust: Ros Eeles, Susan Shanley, Nazneen Rahman, Richard Houlston, Elizabeth Bancroft, Elizabeth Page, Audrey Ardern- Jones, Kelly Kohut, Jennifer Wiggins, Elena Castro, Anita Mitra, Lisa Robertson. North Trent Clinical Genetics Service, Sheffield: Jackie Cook, Oliver Quarrell, Cathryn Bardsley. South West Thames Regional Genetics Service, London: Shirley Hodgson, Sheila Goff, Glen Brice, Lizzie Winchester, Charlotte Eddy, Vishakha Tripathi, Virginia Attard. Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton: Diana Eccles, Anneke Lucassen, Gillian Crawford, Donna McBride, Sarah Smalley. EMBRACE is supported by Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles is supported by Cancer Research UK Grant C5047/A8385.; CI received support from the Familial Cancer Registry and the Tissue Culture Shared Registry at Georgetown University (NIH/NCI grant P30-CA051008), the Cancer Genetics Network (HHSN261200744000C), and Swing Fore the Cure.; This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office and the GOG Tissue Bank (CA 27469), and to the GOG Statistical and Data Center (CA 37517 and CA 101165). We thank the investigators of the Australia New Zealand Gynaecological Oncology Group (ANZGOG). GOG's participation was sponsored by GOG's Cancer Prevention and Control Committee, and supported through funding provided by both intramural (Clinical Genetics Branch, DCEG) and extramural (Community Oncology and Prevention Trials Program - COPTRG) NCI programs.; The HCSC study was partially supported by Instituto de Salud Carlos III; RD06/0020/0021. We wish to thank Dr. Pedro Perez-Segura and Dr. Atocha Romero for their contribution to this study.; HEBON Collaborating Centres: Coordinating center: Netherlands Cancer Institute, Amsterdam, NL: F.B.L. Hogervorst, S. Verhoef, M. Verheus, L.J. van `t Veer, F.E. van Leeuwen, M.A. Rookus; Erasmus Medical Center, Rotterdam, NL: M. Collee, A.M.W. van den Ouweland, A. Jager, M.J. Hooning, M.M.A. TilanusLinthorst, C. Seynaeve; Leiden University Medical Center, NL, Leiden: C.J. van Asperen, J.T. Wijnen, M.P. Vreeswijk, R.A. Tollenaar, P. Devilee; Radboud University Nijmegen Medical Center, Nijmegen, NL: M.J. Ligtenberg, N. Hoogerbrugge; University Medical Center Utrecht, Utrecht, NL: M.G. Ausems, R.B. van der Luijt; Amsterdam Medical Center, NL: C.M. Aalfs, T.A. van Os; VU University Medical Center, Amsterdam, NL: J.J.P. Gille, Q. Waisfisz, H.E.J. Meijers-Heijboer; University Hospital Maastricht, Maastricht, NL: E.B. GomezGarcia, C.E. van Roozendaal, Marinus J. Blok, B. Caanen; University Medical Center Groningen University, NL: J.C. Oosterwijk, A.H. van der Hout, M.J. Mourits; The Netherlands Foundation for the detection of hereditary tumours, Leiden, NL: H.F. Vasen. The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756 and the ZonMW grant 91109024.; HEBCS acknowledge Drs. Kristiina Aittomaki, Kirsimari Aaltonen and Carl Blomqvist and Tuomas Heikkinen and research nurse Irja Erkkil for their help with the patient data and samples. The HEBCS study has been financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society, and the Sigrid Juselius Foundation.; Contract grant sponsor: Asociacion Espanola Contra el Cancer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia. Contract grant numbers: ISCIIIRETIC RD06/0020/1051, PI10/01422, PI10/31488 and 2009SGR290.; The ILUH group was supported by the Icelandic Association "Walking for Breast Cancer Research" and by the Landspitali University Hospital Research Fund.; This study was supported by Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR) and "Ministero della Salute" ("Progetto Tumouri Femminili and grant numbers RFPS 2006-5-341353, ACC2/R6.9"); We wish to thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (funded 2001-2009 by NHMRC and currently by the National Breast Cancer Foundation and Cancer Australia #628333) for their contributions to this resource, and the many families who contribute to kConFab. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. ABS is funded by an NHMRC Senior Research Fellowship.; The research of Drs. Greene and Loud was supported by the Intramural Research Program of the US National Cancer Institute at the National Institutes of Health, and by support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc, Rockville, MD.; This work has been supported by the Russian Federation for Basic Research (grants 10-04-92601, 10-04-92110, 11-04-00227) the Federal Agency for Science and Innovations (contract 16.512.11.2237) and through a Royal Society International Joint grant (JP090615).; The Hong Kong Hereditary Breast Cancer Family Registry thank Dr. Ellen Li Charitable Foundation for their support; The study was supported by Norwegian EEA Financial Mechanism (HU0115/NA/2008-3/P-9) and by Hungarian Research Grant KTIA-OTKA (CK-80745).; Leigha Senter and Kevin Sweet were instrumental in accrual of study participants, ascertainment of medical records and database management. We thank the Human Genetics Sample Bank for preparation of samples. This study was supported by the Ohio State University Comprehensive Cancer Center.; This work was supported by Cancer Care Ontario, the "CIHR Team in Familial Risks of Breast Cancer" program, and the US National Cancer Institute, National Institutes of Health under RFA #CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the BCFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. We wish to thank Teresa Selander, Nayana Weerasooriya and members of the Ontario Cancer Genetics Network for their contributions to the study.; The study was supported by the National Institutes of Health (R01 CA74415 to SLN)) and the Morris and Horowitz Families Endowment.; UKFOCR was supported by a project grant from CRUK to Paul Pharoah. We thank Paul Pharoah, Susan Ramus, Carole Pye, Patricia Harrington and Eva Wozniak for their contributions towards the UKFOCR. We would like to acknowledge the Roswell Park Alliance Foundation for their continued support of the Gilda Radner Ovarian Family Cancer Registry. GRFOCR would like to acknowledge Kirsten Moysich and Lara Sucheston (Department of Cancer Prevention and Control).; We thank Ms. JoEllen Weaver for her help collecting patient data and samples. AKG was funded by U01CA69631, 5U01CA113916, and the Eileen Stein Jacoby Fund while at FCCC. The author acknowledges support from The University of Kansas Cancer Center and the Kansas Bioscience Authority Eminent Scholar Program. AKG is the Chancellors Distinguished Chair in Biomedical Sciences endowed Professor.; This research was supported by the Breast Cancer Research Foundation (to KLN) and the Komen Foundation for the Cure (to SMD).; This work is supported by funding from the American Cancer Society Clinical Research Professorship (SIOP-06-258-COUN). NR 39 TC 38 Z9 38 U1 4 U2 22 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2012 VL 14 IS 1 AR R33 DI 10.1186/bcr3121 PG 18 WC Oncology SC Oncology GA 987UU UT WOS:000307444100042 PM 22348646 ER PT J AU Garay, JP Karakas, B Abukhdeir, AM Cosgrove, DP Gustin, JP Higgins, MJ Konishi, H Konishi, Y Lauring, J Mohseni, M Wang, GM Jelovac, D Weeraratna, A Baust, CAS Morin, PJ Toubaji, A Meeker, A De Marzo, AM Lewis, G Subhawong, A Argani, P Park, BH AF Garay, Joseph P. Karakas, Bedri Abukhdeir, Abde M. Cosgrove, David P. Gustin, John P. Higgins, Michaela J. Konishi, Hiroyuki Konishi, Yuko Lauring, Josh Mohseni, Morassa Wang, Grace M. Jelovac, Danijela Weeraratna, Ashani Baust, Cheryl A. Sherman Morin, Patrice J. Toubaji, Antoun Meeker, Alan De Marzo, Angelo M. Lewis, Gloria Subhawong, Andrea Argani, Pedram Park, Ben H. TI The growth response to androgen receptor signaling in ER alpha-negative human breast cells is dependent on p21 and mediated by MAPK activation SO BREAST CANCER RESEARCH LA English DT Article ID CANCER-CELLS; EPITHELIAL-CELLS; PROSTATE-CANCER; MEDROXYPROGESTERONE ACETATE; GENE-EXPRESSION; PROTEIN-KINASE; G(1) ARREST; ESTROGEN; LINES; OVEREXPRESSION AB Introduction: Although a high frequency of androgen receptor (AR) expression in human breast cancers has been described, exploiting this knowledge for therapy has been challenging. This is in part because androgens can either inhibit or stimulate cell proliferation in pre-clinical models of breast cancer. In addition, many breast cancers co-express other steroid hormone receptors that can affect AR signaling, further obfuscating the effects of androgens on breast cancer cells. Methods: To create better-defined models of AR signaling in human breast epithelial cells, we took estrogen receptor (ER)-alpha-negative and progesterone receptor (PR)-negative human breast epithelial cell lines, both cancerous and non cancerous, and engineered them to express AR, thus allowing the unambiguous study of AR signaling. We cloned a full-length cDNA of human AR, and expressed this transgene in MCF-10A non-tumorigenic human breast epithelial cells and MDA-MB-231 human breast-cancer cells. We characterized the responses to AR ligand binding using various assays, and used isogenic MCF-10A p21 knock-out cell lines expressing AR to demonstrate the requirement for p21 in mediating the proliferative responses to AR signaling in human breast epithelial cells. Results: We found that hyperactivation of the mitogen-activated protein kinase (MAPK) pathway from both AR and epidermal growth factor receptor (EGFR) signaling resulted in a growth-inhibitory response, whereas MAPK signaling from either AR or EGFR activation resulted in cellular proliferation. Additionally, p21 gene knock-out studies confirmed that AR signaling/activation of the MAPK pathway is dependent on p21. Conclusions: These studies present a new model for the analysis of AR signaling in human breast epithelial cells lacking ER alpha/PR expression, providing an experimental system without the potential confounding effects of ER alpha/PR crosstalk. Using this system, we provide a mechanistic explanation for previous observations ascribing a dual role for AR signaling in human breast cancer cells. As previous reports have shown that approximately 40% of breast cancers can lack p21 expression, our data also identify potential new caveats for exploiting AR as a target for breast cancer therapy. C1 [Garay, Joseph P.; Karakas, Bedri; Abukhdeir, Abde M.; Cosgrove, David P.; Gustin, John P.; Higgins, Michaela J.; Konishi, Hiroyuki; Konishi, Yuko; Lauring, Josh; Mohseni, Morassa; Wang, Grace M.; Jelovac, Danijela; Toubaji, Antoun; Meeker, Alan; De Marzo, Angelo M.; Lewis, Gloria; Subhawong, Andrea; Argani, Pedram; Park, Ben H.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21218 USA. [Gustin, John P.; Park, Ben H.] Johns Hopkins Univ, Whiting Sch Engn, Dept Chem & Biomol Engn, Baltimore, MD USA. [Weeraratna, Ashani; Baust, Cheryl A. Sherman; Morin, Patrice J.] NIA, Lab Mol Biol & Immunol, Baltimore, MD 21224 USA. RP Park, BH (reprint author), Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21218 USA. EM bpark2@jhmi.edu RI KONISHI, Yuko/B-2599-2016 FU ASCO Foundation Young Investigator Award; DOD Breast Cancer Research Program [BC087658, W81XWH-06-1-0325, BC083057]; Susan G Komen for the Cure [PDF0707944, KG090199, BCTR0707684]; Flight Attendant Medical Research Institute (FAMRI); V Foundation; Maryland Cigarette Restitution Fund; Avon Foundation; NIH [CA088843]; Research Supplement to Promote Diversity in Health-Related Research [CA109274, GM007309, CA009071, CA09071]; Intramural Research Program of the NIH, National Institute on Aging; GlaxoSmithKline (GSK); GSK FX Grant support was provided by an ASCO Foundation Young Investigator Award (MJH, DPC); the DOD Breast Cancer Research Program BC087658 (MJH), W81XWH-06-1-0325 (JP Gustin), BC083057 (MM); Susan G Komen for the Cure PDF0707944 (AMA, MJH), KG090199 (JL), BCTR0707684 (BHP); the Flight Attendant Medical Research Institute (FAMRI) (JL, HK); the V Foundation (JL); the Maryland Cigarette Restitution Fund (JL); the Avon Foundation (JL, BHP); NIH CA088843 (JL, BHP); CA109274 (JP Garay is a recipient of a Research Supplement to Promote Diversity in Health-Related Research, BHP), GM007309 (GMW), CA009071 (DPC), and CA09071 (DJ). This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. None of these funding agencies had any role in study design, in the collection, analysis, and interpretation of data, in the writing of the manuscript, or in the decision to submit the manuscript for publication.; B.H.P. has received previous research funding from GlaxoSmithKline (GSK) although none of the studies reported here were supported by GSK. B.H.P. is a consultant for GSK and is on the scientific advisory board for Horizon Discovery, LTD and is entitled to payments for these services. These arrangements are managed according to the Johns Hopkins University conflict of interest policy. All of the other authors declare that they have no competing interests. NR 63 TC 25 Z9 26 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2012 VL 14 IS 1 AR R27 DI 10.1186/bcr3112 PG 17 WC Oncology SC Oncology GA 987UU UT WOS:000307444100036 PM 22321971 ER PT J AU Moiola, C De Luca, P Cotignola, J Gardner, K Vazquez, E De Siervi, A AF Moiola, Cristian De Luca, Paola Cotignola, Javier Gardner, Kevin Vazquez, Elba De Siervi, Adriana TI Dynamic Coregulatory Complex Containing BRCA1, E2F1 and CtIP Controls ATM Transcription SO CELLULAR PHYSIOLOGY AND BIOCHEMISTRY LA English DT Article DE ATM; BRCA1; Transcription; DNA damage; Prostate cancer ID DNA-DAMAGE RESPONSE; PROSTATE-CANCER CELLS; ATAXIA-TELANGIECTASIA; IN-VIVO; GENETIC INSTABILITY; PROTEIN; IDENTIFICATION; PROGRESSION; REPAIR; RISK AB Chromosomal instability is a key feature in cancer progression. Recently we have reported that BRCA1 regulates the transcription of several genes in prostate cancer, including ATM (ataxia telangiectasia mutated). Although it is well accepted that ATM is a pivotal mediator in genotoxic stress, it is unknown whether ATM transcription is regulated during the molecular response to DNA damage. Here we investigate ATM transcription regulation in human prostate tumor PC3 cell line. We have found that doxorubicin and mitoxantrone repress ATM transcription in PC3 cells but etoposide and methotrexate do not affect ATM expression. We have demonstrated that BRCA1 binds to ATM promoter and after doxorubicin exposure, it is released. BRCA1 overexpression increases ATM transcription and this enhancement is abolished by BRCA1 depletion. Moreover, BRCA1-BRCT domain loss impairs the ability of BRCA1 to regulate ATM promoter activity, strongly suggesting that BRCT domain is essential for ATM regulation by BRCA1. BRCA1-overexpressing PC3 cells exposed to KU55933 ATM kinase inhibitor showed significant decreased ATM promoter activity compared to untreated cells, suggesting that ATM transcriptional regulation by BRCA1 is partially mediated by the ATM kinase activity. In addition, we have demonstrated E2F1 binding to ATM promoter before and after doxorubicin exposure. E2F1 overexpression diminishes ATM transcription after doxorubicin exposure which is impaired by E2F1 dominant negative mutants. Finally, the co-regulator of transcription CtIP increases ATM transcription. Altogether, BRCA1/E2F1/CtIP binding to ATM promoter activates ATM transcription. Doxorubicin exposure releases BRCA1 and CtIP from ATM promoter still keeping E2F1 recruited and, in turn, represses ATM expression. Copyright (c) 2012 S Karger AG, Basel C1 [De Siervi, Adriana] Univ Buenos Aires, Fac Ciencias Exactas & Nat, Dept Quim Biol, Sch Sci FCEN,CONICET, Buenos Aires, DF, Argentina. [Gardner, Kevin] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP De Siervi, A (reprint author), Univ Buenos Aires, Fac Ciencias Exactas & Nat, Dept Quim Biol, Sch Sci FCEN,CONICET, Intendente Guiraldes 2160 Pab 2,2Do Piso,CM1,Ciud, Buenos Aires, DF, Argentina. EM adesiervi@qb.fcen.uba.ar OI Cotignola, Javier/0000-0003-4473-9854 FU Argentinean Agency of Science and Technology (ANPCyT) [PICT 2006-00228, PICT 2006-00367, PICT 2010-431] FX This research has been supported by the Argentinean Agency of Science and Technology (ANPCyT, PICT 2006-00228, PICT 2006-00367 and PICT 2010-431). NR 31 TC 9 Z9 9 U1 0 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-8987 J9 CELL PHYSIOL BIOCHEM JI Cell. Physiol. Biochem. PY 2012 VL 30 IS 3 BP 596 EP 608 DI 10.1159/000341441 PG 13 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 989AW UT WOS:000307533600009 PM 22832221 ER PT J AU Chowell, G Ayala, A Berisha, V Viboud, C Schumacher, M AF Chowell, G. Ayala, A. Berisha, V. Viboud, C. Schumacher, M. TI Risk Factors for Mortality among 2009 A/H1N1 Influenza Hospitalizations in Maricopa County, Arizona, April 2009 to March 2010 SO COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE LA English DT Article ID PANDEMIC H1N1 2009; CRITICALLY-ILL PATIENTS; A H1N1; UNITED-STATES; VIRUS-INFECTION; DEATH; OUTCOMES; A(H1N1); OBESITY; CANADA AB We analyzed individual-level data on pandemic influenza A/H1N1pdm hospitalizations from the enhanced surveillance system of the Maricopa County Department of Public Health, AZ, USA from April 1st, 2009 to March 31st, 2010. We also assessed the the risk of death among A/H1N1 hospitalizations using multivariate logistic regression. Hospitalization rates were significantly higher among Native Americans (risk ratio (RR) = 6.2; 95% CI: 6.15, 6.21), non-Hispanic Black (RR = 3.84; 95% CI: 3.8, 3.9), and Hispanics (RR = 2.0; 95% CI: 2.0, 2.01) compared to non-Hispanic Whites. Throughout the spring, 59.2% of hospitalized patients received antiviral treatment; the proportion of patients treated increased significantly during the fall to 74.4% (Chi-square test, P < 0.0001). In our best-fit logisticmodel, the adjusted risk of death among A/H1N1 inpatients was significantly higher during the fall wave (August 16, 2009 to March 31, 2010, OR = 3.94; 95% CI: 1.72, 9.03) compared to the spring wave (April 1, 2009 to August 15, 2009). Moreover, chronic lung disease (OR = 3.5; 95% CI: 1.7, 7.4), cancer within the last 12 months (OR = 4.3; 95% CI: 1.3, 14.8), immuno-suppression (OR = 4.0; 95% CI: 1.84, 8.9), and admission delays (OR = 4.6; 95% CI: 2.2, 9.5) were significantly associated with an increased the risk of death among A/H1N1 inpatients. C1 [Chowell, G.] Arizona State Univ, Sch Human Evolut & Social Change, Tempe, AZ 85287 USA. [Chowell, G.; Viboud, C.] NIH, Div Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Ayala, A.; Berisha, V.; Schumacher, M.] Maricopa Cty Dept Publ Hlth, Off Epidemiol, Phoenix, AZ 85012 USA. RP Chowell, G (reprint author), Arizona State Univ, Sch Human Evolut & Social Change, Tempe, AZ 85287 USA. EM gchowell@asu.edu RI Chowell, Gerardo/F-5038-2012 OI Chowell, Gerardo/0000-0003-2194-2251 FU International Influenza Unit, Office of Global Health Affairs, Department of Health and Human Services FX The authors would like to thank their partners at the Maricopa County Office of the Medical Examiner, the Arizona Department of Health Services, the Centers for Disease Control and Prevention, infection preventionists at Maricopa County local hospitals, as well as all MCDPH staff who helped with case reporting and case investigation of Novel H1N1-related cases. They thank Liva Nohre for providing statistical analyses input and Amy Prestanski for facilitating 2009 population data for Maricopa County. This research was conducted in the context of the MISMS (Multinational Influenza Seasonal Mortality Study), an ongoing international collaborative effort to understand influenza epidemiological and evolutionary patterns, led by the Fogarty International Center, National Institutes of Health (http://www.origem.info/misms/index.php). The MISMS study is funded by the International Influenza Unit, Office of Global Health Affairs, Department of Health and Human Services. NR 35 TC 4 Z9 4 U1 0 U2 3 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1748-670X J9 COMPUT MATH METHOD M JI Comput. Math. Method Med. PY 2012 AR 914196 DI 10.1155/2012/914196 PG 8 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 991LD UT WOS:000307701600001 ER PT J AU Bach, LH Gandolfi, B Grahn, JC Millon, LV Kent, MS Narfstrom, K Cole, SA Mullikin, JC Grahn, RA Lyons, LA AF Bach, L. H. Gandolfi, B. Grahn, J. C. Millon, L. V. Kent, M. S. Narfstrom, K. Cole, S. A. Mullikin, J. C. Grahn, R. A. Lyons, L. A. TI A High-Resolution 15,000(Rad) Radiation Hybrid Panel for the Domestic Cat SO CYTOGENETIC AND GENOME RESEARCH LA English DT Article DE Felis catus; Genetic mapping; Whole-genome amplification ID GENETIC-LINKAGE MAP; GENOME SEQUENCE; FELIS-CATUS; ZEBRAFISH GENOME; RHESUS MACAQUE; CONSTRUCTION; THROUGHPUT; MUTATION; DISEASE; MICROSATELLITES AB The current genetic and recombination maps of the cat have fewer than 3,000 markers and a resolution limit greater than 1 Mb. To complement the first-generation domestic cat maps, support higher resolution mapping studies, and aid genome assembly in specific areas as well as in the whole genome, a 15,000 Rad radiation hybrid (RH) panel for the domestic cat was generated. Fibroblasts from the female Abyssinian cat that was used to generate the cat genomic sequence were fused to a Chinese hamster cell line (A23), producing 150 hybrid lines. The clones were initially characterized using 39 short tandem repeats (STRs) and 1,536 SNP markers. The utility of whole-genome amplification in preserving and extending RH panel DNA was also tested using 10 STR markers; no significant difference in retention was observed. The resolution of the 15,000 Rad RH panel was established by constructing framework maps across 10 different 1-Mb regions on different feline chromosomes. In these regions, 2-point analysis was used to estimate RH distances, which compared favorably with the estimation of physical distances. The study demonstrates that the 15,000 Rad RH panel constitutes a powerful tool for constructing high-resolution maps, having an average resolution of 40.1 kb per marker across the ten 1-Mb regions. In addition, the RH panel will complement existing genomic resources for the domestic cat, aid in the accurate re-assemblies of the forthcoming cat genomic sequence, and support cross-species genomic comparisons. Copyright (C) 2012 S. Karger AG, Basel C1 [Millon, L. V.; Lyons, L. A.] Univ Calif Davis, Sch Vet Med, Vet Genet Lab, Davis, CA 95616 USA. [Narfstrom, K.] Univ Missouri Columbia, Coll Vet Med, Columbia, MO USA. [Cole, S. A.] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Mullikin, J. C.] NHGRI, Comparat Genom Unit, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Lyons, LA (reprint author), Univ Calif Davis, Sch Vet Med, Vet Genet Lab, 3A Shields Ave, Davis, CA 95616 USA. EM lalyons@ucdavis.edu FU NIH-NCRR [RR016094]; Center for Companion Animal Health at UC Davis; Intramural Research Program of the National Human Genome Research Institute; National Institutes of Health; George and Phyllis Miller Feline Health Fund of the San Francisco Foundation; NCRR, NIH [C06 RR013556] FX Funding for this project was provided by NIH-NCRR RR016094, the Center for Companion Animal Health at UC Davis, the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health, and the George and Phyllis Miller Feline Health Fund of the San Francisco Foundation. This investigation was partially conducted in a facility constructed with support from Research Facilities Improvement Program Grant Number C06 RR013556 from NCRR, NIH. Cat genome sequence for SNP detection was provided by Dr. Wesley Warren of the Genome Institute at Washington University School of Medicine. The authors would like to thank Paul Lathrop and Hasan Alhaddad for technical support and advice. NR 52 TC 4 Z9 4 U1 0 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2012 VL 137 IS 1 BP 7 EP 14 DI 10.1159/000339416 PG 8 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 988NU UT WOS:000307498600002 PM 22777158 ER PT J AU Marcus, PM Lenz, S Sammons, D Black, W Garg, K AF Marcus, Pamela M. Lenz, Suzanne Sammons, Donna Black, William Garg, Kavita TI Recruitment methods employed in the National Lung Screening Trial SO JOURNAL OF MEDICAL SCREENING LA English DT Article ID PREVENTION TRIAL; SPIRAL CT; CANCER; DESIGN; FEASIBILITY; CARET AB Objectives To report participant recruitment experiences in a large, US randomized controlled trial (RCT) of lung cancer screening, with the aim of providing information that may be of use to researchers who wish to conduct similar future studies. Setting The National Lung Screening Trial (NLST), an RCT that demonstrated a 20% lung cancer mortality reduction with low dose helical computed tomography screening, relative to single-view chest radiograph screening. Thirty-three US medical centres recruited 53,454 participants from August 2002 through April 2004. Methods After recruitment was completed, centre co-ordinators were asked to complete a questionnaire addressing the extent to which specific methods were used and, for each specific method, numbers enrolled and total cost of the effort. Cost per enrollee was calculated. Coordinators also were asked to report lessons learned. Results Twenty-two centres returned questionnaires. Use of recruitment method varied by centre. Among centres reporting number enrolled by method, about 19,000 participants were enrolled with direct mail, about 4200 with mass media, and about 1000 with community outreach. Cost per enrollee varied across centres but medians were (US) $101 (direct mail), $79 (mass media), and $4 (community outreach). Co-ordinators reported that it was important to know where to find persons likely to be eligible and interested, and how best to approach them. Conclusions Most NLST participants were recruited through direct mail, although median cost per participant was highest for that method. C1 [Marcus, Pamela M.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Lenz, Suzanne; Black, William] Dartmouth Hitchcock Med Ctr, Dept Radiol, Lebanon, NH 03766 USA. [Sammons, Donna; Garg, Kavita] Univ Colorado Denver, Sch Med, Dept Radiol, Aurora, CO USA. [Black, William] Dartmouth Hitchcock Med Ctr, Dept Community & Family Med, Lebanon, NH 03766 USA. RP Marcus, PM (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,Suite 4106, Bethesda, MD 20892 USA. EM marcusp@mail.nih.gov FU Division of Cancer Prevention [NO1CN25476, NO1CN25511, NO1CN25512, NO1CN25513, NO1CN25514, NO1CN25515, NO1CN25516, NO1CN25518, NO1CN25522, NO1CN25524, NO1CN75022]; National Cancer Institute; NIH; DHHS; Cancer Imaging Program, Division of Cancer Treatment and Diagnosis, NCI [U01 CA80098, CA79778] FX This research was supported by eleven contracts (NO1CN25476, NO1CN25511, NO1CN25512, NO1CN25513, NO1CN25514, NO1CN25515, NO1CN25516, NO1CN25518, NO1CN25522, NO1CN25524, NO1CN75022) from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS, and by grants (U01 CA80098 and CA79778) to the American College of Radiology Imaging Network (ACRIN) under a co-operative agreement with the Cancer Imaging Program, Division of Cancer Treatment and Diagnosis, NCI. NR 10 TC 5 Z9 5 U1 0 U2 1 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0969-1413 J9 J MED SCREEN JI J. Med. Screen. PY 2012 VL 19 IS 2 BP 94 EP 102 DI 10.1258/jms.2012.012016 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 982HV UT WOS:000307034700009 PM 22653572 ER PT J AU Villa, A Kreimer, AR Polimeni, A Cicciu, D Strohmenger, L Gherlone, E Abati, S AF Villa, Alessandro Kreimer, Aimee R. Polimeni, Antonella Cicciu, Domenico Strohmenger, Laura Gherlone, Enrico Abati, Silvio TI Self-Reported Oral Hygiene Habits among Dental Patients in Italy SO MEDICAL PRINCIPLES AND PRACTICE LA English DT Article DE Compliance; Education; Oral hygiene ID CARDIOVASCULAR-DISEASE; PERIODONTAL-DISEASE; HEALTH; COMPLICATIONS; METAANALYSIS; PREGNANCY; ATTITUDES; ADULTS AB Objective: The objective of this survey was to assess oral hygiene habits and compliance with guidelines for good oral health set forth by the Italian Ministry of Health (IMH). Subjects and Methods: A sample of 2,200 self-administered questionnaires was sent to four dental clinics across Italy to assess sociodemographic information, oral hygiene habits, frequency of dental visits and services received at previous visits among a population of adult patients. Results: Of the 2,200 questionnaires, 1,201 (54.6%) were returned. Findings showed that full compliance with the IMH recommendations was low (12%): a small number of patients (n = 223, 18.6%) visited a dentist every 6 months and only 256 (23.5%) brushed their teeth at least twice a day. Conclusion: Our data showed that regular attendance (at least 1 visit/year) at dental clinics for routine check-up and brushing teeth at least twice a day were poor. Therefore, we recommend that clinicians educate and motivate their patients about the benefits of healthy oral hygiene practices. Copyright (c) 2012 S. Karger AG, Basel C1 [Villa, Alessandro; Strohmenger, Laura; Abati, Silvio] Univ Milan, Dipartimento Med Chirurg & Odontoiatria, Clin Odontoiatr, IT-20142 Milan, Italy. [Villa, Alessandro; Kreimer, Aimee R.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Gherlone, Enrico] Univ Vita Salute San Raffaele, Hosp San Raffaele, Dept Dent, Milan, Italy. [Polimeni, Antonella] Univ Roma La Sapienza, Dent Clin, Dept Oral & Maxillofacial Sci, Rome, Italy. [Cicciu, Domenico] Univ Messina, Policlin Univ, Dept Dent, Messina, Italy. RP Villa, A (reprint author), Univ Milan, Dipartimento Med Chirurg & Odontoiatria, Clin Odontoiatr, Via Beldiletto 1-3, IT-20142 Milan, Italy. EM alessandro.villa@unimi.it RI Abati, Silvio/I-9286-2012; Kreimer, Aimee/H-1687-2015; Gherlone, Enrico/M-7376-2016; OI Villa, Alessandro/0000-0002-1966-6000 FU Italian Ministry of Health (Ministero del Lavoro, della salute e delle politiche sociali, CCM) FX This study was supported through a grant from the Italian Ministry of Health (Ministero del Lavoro, della salute e delle politiche sociali, CCM). NR 21 TC 2 Z9 2 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1011-7571 J9 MED PRIN PRACT JI Med. Princ. Pract. PY 2012 VL 21 IS 5 BP 452 EP 456 DI 10.1159/000336786 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 986WC UT WOS:000307375300007 PM 22488025 ER PT S AU Kiyatkin, EA Sharma, HS AF Kiyatkin, Eugene A. Sharma, Hari Shanker BE Sharma, HS TI ENVIRONMENTAL CONDITIONS MODULATE NEUROTOXIC EFFECTS OF PSYCHOMOTOR STIMULANT DRUGS OF ABUSE SO NEW PERSPECTIVES OF CENTRAL NERVOUS SYSTEM INJURY AND NEUROPROTECTION SE International Review of Neurobiology LA English DT Review; Book Chapter ID BLOOD-BRAIN-BARRIER; CENTRAL-NERVOUS-SYSTEM; METHAMPHETAMINE-INDUCED HYPERTHERMIA; NORMOTENSIVE YOUNG-RATS; SPINAL-CORD; SUBSTITUTED AMPHETAMINES; TEMPERATURE HOMEOSTASIS; SEXUAL INTERACTION; REACTIVE GLIOSIS; OXIDATIVE STRESS AB Psychomotor stimulants such as methamphetamine (METH), amphetamine, and 3,4-metylenedioxymethamphetamine (MDMA or ecstasy) are potent addictive drugs. While it is known that their abuse could result in adverse health complications, including neurotoxicity, both the environmental conditions and activity states associated with their intake could strongly enhance drug toxicity, often resulting in life-threatening health complications. In this review, we analyze results of animal experiments that suggest that even moderate increases in environmental temperatures and physiological activation, the conditions typical of human raves parties, dramatically potentiate brain hyperthermic effects of METH and MDMA. We demonstrate that METH also induces breakdown of the blood brain barrier, acute glial activation, brain edema, and structural abnormalities of various subtypes of brain cells; these effects are also strongly enhanced when the drug is used at moderately warm environmental conditions. We consider the mechanisms underlying environmental modulation of acute drug neurotoxicity and focus on the role of brain temperature, a critical homeostatic parameter that could be affected by metabolism-enhancing drugs and environmental conditions and affect neural activity and functions. C1 [Kiyatkin, Eugene A.] NIDA, Behav Neurosci Branch, Intramural Res Program NIDA IRP, NIH, Baltimore, MD USA. [Sharma, Hari Shanker] Uppsala Univ, Lab Cerebrovasc Res, Dept Surg Sci Anesthesiol & Intens Care Med, Univ Hosp, Uppsala, Sweden. RP Kiyatkin, EA (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program NIDA IRP, NIH, Baltimore, MD USA. RI Sharma, Hari/G-4508-2016 FU Intramural NIH HHS [ZIA DA000445-12] NR 76 TC 10 Z9 10 U1 1 U2 6 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 BN 978-0-12-386986-9 J9 INT REV NEUROBIOL JI Int. Rev. Neurobiol. PY 2012 VL 102 BP 147 EP 171 DI 10.1016/B978-0-12-386986-9.00006-5 PG 25 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BBU39 UT WOS:000308201000007 PM 22748829 ER PT J AU Marcum, CS Bevc, CA Butts, CT AF Marcum, Christopher Steven Bevc, Christine A. Butts, Carter T. TI Mechanisms of Control in Emergent Interorganizational Networks SO POLICY STUDIES JOURNAL LA English DT Review DE organizations; social control; social networks; disaster response; authority ID MULTINATIONAL-CORPORATIONS; CRISIS MANAGEMENT; DISASTER; COMMUNICATION; COORDINATION; CENTRALITY; POWER; ORGANIZATIONS; GOVERNANCE; SYSTEMS AB The delegation of decision-making capacity from one actor to anotherknown variously as authority or controlis a central phenomenon of organizational sociology. Despite its theoretical and practical significance, however, the dynamics of control within disrupted settings (such as disasters) remain poorly understood. Here, we shed light on this question by a reexamination of historical data on multiorganizational disaster response networks, using recently developed statistical methods for robust inference from error-prone informant reports. Specifically, we test competing hypotheses about the relationship of control during the response process to the structure of interorganizational communication. We find that both the realized and normative response hierarchies are likely shaped by coordination among both nonadjacent alters and along indirect channels. Our results suggested that the communication structure of these networks is consistent with a control at a distance model of command. This article makes a substantial contribution to understanding the role of network structure in the emergence of control between organizations in disrupted settings. Additionally, our innovative approach to network inference will guide researchers in dealing with error-prone data in their own research on policy networks. C1 [Marcum, Christopher Steven] RAND Corp, NIA, Santa Monica, CA 90406 USA. [Butts, Carter T.] Univ Calif Irvine, Irvine, CA USA. RP Marcum, CS (reprint author), RAND Corp, NIA, Santa Monica, CA 90406 USA. EM cmarcum@rand.org OI Marcum, Christopher/0000-0002-0899-6143 NR 108 TC 9 Z9 9 U1 3 U2 30 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0190-292X J9 POLICY STUD J JI Policy Stud. J. PY 2012 VL 40 IS 3 BP 516 EP 546 DI 10.1111/j.1541-0072.2012.00463.x PG 31 WC Political Science; Public Administration SC Government & Law; Public Administration GA 982CV UT WOS:000307020200007 ER PT J AU Gilbert, JA Bao, YM Wang, H Sansone, SA Edmunds, SC Morrison, N Meyer, F Schriml, LM Davies, N Sterk, P Wilkening, J Garrity, GM Field, D Robbins, R Smith, DP Mizrachi, I Moreau, C AF Gilbert, Jack A. Bao, Yiming Wang, Hui Sansone, Susanna-Assunta Edmunds, Scott C. Morrison, Norman Meyer, Folker Schriml, Lynn M. Davies, Neil Sterk, Peter Wilkening, Jared Garrity, George M. Field, Dawn Robbins, Robert Smith, Daniel P. Mizrachi, Ilene Moreau, Corrie TI Report of the 13th Genomic Standards Consortium Meeting, Shenzhen, China, March 4-7, 2012 SO STANDARDS IN GENOMIC SCIENCES LA English DT Article DE Genomic Standards Consortium; microbiome; microbial metagenomics; fungal genomics; viral genomics; Genomic Observatories Network ID MINIMUM INFORMATION; MICROBIOME; EARTH AB This report details the outcome of the 13th Meeting of the Genomic Standards Consortium. The three-day conference was held at the Kingkey Palace Hotel, Shenzhen, China, on March 5-7, 2012, and was hosted by the Beijing Genomics Institute. The meeting, titled From Genomes to Interactions to Communities to Models, highlighted the role of data standards associated with genomic, metagenomic, and amplicon sequence data and the contextual information associated with the sample. To this end the meeting focused on genomic projects for animals, plants, fungi, and viruses; metagenomic studies in host-microbe interactions; and the dynamics of microbial communities. In addition, the meeting hosted a Genomic Observatories Network session, a Genomic Standards Consortium biodiversity working group session, and a Microbiology of the Built Environment session sponsored by the Alfred P. Sloan Foundation. C1 [Gilbert, Jack A.; Meyer, Folker; Wilkening, Jared; Smith, Daniel P.] Argonne Natl Lab, Argonne, IL 60439 USA. [Gilbert, Jack A.] Univ Chicago, Dept Ecol & Evolut, Chicago, IL 60637 USA. [Bao, Yiming] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Wang, Hui; Field, Dawn] Ctr Ecol & Hydrol, Wallingford, Oxon, England. [Sansone, Susanna-Assunta; Sterk, Peter] Univ Oxford, E Res Ctr, Oxford, England. [Edmunds, Scott C.] BGI Hong Kong Ltd, GigaSci, Hong Kong, Hong Kong, Peoples R China. [Morrison, Norman] Univ Manchester, Sch Comp Sci, Manchester, Lancs, England. [Schriml, Lynn M.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Garrity, George M.] Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA. [Robbins, Robert] Univ Calif San Diego, La Jolla, CA 92093 USA. [Mizrachi, Ilene] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Moreau, Corrie] Field Museum, Chicago, IL 60605 USA. RP Gilbert, JA (reprint author), Argonne Natl Lab, 9700 S Cass Ave, Argonne, IL 60439 USA. EM gilbertjack@anl.gov RI Garrity, George/F-7551-2013; Davies, Neil/E-5863-2012; Wang, Hui/E-6764-2012; OI Sterk, Peter/0000-0003-1668-7778; Garrity, George/0000-0002-4465-7034; Davies, Neil/0000-0001-8085-5014; Sansone, Susanna-Assunta/0000-0001-5306-5690; Meyer, Folker/0000-0003-1112-2284; Moreau, Corrie/0000-0003-1139-5792; Edmunds, Scott/0000-0001-6444-1436 FU US Department of Energy [DE-AC02-06CH11357]; US National Science Foundation through the research coordination network award [RCN4GSC, DBI-0840989]; Eppendorf; MoBio; BGI; Lucigen; Hua Yue Enterprise Holdings Ltd.; Gordon and Betty Moore Foundation FX This work was supported in part by the US Department of Energy under Contract DE-AC02-06CH11357 and in part by the US National Science Foundation through the research coordination network award RCN4GSC, DBI-0840989. We thank Eppendorf, MoBio, BGI, Lucigen, and Hua Yue Enterprise Holdings Ltd. for their sponsorship of the meeting. We also thank the Gordon and Betty Moore Foundation for support and the U.S. Department of Energy for supporting the attendance of Greg Caporaso, Daniel Smith, Andreas Wilkening, Austin Davis-Richardson, and Patrick Chain through a young investigators travel award. NR 21 TC 2 Z9 2 U1 0 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1944-3277 J9 STAND GENOMIC SCI JI Stand. Genomic Sci. PY 2012 VL 6 IS 2 BP 276 EP 286 DI 10.4056/sigs.2876184 PG 11 WC Genetics & Heredity; Microbiology SC Genetics & Heredity; Microbiology GA 978QC UT WOS:000306759300013 PM 22768370 ER PT J AU Zhu, L Guo, N Li, QZ Ma, Y Jacboson, O Lee, S Choi, HS Mansfield, JR Niu, G Chen, XY AF Zhu, Lei Guo, Ning Li, Quanzheng Ma, Ying Jacboson, Orit Lee, Seulki Choi, Hak Soo Mansfield, James R. Niu, Gang Chen, Xiaoyuan TI Dynamic PET and Optical Imaging and Compartment Modeling using a Dual-labeled Cyclic RGD Peptide Probe SO THERANOSTICS LA English DT Article DE dual modality imaging; dynamic imaging; kinetic modeling; Singular value decomposition (SVD); integrin alpha(v)beta(3); RGD peptide ID POSITRON-EMISSION-TOMOGRAPHY; SMALL-ANIMAL PET; IN-VIVO; ALPHA(V)BETA(3)-INTEGRIN EXPRESSION; TUMOR ANGIOGENESIS; GRAPHICAL ANALYSIS; INTEGRIN; LIMITATIONS; THERAPY; TARGET AB Purpose: The aim of this study is to determine if dynamic optical imaging could provide comparable kinetic parameters to that of dynamic PET imaging by a near-infrared dye/Cu-64 dual-labeled cyclic RGD peptide. Methods: The integrin alpha(v)beta(3) binding RGD peptide was conjugated with a macrocyclic chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) for copper labeling and PET imaging and a near-infrared dye ZW-1 for optical imaging. The in vitro biological activity of RGD-C(DOTA)-ZW-1 was characterized by cell staining and receptor binding assay. Sixty-min dynamic PET and optical imaging were acquired on a MDA-MB-435 tumor model. Singular value decomposition (SVD) method was applied to compute the dynamic optical signal from the two-dimensional optical projection images. Compartment models were used to quantitatively analyze and compare the dynamic optical and PET data. Results: The dual-labeled probe Cu-64-RGD-C(DOTA)-ZW-1 showed integrin specific binding in vitro and in vivo. The binding potential (Bp) derived from dynamic optical imaging (1.762 +/- 0.020) is comparable to that from dynamic PET (1.752 +/- 0.026). Conclusion: The signal un-mixing process using SVD improved the accuracy of kinetic modeling of 2D dynamic optical data. Our results demonstrate that 2D dynamic optical imaging with SVD analysis could achieve comparable quantitative results as dynamic PET imaging in preclinical xenograft models. C1 [Zhu, Lei; Guo, Ning; Ma, Ying; Jacboson, Orit; Lee, Seulki; Niu, Gang; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Zhu, Lei] Xiamen Univ, Ctr Mol Imaging & Translat Med, Xiamen 361005, Fujian, Peoples R China. [Guo, Ning] Huazhong Univ Sci & Technol, Dept Biomed Engn, Wuhan 430074, Hubei, Peoples R China. [Li, Quanzheng] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Cambridge, MA 02138 USA. [Choi, Hak Soo] Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Boston, MA 02215 USA. [Choi, Hak Soo] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Mansfield, James R.] Caliper Life Sci Inc, Hopkinton, MA 01748 USA. RP Niu, G (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. EM gang.niu@nih.gov; shawn.chen@nih.gov RI Choi, Hak Soo/C-9954-2011; Zhu, Lei/P-9786-2016 OI Zhu, Lei/0000-0002-1820-4795 FU National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH); NIH Pathway to Independence Award [K99/R00] FX This work was supported by the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). S. L. is partially supported by an NIH Pathway to Independence (K99/R00) Award. NR 41 TC 15 Z9 15 U1 0 U2 18 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2012 VL 2 IS 8 BP 746 EP 756 DI 10.7150/thno.4762 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 990RK UT WOS:000307648500001 PM 22916074 ER PT J AU Li, KG Davison, KK Jurkowski, JM AF Li, Kaigang Davison, Kirsten K. Jurkowski, Janine M. TI Mental Health and Family Functioning as Correlates of a Sedentary Lifestyle Among Low-Income Women with Young Children SO WOMEN & HEALTH LA English DT Article DE low-income women; television viewing; leisure-time physical activity; depression; stress ID TIME PHYSICAL-ACTIVITY; DEPRESSIVE SYMPTOMS; LEISURE-TIME; PROGRAM-DEVELOPMENT; AFRICAN-AMERICAN; SOCIAL SUPPORT; MOTHERS; ADULTS; BEHAVIORS; OBESITY AB The authors in this cross-sectional study examined mental health and family environmental factors related to a sedentary lifestyle, including lack of leisure-time physical activity and high levels of television viewing, among low-income mothers/female guardians of preschool-aged children. A self-administered questionnaire was completed by 131 mothers in 2010. Primary outcome measures included television viewing time (minutes/day) and leisure-time physical activity (<150 versus >= 150 minutes per week). Independent variables included depressive symptoms, perceived stress, and family functioning. Demographic factors (age, marriage, work status, education, number of children in the household, and race/ethnicity) were examined as potential covariates. Participating women watched television on average 186.1 minutes/day (i.e., >3 hours). Additionally, 36% of women engaged in less than the recommended 150-minute leisure-time physical activity per week. Hierarchical multiple regression analyses indicated that greater depressive symptoms (B = 76.4, p < 0.01) and lower family functioning (B = 33.0, p < 0.05) were independently related to greater television viewing when controlling for other variables. No independent factors were identified for lack of leisure-time physical activity when controlling for other covariates. Findings suggest that health promotion efforts to promote an active lifestyle among low-income women with young children should address mental health and family functioning factors, especially depressive symptoms. C1 [Li, Kaigang; Jurkowski, Janine M.] SUNY Albany, Dept Hlth Policy Management & Behav, Albany, NY 12222 USA. [Davison, Kirsten K.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. RP Li, KG (reprint author), NICHHD, Prevent Res Branch, 6100 Execut Blvd,7B13C,1 Univ Pl, Bethesda, MD 20892 USA. EM lik2@mail.nih.gov FU NIMHD NIH HHS [R24MD004865, R24 MD004865] NR 44 TC 4 Z9 4 U1 1 U2 11 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0363-0242 J9 WOMEN HEALTH JI Women Health PY 2012 VL 52 IS 6 BP 606 EP 619 DI 10.1080/03630242.2012.705243 PG 14 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 990UG UT WOS:000307656700006 PM 22860706 ER PT J AU Bian, L Huang, YX Mao, L Lim, E Lee, G Yang, Y Cohen, M Wilson, D AF Bian, Ling Huang, Yuxia Mao, Liang Lim, Eunjung Lee, Gyoungju Yang, Yan Cohen, Murray Wilson, Deborah TI Modeling Individual Vulnerability to Communicable Diseases: A Framework and Design SO ANNALS OF THE ASSOCIATION OF AMERICAN GEOGRAPHERS LA English DT Article DE daytime; nighttime; and pastime populations; individual-based epidemiology model; mobility; social network ID INFECTIOUS-DISEASE; INFLUENZA; TIME; TRANSMISSION AB Reports on dangerous communicable diseases, such as severe acute respiratory syndrome (SARS) and H1N1 flu, have repeatedly stressed the importance of individuals in disease transmission. Still in its infancy, individual-based modeling faces many challenges. From the perspective of modeling approaches, this article explores (1) the framework of a three-population (daytime, nighttime, and pastime population) and two-scale (local and societal scale) social network; (2) a design that can represent heterogeneous, mobile, interacting individuals and their individualized vulnerability to infection; and (3) a simulation of individuals' vulnerability to influenza in an urban area in the Northeastern United States to illustrate the proposed framework and design. Simulation results correspond well to the reported epidemic information. The findings offer a valuable platform to devise much-needed spatially and temporally oriented control and intervention strategies for communicable diseases. C1 [Bian, Ling; Yang, Yan] SUNY Buffalo, Dept Geog, Amherst, NY 14261 USA. [Huang, Yuxia] Texas A&M Univ, Sch Engn & Comp Sci, Corpus Christi, TX 78412 USA. [Mao, Liang] Univ Florida, Dept Geog, Gainesville, FL 32611 USA. [Lim, Eunjung] Univ Maryland, Dept Geospatial Sci, College Pk, MD 20742 USA. [Lee, Gyoungju] Korea Natl Univ Transportat, Dept Urban Engn, Chungbuk 380702, South Korea. [Cohen, Murray] Consultants Dis & Injury Control Inc, Atlanta, GA 30338 USA. [Wilson, Deborah] NIH, Off Res Safety, Bethesda, MD 20892 USA. RP Bian, L (reprint author), SUNY Buffalo, Dept Geog, Amherst, NY 14261 USA. EM lbian@buffalo.edu; lucy.huang@tamucc.edu; liangmao@ufl.edu; elim@umd.edu; lgjracer@cjnu.ac.kr; yanyang@buffalo.edu; CDICmurray@aol.com; wilsodeb@ors.od.nih.gov NR 28 TC 6 Z9 6 U1 1 U2 10 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0004-5608 J9 ANN ASSOC AM GEOGR JI Ann. Assoc. Am. Geogr. PY 2012 VL 102 IS 5 SI SI BP 1016 EP 1025 DI 10.1080/00045608.2012.674844 PG 10 WC Geography SC Geography GA 984BX UT WOS:000307165000015 ER PT J AU Wheeler, DC Ward, MH Waller, LA AF Wheeler, David C. Ward, Mary H. Waller, Lance A. TI Spatial-Temporal Analysis of Cancer Risk in Epidemiologic Studies with Residential Histories SO ANNALS OF THE ASSOCIATION OF AMERICAN GEOGRAPHERS LA English DT Article DE cancer; case-control study; cluster analysis; epidemiology; generalized additive model; non-Hodgkin lymphoma ID NON-HODGKIN-LYMPHOMA; UNITED-STATES; SMALL-AREA; HEALTH; ENVIRONMENT; REGRESSION; MORTALITY; ISSUES AB Exploring spatial-temporal patterns of disease incidence identifies areas of significantly elevated risk and can lead to discoveries of disease risk factors. One popular way to investigate patterns in risk over space and time is spatial-temporal cluster detection analysis. The identification of significant clusters could lead to etiological hypotheses to explain the pattern of elevated risk and to additional epidemiologic studies to explore these hypotheses. Several methodological issues and data challenges that arise in space-time cluster analysis of chronic diseases, such as cancer, include poor spatial precision of residence locations, long disease latencies, and adjustment for known risk factors. This article reviews the key challenges faced when performing cluster analyses of chronic diseases and presents a spatial-temporal analysis of non-Hodgkin lymphoma (NHL) risk addressing these challenges. Residential histories, collected as part of a population-based case-control study of NHL (the National Cancer Institute [NCI] Surveillance, Epidemiology, and End Results [SEER] NHL study) in four SEER centers (Detroit metropolitan area, Los Angeles, Seattle metropolitan area, and Iowa) were geocoded. In this analysis, we explored previously detected spatial-temporal clusters and adjusted for exposure to polychlorinated biphenyls (PCBs) and genetic polymorphisms in four genes, previously found to be associated with NHL, using a generalized additive model framework. We found that the genetic factors and PCB exposure did not fully explain previously detected areas of elevated risk. C1 [Wheeler, David C.] Virginia Commonwealth Univ, Sch Med, Dept Biostat, Richmond, VA 23298 USA. [Ward, Mary H.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Waller, Lance A.] Emory Univ, Rollins Sch Publ Hlth, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA. RP Wheeler, DC (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Biostat, 1 Capitol Sq,7th Floor,Room 733,830 E Main St,POB, Richmond, VA 23298 USA. EM dcwheels@gmail.com; wardm@mail.nih.gov; lwaller@emory.edu NR 32 TC 5 Z9 6 U1 3 U2 12 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0004-5608 EI 1467-8306 J9 ANN ASSOC AM GEOGR JI Ann. Assoc. Am. Geogr. PY 2012 VL 102 IS 5 SI SI BP 1049 EP 1057 DI 10.1080/00045608.2012.671131 PG 9 WC Geography SC Geography GA 984BX UT WOS:000307165000018 ER PT J AU Wei, YY Zeng, W Wan, R Wang, J Zhou, Q Qiu, SJ Singh, SR AF Wei, Yiyong Zeng, Wen Wan, Rong Wang, Jun Zhou, Qi Qiu, Shijing Singh, Shree Ram TI CHONDROGENIC DIFFERENTIATION OF INDUCED PLURIPOTENT STEM CELLS FROM OSTEOARTHRITIC CHONDROCYTES IN ALGINATE MATRIX SO EUROPEAN CELLS & MATERIALS LA English DT Article DE Chondrocytes; chondrogenesis; differentiation; co-culture ID PATIENT; OPPORTUNITIES; DERIVATION; DISEASE AB Induced pluripotent stem cells (iPSCs) have the potential to revolutionise cell therapy; however, it remains unclear whether iPSCs can be generated from human osteoarthritic chondrocytes (OCs) and subsequently induced to differentiate into chondrocytes. In the present study, we investigated the differentiation potential of OCs into iPSCs using defined transcription factors and explored the possibility of using these OC-derived iPSCs for chondrogenesis. Our study demonstrates that iPSCs can be generated from OCs and that these iPSCs are indistinguishable from human embryonic stem cells (hESCs). To promote chondrogenic differentiation, we used lentivirus to transduce iPSCs seeded in alginate matrix with transforming growth factor-beta 1 (TGF-beta 1) and then in vitro co-cultured these iPSCs with chondrocytes. Gene expression analysis showed that this combinational strategy promotes the differentiation of the established iPSCs into chondrocytes in alginate matrix. Increased expression of cartilage-related genes, including collagen II, aggrecan, and cartilage oligomeric matrix protein (COMP), and decreased gene expression of the degenerative cartilage marker, vascular endothelial growth factor (VEGF), were observed. The histological results revealed a dense sulphated extracellular matrix in the co-culture of TGF-beta 1-transfected iPSCs with chondrocytes in alginate matrix. Additionally, in vivo chondroinductive activity was also evaluated. Histological examination revealed that more new cartilage was formed in the co-culture of TGF-beta 1-transfected iPSCs with chondrocytes in alginate matrix. Taken together, our data indicate that iPSCs can be generated from OCs by defined factors and the combinational strategy results in significantly improved chondrogenesis of OC-derived iPSCs. This work adds to our understanding of potential solutions to osteoarthritic cell replacement problem. C1 [Wei, Yiyong; Zeng, Wen; Wan, Rong; Wang, Jun; Zhou, Qi; Qiu, Shijing] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Inst Traumatol & Orthopaed,Dept Orthopaed, Shanghai 200025, Peoples R China. [Qiu, Shijing] Henry Ford Hosp, Bone & Mineral Res Lab, Detroit, MI 48202 USA. [Singh, Shree Ram] NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21701 USA. RP Wei, YY (reprint author), Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Inst Traumatol & Orthopaed,Dept Orthopaed, Shanghai 200025, Peoples R China. EM dr.yiyongwei@yahoo.com; singhshr@mail.nih.gov RI Singh, Shree Ram/B-7614-2008 OI Singh, Shree Ram/0000-0001-6545-583X FU Shanghai Municipal Education Commission [09YZ107]; National Institutes of Health, National Cancer Institute FX This work was supported by Innovation Program of Shanghai Municipal Education Commission (No. 09YZ107) and the Intramural Research Program of the National Institutes of Health, National Cancer Institute. NR 14 TC 56 Z9 61 U1 1 U2 13 PU AO RESEARCH INSTITUTE DAVOS-ARI PI DAVOS PA CLAVADELERSTRASSE 8, DAVOS, CH 7270, SWITZERLAND SN 1473-2262 J9 EUR CELLS MATER JI Eur. Cells Mater. PD JAN-JUN PY 2012 VL 23 BP 1 EP 12 PG 12 WC Cell & Tissue Engineering; Engineering, Biomedical; Materials Science, Biomaterials SC Cell Biology; Engineering; Materials Science GA 989IT UT WOS:000307554200001 PM 22241609 ER PT S AU Gordenin, DA AF Gordenin, Dmitry A. BE Mothersill, CE Korogodina, V Seymour, CB TI Hypermutability Associated with Double-Strand Break Repair SO RADIOBIOLOGY AND ENVIRONMENTAL SECURITY SE NATO Science for Peace and Security Series C-Environmental Security LA English DT Proceedings Paper CT NATO Advanced Research Workshop on Radiological Issues Pertaining to Environmental Security and Ecoterrorism CY OCT 09-14, 2010 CL Alushta, UKRAINE DE DNA repair; Mutagenesis; Double-strand breaks; Multiple mutations ID DNA-DAMAGE; SACCHAROMYCES-CEREVISIAE; SOMATIC HYPERMUTATION; MUTATION-RATE; PROTEIN EVOLUTION; ADAPTIVE MUTATION; REPLICATION FORK; GENE CONVERSION; SEQUENCE SPACE; HIGH-FIDELITY AB Double-strand breaks (DSBs) are the most toxic kind of DNA damage caused by ionizing radiation as well as by a number of other environmental factors and drugs. DSBs lead to gross chromosome rearrangements, genetic disease, and cancer or cell death. However cells can be programmed to generate DSBs in their own DNA. Programmed DSBs are a key element of many biological functions such as meiotic recombination and segregation, adaptive immunity, regulation switches and viral life cycles. Either damage-induced or programmed DSBs should be repaired in order to retain cell viability. Over the last years it has been established that DSB repair can be associated with up to 10,000-fold increase in frequency of base substitutions and small insertions/deletions (indels). This localized hypermutability represents additional genotoxic threat as well as a potential for generating rare multiple mutant alleles with high fitness without overloading the rest of the genome with mutations. C1 Natl Inst Environm Hlth Sci, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Gordenin, DA (reprint author), Natl Inst Environm Hlth Sci, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. EM Gordenin@niehs.nih.gov NR 62 TC 1 Z9 1 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1871-4668 BN 978-94-007-1938-5 J9 NATO SCI PEACE SECUR JI NATO Sci. Peace Secur. Ser. C- Environ. Secur. PY 2012 BP 1 EP 11 DI 10.1007/978-94-007-1939-2_1 PG 11 WC Biophysics; Public, Environmental & Occupational Health; Nuclear Science & Technology SC Biophysics; Public, Environmental & Occupational Health; Nuclear Science & Technology GA BBK53 UT WOS:000307200400001 ER PT S AU Drake, JW AF Drake, John W. BE Mothersill, CE Korogodina, V Seymour, CB TI A Test of Kimura's Mutation-Rate Conjecture SO RADIOBIOLOGY AND ENVIRONMENTAL SECURITY SE NATO Science for Peace and Security Series C-Environmental Security LA English DT Proceedings Paper CT NATO Advanced Research Workshop on Radiological Issues Pertaining to Environmental Security and Ecoterrorism CY OCT 09-14, 2010 CL Alushta, UKRAINE DE Mutation; Mutation rate; Ribovirus; Thermophile ID CHARACTER AB Mutation is the first of the four great engines of evolution and the prime source of heritable variation in all living and semi-living organisms and their molecular parasites. As a result, the processes and products of mutation have been deeply explored at both the phenomenological and the mechanistic levels for more than a century. There has been notable progress at both levels over the last half century, with the result that the phylogeny of mutation has become fairly well codified, especially the rates and kinds of mutation in as diverse organisms as could be probed. These explorations began to coalesce in the 1990s and soon comprised a small number of broad generalizations. These include very high genomic mutation rates in riboviruses and some higher eukaryotes, and strikingly similar genomic mutation rates in most DNA microbes. However, highly informative exceptions have recently been observed. C1 Natl Inst Environm Hlth Sci, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Drake, JW (reprint author), Natl Inst Environm Hlth Sci, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. EM drake@niehs.nih.gov NR 16 TC 1 Z9 1 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1871-4668 BN 978-94-007-1938-5 J9 NATO SCI PEACE SECUR JI NATO Sci. Peace Secur. Ser. C- Environ. Secur. PY 2012 BP 13 EP 18 DI 10.1007/978-94-007-1939-2_2 PG 6 WC Biophysics; Public, Environmental & Occupational Health; Nuclear Science & Technology SC Biophysics; Public, Environmental & Occupational Health; Nuclear Science & Technology GA BBK53 UT WOS:000307200400002 ER PT S AU Resnick, MA AF Resnick, Michael A. BE Mothersill, CE Korogodina, V Seymour, CB TI Endless Pursuit of DNA Double-Strand Break Ends SO RADIOBIOLOGY AND ENVIRONMENTAL SECURITY SE NATO Science for Peace and Security Series C-Environmental Security LA English DT Proceedings Paper CT NATO Advanced Research Workshop on Radiological Issues Pertaining to Environmental Security and Ecoterrorism CY OCT 09-14, 2010 CL Alushta, UKRAINE DE DNA repair; Double-strand breaks; Resection; MRX; RAD52; Mutations; Genome stability; Ionizing radiation; UV; Chromosome breaks; Tetraploidy; Recombination ID GENOME INSTABILITY; REPAIR; YEAST; RECOMBINATION; COMPLEX AB In the pursuit of radiation-induced cellular damage that manifests in cell killing and genome instability, but is reversible by the phenomenon of liquid holding, DNA double-strand breaks (DSBs) have been shown to be the major culprit. It is now widely accepted that DSBs provide both beneficial and deleterious effects and that elaborate systems were evolved to address their detection, processing and repair. Understanding the mechanisms of DSB induction, processing and eventual biological consequences as well as just the detection of DSBs remain a challenge - especially for randomly induced breaks. Given the large number of extensive reviews available and the limited space here, I have chosen to focus on summarizing recent novel findings from our group using the budding yeast Saccharomyces cerevisiae that are relevant to many molecular and genetic aspects of DSB repair and impact on genome stability. Included are the systems we have developed that address (1) induction of random primary and secondary DSBs; (2) processing of DSB ends; (3) genetic control of DSB induction and repair; (4) genome instabilities associated with DSBs including rearrangements and hypermutability associated with resected ends; and (5) physical factors that determine the transition from DSB to chromosome break or recombination. Using a circular chromosome, we find that resection of random, dirty-end DSBs induced by ionizing radiation or derived from MMS single-strand damage is rapid and is primarily due to the MRX complex. Interestingly, the transition from DSB to chromosome break at a unique DSB in yeast is largely prevented by the nuclease function of exonuclease 1 as determined from separation of fluorescent markers that flank a DSB. Based on a tetraploid gene-dosage model, the role of the chromosome structural complex cohesin is not only to enhance DSB repair between sister chromatids, but it also directs recombinational repair events to sisters thereby preventing loss of heterozygosity. Notably, DSBs greatly sensitizes cells to localized mutability as well as gross rearrangements. Overall, these findings demonstrate the genomic vulnerability to DSBs and the genetic investment in their orderly processing. C1 Natl Inst Environm Hlth Sci, CSG, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Resnick, MA (reprint author), Natl Inst Environm Hlth Sci, CSG, Mol Genet Lab, NIH, Box 12233, Res Triangle Pk, NC 27709 USA. EM resnick@niehs.nih.gov NR 22 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1871-4668 BN 978-94-007-1938-5 J9 NATO SCI PEACE SECUR JI NATO Sci. Peace Secur. Ser. C- Environ. Secur. PY 2012 BP 245 EP 257 DI 10.1007/978-94-007-1939-2_21 PG 13 WC Biophysics; Public, Environmental & Occupational Health; Nuclear Science & Technology SC Biophysics; Public, Environmental & Occupational Health; Nuclear Science & Technology GA BBK53 UT WOS:000307200400021 ER PT J AU Wang, DD Akiyama, K Zhang, HY Yamaza, T Li, X Feng, XB Wang, H Hua, BZ Liu, BJ Xu, HJ Chen, WJ Shi, ST Sun, LY AF Wang, Dandan Akiyama, Kentaro Zhang, Huayong Yamaza, Takayoshi Li, Xia Feng, Xuebing Wang, Hong Hua, Bingzhu Liu, Bujun Xu, Huji Chen, Wanjun Shi, Songtao Sun, Lingyun TI Double Allogenic Mesenchymal Stem Cells Transplantations Could Not Enhance Therapeutic Effect Compared with Single Transplantation in Systemic Lupus Erythematosus SO CLINICAL & DEVELOPMENTAL IMMUNOLOGY LA English DT Article ID VERSUS-HOST-DISEASE; STROMAL CELLS; LIVER-CIRRHOSIS; MRL/LPR MICE; SCLEROSIS; TRIAL; IMMUNOTHERAPY; IMPROVEMENT; NEPHRITIS; EFFICACY AB The clinical trial of allogenic mesenchymal stem cells (MSCs) transplantation for refractory SLE patients has shown significant safety and efficacy profiles. However, the optimum frequency of the MSCs transplantation (MSCT) is unknown. This study was undertaken to observe whether double transplantations of MSCs is superior to single transplantation. Fifty-eight refractory SLE patients were enrolled in this study, in which 30 were randomly given single MSCT, and the other 28 were given double MSCT. Patients were followed up for rates of survival, disease remission, and relapse, as well as transplantation-related adverse events. SLE disease activity index (SLEDAI) and serologic features were evaluated. Our results showed that no remarkable differences between single and double allogenic MSCT were found in terms of disease remission and relapse, amelioration of disease activity, and serum indexes in an SLE clinical trial with more than one year followup. This study demonstrated that single MSCs transplantation at the dose of one million MSCs per kilogram of body weight was sufficient to induce disease remission for refractory SLE patients. C1 [Akiyama, Kentaro; Yamaza, Takayoshi; Shi, Songtao] Univ So Calif, Sch Dent, Ctr Craniofacial Mol Biol, Los Angeles, CA 90033 USA. [Wang, Dandan; Zhang, Huayong; Li, Xia; Feng, Xuebing; Wang, Hong; Hua, Bingzhu; Liu, Bujun; Sun, Lingyun] Nanjing Univ, Dept Rheumatol & Immunol, Affiliated Drum Tower Hosp, Nanjing 210008, Peoples R China. [Xu, Huji] Second Mil Med Univ, Changzheng Hosp, Dept Rheumatol & Immunol, Shanghai 200003, Peoples R China. [Chen, Wanjun] Natl Inst Dent & Craniofacial Res, Mucosal Immunol Unit, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Shi, ST (reprint author), Univ So Calif, Sch Dent, Ctr Craniofacial Mol Biol, Los Angeles, CA 90033 USA. EM songtaos@usc.edu; lingyunsun2001@yahoo.com.cn OI Feng, Xuebing/0000-0002-9837-9690 FU National Natural Science Foundation of China [30972736]; Major International (Regional) Joint Research Project [81120108021]; Jiangsu Province Natural Science Foundation [BK2009034]; Jiangsu Province Kejiao Xingwei Program; National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services [R01DE017449, R01 DE019932, R01 DE019413]; Intramural Research Program of the National Institute of Dental and Craniofacial Research, National Institutes of Health FX This work was supported by National Natural Science Foundation of China (no. 30972736), Major International (Regional) Joint Research Project (81120108021), Jiangsu Province Natural Science Foundation (BK2009034), Jiangsu Province Kejiao Xingwei Program (to L. Sun), and National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services (R01DE017449, R01 DE019932, and R01 DE019413 to S. Shi). This work was supported in part by the Intramural Research Program of the National Institute of Dental and Craniofacial Research, National Institutes of Health (to W. Chen). NR 31 TC 11 Z9 11 U1 1 U2 14 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1740-2522 EI 1740-2530 J9 CLIN DEV IMMUNOL JI Clin. Dev. Immunol. PY 2012 AR 273291 DI 10.1155/2012/273291 PG 7 WC Immunology SC Immunology GA 989VU UT WOS:000307589700001 ER PT S AU Lavoie-Courchesne, S Rioux, P Chouinard-Decorte, F Sherif, T Rousseau, ME Das, S Adalat, R Doyon, J Craddock, C Margulies, D Chu, C Lyttelton, O Evans, AC Bellec, P AF Lavoie-Courchesne, S. Rioux, P. Chouinard-Decorte, F. Sherif, T. Rousseau, M. -E. Das, S. Adalat, R. Doyon, J. Craddock, C. Margulies, D. Chu, C. Lyttelton, O. Evans, A. C. Bellec, P. GP IOP TI Integration of a neuroimaging processing pipeline into a pan-canadian computing grid SO HIGH PERFORMANCE COMPUTING SYMPOSIUM 2011 SE Journal of Physics Conference Series LA English DT Proceedings Paper CT High Performance Computing Symposium (HPCS) CY JUN 15-17, 2011 CL Univ Quebec, Montreal, CANADA SP McGill, Univ Concordia, IBM, Intel, Univ Montreal, Vice-Rectorat Rech, Fac Arts & Sci, Fac Medecine, UQAM, RMGA, Reseau Informat Sci Quebec (RISQ), Dell, Data Direct Networks, Adapt Comp, NVIDIA, Mellanox Technol, QLog, Xyratex, Canarie, Spectra, Microsoft, Sgi, Azuris, Fonex, Force 10, AMD HO Univ Quebec ID FMRI AB The ethos of the neuroimaging field is quickly moving towards the open sharing of resources, including both imaging databases and processing tools. As a neuroimaging database represents a large volume of datasets and as neuroimaging processing pipelines are composed of heterogeneous, computationally intensive tools, such open sharing raises specific computational challenges. This motivates the design of novel dedicated computing infrastructures. This paper describes an interface between PSOM, a code-oriented pipeline development framework, and CBRAIN, a web-oriented platform for grid computing. This interface was used to integrate a PSOM-compliant pipeline for preprocessing of structural and functional magnetic resonance imaging into CBRAIN. We further tested the capacity of our infrastructure to handle a real large-scale project. A neuroimaging database including close to 1000 subjects was preprocessed using our interface and publicly released to help the participants of the ADHD-200 international competition. This successful experiment demonstrated that our integrated grid-computing platform is a powerful solution for high-throughput pipeline analysis in the field of neuroimaging. C1 [Lavoie-Courchesne, S.; Chouinard-Decorte, F.; Doyon, J.; Bellec, P.] Ctr Rech Inst Geriatr Montreal, Montreal, PQ, Canada. [Lavoie-Courchesne, S.; Doyon, J.; Bellec, P.] Univ Montreal, Dept Informat & Recherche Operationnell, Montreal, PQ, Canada. [Lavoie-Courchesne, S.; Rioux, P.; Chouinard-Decorte, F.; Rousseau, M. -E.; Das, S.; Adalat, R.; Evans, A. C.] McGill Univ, Montreal Neurolog Inst, McConnell Brain Imaging Ctr, Montreal, PQ H3A 2T5, Canada. [Craddock, C.] Virginia Tech Carilion Res Inst, Roanoke, VA USA. [Margulies, D.] Max Planck Inst Human Cognit & Brain Sci, Leipzig, DE, Germany. [Chu, C.] NIH, NIMH, Lab Brain & Cognit, Sect Funct Imaging Methods, Bethesda, MD USA. [Lyttelton, O.] Univ Ottawa, Heller Inst Med Res, Royal Ottawa Hlth Care Grp, Brain Imaging & Neuroeth Unit, Ottawa, ON K1N 6N5, Canada. [Margulies, D.; Chu, C.; Lyttelton, O.; Bellec, P.] Neurol Res Inst, Chicago, IL USA. RP Lavoie-Courchesne, S (reprint author), Ctr Rech Inst Geriatr Montreal, Montreal, PQ, Canada. EM lavoiecs@iro.umontreal.ca; bellecp@iro.umontreal.ca RI Craddock, Cameron/P-1980-2014; OI Craddock, Cameron/0000-0002-4950-1303; Rousseau, Marc-Etienne/0000-0001-6281-1691; Bellec, Pierre/0000-0002-9111-0699 FU pilot project grant of the Quebec bioimaging network (QBIN); fonds de recherche en saneduQuebec (FRSQ); Canada's advanced research and innovation network (CANARIE) FX The authors are grateful to the members of the ADHD-200 consortium for publicly releasing the eponym data sample. SLC and PB were partly supported by a pilot project grant of the Quebec bioimaging network (QBIN), fonds de recherche en saneduQuebec (FRSQ). The CBRAIN project is funded by Canadas advanced research and innovation network (CANARIE). NR 21 TC 6 Z9 6 U1 0 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1742-6588 J9 J PHYS CONF SER PY 2012 VL 341 AR 012032 DI 10.1088/1742-6596/341/1/012032 PG 18 WC Computer Science, Interdisciplinary Applications; Engineering, Electrical & Electronic; Physics, Applied SC Computer Science; Engineering; Physics GA BAX11 UT WOS:000305907300032 ER PT S AU Wen, H Wolfe, DE Liu, CA Xiao, XH Lynch, SK Gomella, AA Bennett, EE Morgan, NY AF Wen, Han Wolfe, Doug E. Liu, Chian Xiao, Xianghui Lynch, Susanna K. Gomella, Andrew A. Bennett, Eric E. Morgan, Nicole Y. BE Momose, A Yashiro, W TI Towards Nanometer Period Gratings for Hard X-Ray Phase-Contrast Imaging SO INTERNATIONAL WORKSHOP ON X-RAY AND NEUTRON PHASE IMAGING WITH GRATINGS SE AIP Conference Proceedings LA English DT Proceedings Paper CT International Workshop on X-ray and Neutron Phase Imaging with Gratings (XNPIG) CY MAR 05-07, 2012 CL Tokyo, JAPAN SP Japan Sci & Technol Agcy (JST), Univ Tokyo, Grad Sch Frontier Sci, Munich-Ctr Adv Photon, Konica Minolta Sci & Technol Fdn, Soc Photograph Sci & Technol Japan, Japanese Soc Synchrotron Radiat Res, Photon Factory Users Soc, Phase Measurement Grp, SPring-8 Users Soc, Biol Micro/Nano Imaging Grp DE x-ray; phase contrast; grating; multilayer; fabrication; nanometer; sub-micron; grating period; CT; dark-field ID INTERFEROMETER; BEAM AB Transmission grating-based x-ray interferometers have been developed into wide-field imaging devices that are sensitive to x-ray refraction and diffraction in the sample. While current grating designs rely on UV and x-ray lithography processes to produce periodic vertical structures, it becomes prohibitively difficult to make the grating periods below 1 - 2 microns due to the high aspect ratios of the structures. Since the phase-contrast sensitivity is inversely related to the grating period, we describe a new grating design for sub-micron to nanometer grating periods. In this design, multiple bi-layers of two alternating materials are deposited on a stair like substrate, and mostly on the floor surfaces of the steps only. The incident x-ray beam is parallel to the planes of the layers (side illumination). Thus, the multilayer structure on each step serves as a micro grating whose grating period is the thickness of a bi-layer. The array of micro gratings over the whole length of the stair can act as a single continuous grating, when certain continuity conditions between neighboring steps are met. Since the layer thickness can be as small as tens of nanometers, as has been demonstrated in multilayer x-ray zone plates, this design allows nanometer grating periods over large grating areas. Here we describe a prototype intensity grating of 440 nm period. We show x-ray projection images of the grating which were obtained by contact lithography. C1 [Wen, Han; Lynch, Susanna K.; Gomella, Andrew A.; Bennett, Eric E.; Morgan, Nicole Y.] NHLBI, Imaging Phys Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. [Wolfe, Doug E.] Penn State Univ, Appl Res Lab, Adv Coating Lab, University Pk, PA 16802 USA. [Liu, Chian; Xiao, Xianghui] Argonne Natl Lab, Xray Sci Div, Argonne, IL 60439 USA. RP Wen, H (reprint author), NHLBI, Imaging Phys Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Wen, Han/G-3081-2010 OI Wen, Han/0000-0001-6844-2997 NR 8 TC 0 Z9 0 U1 0 U2 1 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-1072-5 J9 AIP CONF PROC PY 2012 VL 1466 BP 57 EP 60 DI 10.1063/1.4742269 PG 4 WC Physics, Applied SC Physics GA BBI83 UT WOS:000306995500009 ER PT S AU Marathe, S Xiao, XH Wojcik, MJ Divan, R Butler, LG Ham, K Fezzaa, K Erdmann, M Wen, HH Lee, WK Macrander, AT De Carlo, F Mancini, DC Assoufid, L AF Marathe, Shashidhara Xiao, Xianghui Wojcik, Michael J. Divan, Ralu Butler, Leslie G. Ham, Kyungmin Fezzaa, Kamel Erdmann, Mark Wen, Han H. Lee, Wah-Keat Macrander, Albert T. De Carlo, Francesco Mancini, Derrick C. Assoufid, Lahsen BE Momose, A Yashiro, W TI Development of Grating-based X-ray Talbot Interferometry at the Advanced Photon Source SO INTERNATIONAL WORKSHOP ON X-RAY AND NEUTRON PHASE IMAGING WITH GRATINGS SE AIP Conference Proceedings LA English DT Proceedings Paper CT International Workshop on X-ray and Neutron Phase Imaging with Gratings (XNPIG) CY MAR 05-07, 2012 CL Tokyo, JAPAN SP Japan Sci & Technol Agcy (JST), Univ Tokyo, Grad Sch Frontier Sci, Munich-Ctr Adv Photon, Konica Minolta Sci & Technol Fdn, Soc Photograph Sci & Technol Japan, Japanese Soc Synchrotron Radiat Res, Photon Factory Users Soc, Phase Measurement Grp, SPring-8 Users Soc, Biol Micro/Nano Imaging Grp DE X-ray interferometry; phase-contrast imaging; grating AB We report on the ongoing effort to develop hard x-ray Talbot interferometry at the Advanced Photon Source (APS), Argonne National Laboratory, USA. We describe the design of the interferometer and preliminary results obtained at 25 keV using a feather and a phantom sample lithographically fabricated of gold. We mention the future developmental goals and applications of this technique as a metrology tool for x-ray optics and beam wavefront characterization. C1 [Marathe, Shashidhara; Xiao, Xianghui; Fezzaa, Kamel; Erdmann, Mark; Macrander, Albert T.; De Carlo, Francesco; Assoufid, Lahsen] Argonne Natl Lab, Adv Photon Source, 9700 S Cass Ave, Argonne, IL 60439 USA. [Wojcik, Michael J.; Divan, Ralu; Mancini, Derrick C.] Argonne Natl Lab, Ctr Nanoscale Mat, 9700 S Cass Ave, Argonne, IL 60439 USA. [Butler, Leslie G.] Louisiana State Univ, Dept Chem, Baton Rouge, LA 70803 USA. [Ham, Kyungmin] Louisiana State Univ, CAMD, Baton Rouge, LA 70803 USA. [Wen, Han H.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. [Lee, Wah-Keat] Brookhaven Natl Lab, Photon Sci Directorate, Upton, NY 11973 USA. RP Assoufid, L (reprint author), Argonne Natl Lab, Adv Photon Source, 9700 S Cass Ave, Argonne, IL 60439 USA. EM assoufid@aps.anl.gov FU U.S. DOE [DE-AC02-06CH11357]; NSF [CHE-0910937] FX Use of the Advanced Photon Source and Center for Nanoscale Materials, Office of Science User Facilities operated for the U.S. Department of Energy (DOE) Office of Science by Argonne National Laboratory, was supported by the U.S. DOE under Contract No. DE-AC02-06CH11357. LGB and KM thank the NSF (CHE-0910937) for support of tomography studies. We thank Prof. Dominique G. Homberger and Mr. Jonathan A. Bonin, both at the Dept. of Biological Sciences, Louisiana State University, Baton Rouge, for tailoring the feather sample precisely for the constraints of the phase-contrast imaging field-of-view, as well as for the mesoscopic image of the sample and the identification of the imaged structures. We would like to acknowledge the information provided by and discussions with Timm Weitkamp (SOLEIL) and Jurgen Mohr (KIT). NR 11 TC 5 Z9 5 U1 0 U2 2 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-1072-5 J9 AIP CONF PROC PY 2012 VL 1466 BP 249 EP 254 DI 10.1063/1.4742300 PG 6 WC Physics, Applied SC Physics GA BBI83 UT WOS:000306995500040 ER PT J AU Mentor-Marcel, RA Bobe, G Sardo, C Wang, LS Kuo, CT Stoner, G Colburn, NH AF Mentor-Marcel, Roycelynn A. Bobe, Gerd Sardo, Christine Wang, Li-Shu Kuo, Chieh-Ti Stoner, Gary Colburn, Nancy H. TI Plasma Cytokines as Potential Response Indicators to Dietary Freeze-Dried Black Raspberries in Colorectal Cancer Patients SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID PREMALIGNANT ORAL LESIONS; COLONY-STIMULATING FACTOR; ANTIOXIDANTS; INFLAMMATION; PREVENTION; BERRIES; CELLS; GEL AB Oral consumption of freeze-dried black raspberries attenuated neoplastic changes in colorectal tissue markers of apoptosis, cell proliferation, and angiogenesis in colorectal cancer (CRC) patients. To determine whether plasma concentrations of interleukin (IL)-1 beta, IL-2, IL-6, IL-8, IL-10, IL-12p70, granulocyte macrophage colony stimulating factor (GM-CSF), interferon-gamma, and tumor necrosis factor-alpha (TNF-alpha) were associated with berry treatment and changes in colorectal tissue markers of apoptosis, cell proliferation, and angiogenesis, plasma and biopsy samples of adenocarcinoma and adjacent normal-appearing colorectal tissue were collected before and during berry treatment from 24 CRC patients who had not received prior therapy and drank a slurry of black raspberry powder (20 g in 100 ml drinking water) 3 times a day for 1 to 9 wk. Plasma concentrations of GM-CSF (+0.12 +/- 0.04 pg/mL; P = 0.01) and IL-8 (-1.61 +/- 0.71 pg/mL; P = 0.04) changed in patients receiving berries for more than 10 days. These changes were correlated with beneficial changes in markers of proliferation (r(Delta GM-CSF), (Delta Ki67 carcinoma -) (normal) = -0.51) and apoptosis (r(Delta IL-8, Delta TUNEL carcinoma - normal) = -0.52) observed in colorectal tissue taken within the same week. Plasma concentrations of GM-CSF and IL-8 may serve as noninvasive indicators to monitor tissue response to berry-based interventions for CRC. C1 [Mentor-Marcel, Roycelynn A.; Bobe, Gerd; Colburn, Nancy H.] NCI, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21701 USA. [Sardo, Christine; Wang, Li-Shu; Kuo, Chieh-Ti; Stoner, Gary] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Stoner, Gary] Ohio State Univ, Coll Med, Dept Internal Med, Div Hematol & Oncol, Columbus, OH 43210 USA. RP Bobe, G (reprint author), Oregon State Univ, Linus Pauling Inst, Linus Pauling Sci Ctr 373, Corvallis, OR 97331 USA. EM gerd.bobe@oregonstate.edu FU U.S. Department of Agriculture [38903-03560]; National Cancer Institute [CA103180, CA148818]; Intramural Research Program, National Cancer Institute, National Institutes of Health, Bethesda, MD FX This study was funded by U.S. Department of Agriculture Grant 38903-03560, National Cancer Institute Grants CA103180 and CA148818, and the Intramural Research Program, National Cancer Institute, National Institutes of Health, Bethesda, MD. NR 22 TC 12 Z9 12 U1 0 U2 3 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2012 VL 64 IS 6 BP 820 EP 825 DI 10.1080/01635581.2012.697597 PG 6 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 986OT UT WOS:000307353000005 PM 22823889 ER PT J AU Deziel, NC Buckley, TJ Sinha, R Abubaker, S Platz, EA Strickland, PT AF Deziel, Nicole C. Buckley, Timothy J. Sinha, Rashmi Abubaker, Salahaddhin Platz, Elizabeth A. Strickland, Paul T. TI Comparability and repeatability of methods for estimating the dietary intake of the heterocyclic amine contaminant 2-amino-1-methyl-6-phenylimidazo[4,5b]pyridine (PhIP) SO FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT LA English DT Article DE heterocyclic amines; biomonitoring; meat; food frequency questionnaire; PhIP ID FOOD FREQUENCY QUESTIONNAIRE; CRUCIFEROUS VEGETABLE CONSUMPTION; MEAT-MUTAGEN INTAKE; AROMATIC-AMINES; BREAST-CANCER; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO(4,5-B)PYRIDINE PHIP; COLORECTAL ADENOMA; PANCREATIC-CANCER; URINARY-EXCRETION; HYDROLYZED URINE AB Inconsistent risk estimates for dietary heterocyclic amine (HCA) exposure and cancers may be due to differences in exposure assessment methods and the associated measurement error. We evaluated repeatability and comparability of intake estimates of the HCA 2-amino-1-methyl-6-phenylimidazo[4,5b]pyridine (PhIP) among two food frequency questionnaire (FFQ) collections, three diary collections, and three measurements of urinary PhIP and its metabolites in 36 non-smokers in Baltimore, Maryland, during 2004-2005. Collections spanned similar to 9 months. Method repeatability was characterised with intraclass correlation coefficients (ICCs). Comparability among methods was assessed with Spearman correlation coefficients. Within-subject variability in PhIP intake was comparably high across all methods (ICCs of 0.20, 0.30, and 0.15 for FFQ, diary, and creatinine-adjusted urinary PhIP, respectively). Mean diary-based PhIP intake and mean urinary PhIP concentration were strongly correlated when restricting the analysis to participants with at least one non-zero diary-based estimate of PhIP intake (n = 15, r = 0.75, p = 0.001), but not in the full study population (n = 36, r = 0.18, p = 0.28). Mean PhIP intake from the FFQ was not associated with that either based on the diary or urinary PhIP separately, but was modestly correlated with a metric that combined the diary-and biomarker-based approaches (r = 0.30, p = 0.08). The high within-subject variability will result in significantly attenuated associations if a single measure is used to estimate exposure within an epidemiologic study. Improved HCA assessment tools, such as a combination of methods or validated biomarkers that capture long term exposure, are needed. C1 [Deziel, Nicole C.; Buckley, Timothy J.; Abubaker, Salahaddhin; Strickland, Paul T.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA. [Buckley, Timothy J.] Ohio State Coll Publ Hlth, Dept Environm Hlth Sci, Columbus, OH USA. [Sinha, Rashmi] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Deziel, NC (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, 615 N Wolfe St, Baltimore, MD USA. EM dezielnc@mail.nih.gov RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 FU Johns Hopkins Center for a Livable Future; NIOSH Johns Hopkins Education and Research Center [T42-OH-008428]; Pilot Project Grant, Maryland Cigarette Restitution Fund Research Grant FX This research was funded by the Johns Hopkins Center for a Livable Future Student Innovation Grant, NIOSH Johns Hopkins Education and Research Center Training Grant (T42-OH-008428) and Pilot Project Grant, Maryland Cigarette Restitution Fund Research Grant to Johns Hopkins Medical Institutions. The authors thank Julitta Brannock and Kathy Schultz for assistance in recruiting and data collections. NR 60 TC 4 Z9 4 U1 0 U2 8 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1944-0049 J9 FOOD ADDIT CONTAM A JI Food Addit. Contam. Part A-Chem. PY 2012 VL 29 IS 8 BP 1202 EP 1211 DI 10.1080/19440049.2012.682657 PG 10 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 976AN UT WOS:000306553000004 PM 22571725 ER PT J AU Shiloh, S Wade, CH Roberts, JS Alford, SH Biesecker, BB AF Shiloh, S. Wade, C. H. Roberts, J. S. Alford, S. Hensley Biesecker, B. B. TI Integrating attitudes about multiple diseases to reach a decision about multiplex genetic testing SO PSYCHOLOGY & HEALTH LA English DT Meeting Abstract C1 [Shiloh, S.] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. [Wade, C. H.] Univ Washington, Bothell, WA USA. [Roberts, J. S.] Univ Michigan, Ann Arbor, MI 48109 USA. [Alford, S. Hensley] Henry Ford Hlth Syst, Biostat & Res Epidemiol, Detroit, MI USA. [Biesecker, B. B.] NHGRI, NIH, Social & Behav Res Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0887-0446 J9 PSYCHOL HEALTH JI Psychol. Health PY 2012 VL 27 SU 1 SI SI BP 117 EP 118 PG 2 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary SC Public, Environmental & Occupational Health; Psychology GA 984ZH UT WOS:000307232000276 ER PT J AU Han, DD Wen, L Chen, YL AF Han, Dandan Wen, Luan Chen, Yonglong TI Molecular Cloning of phd1 and Comparative Analysis of phd1, 2, and 3 Expression in Xenopus laevis SO SCIENTIFIC WORLD JOURNAL LA English DT Article ID HYDROXYLASE DOMAIN PROTEIN-2; IN-SITU HYBRIDIZATION; PROLYL; MICE; HIF; POLYCYTHEMIA; DEFECTS; EMBRYOS AB Intensive gene targeting studies in mice have revealed that prolyl hydroxylase domain proteins (PHDs) play important roles in murine embryonic development; however, the expression patterns and function of these genes during embryogenesis of other vertebrates remain largely unknown. Here we report the molecular cloning of phd1 and systematic analysis of phd1, phd2, and phd3 expression in embryos as well as adult tissues of Xenopus laevis. All three phds are maternally provided during Xenopus early development. The spatial expression patterns of phds genes in Xenopus embryos appear to define a distinct synexpression group. Frog phd2 and phd3 showed complementary expression in adult tissues with phd2 transcription levels being high in the eye, brain, and intestine, but low in the liver, pancreas, and kidney. On the contrary, expression levels of phd3 are high in the liver, pancreas, and kidney, but low in the eye, brain, and intestine. All three phds are highly expressed in testes, ovary, gall bladder, and spleen. Among three phds, phd3 showed strongest expression in heart. C1 [Han, Dandan; Wen, Luan; Chen, Yonglong] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Key Lab Regenerat Biol, Guangzhou 510530, Guangdong, Peoples R China. [Han, Dandan; Wen, Luan] Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China. [Wen, Luan] Natl Inst Child Hlth & Human Dev NICHD, NIH, Sect Mol Morphogenesis, Lab Gene Regulat & Dev,Program Cell Regulat & Met, Bethesda, MD 20892 USA. RP Chen, YL (reprint author), Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Key Lab Regenerat Biol, Guangzhou 510530, Guangdong, Peoples R China. EM chen_yonglong@gibh.ac.cn RI chen, yonglong/I-8439-2012 FU National Basic Research Program of China [2009CB941202]; Chinese Academy of Sciences [KSCX2-YW-R-083] FX This work was supported in part by funds from the National Basic Research Program of China (2009CB941202) and the Key Project of Knowledge Innovation Program of the Chinese Academy of Sciences (KSCX2-YW-R-083). NR 20 TC 2 Z9 2 U1 0 U2 7 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1537-744X J9 SCI WORLD J JI Sci. World J. PY 2012 AR 689287 DI 10.1100/2012/689287 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 982TE UT WOS:000307067500001 ER PT J AU Pandya, H Debinski, W AF Pandya, Hetal Debinski, Waldemar TI Toward Intracellular Targeted Delivery of Cancer Therapeutics Progress and Clinical Outlook for Brain Tumor Therapy SO BIODRUGS LA English DT Article ID PSEUDOMONAS EXOTOXIN-A; NUCLEAR-LOCALIZATION SEQUENCE; EMITTING RADIOTHERAPEUTIC AGENT; CONVECTION-ENHANCED DELIVERY; IN-VIVO; DIPHTHERIA-TOXIN; DRUG-DELIVERY; BREAST-CANCER; SOLID TUMORS; DOMAIN-II AB A number of anti-cancer drugs have their targets localized to particular intracellular compartments. These drugs reach the targets mainly through diffusion, dependent on biophysical and biochemical forces that allow cell penetration. This means that both cancer cells and normal cells will be subjected to such diffusion; hence many of these drugs, like chemotherapeutics, are potentially toxic and the concentration achieved at the site of their action is often suboptimal. The same relates to radiation that indiscriminately affects normal and diseased cells. However, nature-designed systems enable compounds present in the extracellular environment to end up inside the cell and even travel to more specific intracellular compartments. For example, viruses and bacterial toxins can more or less specifically recognize eukaryotic cells, enter these cells, and direct some protein portions to designated intracellular areas. These phenomena have led to creative thinking, such as employing viruses or bacterial toxins for cargo delivery to cells and, more specifically, to cancer cells. Proteins can be genetically engineered in order to not only mimic what viruses and bacterial toxins can do, but also to add new functions, extending or changing the intracellular routes. It is possible to make conjugates or, more preferably, single-chain proteins that recognize cancer cells and deliver cargo inside the cells, even to the desired subcellular compartment. These findings offer new opportunities to deliver drugs/labels only to cancer cells and only to their site of action within the cells. The development of such dual-specificity vectors for targeting cancer cells is an attractive and potentially safer and more efficacious way of delivering drugs. We provide examples of this approach for delivering brain cancer therapeutics, using a specific biomarker on glioblastoma tumor cells. C1 [Pandya, Hetal; Debinski, Waldemar] Wake Forest Sch Med, Brain Tumor Ctr Excellence, Dept Neurosurg, Winston Salem, NC 27157 USA. [Pandya, Hetal; Debinski, Waldemar] Wake Forest Sch Med, Brain Tumor Ctr Excellence, Dept Radiat Oncol, Winston Salem, NC 27157 USA. [Pandya, Hetal; Debinski, Waldemar] Wake Forest Sch Med, Brain Tumor Ctr Excellence, Dept Canc Biol, Winston Salem, NC 27157 USA. [Pandya, Hetal] NINDS, Surg Neurol Branch, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. RP Debinski, W (reprint author), Wake Forest Sch Med, Brain Tumor Ctr Excellence, Dept Neurosurg, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM debinski@wakehealth.edu FU NCI grant [R01 CA74145] FX This study was supported by the NCI grant R01 CA74145. Wake Forest Office of Technology Asset Management has filed a patent application for the 'IL-13R alpha 2-targeted intracellular delivery proteins' (assignees: Waldemar Debinski, Hetal Pandya and Denise Gibo). NR 90 TC 1 Z9 1 U1 0 U2 7 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1173-8804 J9 BIODRUGS JI Biodrugs PY 2012 VL 26 IS 4 BP 235 EP 244 PG 10 WC Oncology; Immunology; Pharmacology & Pharmacy SC Oncology; Immunology; Pharmacology & Pharmacy GA 978VD UT WOS:000306773000004 PM 22671766 ER PT J AU Gotts, SJ Chow, CC Martin, A AF Gotts, Stephen J. Chow, Carson C. Martin, Alex TI Repetition priming and repetition suppression: A case for enhanced efficiency through neural synchronization SO COGNITIVE NEUROSCIENCE LA English DT Article DE Repetition priming; Repetition suppression; Synchrony; Prediction; Expectation ID INFERIOR TEMPORAL CORTEX; MONKEY INFEROTEMPORAL CORTEX; EVENT-RELATED POTENTIALS; HUMAN VISUAL-CORTEX; SHORT-TERM-MEMORY; COMPLEMENTARY-LEARNING-SYSTEMS; LOCAL-FIELD POTENTIALS; TOP-DOWN; IMPLICIT MEMORY; FMRI-ADAPTATION AB Stimulus repetition in identification tasks leads to improved behavioral performance ("repetition priming") but attenuated neural responses ("repetition suppression") throughout task-engaged cortical regions. While it is clear that this pervasive brain-behavior relationship reflects some form of improved processing efficiency, the exact form that it takes remains elusive. In this Discussion Paper, we review four different theoretical proposals that have the potential to link repetition suppression and priming, with a particular focus on a proposal that stimulus repetition affects improved efficiency through enhanced neural synchronization. We argue that despite exciting recent work on the role of neural synchronization in cognitive processes such as attention and perception, similar studies in the domain of learning and memory -and priming, in particular-have been lacking. We emphasize the need for new studies with adequate spatiotemporal resolution, formulate several novel predictions, and discuss our ongoing efforts to disentangle the current proposals. C1 [Gotts, Stephen J.; Martin, Alex] NIMH, Sect Cognit Neuropsychol, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Chow, Carson C.] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD USA. RP Gotts, SJ (reprint author), NIMH, Sect Cognit Neuropsychol, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. EM gottss@mail.nih.gov RI Chow, Carson/A-7970-2009; Gotts, Stephen/J-4842-2012 FU National Institute of Mental Health, NIH, Division of Intramural Research FX The authors would like to thank Nathan Crone, David Plaut, Jay McClelland, David McMahon, Carl Olson, and Avniel Ghuman for helpful discussions. The preparation of this paper was supported by the National Institute of Mental Health, NIH, Division of Intramural Research. NR 193 TC 52 Z9 52 U1 7 U2 39 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1758-8928 J9 COGN NEUROSCI-UK JI Cogn. Neurosci PY 2012 VL 3 IS 3-4 SI SI BP 227 EP + DI 10.1080/17588928.2012.670617 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 979QJ UT WOS:000306834600018 PM 23144664 ER PT J AU McMahon, DBT AF McMahon, David B. T. TI All in the timing: Priming, repetition suppression, and synchrony SO COGNITIVE NEUROSCIENCE LA English DT Editorial Material AB The terms "priming" and "repetition suppression" are commonly used to refer to phenomena occurring on time scales that can differ by several orders of magnitude, ranging from seconds to days or even years. The models discussed by Gotts et al. provide a thought-provoking theoretical framework for relating neuronal and behavioral plasticity. I argue that whereas both the sharpening and the Bayesian models may mediate the gradual acquisition of perceptual expertise, they are unlikely to account for more rapid behavioral changes. The synchrony model, however, could potentially operate within the timing constraints imposed by the fastest forms of repetition priming. C1 NIMH, Sect Cognit Neurophysiol & Imaging, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RP McMahon, DBT (reprint author), NIMH, Sect Cognit Neurophysiol & Imaging, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. EM mcmahond@mail.nih.gov FU NIMH FX The author is supported by the NIMH Intramural Research Program. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1758-8928 J9 COGN NEUROSCI-UK JI Cogn. Neurosci PY 2012 VL 3 IS 3-4 SI SI BP 244 EP 246 DI 10.1080/17588928.2012.689969 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 979QJ UT WOS:000306834600024 PM 24171751 ER PT J AU Gotts, SJ Chow, CC Martin, A AF Gotts, Stephen J. Chow, Carson C. Martin, Alex TI Repetition priming and repetition suppression: Multiple mechanisms in need of testing SO COGNITIVE NEUROSCIENCE LA English DT Article DE Repetition priming; Repetition suppression; Synchrony; Prediction; Bayesian AB In our Discussion Paper, we reviewed four theoretical proposals that have the potential to link the neural and behavioral phenomena of Repetition Suppression and Repetition Priming. We argued that among these proposals, the Synchrony and Bayesian Explaining Away models appear to be the most promising in addressing existing data, and we articulated a series of predictions to distinguish between them. The commentaries have helped to clarify some of these predictions, have highlighted additional evidence supporting the Facilitation and Sharpening models, and have emphasized dissociations by repetition lag and brain location. Our reply addresses these issues in turn, and we argue that progress will require the testing of Repetition Suppression, changes in neural tuning, and changes in synchronization throughout the brain and over a variety of lags and task contexts. C1 [Gotts, Stephen J.; Martin, Alex] NIMH, Sect Cognit Neuropsychol, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Chow, Carson C.] Natl Inst Diabet & Digest & Kidney Dis NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. RP Gotts, SJ (reprint author), NIMH, Sect Cognit Neuropsychol, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. EM gottss@mail.nih.gov RI Chow, Carson/A-7970-2009; Gotts, Stephen/J-4842-2012 FU National Institute of Mental Health, NIH, Division of Intramural Research FX The preparation of this paper was supported by the National Institute of Mental Health, NIH, Division of Intramural Research. NR 0 TC 8 Z9 8 U1 0 U2 4 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1758-8928 J9 COGN NEUROSCI-UK JI Cogn. Neurosci PY 2012 VL 3 IS 3-4 SI SI BP 250 EP 253 DI 10.1080/17588928.2012.697054 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 979QJ UT WOS:000306834600028 PM 24171755 ER PT J AU Benson, PJ Beedie, SA St Clair, DM AF Benson, P. J. Beedie, S. A. St Clair, D. M. TI THE CONTINUUM HYPOTHESIS: MULTIDIMENSIONAL EYE MOVEMENT PHENOTYPES IN NOSOLOGY AND TAXONOMY SO EUROPEAN PSYCHIATRY LA English DT Meeting Abstract C1 [Benson, P. J.] Univ Aberdeen, Kings Coll, Sch Psychol, Aberdeen, Scotland. Univ Aberdeen, Royal Cornhill Hosp, Div Mental Hlth, Aberdeen, Scotland. NIMH, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PY 2012 VL 27 SU 1 MA P-1213 PG 1 WC Psychiatry SC Psychiatry GA 977WL UT WOS:000306695402235 ER PT J AU Nouzova, E Beedie, SA Wallace, L Shephard, E Kuriakose, J Kulkarni, M Shand, AJ Walker, N St Clair, DM Benson, PJ AF Nouzova, E. Beedie, S. A. Wallace, L. Shephard, E. Kuriakose, J. Kulkarni, M. Shand, A. J. Walker, N. St Clair, D. M. Benson, P. J. TI SPECIFICITY AND CHARACTERISTICS OF EYE MOVEMENT DYSFUNCTION IN ADULT MAJOR DEPRESSIVE DISORDER SO EUROPEAN PSYCHIATRY LA English DT Meeting Abstract C1 [Nouzova, E.; Beedie, S. A.; Wallace, L.; Shephard, E.; Benson, P. J.] Univ Aberdeen, Sch Psychol, Aberdeen, Scotland. [Shand, A. J.; St Clair, D. M.] Univ Aberdeen, Div Mental Hlth, Royal Cornhill Hosp, Aberdeen, Scotland. [Kuriakose, J.; Kulkarni, M.; Shand, A. J.] Royal Cornhill Hosp, Aberdeen, Scotland. [Walker, N.] Crown House, Greenock, Scotland. [St Clair, D. M.] NIMH, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PY 2012 VL 27 SU 1 MA P-513 PG 1 WC Psychiatry SC Psychiatry GA 977WL UT WOS:000306695401133 ER PT J AU Guo, W Shugart, YY AF Guo, Wei Shugart, Yin Yao TI Detecting Rare Variants for Quantitative Traits Using Nuclear Families SO HUMAN HEREDITY LA English DT Article DE Rare variants; Nuclear families; Quantitative traits; Weights; Penalized regression ID ASSOCIATION; REGULARIZATION; REGRESSION; COMMON; SELECTION; DISEASES AB With the advent of sequencing technology opening up a new era of personal genome sequencing, huge amounts of rare variant data have suddenly become available to researchers seeking genetic variants related to human complex disorders. There is an urgent need for the development of novel statistical methods to analyze rare variants in a statistically powerful manner. While a number of statistical tests have already been developed to analyze collapsed rare variants identified by association tests in case-control studies, to date, only two FBAT tests-for-rare (described in the updated FBAT version v2.0.4) have applied collapsing methods analogously in family-based designs. For further research in this area, this study aims to introduce three new beta-determined weight tests for detecting rare variants for quantitative traits in nuclear families. In addition to evaluating the performance of these new methods, it also evaluates that of the two FBAT tests-for-rare, using extensive simulations of situations with and without linkage disequilibrium. Results from these simulations suggest that the four tests using beta-determined weights outperform the two collapsing methods used in FBAT (-v0 and -v1). In addition, both the linear combination method (detailed in the FBAT menu v2.0.4) and the multiple regression method (mixing LASSO and Ridge penalties) performed better than the other two beta-determined weight tests we proposed. Following testing and evaluation, we submitted four new beta-determined weight methods of statistical analysis in a computer program to the Comprehensive R Archive Network (CRAN) for general use. Copyright (C) 2012 S. Karger AG, Basel C1 [Guo, Wei; Shugart, Yin Yao] NIMH, Div Intramural Div Program, NIH, Bethesda, MD 20892 USA. [Guo, Wei] NE Normal Univ, Key Lab Appl Stat, Minist Educ, Changchun, Peoples R China. [Guo, Wei] NE Normal Univ, Sch Math & Stat, Changchun, Peoples R China. RP Shugart, YY (reprint author), NIMH, Div Intramural Res Program, NIH, Bldg 35,Room 3A 1000,35 Convent Dr, Bethesda, MD 20892 USA. EM kaylyao@mail.nih.gov FU National Natural Science Foundation of China [10901031] FX Before Dr. Guo moved to the Intramural Research Program at the National Institute of Mental Health, this work was partially supported by the National Natural Science Foundation of China (grant No. 10901031). NR 19 TC 6 Z9 6 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2012 VL 73 IS 3 BP 148 EP 158 DI 10.1159/000338439 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 977QR UT WOS:000306680000003 PM 22699804 ER PT J AU Li, HL Gail, MH AF Li, Huilin Gail, Mitchell H. TI Efficient Adaptively Weighted Analysis of Secondary Phenotypes in Case-Control Genome-Wide Association Studies SO HUMAN HEREDITY LA English DT Article DE Adaptively weighted analysis; Case-control study; Genome-wide association study; Maximum likelihood; Secondary phenotype AB We propose and compare methods of analysis for detecting associations between genotypes of a single nucleotide polymorphism (SNP) and a dichotomous secondary phenotype (X), when the data arise from a case-control study of a primary dichotomous phenotype (D), which is not rare. We considered both a dichotomous genotype (G) as in recessive or dominant models and an additive genetic model based on the number of minor alleles present. To estimate the log odds ratio beta(1) relating X to G in the general population, one needs to understand the conditional distribution [D | X, G] in the general population. For the most general model, [D | X, G], one needs external data on P(D = 1) to estimate A. We show that for this 'full model', the maximum likelihood (FM) corresponds to a previously proposed weighted logistic regression (WL) approach if G is dichotomous. For the additive model, WL yields results numerically close, but not identical, to those of the maximum likelihood FM. Efficiency can be gained by assuming that [D | X, G] is a logistic model with no interaction between X and G (the 'reduced model'). However, the resulting maximum likelihood (RM) can be misleading in the presence of interactions. We therefore propose an adaptively weighted approach (AW) that captures the efficiency of RM but is robust to the occasional SNP that might interact with the secondary phenotype to affect the risk of the primary disease. We study the robustness of FM, WL, RM and AW to misspecification of P(D = 1). In principle, one should be able to estimate A without external information on P(D = 1) under the reduced model. However, our simulations show that the resulting inference is unreliable. Therefore, in practice one needs to introduce external information on P(D = 1), even in the absence of interactions between X and G. Copyright (C) 20125. Karger AG, Basel C1 [Li, Huilin] NYU, Sch Med, Dept Populat Hlth, Div Biostat, New York, NY 10016 USA. [Gail, Mitchell H.] NCI, Div Canc Epidemiol & Genet, Biostat Branch, NIH, Rockville, MD USA. RP Li, HL (reprint author), NYU, Sch Med, Dept Populat Hlth, Div Biostat, 650 1st Ave,547, New York, NY 10016 USA. EM huilin.li@nyumc.org FU Division of Cancer Epidemiology and Genetics of the National Cancer Institute FX Part of Dr. Li's research and Dr. Gail's research were supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics of the National Cancer Institute. This research has utilized the high-performance computational capabilities of the Biowulf PC/Linux cluster at the National Institutes of Health, Bethesda, Md., USA, and at the Center for Health Informatics and Bioinformatics at New York University Langone Medical Center, New York, N.Y., USA. NR 7 TC 6 Z9 6 U1 0 U2 8 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2012 VL 73 IS 3 BP 159 EP 173 DI 10.1159/000338943 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 977QR UT WOS:000306680000004 PM 22710642 ER PT J AU Maojo, V Fritts, M de la Iglesia, D Cachau, RE Garcia-Remesal, M Mitchell, JA Kulikowski, C AF Maojo, Victor Fritts, Martin de la Iglesia, Diana Cachau, Raul E. Garcia-Remesal, Miguel Mitchell, Joyce A. Kulikowski, Casimir TI Nanoinformatics: a new area of research in nanomedicine SO INTERNATIONAL JOURNAL OF NANOMEDICINE LA English DT Review DE biomedical informatics; nanomedicine; nanotoxicology; ontologies; electronic health records ID OF-THE-ART; DRUG-DELIVERY; IN-VIVO; CANCER-THERAPY; TRANSLATIONAL MEDICINE; BIOMEDICAL INFORMATICS; MOLECULAR-BIOLOGY; BIO-TECHNOLOGIES; CLINICAL-TRIALS; NUCLEIC-ACIDS AB Over a decade ago, nanotechnologists began research on applications of nanomaterials for medicine. This research has revealed a wide range of different challenges, as well as many opportunities. Some of these challenges are strongly related to informatics issues, dealing, for instance, with the management and integration of heterogeneous information, defining nomenclatures, taxonomies and classifications for various types of nanomaterials, and research on new modeling and simulation techniques for nanoparticles. Nanoinformatics has recently emerged in the USA and Europe to address these issues. In this paper, we present a review of nanoinformatics, describing its origins, the problems it addresses, areas of interest, and examples of current research initiatives and informatics resources. We suggest that nanoinformatics could accelerate research and development in nanomedicine, as has occurred in the past in other fields. For instance, biomedical informatics served as a fundamental catalyst for the Human Genome Project, and other genomic and -omics projects, as well as the translational efforts that link resulting molecular-level research to clinical problems and findings. C1 [Maojo, Victor; de la Iglesia, Diana; Garcia-Remesal, Miguel] Univ Politecn Madrid, Fac Informat, Dept Inteligencia Artificial, Biomed Informat Grp, E-28660 Madrid, Spain. [Cachau, Raul E.] NCI, Adv Biomed Comp Ctr, SAIC Frederick Inc, Frederick, MD 21701 USA. [Fritts, Martin] NIST, Gaithersburg, MD 20899 USA. [Mitchell, Joyce A.] Univ Utah, Dept Biomed Informat, Salt Lake City, UT 84112 USA. [Kulikowski, Casimir] Rutgers State Univ, Dept Comp Sci, Piscataway, NJ 08855 USA. RP Maojo, V (reprint author), Univ Politecn Madrid, Fac Informat, Dept Inteligencia Artificial, Biomed Informat Grp, E-28660 Madrid, Spain. EM vmaojo@fi.upm.es RI Garcia-Remesal, Miguel/G-3147-2013; Geracitano, Laura/E-6926-2013 OI Garcia-Remesal, Miguel/0000-0002-7532-9471; FU European Commission (ACTION-Grid Support Action) [FP7-224176]; INBIOMEDvision (Coordination and Support Action) [FP7-270107]; Spanish Ministry of Economy and Competitiveness [FIS/AES PS09/00069, RETICS COMBIOMED RD07/0067/0006, Ibero-NBIC CYTED 209RT0366]; Consejo Social of the Universidad Politecnica de Madrid; Comunidad de Madrid; National Center for Research Resources/National Center for Advancing Translational Sciences (Public Health Services) [UL1-RR025764, UL1RR025764-02S2]; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX The work of the authors in this area of research has been partially funded by the European Commission (the ACTION-Grid Support Action, FP7-224176), and the INBIOMEDvision (Coordination and Support Action, FP7-270107), the Spanish Ministry of Economy and Competitiveness (FIS/AES PS09/00069, RETICS COMBIOMED RD07/0067/0006, Ibero-NBIC CYTED 209RT0366), the Consejo Social of the Universidad Politecnica de Madrid, the Comunidad de Madrid and the National Center for Research Resources/National Center for Advancing Translational Sciences (Public Health Services research grants UL1-RR025764 and UL1RR025764-02S2). This project has also been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 125 TC 16 Z9 17 U1 2 U2 43 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-2013 J9 INT J NANOMED JI Int. J. Nanomed. PY 2012 VL 7 BP 3867 EP 3890 DI 10.2147/IJN.S24582 PG 24 WC Nanoscience & Nanotechnology; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA 977KS UT WOS:000306659400001 PM 22866003 ER PT J AU Narver, HL AF Narver, Heather L. TI Oxytocin in the Treatment of Dystocia in Mice SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID LOW-DOSE OXYTOCIN; RAT UTERUS; PARTNER PREFERENCE; MATERNAL-BEHAVIOR; LABOR INDUCTION; GENE-EXPRESSION; RECEPTOR GENE; PARTURITION; MOUSE; PROSTAGLANDIN AB Physicians and veterinarians often prescribe oxytocin to treat dystocia. However, oxytocin administration to pregnant women or animals is not without risk. In the venue of laboratory animal medicine, the use of oxytocin may present confounding variables to research. Although oxytocin has been studied extensively, many of its physiologic effects and interactions with other hormones remain unclear. Investigator concerns about adverse and confounding effects of oxytocin in their research mice prompted the current review of oxytocin and its use to treat murine dystocia. Well-controlled studies of oxytocin in dystocic mice have not been conducted. However, in humans and other animals, inconsistent and adverse effects are well-documented. Limited knowledge of the complex physiologic and molecular mechanisms of action of oxytocin and scant support for the efficacy of oxytocin in dystocic mice fail to meet the standards of evidence-based veterinary medical practice. The administration of oxytocin is contraindicated in many cases of dystocia in research mice, and its use in dystocic mice may be unfounded. A brief review of oxytocin and the physiologic mechanisms of parturition are provided to support this conclusion. Alternative treatments for murine dystocia are discussed, and a holistic approach is advocated to better serve animal welfare and to safeguard the integrity of valuable research. Laboratory animal veterinarians overseeing the development of guidelines or standard operating procedures for technician or investigator treatment of dystocic mice should understand the effects of oxytocin administration in light of relevant research. C1 NINDS, Anim Hlth Care Sect, NIH, Bethesda, MD 20892 USA. RP Narver, HL (reprint author), NINDS, Anim Hlth Care Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM narverh@mail.nih.gov NR 89 TC 1 Z9 1 U1 1 U2 8 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD JAN PY 2012 VL 51 IS 1 BP 10 EP 17 PG 8 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 978UU UT WOS:000306772100002 PM 22330862 ER PT J AU Calabrese, SK Martin, S Wolters, PL Toledo-Tamula, MA Brennan, TL Wood, LV AF Calabrese, Sarah K. Martin, Staci Wolters, Pamela L. Toledo-Tamula, Mary A. Brennan, Tara L. Wood, Lauren V. TI Diagnosis disclosure, medication hiding, and medical functioning among perinatally infected, HIV-positive children and adolescents SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE pediatric HIV; disclosure; HAART; medical functioning ID SOCIAL SUPPORT; ADHERENCE; YOUTH; PROGRESSION; AIDS AB Little is known about the immunological and virological impact of diagnosis disclosure among HIV-positive children and adolescents. The current cross-sectional study examined medication hiding as a mediator of the relationship between disclosure to friends and three medical outcomes: CD4+ absolute count, CD4+ percentage, and viral load. Participants included 25 perinatally infected, HIV-positive children and adolescents ages 11-18 years from the US. Diagnosis disclosure and medication hiding were self-reported by participants and medical markers were derived from blood samples drawn during the same clinic visit. Bootstrapping analyses revealed that disclosure to at least one friend (versus no friends) was associated with less medication hiding, which was associated with higher CD4+ absolute counts and percentages but not viral load. Further, among the subset of participants who had disclosed to at least one friend (n = 19), those who reported disclosing to 11 or more versus 1-10 friends were less likely to hide medication taking, which was associated with higher CD4+ absolute counts. Findings suggest HIV-positive children and adolescents' diagnosis disclosure to friends corresponds to less medication hiding, ultimately yielding better immune functioning. Health care providers should be cognizant of these potential medical benefits associated with disclosure when offering support around disclosure decision-making. C1 [Calabrese, Sarah K.; Martin, Staci; Wolters, Pamela L.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Calabrese, Sarah K.] Yale Univ, Ctr Interdisciplinary Res AIDS, New Haven, CT USA. [Toledo-Tamula, Mary A.] NCI Frederick, Clin Res Directorate CMRP, SAIC Frederick Inc, Frederick, MD USA. [Brennan, Tara L.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Wood, Lauren V.] NCI, Frederick Canc Res & Dev Ctr, Vaccine Branch, Bethesda, MD 20892 USA. RP Martin, S (reprint author), NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. EM martins@mail.nih.gov FU CCR NIH HHS [HHSN261200800001C]; Intramural NIH HHS; NCI NIH HHS [HHSN261200800001E]; NIMH NIH HHS [F31 MH085584, F31-MH085584]; PHS HHS [HHSN261200477004C, HHSN261200800001E] NR 10 TC 12 Z9 12 U1 2 U2 8 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PY 2012 VL 24 IS 9 BP 1092 EP 1096 DI 10.1080/09540121.2012.699670 PG 5 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 975FJ UT WOS:000306492700005 PM 22799616 ER PT J AU Hipp, J Monaco, J Kunju, LP Cheng, J Yagi, Y Rodriguez-Canales, J Emmert-Buck, MR Hewitt, S Feldman, MD Tomaszewski, JE Toner, M Tompkins, RG Flotte, T Lucas, D Gilbertson, JR Madabhushi, A Balis, U AF Hipp, Jason Monaco, James Kunju, L. Priya Cheng, Jerome Yagi, Yukako Rodriguez-Canales, Jaime Emmert-Buck, Michael R. Hewitt, Stephen Feldman, Michael D. Tomaszewski, John E. Toner, Mehmet Tompkins, Ronald G. Flotte, Thomas Lucas, David Gilbertson, John R. Madabhushi, Anant Balis, Ulysses TI Integration of architectural and cytologic driven image algorithms for prostate adenocarcinoma identification SO ANALYTICAL CELLULAR PATHOLOGY LA English DT Article DE Pathology informatics; whole slide imaging; computer aided diagnosis; SIVQ; PPMM; digital imaging; prostate cancer; cancer ID RADICAL PROSTATECTOMY; INDEPENDENT PREDICTOR; ANTIGEN RECURRENCE; CANCER; CARCINOMA; TUMOR; PERCENTAGE; SPECIMENS; PATHOLOGY; DIAMETER AB Introduction: The advent of digital slides offers new opportunities within the practice of pathology such as the use of image analysis techniques to facilitate computer aided diagnosis (CAD) solutions. Use of CAD holds promise to enable new levels of decision support and allow for additional layers of quality assurance and consistency in rendered diagnoses. However, the development and testing of prostate cancer CAD solutions requires a ground truth map of the cancer to enable the generation of receiver operator characteristic (ROC) curves. This requires a pathologist to annotate, or paint, each of the malignant glands in prostate cancer with an image editor software - a time consuming and exhaustive process. Recently, two CAD algorithms have been described: probabilistic pairwise Markov models (PPMM) and spatially-invariant vector quantization (SIVQ). Briefly, SIVQ operates as a highly sensitive and specific pattern matching algorithm, making it optimal for the identification of any epithelial morphology, whereas PPMM operates as a highly sensitive detector of malignant perturbations in glandular lumenal architecture. Methods: By recapitulating algorithmically how a pathologist reviews prostate tissue sections, we created an algorithmic cascade of PPMM and SIVQ algorithms as previously described by Doyle el al. [1] where PPMM identifies the glands with abnormal lumenal architecture, and this area is then screened by SIVQ to identify the epithelium. Results: The performance of this algorithm cascade was assessed qualitatively (with the use of heatmaps) and quantitatively (with the use of ROC curves) and demonstrates greater performance in the identification of malignant prostatic epithelium. Conclusion: This ability to semi-autonomously paint nearly all the malignant epithelium of prostate cancer has immediate applications to future prostate cancer CAD development as a validated ground truth generator. In addition, such an approach has potential applications as a pre-screening/quality assurance tool. C1 [Hipp, Jason; Kunju, L. Priya; Cheng, Jerome; Lucas, David; Balis, Ulysses] Univ Michigan, Dept Pathol, Catherine, MI USA. [Monaco, James; Madabhushi, Anant] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA. [Yagi, Yukako] MGH Pathol Imaging & Commun Technol PICT Ctr, Boston, MA USA. [Rodriguez-Canales, Jaime; Emmert-Buck, Michael R.; Hewitt, Stephen] NCI, Pathol Lab, NIH, Adv Technol Ctr, Gaithersburg, MD USA. [Flotte, Thomas] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Toner, Mehmet; Tompkins, Ronald G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. [Gilbertson, John R.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Feldman, Michael D.] Univ Penn, Dept Pathol & Lab Med, Perlman Sch Med, Div Surg Pathol,Founders Hosp 6, Philadelphia, PA 19104 USA. [Tomaszewski, John E.] SUNY Buffalo, Sch Med & Biomed Sci, Buffalo, NY 14260 USA. RP Balis, U (reprint author), Univ Michigan Hlth Syst, Dept Pathol, M4233A Med Sci 1,1301 Catherine, Ann Arbor, MI 48109 USA. EM anantm@rci.rutgers.edu; Ulysses@med.umich.edu OI Rodriguez-Canales, Jaime/0000-0002-0885-2377; Hewitt, Stephen/0000-0001-8283-1788 FU Wallace H. Coulter Foundation; National Cancer Institute [R01CA136535-01, R03CA143991-01]; Burroughs Wellcome Fund; Center for Cancer Research of the National Cancer Institute, NIH, Bethesda, MD FX This work was made possible via grants from the Wallace H. Coulter Foundation, National Cancer Institute (Grant Nos. R01CA136535-01 and R03CA143991-01), and Burroughs Wellcome Fund (Collaborative Research Travel Grant) supported in part by the Center for Cancer Research of the National Cancer Institute, NIH, Bethesda, MD. NR 29 TC 6 Z9 6 U1 0 U2 6 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 2210-7177 J9 ANAL CELL PATHOL JI Anal. Cell. Pathol. PY 2012 VL 35 IS 4 BP 251 EP 265 DI 10.3233/ACP-2012-0054 PG 15 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 976AO UT WOS:000306553100003 PM 22425661 ER PT J AU Ferrucci, R Giannicola, G Rosa, M Fumagalli, M Boggio, PS Hallett, M Zago, S Priori, A AF Ferrucci, Roberta Giannicola, Gaia Rosa, Manuela Fumagalli, Manuela Boggio, Paulo Sergio Hallett, Mark Zago, Stefano Priori, Alberto TI Cerebellum and processing of negative facial emotions: Cerebellar transcranial DC stimulation specifically enhances the emotional recognition of facial anger and sadness SO COGNITION & EMOTION LA English DT Article DE Cerebellum; Cerebellar dysfunction; Prefrontal cortex; Emotion; Facial emotion recognition; Emotional disturbances; tDCS ID COGNITIVE-AFFECTIVE SYNDROME; HUMAN MOTOR CORTEX; MAGNETIC STIMULATION; WORKING-MEMORY; EXPRESSIONS; EXCITABILITY; FACES; MODULATION; BRAIN; ATTRIBUTION AB Some evidence suggests that the cerebellum participates in the complex network processing emotional facial expression. To evaluate the role of the cerebellum in recognising facial expressions we delivered transcranial direct current stimulation (tDCS) over the cerebellum and prefrontal cortex. A facial emotion recognition task was administered to 21 healthy subjects before and after cerebellar tDCS; we also tested subjects with a visual attention task and a visual analogue scale (VAS) for mood. Anodal and cathodal cerebellar tDCS both significantly enhanced sensory processing in response to negative facial expressions (anodal tDCS, p=.0021; cathodal tDCS, p=.018), but left positive emotion and neutral facial expressions unchanged (p>.05). tDCS over the right prefrontal cortex left facial expressions of both negative and positive emotion unchanged. These findings suggest that the cerebellum is specifically involved in processing facial expressions of negative emotion. C1 [Priori, Alberto] Univ Milan, Fdn IRCCS Ca Granda, Ctr Clin Neurostimolaz Neurotecnol & Disordini Mo, Dipartimento Sci Neurol,Osped Maggiore Policlin, I-20122 Milan, Italy. [Ferrucci, Roberta; Fumagalli, Manuela; Zago, Stefano; Priori, Alberto] Univ Milan, Dipartimento Sci Neurol, I-20122 Milan, Italy. [Boggio, Paulo Sergio] Univ Prebiteriana Mackenzie, Ctr Hlth & Biol Sci, Social & Cognit Neurosci Lab, Sao Paulo, Brazil. [Hallett, Mark] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, Bethesda, MD USA. RP Priori, A (reprint author), Univ Milan, Fdn IRCCS Ca Granda, Ctr Clin Neurostimolaz Neurotecnol & Disordini Mo, Dipartimento Sci Neurol,Osped Maggiore Policlin, Via F Sforza 35, I-20122 Milan, Italy. EM alberto.priori@unimi.it RI Boggio, Paulo/K-6272-2012; Zago, Stefano/I-5838-2015; Ferrucci, Roberta/K-6081-2016 OI Boggio, Paulo/0000-0002-6109-0447; Zago, Stefano/0000-0001-6578-4385; Ferrucci, Roberta/0000-0001-5109-9483 FU Intramural NIH HHS [ZIA NS002667-27] NR 40 TC 35 Z9 35 U1 5 U2 21 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0269-9931 J9 COGNITION EMOTION JI Cogn. Emot. PY 2012 VL 26 IS 5 BP 786 EP 799 DI 10.1080/02699931.2011.619520 PG 14 WC Psychology, Experimental SC Psychology GA 975WL UT WOS:000306542100002 PM 22077643 ER PT J AU Mathews, DC Henter, ID Zarate, CA AF Mathews, Daniel C. Henter, Ioline D. Zarate, Carlos A., Jr. TI Targeting the Glutamatergic System to Treat Major Depressive Disorder Rationale and Progress to Date SO DRUGS LA English DT Article ID METHYL-D-ASPARTATE; NMDA RECEPTOR ANTAGONISTS; GLYCOGEN-SYNTHASE KINASE-3; FORCED SWIMMING TEST; MAGNETIC-RESONANCE-SPECTROSCOPY; TREATMENT-RESISTANT DEPRESSION; EXCITATORY AMINO-ACIDS; NF-KAPPA-B; ANTIDEPRESSANT-LIKE ACTIONS; FAMILY-BASED ASSOCIATION AB Major depressive disorder (MDD) is a severe, debilitating medical illness that affects millions of individuals worldwide. The young age of onset and chronicity of the disorder has a significant impact on the long-term disability that affected individuals face. Most existing treatments have focused on the 'monoamine hypothesis' for rational design of compounds. However, patients continue to experience low remission rates, residual subsyndromal symptoms, relapses and overall functional impairment. In this context, growing evidence suggests that the glutamatergic system is uniquely central to the neurobiology and treatment of MDD. Here, we review data supporting the involvement of the glutamatergic system in the pathophysiology of MDD, and discuss the efficacy of glutamatergic agents as novel therapeutics. Preliminary clinical evidence has been promising, particularly with regard to the N-methyl-D-aspartate (NMDA) antagonist ketamine as a 'proof-of-concept' agent. The review also highlights potential molecular and inflammatory mechanisms that may contribute to the rapid antidepressant response seen with ketamine. Because existing pharmacological treatments for MDD are often insufficient for many patients, the next generation of treatments needs to be more effective, rapid acting and better tolerated than currently available medications. There is extant evidence that the glutamatergic system holds considerable promise for developing the next generation of novel and mechanistically distinct agents for the treatment of MDD. C1 [Mathews, Daniel C.; Zarate, Carlos A., Jr.] NIMH, NIH, Intramural Res Program, Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20892 USA. [Henter, Ioline D.] NIMH, NIH, Mol Imaging Branch, Bethesda, MD 20892 USA. RP Zarate, CA (reprint author), 10 Ctr Dr CRC,Unit 7 SE,Room 7, Bethesda, MD 20892 USA. EM zaratec@mail.nih.gov FU National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH; Bethesda, MD, USA); 7SE Research Unit of the NIMH-NIH; IRP-NIMH-NIH; NARSAD; Brain and Behavior Foundation FX The authors gratefully acknowledge the support of the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH; Bethesda, MD, USA), and thank the 7SE Research Unit of the NIMH-NIH for their support.; Role of funding source: This review was supported by the IRP-NIMH-NIH. The NIMH had no further role in the writing of this review, or in the decision to submit the paper for publication.; Financial disclosures: The authors gratefully acknowledge the support of the IRP-NIMH-NIH, and the NARSAD Independent Investigator Award and Brain and Behavior Foundation Bipolar Research Award (Dr Zarate). Dr Mathews and Ioline Henter have no conflict of interest to disclose, financial or otherwise. Dr Zarate is listed as a co-inventor on a patent application for the use of ketamine and its metabolites in major depression. Dr Zarate has assigned his rights in the patent to the US Government but will share a percentage of any royalties that may be received by the Government. NR 230 TC 58 Z9 61 U1 1 U2 25 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PY 2012 VL 72 IS 10 BP 1313 EP 1333 PG 21 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 976LB UT WOS:000306585100002 PM 22731961 ER PT J AU Kucka, M Kretschmannova, K Stojilkovic, SS Zemkova, H Tomic, M AF Kucka, M. Kretschmannova, K. Stojilkovic, S. S. Zemkova, H. Tomic, M. TI Dependence of Spontaneous Electrical Activity and Basal Prolactin Release on Nonselective Cation Channels in Pituitary Lactotrophs SO PHYSIOLOGICAL RESEARCH LA English DT Article DE TRPC channels; GH(3) cells; Calcium influx; Action potentials; Resting membrane potential ID BACKGROUND SODIUM CONDUCTANCE; DOPAMINE-RECEPTORS; ACTION-POTENTIALS; CALCIUM CHANNELS; HORMONE RELEASE; CELLS; RAT; SECRETION; NEURONS; INFLUX AB All secretory anterior pituitary cells fire action potentials spontaneously and exhibit a high resting cation conductance, but the channels involved in the background permeability have not been identified. In cultured lactotrophs and immortalized GH(3) cells, replacement of extracellular Na+ with large organic cations, but not blockade of voltage-gated Na+ influx, led to an instantaneous hyperpolarization of cell membranes that was associated with a cessation of spontaneous firing. When cells were clamped at -50 mV, which was close to the resting membrane potential in these cells, replacement of bath Na+ with organic cations resulted in an outward-like current, reflecting an inhibition of the inward holding membrane current and indicating loss of a background-depolarizing conductance. Quantitative RTPCR analysis revealed the high expression of mRNA transcripts for TRPC1 and much lower expression of TRPC6 in both lactotrophs and GH(3) cells. Very low expression of TRPC3, TRPC4, and TRPC5 mRNA transcripts were also present in pituitary but not GH(3) cells. 2-APB and SKF-96365, relatively selective blockers of TRPC channels, inhibited electrical activity, Ca2+ influx and prolactin release in a concentration-dependent manner. Gd3+, a common Ca2+ channel blocker, and flufenamic acid, an inhibitor of non-selective cation channels, also inhibited electrical activity, Ca2+ influx and prolactin release. These results indicate that nonselective cation channels, presumably belonging to the TRPC family, contribute to the background depolarizing conductance and firing of action potentials with consequent contribution to Ca2+ influx and hormone release in lactotrophs and GH(3) cells. C1 [Zemkova, H.] Acad Sci Czech Republic, Inst Physiol, Vvi, Dept Cellular & Mol Neuroendocrinol, CR-14220 Prague 4, Czech Republic. [Kucka, M.; Kretschmannova, K.; Stojilkovic, S. S.; Zemkova, H.; Tomic, M.] NICHD, Sect Cellular Signaling, PDN, NIH, Bethesda, MD USA. RP Zemkova, H (reprint author), Acad Sci Czech Republic, Inst Physiol, Vvi, Dept Cellular & Mol Neuroendocrinol, Videnska 1083, CR-14220 Prague 4, Czech Republic. EM zemkova@biomed.cas.cz RI Zemkova, Hana/C-1844-2012; Tomic, Melanija/C-3371-2016 FU National Institute of Child Health and Human Development; Grant Agency of the Czech Republic [305/07/0681]; Project Excellence [P304/12/G069] FX The authors were supported by the Intramural Research Program of the National Institute of Child Health and Human Development, the Grant Agency of the Czech Republic (305/07/0681) and the Project Excellence (P304/12/G069). NR 33 TC 2 Z9 2 U1 1 U2 3 PU ACAD SCIENCES CZECH REPUBLIC, INST PHYSIOLOGY PI PRAGUE 4 PA VIDENSKA 1083, PRAGUE 4 142 20, CZECH REPUBLIC SN 0862-8408 EI 1802-9973 J9 PHYSIOL RES JI Physiol. Res. PY 2012 VL 61 IS 3 BP 267 EP 275 PG 9 WC Physiology SC Physiology GA 975JQ UT WOS:000306508000005 PM 22480423 ER PT J AU Phillips, KA Epstein, DH Preston, KL AF Phillips, Karran A. Epstein, David H. Preston, Kenzie L. TI Ecological Momentary Assessment of Self-Identified Reasons for Specific Instances of Drug Use Among Participants With and Without Hepatitis C SO SUBSTANCE ABUSE LA English DT Meeting Abstract C1 [Phillips, Karran A.; Epstein, David H.; Preston, Kenzie L.] NIDA IRP, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 J9 SUBST ABUS JI Subst. Abus. PY 2012 VL 33 IS 2 BP 199 EP 200 PG 2 WC Substance Abuse SC Substance Abuse GA 974UZ UT WOS:000306464200019 ER PT J AU Chandran, PL Paik, DC Holmes, JW AF Chandran, Preethi L. Paik, David C. Holmes, Jeffrey W. TI Structural Mechanism for Alteration of Collagen Gel Mechanics by Glutaraldehyde Crosslinking SO CONNECTIVE TISSUE RESEARCH LA English DT Article DE collagen gel; crosslink; glutaraldehyde; biaxial mechanics ID AORTIC-VALVE CUSP; BOVINE PERICARDIUM; VISCOELASTIC PROPERTIES; BIOPROSTHETIC VALVES; BIOLOGICAL-MATERIALS; AQUEOUS-SOLUTION; FIBER ALIGNMENT; PART II; MODEL; BEHAVIOR AB Soft collagenous tissues that are loaded in vivo undergo crosslinking during aging and wound healing. Bioprosthetic tissues implanted in vivo are also commonly crosslinked with glutaraldehyde (GA). While crosslinking changes the mechanical properties of the tissue, the nature of the mechanical changes and the underlying microstructural mechanism are poorly understood. In this study, a combined mechanical, biochemical and simulation approach was employed to identify the microstructural mechanism by which crosslinking alters mechanical properties. The model collagenous tissue used was an anisotropic cell-compacted collagen gel, and the model crosslinking agent was monomeric GA. The collagen gels were incrementally crosslinked by either increasing the GA concentration or increasing the crosslinking time. In biaxial loading experiments, increased crosslinking produced (1) decreased strain response to a small equibiaxial preload, with little change in response to subsequent loading and (2) decreased coupling between the fiber and cross-fiber direction. The mechanical trend was found to be better described by the lysine consumption data than by the shrinkage temperature. The biaxial loading of incrementally crosslinked collagen gels was simulated computationally with a previously published network model. Crosslinking was represented by increased fibril stiffness or by increased resistance to fibril rotation. Only the latter produced mechanical trends similar to that observed experimentally. Representing crosslinking as increased fibril stiffness did not reproduce the decreased coupling between the fiber and cross-fiber directions. The study concludes that the mechanical changes in crosslinked collagen gels are caused by the microstructural mechanism of increased resistance to fibril rotation. C1 [Chandran, Preethi L.] Columbia Univ, Dept Biomed Engn, New York, NY USA. [Paik, David C.] Columbia Univ, Dept Ophthalmol, New York, NY 10027 USA. [Holmes, Jeffrey W.] Univ Virginia, Dept Biomed Engn, Charlottesville, VA USA. [Holmes, Jeffrey W.] Univ Virginia, Dept Med, Charlottesville, VA USA. RP Chandran, PL (reprint author), NIBIB NICHD, NIH, Bethesda, MD 20892 USA. EM chandranlp@mail.nih.gov FU NIH [R01 HL075639] FX This work was supported by NIH R01 HL075639 (JWH). The authors acknowledge Dr. Michael Sacks for sharing the design of his custom biaxial stretcher and Drs. Kevin Costa, Gregory Fomovsky and Eun-Jung Lee for input regarding the design and interpretation of the studies. NR 54 TC 9 Z9 9 U1 2 U2 32 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0300-8207 J9 CONNECT TISSUE RES JI Connect. Tissue Res. PY 2012 VL 53 IS 4 BP 285 EP 297 DI 10.3109/03008207.2011.640760 PG 13 WC Cell Biology; Orthopedics SC Cell Biology; Orthopedics GA 971FY UT WOS:000306190400002 PM 22775003 ER PT J AU Branson, CE Clemmey, P Harrell, P Subramaniam, G Fishman, M AF Branson, Christopher E. Clemmey, Philip Harrell, Paul Subramaniam, Geetha Fishman, Marc TI Polysubstance Use and Heroin Relapse Among Adolescents Following Residential Treatment SO JOURNAL OF CHILD & ADOLESCENT SUBSTANCE ABUSE LA English DT Article DE adolescent; heroin; opioid; polysubstance use; relapse ID METHADONE-MAINTENANCE TREATMENT; TREATMENT OUTCOMES; CANNABIS USE; COCAINE USE; DEPENDENT ADOLESCENTS; ALCOHOL-CONSUMPTION; OPIATE-DEPENDENCE; SUBSTANCE USE; ADDICTS; BALTIMORE AB This study examined posttreatment patterns of polysubstance use and heroin relapse in a sample of 43 adolescents (ages 14-20) entering short-term residential treatment for primary heroin use. At 12-month follow-up, youths that achieved heroin abstinence (N = 19) were significantly less likely than youths that relapsed to heroin (N = 24) to endorse polysubstance use and cannabis, cocaine, or benzodiazepine use. Furthermore, heroin-abstinent youths significantly reduced their cannabis and cocaine use across the study period while youths that relapsed made initial reductions before returning to their pretreatment levels of use for these drugs. Clinical implications for heroin-using youths and areas for future research are discussed. C1 [Branson, Christopher E.; Clemmey, Philip] Columbia Univ, St Lukes Roosevelt Hosp Ctr, New York, NY 10025 USA. [Branson, Christopher E.; Clemmey, Philip] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Harrell, Paul] American Univ, Washington, DC 20016 USA. [Subramaniam, Geetha] NIDA, Bethesda, MD 20892 USA. [Fishman, Marc] Johns Hopkins Univ, Baltimore, MD USA. [Fishman, Marc] Mt Manor Treatment Ctr, Baltimore, MD USA. RP Branson, CE (reprint author), Columbia Univ, St Lukes Roosevelt Hosp Ctr, 411 W 114th St,Suite 2A, New York, NY 10025 USA. EM cbranson@chpnet.org OI Harrell, Paul/0000-0001-6588-7878 NR 35 TC 1 Z9 1 U1 1 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1067-828X J9 J CHILD ADOLES SUBST JI J. Child Adolesc. Subst. Abus. PY 2012 VL 21 IS 3 BP 204 EP 221 DI 10.1080/1067828X.2012.689803 PG 18 WC Substance Abuse SC Substance Abuse GA 972ZB UT WOS:000306319100002 ER PT J AU Arab, L Su, LJ Steck, SE Ang, A Fontham, ETH Bensen, JT Mohler, JL AF Arab, Lenore Su, L. Joseph Steck, Susan E. Ang, Alfonso Fontham, Elizabeth T. H. Bensen, Jeannette T. Mohler, James L. TI Coffee Consumption and Prostate Cancer Aggressiveness Among African and Caucasian Americans in a Population-Based Study SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID RISK-FACTORS; FOOD; MEN; METAANALYSIS; CAFFEINE; ALCOHOL; COHORT AB This study evaluated the relationship between caffeinated and decaffeinated coffee and prostate cancer (CaP) aggressiveness using data from a population-based incident CaP study within the North Carolina-Louisiana Prostate Cancer Project (PCaP). Classification of CaP aggressiveness at diagnosis was based on clinical criteria for 1,049 African-American (AA) and 1,083 Caucasian-American (CA) research subjects. Coffee consumption was measured using a modified NCI Dietary History Questionnaire. No significant associations were found between CaP aggressiveness and consumption of either caffeinated or decaffeinated coffee. The OR for high aggressive CaP among consumers of more than 4 cups per day was 0.92 (95% CI = 0.61, 1.39), compared to non-coffeedrinkers. Results stratified by race found no significant associations and no noticeable trends in either AAs (P for trend = 0.62) or CAs (P for trend = 0.42). In contrast to a recent report on a select population that has less complete information on CaP aggressiveness suggesting that coffee prevents aggressive CaP, this rapid case ascertainment population-based study, in a biracial population with differing risks of CaP did not demonstrate a protective relationship between high coffee consumption and risk of high aggressive CaP. C1 [Arab, Lenore; Ang, Alfonso] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Su, L. Joseph] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Steck, Susan E.] Univ S Carolina, Canc Prevent & Control Program, Dept Epidemiol & Biostat, Columbia, SC 29208 USA. [Fontham, Elizabeth T. H.] Louisiana State Univ, Sch Publ Hlth, New Orleans, LA USA. [Bensen, Jeannette T.; Mohler, James L.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Mohler, James L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Mohler, James L.] SUNY Buffalo, Sch Med & Biotechnol, Buffalo, NY 14260 USA. RP Arab, L (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, 12-262 Factor Bldg,Box 951736, Los Angeles, CA 90095 USA. EM Larab@ucla.edu RI Steck, Susan/G-5736-2013 FU Department of Defense [DAMD 17-03-2-0052] FX PCaP is carried out as a collaborative study supported by the Department of Defense grant DAMD 17-03-2-0052. The authors thank the staff, advisory committees, and research subjects participating in the PCaP study for their important contributions. NR 23 TC 8 Z9 9 U1 1 U2 9 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2012 VL 64 IS 5 BP 637 EP 642 DI 10.1080/01635581.2012.676144 PG 6 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 970HA UT WOS:000306117700002 PM 22564042 ER PT J AU Inoue-Choi, M Ward, MH Cerhan, JR Weyer, PJ Anderson, KE Robien, K AF Inoue-Choi, Maki Ward, Mary H. Cerhan, James R. Weyer, Peter J. Anderson, Kristin E. Robien, Kim TI Interaction of Nitrate and Folate on the Risk of Breast Cancer Among Postmenopausal Women SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID N-NITROSO COMPOUNDS; DRINKING-WATER NITRATE; DNA ADDUCT FORMATION; GASTRIC-CANCER; OLDER WOMEN; ENVIRONMENTAL-POLLUTANT; ANTIOXIDANT VITAMIN; COMPOUND FORMATION; BLADDER-CANCER; DIETARY-FOLATE AB Ingested nitrate can be endogenously reduced to nitrite, which may form N-nitroso compounds, known potent carcinogens. However, some studies have reported no or inverse associations between dietary nitrate intake and cancer risk. These associations may be confounded by a protective effect of folate, which plays a vital role in DNA repair. We evaluated the interaction of dietary and water nitrate intake with total folate intake on breast cancer risk in the Iowa Women's Health Study. Dietary intake was assessed at study baseline. Nitrate intake from public water was assessed using a historical database on Iowa municipal water supplies. After baseline exclusions, 34,388 postmenopausal women and 2,875 incident breast cancers were included. Overall, neither dietary nor water nitrate was associated with breast cancer risk. Among those with folate intake >= 400 mu g/day, breast cancer risk was significantly increased in public water users with the highest nitrate quintile (HR = 1.40, 95% CI = 1.05-1.87) and private well users (HR = 1.38, 95% CI = 1.05-1.82) compared to public water users with the lowest nitrate quintile; in contrast, there was no association among those with lower folate intake. Our findings do not support a previous report of increased risk of breast cancer among individuals with high dietary nitrate but low folate intake. C1 [Inoue-Choi, Maki; Anderson, Kristin E.; Robien, Kim] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Ward, Mary H.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Cerhan, James R.] Mayo Clin, Coll Med, Div Epidemiol, Rochester, MN USA. [Weyer, Peter J.] Univ Iowa, Ctr Hlth Effects Environm Contaminat, Coralville, IA USA. [Anderson, Kristin E.; Robien, Kim] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. RP Inoue-Choi, M (reprint author), 1300 S 2nd St,Suite 300, Minneapolis, MN 55454 USA. EM inou0021@umn.edu OI Cerhan, James/0000-0002-7482-178X; Robien, Kim/0000-0002-2120-2280 FU National Cancer Institute [R01 CA39742] FX This study was supported by National Cancer Institute (R01 CA39742). NR 61 TC 6 Z9 7 U1 1 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0163-5581 EI 1532-7914 J9 NUTR CANCER JI Nutr. Cancer PY 2012 VL 64 IS 5 BP 685 EP 694 DI 10.1080/01635581.2012.687427 PG 10 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 970HA UT WOS:000306117700007 PM 22642949 ER PT J AU Wheeler, DC Waller, LA AF Wheeler, David C. Waller, Lance A. TI Spatial analysis linking landscape features and genetic population structure in cougars (Puma concolor) in the northern Rocky Mountains SO STATISTICS AND ITS INTERFACE LA English DT Article DE Bayesian; Classification; Landscape genetics; Microsatellite; Geneland ID CORRELATED ALLELE FREQUENCIES; MULTILOCUS GENOTYPE DATA; F-STATISTICS; FLOW; DIVERSITY; INFERENCE; DIFFERENTIATION; CALIFORNIA; CARNIVORE; DISTANCE AB Landscape genetics is a field of research that seeks to understand the drivers of the observed spatial distribution of genetic variation in a species of plant or animal using methods from population genetics, landscape ecology, geography, and spatial statistics. One of the important research areas in landscape genetics is to identify landscape barriers to genetic flow. Barriers can limit interaction of organisms and hence lead to genetic structure (i.e. frequency of genotypes) in a population that becomes increasingly spatially structured over time. Here, we investigate model-based spatial methods to assess the relationship between landscape and genotype distributions of cougars (Puma concolor) in Western North America. Previous research has assessed genetic differentiation in cougars in North America using a non-spatial Bayesian clustering model and found evidence of genetic population structure in cougars, with suggestive but indistinct spatial boundaries between subpopulations. To determine if including spatial information on samples in a classification model would refine the observed spatial signal within the genetic population structure, we applied Bayesian classification models to microsatellite loci data with associated spatial locations. The spatial model revealed two clearly differentiated cougar subpopulations, in contrast to the two overlapping subpopulations suggested by methods not accounting for space. We also explored through geographic information systems and generalized linear models whether resulting genetic population structure boundaries aligned with landscape features. The spatial correspondence of genetic subpopulations and a major river and road is suggestive of possible landscape barriers to cougar movement. This study demonstrates that the use of explicit spatial information and Bayesian classification models adds novel insight when investigating genetic population structure in a species. C1 [Waller, Lance A.] Emory Univ, Dept Biost & Bioinformat, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Wheeler, David C.] NCI, Rockville, MD 20852 USA. RP Waller, LA (reprint author), Emory Univ, Dept Biost & Bioinformat, Rollins Sch Publ Hlth, 1518 Clifton Rd,NE,3rd Floor, Atlanta, GA 30322 USA. EM dcwheels@gmail.com; lwaller@memory.edu FU NIEHS (NIH) [R01 ES015525] FX This research is supported in part by NIEHS (NIH) grant R01 ES015525 (LAW). The views presented herein represent those of the author and do not necessarily represent those of NIEHS or NIH. NR 67 TC 1 Z9 2 U1 1 U2 45 PU INT PRESS BOSTON, INC PI SOMERVILLE PA PO BOX 43502, SOMERVILLE, MA 02143 USA SN 1938-7989 J9 STAT INTERFACE JI Stat. Interface PY 2012 VL 5 IS 2 SI SI BP 183 EP 193 PG 11 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA 972II UT WOS:000306270100004 ER PT J AU Li, HL Gail, MH AF Li, Huilin Gail, Mitchell H. TI Power of the Cochran-Armitage trend test when exposure scores are based on empirical quantiles of exposure SO STATISTICS AND ITS INTERFACE LA English DT Article DE Case-control design; Cochran-Armitage trend test; Cohort design; Exposure assessment; Power ID PROPORTIONS AB Epidemiologists often categorize exposures based on quantiles of exposure and use the Cochran-Armitage trend test based on such categories to detect associations between disease and exposure. Power calculations typically assume that the population quantiles are known, but in practice quantiles are often estimated from the sample data. We evaluated the power of the Cochran-Armitage trend test for cohort designs and for case-control designs in which sample quantiles of exposure in the cohort or in controls from a case-control study, respectively, are used to define the cut-points that separate exposure score categories. We give the asymptotic formulas for size and power for the Cochran-Armitage test based on empirical quantiles separately for cohort and case-control designs, together with efficient simulation methods to estimate size and power. Numerical results indicate that estimation of sample quantiles has only a slight effect on power for cohort studies with at least four categories or with more than 280 subjects. However, estimating quantiles can reduce power appreciably in smaller studies with fewer than four exposure categories. For case-control studies of rare diseases, the power loss is limited with more than 120 cases plus controls if the odds ratio comparing the highest exposure category to the lowest category is greater than 0.5. However, if that odd ratio is smaller than 0.5, only samples with more than 360 cases plus controls can guarantee a small loss of power, and increasing the number of exposure categories does not eliminate the loss of power. C1 [Li, Huilin] NYU, Sch Med, Div Biostat, New York, NY 10016 USA. [Gail, Mitchell H.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Li, HL (reprint author), NYU, Sch Med, Div Biostat, 650 1st Ave,Room 547, New York, NY 10016 USA. EM huilin.li@nyumc.org; gailm@mail.nih.gov FU Division of Cancer Epidemiology and Genetics of the National Cancer Institute FX Part of Dr. Li's research was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics of the National Cancer Institute. NR 9 TC 0 Z9 0 U1 1 U2 8 PU INT PRESS BOSTON, INC PI SOMERVILLE PA PO BOX 43502, SOMERVILLE, MA 02143 USA SN 1938-7989 J9 STAT INTERFACE JI Stat. Interface PY 2012 VL 5 IS 2 SI SI BP 237 EP 251 PG 15 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA 972II UT WOS:000306270100008 ER PT J AU Pardini, M Krueger, F Koenigs, M Raymont, V Hodgkinson, C Zoubak, S Goldman, D Grafman, J AF Pardini, M. Krueger, F. Koenigs, M. Raymont, V. Hodgkinson, C. Zoubak, S. Goldman, D. Grafman, J. TI Fatty-acid amide hydrolase polymorphisms and post-traumatic stress disorder after penetrating brain injury SO TRANSLATIONAL PSYCHIATRY LA English DT Article DE endocannabinoids; post-traumatic stress disorder; single-nucleotide polymorphisms ID ENDOCANNABINOID SYSTEM; PREFRONTAL CORTEX; COMBAT VETERANS; INVENTORY; LESIONS; TRAUMA; PTSD AB The past few years have seen an increase in the clinical awareness of post-traumatic stress disorder (PTSD), one of the most disabling and least understood behavioral disorders. Although the biological bases of PTSD are poorly understood, fatty-acid amide hydrolase (FAAH) activity has been linked with arousability and aversive-memories extinction, that is, two key features of PTSD. In this study, we investigated the association between the FAAH genetic polymorphisms and PTSD development and maintenance. We assessed PTSD frequency in a group of male Vietnam war veterans who suffered combat-related penetrating traumatic brain injury, that is, a relatively homogeneous population regarding the nature of the events that led to PTSD. We showed that rs2295633, a single-nucleotide polymorphism of FAAH, was significantly associated with PTSD diagnosis in subjects without lesions in the ventromedial prefrontal cortex. Moreover, the presence of the C allele was associated with more severe re-experiencing of trauma and more negative reported childhood experiences. In conclusion, our data suggest that FAAH has an important role in PTSD through modulation of aversive memories and point to both a novel therapeutic target and a possible risk marker for this condition. Translational Psychiatry (2012) 2, e75; doi:10.1038/tp.2012.1; published online 31 January 2012 C1 [Grafman, J.] Kessler Fdn Res Ctr, Traumat Brain Injury Res Lab, W Orange, NJ 07052 USA. [Pardini, M.; Grafman, J.] Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, NIH, Bethesda, MD USA. [Pardini, M.] Univ Genoa, Dept Neurosci Ophthalmol & Genet, Genoa, Italy. [Pardini, M.] Univ Genoa, Magnet Resonance Res Ctr Nervous Syst Dis, Genoa, Italy. [Krueger, F.] George Mason Univ, Dept Mol Neurosci, Fairfax, VA 22030 USA. [Krueger, F.] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA. [Koenigs, M.] Univ Wisconsin, Dept Psychiat, Madison, WI 53706 USA. [Raymont, V.] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA. [Raymont, V.] Univ London Imperial Coll Sci Technol & Med, Dept Med, London, England. [Hodgkinson, C.; Zoubak, S.; Goldman, D.] NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA. RP Grafman, J (reprint author), Kessler Fdn Res Ctr, Traumat Brain Injury Res Lab, 1199 Pleasant Valley Way, W Orange, NJ 07052 USA. EM FKruger@gmu.edu; jgrafman@kesslerfoundation.org RI Schueter, nicos/A-3625-2014; Pardini, Matteo/F-8414-2010; Goldman, David/F-9772-2010; OI Pardini, Matteo/0000-0002-4740-1982; Goldman, David/0000-0002-1724-5405; Koenigs, Michael/0000-0002-5799-4881 FU US National Institute of Neurological Disorders and Stroke; US Army Medical Research and Material Command FX The work was supported by the US National Institute of Neurological Disorders and Stroke intramural research program and a project grant from the US Army Medical Research and Material Command administrated by the Henry M Jackson Foundation (Vietnam Head Injury Study Phase III: a 30-year post-injury follow-up study). NR 22 TC 7 Z9 7 U1 3 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2158-3188 J9 TRANSL PSYCHIAT JI Transl. Psychiatr. PD JAN PY 2012 VL 2 AR e75 DI 10.1038/tp.2012.1 PG 5 WC Psychiatry SC Psychiatry GA 971PZ UT WOS:000306217600011 PM 22832737 ER PT J AU Moore, HM AF Moore, Helen M. TI Untitled SO BIOPRESERVATION AND BIOBANKING LA English DT Editorial Material C1 NCI, Off Biorepositories & Biospecimen Res, Bethesda, MD 20892 USA. RP Moore, HM (reprint author), NCI, Off Biorepositories & Biospecimen Res, 11400 Rockville Pike,Suite 700, Bethesda, MD 20892 USA. EM moorehe@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1947-5535 J9 BIOPRESERV BIOBANK JI Biopreserv. Biobank. PY 2012 VL 10 IS 3 BP 235 EP 235 DI 10.1089/bio.2012.1031 PG 1 WC Cell Biology; Chemistry, Applied; Medical Laboratory Technology SC Cell Biology; Chemistry; Medical Laboratory Technology GA 966YL UT WOS:000305873200001 PM 24835060 ER PT J AU Prosser, LA Ohlrich, LB Curatalo, LA Alter, KE Damiano, DL AF Prosser, Laura A. Ohlrich, Laurie B. Curatalo, Lindsey A. Alter, Katharine E. Damiano, Diane L. TI Feasibility and preliminary effectiveness of a novel mobility training intervention in infants and toddlers with cerebral palsy SO DEVELOPMENTAL NEUROREHABILITATION LA English DT Article DE Cerebral palsy; rehabilitation; motor development; gross motor function; gait; infants; toddlers; weight support technology; mobility training ID GROSS MOTOR FUNCTION; FUNCTION CLASSIFICATION-SYSTEM; RANDOMIZED CLINICAL-TRIAL; REHABILITATION; CHILDREN; THERAPY; STROKE; ADULTS; STABILITY; OUTCOMES AB Objective: To design a novel mobility training intervention incorporating infant motor learning and neurorehabilitation principles and investigate its feasibility, tolerability and effect on motor development in toddlers with cerebral palsy (CP). Methods: A single-subject research design with repeated measures during 6-week baseline and intervention phases and after treatment withdrawal was used. Five participants attended therapy utilizing novel dynamic weight assistance technology, which allowed practice of motor skills beyond participants' current abilities. Results: Average attendance and engagement rates exceeded 90%. Gains in gross motor function were observed after treatment that exceeded the expected rate in four of the five participants. Rates of motor development during treatment were 10.8, 3.8, 7.0, 15.1, and 0.3 times greater than during baseline for the five participants, respectively. Conclusions: This intervention was tolerated and demonstrated the potential to alter the trajectory of motor development in CP, providing proof of concept for further investigation. C1 [Prosser, Laura A.] Childrens Hosp Philadelphia, Div Rehabil Med, Philadelphia, PA 19104 USA. [Ohlrich, Laurie B.; Curatalo, Lindsey A.; Alter, Katharine E.; Damiano, Diane L.] NIH, Funct & Appl Biomech Sect, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA. [Alter, Katharine E.] Mt Washington Pediat Hosp, Dept Phys Med, Baltimore, MD USA. RP Prosser, LA (reprint author), Childrens Hosp Philadelphia, Div Rehabil Med, 34th & Civ Ctr Blvd,MSC C02-1130, Philadelphia, PA 19104 USA. EM prosserl@email.chop.edu RI Prosser, Laura/C-1242-2009; Damiano, Diane/B-3338-2010 OI Damiano, Diane/0000-0002-2770-5356 FU National Institutes of Health Clinical Center FX The authors acknowledge Cristiane Zampieri-Gallagher, PT, PhD for her assistance with data collection, and Joe Hidler, PhD for software development to allow use of the technology with small children. This research was supported by the Intramural Research Program of the National Institutes of Health Clinical Center. NR 33 TC 10 Z9 10 U1 1 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1751-8423 J9 DEV NEUROREHABIL JI Dev. Neurorehabil. PY 2012 VL 15 IS 4 BP 259 EP 266 DI 10.3109/17518423.2012.687782 PG 8 WC Clinical Neurology; Pediatrics; Rehabilitation SC Neurosciences & Neurology; Pediatrics; Rehabilitation GA 968FY UT WOS:000305963900003 PM 22670679 ER PT J AU Black, A Berg, CD AF Black, Amanda Berg, Christine D. TI Prostate-Specific Antigen Screening for Prostate Cancer in Older Men in the United States of America SO GERONTOLOGY LA English DT Article DE Prostate cancer; Prostate-specific antigen; Older men; Screening; Prostate cancer mortality ID RADICAL PROSTATECTOMY; 30-DAY MORTALITY; ELDERLY-MEN; TRIAL; RISK; COMORBIDITY; DIAGNOSIS; SURVIVAL; CONTEXT; SWEDEN AB Prostate cancer, like many diseases, is more common in older men. Although an estimated 1 in 7 men will be diagnosed with it, the majority of these men will not die from prostate cancer. The latent nature of this disease, the use of screening with prostate-specific antigen (PSA) testing and the greater risk of dying from causes other than prostate cancer contribute to this disparity. As the US population continues to age, prostate cancer screening and disease management presents an increasingly important public health issue. We discuss the current PSA screening recommendations and practices in the USA and the benefits and harms of screening older populations. Copyright (C) 2012 S. Karger AG, Basel C1 [Black, Amanda; Berg, Christine D.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Berg, Christine D.] NCI, Canc Prevent Div, Rockville, MD 20852 USA. RP Berg, CD (reprint author), NCI, Div Canc Epidemiol & Genet, 6130 Execut Blvd,Suite 3112, Rockville, MD 20852 USA. EM bergc@mail.nih.gov RI Berg , Christine/K-1047-2014 NR 36 TC 1 Z9 1 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0304-324X J9 GERONTOLOGY JI Gerontology PY 2012 VL 58 IS 4 BP 331 EP 336 DI 10.1159/000334242 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 969PG UT WOS:000306067100006 PM 22343605 ER PT J AU Diao, GQ Ning, J Qin, J AF Diao, Guoqing Ning, Jing Qin, Jing TI Maximum Likelihood Estimation for Semiparametric Density Ratio Model SO INTERNATIONAL JOURNAL OF BIOSTATISTICS LA English DT Article DE semiparametric density ratio model; conditional likelihood; generalized linear model; nonparametric maximum likelihood estimation; semiparametric efficiency ID SELECTION BIAS MODELS; GOODNESS-OF-FIT; REGRESSION-MODELS; LOGISTIC-REGRESSION; EMPIRICAL DISTRIBUTIONS AB In the statistical literature, the conditional density model specification is commonly used to study regression effects. One attractive model is the semiparametric density ratio model, under which the conditional density function is the product of an unknown baseline density function and a known parametric function containing the covariate information. This model has a natural connection with generalized linear models and is closely related to biased sampling problems. Despite the attractive features and importance of this model, most existing methods are too restrictive since they are based on multi-sample data or conditional likelihood functions. The conditional likelihood approach can eliminate the unknown baseline density but cannot estimate it. We propose efficient estimation procedures based on the nonparametric likelihood. The nonparametric likelihood approach allows for general forms of covariates and estimates the regression parameters and the baseline density simultaneously. Therefore, the nonparametric likelihood approach is more versatile than the conditional likelihood approach especially when estimation of the conditional mean or other quantities of the outcome is of interest. We show that the nonparametric maximum likelihood estimators are consistent, asymptotically normal, and asymptotically efficient. Simulation studies demonstrate that the proposed methods perform well in practical settings. A real example is used for illustration. C1 [Diao, Guoqing] George Mason Univ, Fairfax, VA 22030 USA. [Ning, Jing] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Qin, Jing] NIAID, Biostat Res Brance, NIH, Bethesda, MD 20892 USA. RP Diao, GQ (reprint author), George Mason Univ, Fairfax, VA 22030 USA. FU National Cancer Institute [CA150698] FX The authors are grateful to the Associate Editor and the two anonymous referees for their careful reading of the earlier version of the manuscript, and providing valuable comments and suggestions. The first author's research was supported in part by National Cancer Institute grant CA150698. NR 29 TC 2 Z9 2 U1 0 U2 8 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1557-4679 J9 INT J BIOSTAT JI Int. J. Biostat. PY 2012 VL 8 IS 1 AR 16 DI 10.1515/1557-4679.1372 PG 29 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 968BZ UT WOS:000305953300004 ER PT J AU Subramanian, P Deshpande, M Locatelli-Hoops, S Moghaddam-Taaheri, S Gutierrez, D Fitzgerald, DP Guerrier, S Rapp, M Notario, V Becerra, SP AF Subramanian, P. Deshpande, M. Locatelli-Hoops, S. Moghaddam-Taaheri, S. Gutierrez, D. Fitzgerald, D. P. Guerrier, S. Rapp, M. Notario, V. Becerra, S. P. TI Identification of Pigment Epithelium-Derived Factor Protein Forms with Distinct Activities on Tumor Cell Lines SO JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY LA English DT Article ID FACTOR PEDF; NEUROTROPHIC ACTIVITY; DOWN-REGULATION; BINDING-SITE; GROWTH; METASTASIS; CANCER; OVEREXPRESSION; ANGIOGENESIS; INHIBITION AB Purpose. Pigment epithelium-derived factor (PEDF) is a multifunctional serpin. The purpose of this study is to identify PEDF protein forms and investigate their biological activities on tumor cell lines. Methods. Recombinant human PEDF proteins were purified by cation- and anion-exchange column chromatography. They were subjected to SDS-PAGE, IEF, deglycosylation, heparin affinity chromatography, and limited proteolysis. Cell viability, real-time electrical impedance of cells, and wound healing assays were performed using bladder and breast cancer cell lines, rat retinal R28, and human ARPE-19 cells. Results. Two PEDF protein peaks were identified after anion-exchange column chromatography: PEDF-1 eluting with lower ionic strength than PEDF-2. PEDF-1 had higher pI value and lower apparent molecular weight than PEDF-2. Both PEDF forms were glycosylated, bound to heparin, and had identical patterns by limited proteolysis. However, PEDF-2 emerged as being highly potent in lowering cell viability in all tumor cell lines tested, and in inhibiting tumor and ARPE-19 cell migration. In contrast, PEDF-1 minimally affected tumor cell viability and cell migration but protected R28 cells against death caused by serum starvation. Conclusion. Two distinct biochemical forms of PEDF varying in overall charge have distinct biological effects on tumor cell viability and migration. The existence of PEDF forms may explain the multifunctional modality of PEDF. C1 [Subramanian, P.; Deshpande, M.; Locatelli-Hoops, S.; Moghaddam-Taaheri, S.; Guerrier, S.; Rapp, M.; Becerra, S. P.] NEI, Sect Prot Struct & Funct, LRCMB, Bethesda, MD 20892 USA. [Gutierrez, D.] NCI, CCR, Bethesda, MD 20892 USA. [Fitzgerald, D. P.] Otsuka Maryland Med Labs, Rockville, MD 20850 USA. [Fitzgerald, D. P.; Notario, V.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. RP Becerra, SP (reprint author), NEI, Sect Prot Struct & Funct, LRCMB, Bethesda, MD 20892 USA. EM becerrap@nei.nih.gov FU National Institutes of Health NEI Intramural Research Program; National Cancer Institute Grant [CA134727] FX This work was supported, in part, by National Institutes of Health NEI Intramural Research Program and by National Cancer Institute Grant CA134727 (to V. Notario). The authors thank Natalia Balko for assistance in purification of PEDF protein and Gail Seigel for generously providing R28 cells. NR 34 TC 4 Z9 4 U1 0 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1110-7243 J9 J BIOMED BIOTECHNOL JI J. Biomed. Biotechnol. PY 2012 AR 425907 DI 10.1155/2012/425907 PG 12 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 968TD UT WOS:000306006800001 ER PT J AU Ito, Y Nakamura, T Yanagiba, Y Ramdhan, DH Yamagishi, N Naito, H Kamijima, M Gonzalez, FJ Nakajima, T AF Ito, Yuki Nakamura, Toshiki Yanagiba, Yukie Ramdhan, Doni Hikmat Yamagishi, Nozomi Naito, Hisao Kamijima, Michihiro Gonzalez, Frank J. Nakajima, Tamie TI Plasticizers May Activate Human Hepatic Peroxisome Proliferator-Activated Receptor alpha Less Than That of a Mouse but May Activate Constitutive Androstane Receptor in Liver SO PPAR RESEARCH LA English DT Article ID NUCLEAR RECEPTOR; PPAR-ALPHA; RAT-LIVER; DI(2-ETHYLHEXYL) PHTHALATE; HEPATOCELLULAR PROLIFERATION; IARC EVALUATION; HUMAN RELEVANCE; X-RECEPTOR; CAR; DEHP AB Dibutylphthalate (DBP), di(2-ethylhexyl) phthalate (DEHP), and di(2-ethylhexyl) adipate (DEHA) are used as plasticizers. Their metabolites activate peroxisome proliferator-activated receptor (PPAR) alpha, which may be related to their toxicities. However, species differences in the receptor functions between rodents and human make it difficult to precisely extrapolate their toxicity from animal studies to human. In this paper, we compared the species differences in the activation of mouse and human hepatic PPAR alpha by these plasticizers using wild-type (mPPAR alpha) and humanized PPAR alpha (hPPAR alpha) mice. At 12 weeks old, each genotyped male mouse was classified into three groups, and fed daily for 2 weeks per os with corn oil (vehicle control), 2.5 or 5.0 mmol/kg DBP (696, 1392 mg/kg), DEHP (977, 1953 mg/kg), and DEHA (926, 1853 mg/kg), respectively. Generally, hepatic PPAR alpha of mPPAR alpha mice was more strongly activated than that of hPPAR alpha mice when several target genes involving beta-oxidation of fatty acids were evaluated. Interestingly, all plasticizers also activated hepatic constitutive androstane receptor (CAR) more in hPPAR alpha mice than in mPPAR alpha mice. Taken together, these plasticizers activated mouse and human hepatic PPAR alpha as well as CAR. The activation of PPAR alpha was stronger in mPPAR alpha mice than in hPPAR alpha mice, while the opposite was true of CAR. C1 [Ito, Yuki; Kamijima, Michihiro] Nagoya City Univ, Dept Occupat & Environm Hlth, Grad Sch Med Sci, Mizuho Ku, Nagoya, Aichi 4678601, Japan. [Ito, Yuki; Nakamura, Toshiki; Yanagiba, Yukie; Ramdhan, Doni Hikmat; Yamagishi, Nozomi; Naito, Hisao; Nakajima, Tamie] Nagoya Univ, Dept Occupat & Environm Hlth, Grad Sch Med, Nagoya, Aichi 4668550, Japan. [Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Ito, Y (reprint author), Nagoya City Univ, Dept Occupat & Environm Hlth, Grad Sch Med Sci, Mizuho Ku, Kawasumi 1,Mizuho Cho, Nagoya, Aichi 4678601, Japan. EM yukey@med.nagoya-cu.ac.jp FU Scientific Research from the Japan Society for the Promotion of Science [B. 14370121, 17390169]; Food Safety Commission, Japan [1002]; Health and Labour Sciences Research Grants from Research on Food Safety of the Ministry of Health, Labour and Welfare in Japan FX This study was supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (B. 14370121, 17390169), Food Safety Commission, Japan (1002), and Health and Labour Sciences Research Grants from Research on Food Safety of the Ministry of Health, Labour and Welfare in Japan. NR 46 TC 11 Z9 11 U1 3 U2 12 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-4757 J9 PPAR RES JI PPAR Res. PY 2012 AR 201284 DI 10.1155/2012/201284 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 968YS UT WOS:000306022200001 ER PT S AU Chandrangsu, M Burbelo, PD Iadarola, MJ Smith, PD Morgan, NY AF Chandrangsu, Matt Burbelo, Peter D. Iadarola, Michael J. Smith, Paul D. Morgan, Nicole Y. BE Cullum, BM McLamore, ES TI Development of microLIPS (Luciferase Immunoprecipitation Systems): a novel microfluidic assay for rapid serum antibody detection SO SMART BIOMEDICAL AND PHYSIOLOGICAL SENSOR TECHNOLOGY IX SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Smart Biomedical and Physiological Sensor Technology IX CY APR 26, 2012 CL Baltimore, MD SP SPIE DE antibody detection; microfluidic; immunoassay; biosensor; LIPS; point-of-care ID POLYMER BRUSHES; DIAGNOSTICS; MICROARRAYS; BINDING; DEVICES AB There is considerable interest in the development of rapid, point-of-care antibody detection for the diagnosis of infectious and auto-immune diseases. In this paper, we present work on the development of a self-contained microfluidic format for the Luciferase Immunoprecipitation Systems (LIPS) assay. Whereas the majority of immunoassays for antigen-specific antibodies employ either bacteria- or yeast-expressed proteins and require the use of secondary antibodies, the LIPS technique uses a fusion protein comprised of a Renilla luciferase reporter and the antigen of interest produced via mammalian cell culture, ensuring the addition of mammalian post-translational modifications. Patient serum is mixed with the fusion protein and passed over immobilized Protein A/G; after washing, the only remaining luciferase-tagged antigens are those retained by specific antibodies. These can be quantitatively measured using chemiluminescence upon the introduction of coelenterazine. The assay has been successfully employed for a wide variety of diseases in a microwell format. We report on a recent demonstration of rapid HSV-2 diagnosis with the LIPS assay in a microfluidic format, using one microliter of serum and obtaining results in under ten minutes. We will also discuss recent progress on two fronts, both aimed at the deployment of this technology in the field: first, simplifying assay operation through the automation of flow control using power-free means; and second, efforts to increase signal levels, primarily through strategies to increase antibody binding capacity, in order to move towards portable battery powered electronics. C1 [Chandrangsu, Matt; Smith, Paul D.; Morgan, Nicole Y.] Natl Inst Biomed Imaging & Bioengn, Microfabricat & Microfluid Unit, Bethesda, MD 20892 USA. RP Chandrangsu, M (reprint author), Natl Inst Biomed Imaging & Bioengn, Microfabricat & Microfluid Unit, Bethesda, MD 20892 USA. NR 24 TC 0 Z9 0 U1 1 U2 4 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9045-2 J9 PROC SPIE PY 2012 VL 8367 AR 83670C DI 10.1117/12.919069 PG 11 WC Engineering, Biomedical; Instruments & Instrumentation; Optics; Physics, Applied SC Engineering; Instruments & Instrumentation; Optics; Physics GA BAY34 UT WOS:000306053200008 ER PT J AU O'Seaghdha, CM Hwang, SJ Holden, R Booth, SL Fox, CS AF O'Seaghdha, Conall M. Hwang, Shih-Jen Holden, Rachel Booth, Sarah L. Fox, Caroline S. TI Phylloquinone and Vitamin D Status: Associations with Incident Chronic Kidney Disease in the Framingham Offspring Cohort SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Chronic kidney disease; Vitamin K; Vitamin D ID CORONARY-HEART-DISEASE; STAGE RENAL-DISEASE; GLOMERULAR-FILTRATION-RATE; K EPOXIDE REDUCTASE; VASCULAR CALCIFICATION; D ANALOG; ARTERY CALCIFICATION; BIOCHEMICAL MEASURES; RECEPTOR ANTAGONIST; SERUM CREATININE AB Background: Cardiovascular risk factors are associated with the development of chronic kidney disease (CKD), and CKD and vascular disease are etiologically linked. Evidence suggests deficiencies of vitamins D and K may adversely affect the cardiovascular system, but data from longitudinal studies are lacking. We hypothesized that deficiencies of vitamins D and K may be associated with incident CKD and/or incident albuminuria amongst members of the general population. Methods: We analyzed 1,442 Framingham Heart Study participants (mean age 58 years; 50.5% women), free of CKD (eGFR <60 ml/min/1.73 m(2)), with a mean follow-up of 7.8 years in 2005-2008. Incident albuminuria was defined using sex-specific cut-offs of urine albumin-to-creatinine ratio (>= 17 mg/g men and >= 25 mg/g women). Baseline log plasma phylloquinone (vitamin K-1) and 25(OH) D levels, analyzed as continuous variables and by quartile, were related to risk of incident CKD (n = 108) and incident albuminuria (n = 106) using logistic regression models adjusted for standard risk factors. Results: Participants in the highest phylloquinone quartile (>= 1.78 nmol/l) had an increased risk of CKD (multivariable-adjusted OR Q(4) vs. Q(1) 2.39; p = 0.006) and albuminuria at follow-up (multivariable-adjusted OR Q(4) vs. Q(1) 1.95; p = 0.05), whereas no association was observed with continuous phylloquinone levels for either endpoint. Deficiency of 25(OH) D was not associated with incident CKD or albuminuria in either analysis. Conclusions: Contrary to our hypothesis, higher plasma phylloquinone levels are associated with an increased risk of incident CKD. Whether plasma phylloquinone is a marker for another unmeasured risk factor requires further study. External validation is necessary given the unexpected nature of these results. Copyright (C) 2012 S. Karger AG, Basel C1 [O'Seaghdha, Conall M.; Hwang, Shih-Jen; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [O'Seaghdha, Conall M.; Hwang, Shih-Jen; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA. [O'Seaghdha, Conall M.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. [Booth, Sarah L.] Tufts Univ, Human Nutr Res Ctr Aging, Jean Mayer US Dept Agr, Boston, MA 02111 USA. [Holden, Rachel] Queens Univ, Div Nephrol, Kingston, ON, Canada. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov FU US Department of Agriculture [58-1950-4-401]; National Institute of Health [AG14759]; National Heart, Lung, and Blood Institute [N01-HC-25195] FX This material is based upon work supported by the US Department of Agriculture, under agreement No. 58-1950-4-401, the National Institute of Health (AG14759). The Framingham Heart Study is supported by the National Heart, Lung, and Blood Institute (N01-HC-25195). The funding source had no role in the design, conduct, or reporting of the study or in the decision to submit the report for publication. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the US Department of Agriculture. NR 51 TC 7 Z9 7 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2012 VL 36 IS 1 BP 68 EP 77 DI 10.1159/000339005 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 966BR UT WOS:000305812300009 PM 22722822 ER PT S AU Sneddon, TP Church, DM AF Sneddon, Tam P. Church, Deanna M. BE Feuk, L TI Online Resources for Genomic Structural Variation SO GENOMIC STRUCTURAL VARIANTS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Copy number variant; Insertion/deletion; Structural variation; dbVar; DGVa; Database of Genomic Variants ID COPY NUMBER VARIATION; SEQUENCE VARIATION; ARRAY CGH; POLYMORPHISM; MICRODELETION; VARIANTS; DATABASE; DISEASE; AUTISM; MAP AB Genomic structural variation (SV) can be thought of on a continuum from a single base pair insertion/deletion (INDEL) to large megabase-scale rearrangements involving insertions, deletions, duplications, inversions, or translocations of whole chromosomes or chromosome arms. These variants can occur in coding or noncoding DNA, they can be inherited or arise sporadically in the germline or somatic cells. Many of these events are segregating in the population and can be considered common alleles while others are new alleles and thus rare events. All species studied to date harbor structural variants and these may be benign, contributing to phenotypes such as sensory perception and immunity, or pathogenic resulting in genomic disorders including DiGeorge/velocardiofacial, Smith-Margenis, Williams-Beuren, and Prader-Willi syndromes. As structural variants are identified, validated, and their significance, origin, and prevalence are elucidated, it is of critical importance that these data be collected and collated in a way that can be easily accessed and analyzed. This chapter describes current structural variation online resources (see Fig. 1 and Table 1), highlights the challenges in capturing, storing, and displaying SV data, and discusses how dbVar and DGVa, the genomic structural variation databases developed at NCBI and EBI, respectively, were designed to address these issues. C1 [Sneddon, Tam P.; Church, Deanna M.] NIH, NCBI, Natl Lib Med, Bethesda, MD 20892 USA. RP Sneddon, TP (reprint author), NIH, NCBI, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. OI Sneddon, Tam Paterson/0000-0003-1137-8992 FU Intramural NIH HHS [Z99 LM999999] NR 70 TC 3 Z9 3 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-506-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 838 BP 273 EP 289 DI 10.1007/978-1-61779-507-7_13 D2 10.1007/978-1-61779-507-7 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BZG39 UT WOS:000301511800013 PM 22228017 ER PT J AU DellaValle, CT Hoppin, JA Hines, CJ Andreotti, G Alavanja, MCR AF DellaValle, Curt T. Hoppin, Jane A. Hines, Cynthia J. Andreotti, Gabriella Alavanja, Michael C. R. TI Risk-Accepting Personality and Personal Protective Equipment Use Within the Agricultural Health Study SO JOURNAL OF AGROMEDICINE LA English DT Article DE Agricultural Health Study; personal protective equipment; pesticide; risk-accepting behavior ID PESTICIDE APPLICATORS; CANCER-RISK; SAFE USE; FARMERS; BEHAVIORS; EXPOSURE; SMALLHOLDERS; FARMWORKERS; CALIFORNIA; KNOWLEDGE AB Pesticide exposures can be reduced by use of personal protective equipment as well as proper mixing and application practices. The authors examined the effects of risk-accepting personality on personal protective equipment (PPE) use and mixing and application practices among private pesticide applicators and their spouses within the Agricultural Health Study (AHS) in Iowa and North Carolina and commercial applicators in Iowa. The AHS follow-up questionnaire included four questions designed to assess attitudes toward risk. Analysis was limited to those who were currently working on a farm or registered as a commercial applicator and indicated current pesticide use (n = 25,166). Respondents who answered three or more questions in the affirmative (private applicators: n = 4160 [21%]; commercial applicators: n = 199 [14%]; spouses: n = 829 [23%]) were classified as having a risk-accepting personality. Logistic regression was used to evaluate specific work practices associated with risk-accepting attitudes. Among private applicators, the likelihood of using any PPE when mixing or loading pesticides was lower among risk-acceptors compared to risk-averse individuals (odds ratio [OR] = 0.72, 95% confidence interval [CI]: 0.65-0.79). A similar relationship was observed among commercial applicators (OR = 0.77, 95% CI: 0.34-1.77) but not among spouses (OR = 1.09, 95% CI: 0.90-1.33). Among private applicators, risk-acceptors were more likely than the risk-averse to apply pesticides within 50 feet of the home (OR = 1.21, 95% CI: 1.01-1.44), compared to further than 1/4 mile. These findings suggest that the decisions to use personal protective equipment and properly handle/apply pesticides may be driven by risk-accepting personality traits. C1 [DellaValle, Curt T.; Andreotti, Gabriella; Alavanja, Michael C. R.] Natl Canc Inst, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD USA. [Hoppin, Jane A.] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. [Hines, Cynthia J.] NIOSH, Cincinnati, OH 45226 USA. RP DellaValle, CT (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, NIH DHHS, 6120 Execut Blvd,EPS 8011, Bethesda, MD 20892 USA. EM dellavallec@mail.nih.gov FU National Institutes of Health; National Institute of Environmental Health Sciences [Z01-ES049030]; National Cancer Institute [Z01-CP010119] FX This work was supported by the intramural research program of the National Institutes of Health, the National Institute of Environmental Health Sciences (Z01-ES049030) and National Cancer Institute (Z01-CP010119). NR 25 TC 3 Z9 3 U1 2 U2 13 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1059-924X J9 J AGROMEDICINE JI J. Agromedicine PY 2012 VL 17 IS 3 BP 264 EP 276 DI 10.1080/1059924X.2012.686390 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 965IS UT WOS:000305761700002 PM 22732067 ER PT J AU Wang, H Gao, HK Guo, N Niu, G Ma, Y Kiesewetter, DO Chen, XY AF Wang, Hui Gao, Haokao Guo, Ning Niu, Gang Ma, Ying Kiesewetter, Dale O. Chen, Xiaoyuan TI Site-Specific Labeling of scVEGF with Fluorine-18 for Positron Emission Tomography Imaging SO THERANOSTICS LA English DT Article DE Site-specific protein labeling; FBEM-scVEGF; PET imaging; VEGFR ID TUMOR-ANGIOGENESIS; VEGF; EXPRESSION; CANCER; VASCULATURE; BEVACIZUMAB; XENOGRAFT; AGENTS; GENES AB Vascular endothelial growth factor (VEGF) is one of the most important mediators of angiogenesis. Single-chain (sc)-VEGF protein containing an N-terminal Cys-tag has been designed for site-specific modification with a variety of imaging and therapeutic moieties. Site-specific labeling of scVEGF with thiol-reactive prosthetic group, N-[2-(4-F-18-fluorobenzamido) ethyl] maleimide ([F-18]FBEM) for positron emission tomography (PET) imaging of VEFGR may provide a new tracer which has great potential for clinical translation. Methods: [F-18]FBEM-scVEGF was synthesized by site-specific conjugation of F-18-FBEM to a thiol group in Cys-tag of scVEGF at room temperature. The functional activity after labeling was tested by immunofluorescence staining, cellular uptake and efflux. The tumor targeting and in vivo properties were evaluated by biodistribution and microPET studies in tumor-bearing mice. Results: The radiolabeling yield and specific activity of [F-18]FBEM-scVEGF were 20.6 +/- 15.1% (based on starting [F-18]FBEM, uncorrected, n = 5) and 58.8 +/- 12.4 GBq/mu mol, respectively. Noninvasive microPET and direct tissue sampling experiments demonstrated that [F-18]FBEM-scVEGF had VEGFR specific tumor uptake in MDA-MB-435, U87MG and 4T1 xenograft models. The optimal tumor uptake was achieved at 2 h p.i., which can be partially, but significantly blocked by co-injection of non-labeled scVEGF protein. Overall, [F-18]FBEM-scVEGF showed VEGFR specific tumor uptake. Conclusion: The scVEGF was site-specifically labeled with F-18 via [F-18]FBEM prosthetic group and the tracer [F-18]FBEM-scVEGF exhibited high receptor binding affinity and tumor targeting efficacy. Further study of [F-18]FBEM-scVEGF to evaluate angiogenesis in cancer and other disease types is warranted. C1 [Wang, Hui; Gao, Haokao; Guo, Ning; Niu, Gang; Ma, Ying; Kiesewetter, Dale O.; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. RP Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, 31 Ctr Dr,Suite 1C14, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov FU Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institute of Health (NIH); Radiology and Imaging Sciences Department, NIH Clinical Center; Intramural Research Program, NIBIB, NIH FX This work was supported by the Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institute of Health (NIH). H. W. holds an Imaging Science Training Fellowship, which is jointly supported by the Radiology and Imaging Sciences Department, NIH Clinical Center and the Intramural Research Program, NIBIB, NIH. We acknowledged the NIH/CC cyclotron facility for isotope production. NR 20 TC 16 Z9 16 U1 3 U2 11 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2012 VL 2 IS 6 BP 607 EP 617 DI 10.7150/thno.4611 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 965JY UT WOS:000305765100006 PM 22768028 ER PT S AU Hall, FS Markou, A Levin, ED Uhl, GR AF Hall, F. Scott Markou, Athina Levin, Edward D. Uhl, George R. BE Uhl, GR TI Mouse models for studying genetic influences on factors determining smoking cessation success in humans SO ADDICTION REVIEWS SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE nicotine; smoking cessation; quit success; genetics ID NICOTINIC ACETYLCHOLINE-RECEPTOR; GENOME-WIDE ASSOCIATION; CONDITIONED PLACE PREFERENCE; ANXIETY-LIKE BEHAVIOR; SPATIAL WORKING-MEMORY; REACTION-TIME-TASK; CALCIUM-CHANNEL ANTAGONISTS; WITHDRAWAL-INDUCED DEFICITS; ACOUSTIC STARTLE RESPONSE; INDUCED LEARNING-DEFICITS AB Humans differ in their ability to quit using addictive substances, including nicotine, the major psychoactive ingredient in tobacco. For tobacco smoking, a substantial body of evidence, largely derived from twin studies, indicates that approximately half of these individual differences in ability to quit are heritable genetic influences that likely overlap with those for other addictive substances. Both twin and molecular genetic studies support overlapping influences on nicotine addiction vulnerability and smoking cessation success, although there is little formal analysis of the twin data that support this important point. None of the current datasets provides clarity concerning which heritable factors might provide robust dimensions around which individuals differ in ability to quit smoking. One approach to this problem is to test mice with genetic variations in genes that contain human variants that alter quit success. This review considers which features of quit success should be included in a comprehensive approach to elucidate the genetics of quit success, and how those features may be modeled in mice. C1 [Markou, Athina] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Levin, Edward D.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [Hall, F. Scott; Uhl, George R.] NIDA, Mol Neurobiol Branch, NIH IRP, Baltimore, MD USA. RP Uhl, GR (reprint author), NIDA IRP, Mol Neurobiol Branch, 333 Cassell Dr, Baltimore, MD 21224 USA. EM guhl@intra.nida.nih.gov RI Hall, Frank/C-3036-2013 OI Hall, Frank/0000-0002-0822-4063 FU Intramural NIH HHS [Z99 DA999999]; NIDA NIH HHS [DA 027840, DA023209, P50 DA027840, R01 DA023209, U19 DA027990] NR 327 TC 4 Z9 4 U1 5 U2 11 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 BN 978-1-57331-850-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2012 VL 1248 BP 39 EP 70 DI 10.1111/j.1749-6632.2011.06415.x PG 32 WC Substance Abuse; Multidisciplinary Sciences SC Substance Abuse; Science & Technology - Other Topics GA BAV99 UT WOS:000305677500003 PM 22304675 ER PT S AU Morales, M Pickel, VM AF Morales, Marisela Pickel, Virginia M. BE Uhl, GR TI Insights to drug addiction derived from ultrastructural views of the mesocorticolimbic system SO ADDICTION REVIEWS SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE drug addiction; mesocorticolimbic dopamine system; prefrontal cortex; ventral tegmental area; nucleus accumbens ID VENTRAL TEGMENTAL AREA; MIDBRAIN DOPAMINE NEURONS; RAT PREFRONTAL CORTEX; LONG-TERM POTENTIATION; NEUROTENSIN-LIKE IMMUNOREACTIVITY; GLUTAMATE-LIKE IMMUNOREACTIVITY; ELECTRON-MICROSCOPIC ANALYSIS; AMPA RECEPTOR PLASTICITY; NUCLEUS-ACCUMBENS-SEPTI; GABA-CONTAINING NEURONS AB Drugs of abuse increase the release of dopamine from mesocorticolimbic neurons in the ventral tegmental area. Thus, insights into the cytoarchitecture and the synaptic circuitry affecting the activity of dopaminergic neurons in this area are fundamental for understanding the commonalities produced by mechanistically distinct drugs of abuse. Electron microscopic immunolabeling has provided these insights and also shown the critical relationships between the dopaminergic axon terminals and their targeted neurons in the prefrontal cortex and in the both the dorsal and ventral striatum. These brain regions are among those where dopamine and associated neurotransmitters are most implicated in the transition from recreational to compulsive consumption of reinforcing drugs. Thus, the synaptic circuitry and drug-induced plasticity occurring in the ventral tegmental area and in dopamine-targeted regions are reviewed, as both are essential for understanding the long-lasting changes produced by addictive substances. C1 [Morales, Marisela] NIDA, Neuronal Networks Sect, NIH, Intramural Res Program, Baltimore, MD 21224 USA. [Pickel, Virginia M.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. RP Morales, M (reprint author), NIDA, Neuronal Networks Sect, NIH, Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM mmorales@intra.nida.nih.gov NR 196 TC 29 Z9 29 U1 0 U2 16 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 BN 978-1-57331-850-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2012 VL 1248 BP 71 EP 88 DI 10.1111/j.1749-6632.2011.06299.x PG 18 WC Substance Abuse; Multidisciplinary Sciences SC Substance Abuse; Science & Technology - Other Topics GA BAV99 UT WOS:000305677500004 PM 22171551 ER PT S AU Albert, DA Ward, A Allweiss, P Graves, DT Knowler, WC Kunzel, C Leibel, RL Novak, KF Oates, TW Papapanou, PN Schmidt, AM Taylor, GW Lamster, IB Lalla, E AF Albert, David A. Ward, Angela Allweiss, Pamela Graves, Dana T. Knowler, William C. Kunzel, Carol Leibel, Rudolph L. Novak, Karen F. Oates, Thomas W. Papapanou, Panos N. Schmidt, Ann Marie Taylor, George W. Lamster, Ira B. Lalla, Evanthia GP Annals NY Acad Sci TI Diabetes and oral disease: implications for health professionals SO ANNALS MEETING REPORTS SE Annals of the New York Academy of Sciences LA English DT Article DE diabetes; oral disease; meeting report; complications; periodontal disease; management; interprofessional care ID QUALITY-OF-LIFE; PERIODONTAL-DISEASE; GLYCEMIC CONTROL; DENTAL OFFICE; PERINATAL OUTCOMES; PREGNANCY OUTCOMES; FOLLOW-UP; BONE LOSS; MELLITUS; PREVENTION AB "Diabetes and Oral Disease: Implications for Health Professionals" was a one-day conference convened by the Columbia University College of Dental Medicine, the Columbia University College of Physicians and Surgeons, and the New York Academy of Sciences on May 4, 2011 in New York City. The program included an examination of the bidirectional relationship between oral disease and diabetes and the interprofessional working relationships for the care of people who have diabetes. The overall goal of the conference was to promote discussion among the healthcare professions who treat people with diabetes, encourage improved communication and collaboration among them, and, ultimately, improve patient management of the oral and overall effects of diabetes. Attracting over 150 members of the medical and dental professions from eight different countries, the conference included speakers from academia and government and was divided into four sessions. This report summarizes the scientific presentations of the event.(a) C1 [Albert, David A.; Ward, Angela; Kunzel, Carol; Papapanou, Panos N.; Lamster, Ira B.; Lalla, Evanthia] Columbia Univ, Coll Dent Med, New York, NY 10032 USA. [Allweiss, Pamela] Ctr Dis Control & Prevent, Atlanta, GA USA. [Allweiss, Pamela] Univ Kentucky, Coll Publ Hlth, Lexington, KY USA. [Graves, Dana T.] Univ Penn, Sch Dent Med, Philadelphia, PA 19104 USA. [Knowler, William C.] NIDDKD, NIH, Phoenix, AZ USA. [Leibel, Rudolph L.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Novak, Karen F.] Amer Dent Educ Assoc, Washington, DC USA. [Oates, Thomas W.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Schmidt, Ann Marie] NYU, Sch Med, New York, NY USA. [Taylor, George W.] Univ Calif San Francisco, Sch Dent, San Francisco, CA USA. RP Albert, DA (reprint author), Columbia Univ, Coll Dent Med, 630 W 168th St,Box 20, New York, NY 10032 USA. EM daa1@columbia.edu; el94@columbia.edu FU National Institute of Diabetes and Digestive and Kidney Diseases FX Dr. Knowler is supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. NR 71 TC 6 Z9 7 U1 2 U2 21 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 BN 978-1-57331-886-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2012 VL 1255 BP 1 EP 15 DI 10.1111/j.1749-6632.2011.06460.x PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BAV38 UT WOS:000305606100001 PM 22409777 ER PT J AU Shen, H Luo, Y Liu, HS Yu, SJ Yang, Y Hoffer, BJ Wang, Y AF Shen, H. Luo, Y. Liu, H-S. Yu, S. J. Yang, Y. Hoffer, B. J. Wang, Y. TI Posttreatment of Stroke With Cocaine- and Amphetamine-Regulated Transcript SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 19th Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair CY APR 26-28, 2012 CL Clearwater Beach, FL SP Amer Soc Neural Therapy & Repair C1 [Shen, H.; Luo, Y.; Liu, H-S.; Yu, S. J.; Yang, Y.; Hoffer, B. J.; Wang, Y.] Natl Inst Drug Abuse, Neural Protect & Regenerat Sect, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2012 VL 21 IS 4 BP 790 EP 790 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 961VP UT WOS:000305497900063 ER PT J AU Zhang, Y Granholm, AC Shan, L Diaz, O Malik, N Olson, L Huh, K Hoffer, BJ Lupica, CR Hoffman, AF Backman, CM AF Zhang, Y. Granholm, A-C Shan, L. Diaz, O. Malik, N. Olson, L. Huh, K. Hoffer, B. J. Lupica, C. R. Hoffman, A. F. Baeckman, C. M. TI Enhanced Dopamine Graft Neuron Survival, Dopaminergic Function, and Neurite Outgrowth in Mitopark Mice Transplanted With Embryonic PTEN-Deficient Dopamine Neurons SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 19th Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair CY APR 26-28, 2012 CL Clearwater Beach, FL SP Amer Soc Neural Therapy & Repair C1 [Zhang, Y.; Shan, L.; Diaz, O.; Malik, N.; Huh, K.; Hoffer, B. J.; Baeckman, C. M.] NIDA, Integrat Neurosci Res Branch, NIH, Baltimore, MD USA. [Granholm, A-C] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Granholm, A-C] Med Univ S Carolina, Ctr Aging, Charleston, SC 29425 USA. [Olson, L.] NIDA, Cellular Neurobiol Res Branch, NIH, Baltimore, MD USA. [Lupica, C. R.; Hoffman, A. F.] Karolinska Inst, Dept Neurosci, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 1 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2012 VL 21 IS 4 BP 796 EP 796 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 961VP UT WOS:000305497900080 ER PT J AU Morozova, TV Goldman, D Mackay, TFC Anholt, RRH AF Morozova, Tatiana V. Goldman, David Mackay, Trudy F. C. Anholt, Robert R. H. TI The genetic basis of alcoholism: multiple phenotypes, many genes, complex networks SO GENOME BIOLOGY LA English DT Review DE Addiction; alcohol sensitivity; disease susceptibility; genome-wide association studies; human genetics; model organisms ID GENOME-WIDE ASSOCIATION; QUANTITATIVE TRAIT LOCI; ADDICTION MOLECULAR-GENETICS; ETHANOL SENSITIVITY; DROSOPHILA-MELANOGASTER; FRONTAL-CORTEX; RECEPTOR GENE; TRANSCRIPTIONAL RESPONSE; BEHAVIORAL-RESPONSES; COCAINE DEPENDENCE AB Alcoholism is a significant public health problem. A picture of the genetic architecture underlying alcohol-related phenotypes is emerging from genome-wide association studies and work on genetically tractable model organisms. C1 [Morozova, Tatiana V.; Anholt, Robert R. H.] N Carolina State Univ, Dept Biol, Raleigh, NC 27695 USA. [Morozova, Tatiana V.; Mackay, Trudy F. C.; Anholt, Robert R. H.] N Carolina State Univ, WM Keck Ctr Behav Biol, Raleigh, NC 27695 USA. [Goldman, David] NIAAA, NIH, Bethesda, MD 20892 USA. [Mackay, Trudy F. C.; Anholt, Robert R. H.] N Carolina State Univ, Dept Genet, Raleigh, NC 27695 USA. RP Anholt, RRH (reprint author), N Carolina State Univ, Dept Biol, Box 7617, Raleigh, NC 27695 USA. EM anholt@ncsu.edu RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU National Institutes of Health [AA016569] FX This work was supported by grant AA016569 (TFCM and RRHA) from the National Institutes of Health. We apologize to those authors whose papers have not been cited in this review. Due to space restrictions we were not able to refer to all publications in the alcohol-related field. NR 103 TC 22 Z9 22 U1 2 U2 24 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-7596 J9 GENOME BIOL JI Genome Biol. PY 2012 VL 13 IS 2 AR 239 DI 10.1186/gb-2012-13-2-239 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 960MD UT WOS:000305391700013 PM 22348705 ER PT J AU Siddiqui, S Fang, M Ni, B Lu, DY Martin, B Maudsley, S AF Siddiqui, Sana Fang, Meng Ni, Bin Lu, Daoyuan Martin, Bronwen Maudsley, Stuart TI Central Role of the EGF Receptor in Neurometabolic Aging SO INTERNATIONAL JOURNAL OF ENDOCRINOLOGY LA English DT Review ID EPIDERMAL-GROWTH-FACTOR; PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE-ACTIVITY; PANCREATIC-ISLET CELLS; CENTRAL NERVOUS-SYSTEM; LIVER PLASMA-MEMBRANE; DIETARY ENERGY-INTAKE; FACTOR MESSENGER-RNA; ALPHA TGF-ALPHA; ALZHEIMERS-DISEASE AB A strong connection between neuronal and metabolic health has been revealed in recent years. It appears that both normal and pathophysiological aging, as well as neurodegenerative disorders, are all profoundly influenced by this "neurometabolic" interface, that is, communication between the brain and metabolic organs. An important aspect of this "neurometabolic" axis that needs to be investigated involves an elucidation of molecular factors that knit these two functional signaling domains, neuronal and metabolic, together. This paper attempts to identify and discuss a potential keystone signaling factor in this "neurometabolic" axis, that is, the epidermal growth factor receptor (EGFR). The EGFR has been previously demonstrated to act as a signaling nexus for many ligand signaling modalities and cellular stressors, for example, radiation and oxidative radicals, linked to aging and degeneration. The EGFR is expressed in a wide variety of cells/tissues that pertain to the coordinated regulation of neurometabolic activity. EGFR signaling has been highlighted directly or indirectly in a spectrum of neurometabolic conditions, for example, metabolic syndrome, diabetes, Alzheimer's disease, cancer, and cardiorespiratory function. Understanding the positioning of the EGFR within the neurometabolic domain will enhance our appreciation of the ability of this receptor system to underpin highly complex physiological paradigms such as aging and neurodegeneration. C1 [Siddiqui, Sana; Fang, Meng; Ni, Bin; Lu, Daoyuan; Maudsley, Stuart] NIA, Receptor Pharmacol Unit, Baltimore, MD 21224 USA. [Martin, Bronwen] NIA, Metab Unit, Baltimore, MD 21224 USA. RP Maudsley, S (reprint author), NIA, Receptor Pharmacol Unit, Baltimore, MD 21224 USA. EM maudsleyst@mail.nih.gov FU Intramural Research Program of the National Institute on Aging, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. NR 183 TC 4 Z9 4 U1 1 U2 5 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-8337 J9 INT J ENDOCRINOL JI Int. J. Endocrinol. PY 2012 AR 739428 DI 10.1155/2012/739428 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 963NF UT WOS:000305627000001 ER PT J AU Michaelides, M Thanos, PK Volkow, ND Wang, GJ AF Michaelides, Michael Thanos, Panayotis K. Volkow, Nora D. Wang, Gene-Jack TI Dopamine-related frontostriatal abnormalities in obesity and binge-eating disorder: Emerging evidence for developmental psychopathology SO INTERNATIONAL REVIEW OF PSYCHIATRY LA English DT Article ID FOOD STIMULI; NEURAL MECHANISMS; RAT MODEL; GASTRIC STIMULATION; PREFRONTAL CORTEX; REWARD CIRCUITRY; BRAIN ACTIVATION; DORSAL STRIATUM; CALORIE FOODS; WEIGHT-GAIN AB Obesity and binge-eating disorder (BED) frequently arise in adolescence, which is a critical developmental time period where self-regulatory processes are formed. Indeed, both obesity and BED are thought to arise partly due to deficits in self-regulatory processes (i.e. lack of inhibitory control to overeat or binge). Recent neuroimaging studies have implicated the frontal cortex, a brain region involved in regulating inhibitory-control, and the striatum, which is thought to be involved in food reward, satiety and pleasure, in mediating responses to food cues and feeding in normal-weight individuals as well as obese and BED subjects. Intriguingly, frontostriatal circuits have been observed to be preferentially modulated in obese adults and similar associations have been observed in obese/overweight adolescents. Furthermore, brain dopamine (DA) is selectively altered in striatum in obese relative to normal-weight individuals, and frontostriatal regions constitute a major component of DA circuitry. The aim of this review will be to present the main findings from neuroimaging studies in obese and BED adults and adolescents, as these relate to frontostriatal circuitry, and to emphasize the potential for using functional neuroimaging in both humans and animals with the scope of obtaining information on developmental and molecular contributions to obesity and BED. C1 [Wang, Gene-Jack] Brookhaven Natl Lab, Dept Med, Behav Neuropharmacol & Neuroimaging Lab, Upton, NY 11973 USA. [Michaelides, Michael] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY USA. [Wang, Gene-Jack] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Thanos, Panayotis K.; Volkow, Nora D.] NIAAA, Lab Neuroimaging, Bethesda, MD USA. [Thanos, Panayotis K.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. [Thanos, Panayotis K.] SUNY Stony Brook, Dept Neurosci, Stony Brook, NY 11794 USA. RP Wang, GJ (reprint author), Brookhaven Natl Lab, Dept Med, Behav Neuropharmacol & Neuroimaging Lab, 30 Bell Ave,Bldg 490, Upton, NY 11973 USA. EM gjwang@bnl.gov RI Michaelides, Michael/K-4736-2013 OI Michaelides, Michael/0000-0003-0398-4917 FU Intramural NIH HHS [ZIA AA000550-08]; NIAAA NIH HHS [Z01 AA000550]; NIDA NIH HHS [5T32DA007135, R01DA00280, R01DA7092, T32 DA007135]; NIMH NIH HHS [R01 MH066961, R01MH66961] NR 53 TC 15 Z9 15 U1 6 U2 25 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0954-0261 J9 INT REV PSYCHIATR JI Int. Rev. Psych. PY 2012 VL 24 IS 3 BP 211 EP 218 DI 10.3109/09540261.2012.679918 PG 8 WC Psychiatry SC Psychiatry GA 962XJ UT WOS:000305582600005 PM 22724642 ER PT J AU Zhao, WN He, J Zhang, YM Ito, Y Su, Q Sun, WJ AF Zhao, Wenna He, Jiao Zhang, Yongmin Ito, Yoichiro Su, Qi Sun, Wenji TI PREPARATIVE ISOLATION AND PURIFICATION OF ALKALOIDS FROM PICRASMA QUASSIODES (D. DON) BENN. BY HIGH-SPEED COUNTERCURRENT CHROMATOGRAPHY SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE alkaloids; high-speed countercurrent chromatography; Picrasma quassiodes; 1-methoxycarbonyl-beta-carboline; 3-methylcanthin-2,6-dione; 4-methoxy-5-hydroxycanthin-6-one ID BETA-CARBOLINE ALKALOIDS; SEPARATION AB By using a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (2: 2: 2: 2, v/v/v/v), a high-speed counter-current chromatography technique was successfully used for isolation and purification of three alkaloids from Picrasma quassiodes (D. Don) Benn. for the first time. A total of 22.1 mg of 3-methylcanthin-2,6-dione, 4.9 mg of 4-methoxy-5-hydroxycanthin-6-one and 1.2 mg of 1-methoxycarbonyl-beta-carboline were obtained from 100 mg of crude extract of Picrasma quassiodes (D. Don) Benn. in less than 5 hr, with purities of 89.30%, 98.32%, and 98.19%, respectively. The target compounds were identified by ESI-MS, H-1 NMR, and C-13 NMR. C1 [Zhao, Wenna; He, Jiao; Su, Qi; Sun, Wenji] NW Univ Xian, Biomed Key Lab Shaanxi Prov, Xian 710069, Peoples R China. [Zhang, Yongmin] Univ Paris 06, Inst Parisien Chim Mol, Paris, France. [Ito, Yoichiro] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. RP Sun, WJ (reprint author), NW Univ Xian, Biomed Key Lab Shaanxi Prov, 229 Taibai N Rd, Xian 710069, Peoples R China. EM cxbml@nwu.edu.cn FU Northwest University Graduate Innovation and Creativity Funds of the People's Republic of China [10YZZ34] FX The authors thank Prof. Zhongfu Wang of the Key Laboratory of Resource Biology and Biotechnology in western China for assistance in ESI-MS experiments. Financial support from Northwest University Graduate Innovation and Creativity Funds of the People's Republic of China (10YZZ34) is gratefully acknowledged. NR 14 TC 2 Z9 2 U1 2 U2 16 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2012 VL 35 IS 11 BP 1597 EP 1606 DI 10.1080/10826076.2011.621150 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 962TC UT WOS:000305566900010 PM 22798720 ER PT S AU Ghosh, P Antani, SK Long, LR Thoma, GR AF Ghosh, Payel Antani, Sameer K. Long, L. Rodney Thoma, George R. BE VanGinneken, B Novak, CL TI Unsupervised Segmentation of Lungs from Chest Radiographs SO MEDICAL IMAGING 2012: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Computer-Aided Diagnosis CY FEB 07-09, 2012 CL San Diego, CA SP SPIE, Agilent Technol, Diamond SA, DQE Instruments Inc, eMagin, Isuzu Glass Co Ltd, Medtron, Inc, Ocean Thin Films Inc DE Chest radiographs; Segmentation; Region characterization; Cellular automata ID DIAGNOSIS AB This paper describes our preliminary investigations for deriving and characterizing coarse-level textural regions present in the lung field on chest radiographs using unsupervised grow-cut (UGC), a cellular automaton based unsupervised segmentation technique. The segmentation has been performed on a publicly available data set of chest radiographs. The algorithm is useful for this application because it automatically converges to a natural segmentation of the image from random seed points using low-level image features such as pixel intensity values and texture features. Our goal is to develop a portable screening system for early detection of lung diseases for use in remote areas in developing countries. This involves developing automated algorithms for screening x-rays as normal/abnormal with a high degree of sensitivity, and identifying lung disease patterns on chest x-rays. Automatically deriving and quantitatively characterizing abnormal regions present in the lung field is the first step toward this goal. Therefore, region-based features such as geometrical and pixel-value measurements were derived from the segmented lung fields. In the future, feature selection and classification will be performed to identify pathological conditions such as pulmonary tuberculosis on chest radiographs. Shape-based features will also be incorporated to account for occlusions of the lung field and by other anatomical structures such as the heart and diaphragm. C1 [Ghosh, Payel; Antani, Sameer K.; Long, L. Rodney; Thoma, George R.] NIH, Lister Hill Ctr Biomed Commun, US Natl Lib Med, Bethesda, MD 20892 USA. RP Ghosh, P (reprint author), NIH, Lister Hill Ctr Biomed Commun, US Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. OI Antani, Sameer/0000-0002-0040-1387 NR 12 TC 0 Z9 0 U1 0 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8964-7 J9 PROC SPIE PY 2012 VL 8315 AR 831532 DI 10.1117/12.911574 PG 6 WC Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BAT32 UT WOS:000305454600109 ER PT S AU Liu, JM Hua, J Chellappa, V Petrick, N Sahiner, B Farooqui, M Marti, G Wiestner, A Summers, RM AF Liu, Jiamin Hua, Jeremy Chellappa, Vivek Petrick, Nicholas Sahiner, Berkman Farooqui, Mohammed Marti, Gerald Wiestner, Adrian Summers, Ronald M. BE VanGinneken, B Novak, CL TI Automatic Detection of Axillary Lymphadenopathy on CT Scans of Untreated Chronic Lymphocytic Leukemia Patients SO MEDICAL IMAGING 2012: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Computer-Aided Diagnosis CY FEB 07-09, 2012 CL San Diego, CA SP SPIE, Agilent Technol, Diamond SA, DQE Instruments Inc, eMagin, Isuzu Glass Co Ltd, Medtron Inc, Ocean Thin Films Inc DE lymph node detection; multi-scale Hessian analysis; lymphadenopathy ID SEGMENTATION; IMAGES; QUANTITATION AB Patients with chronic lymphocytic leukemia (CLL) have an increased frequency of axillary lymphadenopathy. Pretreatment CT scans can be used to upstage patients at the time of presentation and post-treatment CT scans can reduce the number of complete responses. In the current clinical workflow, the detection and diagnosis of lymph nodes is usually performed manually by examining all slices of CT images, which can be time consuming and highly dependent on the observer's experience. A system for automatic lymph node detection and measurement is desired. We propose a computer aided detection (CAD) system for axillary lymph nodes on CT scans in CLL patients. The lung is first automatically segmented and the patient's body in lung region is extracted to set the search region for lymph nodes. Multi-scale Hessian based blob detection is then applied to detect potential lymph nodes within the search region. Next, the detected potential candidates are segmented by fast level set method. Finally, features are calculated from the segmented candidates and support vector machine (SVM) classification is utilized for false positive reduction. Two blobness features, Frangi's and Li's, are tested and their free-response receiver operating characteristic (FROC) curves are generated to assess system performance. We applied our detection system to 12 patients with 168 axillary lymph nodes measuring greater than 10 mm. All lymph nodes are manually labeled as ground truth. The system achieved sensitivities of 81% and 85% at 2 false positives per patient for Frangi's and Li's blobness, respectively. C1 [Liu, Jiamin; Hua, Jeremy; Chellappa, Vivek; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. RP Liu, JM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. NR 18 TC 1 Z9 1 U1 0 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8964-7 J9 PROC SPIE PY 2012 VL 8315 AR 83150B DI 10.1117/12.911836 PG 7 WC Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BAT32 UT WOS:000305454600010 ER PT S AU Liu, JF Subramanian, KR Yoo, TS AF Liu, Jianfei Subramanian, Kalpathi R. Yoo, Terry S. BE VanGinneken, B Novak, CL TI A Phantom Design for Validating Colonoscopy Tracking SO MEDICAL IMAGING 2012: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Computer-Aided Diagnosis CY FEB 07-09, 2012 CL San Diego, CA SP SPIE, Agilent Technol, Diamond SA, DQE Instruments Inc, eMagin, Isuzu Glass Co Ltd, Medtron, Inc, Ocean Thin Films Inc DE Colonoscopy Tracking; Optical Flow; Robust Regression; Egomotion Determination AB Phantom experiments are useful and frequently used in validating algorithms or techniques in applications where it is difficult or impossible to generate accurate ground-truth. In this work we present a phantom design and experiments to validate our colonoscopy tracking algorithms, that serve to keep both virtual colonoscopy and optical colonoscopy images aligned (in location and orientation). We describe the construction of two phantoms, capable of respectively moving along a straight and a curved path. The phantoms are motorized so as to be able to move at a near constant speed. Experiments were performed at three speeds: 10, 15 and 20mm/sec, to simulate motion velocities during colonoscopy procedures. The average velocity error was within 3mm/sec in both straight and curved phantoms. Displacement error was within 7mm over a total distance of 288mm in the straight phantom, and less than 7mm over 287mm in the curved phantom. Multiple trials were performed of each experiment(and their errors averaged) to ensure repeatability. C1 [Subramanian, Kalpathi R.] Univ N Carolina, Charlotte Visualizat Ctr, Dept Comp Sci, 9201 Univ City Blvd, Charlotte, NC 28223 USA. [Liu, Jianfei] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. [Yoo, Terry S.] NIH, Natl Lib Med, Off High Performance Comp & Commun, Bethesda, MD 20892 USA. RP Subramanian, KR (reprint author), Univ N Carolina, Charlotte Visualizat Ctr, Dept Comp Sci, 9201 Univ City Blvd, Charlotte, NC 28223 USA. EM jianfei.liu@nih.gov; krs@uncc.edu; yoo@nlm.nih.gov NR 9 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8964-7 J9 PROC SPIE PY 2012 VL 8315 AR 83151N DI 10.1117/12.912395 PG 8 WC Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BAT32 UT WOS:000305454600058 ER PT S AU McKenna, MT Wang, SJ Nguyen, TB Burns, JE Petrick, N Sahiner, B Summers, RM AF McKenna, Matthew T. Wang, Shijun Nguyen, Tan B. Burns, Joseph E. Petrick, Nicholas Sahiner, Berkman Summers, Ronald M. BE VanGinneken, B Novak, CL TI Computer Vision Approach to Detect Colonic Polyps in Computed Tomographic Colonography SO MEDICAL IMAGING 2012: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Computer-Aided Diagnosis CY FEB 07-09, 2012 CL San Diego, CA SP SPIE, Agilent Technol, Diamond SA, DQE Instruments Inc, eMagin, Isuzu Glass Co Ltd, Medtron, Inc, Ocean Thin Films Inc DE Computed tomographic colonography; video analysis; computer-aided detection ID CT COLONOGRAPHY; AIDED DETECTION AB In this paper, we present evaluation results for a novel colonic polyp classification method for use as part of a computed tomographic colonography (CTC) computer-aided detection (CAD) algorithm. Inspired by the interpretative methodology of radiologists using 3D fly-through mode in CTC reading, we have developed an algorithm which utilizes sequences of images (referred to here as videos) for classification of CAD marks. First, we generated an initial list of polyp candidates using an existing CAD system. For each of these candidates, we created a video composed of a series of intraluminal, volume-rendered images focusing on the candidate from multiple viewpoints. These videos illustrated the shape of the polyp candidate and gathered contextual information of diagnostic importance. We calculated the histogram of oriented gradients (HOG) feature on each frame of the video and utilized a support vector machine for classification. We tested our method by analyzing a CTC data set of 50 patients from three medical centers. Our proposed video analysis method for polyp classification showed significantly better performance than an approach using only the 2D CT slice data. The areas under the ROC curve for these methods were 0.88 (95% CI: [0.84, 0.91]) and 0.80 (95% CI: [0.75, 0.84]) respectively (p=0.0005). C1 [McKenna, Matthew T.; Wang, Shijun; Nguyen, Tan B.; Burns, Joseph E.; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10,Room 1C224D,MSC 1182, Bethesda, MD 20892 USA. RP McKenna, MT (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10,Room 1C224D,MSC 1182, Bethesda, MD 20892 USA. FU Intramural Research Programs of the NIH Clinical Center; Food and Drug Administration FX This work was supported by the Intramural Research Programs of the NIH Clinical Center and the Food and Drug Administration. We thank Drs. Perry Pickhardt, J. Richard Choi, and William Schindler for providing CTC data. No official endorsement by the National Institutes of Health or the Food and Drug Administration of any equipment or product of any company mentioned in the publication should be inferred. NR 12 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8964-7 J9 PROC SPIE PY 2012 VL 8315 AR 83151S DI 10.1117/12.911657 PG 7 WC Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BAT32 UT WOS:000305454600063 ER PT S AU Wiese, T Yao, JH Burns, JE Summers, RM AF Wiese, Tatjana Yao, Jianhua Burns, Joseph E. Summers, Ronald M. BE VanGinneken, B Novak, CL TI Detection of Sclerotic Bone Metastases in the Spine Using Watershed Algorithm and Graph Cut SO MEDICAL IMAGING 2012: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Computer-Aided Diagnosis CY FEB 07-09, 2012 CL San Diego, CA SP SPIE, Agilent Technol, Diamond SA, DQE Instruments Inc, eMagin, Isuzu Glass Co Ltd, Medtron Inc, Ocean Thin Films Inc DE sclerotic bone metastasis; watershed algorithm; graph cut; computer-aided detection AB The early detection of bone metastases is important for determining the prognosis and treatment of a patient. We developed a CAD system which detects sclerotic bone metastases in the spine on CT images. After the spine is segmented from the image, a watershed algorithm detects lesion candidates. The over-segmentation problem of the watershed algorithm is addressed by the novel incorporation of a graph-cuts driven merger. 30 quantitative features for each detection are computed to train a support vector machine (SVM) classifier. The classifier was trained on 12 clinical cases and tested on 10 independent clinical cases. Ground truth lesions were manually segmented by an expert. The system prior to classification detected 87% (72/83) of the manually segmented lesions with volume greater than 300 mm(3). On the independent test set, the sensitivity was 71.2% (95% confidence interval (63.1%, 77.3%)) with 8.8 false positives per case. C1 [Wiese, Tatjana; Yao, Jianhua; Summers, Ronald M.] NIH, Radiol & Imaging Sci Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Wiese, T (reprint author), NIH, Radiol & Imaging Sci Dept, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM jyao@cc.nih.gov NR 7 TC 1 Z9 1 U1 1 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8964-7 J9 PROC SPIE PY 2012 VL 8315 AR 831512 DI 10.1117/12.911700 PG 8 WC Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BAT32 UT WOS:000305454600037 ER PT S AU Yao, JH Burns, JE Wiese, T Summers, RM AF Yao, Jianhua Burns, Joseph E. Wiese, Tatjana Summers, Ronald M. BE VanGinneken, B Novak, CL TI Quantitative Vertebral Compression Fracture Evaluation Using a Height Compass SO MEDICAL IMAGING 2012: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Computer-Aided Diagnosis CY FEB 07-09, 2012 CL San Diego, CA SP SPIE, Agilent Technol, Diamond SA, DQE Instruments Inc, eMagin, Isuzu Glass Co Ltd, Medtron, Inc, Ocean Thin Films Inc DE computer-aided diagnosis; compression fracture; height compass ID SEGMENTATION; SPINE; IMAGES; CT AB Vertebral compression fractures can be caused by even minor trauma in patients with pathological conditions such as osteoporosis, varying greatly in vertebral body location and compression geometry. The location and morphology of the compression injury can guide decision making for treatment modality (vertebroplasty versus surgical fixation), and can be important for pre-surgical planning. We propose a height compass to evaluate the axial plane spatial distribution of compression injury (anterior, posterior, lateral, and central), and distinguish it from physiologic height variations of normal vertebrae. The method includes four steps: spine segmentation and partition, endplate detection, height compass computation and compression fracture evaluation. A height compass is computed for each vertebra, where the vertebral body is partitioned in the axial plane into 17 cells oriented about concentric rings. In the compass structure, a crown-like geometry is produced by three concentric rings which are divided into 8 equal length arcs by rays which are subtended by 8 common central angles. The radius of each ring increases multiplicatively, with resultant structure of a central node and two concentric surrounding bands of cells, each divided into octants. The height value for each octant is calculated and plotted against octants in neighboring vertebrae. The height compass shows intuitive display of the height distribution and can be used to easily identify the fracture regions. Our technique was evaluated on 8 thoraco-abdominal CT scans of patients with reported compression fractures and showed statistically significant differences in height value at the sites of the fractures. C1 [Yao, Jianhua; Wiese, Tatjana; Summers, Ronald M.] NIH, Radiol & Imaging Sci Dept, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. RP Yao, JH (reprint author), NIH, Radiol & Imaging Sci Dept, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM jyao@cc.nih.gov FU Intramural Research Program at National Institutes of Health, Clinical Center FX This work was supported by the Intramural Research Program at National Institutes of Health, Clinical Center. NR 14 TC 2 Z9 2 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8964-7 J9 PROC SPIE PY 2012 VL 8315 AR 83151X DI 10.1117/12.911703 PG 8 WC Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BAT32 UT WOS:000305454600068 ER PT J AU Bornstein, MH AF Bornstein, Marc H. TI Cultural Approaches to Parenting SO PARENTING-SCIENCE AND PRACTICE LA English DT Article ID BEHAVIORS; BELIEFS; MOTHERS; INFANT AB This article first introduces some main ideas behind culture and parenting and next addresses philosophical rationales and methodological considerations central to cultural approaches to parenting, including a brief account of a cross-cultural study of parenting. It then focuses on universals, specifics, and distinctions between form (behavior) and function (meaning) in parenting as embedded in culture. The article concludes by pointing to social policy implications as well as future directions prompted by a cultural approach to parenting. C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM Marc_H_Bornstein@nih.gov FU Intramural NIH HHS [ZIA HD001119-24] NR 39 TC 25 Z9 26 U1 2 U2 23 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 1529-5192 J9 PARENT-SCI PRACT JI Parent.-Sci. Pract. PY 2012 VL 12 IS 2-3 SI SI BP 212 EP 221 DI 10.1080/15295192.2012.683359 PG 10 WC Family Studies; Psychology, Developmental SC Family Studies; Psychology GA 961RZ UT WOS:000305487200014 PM 22962544 ER PT J AU Dunnick, JK Brix, A Cunny, H Vallant, M Shockley, KR AF Dunnick, J. K. Brix, A. Cunny, H. Vallant, M. Shockley, K. R. TI Characterization of Polybrominated Diphenyl Ether Toxicity in Wistar Han Rats and Use of Liver Microarray Data for Predicting Disease Susceptibilities SO TOXICOLOGIC PATHOLOGY LA English DT Article DE polybrominated diphenyl ethers; liver toxicity; lipid metabolism ID BROMINATED FLAME RETARDANTS; THYROID-HORMONE DISRUPTION; GENE-EXPRESSION; IN-VITRO; TOXICOGENOMIC ANALYSIS; ENDOCRINE DISRUPTORS; REPRODUCTIVE HEALTH; METABOLIC SYNDROME; MIXTURE DE-71; C57BL/6 MICE AB The toxicity of polybrominated diphenyl ethers (PBDEs), flame-retardant components, was characterized in offspring from Wistar Han dams exposed by gavage to a PBDE mixture (DE71) starting at gestation day 6 and continuing to weaning on postnatal day (PND) 21. Offspring from the dams underwent PBDE direct dosing by gavage at the same dose as their dams from PND 12 to PND 21, and then after weaning for another thirteen weeks. Liver samples were collected at PND 22 and week 13 for liver gene expression analysis (Affymetrix Rat Genome 230 2.0 Array). Treatment with PBDE induced 1,066 liver gene transcript changes in females and 1,200 transcriptional changes in males at PND 22 (false discovery rate < 0.01), but only 263 liver transcriptional changes at thirteen weeks in male rats (false discovery rate < 0.05). No significant differences in dose response were found between male and female pups. Transcript changes at PND 22 coded for proteins in xenobiotic, sterol, and lipid metabolism, and cell cycle regulation, and overlapped rodent liver transcript patterns after a high-fat diet or phenobarbital exposure. These findings, along with the observed PBDE-induced liver hypertrophy and vacuolization, suggest that long-term PBDE exposure has the potential to modify cell functions that contribute to metabolic disease and/or cancer susceptibilities. C1 [Dunnick, J. K.; Brix, A.; Cunny, H.; Vallant, M.; Shockley, K. R.] NIEHS, Res Triangle Pk, NC 27709 USA. RP Dunnick, JK (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM dunnickj@niehs.nih.gov FU National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC; Southern Research Institute, under NIEHS [NO1-ES-45516]; NIEHS [ES 55547]; [N01-ES-55536] FX This work was supported by the intramural program of the National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC. However, the statements, opinions, or conclusions contained therein do not necessarily represent the statements, opinions, or conclusions of NIEHS, NIH or the United States government. The in-life portion of this study was conducted under the supervision of Dr. C. Hebert, Southern Research Institute, under NIEHS contract NO1-ES-45516 and the microarray analysis under contract N01-ES-55536. Statistical support was provided under NIEHS contract ES 55547. We thank G. Kissling, A. Merrick, and M. Sanders, NIEHS, for their review of the manuscript. NR 95 TC 10 Z9 10 U1 1 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 EI 1533-1601 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN PY 2012 VL 40 IS 1 BP 93 EP 106 DI 10.1177/0192623311429973 PG 14 WC Pathology; Toxicology SC Pathology; Toxicology GA 961JA UT WOS:000305459500009 PM 22267650 ER PT S AU Wu, XW Damjanovic, A Brooks, BR AF Wu, Xiongwu Damjanovic, Ana Brooks, Bernard R. BE Rice, SA Dinner, AR TI EFFICIENT AND UNBIASED SAMPLING OF BIOMOLECULAR SYSTEMS IN THE CANONICAL ENSEMBLE: A REVIEW OF SELF-GUIDED LANGEVIN DYNAMICS SO ADVANCES IN CHEMICAL PHYSICS, VOL 150 SE Advances in Chemical Physics LA English DT Review; Book Chapter ID HYDROPHOBIC GRAPHITE SURFACE; ISOTHERMAL-ISOBARIC ENSEMBLE; PROTEIN-FOLDING SIMULATIONS; IONIC COMPLEMENTARY PEPTIDE; ALANINE-BASED PEPTIDE; MOLECULAR-DYNAMICS; CONFORMATIONAL SEARCH; GENETIC ALGORITHM; REPLICA-EXCHANGE; AQUEOUS-SOLUTION C1 [Wu, Xiongwu; Damjanovic, Ana; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. [Damjanovic, Ana] Johns Hopkins Univ, Dept Biophys, Baltimore, MD 21218 USA. RP Wu, XW (reprint author), NHLBI, Lab Computat Biol, NIH, 5635 Fishers Lane, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 HL999999]; NIGMS NIH HHS [R01 GM073838] NR 85 TC 18 Z9 18 U1 3 U2 35 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0065-2385 BN 978-1-118-19771-4; 978-1-118-16784-7 J9 ADV CHEM PHYS JI Adv. Chem. Phys. PY 2012 VL 150 BP 255 EP 326 D2 10.1002/978-1-118-19771-4 PG 72 WC Physics, Atomic, Molecular & Chemical SC Physics GA BAQ86 UT WOS:000305233100006 PM 23913991 ER PT J AU Kaplan, JS Arnkoff, DB Glass, CR Tinsley, R Geraci, M Hernandez, E Luckenbaugh, D Drevets, WC Carlson, PJ AF Kaplan, Johanna S. Arnkoff, Diane B. Glass, Carol R. Tinsley, Ruth Geraci, Marilla Hernandez, Elisa Luckenbaugh, David Drevets, Wayne C. Carlson, Paul J. TI Avoidant coping in panic disorder: a yohimbine biological challenge study SO ANXIETY STRESS AND COPING LA English DT Article DE panic disorder; yohimbine; biological challenge; avoidance; coping ID DSM-III-R; STRUCTURED CLINICAL INTERVIEW; ANXIETY SENSITIVITY INDEX; CARBON-DIOXIDE CHALLENGE; DEPRESSION RATING-SCALE; HIERARCHICAL STRUCTURE; INTRAVENOUS YOHIMBINE; EMOTIONAL AVOIDANCE; SOCIAL PHOBIA; ENRICHED AIR AB Few studies have addressed whether the use of avoidance-oriented coping strategies is related to the development of panic in patients with panic disorder(PD). Self-report, clinician-rated, and physiological data were collected from 42 individuals who participated in a yohimbine biological challenge study, performed under double-blind, placebo-controlled conditions. Participants included 20 healthy controls and 22 currently symptomatic patients who met DSM-IV- TR diagnostic criteria for PD. Consistent with prediction, patients with PD who had higher perceived efficacy of avoidance-oriented strategies in reducing anxiety-related thoughts reported increased severity in panic symptoms during the yohimbine challenge condition as compared to the placebo. Further, patients with PD who had more fear of cognitive dyscontrol, cardiovascular symptoms, and publicly observable anxiety also reported increased severity in panic symptoms during the challenge. Healthy controls who had more fear of cardiovascular symptoms similarly reported increased severity in panic symptoms during the challenge. No effects were found for heart rate response to the challenge agent. These results provide support for the role of avoidance-oriented coping strategies and fear of anxiety-related symptoms as risk and maintenance factors in the development of panic symptoms, particularly within a biological challenge model. C1 [Kaplan, Johanna S.; Tinsley, Ruth; Geraci, Marilla; Hernandez, Elisa; Luckenbaugh, David; Drevets, Wayne C.; Carlson, Paul J.] NIMH, Mood & Anxiety Disorders Program, NIH, DHHS, Bethesda, MD 20892 USA. [Kaplan, Johanna S.; Arnkoff, Diane B.; Glass, Carol R.; Hernandez, Elisa] Catholic Univ Amer, Dept Psychol, Washington, DC 20064 USA. RP Kaplan, JS (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, DHHS, Bethesda, MD 20892 USA. EM johannaskaplan@gmail.com NR 63 TC 2 Z9 2 U1 5 U2 11 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1061-5806 J9 ANXIETY STRESS COPIN JI Anxiety Stress Coping PY 2012 VL 25 IS 4 BP 425 EP 442 DI 10.1080/10615806.2011.609587 PG 18 WC Neurosciences; Psychiatry; Psychology, Multidisciplinary SC Neurosciences & Neurology; Psychiatry; Psychology GA 959DF UT WOS:000305291000006 PM 21864204 ER PT B AU Giubellino, A AF Giubellino, Alessio BE Chatterjee, M Kashfi, K TI GRB2 Signaling as a Molecular Target for Cancer SO CELL SIGNALING & MOLECULAR TARGETS IN CANCER LA English DT Article; Book Chapter ID GROWTH-FACTOR RECEPTOR; FOCAL-ADHESION KINASE; WISKOTT-ALDRICH-SYNDROME; PROTEIN-TYROSINE KINASES; CHRONIC MYELOGENOUS LEUKEMIA; DOMAIN-BINDING ANTAGONIST; ACTIN-BASED MOTILITY; ADAPTER PROTEIN; SH3 DOMAIN; BREAST-CANCER C1 NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Giubellino, A (reprint author), NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. EM giubella@mail.nih.gov OI Giubellino, Alessio/0000-0002-5352-0662 NR 148 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-0729-4 PY 2012 BP 1 EP 22 DI 10.1007/978-1-4614-0730-0_1 D2 10.1007/978-1-4614-0730-0 PG 22 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA BYP69 UT WOS:000299652000001 ER PT B AU Liu, QZ Sabatino, M Stroncek, DF Jin, P Marincola, FM Wang, E AF Liu, Qiuzhen Sabatino, Marianna Stroncek, David F. Jin, Ping Marincola, Francesco M. Wang, Ena BE Murphy, MJ TI Melanoma Cell Propagation: Cancer Stem Cell, Clonal Evolution and Interconversion Models of Tumorigenicity SO DIAGNOSTIC AND PROGNOSTIC BIOMARKERS AND THERAPEUTIC TARGETS IN MELANOMA SE Current Clinical Pathology LA English DT Article; Book Chapter ID ACUTE MYELOID-LEUKEMIA; TUMOR-INITIATING CELLS; MALIGNANT-MELANOMA; BREAST-CANCER; METASTATIC MELANOMA; GENE-EXPRESSION; MULTIDRUG-RESISTANCE; HUMAN MELANOCYTES; ABC TRANSPORTERS; MOUSE MODEL C1 [Liu, Qiuzhen; Marincola, Francesco M.; Wang, Ena] NIH, IDIS, Ctr Clin, Bethesda, MD 20892 USA. [Sabatino, Marianna; Stroncek, David F.; Jin, Ping] NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD USA. RP Wang, E (reprint author), NIH, IDIS, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM ewang@mail.nih.gov NR 108 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-432-6 J9 CURR CLIN PATHOL PY 2012 BP 227 EP 241 DI 10.1007/978-1-60761-433-3_17 D2 10.1007/978-1-60762-433-3 PG 15 WC Oncology; Dermatology; Pathology SC Oncology; Dermatology; Pathology GA BAF46 UT WOS:000304018300017 ER PT B AU Armani, M Cummins, Z Gong, J Mathai, P Probst, R Ropp, C Waks, E Walker, S Shapiro, B AF Armani, Mike Cummins, Zach Gong, Jian Mathai, Pramod Probst, Roland Ropp, Chad Waks, Edo Walker, Shawn Shapiro, Benjamin BE Gorman, JJ Shapiro, B TI Feedback Control of Microflows SO FEEDBACK CONTROL OF MEMS TO ATOMS LA English DT Article; Book Chapter ID SINGLE QUANTUM-DOT; OPTICAL TWEEZERS; CAPILLARY-ELECTROPHORESIS; MICROFLUIDIC SYSTEMS; MULTIPLE PARTICLES; PATCH-CLAMP; CELL; MODEL; CHIP; FLOW C1 [Armani, Mike; Cummins, Zach; Probst, Roland; Shapiro, Benjamin] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. [Shapiro, Benjamin] Univ Maryland, Syst Res Inst, College Pk, MD 20742 USA. [Walker, Shawn] Louisiana State Univ, Dept Math, Baton Rouge, LA 70803 USA. [Walker, Shawn] Louisiana State Univ, CCT, Baton Rouge, LA 70803 USA. [Waks, Edo] Univ Maryland, IREAP, College Pk, MD 20742 USA. [Gong, Jian] Univ Calif Los Angeles, Micromfg Lab, Los Angeles, CA USA. [Armani, Mike] NCI, Pathogenet Unit, Pathol Lab, Bethesda, MD 20892 USA. RP Shapiro, B (reprint author), Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. EM armanimd@mail.nih.gov; benshap@umd.edu NR 119 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-5831-0 PY 2012 BP 269 EP 319 DI 10.1007/978-1-4419-5832-7_9 D2 10.1007/978-1-44195832-7 PG 51 WC Engineering, Electrical & Electronic; Nanoscience & Nanotechnology SC Engineering; Science & Technology - Other Topics GA BAD47 UT WOS:000303840900009 ER PT J AU Baker, SG Van Calster, B Steyerberg, EW AF Baker, Stuart G. Van Calster, Ben Steyerberg, Ewout W. TI Evaluating a New Marker for Risk Prediction Using the Test Tradeoff: An Update SO INTERNATIONAL JOURNAL OF BIOSTATISTICS LA English DT Article DE decision curves; relative utility curves; receiver-operating characteristic curve; risk threshold; test tradeoff ID DECISION CURVE ANALYSIS; OPERATING CHARACTERISTIC CURVES; RELATIVE UTILITY CURVES; DIAGNOSTIC-TESTS; ROC CURVE; MODELS; CANCER; VALIDATION; HEALTH; CLASSIFICATION AB Most of the methodological literature on evaluating an additional marker for risk prediction involves purely statistical measures of classification performance. A disadvantage of a purely statistical measure is the difficulty in deciding the improvement in the measure that would make inclusion of the additional marker worthwhile. In contrast, a medical decision making approach can weigh the cost or harm of ascertaining an additional marker against the benefit of a higher true positive rate for a given false positive rate that may be associated with risk prediction involving the additional marker. An appealing form of the medical decision making approach involves the risk threshold, which is the risk at which the expected utility of treatment and no treatment is the same. In this framework, a readily interpretable evaluation of the net benefit of an additional marker is the test tradeoff corresponding to the risk threshold. The test tradeoff is the minimum number of tests for a new marker that need to be traded for a true positive to yield an increase in the net benefit of risk prediction with the additional marker. For a sensitivity analysis the test tradeoff is computed over multiple risk thresholds. This article updates the theory and estimation of the test tradeoff. An example is provided. C1 [Baker, Stuart G.] NCI, Bethesda, MD 20892 USA. [Van Calster, Ben] Katholieke Univ Leuven, Louvain, Belgium. RP Baker, SG (reprint author), NCI, Bethesda, MD 20892 USA. OI Van Calster, Ben/0000-0003-1613-7450 FU National Institutes of Health; Research Foundation - Flanders (FWO) [1.2.516.09N]; Center for Translational Molecular Medicine [03O-203] FX SGB was supported by the National Institutes of Health. BVC is supported by a postdoctoral fellowship from the Research Foundation - Flanders (FWO) (grant 1.2.516.09N). ES was supported by the Center for Translational Molecular Medicine (PCMM project, grant 03O-203). NR 37 TC 7 Z9 7 U1 3 U2 11 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 2194-573X J9 INT J BIOSTAT JI Int. J. Biostat. PY 2012 VL 8 IS 1 AR 5 DI 10.1515/1557-4679.1395 PG 38 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 956IQ UT WOS:000305083700005 ER PT S AU Zhuge, Y Udupa, JK Ciesielski, KC Falcao, AX Miranda, PAV Miller, RW AF Zhuge, Ying Udupa, Jayaram K. Ciesielski, Krzysztof C. Falcao, Alexandre X. Miranda, Paulo A. V. Miller, Robert W. BE Holmes, DR Wong, KH TI GPU-Based Iterative Relative Fuzzy Connectedness Image Segmentation SO MEDICAL IMAGING 2012: IMAGE-GUIDED PROCEDURES, ROBOTIC INTERVENTIONS, AND MODELING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image-Guided Procedures, Robotic Interventions and Modeling CY FEB 05-07, 2012 CL San Diego, CA SP SPIE, Agilent Technol, Diamond SA, DQE Instruments Inc, eMagin, Isuzu Glass Co Ltd, Medtron Inc, Ocean Thin Films Inc DE Image segmentation; fuzzy connectedness; graph-based methods; GPU implementations ID OBJECT DEFINITION; ALGORITHMS; SYSTEM; VOLUME; GRAPH; CUT AB This paper presents a parallel algorithm for the top of the line among the fuzzy connectedness algorithm family, namely the iterative relative fuzzy connectedness (IRFC) segmentation method. The algorithm of IRFC, realized via image foresting transform (IFT), is implemented by using NVIDIA's compute unified device architecture (CUDA) platform for segmenting large medical image data sets. In the IRFC algorithm, there are two major computational tasks: (i) computing the fuzzy affinity relations, and (ii) computing the fuzzy connectedness relations and tracking labels for objects of interest. Both tasks are implemented as CUDA kernels, and a substantial improvement in speed for both tasks is achieved. Our experiments based on three data sets of small, medium, and large data size demonstrate the efficiency of the parallel algorithm, which achieves a speed-up factor of 2.4x, 17.0x, and 42.7x, correspondingly, for the three data sets on the NVIDIA Tesla C1060 over the implementation of the algorithm in CPU. C1 [Zhuge, Ying; Miller, Robert W.] Natl Canc Inst, Natl Inst Hlth, Radiat Oncol Branch, Bethesda, MD 20892 USA. RP Zhuge, Y (reprint author), Natl Canc Inst, Natl Inst Hlth, Radiat Oncol Branch, Bethesda, MD 20892 USA. EM zhugey@mail.nih.gov; jay@mail.med.upenn.edu; rwmiller@mail.nih.gov RI Falcao, Alexandre/F-8361-2012; Miranda, Paulo/C-2342-2012 OI Miranda, Paulo/0000-0001-6496-697X NR 25 TC 1 Z9 1 U1 0 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8965-4 J9 PROC SPIE PY 2012 VL 8316 AR 831604 DI 10.1117/12.911794 PG 11 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BAP67 UT WOS:000305070200004 ER PT S AU Gopich, IV Szabo, A AF Gopich, Irina V. Szabo, Attila BE Komatsuzaki, T Kawakami, M Takahashi, S Yang, H Silbey, RJ TI THEORY OF SINGLE-MOLECULE FRET EFFICIENCY HISTOGRAMS SO SINGLE-MOLECULE BIOPHYSICS: EXPERIMENT AND THEORY, VOL 146 SE Advances in Chemical Physics LA English DT Review; Book Chapter ID RESONANCE ENERGY-TRANSFER; PHOTON-COUNTING HISTOGRAM; FLUORESCENCE SPECTROSCOPY; CONFORMATIONAL DYNAMICS; STRUCTURAL HETEROGENEITIES; ARRIVAL TRAJECTORIES; DIFFUSING MOLECULES; PROTEIN COLLAPSE; TIME-SERIES; DISTRIBUTIONS C1 [Gopich, Irina V.; Szabo, Attila] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Gopich, IV (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. RI Szabo, Attila/H-3867-2012 NR 69 TC 11 Z9 11 U1 2 U2 25 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0065-2385 BN 978-1-118-13137-4 J9 ADV CHEM PHYS JI Adv. Chem. Phys. PY 2012 VL 146 BP 245 EP 297 D2 10.1002/978-1-118-13137-4 PG 53 WC Physics, Atomic, Molecular & Chemical SC Physics GA BAQ87 UT WOS:000305236600011 ER PT S AU Wu, PA Cowen, EW AF Wu, Peggy A. Cowen, Edward W. BE Hausermann, P Steiger, J Passweg, J TI Cutaneous Graft-versus-Host Disease - Clinical Considerations and Management SO TRANSPLANTATION DERMATOLOGY SE Current Problems in Dermatology LA English DT Article; Book Chapter ID MESENCHYMAL STEM-CELLS; CONSENSUS DEVELOPMENT PROJECT; RENAL-TRANSPLANT RECIPIENTS; WORKING GROUP-REPORT; MYCOPHENOLATE-MOFETIL; SYSTEMIC-SCLEROSIS; IMATINIB MESYLATE; TOPICAL PIMECROLIMUS; REFRACTORY ACUTE; INITIAL THERAPY AB Graft-versus-host disease (GVHD) is the primary cause of non-relapse-related morbidity and mortality in patients who undergo hematopoietic stem cell transplantation. Dermatologic manifestations are common in both acute and chronic GVHD. In the acute setting, skin involvement often provides the first indication of GVHD and may progress to erythroderma and even skin necrolysis. In the chronic phase, skin involvement is extraordinarily polymorphic, potentially involves all layers of the skin and subcutaneous tissue, and presents in sclerotic and nonsclerotic forms. Management of cutaneous disease is challenging and ideally employs a multi-disciplinary approach and an understanding of the multiple medical issues facing patients with GVHD. The dermatologist plays a key role in caring for the patient with GVHD by providing an accurate diagnosis, determination of disease activity and response to treatment, and appropriate consideration of all available treatment modalities, including topical, systemic, and physical interventions (e.g. phototherapy, extracorporeal photopheresis). This chapter describes the cutaneous manifestations of acute and chronic GVHD and provides an evidence-based review of current treatment interventions for patients with GVHD skin disease. Copyright (C) 2012 S. Karger AG, Basel C1 [Cowen, Edward W.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Wu, Peggy A.] Beth Israel Deaconess Med Ctr, Dept Dermatol, Boston, MA 02215 USA. RP Cowen, EW (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,MSC 1908, Bethesda, MD 20892 USA. EM cowene@mail.nih.gov NR 68 TC 2 Z9 5 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1421-5721 BN 978-3-8055-9856-9 J9 CURR PROBL DERMATOL JI Curr.Probl.Dermatol. PY 2012 VL 43 BP 101 EP 115 PG 15 WC Dermatology SC Dermatology GA BAB35 UT WOS:000303688500010 PM 22377924 ER PT S AU Sowerwine, KJ Holland, SM Freeman, AF AF Sowerwine, Kathryn J. Holland, Steven M. Freeman, Alexandra F. GP Annals NY Acad Sci TI Hyper-IgE syndrome update SO YEAR IN HUMAN AND MEDICAL GENETICS: INBORN ERRORS OF IMMUNITY III SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE autosomal dominant hyper-IgE syndrome; Job's syndrome; signal transducer and activator of transcription 3; Th17 cells ID HYPERIMMUNOGLOBULIN-E SYNDROME; CHRONIC MUCOCUTANEOUS CANDIDIASIS; RECURRENT INFECTION SYNDROME; CORONARY-ARTERY ANEURYSMS; JOBS-SYNDROME; SIGNAL TRANSDUCER; ATOPIC-DERMATITIS; STAT3 MUTATIONS; CRANIAL SYNOSTOSIS; SYNDROME HIES AB Autosomal dominant hyper-IgE syndrome (AD-HIES) or Job's syndrome is a primary immunodeficiency with a wide array of clinical features caused by dominant negative mutations in STAT3. In recent years, not only the clinical phenotype of the disease has been expanded with recognition of features such as arterial aneurysms, but also our understanding of the pathogenesis of the disease has greatly improved. C1 [Sowerwine, Kathryn J.; Holland, Steven M.; Freeman, Alexandra F.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Freeman, AF (reprint author), NIH Bldg 10,Room 11N234, Bethesda, MD 20892 USA. EM freemaal@mail.nih.gov FU Intramural NIH HHS [Z01 AI000646-16] NR 70 TC 43 Z9 46 U1 3 U2 9 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 BN 978-1-57331-878-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2012 VL 1250 BP 25 EP 32 DI 10.1111/j.1749-6632.2011.06387.x PG 8 WC Genetics & Heredity; Immunology; Multidisciplinary Sciences SC Genetics & Heredity; Immunology; Science & Technology - Other Topics GA BAU73 UT WOS:000305559400003 PM 22268731 ER PT J AU Montoya, ID AF Montoya, Ivan D. TI Advances in the Development of Biologics to Treat Drug Addictions and Overdose SO ADICCIONES LA Spanish DT Editorial Material DE Biologics; vaccines; antibodies; enzymes; drug abuse; overdose ID THERAPEUTIC COCAINE VACCINE; MORPHINE/HEROIN VACCINE; ACTIVE IMMUNIZATION; SUBSTANCE-ABUSE; METHAMPHETAMINE; HYDROLASE; RELAPSE; RATS; BUTYRYLCHOLINESTERASE; IMMUNOTHERAPIES AB Drug addictions are complex disorders that require multiple approaches, including the use of pharmacotherapies. Currently, these therapies are based on "small" molecules or chemicals that penetrate the blood-brain barrier, reach the brain, and produce their effects on neurotransmitter systems. Unfortunately, they often do not have the desired efficacy or may cause undesirable side effects, especially at the central nervous system (CNS) level. A novel approach is the use of biologics to treat drug addictions. Biologics are usually complex and "large" molecules, which do not cross the blood-brain barrier and, thus, have no CNS effects. In principle, it appears that the efficacy of biologics to treat drug addiction is by preventing the access of the drug of abuse to the brain, preventing the activation of brain reward systems, and eventually producing the extinction of addiction. Biologic therapeutics includes immunotherapies, such as vaccines or antibodies, as well as enzymes. New products as well as new and more efficient methods of production, are offering vast opportunities to advance the discovery and development of biologics to treat addictions as well as drug overdose. These products include new vaccines with greater specificity and ability to produce antibodies, new methods and techniques to produce vaccines and antibodies, as well as new enzymes with high efficiency to metabolize cocaine. The purpose of the article is to provide a general overview of the development of biologics for the treatment of drug addictions and overdose. C1 NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, Bethesda, MD 20892 USA. RP Montoya, ID (reprint author), NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, Bethesda, MD 20892 USA. EM imontoya@mail.nih.gov NR 49 TC 4 Z9 4 U1 1 U2 12 PU SOCIDROGALCOHOL PI PALMA DE MALLORCA PA RAMBLA 15, 2A, 3A,, PALMA DE MALLORCA, BALEARES 07003, SPAIN SN 0214-4840 J9 ADICCIONES JI Adicciones PY 2012 VL 24 IS 2 BP 95 EP 103 PG 9 WC Substance Abuse SC Substance Abuse GA 952HS UT WOS:000304784000002 PM 22648312 ER PT J AU Miller, FG Truog, RD AF Miller, Franklin G. Truog, Robert D. TI Going All the Way: Ethical Clarity and Ethical Progress SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material ID BRAIN-DEATH C1 [Miller, Franklin G.] NIH, Dept Bioeth, Bethesda, MD 20892 USA. [Truog, Robert D.] Harvard Univ, Sch Med, Boston, MA USA. [Truog, Robert D.] Childrens Hosp, Boston, MA 02115 USA. RP Miller, FG (reprint author), NIH, Dept Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM fmiller@nih.gov NR 7 TC 0 Z9 0 U1 0 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2012 VL 12 IS 6 BP 10 EP 11 DI 10.1080/15265161.2012.671890 PG 3 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 950SS UT WOS:000304669900003 PM 22650452 ER PT J AU Dawson, L AF Dawson, Liza TI The Devil in the Details: Thorough Assessment of Evidence and Ethics Is Needed in Evaluating New HIV Prevention Methods SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material ID AIDS TRIALS C1 NIAID, Div Aids, NIH, Res Eth Team,Basic Sci Program, Bethesda, MD 20817 USA. RP Dawson, L (reprint author), NIAID, Div Aids, NIH, Res Eth Team,Basic Sci Program, 6700B Rockledge Dr, Bethesda, MD 20817 USA. EM dawsonl@niaid.nih.gov NR 5 TC 4 Z9 4 U1 0 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2012 VL 12 IS 6 BP 33 EP 34 DI 10.1080/15265161.2012.672621 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 950SS UT WOS:000304669900010 PM 22650459 ER PT J AU Yin, HE Nguyen, CQ Samuni, Y Uede, T Peck, AB Chiorini, JA AF Yin, Hongen Nguyen, Cuong Q. Samuni, Yuval Uede, Toshimitsu Peck, Ammon B. Chiorini, John A. TI Local delivery of AAV2-CTLA4IgG decreases sialadenitis and improves gland function in the C57BL/6.NOD-Aec1Aec2 mouse model of Sjogren's syndrome SO ARTHRITIS RESEARCH & THERAPY LA English DT Article DE Sjogren's Syndrome; salivary gland dysfunction; adeno-associated virus (AAV); CTLA4IgG fusion protein; prevention ID REGULATORY T-CELLS; SALIVARY-GLAND; AUTOIMMUNE-DISEASE; SELF-TOLERANCE; GENE-TRANSFER; EXPRESSION; VECTORS; ANTIGEN; TRANSDUCTION; ABATACEPT AB Introduction: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a key negative costimulatory molecule that displays a wide range of anti-inflammatory properties and is currently approved to treat rheumatoid arthritis as a recombinant fusion protein (CTLA4IgG). To better understand the role of CTLA4IgG in primary Sjogren's syndrome (pSS), we generated a recombinant adeno-associated virus vector serotype 2 (AAV2) expressing a chimera of mouse CTLA-4 fused with a human immunoglobulin (AAV2-CTLA4IgG) and observed the effect of this molecule in C57BL/6.NOD-Aec1Aec2 mice, an animal model of pSS. Methods: A recombinant adeno-associated virus-2 (AAV-2) vector was constructed encoding a CTLA4IgG fusion protein. The AAV2-CTLA4IgG vector and an AAV2 control vector encoding beta galactosidase (LacZ) were administered by retrograde cannulation of the submandibular glands of C57BL/6.NOD-Aec1Aec2 mice. Protein expression was measured by ELISA and salivary glands were assessed for inflammation and activity. Results: Recombinant CTLA4IgG blocked B7 expression on macrophages in vitro. In vivo, localized expression of CTLA4IgG in the salivary glands of C57BL/6.NOD-Aec1Aec2 mice inhibited the loss of salivary gland activity and decreased T and B cell infiltration as well as dendritic cells and macrophages in the glands compared with control mice. In addition a decrease in several proinflammatory cytokines and an increase in transforming growth factor beta-1 (TGF-beta 1) expression were also observed. Conclusions: These data suggest expression of CTLA4IgG in the salivary gland can decrease the inflammation and improve the xerostomia reported in these mice. C1 [Yin, Hongen; Samuni, Yuval; Chiorini, John A.] Natl Inst Dent & Cranial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. [Nguyen, Cuong Q.; Peck, Ammon B.] Univ Florida, Coll Dent, Dept Oral Biol, Gainesville, FL 32610 USA. [Uede, Toshimitsu] Hokkaido Univ, Inst Immunol Sci, Sect Immunopathogenesis, Sapporo, Hokkaido 060, Japan. RP Chiorini, JA (reprint author), Natl Inst Dent & Cranial Res, Mol Physiol & Therapeut Branch, NIH, 10 Ctr Dr,MSC1190, Bethesda, MD 20892 USA. EM jchiorini@dir.nidcr.nih.gov FU NIH NIDCR FX This work was supported by an NIH NIDCR intramural research grant to JAC. None of the authors have a financial disclosure. NR 36 TC 12 Z9 12 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2012 VL 14 IS 1 AR R40 DI 10.1186/ar3753 PG 11 WC Rheumatology SC Rheumatology GA 951CQ UT WOS:000304698800054 PM 22369699 ER PT J AU Cheng, Q Chang, JT Geradts, J Neckers, LM Haystead, T Spector, NL Lyerly, HK AF Cheng, Qing Chang, Jeffrey T. Geradts, Joseph Neckers, Leonard M. Haystead, Timothy Spector, Neil L. Lyerly, H. Kim TI Amplification and high-level expression of heat shock protein 90 marks aggressive phenotypes of human epidermal growth factor receptor 2 negative breast cancer SO BREAST CANCER RESEARCH LA English DT Article ID MOLECULAR SUBTYPES; DISTANT METASTASIS; HSP90; SIGNATURE; PATTERNS; THERAPY; GENOME; GENES; CHEMOTHERAPY; SENSITIVITY AB Introduction: Although human epidermal growth factor receptor 2 (HER2) positive or estrogen receptor (ER) positive breast cancers are treated with clinically validated anti-HER2 or anti-estrogen therapies, intrinsic and acquired resistance to these therapies appears in a substantial proportion of breast cancer patients and new therapies are needed. Identification of additional molecular factors, especially those characterized by aggressive behavior and poor prognosis, could prioritize interventional opportunities to improve the diagnosis and treatment of breast cancer. Methods: We compiled a collection of 4,010 breast tumor gene expression data derived from 23 datasets that have been posted on the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. We performed a genome-scale survival analysis using Cox-regression survival analyses, and validated using Kaplan-Meier Estimates survival and Cox Proportional-Hazards Regression survival analyses. We conducted a genome-scale analysis of chromosome alteration using 481 breast cancer samples obtained from The Cancer Genome Atlas (TCGA), from which combined expression and copy number data were available. We assessed the correlation between somatic copy number alterations and gene expression using analysis of variance (ANOVA). Results: Increased expression of each of the heat shock protein (HSP) 90 isoforms, as well as HSP transcriptional factor 1 (HSF1), was correlated with poor prognosis in different subtypes of breast cancer. High-level expression of HSP90AA1 and HSP90AB1, two cytoplasmic HSP90 isoforms, was driven by chromosome coding region amplifications and were independent factors that led to death from breast cancer among patients with triple-negative (TNBC) and HER2-/ER+ subtypes, respectively. Furthermore, amplification of HSF1 was correlated with higher HSP90AA1 and HSP90AB1 mRNA expression among the breast cancer cells without amplifications of these two genes. A collection of HSP90AA1, HSP90AB1 and HSF1 amplifications defined a subpopulation of breast cancer with up-regulated HSP90 gene expression, and up-regulated HSP90 expression independently elevated the risk of recurrence of TNBC and poor prognosis of HER2-/ER+ breast cancer. Conclusions: Up-regulated HSP90 mRNA expression represents a confluence of genomic vulnerability that renders HER2 negative breast cancers more aggressive, resulting in poor prognosis. Targeting breast cancer with upregulated HSP90 may potentially improve the effectiveness of clinical intervention in this disease. C1 [Cheng, Qing; Lyerly, H. Kim] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Geradts, Joseph; Lyerly, H. Kim] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [Haystead, Timothy] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. [Spector, Neil L.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Chang, Jeffrey T.] Univ Texas Hlth Sci Ctr, Dept Integrat Biol & Pharmacol, Houston, TX 77030 USA. [Neckers, Leonard M.] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Cheng, Q (reprint author), Duke Univ, Med Ctr, Dept Surg, Box 2606,203 Res Dr, Durham, NC 27710 USA. EM q.cheng@duke.edu; kim.lyerly@dm.duke.edu RI Lyerly, Herbert/B-6528-2014 OI Lyerly, Herbert/0000-0002-0063-4770 FU Komen Breast Cancer [SAC100012]; [NIH K12-CA100639-08] FX We gratefully acknowledge the contribution from NCBI Gene Expression Omnibus and The Cancer Genome Atlas project in providing molecular analysis data. We also thank Dr. Wei Sun (Department of Biostatistics, University of North Carolina-Chapel Hill) for his help in using the genoCN software; Dr. Kai Wang (Zilkha Neurogenetic Institute, University of Southern California) for his help in using the Penncnv_Affy software; and Mark DeLong, Ph.D., Peyton Vaughn and Alan Cowles (Duke Institute for Genome Sciences and Policy, IT) for computer technical support and advice. This work was supported in part by grant NIH K12-CA100639-08 to QC and Komen Breast Cancer SAC100012 to HKL. NR 65 TC 38 Z9 38 U1 3 U2 17 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2012 VL 14 IS 2 AR R62 DI 10.1186/bcr3168 PG 15 WC Oncology SC Oncology GA 952DZ UT WOS:000304771800037 PM 22510516 ER PT J AU He, CY Chasman, DI Dreyfus, J Hwang, SJ Ruiter, R Sanna, S Buring, JE Fernandez-Rhodes, L Franceschini, N Hankinson, SE Hofman, A Lunetta, KL Palmieri, G Porcu, E Rivadeneira, F Rose, LM Splansky, GL Stolk, L Uitterlinden, AG Chanock, SJ Crisponi, L Demerath, EW Murabito, JM Ridker, PM Stricker, BH Hunter, DJ AF He, Chunyan Chasman, Daniel I. Dreyfus, Jill Hwang, Shih-Jen Ruiter, Rikje Sanna, Serena Buring, Julie E. Fernandez-Rhodes, Lindsay Franceschini, Nora Hankinson, Susan E. Hofman, Albert Lunetta, Kathryn L. Palmieri, Giuseppe Porcu, Eleonora Rivadeneira, Fernando Rose, Lynda M. Splansky, Greta L. Stolk, Lisette Uitterlinden, Andre G. Chanock, Stephen J. Crisponi, Laura Demerath, Ellen W. Murabito, Joanne M. Ridker, Paul M. Stricker, Bruno H. Hunter, David J. TI Reproductive aging-associated common genetic variants and the risk of breast cancer SO BREAST CANCER RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; CONFER SUSCEPTIBILITY; NATURAL MENOPAUSE; IDENTIFIES 2; LOCI; AGE; MENARCHE; METAANALYSIS; ESTROGEN; ALLELES AB Introduction: A younger age at menarche and an older age at menopause are well established risk factors for breast cancer. Recent genome-wide association studies have identified several novel genetic loci associated with these two traits. However, the association between these loci and breast cancer risk is unknown. Methods: In this study, we investigated 19 and 17 newly identified single nucleotide polymorphisms (SNPs) from the ReproGen Consortium that have been associated with age at menarche and age at natural menopause, respectively, and assessed their associations with breast cancer risk in 6 population-based studies among up to 3,683 breast cancer cases and 34,174 controls in white women of European ancestry. In addition, we used these SNPs to calculate genetic risk scores (GRSs) based on their associations with each trait. Results: After adjusting for age and potential population stratification, two age at menarche associated SNPs (rs1079866 and rs7821178) and one age at natural menopause associated SNP (rs2517388) were associated with breast cancer risk (p values, 0.003, 0.009 and 0.023, respectively). The odds ratios for breast cancer corresponding to per-risk-allele were 1.14 (95% CI, 1.05 to 1.24), 1.08 (95% CI, 1.02 to 1.15) and 1.10 (95% CI, 1.01 to 1.20), respectively, and were in the direction predicted by their associations with age at menarche or age at natural menopause. These associations did not appear to be attenuated by further controlling for self-reported age at menarche, age at natural menopause, or known breast cancer susceptibility loci. Although we did not observe a statistically significant association between any GRS for reproductive aging and breast cancer risk, the 4(th) and 5(th) highest quintiles of the younger age at menarche GRS had odds ratios of 1.14 (95% CI, 1.01 to 1.28) and 1.13 (95% CI, 1.00 to 1.27), respectively, compared to the lowest quintile. Conclusions: Our study suggests that three genetic variants, independent of their associations with age at menarche or age at natural menopause, were associated with breast cancer risk and may contribute modestly to breast cancer risk prediction; however, the combination of the 19 age at menarche or the 17 age at natural menopause associated SNPs did not appear to be useful for identifying a high risk subgroup for breast cancer. C1 [He, Chunyan] Indiana Univ Sch Med, Dept Publ Hlth, Indianapolis, IN 46202 USA. [He, Chunyan] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46202 USA. [Chasman, Daniel I.; Buring, Julie E.; Rose, Lynda M.; Ridker, Paul M.] Harvard Univ, Sch Med, Div Prevent Med, Brigham & Womens Hosp, Boston, MA 02215 USA. [Dreyfus, Jill; Demerath, Ellen W.] Univ Minnesota, Div Epidemiol & Community Hlth, Sch Publ Hlth, Minneapolis, MN 55454 USA. [Hwang, Shih-Jen; Lunetta, Kathryn L.; Splansky, Greta L.; Murabito, Joanne M.] NHLBI, Framingham Heart Study, Framingham, MA 01701 USA. [Ruiter, Rikje; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.; Stricker, Bruno H.] Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands. [Sanna, Serena; Porcu, Eleonora; Crisponi, Laura] Cittadella Univ Monserrato, Ist Ric Genet & Biomed, Consiglio Nazl Ric, I-09042 Cagliari, Italy. [Fernandez-Rhodes, Lindsay; Franceschini, Nora] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA. [Hankinson, Susan E.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hankinson, Susan E.; Hunter, David J.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Hankinson, Susan E.; Hunter, David J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Palmieri, Giuseppe] CNR, Unit Canc Genet, Ist Chim Biomol, I-07100 Sassari, Italy. [Rivadeneira, Fernando; Stolk, Lisette; Uitterlinden, Andre G.; Stricker, Bruno H.] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands. [Rivadeneira, Fernando; Stolk, Lisette; Uitterlinden, Andre G.] Netherlands Consortium Healthy Aging, Rotterdam, Netherlands. [Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Hunter, David J.] Broad Inst Harvard Univ & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. RP He, CY (reprint author), Indiana Univ Sch Med, Dept Publ Hlth, 980 W Walnut St,R3-C241, Indianapolis, IN 46202 USA. EM chunhe@iupui.edu RI Rivadeneira, Fernando/O-5385-2015; OI Rivadeneira, Fernando/0000-0001-9435-9441; Murabito, Joanne/0000-0002-0192-7516; Lunetta, Kathryn/0000-0002-9268-810X; sanna, serena/0000-0002-3768-1749; Palmieri, Giuseppe/0000-0002-4350-2276 FU NCI [CA 40356, U01-CA98233, CA 047988]; National Heart, Lung, and Blood Institute (NHLBI) [HL 043851, HL69757, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367, R01HL086694, RC2 HL102419]; Donald W Reynolds Foundation; Fondation Leducq; Amgen (Thousand Oaks, CA, USA); National Institutes of Health (NIH) from the National Institute of Aging (NIA) [NO1-AG-1-2109]; Research Institute for Diseases in the Elderly (RIDE2) [014-93-015]; Netherlands Genomics Initiative/NWO [050-060-810]; Erasmus Medical Center, Rotterdam; Erasmus University, Rotterdam; Netherlands Organisation for Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam; Cohorts for Heart and Aging Research in Genome Epidemiology (CHARGE) Consortium; NHLBI's FHS [N01-HC-25195]; Affymetrix, Inc. (Santa Clara, CA, USA) [N02-HL-6-4278]; Department of Medicine at Boston University School of Medicine; Boston Medical Center; National Human Genome Research Institute [U01HG004402]; NIH [HHSN268200625226C, UL1RR025005]; NIH Roadmap for Medical Research [UL1RR025005] FX The NHS breast cancer GWAS scan was performed as part of the Cancer Genetic Markers of Susceptibility initiative of the National Cancer Institute (NCI). We particularly acknowledge the contributions of Robert Hoover, Amy Hutchinson, Kevin Jacobs, and Gilles Thomas. The present research is supported by CA 40356 and U01-CA98233 from the NCI. We acknowledge the study participants in the NHS for their contribution in making this study possible. The WGHS is supported by HL 043851 and HL69757 from the National Heart, Lung, and Blood Institute (NHLBI) and CA 047988 from the NCI, the Donald W Reynolds Foundation, and the Fondation Leducq, and collaborative scientific support and funding for genotyping were provided by Amgen (Thousand Oaks, CA, USA). We thank Joseph Miletich and Alex Parker and the technical staff at Amgen for their collaboration and scientific support in performing the genotyping for the WGHS. The SardiNIA Breast Cancer Study was funded by National Institutes of Health (NIH) contract NO1-AG-1-2109 from the National Institute of Aging (NIA) to the SardiNIA team (principal investigator: Manuela Uda). We thank Grazia Palomba, Antonio Cossu, Francesco Tanda, Mario Budroni, and the other members of the Sardinian Translational Oncology Group for their contribution in collecting Sardinian patients with breast cancer. The generation and management of GWAS genotype data for the Rotterdam Study are supported by The Netherlands Organisation for Scientific Research (NWO) Investments (175.010.2005.011 and 911-03-012). This study is funded by the Research Institute for Diseases in the Elderly (RIDE2) (014-93-015) and The Netherlands Genomics Initiative/NWO project 050-060-810. We thank Pascal Arp, Mila Jhamai, Marijn Verkerk, Lizbeth Herrera, and Marjolein Peters for their help in creating the GWAS database and Karol Estrada and Maksim V Struchalin for their support in creation and analysis of imputed data. The Rotterdam Study is funded by the Erasmus Medical Center and Erasmus University, Rotterdam; the Netherlands Organisation for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Ministry of Education, Culture and Science; the Ministry for Health, Welfare and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. The authors are grateful to the study participants, the staff from the Rotterdam Study, and the participating general practitioners and pharmacists. The authors acknowledge the essential role of the Cohorts for Heart and Aging Research in Genome Epidemiology (CHARGE) Consortium in the development and support of this manuscript. CHARGE members consist of The Netherlands' Rotterdam Study, the FHS, the Cardiovascular Health Study, the NHLBI's ARIC study, and the NIA's Iceland Age, Gene/Environment Susceptibility (AGES) study. The FHS phenotype-genotype analyses were supported in part by the NIA (Genetics of Reproductive Life Period and Health Outcomes, R21AG032598; JMM, KLL). The FHS of the NHLBI of the NIH and Boston University School of Medicine was supported by NHLBI's FHS contract N01-HC-25195 and its contract with Affymetrix, Inc. (Santa Clara, CA, USA) for genotyping services (contract N02-HL-6-4278). Analyses reflect intellectual input and resource development from the FHS investigators participating in the SNP Health Association Resource (SHARe) project.; A portion of this research was conducted by using the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. The ARIC study is carried out as a collaborative study supported by NHLBI contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367, R01HL086694, and RC2 HL102419; National Human Genome Research Institute contract U01HG004402; and NIH contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by grant UL1RR025005, a component of the NIH, and NIH Roadmap for Medical Research. NR 32 TC 8 Z9 8 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2012 VL 14 IS 2 AR R54 DI 10.1186/bcr3155 PG 15 WC Oncology SC Oncology GA 952DZ UT WOS:000304771800029 PM 22433456 ER PT J AU Roman-Perez, E Casbas-Hernandez, P Pirone, JR Rein, J Carey, LA Lubet, RA Mani, SA Amos, KD Troester, MA AF Roman-Perez, Erick Casbas-Hernandez, Patricia Pirone, Jason R. Rein, Jessica Carey, Lisa A. Lubet, Ronald A. Mani, Sendurai A. Amos, Keith D. Troester, Melissa A. TI Gene expression in extratumoral microenvironment predicts clinical outcome in breast cancer patients SO BREAST CANCER RESEARCH LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; TGF-BETA; TUMOR MICROENVIRONMENT; MOLECULAR PORTRAITS; E-CADHERIN; PROGRESSION; SURVIVAL; TRANSFORMATION; PROGNOSIS; CELLS AB Introduction: A gene expression signature indicative of activated wound responses is common to more than 90% of non-neoplastic tissues adjacent to breast cancer, but these tissues also exhibit substantial heterogeneity. We hypothesized that gene expression subtypes of breast cancer microenvironment can be defined and that these microenvironment subtypes have clinical relevance. Methods: Gene expression was evaluated in 72 patient-derived breast tissue samples adjacent to invasive breast cancer or ductal carcinoma in situ. Unsupervised clustering identified two distinct gene expression subgroups that differed in expression of genes involved in activation of fibrosis, cellular movement, cell adhesion and cell-cell contact. We evaluated the prognostic relevance of extratumoral subtype (comparing the Active group, defined by high expression of fibrosis and cellular movement genes, to the Inactive group, defined by high expression of claudins and other cellular adhesion and cell-cell contact genes) using clinical data. To establish the biological characteristics of these subtypes, gene expression profiles were compared against published and novel tumor and tumor stroma-derived signatures (Twist-related protein 1 (TWIST1) overexpression, transforming growth factor beta (TGF-beta)-induced fibroblast activation, breast fibrosis, claudin-low tumor subtype and estrogen response). Histological and immunohistochemical analyses of tissues representing each microenvironment subtype were performed to evaluate protein expression and compositional differences between microenvironment subtypes. Results: Extratumoral Active versus Inactive subtypes were not significantly associated with overall survival among all patients (hazard ratio (HR) = 1.4, 95% CI 0.6 to 2.8, P = 0.337), but there was a strong association with overall survival among estrogen receptor (ER) positive patients (HR = 2.5, 95% CI 0.9 to 6.7, P = 0.062) and hormone-treated patients (HR = 2.6, 95% CI 1.0 to 7.0, P = 0.045). The Active subtype of breast microenvironment is correlated with TWIST-overexpression signatures and shares features of claudin-low breast cancers. The Active subtype was also associated with expression of TGF-b induced fibroblast activation signatures, but there was no significant association between Active/Inactive microenvironment and desmoid type fibrosis or estrogen response gene expression signatures. Consistent with the RNA expression profiles, Active cancer-adjacent tissues exhibited higher density of TWIST nuclear staining, predominantly in epithelium, and no evidence of increased fibrosis. Conclusions: These results document the presence of two distinct subtypes of microenvironment, with Active versus Inactive cancer-adjacent extratumoral microenvironment influencing the aggressiveness and outcome of ER-positive human breast cancers. C1 [Roman-Perez, Erick; Troester, Melissa A.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Casbas-Hernandez, Patricia] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. [Pirone, Jason R.; Rein, Jessica; Carey, Lisa A.; Amos, Keith D.; Troester, Melissa A.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Lubet, Ronald A.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Mani, Sendurai A.] Univ Texas Houston, Dept Mol Pathol, Houston, TX 77053 USA. [Mani, Sendurai A.] Univ Texas MD Anderson Canc Ctr, Metastasis Res Ctr, Houston, TX 77053 USA. [Amos, Keith D.] Univ N Carolina, UNC Dept Surg, Chapel Hill, NC 27599 USA. RP Troester, MA (reprint author), Univ N Carolina, Dept Epidemiol, Campus Box 7435, Chapel Hill, NC 27599 USA. EM troester@unc.edu RI Mani, Sendurai/A-7244-2009 OI Mani, Sendurai/0000-0002-5918-4276 FU National Cancer Institute [R01 CA155243]; National Institutes of Environmental Health Sciences [U01-ES019472, R01-CA138255]; Breast SPORE Career Development Award [P50CA058223]; Avon Foundation; University of North Carolina; HHMI through the Med into Grad Initiative FX This project was supported by grants from the National Cancer Institute and National Institutes of Environmental Health Sciences (U01-ES019472, R01-CA138255), a Breast SPORE (P50CA058223) Career Development Award to M. A. T., a grant from the Avon Foundation, and the University Cancer Research Fund at the University of North Carolina. P. C-H is a Howard Hughes Medical Institute (HHMI) Med into Grad Scholar supported in part by a grant to the University of North Carolina at Chapel Hill from HHMI through the Med into Grad Initiative. S. A. M. laboratory is supported by a grant from National Institute of Cancer (R01 CA155243). We are grateful to Jonine Figueroa, Mark Sherman and Gretchen Gierach at the National Cancer Institute for contributing samples from the Polish Women's Breast Cancer study and for helpful comments on this work and to Amy Drobish for assistance with medical records abstraction for patient clinical samples. NR 47 TC 29 Z9 29 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2012 VL 14 IS 2 AR R51 DI 10.1186/bcr3152 PG 12 WC Oncology SC Oncology GA 952DZ UT WOS:000304771800026 PM 22429463 ER PT J AU Sano, K Mitsunaga, M Nakajima, T Choyke, PL Kobayashi, H AF Sano, Kohei Mitsunaga, Makoto Nakajima, Takahito Choyke, Peter L. Kobayashi, Hisataka TI In vivo breast cancer characterization imaging using two monoclonal antibodies activatably labeled with near infrared fluorophores SO BREAST CANCER RESEARCH LA English DT Article ID EXPRESSION; RECEPTORS AB Introduction: The gene expression profiles of cancer cells are closely related to their aggressiveness and metastatic potential. Antibody-based immunohistochemistry (IHC) of tissue specimens is a common method of identifying expressed proteins in cancer cells and increasingly inform treatment decisions. Molecular imaging is a potential method of performing similar IHC studies in vivo without the requirement for biopsy or tumor excision. To date, antibody-based imaging has been limited by high background levels related to slow clearance, making such imaging practical. However, optically activatable imaging agents, which are only fluorescent when bound to their cognate receptor, open the possibility of doing in vivo multi-color IHC. Methods: We describe the use of activatable, near infrared fluorescence-labeled AlexaFluor680 (Alexa680) conjugated panitumumab (Pan) targeted against human epidermal growth factor receptor (EGFR) (Pan-Alexa680) and Indocyanine Green (ICG) conjugated trastuzumab (Tra) targeted against human epidermal growth factor receptor type 2 (HER2) (Tra-ICG) were synthesized and evaluated in cells in vitro and in an orthotopic breast cancer mouse model in vivo. Results: Pan-Alexa680 (self-quenched; SQ) and Tra-ICG were initially quenched but demonstrated a 5.2- and 50-fold dequenching capacity under detergent treatment, respectively. In vitro microscopy and flow cytometry using MDA-MB-468 (EGFR+/HER2-) and 3T3/HER2 cells (EGFR-/HER2+), demonstrated specific fluorescence signal for each cell type based on binding to Pan-Alexa680(SQ) or Tra-ICG. An in vivo imaging study employing a cocktail of Pan-Alexa680(SQ) and Tra-ICG (each 50 mu g) was injected into mice with orthotopic MDA-MB-468 and 3T3/HER2 tumors in the breast. Each probe visualized only the target-specific breast tumor. Conclusions: Multi-color target-specific fluorescence breast cancer imaging can be achieved in vivo by employing two activatable fluorescent probes administered as a cocktail. The images allowed us to see a specific receptor expression in each breast tumor without post-image processing. C1 [Sano, Kohei; Mitsunaga, Makoto; Nakajima, Takahito; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,RoomB3B69,10 Ctr Dr, Bethesda, MD 20892 USA. EM kobayash@mail.nih.gov FU US National Institutes of Health, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the US National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 18 TC 23 Z9 24 U1 5 U2 20 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2012 VL 14 IS 2 AR R61 DI 10.1186/bcr3167 PG 8 WC Oncology SC Oncology GA 952DZ UT WOS:000304771800036 PM 22510481 ER PT J AU Yang, XHR Figueroa, JD Falk, RT Zhang, H Pfeiffer, RM Hewitt, SM Lissowska, J Peplonska, B Brinton, L Garcia-Closas, M Sherman, ME AF Yang, Xiaohong R. Figueroa, Jonine D. Falk, Roni T. Zhang, Hong Pfeiffer, Ruth M. Hewitt, Stephen M. Lissowska, Jolanta Peplonska, Beata Brinton, Louise Garcia-Closas, Montserrat Sherman, Mark E. TI Analysis of terminal duct lobular unit involution in luminal A and basal breast cancers SO BREAST CANCER RESEARCH LA English DT Article ID HORMONE-RECEPTOR; RISK-FACTORS; POPULATION; ESTROGEN; CELLS AB Introduction: Involution of terminal duct lobular units (TDLUs), the structures that give rise to most breast cancers, has been associated with reduced breast cancer risk. Data suggest that the etiology and pathogenesis of luminal A and core basal phenotype (CBP) breast cancers differ, but associations with TDLU involution are unknown. Accordingly, we performed a masked microscopic assessment of TDLU involution in benign tissues associated with luminal A and CBP breast cancers diagnosed among women less than age 55 years. Methods: Cases were participants in a population-based case-control study conducted in Poland. Increased TDLU involution was defined as fewer acini per TDLU or shorter TDLU diameter. Luminal A was defined as estrogen receptor (ER) positive and/or progesterone receptor (PR) positive and human epidermal growth factor receptor 2 (HER2) negative and CBP as negative for ER, PR, and HER2 with expression of basal cytokeratins or epidermal growth factor receptor (EGFR). We performed logistic regression to evaluate associations between TDLU involution and tumor subtypes, adjusted for clinical characteristics and breast cancer risk factors. Results: Among 232 luminal A and 49 CBP cancers associated with evaluable TDLUs, CBP tumors were associated with significantly greater average number of acini per TDLU (odds ratio (OR) = 3.36, 95% confidence interval (CI) = 1.36 to 8.32, P = 0.009) and larger average TDLU diameter (OR = 2.49, 95% CI = 1.08 to 5.74, P = 0.03; comparing highest to lowest group, adjusted for age and study site). Conclusions: We suggest that TDLU involution is less marked in benign tissues surrounding CBP as compared to luminal A cancers, which may reflect differences in the etiology and pathogenesis of these tumor subtypes. C1 [Yang, Xiaohong R.; Figueroa, Jonine D.; Falk, Roni T.; Zhang, Hong; Pfeiffer, Ruth M.; Brinton, Louise; Garcia-Closas, Montserrat; Sherman, Mark E.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Zhang, Hong] Fudan Univ, Inst Biostat, Sch Life Sci, Shanghai 200433, Peoples R China. [Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Lissowska, Jolanta] Canc Ctr & M Sklodowska Curie Inst Oncol, Dept Canc Epidemiol & Prevent, PL-02781 Warsaw, Poland. [Peplonska, Beata] Nofer Inst Occupat Med, PL-91348 Lodz, Poland. [Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England. RP Yang, XHR (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM royang@mail.nih.gov RI Peplonska, Beata/F-6004-2010; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Hewitt, Stephen/0000-0001-8283-1788; Lissowska, Jolanta/0000-0003-2695-5799 FU NIH, NCI, DCEG FX This research was supported in part by the Intramural Research Program of the NIH, NCI, DCEG. NR 33 TC 14 Z9 14 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2012 VL 14 IS 2 AR R64 DI 10.1186/bcr3170 PG 8 WC Oncology SC Oncology GA 952DZ UT WOS:000304771800039 PM 22513288 ER PT J AU Knutson, KM Krueger, F Dal Monte, O Raymont, V Snyder, AD Kirsch, HE Wassermann, EM Grafman, J AF Knutson, K. M. Krueger, F. Dal Monte, O. Raymont, V. Snyder, A. D. Kirsch, H. E. Wassermann, E. M. Grafman, J. TI Gustatory cortical lesions affect motivation for snack foods SO COGNITIVE NEUROSCIENCE LA English DT Article DE Voxel-based lesion symptom mapping; Traumatic brain injury; Primary gustatory cortex ID VENTROMEDIAL PREFRONTAL CORTEX; ORBITOFRONTAL CORTEX; DECISION-MAKING; BRAIN; ACTIVATION; SOFTWARE; VALUES; DAMAGE AB Most neuropsychological research using food as a reward uses single-bid auctions. We wished to determine whether focal brain lesions would affect the ability and motivation to win snack food items in a computerized auction allowing multiple bids. This allowed us to assess participants' abilities under more complex conditions. We enrolled 154 male penetrating traumatic brain injury (pTBI) veterans, mean age 58, from the Vietnam Head Injury Study registry, and 53 male uninjured veterans, mean age 59. We used voxel-based lesion symptom mapping (VLSM) to identify effects of brain lesions on the ability to win items and on participants' answers to statements regarding their level of motivation and evaluation of how well they performed. Number of items won was not significantly associated with any lesions; however, lesions in gustatory cortex (GC) affected motivation and self-evaluation. Our findings provide further evidence of the primary GC's role in motivation for food and drink. C1 [Krueger, F.] George Mason Univ, Dept Mol Neurosci, Fairfax, VA 22030 USA. [Knutson, K. M.; Dal Monte, O.; Wassermann, E. M.] Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, NIH, Bethesda, MD USA. [Krueger, F.] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA. [Dal Monte, O.] Univ Turin, Dept Neuropsychol, Turin, Italy. [Dal Monte, O.] Henry M Jackson Fdn, Rockville, MD USA. [Raymont, V.] Univ London Imperial Coll Sci Technol & Med, Dept Med, London, England. [Raymont, V.] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA. [Snyder, A. D.] Virginia Tech, Caril Sch Med, Roanoke, VA USA. [Snyder, A. D.] Univ Chicago, Dept Econ, Chicago, IL 60637 USA. [Kirsch, H. E.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Kirsch, H. E.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA. [Kirsch, H. E.] Univ Calif San Francisco, Dept Biomed Imaging, San Francisco, CA 94143 USA. [Grafman, J.] Kessler Fdn Res Ctr, Traumat Brain Injury Res Lab, W Orange, NJ 07052 USA. RP Krueger, F (reprint author), George Mason Univ, Dept Mol Neurosci, 4400 Univ Dr,Mail Stop 2A1, Fairfax, VA 22030 USA. EM fkrueger@gmu.edu; jgrafman@kesslerfoundation.org OI Knutson, Kristine/0000-0003-4626-4514; Grafman, Jordan H./0000-0001-8645-4457; dal monte, olga/0000-0002-7823-4769 FU United States National Institutes of Health, National Institute of Neurological Disorders and Stroke; United States Army Medical Research and Material Command [DAMD17-01-1-0675]; Center for Neuroscience and Regenerative Medicine via Henry M. Jackson Foundation; National Naval Medical Center FX We especially thank the Vietnam War veterans who participated in this study. We thank the National Naval Medical Center for their support and provision of their facilities, S. Bonifant, B. Cheon, C. Ngo, A. Greathouse, K. Reding, and G. Tasick for their invaluable help with the testing of participants and organization of this study, and Sungyoung Auh for statistical help. SAS and all other SAS Institute Inc. product or service names are registered trademarks or trademarks of SAS Institute Inc., Cary, NC, USA.; The authors declare no conflict of interest. The work was supported by the United States National Institutes of Health, National Institute of Neurological Disorders and Stroke, intramural research program, and a project grant from the United States Army Medical Research and Material Command administrated by the Henry M. Jackson Foundation (Vietnam Head Injury Study Phase III: A 30-year post injury follow-up study, Grant DAMD17-01-1-0675). Olga Dal Monte was supported with funding from the Center for Neuroscience and Regenerative Medicine via the Henry M. Jackson Foundation. Note that the views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, the Department of Defense, nor the United States Government. NR 34 TC 1 Z9 1 U1 1 U2 4 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1758-8928 J9 COGN NEUROSCI-UK JI Cogn. Neurosci PY 2012 VL 3 IS 2 BP 131 EP 138 DI 10.1080/17588928.2012.688018 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 955OA UT WOS:000305028800009 PM 24168694 ER PT J AU Rai, V Nadar, SR Upadhyay, RK AF Rai, Vikas Nadar, Sreenivasan R. Upadhyay, Ranjit K. TI Nonlinear Phenomena in Biology and Medicine SO COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE LA English DT Editorial Material ID DYNAMICS C1 [Rai, Vikas] Jazan Univ, Fac Sci, Dept Math, Jizan 45142, Saudi Arabia. [Nadar, Sreenivasan R.] NIMH, Bethesda, MD 20892 USA. [Upadhyay, Ranjit K.] Indian Sch Mines, Dhanbad 826004, Bihar, India. RP Rai, V (reprint author), Jazan Univ, Fac Sci, Dept Math, Jizan 45142, Saudi Arabia. EM rvikas41@hotmail.com OI Rai, Vikas/0000-0001-7301-7872; Rajamoni Nadar, Sreenivasan/0000-0002-3970-1854 NR 3 TC 0 Z9 0 U1 0 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1748-670X J9 COMPUT MATH METHOD M JI Comput. Math. Method Med. PY 2012 AR 183879 DI 10.1155/2012/183879 PG 2 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 955XH UT WOS:000305053700001 ER PT J AU Avila, F Das, PJ Kutzler, M Owens, E Perelman, P Raudsepp, T AF Avila, F. Das, P. J. Kutzler, M. Owens, E. Perelman, P. Raudsepp, T. TI Development and Application of Molecular Tools for Camelid Cytogenetics SO CYTOGENETIC AND GENOME RESEARCH LA English DT Meeting Abstract CT 42nd Biennial American Cytogenetics Conference (ACC) CY APR 19-22, 2012 CL San Antonio, TX C1 [Avila, F.; Das, P. J.; Raudsepp, T.] Texas A&M Univ, Dept Vet Integrat Biosci, College Stn, TX USA. [Owens, E.] Texas A&M Univ, Dept Vet Pathobiol, College Stn, TX USA. [Kutzler, M.] Oregon State Univ, Dept Anim Sci, Coll Agr Sci, Corvallis, OR 97331 USA. [Perelman, P.] NCI, Lab Genom Divers, Frederick, MD 21701 USA. RI Perelman, Polina/N-8088-2015 OI Perelman, Polina/0000-0002-0982-5100 NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2012 VL 136 IS 4 MA 11 BP 328 EP 328 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 955BV UT WOS:000304993000023 ER PT J AU Kearney, HM Allen, WP Chaubey, A DuPont, BR Kaiser-Rogers, KA Rehder, CW South, ST Tepperberg, J Wolff, DJ Paschall, J Lassiter, S Hill, TJ AF Kearney, H. M. Allen, W. P. Chaubey, A. DuPont, B. R. Kaiser-Rogers, K. A. Rehder, C. W. South, S. T. Tepperberg, J. Wolff, D. J. Paschall, J. Lassiter, S. Hill, T. J. TI The Carolinas Array Group Database (CAGdb): A Platform-Independent Database of Microarray Findings Shared across Multiple Institutions to Aid in Laboratory Data Management, CNV Interpretation and Submission to ISCA/NCBI ClinVar Datasets SO CYTOGENETIC AND GENOME RESEARCH LA English DT Meeting Abstract CT 42nd Biennial American Cytogenetics Conference (ACC) CY APR 19-22, 2012 CL San Antonio, TX C1 [Kearney, H. M.; Allen, W. P.] Mission Hlth Syst, Fullerton Genet Ctr, Asheville, NC USA. [Chaubey, A.; DuPont, B. R.] Greenwood Genet Ctr, Greenwood, SC 29646 USA. [Kaiser-Rogers, K. A.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC USA. [Rehder, C. W.] Duke Univ, Durham, NC USA. [South, S. T.] Univ Utah, Dept Pediat & Pathol, ARUP Labs, Salt Lake City, UT USA. [Tepperberg, J.] LabCorp, Ctr Mol Biol & Pathol, Cytogenet Lab, Res Triangle Pk, NC USA. [Wolff, D. J.] Med Univ S Carolina, Charleston, SC 29425 USA. [Paschall, J.] NIH, NCBI, Natl Lib Med, Bethesda, MD 20892 USA. [Lassiter, S.; Hill, T. J.] Ninjanetix, Raleigh, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2012 VL 136 IS 4 MA 21 BP 332 EP 332 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 955BV UT WOS:000304993000033 ER PT J AU Riggs, ER Kaminsky, EB Patel, V Faucett, WA Thorland, E Church, D Paschall, J Jackson, L Aradhya, S Kuhn, R Nussbaum, R Rehm, H Wapner, R Ledbetter, DH Martin, CL AF Riggs, E. R. Kaminsky, E. B. Patel, V. Faucett, W. A. Thorland, E. Church, D. Paschall, J. Jackson, L. Aradhya, S. Kuhn, R. Nussbaum, R. Rehm, H. Wapner, R. Ledbetter, D. H. Martin, C. L. TI Towards a Universal Database of Human Genomic Variation: Lessons Learned from the ISCA Consortium SO CYTOGENETIC AND GENOME RESEARCH LA English DT Meeting Abstract CT 42nd Biennial American Cytogenetics Conference (ACC) CY APR 19-22, 2012 CL San Antonio, TX C1 [Riggs, E. R.; Kaminsky, E. B.; Patel, V.; Martin, C. L.] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA. [Faucett, W. A.; Ledbetter, D. H.] Geisinger Hlth Syst, Danville, PA USA. [Thorland, E.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Church, D.; Paschall, J.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Jackson, L.] Drexel Univ, Coll Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Jackson, L.] Childrens Hosp Philadelphia, Div Genet, Philadelphia, PA 19104 USA. [Aradhya, S.] GeneDx, Gaithersburg, MD USA. [Kuhn, R.] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA. [Nussbaum, R.] Univ Calif San Francisco, Dept Med, Div Med Genet, San Francisco, CA USA. [Rehm, H.] Partners HealthCare Ctr Personalized Genet Med, Mol Med Lab, Cambridge, MA USA. [Wapner, R.] Columbia Univ, Med Ctr, Dept Obstet & Gynecol, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2012 VL 136 IS 4 MA 23 BP 333 EP 333 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 955BV UT WOS:000304993000035 ER PT J AU Shamloo, BK Chhabra, P Freedman, AN Potosky, A Malin, J Smith, SW AF Shamloo, Behrooz K. Chhabra, Pankdeep Freedman, Andrew N. Potosky, Arnold Malin, Jennifer Smith, Sheila Weiss TI Novel Adverse Events of Bevacizumab in the US FDA Adverse Event Reporting System Database A Disproportionality Analysis SO DRUG SAFETY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; NITRIC-OXIDE SYNTHASE; METASTATIC COLORECTAL-CANCER; INTRAVITREAL BEVACIZUMAB; TUMOR-GROWTH; ANGIOGENESIS; CARCINOMA; RECEPTOR; CELLS; SURVEILLANCE AB Background: Bevacizumab is the first in its class, vascular endothelial growth factor (VEGF) inhibitor that was initially approved by the US FDA in 2004 for the treatment of metastatic colon cancer and other solid tumors. Pre-approval clinical trials, particularly for oncology drugs, are limited in their ability to detect certain adverse effects and, therefore, the FDA and pharmaceutical sponsors collect and monitor reports of adverse events (AEs) following approval. Objective: The purpose of this study was to screen the FDA's Adverse Event Reporting System (AERS) database for novel AEs that may be attributed to bevacizumab. Methods: The FDA AERS database was used to identify all AE reports for bevacizumab from February 2004 to September 2009. Disproportionality analysis was conducted for bevacizumab against all other drugs in the background by setting statistical significance at proportional reporting ratio (PRR) >= 2, observed case count >= 3 and chi-square >= 4. Subsequent clinical evaluation was performed to determine the clinical relevance of the findings and to group related events. Results: A total of 523 Preferred Terms (PTs) were disproportionally reported; following clinical review 63 (12%) were found to be both unlabelled and of clinical importance. These PTs were grouped into 15 clinical disorder groups. Among the clinical disorders, electrolyte abnormalities had the greatest number of reports (n=426) followed by cardiovascular events (n=421), gastrointestinal events (n=345), nervous system disorders (n=106) and pneumonitis (n=96). On sensitivity analysis, a number of clinically important unlabelled disorders, such as necrotizing fasciitis, vessel wall disorders, arrhythmia and conduction disorder and autoimmune thrombocytopenia still met the statistical significance criteria. Conclusions: During the study period, out of 12 010 AE reports mentioning bevacizumab, it was listed as the suspect drug in 94.2% of the reports. Our disproportionality analysis identified many events that are already recognized as AEs of bevacizumab, but it also identified a number of clinically important unlabelled terms, which if confirmed in future studies would have potential implications for use of bevacizumab in clinical practice. C1 [Chhabra, Pankdeep; Smith, Sheila Weiss] Univ Maryland, Ctr Drug Safety, Sch Pharm, Baltimore, MD 21201 USA. [Shamloo, Behrooz K.] Univ Nevada, Sch Med, Nevada Canc Inst, Las Vegas, NV 89154 USA. [Freedman, Andrew N.] NCI, NIH, Bethesda, MD 20892 USA. [Potosky, Arnold] Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC USA. [Malin, Jennifer] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Smith, SW (reprint author), Univ Maryland, Ctr Drug Safety, Sch Pharm, 220 Arch St,12th Floor, Baltimore, MD 21201 USA. EM sweiss@rx.umaryland.edu NR 37 TC 10 Z9 11 U1 0 U2 2 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PY 2012 VL 35 IS 6 BP 507 EP 518 PG 12 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 955TF UT WOS:000305043100008 PM 22612854 ER PT J AU Kumar, M Nagpal, R Kumar, R Hemalatha, R Verma, V Kumar, A Chakraborty, C Singh, B Marotta, F Jain, S Yadav, H AF Kumar, Manoj Nagpal, Ravinder Kumar, Rajesh Hemalatha, R. Verma, Vinod Kumar, Ashok Chakraborty, Chaitali Singh, Birbal Marotta, Francesco Jain, Shalini Yadav, Hariom TI Cholesterol-Lowering Probiotics as Potential Biotherapeutics for Metabolic Diseases SO EXPERIMENTAL DIABETES RESEARCH LA English DT Review ID BILE-SALT HYDROLASE; SERUM-LIPID LEVELS; LACTOBACILLUS-ACIDOPHILUS; BIFIDOBACTERIUM-LONGUM; LISTERIA-MONOCYTOGENES; DENSITY-LIPOPROTEIN; FERMENTED MILK; IN-VITRO; RATS; DECONJUGATION AB Cardiovascular diseases are one of the major causes of deaths in adults in the western world. Elevated levels of certain blood lipids have been reported to be the principal cause of cardiovascular disease and other disabilities in developed countries. Several animal and clinical trials have shown a positive association between cholesterol levels and the risks of coronary heart disease. Current dietary strategies for the prevention of cardiovascular disease advocate adherence to low-fat/low-saturated-fat diets. Although there is no doubt that, in experimental conditions, low-fat diets offer an effective means of reducing blood cholesterol concentrations on a population basis, these appear to be less effective, largely due to poor compliance, attributed to low palatability and acceptability of these diets to the consumers. Due to the low consumer compliance, attempts have been made to identify other dietary components that can reduce blood cholesterol levels. Supplementation of diet with fermented dairy products or lactic acid bacteria containing dairy products has shown the potential to reduce serum cholesterol levels. Various approaches have been used to alleviate this issue, including the use of probiotics, especially Bifidobacterium spp. and Lactobacillus spp.. Probiotics, the living microorganisms that confer health benefits on the host when administered in adequate amounts, have received much attention on their proclaimed health benefits which include improvement in lactose intolerance, increase in natural resistance to infectious disease in gastrointestinal tract, suppression of cancer, antidiabetic, reduction in serum cholesterol level, and improved digestion. In addition, there are numerous reports on cholesterol removal ability of probiotics and their hypocholesterolemic effects. Several possible mechanisms for cholesterol removal by probiotics are assimilation of cholesterol by growing cells, binding of cholesterol to cellular surface, incorporation of cholesterol into the cellular membrane, deconjugation of bile via bile salt hydrolase, coprecipitation of cholesterol with deconjugated bile, binding action of bile by fibre, and production of short-chain fatty acids by oligosaccharides. The present paper reviews the mechanisms of action of anti-cholesterolemic potential of probiotic microorganisms and probiotic food products, with the aim of lowering the risks of cardiovascular and coronary heart diseases. C1 [Jain, Shalini] NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Yadav, Hariom] NIDDKD, Endocrinol Diabet & Obes Branch, NIH, Bethesda, MD 20892 USA. [Kumar, Manoj; Kumar, Rajesh; Hemalatha, R.] Natl Inst Nutr, Dept Immunol & Microbiol, Hyderabad 50007, Andhra Pradesh, India. [Nagpal, Ravinder] Shaheed Udham Singh Coll Res & Technol, Radaur, Haryana, India. [Verma, Vinod] Natl Heart Ctr, Res & Dev Unit, Singapore 1687521, Singapore. [Kumar, Ashok] MLK Postgrad Coll, Dept Zool, Balrampur 271201, India. [Chakraborty, Chaitali] ITS Paramed Coll, Dept Biotechnol, Ghaziabad 201206, India. [Singh, Birbal] Indian Vet Res Inst, Reg Stn, Palampur 176061, Himachal Prades, India. [Marotta, Francesco] S Giuseppe Hosp, Hepatogastroenterol Unit, I-20123 Milan, Italy. RP Jain, S (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM shalini2601@gmail.com; yadavhariom@gmail.com OI Yadav, Hariom/0000-0003-4504-1597 NR 108 TC 51 Z9 51 U1 4 U2 60 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-5214 J9 EXP DIABETES RES JI Exp. Diabetes Res. PY 2012 AR 902917 DI 10.1155/2012/902917 PG 14 WC Endocrinology & Metabolism; Medicine, Research & Experimental SC Endocrinology & Metabolism; Research & Experimental Medicine GA 954TE UT WOS:000304969100001 ER PT J AU Stranahan, AM Martin, B Chadwick, W Park, SS Wang, LY Becker, KG Wood, WH Zhang, YQ Maudsley, S AF Stranahan, Alexis M. Martin, Bronwen Chadwick, Wayne Park, Sung-Soo Wang, Liyun Becker, Kevin G. Wood, William H., III Zhang, Yongqing Maudsley, Stuart TI Metabolic Context Regulates Distinct Hypothalamic Transcriptional Responses to Antiaging Interventions SO INTERNATIONAL JOURNAL OF ENDOCRINOLOGY LA English DT Article ID DIETARY ENERGY-INTAKE; CALORIC RESTRICTION; ARCUATE NUCLEUS; GENE-EXPRESSION; FATTY RATS; PROTEIN; LEPTIN; BRAIN; EXERCISE; MICE AB The hypothalamus is an essential relay in the neural circuitry underlying energy metabolism that needs to continually adapt to changes in the energetic environment. The neuroendocrine control of food intake and energy expenditure is associated with, and likely dependent upon, hypothalamic plasticity. Severe disturbances in energy metabolism, such as those that occur in obesity, are therefore likely to be associated with disruption of hypothalamic transcriptomic plasticity. In this paper, we investigated the effects of two well-characterized antiaging interventions, caloric restriction and voluntary wheel running, in two distinct physiological paradigms, that is, diabetic (db/db) and nondiabetic wild-type (C57/Bl/6) animals to investigate the contextual sensitivity of hypothalamic transcriptomic responses. We found that, both quantitatively and qualitatively, caloric restriction and physical exercise were associated with distinct transcriptional signatures that differed significantly between diabetic and nondiabetic mice. This suggests that challenges to metabolic homeostasis regulate distinct hypothalamic gene sets in diabetic and non-diabetic animals. A greater understanding of how genetic background contributes to hypothalamic response mechanisms could pave the way for the development of more nuanced therapeutics for the treatment of metabolic disorders that occur in diverse physiological backgrounds. C1 [Stranahan, Alexis M.] Georgia Hlth Sci Univ, Dept Physiol, Augusta, GA 30912 USA. [Martin, Bronwen] NIA, Metab Unit, Intramural Res Program, Baltimore, MD 21224 USA. [Chadwick, Wayne; Park, Sung-Soo; Wang, Liyun; Maudsley, Stuart] NIA, Receptor Pharmacol Unit, Intramural Res Program, Baltimore, MD 21224 USA. [Becker, Kevin G.; Wood, William H., III; Zhang, Yongqing] NIA, Gene Express & Genom Unit, Intramural Res Program, Baltimore, MD 21224 USA. RP Stranahan, AM (reprint author), Georgia Hlth Sci Univ, Dept Physiol, Augusta, GA 30912 USA. EM astranahan@georgiahealth.edu OI Becker, Kevin/0000-0002-6794-6656 FU National Institute on Aging, National Institutes of Health FX This paper was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. The authors wish to thank Dr. Michela Gallagher (Johns Hopkins University) for the use of resources for in situ hybridization experiments. NR 62 TC 5 Z9 5 U1 0 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-8337 J9 INT J ENDOCRINOL JI Int. J. Endocrinol. PY 2012 AR 732975 DI 10.1155/2012/732975 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 955JH UT WOS:000305013500001 ER PT S AU Linguraru, MG Richbourg, WJ Pamulapati, V Wang, SJ Summers, RM AF Linguraru, Marius George Richbourg, William J. Pamulapati, Vivek Wang, Shijun Summers, Ronald M. BE Molthen, RC Weaver, JB TI Robust Automated Detection, Segmentation and Classification of Hepatic Tumors from CT Data SO MEDICAL IMAGING 2012: BIOMEDICAL APPLICATIONS IN MOLECULAR, STRUCTURAL, AND FUNCTIONAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Biomedical Applications in Molecular, Structural and Functional Imaging CY FEB 05-07, 2012 CL San Diego, CA SP SPIE, Agilent Technol, Diamond SA, DQE Instruments Inc, eMagin, Isuzu Glass Co Ltd, Medtron Inc, Ocean Thin Films Inc DE Liver; CT; tumor; detection; segmentation; classification ID FEATURE-SELECTION AB The manuscript presents the automated detection and segmentation of hepatic tumors from abdominal CT images with variable acquisition parameters. After obtaining an initial segmentation of the liver, optimized graph cuts segment the liver tumor candidates using shape and enhancement constraints. One hundred and fifty-seven features are computed for the tumor candidates and support vector machines are used to select features and separate true and false detections. Training and testing are performed using leave-one-patient-out on 14 patients with a total of 79 tumors. After selection, the feature space is reduced to eight. The resulting sensitivity for tumor detection was 100% at 2.3 false positives/case. For the true tumors, 74.1% overlap and 1.6mm average surface distance were recorded between the ground truth and the results of the automated method. Results from test data demonstrate the method's robustness to analyze livers from difficult clinical cases to allow the diagnoses and temporal monitoring of patients with hepatic cancer. C1 [Linguraru, Marius George; Richbourg, William J.; Pamulapati, Vivek; Wang, Shijun; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. RP Linguraru, MG (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. NR 20 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8966-1 J9 PROC SPIE PY 2012 VL 8317 AR 83170J DI 10.1117/12.910617 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BAN07 UT WOS:000304813000018 ER PT S AU Chen, XJ Summers, RM Nacif, MS Liu, ST Bluemke, DA Yao, JH AF Chen, Xinjian Summers, Ronald M. Nacif, Marcelo Souto Liu, Songtao Bluemke, David A. Yao, Jianhua BE Haynor, DR Ourselin, S TI A framework of whole heart extracellular volume fraction estimation for low dose cardiac CT images SO MEDICAL IMAGING 2012: IMAGE PROCESSING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Processing CY FEB 06-09, 2012 CL San Diego, CA SP SPIE, Agilent Technol, Diamond SA, DQE Instruments Inc, eMagin, Isuzu Glass Co Ltd, Medtron Inc, Ocean Thin Films Inc DE Myocardium Segmentation; Registration; Demons; Graph Cut; Live Wire ID COMPUTED-TOMOGRAPHY; ALGORITHMS AB Cardiac magnetic resonance imaging (CMRI) has been well validated and allows quantification of myocardial fibrosis in comparison to overall mass of the myocardium. Unfortunately, CMRI is relatively expensive and is contraindicated in patients with intracardiac devices. Cardiac CT (CCT) is widely available and has been validated for detection of scar and myocardial stress/rest perfusion. In this paper, we sought to evaluate the potential of low dose CCT for the measurement of myocardial whole heart extracellular volume (ECV) fraction. A novel framework was proposed for CCT whole heart ECV estimation, which consists of three main steps. First, a shape constrained graph cut (GC) method was proposed for myocardium and blood pool segmentation for post-contrast image. Second, the symmetric Demons deformable registrations method was applied to register pre-contrast to post-contrast images. Finally, the whole heart ECV value was computed. The proposed method was tested on 7 clinical low dose CCT datasets with pre-contrast and post-contrast images. The preliminary results demonstrated the feasibility and efficiency of the proposed method. C1 [Chen, Xinjian; Summers, Ronald M.; Nacif, Marcelo Souto; Liu, Songtao; Bluemke, David A.; Yao, Jianhua] NIH, Radiol & Imaging Sci Dept, Ctr Clin, Bethesda, MD 20814 USA. RP Chen, XJ (reprint author), NIH, Radiol & Imaging Sci Dept, Ctr Clin, Bethesda, MD 20814 USA. EM jyao@mail.nih.gov OI Bluemke, David/0000-0002-8323-8086 NR 13 TC 2 Z9 2 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8963-0 J9 PROC SPIE PY 2012 VL 8314 AR 831429 DI 10.1117/12.911475 PG 7 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BAN14 UT WOS:000304820000078 ER PT J AU Heinze, RJ Sekerina, S Winkler, I Biertumpfel, C Oretskaya, TS Kubareva, E Friedhoff, P AF Heinze, Roger J. Sekerina, Svetlana Winkler, Ines Biertuempfel, Christian Oretskaya, Tatiana S. Kubareva, Elena Friedhoff, Peter TI Covalently trapping MutS on DNA to study DNA mismatch recognition and signaling SO MOLECULAR BIOSYSTEMS LA English DT Article ID REPAIR PROTEIN MUTS; CRYSTAL-STRUCTURES; MOLECULAR SWITCH; ATPASE ACTIVITY; COMPLEX; BINDING AB The DNA repair protein MutS forms clamp-like structures on DNA that search for and recognize base mismatches leading to ATP-transformed signaling clamps. In this study, the mobile MutS clamps were trapped on DNA in a functional state using single-cysteine variants of MutS and thiol-modified homoduplex or heteroduplex DNA. This approach allows stabilization of various transient MutS-DNA complexes and will enable their structural and functional analysis. C1 [Heinze, Roger J.; Winkler, Ines; Friedhoff, Peter] Univ Giessen, Inst Biochem, D-35392 Giessen, Germany. [Sekerina, Svetlana; Oretskaya, Tatiana S.; Kubareva, Elena] Lomonosov Moscow State Univ, Dept Chem, Belozersky Inst Phys Chem Biol, Moscow 119991, Russia. [Biertuempfel, Christian] NIDDKD, NIH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Friedhoff, P (reprint author), Univ Giessen, Inst Biochem, FB 08,Heinrich Buff Ring 58, D-35392 Giessen, Germany. EM kubareva@belozersky.msu.ru; Friedhoff@chemie.bio.uni-giessen.de RI Oretskaya, Tatiana/E-2556-2012; Kubareva, Elena/I-3184-2012; Sekerina, Svetlana/I-6428-2012; OI Biertumpfel, Christian/0000-0002-7528-6547 FU European Community [HEALTH-F4-2008-223545]; Deutsche Forschungs-gemeinschaft [GRK 1384]; Russian Foundation for Basic Research [RFBR-DFG 11-04-91336] FX This work was supported by European Community Seventh Framework Program FP7/2007-2013 under Grant HEALTH-F4-2008-223545 (to P.F., I.W., and R.J.H.), Deutsche Forschungs-gemeinschaft Grant GRK 1384 (to P.F. and R.J.H.) and Russian Foundation for Basic Research Grant RFBR-DFG 11-04-91336 (to T.O. and S.S.). NR 32 TC 4 Z9 4 U1 0 U2 12 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PY 2012 VL 8 IS 7 BP 1861 EP 1864 DI 10.1039/c2mb25086a PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 953QA UT WOS:000304884700002 PM 22627921 ER PT J AU Kimura, T Nakajima, T Kamijo, Y Tanaka, N Wang, LX Hara, A Sugiyama, E Tanaka, E Gonzalez, FJ Aoyama, T AF Kimura, Takefumi Nakajima, Takero Kamijo, Yuji Tanaka, Naoki Wang, Lixuan Hara, Atsushi Sugiyama, Eiko Tanaka, Eiji Gonzalez, Frank J. Aoyama, Toshifumi TI Hepatic Cerebroside Sulfotransferase Is Induced by PPAR alpha Activation in Mice SO PPAR RESEARCH LA English DT Article ID ACYL-COA DEHYDROGENASE; AMINO-ACID-SEQUENCE; RECEPTOR-ALPHA; LIPOPROTEIN METABOLISM; DISTINCT SPECIFICITIES; GENE-PRODUCT; LIVER; SULFOGLYCOLIPIDS; EXPRESSION; SULFATIDE AB Sulfatides are one of the major sphingoglycolipids in mammalian serum and are synthesized and secreted mainly from the liver as a component of lipoproteins. Recent studies revealed a protective role for serum sulfatides against arteriosclerosis and hypercoagulation. Although peroxisome proliferator-activated receptor (PPAR) alpha has important functions in hepatic lipoprotein metabolism, its association with sulfatides has not been investigated. In this study, sulfatide levels and the expression of enzymes related to sulfatide metabolism were examined using wild-type (+/+), Ppara-heterozygous (+/-), and Ppara-null (-/-) mice given a control diet or one containing 0.1% fenofibrate, a clinically used hypolipidemic drug and PPAR alpha activator. Fenofibrate treatment increased serum and hepatic sulfatides in Ppara (+/+) and (+/-) mice through a marked induction of hepatic cerebroside sulfotransferase (CST), a key enzyme in sulfatide synthesis, in a PPAR alpha-dependent manner. Furthermore, increases in CST mRNA levels were correlated with mRNA elevations of several known PPAR alpha target genes, and such changes were not observed for other sulfatide-metabolism enzymes in the liver. These results suggest that PPAR alpha activation enhances hepatic sulfatide synthesis via CST induction and implicate CST as a novel PPAR alpha target gene.\ C1 [Kimura, Takefumi; Nakajima, Takero; Kamijo, Yuji; Tanaka, Naoki; Wang, Lixuan; Hara, Atsushi; Aoyama, Toshifumi] Shinshu Univ, Grad Sch Med, Inst Aging & Adaptat, Dept Metab Regulat, Matsumoto, Nagano 3908621, Japan. [Kimura, Takefumi; Tanaka, Eiji] Shinshu Univ, Sch Med, Dept Gastroenterol, Matsumoto, Nagano 3908621, Japan. [Kamijo, Yuji] Shinshu Univ, Sch Med, Dept Nephrol, Matsumoto, Nagano 3908621, Japan. [Tanaka, Naoki; Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Sugiyama, Eiko] Nagano Prefectural Coll, Dept Nutr Sci, Nagano 3808525, Japan. RP Kamijo, Y (reprint author), Shinshu Univ, Grad Sch Med, Inst Aging & Adaptat, Dept Metab Regulat, 3-1-1 Asahi, Matsumoto, Nagano 3908621, Japan. EM yujibeat@shinshu-u.ac.jp RI Kimura, Takefumi/D-3412-2011 OI Kimura, Takefumi/0000-0002-1481-1029 NR 38 TC 3 Z9 3 U1 0 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-4757 J9 PPAR RES JI PPAR Res. PY 2012 AR 174932 DI 10.1155/2012/174932 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 955KG UT WOS:000305017000001 ER PT J AU Sloboda, Z Glantz, MD Tarter, RE AF Sloboda, Zili Glantz, Meyer D. Tarter, Ralph E. TI Revisiting the Concepts of Risk and Protective Factors for Understanding the Etiology and Development of Substance Use and Substance Use Disorders: Implications for Prevention SO SUBSTANCE USE & MISUSE LA English DT Article DE development; environment; genetics; neurobiology; protection; psychopathology; risk; vulnerability ID ALCOHOL-USE DISORDERS; ANTISOCIAL PERSONALITY-DISORDER; DEFICIT HYPERACTIVITY DISORDER; CANNABIS USE DISORDER; ILLICIT DRUG-USE; ANXIETY DISORDERS; YOUNG ADULTHOOD; MAJOR DEPRESSION; MENTAL-DISORDERS; MARIJUANA USE AB Over the past 20 years we have accumulated a greater knowledge and understanding of the genetic, neurobiological, and behavioral factors that may be associated with young people initiating the use of drugs and other substances and to progressing from use to abuse and dependence. This knowledge suggests that individuals may be "predisposed" to substance use disorders (SUD) and that the actual engagement in these behaviors depends on their environmental experiences from micro to macro levels. This paper summarizes this knowledge base and supports a developmental framework that examines the interaction of posited genetic, psychological, and neurobiological "predispositions" to SUD and those environmental influences that exacerbate this vulnerability. C1 [Sloboda, Zili] JBS Int Inc, Res & Dev Grp, Res & Dev, Bethesda, MD 20852 USA. [Glantz, Meyer D.] NIDA, Div Epidemiol Serv & Prevent Res, NIH, Bethesda, MD 20892 USA. [Tarter, Ralph E.] Univ Pittsburgh, Ctr Educ & Drug Abuse Res, Pittsburgh, PA USA. [Glantz, Meyer D.] NIDA, Div Epidemiol & Prevent Res DESPR, NIH, Bethesda, MD 20892 USA. [Glantz, Meyer D.] NIDA, Epidemiol Res Branch, Bethesda, MD 20892 USA. [Glantz, Meyer D.] NIDA, Vulnerabil Res Program, Bethesda, MD 20892 USA. RP Sloboda, Z (reprint author), JBS Int Inc, Res & Dev Grp, Res & Dev, 5515 Secur Lane,Suite 800, Bethesda, MD 20852 USA. EM zsloboda@jbsinternational.com NR 197 TC 14 Z9 15 U1 17 U2 40 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1082-6084 EI 1532-2491 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2012 VL 47 IS 8-9 BP 944 EP 962 DI 10.3109/10826084.2012.663280 PG 19 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 954AH UT WOS:000304915500008 PM 22676565 ER PT J AU Pecoraro, A Ma, M Woody, GE AF Pecoraro, Anna Ma, Michelle Woody, George E. TI The Science and Practice of Medication-Assisted Treatments for Opioid Dependence SO SUBSTANCE USE & MISUSE LA English DT Article DE opioid addiction; methadone; buprenorphine; heroin; diamorphine; history ID METHADONE-MAINTENANCE PROGRAMS; SUBSTANCE USE DISORDERS; DRUG-USERS; ADDICTION TREATMENT; HEROIN-ADDICTION; CONTINGENCY MANAGEMENT; HARM REDUCTION; COMMUNITY REINFORCEMENT; CONCEPTUAL-FRAMEWORK; NALTREXONE TREATMENT AB This paper briefly reviews the evolution of opioid addiction treatment from humanitarian to scientific and evidence-based, the evidence bases supporting major medication-assisted treatments and adjunctive psychosocial techniques, as well as challenges faced by clinicians and treatment providers seeking to provide those treatments. Attitudes, politics, policy, and financial issues are discussed. C1 [Pecoraro, Anna; Woody, George E.] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19106 USA. [Pecoraro, Anna; Ma, Michelle; Woody, George E.] NIDA Clin Trials Network, Philadelphia, PA USA. [Ma, Michelle] Univ Michigan, Sch Med, Ann Arbor, MI USA. RP Woody, GE (reprint author), Univ Penn, Perelman Sch Med, Dept Psychiat, 600 Publ Ledger Bldg,150 S Independence Mall W, Philadelphia, PA 19106 USA. EM woody@tresearch.org NR 174 TC 13 Z9 13 U1 2 U2 12 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1082-6084 EI 1532-2491 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2012 VL 47 IS 8-9 BP 1026 EP 1040 DI 10.3109/10826084.2012.663292 PG 15 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 954AH UT WOS:000304915500013 PM 22676570 ER PT B AU Fenton, SE Beck, LM Borde, AR Rayner, JL AF Fenton, Suzanne E. Beck, Lydia M. Borde, Aditi R. Rayner, Jennifer L. BE DiamantiKandarakis, E Gore, AC TI Developmental Exposure to Environmental Endocrine Disruptors and Adverse Effects on Mammary Gland Development SO ENDOCRINE DISRUPTORS AND PUBERTY SE Contemporary Endocrinology LA English DT Article; Book Chapter DE Breast; Endocrine disruptor; Lactation; Mammary gland; Terminal end buds; Tumor development ID BISPHENOL-A ALTERS; RESTRICTED GESTATIONAL EXPOSURES; BREAST-CANCER RISK; LONG-EVANS RATS; FEMALE RAT; PERFLUOROOCTANOIC ACID; IN-UTERO; NEONATAL EXPOSURE; PRENATAL EXPOSURE; GROWTH-FACTOR AB The breast or mammary gland is an organ highly dependent upon hormones and other endogenous growth catalysts for normal development. Environmental chemical exposures have been associated with altered breast developmental timing in populations of girls, and several chemicals and dietary agents are known to induce delayed or accelerated mammary gland development in rodent models. These alterations in development are more likely to occur if exposure to endocrine disruptors coincides with periods of rapid cellular proliferation. These periods of growth include prenatal, peripubertal, and pregnant/lactational mammary development. This chapter will outline the studies that have shown significant effects of environmental chemicals on mammary gland development in rodent models and discuss the relationship of these data to later life adverse health repercussions. C1 [Fenton, Suzanne E.] Natl Inst Environm Hlth Sci, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Beck, Lydia M.; Borde, Aditi R.] Natl Inst Environm Hlth Sci, Summers Discovery Internship Program, Res Triangle Pk, NC USA. [Beck, Lydia M.] Univ Missouri, Sch Med, Columbia, MO USA. [Rayner, Jennifer L.] SRC Inc, Arlington, VA USA. RP Fenton, SE (reprint author), Natl Inst Environm Hlth Sci, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. EM fentonse@niehs.nih.gov NR 74 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-560-6 J9 CONTEMP ENDOCRINOL S PY 2012 BP 201 EP 224 DI 10.1007/978-1-60761-561-3_7 D2 10.1007/978-1-60761-561-3 PG 24 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BYU27 UT WOS:000300380600007 ER PT B AU Hatch, EE Nelson, JW Troisi, R Titus, L AF Hatch, Elizabeth E. Nelson, Jessica W. Troisi, Rebecca Titus, Linda BE DiamantiKandarakis, E Gore, AC TI Developmental Exposure to Endocrine Disrupting Chemicals: Is There a Connection with Birth and Childhood Weights? SO ENDOCRINE DISRUPTORS AND PUBERTY SE Contemporary Endocrinology LA English DT Article; Book Chapter DE Birth weight; Developmental origins of health and disease; Endocrine-disrupting chemicals; In utero exposures; Obesity ID BODY-MASS INDEX; POLYCHLORINATED-BIPHENYLS PCBS; FOR-GESTATIONAL-AGE; DICHLORODIPHENYL DICHLOROETHENE DDE; IN-UTERO; DIETHYLSTILBESTROL DES; MATERNAL SMOKING; PRENATAL EXPOSURE; FETAL-GROWTH; INSULIN-RESISTANCE AB Childhood obesity has increased dramatically over the last several decades in developed countries, and more recently in developing countries. Most research on causes of obesity has focused on various aspects of diet and lack of physical activity as the primary risk factors. Clearly, a balance between energy intake and energy expenditure is critical to maintain a healthy body weight, but other factors have also been linked to the obesity epidemic. One area of concern is increasing exposure to endocrine disrupting chemicals (EDCs), especially during the prenatal period. Animal studies have suggested that fetal exposure to certain EDCs may cause systemic alterations in aspects of 'fetal programming' related to adipocyte differentiation and function, appetite regulation, and other body systems involved in weight homeostasis. One plausible pathway between prenatal exposures to EDCs and obesity might be through effects on fetal growth, since both growth retardation and high birth weight have been associated with later obesity. Some studies have found associations between several classes of EDCs, including PCBs, organochlorine pesticides such as DDT and hexachlorobenzene (HCB), phenols, and PFCs and fetal growth retardation. Although animal data have suggested that EDCs can affect offspring obesity, thus far, data from human epidemiological studies that have directly examined prenatal EDC exposure in relation to childhood growth are not sufficient to draw conclusions. Several methodologic challenges exist in conducting these studies, including timing of measurement of EDCs in gestation, accounting for potential confounders occurring during pregnancy and childhood, and accurately measuring adiposity. C1 [Hatch, Elizabeth E.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Nelson, Jessica W.] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Troisi, Rebecca] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Titus, Linda] Dartmouth Med Sch, Dept Community & Family Med & Pediat, Lebanon, NH USA. [Titus, Linda] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. RP Hatch, EE (reprint author), Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. EM eehatch@bu.edu NR 189 TC 0 Z9 0 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-560-6 J9 CONTEMP ENDOCRINOL S PY 2012 BP 283 EP 321 DI 10.1007/978-1-60761-561-3_12 D2 10.1007/978-1-60761-561-3 PG 39 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BYU27 UT WOS:000300380600012 ER PT J AU Mechanic, LE Chen, HS Amos, CI Chatterjee, N Cox, NJ Divi, RL Fan, RZ Harris, EL Jacobs, K Kraft, P Leal, SM McAllister, K Moore, JH Paltoo, DN Province, MA Ramos, EM Ritchie, MD Roeder, K Schaid, DJ Stephens, M Thomas, DC Weinberg, CR Witte, JS Zhang, SP Zollner, S Feuer, EJ Gillanders, EM AF Mechanic, Leah E. Chen, Huann-Sheng Amos, Christopher I. Chatterjee, Nilanjan Cox, Nancy J. Divi, Rao L. Fan, Ruzong Harris, Emily L. Jacobs, Kevin Kraft, Peter Leal, Suzanne M. McAllister, Kimberly Moore, Jason H. Paltoo, Dina N. Province, Michael A. Ramos, Erin M. Ritchie, Marylyn D. Roeder, Kathryn Schaid, Daniel J. Stephens, Matthew Thomas, Duncan C. Weinberg, Clarice R. Witte, John S. Zhang, Shunpu Zoellner, Sebastian Feuer, Eric J. Gillanders, Elizabeth M. TI Next Generation Analytic Tools for Large Scale Genetic Epidemiology Studies of Complex Diseases SO GENETIC EPIDEMIOLOGY LA English DT Article DE gene-gene interactions; gene-environment interactions; rare variants; next generation sequencing; complex phenotypes; simulations; computational resources ID GENOME-WIDE ASSOCIATION; MULTIFACTOR-DIMENSIONALITY REDUCTION; RARE VARIANTS; BREAST-CANCER; MENDELIAN RANDOMIZATION; ENVIRONMENT INTERACTION; MISSING HERITABILITY; METABOLIC TRAITS; COMMON DISEASES; SUSCEPTIBILITY AB Over the past several years, genome-wide association studies (GWAS) have succeeded in identifying hundreds of genetic markers associated with common diseases. However, most of these markers confer relatively small increments of risk and explain only a small proportion of familial clustering. To identify obstacles to future progress in genetic epidemiology research and provide recommendations to NIH for overcoming these barriers, the National Cancer Institute sponsored a workshop entitled "Next Generation Analytic Tools for Large-Scale Genetic Epidemiology Studies of Complex Diseases'' on September 15-16, 2010. The goal of the workshop was to facilitate discussions on (1) statistical strategies and methods to efficiently identify genetic and environmental factors contributing to the risk of complex disease; and (2) how to develop, apply, and evaluate these strategies for the design, analysis, and interpretation of large-scale complex disease association studies in order to guide NIH in setting the future agenda in this area of research. The workshop was organized as a series of short presentations covering scientific (gene-gene and gene-environment interaction, complex phenotypes, and rare variants and next generation sequencing) and methodological (simulation modeling and computational resources and data management) topic areas. Specific needs to advance the field were identified during each session and are summarized. Genet. Epidemiol. 36 : 22-35, 2012. (C) 2011 Wiley Periodicals, Inc. C1 [Mechanic, Leah E.; Divi, Rao L.; Gillanders, Elizabeth M.] NCI, Div Canc Control & Populat Sci, Epidemiol & Genet Res Program, Host Susceptibil Factors Branch,NIH, Bethesda, MD 20892 USA. [Chen, Huann-Sheng; Zhang, Shunpu; Feuer, Eric J.] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Amos, Christopher I.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Chatterjee, Nilanjan] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Cox, Nancy J.] Univ Chicago, Dept Med, Med Genet Sect, Chicago, IL 60637 USA. [Fan, Ruzong] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. [Harris, Emily L.] Natl Inst Dent & Craniofacial Res, Translat Genom Res Branch, Div Extramural Res, NIH, Bethesda, MD USA. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Leal, Suzanne M.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [McAllister, Kimberly] NIEHS, Susceptibil & Populat Hlth Branch, NIH, Res Triangle Pk, NC 27709 USA. [Moore, Jason H.] Dartmouth Coll, Inst Quantitat Biomed Sci, Lebanon, NH 03756 USA. [Paltoo, Dina N.] NHLBI, Div Heart & Vasc Dis, NIH, Bethesda, MD 20892 USA. [Province, Michael A.] Washington Univ, Sch Med, Div Stat Genom, St Louis, MO USA. [Ramos, Erin M.] NHGRI, Off Populat Genom, NIH, Bethesda, MD 20892 USA. [Ritchie, Marylyn D.] Penn State Univ, Ctr Syst Genom Biochem & Mol Biol, University Pk, PA 16802 USA. [Roeder, Kathryn] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. [Schaid, Daniel J.] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA. [Stephens, Matthew] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Stephens, Matthew] Univ Chicago, Dept Stat, Chicago, IL 60637 USA. [Thomas, Duncan C.] Univ So Calif, Keck Sch Med, Prevent Med Div Biostat, Los Angeles, CA 90033 USA. [Weinberg, Clarice R.] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. [Witte, John S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Witte, John S.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Zoellner, Sebastian] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. RP Mechanic, LE (reprint author), NCI, Div Canc Control & Populat Sci, Epidemiol & Genet Res Program, Host Susceptibil Factors Branch,NIH, 6130 Execut Blvd,Room 5126, Bethesda, MD 20892 USA. EM mechanil@mail.nih.gov RI Ritchie, Marylyn/C-1114-2012; Chen, Huann-Sheng/D-6328-2013 OI Chen, Huann-Sheng/0000-0002-5905-8050 FU NCI NIH HHS [P30 CA023108]; NHGRI NIH HHS [U54 HG006493, U54 HG006493-01, UM1 HG006493]; NHLBI NIH HHS [RC2 HL102926, RC2 HL102926-01]; NIAID NIH HHS [R01 AI059694]; NIGMS NIH HHS [P20 GM103534]; NLM NIH HHS [R01 LM009012, R01 LM010098] NR 82 TC 32 Z9 32 U1 0 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JAN PY 2012 VL 36 IS 1 BP 22 EP 35 DI 10.1002/gepi.20652 PG 14 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 918JB UT WOS:000302244400004 PM 22147673 ER PT J AU Bousquet, J Anto, JM Demoly, P Schunemann, HJ Togias, A Akdis, M Auffray, C Bachert, C Bieber, T Bousquet, PJ Carlsen, KH Casale, TB Cruz, AA Keil, T Carlsen, KCL Maurer, M Ohta, K Papadopoulos, NG Rodriguez, MR Samolinski, B Agache, I Andrianarisoa, A Ang, CS Annesi-Maesano, I Ballester, F Baena-Cagnani, CE Basagana, X Bateman, ED Bel, EH Bedbrook, A Beghe, B Beji, M Ben Kheder, A Benet, M Bennoor, KS Bergmann, KC Berrissoul, F Jensen, CB Bleecker, ER Bonini, S Boner, AL Boulet, LP Brightling, CE Brozek, JL Bush, A Busse, WW Camargos, PAM Canonica, GW Carr, W Cesario, A Chen, YZ Chiriac, AM Costa, DJ Cox, L Custovic, A Dahl, R Darsow, U Didi, T Dolen, WK Douagui, H Dubakiene, R El-Meziane, A Fonseca, JA Fokkens, WJ Fthenou, E Gamkrelidze, A Garcia-Aymerich, J van Wijk, RG Gimeno-Santos, E Guerra, S Haahtela, T Haddad, H Hellings, PW Hellquist-Dahl, B Hohmann, C Howarth, P Hourihane, JO Humbert, M Jacquemin, B Just, J Kalayci, O Kaliner, MA Kauffmann, F Kerkhof, M Khayat, G N'Goran, BK Kogevinas, M Koppelman, GH Kowalski, ML Kull, I Kuna, P Larenas, D Lavi, I Le, LT Lieberman, P Lipworth, B Mahboub, B Makela, MJ Martin, F Martinez, FD Marshall, GD Mazon, A Melen, E Meltzer, EO Mihaltan, F Mohammad, Y Mohammadi, A Momas, I Morais-Almeida, M Mullol, J Muraro, A Naclerio, R Nafti, S Namazova-Baranova, L Nawijn, MC Nyembue, TD Oddie, S O'Hehir, RE Okamoto, Y Orru, MP Ozdemir, C Ouedraogo, GS Palkonen, S Panzner, P Passalacqua, G Pawankar, R Pigearias, B Pin, I Pinart, M Pison, C Popov, TA Porta, D Postma, DS Price, D Rabe, KF Ratomaharo, J Reitamo, S Rezagui, D Ring, J Roberts, R Roca, J Rogala, B Romano, A Rosado-Pinto, J Ryan, D Sanchez-Borges, M Scadding, GK Sheikh, A Simons, FER Siroux, V Schmid-Grendelmeier, PD Smit, HA Sooronbaev, T Stein, RT Sterk, PJ Sunyer, J Terreehorst, I Toskala, E Tremblay, Y Valenta, R Valeyre, D Vandenplas, O van Weel, C Vassilaki, M Varraso, R Viegi, G Wang, DY Wickman, M Williams, D Wohrl, S Wright, J Yorgancioglu, A Yusuf, OM Zar, HJ Zernotti, ME Zidarn, M Zhong, N Zuberbier, T AF Bousquet, J. Anto, J. M. Demoly, P. Schuenemann, H. J. Togias, A. Akdis, M. Auffray, C. Bachert, C. Bieber, T. Bousquet, P. J. Carlsen, K. H. Casale, T. B. Cruz, A. A. Keil, T. Carlsen, K. C. Lodrup Maurer, M. Ohta, K. Papadopoulos, N. G. Rodriguez, M. Roman Samolinski, B. Agache, I. Andrianarisoa, A. Ang, C. S. Annesi-Maesano, I. Ballester, F. Baena-Cagnani, C. E. Basagana, X. Bateman, E. D. Bel, E. H. Bedbrook, A. Beghe, B. Beji, M. Ben Kheder, A. Benet, M. Bennoor, K. S. Bergmann, K. C. Berrissoul, F. Jensen, C. Bindslev Bleecker, E. R. Bonini, S. Boner, A. L. Boulet, L. P. Brightling, C. E. Brozek, J. L. Bush, A. Busse, W. W. Camargos, P. A. M. Canonica, G. W. Carr, W. Cesario, A. Chen, Y. Z. Chiriac, A. M. Costa, D. J. Cox, L. Custovic, A. Dahl, R. Darsow, U. Didi, T. Dolen, W. K. Douagui, H. Dubakiene, R. El-Meziane, A. Fonseca, J. A. Fokkens, W. J. Fthenou, E. Gamkrelidze, A. Garcia-Aymerich, J. van Wijk, R. Gerth Gimeno-Santos, E. Guerra, S. Haahtela, T. Haddad, H. Hellings, P. W. Hellquist-Dahl, B. Hohmann, C. Howarth, P. Hourihane, J. O. Humbert, M. Jacquemin, B. Just, J. Kalayci, O. Kaliner, M. A. Kauffmann, F. Kerkhof, M. Khayat, G. N'Goran, B. Koffi Kogevinas, M. Koppelman, G. H. Kowalski, M. L. Kull, I. Kuna, P. Larenas, D. Lavi, I. Le, L. T. Lieberman, P. Lipworth, B. Mahboub, B. Makela, M. J. Martin, F. Martinez, F. D. Marshall, G. D. Mazon, A. Melen, E. Meltzer, E. O. Mihaltan, F. Mohammad, Y. Mohammadi, A. Momas, I. Morais-Almeida, M. Mullol, J. Muraro, A. Naclerio, R. Nafti, S. Namazova-Baranova, L. Nawijn, M. C. Nyembue, T. D. Oddie, S. O'Hehir, R. E. Okamoto, Y. Orru, M. P. Ozdemir, C. Ouedraogo, G. S. Palkonen, S. Panzner, P. Passalacqua, G. Pawankar, R. Pigearias, B. Pin, I. Pinart, M. Pison, C. Popov, T. A. Porta, D. Postma, D. S. Price, D. Rabe, K. F. Ratomaharo, J. Reitamo, S. Rezagui, D. Ring, J. Roberts, R. Roca, J. Rogala, B. Romano, A. Rosado-Pinto, J. Ryan, D. Sanchez-Borges, M. Scadding, G. K. Sheikh, A. Simons, F. E. R. Siroux, V. Schmid-Grendelmeier, P. D. Smit, H. A. Sooronbaev, T. Stein, R. T. Sterk, P. J. Sunyer, J. Terreehorst, I. Toskala, E. Tremblay, Y. Valenta, R. Valeyre, D. Vandenplas, O. van Weel, C. Vassilaki, M. Varraso, R. Viegi, G. Wang, D. Y. Wickman, M. Williams, D. Woehrl, S. Wright, J. Yorgancioglu, A. Yusuf, O. M. Zar, H. J. Zernotti, M. E. Zidarn, M. Zhong, N. Zuberbier, T. CA WHO Collaborating Ctr Asthma TI Severe Chronic Allergic (and Related) Diseases: A Uniform Approach - A MeDALL - GA(2)LEN - ARIA Position Paper SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article DE Immunoglobulin E; Asthma; Rhinitis; Rhinosinusitis; Urticaria; Atopic dermatitis ID QUALITY-OF-LIFE; ASTHMA CONTROL QUESTIONNAIRE; WORLD-HEALTH-ORGANIZATION; ATOPIC-DERMATITIS; CHRONIC RHINOSINUSITIS; NASAL POLYPOSIS; NONALLERGIC RHINITIS; TASK-FORCE; CHRONIC URTICARIA; RANDOMIZED-TRIAL AB Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies. Copyright (C) 2012 S. Karger AG, Basel C1 [Bousquet, J.; Bousquet, P. J.; Chiriac, A. M.] Hop Arnaud de Villeneuve, Dept Resp Dis, Univ Hosp, Montpellier, France. [Bousquet, J.; Jacquemin, B.; Kauffmann, F.; Varraso, R.] INSERM, CESP Ctr Res Epidemiol & Populat Hlth, U1018, Resp & Environm Epidemiol Team, Villejuif, France. [Anto, J. M.; Basagana, X.; Benet, M.; Garcia-Aymerich, J.; Gimeno-Santos, E.; Guerra, S.; Kogevinas, M.; Lavi, I.; Pinart, M.; Sunyer, J.] Ctr Res Environm Epidemiol CREAL, Barcelona, Spain. [Anto, J. M.; Basagana, X.; Benet, M.; Garcia-Aymerich, J.; Gimeno-Santos, E.; Guerra, S.; Kogevinas, M.; Pinart, M.; Sunyer, J.] IMIM Hosp Mar, Municipal Inst Med Res, Barcelona, Spain. [Anto, J. M.; Garcia-Aymerich, J.; Sunyer, J.] UPF, Barcelona, Spain. [Bousquet, J.; Demoly, P.; Bousquet, P. J.; Bedbrook, A.] WHO Collaborating Ctr Asthma & Rhinitis, Montpellier, France. [Demoly, P.] Hop Arnaud de Villeneuve, INSERM, U657, Univ Hosp Montpellier, Montpellier, France. [Schuenemann, H. J.; Brozek, J. L.] McMaster Univ, Dept Clin Epidemiol & Biostat & Med, Hamilton, ON, Canada. [Togias, A.] NIAID, Bethesda, MD 20892 USA. [Akdis, M.] Univ Zurich, Swiss Inst Allergy & Asthma Res SIAF, Davos, Switzerland. [Auffray, C.] CNRS Inst Biol Sci, Villejuif, France. [Bachert, C.] Univ Hosp Ghent, URL Upper Airways Res Lab, Ghent, Belgium. [Bieber, T.] Univ Med Ctr, Dept Dermatol & Allergy, Bonn, Germany. [Carlsen, K. H.; Carlsen, K. C. Lodrup] Univ Oslo, Oslo Univ Hosp, Dept Paediat, Oslo, Norway. [Casale, T. B.] Creighton Univ, Dept Med, Div Allergy & Immunol, Omaha, NE 68178 USA. [Cruz, A. A.] Univ Fed Bahia, Sch Med, ProAR FMB, Salvador, BA, Brazil. [Keil, T.; Hohmann, C.] Charite, Inst Social Med Epidemiol & Hlth Econ, D-13353 Berlin, Germany. [Maurer, M.; Bergmann, K. C.; Zuberbier, T.] Charite, Allergy Ctr Charite, Dept Dermatol, D-13353 Berlin, Germany. [Ohta, K.] Teikyo Univ, Sch Med, Dept Med, Div Resp Med & Allergol, Tokyo 173, Japan. [Papadopoulos, N. G.] Univ Athens, Dept Allergy, Pediat Clin 2, Athens, Greece. [Rodriguez, M. Roman] Son Pisa Primary Care Ctr, IB Salut Balear Hlth Serv, Palma de Mallorca, Spain. [Samolinski, B.] Med Univ Warsaw, Dept Prevent Environm Hazards & Allergol, Warsaw, Poland. [Agache, I.] Transylvania Univ, Fac Med, Brasov, Romania. [Andrianarisoa, A.] Minist Hlth, Publ Hosp Med Serv, Antananarivo, Madagascar. [Annesi-Maesano, I.] INSERM, EPAR U707, Paris, France. [Annesi-Maesano, I.] EPAR UMR S UPMC, Paris, France. [Ballester, F.; Mazon, A.] Univ Valencia, Valencia, Spain. [Ballester, F.; Mazon, A.] Ctr Publ Hlth Res CSISP, Valencia, Spain. [Baena-Cagnani, C. E.; Zernotti, M. E.] Catholic Univ, Fac Med, Cordoba, Argentina. [Baena-Cagnani, C. E.] Univ Genoa, Sch Specializat, Genoa, Italy. [Bateman, E. D.] Univ Cape Town, Fac Hlth Sci, ZA-7925 Cape Town, South Africa. [Bel, E. H.; Sterk, P. J.] Univ Amsterdam, Acad Med Ctr, Dept Pulmonol, NL-1012 WX Amsterdam, Netherlands. [Beghe, B.] Univ Southampton, Div Human Genet Infect, Sch Med, Southampton, Hants, England. [Beghe, B.] Univ Southampton, Div Human Genet Infect Inflammat & Repair, Sch Med, Southampton, Hants, England. [Beji, M.] Ctr Hositalo Univ Rabta, Serv Pneumol Allergol, Tunis, Tunisia. [Ben Kheder, A.] Hop A Mami, Ariana, Tunisia. [Bennoor, K. S.] Natl Inst Dis Chest & Hosp, Dhaka, Bangladesh. [Ang, C. S.; Berrissoul, F.] Natl Inst Dis Chest & Hosp, Air Khmer, Cambodia. [Jensen, C. Bindslev] Odense Univ Hosp, DK-5000 Odense, Denmark. [Bleecker, E. R.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Bonini, S.] Inst Neurobiol & Mol Med CNR, Rome, Italy. [Bonini, S.] Univ Naples 2, Dept Med, Naples, Italy. [Boner, A. L.] Univ Verona, Dept Paediat, I-37100 Verona, Italy. [Boulet, L. P.] Hop Laval, Inst Cardiol & Pneumol, Quebec City, PQ, Canada. [Boulet, L. P.] Univ Laval, Quebec City, PQ, Canada. [Brightling, C. E.] Inst Lung Hlth, Leicester, Leics, England. [Bush, A.] Royal Brompton Hosp, Dept Paediat Resp Med, London SW3 6LY, England. [Bush, A.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. [Busse, W. W.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI USA. [Camargos, P. A. M.] Univ Fed Minas Gerais, Sch Med, Dept Pediat, Belo Horizonte, MG, Brazil. [Canonica, G. W.; Passalacqua, G.] Univ Genoa, Dept Internal Med, DIMI, I-16126 Genoa, Italy. [Carr, W.] So Calif Res, Mission Viejo, CA USA. [Cesario, A.] IRCCS San Raffaele Pisana, Rome, Italy. [Cesario, A.] Catholic Univ, Dept Thorac Surg, Rome, Italy. [Chen, Y. Z.] Capital Inst Pediat, Asthma Clin & Educ Ctr, Beijing, Peoples R China. [Chen, Y. Z.] Ctr Asthma Res & Educ, Beijing, Peoples R China. [Costa, D. J.] Univ Montpellier, Primary Care Dept, F-34059 Montpellier, France. [Cox, L.] Nova SE Univ, Coll Osteopath Med, Davie, FL USA. [Custovic, A.] Univ Manchester, Manchester, Lancs, England. [Dahl, R.; Hellquist-Dahl, B.] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. [Darsow, U.] Tech Univ Munich, Dept Dermatol & Allergy Biederstein, Munich, Germany. [Didi, T.] Ctr Hosp Reg Annecy, Serv Pneumol, Annecy, France. [Dolen, W. K.] Med Coll Georgia, Augusta, GA 30912 USA. [Douagui, H.] Ctr Hosp Univ Beni Messous, Serv Pneumoallergol, Algiers, Algeria. [Dubakiene, R.] GA2LEN Collaborating Ctr, Vilnius, Lithuania. [Dubakiene, R.] Vilnius Univ, Fac Med, Vilnius, Lithuania. [El-Meziane, A.] Soc Marocaine Malad Resp, Casablanca, Morocco. [El-Meziane, A.] Ctr Commercial Nadia, Ctr Resp Dis & Allergy, Casablanca, Morocco. [Fonseca, J. A.] Univ Porto, Sch Med, Dept Hlth Informat & Decis Sci, P-4100 Oporto, Portugal. [Fonseca, J. A.] Univ Porto, Sch Med, CINTESIS, P-4100 Oporto, Portugal. [Fonseca, J. A.] Hosp Sao Joao, Oporto, Portugal. [Fonseca, J. A.] Inst & Hosp CUF, Oporto, Portugal. [Fokkens, W. J.] Univ Amsterdam, Dept Otorhinolaryngol, Amsterdam, Netherlands. [Fthenou, E.; Vassilaki, M.] Univ Crete, Fac Med, Dept Social Med, Iraklion, Crete, Greece. [Gamkrelidze, A.] WHO CO Georgia, Tbilisi, Rep of Georgia. [van Wijk, R. Gerth] Erasmus MC, Dept Internal Med, Sect Allergol, Rotterdam, Netherlands. [Guerra, S.] Univ Arizona, Tucson, AZ USA. [Haahtela, T.; Makela, M. J.; Reitamo, S.] Helsinki Univ Hosp, Dept Dermatol, Skin & Allergy Hosp, Helsinki, Finland. [Haddad, H.] Ctr Hosp Tarbes Lourdes, AFLP, Bigorre, France. [Haddad, H.] Ctr Hosp Tarbes Lourdes, Serv Pneumol, Bigorre, France. [Hellings, P. W.] Univ Hosp Leuven, Dept Otorhinolaryngol Head & Neck Surg, Louvain, Belgium. [Hourihane, J. O.] Natl Univ Ireland Univ Coll Cork, Cork, Ireland. [Howarth, P.] Univ Southampton, Southampton, Hants, England. [Humbert, M.] Univ Paris 11, Serv Pneumol, Hop Antoine Beclere, Clamart, France. [Jacquemin, B.; Kauffmann, F.; Varraso, R.] Univ Paris 11, UMRS 1018, Villejuif, France. [Just, J.] Univ Paris 06, Grp Hosp Trousseau La Roche Guyon, APHP, Ctr Asthme & Allergies, F-75252 Paris 05, France. [Kalayci, O.] Hacettepe Univ, Sch Med, Pediat Allergy & Asthma Unit, Ankara, Turkey. [Kaliner, M. A.] George Washington Univ, Sch Med, Washington, DC USA. [Kaliner, M. A.] Inst Asthma & Allergy, Chevy Chase, MD USA. [Kerkhof, M.] Univ Groningen, Dept Epidemiol, GRIAC Res Inst, Univ Med Ctr Groningen, Groningen, Netherlands. [Khayat, G.] Univ St Joseph, Fac Med, Beirut, Lebanon. [Khayat, G.] Hotel Dieu France, Serv Pneumol, Beirut, Lebanon. [N'Goran, B. Koffi] Ctr Hosp Univ, Serv Malad Resp, Abidjan Cocody, Cote Ivoire. [Kogevinas, M.] Natl Sch Publ Hlth, Dept Nutr, Athens, Greece. [Koppelman, G. H.] Univ Groningen, Univ Med Ctr Groningen, Dept Pediat Pulmonol & Pediat Allergol, Beatrix Childrens Hosp,GRIAC Res Inst, Groningen, Netherlands. [Kowalski, M. L.] Med Univ Lodz, Dept Immunol Rheumatol & Allergy, Lodz, Poland. [Kull, I.] Karolinska Inst, Ctr Allergy Res, Stockholm, Sweden. [Kull, I.] Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden. [Kuna, P.] Med Univ Lodz, Barlicki Univ Hosp, Lodz, Poland. [Larenas, D.] Hosp Med Sur, Dept Allergy, Mexico City, DF, Mexico. [Le, L. T.] Univ Med & Pharm, Ho Chi Minh City, Vietnam. [Lieberman, P.] Univ Tennessee, Coll Med, Memphis, TN USA. [Lipworth, B.] Univ Dundee, Asthma & Allergy Res Grp, Dundee, Scotland. [Mahboub, B.] Dubai Hlth Author, Pulm & Allergy Unit, Dubai, U Arab Emirates. [Mahboub, B.] Univ Sharjah, Sharjah, U Arab Emirates. [Martinez, F. D.] Univ Arizona, Arizona Resp Ctr, Tucson, AZ USA. [Marshall, G. D.] Univ Mississippi, Med Ctr, Div Clin Immunol & Allergy, Jackson, MS 39216 USA. [Melen, E.] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. [Melen, E.] Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden. [Meltzer, E. O.] Univ Calif San Diego, Allergy & Asthma Med Grp, San Diego, CA 92103 USA. [Meltzer, E. O.] Univ Calif San Diego, Res Ctr, San Diego, CA 92103 USA. [Mihaltan, F.] Inst Pneumol Marius Nasta, Bucharest, Romania. [Mohammad, Y.] Tishreen Univ, Sch Med, Dept Internal Med, WHO EMRO CC CRD, Latakia, Syria. [Mohammadi, A.] Assoc Franco Marocaine Pathol Thorac AFMAPATH, Marrakech, Morocco. [Momas, I.] Paris Descartes Univ, Dept Publ Hlth & Biostat, EA 4064, Paris, France. [Momas, I.] Paris Municipal Dept Social Act Childhood & Hlth, Paris, France. [Morais-Almeida, M.] CUF Descobertas Hosp, Immunoallergy Dept, Lisbon, Portugal. [Mullol, J.] IDIBAPS, Hosp Clin, Rhinol Unit, Barcelona, Spain. [Mullol, J.] IDIBAPS, Hosp Clin, ENT Dept, Smell Clin, Barcelona, Spain. [Muraro, A.] Univ Padua, Dept Pediat, Padua, Italy. [Naclerio, R.] Univ Chicago, Chicago, IL 60637 USA. [Nafti, S.] Mustapha Hosp, Algiers, Algeria. [Namazova-Baranova, L.] Sci Ctr Childrens Hlth RAMS, Moscow, Russia. [Nawijn, M. C.] Univ Groningen, Lab Allergol & Pulm Dis, Dept Pathol & Med Biol, GRIAC Res Inst,Univ Med Ctr Groningen, Groningen, Netherlands. [Nyembue, T. D.] Kinshasa Univ, Kinshasa, Zaire. [Oddie, S.; Wright, J.] Bradford Teaching Hosp Fdn Trust, Bradford Inst Hlth Res, Bradford, W Yorkshire, England. [Oddie, S.] Bradford Royal Infirm, Bradford BD9 6RJ, W Yorkshire, England. [O'Hehir, R. E.] Alfred Hosp, Melbourne, Vic, Australia. [O'Hehir, R. E.] Monash Univ, Melbourne, Vic 3004, Australia. [Okamoto, Y.] Chiba Univ Hosp, Dept Otorhinolaryngol, Chiba, Japan. [Ozdemir, C.] Marmara Univ, Div Pediat Allergy & Immunol, Istanbul, Turkey. [Ozdemir, C.] Marmara Univ, Mem Hlth Grp, Istanbul, Turkey. [Ouedraogo, G. S.] Ctr Hosp Univ Pediat Charles de Gaulle, Ouagadougou, Burkina Faso. [Palkonen, S.] EFA European Federat Allergy & Airways Dis Patien, Brussels, Belgium. [Panzner, P.] Fac Med Plzen, Dept Immunol & Allergol, Plzen, Czech Republic. [Panzner, P.] Charles Univ Prague, Prague, Czech Republic. [Pawankar, R.] Nippon Med Sch, Bunkyo Ku, Tokyo 113, Japan. [Pigearias, B.] NICE, Paris, France. [Pigearias, B.] Soc Pneumol Langue Francaise, Paris, France. [Pin, I.] CHU Grenoble, F-38043 Grenoble, France. [Pin, I.] Inst Albert Bonniot, INSERM, U823, Grenoble, France. [Pin, I.] Univ Grenoble 1, Grenoble, France. [Pison, C.] Univ Hosp Grenoble, Dept Pulmonol, Grenoble, France. [Pison, C.] Inserm 884, Grenoble, France. [Pison, C.] Univ Grenoble, Grenoble, France. [Popov, T. A.] Med Univ Sofia, Clin Allergy & Asthma, Sofia, Bulgaria. [Popov, T. A.] Alexanders Univ Hosp, Sofia, Bulgaria. [Porta, D.] Reg Hlth Serv Lazio Reg, Dept Epidemiol, Rome, Italy. [Postma, D. S.] Univ Groningen, Dept Pulmonol, GRIAC Res Inst, Univ Med Ctr Groningen, Groningen, Netherlands. [Price, D.] Univ Aberdeen, GPIAG, Aberdeen, Scotland. [Rabe, K. F.] Leiden Univ, Med Ctr, Dept Pulmonol, Leiden, Netherlands. [Ratomaharo, J.; Sterk, P. J.] Hop Prive Athis Mons, Serv Pneumol, Athis Mons, France. [Rezagui, D.] AFAP, Munich, Germany. [Ring, J.] Tech Univ Munich, Munich, Germany. [Roberts, R.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Roca, J.] Univ Barcelona, CIBERES, Hosp Clin, Inst Clin Torax,IDIBAPS, Barcelona, Spain. [Rogala, B.] Silesian Univ, Sch Med, Zabrze, Poland. [Romano, A.] UCSC Allergy Unit, Dept Internal Med & Geriatr, Rome, Italy. [Rosado-Pinto, J.] Hosp Luz, Immunoallergy Dept, Lisbon, Portugal. [Rosado-Pinto, J.] Hosp Dona Estefania, Lisbon, Portugal. [Ryan, D.] Woodbrook Med Ctr, Loughborough, Leics, England. [Ryan, D.] Univ Aberdeen, Aberdeen, Scotland. [Sanchez-Borges, M.] Ctr Med Docente La Trinidad, Dept Allergy & Clin Immunol, Caracas, Venezuela. [Scadding, G. K.] UCL, Royal Natl TNE Hosp, London, England. [Sheikh, A.] Univ Edinburgh, Sch Med, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [Simons, F. E. R.] Univ Manitoba, Fac Med, Winnipeg, MB, Canada. [Siroux, V.] INSERM, U823, Team Environm Epidemiol Appl Reprod & Resp, Grenoble, France. [Siroux, V.] Univ Grenoble 1, Grenoble, France. [Schmid-Grendelmeier, P. D.] Univ Zurich Hosp, Dept Dermatol, Allergy Unit, CH-8091 Zurich, Switzerland. [Smit, H. A.] Univ Utrecht, Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Sooronbaev, T.; Stein, R. T.] Natl Ctr Cardiol & Internal Med, Bishkek, Kyrgyzstan. [Stein, R. T.] Pontificia Univ Catolica RGS, Sch Med, Porto Alegre, RS, Brazil. [Terreehorst, I.] AMC Hosp, Dept ENT & Paediat, Amsterdam, Netherlands. [Toskala, E.] Finnish Inst Occupat Hlth, Helsinki, Finland. [Tremblay, Y.] Univ Laval, Fac Med, Dept Obstetr & Gynecol Axis Reprod Perinatal & Ch, Quebec City, PQ G1K 7P4, Canada. [Valenta, R.] Med Univ Vienna, Christian Doppler Lab Allergy Res, Ctr Pathophysiol Infectiol & Immunol, Div Immunopathol,Dept Pathophysiol & Allergy Res, Vienna, Austria. [Valeyre, D.] Univ Paris 13, PRES Sorbonne Paris Cite, Bobigny, France. [Valeyre, D.] Avicenne Hosp, AP HP, Bobigny, France. [Vandenplas, O.] Catholic Univ Louvain, Univ Hosp Mt Godinne, Yvoir, Belgium. [van Weel, C.] Radboud Univ Nijmegen, Med Ctr, Dept Primary & Community Care, Nijmegen, Netherlands. [Viegi, G.] CNR Inst Biomed & Mol Immunol IBIM, Palermo, Italy. [Viegi, G.] Clin Physiol IFC, Pisa, Italy. [Wang, D. Y.] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore 117595, Singapore. [Wickman, M.] Karolinska Inst, Sachs Childrens Hosp, Stockholm, Sweden. [Wickman, M.] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. [Williams, D.] Univ N Carolina, Sch Pharm, Chapel Hill, NC 27515 USA. [Woehrl, S.] Med Univ Vienna, Dept Dermatol Allergy & Infect Dis DIAID, Div Immunol, Vienna, Austria. [Yorgancioglu, A.] Celal Bayar Univ, Sch Med, Dept Pulmonol, Manisa, Turkey. [Yusuf, O. M.] Allergy & Asthma Inst, Islamabad, Pakistan. [Zar, H. J.] Univ Cape Town, Dept Paediat & Child Hlth, ZA-7925 Cape Town, South Africa. [Zar, H. J.] Univ Cape Town, Sch Child & Adolescent Hlth, Red Cross Childrens Hosp, ZA-7925 Cape Town, South Africa. [Zidarn, M.] Univ Clin Resp & Allerg Dis, Golnik, Slovenia. [Zhong, N.] Guangzhou Med Univ, Guangzhou Inst Resp Dis, Guangzhou, Guangdong, Peoples R China. [Zhong, N.] Guangzhou Med Univ, State Key Lab Resp Dis, Guangzhou, Guangdong, Peoples R China. [Zuberbier, T.] Charite, Network Excellence, Global Allergy & Asthma European Network GA2LEN, D-13353 Berlin, Germany. RP Bousquet, J (reprint author), Ctr Hosp Univ, FR-34295 Montpellier 05, France. EM jean.bousquet@inserm.fr RI O'Hehir, Robyn/H-3627-2011; CESARIO, Alfredo/O-4215-2015; Wohrl, Stefan/B-6954-2013; Bindslev-Jensen, Carsten/H-1877-2011; Annesi-Maesano, Isabella/D-9173-2016; van Weel, Chris/D-4375-2009; Pinart, Mariona/L-1931-2015; Porta, Daniela/J-9042-2016; Custovic, Adnan/A-2435-2012; Cruz, Alvaro/I-1676-2012; Varraso, Raphaelle/R-8740-2016; Basagana, Xavier/C-3901-2017; Kogevinas, Manolis/C-3918-2017; Sunyer, J/G-6909-2014; Anto, J/H-2676-2014; Garcia-Aymerich, J/G-6867-2014; Sheikh, Aziz /D-2818-2009; Wright, John/H-1624-2012; Namazova-Baranova, Leyla/D-4934-2013; Stein, Renato/K-2568-2014; Fonseca, Joao/B-7562-2008; Dahl, Ronahl/F-8170-2013; Casale, Thomas/K-4334-2013; Stein, Renato/G-2975-2012; siroux, valerie/N-1865-2013; PIN, Isabelle/N-3020-2013; FMUP, CINTESIS/C-6631-2014 OI Price, David/0000-0002-9728-9992; O'Hehir, Robyn/0000-0002-3489-7595; CESARIO, Alfredo/0000-0003-4687-0709; Namazova-Baranova, Leyla/0000-0002-2209-7531; Ryan, Dermot/0000-0002-4115-7376; Popov, Todor/0000-0001-5052-5866; Kull, Inger/0000-0001-6096-3771; Makela, Mika/0000-0002-2933-3111; Panzner, Petr/0000-0002-1291-450X; Wohrl, Stefan/0000-0002-6324-0007; Papadopoulos, Nikolaos/0000-0002-2508-3872; Terreehorst, Ingrid/0000-0002-3264-2740; Fthenou, Eleni/0000-0002-1178-6841; Mazon, Angel/0000-0001-5639-1037; Bindslev-Jensen, Carsten/0000-0002-8940-038X; Bousquet, Philippe Jean/0000-0002-0217-5483; Bonini, Sergio/0000-0003-0079-3031; van Weel, Chris/0000-0003-3653-4701; Pinart, Mariona/0000-0002-8223-1325; Porta, Daniela/0000-0002-3431-2729; Custovic, Adnan/0000-0001-5218-7071; Cruz, Alvaro/0000-0002-7403-3871; Varraso, Raphaelle/0000-0002-3338-7825; Basagana, Xavier/0000-0002-8457-1489; Sunyer, J/0000-0002-2602-4110; Anto, J/0000-0002-4736-8529; Garcia-Aymerich, J/0000-0002-7097-4586; Sheikh, Aziz /0000-0001-7022-3056; Wright, John/0000-0001-9572-7293; Fonseca, Joao/0000-0002-0887-8796; Casale, Thomas/0000-0002-3149-7377; FMUP, CINTESIS/0000-0001-7248-2086 NR 133 TC 39 Z9 40 U1 3 U2 46 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 EI 1423-0097 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PY 2012 VL 158 IS 3 BP 216 EP 231 DI 10.1159/000332924 PG 16 WC Allergy; Immunology SC Allergy; Immunology GA 948EA UT WOS:000304485200003 ER PT J AU Morrell, CH Brant, LJ Sheng, S Metter, EJ AF Morrell, Christopher H. Brant, Larry J. Sheng, Shan Metter, E. Jeffrey TI Screening for prostate cancer using multivariate mixed-effects models SO JOURNAL OF APPLIED STATISTICS LA English DT Article DE classification; disease screening; longitudinal data; sensitivity; specificity ID LONGITUDINAL BIOMARKERS; JOINT ANALYSIS; MISSING DATA; ANTIGEN; RISK; OUTCOMES; DISEASE; MEN; EVENT; TESTOSTERONE AB Using several variables known to be related to prostate cancer, a multivariate classification method is developed to predict the onset of clinical prostate cancer. A multivariate mixed-effects model is used to describe longitudinal changes in prostate-specific antigen (PSA), a free testosterone index (FTI), and body mass index (BMI) before any clinical evidence of prostate cancer. The patterns of change in these three variables are allowed to vary depending on whether the subject develops prostate cancer or not and the severity of the prostate cancer at diagnosis. An application of Bayes' theorem provides posterior probabilities that we use to predict whether an individual will develop prostate cancer and, if so, whether it is a high-risk or a low-risk cancer. The classification rule is applied sequentially one multivariate observation at a time until the subject is classified as a cancer case or until the last observation has been used. We perform the analyses using each of the three variables individually, combined together in pairs, and all three variables together in one analysis. We compare the classification results among the various analyses and a simulation study demonstrates how the sensitivity of prediction changes with respect to the number and type of variables used in the prediction process. C1 [Morrell, Christopher H.] Loyola Univ Maryland, Dept Math & Stat, Baltimore, MD 21210 USA. [Morrell, Christopher H.; Brant, Larry J.; Sheng, Shan] NIA, Baltimore, MD 21224 USA. [Metter, E. Jeffrey] NIA, Baltimore, MD 21225 USA. RP Morrell, CH (reprint author), Loyola Univ Maryland, Dept Math & Stat, 4501 N Charles St, Baltimore, MD 21210 USA. EM chm@loyola.edu FU NIH, National Institute on Aging FX This research was supported (in part) by the Intramural Research Program of the NIH, National Institute on Aging. We thank the editor and two reviewers for comments that helped to improve the paper. NR 44 TC 3 Z9 3 U1 1 U2 7 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0266-4763 J9 J APPL STAT JI J. Appl. Stat. PY 2012 VL 39 IS 6 BP 1151 EP 1175 DI 10.1080/02664763.2011.644523 PG 25 WC Statistics & Probability SC Mathematics GA 948DS UT WOS:000304484400001 PM 22679342 ER PT J AU Byrne, MM Kornfeld, J Vanderpool, R Belanger, M AF Byrne, Margaret M. Kornfeld, Julie Vanderpool, Robin Belanger, Marc TI Discussions of Cancer Clinical Trials with the National Cancer Institute's Cancer Information Service SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID QUESTION PROMPT LIST; BREAST-CANCER; INFORMED-CONSENT; LUNG-CANCER; PARTICIPATION; BARRIERS; ENROLLMENT; AWARENESS; WILLINGNESS; ONCOLOGISTS AB Clinical trials are essential for the development of new and effective treatments for cancer; however, participation rates are low. One reason for this is lack of knowledge about clinical trials. This study assessed how often clinical trials are discussed on calls to National Cancer Institute's Cancer Information Service (CIS). The authors quantitatively analyzed 283,094 calls to the CIS (1-800-4-CANCER) over 3 years (2006-2008). They calculated descriptive statistics and multivariate regressions to determine whether specific caller characteristics are associated with the presence of a clinical trials discussion. In addition, 2 focus groups were conducted with CIS information specialists (n = 12) to provide insight into the findings. The authors found that approximately 9.3% of CIS calls discussed clinical trials, with higher percentages for patients (12.5%) and family members (15.4%). Calls with Hispanics, Blacks, and Spanish speakers were less likely to include a conversation. For all cancers, patients who are in treatment or experiencing a recurrence were statistically significantly more likely to discuss clinical trials. CIS information specialists reported callers' limited knowledge of clinical trials. The CIS has the unique ability to make a substantial effect in educating patients about clinical trials as an option in cancer treatment and care. C1 [Byrne, Margaret M.; Kornfeld, Julie] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA. [Vanderpool, Robin] Univ Kentucky, Coll Publ Hlth, Dept Hlth Behav, Lexington, KY USA. [Belanger, Marc] NCI, Coastal Canc Informat Serv, Miami, FL USA. RP Byrne, MM (reprint author), Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, 1120 NW 14th St, Miami, FL 33136 USA. EM mbyrne2@med.miami.edu FU NCI NIH HHS [N02 CO051107]; PHS HHS [N02C051107-12-0-0] NR 38 TC 3 Z9 3 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2012 VL 17 IS 3 BP 319 EP 337 DI 10.1080/10810730.2011.626500 PG 19 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 948CI UT WOS:000304480800006 PM 22150169 ER PT J AU Wininger, M Kim, NH Craelius, W AF Wininger, Michael Kim, Nam H. Craelius, William TI Reformulation in the Phase Plane Enhances Smoothness Rater Accuracy in Stroke SO JOURNAL OF MOTOR BEHAVIOR LA English DT Article DE jerk; movement; phase plane; single joint; stroke ID MOTOR CONTROL; MOVEMENT; JERK; RECOVERY AB To improve the characterization of motor impairment, we compared the sensitivities of a phase plane metric with temporal domain measures derived from integrated squared jerk (ISJ). Five subjects with stroke and a cohort of 21 neurologically intact volunteers performed self-paced, isolated elbow flexions. Analysis of angular trajectories from the stroke group revealed that temporal domain metrics failed to detect a performance deficit at the p < .05 level, while the phase plane metric did resolve a deficit (p < .01). When applied to a subset of movements with arrest periods, the phase measure also uniquely identified impairment (Wilcoxon rank-sum test, p < .001). Finally, when tested on a data-driven model, the phase measure, but not temporal metrics, increased monotonically with the severity of trajectory distortions. We conclude that motion smoothness can be accurately measured in the phase plane. C1 [Wininger, Michael] NIMH, Clin Disorders Branch, Neuropathol Sect, Bethesda, MD 20892 USA. [Wininger, Michael] VA Connecticut Healthcare Syst, VA Cooperat Studies Program Coordinating Ctr, West Haven, CT USA. [Kim, Nam H.; Craelius, William] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA. RP Wininger, M (reprint author), NIMH, Clin Disorders Branch, Neuropathol Sect, Bldg 10,Room 4N313D, Bethesda, MD 20892 USA. EM Michael.Wininger@nih.gov FU NSF-IGERT [DGE 033196]; NIDRR RERC FX The authors gratefully acknowledge Steven Escaldi, DO, and Eileen Crandall, PT, for patient administration, David I. Shreiber, PhD; Troy Shinbrot, PhD; and Don Yungher, PhD, for helpful suggestions, and an anonymous reviewer for guidance in the completion and writing of this work. This work was funded in part by NSF-IGERT fellowship to Michael Wininger (DGE 033196, Prabhas Moghe, PI), and a NIDRR RERC grant to William Craelius. NR 23 TC 4 Z9 4 U1 1 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0022-2895 J9 J MOTOR BEHAV JI J. Mot. Behav. PY 2012 VL 44 IS 3 BP 149 EP 159 DI 10.1080/00222895.2012.663012 PG 11 WC Neurosciences; Psychology; Psychology, Experimental; Sport Sciences SC Neurosciences & Neurology; Psychology; Sport Sciences GA 949TT UT WOS:000304599500002 PM 22420840 ER PT J AU Kent, EE Parry, C Montoya, MJ Sender, LS Morris, RA Anton-Culver, H AF Kent, Erin E. Parry, Carla Montoya, Michael J. Sender, Leonard S. Morris, Rebecca A. Anton-Culver, Hoda TI "You're too young for this": Adolescent and Young Adults' Perspectives on Cancer Survivorship SO JOURNAL OF PSYCHOSOCIAL ONCOLOGY LA English DT Article DE adolescent and young adult; qualitative research; focus groups; cancer survivorship ID HEALTH-CARE; OUTCOMES; ASSOCIATION; CHALLENGES; ONCOLOGY; IMPACT; NEEDS; WORK AB Adolescent and young adult cancer survivors face unique challenges not systematically addressed by cancer clinicians. Four focus groups and two individual interviews were conducted with 19 survivors to profile experiences and identify key concerns for future interventions. The resultant themes reflect cancer care continuum challenges (such as delays in diagnosis, problems with adherence), psychosocial concerns (such as infertility and reproductive concerns, changing social relationships, financial burden), and the paradox of being diagnosed with cancer as a young adult. Future intervention development for adolescent and young adult survivors should involve patient voices at each stage of the research process. C1 [Kent, Erin E.] NCI, Canc Prevent Fellowship Program, NIH, Rockville, MD 20852 USA. [Kent, Erin E.; Parry, Carla] NCI, Off Canc Survivorship, NIH, Rockville, MD 20852 USA. [Kent, Erin E.; Anton-Culver, Hoda] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA. [Montoya, Michael J.] Univ Calif Irvine, Dept Anthropol, Dept Chicano Latino Studies, Irvine, CA USA. [Montoya, Michael J.] Univ Calif Irvine, Dept Populat Hlth & Prevent, Irvine, CA USA. [Sender, Leonard S.] Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Irvine, CA USA. [Sender, Leonard S.; Morris, Rebecca A.] CHOC Childrens Hosp Orange Cty, Orange, CA USA. [Anton-Culver, Hoda] Univ Calif Irvine, Genet Epidemiol Res Inst, Irvine, CA USA. RP Kent, EE (reprint author), NCI, Canc Prevent Fellowship Program, NIH, 6116 Execut Blvd,Suite 404, Rockville, MD 20852 USA. EM erin.kent@nih.gov FU NCCDPHP CDC HHS [R36 DP002012, R36DP002012-01] NR 43 TC 21 Z9 22 U1 1 U2 9 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0734-7332 J9 J PSYCHOSOC ONCOL JI J. Psychosoc. Oncol. PY 2012 VL 30 IS 2 BP 260 EP 279 DI 10.1080/07347332.2011.644396 PG 20 WC Psychology, Social SC Psychology GA 948XT UT WOS:000304537800007 PM 22416959 ER PT J AU Petralia, RS AF Petralia, Ronald S. TI Distribution of Extrasynaptic NMDA Receptors on Neurons SO SCIENTIFIC WORLD JOURNAL LA English DT Review ID VESICULAR GLUTAMATE RELEASE; EARLY POSTNATAL-DEVELOPMENT; SOMATIC SENSORY CORTEX; AXONAL GROWTH CONES; HIPPOCAMPAL SYNAPSES; SYNAPTIC PLASTICITY; POSTSYNAPTIC DENSITY; WHITE-MATTER; ASTROCYTIC GLUTAMATE; SURFACE TRAFFICKING AB NMDA receptors are found in both synaptic and extrasynaptic locations on neurons. NMDA receptors also can be found on neurons in early stages prior to synaptogenesis, where they may be involved in migration and differentiation. Extrasynaptic NMDA receptors typically are associated with contacts with adjacent processes such as axons and glia. Extrasynaptic NMDA receptor clusters vary in size and may form associations with scaffolding proteins such as PSD-95 and SAP102. The best-characterized extrasynaptic NMDA receptors contain NR1 and NR2B subunits. Extrasynaptic NMDA receptors may be activated by glutamate spillover from synapses or from ectopic release of glutamate. Consequently, extrasynaptic NMDA receptor activation may occur under different circumstances than that for synaptic NMDA receptors, indicating different functional consequences for the neuron. In some cases, activation of extrasynaptic NMDA receptors may have a negative influence on the neuron, leading to cell damage and death, as may occur in some major diseases of the nervous system. C1 NIDCD, Adv Imaging Core, NIH, Bethesda, MD 20892 USA. RP Petralia, RS (reprint author), NIDCD, Adv Imaging Core, NIH, 50 South Dr 50-4142, Bethesda, MD 20892 USA. EM petralia@nidcd.nih.gov FU NIDCD FX This work was supported by the NIDCD Intramural Research Program. NR 94 TC 36 Z9 37 U1 0 U2 13 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1537-744X J9 SCI WORLD J JI Sci. World J. PY 2012 AR 267120 DI 10.1100/2012/267120 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 952EX UT WOS:000304774600001 ER PT B AU Van Doorslaer, K Sekhar, V Khan, J McBride, AA AF Van Doorslaer, Koenraad Sekhar, Vandana Khan, Jameela McBride, Alison A. BE Gaston, K TI Replication and Maintenance of Viral Genomes by Association with Host Chromatin SO SMALL DNA TUMOUR VIRUSES LA English DT Article; Book Chapter ID EPSTEIN-BARR-VIRUS; SARCOMA-ASSOCIATED-HERPESVIRUS; PAPILLOMAVIRUS E2 PROTEIN; DNA-BINDING DOMAIN; NUCLEAR ANTIGEN 1; MATRIX ATTACHMENT REGIONS; FACILITATE EXTRACHROMOSOMAL PERSISTENCE; TRANSCRIPTION FACTOR HUBF; MINOR CAPSID PROTEIN; BOVINE PAPILLOMAVIRUS AB Papillomaviruses persistently infect dividing epithelial cells. This cellular environment presents papillomaviruses with the challenge of having to replicate and retain their genome in proliferating cells. Papillomaviruses have evolved to maintain their genome as an extra-chromosomal element. The viral E2 protein binds to the viral genome and tethers it to the host chromosomes. This chapter will review some of the recent work showing how different papillomaviruses have evolved variations on this theme. Where appropriate, parallels will be drawn with other persistent, double-stranded DNA viruses. C1 [Van Doorslaer, Koenraad; Sekhar, Vandana; Khan, Jameela; McBride, Alison A.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Van Doorslaer, K (reprint author), NIAID, Viral Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM vandoorslaerkm@mail.nih.gov; sekharv@mail.nih.gov; khanj2@mail.nih.gov; amcbride@niaid.nih.gov NR 170 TC 0 Z9 0 U1 1 U2 2 PU CAISTER ACADEMIC PRESS PI WYMONDHAM PA 32 HEWITTS LANE, WYMONDHAM NR 18 0JA, ENGLAND BN 978-1-904455-99-8 PY 2012 BP 125 EP 150 PG 26 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BYP81 UT WOS:000299670200007 ER PT J AU Grimm, KJ An, Y McArdle, JJ AF Grimm, Kevin J. An, Yang McArdle, John J. TI Recent Changes Leading to Subsequent Changes: Extensions of Multivariate Latent Difference Score Models SO STRUCTURAL EQUATION MODELING-A MULTIDISCIPLINARY JOURNAL LA English DT Article DE latent difference score; dynamic; longitudinal; growth; memory; brain ID LONGITUDINAL DATA; DYNAMIC CHANGES; OLDER-ADULTS; BRAIN; GROWTH; DEPRESSION; MCI AB Latent difference score models (e.g., McArdle & Hamagami, 2001) are extended to include effects from prior changes to subsequent changes. This extension of latent difference scores allows for testing hypotheses where recent changes, as opposed to recent levels, are a primary predictor of subsequent changes. These models are applied to bivariate longitudinal data collected as part of the Baltimore Longitudinal Study of Aging on memory performance, measured by the California Verbal Learning Test, and lateral ventricle size, measured by structural MRIs. Results indicate that recent increases in the lateral ventricle size were a leading indicator of subsequent declines in memory performance from age 60 to 90. C1 [Grimm, Kevin J.] Univ Calif Davis, Dept Psychol, Davis, CA 95616 USA. [An, Yang] NIA, Bethesda, MD 20892 USA. [McArdle, John J.] Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. RP Grimm, KJ (reprint author), Univ Calif Davis, Dept Psychol, 1 Shields Ave, Davis, CA 95616 USA. EM kjgrimm@ucdavis.edu OI Zonderman, Alan B/0000-0002-6523-4778 FU National Institute on Aging of the National Institutes of Health; National Science Foundation REECE [DRL-0815787] FX The National Institute on Aging Intramural Research Program of the National Institutes of Health supported this research. Kevin J. Grimm was funded by National Science Foundation REECE Program Grant (DRL-0815787). The opinions and views expressed in this article are those of the authors and do not necessarily represent the views and opinions of the funding agencies. NR 35 TC 27 Z9 27 U1 4 U2 25 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1070-5511 J9 STRUCT EQU MODELING JI Struct. Equ. Modeling PY 2012 VL 19 IS 2 BP 268 EP 292 DI 10.1080/10705511.2012.659627 PG 25 WC Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Mathematics; Mathematical Methods In Social Sciences GA 945JW UT WOS:000304270100006 PM 23637519 ER PT J AU Duan, Q Laine, AF Suri, JS AF Duan, Qi Laine, Andrew F. Suri, Jasjit S. BE Sanches, JM Laine, AF Suri, JS TI Real-Time 4D Cardiac Segmentation by Active Geometric Functions SO ULTRASOUND IMAGING: ADVANCES AND APPLICATIONS LA English DT Article; Book Chapter ID FUZZY-CONNECTEDNESS; MR-IMAGES; QUANTIFICATION; CONTOURS; MODELS; SNAKES; FLOW AB Recent advances in 4D imaging and real-time imaging provide image data with clinically important dynamic information at high spatial or temporal resolution. The enormous amount of information contained in these data, on the other hand, has also raised a challenge for traditional image analysis algorithms in terms of efficiency. In this chapter, a novel deformable model framework, active geometric functions (AGFs), is introduced for the real-time segmentation problem. As an implicit deformable framework in parallel with level-set, AGF has mathematical advantages in efficiency and computational complexity as well as several flexible features similar to level-set framework. The performance of AGF is demonstrated in two cardiac applications: endocardial segmentation in 4D ultrasound and myocardial segmentation in MRI with super high temporal resolution. In both applications, AGF can perform accurate real-time segmentation in several milliseconds per frame, which was less than the acquisition time per frame. Segmentation results are compared to manual tracing with comparable performance with inter-observer variability. The ability of such real-time segmentation will not only facilitate the traditional diagnoses and workflow but also open the paths for novel applications such as interventional guidance and interactive image acquisition with online segmentation. C1 [Duan, Qi] NINDS, NIH, Bethesda, MD 20892 USA. [Laine, Andrew F.] Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA. [Suri, Jasjit S.] Biomed Technol Inc, Denver, CO USA. [Suri, Jasjit S.] Idaho State Univ Affiliated, Pocatello, ID USA. RP Duan, Q (reprint author), NINDS, NIH, 10 Ctr Dr,Bldg 10,Room B1D728,MSC 1065, Bethesda, MD 20892 USA. EM Qi.Duan@nih.gov; laine@columbia.edu; jsuri@comcast.net RI Duan, Qi/J-7916-2016 OI Duan, Qi/0000-0002-2407-6611 NR 30 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-1179-6 PY 2012 BP 225 EP 253 DI 10.1007/978-1-4614-1180-2_10 D2 10.1007/978-1-4614-1180-2 PG 29 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BYR11 UT WOS:000299835400011 ER PT S AU Wickner, RB Kryndushkin, D Shewmaker, F McGlinchey, R Edskes, HK AF Wickner, Reed B. Kryndushkin, Dmitry Shewmaker, Frank McGlinchey, Ryan Edskes, Herman K. BE Sigurdsson, EM Calero, M Gasset, M TI Study of Amyloids Using Yeast SO AMYLOID PROTEINS: METHODS AND PROTOCOLS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Protein transformation; Cytoduction; Mass per length; Electron diffraction ID SOLID-STATE NMR; HET-S PRION; DE-NOVO APPEARANCE; SACCHAROMYCES-CEREVISIAE; PSI+ PRION; FLUORESCENT PROTEIN; MAMMALIAN-CELLS; EXPERIMENTAL CONSTRAINTS; GUANIDINE-HYDROCHLORIDE; STRUCTURAL MODEL AB We detail some of the genetic, biochemical, and physical methods useful in studying amyloids in yeast, particularly the yeast prions. These methods include cytoduction (cytoplasmic mixing), infection of cells with prion amyloids, use of green fluorescent protein fusions with amyloid-forming proteins for cytology, protein purification and amyloid formation, and electron microscopy of filaments. C1 [Wickner, Reed B.; Kryndushkin, Dmitry; McGlinchey, Ryan; Edskes, Herman K.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD USA. [Kryndushkin, Dmitry; Shewmaker, Frank] Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA. RP Wickner, RB (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD USA. FU Intramural NIH HHS [ZIA DK024950-04, ZIA DK024950-05] NR 98 TC 2 Z9 2 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-550-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 849 BP 321 EP 346 DI 10.1007/978-1-61779-551-0_22 D2 10.1007/978-1-61779-551-0 PG 26 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BAG17 UT WOS:000304068900022 PM 22528100 ER PT S AU Schmidt, SD Nixon, RA Mathews, PM AF Schmidt, Stephen D. Nixon, Ralph A. Mathews, Paul M. BE Sigurdsson, EM Calero, M Gasset, M TI Tissue Processing Prior to Analysis of Alzheimer's Disease Associated Proteins and Metabolites, Including A beta SO AMYLOID PROTEINS: METHODS AND PROTOCOLS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE A beta; Alzheimer's disease; Amyloid; Amyloid precursor protein; APP; Brain; Dissection; Fractionation; Homogenization; Membrane protein; SDS-PAGE; Western blot analysis ID AMYLOID PRECURSOR PROTEIN; MOUSE MODEL; IN-VIVO; CEREBRAL-HEMORRHAGE; TRANSGENIC MICE; MEMORY DEFICITS; BRAIN; APP; SECRETION; PRESENILIN-1 AB Amyloid-containing tissue, whether from human patients or an animal model of a disease, is typically characterized by various biochemical and immunohistochemical techniques, many of which are described in detail in this volume. In this chapter, we describe a straightforward technique for the homogenization of tissue prior to these analyses. The technique is particularly well suited for performing a large number of different biochemical analyses on a single mouse brain hemisphere. Starting with this homogenate multiple characterizations can be done, including western blot analysis and isolation of membrane-associated proteins, both of which are described here. Additional analyses can readily be performed on the tissue homogenate, including the ELISA quantitation of A beta in the brain of a transgenic mouse model of beta-amyloid deposition. The ELISA technique is described in detail in Chapter 34. C1 [Schmidt, Stephen D.; Nixon, Ralph A.; Mathews, Paul M.] Nathan S Kline Inst Psychiat Res, Ctr Dementia Res, Orangeburg, NY 10962 USA. [Schmidt, Stephen D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Nixon, Ralph A.; Mathews, Paul M.] NYU, Sch Med, Dept Psychiat, New York, NY USA. [Nixon, Ralph A.] NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA. RP Schmidt, SD (reprint author), Nathan S Kline Inst Psychiat Res, Ctr Dementia Res, Orangeburg, NY 10962 USA. OI Mathews, Paul/0000-0003-1742-7687 FU NIA NIH HHS [AG017617] NR 29 TC 6 Z9 6 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-550-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 849 BP 493 EP 506 DI 10.1007/978-1-61779-551-0_33 D2 10.1007/978-1-61779-551-0 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BAG17 UT WOS:000304068900033 PM 22528111 ER PT S AU Schmidt, SD Mazzella, MJ Nixon, RA Mathews, PM AF Schmidt, Stephen D. Mazzella, Matthew J. Nixon, Ralph A. Mathews, Paul M. BE Sigurdsson, EM Calero, M Gasset, M TI A beta Measurement by Enzyme-Linked Immunosorbent Assay SO AMYLOID PROTEINS: METHODS AND PROTOCOLS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE A beta; Amyloid; Enzyme-linked immunosorbent assay; ELISA; Extraction; Quantification; Quantitation; Alzheimer's disease; Amyloid precursor protein; APP; Formic acid; Brain ID AMYLOID-PRECURSOR-PROTEIN; FAMILIAL ALZHEIMERS-DISEASE; HEREDITARY CEREBRAL-HEMORRHAGE; TRANSGENIC MICE; MOUSE MODEL; IN-VIVO; MEMORY DEFICITS; PRESENILIN-1; GENE; BRAIN AB The neuritic plaque in the brain of Alzheimer's disease patients consists of an amyloid composed primarily of A beta, an approximately 4-kDa peptide derived from the amyloid precursor protein. Multiple lines of evidence suggest that A beta plays a key role in the pathogenesis of the disease, and potential treatments that target A beta production and/or A beta accumulation in the brain as beta-amyloid are being aggressively pursued. Methods to quantitate the A beta peptide are, therefore, invaluable to most studies aimed at a better understanding of the molecular etiology of the disease and in assessing potential therapeutics. Although other techniques have been used to measure A beta in the brains of AD patients and beta-amyloid-depositing transgenic mice, the enzyme-linked immunosorbent assay (ELISA) is one of the most commonly used, reliable, and sensitive methods for quantitating the A beta peptide. Here we describe methods for the recovery of both soluble and deposited A beta from brain tissue and the subsequent quantitation of the peptide by sandwich ELISA. C1 [Schmidt, Stephen D.; Mazzella, Matthew J.; Nixon, Ralph A.; Mathews, Paul M.] Nathan S Kline Inst Psychiat Res, Ctr Dementia Res, Orangeburg, NY 10962 USA. [Schmidt, Stephen D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Nixon, Ralph A.; Mathews, Paul M.] NYU, Sch Med, Dept Psychiat, New York, NY USA. [Nixon, Ralph A.] NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA. RP Schmidt, SD (reprint author), Nathan S Kline Inst Psychiat Res, Ctr Dementia Res, Orangeburg, NY 10962 USA. OI Mathews, Paul/0000-0003-1742-7687 FU NIA NIH HHS [AG017617] NR 43 TC 8 Z9 8 U1 0 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-550-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 849 BP 507 EP 527 DI 10.1007/978-1-61779-551-0_34 D2 10.1007/978-1-61779-551-0 PG 21 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BAG17 UT WOS:000304068900034 PM 22528112 ER PT S AU Addington, J Heinssen, R AF Addington, Jean Heinssen, Robert BE NolenHoeksema, S TI Prediction and Prevention of Psychosis in Youth at Clinical High Risk SO ANNUAL REVIEW OF CLINICAL PSYCHOLOGY, VOL 8 SE Annual Review of Clinical Psychology LA English DT Article; Book Chapter DE psychosis; risk; treatment; schizophrenia ID ULTRA-HIGH-RISK; RANDOMIZED CONTROLLED-TRIAL; COGNITIVE-BEHAVIORAL THERAPY; PRODROMAL PHASE; YOUNG-PEOPLE; 1ST EPISODE; 1ST-EPISODE PSYCHOSIS; EARLY INTERVENTION; FOLLOW-UP; SCHIZOPHRENIA-SPECTRUM AB Most individuals with schizophrenia retrospectively report a prodromal period characterized by increasing problems in thinking, feeling, and behaving. However, it is less clear how many individuals who display prodromal symptoms will subsequently develop a psychotic illness. Thus, a precondition for early intervention in psychosis is the accurate detection of those who may be at true risk of developing a psychotic illness. The aim of this article is to review current work addressing prediction and prevention in the prodrome to psychosis. First, we describe research efforts to develop and test operational criteria for prospectively assessing psychosis liability over time. Second, the clinical, functional, and biological features of the prodrome are presented, along with a discussion of the variables most frequently associated with psychosis onset. Next, treatment studies are reviewed. The review concludes with a framework for future early identification and treatment studies. C1 [Addington, Jean] Univ Calgary, Dept Psychiat, Hotchkiss Brain Inst, Calgary, AB T2N 4N1, Canada. [Heinssen, Robert] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. RP Addington, J (reprint author), Univ Calgary, Dept Psychiat, Hotchkiss Brain Inst, Calgary, AB T2N 4N1, Canada. EM jmadding@ucalgary.ca NR 108 TC 52 Z9 53 U1 13 U2 26 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1548-5943 BN 978-0-8243-3908-1 J9 ANNU REV CLIN PSYCHO JI Annu. Rev. Clin. Psychol. PY 2012 VL 8 BP 269 EP + DI 10.1146/annurev-clinpsy-032511-143146 PG 22 WC Psychology, Clinical; Psychology SC Psychology GA BAH99 UT WOS:000304200200012 PM 22224837 ER PT S AU Brenchley, JM Douek, DC AF Brenchley, Jason M. Douek, Daniel C. BE Paul, WE TI Microbial Translocation Across the GI Tract SO ANNUAL REVIEW OF IMMUNOLOGY, VOL 30 SE Annual Review of Immunology LA English DT Review; Book Chapter DE intestinal permeability; innate immunity; inflammation ID INFLAMMATORY-BOWEL-DISEASE; VERSUS-HOST-DISEASE; LIPOPOLYSACCHARIDE-BINDING PROTEIN; TUMOR-NECROSIS-FACTOR; T-CELL DEPLETION; PLACEBO-CONTROLLED TRIAL; FATTY LIVER-DISEASE; ACTIVE ANTIRETROVIRAL THERAPY; PLASMACYTOID DENDRITIC CELLS; INTESTINAL EPITHELIAL-CELLS AB The lumen of the gastrointestinal (GI) tract is home to an enormous quantity of different bacterial species, our microbiota, that thrive in an often symbiotic relationship with the host. Given that the healthy host must regulate contact between themicrobiota and its immune system to avoid overwhelming systemic immune activation, humans have evolved several mechanisms to attenuate systemic microbial translocation (MT) and its consequences. However, several diseases are associated with the failure of one or more of these mechanisms, with consequent immune activation and deleterious effects on health. Here, we discuss the mechanisms underlying MT, diseases associated with MT, and therapeutic interventions that aim to decrease it. C1 [Brenchley, Jason M.] NIAID, Program Barrier Immun & Repair, NIH, Bethesda, MD 20892 USA. [Brenchley, Jason M.] NIAID, Immunopathogenesis Unit, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Brenchley, JM (reprint author), NIAID, Program Barrier Immun & Repair, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM jbrenchl@mail.nih.gov; ddouek@mail.nih.gov FU Intramural NIH HHS [Z01 AI001029-01, ZIA AI005034-09] NR 216 TC 102 Z9 104 U1 3 U2 34 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3030-9 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2012 VL 30 BP 149 EP 173 DI 10.1146/annurev-immunol-020711-075001 PG 25 WC Immunology SC Immunology GA BAH94 UT WOS:000304198100007 PM 22224779 ER PT S AU Shaffer, AL Young, RM Staudt, LM AF Shaffer, Arthur L., III Young, Ryan M. Staudt, Louis M. BE Paul, WE TI Pathogenesis of Human B Cell Lymphomas SO ANNUAL REVIEW OF IMMUNOLOGY, VOL 30 SE Annual Review of Immunology LA English DT Review; Book Chapter DE transcription factor; genomics; epigenetics; cancer; mutation; signaling ID NF-KAPPA-B; CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKIN-LYMPHOMA; GERMINAL-CENTER FORMATION; TUMOR-SUPPRESSOR GENE; REED-STERNBERG CELLS; TOLL-LIKE RECEPTORS; V-H GENES; PU.1/IRF-4/DNA TERNARY COMPLEX; ONCOGENIC CARD11 MUTATIONS AB The mechanisms that drive normal B cell differentiation and activation are frequently subverted by B cell lymphomas for their unlimited growth and survival. B cells are particularly prone to malignant transformation because the machinery used for antibody diversification can cause chromosomal translocations and oncogenic mutations. The advent of functional and structural genomics has greatly accelerated our understanding of oncogenic mechanisms in lymphomagenesis. The signaling pathways that normal B cells utilize to sense antigens are frequently derailed in B cell malignancies, leading to constitutive activation of prosurvival pathways. These malignancies co-opt transcriptional regulatory systems that characterize their normal B cell counterparts and frequently alter epigenetic regulators of chromatin structure and gene expression. These mechanistic insights are ushering in an era of targeted therapies for these cancers based on the principles of pathogenesis. C1 [Shaffer, Arthur L., III; Young, Ryan M.; Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Shaffer, AL (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM lstaudt@mail.nih.gov FU Intramural NIH HHS NR 367 TC 152 Z9 156 U1 2 U2 44 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3030-9 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2012 VL 30 BP 565 EP 610 DI 10.1146/annurev-immunol-020711-075027 PG 46 WC Immunology SC Immunology GA BAH94 UT WOS:000304198100022 PM 22224767 ER PT S AU Trinchieri, G AF Trinchieri, Giorgio BE Paul, WE TI Cancer and Inflammation: An Old Intuition with Rapidly Evolving New Concepts SO ANNUAL REVIEW OF IMMUNOLOGY, VOL 30 SE Annual Review of Immunology LA English DT Review; Book Chapter DE microbiota; obesity; energy metabolism; DNA damage; colorectal cancer ID ONCOGENE-INDUCED SENESCENCE; GENOME-WIDE ASSOCIATION; NITRIC-OXIDE SYNTHASE; DIET-INDUCED OBESITY; BODY-MASS INDEX; NF-KAPPA-B; COLORECTAL-CANCER; GUT MICROBIOTA; INTESTINAL MICROBIOTA; BOWEL-DISEASE AB Recent scientific advances have contributed much to the dissection of the complex molecular and cellular pathways involved in the connection between cancer and inflammation. The evidence for this connection in humans is based on the association between infection or chronic sterile inflammation and cancer. The decreased incidence of tumors in individuals who have used nonsteroidal anti-inflammatory drugs is supportive of a role for inflammation in cancer susceptibility. The increased incidence of tumors in overweight patients points to a role for adipose tissue inflammation and energy metabolism in cancer. Energy metabolism, obesity, and genetic instability are regulated in part by the relationship of the organism with commensal bacteria that affect inflammation with both local and systemic effects. Different aspects of inflammation appear to regulate all phases of malignant disease, including susceptibility, initiation, progression, dissemination, morbidity, and mortality. C1 NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Trinchieri, G (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Frederick, MD 21702 USA. EM trinchig@mail.nih.gov NR 189 TC 166 Z9 171 U1 4 U2 55 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3030-9 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2012 VL 30 BP 677 EP 706 DI 10.1146/annurev-immunol-020711-075008 PG 30 WC Immunology SC Immunology GA BAH94 UT WOS:000304198100025 PM 22224761 ER PT S AU Kanno, Y Vahedi, G Hirahara, K Singleton, K O'Shea, JJ AF Kanno, Yuka Vahedi, Golnaz Hirahara, Kiyoshi Singleton, Kentner O'Shea, John J. BE Paul, WE TI Transcriptional and Epigenetic Control of T Helper Cell Specification: Molecular Mechanisms Underlying Commitment and Plasticity SO ANNUAL REVIEW OF IMMUNOLOGY, VOL 30 SE Annual Review of Immunology LA English DT Review; Book Chapter DE cytokine; transcription factor; epigenome; next-generation sequencing; genome-wide ID CHROMATIN-REMODELING COMPLEXES; LOCUS-CONTROL REGION; LONG NONCODING RNA; ROR-GAMMA-T; GENE-EXPRESSION; HUMAN GENOME; DNA METHYLATION; IMMUNE-SYSTEM; HYPERSENSITIVE SITES; REGULATORY ELEMENTS AB T helper cell differentiation occurs in the context of the extracellular cytokine milieu evoked by diverse microbes and other pathogenic stimuli along with T cell receptor stimulation. The culmination of these signals results in specification of T helper lineages, which occurs through the combinatorial action of multiple transcription factors that establish distinctive transcriptomes. In this manner, inducible, but constitutively active, master regulators work in conjunction with factors such as the signal transducer and activator of transcriptions (STATs) that sense the extracellular environment. The acquisition of a distinctive transcriptome also depends on chromatin modifications that impact key cis elements as well as the changes in global genomic organization. Thus, signal transduction and epigenetics are linked in these processes of differentiation. In this review, recent advances in understanding T helper lineage specification and deciphering the action of transcription factors are summarized with emphasis on comprehensive views of the dynamic T cell epigenome. C1 [Kanno, Yuka; Vahedi, Golnaz; Hirahara, Kiyoshi; Singleton, Kentner; O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. RP Kanno, Y (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. EM kannoy@mail.nih.gov RI Kanno, Yuka/B-5802-2013; Hirahara, Kiyoshi/E-2460-2017; OI Hirahara, Kiyoshi/0000-0002-9128-9449; Kanno, Yuka/0000-0001-5668-9319 FU Intramural NIH HHS [Z99 AR999999] NR 162 TC 138 Z9 147 U1 3 U2 18 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3030-9 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2012 VL 30 BP 707 EP 731 DI 10.1146/annurev-immunol-020711-075058 PG 25 WC Immunology SC Immunology GA BAH94 UT WOS:000304198100026 PM 22224760 ER PT J AU Meier, ER Miller, JL AF Meier, Emily Riehm Miller, Jeffery L. TI Sickle Cell Disease in Children SO DRUGS LA English DT Review ID ACUTE CHEST SYNDROME; BONE-MARROW-TRANSPLANTATION; TRANSFUSIONAL IRON OVERLOAD; ACUTE SPLENIC SEQUESTRATION; GAMMA-GLOBIN SYNTHESIS; ZINC-FINGER NUCLEASES; FETAL-HEMOGLOBIN; RISK-FACTORS; NATURAL-HISTORY; NITRIC-OXIDE AB Early identification of infants with sickle cell disease (SCD) by newborn screening, now universal in all 50 states in the US, has improved survival, mainly by preventing overwhelming sepsis with the early use of prophylactic penicillin. Routine transcranial Doppler screening with the institution of chronic transfusion decreases the risk of stroke from 10% to 1% in paediatric SCD patients. Hydroxyurea decreases the number and frequency of painful crises, acute chest syndromes and number of blood transfusions in children with SCD. Genetic research continues to be driven toward the prevention and ultimate cure of SCD before adulthood. This review focuses on clinical manifestations and therapeutic strategies for paediatric SCD as well as the evolving topic of gene-focused prevention and therapy. C1 [Meier, Emily Riehm; Miller, Jeffery L.] NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA. [Meier, Emily Riehm] Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Washington, DC 20010 USA. [Meier, Emily Riehm] George Washington Univ, Med Ctr, Dept Pediat, Washington, DC 20037 USA. RP Miller, JL (reprint author), NIDDK, Mol Med Branch, NIH, 10 Ctr Dr,Bldg 10,Room 9N311, Bethesda, MD 20892 USA. EM jm7f@nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases FX The Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases supported this work. The authors thank Y. Terry Lee and Colleen Byrnes for their assistance in the preparation of this manuscript. NR 102 TC 6 Z9 6 U1 1 U2 9 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PY 2012 VL 72 IS 7 BP 895 EP 906 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 945RM UT WOS:000304293700003 PM 22519940 ER PT J AU Nelson, W AF Nelson, Wendy TI Too Much Information? SO HASTINGS CENTER REPORT LA English DT Letter C1 NCI, Bethesda, MD 20892 USA. RP Nelson, W (reprint author), NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0093-0334 J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD JAN-FEB PY 2012 VL 42 IS 1 BP 5 EP 6 PG 2 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA 946YU UT WOS:000304394500007 PM 22616386 ER PT J AU Largent, EA Pearson, SD AF Largent, Emily A. Pearson, Steven D. TI Which ORPHANS Will Find a HOME? The Rule of Rescue in Resource Allocation for Rare Diseases SO HASTINGS CENTER REPORT LA English DT Article ID CELL LUNG-CANCER; DRUGS; PRIORITY; THERAPY; COST; CARE C1 [Largent, Emily A.] NIH, Dept Bioeth, Bethesda, MD 20892 USA. [Pearson, Steven D.] Massachusetts Gen Hosp, Inst Clin & Econ Review, Boston, MA 02114 USA. RP Largent, EA (reprint author), Harvard Univ, PhD Program Hlth Policy, Cambridge, MA 02138 USA. NR 30 TC 14 Z9 14 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0093-0334 J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD JAN-FEB PY 2012 VL 42 IS 1 BP 27 EP 34 DI 10.1002/HAST.12 PG 8 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA 946YU UT WOS:000304394500017 PM 22616398 ER PT J AU Shriner, D AF Shriner, Daniel TI Improved Eigenanalysis of Discrete Subpopulations and Admixture Using the Minimum Average Partial Test SO HUMAN HEREDITY LA English DT Article DE Admixture; Population stratification; Population structure; Principal components analysis ID SAMPLE COVARIANCE MATRICES; LARGEST EIGENVALUE; COMPONENTS; NUMBER; STRATIFICATION; POPULATIONS; MAP AB Principal components analysis of genetic data has benefited from advances in random matrix theory. The Tracy-Widom distribution has been identified as the limiting distribution of the lead eigenvalue, enabling formal hypothesis testing of population structure. Additionally, a phase change exists between small and large eigenvalues, such that population divergence below a threshold of F-ST is impossible to detect and above which it is always detectable. I show that the plug-in estimate of the effective number of markers in the EIGEN-SOFT software often exceeds the rank of the sample covariance matrix, leading to a systematic overestimation of the number of significant principal components. I describe an alternative plug-in estimate that eliminates the problem. This improvement is not just an asymptotic result but is directly applicable to finite samples. The minimum average partial test, based on minimizing the average squared partial correlation between individuals, can detect population structure at smaller F-ST values than the corrected test. The minimum average partial test is applicable to both unadmixed and admixed samples, with arbitrary numbers of discrete subpopulations or parental populations, respectively. Application of the minimum average partial test to the 11 HapMap Phase III samples, comprising 8 unadmixed samples and 3 admixed samples, revealed 13 significant principal components. Copyright (C) 2012 S. Karger AG, Basel C1 NHGRI, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA. RP Shriner, D (reprint author), NHGRI, Ctr Res Genom & Global Hlth, Bldg 12A,Room 4047,12 South Dr,MSC 5635, Bethesda, MD 20892 USA. EM shrinerda@mail.nih.gov FU Center for Research on Genomics and Global Health (CRGGH); National Human Genome Research Institute; National Institute of Diabetes and Digestive and Kidney Diseases; Center for Information Technology; Office of the Director at the National Institutes of Health [Z01HG200362] FX The contents of this publication are solely the responsibility of the author and do not necessarily represent the official view of the National Institutes of Health. This research was supported by the Intramural Research Program of the Center for Research on Genomics and Global Health (CRGGH). The CRGGH is supported by the National Human Genome Research Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Center for Information Technology, and the Office of the Director at the National Institutes of Health (Z01HG200362). I thank Ao Yuan for mathematical assistance, Nick Patterson, Adeyemo Ade-bowale, and Guanjie Chen for helpful discussions, Charles Rotimi for critically reviewing the manuscript, and the anonymous reviewers for their comments. NR 18 TC 5 Z9 5 U1 1 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2012 VL 73 IS 2 BP 73 EP 83 DI 10.1159/000335899 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 945RA UT WOS:000304292500002 PM 22441298 ER PT J AU Partanen, A Yarmolenko, PS Viitala, A Appanaboyina, S Haemmerich, D Ranjan, A Jacobs, G Woods, D Enholm, J Wood, BJ Dreher, MR AF Partanen, Ari Yarmolenko, Pavel S. Viitala, Antti Appanaboyina, Sunil Haemmerich, Dieter Ranjan, Ashish Jacobs, Genevieve Woods, David Enholm, Julia Wood, Bradford J. Dreher, Matthew R. TI Mild hyperthermia with magnetic resonance-guided high-intensity focused ultrasound for applications in drug delivery SO INTERNATIONAL JOURNAL OF HYPERTHERMIA LA English DT Article DE Drug delivery; liposome; mild hyperthermia; MR-HIFU; temperature sensitive liposome; thermotherapy ID TEMPERATURE-SENSITIVE LIPOSOMES; TUMOR XENOGRAFT MODEL; PROTON CHEMICAL-SHIFT; IN-VIVO EVALUATIONS; LOCAL HYPERTHERMIA; PHASED-ARRAY; MR THERMOMETRY; TARGETED DELIVERY; MURINE TUMORS; SOLID TUMORS AB Purpose: Mild hyperthermia (40-45 degrees C) is a proven adjuvant for radiotherapy and chemotherapy. Magnetic resonance guided high intensity focused ultrasound (MR-HIFU) can non-invasively heat solid tumours under image guidance. Low temperature-sensitive liposomes (LTSLs) release their drug cargo in response to heat (>40 degrees C) and may improve drug delivery to solid tumours when combined with mild hyperthermia. The objective of this study was to develop and implement a clinically relevant MR-HIFU mild hyperthermia heating algorithm for combination with LTSLs. Materials and methods: Sonications were performed with a clinical MR-HIFU platform in a phantom and rabbits bearing VX2 tumours (target = 4-16 mm). A binary control algorithm was used for real-time mild hyperthermia feedback control (target = 40-41 degrees C). Drug delivery with LTSLs was measured with HPLC. Data were compared to simulation results and analysed for spatial targeting accuracy (offset), temperature accuracy (mean), homogeneity of heating (standard deviation (SD), T10 and T90), and thermal dose (CEM43). Results: Sonications in a phantom resulted in better temperature control than in vivo. Sonications in VX2 tumours resulted in mean temperatures between 40.4 degrees C and 41.3 degrees C with a SD of 1.0-1.5 degrees C (T10 = 41.7-43.7 degrees C, T90 = 39.0-39.6 degrees C), in agreement with simulations. 3D spatial offset was 0.1-3.2mm in vitro and 0.6-4.8mm in vivo. Combination of MR-HIFU hyperthermia and LTSLs demonstrated heterogeneous delivery to a partially heated VX2 tumour, as expected. Conclusions: An MR-HIFU mild hyperthermia heating algorithm was developed, resulting in accurate and homogeneous heating within the targeted region in vitro and in vivo, which is suitable for applications in drug delivery. C1 [Partanen, Ari; Yarmolenko, Pavel S.; Ranjan, Ashish; Jacobs, Genevieve; Woods, David; Wood, Bradford J.; Dreher, Matthew R.] NCI, Ctr Intervent Oncol, Ctr Clin, NIH, Bethesda, MD 20892 USA. [Partanen, Ari] Univ Helsinki, Dept Phys, Helsinki, Finland. [Partanen, Ari] Philips Healthcare, Cleveland, OH USA. [Yarmolenko, Pavel S.] Duke Univ, Dept Biomed Engn, Durham, NC 27706 USA. [Viitala, Antti; Enholm, Julia] Philips Med Syst, Vantaa, Finland. [Appanaboyina, Sunil; Haemmerich, Dieter] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. RP Dreher, MR (reprint author), NCI, Ctr Intervent Oncol, Ctr Clin, NIH, 9000 Rockville Pike,Bldg 10,Room 2N212,MSC 1182, Bethesda, MD 20892 USA. EM dreherm@cc.nih.gov OI Partanen, Ari/0000-0003-1985-149X; Haemmerich, Dieter/0000-0003-1127-7024 FU Center for Interventional Oncology; Cooperative Research and Development Agreement (CRADA); Philips Healthcare; National Institutes of Health (NIH); Celsion Corporation FX This research was supported by the Center for Interventional Oncology and Intramural Research Program of the National Institutes of Health (NIH), and through a Cooperative Research and Development Agreement (CRADA) with Philips Healthcare and Celsion Corporation. Ari Partanen, Antti Viitala, and Julia Enholm are paid employees of Philips Healthcare. The mention of commercial products, their source, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the National Institutes of Health. The authors alone are responsible for the content and writing of the paper. NR 90 TC 51 Z9 53 U1 0 U2 24 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0265-6736 J9 INT J HYPERTHER JI Int. J. Hyperthermia PY 2012 VL 28 IS 4 BP 320 EP 336 DI 10.3109/02656736.2012.680173 PG 17 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 946LF UT WOS:000304352400006 PM 22621734 ER PT J AU Gasselhuber, A Dreher, MR Partanen, A Yarmolenko, PS Woods, D Wood, BJ Haemmerich, D AF Gasselhuber, Astrid Dreher, Matthew R. Partanen, Ari Yarmolenko, Pavel S. Woods, David Wood, Bradford J. Haemmerich, Dieter TI Targeted drug delivery by high intensity focused ultrasound mediated hyperthermia combined with temperature-sensitive liposomes: Computational modelling and preliminary in vivo validation SO INTERNATIONAL JOURNAL OF HYPERTHERMIA LA English DT Article DE drug delivery; focused ultrasound; hyperthermia; liposome; MR-HIFU; TSL ID TUMOR-MODEL; THERMOSENSITIVE LIPOSOMES; THERMAL ABLATION; CONTENT RELEASE; SOLID TUMORS; DOXORUBICIN; PERFUSION; CANCER; CELL; MRI AB Purpose: To develop and validate a computational model that simulates 1) tissue heating with high intensity focused ultrasound (HIFU), and 2) resulting hyperthermia-mediated drug delivery from temperature-sensitive liposomes (TSL). Materials and methods: HIFU heating in tissue was simulated using a heat transfer model based on the bioheat equation, including heat-induced cessation of perfusion. A spatio-temporal multi-compartment pharmacokinetic model simulated intravascular release of doxorubicin from TSL, its transport into interstitium, and cell uptake. Two heating schedules were simulated, each lasting 30 min: 1) hyperthermia at 43 degrees C (HT) and 2) hyperthermia followed by a high temperature (50 degrees C for 20 s) pulse (HT+). As preliminary model validation, in vivo studies were performed in thigh muscle of a New Zealand White rabbit, where local hyperthermia with a clinical magnetic resonance-guided HIFU system was applied following TSL administration. Results: HT produced a defined region of high doxorubicin concentration (cellular concentration similar to 15-23 mu g/g) in the target region. Cellular drug uptake was directly related to HT duration, with increasing doxorubicin uptake up to similar to 2h. HT+ enhanced drug delivery by similar to 40% compared to HT alone. Temperature difference between model and experiment within the hyperthermia zone was on average 0.54 degrees C. Doxorubicin concentration profile agreed qualitatively with in vivo fluorescence profile. Conclusions: Computational models can predict temperature and delivered drug from combination of HIFU with TSL. Drug delivery using TSL may be enhanced by prolonged hyperthermia up to 2 h or by local cessation of vascular perfusion with a high temperature pulse following hyperthermia. C1 [Gasselhuber, Astrid; Haemmerich, Dieter] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Dreher, Matthew R.; Partanen, Ari; Yarmolenko, Pavel S.; Woods, David; Wood, Bradford J.] NCI, Ctr Intervent Oncol, Ctr Clin, NIH, Bethesda, MD 20892 USA. [Partanen, Ari] Univ Helsinki, Dept Phys, Helsinki, Finland. [Partanen, Ari] Philips Healthcare, Cleveland, OH USA. [Yarmolenko, Pavel S.] Duke Univ, Dept Biomed Engn, Durham, NC 27706 USA. [Haemmerich, Dieter] Clemson Univ, Dept Bioengn, Clemson, SC USA. RP Haemmerich, D (reprint author), Med Univ S Carolina, Dept Pediat, 165 Ashley Ave,MSC 915 Charleston, Charleston, SC 29425 USA. EM haemmerich@ieee.org OI Partanen, Ari/0000-0003-1985-149X; Haemmerich, Dieter/0000-0003-1127-7024 FU US National Institutes of Health (NIH) [R01CA118990, R21CA135519]; NIH Center for Interventional Oncology; NIH; Philips; NIH from the National Center for Research Resources [C06 RR018823] FX This work was supported by US National Institutes of Health (NIH) grants R01CA118990, R21CA135519 to DH, by the NIH Center for Interventional Oncology and the NIH Intramural Research Program, and by a cooperative research agreement between NIH and Philips. NIH and Celsion Corporation have a Cooperative Research and Development Agreement. Part of the work was conducted in a facility constructed with support from the NIH, grant number C06 RR018823 from the Extramural Research Facilities Program of the National Center for Research Resources. A.P. is employed by Philips Healthcare. The other authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. NR 55 TC 47 Z9 51 U1 1 U2 25 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0265-6736 J9 INT J HYPERTHER JI Int. J. Hyperthermia PY 2012 VL 28 IS 4 BP 337 EP 348 DI 10.3109/02656736.2012.677930 PG 12 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 946LF UT WOS:000304352400007 PM 22621735 ER PT S AU Kang, EM Malech, HL AF Kang, Elizabeth M. Malech, Harry L. BE Friedmann, T TI GENE THERAPY FOR CHRONIC GRANULOMATOUS DISEASE SO METHODS IN ENZYMOLOGY, VOL 507: GENE TRANSFER VECTORS FOR CLINICAL APPLICATION SE Methods in Enzymology LA English DT Review; Book Chapter ID SEVERE COMBINED IMMUNODEFICIENCY; BLOOD CD34(+) CELLS; BONE-MARROW-CELLS; LENTIVIRAL VECTOR; NADPH OXIDASE; HOST-DEFENSE; X-CGD; HEMATOPOIETIC ALLOGRAFT; FUNCTIONAL CORRECTION; RETROVIRAL VECTOR AB Mutations in phagocyte NADPH oxidase cause CGD, resulting in recurrent infections and granulomatous inflammation. Hematopoietic stem cell (HSC) transplant can cure CGD, but most patients lack a suitable donor. We conducted a clinical trial of ex vivo autologous HSC gene transfer as salvage therapy for three patients with X-linked CGD (X-CGD) who had incurable infection. Patients received nonmyeloablative busulfan conditioning and then were infused with amphotropic MFGS-gp91phox murine retrovirus vector-transduced autologous HSC, resulting in early gene marking and high-level oxidase function correction of 24%, 5%, and 4% of circulating neutrophils. Subjects #1 and #3 fully resolved infection and have maintained gene marking at 5 years at 0.7% and 0.03% oxidase-normal neutrophils. Subject #2 lost gene marking by 4 weeks and at 6 months succumbed to his infection. The two surviving subjects have normal blood count and bone marrow exam, with no evidence for clonal dominance of vector inserts. We conclude that gene therapy salvage treatment for severe infection unresponsive to conventional therapy can provide life-saving clinical benefit to CGD patients lacking a suitable donor. We are developing lentivectors for our next generation gene therapy of CGD. We are also exploring novel alternate approaches to gene therapy using zinc finger nuclease-mediated gene targeting of induced pluripotent stem cells derived from CGD patients. C1 [Kang, Elizabeth M.; Malech, Harry L.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Kang, EM (reprint author), NIAID, Host Def Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. OI Malech, Harry/0000-0001-5874-5775 NR 58 TC 16 Z9 18 U1 1 U2 8 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-386509-0 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2012 VL 507 BP 125 EP 154 DI 10.1016/B978-0-12-386509-0.00007-7 PG 30 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BAD94 UT WOS:000303896000007 PM 22365772 ER PT S AU O'Reilly, M Shipp, A Rosenthal, E Jambou, R Shih, T Montgomery, M Gargiulo, L Patterson, A Corrigan-Curay, J AF O'Reilly, Marina Shipp, Allan Rosenthal, Eugene Jambou, Robert Shih, Tom Montgomery, Maureen Gargiulo, Linda Patterson, Amy Corrigan-Curay, Jacqueline BE Friedmann, T TI NIH OVERSIGHT OF HUMAN GENE TRANSFER RESEARCH INVOLVING RETROVIRAL, LENTIVIRAL, AND ADENO-ASSOCIATED VIRUS VECTORS AND THE ROLE OF THE NIH RECOMBINANT DNA ADVISORY COMMITTEE SO METHODS IN ENZYMOLOGY, VOL 507: GENE TRANSFER VECTORS FOR CLINICAL APPLICATION SE Methods in Enzymology LA English DT Review; Book Chapter ID THERAPY; ACTIVATION; SCID-X1; CELLS AB In response to public and scientific concerns regarding human gene transfer research, the National Institutes of Health (NIH) developed a transparent oversight system that extends to human gene transfer protocols that are either conducted with NIH funding or conducted at institutions that receive NIH funding for recombinant DNA research. The NIH Recombinant DNA Advisory Committee (RAC) has been the primary advisory body to NIH regarding the conduct of this research. Human gene transfer research proposals that are subject to the NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines) must be submitted to the NIH Office of Biotechnology Activities (OBA), and protocols that raise novel scientific, safety, medical, ethical, or social issues are publicly discussed at the RAC's quarterly public meetings. OBA also convenes gene transfer safety symposia and policy conferences to provide a public forum for scientific experts to discuss emerging issues in the field. This transparent system of review promotes the rapid exchange of important scientific information and dissemination of data. The goal is to optimize the conduct of individual research protocols and to advance gene transfer research generally. This process has fostered the development of retroviral, lentiviral, and adeno-associated viral vector mediated gene delivery. C1 [O'Reilly, Marina; Shipp, Allan; Rosenthal, Eugene; Jambou, Robert; Shih, Tom; Montgomery, Maureen; Gargiulo, Linda; Patterson, Amy; Corrigan-Curay, Jacqueline] NIH, Off Biotechnol Activ, Bethesda, MD 20892 USA. RP O'Reilly, M (reprint author), NIH, Off Biotechnol Activ, Bldg 10, Bethesda, MD 20892 USA. NR 17 TC 6 Z9 6 U1 0 U2 7 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-386509-0 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2012 VL 507 BP 313 EP 335 DI 10.1016/B978-0-12-386509-0.00016-8 PG 23 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BAD94 UT WOS:000303896000016 PM 22365781 ER PT B AU O'Konek, JJ Berzofsky, JA Terabe, M AF O'Konek, Jessica J. Berzofsky, Jay A. Terabe, Masaki BE Terabe, M Berzofsky, JA TI Immune Regulation of Tumor Immunity by NKT Cells SO NATURAL KILLER T CELLS: BALANCING THE REGULATION OF TUMOR IMMUNITY SE Cancer Drug Discovery and Development LA English DT Article; Book Chapter ID KILLER T-CELLS; ALPHA-GALACTOSYLCERAMIDE KRN7000; IN-VIVO; DENDRITIC CELLS; IFN-GAMMA; FUNCTIONALLY DISTINCT; IMMUNOREGULATORY AXIS; CUTTING EDGE; IMMUNOSUPPRESSIVE ACTIVITY; ANTITUMOR IMMUNITY AB While NKT cells comprise only a very small percentage of lymphoctyes, they play very important roles in many disease settings, including cancer. NKT cells can be subdivided into at least two groups that play opposing roles in cancer and also counterregulate each other. While type I NKT cells can promote strong antitumor immunity, type II NKT cells suppress antitumor immune responses and play more of a regulatory role, similar to Tregs and MDSCs. The balance between type I and type II NKT cells can determine whether immune responses to tumors will be activated, resulting in tumor elimination, or will be suppressed, allowing the tumor to grow. Understanding the interactions between NKT cells may aid in the development of new immunotherapies for cancer which can shift the balance of this immunoregulatory axis towards immune activation and tumor killing. C1 [O'Konek, Jessica J.; Berzofsky, Jay A.; Terabe, Masaki] NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA. RP Terabe, M (reprint author), NCI, Vaccine Branch, NIH, Bldg 10,Room 6B12,9000 Rockville Pike, Bethesda, MD 20892 USA. EM terabe@mail.nih.gov; terabe@mail.nih.gov NR 121 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-4614-0612-9 J9 CANCER DRUG DISCOV D JI Canc. Drug. Disc. Dev. PY 2012 BP 55 EP 70 DI 10.1007/978-1-4614-0613-6_4 D2 10.1007/978-1-4614-0613-6 PG 16 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA BAG87 UT WOS:000304124800004 ER PT J AU Xu, XM Turanov, AA Carlson, BA Yoo, MH Gladyshev, VN Hatfield, DL AF Xu, Xue-Ming Turanov, Anton A. Carlson, Bradley A. Yoo, Min-Hyuk Gladyshev, Vadim N. Hatfield, Dolph L. BE Hatfield, DL Berry, MJ Gladyshev, VN TI Selenocysteine Biosynthesis and the Replacement of Selenocysteine with Cysteine in the Pathway SO SELENIUM: ITS MOLECULAR BIOLOGY AND ROLE IN HUMAN HEALTH, THIRD EDITION LA English DT Article; Book Chapter ID SYNTHETASE 2 SPS2; TRANSFER-RNA; SELENOPHOSPHATE SYNTHETASE; ESCHERICHIA-COLI; SELENOPROTEIN SYNTHESIS; IN-VIVO; LIVER; IDENTIFICATION; EUKARYOTES; MACHINERY AB The biosynthetic pathway of selenocysteine (Sec), the 21st amino acid in the genetic code, has been established in eukaryotes and archaea using comparative genomic and experimental approaches. In addition, cysteine (Cys) was found to arise in place of selenocysteine in thioredoxin reductase (TR) in NIH 3T3 cells and in mice. An analysis of the selenocysteine biosynthetic pathway demonstrated that replacement of selenide with sulfide in generating the active cysteine donor, thiophosphate, resulted in cysteine being donated to the acceptor molecule, which is likely dehydroalanyl-tRNA([Ser]Sec), yielding Cys-tRNA([Ser]Sec). The identification of the pathways for biosynthesis of selenocysteine and cysteine in mammals is discussed in this chapter. C1 [Xu, Xue-Ming; Carlson, Bradley A.; Yoo, Min-Hyuk; Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Turanov, Anton A.; Gladyshev, Vadim N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet,Dept Med, Boston, MA 02115 USA. RP Hatfield, DL (reprint author), NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM hatfield@mail.nih.gov; hatfield@mail.nih.gov NR 29 TC 1 Z9 1 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-1025-6 PY 2012 BP 23 EP 31 DI 10.1007/978-1-4614-1025-6_2 D2 10.1007/978-1-4614-1025-6 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BZZ25 UT WOS:000303410300002 ER PT J AU Dunn, BK Taylor, PR AF Dunn, Barbara K. Taylor, Philip R. BE Hatfield, DL Berry, MJ Gladyshev, VN TI Prostate Cancer Prevention and the Selenium and Vitamin E Cancer Prevention Trial (SELECT): A Selenium Perspective SO SELENIUM: ITS MOLECULAR BIOLOGY AND ROLE IN HUMAN HEALTH, THIRD EDITION LA English DT Article; Book Chapter ID BETA-CAROTENE; ALPHA-TOCOPHEROL; CLINICAL-TRIALS; SUPPLEMENTATION; RISK; CHEMOPREVENTION; GROWTH AB The Selenium and Vitamin E Cancer Prevention Trial (SELECT) randomized 35,533 healthy men, >= 55 years (>= 50 years if African American), with normal digital rectal exams and prostate-specific antigens <4 ng/mL, to (i) 200 mu g/day l-selenomethionine, (ii) 400 IU/day all-rac-alpha-tocopheryl acetate (vitamin E), (iii) both supplements, or (iv) placebo for a median of 5.5 years (range 4.2-7.3 years). The hypotheses underlying SELECT, that selenium and vitamin E individually and together decrease prostate cancer incidence, derived from epidemiologic and laboratory evidence and significant secondary endpoints in the Nutritional Prevention of Cancer (NPC) (selenium) and Alpha-Tocopherol Beta-Carotene (vitamin E) trials. Results from SELECT showed that prostate cancer incidence did not differ among the four arms: hazard ratios (HRs) (99% CIs) for prostate cancer: 1.13 (99% CI, 0.95-1.35; p=0.06; n=473) for vitamin E, 1.04 (99% CI, 0.87-1.24; p=0.62; n=432) for selenium, and 1.05 (99% CI, 0.88-1.25; p=0.52; n=437) for selenium + vitamin E vs. 1.00 (n=416) for placebo. Statistically nonsignificant increased risks of prostate cancer with vitamin E alone (RR 1.13; p=0.06) and newly diagnosed type 2 diabetes mellitus with selenium alone (RR 1.07; p=0.16) were observed. SELECT data show that neither selenium nor vitamin E, alone or together, in the doses and formulations used, prevented prostate cancer in this heterogeneous population of healthy men. Although there are many potential explanations for the null findings in SELECT, the most likely reasons appear to be a mismatch between the target population and the intervention agents selected, or that effects were limited to as-yet-undetermined subgroups of susceptible men. C1 [Taylor, Philip R.] NCI, Div Canc Epidemiol & Genet, Bethesda, MA USA. [Dunn, Barbara K.] NCI, Canc Prevent Div, Bethesda, MA USA. [Dunn, Barbara K.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Taylor, PR (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MA USA. EM ptaylor@mail.nih.gov NR 36 TC 2 Z9 2 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-1025-6 PY 2012 BP 297 EP 311 DI 10.1007/978-1-4614-1025-6_23 D2 10.1007/978-1-4614-1025-6 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BZZ25 UT WOS:000303410300023 ER PT J AU Yoo, MH Carlson, BA Tsuji, PA Tobe, R Naranjo-Suarez, S Lee, BJ Davis, CD Gladyshev, VN Hatfield, DL AF Yoo, Min-Hyuk Carlson, Bradley A. Tsuji, Petra A. Tobe, Ryuta Naranjo-Suarez, Salvador Lee, Byeong Jae Davis, Cindy D. Gladyshev, Vadim N. Hatfield, Dolph L. BE Hatfield, DL Berry, MJ Gladyshev, VN TI Selenoproteins Harboring a Split Personality in Both Preventing and Promoting Cancer SO SELENIUM: ITS MOLECULAR BIOLOGY AND ROLE IN HUMAN HEALTH, THIRD EDITION LA English DT Article; Book Chapter ID THIOREDOXIN REDUCTASE; ENDOPLASMIC-RETICULUM; 15-KDA SELENOPROTEIN; SELENIUM-COMPOUNDS; TRANSGENIC MICE; SEP15; CELLS; CHEMOPREVENTION; DEFICIENCY; THERAPY AB Selenium has long been known to have a role in preventing cancer, but only in recent years has a deficiency in this element also been shown to function in preventing cancer. Selenoproteins have also been shown to serve as selenium-containing components in cancer prevention, but we are learning that specific members of this protein class can also function in cancer promotion. The involvement of two of these selenoproteins, thioredoxin reductase 1 and the 15 kDa selenoprotein, in promoting cancer is examined in this chapter. C1 [Yoo, Min-Hyuk; Carlson, Bradley A.; Tsuji, Petra A.; Tobe, Ryuta; Naranjo-Suarez, Salvador; Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Tsuji, Petra A.] Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Lee, Byeong Jae] Seoul Natl Univ, Dept Biol Sci, Interdisciplinary Program Bioinformat, Seoul, South Korea. [Davis, Cindy D.] NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Gladyshev, Vadim N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet,Dept Med, Boston, MA 02115 USA. RP Hatfield, DL (reprint author), NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM hatfield@mail.nih.gov; hatfield@mail.nih.gov NR 42 TC 7 Z9 7 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-1025-6 PY 2012 BP 325 EP 333 DI 10.1007/978-1-4614-1025-6_25 D2 10.1007/978-1-4614-1025-6 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BZZ25 UT WOS:000303410300025 ER PT J AU Tsuji, PA Davis, CD Milner, JA AF Tsuji, Petra A. Davis, Cindy D. Milner, John A. BE Hatfield, DL Berry, MJ Gladyshev, VN TI Selenium: Dietary Sources and Human Requirements SO SELENIUM: ITS MOLECULAR BIOLOGY AND ROLE IN HUMAN HEALTH, THIRD EDITION LA English DT Article; Book Chapter ID NUTRITION EXAMINATION SURVEY; HPLC-ICP-MS; NATIONAL-HEALTH; CANCER RISK; SAMPLES; BIOAVAILABILITY; POLYMORPHISMS; FOOD; SELENOMETHIONINE; SELENOPROTEINS AB Selenium is an essential trace mineral. Typically, in humans, grains and animal products are the primary exposure source. Inadequate information exists about the benefits provided by dietary selenium supplements. Current recommended dietary amounts for healthy adults in the US are 55 mu g/day for men and women. In the general US population, higher amounts can be obtained through consumption of typical foods. Regardless, controversies prevail about adequate amounts for health and the individual needs depending on genetic and environmental variables. Information regarding specific target populations potentially sensitive to selenium status continues to be an area of much needed research. C1 [Tsuji, Petra A.] Ctr Canc Res, Lab Canc Prevent, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Tsuji, Petra A.] Ctr Canc Res, Lab Canc Prevent, Mol Biol Selenium Sect, Bethesda, MD 20892 USA. [Tsuji, Petra A.; Davis, Cindy D.; Milner, John A.] NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. RP Tsuji, PA (reprint author), Ctr Canc Res, Lab Canc Prevent, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. EM tsujipa@mail.nih.gov NR 83 TC 2 Z9 5 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-1025-6 PY 2012 BP 517 EP 529 DI 10.1007/978-1-4614-1025-6_41 D2 10.1007/978-1-4614-1025-6 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BZZ25 UT WOS:000303410300041 ER PT J AU Carlson, BA Yoo, MH Tsuji, PA Tobe, R Naranjo-Suarez, S Chen, F Feigenbaum, L Tessarollo, L Lee, BJ Gladyshev, VN Hatfield, DL AF Carlson, Bradley A. Yoo, Min-Hyuk Tsuji, Petra A. Tobe, Ryuta Naranjo-Suarez, Salvador Chen, Fang Feigenbaum, Lionel Tessarollo, Lino Lee, Byeong Jae Gladyshev, Vadim N. Hatfield, Dolph L. BE Hatfield, DL Berry, MJ Gladyshev, VN TI Mouse Models that Target Removal or Overexpression of the Selenocysteine tRNA([Ser]Sec) Gene to Elucidate the Role of Selenoproteins in Health and Development SO SELENIUM: ITS MOLECULAR BIOLOGY AND ROLE IN HUMAN HEALTH, THIRD EDITION LA English DT Article; Book Chapter ID TRANSFER-RNA GENE; SELENIUM; EXPRESSION; MICE; TRSP; METHYLATION; EUKARYOTES; DISRUPTION; RADIATION; SEQUENCE AB Several mouse models targeting the selenocysteine (Sec) tRNA([Ser]Sec) gene for removal or overexpression have been generated and they include: (I) mice carrying a conditional knockout of the Sec tRNA gene; (2) transgenic mice encoding wild type or mutant Sec tRNA transgenes; and (3) conditional knockout/transgenic or standard knockow/transgenic mice carrying wild type or mutant Sec tRNA transgenes. These models have provided powerful tools for elucidating the roles of selenoproteins in development and health. C1 [Carlson, Bradley A.; Yoo, Min-Hyuk; Tsuji, Petra A.; Naranjo-Suarez, Salvador; Chen, Fang; Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Tsuji, Petra A.] NCI, Canc Prevent Fellowship Program, NIH, Bethesda, MD 20892 USA. [Feigenbaum, Lionel] Sci Applicat Int Corp, Lab Anim Sci Program, Frederick, MD 21702 USA. [Tessarollo, Lino] NCI, Neural Dev Grp, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA. [Lee, Byeong Jae] Seoul Natl Univ, Dept Biol Sci, Interdisciplinary Program Bioinformat, Seoul, South Korea. [Gladyshev, Vadim N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet,Dept Med, Boston, MA 02115 USA. RP Carlson, BA (reprint author), NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM carlsonb@mail.nih.gov NR 43 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-1025-6 PY 2012 BP 561 EP 572 DI 10.1007/978-1-4614-1025-6_44 D2 10.1007/978-1-4614-1025-6 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BZZ25 UT WOS:000303410300044 ER PT J AU Cohen, SS Fowke, JH Cai, QY Buchowski, MS Signorello, LB Hargreaves, MK Zheng, W Blot, WJ Matthews, CE AF Cohen, Sarah S. Fowke, Jay H. Cai, Qiuyin Buchowski, Maciej S. Signorello, Lisa B. Hargreaves, Margaret K. Zheng, Wei Blot, William J. Matthews, Charles E. TI Differences in the Association between Serum Leptin Levels and Body Mass Index in Black and White Women: A Report from the Southern Community Cohort Study SO ANNALS OF NUTRITION AND METABOLISM LA English DT Article DE Leptin; Body mass index; Race; Adipokines ID FOOD FREQUENCY QUESTIONNAIRE; UNITED-STATES; RACIAL-DIFFERENCES; CIGARETTE-SMOKING; FAT DISTRIBUTION; ADIPOSE-TISSUE; LIFE-STYLE; OBESITY; POPULATION; INSULIN AB Background/Aims: Leptin may be an important link between obesity and many high-burden diseases, including cancer and cardiovascular disease, but leptin levels and correlates in individuals of diverse racial backgrounds have not been well characterized despite racial differences in incidence and mortality patterns for many obesity-related diseases. Methods: In a cross-sectional study of 915 white and 892 black women enrolled in the Southern Community Cohort Study (age 40-79 years, half postmenopausal), serum leptin levels were compared between the race groups and across categories of body mass index (BMI). Potential correlates of leptin were assessed via race-stratified linear regression models. Results: Blacks had higher unadjusted leptin levels than whites (geometric mean 22.4 vs. 19.0 ng/ml; p < 0.0001). Leptin increased with increasing BMI, and racial differences in leptin were most pronounced in women with BMI >= 25. Significant correlates of leptin included BMI, age, alcohol consumption, cigarette smoking, diabetes (both races) and fat consumption (black women only). Leptin remained higher in black women (22.7 vs. 18.8 ng/ml) after adjustment for these factors. Conclusions: Persistent racial differences in leptin concentrations exist after adjustment for BMI and other factors. Leptin assessment may be informative in future studies that investigate racial differences in the development of obesity-related diseases. Copyright (C) 2012 S. Karger AG, Basel C1 [Cohen, Sarah S.; Signorello, Lisa B.; Blot, William J.] Int Epidemiol Inst, Rockville, MD 20850 USA. [Matthews, Charles E.] NCI, Nutr Epidemiol Branch, Rockville, MD USA. [Fowke, Jay H.; Cai, Qiuyin; Buchowski, Maciej S.; Signorello, Lisa B.; Zheng, Wei; Blot, William J.] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA. [Fowke, Jay H.; Cai, Qiuyin; Buchowski, Maciej S.; Signorello, Lisa B.; Zheng, Wei; Blot, William J.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Hargreaves, Margaret K.] Meharry Med Coll, Dept Internal Med, Nashville, TN 37208 USA. RP Cohen, SS (reprint author), Int Epidemiol Inst, 1455 Res Blvd,Suite 550, Rockville, MD 20850 USA. EM sarah@ieixmail.com RI Buchowski, Maciej/A-2683-2008; matthews, Charles/E-8073-2015 OI Buchowski, Maciej/0000-0002-0566-1743; matthews, Charles/0000-0001-8037-3103 FU Susan G. Komen for the Cure [OP05-0927-DR1]; National Cancer Institute [R01 CA92447]; Vanderbilt-Ingram Cancer Center [P30 CA68485] FX This project was funded in part by grant OP05-0927-DR1 from Susan G. Komen for the Cure. The SCCS is funded by grant R01 CA92447 from the National Cancer Institute. Serum sample preparation was conducted at the Survey and Biospecimen Shared Resource, which is supported in part by the Vanderbilt-Ingram Cancer Center (P30 CA68485). NR 32 TC 10 Z9 10 U1 2 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 EI 1421-9697 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2012 VL 60 IS 2 BP 90 EP 97 DI 10.1159/000336180 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 941LR UT WOS:000303965200002 PM 22353927 ER PT J AU Gong, R Chen, WZ Dimitrov, DS AF Gong, Rui Chen, Weizao Dimitrov, Dimiter S. TI Candidate Antibody-Based Therapeutics Against HIV-1 SO BIODRUGS LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODY; PROTEIN-DISULFIDE-ISOMERASE; BROADLY NEUTRALIZING ANTIBODIES; TYPE-1 ENVELOPE GLYCOPROTEIN; CROSS-CLADE NEUTRALIZATION; PROXIMAL EXTERNAL REGION; CORECEPTOR BINDING-SITE; NEONATAL-FC-RECEPTOR; PBL-SCID MICE AB Antibody-based therapeutics have been successfully used for the treatment of various diseases and as research tools. Several well characterized, broadly neutralizing monoclonal antibodies (bnmAbs) targeting HIV-1 envelope glycoproteins or related host cell surface proteins show sterilizing protection of animals, but they are not effective when used for therapy of an established infection in humans. Recently, a number of novel bnmAbs, engineered antibody domains (eAds), and multifunctional fusion proteins have been reported which exhibit exceptionally potent and broad neutralizing activity against a wide range of HIV-1 isolates from diverse genetic subtypes. eAds could be more effective in vivo than conventional full-size antibodies generated by the human immune system. Because of their small size (12 similar to 15 kD), they can better access sterically restricted epitopes and penetrate densely packed tissue where HIV-1 replicates than the larger full-size antibodies. HIV-1 possesses a number of mechanisms to escape neutralization by full-size antibodies but could be less likely to develop resistance to eAds. Here, we review the in vitro and in vivo antiviral efficacies of existing HIV-1 bnmAbs, summarize the development of eAds and multispecific fusion proteins as novel types of HIV-1 inhibitors, and discuss possible strategies to generate more potent antibody-based candidate therapeutics against HIV-1, including some that could be used to eradicate the virus. C1 [Gong, Rui; Chen, Weizao; Dimitrov, Dimiter S.] NIH, PIG, FNLCR, Frederick, MD 21702 USA. RP Gong, R (reprint author), NIH, PIG, FNLCR, Bldg 469,Rm 140, Frederick, MD 21702 USA. EM gongr@mail.nih.gov FU NIH; NCI; CCR; IATAP of the NIH FX We thank members of our group for useful discussions. This article was supported by the Intramural Research Program of the NIH, NCI, CCR, and the IATAP of the NIH. NR 238 TC 7 Z9 9 U1 3 U2 7 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1173-8804 J9 BIODRUGS JI Biodrugs PY 2012 VL 26 IS 3 BP 143 EP 162 PG 20 WC Oncology; Immunology; Pharmacology & Pharmacy SC Oncology; Immunology; Pharmacology & Pharmacy GA 946FR UT WOS:000304337400002 PM 22462520 ER PT J AU Biswas, D Cao, Z Keefer, LK Saavedra, JE AF Biswas, Debanjan Cao, Zhao Keefer, Larry K. Saavedra, Joseph E. TI Nitrous oxide as a primary product in base-mediated beta-elimination reactions of diazeniumdiolated benzylamine derivatives SO CHEMICAL COMMUNICATIONS LA English DT Article ID NITRIC-OXIDE; CHEMISTRY; DONORS; NO; RELEASE; ION AB We report an unexpected beta-elimination pathway by which diazeniumdiolated benzylamines of structure Bn-N(R)-N(O)=N-OR' undergo base-mediated fragmentation to generate N2O as the only gaseous product. The reaction is especially rapid for R = 2-hydroxyethyl in which the hydroxyl group anchimerically assists benzylic proton removal with concomitant expulsion of PhCH=NR and R'OH. C1 [Biswas, Debanjan; Keefer, Larry K.] NCI, Drug Design Sect, Biol Chem Lab, Frederick, MD 21702 USA. [Cao, Zhao; Saavedra, Joseph E.] NCI, Basic Sci Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Biswas, D (reprint author), NCI, Drug Design Sect, Biol Chem Lab, Frederick, MD 21702 USA. EM biswasd@mail.nih.gov RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX This project has been funded with Federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E, and by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 13 TC 0 Z9 0 U1 1 U2 2 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 J9 CHEM COMMUN JI Chem. Commun. PY 2012 VL 48 IS 47 BP 5931 EP 5933 DI 10.1039/c2cc32284f PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 943PF UT WOS:000304135900039 PM 22572739 ER PT J AU Jones, HE Finnegan, LP Kaltenbach, K AF Jones, Hendree E. Finnegan, Loretta P. Kaltenbach, Karol TI Methadone and Buprenorphine for the Management of Opioid Dependence in Pregnancy SO DRUGS LA English DT Article ID FETAL HEART-RATE; NEONATAL ABSTINENCE SYNDROME; BIOPHYSICAL PROFILE; HEROIN USER; IMPLANTABLE NALTREXONE; NARCOTIC WITHDRAWAL; NEWBORN-INFANTS; SUBSTANCE-ABUSE; DRUG-ADDICTION; EXPOSURE AB This article provides an overview and discussion of the collective maternal, fetal and neonatal outcome research on women maintained on methadone or buprenorphine during pregnancy. Its focus is on an assessment of the comparative effectiveness of methadone and buprenorphine pharmacotherapy, with particular attention given to recent findings from the literature. Recommendations for clinical practice are outlined, and directions for future research are presented. Findings from comparative studies of methadone and buprenorphine underscore the efficacy of both medications in preventing relapse to illicit opioid use in the treatment of opioid-dependent pregnant patients, as well as the simplicity of induction onto methadone and patient retention while receiving such therapy. Fetal monitoring suggests that buprenorphine results in less fetal cardiac and movement suppression than does methadone. The clinical implications of these findings need future exploration. For the neonate, evidence from studies using a wide range of designs, including retrospective chart reviews, prospective observational studies, and randomized clinical trials, show consistent results, with prenatal exposure to buprenorphine resulting in less severe neonatal abstinence syndrome relative to methadone. Any medication given to pregnant women should be prescribed only after considering the risk : benefit ratio for the maternal-fetal dyad. Medication choices for each opioid-dependent patient during pregnancy need to be made on a patient-by-patient basis, taking into consideration the patient's opioid dependence history, previous and current treatment experiences, medical circumstances and treatment preferences. Moreover, for a full remission of opioid addiction to be sustainable, both post-partum and across the lifespan, treatment providers must not rely solely on medication to treat their patients but should also utilize women-specific comprehensive treatment models that address the underlying multifaceted complexities of their patient's lives. C1 [Jones, Hendree E.] RTI Int, Res Triangle Pk, NC 27709 USA. [Jones, Hendree E.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Jones, Hendree E.] Johns Hopkins Univ, Sch Med, Dept Obstet & Gynecol, Baltimore, MD 21205 USA. [Finnegan, Loretta P.] Finnegan Consulting LLC, Avalon, NJ USA. [Finnegan, Loretta P.] NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA. [Kaltenbach, Karol] Thomas Jefferson Univ, Jefferson Med Coll, Dept Pediat, Philadelphia, PA 19107 USA. [Kaltenbach, Karol] Thomas Jefferson Univ, Jefferson Med Coll, Dept Psychiat & Human Behav, Philadelphia, PA 19107 USA. RP Jones, HE (reprint author), RTI Int, 3040 E Cornwallis Rd, Res Triangle Pk, NC 27709 USA. EM hjones@rti.org FU National Institute on Drug Abuse [RO1 DA 15738]; Purdue Pharma, Stamford, CT, USA FX KK was supported by the National Institute on Drug Abuse (RO1 DA 15738) during the preparation of this manuscript. Preparation of this paper was supported, in part, by the National Institute on Drug Abuse but this institute played no role in the (i) collection, analysis and interpretation of data; (ii) writing of the paper; or (iii) decision to submit or where to submit the paper for publication.; HEJ and KK received free active and placebo tablets from Reckitt-Benckiser Inc. to conduct the MOTHER study. HEJ has received reimbursement for time and travel from Reckitt-Benckiser Inc. for several presentations related to data from randomized controlled studies on this topic. LPF is funded as a consultant to Purdue Pharma, Stamford, CT, USA, for a project regarding NAS, which has not yet commenced. NR 78 TC 33 Z9 34 U1 2 U2 19 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PY 2012 VL 72 IS 6 BP 747 EP 757 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 943OC UT WOS:000304132700001 PM 22512363 ER PT J AU Jo, J Hara, M Ahlgren, U Sorenson, RL Periwal, V AF Jo, Junghyo Hara, Manami Ahlgren, Ulf Sorenson, Robert L. Periwal, Vipul TI Mathematical models of pancreatic islet size distributions SO ISLETS LA English DT Review ID BETA-CELL TURNOVER; IN-SITU; CONFOCAL MICROSCOPY; POLYCLONAL ORIGIN; MICE; MOUSE; LANGERHANS; VOLUME; QUANTIFICATION; NUMBER AB The islets of Langerhans, ranging in size from clusters of a few cells to several thousand cells, are scattered near large blood vessels. While the beta-cell mass in mammals is proportional to body weight, the size ranges of islets are similar between species with different body sizes, possibly reflecting an optimal functional size. The large range of islet sizes suggests a stochastic developmental process. It is not fully understood how islets develop to reach such size distributions, and how their sizes change under certain physiological and pathological conditions such as development, pregnancy, aging, obesity, and diabetes. The lack of a high-resolution in vivo imaging technique for pancreatic islets implies that the only data available to elucidate the dynamics of islet development are cross-sectional quantifications of islet size distributions. In this review, we infer biological processes affecting islet morphology in the large by examining changes of islet size distributions. Neonatal islet formation and growth is shown as a particular example of developing a mathematical model of islet size distribution. Application of this modeling to elucidate islet changes under other conditions is also discussed. C1 [Jo, Junghyo; Periwal, Vipul] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. [Hara, Manami] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Ahlgren, Ulf] Umea Univ, Umea Ctr Mol Med, Umea, Sweden. [Sorenson, Robert L.] Univ Minnesota, Sch Med, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. RP Periwal, V (reprint author), NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. EM vipulp@mail.nih.gov RI Periwal, Vipul/I-1728-2012; Jo, Junghyo/D-4889-2011; OI Ahlgren, Ulf/0000-0001-5923-8572 FU NIH; NIDDK FX The study is supported by the intramural research program of the NIH, NIDDK.S NR 52 TC 7 Z9 7 U1 3 U2 9 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1938-2014 J9 ISLETS JI Islets PD JAN-FEB PY 2012 VL 4 IS 1 DI 10.4161/isl.18660 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 941RG UT WOS:000303980000002 PM 22504860 ER PT B AU Larochelle, A Dunbar, CE AF Larochelle, Andre Dunbar, Cynthia E. BE Fruehauf, S Zeller, WJ Calandra, G TI Mobilization for Gene Therapy SO NOVEL DEVELOPMENTS IN STEM CELL MOBILIZATION: FOCUS ON CXCR4 LA English DT Article; Book Chapter ID STEM-CELL FACTOR; COLONY-STIMULATING FACTOR; CHRONIC GRANULOMATOUS-DISEASE; BLOOD PROGENITOR CELLS; SEVERE COMBINED IMMUNODEFICIENCY; HUMAN HEMATOPOIETIC STEM; WISKOTT-ALDRICH-SYNDROME; NON-HODGKINS-LYMPHOMA; BONE-MARROW-TRANSPLANTATION; MULTIPLE-MYELOMA PATIENTS C1 [Larochelle, Andre; Dunbar, Cynthia E.] NHLBI, Mol Hematopoiesis Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Larochelle, A (reprint author), NHLBI, Mol Hematopoiesis Sect, Hematol Branch, NIH, 9000 Rockville Pike,Bldg 10CRC,Rm 3E-5256, Bethesda, MD 20892 USA. EM larochea@nhlbi.nih.gov NR 149 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-1959-4 PY 2012 BP 457 EP 485 DI 10.1007/978-1-4614-1960-0_24 D2 10.1007/978-1-46141960-0 PG 29 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA BAD86 UT WOS:000303895200024 ER PT S AU Wang, D Kim, H Wang, XM Dionne, R AF Wang, Dan Kim, Hyungsuk Wang, Xiao-Min Dionne, Raymond BE Luo, ZD TI Genomic Methods for Clinical and Translational Pain Research SO PAIN RESEARCH: METHODS AND PROTOCOLS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Pain; Genome-wide association study; Single nucleotide polymorphism; Whole-genome sampling analysis; Copy number variation; Global gene expression analysis; Microarray ID OPIOID RECEPTOR GENE; WIDE ASSOCIATION; GTP CYCLOHYDROLASE; INFLAMMATORY PAIN; EXPRESSION; HUMANS; POLYMORPHISM; SENSITIVITY; INHIBITORS; ANALGESIA AB Pain is a complex sensory experience for which the molecular mechanisms arc yet to be fully elucidated. Individual differences in pain sensitivity are mediated by a complex network of multiple gene polymorphisms, physiological and psychological processes, and environmental factors. Here, we present the methods for applying unbiased molecular-genetic approaches, genome-wide association study (GWAS), and global gene expression analysis, to help better understand the molecular basis of pain sensitivity in humans and variable responses to analgesic drugs. C1 [Wang, Dan; Kim, Hyungsuk; Wang, Xiao-Min; Dionne, Raymond] NINR, NIH, Bethesda, MD 20892 USA. RP Wang, D (reprint author), NINR, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [ZIA NR000015-05] NR 23 TC 4 Z9 4 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-560-2 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 851 BP 9 EP 46 DI 10.1007/978-1-61779-561-9_2 D2 10.1007/978-1-61779-561-9 PG 38 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA BAD97 UT WOS:000303896300002 PM 22351080 ER PT B AU Schmidt, LS Srinivasan, R Linehan, WM AF Schmidt, Laura S. Srinivasan, Ramaprasad Linehan, W. Marston BE Figlin, RA Rathmell, WK Rini, BI TI The Genetic Basis of Kidney Cancer and Implications for Targeted Therapies SO RENAL CELL CARCINOMA: TRANSLATIONAL BIOLOGY, PERSONALIZED MEDICINE, AND NOVEL THERAPEUTIC TARGETS LA English DT Article; Book Chapter ID BIRT-HOGG-DUBE; RENAL-CELL CARCINOMA; TUMOR-SUPPRESSOR GENE; HIPPEL-LINDAU-DISEASE; TUBEROUS SCLEROSIS COMPLEX; FUMARATE-HYDRATASE DEFICIENCY; PARENCHYMAL SPARING SURGERY; TYROSINE KINASE RECEPTOR; C-MET MUTATIONS; HEREDITARY LEIOMYOMATOSIS C1 [Schmidt, Laura S.; Srinivasan, Ramaprasad; Linehan, W. Marston] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Schmidt, Laura S.] NCI, SAIC Frederick Inc, Basic Sci Program, Frederick, MD 21701 USA. RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, NIH, BLDG 10 CRC Room 1-5940,10 Ctr Dr MSC 1107, Bethesda, MD 20892 USA. EM schmidtl@mail.nih.gov; ramasrin@mail.nih.gov; wml@nih.gov NR 127 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-2399-7 PY 2012 BP 3 EP 25 DI 10.1007/978-1-4614-2400-0_1 D2 10.1007/978-1-4615-2400-0 PG 23 WC Oncology SC Oncology GA BZZ35 UT WOS:000303413500001 ER PT J AU Lee, S Kim, K AF Lee, Seulki Kim, Kwangmeyung TI Protease Activity: Meeting Its Theranostic Potential SO THERANOSTICS LA English DT Editorial Material DE Biomarkers; diagnosis; drug development; molecular imaging; proteases; theranostics AB This themed issue provides up-to-date review and research articles covering the theranostic applications in the combined fields of protease research, diagnostics and drug development. C1 [Lee, Seulki] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Kim, Kwangmeyung] Korea Inst Sci & Technol, Biomed Res Inst, Ctr Theragnosis, Seoul, South Korea. RP Lee, S (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. EM seulki.lee@nih.gov; kim@kist.re.kr NR 14 TC 6 Z9 6 U1 2 U2 10 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2012 VL 2 IS 2 BP 125 EP 126 DI 10.7150/thno.4129 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 942FN UT WOS:000304029500001 PM 22400061 ER PT J AU Choi, KY Swierczewska, M Lee, S Chen, XY AF Choi, Ki Young Swierczewska, Magdalena Lee, Seulki Chen, Xiaoyuan TI Protease-Activated Drug Development SO THERANOSTICS LA English DT Review DE Protease; activatable probe; Alzheimer's disease; cancer; caspase; cathepsin; kallikrein; MMP; PSA; serine protease; aspartyl protease ID PROSTATE-SPECIFIC ANTIGEN; ALBUMIN-BINDING PRODRUG; L-LEUCYL-DOXORUBICIN; SENSITIVE PHOTODYNAMIC AGENTS; COPOLYMER-BOUND ADRIAMYCIN; SQUAMOUS-CELL CARCINOMAS; TRANSGENIC MOUSE MODEL; BREAST-CANCER PATIENTS; HUMAN CATHEPSIN-B; MATRIX METALLOPROTEINASES AB In this extensive review, we elucidate the importance of proteases and their role in drug development in various diseases with an emphasis on cancer. First, key proteases are introduced along with their function in disease progression. Next, we link these proteases as targets for the development of prodrugs and provide clinical examples of protease-activatable prodrugs. Finally, we provide significant design considerations needed for the development of the next generation protease-targeted and protease-activatable prodrugs. C1 [Choi, Ki Young; Swierczewska, Magdalena; Lee, Seulki; Chen, Xiaoyuan] NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA. [Swierczewska, Magdalena] SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA. RP Lee, S (reprint author), NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA. EM Seulki.Lee@nih.gov; Shawn.Chen@nih.gov RI CHOI, KI YOUNG/Q-7177-2016 FU National Institutes of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH); NIH [K99/R00] FX This work was supported by the Intramural Research Program (IRP) of the National Institutes of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). S.L. is partially supported by the NIH Pathway to Independence (K99/R00) Award. NR 261 TC 71 Z9 71 U1 9 U2 63 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2012 VL 2 IS 2 BP 156 EP 178 DI 10.7150/thno.4068 PG 23 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 942FN UT WOS:000304029500005 PM 22400063 ER PT J AU Niu, G Chen, XY AF Niu, Gang Chen, Xiaoyuan TI Molecular Imaging with Activatable Reporter Systems SO THERANOSTICS LA English DT Review DE Molecular imaging; reporter gene; activatable; optical imaging; PET ID PROTEIN-PROTEIN INTERACTIONS; POSITRON-EMISSION-TOMOGRAPHY; SPLIT RENILLA LUCIFERASE; SODIUM-IODIDE SYMPORTER; LIVING SUBJECTS; GENE-EXPRESSION; FIREFLY LUCIFERASE; IN-VIVO; FRAGMENT COMPLEMENTATION; TRANSGENE EXPRESSION AB Molecular imaging is a newly emerged multiple disciplinary field that aims to visualize, characterize and quantitatively measure biological processes at cellular and molecular levels in humans and other living systems. A reporter gene is a piece of DNA encoding reporter protein, which presents as a readily measurable phenotype that can be distinguished easily from the background of endogenous protein. After being transferred into cells of organ systems (transgenes), the reporter gene can be utilized to visualize transcriptional and posttranscriptional regulation of gene expression, protein-protein interactions, or trafficking of proteins or cells in living subjects. Herein, we review previous classification of reporter genes and regroup the reporter gene based imaging as basic, inducible and activatable, based on the regulation of reporter gene transcription and post-translational modification of reporter proteins. We then focus on activatable reporters, in which the signal can be activated at the posttranslational level for visualizing protein-protein interactions, protein phosphorylation or tertiary structure changes. The applications of several types of activatable reporters will also be summarized. We conclude that activatable reporter imaging can benefit both basic biomedical research and drug development. C1 [Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. RP Niu, G (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, 9 Mem Dr,9-1W111, Bethesda, MD 20892 USA. EM niug@mail.nih.gov; shawn.chen@nih.gov FU National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health FX The work was supported by the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health. NR 82 TC 20 Z9 20 U1 1 U2 19 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2012 VL 2 IS 4 BP 413 EP 423 DI 10.7150/thno.3940 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 942GE UT WOS:000304031200009 PM 22539937 ER PT S AU Wang, SQ Samakovlis, C AF Wang, Shenqiu Samakovlis, Christos BE Plaza, S Payre, F TI GRAINY HEAD AND ITS TARGET GENES IN EPITHELIAL MORPHOGENESIS AND WOUND HEALING SO TRANSCRIPTIONAL SWITCHES DURING DEVELOPMENT SE Current Topics in Developmental Biology LA English DT Review; Book Chapter ID DROSOPHILA TRACHEAL SYSTEM; TUBE-SIZE CONTROL; DEVELOPMENTAL TRANSCRIPTION FACTORS; SEPTATE JUNCTION FUNCTION; DOMINANT HEARING-LOSS; CELL-MIGRATION; FACTOR CP2; EPIDERMAL DIFFERENTIATION; CUTICLE DIFFERENTIATION; NEURAL PROLIFERATION AB The Grainy head (Grh) family of transcription factors is characterized by a unique DNA-binding domain that binds to a conserved consensus sequence. Nematodes and flies have a single grh gene, whereas mice and humans have evolved three genes encoding Grainy head-like (Grhl) factors. We review the biological function of Grh in different animals and the mechanisms modulating its activity. grh and grhl genes play a remarkably conserved role in epithelial organ development and extracellular barrier repair after tissue damage. Recent studies in flies and vertebrates suggest that Grh factors may be primary determinants of cell adhesion and epithelial tissue formation. Grh proteins can dimerize and act as activators or repressors in different developmental contexts. In flies, tissue-specific, alternative splicing generates different Grh isoforms with different DNA-binding specificities and functions. Grh activity is also modulated by receptor tyrosine kinases: it is phosphorylated by extracellular signal regulated kinase, and this phosphorylation is selectively required for epidermal barrier repair. Two mechanisms have been proposed to explain the repressive function of Grh on target gene transcription. First, Grh can target the Polycomb silencing complex to specific response elements. Second, it can directly compete for DNA binding with transcriptional activators. Understanding the molecular mechanisms of gene regulation by Grh factors is likely to elucidate phylogenetically conserved mechanisms of epithelial cell morphogenesis and regeneration upon tissue damage. C1 [Wang, Shenqiu; Samakovlis, Christos] Stockholm Univ, Dept Dev Biol, Wenner Gren Inst, S-10691 Stockholm, Sweden. RP Wang, SQ (reprint author), NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. NR 129 TC 14 Z9 15 U1 1 U2 11 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0070-2153 BN 978-0-12-386499-4 J9 CURR TOP DEV BIOL JI Curr. Top. Dev. Biol. PY 2012 VL 98 BP 35 EP 63 DI 10.1016/B978-0-12-386499-4.00002-1 PG 29 WC Developmental Biology SC Developmental Biology GA BAD90 UT WOS:000303895600003 PM 22305158 ER PT S AU Lichti-Kaiser, K ZeRuth, G Kang, HS Vasanth, S Jetten, AM AF Lichti-Kaiser, Kristin ZeRuth, Gary Kang, Hong Soon Vasanth, Shivakumar Jetten, Anton M. BE Litwack, G TI GLI-SIMILAR PROTEINS: THEIR MECHANISMS OF ACTION, PHYSIOLOGICAL FUNCTIONS, AND ROLES IN DISEASE SO VITAMINS AND HORMONES: HEDGEHOG SIGNALING SE Vitamins and Hormones LA English DT Review; Book Chapter ID ZINC-FINGER PROTEIN; POLYCYSTIC KIDNEY-DISEASE; NEONATAL DIABETES-MELLITUS; BETA-CELL FUNCTION; INTRAFLAGELLAR TRANSPORT PROTEINS; HEDGEHOG SIGNALING REGULATION; INSULIN GENE-TRANSCRIPTION; PRIMARY CILIA; REPRESSOR FUNCTIONS; PANCREAS DEVELOPMENT AB Gli-similar (Glis) 1-3 proteins constitute a subfamily of Kruppel-like zinc-finger proteins that are closely related to members of the Gli family. Glis proteins have been implicated in several pathologies, including cystic kidney disease, diabetes, hypothyroidism, fibrosis, osteoporosis, psoriasis, and cancer. In humans, a mutation in the Glis2 gene has been linked to the development of nephronophthisis (NPHP), a recessive cystic kidney disease, while mutations in Glis3 lead to an extended multisystem phenotype that includes the development of neonatal diabetes, polycystic kidneys, congenital hypothyroidism, and facial dysmorphism. Glis3 has also been identified as a risk locus for type-1 and type-2 diabetes and additional studies have revealed a role for Glis3 in pancreatic endocrine development, beta-cell maintenance, and insulin regulation. Similar to Gli1-3, Glis2 and 3 have been reported to localize to the primary cilium. These studies appear to suggest that Glis proteins are part of a primary cilium-associated signaling pathway(s). It has been hypothesized that Glis proteins are activated through posttranslational modifications and subsequently translocate to the nucleus where they regulate transcription by interacting with Glis-binding sites in the promoter regions of target genes. This chapter summarizes the current state of knowledge regarding mechanisms of action of the Glis family of proteins, their physiological functions, as well as their roles in disease. (C) 2012 Elsevier Inc. C1 [Lichti-Kaiser, Kristin; ZeRuth, Gary; Kang, Hong Soon; Vasanth, Shivakumar; Jetten, Anton M.] NIEHS, Cell Biol Sect, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. RP Lichti-Kaiser, K (reprint author), NIEHS, Cell Biol Sect, Div Intramural Res, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. OI Jetten, Anton/0000-0003-0954-4445 FU Intramural NIH HHS [Z01 ES100485-07]; NIEHS NIH HHS [Z01 ES100485] NR 148 TC 16 Z9 16 U1 0 U2 5 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0083-6729 BN 978-0-12-394622-5 J9 VITAM HORM JI Vitam. Horm. PY 2012 VL 88 BP 141 EP 171 DI 10.1016/B978-0-12-394622-5.00007-9 PG 31 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA BAD91 UT WOS:000303895700007 PM 22391303 ER PT J AU Palmer, S Boltz, VF Chow, JY Martinson, NA McIntyre, JA Gray, GE Hopley, MJ Mayers, D Robinson, P Hall, DB Maldarelli, F Coffin, JM Mellors, JW AF Palmer, Sarah Boltz, Valerie F. Chow, Jeremy Y. Martinson, Neil A. McIntyre, James A. Gray, Glenda E. Hopley, Mark J. Mayers, Douglas Robinson, Patrick Hall, David B. Maldarelli, Frank Coffin, John M. Mellors, John W. CA 1100 1413 Trial Investigators TI Short-course Combivir after single-dose nevirapine reduces but does not eliminate the emergence of nevirapine resistance in women SO ANTIVIRAL THERAPY LA English DT Article ID TO-CHILD TRANSMISSION; IMMUNODEFICIENCY-VIRUS TYPE-1; HIV-1 DRUG-RESISTANCE; REVERSE-TRANSCRIPTASE; ANTIRETROVIRAL THERAPY; RANDOMIZED-TRIAL; LOW-FREQUENCY; PERSISTENCE; VARIANTS; INTRAPARTUM AB Background: In the Treatment Options Preservation Study (TOPS) trial, 4 or 7 days of Combivir (CBV; zidovudine/lamivudine) with maternal single-dose nevirapine (sdNVP) significantly reduced the emergence of NVP resistance as determined by virus population genotyping. To detect NVP resistance with greater sensitivity, we analysed TOPS samples by allele-specific real-time PCR (ASP). Methods: In a random subset of women from each arm of the trial, plasma samples from before and 6 weeks after sdNVP were analysed using ASP at codons 103, 181, 184 and 190. Results: Samples were analysed from 27 women in the sdNVP arm and 24 each in the CBV 4-day (sdNVP/CBV4) and 7-day (sdNVP/CBV7) arms. ASP detected NVP-resistant variants in week 6 samples from 70% of women in the sdNVP arm, 29% in the sdNVP/CBV4 arm and 33% in sdNVP/CBV7 arm (P<0.01 for sdNVP/CBV4 or sdNVP/CBV7 versus sdNVP; P= 1.0 for sdNVP/CBV4 versus sdNVP/CBV7). Lamivudine resistance was detected by ASP in only 1 of 51 women who received CBV. Conclusions: Short-course CBV significantly reduced but did not eliminate the emergence of NVP resistance after sdNVP. NVP-resistant variants were detected in about one-third of women despite CBV treatment, but the duration of persistence and clinical impact of these variants in response to antiretroviral therapy is uncertain. C1 [Chow, Jeremy Y.; Mellors, John W.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Palmer, Sarah; Boltz, Valerie F.; Maldarelli, Frank] NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA. [Palmer, Sarah] Swedish Inst Infect Dis Control, Dept Virol, Solna, Sweden. [Palmer, Sarah] Karolinska Inst, Solna, Sweden. [Martinson, Neil A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Martinson, Neil A.; McIntyre, James A.; Gray, Glenda E.] Chris Hani Baragwanath Hosp, Perinatal HIV Res Unit, Johannesburg, South Africa. [Martinson, Neil A.; McIntyre, James A.; Gray, Glenda E.] Univ Witwatersrand, Johannesburg, South Africa. [McIntyre, James A.] Anova Hlth Inst, Johannesburg, South Africa. [Hopley, Mark J.] Boehringer Ingelheim ZA, Johannesburg, South Africa. [Mayers, Douglas; Robinson, Patrick; Hall, David B.] Boehringer Ingelheim Pharmaceut, Ridgefield, CT USA. [Coffin, John M.] Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. RP Mellors, JW (reprint author), Univ Pittsburgh, Pittsburgh, PA 15260 USA. EM jwm1@pitt.edu FU Boehringer Ingelheim; SAIC [HHSN261200900346P, 25XS119]; FM Kirby Foundation; Swedish Research Council; GlaxoSmithKline FX Boehringer Ingelheim, the manufacturer of NVP, funded the 1100.1413 trial. Allele-specific PCR and single-genome sequencing were supported by the National Cancer intramural programme and contracts from SAIC to JMC (number HHSN261200900346P) and JWM (number 25XS119). JMC was a Research Professor of the American Cancer Society with support from the FM Kirby Foundation. SP is funded in part by the Swedish Research Council.; MH, DBH and PR are employed by Boehringer Ingelheim, the sponsor of the 1100.1413 study, and DM was employed by Boehringer Ingelheim at the time of the study. JAM and GEG have received research funding, travel grants and speaker's honoraria from Boehringer Ingelheim and GlaxoSmithKline. JWM is a consultant for Merck, Gilead Sciences and RFS Pharma and owns share options in RFS Pharma. All other authors declare no competing interests. NR 29 TC 7 Z9 7 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2012 VL 17 IS 2 BP 327 EP 336 DI 10.3851/IMP1946 PG 10 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 941TC UT WOS:000303987200009 PM 22293443 ER PT J AU Alavanja, MCR Bonner, MR AF Alavanja, Michael C. R. Bonner, Matthew R. TI OCCUPATIONAL PESTICIDE EXPOSURES AND CANCER RISK: A REVIEW SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART B-CRITICAL REVIEWS LA English DT Review ID NON-HODGKINS-LYMPHOMA; ENVIRONMENTAL DDT EXPOSURE; AGRICULTURAL HEALTH; PROSTATE-CANCER; PANCREATIC-CANCER; UNITED-STATES; MANUFACTURING WORKERS; TRIAZINE HERBICIDES; CUTANEOUS MELANOMA; ORGANOPHOSPHORUS PESTICIDES AB A review of the epidemiological literature linking pesticides to cancers in occupational studies worldwide was conducted, with particular focus on those articles published after the release of IARC Monograph 53 (1991): Occupational Exposures in Insecticide Applications and Some Pesticides. Important new data are now available. Chemicals in every major functional class of pesticides including insecticides, herbicide, fungicides, and fumigants have been observed to have significant associations with an array of cancer sites. Moreover, associations were observed with specific chemicals in many chemical classes of pesticides such as chlorinated, organophosphate, and carbamate insecticides and phenoxy acid and triazine herbicides. However, not every chemical in these classes was found to be carcinogenic in humans. Twenty-one pesticides identified subsequent to the last IARC review showed significant exposure-response associations in studies of specific cancers while controlling for major potential confounders. This list is not an exhaustive review and many of these observations need to be evaluated in other epidemiological studies and in conjunction with data from toxicology and cancer biology. Nonetheless, it is reasonable and timely for the scientific community to provide a multidisciplinary expert review and evaluation of these pesticides and their potential to produce cancer in occupational settings. C1 [Alavanja, Michael C. R.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Bonner, Matthew R.] SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Social & Prevent Med, Buffalo, NY 14260 USA. RP Alavanja, MCR (reprint author), NCI, Div Canc Epidemiol & Genet, 1620 Execut Blvd, Bethesda, MD 20892 USA. EM alavanjm@mail.nih.gov FU National Institutes of Health, National Cancer Institute [Z01CP010119] FX This work was funded, in part, by the Intramural Research Program of the National Institutes of Health, National Cancer Institute (Z01CP010119). NR 144 TC 61 Z9 66 U1 9 U2 66 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1093-7404 EI 1521-6950 J9 J TOXICOL ENV HEAL B JI J. Toxicol. Env. Health-Pt b-Crit. Rev. PY 2012 VL 15 IS 4 BP 238 EP 263 DI 10.1080/10937404.2012.632358 PG 26 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 940UW UT WOS:000303919600003 PM 22571220 ER PT J AU Quaia, C Sheliga, BM FitzGibbon, EJ Optican, LM AF Quaia, Christian Sheliga, Boris M. FitzGibbon, Edmond J. Optican, Lance M. TI Ocular following in humans: Spatial properties SO JOURNAL OF VISION LA English DT Article DE ocular following; spatial frequency; stimulus ID PRIMARY VISUAL-CORTEX; CENTER-SURROUND INTERACTIONS; BEHAVIORAL RECEPTIVE-FIELD; TRACKING EYE-MOVEMENTS; MACAQUE V1 NEURONS; MOTION INTEGRATION; CONTRAST SENSITIVITY; SUMMATION PROPERTIES; TEMPORAL DYNAMICS; APPARENT CONTRAST AB Ocular following responses (OFRs) are tracking eye movements elicited at ultrashort latency by the sudden movement of a textured pattern. Here we report the results of our study of their dependency on the spatial arrangement of the motion stimulus. Unlike previous studies that looked at the effect of stimulus size, we investigated the impact of stimulus location and how two distinct stimuli, presented together, collectively determine the OFR. We used as stimuli vertical gratings that moved in the horizontal direction and that were confined to either one or two 0.58 degrees high strips, spanning the width of the screen. We found that the response to individual strips varied as a function of the location and spatial frequency (SF) of the stimulus. The response decreased as the stimulus eccentricity increased, but this relationship was more accentuated at high than at low spatial frequencies. We also found that when pairs of stimuli were presented, nearby stimuli interacted strongly, so that the response to the pair was barely larger than the response to a single strip in the pair. This suppressive effect faded away as the separation between the strips increased. The variation of the suppressive interaction with strip separation, paired with the dependency on eccentricity of the responses to single strips, caused the peak response for strip pairs to be achieved at a specific separation, which varied as a function of SF. C1 [Quaia, Christian; Sheliga, Boris M.; FitzGibbon, Edmond J.; Optican, Lance M.] NEI, Sensorimotor Res Lab, Bethesda, MD 20815 USA. RP Quaia, C (reprint author), NEI, Sensorimotor Res Lab, 49 Convert Dr,Rm 2A50, Bethesda, MD 20815 USA. EM quaiac@nei.nih.gov FU National Eye Institute, NIH FX This research was supported by the Intramural Research Program of the National Eye Institute, NIH. We thank Bruce Cumming, Richard Krauzlis, and three anonymous reviewers for their constructive comments. NR 63 TC 9 Z9 9 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 1534-7362 J9 J VISION JI J. Vision PY 2012 VL 12 IS 4 AR 13 DI 10.1167/12.4.13 PG 29 WC Ophthalmology SC Ophthalmology GA 940RI UT WOS:000303910300013 ER PT J AU de Souza, RF Aravind, L AF de Souza, Robson Francisco Aravind, L. TI Identification of novel components of NAD-utilizing metabolic pathways and prediction of their biochemical functions SO MOLECULAR BIOSYSTEMS LA English DT Article ID REVERSIBLE ADP-RIBOSYLATION; PROTEIN HOMOLOGY DETECTION; PYRIDINE-NUCLEOTIDE CYCLE; CRYSTAL-STRUCTURE; SULFUR TRANSFER; NUCLEIC-ACID; TRANSFER-RNA; POLY(ADP-RIBOSE) GLYCOHYDROLASE; COMPARATIVE GENOMICS; SIR2 FAMILY AB Nicotinamide adenine dinucleotide (NAD) is a ubiquitous cofactor participating in numerous redox reactions. It is also a substrate for regulatory modifications of proteins and nucleic acids via the addition of ADP-ribose moieties or removal of acyl groups by transfer to ADP-ribose. In this study, we use in-depth sequence, structure and genomic context analysis to uncover new enzymes and substrate-binding proteins in NAD-utilizing metabolic and macromolecular modification systems. We predict that Escherichia coli YbiA and related families of domains from diverse bacteria, eukaryotes, large DNA viruses and single strand RNA viruses are previously unrecognized components of NAD-utilizing pathways that probably operate on ADP-ribose derivatives. Using contextual analysis we show that some of these proteins potentially act in RNA repair, where NAD is used to remove 2'-3' cyclic phosphodiester linkages. Likewise, we predict that another family of YbiA-related enzymes is likely to comprise a novel NAD-dependent ADP-ribosylation system for proteins, in conjunction with a previously unrecognized ADP-ribosyltransferase. A similar ADP-ribosyltransferase is also coupled with MACRO or ADP-ribosylglycohydrolase domain proteins in other related systems, suggesting that all these novel systems are likely to comprise pairs of ADP-ribosylation and ribosylglycohydrolase enzymes analogous to the DraG-DraT system, and a novel group of bacterial polymorphic toxins. We present evidence that some of these coupled ADP-ribosyltransferases/ribosylglycohydrolases are likely to regulate certain restriction modification enzymes in bacteria. The ADP-ribosyltransferases found in these, the bacterial polymorphic toxin and host-directed toxin systems of bacteria such as Waddlia also throw light on the evolution of this fold and the origin of eukaryotic polyADP-ribosyltransferases and NEURL4-like ARTs, which might be involved in centrosomal assembly. We also infer a novel biosynthetic pathway that might be involved in the synthesis of a nicotinate-derived compound in conjunction with an asparagine synthetase and AMPylating peptide ligase. We use the data derived from this analysis to understand the origin and early evolutionary trajectories of key NAD-utilizing enzymes and present targets for future biochemical investigations. C1 [de Souza, Robson Francisco; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [de Souza, Robson Francisco] Univ Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, BR-05508 Sao Paulo, Brazil. RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM aravind@ncbi.nlm.nih.gov FU National Library of Medicine, National Institutes of Health, USA FX The authors are supported by the intra-mural funds of the National Library of Medicine, National Institutes of Health, USA. NR 109 TC 24 Z9 24 U1 0 U2 11 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X EI 1742-2051 J9 MOL BIOSYST JI Mol. Biosyst. PY 2012 VL 8 IS 6 BP 1661 EP 1677 DI 10.1039/c2mb05487f PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 939AR UT WOS:000303776200007 PM 22399070 ER PT J AU Gochuico, BR Huizing, M Golas, GA Scher, CD Tsokos, M Denver, SD Frei-Jones, MJ Gahl, WA AF Gochuico, Bernadette R. Huizing, Marjan Golas, Gretchen A. Scher, Charles D. Tsokos, Maria Denver, Stacey D. Frei-Jones, Melissa J. Gahl, William A. TI Interstitial Lung Disease and Pulmonary Fibrosis in Hermansky-Pudlak Syndrome Type 2, an Adaptor Protein-3 Complex Disease SO MOLECULAR MEDICINE LA English DT Article ID LAMELLAR BODY DEGENERATION; BETA-3A SUBUNIT; MOUSE MODEL; AP-3 ADAPTER; MUTATIONS; AP3B1; STANDARDIZATION; PNEUMOCYTES; BIOGENESIS; PNEUMONIA AB Pulmonary fibrosis develops in Hermansky-Pudlak syndrome (HPS) types 1 and 4. Limited information is available about lung disease in HPS type 2 (HPS-2), which is characterized by abnormal function of the adaptor protein-3 (AP-3) complex. To define lung disease in HPS-2, one child and two adults with HPS-2 were evaluated at the National Institutes of Health on at least two visits, and another child was evaluated at the University of Texas Health Science Center San Antonio. All four subjects with HPS-2 had findings of interstitial lung disease (ILD) on a high-resolution computed tomography scan of the chest. The predominant feature was ground glass opacification. Subject 1, a 14-year-old male, and subject 4, a 4-year-old male, had severe ILD, pulmonary fibrosis, secondary pulmonary hypertension and recurrent lung infections. Lung biopsy performed at 20 months of age in subject 1 revealed interstitial fibrosis and prominent type II pneumocyte hyperplasia without lamellar body enlargement. Subject 2, a 27-year-old male smoker, had mild ILD. Subject 3, a 22-year-old male nonsmoker and brother of subject 2, had minimal ILD. Severe impairment of gas exchange was found in subjects 1 and 4 and not in subjects 2 or 3. Plasma concentrations of transforming growth factor-beta 1 and interleukin-17A correlated with severity of HPS-2 ILD. These data show that children and young adults with HPS-2 and functional defects of the AP-3 complex are at risk for ILD and pulmonary fibrosis. C1 [Gochuico, Bernadette R.; Huizing, Marjan; Gahl, William A.] NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Golas, Gretchen A.; Gahl, William A.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA. [Golas, Gretchen A.; Gahl, William A.] NIH, Off Rare Dis Res, Bethesda, MD 20892 USA. [Scher, Charles D.] Tulane Univ, Sch Med, Dept Pediat, Hematol Oncol Sect, New Orleans, LA 70112 USA. [Tsokos, Maria] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Denver, Stacey D.; Frei-Jones, Melissa J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Gochuico, BR (reprint author), 10 Ctr Dr,MSC 1851, Bethesda, MD 20892 USA. EM gochuicb@mail.nih.gov FU National Human Genome Research Institute; National Cancer Institute, National Institutes of Health, Bethesda, MD FX We thank Philip J Daroca, Jr, and the Electron Microscopy Laboratory of Tulane Medical Center for providing electron microscopy images. We also thank our patients who participated in this study for their contributions to this research. This study was supported by the Intramural Research Program of the National Human Genome Research Institute and the National Cancer Institute, National Institutes of Health, Bethesda, MD. NR 38 TC 26 Z9 26 U1 3 U2 4 PU FEINSTEIN INST MED RES PI MANHASSET PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD JAN PY 2012 VL 18 IS 1 BP 56 EP 64 DI 10.2119/molmed.2011.00198 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 941KR UT WOS:000303962600007 PM 22009278 ER PT J AU Tsai, DH Elzey, S DelRio, FW Keene, AM Tyner, KM Clogston, JD MacCuspie, RI Guha, S Zachariah, MR Hackley, VA AF Tsai, De-Hao Elzey, Sherrie DelRio, Frank W. Keene, Athena M. Tyner, Katherine M. Clogston, Jeffrey D. MacCuspie, Robert I. Guha, Suvajyoti Zachariah, Michael R. Hackley, Vincent A. TI Tumor necrosis factor interaction with gold nanoparticles SO NANOSCALE LA English DT Article ID TRANSFORM-INFRARED-SPECTROSCOPY; DIFFERENTIAL MOBILITY ANALYSIS; PLASMA-PROTEIN ADSORPTION; BOVINE SERUM-ALBUMIN; COLLOIDAL GOLD; SOLID-SURFACES; DRUG-DELIVERY; TNF-ALPHA; POLYMERIC NANOPARTICLES; POLY(ETHYLENE GLYCOL) AB We report on a systematic investigation of molecular conjugation of tumor necrosis factor-alpha (TNF) protein onto gold nanoparticles (AuNPs) and the subsequent binding behavior to its antibody (anti-TNF). We employ a combination of physical and spectroscopic characterization methods, including electrospray-differential mobility analysis, dynamic light scattering, polyacrylamide gel electrophoresis, attenuated total reflectance-Fourier transform infrared spectroscopy, fluorescence assay, and enzyme-linked immunosorbent assay. The native TNF used in this study exists in the active homotrimer configuration prior to conjugation. After binding to AuNPs, the maximum surface density of TNF is (0.09 +/- 0.02) nm(-2) with a binding constant of 3 x 10(6) (mol L-1)(-1). Dodecyl sulfate ions induce desorption of monomeric TNF from the AuNP surface, indicating a relatively weak intermolecular binding within the AuNP-bound TNF trimers. Anti-TNF binds to both TNF-conjugated and citrate-stabilized AuNPs, showing that non-specific binding is significant. Based on the number of anti-TNF molecules adsorbed, a substantially higher binding affinity was observed for the TNF-conjugated surface. The inclusion of thiolated polyethylene glycol (SH-PEG) on the AuNPs inhibits the binding of anti-TNF, and the amount of inhibition is related to the number ratio of surface bound SH-PEG to TNF and the way in which the ligands are introduced. This study highlights the challenges in quantitatively characterizing complex hybrid nanoscale conjugates, and provides insight on TNF-AuNP formation and activity. C1 [Tsai, De-Hao; Elzey, Sherrie; DelRio, Frank W.; MacCuspie, Robert I.; Guha, Suvajyoti; Zachariah, Michael R.; Hackley, Vincent A.] NIST, Mat Measurement Lab, Gaithersburg, MD 20899 USA. [Keene, Athena M.; Tyner, Katherine M.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Clogston, Jeffrey D.] NCI Frederick, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Guha, Suvajyoti; Zachariah, Michael R.] Univ Maryland, Dept Mech Engn, College Pk, MD 20740 USA. [Guha, Suvajyoti; Zachariah, Michael R.] Univ Maryland, Dept Chem, College Pk, MD 20740 USA. RP Hackley, VA (reprint author), NIST, Mat Measurement Lab, Gaithersburg, MD 20899 USA. EM vince.hackley@nist.gov RI Tsai, De-Hao/K-6702-2012; Nanotechnology Characterization Lab, NCL/K-8454-2012; OI Tsai, De-Hao/0000-0002-2669-3007; Guha, Suvajyoti/0000-0002-7622-2721; MacCuspie, Robert/0000-0002-6618-6499; Hackley, Vincent/0000-0003-4166-2724 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Center for Drug Evaluation and Research FX The authors acknowledge Anil Patri and Sarah Skoczen of the National Cancer Institute's Nanotechnology Characterization Laboratory, and Jiwen Zheng at FDA for helpful discussions and for assistance with PAGE measurements. The authors also thank Robert Cook, Sang-Min Lee, Tae Joon Cho, and Lei Zhou at NIST for manuscript review and insightful comments. This research was performed while S. E. held a National Research Council Research Associateship Award at NIST. This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract no. HHSN261200800001E. This project was supported in part by an appointment of AMK to the Research Participation Program at the Center for Drug Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 76 TC 18 Z9 20 U1 3 U2 30 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-3364 J9 NANOSCALE JI Nanoscale PY 2012 VL 4 IS 10 BP 3208 EP 3217 DI 10.1039/c2nr30415e PG 10 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 936QB UT WOS:000303604000033 PM 22481570 ER PT J AU Munasinghe, J Zhang, ZJ Kong, EY Heffer, A Mukherjee, AB AF Munasinghe, Jeeva Zhang, Zhongjian Kong, Eryan Heffer, Alison Mukherjee, Anil B. TI Evaluation of Neurodegeneration in a Mouse Model of Infantile Batten Disease by Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy SO NEURODEGENERATIVE DISEASES LA English DT Article DE Neurodegeneration; Neuronal ceroid lipofuscinosis; Infantile neuronal ceroid lipofuscinosis; Infantile batten disease; Magnetic resonance imaging; Magnetic resonance spectroscopy ID NEURONAL CEROID-LIPOFUSCINOSIS; PALMITOYL-PROTEIN THIOESTERASE; CEREBRAL BLOOD-VOLUME; APPARENT DIFFUSION-COEFFICIENT; RAT-BRAIN; APOPTOSIS; MICE; INCL; MRI; DISRUPTION AB Neuronal ceroid lipofuscinoses (NCLs) represent a group of common hereditary childhood neurodegenerative storage disorders that have no effective treatment. Mutations in eight different genes cause various forms of NCLs. Infantile NCL (INCL), the most lethal disease, is caused by inactivating mutations in the palmitoyl-protein thioesterase-1 (PPT1) gene. The availability of Ppt1-knockout (Ppt1-KO) mice, which recapitulate virtually all clinical and pathological features of INCL, provides an opportunity to test the effectiveness of novel therapeutic strategies in vivo. However, such studies will require noninvasive methods that can be used to perform serial evaluations of the same animal receiving an experimental therapy. Thus, the development of noninvasive method(s) of evaluation is urgently needed. Here, we report our evaluation of the progression of neurodegeneration in Ppt1-KO mice starting at 3 months of age by MRI and MR spectroscopy (MRS) and repeating these tests using the same mice at 4, 5 and 6 months of age. Our results showed progressive cerebral atrophy, which was associated with histological loss of neuronal content and increase in astroglia. Remarkably, while the brain volumes in Ppt1-KO mice progressively declined with advancing age, the MRS signals, which were significantly lower than those of their wild-type littermates, remained virtually unchanged from 3 to 6 months of age. In addition, our results also showed an abnormality in cerebral blood flow in these mice, which showed progression with age. Our findings provide methods to serially examine the brains of mouse models of neurodegenerative diseases (e.g. Ppt1-KO mice) using noninvasive and non-lethal procedures such as MRI and MRS. These methods may be useful in studies to understand the progression of neuropathology in animal models of neurodegenerative diseases as they allow repeated evaluations of the same animal in which experimental therapies are tested. Copyright (C) 2012 S. Karger AG, Basel C1 [Zhang, Zhongjian; Kong, Eryan; Heffer, Alison; Mukherjee, Anil B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Munasinghe, Jeeva] Natl Inst Neurol Disorders & Stroke, In Vivo NMR Ctr HNQ2 3, NIH, Bethesda, MD USA. RP Mukherjee, AB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, Bldg 10,Room 9D42,10 Ctr Dr, Bethesda, MD 20892 USA. EM mukherja@exchange.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health; Batten Disease Support and Research Association (BDSRA) FX We thank S. L. Hofmann for the generous gift of the Ppt1-KO mice and for helpful comments and suggestions on the manuscript. We also thank J.Y. Chou, I. Owens and S. W. Levin for critical review of the manuscript and helpful suggestions. We are grateful to Ms. Mary Angstadt of the MRI center, NINDS, for help with preparation of the animals for MRI/MRS. This research was supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, and The Batten Disease Support and Research Association (BDSRA). NR 45 TC 4 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2012 VL 9 IS 4 BP 159 EP 169 DI 10.1159/000334838 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 940AJ UT WOS:000303862100001 PM 22327870 ER PT J AU Bricceno, KV Fischbeck, KH Burnett, BG AF Bricceno, Katherine V. Fischbeck, Kenneth H. Burnett, Barrington G. TI Neurogenic and Myogenic Contributions to Hereditary Motor Neuron Disease SO NEURODEGENERATIVE DISEASES LA English DT Article DE Hereditary motor neuron disease; Spinal muscular atrophy; Spinal and bulbar muscular atrophy ID SPINAL MUSCULAR-ATROPHY; ANDROGEN RECEPTOR GENE; ACTIN MESSENGER-RNA; RECESSIVE BULBOSPINAL NEURONOPATHY; INCLUSION-BODY FORMATION; FAST AXONAL-TRANSPORT; SEVERE SMA MICE; MOUSE MODEL; SKELETAL-MUSCLE; EXPANDED POLYGLUTAMINE AB Spinal muscular atrophy and spinal and bulbar muscular atrophy are characterized by lower motor neuron loss and muscle atrophy. Although it is accepted that motor neuron loss is a primary event in disease pathogenesis, inherent defects in muscle may also contribute to the disease progression and severity. In this review, we discuss the relative contributions of primary pathological processes in the motor axons, neuromuscular junctions and muscle to disease manifestations. Characterizing these contributions helps us to better understand the disease mechanisms and to better target therapeutic intervention. Copyright (C) 2012 S. Karger AG, Basel C1 [Burnett, Barrington G.] NINDS, Neurogenet Branch, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. [Bricceno, Katherine V.] George Washington Univ, Inst Biomed Sci, Washington, DC USA. RP Burnett, BG (reprint author), NINDS, Neurogenet Branch, Porter Neurosci Res Ctr, NIH, Bldg 35,Room 2A-1012,35 Convent Dr,MSC 3705, Bethesda, MD 20892 USA. EM burnettb@ninds.nih.gov NR 112 TC 3 Z9 3 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2012 VL 9 IS 4 BP 199 EP 209 DI 10.1159/000335311 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 940AJ UT WOS:000303862100005 PM 22327341 ER PT J AU Chang, SW Sharan, SK AF Chang, Suhwan Sharan, Shyam K. TI Epigenetic control of an oncogenic microRNA, miR-155, by BRCA1 SO ONCOTARGET LA English DT Editorial Material C1 [Chang, Suhwan; Sharan, Shyam K.] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Chang, SW (reprint author), NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. EM sharans@mail.nih.gov NR 9 TC 15 Z9 16 U1 0 U2 0 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JAN PY 2012 VL 3 IS 1 BP 5 EP 6 PG 2 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 940SS UT WOS:000303914000003 PM 22403740 ER PT J AU Dumas, F Houck, ML Bigoni, F Perelman, P Romanenko, SA Stanyon, R AF Dumas, F. Houck, M. L. Bigoni, F. Perelman, P. Romanenko, S. A. Stanyon, R. TI Chromosome Painting of the Pygmy Tree Shrew Shows that No Derived Cytogenetic Traits Link Primates and Scandentia SO CYTOGENETIC AND GENOME RESEARCH LA English DT Article DE Ancestral associations; Molecular cytogenetics; Phylogeny; Tupaia ID EVOLUTION; MAMMALS; TUPAIA; KARYOTYPE; LEMURS AB We hybridized human chromosome paints on metaphases of the pygmy tree shrew (Tupaia minor, Scandentia). The lack of the ancestral mammalian 4/8 association in both Primates and Scandentia was long considered a cytogenetic land-mark that phylogenetically linked these mammalian orders. However, our results show that the association 4/8 is present in Tupaia along with not previously reported associations for 1/18 and 7/10. Altogether there are 11 syntenic associations of human chromosome segments in the pygmy tree shrew karyotype: 1/18, 2/21, 3/21, 4/8, 7/10, 7/16, 11/20, 12/22 (twice), 14/15 and 16/19. Our data remove any cytogenetic evidence that Scandentia has a preferential phylogenetic relationship with Primates. Copyright (C) 2012 S. Karger AG, Basel C1 [Bigoni, F.; Stanyon, R.] Univ Florence, Dept Evolutionary Biol Leo Pardi, IT-50122 Florence, Italy. [Dumas, F.] Univ Palermo, Dept Environm Biol & Biodivers, Sect Anim Biol & Biol Anthropol G Reverberi, Palermo, Italy. [Houck, M. L.] San Diego Zoo Inst Conservat Res, Escondido, CA USA. [Perelman, P.] NCI, Lab Genome Divers, Frederick, MD 21701 USA. [Perelman, P.; Romanenko, S. A.] SB RAS, Inst Mol & Cellular Biol, Novosibirsk, Russia. RP Stanyon, R (reprint author), Univ Florence, Dept Evolutionary Biol Leo Pardi, Via Proconsolo 12, IT-50122 Florence, Italy. EM roscoe.stanyon@unifi.it RI Romanenko, Svetlana/N-2500-2015; Perelman, Polina/N-8088-2015; OI Perelman, Polina/0000-0002-0982-5100; Stanyon, Roscoe/0000-0002-7229-1092 FU MUR (Ministero della Universita e della Ricerca); MCB; RFBR FX R.S. and F.B. were supported by a grant from MUR (Ministero della Universita e della Ricerca). S.A.R. and P.P. were supported by MCB and RFBR grants. The authors also thank Luca Sineo for helpful suggestions. We dedicate this article to the memory of our friend and late colleague Gary Stone. NR 27 TC 4 Z9 4 U1 0 U2 11 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2012 VL 136 IS 3 BP 175 EP 179 DI 10.1159/000336976 PG 5 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 933ZA UT WOS:000303404900004 PM 22488112 ER PT S AU Makalowski, W Pande, A Gotea, V Makalowska, I AF Makalowski, Wojciech Pande, Amit Gotea, Valer Makalowska, Izabela BE Anisimova, M TI Transposable Elements and Their Identification SO EVOLUTIONARY GENOMICS: STATISICAL AND COMPUTATIONAL METHODS, VOL 1 SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Transposable elements; Transposons; Mobile elements; Repetitive elements; Genome analysis; Genome evolution; Junk DNA; RepeatMasker; TinT; TEclass ID LENGTH LTR RETROTRANSPOSONS; SEQUENCE IS903 TRANSPOSASE; ROLLING-CIRCLE TRANSPOSONS; DE-NOVO IDENTIFICATION; PENELOPE-LIKE ELEMENTS; REPETITIVE ELEMENTS; DNA-SEQUENCES; GENOME EVOLUTION; COMBINATORIAL ALGORITHMS; PROCESSED PSEUDOGENES AB Most genomes are populated by thousands of sequences that originated from mobile elements. On the one hand, these sequences present a real challenge in the process of genome analysis and annotation. On the other hand, there arc very interesting biological subjects involved in many cellular processes. Here, we present an overview of transposable elements (TEs) biodiversity and their impact on genomic evolution. Finally, we discuss different approaches to the TEs detection and analyses. C1 [Makalowski, Wojciech; Pande, Amit] Univ Munster, Inst Bioinformat, Munster, Germany. [Makalowska, Izabela] Adam Mickiewicz Univ, Lab Bioinformat, Poznan, Poland. [Gotea, Valer] NHGRI, NIH, Rockville, MD USA. RP Makalowski, W (reprint author), Univ Munster, Inst Bioinformat, Munster, Germany. RI Makalowski, Wojciech/I-2843-2016; OI Gotea, Valer/0000-0001-7857-3309 NR 120 TC 16 Z9 16 U1 2 U2 11 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-581-7 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 855 BP 337 EP 359 DI 10.1007/978-1-61779-582-4_12 D2 10.1007/978-1-61779-582-4 PN 1 PG 23 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Genetics & Heredity; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Genetics & Heredity; Mathematical & Computational Biology GA BZW31 UT WOS:000303131100012 PM 22407715 ER PT S AU Puigbo, P Wolf, YI Koonin, EV AF Puigbo, Pere Wolf, Yuri I. Koonin, Eugene V. BE Anisimova, M TI Genome-Wide Comparative Analysis of Phylogenetic Trees: The Prokaryotic Forest of Life SO EVOLUTIONARY GENOMICS: STATISTICAL AND COMPUTATIONAL METHODS, VOL 2 SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Forest of life; Tree of life; Phylogenomic methods; Tree comparison; Map of quartets ID HORIZONTAL GENE-TRANSFER; TRANSFER-RNA SYNTHETASES; MICROBIAL EVOLUTION; HIGH-THROUGHPUT; TRANSFER EVENTS; DISTANCE; PHYLOME; PHYLOGENOMICS; SIMILARITY; ALGORITHM AB Genome-wide comparison of phylogenetic trees is becoming an increasingly common approach in evolutionary genomics, and a variety of approaches for such comparison have been developed. In this article, we present several methods for comparative analysis of large numbers of phylogenetic trees. To compare phylogenetic trees taking into account the bootstrap support for each internal branch, the Boot-Split Distance (BSD) method is introduced as an extension of the previously developed Split Distance method for tree comparison. The BSD method implements the straightforward idea that comparison of phylogenetic trees can be made more robust by treating tree splits differentially depending on the bootstrap support. Approaches are also introduced for detecting tree-like and net-like evolutionary trends in the phylogenetic Forest of Life (FOL), i.e., the entirety of the phylogenetic trees for conserved genes of prokaryotes. The principal method employed for this purpose includes mapping quartets of species onto trees to calculate the support of each quartet topology and so to quantify the tree and net contributions to the distances between species. We describe the application of these methods to analyze the FOL and the results obtained with these methods. These results support the concept of the Tree of Life (TOL) as a central evolutionary trend in the FOL as opposed to the traditional view of the TOL as a "species tree." C1 [Puigbo, Pere; Wolf, Yuri I.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Puigbo, P (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 LM999999] NR 80 TC 7 Z9 7 U1 0 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-584-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 856 BP 53 EP 79 DI 10.1007/978-1-61779-585-5_3 D2 10.1007/978-1-61779-585-5 PN 2 PG 27 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Genetics & Heredity; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Genetics & Heredity; Mathematical & Computational Biology GA BZW32 UT WOS:000303131200003 PM 22399455 ER PT J AU Kennedy, SW Allaire, JC Gamaldo, AA Whitfield, KE AF Kennedy, Sarah W. Allaire, Jason C. Gamaldo, Alyssa A. Whitfield, Keith E. TI RACE DIFFERENCES IN INTELLECTUAL CONTROL BELIEFS AND COGNITIVE FUNCTIONING SO EXPERIMENTAL AGING RESEARCH LA English DT Article ID PERCEIVED CONTROL; OLDER-ADULTS; EVERYDAY COGNITION; STRATEGY USE; COMMUNITY RESIDENTS; AFRICAN-AMERICANS; AGE-DIFFERENCES; MEMORY; PERFORMANCE; MACARTHUR AB Background/Study Context: The current study examined the relationship between intellectual control and cognition and related the results to everyday problem solving in a mixed ethnicity sample of 35% African American and 65% Caucasian elders. Methods: Participants completed the Personality in Intellectual Aging Contexts Inventory (PIC; Lachman et al., 1982, Journal of Research in Personality, 16, 485-501), Everyday Cognition Battery (ECB; Allaire & Marsiske, 1999, Psychology & Aging, 14, 627-644; 2002, Psychology & Aging, 17, 101-115), and a battery of basic cognitive ability tests assessing memory, inductive reasoning, and verbal meaning. Results: Results indicated that African Americans had significantly lower intellectual control beliefs relative to Caucasian older adults. Regression models suggested that relationship between control beliefs and cognition was moderated by education and race. Decomposing the interactions with simple slope analysis revealed that across cognitive abilities, better cognitive performance was related to higher control beliefs in African Americans with at least 13 years of education. A similar relationship was also found in Caucasian elders with lower education. Conclusion: African American elders' reaching a higher level of education may provide a basis for which individual differences in intellectual control beliefs are activated and thereby more strongly associated with cognitive performance. C1 [Allaire, Jason C.] N Carolina State Univ, Dept Psychol, Raleigh, NC 27695 USA. [Kennedy, Sarah W.] Dept Hlth & Human Serv, Div Aging & Adult Serv, Raleigh, NC USA. [Gamaldo, Alyssa A.] NIA, Lab Behav Neurosci, Baltimore, MD 21224 USA. [Whitfield, Keith E.] Duke Univ, Dept Psychol & Neurosci, Durham, NC USA. RP Allaire, JC (reprint author), N Carolina State Univ, Dept Psychol, 640 Poe Hall,Box 7650, Raleigh, NC 27695 USA. EM jason_allaire@ncsu.edu FU NIH, National Institute on Aging FX This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. The authors wish to express their appreciation to Shevaun Neupert for her comments on earlier drafts. NR 49 TC 1 Z9 1 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0361-073X J9 EXP AGING RES JI Exp. Aging Res. PY 2012 VL 38 IS 3 BP 247 EP 264 DI 10.1080/0361073X.2012.672122 PG 18 WC Geriatrics & Gerontology; Psychology SC Geriatrics & Gerontology; Psychology GA 936LT UT WOS:000303592600001 PM 22540381 ER PT B AU Leitner, WW AF Leitner, Wolfgang W. BE Thalhamer, J Weiss, R Scheiblhofer, S TI Immune-Activating Mechanisms of Replicase-Based DNA and RNA Vaccines and Their Role in Immune-Apoptosis SO GENE VACCINES LA English DT Article; Book Chapter ID SEMLIKI-FOREST-VIRUS; SUPPRESS GENE-EXPRESSION; I INTERFERONS; MEASLES-VACCINE; VECTORS; IMMUNOGENICITY; RESPONSES; EFFICACY; ENHANCEMENT; INFECTION C1 NIAID, NIH, Basic Immunol Branch, Bethesda, MD 20892 USA. RP Leitner, WW (reprint author), NIAID, NIH, Basic Immunol Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM wleiter@niaid.nih.gov NR 53 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, A-1201 VIENNA, AUSTRIA BN 978-3-7091-0438-5 PY 2012 BP 67 EP 88 DI 10.1007/978-3-7091-0439-2_3 D2 10.1007/978-3-7091-0439-2 PG 22 WC Immunology; Microbiology SC Immunology; Microbiology GA BAB18 UT WOS:000303686200003 ER PT B AU Deng, CX AF Deng, Chu-Xia BE Green, JE Ried, T TI The Use of Cre-loxP Technology and Inducible Systems to Generate Mouse Models of Cancer SO GENETICALLY ENGINEERED MICE FOR CANCER RESEARCH: DESIGN, ANALYSIS, PATHWAYS, VALIDATION AND PRE-CLINICAL TESTING LA English DT Article; Book Chapter ID CONDITIONAL KNOCKOUT MICE; SQUAMOUS-CELL CARCINOMA; TUMOR-SUPPRESSOR GENE; INTRAHEPATIC CHOLANGIOCELLULAR CARCINOMA; EARLY EMBRYONIC LETHALITY; DNA-DAMAGE REPAIR; BREAST-CANCER; IN-VIVO; MAMMARY-GLAND; RAS ONCOGENE C1 NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Deng, CX (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, 10-9N105,10 Ctr Dr, Bethesda, MD 20892 USA. EM chuxiad@bdg10.niddk.nih.gov RI deng, chuxia/N-6713-2016 NR 139 TC 3 Z9 3 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-69803-8 PY 2012 BP 17 EP 36 DI 10.1007/978-0-387-69805-2_2 D2 10.1007/978-0-387-69805-2 PG 20 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA BZX47 UT WOS:000303216200002 ER PT B AU Philip, S Sharan, SK AF Philip, Subha Sharan, Shyam K. BE Green, JE Ried, T TI Using Recombineering Technology to Create Genetically Engineered Mouse Models SO GENETICALLY ENGINEERED MICE FOR CANCER RESEARCH: DESIGN, ANALYSIS, PATHWAYS, VALIDATION AND PRE-CLINICAL TESTING LA English DT Article; Book Chapter ID BACTERIAL ARTIFICIAL CHROMOSOMES; EMBRYONIC STEM-CELLS; GENOTYPE-BASED SCREEN; ESCHERICHIA-COLI; TRANSGENIC MICE; ALLELIC SERIES; SACCHAROMYCES-CEREVISIAE; UNCONVENTIONAL MYOSIN; PROTEIN COMPLEXES; TARGETING VECTOR C1 [Philip, Subha; Sharan, Shyam K.] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Sharan, SK (reprint author), NCI, Mouse Canc Genet Program, Ctr Canc Res, Bldg 560,Room 32-31C,1050 Boyles St, Frederick, MD 21702 USA. EM sharans@mail.nih.gov NR 69 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-69803-8 PY 2012 BP 37 EP 56 DI 10.1007/978-0-387-69805-2_3 D2 10.1007/978-0-387-69805-2 PG 20 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA BZX47 UT WOS:000303216200003 ER PT B AU Li, Y Ferris, A Lewis, BC Orsulic, S Williams, BO Holland, EC Hughes, SH AF Li, Yi Ferris, Andrea Lewis, Brian C. Orsulic, Sandra Williams, Bart O. Holland, Eric C. Hughes, Stephen H. BE Green, JE Ried, T TI The RCAS/TVA Somatic Gene Transfer Method in Modeling Human Cancer SO GENETICALLY ENGINEERED MICE FOR CANCER RESEARCH: DESIGN, ANALYSIS, PATHWAYS, VALIDATION AND PRE-CLINICAL TESTING LA English DT Article; Book Chapter ID ROUS-SARCOMA-VIRUS; AVIAN RETROVIRAL VECTORS; HUMAN-IMMUNODEFICIENCY-VIRUS; MAMMARY EPITHELIAL-CELLS; HEPATOCELLULAR-CARCINOMA CELLS; PATHWAY-TARGETED THERAPY; IN-VIVO; MOUSE MODEL; STEM-CELLS; LEUKOSIS VIRUS C1 [Li, Yi] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA. [Li, Yi] Baylor Coll Med, Dept Mol & Cell Biol, Houston, TX 77030 USA. [Ferris, Andrea; Hughes, Stephen H.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Lewis, Brian C.] Univ Massachusetts, Med Ctr, Program Gene Funct & Express, Worcester, MA 01605 USA. [Orsulic, Sandra] Cedars Sinai Med Ctr, Womens Canc Res Inst, Los Angeles, CA 90048 USA. [Williams, Bart O.] Van Andel Res Inst, Mol Med & Virol Grp, Grand Rapids, MI 49503 USA. [Holland, Eric C.] Mem Sloan Kettering Canc Ctr, Program Canc Biol & Genet, New York, NY 10021 USA. RP Li, Y (reprint author), Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA. EM liyi@bcm.edu NR 99 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-69803-8 PY 2012 BP 83 EP 111 DI 10.1007/978-0-387-69805-2_5 D2 10.1007/978-0-387-69805-2 PG 29 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA BZX47 UT WOS:000303216200005 ER PT B AU Ried, T Difilippantonio, MJ AF Ried, Thomas Difilippantonio, Michael J. BE Green, JE Ried, T TI Characterization of Chromosomal Translocations in Mouse Models of Hematological Malignancies Using Spectral Karyotyping, FISH, and Immunocytochemistry SO GENETICALLY ENGINEERED MICE FOR CANCER RESEARCH: DESIGN, ANALYSIS, PATHWAYS, VALIDATION AND PRE-CLINICAL TESTING LA English DT Article; Book Chapter ID SINGLE-STRANDED-DNA; IN-SITU HYBRIDIZATION; ATM-DEFICIENT MICE; T(12/15)-POSITIVE BALB/C PLASMACYTOMAS; MAMMARY-GLAND ADENOCARCINOMAS; HUMAN BREAST-CANCER; GENOMIC INSTABILITY; QUINACRINE FLUORESCENCE; SOMATIC HYPERMUTATION; GENE AMPLIFICATION C1 [Difilippantonio, Michael J.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Ried, Thomas] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Difilippantonio, MJ (reprint author), NCI, Div Canc Treatment & Diag, NIH, 31 Ctr Dr,Suite 3A44, Bethesda, MD 20892 USA. EM difilipm@mail.nih.gov NR 102 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-69803-8 PY 2012 BP 193 EP 207 DI 10.1007/978-0-387-69805-2_9 D2 10.1007/978-0-387-69805-2 PG 15 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA BZX47 UT WOS:000303216200009 ER PT B AU Zhu, M Michalowski, AM Green, JE AF Zhu, Min Michalowski, Aleksandra M. Green, Jeffrey E. BE Green, JE Ried, T TI Expression Profiling of Mouse Models of Human Cancer: Model Categorization and Guidance for Preclinical Testing SO GENETICALLY ENGINEERED MICE FOR CANCER RESEARCH: DESIGN, ANALYSIS, PATHWAYS, VALIDATION AND PRE-CLINICAL TESTING LA English DT Article; Book Chapter ID COMPARATIVE FUNCTIONAL GENOMICS; HUMAN BREAST-TUMORS; HUMAN LUNG-CANCER; GENE-EXPRESSION; PROSTATE-CANCER; TRANSGENIC MICE; PANCREATIC-CANCER; DNA MICROARRAYS; APC(MIN/+) MOUSE; CLASS PREDICTION C1 [Zhu, Min; Michalowski, Aleksandra M.; Green, Jeffrey E.] NCI, Transgen Oncogenesis & Genom Sect, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA. RP Green, JE (reprint author), NCI, Transgen Oncogenesis & Genom Sect, Lab Canc Biol & Genet, Ctr Canc Res, Bldg 37,Room 4054,37 Convent Dr, Bethesda, MD 20892 USA. EM jegreen@nih.gov NR 96 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-69803-8 PY 2012 BP 209 EP 234 DI 10.1007/978-0-387-69805-2_10 D2 10.1007/978-0-387-69805-2 PG 26 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA BZX47 UT WOS:000303216200010 ER PT B AU Sage, J Attardi, L Van Dyke, T AF Sage, Julien Attardi, Laura Van Dyke, Terry BE Green, JE Ried, T TI Roles of p53 and pRB Tumor Suppressor Networks in Human Cancer: Insight from Studies in the Engineered Mouse SO GENETICALLY ENGINEERED MICE FOR CANCER RESEARCH: DESIGN, ANALYSIS, PATHWAYS, VALIDATION AND PRE-CLINICAL TESTING LA English DT Article; Book Chapter ID RETINOBLASTOMA GENE FAMILY; LI-FRAUMENI-SYNDROME; APOPTOSIS IN-VIVO; RB-RELATED P107; CELL-CYCLE; P53-DEPENDENT APOPTOSIS; MUTANT P53; T-ANTIGEN; V(D)J RECOMBINATION; RETINAL DEVELOPMENT C1 [Van Dyke, Terry] NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA. [Sage, Julien] Stanford Univ, Dept Pediat & Genet, Stanford, CA 94305 USA. [Attardi, Laura] Stanford Univ, Sch Med, Dept Radiat & Canc Biol, Stanford, CA 94305 USA. RP Van Dyke, T (reprint author), NCI, Mouse Canc Genet Program, 1050 Boyles St,Bldg 560,Room 32-32, Frederick, MD 21702 USA. EM vandyket@mail.nih.gov NR 103 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-69803-8 PY 2012 BP 293 EP 308 DI 10.1007/978-0-387-69805-2_14 D2 10.1007/978-0-387-69805-2 PG 16 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA BZX47 UT WOS:000303216200014 ER PT B AU Hollingshead, M Ahalt, M Alcoser, S AF Hollingshead, Melinda Ahalt, Michelle Alcoser, Sergio BE Green, JE Ried, T TI Transplanted Tumor Models for Preclinical Drug Testing and the Potential Benefit of Genetically Engineered Mouse Models SO GENETICALLY ENGINEERED MICE FOR CANCER RESEARCH: DESIGN, ANALYSIS, PATHWAYS, VALIDATION AND PRE-CLINICAL TESTING LA English DT Article; Book Chapter ID ATHYMIC NUDE MICE; CANCER MODELS; SCREENING-PROGRAM; ORTHOTOPIC MODELS; MALIGNANT-TUMORS; ADENO-CARCINOMA; CLINICAL-TRIALS; CELL LINES; SCID MOUSE; IN-VITRO C1 [Hollingshead, Melinda; Ahalt, Michelle; Alcoser, Sergio] NCI, Dev Therapeut Program, Frederick, MD 21702 USA. RP Hollingshead, M (reprint author), NCI, Dev Therapeut Program, 1050 Boyles St,Bldg 1052-239, Frederick, MD 21702 USA. EM hollingm@mail.nih.gov NR 79 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-69803-8 PY 2012 BP 465 EP 476 DI 10.1007/978-0-387-69805-2_22 D2 10.1007/978-0-387-69805-2 PG 12 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA BZX47 UT WOS:000303216200022 ER PT B AU Ebner, R Strovel, JW Horrigan, SK Carter, KC AF Ebner, Reinhard Strovel, Jeffrey W. Horrigan, Stephen K. Carter, Kenneth C. BE Green, JE Ried, T TI Mighty, But How Useful? The Emerging Role of Genetically Engineered Mice in Cancer Drug Discovery and Development SO GENETICALLY ENGINEERED MICE FOR CANCER RESEARCH: DESIGN, ANALYSIS, PATHWAYS, VALIDATION AND PRE-CLINICAL TESTING LA English DT Article; Book Chapter ID HUMAN-TUMOR XENOGRAFTS; ACUTE PROMYELOCYTIC LEUKEMIA; MOUSE MODELS; IN-VITRO; CLINICAL-TRIALS; GENE-EXPRESSION; CELL-LINE; PHARMACEUTICAL-INDUSTRY; IMMUNODEFICIENT MICE; KNOCKOUTS MODEL C1 [Ebner, Reinhard] NCI, Sect Canc Genom, NIH, Bethesda, MD 20892 USA. [Strovel, Jeffrey W.; Horrigan, Stephen K.; Carter, Kenneth C.] Noble Lift Sci Inc, Gaithersburg, MD 20878 USA. RP Ebner, R (reprint author), NCI, Sect Canc Genom, NIH, Bethesda, MD 20892 USA. EM reinhard.ebner@yahoo.com NR 136 TC 0 Z9 0 U1 2 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-69803-8 PY 2012 BP 591 EP 618 DI 10.1007/978-0-387-69805-2_28 D2 10.1007/978-0-387-69805-2 PG 28 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA BZX47 UT WOS:000303216200028 ER PT J AU Kumar, R Chakraborti, A Aggarwal, AK Vohra, H Sagar, V Dhanda, V Sharma, YP Majumdar, S Hoe, N Krause, RM AF Kumar, R. Chakraborti, A. Aggarwal, A. K. Vohra, H. Sagar, V. Dhanda, V. Sharma, Y. P. Majumdar, S. Hoe, N. Krause, R. M. TI Streptococcus pyogenes pharyngitis & impetigo in a rural area of Panchkula district in Haryana, India SO INDIAN JOURNAL OF MEDICAL RESEARCH LA English DT Letter ID GROUP-A STREPTOCOCCUS; NORTHERN INDIA; EPIDEMIOLOGY; INFECTIONS; POPULATION; COMMUNITY; BURDEN; THROAT; SKIN C1 [Kumar, R.; Aggarwal, A. K.] Postgrad Inst Educ & Res PGIMER, Sch Publ Hlth, Chandigarh, India. [Chakraborti, A.; Vohra, H.; Sagar, V.; Dhanda, V.; Majumdar, S.] Postgrad Inst Educ & Res PGIMER, Dept Expt Med & Biotechnol, Chandigarh, India. [Sharma, Y. P.] Postgrad Inst Educ & Res PGIMER, Dept Cardiol, Chandigarh, India. [Hoe, N.; Krause, R. M.] NIAID, NIH, Bethesda, MD USA. RP Kumar, R (reprint author), PGIMER, Sch Publ Hlth, Chandigarh 160012, India. EM dr.rajeshkumar@gmail.com NR 17 TC 3 Z9 3 U1 0 U2 0 PU INDIAN COUNCIL MEDICAL RES PI NEW DELHI PA PO BOX 4911 ANSARI NAGAR, NEW DELHI 110029, INDIA SN 0971-5916 J9 INDIAN J MED RES JI Indian J. Med. Res. PD JAN PY 2012 VL 135 IS 1 BP 133 EP 136 PG 4 WC Immunology; Medicine, General & Internal; Medicine, Research & Experimental SC Immunology; General & Internal Medicine; Research & Experimental Medicine GA 934XP UT WOS:000303480400024 PM 22382196 ER PT B AU O'Konek, JJ Terabe, M Berzofsky, JA AF O'Konek, Jessica J. Terabe, Masaki Berzofsky, Jay A. BE Wang, RF TI The Role of NKT Cells in the Immune Regulation of Neoplastic Disease SO INNATE IMMUNE REGULATION AND CANCER IMMUNOTHERAPY LA English DT Article; Book Chapter ID KILLER-T-CELLS; LIGAND ALPHA-GALACTOSYLCERAMIDE; ERADICATES ESTABLISHED TUMORS; IN-VIVO; DENDRITIC CELLS; CANCER-PATIENTS; CUTTING EDGE; IMMUNOREGULATORY AXIS; ANTITUMOR IMMUNITY; SUPPRESSOR-CELLS C1 [O'Konek, Jessica J.; Terabe, Masaki; Berzofsky, Jay A.] NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA. RP Terabe, M (reprint author), NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA. EM okonekj@mail.nih.gov; terabe@mail.nih.gov NR 147 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9913-9 PY 2012 BP 7 EP 21 DI 10.1007/978-1-4419-9914-6_2 D2 10.1007/978-1-4419-9914-6 PG 15 WC Oncology; Immunology SC Oncology; Immunology GA BZX39 UT WOS:000303215400002 ER PT B AU Konkel, JE Chen, WJ AF Konkel, Joanne E. Chen, WanJun BE Wang, RF TI Role of TGF-beta in Immune Suppression and Inflammation SO INNATE IMMUNE REGULATION AND CANCER IMMUNOTHERAPY LA English DT Article; Book Chapter ID GROWTH-FACTOR-BETA; REGULATORY T-CELLS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; TRANSFORMING GROWTH-FACTOR-BETA-1; CYTOKINE PRODUCTION; DENDRITIC CELLS; IN-VITRO; AUTOIMMUNE ENCEPHALOMYELITIS; LANGERHANS CELLS; DOWN-REGULATION C1 [Konkel, Joanne E.; Chen, WanJun] Natl Inst Dent & Craniofacial Res, Mucosal Immun Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Chen, WJ (reprint author), Natl Inst Dent & Craniofacial Res, Mucosal Immun Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. EM wchen@dir.nidcr.nih.gov NR 65 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9913-9 PY 2012 BP 289 EP 301 DI 10.1007/978-1-4419-9914-6_16 D2 10.1007/978-1-4419-9914-6 PG 13 WC Oncology; Immunology SC Oncology; Immunology GA BZX39 UT WOS:000303215400016 ER PT J AU Nilsen, W Kumar, S Shar, A Varoquiers, C Wiley, T Riley, WT Pavel, M Atienza, AA AF Nilsen, Wendy Kumar, Santosh Shar, Albert Varoquiers, Carrie Wiley, Tisha Riley, William T. Pavel, Misha Atienza, Audie A. TI Advancing the Science of mHealth SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID DESIGN; TRIALS AB Mobile health (mHealth) technologies have the potential to greatly impact health research, health care, and health outcomes, but the exponential growth of the technology has outpaced the science. This article outlines two initiatives designed to enhance the science of mHealth. The mHealth Evidence Workshop used an expert panel to identify optimal methodological approaches for mHealth research. The NIH mHealth Training Institutes address the silos among the many academic and technology areas in mHealth research and is an effort to build the interdisciplinary research capacity of the field. Both address the growing need for high quality mobile health research both in the United States and internationally. mHealth requires a solid, interdisciplinary scientific approach that pairs the rapid change associated with technological progress with a rigorous evaluation approach. The mHealth Evidence Workshop and the NIH mHealth Training Institutes were both designed to address and further develop this scientific approach to mHealth. C1 [Nilsen, Wendy] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. [Kumar, Santosh] Univ Memphis, Dept Comp Sci, Memphis, TN 38152 USA. [Shar, Albert] Robert Wood Johnson Fdn, Princeton, NJ 08540 USA. [Varoquiers, Carrie] McKesson Fdn, San Francisco, CA USA. [Wiley, Tisha] NIDA, NIH, Bethesda, MD 20892 USA. [Riley, William T.] NHLBI, NIH, Bethesda, MD 20892 USA. [Pavel, Misha] Natl Sci Fdn, Arlington, VA 22230 USA. [Atienza, Audie A.] US Dept HHS, Off Secretary, Washington, DC 20201 USA. RP Nilsen, W (reprint author), NIH, Off Behav & Social Sci Res, Bldg 10, Bethesda, MD 20892 USA. EM nilsenwj@od.nih.gov OI Wiley, Tisha/0000-0001-6399-1647 NR 11 TC 39 Z9 40 U1 2 U2 24 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2012 VL 17 SU 1 BP 5 EP 10 DI 10.1080/10810730.2012.677394 PG 6 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 936LK UT WOS:000303591700003 PM 22548593 ER PT J AU Burger, J Gochfeld, M Jeitner, C Donio, M Pittfield, T AF Burger, Joanna Gochfeld, Michael Jeitner, Christian Donio, Mark Pittfield, Taryn TI LEAD (Pb) IN BIOTA AND PERCEPTIONS OF Pb EXPOSURE AT A RECENTLY DESIGNATED SUPERFUND BEACH SITE IN NEW JERSEY SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID INTUITIVE TOXICOLOGY; METAL CONTAMINATION; FUCUS-VESICULOSUS; FISH CONSUMPTION; PERCEIVED RISK; CHEMICAL RISKS; LAY JUDGMENTS; PEOPLE FISH; BLOOD LEAD; CADMIUM AB The Raritan Bay Slag Site (New Jersey) was designated a Superfund site in 2009 because the seawall, jetties, and sediment contained lead (Pb). Our objective was to compare Pb and mercury (Hg) levels in biota and public perceptions of exposure at the Superfund and reference sites. Samples (algae, invertebrates, fish) were collected from the Raritan Bay Slag Site and reference sites and analyzed for Pb and Hg. Waterfront users were interviewed using a standard questionnaire. Levels of Pb in aquatic organisms were compared to ecological and human health safety standards. Lead levels were related to location, trophic level, and mobility. Lead levels in biota were highest at the western side of the West Jetty. Mean Pb levels were highest for algae (Fucus = 53,600 +/- 6990 ng/g = ppb [wet weight], Ulva = 23,900 +/- 2430 ppb), intermediate for grass shrimp (7270 +/- 1300 ppb, 11,600 +/- 3340 ppb), and lowest for fish (Atlantic silversides 218 +/- 44 ppb). Within species, Pb levels varied significantly across the sampling sites. Lead levels in algae, sometimes ingested by individuals, were sufficiently high to exceed human safety levels. Mercury levels did not differ between the Superfund and reference sites. Despite the fence and warnings, people (1) used the Superfund and reference sites similarly, (2) had similar fish consumption rates, and (3) were not concerned about Pb, although most individuals knew the metal was present. The fish sampled posed no apparent risk for human consumers, but the algae did. C1 [Burger, Joanna; Jeitner, Christian; Pittfield, Taryn] Rutgers State Univ, Div Life Sci, Piscataway, NJ 08854 USA. [Burger, Joanna; Gochfeld, Michael; Jeitner, Christian; Donio, Mark; Pittfield, Taryn] Rutgers State Univ, Consortium Risk Evaluat Stakeholder Participat, Piscataway, NJ 08854 USA. [Burger, Joanna; Gochfeld, Michael; Donio, Mark] Environm & Occupat Hlth Sci Inst, Piscataway, NJ USA. [Gochfeld, Michael] UMDNJ Robert Wood Johnson Med Sch, Piscataway, NJ USA. [Burger, Joanna; Gochfeld, Michael] NJ NIEHS Ctr Environm Exposures & Dis, Piscataway, NJ USA. RP Burger, J (reprint author), Rutgers State Univ, Div Life Sci, 604 Allison Rd, Piscataway, NJ 08854 USA. EM burger@biology.rutgers.edu FU NJ-NIEHS Center for Environmental Exposures and Disease [P30ES005022]; Environmental and Occupational Health Sciences Institute; Consortium for Risk Evaluation [DE-FC01-06Ew07053] FX We thank P. Lioy, D. Wartenberg, and N. Fiedler for valuable comments during the research. This work was supported financially and logistically by the NJ-NIEHS Center for Environmental Exposures and Disease (P30ES005022), the Environmental and Occupational Health Sciences Institute, and the Consortium for Risk Evaluation (DE-FC01-06Ew07053). The views expressed in this article are those of the authors and do not represent those of the funding agencies. NR 51 TC 3 Z9 3 U1 0 U2 12 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PY 2012 VL 75 IS 5 BP 272 EP 287 DI 10.1080/15287394.2012.652058 PG 16 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 936ME UT WOS:000303593700002 PM 22409490 ER PT J AU Rezvani, G Lui, JCK Barnes, KM Baron, J AF Rezvani, Geoffrey Lui, Julian C. K. Barnes, Kevin M. Baron, Jeffrey TI A set of imprinted genes required for normal body growth also promotes growth of rhabdomyosarcoma cells SO PEDIATRIC RESEARCH LA English DT Article ID IGF-I RECEPTOR; MATERNAL-BEHAVIOR; POSTNATAL-GROWTH; SOMATIC GROWTH; EWINGS-SARCOMA; LINES; EXPRESSION; CARCINOMA; CHEMOSENSITIVITY; TUMORIGENESIS AB INTRODUCTION: In many normal tissues, proliferation rates decline postnatally, causing somatic growth to slow. Previous evidence suggests that this decline is due, in part, to decline in the expression of growth-promoting imprinted genes including Mest, Plagl1, Peg3, Dlk1, and Igf2. Embryonal cancers are composed of cells that maintain embryonic characteristics and proliferate rapidly in childhood. We hypothesized that the abnormal persistent rapid proliferation in embryonal cancers occurs in part because of abnormal persistent high expression of growth-promoting imprinted genes. RESULTS: Analysis of microarray data showed elevated expression of MEST, PLAGL1, PEG3, DLK1, and IGF2 in various embryonal cancers, especially rhabdomyosarcoma, as compared to nonembryonal cancers and normal tissues. Similarly, mRNA expression, assessed by real-time PCR, of MEST, PEG3, and IGF2 in rhabdomyosarcoma cell lines was increased as compared to nonembryonal cancer cell lines. Furthermore, siRNA-mediated knockdown of MEST, PLAGL1, PEG3, and IGF2 expression inhibited proliferation in Rh30 rhabdomyosarcoma cells. DISCUSSION: These findings suggest that the normal postnatal downregulation of growth-promoting imprinted genes fails to occur in some embryonal cancers, particularly rhabdomyosarcoma, and contributes to the persistent rapid proliferation of rhabdomyosarcoma cells and, more generally, that failure of the mechanisms responsible for normal somatic growth deceleration can promote tumorigenesis. C1 [Rezvani, Geoffrey; Lui, Julian C. K.; Barnes, Kevin M.; Baron, Jeffrey] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. RP Rezvani, G (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. EM grezvani@drexelmed.edu RI Lui, Chun Kin Julian/E-2253-2012 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health FX This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. NR 43 TC 18 Z9 19 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD JAN PY 2012 VL 71 IS 1 BP 32 EP 38 DI 10.1038/pr.2011.6 PG 7 WC Pediatrics SC Pediatrics GA 934OL UT WOS:000303453600006 PM 22289848 ER PT J AU Pau, AK Penzak, SR Boyd, SD McLaughlin, M Morse, CG AF Pau, Alice K. Penzak, Scott R. Boyd, Sarita D. McLaughlin, Mary Morse, Caryn G. TI Impaired Maraviroc and Raltegravir Clearance in a Human Immunodeficiency Virus-Infected Patient with End-Stage Liver Disease and Renal Impairment: A Management Dilemma SO PHARMACOTHERAPY LA English DT Article DE maraviroc; raltegravir; human immunodeficiency virus; HIV; liver failure; renal failure; pharmacokinetics; therapeutic drug monitoring; TDM ID TREATMENT-EXPERIENCED PATIENTS; HEALTHY-VOLUNTEERS; HIV-1 INTEGRASE; PHARMACOKINETICS; SAFETY; TOLERABILITY; INHIBITOR; MK-0518 AB Current product labels for maraviroc and raltegravir provide no dosing guidance for patients with end-stage liver disease and worsening renal function. We describe a 41-year-old man with human immunodeficiency virus (HIV) infection and rapidly progressive liver failure and vanishing bile duct syndrome at presentation. Despite discontinuation of all potential offending drugs, the patient's liver function continued to deteriorate. To achieve and maintain HIV suppression while awaiting liver transplantation, a regimen consisting of maraviroc, raltegravir, and enfuvirtide was started. These agents were chosen because the patient was not exposed to them before the onset of liver failure. While receiving product label-recommended twice-daily dosing of these drugs, he achieved and maintained HIV suppression. During a complicated and prolonged hospitalization, the patient also developed renal dysfunction. As hepatic metabolism is the primary route of clearance of maraviroc and raltegravir, we predicted that using approved doses of these drugs could result in significant drug accumulation. Since the safety profiles of supratherapeutic concentrations of these agents are not well defined, we chose to use therapeutic drug monitoring to guide further dosing. The reported concentrations showed severely impaired metabolic clearance of both drugs, with markedly prolonged elimination half-lives of 189 hours for maraviroc and 61 hours for raltegravir. Previously reported half-lives for maraviroc and raltegravir in HIV-infected patients with normal hepatic and renal function are 1418 hours and 9-12 hours, respectively. Based on these results, the dosing intervals were extended from twice/day to twice/week for maraviroc and every 48 hours for raltegravir. Unfortunately, the patient's clinical condition continued to deteriorate, and he eventually died of complications related to end-stage liver disease. This case illustrates the difficulties in managing antiretroviral therapy in an HIV-infected patient with combined severe liver and renal failure. Prolonged excessively high exposure to maraviroc and raltegravir is likely to result in some level of concentration-dependent toxicity. Until more data are available, therapeutic drug monitoring remains the only evidence-based approach to optimize dosage selection of these drugs in this patient population. C1 [Pau, Alice K.] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA. [McLaughlin, Mary] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Morse, Caryn G.] NIAID, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA. [Penzak, Scott R.] NIH, Dept Pharm, Clin Pharmacokinet Lab, Clin Res Ctr, Bethesda, MD 20892 USA. [Boyd, Sarita D.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Pau, AK (reprint author), NIAID, Div Clin Res, NIH, Bldg 10,Room 11C103,MSC 1880,10 Ctr Dr, Bethesda, MD 20892 USA. EM apau@niaid.nih.gov OI Morse, Caryn/0000-0002-1177-4365 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This work was supported in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and in part with federal funds from the National Cancer Institute, National Institutes of Health (contract no. HHSN261200800001E). The content of this publication does not necessarily reflect the views or policies of the U.S. Department of Health and Human Services, nor does mention of trade. NR 18 TC 5 Z9 5 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD JAN PY 2012 VL 32 IS 1 BP E1 EP E6 DI 10.1002/PHAR.1003 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 933DZ UT WOS:000303341200001 PM 22392831 ER PT J AU Ferrer, RA Dillard, AJ Klein, WMP AF Ferrer, Rebecca A. Dillard, Amanda J. Klein, William M. P. TI Projection, conformity and deviance regulation: A prospective study of alcohol use SO PSYCHOLOGY & HEALTH LA English DT Article DE alcohol consumption; descriptive norms; conformity; projection; deviance ID PERSONALIZED NORMATIVE FEEDBACK; ADOLESCENTS DRUG-USE; COLLEGE-STUDENTS; BINGE-DRINKING; SOCIAL NORMS; PLURALISTIC IGNORANCE; UNIVERSITY-STUDENTS; BRIEF INTERVENTION; PERCEIVED NORMS; PEER INFLUENCES AB We examine how alcohol-related attitudes and behaviour are related to injunctive and descriptive norms over time, and how these perceptions are linked to the experience of alcohol-related problems. In a longitudinal study of alcohol use (n=239, over three time points), we explored the presence of projection, conformity and deviance in college students - a group in the process of identity formation and redefining peer relationships. We found that the first year of college was characterised by both conformity and projection, and that positive attitudes towards alcohol, greater drinking, and higher descriptive norms were associated prospectively with more alcohol-related problems. However, in the second year, the pattern changed such that alcohol consumption behaviour was characterised by deviance such that those who believed others engaged in more drinking reported relatively lower consumption. The longitudinal findings support deviance regulation theory (Blanton, H., & Christie, C. (2003). Deviance regulation: A theory of action and identity. Review of General Psychology, 7, 115-149), which states that individuals form identities by deviating from peers in ways they perceive as desirable. In general, one must consider the role and stage of identity development when making predictions about how attitudes and perceived norms influence alcohol use and the experience of alcohol-related problems. C1 [Ferrer, Rebecca A.; Klein, William M. P.] NCI, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Dillard, Amanda J.] Grand Valley State Univ, Dept Psychol, Allendale, MI 49401 USA. RP Ferrer, RA (reprint author), NCI, Behav Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,MSC 7326, Bethesda, MD 20892 USA. EM ferrerra@mail.nih.gov NR 65 TC 5 Z9 5 U1 3 U2 28 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0887-0446 EI 1476-8321 J9 PSYCHOL HEALTH JI Psychol. Health PY 2012 VL 27 IS 6 BP 688 EP 703 DI 10.1080/08870446.2011.620106 PG 16 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary SC Public, Environmental & Occupational Health; Psychology GA 936GX UT WOS:000303580000004 PM 22172018 ER PT B AU Rodriguez, IR AF Rodriguez, Ignacio R. BE Stratton, RD Hauswirth, WW Gardner, TW TI Deposition and Oxidation of Lipoproteins in Bruch's Membrane and Choriocapillaris Are "Age-Related" Risk Factors with Implications in Age-Related Macular Degeneration SO STUDIES ON RETINAL AND CHOROIDAL DISORDERS SE Oxidative Stress in Applied Basic Research and Clinical Practice LA English DT Article; Book Chapter ID LOW-DENSITY-LIPOPROTEIN; POLYUNSATURATED FATTY-ACIDS; OXIDIZED LDL; IN-VITRO; 7-KETOCHOLESTEROL-INDUCED APOPTOSIS; CHOLESTEROL ACYLTRANSFERASE; OXYSTEROL FORMATION; RPE CELLS; RETINA; MECHANISMS AB This chapter reviews the deposition and oxidation of LDL in Bruch's membrane (BrM), the retinal pigment epithelium (RPE), and the choriocapillaris (CH) and the potential consequences of this deposition in relation to age-related macular degeneration (AMD). Lipid deposition and oxidation are age-related effects that when considered systemically play an important role in most if not all age-related diseases. Oxidized lipid deposits are found throughout the vascular system where they can initiate chronic inflammatory responses that cause cellular stress and loss of function. Aging is a complex multifactorial process that sets the stage for genetic and environmental factors that initiate the pathogenesis of AMD and other age-related diseases. C1 NEI, Lab Retinal Cell & Mol Biol, Bethesda, MD 20892 USA. RP Rodriguez, IR (reprint author), NEI, Lab Retinal Cell & Mol Biol, Bldg 6,136,6 Ctr Dr, Bethesda, MD 20892 USA. EM rodriguezir@nei.nih.gov NR 69 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-61779-605-0 J9 OXID STRESS APPL BAS JI Oxid. Stress Appl. Basic Res. Clin. Pract. PY 2012 BP 321 EP 335 DI 10.1007/978-1-61779-606-7_15 D2 10.1007/978-1-61779-606-7 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology; Ophthalmology SC Biochemistry & Molecular Biology; Cell Biology; Ophthalmology GA BAB19 UT WOS:000303686500015 ER PT B AU Tuo, JS AF Tuo, Jingsheng BE Stratton, RD Hauswirth, WW Gardner, TW TI The Role of Oxidative Stress in the Retinal Lesion of Ccl2/Cx3cr1 Deficiency Mouse on rd8 Background SO STUDIES ON RETINAL AND CHOROIDAL DISORDERS SE Oxidative Stress in Applied Basic Research and Clinical Practice LA English DT Article; Book Chapter ID POLYUNSATURATED FATTY-ACIDS; BASAL LAMINAR DEPOSIT; MACULAR DEGENERATION; PARKINSONS-DISEASE; ANIMAL-MODEL; DIETARY-FAT; TRANSGENIC MICE; BLUE-LIGHT; EXPRESSION; CELLS AB The Ccl2(-/-)/Cx3cr1(-/-) deficiency mouse on rd8 background spontaneously develops a broad spectrum of age-related macular degeneration (AMD)-like lesions including abnormal retinal pigment epithelium, focal photoreceptor degeneration, and lipofuscin accumulation. Studies suggest that disturbance of multiple factors/pathways is involved in the pathogenesis of the retinal lesion of Ccl2(-/-)/Cx3cr1(-/-)/rd8, which include endoplasmic reticulum stress, inflammatory response, malfunction of microglia, and oxidative stress. This chapter summarizes the retinal pathological/molecular features of Ccl2(-/-)/Cx3cr1(-/-)/rd8; presents the evidences of enhanced oxidative stress relevant molecules in the retina of Ccl2(-/-)/Cx3cr1(-/-)/rd8; reports two studies that directly or indirectly manipulated the status of oxidative stress to intervene the development of the retinal lesion of Ccl2(-/-)/Cx3cr1(-/-)/rd8; and suggests that the oxidative stress plays an important role in causing the mouse retinal lesions that mimic human AMD lesions. C1 NEI, Immunol Lab, NIH NEI, Bethesda, MD 20892 USA. RP Tuo, JS (reprint author), NEI, Immunol Lab, NIH NEI, 10-10N103,10 Ctr Dr, Bethesda, MD 20892 USA. EM tuoj@nei.nih.gov NR 58 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-61779-605-0 J9 OXID STRESS APPL BAS JI Oxid. Stress Appl. Basic Res. Clin. Pract. PY 2012 BP 355 EP 365 DI 10.1007/978-1-61779-606-7_17 D2 10.1007/978-1-61779-606-7 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology; Ophthalmology SC Biochemistry & Molecular Biology; Cell Biology; Ophthalmology GA BAB19 UT WOS:000303686500017 ER PT S AU Bukalo, O Dityatev, A AF Bukalo, Olena Dityatev, Alexander BE Kreutz, MR Sala, C TI Synaptic Cell Adhesion Molecules SO SYNAPTIC PLASTICITY: DYNAMICS, DEVELOPMENT AND DISEASE SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE Cell adhesion; NCAM; Scaffold; Synaptic plasticity; Synaptogenesis ID LONG-TERM POTENTIATION; DENDRITIC SPINE DEVELOPMENT; PERISOMATIC INHIBITORY SYNAPSES; PROTEIN-TYROSINE-PHOSPHATASES; PUNCTA ADHERENTIA JUNCTIONS; N-CADHERIN; POLYSIALIC ACID; NMDA RECEPTORS; EPHB RECEPTORS; NERVOUS-SYSTEM AB During development of the nervous system following axon pathfinding, synaptic connections are established between neurons. Specific cell adhesion molecules (CAMs) accumulate at pre- and postsynaptic sites and trigger synaptic differentiation through interactions with intra- and extracellular scaffolds. These interactions are important to align pre- and postsynaptic transduction machineries and to couple the sites of cell-to-cell adhesion to the cytoskeleton and signaling complexes necessary to accumulate and recycle presynaptic vesicles, components of exo- and endocytic zones, and postsynaptic receptors. In mature brains, CAMs contribute to regulation of synaptic efficacy and plasticity, partially via direct interactions with postsynaptic neurotransmitter receptors and presynaptic voltage-gated ion channels. This chapter is to highlight the major classes of synaptic CAMs, their multiple functions, and the multistage concerted interactions between different CAMs and other components of synapses. C1 [Dityatev, Alexander] Ist Italiano Tecnol, Dept Neurosci & Brain Technol, I-16163 Genoa, Italy. [Dityatev, Alexander] Univ Nizhny Novgorod, Lab Brain Extracellular Matrix Res, Nizhnii Novgorod 603950, Russia. [Bukalo, Olena] NICHHD, NIH, Bethesda, MD 20892 USA. RP Dityatev, A (reprint author), Ist Italiano Tecnol, Dept Neurosci & Brain Technol, Via Morego 30, I-16163 Genoa, Italy. EM bukalool@mail.nih.gov; alexander.dityatev@iit.it OI Dityatev, Alexander/0000-0002-0472-0553 FU Intramural NIH HHS NR 155 TC 20 Z9 20 U1 2 U2 8 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-3-7091-0931-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2012 VL 970 BP 97 EP 128 DI 10.1007/978-3-7091-0932-8_5 D2 10.1007/978-3-7091-0932-8 PG 32 WC Biology; Medicine, Research & Experimental; Neurosciences SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine; Neurosciences & Neurology GA BAA81 UT WOS:000303541700005 PM 22351053 ER PT S AU Sukumaran, M Penn, AC Greger, IH AF Sukumaran, Madhav Penn, Andrew C. Greger, Ingo H. BE Kreutz, MR Sala, C TI AMPA Receptor Assembly: Atomic Determinants and Built-In Modulators SO SYNAPTIC PLASTICITY: DYNAMICS, DEVELOPMENT AND DISEASE SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE Alternative splicing; AMPA receptor biosynthesis; Endoplasmic reticulum; Ligand binding domain; N-(amino) terminal domain; RNA editing; Synaptic plasticity ID LONG-TERM POTENTIATION; ETHYLMALEIMIDE-SENSITIVE FACTOR; IONOTROPIC GLUTAMATE RECEPTORS; DOMAIN-CONTAINING PROTEINS; SYNAPTIC PLASTICITY; SUBUNIT COMPOSITION; SURFACE EXPRESSION; NMDA RECEPTORS; ENDOPLASMIC-RETICULUM; EXCITATORY SYNAPSES AB Glutamate-gated ion channels (iGluRs) predominantly operate as heterotetramers to mediate excitatory neurotransmission at glutamatergic synapses. The subunit composition of the receptors determines their targeting to synaptic sites and signalling properties and is therefore a fundamental parameter for neuronal computations. iGluRs assemble as obligatory or preferential heteromers; the mechanisms underlying this selective assembly are only starting to emerge. Here we review recent work in the field and provide an in-depth update on atomic determinants in the assembly domains, which have been facilitated by recent advances in iGluR structural biology. We also discuss the role of alternative RNA processing in the ligand-binding domain, which modulates a central subunit interface and has the capacity to modulate receptor formation in response to external cues. Finally, we review the emerging physiological significance of signalling via distinct iGluR heterotetramers and provide examples of how recruitment of functionally diverse receptors modulates excitatory neurotransmission under physiological and pathological conditions. C1 [Greger, Ingo H.] MRC Lab Mol Biol, Div Neurobiol, Cambridge CB2 0QH, England. [Sukumaran, Madhav] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Cellular & Synapt MRC LMB & Neurophysiol, NIH, Bethesda, MD 20892 USA. [Penn, Andrew C.] Univ Bordeaux, Interdisciplinary Inst Neurosci, UMR 5297, F-33000 Bordeaux, France. [Penn, Andrew C.] CNRS, Interdisciplinary Inst Neurosci, UMR 5297, F-33000 Bordeaux, France. RP Greger, IH (reprint author), MRC Lab Mol Biol, Div Neurobiol, Hills Rd, Cambridge CB2 0QH, England. EM ig@mrc-lmb.cam.ac.uk FU Medical Research Council [MC_U105174197] NR 122 TC 15 Z9 15 U1 1 U2 6 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-3-7091-0931-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2012 VL 970 BP 241 EP 264 DI 10.1007/978-3-7091-0932-8_11 D2 10.1007/978-3-7091-0932-8 PG 24 WC Biology; Medicine, Research & Experimental; Neurosciences SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine; Neurosciences & Neurology GA BAA81 UT WOS:000303541700011 PM 22351059 ER PT J AU Nguyen, AB Hood, KB Belgrave, FZ AF Nguyen, Anh B. Hood, Kristina B. Belgrave, Faye Z. TI The Relationship Between Religiosity and Cancer Screening Among Vietnamese Women in the United States: The Moderating Role of Acculturation SO WOMEN & HEALTH LA English DT Article DE behavior; cancer; ethnicity; psychosocial; self-efficacy; screening ID HEALTH PROMOTION PROGRAMS; AMERICAN IMMIGRANTS; SELF-REPORTS; BREAST; CARE; ORIENTATION; MAMMOGRAPHY; BEHAVIORS; SCALE; ADOLESCENTS AB In this study the authors explore the relationship between intrinsic, personal extrinsic, and social extrinsic religiosity to breast and cervical cancer screening efficacy and behavior among Vietnamese women recruited from a Catholic Vietnamese church and a Buddhist temple in the Richmond, Virginia metropolitan area. The potential moderating effect of acculturation was of interest. Participants were 111 Vietnamese women who participated in a larger cancer screening intervention. Data collection began early fall of 2010 and ended in late spring 2011. High levels of acculturation were associated with increased self-efficacy for Pap tests and having received a Pap test. Acculturation moderated the relationships between religiosity and self-efficacy for breast and cervical cancer screening. Higher levels of social extrinsic religiosity were associated with increased efficacy for cancer screening among less acculturated women. Acculturation also moderated the relationship between religiosity and breast cancer screening. Specifically, for less acculturated women, increasing levels of intrinsic religiosity and personal extrinsic religiosity were associated with lower likelihood probability of Pap testing. For highly acculturated women, increasing levels of intrinsic religiosity and personal extrinsic religiosity were associated with higher likelihood probability of Pap testing. The authors' findings demonstrate the need for further investigation of the dynamic interplay of multi-level factors that influence cancer screening. C1 [Nguyen, Anh B.] Natl Canc Inst, Canc Prevent Fellowship Program, Bethesda, MD USA. [Hood, Kristina B.; Belgrave, Faye Z.] Virginia Commonwealth Univ, Richmond, VA USA. RP Nguyen, AB (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave,Box 656, Boston, MA 02115 USA. EM bao2no1@gmail.com OI Hood, Kristina/0000-0003-4817-9882 NR 59 TC 1 Z9 2 U1 2 U2 8 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0363-0242 J9 WOMEN HEALTH JI Women Health PY 2012 VL 52 IS 3 BP 292 EP 313 DI 10.1080/03630242.2012.666225 PG 22 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 936FA UT WOS:000303575100006 PM 22533901 ER PT J AU Boyce, CA Willis, TD Beatty, L AF Boyce, Cheryl Anne Willis, Tamara D. Beatty, Lula TI A Call to Action for Health Disparities in Boys and Men: Innovative Research on Addiction, Trauma, and Related Comorbidities SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID POPULATIONS; BLACK C1 [Boyce, Cheryl Anne; Willis, Tamara D.; Beatty, Lula] NIDA, NIH, Dept Hlth & Human Services, Bethesda, MD 20892 USA. RP Boyce, CA (reprint author), NIMH, NIH, DHHS, DPTR, 6001 Execut Blvd,Rm 6200,MSC 9617, Bethesda, MD 20892 USA. EM cboyce@nida.nih.gov NR 8 TC 0 Z9 0 U1 1 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PY 2012 VL 102 SU 2 BP S168 EP S170 DI 10.2105/AJPH.2012.300793 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 928FV UT WOS:000302969500005 PM 22497200 ER PT J AU Hill, CV Lynne-Landsman, SD Boyce, CA AF Hill, Carl V. Lynne-Landsman, Sarah D. Boyce, Cheryl Anne TI MATERNAL AND CHILD HEALTH DISPARITIES: CONSIDERING THE INFLUENCE OF FATHERS SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter C1 [Hill, Carl V.; Boyce, Cheryl Anne] NICHHD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Lynne-Landsman, Sarah D.] Univ Florida, Gainesville, FL USA. [Boyce, Cheryl Anne] NIDA, Bethesda, MD 20892 USA. RP Hill, CV (reprint author), NICHD, NIH, DHHS, 6100 Execut Blvd, Bethesda, MD 20892 USA. EM hillcv@mail.nih.gov NR 4 TC 1 Z9 1 U1 1 U2 3 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PY 2012 VL 102 SU 2 BP S164 EP S165 DI 10.2105/AJPH.2012.300792 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 928FV UT WOS:000302969500001 PM 22497199 ER PT J AU Jones, DJ Crump, AD Lloyd, JJ AF Jones, Dionne J. Crump, Aria D. Lloyd, Jacqueline J. TI Health Disparities in Boys and Men of Color SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 [Jones, Dionne J.; Crump, Aria D.; Lloyd, Jacqueline J.] NIDA, Div Epidemiol Serv & Prevent Res, NIH, Bethesda, MD 20892 USA. RP Jones, DJ (reprint author), NIDA, Div Epidemiol Serv & Prevent Res, NIH, Bethesda, MD 20892 USA. EM djones1@nida.nih.gov NR 8 TC 3 Z9 3 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PY 2012 VL 102 SU 2 BP S170 EP S172 DI 10.2105/AJPH.2011.300646 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 928FV UT WOS:000302969500006 PM 22401517 ER PT J AU McCann, DJ Li, SH AF McCann, David J. Li, Shou-Hua TI A Novel, Nonbinary Evaluation of Success and Failure Reveals Bupropion Efficacy Versus Methamphetamine Dependence: Reanalysis of a Multisite Trial SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Article DE Abstinence; Bupropion; Methamphetamine; Responder-based analysis ID MEN; SEX AB A multisite, double-blind, placebo-controlled trial of bupropion for methamphetamine dependence was reanalyzed using a novel, nonbinary method of evaluating success and failure. The original analysis focused on a group response endpoint (the change in percentage of participants with methamphetamine-free urines each week over the course of the trial) and no significant bupropion effect was observed in the total population of study participants. In this reanalysis, individual participants were regarded as treatment success if they achieved multiple weeks of abstinence lasting through the end of the study, and their degree of success was quantified by calculating the number of beyond-threshold weeks of success (NOBWOS). Thus, setting the threshold at 1 week of end-of-study abstinence (EOSA), treatment successes were assigned NOBWOS values ranging from 1 to 11, with 1 corresponding to 2 weeks EOSA and 11 corresponding to abstinence throughput the entire 12-week trial. Treatment failures were assigned a value of 0. Comparison of NOBWOS values revealed a significant effect of bupropion to facilitate abstinence (P= 0.0176). In the bupropion group, 20% of participants achieved 2 or more weeks EOSA, 14% achieved 6 or more weeks EOSA, and 6% were abstinent throughout the trial; this compares with 7%, 4%, and 1% in the placebo group, respectively. On the basis of the NOBWOS analysis, bupropion seems to effectively facilitate the achievement of abstinence in methamphetamine-dependent individuals. C1 [McCann, David J.; Li, Shou-Hua] NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Bethesda, MD 20892 USA. RP McCann, DJ (reprint author), NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, 6001 Execut Blvd,Room 4123,MSC 9551, Bethesda, MD 20892 USA. EM dmccann@nih.gov NR 16 TC 17 Z9 17 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2012 VL 18 IS 5 BP 414 EP 418 DI 10.1111/j.1755-5949.2011.00263.x PG 5 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 931CS UT WOS:000303192700009 PM 22070720 ER PT J AU DeFrank, JT Rimer, BK Bowling, JM Earp, JA Breslau, ES Brewer, NT AF DeFrank, Jessica T. Rimer, Barbara K. Bowling, J. Michael Earp, Jo Anne Breslau, Erica S. Brewer, Noel T. TI Influence of false-positive mammography results on subsequent screening: do physician recommendations buffer negative effects? SO JOURNAL OF MEDICAL SCREENING LA English DT Article ID BREAST-CANCER; ABNORMAL MAMMOGRAMS; PSYCHOSOCIAL OUTCOMES; WOMENS EXPERIENCES; CUMULATIVE RISK; RE-ATTENDANCE; PROGRAM; IMPACT; RECALL; ASSOCIATION AB Objective Cancer screening guidelines often include discussion about the unintended negative consequences of routine screening. This prospective study examined effects of false-positive mammography results on women's adherence to subsequent breast cancer screening and psychological well-being. We also assessed whether barriers to screening exacerbated the effects of false-positive results. Methods We conducted secondary analyses of data from telephone interviews and medical claims records for 2406 insured women. The primary outcome was adherence to screening guidelines, defined as adherent (10-14 months), delayed (15-34 months), or no subsequent mammogram on record. Results About 8% of women reported that their most recent screening mammograms produced false-positive results. In the absence of self-reported advice from their physicians to be screened, women were more likely to have no subsequent mammograms on record if they received false-positive results than if they received normal results (18% vs. 7%, OR = 3.17, 95% CI = 1.30, 7.70). Receipt of false-positive results was not associated with this outcome for women who said their physicians had advised regular screening in the past year (7% vs. 10%, OR = 0.74, 95% CI = 0.38, 1.45). False-positive results were associated with greater breast cancer worry (P<.01), thinking more about the benefits of screening (P <.001), and belief that abnormal test results do not mean women have cancer (P<.01), regardless of physicians' screening recommendations. Conclusion False-positive mammography results, coupled with reports that women's physicians did not advise regular screening, could lead to non-adherence to future screening. Abnormal mammograms that do not result in cancer diagnoses are opportunities for physicians to stress the importance of regular screening. C1 [DeFrank, Jessica T.; Bowling, J. Michael; Earp, Jo Anne; Brewer, Noel T.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Behav, Chapel Hill, NC 27599 USA. [Rimer, Barbara K.; Bowling, J. Michael; Earp, Jo Anne; Brewer, Noel T.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Breslau, Erica S.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA. RP DeFrank, JT (reprint author), Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Behav, 325 Rosenav Hall,CB 7440, Chapel Hill, NC 27599 USA. EM jessica_defrank@unc.edu FU UNC (NCI) [CA116339]; American Cancer Society [MSRG-06-259-01-CPPB]; National Cancer Institute [5R01CA105786] FX Funding for this research comes from the UNC Cancer Care and Quality Training Program (NCI R25 Grant, CA116339) and the American Cancer Society (MSRG-06-259-01-CPPB). PRISM was supported by National Cancer Institute grant 5R01CA105786. NR 39 TC 10 Z9 10 U1 1 U2 6 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0969-1413 J9 J MED SCREEN JI J. Med. Screen. PY 2012 VL 19 IS 1 BP 35 EP 41 DI 10.1258/jms.2012.011123 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 933PG UT WOS:000303373800006 PM 22438505 ER PT J AU Ramasamy, S Kundu, TK Antholine, W Manoharan, PT Rifkind, JM AF Ramasamy, Somasundaram Kundu, Tapan K. Antholine, William Manoharan, Periakaruppan T. Rifkind, Joseph M. TI Internal spin trapping of thiyl radical during the complexation and reduction of cobalamin with glutathione and dithiothrietol SO JOURNAL OF PORPHYRINS AND PHTHALOCYANINES LA English DT Article DE cobalamin; glutathione; dithiothreitol; electron paramagnetic resonance; visible spectroscopy; thyil radicals ID ELECTRON-PARAMAGNETIC-RESONANCE; METHIONINE SYNTHASE; CRYSTAL-STRUCTURE; VITAMIN B12; GLUTATHIONYLCOBALAMIN; COENZYME; ENZYMES; B-12; AQUACOBALAMIN; INTERMEDIATE AB The activation of cobalamin requires a reduction from cobalamin(III) to cobalamin(II). The reduction by glutathione and dithiothreitol was followed using visible spectroscopy and electron paramagnetic resonance. In addition the oxidation of glutathione was monitored. Glutathione first reacts with oxidized cobalamin(III). The binding of a second glutathione required for the reduction to cobalamin(II) is presumably located in the dimethyl benzimidazole ribonucleotide ligand cavity. The reduction of cobalamin(III) by dithiothreitol, which contains two thiols, is much faster even though no stable cobalamin(III) complex is formed. The reduction, by both thiol reagents, results in the formation of thiyl radicals, some of which are released to form oxidized thiol products and some of which remain associated with the reduced cobalamin. In the reduced state the intrinsic lower affinity for the benzimidazole base, coupled with a trans effect from the initial glutathione bound to the beta-axial site and a possible lowering of the pH results in an equilibrium between base-on and base-off complexes. The dissociation of the base facilitates a closer approach of the thiyl radical to the cobalamin(II) a-axial site resulting in a complex with ferromagnetic exchange coupling between the metal ion and the thiyl radical. This is a unique example of "internal spin trapping" of a thiyl radical formed during reduction. The finding that the reduction involves a peripheral site and that thiyl radicals produced during the reduction remain associated with the reduced cobalamin provide important new insights into our understanding of the formation and function of cobalamin enzymes. C1 [Ramasamy, Somasundaram; Rifkind, Joseph M.] NIA, Mol Dynam Sect, NIH, Baltimore, MD 21224 USA. [Kundu, Tapan K.; Manoharan, Periakaruppan T.] Indian Inst Technol Madras, Sophisticated Analyt Instruments Facil, Madras 600036, Tamil Nadu, India. [Kundu, Tapan K.; Manoharan, Periakaruppan T.] Indian Inst Technol Madras, Dept Chem, Madras 600036, Tamil Nadu, India. [Manoharan, Periakaruppan T.] Indira Gandhi Natl Open Univ, Sch Sci, New Delhi 110068, India. [Antholine, William] Med Coll Wisconsin, Dept Biophys, Milwaukee, WI 53226 USA. RP Rifkind, JM (reprint author), NIA, Mol Dynam Sect, NIH, 251 Bayview Blvd Baltimore, Baltimore, MD 21224 USA. EM ptm@iitm.ac.in; rifkindj@mail.nih.gov FU NIH, National Institute on Aging; DST, Govt. of India [SP/SI/F18/00]; Ramanna Fellowship [SR/S1/RFIC-02/2006]; JNCASR Bangalore; IGNOU, New Delhi FX This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. PTM thanks the DST, Govt. of India for a research scheme (SP/SI/F18/00) and Ramanna Fellowship (SR/S1/RFIC-02/2006); PTM also thanks the JNCASR Bangalore for an Honorary Professorship and IGNOU, New Delhi for Sir C.V. Raman Chair Professorship. NR 44 TC 4 Z9 4 U1 1 U2 10 PU WORLD SCI PUBL CO INC PI HACKENSACK PA 27 WARREN ST, STE 401-402, HACKENSACK, NJ 07601 USA SN 1088-4246 J9 J PORPHYR PHTHALOCYA JI J. Porphyr. Phthalocyanines PD JAN PY 2012 VL 16 IS 1 BP 25 EP 38 DI 10.1142/S1088424611004051 PG 14 WC Chemistry, Multidisciplinary SC Chemistry GA 931HA UT WOS:000303205800003 PM 22707875 ER PT J AU McBride, CM Bowen, MS Shully, SD Khoury, MJ AF McBride, Colleen M. Bowen, M. Scott Shully, Sheri D. Khoury, Muin J. TI Introduction to the 4th National Conference on Genomics and Public Health SO PUBLIC HEALTH GENOMICS LA English DT Editorial Material C1 [McBride, Colleen M.] NHGRI, NIH, Bethesda, MD 20892 USA. [Bowen, M. Scott; Khoury, Muin J.] CDC, Off Publ Hlth Genom, Atlanta, GA 30333 USA. [Shully, Sheri D.] NCI, NIH, Bethesda, MD 20892 USA. [Khoury, Muin J.] NCI, NIH, Atlanta, GA USA. RP McBride, CM (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-4246 J9 PUBLIC HEALTH GENOM JI Pub. Health Genomics PY 2012 VL 15 IS 3-4 BP 117 EP 117 DI 10.1159/000336597 PG 1 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA 932CJ UT WOS:000303267500001 PM 22488452 ER PT J AU Zimmern, RL Khoury, MJ AF Zimmern, R. L. Khoury, M. J. TI The Impact of Genomics on Public Health Practice: The Case for Change SO PUBLIC HEALTH GENOMICS LA English DT Article DE Genetics; Genomics; Health policy; Personalised medicine; Public health; Translation ID POPULATION HEALTH; MEDICINE GENOMICS AB Public health practice will not be able in the 21st century to ignore the impact of genomics, cell and molecular biology. It will need to take into consideration issues that include, among others: the complementary nature of social and biological models of disease, genetic exceptionalism, the readiness of public and patient to respond to genomic information, the relationship between individuals and populations, and concepts of population stratification. Health systems will need to adapt their practice and organisation to include new sequencing technologies, bioinformatic expertise and proper evaluation of genetic and molecular tests. Links with the commercial sector will increase in importance. The impact on developing countries cannot be ignored and will require special attention. Copyright (c) 2012 S. Karger AG, Basel C1 [Zimmern, R. L.] Fdn Genom & Populat Hlth, Cambridge CB1 8RN, England. [Khoury, M. J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Khoury, M. J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA. RP Zimmern, RL (reprint author), Fdn Genom & Populat Hlth, 2 Worts Causeway, Cambridge CB1 8RN, England. EM ron.zimmern@phgfoundation.org NR 30 TC 16 Z9 16 U1 1 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-4246 J9 PUBLIC HEALTH GENOM JI Pub. Health Genomics PY 2012 VL 15 IS 3-4 BP 118 EP 124 DI 10.1159/000334840 PG 7 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA 932CJ UT WOS:000303267500002 PM 22488453 ER PT J AU Hesse, BW Arora, NK Khoury, MJ AF Hesse, B. W. Arora, N. K. Khoury, M. J. TI Implications of Internet Availability of Genomic Information for Public Health Practice SO PUBLIC HEALTH GENOMICS LA English DT Article DE Direct-to-consumer advertising; Health communication; Internet; Self-regulation ID PERSONALIZED MEDICINE; GENETIC INFORMATION; CONSUMERS; CARE; PARTICIPATION; APOMEDIATION; BEHAVIOR; SEARCH; IMPACT; AGENDA AB Tensions in the field have emerged over how best to communicate to the public about genomic discoveries in an era of direct-to-consumer (DTC) DNA testing services available through the Internet. Concerns over what the psychological and behavioral response might be to a nuanced, multiplex risk message have spurred some to offer caution in communicating to the public about personalized risk until the necessary research has been completed on how to communicate effectively. The popularization of DTC testing services, along with a spreading Internet culture on transparency for personal data, may make 'waiting to communicate' a moot point. To steer communication efforts in the midst of increasing access to personal genomic information, a self-regulation framework is presented. The framework emphasizes the importance of presenting a coherent message in all communiques about public health genomics. Coherence should be based on an evidence-based model of how the public processes information about health conditions and an emphasis on risk-to-action links. Recommendations from the President's Council of Advisors for Science and Technology are reviewed as a way of identifying targets of opportunity for structured communications both within the healthcare system and in the broader external ecosystem of publicly available health information technologies. Copyright (c) 2012 S. Karger AG, Basel C1 [Hesse, B. W.; Arora, N. K.; Khoury, M. J.] NCI, NIH, Bethesda, MD 20892 USA. [Khoury, M. J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA. RP Hesse, BW (reprint author), NCI, NIH, 6130 Execut Blvd,MSC 7365, Bethesda, MD 20892 USA. EM hesseb@mail.nih.gov OI Hesse, Bradford/0000-0003-1142-1161 NR 71 TC 4 Z9 6 U1 2 U2 11 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-4246 EI 1662-8063 J9 PUBLIC HEALTH GENOM JI Pub. Health Genomics PY 2012 VL 15 IS 3-4 BP 201 EP 208 DI 10.1159/000335892 PG 8 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA 932CJ UT WOS:000303267500012 PM 22488463 ER PT J AU Wagner, L Paquin, R Persky, S AF Wagner, L. Paquin, R. Persky, S. TI Genetics Blogs as a Public Health Tool: Assessing Credibility and Influence SO PUBLIC HEALTH GENOMICS LA English DT Article DE Blog; Genetics; Genomics; Health communication; Internet ID INFORMATION; WEB; COMMUNICATION; FEATURES; INTERNET AB The Internet is becoming an important source of information about genetics and holds promise for public health applications. However, the public has concerns about the credibility of online genetics information. We conducted a content analysis of genetics blogs (n = 94). Specifically, we assessed the prevalence of various genetics-related topics and perceived credibility indicators. The relationship between content indicators, credibility indicators, and blog influence, measured as links between blogs, was evaluated. Coverage of issues related to health or self-knowledge (31%) and life science (26%) was most common among genetics blogs. In terms of credibility indicators, most blogs disclosed authors' full names (81%) and biographical information (67%). Many blog authors reported having genetics (67%) or life science expertise (59%). However, only 7% of blogs were affiliated with educational or medical institutions. Overall, blogs that focused on ancestry, that had authors with life science expertise, and that posted more frequently tended to be more influential. Findings suggest that life scientists and those who blog frequently may figure more centrally in shaping the genetics information available to the public via blogs. There is room for institutions that are likely to be perceived as credible sources of genetics information to assume a greater presence through blogs. Copyright (c) 2012 S. Karger AG, Basel C1 [Wagner, L.; Paquin, R.; Persky, S.] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA. [Paquin, R.] Univ Penn, Annenberg Sch Commun, Philadelphia, PA 19104 USA. RP Wagner, L (reprint author), Dept Hlth Behav, 302 Rosenau Hall,S Columbia St,CB 7440, Chapel Hill, NC 27599 USA. EM lkwagner@lives.unc.edu OI Paquin, Ryan/0000-0002-0947-7409 FU National Human Genome Research Institute, National Institutes of Health FX Supported by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. The authors thank Wafa Khadraoui and Sabrina Mathenia for coding assistance. They thank Colleen McBride for her insightful comments on an earlier draft of this paper. NR 26 TC 3 Z9 3 U1 2 U2 11 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-4246 J9 PUBLIC HEALTH GENOM JI Pub. Health Genomics PY 2012 VL 15 IS 3-4 BP 218 EP 225 DI 10.1159/000336537 PG 8 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA 932CJ UT WOS:000303267500014 PM 22488465 ER PT S AU Picker, LJ Hansen, SG Lifson, JD AF Picker, Louis J. Hansen, Scott G. Lifson, Jeffrey D. BE Caskey, CT Austin, CP Hoxie, JA TI New Paradigms for HIV/AIDS Vaccine Development SO ANNUAL REVIEW OF MEDICINE, VOL 63 SE Annual Review of Medicine LA English DT Review; Book Chapter DE HIV/SIV; T cell vaccines; antibody vaccines; immune evasion; nonhuman primate models ID SIMIAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; TEST-OF-CONCEPT; PREVENT HIV-1 INFECTION; RHESUS MACAQUES; DISEASE PROGRESSION; IMMUNE-RESPONSES; SIV CHALLENGE; ANTIBODY NEUTRALIZATION; SIVMAC251 CHALLENGE AB HIV-1 and its simian counterpart SIV have been exquisitely tailored by evolution to evade host immunity. By virtue of specific adaptations that thwart individual innate or adaptive immune mechanisms, and an overall replication strategy that provides for rapid establishment of a large, systemic viral population, capable of dynamic adaptation to almost all immune selection pressures, these viruses, once established, almost invariably stay one step ahead of the host's immune system, and in the vast majority of infected individuals, replicate indefinitely. Although many vaccine approaches tested to date have been able to enhance the magnitude of the immune responses to HIV/SIV infection, most of these responses, whether cellular or humoral, have largely failed to be both effectively antiviral and targeted to prevent the emergence of fully functional escape variants. Recent advances, however, have provided strong evidence that the initial stages of infection following mucosal transmission of these viruses are more vulnerable to immune intervention, and have led to the development of vaccine strategies that elicit responses able to effectively intervene in these early stages of infection, either preventing acquisition of infection or establishing early, stringent, and durable control. Here, we place HIV/AIDS vaccine development in the context of the basic immunobiology of HIV and SIV, review the evidence for their vulnerability to immune responses immediately after mucosal transmission, and discuss how this newly recognized vulnerability might be exploited for the development of an effective HIV/AIDS vaccine. C1 [Picker, Louis J.; Hansen, Scott G.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Dept Mol Microbiol, Beaverton, OR 97006 USA. [Picker, Louis J.; Hansen, Scott G.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Dept Pathol & Immunol, Beaverton, OR 97006 USA. [Picker, Louis J.; Hansen, Scott G.] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA. [Lifson, Jeffrey D.] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Picker, LJ (reprint author), Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Dept Mol Microbiol, Beaverton, OR 97006 USA. EM pickerl@ohsu.edu FU CCR NIH HHS [HHSN261200800001C]; NCI NIH HHS [HHSN261200800001E]; NCRR NIH HHS [K01 RR000163, P51 RR000163, RR00163]; NIAID NIH HHS [AI095113, R01 AI060392, R56 AI060392, AI060392, R01 AI095113, R37 AI054292]; NIDCR NIH HHS [DE02129, R01 DE021291]; PHS HHS [HHSN261200800001E] NR 83 TC 72 Z9 72 U1 2 U2 24 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4219 BN 978-0-8243-0563-5 J9 ANNU REV MED JI Annu. Rev. Med. PY 2012 VL 63 BP 95 EP 111 DI 10.1146/annurev-med-042010-085643 PG 17 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BZK46 UT WOS:000301838400006 PM 21942424 ER PT S AU Carrington, M Walker, BD AF Carrington, Mary Walker, Bruce D. BE Caskey, CT Austin, CP Hoxie, JA TI Immunogenetics of Spontaneous Control of HIV SO ANNUAL REVIEW OF MEDICINE, VOL 63 SE Annual Review of Medicine LA English DT Review; Book Chapter DE HLA-B; HLA-C 3 ' UTR; genome-wide association study; cytotoxic T lymphocytes; microRNA ID IMMUNODEFICIENCY-VIRUS TYPE-1; MAJOR HISTOCOMPATIBILITY COMPLEX; CELL-SURFACE EXPRESSION; CYTOTOXIC T-LYMPHOCYTES; HLA-C EXPRESSION; CLASS-I; HOMOSEXUAL-MEN; MESSENGER-RNA; DISEASE PROGRESSION; HEAVY-CHAIN AB Host genetic variation is presently estimated to account for about one-fourth of the observed differences in control of HIV across infected individuals. Genome-wide association studies have confirmed that polymorphism within the HLA class I locus is the primary host genetic contributor to determining outcome after infection. Here we progress beyond the genetic associations alone to consider the functional explanations for these correlations. In this process, the complex and multidimensional effects of HLA molecules in viral disease become apparent. C1 [Carrington, Mary] NCI Frederick, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 20882 USA. [Carrington, Mary; Walker, Bruce D.] Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA. RP Carrington, M (reprint author), NCI Frederick, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 20882 USA. EM carringm@mail.nih.gov; bwalker@partners.org FU CCR NIH HHS [HHSN261200800001C]; Intramural NIH HHS; NCI NIH HHS [HHSN261200800001E, HHSN261200800001E]; NIAID NIH HHS [AI30914, R01 AI030914]; PHS HHS [HHSN261200800001E] NR 63 TC 42 Z9 42 U1 0 U2 10 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4219 BN 978-0-8243-0563-5 J9 ANNU REV MED JI Annu. Rev. Med. PY 2012 VL 63 BP 131 EP 145 DI 10.1146/annurev-med-062909-130018 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BZK46 UT WOS:000301838400008 PM 22248321 ER PT S AU Aviv, A Levy, D AF Aviv, Abraham Levy, Daniel BE Caskey, CT Austin, CP Hoxie, JA TI Telomeres, Atherosclerosis, and the Hemothelium: The Longer View SO ANNUAL REVIEW OF MEDICINE, VOL 63 SE Annual Review of Medicine LA English DT Review; Book Chapter DE hematopoietic stem cells; aging; birth; endothelial progenitor cells; genes ID ENDOTHELIAL PROGENITOR CELLS; CARDIOVASCULAR RISK-FACTORS; GENOME-WIDE ASSOCIATION; BONE-MARROW; STEM-CELLS; MYOCARDIAL-INFARCTION; INSULIN-RESISTANCE; OXIDATIVE STRESS; LENGTH; DISEASE AB The model we propose to explain the links between atherosclerosis and telomere dynamics (birth telomere length and its age-dependent shortening) in leukocytes takes cues from three facts: atherosclerosis is a disease of the vascular endothelium; the hematopoietic system and the vascular endothelium share a common embryonic origin; interindividual variation in leukocyte telomere length (LTL) in the general population has a genetic explanation. The model posits that LTL dynamics mirror telomere dynamics in hematopoietic stem cells (HSCs), where telomere length is an index of HSC reserves. Diminished HSC reserves at birth, their accelerated attrition rate afterward, or both are are reflected in shortened LTL during adulthood-a phenomenon that confers increased risk for atherosclerosis. We explain how telomere length in HSCs serves as both a biomarker of atherosclerosis and a determinant of its development. Our model comes down to this proposition: Shortened LTL predicts increased atherosclerotic risk because the injurious component of atherosclerosis exceeds the repair capacity of HSC reserves, which largely depend on HSC telomere length. C1 [Aviv, Abraham] Univ Med & Dent New Jersey, New Jersey Med Sch, Ctr Human Dev & Aging, Newark, NJ 07103 USA. [Levy, Daniel] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20824 USA. RP Aviv, A (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Ctr Human Dev & Aging, 185 S Orange Ave, Newark, NJ 07103 USA. EM avivab@umdnj.edu; levyd@nhlbi.nih.gov FU Intramural NIH HHS [Z01 HL006001-01, Z01 HL006001-02, Z99 HL999999]; NIA NIH HHS [AG020132, AG030678, AG16592, R01 AG020132, R01 AG030678, R01 AG016592] NR 59 TC 10 Z9 10 U1 0 U2 5 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4219 BN 978-0-8243-0563-5 J9 ANNU REV MED JI Annu. Rev. Med. PY 2012 VL 63 BP 293 EP 301 DI 10.1146/annurev-med-050311-104846 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BZK46 UT WOS:000301838400019 PM 22017444 ER PT S AU Johnson, CH Patterson, AD Idle, JR Gonzalez, FJ AF Johnson, Caroline H. Patterson, Andrew D. Idle, Jeffrey R. Gonzalez, Frank J. BE Insel, PA Amara, SG Blaschke, TF TI Xenobiotic Metabolomics: Major Impact on the Metabolome SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 52 SE Annual Review of Pharmacology and Toxicology LA English DT Review; Book Chapter DE pharmacometabolomics; gut microflora; interindividual variation; metabotype; UPLC; mass spectrometry ID PREGNANE-X-RECEPTOR; SPECTROMETRY-BASED METABOLOMICS; QTOFMS-BASED METABOLOMICS; FLIGHT MASS-SPECTROMETRY; GAMMA-IRRADIATED RATS; HUMAN DRUG-METABOLISM; ST-JOHNS-WORT; MOUSE MODEL; INTESTINAL MICROBIOTA; GAS-CHROMATOGRAPHY AB Xenobiotics are encountered by humans on a daily basis and include drugs, environmental pollutants, cosmetics, and even components of the diet. These chemicals undergo metabolism and detoxication to produce numerous metabolites, some of which have the potential to cause unintended effects such as toxicity. They can also block the action of enzymes or receptors used for endogenous metabolism or affect the efficacy and/or bioavailability of a coadministered drug. Therefore, it is essential to determine the full metabolic effects that these chemicals have on the body. Metabolomics, the comprehensive analysis of small molecules in a biofluid, can reveal biologically relevant perturbations that result from xenobiotic exposure. This review discusses the impact that genetic, environmental, and gut microflora variation has on the metabolome, and how these variables may interact, positively and negatively, with xenobiotic metabolism. C1 [Johnson, Caroline H.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Patterson, Andrew D.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. [Patterson, Andrew D.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. [Idle, Jeffrey R.] Univ Bern, Dept Clin Res, Hepatol Res Grp, CH-3010 Bern, Switzerland. RP Johnson, CH (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM caroline.johnson@nih.gov; adp117@psu.edu; jeff.idle@ikp.unibe.ch; gonzalef@mail.nih.gov RI Patterson, Andrew/G-3852-2012; OI Patterson, Andrew/0000-0003-2073-0070; Idle, Jeff/0000-0002-6143-1520 FU Intramural NIH HHS NR 91 TC 74 Z9 75 U1 4 U2 53 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0362-1642 BN 978-0-8243-0452-2 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 2012 VL 52 BP 37 EP 56 DI 10.1146/annurev-pharmtox-010611-134748 PG 20 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BZK49 UT WOS:000301839600003 PM 21819238 ER PT S AU Volkow, ND Wang, GJ Fowler, JS Tomasi, D AF Volkow, Nora D. Wang, Gene-Jack Fowler, Joanna S. Tomasi, Dardo BE Insel, PA Amara, SG Blaschke, TF TI Addiction Circuitry in the Human Brain SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 52 SE Annual Review of Pharmacology and Toxicology LA English DT Review; Book Chapter DE conditioning; executive function; accumbens; dorsal striatum; orbitofrontal cortex; cingulate gyrus ID SYNAPTIC DOPAMINE CONCENTRATIONS; SELF-ADMINISTER COCAINE; ORBITOFRONTAL CORTEX; NUCLEUS-ACCUMBENS; RHESUS-MONKEYS; BASAL GANGLIA; RECEPTOR AVAILABILITY; LIMBIC ACTIVATION; NEURAL MECHANISMS; LATERAL HABENULA AB A major challenge in understanding substance-use disorders lies in uncovering why some individuals become addicted when exposed to drugs, whereas others do not. Although genetic, developmental, and environmental factors are recognized as major contributors to a person's risk of becoming addicted, the neurobiological processes that underlie this vulnerability are still poorly understood. Imaging studies suggest that individual variations in key dopamine-modulated brain circuits, including circuits involved in reward, memory, executive function, and motivation, contribute to some of the differences in addiction vulnerability. A better understanding of the main circuits affected by chronic drug use and the influence of social stressors, developmental trajectories, and genetic background on these circuits is bound to lead to a better understanding of addiction and to more effective strategies for the prevention and treatment of substance-use disorders. C1 [Volkow, Nora D.] NIDA, NIH, Bethesda, MD 20892 USA. [Volkow, Nora D.; Tomasi, Dardo] NIAAA, NIH, Bethesda, MD 20892 USA. [Wang, Gene-Jack; Fowler, Joanna S.] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. RP Volkow, ND (reprint author), NIDA, NIH, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov RI Tomasi, Dardo/J-2127-2015 FU Intramural NIH HHS [ZIA AA000550-08] NR 90 TC 159 Z9 166 U1 8 U2 66 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0362-1642 BN 978-0-8243-0452-2 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 2012 VL 52 BP 321 EP 336 DI 10.1146/annurev-pharmtox-010611-134625 PG 16 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BZK49 UT WOS:000301839600016 PM 21961707 ER PT S AU Fenton, SE Reed, C Newbold, RR AF Fenton, Suzanne E. Reed, Casey Newbold, Retha R. BE Insel, PA Amara, SG Blaschke, TF TI Perinatal Environmental Exposures Affect Mammary Development, Function, and Cancer Risk in Adulthood SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 52 SE Annual Review of Pharmacology and Toxicology LA English DT Review; Book Chapter DE puberty; mammary gland; developmental basis of adult disease; environmental factors; diet; breast cancer ID SPRAGUE-DAWLEY RATS; BISPHENOL-A ALTERS; ENDOCRINE-DISRUPTING CHEMICALS; PUBLIC-HEALTH IMPLICATIONS; LONG-EVANS RATS; GLAND DEVELOPMENT; BREAST-CANCER; FEMALE RAT; PRENATAL EXPOSURE; IN-UTERO AB Puberty is an important transition that enables reproduction of mammalian species. Precocious puberty, specifically early thelarche ( the appearance of breast "buds"), in girls of multiple ethnic backgrounds is a major health problem in the United States and other countries. The cause for a continued decrease in the age of breast development in girls is unknown, but environmental factors likely play a major role. Laboratory and epidemiological studies have identified several individual environmental factors that affect breast development, but further progress is needed. Current research needs include increased attention to and recording of prenatal and neonatal environmental exposures, testing of marketed chemicals for effects on the mammary gland, and understanding of the mammary gland-specific mechanisms that are altered by chemicals. Such research is required to halt the increasing trend toward puberty at earlier ages. C1 [Fenton, Suzanne E.; Reed, Casey; Newbold, Retha R.] NIEHS, Div Natl Toxicol Program, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Fenton, SE (reprint author), NIEHS, Div Natl Toxicol Program, NIH, US Dept HHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM fentonse@niehs.nih.gov; newbold1@niehs.nih.gov FU Intramural NIH HHS [ZIA ES102785-02] NR 149 TC 27 Z9 27 U1 0 U2 11 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0362-1642 BN 978-0-8243-0452-2 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 2012 VL 52 BP 455 EP 479 DI 10.1146/annurev-pharmtox-010611-134659 PG 25 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BZK49 UT WOS:000301839600022 PM 22017681 ER PT J AU Tan, C Gery, I AF Tan, Cuiyan Gery, Igal TI The Unique Features of Th9 Cells and their Products SO CRITICAL REVIEWS IN IMMUNOLOGY LA English DT Article DE IL-9; Th9; inflammation; eye; lymphocyte subsets ID CD4(+) T-CELLS; TGF-BETA; AIRWAY INFLAMMATION; CYTOKINE PRODUCTION; IL-9 EXPRESSION; INTERLEUKIN 9; MAST-CELLS; DIFFERENTIATION; PROMOTES; DISEASE AB Although it was discovered more than two decades ago, new information concerning the biological activities of IL-9 has been provided in recent years, after the isolation of cells that selectively produce this cytokine, designated "Th9." Th9 cells are generated in vitro by polarization, mainly by TGF-beta and IL-4, during activation with the specific antigen, or with anti-CD3/CD28 antibodies. This review deals mainly with Th9 generated by the former, "physiological" mode of activation. Of particular interest is the unique production kinetics of IL-9: the cytokine is produced very rapidly, but after reaching its peak (day 3 in our studies), it declines sharply to trace levels. In addition to IL-9, Th9 cells also produce similar amounts of another cytokine, IL-10, but the production kinetics of these two cytokines are strikingly different. Antigen-activated Th9 in our studies also developed pathogenic capacity, but only during the short time period of peak IL-9 production. Interestingly, no IL-9-producing cells were detected in sites of inflammation induced by 119, in contrast to Th1 and Th17. The unique features of Th9 cells and their products are discussed with regards to the known and assumed functions of the cytokine. C1 [Tan, Cuiyan; Gery, Igal] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Gery, I (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Rm 10N208, Bethesda, MD 20892 USA. EM geryi@nei.nih.gov FU National Eye Institute, NIH FX The research cited in this paper was supported by the Intramural Research Program of the National Eye Institute, NIH. NR 48 TC 29 Z9 31 U1 0 U2 7 PU BEGELL HOUSE INC PI REDDING PA 50 CROSS HIGHWAY, REDDING, CT 06896 USA SN 1040-8401 J9 CRIT REV IMMUNOL JI Crit. Rev. Immunol. PY 2012 VL 32 IS 1 BP 1 EP 10 PG 10 WC Immunology SC Immunology GA 926IV UT WOS:000302825400001 PM 22428852 ER PT J AU Goldsmith, J Crainiceanu, CM Caffo, B Reich, D AF Goldsmith, Jeff Crainiceanu, Ciprian M. Caffo, Brian Reich, Daniel TI Longitudinal penalized functional regression for cognitive outcomes on neuronal tract measurements SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE Bayesian inference; Functional regression; Mixed models; Smoothing splines ID SMOOTHING SPLINES ESTIMATORS; GENERALIZED LINEAR-MODELS; MULTIPLE-SCLEROSIS; CURVES; MATTER; MRI AB . We describe and analyse a longitudinal diffusion tensor imaging study relating changes in the microstructure of intracranial white matter tracts to cognitive disability in multiple-sclerosis patients. In this application the scalar outcome and the functional exposure are measured longitudinally. This data structure is new and raises challenges that cannot be addressed with current methods and software. To analyse the data, we introduce a penalized functional regression model and inferential tools designed specifically for these emerging types of data. Our proposed model extends the generalized linear mixed model by adding functional predictors; this method is computationally feasible and is applicable when the functional predictors are measured densely, sparsely or with error. On-line supplements compare two implementations, one likelihood based and the other Bayesian, and provide the software that is used in simulations; the likelihood-based implementation is included as the lpfr() function in the R package refund that is available in the Comprehensive R Archive Network. C1 [Goldsmith, Jeff] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21210 USA. [Crainiceanu, Ciprian M.] Johns Hopkins Univ, Baltimore, MD USA. [Reich, Daniel] NIH, Bethesda, MD 20892 USA. RP Goldsmith, J (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, 615 N Wolfe St, Baltimore, MD 21210 USA. EM jgoldsmi@jhsph.edu RI Reich, Daniel/E-5701-2010 OI Reich, Daniel/0000-0002-2628-4334 FU National Institute of Neurological Disorders and Stroke [R01NS060910]; National Multiple Sclerosis Society; EMD Serono FX The research of Goldsmith, Crainiceanu and Caffo was supported by award R01NS060910 from the National Institute of Neurological Disorders and Stroke. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Neurological Disorders and Stroke or the National Institutes of Health. This research was partially supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke. Scans were funded by grants from the National Multiple Sclerosis Society and EMD Serono to Peter Calabresi, whose support we gratefully acknowledge. NR 34 TC 14 Z9 14 U1 1 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0035-9254 J9 J R STAT SOC C-APPL JI J. R. Stat. Soc. Ser. C-Appl. Stat. PY 2012 VL 61 BP 453 EP 469 DI 10.1111/j.1467-9876.2011.01031.x PN 3 PG 17 WC Statistics & Probability SC Mathematics GA 926XQ UT WOS:000302866200004 PM 22679339 ER PT J AU Mok, SI Munasinghe, JP Young, WS AF Mok, Stephanie I. Munasinghe, Jeeva P. Young, W. Scott TI Infusion-based manganese-enhanced MRI: a new imaging technique to visualize the mouse brain SO BRAIN STRUCTURE & FUNCTION LA English DT Article DE MRI; Manganese; Oxytocin; Osmotic pump; Infusion ID TOXICITY AB Manganese-enhanced magnetic resonance imaging is a technique that employs the divalent ion of the paramagnetic metal manganese (Mn2+) as an effective contrast agent to visualize, in vivo, the mammalian brain. As total achievable contrast is directly proportional to the net amount of Mn2+ accumulated in the brain, there is a great interest in optimizing administration protocols to increase the effective delivery of Mn2+ to the brain while avoiding the toxic effects of Mn2+ overexposure. In this study, we investigated outcomes following continuous slow systemic infusion of manganese chloride (MnCl2) into the mouse via mini-osmotic pump administration. The effects of increasing fractionated rates of Mn2+ infusion on signal enhancement in regions of the brain were analyzed in a three-treatment study. We acquired whole-brain 3-D T1-weighted images and performed region of interest quantitative analysis to compare mean normalized signal in Mn2+ treatments spanning 3, 7, or 14 days of infusion (rates of 1, 0.5, and 0.25 mu L/h, respectively). Evidence of Mn2+ transport at the conclusion of each infusion treatment was observed throughout the brains of normally behaving mice. Regions of particular Mn2+ accumulation include the olfactory bulbs, cortex, infralimbic cortex, habenula, thalamus, hippocampal formation, amygdala, hypothalamus, inferior colliculus, and cerebellum. Signals measured at the completion of each infusion treatment indicate comparable means for all examined fractionated rates of Mn2+ infusion. In this current study, we achieved a significantly higher dose of Mn2+ (180 mg/kg) than that employed in previous studies without any observable toxic effects on animal physiology or behavior. C1 [Mok, Stephanie I.; Young, W. Scott] NIMH, Sect Neural Gene Express, NIH, DHHS, Bethesda, MD 20892 USA. [Munasinghe, Jeeva P.] NINDS, Vivo NMR Ctr, NIH, DHHS, Bethesda, MD 20892 USA. RP Young, WS (reprint author), NIMH, Sect Neural Gene Express, NIH, DHHS, 9000 Rockville Pike,Bldg 49,Room 5A51, Bethesda, MD 20892 USA. EM wsy@mail.nih.gov RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 FU NIMH [Z01-MH-002498-22]; NIH FX We would like to acknowledge the technical assistance of Vivian Diaz and the advice of Dr. Afonso C. Silva. We appreciate the helpful suggestions and statistical advice of Dr. Jerome Pagani. This research was supported in part by the NIMH Intramural Research Program (Z01-MH-002498-22) and the NIH Oxford-Cambridge Scholars Program. NR 23 TC 8 Z9 8 U1 1 U2 3 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2653 J9 BRAIN STRUCT FUNCT JI Brain Struct. Funct. PD JAN PY 2012 VL 217 IS 1 BP 107 EP 114 DI 10.1007/s00429-011-0324-y PG 8 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA 922UC UT WOS:000302572800009 PM 21597966 ER PT J AU Moussouttas, M Huynh, TT Khoury, J Lai, EW Dombrowski, K Pello, S Pacak, K AF Moussouttas, Michael Huynh, Thanh T. Khoury, John Lai, Edwin W. Dombrowski, Keith Pello, Scott Pacak, Karel TI Cerebrospinal Fluid Catecholamine Levels as Predictors of Outcome in Subarachnoid Hemorrhage SO CEREBROVASCULAR DISEASES LA English DT Article DE Subarachnoid hemorrhage; Sympathetic nervous system; Catecholamines; Cerebrospinal fluid; Prognosis; Outcome ID INTERCELLULAR-ADHESION MOLECULE-1; SYMPATHETIC NERVOUS ACTIVITY; GRADING SCALE; CEREBRAL-ARTERIES; BLOOD BIOMARKERS; DELAYED ISCHEMIA; PLASMA; ADRENALINE; STRESS; STROKE AB Objective: Subarachnoid hemorrhage (SAH) is associated with marked sympathetic activation at the time of ictus. The purpose of this study is to determine whether early central catecholamine levels measured from cerebrospinal fluid (CSF) relate to outcome in patients with SAH. Methods: Observational study of consecutive SAH grade 3-5 patients who underwent ventriculostomy placement, but did not undergo open craniotomy for aneurysm obliteration. CSF samples were obtained during the first 48 h following symptom onset and assayed for catecholamine levels. Statistical analyses were performed to determine whether the levels predicted mortality by day 15 or mortality/disability by day 30. Results: For the 102 patients included, mean age was 58, and 73% were female - 21% experienced day-15 mortality, and 32% experienced mortality/disability by day 30. Early mortality was related to Hunt-Hess (H/H) grade (p < 0.001), neurogenic cardiomyopathy (NC) (p = 0.003), cerebral infarction (p = 0.001), elevated intracranial pressure (ICP) (p = 0.029), epinephrine (EPI) level (p = 0.002) and norepinephrine/3,4-dihydroxyphenylglycol (NE/DHPG) ratio (p = 0.003). Mortality/disability was related to H/H grade (p < 0.001), NC (p = 0.018), infarction (p < 0.001), elevated ICP (p = 0.002), EPI (p = 0.004) and NE/DHPG (p = 0.014). Logistic regression identified age [OR 1.09 (95% CI 1.01-1.17)], H/H grade [9.52 (1.19-77)], infarction [10.87 (1.22-100)], ICP elevation [32.26 (2-500)], EPI [1.06 (1.01-1.10)], and (inversely) DHPG [0.99 (0.99-1.00)] as independent predictors of early mortality. For mortality/disability, H/H grade [OR 21.74 (95% CI 5.62-83)], ICP elevation [18.52 (1.93-166)], and EPI [1.05 (1.02-1.09)] emerged as independent predictors. Proportional-hazards analysis revealed age [HR 1.041 (95% CI 1.003-1.08)], H/H grade [6.9 (1.54-31.25)], NC [4.31 (1.5-12.35)], and EPI [1.032 (1.009-1.054)] independently predicted early mortality. Conclusions: CSF catecholamine levels are elevated in SAH patients who experience early mortality or disability. EPI may potentially serve as useful index of outcome in this population of patients with SAH. Copyright (C) 2012 S. Karger AG, Basel C1 [Moussouttas, Michael] Thomas Jefferson Med Ctr, Cerebrovasc & Neurocrit Care Div, Philadelphia, PA USA. [Khoury, John; Dombrowski, Keith; Pello, Scott] Thomas Jefferson Med Ctr, Dept Neurol, Philadelphia, PA USA. [Huynh, Thanh T.; Lai, Edwin W.; Pacak, Karel] NIH, Sect Med Neuroendocrinol, Reprod & Adult Endocrinol Program, Bethesda, MD 20892 USA. RP Moussouttas, M (reprint author), 900 Walnut St,Suite 200, Philadelphia, PA 19107 USA. EM arista1@pol.net FU NIH/NICHD FX The authors express gratitude to the nurses of the neurological intensive care unit from the Jefferson Hospital of Neurosciences at Thomas Jefferson University Medical Center for their assistance in this project. This project represents a collaboration between the Neurocritical Care Division in the Department of Neurology at Thomas Jefferson Medical Center, and the Section on Neuroendocrinology of the Reproductive and Adult Endocrinology Program at the National Institutes of Health. This research study was supported in part by the Intramural Research Program of the NIH/NICHD. NR 61 TC 12 Z9 12 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2012 VL 33 IS 2 BP 173 EP 181 DI 10.1159/000334660 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 916XQ UT WOS:000302136900012 PM 22222551 ER PT J AU Zhang, ZJ Wang, XM McAlonan, GM AF Zhang, Zhang-Jin Wang, Xiao-Min McAlonan, Grainne M. TI Neural Acupuncture Unit: A New Concept for Interpreting Effects and Mechanisms of Acupuncture SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Review ID GENE-RELATED PEPTIDE; NITRIC-OXIDE SYNTHASE; RAT GLABROUS SKIN; RANDOMIZED CONTROLLED-TRIALS; PRIMARY AFFERENT TERMINALS; SYMPATHETIC-NERVE ACTIVITY; MATERNALLY-SEPARATED RATS; NEUROPEPTIDE-Y EXPRESSION; ROOT GANGLION NEURONS; SPINAL DORSAL-HORN AB When an acupuncture needle is inserted into a designated point on the body and mechanical or electrical stimulation is delivered, various neural and neuroactive components are activated. The collection of the activated neural and neuroactive components distributed in the skin, muscle, and connective tissues surrounding the inserted needle is defined as a neural acupuncture unit (NAU). The traditionally defined acupoints represent an anatomical landmark system that indicates local sites where NAUs may contain relatively dense and concentrated neural and neuroactive components, upon which acupuncture stimulation would elicit a more efficient therapeutic response. The NAU-based local mechanisms of biochemical and biophysical reactions play an important role in acupuncture-induced analgesia. Different properties of NAUs are associated with different components of needling sensation. There exist several central pathways to convey NAU-induced acupuncture signals, Electroacupuncture (EA) frequency-specific neurochemical effects are related to different peripheral and central pathways transmitting afferent signals from different frequency of NAU stimulation. More widespread and intense neuroimaging responses of brain regions to acupuncture may be a consequence of more efficient NAU stimulation modes. The introduction of the conception of NAU provides a new theoretical approach to interpreting effects and mechanisms of acupuncture in modern biomedical knowledge framework. C1 [Zhang, Zhang-Jin] Univ Hong Kong, LKS Fac Med, Sch Chinese Med, Pokfulam, Hong Kong, Peoples R China. [Wang, Xiao-Min] NINR, NIH, Bethesda, MD 20892 USA. [McAlonan, Grainne M.] Kings Coll London, Inst Psychiat, Dept Forens & Neurodev Sci, London, England. RP Zhang, ZJ (reprint author), Univ Hong Kong, LKS Fac Med, Sch Chinese Med, 10 Sassoon Rd, Pokfulam, Hong Kong, Peoples R China. EM zhangzj@hku.hk OI McAlonan, Grainne/0000-0002-4466-2343 FU Hong Kong Food and Health Bureau [06070831]; Hong Kong Research Grant Council (RGC) [786611]; HKU [10400876] FX This paper was derived from acupuncture research projects supported by Health and Health Services Research Fund (HHSRF) of Hong Kong Food and Health Bureau (Ref. no.: 06070831), General Research Fund (GRF) of Hong Kong Research Grant Council (RGC) (Ref. no.: 786611), and HKU intramural funds (Ref. no.: 10400876). The authors are grateful to Dr. Tun-Tak Ng and Ms. Kun Wai for their help in preparing illustrations, Professor Yan Zhao and Professor Yi Guo for kindly providing the original illustrations for Figure 3(b). NR 225 TC 30 Z9 31 U1 2 U2 21 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1741-427X J9 EVID-BASED COMPL ALT JI Evid.-based Complement Altern. Med. PY 2012 AR 429412 DI 10.1155/2012/429412 PG 23 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 923CX UT WOS:000302597800001 ER PT J AU Abu-Asab, M Koithan, M Shaver, J Amri, H AF Abu-Asab, Mones Koithan, Mary Shaver, Joan Amri, Hakima TI Analyzing Heterogeneous Complexity in Complementary and Alternative Medicine Research: A Systems Biology Solution via Parsimony Phylogenetics SO FORSCHENDE KOMPLEMENTARMEDIZIN LA English DT Review DE Heterogeneity; Parsimony; Phylogenetics; Synapomorphies; Systems biology; Clinical trial design; Complementary and alternative medicine ID TRADITIONAL CHINESE MEDICINE; RANDOMIZED CONTROLLED-TRIALS; EPIGENETIC HETEROGENEITY; GENE-EXPRESSION; CANCER; REVEALS; METABOLOMICS; ASSOCIATION; CONNECTION; NETWORKS AB Systems biology offers cutting-edge tools for the study of complementary and alternative medicine (CAM). The advent of 'omics' techniques and the resulting avalanche of scientific data have introduced an unprecedented level of complexity and heterogeneous data to biomedical research, leading to the development of novel research approaches. Statistical averaging has its limitations and is unsuitable for the analysis of heterogeneity, as it masks diversity by homogenizing otherwise heterogeneous populations. Unfortunately, most researchers are unaware of alternative methods of analysis capable of accounting for individual variability. This paper describes a systems biology solution to data complexity through the application of parsimony phylogenetic analysis. Maximum parsimony (MP) provides a data-based modeling paradigm that will permit a priori stratification of the study cohort(s), better assessment of early diagnosis, prognosis, and treatment efficacy within each stratum, and a method that could be used to explore, identify and describe complex human patterning. C1 [Amri, Hakima] Georgetown Univ, Sch Med, Dept Biochem Cellular & Mol Biol, Washington, DC 20007 USA. [Abu-Asab, Mones] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Koithan, Mary; Shaver, Joan] Univ Arizona, Coll Nursing, Tucson, AZ 85721 USA. [Koithan, Mary] Univ Arizona, Dept Family & Community Med, Tucson, AZ USA. RP Amri, H (reprint author), Georgetown Univ, Sch Med, Dept Biochem Cellular & Mol Biol, Washington, DC 20007 USA. EM amrih@georgetown.edu OI Abu-Asab, Mones/0000-0002-4047-1232 FU Intramural NIH HHS [Z99 EY999999] NR 42 TC 5 Z9 5 U1 2 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7096 J9 FORSCH KOMPLEMENTMED JI Forsch. Komplement.med. PY 2012 VL 19 SU 1 BP 42 EP 48 DI 10.1159/000335190 PG 7 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 920XJ UT WOS:000302442000008 PM 22327551 ER PT J AU Hussain, S Al-Nsour, F Rice, AB Marshburn, J Ji, ZX Zink, JI Yingling, B Walker, NJ Garantziotis, S AF Hussain, Salik Al-Nsour, Faris Rice, Annette B. Marshburn, Jamie Ji, Zhaoxia Zink, Jeffery I. Yingling, Brenda Walker, Nigel J. Garantziotis, Stavros TI Cerium dioxide nanoparticles do not modulate the lipopolysaccharide-induced inflammatory response in human monocytes SO INTERNATIONAL JOURNAL OF NANOMEDICINE LA English DT Article DE cerium dioxide; nanoparticle; nanomedicine; inflammation; human monocyte; lipopolysaccharides ID OXIDE NANOPARTICLES; OXIDATIVE STRESS; CARBON-BLACK; AIR-POLLUTION; SURFACE-AREA; LUNG; MICE; EXPOSURE; CEO2; MORTALITY AB Background: Cerium dioxide (CeO2) nanoparticles have potential therapeutic applications and are widely used for industrial purposes. However, the effects of these nanoparticles on primary human cells are largely unknown. The ability of nanoparticles to exacerbate pre-existing inflammatory disorders is not well documented for engineered nanoparticles, and is certainly lacking for CeO2 nanoparticles. We investigated the inflammation-modulating effects of CeO2 nanoparticles at noncytotoxic concentrations in human peripheral blood monocytes. Methods: CD14(+) cells were isolated from peripheral blood samples of human volunteers. Cells were exposed to either 0.5 or 1 mu g/mL of CeO2 nanoparticles over a period of 24 or 48 hours with or without lipopolysaccharide (10 ng/mL) prestimulation. Modulation of the inflammatory response was studied by measuring secreted tumor necrosis factor-alpha, interleukin-1beta, macrophage chemotactic protein-1, interferon-gamma, and interferon gamma-induced protein 10. Results: CeO2 nanoparticle suspensions were thoroughly characterized using dynamic light scattering analysis (194 nm hydrodynamic diameter), zeta potential analysis (-14 mV), and transmission electron microscopy (irregular-shaped particles). Transmission electron microscopy of CD14(+) cells exposed to CeO2 nanoparticles revealed that these nanoparticles were efficiently internalized by monocytes and were found either in vesicles or free in the cytoplasm. However, no significant differences in secreted cytokine profiles were observed between CeO2 nanoparticle-treated cells and control cells at noncytotoxic doses. No significant effects of CeO2 nanoparticle exposure subsequent to lipopolysaccharide priming was observed on cytokine secretion. Moreover, no significant difference in lipopolysaccharide-induced cytokine production was observed after exposure to CeO2 nanoparticles followed by lipopolysaccharide exposure. Conclusion: CeO2 nanoparticles at noncytotoxic concentrations neither modulate pre-existing inflammation nor prime for subsequent exposure to lipopolysaccharides in human monocytes from healthy subjects. C1 [Hussain, Salik; Al-Nsour, Faris; Rice, Annette B.; Marshburn, Jamie; Yingling, Brenda; Garantziotis, Stavros] NIEHS, Clin Res Unit, NIH, Res Triangle Pk, NC 27709 USA. [Ji, Zhaoxia; Zink, Jeffery I.] Univ Calif Los Angeles, UC Ctr Environm Implicat Nanotechnol, Los Angeles, CA USA. [Walker, Nigel J.] NIEHS, Div Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. RP Hussain, S (reprint author), NIEHS, Clin Res Unit, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM salik.hussain@nih.gov RI Walker, Nigel/D-6583-2012; Hussain, Salik/O-1687-2016; Garantziotis, Stavros/A-6903-2009 OI Walker, Nigel/0000-0002-9111-6855; Garantziotis, Stavros/0000-0003-4007-375X FU National Institute of Environmental Health Sciences FX This research was supported in part by the Intramural Research Program of the National Institute of Environmental Health Sciences. We gratefully acknowledge all volunteers who participated in this study. Shyamal Peddada is gratefully acknowledged for excellent statistical advice. We also thank Nicole Edwards and Gina Musselwhite for support in patient recruitment, and Erika Gutierrez, Connie Cummings, and Deloris Sutton for their technical assistance. NR 38 TC 8 Z9 8 U1 1 U2 17 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-2013 J9 INT J NANOMED JI Int. J. Nanomed. PY 2012 VL 7 BP 1387 EP 1397 DI 10.2147/IJN.S29429 PG 11 WC Nanoscience & Nanotechnology; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA 924YC UT WOS:000302726200001 PM 22457596 ER PT J AU Wade, CH Shiloh, S Woolford, SW Roberts, JS Alford, SH Marteau, TM Biesecker, BB AF Wade, Christopher H. Shiloh, Shoshana Woolford, Samuel W. Roberts, J. Scott Alford, Sharon Hensley Marteau, Theresa M. Biesecker, Barbara B. TI Modelling decisions to undergo genetic testing for susceptibility to common health conditions: An ancillary study of the Multiplex Initiative SO PSYCHOLOGY & HEALTH LA English DT Article DE genetic testing; Multiplex Initiative; health behaviour; common disease; structural equation modelling; personalised medicine; USA ID BREAST-CANCER SUSCEPTIBILITY; RISK PERCEPTIONS; PLANNED BEHAVIOR; PERCEIVED RISK; WORRY; POPULATION; ATTITUDES; INFORMATION; PERSPECTIVE; INTENTIONS AB New genetic tests reveal risks for multiple conditions simultaneously, although little is understood about the psychological factors that affect testing uptake. We assessed a conceptual model called the multiplex genetic testing model (MGTM) using structural equation modelling. The MGTM delineates worry, perceived severity, perceived risk, response efficacy and attitudes towards testing as predictors of intentions and behaviour. Participants were 270 healthy insured adults aged 25-40 from the Multiplex Initiative conducted within a health care system in Detroit, MI, USA. Participants were offered a genetic test that assessed risk for eight common health conditions. Confirmatory factor analysis revealed that worry, perceived risk and severity clustered into two disease domains: cancer or metabolic conditions. Only perceived severity of metabolic conditions was correlated with general response efficacy (beta = 0.13, p < 0.05), which predicted general attitudes towards testing (beta = 0.24, p < 0.01). Consistent with our hypothesised model, attitudes towards testing were the strongest predictors of intentions to undergo testing (beta = 0.49, p < 0.01), which in turn predicted testing uptake (OR 17.7, beta = 0.97, p < 0.01). The MGTM explained a striking 48% of the variance in intentions and 94% of the variation in uptake. These findings support use of the MGTM to explain psychological predictors of testing for multiple health conditions. C1 [Wade, Christopher H.] Univ Washington, Dept Nursing & Hlth Studies, Bothell, WA 98011 USA. [Shiloh, Shoshana] Tel Aviv Univ, Dept Psychol, IL-69978 Tel Aviv, Israel. [Woolford, Samuel W.] Bentley Univ, Dept Math Sci, Waltham, MA USA. [Roberts, J. Scott] Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. [Alford, Sharon Hensley] Henry Ford Hlth Syst, Dept Biostat & Res Epidemiol, Detroit, MI USA. [Marteau, Theresa M.] Kings Coll London, Dept Psychol, London WC2R 2LS, England. [Biesecker, Barbara B.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. RP Wade, CH (reprint author), Univ Washington, Dept Nursing & Hlth Studies, Bothell, WA 98011 USA. EM cwade@uwb.edu OI Marteau, Theresa/0000-0003-3025-1129 FU Intramural NIH HHS [Z99 HG999999]; NCI NIH HHS [U19CA 079689, U19 CA079689]; NHGRI NIH HHS [HHSN268200782096C]; PHS HHS [HHSN268200782096C] NR 42 TC 8 Z9 8 U1 1 U2 9 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0887-0446 EI 1476-8321 J9 PSYCHOL HEALTH JI Psychol. Health PY 2012 VL 27 IS 4 BP 430 EP 444 DI 10.1080/08870446.2011.586699 PG 15 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary SC Public, Environmental & Occupational Health; Psychology GA 920OX UT WOS:000302416900003 PM 21660870 ER PT J AU Kristinsson, SY Goldin, LR Turesson, I Bjorkholm, M Landgren, O AF Kristinsson, Sigurdur Y. Goldin, Lynn R. Turesson, Ingemar Bjorkholm, Magnus Landgren, Ola TI Familial Aggregation of Lymphoplasmacytic Lymphoma/Waldenstrom Macroglobulinemia with Solid Tumors and Myeloid Malignancies SO ACTA HAEMATOLOGICA LA English DT Review DE Autoimmunity; Familial aggregation; Hematological malignancies; Lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia; Monoclonal gammopathy of undetermined significance; Solid tumors; Susceptibility ID CHRONIC LYMPHOCYTIC-LEUKEMIA; POPULATION-BASED SAMPLES; NON-HODGKIN-LYMPHOMA; WALDENSTROMS MACROGLOBULINEMIA; 1ST-DEGREE RELATIVES; RISK; SWEDEN; SUSCEPTIBILITY; NEOPLASMS; PATTERNS AB Lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM) is a B-cell disorder resulting from the accumulation, predominantly in the bone marrow, of clonally related lymphoplasmacytic cells. LPL/WM is a very rare disease, with an incidence rate of 3-4 cases per million people per year. Currently, the causes of LPL/WM are poorly understood; however, there are emerging data to support a role for immune-related factors in the pathogenesis of LPL/WM. In addition, data show that genetic factors are of importance in the etiology of LPL/WM. In this paper, we will review the current knowledge about familiality of LPL/WM and provide novel data on solid tumors and myeloid malignancies in first-degree relatives of LPL/WM patients. Copyright (C) 2012 S. Karger AG, Basel C1 [Kristinsson, Sigurdur Y.; Bjorkholm, Magnus; Landgren, Ola] Karolinska Univ Hosp, Dept Med, Div Hematol, Solna, Sweden. [Kristinsson, Sigurdur Y.; Bjorkholm, Magnus; Landgren, Ola] Karolinska Inst, Stockholm, Sweden. [Turesson, Ingemar] Skane Univ Hosp, Dept Med, Sect Hematol, Malmo, Sweden. [Turesson, Ingemar; Landgren, Ola] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kristinsson, SY (reprint author), Karolinska Univ Hosp Solna, Div Hematol, Dept Med, SE-17176 Stockholm, Sweden. EM sigurdur.kristinsson@karolinska.se RI Kristinsson, Sigurdur /M-2910-2015 OI Kristinsson, Sigurdur /0000-0002-4964-7476 FU Swedish Cancer Society; Stockholm County Council; Karolinska Institutet Foundations; National Institutes of Health, National Cancer Institute; Roche FX This research was supported by grants from the Swedish Cancer Society, Stockholm County Council, the Karolinska Institutet Foundations, and the Intramural Research Program of the National Institutes of Health, National Cancer Institute, as well as by an unrestricted grant from Roche. The authors thank Ms. Shiva Ayobi, The National Board of Health and Welfare, Stockholm, Sweden, Ms. Susanne Dahllof, Statistics Sweden, Orebro, Sweden, and Ms. Emily Steplowski, Information Management Services, Silver Spring, Md., USA, for their important efforts. NR 25 TC 5 Z9 5 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5792 J9 ACTA HAEMATOL-BASEL JI Acta Haematol. PY 2012 VL 127 IS 3 BP 173 EP 177 DI 10.1159/000335618 PG 5 WC Hematology SC Hematology GA 917UX UT WOS:000302205200009 PM 22310551 ER PT J AU Miller, FG AF Miller, Franklin G. TI Clarifying the Nocebo Effect and Its Ethical Implications SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Miller, FG (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM fmiller@nih.gov FU Intramural NIH HHS NR 4 TC 1 Z9 1 U1 1 U2 8 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2012 VL 12 IS 3 BP 30 EP 31 DI 10.1080/15265161.2011.652799 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 919BW UT WOS:000302296600008 PM 22416746 ER PT J AU Goldstein, DS AF Goldstein, David S. TI Neurocardiology: Therapeutic Implications for Cardiovascular Disease SO CARDIOVASCULAR THERAPEUTICS LA English DT Review DE Autonomic nervous system; dysautonomia; neurocardiology; norepinephrine; sympathetic nervous system ID CONGESTIVE-HEART-FAILURE; NEUROGENIC ORTHOSTATIC HYPOTENSION; SYMPATHETIC-NERVE ACTIVITY; MULTIPLE SYSTEM ATROPHY; NEURALLY-MEDIATED SYNCOPE; POLYMORPHIC VENTRICULAR-TACHYCARDIA; BARORECEPTOR REFLEX FUNCTION; PARKINSONS-DISEASE; VASOVAGAL SYNCOPE; AUTONOMIC FAILURE AB The term neurocardiology refers to physiologic and pathophysiological interplays of the nervous and cardiovascular systems. This selective review provides an update about cardiovascular therapeutic implications of neurocardiology, with emphasis on disorders involving primary or secondary abnormalities of catecholamine systems. Concepts of scientific integrative medicine help understand these disorders. Scientific integrative medicine is not a treatment method or discipline but a way of thinking that applies systems concepts to acute and chronic disorders of regulation. Some of these concepts include stability by negative feedback regulation, multiple effectors, effector sharing, instability by positive feedback loops, allostasis, and allostatic load. Scientific integrative medicine builds on systems biology but is also distinct in several ways. A large variety of drugs and non-drug treatments are now available or under study for neurocardiologic disorders in which catecholamine systems are hyperfunctional or hypofunctional. The future of therapeutics in neurocardiology is not so much in new curative drugs as in applying scientific integrative medical ideas that take into account concurrent chronic degenerative disorders and interactions of multiple drug and non-drug treatments with each other and with those disorders. C1 NINDS, Clin Neurocardiol Sect, Clin Neurosci Program, Div Intramural Res,NIH, Bethesda, MD 20892 USA. RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, Clin Neurosci Program, Div Intramural Res,NIH, Bldg 10,Room 5N220,9000 Rockville Pike,10 Ctr Dr,, Bethesda, MD 20892 USA. EM goldsteind@ninds.nih.gov FU Intramural NIH HHS [ZIA NS003034-09, ZIA NS003125-05, Z99 NS999999, ZIA NS003033-09] NR 157 TC 4 Z9 4 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5914 J9 CARDIOVASC THER JI Cardiovasc. Ther. PY 2012 VL 30 IS 2 BP e89 EP e106 DI 10.1111/j.1755-5922.2010.00244.x PG 18 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 907UE UT WOS:000301443500009 PM 21108771 ER PT J AU Franco, HL Yao, HHC AF Franco, Heather L. Yao, Humphrey H. -C. TI Sex and hedgehog: roles of genes in the hedgehog signaling pathway in mammalian sexual differentiation SO CHROMOSOME RESEARCH LA English DT Article DE Hedgehog; testis; ovary; germ cells; reproductive tract; external genitalia; sex determination ID EXTERNAL GENITALIA DEVELOPMENT; LEYDIG-CELL DEVELOPMENT; EGG CHAMBER FORMATION; DESERT-HEDGEHOG; INDIAN HEDGEHOG; SONIC-HEDGEHOG; MOUSE TESTIS; GONADAL-DYSGENESIS; DHH GENE; DROSOPHILA-GERMLINE AB The chromosome status of the mammalian embryo initiates a multistage process of sexual development in which the bipotential reproductive system establishes itself as either male or female. These events are governed by intricate cell-cell and interorgan communication that is regulated by multiple signaling pathways. The hedgehog signaling pathway was originally identified for its key role in the development of Drosophila, but is now recognized as a critical developmental regulator in many species, including humans. In addition to its developmental roles, the hedgehog signaling pathway also modulates adult organ function, and misregulation of this pathway often leads to diseases, such as cancer. The hedgehog signaling pathway acts through its morphogenetic ligands that signal from ligand-producing cells to target cells over a specified distance. The target cells then respond in a graded manner based on the concentration of the ligands that they are exposed to. Through this unique mechanism of action, the hedgehog signaling pathway elicits cell fate determination, epithelial-mesenchymal interactions, and cellular homeostasis. Here, we review current findings on the roles of hedgehog signaling in the sexually dimorphic development of the reproductive organs with an emphasis on mammals and comparative evidence in other species. C1 [Franco, Heather L.; Yao, Humphrey H. -C.] NIEHS, Reprod Dev Biol Grp, Lab Reprod & Dev Tox, Res Triangle Pk, NC 27709 USA. RP Yao, HHC (reprint author), NIEHS, Reprod Dev Biol Grp, Lab Reprod & Dev Tox, 111 TW Alexander Dr,C4-10, Res Triangle Pk, NC 27709 USA. EM humphrey.yao@nih.gov RI Yao, Humphrey Hung-Chang/B-4795-2010 OI Yao, Humphrey Hung-Chang/0000-0003-2944-8469 FU National Institute of Health FX We would like to thank Gen Yamada and the members of the Yao laboratory for helpful comments on the manuscript. We also thank Sue Edelstein from the NIEHS graphics department for assistance with figures. H.L.F. and H.H-C.Y. are both supported by the National Institute of Health Intramural Research Fund. NR 74 TC 17 Z9 18 U1 3 U2 17 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0967-3849 J9 CHROMOSOME RES JI Chromosome Res. PD JAN PY 2012 VL 20 IS 1 SI SI BP 247 EP 258 DI 10.1007/s10577-011-9254-z PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 919KX UT WOS:000302326100020 PM 22105695 ER PT S AU Evans, ED Anjaneyulu, Y Tchnouwou, PB AF Evans, Eric D. Anjaneyulu, Yerramilli Tchnouwou, Paul B. BE Vitale, K TI Effects of Hurricane Katrina on Land Cover Within the Grand Bay National Estuarine Research Reserve in Mississippi, USA SO ENVIRONMENTAL AND FOOD SAFETY AND SECURITY FOR SOUTH-EAST EUROPE AND UKRAINE SE NATO Science for Peace and Security Series C-Environmental Security LA English DT Proceedings Paper CT NATO Advanced Research Workshop on Environmental and Food Security for South-East Europe and Ukraine CY MAY 17-19, 2011 CL Dnepropetrovsk, UKRAINE SP NATO Sci Affairs Div DE Hurricane Katrina; Grand Bay NERR; Remote sensing; Landsat imagery; Land cover change; Biodiversity; Ecosystems alterations ID NEW-ORLEANS; FOREST; IMPACT AB Hurricane Katrina hit the Mississippi Gulf Coast on August 29, 2005 as a Category 3 hurricane at the mouth of the Pearl River, on the Mississippi/Louisiana border. Katrina is considered one of the costliest natural disasters in United States history. Grand Bay National Wildlife Refuge (GBNWR) is located in the coastal zone of Jackson County in Mississippi, and Mobile County in Alabama. The Mississippi portion of GBNWR is part of the 18,400-acre Grand Bay National Estuarine Research Reserve (NERR), which was designated in 1999. The objectives of this study were to map changes to wetland and forest habitats resulting from hurricane Katrina and to discuss the implications of changes in these habitats on biodiversity within the Grand Bay NERR. Pre- and post-Katrina subsets of the Grand Bay NERR were derived from Landsat images downloaded from The Coastal Change Analysis Program's (C-CAP) website. Unsupervised classification and change detection analysis were applied to each Landsat-derived, 3-band datasets. The land cover change analysis revealed that hurricane Katrina caused a decrease in evergreen forest, and the conversion of evergreen forest into grassland. The major land cover changes were due to the expansion of open water. The increase in open water caused the decrease in estuarine emergent wetlands (salt marsh habitats) and the conversion of one type of land cover into another. These land cover changes could have a profound effect on the flora and fauna located within the reserve. Remote sensing technology appears to be a valuable tool for monitoring and implementing restoration and conservation strategies by the Grand Bay NERR managers. C1 [Evans, Eric D.; Tchnouwou, Paul B.] Jackson State Univ, Dept Biol, NIH RCMI Ctr Environm Hlth, 1400 Lynch St,POB 18540, Jackson, MS 39217 USA. [Anjaneyulu, Yerramilli; Tchnouwou, Paul B.] Jackson State Univ, Trent Lott Geospat Res & Visual Ctr, Coll Sci Engn & Technol, Jackson, MS 39217 USA. RP Tchnouwou, PB (reprint author), Jackson State Univ, Dept Biol, NIH RCMI Ctr Environm Hlth, 1400 Lynch St,POB 18540, Jackson, MS 39217 USA. EM paul.b.tchounwou@jsums.edu FU National Oceanic and Atmospheric Administration ECSC [NA060AR4810164]; National Science Foundation LSMAMP Program [HRD-0115807]; National Institutes of Health RCMI at Jackson State University [G12RR013459] FX This research was supported by National Oceanic and Atmospheric Administration ECSC Grant No. NA060AR4810164, National Science Foundation LSMAMP Program Grant No. HRD-0115807, and National Institutes of Health RCMI Grant No.G12RR013459 at Jackson State University. NR 33 TC 0 Z9 0 U1 2 U2 19 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1871-4668 BN 978-94-007-2955-1; 978-94-007-2953-7; 978-94-007-2952-0 J9 NATO SCI PEACE SECUR JI NATO Sci. Peace Secur. Ser. C- Environ. Secur. PY 2012 DI 10.1007/978-94-007-2953-7_16 PG 16 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA BZM26 UT WOS:000302013700016 ER PT J AU Cox, CR Reid-Arndt, SA Arndt, J Moser, RP AF Cox, Cathy R. Reid-Arndt, Stephanie A. Arndt, Jamie Moser, Richard P. TI Considering the Unspoken: The Role of Death Cognition in Quality of Life Among Women With and Without Breast Cancer SO JOURNAL OF PSYCHOSOCIAL ONCOLOGY LA English DT Article DE mortality awareness; cancer; breast; physical well-being; psychological well-being ID TERROR MANAGEMENT; SELF-ESTEEM; THOUGHT ACCESSIBILITY; FUNCTIONAL ASSESSMENT; HEALTH; MORTALITY; WORLDVIEW; AWARENESS; DYNAMICS; THREAT AB This study examined how breast cancer diagnosis influences underlying cognitions and explicit worries about death, and their roles in health-related quality of life (QOL). Forty-two women who underwent surgery for the removal of either a cancerous or benign breast mass indicated their worries about dying and completed measures of death-thought accessibility and QOL. Women with cancer reported lowered physical, emotional, and functional well-being. Further, although they did not differ in explicit worry about death, women with cancer (compared to those with a benign mass) evidenced greater death-thought accessibility, which in turn mediated the effect of cancer diagnosis on well-being. C1 [Cox, Cathy R.] Texas Christian Univ, Dept Psychol, Ft Worth, TX 76129 USA. [Reid-Arndt, Stephanie A.; Arndt, Jamie] Univ Missouri, Columbia, MO USA. [Moser, Richard P.] NCI, Behav Res Program, NIH, Bethesda, MD 20892 USA. RP Cox, CR (reprint author), Texas Christian Univ, Dept Psychol, 2800 S Univ Dr, Ft Worth, TX 76129 USA. EM c.cox@tcu.edu FU NCI NIH HHS [R01 CA096581-09, R01 CA096581] NR 29 TC 4 Z9 4 U1 0 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0734-7332 J9 J PSYCHOSOC ONCOL JI J. Psychosoc. Oncol. PY 2012 VL 30 IS 1 BP 128 EP 139 DI 10.1080/07347332.2011.633980 PG 12 WC Psychology, Social SC Psychology GA 918AU UT WOS:000302222000007 PM 22269079 ER PT J AU Green, BL Kaltman, SI Chung, JY Holt, MP Jackson, S Dozier, M AF Green, Bonnie L. Kaltman, Stacey I. Chung, Joyce Y. Holt, Melissa P. Jackson, Sadhana Dozier, Mary TI Attachment and Health Care Relationships in Low-Income Women with Trauma Histories: A Qualitative Study SO JOURNAL OF TRAUMA & DISSOCIATION LA English DT Article DE attachment; trauma; primary care; low-income women ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL-COMORBIDITY-SURVEY; ADULT ATTACHMENT; CHILDHOOD ABUSE; SEXUAL-ABUSE; UNRESOLVED ATTACHMENT; RISK-FACTORS; PTSD; REPRESENTATIONS; PERSPECTIVES AB Few studies have examined the relationship between low-income, traumatized women and their health care providers. In this study we interviewed 23 women from primary care and social service settings for the underserved about trauma, attachment, psychiatric symptoms, and reports of their interactions with primary care providers. Nearly all reported trauma exposure, and 17% had current posttraumatic stress disorder. About half were categorized as Unresolved with regard to attachment state of mind. Analyses of a health experiences interview showed that women with Unresolved attachment reported significantly more negative interactions with providers. Attachment may play a role in the relationship between trauma and health care interactions with providers, indicating the need for further study of this relationship and suggesting intervention strategies to help both parties contribute to a more collaborative process. C1 [Green, Bonnie L.; Kaltman, Stacey I.] Georgetown Univ, Dept Psychiat, Sch Med, Washington, DC 20007 USA. [Chung, Joyce Y.] NIMH, Bethesda, MD 20892 USA. [Holt, Melissa P.] Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA. [Jackson, Sadhana] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Dozier, Mary] Univ Delaware, Dept Psychol, Newark, DE USA. RP Green, BL (reprint author), Georgetown Univ, Dept Psychiat, Sch Med, 2115 Wisconsin Ave NW,Suite 200, Washington, DC 20007 USA. EM bgreen01@georgetown.edu FU NIMH NIH HHS [K01 MH 01811, K01 MH001811-05, R01 MH052135, R01 MH074374, R01 MH084135] NR 44 TC 4 Z9 4 U1 3 U2 10 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1529-9732 J9 J TRAUMA DISSOCIATIO JI J. Trauma Dissociation PY 2012 VL 13 IS 2 SI SI BP 190 EP 208 DI 10.1080/15299732.2012.642761 PG 19 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 918BM UT WOS:000302223800005 PM 22375807 ER PT J AU Huang, Y Siwo, G Wuchty, S Ferdig, MT Przytycka, TM AF Huang, Yang Siwo, Geoffrey Wuchty, Stefan Ferdig, Michael T. Przytycka, Teresa M. TI Symmetric Epistasis Estimation (SEE) and its application to dissecting interaction map of Plasmodium falciparum SO MOLECULAR BIOSYSTEMS LA English DT Article ID GENE INTERACTIONS; PERMUTATION TESTS; MULTIPLE LOCI; BINDING; POLYMORPHISMS; ERYTHROCYTE; GENOMEWIDE; DISEASES; PROTEIN; YEAST AB It is being increasingly recognized that many important phenotypic traits, including various diseases, are governed by a combination of weak genetic effects and their interactions. While the detection of epistatic interactions that involve a non-additive effect of two loci on a quantitative trait is particularly challenging, this interaction type is fundamental for the understanding of genome organization and gene regulation. However, current methods that detect epistatic interactions typically rely on the existence of a strong primary effect, considerably limiting the sensitivity of the search. To fill this gap, we developed a new method, SEE (Symmetric Epistasis Estimation), allowing the genome-wide detection of epistatic interactions without the need for a strong primary effect. We applied our approach to progeny crosses of the human malaria parasite P. falciparum and S. cerevisiae. We found an abundance of epistatic interactions in the parasite and a much smaller number of such interactions in yeast. The genome of P. falciparum also harboured several epistatic interaction hotspots that putatively play a role in drug resistance mechanisms. The abundance of observed epistatic interactions might suggest a mechanism of compensation for the extremely limited repertoire of transcription factors. Interestingly, epistatic interaction hotspots were associated with elevated levels of linkage disequilibrium, an observation that suggests selection pressure acting on P. falciparum, potentially reflecting host-pathogen interactions or drug-induced selection. C1 [Huang, Yang; Wuchty, Stefan; Przytycka, Teresa M.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Siwo, Geoffrey; Ferdig, Michael T.] Univ Notre Dame, Eck Inst Global Hlth, Dept Biol Sci, Notre Dame, IN 46556 USA. RP Przytycka, TM (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 8600 Rockville Pike,Bldg 38A, Bethesda, MD 20894 USA. EM przytyck@mail.nih.gov RI Ferdig, Michael/C-6627-2016 FU Intramural NIH HHS [Z01 LM200887-01] NR 32 TC 0 Z9 1 U1 0 U2 0 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PY 2012 VL 8 IS 5 BP 1544 EP 1552 DI 10.1039/c2mb05333k PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 919YR UT WOS:000302368600020 PM 22419061 ER PT J AU Kowdley, GC Merchant, N Richardson, JP Somerville, J Gorospe, M Cunningham, SC AF Kowdley, Gopal C. Merchant, Nishant Richardson, James P. Somerville, Justin Gorospe, Myriam Cunningham, Steven C. TI Cancer Surgery in the Elderly SO SCIENTIFIC WORLD JOURNAL LA English DT Review ID COMPREHENSIVE GERIATRIC ASSESSMENT; SERVICES TASK-FORCE; PANCREATICO-BILIARY TUMORS; COOPERATIVE-ONCOLOGY-GROUP; POOR FUNCTIONAL RECOVERY; BREAST-CANCER; PROSTATE-CANCER; LUNG-CANCER; PREOPERATIVE ASSESSMENT; OLDER WOMEN AB The proportions both of elderly patients in the world and of elderly patients with cancer are both increasing. In the evaluation of these patients, physiologic age, and not chronologic age, should be carefully considered in the decision-making process prior to both cancer screening and cancer treatment in an effort to avoid ageism. Many tools exist to help the practitioner determine the physiologic age of the patient, which allows for more appropriate and more individualized risk stratification, both in the pre- and postoperative periods as patients are evaluated for surgical treatments and monitored for surgical complications, respectively. During and after operations in the oncogeriatric populations, physiologic changes occuring that accompany aging include impaired stress response, increased senescence, and decreased immunity, all three of which impact the risk/benefit ratio associated with cancer surgery in the elderly. C1 [Kowdley, Gopal C.; Merchant, Nishant; Somerville, Justin; Cunningham, Steven C.] St Agnes Hosp Ctr, Dept Surg, Baltimore, MD 21229 USA. [Richardson, James P.] St Agnes Hosp Ctr, Dept Med, Baltimore, MD 21229 USA. [Gorospe, Myriam] NIH, NIA, Lab Mol Biol & Immunol, Baltimore, MD 21224 USA. RP Cunningham, SC (reprint author), St Agnes Hosp Ctr, Dept Surg, 900 Caton Ave, Baltimore, MD 21229 USA. EM scunnin9@jhmi.edu FU National Institute on Aging, US National Institutes of Health FX M. Gorospe was supported by the National Institute on Aging-Intramural Research Program, US National Institutes of Health. NR 99 TC 10 Z9 11 U1 1 U2 5 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1537-744X J9 SCI WORLD J JI Sci. World J. PY 2012 AR 303852 DI 10.1100/2012/303852 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 916EM UT WOS:000302081200001 ER PT J AU Riss, PJ Lu, SY Telu, S Aigbirhio, FI Pike, VW AF Riss, Patrick J. Lu, Shuiyu Telu, Sanjay Aigbirhio, Franklin I. Pike, Victor W. TI CuI-Catalyzed 11C Carboxylation of Boronic Acid Esters: A Rapid and Convenient Entry to 11C-Labeled Carboxylic Acids, Esters, and Amides SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE boronic acid esters; carbon-11; carboxylation; positron emission tomography; radiochemistry ID POSITRON-EMISSION-TOMOGRAPHY; MYOCARDIAL-METABOLISM; ALKENYLBORONIC ESTERS; CARBON-DIOXIDE; C-11; F-18; RADIOPHARMACEUTICALS; PROTEINS; REAGENTS; ACETATE C1 [Riss, Patrick J.; Aigbirhio, Franklin I.] Univ Cambridge, Wolfson Brain Imaging Ctr, Cambridge CB2 0QQ, England. [Riss, Patrick J.; Lu, Shuiyu; Telu, Sanjay; Pike, Victor W.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. RP Riss, PJ (reprint author), Univ Cambridge, Wolfson Brain Imaging Ctr, Box 65 Addenbrookes Hosp, Cambridge CB2 0QQ, England. EM pr340@wbic.cam.ac.uk FU Medical Research Council (UK); NIH (NIMH) FX P.J.R. was supported by a Medical Research Council (UK) postdoctoral fellowship as a visiting volunteer worker at the NIH. S. T., S. L., and V. W. P. were supported by the Intramural Research Program of the NIH (NIMH). We thank Jinsoo Hong (NIMH) for technical assistance and the NIH Clinical PET department (Chief, Dr. P. Herscovitch) for 11C production. NR 36 TC 32 Z9 32 U1 3 U2 25 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2012 VL 51 IS 11 BP 2698 EP 2702 DI 10.1002/anie.201107263 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 904DL UT WOS:000301173800030 PM 22308017 ER PT J AU Huang, JH Hu, KN Ilgen, J Ilgen, G AF Huang, J. -H. Hu, K. -N. Ilgen, J. Ilgen, G. TI Occurrence and stability of inorganic and organic arsenic species in wines, rice wines and beers from Central European market SO FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT LA English DT Article DE beer; wine; trace elements; trace elements (toxic); chromatographic analysis ID SPECIATION; CHROMATOGRAPHY; SPECTROMETRY; BEVERAGES; WATER; GRAIN AB We investigated in total 80 wine samples of different types and seven grape juice and 23 beer samples purchased from markets in Central Europe in order to understand the arsenic (As) speciation and help assess the potential As toxicity via intake of alcoholic beverages. Generally, total As concentrations in most samples investigated were below the drinking water limit 10 mu g l(-1) published by the World Health Organization (WHO); ranging from 0.46 to 21.0 mu g l(-1) As in red and white wines and from 0.75 to 13.4 mu g l(-1) As in beers. In addition, concentrations of total As in rice wine and in rice beer were 0.63-6.07 and 3.69-8.23 mu g l(-1) As, respectively. The total As concentrations in ice wine ranged from 7.94 to 18.8 mu g l(-1) As, significantly higher than in white and red wine. Arsenite predominated as the As species in most of the wine samples, whereas arsenate was the dominant species in rice wine, beer and rice beer. Methyl As components were usually minor components in all wine and beer samples. Monomethylarsonic acid, dimethylarsinic acid and two additional unknown As species were frequently found in grape juice, late harvest and ice wine with higher sweetness. After air exposure, arsenite, arsenate, monomethylarsonic acid and dimethylarsinic acid were stable at 4 degrees C for months, probably due to the acidic conditions of wine and beer samples. The presence of sulfite had little influence on As speciation in wine. Despite the predominance of more toxic arsenite and arsenate in wine and beer, the estimated weekly exposure to As (via consumption of beer, wine and rice wine) is low. The As intake per capita is 6.81 mg from beer, 51.93 mg from wine and 0.88 mg from rice wine, estimated using the median of total As concentration multiplied by the average consumption per capita of the corresponding beverage. C1 [Huang, J. -H.] ETH, Inst Biogeochem & Pollutant Dynam, Swiss Fed Inst Technol Zurich, CH-8092 Zurich, Switzerland. [Hu, K. -N.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Ilgen, J.] Wein Bastion Ulm, D-89077 Ulm, Germany. [Ilgen, G.] Univ Bayreuth, Bayreuth Ctr Ecol & Environm Res BayCEER, D-95440 Bayreuth, Germany. RP Huang, JH (reprint author), ETH, Inst Biogeochem & Pollutant Dynam, Swiss Fed Inst Technol Zurich, CH-8092 Zurich, Switzerland. EM jenhow.huang@env.ethz.ch FU Swiss National Science Foundation [PZ00P2_122212]; National Institute of Diabetes Digestive and Kidney Diseases of the National Institutes of Health FX The authors are grateful to Wein-Bastion (Ulm, Germany) for providing white and red wine samples. They appreciate Christine Stocker, Simone Ott und Barbara Scheitler (University of Bayreuth) for help with laboratory work. The financial support of J. H. H. comes from the Swiss National Science Foundation Ambizione fellowship (PZ00P2_122212). K. N. H. is supported by a fellowship from the Intramural Research Program of the National Institute of Diabetes Digestive and Kidney Diseases of the National Institutes of Health. NR 24 TC 11 Z9 11 U1 11 U2 60 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1944-0049 J9 FOOD ADDIT CONTAM A JI Food Addit. Contam. Part A-Chem. PY 2012 VL 29 IS 1 BP 85 EP 93 DI 10.1080/19440049.2011.615029 PG 9 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 914FI UT WOS:000301934300010 PM 22026389 ER PT J AU Wojtkowska, M Jakalski, M Pienkowska, JR Stobienia, O Karachitos, A Przytycka, TM Weiner, J Kmita, H Makalowski, W AF Wojtkowska, Magorzata Jakalski, Marcin Pienkowska, Joanna R. Stobienia, Olgierd Karachitos, Andonis Przytycka, Teresa M. Weiner, January, III Kmita, Hanna Makalowski, Wojciech TI Phylogenetic Analysis of Mitochondrial Outer Membrane beta-Barrel Channels SO GENOME BIOLOGY AND EVOLUTION LA English DT Article DE mitochondrial beta-barrels; mitochondrial outer membrane; VDAC; Sam50/Tob55; Tom40; Acanthamoeba castellanii; Dictyostelium discoideum ID DEPENDENT ANION CHANNEL; MULTIPLE SEQUENCE ALIGNMENT; ACANTHAMOEBA-CASTELLANII MITOCHONDRIA; PROTEIN IMPORT; TOM COMPLEX; PRECURSOR PROTEINS; EVOLUTIONARY CONSERVATION; DICTYOSTELIUM-DISCOIDEUM; EUKARYOTIC SUPERGROUPS; ALTERNATIVE OXIDASE AB Transport of molecules across mitochondrial outer membrane is pivotal for a proper function of mitochondria. The transport pathways across the membrane are formed by ion channels that participate in metabolite exchange between mitochondria and cytoplasm (voltage-dependent anion-selective channel, VDAC) as well as in import of proteins encoded by nuclear genes (Tom40 and Sam50/Tob55). VDAC, Tom40, and Sam50/Tob55 are present in all eukaryotic organisms, encoded in the nuclear genome, and have beta-barrel topology. We have compiled data sets of these protein sequences and studied their phylogenetic relationships with a special focus on the position of Amoebozoa. Additionally, we identified these protein-coding genes in Acanthamoeba castellanii and Dictyostelium discoideum to complement our data set and verify the phylogenetic position of these model organisms. Our analysis show that mitochondrial beta-barrel channels from Archaeplastida (plants) and Opisthokonta (animals and fungi) experienced many duplication events that resulted in multiple paralogous isoforms and form well-defined monophyletic clades that match the current model of eukaryotic evolution. However, in representatives of Amoebozoa, Chromalveolata, and Excavata (former Protista), they do not form clearly distinguishable clades, although they locate basally to the plant and algae branches. In most cases, they do not posses paralogs and their sequences appear to have evolved quickly or degenerated. Consequently, the obtained phylogenies of mitochondrial outer membrane beta-channels do not entirely reflect the recent eukaryotic classification system involving the six supergroups: Chromalveolata, Excavata, Archaeplastida, Rhizaria, Amoebozoa, and Opisthokonta. C1 [Wojtkowska, Magorzata; Stobienia, Olgierd; Karachitos, Andonis; Kmita, Hanna] Adam Mickiewicz Univ, Lab Bioenerget, Inst Mol Biol & Biotechnol, Fac Biol, Poznan, Poland. [Jakalski, Marcin; Weiner, January, III; Makalowski, Wojciech] Univ Munster, Inst Bioinformat, Fac Med, Munster, Germany. [Pienkowska, Joanna R.] Adam Mickiewicz Univ, Inst Expt Biol, Dept Cell Biol, Fac Biol, Poznan, Poland. [Przytycka, Teresa M.] Natl Lib Med, NCBI, NIH, Computat Biol Branch, Bethesda, MD 20894 USA. RP Kmita, H (reprint author), Adam Mickiewicz Univ, Lab Bioenerget, Inst Mol Biol & Biotechnol, Fac Biol, Poznan, Poland. EM kmita@amu.edu.pl; wojmak@uni-muenster.de RI Weiner, January/D-9470-2012; Makalowski, Wojciech/I-2843-2016; OI Jakalski, Marcin/0000-0002-5481-9148 FU Polish Ministry of Science and Higher Education [N N303 143937]; 6.FP Marie Curie Host Fellowships for the Transfer of Knowledge grant (FUNGEN); IoB funds; National Institutes of Health, U.S. National Library of Medicine FX We are very grateful for the help received from Marcel Deponte and Walter Neupert. This project was supported by the Polish Ministry of Science and Higher Education (Grant N N303 143937) and the 6.FP Marie Curie Host Fellowships for the Transfer of Knowledge grant (FUNGEN). M.J. research was supported by the IoB funds. T.P. is supported by Intramural Research Program of the National Institutes of Health, U.S. National Library of Medicine. NR 91 TC 8 Z9 8 U1 0 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1759-6653 J9 GENOME BIOL EVOL JI Genome Biol. Evol. PY 2012 VL 4 IS 2 BP 110 EP 125 DI 10.1093/gbe/evr130 PG 16 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 914VJ UT WOS:000301980600004 PM 22155732 ER PT J AU He, J Li, J Sun, WJ Zhang, TY Ito, Y AF He, Jiao Li, Jing Sun, Wenji Zhang, Tianyou Ito, Yoichiro TI PREPARATIVE ISOLATION AND PURIFICATION OF THREE GLYCINE-CONJUGATED CHOLIC ACIDS FROM PULVIS FELLIS SUIS BY HIGH-SPEED COUNTERCURRENT CHROMATOGRAPHY COUPLED WITH ELSD DETECTION SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE glycine-conjugated cholic acids; high-speed countercurrent chromatography; Pulvis Fellis Suis; purification; separation; two-phase solvent system ID SEPARATION; ISOFLAVONE AB Coupled with evaporative light scattering detection, a high-speed counter-current chromatography (HSCCC) method was developed for preparative isolation and purification of three glycine-conjugated cholic acids, glycochenodeoxycholic acid (GCDCA), glycohyodeoxycholic acid (GHDCA), and glycohyocholic acid (GHCA) from Pulvis Fellis Suis (Pig gallbladder bile) for the first time. The separation was performed with a two-phase solvent system consisted of chloroform-methanol-water-acetic acid (65:30:10:1.5, v/v/v/v) by eluting the lower phase in the head-to-tail elution mode. The revolution speed of the separation column, flow rate of the mobile phase, and separation temperature were 800 rpm, 2 mL/min and 25 degrees C, respectively. In a single operation, 33 mg of GCDCA, 38 mg of GHDCA, and 23 mg of GHCA were obtained from 200 mg of crude extract with the purity of 95.65%, 96.72%, and 96.63%, respectively, in one-step separation. The HSCCC fractions were analyzed by high-performance liquid chromatography (HPLC) and the structures of the three glycine-conjugated cholic acids were identified by ESI-MS, H-1 NMR, and C-13 NMR. C1 [He, Jiao; Li, Jing; Sun, Wenji] NW Univ Xian, Biomed Key Lab Shaanxi Prov, Xian 710069, Peoples R China. [Zhang, Tianyou] Beijing Inst New Technol Applicat, Beijing, Peoples R China. [Ito, Yoichiro] NHLBI, Bioseparat Technol Lab, NIH, Bethesda, MD 20892 USA. [Ito, Yoichiro] NHLBI, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. RP Sun, WJ (reprint author), NW Univ Xian, Biomed Key Lab Shaanxi Prov, 229 Taibai N Rd, Xian 710069, Peoples R China. EM cxbml@nwu.edu.cn; itoy2@mail.nih.gov FU Northwest University of the People's Republic of China [09YZZ61]; Education Department of Shaanxi Provincial Government of the People's Republic of China [2010JS096] FX This work was financially supported in part by the Project of Graduate Innovation and Creativity Funds of Northwest University of the People's Republic of China (09YZZ61) and the Project of Scientific Research Plan of Education Department of Shaanxi Provincial Government of the People's Republic of China (2010JS096). NR 16 TC 1 Z9 1 U1 0 U2 11 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2012 VL 35 IS 5 BP 737 EP 746 DI 10.1080/10826076.2011.608231 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 916AX UT WOS:000302070000011 PM 23008527 ER PT J AU Zhao, YC Yang, S AF Zhao, Yichuan Yang, Song TI Empirical likelihood confidence intervals for regression parameters of the survival rate SO JOURNAL OF NONPARAMETRIC STATISTICS LA English DT Article DE chi-squared distribution; confidence interval; link function; right censoring ID LINEAR TRANSFORMATION MODELS; QUALITY-ADJUSTED LIFETIME; CENSORED-DATA; SEMIPARAMETRIC ANALYSIS; INFERENCE; BOOTSTRAP; TERM; CONSISTENCY; JACKKNIFE; TIME AB The survival probability of patients plays an important role in biomedical settings. Based on the Jung [(1996), 'Regression Analysis for Long-Term Survival Rate', Biometrika, 83, 227-232] regression model for survival probability, Zhao [(2005), 'Regression Analysis for Long-Term Survival Rate Via Empirical Likelihood', Journal of Nonparametric Statistics, 17, 995-1007] developed an empirical likelihood (EL) confidence region for the vector of regression parameters. However, the proposed EL method does not work for a subset of regression parameters. In this paper, we develop EL confidence regions for any subset or a linear combination of the vectors of the regression parameters under the regression model. We propose two kinds of confidence intervals for the survival rate of a patient with the given covariates. A simulation study is carried out to compare the proposed method with the normal approximation-based method and nonparametric bootstrap method. Finally, we compare the proposed procedure with the existing method using a clinical trial data set. C1 [Zhao, Yichuan] Georgia State Univ, Dept Math & Stat, Atlanta, GA 30303 USA. [Yang, Song] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Zhao, YC (reprint author), Georgia State Univ, Dept Math & Stat, Atlanta, GA 30303 USA. EM dz2007@gmail.com FU Research Initiation; Summer Research Grant; Department of Mathematics and Statistics, Georgia State University FX The authors thank the Editor-in-Chief, Professor Suojin Wang, one associate editor and the referee for careful reading of the manuscript, helpful comments and valuable remarks. These critical comments helped us to improve the previous version of the manuscript significantly. This research was partially supported by a Research Initiation Grant, a Summer Research Grant, Department of Mathematics and Statistics, Georgia State University. NR 28 TC 2 Z9 2 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1048-5252 J9 J NONPARAMETR STAT JI J. Nonparametr. Stat. PY 2012 VL 24 IS 1 BP 59 EP 70 DI 10.1080/10485252.2011.621024 PG 12 WC Statistics & Probability SC Mathematics GA 915VN UT WOS:000302055800005 ER PT J AU Baum, BJ AF Baum, Bruce J. TI The gene as a drug: exploring the possibilities with salivary glands SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 85th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 14-16, 2012 CL Kyoto, JAPAN SP Japanese Pharmacolog Soc C1 [Baum, Bruce J.] NIDCR, Gene Transfer Sect, NIH, USA, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2012 VL 118 SU 1 BP 3P EP 3P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 913MY UT WOS:000301883300009 ER PT J AU Furukawa-Hibi, Y Alkam, T Nitta, A Matsuyama, A Suzuki, K Greig, N Nagai, T Yamada, K AF Furukawa-Hibi, Yoko Alkam, Tursun Nitta, Atsumi Matsuyama, Akihiro Suzuki, Kazuhiko Greig, Nigel Nagai, Taku Yamada, Kiyofumi TI Butyrylcholinesterase inhibitors ameliorate cognitive dysfunction induced by amyloid-beta peptide in mice SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 85th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 14-16, 2012 CL Kyoto, JAPAN SP Japanese Pharmacolog Soc C1 [Furukawa-Hibi, Yoko; Alkam, Tursun; Matsuyama, Akihiro; Nagai, Taku; Yamada, Kiyofumi] Nagoya Univ, Grad Sch Med, Dept Neuropsychopharm & Hosp Pharm, Showa Ku, Nagoya, Aichi 4668560, Japan. [Nitta, Atsumi] Toyama Univ, Fac Pharm Sci, Dept Pharm Therapy & Neuropharm, Toyama 9300194, Japan. [Suzuki, Kazuhiko] Novartis Pharma KK, Translat Sci, Minato Ku, Tokyo 1068618, Japan. [Greig, Nigel] NIA, Drug Design & Dev Sect, Neurosci Lab, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2012 VL 118 SU 1 BP 109P EP 109P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 913MY UT WOS:000301883300371 ER PT J AU Cyphert, JM Padilla-Carlin, DJ Schladweiler, MC Shannahan, JH Nyska, A Kodavanti, UP Gavett, SH AF Cyphert, J. M. Padilla-Carlin, D. J. Schladweiler, M. C. Shannahan, J. H. Nyska, A. Kodavanti, U. P. Gavett, S. H. TI LONG-TERM RESPONSE OF RATS TO SINGLE INTRATRACHEAL EXPOSURE OF LIBBY AMPHIBOLE OR AMOSITE SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID MALIGNANT PLEURAL MESOTHELIOMA; CROCIDOLITE ASBESTOS; MURINE MACROPHAGES; MOLECULAR-CLONING; FISCHER-344 RATS; GENE-EXPRESSION; LUNG; MONTANA; CARCINOGENICITY; INSTILLATION AB In former mine workers and residents of Libby, Montana, exposure to amphibole-contaminated vermiculite has been associated with increased incidences of asbestosis and mesothelioma. In this study, long-term effects of Libby amphibole (LA) exposure were investigated relative to the well-characterized amosite asbestos in a rat model. Rat-respirable fractions of LA and amosite (aerodynamic diameter <= 2.5 mu m) were prepared by water elutriation. Male F344 rats were exposed to a single dose of either saline, amosite (0.65 mg/rat), or LA (0.65 or 6.5 mg/rat) by intratracheal (IT) instillation. One year after exposure, asbestos-exposed rats displayed chronic pulmonary inflammation and fibrosis. Two years postexposure, lung inflammation and fibrosis progressed in a time- and dose-dependent manner in LA-exposed rats, although the severity of inflammation and fibrosis was smaller in magnitude than in animals exposed to amosite. In contrast, gene expression of the fibrosis markers Col 1A2 and Col 3A1 was significantly greater in LA-exposed compared to amosite-exposed rats. There was no apparent evidence of preneoplastic changes in any of the asbestos-exposed groups. However, all asbestos-exposed rats demonstrated a significant increase in the expression of epidermal growth factor receptor (EGFR) 2 yr after instillation. In addition, only LA-exposed rats showed significant elevation in mesothelin (Msln) and Wilms' tumor gene (WT1) expression, suggesting possible induction of tumor pathways. These results demonstrate that a single IT exposure to LA is sufficient to induce significant fibrogenic, but not carcinogenic, effects up to 2 yr after exposure that differ both in quality and magnitude from those elicited by amosite administration at the same mass dose in F344 rats. Data showed that LA was on a mass basis less potent than amosite. C1 [Schladweiler, M. C.; Kodavanti, U. P.; Gavett, S. H.] US EPA, Cardiopulm & Immunotoxicol Branch, Environm Publ Hlth Div, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. [Cyphert, J. M.; Shannahan, J. H.] Univ N Carolina, Sch Med, Curriculum Toxicol, Chapel Hill, NC USA. [Padilla-Carlin, D. J.] Natl Inst Environm Hlth Sci, Ctr Risk & Integrated Sci, Div Extramural Res & Training, Res Triangle Pk, NC USA. [Nyska, A.] Tel Aviv Univ, Sackler Sch Med, Timrat, Israel. RP Gavett, SH (reprint author), US EPA, Cardiopulm & Immunotoxicol Branch, Environm Publ Hlth Div, Natl Hlth & Environm Effects Res Lab, Mail Drop B105-02,109 TW Alexander Dr, Res Triangle Pk, NC 27711 USA. EM Gavett.stephen@epa.gov FU U.S. EPA/UNC [CR 933237]; University of North Carolina at Chapel Hill FX This work was supported by the U.S. EPA/UNC Toxicology Research Program, Training Agreement CR 933237, with the Curriculum in Toxicology, University of North Carolina at Chapel Hill. The authors thank Judy Richards for technical assistance. NR 46 TC 11 Z9 11 U1 0 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PY 2012 VL 75 IS 3 BP 183 EP 200 DI 10.1080/15287394.2012.641203 PG 18 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 917NO UT WOS:000302184800005 PM 22251266 ER PT J AU Tsokos, M Alaggio, RD Dehner, LP Dickman, PS AF Tsokos, Maria Alaggio, Rita D. Dehner, Louis P. Dickman, Paul S. TI Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor and Related Tumors SO PEDIATRIC AND DEVELOPMENTAL PATHOLOGY LA English DT Article DE desmoplastic small round cell tumor; EWS gene rearrangement; EWS/pPNET; Ewing sarcoma; peripheral primitive neuroectodermal tumor ID ROUND-CELL TUMOR; CHILDRENS ONCOLOGY GROUP; EWS-WT1 GENE FUSION; AGGRESSIVE MULTIMODALITY THERAPY; MALIGNANT NEUROEPITHELIAL TUMORS; MESENCHYMAL PROGENITOR CELLS; PERIPHERAL NEURO-BLASTOMA; NATIONAL-WILMS-TUMOR; REGION ASKIN TUMOR; SARCOMA-FAMILY AB Ewing sarcoma/peripheral primitive neuroectodermal tumor (EWS/pPNET) and other tumors with EWS gene rearrangements encompass a malignant and intermediate neoplasm with a broad anatomic distribution and a wide age range but a predilection for soft tissue in children, adolescents, and young adults. The overlapping histologic, immunohistochemical and cytogenetic and molecular genetic features create diagnostic challenges despite significant clinical and prognostic differences. Ewing sarcoma is the 3rd most common sarcoma in children and adolescents, and desmoplastic small round cell tumor is a rare neoplasm that occurs more often in older children, adolescents, and young adults. Pathologic examination is complemented by immunohistochemistry, cytogenetics, and molecular genetics. This article reviews the clinicopathologic features of EWS/pPNET and desmoplastic small round cell tumor in the spectrum of tumors with EWS gene rearrangements. Other tumors with different histopathologic features and an EWS gene rearrangement are discussed elsewhere in this volume. C1 [Dickman, Paul S.] Phoenix Childrens Hosp, Dept Pathol, Phoenix, AZ USA. [Dickman, Paul S.] Univ Arizona, Coll Med, Phoenix, AZ USA. [Tsokos, Maria] NIH, Dept Pathol, Bethesda, MD 20892 USA. [Alaggio, Rita D.] Univ Hosp Padova, Dept Pathol, Padua, Italy. [Dehner, Louis P.] Washington Univ, Dept Pathol, Lauren V Ackerman Div Surg Pathol, Barnes Jewish Hosp,Med Ctr, St Louis, MO 63130 USA. [Dehner, Louis P.] Washington Univ, St Louis Childrens Hosp, Med Ctr, St Louis, MO 63130 USA. RP Dickman, PS (reprint author), Phoenix Childrens Hosp, Dept Pathol, Phoenix, AZ USA. EM pdickman@phoenixchildrens.com NR 236 TC 28 Z9 32 U1 0 U2 4 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1093-5266 EI 1615-5742 J9 PEDIATR DEVEL PATHOL JI Pediatr. Dev. Pathol. PD JAN PY 2012 VL 15 SU 1 BP 108 EP 126 DI 10.2350/11-08-1078-PB.1 PG 19 WC Pathology; Pediatrics SC Pathology; Pediatrics GA 913ZN UT WOS:000301916300006 PM 22420726 ER PT S AU Maas, S AF Maas, Stefan BE Marintchev, A TI POSTTRANSCRIPTIONAL RECODING BY RNA EDITING SO ADVANCES IN PROTEIN CHEMISTRY AND STRUCTURAL BIOLOGY, VOL 86: FIDELITY AND QUALITY CONTROL IN GENE EXPRESSION SE Advances in Protein Chemistry and Structural Biology LA English DT Review; Book Chapter ID DOUBLE-STRANDED-RNA; PRE-MESSENGER-RNA; DYSCHROMATOSIS SYMMETRICA HEREDITARIA; ADENOSINE-DEAMINASE GENE; AMYOTROPHIC-LATERAL-SCLEROSIS; ERYTHEMATOSUS T-LYMPHOCYTES; GLUTAMATE-RECEPTOR RNA; IN-VITRO; Z-DNA; MAMMALIAN-CELLS AB The posuranscriptional recoding of nuclear RNA transcripts has emerged as an important regulatory mechanism during eukaryotic gene expression. In particular the deamination of adenosine to inosine (interpreted by the translational machinery as a guanosine) is a frequent event that can recode the meaning of amino acid codons in translated exons, lead to structural changes in the RNA fold, or may affect splice consensus or regulatory sequence sites in noncoding exons or introns and modulate the biogenesis of small RNAs. The molecular mechanism of how the RNA editing machinery and its substrates recognize and interact with each other is not understood well enough to allow for the ab initio delineation of bona fide RNA editing sites. However, progress in the identification of various physiological modification sites and their characterization has given important insights regarding molecular features and events critical for productive RNA editing reactions. In addition, structural studies using components of the RNA editing machinery and together with editing competent substrate molecules have provided information on the chemical mechanism of adenosine deamination within the context of RNA molecules. Here, I give an overview of the process of adenosine deamination RNA editing and describe its relationship to other RNA processing events and its currently established roles in gene regulation. C1 [Maas, Stefan] Lehigh Univ, Dept Biol Sci, Bethlehem, PA 18015 USA. RP Maas, S (reprint author), NIGMS, NIH, Bethesda, MD 20892 USA. NR 143 TC 17 Z9 20 U1 2 U2 9 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1876-1623 BN 978-0-12-386497-0 J9 ADV PROTEIN CHEM STR JI Adv. Protein Chem. Struct. Biol. PY 2012 VL 86 BP 193 EP 224 DI 10.1016/B978-0-12-386497-0.00006-2 PG 32 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BZG70 UT WOS:000301550900006 PM 22243585 ER PT S AU Mindell, JA AF Mindell, Joseph A. BE Julius, D Clapham, DE TI Lysosomal Acidification Mechanisms SO ANNUAL REVIEW OF PHYSIOLOGY, VOL 74 SE Annual Review of Physiology LA English DT Review; Book Chapter DE V-ATPase; transporter; ClC-7; channel; counterion ID VACUOLAR H+-ATPASE; AUTOSOMAL-DOMINANT OSTEOPETROSIS; CLC CHLORIDE CHANNELS; MUCOLIPIDOSIS TYPE-IV; RAT-LIVER LYSOSOMES; YEAST V-ATPASE; PROTON PUMP; CYSTIC-FIBROSIS; IN-VIVO; PROKARYOTIC HOMOLOG AB Lysosomes, the terminal organelles on the endocytic pathway, digest macromolecules and make their components available to the cell as nutrients. Hydrolytic enzymes specific to a wide range of targets reside within the lysosome; these enzymes are activated by the highly acidic pH (between 4.5 and 5.0) in the organelles' interior. Lysosomes generate and maintain their pH gradients by using the activity of a proton-pumping V-type ATPase, which uses metabolic energy in the form of ATP to pump protons into the lysosome lumen. Because this activity separates electric charge and generates a transmembrane voltage, another ion must move to dissipate this voltage for net pumping to occur. This so-called counterion may be either a cation (moving out of the lysosome) or an anion (moving into the lysosome). Recent data support the involvement of ClC-7, a Cl-/H+ antiporter, in this process, although many open questions remain as to this transporter's involvement. Although functional results also point to a cation transporter, its molecular identity remains uncertain. Both the V-ATPase and the counterion transporter are likely to be important players in the mechanisms determining the steady-state pH of the lysosome interior. Exciting new results suggest that lysosomal pH may be dynamically regulated in some cell types. C1 Natl Inst Neurol Disorders & Stroke, Membrane Transport Biophys Sect, NIH, Bethesda, MD 20892 USA. RP Mindell, JA (reprint author), Natl Inst Neurol Disorders & Stroke, Membrane Transport Biophys Sect, NIH, Bethesda, MD 20892 USA. EM mindellj@ninds.nih.gov OI Mindell, Joseph/0000-0002-6952-8247 NR 92 TC 170 Z9 171 U1 9 U2 49 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4278 BN 978-0-8243-0374-7 J9 ANNU REV PHYSIOL JI Annu. Rev. Physiol. PY 2012 VL 74 BP 69 EP 86 DI 10.1146/annurev-physiol-012110-142317 PG 18 WC Physiology SC Physiology GA BZJ96 UT WOS:000301794000004 PM 22335796 ER PT J AU Swierczewska, M Liu, G Lee, S Chen, XY AF Swierczewska, Magdalena Liu, Gang Lee, Seulki Chen, Xiaoyuan TI High-sensitivity nanosensors for biomarker detection SO CHEMICAL SOCIETY REVIEWS LA English DT Review ID SURFACE-PLASMON RESONANCE; ENHANCED RAMAN-SCATTERING; SINGLE-NANOPARTICLE SERS; FIELD-EFFECT TRANSISTORS; LABEL-FREE DETECTION; ELECTRICAL DETECTION; ULTRASENSITIVE DETECTION; GOLD NANOPARTICLES; ALZHEIMERS-DISEASE; DIFFERENT SHAPES AB High sensitivity nanosensors utilize optical, mechanical, electrical, and magnetic relaxation properties to push detection limits of biomarkers below previously possible concentrations. The unique properties of nanomaterials and nanotechnology are exploited to design biomarker diagnostics. High-sensitivity recognition is achieved by signal and target amplification along with thorough pre-processing of samples. In this tutorial review, we introduce the type of detection signals read by nanosensors to detect extremely small concentrations of biomarkers and provide distinctive examples of high-sensitivity sensors. The use of such high-sensitivity nanosensors can offer earlier detection of disease than currently available to patients and create significant improvements in clinical outcomes. C1 [Swierczewska, Magdalena; Liu, Gang; Lee, Seulki; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Swierczewska, Magdalena] SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA. [Liu, Gang] N Sichuan Med Coll, Sichuan Key Lab Med Imaging, Nanchong 637007, Peoples R China. RP Lee, S (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, 31 Ctr Dr 1C22, Bethesda, MD 20892 USA. EM Seulki.Lee@nih.gov; Shawn.Chen@nih.gov FU National Institutes of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH); Henry M. Jackson Foundation; NIH Pathway to Independence (China) [K99/R00, 2011JQ00322011JQ0032] FX This work was supported by the Intramural Research Program (IRP) of the National Institutes of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) and the Henry M. Jackson Foundation. This work was partially supported by the NIH Pathway to Independence (K99/R00) Award and 2011JQ0032&2011JQ0032 (China). NR 69 TC 83 Z9 86 U1 20 U2 189 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0306-0012 J9 CHEM SOC REV JI Chem. Soc. Rev. PY 2012 VL 41 IS 7 BP 2641 EP 2655 DI 10.1039/c1cs15238f PG 15 WC Chemistry, Multidisciplinary SC Chemistry GA 906OH UT WOS:000301354900009 PM 22187721 ER PT J AU Nagpal, R Behare, PV Kumar, M Mohania, D Yadav, M Jain, S Menon, S Parkash, O Marotta, F Minelli, E Henry, CJK Yadav, H AF Nagpal, R. Behare, P. V. Kumar, M. Mohania, D. Yadav, M. Jain, S. Menon, S. Parkash, O. Marotta, F. Minelli, E. Henry, C. J. K. Yadav, H. TI Milk, Milk Products, and Disease Free Health: An Updated Overview SO CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION LA English DT Review DE Milk; dairy products; synbiotics; functional foods; therapeutic foods ID ANTIBIOTIC-ASSOCIATED DIARRHEA; PLACEBO-CONTROLLED TRIAL; I-CONVERTING-ENZYME; HIGH-FRUCTOSE DIET; PROBIOTIC BACTERIA; DAIRY-PRODUCTS; LACTOBACILLUS-ACIDOPHILUS; LACTOSE-INTOLERANCE; FUNCTIONAL FOODS; BIFIDOBACTERIUM-LONGUM AB The cow and its milk have been held sacred in the world since the dawn of human civilization. Indian ancient Vedic texts describe the virtues of milk and dairy products, as is authenticated by modern scientific principles and proofs. Therefore, milk has been considered as one of the most natural and highly nutritive part of a daily balanced diet. Currently, the integration of advanced scientific knowledge with traditional information is gaining incredible momentum toward developing the concept of potential therapeutic foods. Furthermore, new advances toward understanding the therapeutic roles of milk and milk products have also given a new impetus for unraveling the age old secrets of milk. At present, the best-known examples of therapeutic foods are fermented milk products containing health promoting probiotic bacteria. In the present article, we have tried to review the various aspects of the therapeutic nature of milk and fermented dairy products in a highly up-dated manner, and offer an in-depth insight into the development of targeted therapeutic future foods as per the requirements of consumers. C1 [Yadav, H.] NIDDKD, CRC, DB, NIH, Bethesda, MD 20892 USA. [Nagpal, R.] Lovely Profess Univ, Sch Sci & Technol, Dept Biotechnol, Phagwara, Punjab, India. [Behare, P. V.; Kumar, M.] Natl Dairy Res Inst, Dairy Microbiol Div, Karnal, India. [Mohania, D.] Natl Dairy Res Inst, Anim Biochem Div, Karnal 132001, Haryana, India. [Yadav, M.] Jiwaji Univ, Sch Studies Chem, Gwalior, MP, India. [Jain, S.] Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. [Menon, S.] Birla Inst Technol, Dept Biotechnol, Ranchi, Bihar, India. [Parkash, O.] Natl JALMA Inst Leprosy & Other Mycobacterial Dis, Agra, Uttar Pradesh, India. [Marotta, F.; Minelli, E.] GAIA Age Management Fdn, Nutraceut Nutrigen Unit, Pavia, Italy. [Henry, C. J. K.] Oxford Brookes Univ, Sch Biol & Mol Sci, Oxford OX3 0BP, England. RP Yadav, H (reprint author), NIDDKD, CRC, DB, NIH, 5W5872,Bldg 10, Bethesda, MD 20892 USA. EM yadavhariom@gmail.com OI Yadav, Hariom/0000-0003-4504-1597 NR 119 TC 25 Z9 25 U1 11 U2 72 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-8398 J9 CRIT REV FOOD SCI JI Crit. Rev. Food Sci. Nutr. PY 2012 VL 52 IS 4 BP 321 EP 333 DI 10.1080/10408398.2010.500231 PG 13 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA 908XW UT WOS:000301527400003 PM 22332596 ER PT S AU Imamichi, T Yang, J Huang, DW Sherman, B Lempicki, RA AF Imamichi, Tomozumi Yang, Jun Huang, Da Wei Sherman, Brad Lempicki, Richard A. BE Ley, MD TI Interleukin-27 Induces Interferon-Inducible Genes: Analysis of Gene Expression Profiles Using Aftymetrix Microarray and DAVID SO CYTOKINE PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE IL-27; IFN-inducible genes; Microarray; DAVID; T cells; Macrophages ID IL-27; CYTOKINE; ALGORITHMS; LISTS AB We have previously demonstrated that IL-27 is a novel anti-HIV cytokine, which inhibits HIV replication in CD4 T cells and macrophages as interferon (IFN)-alpha does. To further understand the mechanism of the antiviral effect, we performed Affymetrix DNA microarray and gene functional annotation analysis using DAVID (the Database for Annotation, Visualization, and Integrated Discovery). DAVID is a web-based bioinformatics application that systematically identifies enriched biology associated with large gene list(s) derived from high-throughput genomic experiments, such as microarray. The enriched annotation terms identified by DAVID will give important insights into understanding the biological themes under study. Having used the DAVID bioinformatics tools, we have shown that IL-27 differentially regulates the gene expression between T cells and macrophages. IL-27 significantly induces IFN-inducible genes including antiviral genes in macrophages as does IFN-alpha, suggesting that IL-27 inhibits HIV replication in macrophages via a mechanism similar to that of IFN-alpha. C1 [Imamichi, Tomozumi] NCI, Lab Human Retrovirol, CSP, ADD,Sci Applicat Int Corp SAIC Frederick Inc, Frederick, MD 21702 USA. [Yang, Jun; Huang, Da Wei; Sherman, Brad; Lempicki, Richard A.] NCI, Lab Immunopathogenesis & Bioinformat, CSP, ADD,SAIC Frederick Inc, Frederick, MD 21702 USA. RP Imamichi, T (reprint author), NCI, Lab Human Retrovirol, CSP, ADD,Sci Applicat Int Corp SAIC Frederick Inc, Frederick, MD 21702 USA. RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X NR 14 TC 5 Z9 5 U1 1 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-438-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 820 BP 25 EP 53 DI 10.1007/978-1-61779-439-1_3 D2 10.1007/978-1-61779-439-1 PG 29 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BYN05 UT WOS:000299396700003 PM 22131024 ER PT S AU Chepelev, I AF Chepelev, Iouri BE Kaufmann, M Klinger, C TI Detection of RNA Editing Events in Human Cells Using High-Throughput Sequencing SO FUNCTIONAL GENOMICS: METHODS AND PROTOCOLS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE RNA editing; Single nucleotide variants; High-throughput sequencing; Bioinformatics; Human immunodeficiency virus infection ID HUMAN GENOME; IDENTIFICATION; DATABASE; REPAIR; SITES; SEQ AB RNA editing can lead to amino acid substitutions in protein sequences, alternative pre-mRNA splicing, and changes in gene expression levels. The exact in vivo modes of interaction of the RNA editing enzymes with their targets are not well understood. Alterations in RNA editing have been linked to various human disorders and the improved understanding of the editing mechanism and specificity can explain the phenotypes that result from misregulation of RNA editing. Unbiased high-throughput methods of detection of RNA editing events genome-wide in human cells are necessary for the task of deciphering the RNA editing regulatory code. With the rapidly falling cost of genome resequencing, the future method of choice for the detection of RNA editing events will be whole-genome gDNA and cDNA sequencing. We describe a detailed procedure for the computational identification of RNA editing targets using the data from the deep sequencing of DNA and RNA from the peripheral blood mononuclear cells of a human individual with severe hemophilia A who is resistant to HIV infection. Interestingly, we find that mRNAs of the cyclin-dependent kinase CDK13 and the DNA repair enzyme NEIL1 undergo extensive A -> I RNA editing that leads to amino acid substitutions in protein sequences. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Chepelev, I (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 HL999999] NR 23 TC 5 Z9 7 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-423-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 815 BP 91 EP 102 DI 10.1007/978-1-61779-424-7_8 D2 10.1007/978-1-61779-424-7 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BYN04 UT WOS:000299396500008 PM 22130986 ER PT S AU Davey, AM Liu, WL Sohn, HW Brzostowski, J Pierce, SK AF Davey, Angel M. Liu, Wanli Sohn, Hae Won Brzostowski, Joseph Pierce, Susan K. BE Conn, PM TI UNDERSTANDING THE INITIATION OF B CELL SIGNALING THROUGH LIVE CELL IMAGING SO IMAGING AND SPECTROSCOPIC ANALYSIS OF LIVING CELLS: IMAGING LIVE CELLS IN HEALTH AND DISEASE SE Methods in Enzymology LA English DT Review; Book Chapter ID INTERNAL-REFLECTION FLUORESCENCE; RESONANCE ENERGY-TRANSFER; SINGLE-MOLECULE TRACKING; PLASMA-MEMBRANE; ANTIGEN RECEPTOR; LYMPH-NODE; SUBCAPSULAR SINUS; LIVING CELLS; MICROSCOPY; LEISHMANIASIS AB Antibody responses are initiated by the binding of antigens to clonally distributed cell surface B cell receptors (BCRs) that trigger signaling cascades resulting in B cell activation. Using conventional biochemical approaches, the components of the downstream BCR signaling pathways have been described in considerable detail. However, far less is known about the early molecular events by which the binding of antigens to the BCRs initiates BCR signaling. With the recent advent of high resolution, high speed, live cell, and single molecule imaging technologies, these events are just beginning to be elucidated. Understanding the molecular mechanisms underlying the initiation of BCR signaling may provide new targets for therapeutics to block dysregulated BCR signaling in systemic autoimmune diseases and in B cell tumors and to aid in the design of protein subunit vaccines. In this chapter, we describe the general procedures for using these new imaging techniques to investigate the early events in the initiation of BCR signaling. C1 [Davey, Angel M.; Liu, Wanli; Sohn, Hae Won; Brzostowski, Joseph; Pierce, Susan K.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Pierce, SK (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RI liu, wanli/H-5690-2011 OI liu, wanli/0000-0003-2624-6802 FU Intramural NIH HHS [ZIA AI000898-11] NR 37 TC 3 Z9 3 U1 2 U2 11 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-391856-7 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2012 VL 506 BP 265 EP 290 DI 10.1016/B978-0-12-391856-7.00038-X PG 26 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BZG25 UT WOS:000301476100014 PM 22341229 ER PT J AU Soman, G Kallarakal, AT Michiel, D Yang, XY Saptharishi, N Jiang, HG Giardina, S Gilly, J Mitra, G AF Soman, Gopalan Kallarakal, Abraham T. Michiel, Dennis Yang, Xiaoyi Saptharishi, Nirmala Jiang, Hengguang Giardina, Steve Gilly, John Mitra, George TI Analytical characterization of ch14.18 A mouse-human chimeric disialoganglioside-specific therapeutic antibody SO MABS LA English DT Article DE monoclonal antibodies; chimeric antibody; characterization assays; SEC-MALS; imaged cIEF; N-glycoprofiling; N-glycan analysis; Fc gamma RIIIA:ch14.18 interaction; surface plasmon resonance; complement-dependent cytotoxicity ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ANTIGANGLIOSIDE GD2 ANTIBODY; FC-GAMMA-RIII; MONOCLONAL-ANTIBODIES; ANTI-GD2-ANTIBODY CH14.18; CELL-PROLIFERATION; EFFECTOR FUNCTIONS; NEUROBLASTOMA; CYTOTOXICITY; PERSPECTIVE AB Ch14.18 is a mouse-human chimeric monoclonal antibody to the disialoganglioside (GD2) glycolipid. In the clinic, this antibody has been shown to be effective in the treatment of children with high-risk neuroblastoma, either alone or in combination therapy. Extensive product characterization is a prerequisite to addressing the potential issues of product variability associated with process changes and manufacturing scale-up. Charge heterogeneity, glycosylation profile, molecular state and aggregation, interaction (affinity) with Fc gamma receptors and functional or biological activities are a few of the critical characterization assays for assessing product comparability for this antibody. In this article, we describe the in-house development and qualification of imaged capillary isoelectric focusing to assess charge heterogeneity, analytical size exclusion chromatography with online static and dynamic light scattering (DLS), batch mode DLS for aggregate detection, biosensor (surface plasmon resonance)-based Fc gamma receptor antibody interaction kinetics, N-glycoprofiling with PNGase F digestion, 2-aminobenzoic acid labeling and high performance liquid chromatography and N-glycan analysis using capillary electrophoresis. In addition, we studied selected biological activity assays, such as complement-dependent cytotoxicity. The consistency and reproducibility of the assays are established by comparing the intra-day and inter-day assay results. Applications of the methodologies to address stability or changes in product characteristics are also reported. The study results reveal that the ch14.18 clinical product formulated in phosphate-buffered saline at a concentration of 5 mg/ml and stored at 2-8 degrees C is stable for more than five years. C1 [Soman, Gopalan; Kallarakal, Abraham T.; Michiel, Dennis; Yang, Xiaoyi; Saptharishi, Nirmala; Jiang, Hengguang; Giardina, Steve; Gilly, John; Mitra, George] NCI, Biopharmaceut Dev Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Soman, G (reprint author), NCI, Biopharmaceut Dev Program, SAIC Frederick Inc, Frederick, MD 21701 USA. EM somang@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Division of Cancer Treatment and Diagnosis of the National Cancer Institute; Biological Resources Branch of NCI FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US government. This research was supported in part by the Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the National Cancer Institute.; We would like to acknowledge the support and encouragement from Dr. Stephen P. Creekmore (chief of Biological Resources Branch of NCI) and Dr. Karen Muszynski (Program Director, Biological Resources Branch, NCI). We would also like to acknowledge the technical support from Ms. Eying Chen during the initial stages of this work. The generous supply of purified clinical grade ch14.18 from the Biopharmaceutical Development Program (BDP; SAIC-Frederick, Inc.,) manufacturing group is greatly appreciated. We also would like to thank the BDP process analytics group for providing the infusion mock model processed samples. NR 41 TC 4 Z9 4 U1 0 U2 12 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1942-0862 J9 MABS-AUSTIN JI mAbs PD JAN-FEB PY 2012 VL 4 IS 1 BP 84 EP 100 DI 10.4161/mabs.4.1.18566 PG 17 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 913WH UT WOS:000301907600007 PM 22327432 ER PT J AU Fukushige, T Krause, M AF Fukushige, Tetsunari Krause, Michael TI Myogenic conversion and transcriptional profiling of embryonic blastomeres in Caenorhabditis elegans SO METHODS LA English DT Article DE Myogenesis; Caenorhabditis elegans; Blastomere conversion; Cell fate; HLH-1; Transcription ID C-ELEGANS; GENETIC INTERFERENCE; REGULATORY NETWORK; POLARITY SIGNALS; MUSCLE; LINEAGE; PROTEIN; EXPRESSION; KINASE; POTENT AB Myogenesis has proven to be a powerful paradigm for understanding cell fate specification and differentiation in many model organisms. This includes the nematode Caenorhabditis elegans for which the genetic, cellular, and molecular tools have allowed an in-depth understanding of muscle development. One tool not yet available in C. elegans is a robust, pure and prolific cell culture system to study myogenesis. As an alternative, this chapter describes a method by which the cell fates of early, uncommitted blastomeres in the embryo are converted to a myogenic lineage. This technique permits the nearly synchronous induction of myogenesis in vivo with the potential to generate a nearly homogeneous population of cells. Coupled with the RNA isolation and cDNA amplification methods that are also described, one can now profile gene expression throughout myogenesis using any platform of choice (e.g. expression arrays, next generation sequencing). Although limited by the artificial nature of this developing mass of muscle inside the eggshell, blastomere conversion and transcriptional profiling is a very powerful tool to investigate changes in gene expression associated with myogenesis in C. elegans that is applicable to many different cell types. When coupled with next generation sequencing, the method has the potential to yield a very high-resolution map of changes in gene expression throughout myogenesis. Published by Elsevier Inc. C1 [Fukushige, Tetsunari; Krause, Michael] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Krause, M (reprint author), NIDDK, Mol Biol Lab, NIH, Bldg 5,Room B1-04,9000 Rockville Pike, Bethesda, MD 20892 USA. EM mwkrause@helix.nih.gov OI Krause, Michael/0000-0001-6127-3940 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health FX This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the Intramural Research Program of the National Institutes of Health. NR 24 TC 5 Z9 5 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD JAN PY 2012 VL 56 IS 1 BP 50 EP 54 DI 10.1016/j.ymeth.2011.10.001 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 913VY UT WOS:000301906700008 PM 22019720 ER PT J AU Hernandez, DG Singleton, AB AF Hernandez, Dena G. Singleton, Andrew B. TI Using DNA Methylation to Understand Biological Consequences of Genetic Variability SO NEURODEGENERATIVE DISEASES LA English DT Review DE Methylation; Genetic variability; Quantitative trait loci; Genome-wide association ID GENOME-WIDE ASSOCIATION; BREAST-CANCER CELLS; CPG ISLAND SHORES; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; CHROMATIN; HISTONE; EPIGENOMICS; MECHANISMS; EXPRESSION AB The advent of high-content genomic mapping technologies has provided numerous clues about the genetic architecture of complex disease and the tools with which to understand the biological framework resulting from this architecture. We believe that understanding and mapping epigenetic marks, in particular DNA methylation, which is suited to such assays, offers a timely opportunity in this context. Here, we make an argument for this work, describing this opportunity, the likely path ahead, and the problems and pitfalls associated with such work. Copyright (C) 2011 S. Karger AG, Basel C1 [Hernandez, Dena G.; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Hernandez, DG (reprint author), NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RI Singleton, Andrew/C-3010-2009 FU National Institute on Aging, National Institutes of Health, Department of Health and Human Services [Z01 AG000932-03] FX This work was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services (project No. Z01 AG000932-03). NR 62 TC 5 Z9 5 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2012 VL 9 IS 2 BP 53 EP 59 DI 10.1159/000333097 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 888AH UT WOS:000299975700001 PM 22123027 ER PT S AU Wilhite, SE Barrett, T AF Wilhite, Stephen E. Barrett, Tanya BE Wang, J Tan, AC Tian, T TI Strategies to Explore Functional Genomics Data Sets in NCBI's GEO Database SO NEXT GENERATION MICROARRAY BIOINFORMATICS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Editorial Material; Book Chapter DE Database; Microarray; Next-generation sequence; Gene expression; Epigenomics; Functional genomics; Data mining ID EXPRESSION; INFORMATION; GENES AB The Gene Expression Omnibus (GEO) database is a major repository that stores high-throughput functional genomics data sets that are generated using both microarray-based and sequence-based technologies. Data sets are submitted to GEO primarily by researchers who are publishing their results in journals that require original data to be made freely available for review and analysis. In addition to serving as a public archive for these data, GEO has a suite of tools that allow users to identify, analyze, and visualize data relevant to their specific interests. These tools include sample comparison applications, gene expression profile charts, data set clusters, gcnome browser tracks, and a powerful search engine that enables users to construct complex queries. C1 [Wilhite, Stephen E.; Barrett, Tanya] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Wilhite, SE (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 LM999999] NR 12 TC 12 Z9 14 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-399-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 802 BP 41 EP 53 DI 10.1007/978-1-61779-400-1_3 D2 10.1007/978-1-61779-400-1 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA BYQ68 UT WOS:000299796400003 PM 22130872 ER PT S AU Narlikar, L Jothi, R AF Narlikar, Leelavati Jothi, Raja BE Wang, J Tan, AC Tian, T TI ChIP-Seq Data Analysis: Identification of Protein-DNA Binding Sites with SISSRs Peak-Finder SO NEXT GENERATION MICROARRAY BIOINFORMATICS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE ChIP-Seq; SISSRs; Protein DNA-interaction; Binding sites; Transcription factor; Next-generation sequencing; Genomics ID EMBRYONIC STEM-CELLS; TRANSCRIPTIONAL NETWORK; HUMAN GENOME; PATHWAYS; LOCATION; GENE AB Protein-DNA interactions play key roles in determining gene-expression programs during cellular development and differentiation. Chromatin immunoprecipitation (ChIP) is the most widely used assay for probing such interactions. With recent advances in sequencing technology, ChIP-Seq, an approach that combines ChIP and next-generation parallel sequencing is fast becoming the method of choice for mapping protein DNA interactions on a genome-wide scale. Here, we briefly review the ChIP-Seq approach for mapping protein DNA interactions and describe the use of the SISSRs peak-finder, a software tool for precise identification of protein DNA binding sites from sequencing data generated using ChIP-Seq. C1 [Narlikar, Leelavati; Jothi, Raja] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Narlikar, Leelavati] Univ Pune, Ctr Modeling & Simulat, Pune, Maharashtra, India. RP Narlikar, L (reprint author), NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RI Jothi, Raja/G-3780-2015 FU Intramural NIH HHS [ZIA ES102625-02] NR 25 TC 15 Z9 15 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-399-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 802 BP 305 EP 322 DI 10.1007/978-1-61779-400-1_20 D2 10.1007/978-1-61779-400-1 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA BYQ68 UT WOS:000299796400020 PM 22130889 ER PT B AU Rangel, MC Castro, NP Karasawa, H Nagaoka, T Salomon, DS Bianco, C AF Rangel, Maria Cristina Castro, Nadia P. Karasawa, Hideaki Nagaoka, Tadahiro Salomon, David S. Bianco, Caterina BE Hayat, MA TI Cripto-1: A Common Embryonic Stem Cell and Cancer Cell Marker SO STEM CELLS AND CANCER STEM CELLS: THERAPEUTIC APPLICATIONS IN DISEASE AND INJURY SE Stem Cells and Cancer Stem Cells LA English DT Article; Book Chapter DE Cripto-1; Epidermal growth factor; Embryonic development; Mammary hyperplasias; Papillary adenocarcinomas; Embryonic stem cells ID MAMMARY EPITHELIAL-CELLS; TRANSGENIC MICE; MESENCHYMAL TRANSITION; SIGNALING PATHWAY; PROMOTES; GROWTH; OVEREXPRESSION; TUMORIGENESIS; TUMORS; GLAND AB Human Cripto-1 has been implicated in embryogenesis and tumorigenesis. During early embryonic development, Cripto-1 functions as a coreceptor for transforming growth factor-beta family members, including Nodal/growth differentiation factors 1 and 3, and is essential for mesoderm and endoderm formation and anterior/posterior and left-right axis establishment. In normal adult tissues Cripto-1 is expressed at very low levels, while its expression significantly increases in approximately 50-80% of different types of human carcinomas. Overexpression of Cripto-1 in mouse mammary epithelial cells leads to their transformation in vitro and enhances migration, invasion, branching morphogenesis and epithelial to mesenchymal transition. Transgenic mouse studies have shown that overexpression of Cripto-1 in the mammary gland results in mammary hyperplasias and papillary adenocarcinomas. Furthermore, Cripto-1 is expressed at high levels in different types of human tumors. In conclusion, while during embryogenesis Cripto-1 performs specific and regulatory functions related to cell and tissue patterning, inappropriate expression of Cripto-1 in adult tissues leads to cell transformation and tumor progression. C1 [Rangel, Maria Cristina; Castro, Nadia P.; Karasawa, Hideaki; Nagaoka, Tadahiro; Salomon, David S.; Bianco, Caterina] NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Bianco, C (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM biancoc@mail.nih.gov RI Rangel, Maria Cristina/P-7216-2014 OI Rangel, Maria Cristina/0000-0002-8002-9617 NR 38 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-94-007-2015-2 J9 STEM CELL CANC STEM PY 2012 VL 2 BP 155 EP 166 DI 10.1007/978-94-007-2016-9_17 D2 10.1007/978-94-007-2016-9 PG 12 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA BZJ08 UT WOS:000301749800017 ER PT S AU Buck, CB Trus, BL AF Buck, Christopher B. Trus, Benes L. BE Rossmann, MG Rao, VB TI The Papillomavirus Virion: A Machine Built to Hide Molecular Achilles' Heels SO VIRAL MOLECULAR MACHINES SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID MINOR CAPSID PROTEIN; SURFACE HEPARAN-SULFATE; HUMAN ALPHA-DEFENSINS; CROSS-NEUTRALIZING EPITOPE; BOVINE PAPILLOMAVIRUS; EPIDERMODYSPLASIA VERRUCIFORMIS; EXTRACELLULAR-MATRIX; POLYOMA TYPE; IN-VITRO; CRYOELECTRON MICROSCOPY AB Papillomaviruses are a diverse group of DNA viruses that infect the skin and mucosal tissues of vertebrates. More than 100 distinct human papillomavirus (HPV) genotypes have so far been identified. A subset of HPVs is known to cause human cancer. Although recently developed vaccines protect vaccinated individuals from the two most carcinogenic HPV types, there is a pressing need for next-generation vaccines that might offer broad-spectrum protection against the full range of cancer-causing HPVs. The ongoing development of such vaccines will be facilitated by a deeper understanding of the mechanics of the assembly of the nonenveloped papillomavirus virion, as well as the machinelike structural changes that occur in the virion during the process of infectious entry into host cells. This chapter reviews the field's current knowledge of these two aspects of papillomavirus biology and speculates about areas where further work is needed. C1 [Buck, Christopher B.] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. [Trus, Benes L.] NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. [Trus, Benes L.] NIH, Imaging Sci Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Buck, CB (reprint author), NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. EM buckc@nih.gov OI Buck, Christopher/0000-0003-3165-8094 FU Intramural NIH HHS NR 113 TC 12 Z9 12 U1 0 U2 4 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-0980-9 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2012 VL 726 BP 403 EP 422 DI 10.1007/978-1-4614-0980-9_18 D2 10.1007/978-1-4614-0980-9 PG 20 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA BZG80 UT WOS:000301553300018 PM 22297524 ER PT S AU Cardone, G Heymann, JB Cheng, NQ Trus, BL Steven, AC AF Cardone, Giovanni Heymann, J. Bernard Cheng, Naiqian Trus, Benes L. Steven, Alasdair C. BE Rossmann, MG Rao, VB TI Procapsid Assembly, Maturation, Nuclear Exit: Dynamic Steps in the Production of Infectious Herpesvirions SO VIRAL MOLECULAR MACHINES SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID HERPES-SIMPLEX-VIRUS; DNA-PACKAGING PROTEIN; MAJOR CAPSID PROTEIN; SARCOMA-ASSOCIATED HERPESVIRUS; CRYOELECTRON TOMOGRAPHY; PORTAL PROTEIN; UL25 PROTEIN; 3-DIMENSIONAL STRUCTURE; MOLECULAR ARCHITECTURE; STRUCTURAL-ANALYSIS AB Herpesviruses, a family of animal viruses with large (125-250 kbp) linear DNA genomes, are highly diversified in terms of host range; nevertheless, their virions conform to a common architecture. The genonne is confined at high density within a thick-walled icosahedral capsid with the uncommon (among viruses, generally) but unvarying triangulation number T = 16. The envelope is a membrane in which some 11 different viral glycoproteins are implanted. Between the capsid and the envelope is a capacious compartment called the tegument that accommodates similar to 20-40 different viral proteins (depending on which virus) destined for delivery into a host cell. A strong body of evidence supports the hypothesis that herpesvirus capsids and those of tailed bacteriophages stem from a distant common ancestor, whereas their radically different infection apparatuses - envelope on one hand and tail on the other - reflect subsequent coevolution with divergent hosts. Here we review the molecular components of herpesvirus capsids and the mechanisms that regulate their assembly, with particular reference to the archetypal alphaherpesvirus, herpes simplex virus type 1; assess their duality with the capsids of tailed bacteriophages; and discuss the mechanism whereby, once DNA packaging has been completed, herpesvirus nucleocapsids exit from the nucleus to embark on later stages of the replication cycle. C1 [Cardone, Giovanni; Heymann, J. Bernard; Cheng, Naiqian; Trus, Benes L.; Steven, Alasdair C.] NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. [Trus, Benes L.] NIH, Ctr Informat Technol, Imaging Sci Lab, Bethesda, MD 20892 USA. RP Steven, AC (reprint author), NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. EM stevena@mail.nih.gov OI Heymann, Bernard/0000-0002-8872-5326 FU Intramural NIH HHS [Z01 AR027002-29] NR 94 TC 27 Z9 27 U1 0 U2 9 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-0980-9 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2012 VL 726 BP 423 EP 439 DI 10.1007/978-1-4614-0980-9_19 D2 10.1007/978-1-4614-0980-9 PG 17 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA BZG80 UT WOS:000301553300019 PM 22297525 ER PT J AU Cookson, MR AF Cookson, Mark R. TI Aging-RNA in development and disease SO WILEY INTERDISCIPLINARY REVIEWS-RNA LA English DT Review ID AMYOTROPHIC-LATERAL-SCLEROSIS; GILFORD-PROGERIA-SYNDROME; SPINAL MUSCULAR-ATROPHY; PARKINSONISM PROTEIN DJ-1; GENOME-WIDE ASSOCIATION; CYSTEINE-SULFINIC ACID; NUCLEAR FACTOR TDP-43; PRE-MESSENGER-RNA; GENE-EXPRESSION; ALZHEIMERS-DISEASE AB Given that RNA is involved in virtually all biological processes, it is perhaps not surprising that several RNA-binding proteins are associated with aging and with different age-related disorders. Other articles in this volume will discuss some specific examples of diseases where RNA plays a role that are also associated with aging, such as cancer and inflammation, so here I will discuss some general aspects of how RNA changes with the aging process. I will also discuss some specific examples of RNA-binding proteins that are associated with age-dependent neurological diseases as these provide an interesting framework to examine how lifetime mutations might lead to a late onset disease, although the answers to these questions are still not well understood. (C) 2011 John Wiley & Sons, Ltd. C1 NIA, Cell Biol & Gene Express Unit, Neurogenet Lab, Bethesda, MD 20892 USA. RP Cookson, MR (reprint author), NIA, Cell Biol & Gene Express Unit, Neurogenet Lab, Bethesda, MD 20892 USA. EM cookson@mail.nih.gov FU NIH, National Institute on Aging FX This research was supported by the Intramural Research Program of the NIH, National Institute on Aging. NR 102 TC 7 Z9 7 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1757-7004 J9 WIRES RNA JI Wiley Interdiscip. Rev.-RNA PD JAN-FEB PY 2012 VL 3 IS 1 BP 133 EP 143 DI 10.1002/wrna.109 PG 11 WC Cell Biology SC Cell Biology GA 913GS UT WOS:000301865500010 PM 21898829 ER PT J AU Resnik, DB Stewart, CN AF Resnik, David B. Stewart, C. Neal, Jr. TI Misconduct versus Honest Error and Scientific Disagreement SO ACCOUNTABILITY IN RESEARCH-POLICIES AND QUALITY ASSURANCE LA English DT Article DE ethics; honest error; research misconduct; scientific disagreement AB Researchers sometimes mistakenly accuse their peers of misconduct. It is important to distinguish between misconduct and honest error or a difference of scientific opinion to prevent unnecessary and time-consuming misconduct proceedings, protect scientists from harm, and avoid deterring researchers from using novel methods or proposing controversial hypotheses. While it is obvious to many researchers that misconduct is different from a scientific disagreement or simply an inadvertent mistake in methods, analysis or misinterpretation of data, applying this distinction to real cases is sometimes not easy. Because the line between misconduct and honest error or a scientific dispute is often unclear, research organizations and institutions should distinguish between misconduct and honest error and scientific disagreement in their policies and practices. These distinctions should also be explained during educational sessions on the responsible conduct of research and in the mentoring process. When researchers wrongfully accuse their peers of misconduct, it is important to help them understand the distinction between misconduct and honest error and differences of scientific judgment or opinion, pinpoint the source of disagreement, and identify the relevant scientific norms. They can be encouraged to settle the dispute through collegial discussion and dialogue, rather than a misconduct allegation. C1 [Resnik, David B.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Stewart, C. Neal, Jr.] Univ Tennessee, Knoxville, TN USA. RP Resnik, DB (reprint author), NIEHS, NIH, Box 12233,Mail Drop CU 03, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999] NR 16 TC 4 Z9 5 U1 1 U2 17 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0898-9621 J9 ACCOUNT RES JI Account. Res. PY 2012 VL 19 IS 1 BP 56 EP 63 DI 10.1080/08989621.2012.650948 PG 8 WC Medical Ethics SC Medical Ethics GA 909QZ UT WOS:000301580600006 PM 22268506 ER PT J AU Seo, DC Li, KG AF Seo, Dong-Chul Li, Kaigang TI Longitudinal Trajectories of Perceived Body Weight: Adolescence to Early Adulthood SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Article DE perceived body weight; body mass index; trajectories; adolescents; young adults ID UNITED-STATES; MASS INDEX; SELF-PERCEPTION; LOSS BEHAVIOR; OBESITY; PREVALENCE; OVERWEIGHT; GIRLS; MEDIA; HEALTH AB Objective: To examine longitudinal trajectories of perceived weight from adolescence to early adulthood by gender. Methods: We analyzed 9 waves (1997-2005)of data from the National Longitudinal Survey of Youth (N = 8302) using M plus. Results: Perceived overweight increased over time among girls and did not level off until 23 years of age. Blacks had a lower perceived weight for their actual weight and a slower rate of increase in perceived weight than did whites. Conclusion: Intervention programs designed to prevent or reduce obesity should evaluate weight perceptions for both adolescents and young adults prior to implementing each intervention. C1 [Seo, Dong-Chul] Indiana Univ, Dept Appl Hlth Sci, Bloomington, IN 47405 USA. [Li, Kaigang] NICHHD, NIH, Bethesda, MD 20892 USA. RP Seo, DC (reprint author), Indiana Univ, Dept Appl Hlth Sci, Bloomington, IN 47405 USA. EM seo@indiana.edu OI Seo, Dong-Chul/0000-0002-1972-6237 NR 34 TC 1 Z9 1 U1 4 U2 7 PU PNG PUBLICATIONS PI OAK RIDGE PA 2205-K OAK RIDGE RD, #115, OAK RIDGE, NC 27310 USA SN 1945-7359 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PY 2012 VL 36 IS 2 BP 242 EP 253 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 909ML UT WOS:000301568600009 PM 22370261 ER PT J AU Tripathi, L Kumar, P Singh, R Stables, JP AF Tripathi, Laxmi Kumar, Praveen Singh, Ranjit Stables, James P. TI Design, synthesis and anticonvulsant evaluation of novel N-(4-substituted phenyl)-2-[4-(substituted) benzylidene]-hydrazinecarbothio amides SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE N-(4-Substituted phenyl)-2-[4-(substituted) benzylidene]-hydrazinecarbothioamides; Anticonvulsant activity; Neurotoxicity; Computational study ID ARYL SEMICARBAZONES; THIOSEMICARBAZONES; DISCOVERY; SEIZURES; EPILEPSY AB Thirty six new N-(4-substituted phenyl)-2-[4-(substituted) benzylidene]-hydrazinecarbothioamides were synthesized and evaluated for anticonvulsant activity and neurotoxicity. The anticonvulsant activity was established in three seizure models i.e. MES, scMET and 6 Hz model. The most active compound was 2-[4-(4-chlorophenoxy)benzylidenel-N-(4-fluorophenyl)hydrazinecarbothioamide PC 31 which showed 100% protection at 0.5 h in the 6 Hz test. Compound 2-[4-(4-bromophenoxy) benzylidenel-N-(4-bromophenyl) hydrazinecarbothioamide PC 23 was found to be active in both the MES and 6 Hz test. A computational study was carried out from calculation of a pharmacophore pattern and the prediction of pharmacokinetic properties. Titled compounds have also exhibited good binding properties with epilepsy molecular targets such as glutamate, GABA (A) delta and GABA (A) alpha-1 receptors, in the Lamarckian genetic algorithm based on flexible docking studies. (C) 2011 Elsevier Masson SAS. All rights reserved. C1 [Tripathi, Laxmi; Kumar, Praveen] SD Coll Pharm & Vocat Studies, Dept Pharmaceut Chem, Muzaffarnagar 251001, India. [Singh, Ranjit] Shobhit Univ, Sch Pharmaceut Sci, Meerut 250110, Uttar Pradesh, India. [Stables, James P.] NIH, Preclin Pharmacol Sect, Epilepsy Branch, Bethesda, MD 20892 USA. RP Tripathi, L (reprint author), SD Coll Pharm & Vocat Studies, Dept Pharmaceut Chem, Muzaffarnagar 251001, India. EM tripathilaxmi@rediffmail.com NR 22 TC 11 Z9 11 U1 0 U2 4 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0223-5234 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD JAN PY 2012 VL 47 BP 153 EP 166 DI 10.1016/j.ejmech.2011.10.038 PG 14 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 904BY UT WOS:000301169800017 PM 22082834 ER PT J AU Lin, W Wang, Y Lin, SS Li, CX Zhou, C Wang, SG Huang, HQ Liu, PQ Ye, G Shen, XY AF Lin, Wei Wang, Ying Lin, Sisi Li, Cuixian Zhou, Chun Wang, Shaogui Huang, Heqing Liu, Peiqing Ye, Guan Shen, Xiaoyan TI Induction of cell cycle arrest by the carbazole alkaloid Clauszoline-I from Clausena vestita D. D. Tao via inhibition of the PKC delta phosphorylation SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE Clauszoline-I; Cell cycle arrest; PKC delta; RhoA ID KINASE-C-DELTA; RHO GTPASES; ACTIN CYTOSKELETON; SERINE 643; EXCAVATA; ASSOCIATION; TUMOR; CHK1; AUTOPHOSPHORYLATION; TRANSFORMATION AB Sixteen carbazole alkaloids from Clausena vestita D. D. Tao were extracted, and their anti-tumor activities were evaluated. Among the extracts, Clauszoline-I exhibited an obvious growth inhibitory activity against several cancer cell lines through its ability to induce cell cycle arrest in the S and G2/M phases. A dramatic morphologic change with decreased F-actin staining and RhoA activity was found in Clauszoline-1 treated HepG2 cells, in which the phosphorylation of PKC delta (Ser643) was inhibited. Our results indicated that induction cell cycle arrest by Clauszoline-I might be achieved by decreasing the RhoA activity via the inhibition of PKC delta phosphorylation. (C) 2011 Elsevier Masson SAS. All rights reserved. C1 [Ye, Guan] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. [Lin, Wei; Wang, Ying; Lin, Sisi; Li, Cuixian; Zhou, Chun; Wang, Shaogui; Huang, Heqing; Liu, Peiqing; Shen, Xiaoyan] Sun Yat Sen Univ, Sch Pharmaceut Sci, Lab Pharmacol & Toxicol, Guangzhou 510006, Guangdong, Peoples R China. RP Ye, G (reprint author), NHLBI, Translat Med Branch, NIH, Bldg 10,Room 5N307,MSC 1434, Bethesda, MD 20892 USA. EM yg4847@yahoo.com.cn; shxiaoy@mail.sysu.edu.cn FU National Natural Science Foundation of China [31070924]; Projects of International Cooperation and Exchanges, Science and Technology Planning Project of Guangdong Province, China [1011420600004]; Research Fund for the Doctoral Program of Higher Education of China [20100171110052] FX The present study was supported by the National Natural Science Foundation of China (No. 31070924), the Projects of International Cooperation and Exchanges, Science and Technology Planning Project of Guangdong Province, China (No. 1011420600004), as well as the Research Fund for the Doctoral Program of Higher Education of China (No. 20100171110052). NR 39 TC 16 Z9 19 U1 2 U2 18 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0223-5234 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD JAN PY 2012 VL 47 BP 214 EP 220 DI 10.1016/j.ejmech.2011.10.047 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 904BY UT WOS:000301169800024 PM 22093759 ER PT J AU Aguilera, G Liu, Y AF Aguilera, Greti Liu, Ying TI The molecular physiology of CRH neurons SO FRONTIERS IN NEUROENDOCRINOLOGY LA English DT Review DE Corticotropin releasing hormone (CRH); Hypothalamus; Stress; HPA axis; Transcription; Cyclic AMP response element binding protein (CREB); Transducer of Regulated CREB activity (TORC); Cyclic AMP inducible early repressor ICER; Glucocorticoids ID CORTICOTROPIN-RELEASING-HORMONE; PITUITARY-ADRENAL AXIS; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; MESSENGER-RIBONUCLEIC-ACID; CAMP-RESPONSIVE ELEMENT; PARVOCELLULAR NEUROSECRETORY NEURONS; PHASEOLUS-VULGARIS-LEUKOAGGLUTININ; VASOPRESSIN GENE-TRANSCRIPTION; CENTRAL AMYGDALOID NUCLEUS; BINDING PROTEIN-ACTIVITY AB Corticotropin releasing hormone (CRH) is essential for stress adaptation by mediating hypothalamic-pituitary-adrenal (HPA) axis, behavioral and autonomic responses to stress. Activation of CRH neurons depends on neural afferents from the brain stem and limbic system, leading to sequential CRH release and synthesis. CRH transcription is required to restore mRNA and peptide levels, but termination of the response is essential to prevent pathology associated with chronic elevations of CRH and HPA axis activity. Inhibitory feedback mediated by glucocorticoids and intracellular production of the repressor, Inducible Cyclic AMP Early Repressor (ICER), limit the magnitude and duration of CRH neuronal activation. Induction of CRH transcription is mediated by the cyclic AMP/protein kinase A/cyclic AMP responsive element binding protein (CREB)-dependent pathways, and requires cyclic AMP-dependent nuclear translocation of the CREB co-activator, Transducer of Regulated CREB activity (TORC). This article reviews current knowledge on the mechanisms regulating CRH neuron activity. (C) 2011 Published by Elsevier Inc. C1 [Aguilera, Greti; Liu, Ying] Eunice Kennedy Shiver Inst Child Hlth & Human Dev, Sect Endocrine Physiol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. RP Aguilera, G (reprint author), NICHD, Sect Endocrine Physiol, DEB, NIH,CRC, Bldg 10,Rm 1E-3330,10 Ctr Dr, Bethesda, MD 20892 USA. EM Greti_Aguilera@nih.gov FU National Institute of Child Health and Human Development FX This work was supported by the Intramural Research Program, National Institute of Child Health and Human Development. NR 205 TC 28 Z9 28 U1 2 U2 19 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-3022 J9 FRONT NEUROENDOCRIN JI Front. Neuroendocrinol. PD JAN PY 2012 VL 33 IS 1 BP 67 EP 84 DI 10.1016/j.yfrne.2011.08.002 PG 18 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 906ZU UT WOS:000301388400005 PM 21871477 ER PT J AU Quiroz, J Wilson, JR Roychoudhury, S AF Quiroz, Jorge Wilson, Jeffrey R. Roychoudhury, Satrajit TI Statistical analysis of data from dilution assays with censored correlated counts SO PHARMACEUTICAL STATISTICS LA English DT Article DE censored correlated count data; censored mixed negative binomial regression; hierarchical likelihood; NLMIXED; R programming language AB Frequently, count data obtained from dilution assays are subject to an upper detection limit, and as such, data obtained from these assays are usually censored. Also, counts from the same subject at different dilution levels are correlated. Ignoring the censoring and the correlation may provide unreliable and misleading results. Therefore, any meaningful data modeling requires that the censoring and the correlation be simultaneously addressed. Such comprehensive approaches of modeling censoring and correlation are not widely used in the analysis of dilution assays data. Traditionally, these data are analyzed using a general linear model on a logarithmic-transformed average count per subject. However, this traditional approach ignores the between-subject variability and risks, providing inconsistent results and unreliable conclusions. In this paper, we propose the use of a censored negative binomial model with normal random effects to analyze such data. This model addresses, in addition to the censoring and the correlation, any overdispersion that may be present in count data. The model is shown to be widely accessible through the use of several modern statistical software. Copyright (C) 2012 John Wiley & Sons, Ltd. C1 [Quiroz, Jorge] Merck Res Labs, Kenilworth, NJ 07033 USA. [Wilson, Jeffrey R.] Arizona State Univ, NIH Alzheimer Ctr, Tempe, AZ 85287 USA. [Roychoudhury, Satrajit] Novartis Pharmaceutical Corp, BDM, Florham Pk, NJ USA. RP Quiroz, J (reprint author), Merck Res Labs, Kenilworth, NJ 07033 USA. EM jorge.quiroz@merck.com NR 18 TC 1 Z9 1 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1539-1604 J9 PHARM STAT JI Pharm. Stat. PD JAN-FEB PY 2012 VL 11 IS 1 BP 63 EP 73 DI 10.1002/pst.499 PG 11 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 908JT UT WOS:000301487400009 PM 22275293 ER PT J AU McNally, KL Mitzel, DN Anderson, JM Ribeiro, JMC Valenzuela, JG Myers, TG Godinez, A Wolfinbarger, JB Best, SM Bloom, ME AF McNally, Kristin L. Mitzel, Dana N. Anderson, Jennifer M. Ribeiro, Jose M. C. Valenzuela, Jesus G. Myers, Timothy G. Godinez, Alvaro Wolfinbarger, James B. Best, Sonja M. Bloom, Marshall E. TI Differential salivary gland transcript expression profile in Ixodes scapularis nymphs upon feeding or flavivirus infection SO TICKS AND TICK-BORNE DISEASES LA English DT Article DE Tick vector; Ixodes scapularis; Nymph; Salivary gland; Gene expression; Feeding; Flavivirus ID TICK-BORNE FLAVIVIRUS; LYME-DISEASE AGENT; ENCEPHALITIS-VIRUS; GENOME PROJECT; MAMMALIAN HOST; PROTEIN; VECTOR; TRANSMISSION; IMMUNITY; DAMMINI AB Ixodid ticks are vectors of human diseases such as Lyme disease, babesiosis, anaplasmosis, and tick-borne encephalitis. These diseases cause significant morbidity and mortality worldwide and are transmitted to humans during tick feeding. The tick-host-pathogen interface is a complex environment where host responses are modulated by the molecules in tick saliva to enable the acquisition of a blood meal. Disruption of host responses at the site of the tick bite may also provide an advantage for pathogens to survive and replicate. Thus, the molecules in tick saliva not only aid the tick in securing a nutrient-rich blood meal, but can also enhance the transmission and acquisition of pathogens. To investigate the effect of feeding and flavivirus infection on the salivary gland transcript expression profile in ticks, a first-generation microarray was developed using ESTs from a cDNA library derived from Ixodes scapularis salivary glands. When the salivary gland transcript profile in ticks feeding over the course of 3 days was compared to that in unfed ticks, a dramatic increase in transcripts related to metabolism was observed. Specifically, 578 transcripts were up-regulated compared to 151 down-regulated transcripts in response to feeding. When specific time points post attachment were analyzed, a temporal pattern of gene expression was observed. When Langat virus-infected ticks were compared to mock-infected ticks, transcript expression changes were observed at all 3 days of feeding. Differentially regulated transcripts include putative secreted proteins, lipocalins, Kunitz domain-containing proteins, anti-microbial peptides, and transcripts of unknown function. These studies identify salivary gland transcripts that are differentially regulated during feeding or in the context of flavivirus infection in Ixodes scapularis nymphs, a medically important disease vector. Further analysis of these transcripts may identify salivary factors that affect the transmission or replication of tick-borne flaviviruses. Published by Elsevier GmbH. C1 [McNally, Kristin L.; Mitzel, Dana N.; Wolfinbarger, James B.; Best, Sonja M.; Bloom, Marshall E.] NIAID, Virol Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Anderson, Jennifer M.; Ribeiro, Jose M. C.; Valenzuela, Jesus G.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Myers, Timothy G.; Godinez, Alvaro] NIAID, Genom Technol Sect, Res Technol Branch, NIH, Bethesda, MD 20892 USA. RP Bloom, ME (reprint author), NIAID, Virol Lab, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM mbloom@niaid.nih.gov RI Ribeiro, Jose/J-7011-2015; OI Ribeiro, Jose/0000-0002-9107-0818 FU National Institute of Allergy and Infectious Diseases, NIH FX We thank Anita Mora for technical assistance in the preparation of the tables and the figure. We also thank the Tick-Borne Flavivirus section and the Laboratory of Virology for helpful discussions. This research was supported by the Intramural Research Program at the National Institute of Allergy and Infectious Diseases, NIH. NR 58 TC 20 Z9 20 U1 2 U2 9 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 1877-959X EI 1877-9603 J9 TICKS TICK-BORNE DIS JI Ticks Tick-Borne Dis. PY 2012 VL 3 IS 1 BP 18 EP 26 DI 10.1016/j.ttbdis.2011.09.003 PG 9 WC Infectious Diseases; Microbiology; Parasitology SC Infectious Diseases; Microbiology; Parasitology GA 907EM UT WOS:000301400600004 PM 22309855 ER PT J AU Keller, MF Nalls, MA Singleton, A AF Keller, Margaux F. Nalls, Michael A. Singleton, Andrew TI Genome-wide Complex Trait Analysis (GCTA) as a method to quantify missing heritability in Parkinson's disease. SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract CT 81st Annual Meeting of the American-Association-of-Physical-Anthropologists CY 2012 CL Portland, OR SP Amer Assoc Phys Anthropol C1 [Keller, Margaux F.] Temple Univ, Dept Anthropol, Philadelphia, PA 19122 USA. [Keller, Margaux F.; Nalls, Michael A.; Singleton, Andrew] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2012 VL 147 SU 54 BP 179 EP 179 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 895LW UT WOS:000300498700438 ER PT J AU Weckle, A Hou, ZC Chen, CY Xing, J Sterner, KN Baker, JL Romero, R Wildman, DE AF Weckle, Amy Hou, Zhou-Cheng Chen, Caoyi Xing, Jun Sterner, Kirstin N. Baker, Jennifer L. Romero, Roberto Wildman, Derek E. TI Adaptive evolution and ancestral resurrection of anthropoid estrogen receptor beta. SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract CT 81st Annual Meeting of the American-Association-of-Physical-Anthropologists CY 2012 CL Portland, OR SP Amer Assoc Phys Anthropol C1 [Weckle, Amy; Hou, Zhou-Cheng; Chen, Caoyi; Xing, Jun; Sterner, Kirstin N.; Romero, Roberto; Wildman, Derek E.] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Hou, Zhou-Cheng] China Agr Univ, Dept Anim Genet, Beijing 100193, Peoples R China. [Hou, Zhou-Cheng; Romero, Roberto; Wildman, Derek E.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI 48201 USA. [Baker, Jennifer L.] George Washington Univ, Ctr Adv Study Hominid Paleobiol, Washington, DC 20052 USA. [Wildman, Derek E.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2012 VL 147 SU 54 BP 299 EP 299 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 895LW UT WOS:000300498701347 ER PT J AU Ghosh, AK Anderson, DD Weber, IT Mitsuya, H AF Ghosh, Arun K. Anderson, David D. Weber, Irene T. Mitsuya, Hiroaki TI Enhancing Protein Backbone BindinguA Fruitful Concept for Combating Drug-Resistant HIV SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Review DE antiviral agents; backbone binding; drug resistance; enzymes; proteins ID IMMUNODEFICIENCY-VIRUS TYPE-1; RESOLUTION CRYSTAL-STRUCTURES; LIGAND X-RAY; STRUCTURE-BASED DESIGN; ORALLY BIOAVAILABLE INHIBITOR; HIGH-AFFINITY P2-LIGANDS; DEFICIENCY SYNDROME AIDS; BIOLOGICAL EVALUATION; IN-VITRO; MOLECULAR-BASIS AB The evolution of drug resistance is one of the most fundamental problems in medicine. In HIV/AIDS, the rapid emergence of drug-resistant HIV-1 variants is a major obstacle to current treatments. HIV-1 protease inhibitors are essential components of present antiretroviral therapies. However, with these protease inhibitors, resistance occurs through viral mutations that alter inhibitor binding, resulting in a loss of efficacy. This loss of potency has raised serious questions with regard to effective long-term antiretroviral therapy for HIV/AIDS. In this context, our research has focused on designing inhibitors that form extensive hydrogen-bonding interactions with the enzymes backbone in the active site. In doing so, we limit the proteases ability to acquire drug resistance as the geometry of the catalytic site must be conserved to maintain functionality. In this Review, we examine the underlying principles of enzyme structure that support our backbone-binding concept as an effective means to combat drug resistance and highlight their application in our recent work on antiviral HIV-1 protease inhibitors. C1 [Ghosh, Arun K.; Anderson, David D.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Ghosh, Arun K.; Anderson, David D.] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA. [Weber, Irene T.] Georgia State Univ, Dept Biol, Atlanta, GA 30303 USA. [Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Dept Hematol, Kumamoto 8608556, Japan. [Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Dept Infect Dis, Kumamoto 8608556, Japan. [Mitsuya, Hiroaki] NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. RP Ghosh, AK (reprint author), Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. EM akghosh@purdue.edu FU National Institute of Health [GM53386] FX This work was supported by the National Institute of Health (GM53386). We thank Dr. K. V. Rao (Purdue University) for helpful discussions. NR 133 TC 45 Z9 45 U1 2 U2 18 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2012 VL 51 IS 8 BP 1778 EP 1802 DI 10.1002/anie.201102762 PG 25 WC Chemistry, Multidisciplinary SC Chemistry GA 894SD UT WOS:000300446100006 PM 22290878 ER PT J AU Deveney, CM Connolly, ME Jenkins, SE Kim, P Fromm, SJ Pine, DS Leibenluft, E AF Deveney, Christen M. Connolly, Megan E. Jenkins, Sarah E. Kim, Pilyoung Fromm, Stephen J. Pine, Daniel S. Leibenluft, Ellen TI Neural recruitment during failed motor inhibition differentiates youths with bipolar disorder and severe mood dysregulation SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE Motor inhibition; fMRI; Bipolar disorder ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; OBSESSIVE-COMPULSIVE DISORDER; INFERIOR PREFRONTAL CORTEX; RESPONSE-INHIBITION; ANTERIOR CINGULATE; TRAIT IMPULSIVITY; BRAIN ACTIVATION; ERROR-DETECTION; RATING-SCALE AB Controversy exists about whether non-episodic irritability (operationalized as severe mood dysregulation, SMD) should be considered a developmental presentation of pediatric bipolar disorder (BD). While assessments of brain function may address this controversy, only one fMRI study has compared BD versus SMD. We compared neural activation in BD, SMD, and controls during a motor inhibition task, since motor disinhibition is an important clinical feature in both BD and SMD. During failed inhibition, BD youths exhibited less activation in the right anterior cingulate cortex (ACC) and right nucleus accumbens relative to both SMD and healthy youths. Exploratory analyses indicate that, in BD youths, reduced activation in the right ACC may be independent of comorbid ADHD. These findings highlight neural distinctions between the phenotypically related BD and SMD populations. Published by Elsevier B.V. C1 [Deveney, Christen M.] NIMH, Sect Bipolar Spectrum Disorders, Emot & Dev Branch, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Deveney, CM (reprint author), NIMH, Sect Bipolar Spectrum Disorders, Emot & Dev Branch, NIH,US Dept Hlth & Human Serv, 15K North Dr,MSC 2670, Bethesda, MD 20892 USA. EM deveneycm@mail.nih.gov FU National Institute of Mental Health, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health. We thank the children and families for their participation which made this research possible and the staff of the Emotion and Development Branch at NIMH. NR 55 TC 10 Z9 10 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD JAN PY 2012 VL 89 IS 1 BP 148 EP 155 DI 10.1016/j.biopsycho.2011.10.003 PG 8 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 884NJ UT WOS:000299714500020 PM 22008364 ER PT J AU Chandramohan, V Sampson, JH Pastan, I Bigner, DD AF Chandramohan, Vidyalakshmi Sampson, John H. Pastan, Ira Bigner, Darell D. TI Toxin-Based Targeted Therapy for Malignant Brain Tumors SO CLINICAL & DEVELOPMENTAL IMMUNOLOGY LA English DT Review ID EPIDERMAL-GROWTH-FACTOR; HUMAN GLIOBLASTOMA-MULTIFORME; IL4-PSEUDOMONAS EXOTOXIN NBI-3001; CHONDROITIN SULFATE PROTEOGLYCAN; PLASMINOGEN-ACTIVATOR RECEPTOR; CONVECTION-ENHANCED DELIVERY; INTERLEUKIN-4 IL-4 RECEPTORS; MOUSE XENOGRAFT MODEL; SINGLE-CHAIN ANTIBODY; FACTOR FUSION PROTEIN AB Despite advances in conventional treatment modalities for malignant brain tumors-surgery, radiotherapy, and chemotherapy-the prognosis for patients with high-grade astrocytic tumor remains dismal. The highly heterogeneous and diffuse nature of astrocytic tumors calls for the development of novel therapies. Advances in genomic and proteomic research indicate that treatment of brain tumor patients can be increasingly personalized according to the characteristics of the targeted tumor and its environment. Consequently, during the last two decades, a novel class of investigative drug candidates for the treatment of central nervous system neoplasia has emerged: recombinant fusion protein conjugates armed with cytotoxic agents targeting tumor-specific antigens. The clinical applicability of the tumor-antigen-directed cytotoxic proteins as a safe and viable therapy for brain tumors is being investigated. Thus far, results from ongoing clinical trials are encouraging, as disease stabilization and patient survival prolongation have been observed in at least 109 cases. This paper summarizes the major findings pertaining to treatment with the different antiglioma cytotoxins at the preclinical and clinical stages. C1 [Chandramohan, Vidyalakshmi; Bigner, Darell D.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [Sampson, John H.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Bigner, DD (reprint author), Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. EM bigne001@mc.duke.edu FU NIH, NINDS [5P50 NS20023]; NIH, NCI [R37 CA 011898]; NIH, National Cancer Institute, Center for Cancer Research FX This work was supported by the following NIH grants: NINDS Grant 5P50 NS20023 and NCI Merit Award R37 CA 011898. This work was also supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 147 TC 11 Z9 12 U1 1 U2 12 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1740-2522 J9 CLIN DEV IMMUNOL JI Clin. Dev. Immunol. PY 2012 AR 480429 DI 10.1155/2012/480429 PG 15 WC Immunology SC Immunology GA 905GJ UT WOS:000301260000001 ER PT J AU Lutter, EI Martens, C Hackstadt, T AF Lutter, Erika I. Martens, Craig Hackstadt, Ted TI Evolution and Conservation of Predicted Inclusion Membrane Proteins in Chlamydiae SO COMPARATIVE AND FUNCTIONAL GENOMICS LA English DT Article ID OBLIGATE INTRACELLULAR PATHOGEN; NEIGHBOR-JOINING METHOD; TRACHOMATIS INCLUSION; GENOME SEQUENCE; HOST-CELL; TRYPTOPHAN SYNTHASE; MICROTUBULE NETWORK; TISSUE TROPISM; INFECTED-CELLS; RAB GTPASES AB Chlamydia spp. are obligate intracellular pathogens that replicate within a vacuole termed the inclusion. Chlamydiae extensively modify the inclusion membrane via the insertion of chlamydial inclusion membrane proteins (Incs) which decorate the cytosolic face of the inclusion. We have assessed the overall relatedness and phylogeny of Incs in order to identify potential evolutionary trends. Despite a high degree of conservation among Incs within C. trachomatis serovars, phylogenetic analysis showed that some Incs cluster according to clinical groupings suggesting that certain Incs may contribute to tissue tropism. Bioinformatic predictions identified Incs in five chlamydial species: 55 in C. trachomatis, 68 in C. felis, 92 in C. pneumoniae, 79 in C. caviae, and 54 in C. muridarum. Inc homologues were compared between chlamydial species and 23 core Incs were identified as shared among all species. Genomic expansion of Incs was identified in C. pneumoniae, C. caviae, and C. felis but not C. trachomatis or C. muridarum. C1 [Lutter, Erika I.; Hackstadt, Ted] NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. [Martens, Craig] NIAID, Res Technol Branch, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Hackstadt, T (reprint author), NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. EM ted_hackstadt@nih.gov FU NIH/NIAID FX This work was supported by the Intramural Research Program of the NIH/NIAID. The authors thank Drs. J. Carlson, L. Bauler, J. Mital, A. Omsland, and T. Clark for critical review of the manuscript. NR 62 TC 30 Z9 30 U1 1 U2 10 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1531-6912 J9 COMP FUNCT GENOM JI Compar. Funct. Genom. PY 2012 AR 362104 DI 10.1155/2012/362104 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 905IG UT WOS:000301264900001 ER PT J AU Pradhan, C Jena, SK Nadar, SR Pradhan, N AF Pradhan, Cauchy Jena, Susant K. Nadar, Sreenivasan R. Pradhan, N. TI Higher-Order Spectrum in Understanding Nonlinearity in EEG Rhythms SO COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE LA English DT Article ID SURROGATE-DATA; TIME-SERIES; BISPECTRUM; BRAIN; CHAOS; BICOHERENCE; SIGNALS; SYSTEM; SLEEP; TESTS AB The fundamental nature of the brain's electrical activities recorded as electroencephalogram (EEG) remains unknown. Linear stochastic models and spectral estimates are the most common methods for the analysis of EEG because of their robustness, simplicity of interpretation, and apparent association with rhythmic behavioral patterns in nature. In this paper, we extend the use of higher-order spectrum in order to indicate the hidden characteristics of EEG signals that simply do not arise from random processes. The higher-order spectrum is an extension Fourier spectrum that uses higher moments for spectral estimates. This essentially nullifies all Gaussian random effects, therefore, can reveal non-Gaussian and nonlinear characteristics in the complex patterns of EEG time series. The paper demonstrates the distinguishing features of bispectral analysis for chaotic systems, filtered noises, and normal background EEG activity. The bispectrum analysis detects nonlinear interactions; however, it does not quantify the coupling strength. The squared bicoherence in the nonredundant region has been estimated to demonstrate nonlinear coupling. The bicoherence values are minimal for white Gaussian noises (WGNs) and filtered noises. Higher bicoherence values in chaotic time series and normal background EEG activities are indicative of nonlinear coupling in these systems. The paper shows utility of bispectral methods as an analytical tool in understanding neural process underlying human EEG patterns. C1 [Pradhan, N.] NIMHANS, Dept Psychopharmacol, Bangalore 560029, Karnataka, India. [Pradhan, Cauchy] Ecole Polytech Fed Lausanne, Med Image Proc Lab, CH-1015 Lausanne, Switzerland. [Jena, Susant K.] KNS Inst Technol, Dept Comp Sci & Math, Bangalore 560064, Karnataka, India. [Nadar, Sreenivasan R.] NIMH, MEG Core, Bethesda, MD 20892 USA. RP Pradhan, N (reprint author), NIMHANS, Dept Psychopharmacol, Bangalore 560029, Karnataka, India. EM nprnimhans@gmail.com NR 32 TC 4 Z9 4 U1 1 U2 14 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1748-670X J9 COMPUT MATH METHOD M JI Comput. Math. Method Med. PY 2012 AR 206857 DI 10.1155/2012/206857 PG 8 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 905JC UT WOS:000301267300001 ER PT J AU Moreau, NG Falvo, MJ Damiano, DL AF Moreau, Noelle G. Falvo, Michael J. Damiano, Diane L. TI Rapid force generation is impaired in cerebral palsy and is related to decreased muscle size and functional mobility SO GAIT & POSTURE LA English DT Article DE Rate of force development; Ultrasound; Muscle strength; Muscle architecture; Gait; Dynamometry ID TRAINING-INDUCED CHANGES; HUMAN SKELETAL-MUSCLE; SPASTIC DIPLEGIA; FASCICLE LENGTH; STRENGTH; CHILDREN; RESISTANCE; ARCHITECTURE; PERFORMANCE; FEMORIS AB Limb movements involving contraction times of 50-200 ms occur in many everyday activities, such as gait, which is faster than the time required to generate maximal force. Therefore, the ability to rapidly produce force may be even more important for the performance of functional activities. In this study rate of force development (RFD) and impulse of the knee extensors were examined in 12 ambulatory children with cerebral palsy (CP) (age: 11.9 +/- 2.9 years) and 11 with typical development (TD) (Age: 11.3 +/- 3.0 years). The relationship with muscle architecture and functional mobility was also determined. RFD and impulse were calculated during a maximal isometric knee extension contraction. Rectus femoris (RF) cross-sectional area and RF and vastus lateralis (VL) muscle thickness (MT), fascicle length (FL), and fascicle angle (FA) were measured using ultrasound imaging. Gait temporal-spatial parameters, Pediatric Outcomes Data Collection Instrument (PODCI), and Activities Scale for Kids performance version (ASKp) were collected. Although VL MT was the primary determinant of RFD and impulse in CP. FA and FL were also significant predictors in the TD group. RFD and impulse were significantly lower in CP compared to TD (70% decrease) in addition to maximal strength (50% decrease). RFD and impulse were predictive of measures of functional mobility, including gait, transfers, and sports and higher level activities but not temporal-spatial gait measures. Results suggest that the ability to rapidly generate torque may be of greater importance than maximal strength during certain tasks, such as transfers and sports and higher level activities. (C) 2011 Elsevier B.V. All rights reserved. C1 [Moreau, Noelle G.] Med Univ S Carolina, Dept Hlth Profess, Charleston, SC 29425 USA. [Falvo, Michael J.] VA NJ Hlth Care Syst, Related Injury & Illness Study Ctr WRIISC, E Orange, NJ USA. [Damiano, Diane L.] NIH, Funct & Appl Biomech Sect, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA. RP Moreau, NG (reprint author), Med Univ S Carolina, Dept Hlth Profess, 77 President St,MSC 700, Charleston, SC 29425 USA. EM moreau@musc.edu RI Van Mulders, Benjamin/P-1241-2014; Damiano, Diane/B-3338-2010; OI Damiano, Diane/0000-0002-2770-5356; Falvo, Michael/0000-0001-9348-6676 FU National Center for Medical Rehabilitation Research/National Institutes of Health [T32HD007434-16]; American Physical Therapy Association; NIH Clinical Center; GE Healthcare FX Dr. Moreau was a postdoctoral fellow in the Movement Science Program at Washington University in St. Louis when this study was conducted and was supported by a National Center for Medical Rehabilitation Research/National Institutes of Health grant (T32HD007434-16). This project was also supported by a clinical research grant from the Section on Pediatrics of the American Physical Therapy Association. This research was supported in part by the Intramural Research Program of the NIH Clinical Center. The authors would like to thank Chris Stanley for assistance with data collection and processing, and Dr. Janice Brunstrom-Hernandez and Jennifer Miros, PT, for their support and assistance with recruitment. We would also like to thank Dr. Sharlene Teefey, GE Healthcare and Tania Gordley, Applications Specialist for GE Healthcare Ultrasound, for their support and technical assistance with this project. NR 32 TC 24 Z9 27 U1 2 U2 14 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0966-6362 J9 GAIT POSTURE JI Gait Posture PD JAN PY 2012 VL 35 IS 1 BP 154 EP 158 DI 10.1016/j.gaitpost.2011.08.027 PG 5 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA 892DR UT WOS:000300267400029 PM 21930383 ER PT J AU Yoo, KH Hennighausen, L AF Yoo, Kyung Hyun Hennighausen, Lothar TI EZH2 Methyltransferase and H3K27 Methylation in Breast Cancer SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Review DE EZH2; H3K27 methylation; Breast cancer; BRCA1 ID EMBRYONIC STEM-CELLS; HISTONE METHYLTRANSFERASE; DEVELOPMENTAL REGULATORS; POLYCOMB; EXPRESSION; H3; MECHANISMS; CARCINOMA; COMPLEX; PROTEIN AB Histone modifications are thought to control the regulation of genetic programs in normal physiology and cancer. Methylation (mono-, di-, and tri-methylation) on histone H3 lysine (K) 27 induces transcriptional repression, and thereby participates in controlling gene expression patterns. Enhancer of zeste (EZH) 2, a methyltransferase and component of the polycomb repressive complex 2 (PRC2), plays an essential role in the epigenetic maintenance of the H3K27me3 repressive chromatin mark. Abnormal EZH2 expression has been associated with various cancers including breast cancer. Here, we discuss the contribution of EZH2 and the PRC2 complex in controlling the H3K27 methylation status and subsequent consequences on genomic instability and the cell cycle in breast cancer cells. We also discuss distinct molecular mechanisms used by EZH2 to suppress BRCA1 functions. C1 [Yoo, Kyung Hyun; Hennighausen, Lothar] NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. RP Yoo, KH (reprint author), NIDDK, Lab Genet & Physiol, NIH, Bldg 8,Rm 107, Bethesda, MD 20892 USA. EM ryuk@mail.nih.gov FU National Institutes of Diabetes, Digestive and Kidney Diseases (NIDDK); Korea NRF [NRF-2011-357-C00087] FX This work was supported by the Intramural program of the National Institutes of Diabetes, Digestive and Kidney Diseases (NIDDK). Kyung Hyun Yoo is a recipient of a Korea NRF fellowship (NRF-2011-357-C00087). NR 46 TC 75 Z9 85 U1 4 U2 30 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2012 VL 8 IS 1 BP 59 EP 65 DI 10.7150/ijbs.8.59 PG 7 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 902SH UT WOS:000301059700006 PM 22211105 ER PT J AU Patel, K Dixit, VD Lee, JH Kim, JW Schaffer, EM Nguyen, D Taub, DD AF Patel, Kalpesh Dixit, Vishwa Deep Lee, Jun Ho Kim, Jie Wan Schaffer, Eric M. Dzung Nguyen Taub, Dennis D. TI Identification of Ghrelin Receptor Blocker, D-[Lys3] GHRP-6 as a CXCR4 Receptor Antagonist SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE CXCL12; CXCR4; HIV-1; Ghrelin; GHRP-6; GHS-R1a; Inflammation; Cancer ID GROWTH-HORMONE; NETWORK; CELLS; NEUROENDOCRINE; INHIBITORS; CANCER; STORY AB [D-Lys3]-Growth Hormone Releasing Peptide-6 (DLS) is widely utilized in vivo and in vitro as a selective ghrelin receptor (GHS-R) antagonist. Unexpectedly, we identified that DLS also has the ability to block CXCL12 binding and activity through CXCR4 on T cells and peripheral blood mononuclear cells (PBMCs). Moreover, as CXCR4 has been shown to act as a major co-receptor for HIV-1 entry into CD4 positive host cells, we have also found that DLS partially blocks CXCR4-mediated HIV-1 entry and propagation in activated human PBMCs. These data demonstrate that DLS is not the specific and selective antagonist as thought for GHS-R1a and appears to have additional effects on the CXCR4 chemokine receptor. Our findings also suggest that structural analogues that mimic DLS binding properties may also have properties of blocking HIV infectivity, CXCR4 dependent cancer cell migration and attenuating chemokine-mediated immune cell trafficking in inflammatory disorders. C1 [Patel, Kalpesh; Dixit, Vishwa Deep; Lee, Jun Ho; Kim, Jie Wan; Schaffer, Eric M.; Dzung Nguyen; Taub, Dennis D.] NIA, Lab Mol Biol & Immunol, Intramural Program, NIH, Baltimore, MD 21224 USA. RP Taub, DD (reprint author), NIA, Clin Immunol Sect, Lab Mol Biol & Immunol, Intramural Res Program,NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM Taubd@grc.nia.nih.gov RI Patel, Kalpesh/G-6685-2012 OI Patel, Kalpesh/0000-0002-2952-6773 FU National Institute on Aging, National Institutes of Health FX We would like to thank Mr. Gary Collins for his assistance in the completion of this work. This work was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. NR 26 TC 14 Z9 14 U1 0 U2 1 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2012 VL 8 IS 1 BP 108 EP 117 DI 10.7150/ijbs.8.108 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 902SH UT WOS:000301059700010 PM 22211109 ER PT J AU Feng, DC Park, O Radaeva, S Wang, H Yin, S Kong, XN Zheng, MQ Zakhari, S Kolls, JK Gao, B AF Feng, Dechun Park, Ogyi Radaeva, Svetlana Wang, Hua Yin, Shi Kong, Xiaoni Zheng, Mingquan Zakhari, Sam Kolls, Jay K. Gao, Bin TI Interleukin-22 Ameliorates Cerulein-Induced Pancreatitis in Mice by Inhibiting the Autophagic Pathway SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE IL-22; pancreatitis; autophagy; Bcl-2; Beclin-1 ID T-CELL; ACINAR-CELLS; INFLAMMATION; ACTIVATION; DISEASE; IL-22; HEPATOCYTES; MECHANISMS; APOPTOSIS; CYTOKINE AB Pancreatitis occurs when digestive enzymes are activated in the pancreas. Severe pancreatitis has a 10-30% mortality rate. No specific treatments for pancreatitis exist now. Here, we discovered that interleukin-22 (IL-22) may have therapeutic potential in treating acute and chronic pancreatitis. Wild-type and IL-22 knockout mice were equally susceptible to cerulein-induced acute and chronic pancreatitis, whereas liver-specific IL-22 transgenic mice were completely resistant to cerulein-induced elevation of serum digestive enzymes, pancreatic necrosis and apoptosis, and inflammatory cell infiltration. Treatment of wild-type mice with recombinant IL-22 or adenovirus IL-22 markedly attenuated the severity of cerulein-induced acute and chronic pancreatitis. Mechanistically, we show that the protective effect of IL-22 on pancreatitis was mediated via the induction of Bcl-2 and Bcl-X-L, which bind to Beclin-1 and subsequently inhibit autophagosome formation to ameliorate pancreatitis. In conclusion, IL-22 ameliorates cerulein-induced pancreatitis by inhibiting the autophagic pathway. IL-22 could be a promising therapeutic drug to treat pancreatitis. C1 [Feng, Dechun; Park, Ogyi; Wang, Hua; Yin, Shi; Kong, Xiaoni; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA. [Radaeva, Svetlana; Zakhari, Sam] NIAAA, Div Metab & Hlth Effects, NIH, Bethesda, MD 20892 USA. [Zheng, Mingquan; Kolls, Jay K.] Louisiana State Univ, Hlth Sci Ctr, Dept Genet, New Orleans, LA 70112 USA. RP Gao, B (reprint author), NIAAA, Lab Liver Dis, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA. EM bgao@mail.nih.gov RI Feng, Dechun/Q-5962-2016 FU Intramural NIH HHS; NHLBI NIH HHS [R37 HL079142] NR 38 TC 31 Z9 34 U1 1 U2 6 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2012 VL 8 IS 2 BP 249 EP 257 DI 10.7150/ijbs.3967 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 902SR UT WOS:000301061100008 PM 22253568 ER PT J AU Chen, GQ Deng, CX Li, YP AF Chen, Guiqian Deng, Chuxia Li, Yi-Ping TI TGF-beta and BMP Signaling in Osteoblast Differentiation and Bone Formation SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Review DE Osteoblasts; Bone; TGF signaling; BMP signaling; Smad; Runx2 ID GROWTH-FACTOR-BETA; MESENCHYMAL STEM-CELLS; BRACHYDACTYLY TYPE A2; BMP-9-INDUCED OSTEOGENIC DIFFERENTIATION; CHRONIC KIDNEY-DISEASE; IA RECEPTOR BMPRIA; P38 MAPK PATHWAYS; MORPHOGENETIC PROTEIN; CONDITIONAL DELETION; UBIQUITIN LIGASE AB Transforming growth factor-beta (TGF-beta)/bone morphogenic protein (BMP) signaling is involved in a vast majority of cellular processes and is fundamentally important throughout life. TGF-beta/BMPs have widely recognized roles in bone formation during mammalian development and exhibit versatile regulatory functions in the body. Signaling transduction by TGF-beta/BMPs is specifically through both canonical Smad-dependent pathways (TGF-beta/BMP ligands, receptors and Smads) and non-canonical Smad-independent signaling pathway (e.g. p38 mitogen-activated protein kinase pathway, MAPK). Following TGF-beta/BMP induction, both the Smad and p38 MAPK pathways converge at the Runx2 gene to control mesenchymal precursor cell differentiation. The coordinated activity of Runx2 and TGF-beta/BMP-activated Smads is critical for formation of the skeleton. Recent advances in molecular and genetic studies using gene targeting in mice enable a better understanding of TGF-beta/BMP signaling in bone and in the signaling networks underlying osteoblast differentiation and bone formation. This review summarizes the recent advances in our understanding of TGF-beta/BMP signaling in bone from studies of genetic mouse models and human diseases caused by the disruption of TGF-beta/BMP signaling. This review also highlights the different modes of cross-talk between TGF-beta/BMP signaling and the signaling pathways of MAPK, Wnt, Hedgehog, Notch, and FGF in osteoblast differentiation and bone formation. C1 [Chen, Guiqian; Li, Yi-Ping] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Chen, Guiqian; Li, Yi-Ping] Zhejiang Univ, Life Sci Coll, Inst Genet, Hangzhou 310058, Zhejiang, Peoples R China. [Deng, Chuxia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Li, YP (reprint author), Univ Alabama Birmingham, Dept Pathol, SHEL 810,1825 Univ Blvd, Birmingham, AL 35294 USA. EM Chuxiad@bdg10.niddk.nih.gov; ypli@uab.edu RI deng, chuxia/N-6713-2016 FU NIH [AR44741, AR055307] FX We would like to thank Ms. Christie Paulson and Ms. Mengrui Wu for their excellent assistance with the manuscript. We apologize to the many researchers whose work could not be cited due to space limitations. Work in our laboratory is supported by grants by NIH grant AR44741 (Y.-P. Li) and AR055307 (Y.-P. Li.). NR 172 TC 363 Z9 401 U1 26 U2 196 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2012 VL 8 IS 2 BP 272 EP 288 DI 10.7150/ijbs.2929 PG 17 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 902SR UT WOS:000301061100011 PM 22298955 ER PT J AU Mukherjee, T Boshoff, H Barry, CE AF Mukherjee, Tathagata Boshoff, Helena Barry, Clifton E., III TI Comment on: Identification of antimicrobial activity among FDA-approved drugs for combating Mycobacterium abscessus and Mycobacterium chelonae SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Editorial Material DE M. abscessus; metronidazole; PA-824 ID HELICOBACTER-PYLORI; METRONIDAZOLE; TUBERCULOSIS; RESISTANCE C1 [Mukherjee, Tathagata; Boshoff, Helena; Barry, Clifton E., III] NIAID, TB Res Sect, NIH, Bethesda, MD 20892 USA. RP Barry, CE (reprint author), NIAID, TB Res Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM cbarry@niaid.nih.gov RI Barry, III, Clifton/H-3839-2012 FU Intramural NIH HHS NR 13 TC 4 Z9 4 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD JAN PY 2012 VL 67 IS 1 BP 252 EP 253 DI 10.1093/jac/dkr418 PG 2 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 899RL UT WOS:000300833700046 PM 21984744 ER PT J AU Pedone, C Corsonello, A Bandinelli, S Pizzarelli, F Ferrucci, L Incalzi, RA AF Pedone, Claudio Corsonello, Andrea Bandinelli, Stefania Pizzarelli, Francesco Ferrucci, Luigi Incalzi, Raffaele Antonelli TI Relationship Between Renal Function and Functional Decline: Role of the Estimating Equation SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE Renal function; disability; aged; estimating equations ID CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; SKELETAL-MUSCLE TISSUE; CREATININE CLEARANCE; INSULIN-RESISTANCE; NHANES-III; VITAMIN-D; ASSOCIATION; DYSFUNCTION; INSUFFICIENCY AB Background: Several formulas are available to estimate glomerular filtration rate (GFR) at the bedside. A decrease in GFR has been associated with poorer performance. We hypothesized that it is related to worsening disability as well. The aim of this study was to evaluate whether the Modification of Diet in Renal Disease formulas can predict worsening disability better than the classic Cockcroft-Gault formula or the measured creatinine clearance. Methods: We studied 666 participants in the InCHIANTI study with 6 years of follow-up data. We evaluated whether directly measured creatinine clearance and GFR estimated using the Modification of Diet in Renal Disease and Cockcroft-Gault formulas predict new disability defined as the loss of >= 1 ADL over the 6-year follow-up. Results: The mean age was 73.1 years (SD: 6.1), 57.7% were women. Fewer than 5% of participants were disabled at baseline. Eighty-one (12.2%) participants experienced a decline in activities of daily life score at follow-up. Declining GFR was associated with increasing risk of worsening disability (Mantel-Haenszel P < .001), with an increased steepness in the curve at GFR below 60 mL/min. The relative risks for worsening disability in people with GFR less than 60 mL/min/m were 3.19 (95% CI: 2.12-4.79) and 4.40 (95% CI: 2.80-6.94) using the Modification of Diet in Renal Disease and the Cockcroft-Gault equations, respectively. The corresponding figures obtained with measured creatinine clearance was 3.95 (95% CI: 2.60-6.01). After adjustment for potential confounders, however, these estimates were substantially reduced. Conclusion: Estimation of renal function with the Cockcroft-Gault or Modification of Diet in Renal Disease formulas can help to identify elderly at risk of worsening disability. The mechanism by which reduced kidney function predicts disability should be further investigated. Copyright (C) 2012-American Medical Directors Association, Inc. C1 [Pedone, Claudio; Incalzi, Raffaele Antonelli] Univ Campus Biomed, Area Geriatria, I-00128 Rome, Italy. [Pedone, Claudio] Fdn Alberto Sordi, Rome, Italy. [Corsonello, Andrea] INRCA, Cosenza, Italy. [Bandinelli, Stefania] ASL Firenze, Unita Riabilitaz Geriatr, Florence, Italy. [Pizzarelli, Francesco] Osped S Maria Annunziata, Div Nefrol, Florence, Italy. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [Incalzi, Raffaele Antonelli] Fdn S Raffaele Cittadella Carita, Taranto, Italy. RP Pedone, C (reprint author), Univ Campus Biomed, Area Geriatria, Via Alvaro del Portillo 200, I-00128 Rome, Italy. EM c.pedone@unicampus.it RI Antonelli Incalzi, Raffaele/G-3978-2012; Corsonello, Andrea/A-5637-2013; OI Corsonello, Andrea/0000-0002-7276-3256; Pedone, Claudio/0000-0003-1847-9032; Antonelli Incalzi, Raffaele/0000-0003-2100-2075 FU Intramural NIH HHS [Z01 AG000015-49] NR 31 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD JAN PY 2012 VL 13 IS 1 AR 84.e11 DI 10.1016/j.jamda.2011.01.009 PG 4 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 898HT UT WOS:000300733100032 PM 21450248 ER PT J AU Starks, SE Gerr, F Kamel, F Lynch, CF Jones, MP Alavanja, MC Sandler, DP Hoppin, JA AF Starks, Sarah E. Gerr, Fred Kamel, Freya Lynch, Charles F. Jones, Michael P. Alavanja, Michael C. Sandler, Dale P. Hoppin, Jane A. TI Neurobehavioral function and organophosphate insecticide use among pesticide applicators in the Agricultural Health Study SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE Agricultural workers; Epidemiology; Organophosphates; Neuropsychological testing; Pesticide exposure ID LONG-TERM EXPOSURE; OCCUPATIONAL-EXPOSURE; NEUROLOGICAL SYMPTOMS; SHEEP FARMERS; WORKERS; PERFORMANCE; CHLORPYRIFOS; MERCURY; SAMPLE AB Although persistent decrements in cognitive function have been observed among persons who have recovered from clinically overt organophosphate (OP) pesticide poisoning, little is known about the cognitive effects of chronic OP exposures that do not result in acute poisoning. To examine associations between long-term pesticide use and neurobehavioral (NB) function, NB tests were administered to licensed pesticide applicators enrolled in the Agricultural Health Study (AHS) in Iowa and North Carolina. Between 2006 and 2008, 701 male participants completed nine NB tests to assess memory, motor speed and coordination, sustained attention, verbal learning and visual scanning and processing. Data on ever-use and lifetime days of use of 16 OP pesticides were obtained from AHS interviews conducted before testing between 1993 and 2007 and during the NB visit. The mean age of participants was 61 years (SD = 12). Associations between pesticide use and NB test performance were estimated with linear regression controlling for age and outcome-specific covariates. NB test performance was associated with lifetime days of use of some pesticides. Ethoprop was significantly associated with reduced performance on a test of motor speed and visual scanning. Malathion was significantly associated with poor performance on a test of visual scanning and processing. Conversely, we observed significantly better test performance for five OP pesticides. Specifically, chlorpyrifos, coumaphos, parathion, phorate, and tetrachlorvinphos were associated with better verbal learning and memory; coumaphos was associated with better performance on a test of motor speed and visual scanning: and parathion was associated with better performance on a test of sustained attention. Several associations varied by state. Overall, we found no consistent evidence of an association between OP pesticide use and adverse NB test performance among this older sample of pesticide applicators. Potential reasons for these mostly null results include a true absence of effect as well as possible selective participation by healthier applicators. (C) 2011 Elsevier Inc. All rights reserved. C1 [Starks, Sarah E.; Gerr, Fred] Univ Iowa, Dept Occupat & Environm Hlth, Iowa City, IA 52242 USA. [Kamel, Freya; Sandler, Dale P.; Hoppin, Jane A.] NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Lynch, Charles F.] Univ Iowa, Dept Epidemiol, Iowa City, IA 52242 USA. [Jones, Michael P.] Univ Iowa, Dept Biostat, Iowa City, IA 52242 USA. [Alavanja, Michael C.] NCI, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. RP Gerr, F (reprint author), Univ Iowa, Dept Occupat & Environm Hlth, Univ Iowa Res Pk,103 IREH, Iowa City, IA 52242 USA. EM fred-gerr@uiowa.edu OI Kamel, Freya/0000-0001-5052-6615; Sandler, Dale/0000-0002-6776-0018 FU National Institute of Environmental Health Sciences [R01-ES013067, Z01-ES049030]; NIH; National Cancer Institute [Z01-CP010119] FX This study was supported by grant number R01-ES013067 from the National Institute of Environmental Health Sciences. This work was supported in part by the Intramural Research Program of the NIH, the National Institute of Environmental Health Sciences (Z01-ES049030) and the National Cancer Institute (Z01-CP010119). NR 42 TC 18 Z9 19 U1 0 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JAN-FEB PY 2012 VL 34 IS 1 BP 168 EP 176 DI 10.1016/j.ntt.2011.08.014 PG 9 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 902KN UT WOS:000301037100020 PM 21907279 ER PT J AU Al Rwahnih, M Dolja, VV Daubert, S Koonin, EV Rowhani, A AF Al Rwahnih, Maher Dolja, Valerian V. Daubert, Steve Koonin, Eugene V. Rowhani, Adib TI Genomic and biological analysis of Grapevine leafroll-associated virus 7 reveals a possible new genus within the family Closteroviridae SO VIRUS RESEARCH LA English DT Article DE Grapevine viruses; Leafroll disease; Closteroviridae family; GLRaV-7; Deep sequence analysis; LChV-1; CoV-1 ID BEET-YELLOWS-VIRUS; MULTIPLE SEQUENCE ALIGNMENT; NUCLEOTIDE-SEQUENCE; DEGENERATE PRIMERS; GENETIC DIVERSITY; MOVEMENT PROTEIN; IDENTIFICATION; AMPELOVIRUS; ORGANIZATION; DISEASE AB Deep sequencing analysis of an asymptomatic grapevine revealed a virome containing five RNA viruses and a viroid. Of these, Grapevine leafroll-associated virus 7 (GLRaV-7), an unassigned closterovirus, was by far the most prominently represented sequence in the analysis. Graft-inoculation of the infection to another grape variety confirmed the lack of the leafroll disease symptoms, even though GLRaV-7 could be detected in the inoculated indicator plants. A 16,496 nucleotide-long genomic sequence of this virus was determined from the deep sequencing data. Its genome architecture and the sequences encoding its nine predicted proteins were compared with those of other closteroviruses. The comparison revealed that two other viruses, Little cherry virus-1 and Cordyline virus-1 formed a well supported phylogenetic cluster with GLRaV-7. (C) 2011 Elsevier B.V. All rights reserved. C1 [Al Rwahnih, Maher; Daubert, Steve; Rowhani, Adib] Univ Calif Davis, Dept Plant Pathol, Davis, CA 95616 USA. [Dolja, Valerian V.] Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA. [Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Rowhani, A (reprint author), Univ Calif Davis, Dept Plant Pathol, Davis, CA 95616 USA. EM akrowhani@ucdavis.edu NR 44 TC 34 Z9 35 U1 1 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 EI 1872-7492 J9 VIRUS RES JI Virus Res. PD JAN PY 2012 VL 163 IS 1 BP 302 EP 309 DI 10.1016/j.virusres.2011.10.018 PG 8 WC Virology SC Virology GA 903YU UT WOS:000301160200037 PM 22056321 ER PT J AU Grady, C Rubinstein, YR Groft, SC AF Grady, Christine Rubinstein, Yaffa R. Groft, Stephen C. TI Informed consent and patient registry for the rare disease community: Editorial SO CONTEMPORARY CLINICAL TRIALS LA English DT Editorial Material DE Informed consent; Patient registry; Rare disease; Rare disease community; Patient advocacy group C1 [Rubinstein, Yaffa R.; Groft, Stephen C.] NIH, Off Rare Dis Res, Bethesda, MD 20892 USA. [Grady, Christine] NIH, Ctr Clin, Dept Bioeth, Head Sect Human Subjects Res, Bethesda, MD 20892 USA. RP Rubinstein, YR (reprint author), NIH, Off Rare Dis Res, Bldg 10, Bethesda, MD 20892 USA. EM rubinsty@mail.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 0 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JAN PY 2012 VL 33 IS 1 BP 3 EP 4 DI 10.1016/j.cct.2011.10.005 PG 2 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 889KL UT WOS:000300072500004 PM 22036667 ER PT J AU Rubinstein, YR Groft, SC Chandros, SH Kaneshiro, J Karp, B Lockhart, NC Marshall, PA Moxley, RT Pollen, GB Miller, VR Schwartz, J AF Rubinstein, Yaffa R. Groft, Stephen C. Chandros, Sara Hull Kaneshiro, Julie Karp, Barbara Lockhart, Nicole C. Marshall, Patricia A. Moxley, Richard T., III Pollen, Geraldine B. Miller, Vanessa Rangel Schwartz, Jack TI Informed consent process for patient participation in rare disease registries linked to biorepositories SO CONTEMPORARY CLINICAL TRIALS LA English DT Article C1 [Rubinstein, Yaffa R.; Groft, Stephen C.; Pollen, Geraldine B.] NIH, Off Rare Dis Res, Bethesda, MD 20892 USA. [Chandros, Sara Hull] NHGRI, Off Clin Director, Dept Bioeth, Clin Ctr,NIH, Bethesda, MD 20892 USA. [Kaneshiro, Julie] Off Human Res Protect, Dept Hlth & Human Serv, Rockville, MD USA. [Karp, Barbara] NIH, Combined NeuroSci Inst Review Board, Bethesda, MD 20892 USA. [Lockhart, Nicole C.] NCI, Off Biorepositories & Biospecimen Res, NIH, Bethesda, MD 20892 USA. [Marshall, Patricia A.] Case Western Univ, Cleveland, OH USA. [Miller, Vanessa Rangel] Innolyst Inc, Patient Crossrd, San Mateo, CA USA. [Schwartz, Jack] Univ Maryland, Sch Law, Baltimore, MD 21201 USA. RP Rubinstein, YR (reprint author), NIH, Off Rare Dis Res, 6100 Execut Blvd,Room 3A07,MSC-7518, Bethesda, MD 20892 USA. EM rubinsty@mail.nih.gov FU NHGRI NIH HHS [P50 HG003390] NR 2 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JAN PY 2012 VL 33 IS 1 BP 5 EP 11 DI 10.1016/j.cct.2011.10.004 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 889KL UT WOS:000300072500005 PM 22036955 ER PT J AU Berger, VW AF Berger, Vance W. TI Keep digging until we get the result we want? SO CONTEMPORARY CLINICAL TRIALS LA English DT Letter DE Clinical trial; Run-in phase ID RUN-IN SELECTION; CLINICAL-TRIALS C1 [Berger, Vance W.] NCI, Biometry Res Grp, Bethesda, MD 20892 USA. [Berger, Vance W.] UMBC, Bethesda, MD 20892 USA. RP Berger, VW (reprint author), NCI, Biometry Res Grp, Execut Plaza N,Suite 3131,6130 Execut Blvd,MSC 73, Bethesda, MD 20892 USA. EM vb78c@nih.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JAN PY 2012 VL 33 IS 1 BP 12 EP 12 DI 10.1016/j.cct.2011.09.014 PG 1 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 889KL UT WOS:000300072500006 PM 22001359 ER PT J AU Ulrich, CM Zhou, QP Ratcliffe, SJ Ye, LC Grady, C Watkins-Bruner, D AF Ulrich, Connie M. Zhou, Quiping Ratcliffe, Sarah J. Ye, Lichuan Grady, Christine Watkins-Bruner, Deborah TI Nurse Practitioners' attitudes about cancer clinical trials and willingness to recommend research participation SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Clinical trials; Nurse Practitioners; Recruitment; Retention ID FINANCIAL INCENTIVES; RANDOMIZED-TRIAL; MEDICAL-RESEARCH; RESPONSE RATES; MAIL SURVEYS; KNOWLEDGE; BARRIERS AB Background: Recruitment and retention of human participants in cancer clinical trials remains challenging for all investigators. Nurse Practitioners (NPs) are in a prime position to discuss, educate and refer patients to clinical trials as many NPs work in ethnically and geographically diverse primary care settings in the U.S., yet they remain an untapped resource. We examined NPs' general attitudes toward cancer clinical trial recommendations and assessed their willingness to recommend such trials. Methods: We randomly surveyed 455 primary care NPs in the state of Pennsylvania during 2008 with an adjusted response rate of 55.3%. Descriptive statistics were used to characterize NPs' demographic and practice characteristics, and logistic regression was used to assess the relative influence of the various attitudes and beliefs on the likelihood that the NP would bring up clinical trials as a treatment option. Results: NPs were more likely to bring up the topic of clinical trials with at least some patients if they were comfortable discussing treatment options with their cancer patients (OR=4.29, p=0.001), were comfortable discussing options of entering a clinical trial for treatment (OR=3.54, p=0.003), had adequate time during patients' visit to explain clinical trials (OR=3.40, p=0.008), and if they believed that patients in clinical trials were receiving the best medical treatment (OR=3.34, p=0.019). NPs who were comfortable discussing cancer clinical trials were almost 5 times more likely to think clinical trials were useful (OR=4.70; 95% CI=1.81-12.19; p=0.001). Nearly three-quarters (72.6%) of the entire responder sample reported three or more ethical concerns associated with clinical trials, including issues of randomization, informed consent, and patient burden. Conclusions: NPs are willing to recommend clinical trials but need more education about the benefits and burdens of clinical trials, the associated ethical concerns, and evidence regarding the translatability of research to clinical practice to increase their knowledge and comfort level with discussing clinical trials. (C) 2011 Elsevier Inc. All rights reserved. C1 [Ulrich, Connie M.] Univ Penn, Sch Nursing, Ctr Bioeth, Dept Med Eth, Philadelphia, PA 19106 USA. [Zhou, Quiping] George Mason Univ, Fairfax, VA 22030 USA. [Ratcliffe, Sarah J.] Univ Penn, Dept Biostat, Perelman Sch Med, Philadelphia, PA 19106 USA. [Ye, Lichuan] Boston Coll, Sch Nursing, Boston, MA USA. [Grady, Christine] NIH, Dept Bioeth, Bethesda, MD 20892 USA. [Watkins-Bruner, Deborah] Emory Univ, Nell Hodgson Woodruff Sch Nursing, Atlanta, GA 30322 USA. [Watkins-Bruner, Deborah] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. RP Ulrich, CM (reprint author), Univ Penn, Sch Nursing, Ctr Bioeth, Dept Med Eth, Philadelphia, PA 19106 USA. EM culrich@nursing.upenn.edu OI Ratcliffe, Sarah/0000-0002-6644-8284 FU Pennsylvania Health Research Formula Funds Research [0682001] FX The work reported in this article was supported by a Grant (number: 0682001) from the Pennsylvania Health Research Formula Funds Research Grant subcontracted with the Oncology Nursing Society. The opinions are the personal views of the authors and do not reflect the official policies or positions of the Department of Health and Human Services, NIH, or the Public Health Service. School of Nursing, and Center for Bioethics and the NewCourtlandCenter for Transitions and Health, University of Pennsylvania, Philadelphia, Pennsylvania 19106. NR 23 TC 8 Z9 8 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JAN PY 2012 VL 33 IS 1 BP 76 EP 84 DI 10.1016/j.cct.2011.09.005 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 889KL UT WOS:000300072500015 PM 21983623 ER PT J AU Samuel-Hodge, CD Garcia, BA Johnston, LF Kraschnewski, JL Gustafson, AA Norwood, AF Glasgow, RE Gold, AD Graham, JW Evenson, KR Stearns, SC Gizlice, Z Keyserling, TC AF Samuel-Hodge, Carmen D. Garcia, Beverly A. Johnston, Larry F. Kraschnewski, Jennifer L. Gustafson, Alison A. Norwood, Arnita F. Glasgow, Russell E. Gold, Alison D. Graham, John W. Evenson, Kelly R. Stearns, Sally C. Gizlice, Ziya Keyserling, Thomas C. TI Rationale, design, and sample characteristics of a practical randomized trial to assess a weight loss intervention for low-income women: The Weight-Wise II Program SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Weight loss; Translational research; Practical randomized trial; Low-income; Mid-life women; Health departments; Obesity ID PHYSICAL-ACTIVITY; TRANSLATIONAL RESEARCH; CLINICAL-RESEARCH; PRIMARY-CARE; MANAGEMENT; ADULTS; QUESTIONNAIRE; PREVENTION; REDUCTION; OBESITY AB Obesity is common among low-income mid-life women, yet most published weight loss studies have not focused on this population and have been highly resourced efficacy trials. Thus, practical type 2 translational studies are needed to evaluate weight loss interventions for low-income women. In this paper, we present the rationale, study design, and baseline characteristics of a type 2 translational study that evaluates both the processes and outcomes of a weight loss intervention for low-income women given at 6 county health departments in North Carolina. Key features of this study include random selection of study sites, intervention delivery by current staff at study sites, efforts to integrate the intervention with local community resources, a focus on evaluating the processes of translation using the RE-AIM framework, use of an evidence-based weight loss intervention, a detailed description of participant recruitment and representativeness, and a practical randomized trial designed to assess the effectiveness of the intervention. Of 81 health departments invited to participate, 30 (37%) were eligible and willing, and 6 were selected at random to deliver the intervention. Of 432 potential participants screened by phone, 213 (49%) were eligible and of these, 189 (89%) completed baseline measures and were randomized to receive a 5-month weight loss intervention or a delayed intervention. The mean age was 51, mean BMI 37 kg/m(2), 53% were African American, and 43% had no health insurance. The results of this study should be informative to key stakeholders interested in real world weight loss interventions for low-income mid-life women. (C) 2011 Elsevier Inc. All rights reserved. C1 [Samuel-Hodge, Carmen D.; Evenson, Kelly R.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Samuel-Hodge, Carmen D.; Norwood, Arnita F.] Univ N Carolina, Sch Med, Dept Nutr, Chapel Hill, NC 27599 USA. [Garcia, Beverly A.; Johnston, Larry F.; Gizlice, Ziya] Univ N Carolina, Ctr Hlth Promot & Dis Prevent, Chapel Hill, NC 27599 USA. [Gustafson, Alison A.] Univ Kentucky, Dept Nutr, Lexington, KY 40506 USA. [Glasgow, Russell E.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Graham, John W.] Univ N Carolina, N Carolina Inst Publ Hlth, Chapel Hill, NC 27599 USA. [Stearns, Sally C.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Policy & Management, Chapel Hill, NC 27599 USA. [Keyserling, Thomas C.] Univ N Carolina, Sch Med, Div Gen Internal Med, Chapel Hill, NC 27599 USA. RP Samuel-Hodge, CD (reprint author), Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, 1700 Martin Luther King Jr Blvd,CB 7426, Chapel Hill, NC 27599 USA. EM Carmen_Samuel@unc.edu FU Centers for Disease Control and Prevention (CDC) [5R18DP001144]; University of North Carolina Prevention Research Center (Center for Health Promotion and Disease Prevention) through CDC [U48/DP000059]; Health Resources and Services Administration through a National Research Service [5132 PE14001-20]; National Cancer Institute (NCI) FX This study was supported through funding by the Centers for Disease Control and Prevention (CDC) grant no. 5R18DP001144. Other support was provided by the University of North Carolina Prevention Research Center (Center for Health Promotion and Disease Prevention) through funding by CDC cooperative agreement no. U48/DP000059. Dr. Kraschnewski was supported by the Health Resources and Services Administration through a National Research Service Award Primary Care Research Fellowship (5132 PE14001-20). These funding sources had no involvement with the preparation of this manuscript or the decision to submit for publication. Dr. Glasgow is now with the National Cancer Institute (NCI). This paper does not necessarily reflect the opinions of the NCI. NR 37 TC 12 Z9 12 U1 0 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JAN PY 2012 VL 33 IS 1 BP 93 EP 103 DI 10.1016/j.cct.2011.08.009 PG 11 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 889KL UT WOS:000300072500017 PM 21930244 ER PT J AU Visco, AG Brubaker, L Richter, HE Nygaard, I Paraiso, MF Menefee, SA Schaffer, J Wei, J Chai, T Janz, N Spino, C Meikle, S AF Visco, Anthony G. Brubaker, Linda Richter, Holly E. Nygaard, Ingrid Paraiso, Marie Fidela Menefee, Shawn A. Schaffer, Joseph Wei, John Chai, Toby Janz, Nancy Spino, Cathie Meikle, Susan CA Pelvic Floor Disorders Network TI Anticholinergic versus botulinum toxin A comparison trial for the treatment of bothersome urge urinary incontinence: ABC trial SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Urge incontinence; Urgency urinary incontinence; Overactive bladder; Botulinum toxin; Anticholinergic therapy; Solifenacin; Trospium; Randomized clinical trial ID PHASE-III TRIAL; ANTIMUSCARINIC AGENT SOLIFENACIN; OVERACTIVE BLADDER QUESTIONNAIRE; PLACEBO-CONTROLLED TRIAL; DETRUSOR OVERACTIVITY; DOUBLE-BLIND; TROSPIUM CHLORIDE; CLINICAL-TRIALS; SHORT-FORM; OAB-Q AB This trial compares the change in urgency urinary incontinence episodes over 6 months, tolerability and cost effectiveness between women receiving daily anticholinergic therapy plus a single intra-detrusor injection of saline versus a single intra-detrusor injection of 100 U of botulinum toxin A plus daily oral placebo tablets. We present the rationale and design of a randomized-controlled trial, Anticholinergic versus Botulinum Toxin, Comparison Trial for the Treatment of Bothersome Urge Urinary Incontinence: ABC trial, conducted by the NICHD-funded Pelvic Floor Disorders Network. We discuss the innovative nature of this trial and the challenges related to choice of patient population, maintaining masking, cost effectiveness, ethical considerations, measuring adherence, and placebo development and testing. Enrollment began in April, 2010. 242 participants will be randomized and primary outcome data analysis is anticipated to begin in mid 2012. Several challenges in the trial design are discussed. Randomization to placebo intra-detrusor injections may limit recruitment, potentially impacting generalizability. Other challenges included the heavy marketing of drugs for overactive bladder which could impact recruitment of drug-naive women. In addition, anticholinergic medications often cause dry mouth, making masking difficult. Finally, adverse reporting of transient urinary retention is challenging as there is no standardized definition; yet this is the most common adverse event following intra-detrusor botulinum toxin injection. The ABC trial will help women with urgency urinary incontinence balance efficacy, side effects and cost of anticholinergic medication versus botulinum toxin intra-detrusor injection. The results have the potential to fundamentally change the therapeutic approach to this condition. (C) 2011 Elsevier Inc. All rights reserved. C1 [Visco, Anthony G.] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Div Urogynecol & Reconstruct Pelv Surg, Durham, NC 27710 USA. [Brubaker, Linda] Loyola Univ, Stritch Sch Med, Dept Obstet & Gynecol, Chicago, IL 60611 USA. [Brubaker, Linda] Loyola Univ, Stritch Sch Med, Dept Urol, Chicago, IL 60611 USA. [Richter, Holly E.] Univ Alabama, Dept Obstet & Gynecol, Birmingham, IL USA. [Nygaard, Ingrid] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. [Paraiso, Marie Fidela] Cleveland Clin, Dept Obstet & Gynecol, Cleveland, OH 44106 USA. [Menefee, Shawn A.] Kaiser Permanente San Diego, Dept Obstet & Gynecol, San Diego, CA USA. [Schaffer, Joseph] SW Texas State Univ, Dept Obstet & Gynecol, Dallas, TX USA. [Wei, John] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. [Chai, Toby] Univ Maryland, Dept Urol, College Pk, MD 20742 USA. [Janz, Nancy; Spino, Cathie] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Meikle, Susan] NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Populat Res Ctr, Contracept & Reprod Hlth Branch, Bethesda, MD 20892 USA. RP Visco, AG (reprint author), Duke Univ, Med Ctr, Dept Obstet & Gynecol, Div Urogynecol & Reconstruct Pelv Surg, DUMC 3192, Durham, NC 27710 USA. EM anthony.visco@duke.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [2U01 HD41249, 2U10 HD41250, 2U10 HD41261, 2U10 HD41267, 1U10 HD54136, 1U10 HD54214, 1U10 HD54215, 1U10 HD54241]; NIH Office of Research on Women's Health FX Supported by grants from The Eunice Kennedy Shriver National Institute of Child Health and Human Development, (2U01 HD41249, 2U10 HD41250, 2U10 HD41261, 2U10 HD41267, 1U10 HD54136, 1U10 HD54214, 1U10 HD54215, 1U10 HD54241) and the NIH Office of Research on Women's Health. NR 45 TC 8 Z9 8 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JAN PY 2012 VL 33 IS 1 BP 184 EP 196 DI 10.1016/j.cct.2011.09.019 PG 13 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 889KL UT WOS:000300072500027 PM 22008247 ER PT J AU Winhusen, T Stitzer, M Woody, G Brigham, G Kropp, F Ghitza, U Lindblad, R Adinoff, B Green, C Sharma, G Somoza, E AF Winhusen, Theresa Stitzer, Maxine Woody, George Brigham, Gregory Kropp, Frankie Ghitza, Udi Lindblad, Robert Adinoff, Bryon Green, Cindy Sharma, Gaurav Somoza, Eugene TI Design considerations for a study to evaluate the impact of smoking cessation treatment on stimulant use outcomes in stimulant-dependent individuals SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Cocaine; Methamphetamine; Smoking cessation; Bupropion; Contingency management ID PLACEBO-CONTROLLED TRIAL; CARBON-MONOXIDE LEVELS; CIGARETTE-SMOKING; COCAINE DEPENDENCE; METHAMPHETAMINE DEPENDENCE; CONTINGENCY MANAGEMENT; TREATMENT PROGRAMS; DEPRESSION SCALE; HOSPITAL ANXIETY; ABUSE TREATMENT AB Cigarette smoking is prevalent in cocaine/methamphetamine-dependent patients and associated with significant morbidity and mortality, yet, the provision of smoking cessation treatment in conjunction with substance use disorder (SUD) treatment is not standard practice. This is due, in part, to clinician concern that combining smoking cessation treatment with SUD treatment could lead to poorer SUD outcomes. The NIDA Clinical Trials Network is conducting a 10-week, two-group, randomized trial to evaluate the impact of providing smoking cessation treatment (SCT) with SUD treatment as usual (TAU), compared to TAU alone, in smokers who are in outpatient treatment for cocaine or methamphetamine dependence. Approximately 528 participants, recruited from 12 community treatment programs, will be randomized into the trial. The present paper describes key design decisions made during protocol development. The trial is designed to evaluate the relationship between cigarette smoking and stimulant use, which prior research suggests is linked, and should contribute to our understanding of how best to address the co-occurring problems of nicotine dependence and cocaine/methamphetamine-dependence. Unique aspects of the trial include the primary question of interest, which concerns the impact of providing SCT on SUD outcomes rather than on smoking outcomes, and the intensity of the SCT chosen, which includes bupropion, nicotine replacement, and two psychosocial interventions. (C) 2011 Elsevier Inc. All rights reserved. C1 [Winhusen, Theresa; Brigham, Gregory; Kropp, Frankie; Somoza, Eugene] Univ Cincinnati, Coll Med, Dept Psychiat & Behav Neurosci, Cincinnati, OH 45220 USA. [Stitzer, Maxine] Johns Hopkins Univ, Sch Med, Bayview Med Ctr, Dept Psychiat & Behav Sci, Baltimore, MD 21224 USA. [Woody, George] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19106 USA. [Brigham, Gregory] Maryhaven, Columbus, OH 43207 USA. [Ghitza, Udi] Ctr Clin Trials Network, NIDA, Bethesda, MD 20892 USA. [Adinoff, Bryon] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Adinoff, Bryon] VA N Texas Hlth Care Syst, Dallas, TX 75216 USA. [Green, Cindy] Duke Clin Res Inst, Durham, NC 27705 USA. [Lindblad, Robert; Sharma, Gaurav] EMMES Corp, Rockville, MD 20850 USA. [Somoza, Eugene] Vet Affairs Med Ctr VISN 10, Cincinnati, OH 45220 USA. RP Winhusen, T (reprint author), Univ Cincinnati, Coll Med, Dept Psychiat & Behav Neurosci, 3210 Jefferson Ave, Cincinnati, OH 45220 USA. EM winhusen@carc.uc.edu OI Winhusen, Theresa/0000-0002-3364-0739; Brigham, Gregory/0000-0003-1150-4493 FU NIDA [U10-DA013732] FX This work was supported by NIDA grant: U10-DA013732 to the University of Cincinnati (Dr. Somoza). NR 47 TC 8 Z9 8 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JAN PY 2012 VL 33 IS 1 BP 197 EP 205 DI 10.1016/j.cct.2011.09.018 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 889KL UT WOS:000300072500028 PM 22005174 ER PT J AU Naitza, S Porcu, E Steri, M Taub, DD Mulas, A Xiao, X Strait, J Dei, M Lai, S Busonero, F Maschio, A Usala, G Zoledziewska, M Sidore, C Zara, I Pitzalis, M Loi, A Virdis, F Piras, R Deidda, F Whalen, MB Crisponi, L Concas, A Podda, C Uzzau, S Scheet, P Longo, DL Lakatta, E Abecasis, GR Cao, A Schlessinger, D Uda, M Sanna, S Cucca, F AF Naitza, Silvia Porcu, Eleonora Steri, Maristella Taub, Dennis D. Mulas, Antonella Xiao, Xiang Strait, James Dei, Mariano Lai, Sandra Busonero, Fabio Maschio, Andrea Usala, Gianluca Zoledziewska, Magdalena Sidore, Carlo Zara, Ilenia Pitzalis, Maristella Loi, Alessia Virdis, Francesca Piras, Roberta Deidda, Francesca Whalen, Michael B. Crisponi, Laura Concas, Antonio Podda, Carlo Uzzau, Sergio Scheet, Paul Longo, Dan L. Lakatta, Edward Abecasis, Goncalo R. Cao, Antonio Schlessinger, David Uda, Manuela Sanna, Serena Cucca, Francesco TI A Genome-Wide Association Scan on the Levels of Markers of Inflammation in Sardinians Reveals Associations That Underpin Its Complex Regulation SO PLOS GENETICS LA English DT Article ID C-REACTIVE PROTEIN; MONOCYTE CHEMOATTRACTANT PROTEIN-1; CORONARY-ARTERY-DISEASE; COPY NUMBER VARIATION; 3,000 SHARED CONTROLS; MULTIPLE-SCLEROSIS; COMMON VARIANTS; GENE-EXPRESSION; LOCI; RISK AB Identifying the genes that influence levels of pro-inflammatory molecules can help to elucidate the mechanisms underlying this process. We first conducted a two-stage genome-wide association scan (GWAS) for the key inflammatory biomarkers Interleukin-6 (IL-6), the general measure of inflammation erythrocyte sedimentation rate (ESR), monocyte chemotactic protein-1 (MCP-1), and high-sensitivity C-reactive protein (hsCRP) in a large cohort of individuals from the founder population of Sardinia. By analysing 731,213 autosomal or X chromosome SNPs and an additional,1.9 million imputed variants in 4,694 individuals, we identified several SNPs associated with the selected quantitative trait loci (QTLs) and replicated all the top signals in an independent sample of 1,392 individuals from the same population. Next, to increase power to detect and resolve associations, we further genotyped the whole cohort (6,145 individuals) for 293,875 variants included on the ImmunoChip and MetaboChip custom arrays. Overall, our combined approach led to the identification of 9 genome-wide significant novel independent signals-5 of which were identified only with the custom arrays-and provided confirmatory evidence for an additional 7. Novel signals include: for IL-6, in the ABO gene (rs657152, p = 2.13x10(-29)); for ESR, at the HBB (rs4910472, p = 2.31x10(-11)) and UCN119B/SPPL3 (rs11829037, p = 8.91x10(-10)) loci; for MCP-1, near its receptor CCR2 (rs17141006, p = 7.53x10(-13)) and in CADM3 (rs3026968, p = 7.63x10(-13)); for hsCRP, within the CRP gene (rs3093077, p = 5.73x10(-21)), near DARC (rs3845624, p = 1.43x10(-10)), UNC119B/SPPL3 (rs11829037, p = 1.50x10(-14)), and ICOSLG/AIRE (rs113459440, p = 1.54x10(-08)) loci. Confirmatory evidence was found for IL-6 in the IL6R gene (rs4129267); for ESR at CR1 (rs12567990) and TMEM57 (rs10903129); for MCP-1 at DARC (rs12075); and for hsCRP at CRP (rs1205), HNF1A (rs225918), and APOC-I (rs4420638). Our results improve the current knowledge of genetic variants underlying inflammation and provide novel clues for the understanding of the molecular mechanisms regulating this complex process. C1 [Naitza, Silvia; Porcu, Eleonora; Steri, Maristella; Mulas, Antonella; Dei, Mariano; Lai, Sandra; Busonero, Fabio; Maschio, Andrea; Usala, Gianluca; Sidore, Carlo; Loi, Alessia; Virdis, Francesca; Piras, Roberta; Crisponi, Laura; Cao, Antonio; Uda, Manuela; Sanna, Serena; Cucca, Francesco] CNR, Ist Ric Genet & Biomed, Cagliari, Italy. [Taub, Dennis D.; Strait, James; Longo, Dan L.; Lakatta, Edward; Schlessinger, David] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Xiao, Xiang; Scheet, Paul] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Zoledziewska, Magdalena; Sidore, Carlo; Pitzalis, Maristella; Deidda, Francesca; Uzzau, Sergio; Cucca, Francesco] Univ Sassari, Dipartimento Sci Biomed, I-07100 Sassari, Italy. [Sidore, Carlo; Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Zara, Ilenia; Whalen, Michael B.] Ctr Adv Studies Res & Dev Sardinia CRS4, AGCT Program, Pula, Italy. [Concas, Antonio; Podda, Carlo] CRS4, High Performance Comp & Network, Pula, Italy. [Uzzau, Sergio] Porto Conte Ric, Localita Tramariglio, Sassari, Italy. RP Naitza, S (reprint author), CNR, Ist Ric Genet & Biomed, Cagliari, Italy. EM francesco.cucca@inn.cnr.it RI Abecasis, Goncalo/B-7840-2010; Naitza, Silvia/D-5620-2017; OI sanna, serena/0000-0002-3768-1749; Abecasis, Goncalo/0000-0003-1509-1825; Pitzalis, Maristella/0000-0003-4975-6987; Steri, Anna Maristella/0000-0001-5869-3872; Mulas, Antonella/0000-0002-6856-1483; WHALEN, MICHAELBERNARD/0000-0001-7300-8511; Sidore, Carlo/0000-0001-7504-7477 FU National Institute on Aging (NIA) [NO1-AG-1-2109, 263-MA-410953]; National Institutes of Health (NIH) [HG002651, HL084729]; Fondazione Italiana Sclerosi Multipla (FISM) [2008/R/7]; Italian Ministry of Economy and Finance FX This work was supported by the Intramural Research Program of the National Institute on Aging (NIA), National Institutes of Health (NIH). The SardiNIA team was supported by Contract NO1-AG-1-2109 from the NIA. This study was also partly supported by the Fondazione Italiana Sclerosi Multipla (FISM) Cod. 2008/R/7 and by a grant from the Italian Ministry of Economy and Finance to the CNR for the Project "FaReBio di Qualita" to F Cucca; the efforts of GR Abecasis were supported in part by contract 263-MA-410953 from the NIA to the University of Michigan and by research grant HG002651 and HL084729 from the NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 65 TC 47 Z9 48 U1 0 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD JAN PY 2012 VL 8 IS 1 AR e1002480 DI 10.1371/journal.pgen.1002480 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 891NH UT WOS:000300223400039 PM 22291609 ER PT J AU Yu, K Wacholder, S Wheeler, W Wang, ZM Caporaso, N Landi, MT Liang, FM AF Yu, Kai Wacholder, Sholom Wheeler, William Wang, Zhaoming Caporaso, Neil Landi, Maria Teresa Liang, Faming TI A Flexible Bayesian Model for Studying Gene-Environment Interaction SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; HAPLOTYPE ASSOCIATIONS; SMOKING-BEHAVIOR; LUNG-CANCER; EQUIVALENCE; DISEASE; LOCI AB An important follow-up step after genetic markers are found to be associated with a disease outcome is a more detailed analysis investigating how the implicated gene or chromosomal region and an established environment risk factor interact to influence the disease risk. The standard approach to this study of gene-environment interaction considers one genetic marker at a time and therefore could misrepresent and underestimate the genetic contribution to the joint effect when one or more functional loci, some of which might not be genotyped, exist in the region and interact with the environment risk factor in a complex way. We develop a more global approach based on a Bayesian model that uses a latent genetic profile variable to capture all of the genetic variation in the entire targeted region and allows the environment effect to vary across different genetic profile categories. We also propose a resampling-based test derived from the developed Bayesian model for the detection of gene-environment interaction. Using data collected in the Environment and Genetics in Lung Cancer Etiology (EAGLE) study, we apply the Bayesian model to evaluate the joint effect of smoking intensity and genetic variants in the 15q25.1 region, which contains a cluster of nicotinic acetylcholine receptor genes and has been shown to be associated with both lung cancer and smoking behavior. We find evidence for gene-environment interaction (P-value = 0.016), with the smoking effect appearing to be stronger in subjects with a genetic profile associated with a higher lung cancer risk; the conventional test of gene-environment interaction based on the single-marker approach is far from significant. C1 [Yu, Kai; Wacholder, Sholom; Wang, Zhaoming; Caporaso, Neil; Landi, Maria Teresa] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Wheeler, William] Informat Management Serv Inc, Rockville, MD USA. [Wang, Zhaoming] NCI, Core Genotyping Facil, SAIC Frederick, Frederick, MD 21701 USA. [Liang, Faming] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. RP Yu, K (reprint author), NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. EM yuka@mail.nih.gov FU National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 43 TC 9 Z9 9 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD JAN PY 2012 VL 8 IS 1 AR e1002482 DI 10.1371/journal.pgen.1002482 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 891NH UT WOS:000300223400040 PM 22291610 ER PT J AU De Pascalis, R Chou, AY Bosio, CM Huang, CY Follmann, DA Elkins, KL AF De Pascalis, Roberto Chou, Alicia Y. Bosio, Catharine M. Huang, Chiung-Yu Follmann, Dean A. Elkins, Karen L. TI Development of Functional and Molecular Correlates of Vaccine-Induced Protection for a Model Intracellular Pathogen, F. tularensis LVS SO PLOS PATHOGENS LA English DT Article ID VIRULENT TYPE-A; NECROSIS-FACTOR-ALPHA; T-CELL RESPONSES; FRANCISELLA-TULARENSIS; MYCOBACTERIUM-TUBERCULOSIS; AEROSOL CHALLENGE; INTERFERON-GAMMA; IMMUNOREACTIVE ANTIGENS; TULAREMIA VACCINES; MEMBRANE-PROTEIN AB In contrast with common human infections for which vaccine efficacy can be evaluated directly in field studies, alternative strategies are needed to evaluate efficacy for slowly developing or sporadic diseases like tularemia. For diseases such as these caused by intracellular bacteria, serological measures of antibodies are generally not predictive. Here, we used vaccines varying in efficacy to explore development of clinically useful correlates of protection for intracellular bacteria, using Francisella tularensis as an experimental model. F. tularensis is an intracellular bacterium classified as Category A bioterrorism agent which causes tularemia. The primary vaccine candidate in the U. S., called Live Vaccine Strain (LVS), has been the subject of ongoing clinical studies; however, safety and efficacy are not well established, and LVS is not licensed by the U. S. FDA. Using a mouse model, we compared the in vivo efficacy of a panel of qualitatively different Francisella vaccine candidates, the in vitro functional activity of immune lymphocytes derived from vaccinated mice, and relative gene expression in immune lymphocytes. Integrated analyses showed that the hierarchy of protection in vivo engendered by qualitatively different vaccines was reflected by the degree of lymphocytes' in vitro activity in controlling the intramacrophage growth of Francisella. Thus, this assay may be a functional correlate. Further, the strength of protection was significantly related to the degree of up-regulation of expression of a panel of genes in cells recovered from the assay. These included IFN-gamma, IL-6, IL-12R beta 2, T-bet, SOCS-1, and IL-18bp. Taken together, the results indicate that an in vitro assay that detects control of bacterial growth, and/or a selected panel of mediators, may ultimately be developed to predict the outcome of vaccine efficacy and to complement clinical trials. The overall approach may be applicable to intracellular pathogens in general. C1 [De Pascalis, Roberto; Chou, Alicia Y.; Elkins, Karen L.] US FDA, Lab Mycobacterial Dis & Cellular Immunol, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Bosio, Catharine M.] NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. [Huang, Chiung-Yu; Follmann, Dean A.] NIAID, Biostat Res Branch, Div Clin Res, NIH, Hamilton, MT USA. RP De Pascalis, R (reprint author), US FDA, Lab Mycobacterial Dis & Cellular Immunol, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM karen.elkins@fda.hhs.gov RI Bosio, Catharine/D-7456-2015 FU National Institute of Allergy and Infectious Diseases [Y1-AI-6153-01/224-06-1322] FX This work was supported in part by an interagency agreement with the National Institute of Allergy and Infectious Diseases (Y1-AI-6153-01/224-06-1322). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 73 TC 19 Z9 19 U1 2 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2012 VL 8 IS 1 AR e1002494 DI 10.1371/journal.ppat.1002494 PG 14 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 898UI UT WOS:000300767100037 PM 22275868 ER PT J AU Li, J Hakata, Y Takeda, E Liu, QP Iwatani, Y Kozak, CA Miyazawa, M AF Li, Jun Hakata, Yoshiyuki Takeda, Eri Liu, Qingping Iwatani, Yasumasa Kozak, Christine A. Miyazawa, Masaaki TI Two Genetic Determinants Acquired Late in Mus Evolution Regulate the Inclusion of Exon 5, which Alters Mouse APOBEC3 Translation Efficiency SO PLOS PATHOGENS LA English DT Article ID MURINE LEUKEMIA VIRUSES; IN-VIVO; ENDOGENOUS RETROVIRUSES; HOUSE MOUSE; ANTIRETROVIRAL DEFENSE; HIV-1 INFECTION; EDITING ENZYME; VIF PROTEIN; GENUS MUS; WILD MICE AB Mouse apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like editing complex 3 (mA3), an intracellular antiviral factor, has 2 allelic variations that are linked with different susceptibilities to beta-and gammaretrovirus infections among various mouse strains. In virus-resistant C57BL/6 (B6) mice, mA3 transcripts are more abundant than those in susceptible BALB/c mice both in the spleen and bone marrow. These strains of mice also express mA3 transcripts with different splicing patterns: B6 mice preferentially express exon 5-deficient (Delta 5) mA3 mRNA, while BALB/c mice produce exon 5-containing full-length mA3 mRNA as the major transcript. Although the protein product of the Delta 5 mRNA exerts stronger antiretroviral activities than the full-length protein, how exon 5 affects mA3 antiviral activity, as well as the genetic mechanisms regulating exon 5 inclusion into the mA3 transcripts, remains largely uncharacterized. Here we show that mA3 exon 5 is indeed a functional element that influences protein synthesis at a post-transcriptional level. We further employed in vitro splicing assays using genomic DNA clones to identify two critical polymorphisms affecting the inclusion of exon 5 into mA3 transcripts: the number of TCCT repeats upstream of exon 5 and the single nucleotide polymorphism within exon 5 located 12 bases upstream of the exon 5/intron 5 boundary. Distribution of the above polymorphisms among different Mus species indicates that the inclusion of exon 5 into mA3 mRNA is a relatively recent event in the evolution of mice. The widespread geographic distribution of this exon 5-including genetic variant suggests that in some Mus populations the cost of maintaining an effective but mutagenic enzyme may outweigh its antiviral function. C1 [Li, Jun; Hakata, Yoshiyuki; Takeda, Eri; Miyazawa, Masaaki] Kinki Univ, Sch Med, Dept Immunol, Osaka 589, Japan. [Liu, Qingping; Kozak, Christine A.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Iwatani, Yasumasa] Nagoya Med Ctr, Dept Infect & Immunol, Clin Res Ctr, Nagoya, Aichi, Japan. RP Li, J (reprint author), Kinki Univ, Sch Med, Dept Immunol, Osaka 589, Japan. EM hakata@med.kindai.ac.jp; masaaki@med.kindai.ac.jp FU Ministry of Education, Culture, Sports, Science and Technology of Japan; High-Tech Research Center; Anti-Aging Center; Japan Society for Promotion of Sciences, KAKENHI [21790450]; Ministry of Health, Labor and Welfare of Japan for Research on HIV/AIDS; NIH, NIAID FX This work was supported by grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, including the High-Tech Research Center and Anti-Aging Center projects, those from the Japan Society for Promotion of Sciences, KAKENHI (B), and those from the Ministry of Health, Labor and Welfare of Japan for Research on HIV/AIDS (all given to MM), and by a Grant-in-Aid for Young Scientists (B) from the Japan Society for the Promotion of Sciences, KAKENHI 21790450, given to YH. This work was also supported by the Intramural Research Program of the NIH, NIAID, given to CAK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 68 TC 13 Z9 14 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2012 VL 8 IS 1 AR e1002478 DI 10.1371/journal.ppat.1002478 PG 20 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 898UI UT WOS:000300767100024 PM 22275865 ER PT J AU Antas, P Holland, S Sterling, T AF Antas, Paulo Holland, Steven Sterling, Timothy TI Abnormal spontaneous interleukin 8 receptor expression: a brief report of two cases SO REVISTA DA SOCIEDADE BRASILEIRA DE MEDICINA TROPICAL LA English DT Article DE Interleukin 8 receptor; Lymphocytes; Cytokines ID SUSCEPTIBILITY; POLYMORPHISMS; TUBERCULOSIS; CHEMOKINES; DISEASE; CXCR2; IL-8 AB Interleukin 8 (CXCL8) is an autocrine chemokine specific for the chemoattraction and activation of granulocytes, NKT cells and T lymphocytes. Patients with tuberculosis and latent Mycobacterium tuberculosis infection were assessed for the spontaneous expression of CXCR1 (CD128) and CXCR2 on lymphocytes and monocytes. Compared with ex vivo profiles, increased spontaneous CXCR2 expression and normal CXCR1 expression were found on lymphocytes in two out of 59 individuals. Monocytes showed normal ex vivo profiles for both receptors. After stimulation with purified protein derivative, the in vitro levels of CXCL8 were below the median levels of all patients with prior tuberculosis. Spontaneous CXCR2 modulation did not cause notable variation in the in vitro levels of CXCL8. C1 [Antas, Paulo] Fundacao Oswaldo Cruz, Inst Oswaldo Cruz, Lab Imunol Clin, Rio De Janeiro, Brazil. [Antas, Paulo; Holland, Steven] NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Antas, Paulo; Sterling, Timothy] Vanderbilt Univ, Sch Med, Dept Med, Div Infect Dis, Nashville, TN 37212 USA. [Sterling, Timothy] Vanderbilt Univ, Sch Med, Dept Med, Ctr Hlth Serv Res, Nashville, TN 37212 USA. RP Antas, P (reprint author), Fiocruz MS, IOC, Lab Imunol Clin, Av Brasil 4365, BR-21045900 Rio De Janeiro, Brazil. EM pzuquim@ioc.fiocruz.br FU Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) (Brazil); Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) (Brazil) FX This study was partly financed by Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) (Brazil). P. A. is currently under a Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) research fellowship program (PQ-2, Brazil). NR 10 TC 2 Z9 2 U1 0 U2 1 PU SOC BRASILEIRA MEDICINA TROPICAL PI BRASILIA PA UNIV BRASILIA, NUCLEO MEDICINA TROPICAL E NUTRICAO, CAIXA POSTAL 4356, BRASILIA, DF 70919-970, BRAZIL SN 0037-8682 J9 REV SOC BRAS MED TRO JI Rev. Soc. Bras. Med. Trop. PD JAN-FEB PY 2012 VL 45 IS 1 BP 134 EP 137 PG 4 WC Parasitology; Tropical Medicine SC Parasitology; Tropical Medicine GA 899PT UT WOS:000300829000029 PM 22370847 ER PT J AU Goodwin, RS Baumann, MH Gorelick, DA Schwilke, E Schwope, DM Darwin, WD Kelly, DL Schroeder, JR Ortemann-Renon, C Bonnet, D Huestis, MA AF Goodwin, Robert S. Baumann, Michael H. Gorelick, David A. Schwilke, Eugene Schwope, David M. Darwin, William D. Kelly, Deanna L. Schroeder, Jennifer R. Ortemann-Renon, Catherine Bonnet, Denis Huestis, Marilyn A. TI CB1-Cannabinoid Receptor Antagonist Effects on Cortisol in Cannabis-Dependent Men SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE cortisol; rimonabant; cannabis; antagonist; withdrawal ID CORTICOTROPIN-RELEASING-FACTOR; ENDOCANNABINOID SYSTEM; ETHANOL WITHDRAWAL; RAT-BRAIN; DRUG; MARIJUANA; HUMANS; DELTA-9-TETRAHYDROCANNABINOL; ABSTINENCE; RIMONABANT AB Background: The endocannabinoid system modulates the hypothalamic-pituitary-adrenal (HPA) axis, but the effect of cannabinoid type 1 (CB1) receptor antagonism following chronic CB1 receptor stimulation in humans is unknown. Objectives: To evaluate effects of the CB1 receptor antagonist rimonabant on the HPA axis in cannabis-dependent individuals. Methods: Fourteen daily cannabis smokers received increasingly frequent 20 mg oral Delta 9-tetrahydrocannabinol (THC) doses (60-120 mg/day) over 8 days to standardize cannabis tolerance. Concurrent with the last THC dose, double-blind placebo or rimonabant (20 or 40 mg) was administered. Cannabinoid, rimonabant, and cortisol plasma concentrations were measured 1.5 hours prior to rimonabant administration and 2.0, 5.5, and 12.5 hours post-dose. Results: Ten participants completed before premature study termination due to rimonabant's withdrawal from development. Five participants received 20 mg, three received 40 mg, and two placebo. There was a significant positive association between rimonabant concentration and change in cortisol concentration from baseline (r = .53, p < .01). There also was a borderline significant association between rimonabant dose and cortisol concentrations when the dose-by-time interaction was included. Four of eight participants receiving rimonabant (none of two receiving placebo) had greater cortisol concentrations 2 hours after dosing (at 11: 30) than at 08: 00, while normal diurnal variation should have peak concentrations at 08:00. Conclusion: Rimonabant 20 or 40 mg did not significantly increase plasma cortisol concentrations, consistent with an absence of antagonist-elicited cannabis withdrawal. Scientific Significance: Rimonabant doses >40 mg might elicit cortisol changes, confirming a role for CB1 receptors in modulating the HPA axis in humans. C1 [Schroeder, Jennifer R.; Huestis, Marilyn A.] Natl Inst Drug Abuse, Intramural Res Program, Off Clin Director, NIH, Baltimore, MD 21224 USA. [Baumann, Michael H.] NIH, Clin Psychopharmacol Sect, Intramural Res Program, Baltimore, MD USA. [Kelly, Deanna L.] Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. [Ortemann-Renon, Catherine; Bonnet, Denis] Sanofi Aventis Rech, Montpellier, France. RP Huestis, MA (reprint author), Natl Inst Drug Abuse, Intramural Res Program, Off Clin Director, NIH, 251 Bayview Blvd,Room 05A721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Intramural NIH HHS [Z01 DA000415-10, ZIA DA000415-12, Z01 DA000415-11]; PHS HHS [HHSN271200599091CADB] NR 30 TC 6 Z9 6 U1 0 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0095-2990 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PD JAN PY 2012 VL 38 IS 1 BP 114 EP 119 DI 10.3109/00952990.2011.600398 PG 6 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 896HC UT WOS:000300555300017 PM 21797816 ER PT J AU Sterling, RK Wright, EC Morgan, TR Seeff, LB Hoefs, JC Di Bisceglie, AM Dienstag, JL Lok, AS AF Sterling, Richard K. Wright, Elizabeth C. Morgan, Timothy R. Seeff, Leonard B. Hoefs, John C. Di Bisceglie, Adrian M. Dienstag, Jules L. Lok, Anna S. CA HALT-C Trial Grp TI Frequency of Elevated Hepatocellular Carcinoma (HCC) Biomarkers in Patients With Advanced Hepatitis C SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID GAMMA-CARBOXY PROTHROMBIN; SERUM ALPHA-FETOPROTEIN; UNITED-STATES; LIVER-DISEASE; RISK-FACTORS; DIAGNOSIS; CARBOXYPROTHROMBIN; SURVEILLANCE; SENSITIVITY; CIRRHOSIS AB OBJECTIVES: Prospective studies of serum hepatocellular carcinoma (HCC) biomarkers in patients with advanced hepatitis C are lacking. The aim of this study was to determine the frequencies and performance of elevated alpha-fetoprotein (AFP), AFP-L3, and des-gamma-carboxy prothrombin (DCP) levels as HCC biomarkers in advanced hepatitis C. METHODS: Patients in the HALT-C Trial were tested every 3 months for 42 months. Screening ultrasound was performed every 12 months. Levels of biomarkers were compared in patients in whom HCC did or did not develop. RESULTS: In all, 855 patients were evaluated; HCC developed in 46. Among patients without HCC, 73.2% had AFP consistently <20, 24.5% had at least one AFP between 20 and 199, and 2.3% had at least one AFP value >= 200 ng/ml; 73.7% had DCP consistently <90, 11.6% had at least one DCP between 90 and 149, and 14.7% had at least one DCP value >= 150 mAU/ml. AFP-L3 >= 10% was present at least once in 9.0% and in 17.1% of those with AFP >= 20 ng/ml. Among all patients with elevated biomarkers, a diagnosis of HCC was made in 0-31.6% (depending on the biomarker and cutoff) during the subsequent 24 months. AFP >= 200 ng/ml had the highest specificity (99%), but sensitivity was <= 20%. DCP >= 40 mAU/ml had the highest sensitivity (76%), but specificity was <= 58%. Independent predictors of elevated AFP were gender (female), race (Black), more advanced disease, and HCC. Elevated DCP was associated with more advanced disease and HCC. CONCLUSIONS: Mild-moderate elevations in total AFP and DCP but not in AFP-L3 occur frequently in patients with chronic hepatitis C and advanced fibrosis, are related to factors other than HCC, and are poor predictors of HCC. C1 [Sterling, Richard K.] Virginia Commonwealth Univ, Hepatol Sect, Med Ctr, Richmond, VA 23298 USA. [Wright, Elizabeth C.] NIDDK, Off Director, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Morgan, Timothy R.; Hoefs, John C.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA. [Seeff, Leonard B.] NIDDK, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Seeff, Leonard B.] NIDDK, Liver Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Di Bisceglie, Adrian M.] St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO USA. [Dienstag, Jules L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Lok, Anna S.] Univ Michigan, Sch Med, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI USA. RP Sterling, RK (reprint author), Virginia Commonwealth Univ, Hepatol Sect, Med Ctr, Med Coll Virginia Campus, Richmond, VA 23298 USA. EM RKSterli@vcu.edu OI Yang, Shuman/0000-0002-9638-0890 FU National Institute of Diabetes & Digestive & Kidney Diseases; National Institute of Allergy and Infectious Diseases (NIAID); National Cancer Institute; National Center for Minority Health and Health Disparities; General Clinical Research Center; Clinical and Translational Science Center from the National Center for Research Resources, National Institutes of Health FX This study was supported by the National Institute of Diabetes & Digestive & Kidney Diseases (contract numbers are listed below). Additional support was provided by the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute, the National Center for Minority Health and Health Disparities, and by General Clinical Research Center and Clinical and Translational Science Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers are listed below). Additional funding to conduct this study was supplied by Hoffmann-La Roche (now Genentech) and Wako Chemicals USA through Cooperative Research and Development Agreements (CRADAs) with the National Institutes of Health. NR 37 TC 36 Z9 37 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JAN PY 2012 VL 107 IS 1 BP 64 EP 74 DI 10.1038/ajg.2011.312 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 896NC UT WOS:000300573000011 PM 21931376 ER PT J AU Nakagawa, T Ramdhan, DH Tanaka, N Naito, H Tamada, H Ito, Y Li, YF Hayashi, Y Yamagishi, N Yanagiba, Y Aoyama, T Gonzalez, FJ Nakajima, T AF Nakagawa, Tomohiko Ramdhan, Doni Hikmat Tanaka, Naoki Naito, Hisao Tamada, Hazuki Ito, Yuki Li, Yufei Hayashi, Yumi Yamagishi, Nozomi Yanagiba, Yukie Aoyama, Toshifumi Gonzalez, Frank J. Nakajima, Tamie TI Modulation of ammonium perfluorooctanoate-induced hepatic damage by genetically different PPAR alpha in mice SO ARCHIVES OF TOXICOLOGY LA English DT Article DE Hepatic damage; Human; Mouse; Perfluorooctanoic acid; Peroxisome proliferator-activated receptor ID ACTIVATED-RECEPTOR-ALPHA; PEROXISOME-PROLIFERATOR; MITOCHONDRIAL BIOGENESIS; UNCOUPLING PROTEIN-2; PERFLUOROALKYL ACIDS; ADIPOSE-TISSUE; FATTY-ACIDS; LIVER; GAMMA; MOUSE AB Perfluorooctanoic acid is a ligand for peroxisome proliferator-activated receptor (PPAR alpha). Ammonium perfluorooctanoate (APFO) at 0.1 and 0.3 mg/kg doses activated mouse PPARa, but not human PPAR alpha. This study aimed to clarify whether milligram-order APFO can activate human PPAR alpha, and the receptor is involved in APFO-induced chronic hepatic damage. Male Sv/129 wild-type mPPAR alpha), Ppar alpha-null, and humanized PPAR alpha (hPPAR alpha) mice (8 weeks old) were divided into three groups. The first was treated with water and the other two with 1.0 and 5.0 mg/kg APFO for 6 weeks, orally, respectively. Both doses activated mouse and human PPAR alpha to a similar or lower degree in the latter. APFO dose dependently increased hepatic triglyceride levels in Ppar alpha-null and hPPAR alpha mice, but conversely decreased those in mPPAR alpha ones. APFO-induced hepatic damage differed markedly among the three genotyped groups: single-cell necrosis was observed in all genotyped mice; inflammatory cells and macrovesicular steatosis only in Ppar alpha-null mice; and microvesicular steatosis and hydropic degenerations in hPPAR alpha and Ppar alpha-null mice. The molecular mechanism underlying these differences may be attributable to those of gene expressions involved in lipid homeostasis (PPAR alpha, beta- and x-oxidation enzymes, and diacylglycerol acyltransferases) and uncoupling protein 2. Thus, milligram-order APFO activated both mouse and human PPAR alpha in a different manner, which may reflect histopathologically different types of hepatic damage. C1 [Nakagawa, Tomohiko; Ramdhan, Doni Hikmat; Naito, Hisao; Tamada, Hazuki; Ito, Yuki; Li, Yufei; Hayashi, Yumi; Yamagishi, Nozomi; Yanagiba, Yukie; Nakajima, Tamie] Nagoya Univ, Grad Sch Med, Dept Occupat & Environm Hlth, Showa Ku, Nagoya, Aichi 4668550, Japan. [Ramdhan, Doni Hikmat] Univ Indonesia, Fac Publ Hlth, Dept Occupat Hlth & Safety, Depok 16424, Jawa Barat, Indonesia. [Tanaka, Naoki; Aoyama, Toshifumi] Shinshu Univ, Grad Sch Med, Dept Metab Regulat, Matsumoto, Nagano 3908621, Japan. [Ito, Yuki] Nagoya City Univ, Grad Sch Med Sci, Dept Occupat & Environm Hlth, Nagoya, Aichi 4678601, Japan. [Yanagiba, Yukie] Natl Inst Occupat Safety & Hlth, Kawasaki, Kanagawa 2148585, Japan. [Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Nakajima, T (reprint author), Nagoya Univ, Grad Sch Med, Dept Occupat & Environm Hlth, Showa Ku, 65 Tsurumai Cho, Nagoya, Aichi 4668550, Japan. EM tnasu23@med.nagoya-u.ac.jp RI Ito, Yuki/C-3698-2008 FU Japan Society for the Promotion of Science [14370121, 17390169] FX We wish to thank to Mr. Toshiki Nakamura for his kind assistance with the animal experiments. This study was supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (B. 14370121, 17390169). NR 43 TC 4 Z9 4 U1 0 U2 6 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5761 J9 ARCH TOXICOL JI Arch. Toxicol. PD JAN PY 2012 VL 86 IS 1 BP 63 EP 74 DI 10.1007/s00204-011-0704-3 PG 12 WC Toxicology SC Toxicology GA 896NS UT WOS:000300575100008 PM 21499893 ER PT S AU Yu, PP Wang, H Katagiri, Y Geller, HM AF Yu, Panpan Wang, Hang Katagiri, Yasuhiro Geller, Herbert M. BE Milner, R TI An In Vitro Model of Reactive Astrogliosis and Its Effect on Neuronal Growth SO ASTROCYTES: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Reactive astrogliosis; CSPGs; GAG chains; TGF-beta; Chondroitinase ABC; Neuron-astrocyte coculture; Neurite outgrowth; Spot assay ID NEURITE GROWTH; PROTEOGLYCAN AB Astrogliosis, whereby astrocytes in the central nervous system (CNS) become reactive in response to tissue damage, is a prominent process leading to the formation of the glial scar that inhibits axon regeneration after CNS injury. Upon becoming reactive, astrocytes undergo various molecular and morphological changes including upregulating their expression of GFAP and chondroitin sulfate proteoglycans (CSPGs) as well as other molecules that are inhibitory to axon growth. We have developed an in vitro model of reactive astrogliosis as a result of treating cultured astrocytes with transforming growth factor-beta (TGF-beta), which induces increased expression as well as secretion of CSPGs. These reactive astrocytes show inhibitory effects on neuron growth both in neuron-astrocyte coculture and in neurite guidance spot assay using astrocyte-conditioned medium. These reactive astrocytes provide a vehicle for testing substances that might overcome the glial scar and promote regeneration. C1 [Yu, Panpan; Wang, Hang; Katagiri, Yasuhiro; Geller, Herbert M.] NHLBI, Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Yu, PP (reprint author), NHLBI, Dev Neurobiol Sect, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Yu, Panpan/A-4962-2013; OI Geller, Herbert/0000-0002-7048-6144 FU Intramural NIH HHS [ZIA HL006021-04] NR 7 TC 19 Z9 19 U1 1 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-451-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 814 BP 327 EP 340 DI 10.1007/978-1-61779-452-0_21 D2 10.1007/978-1-61779-452-0 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA BYQ03 UT WOS:000299709200021 PM 22144316 ER PT J AU Atkins, HL Muraro, PA van Laar, JM Pavletic, SZ AF Atkins, Harold L. Muraro, Paolo A. van Laar, Jacob M. Pavletic, Steven Z. TI Autologous Hematopoietic Stem Cell Transplantation for Autoimmune Disease-Is It Now Ready for Prime Time? SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Hematopoietic stem cell transplantation; Autoimmune disease; Multiple sclerosis; Systemic sclerosis ID DOSE IMMUNOSUPPRESSIVE THERAPY; PROGRESSIVE MULTIPLE-SCLEROSIS; SEVERE SYSTEMIC-SCLEROSIS; TERM-FOLLOW-UP; WORKING PARTY; EUROPEAN GROUP; BLOOD; TRIAL; HSCT; MS AB Current systemic therapies are rarely curative for patients with severe life-threatening forms of autoimmune disease (AID). During the past 15 years, autologous hematopoietic stem cell transplantation (HCT) has been demonstrated to cure some patients with severe AID refractory to all other available therapies, and thus AID has become an emerging indication for cell therapy. The sustained clinical effects after autologous HCT are better explained by qualitative change in the reconstituted immune repertoire rather than transient depletion of immune cells. Since 1996, more than 1300 AID patients have been registered by the European Group for Blood and Marrow Transplantion (EBMT) and almost 500 patients by the Center for International Blood and Marrow Transplant Research (CIBMTR). Autologous HCT is most commonly performed for patients with multiple sclerosis (MS) or systemic sclerosis (SSc). Systemic lupus, Crohn's disease, type I diabetes, and juvenile idiopathic arthritis are other common indications. Allogeneic transplants are still considered too toxic for use in AID, except for cases of immune cytopenia. Although biologic therapies have been effective at controlling the manifestations of the disease, they require continuous administration, thus raising questions about their increasing costs, morbidity, and mortality related to prolonged therapy. Perhaps it is a reasonable time to ask, "Is autologous HCT for severe AID now ready for prime time?" Yet, the paucity of controlled studies, the short-term toxicities, and the upcoming availability of second-generation biologic and targeted immunotherapies argues that perhaps HCT for AID should be still limited to clinical trials. In this article, we focus on the results of autologous HCT for MS and SSc because these are the two most commonly transplanted diseases. The promising data that is emerging may establish these diseases as standard indications for HCT. Biol Blood Marrow Transplant 18: S177-S183 (2012) Published by Elsevier Inc. on behalf of American Society for Blood and Marrow Transplantation C1 [Pavletic, Steven Z.] NCI, Graft Versus Host & Autoimmun Unit, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Atkins, Harold L.] Ottawa Hosp, Res Inst, Ottawa, ON, Canada. [Atkins, Harold L.] Ottawa Hosp, Blood & Marrow Transplant Program, Ottawa, ON, Canada. [Muraro, Paolo A.] Imperial Coll Healthcare NHS Trust, London, England. [Muraro, Paolo A.] Univ London Imperial Coll Sci Technol & Med, Ctr Neurosci, Div Expt Med, Dept Med, London, England. [van Laar, Jacob M.] Newcastle Univ, Musculoskeletal Res Grp, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. RP Pavletic, SZ (reprint author), NCI, Graft Versus Host & Autoimmun Unit, Expt Transplantat & Immunol Branch, NIH, Bldg 10-CRC 3-3330, Bethesda, MD 20892 USA. EM pavletis@mail.nih.gov OI Muraro, Paolo/0000-0002-3822-1218 FU Italian MS Society (FISM) [2010/R/24]; UK MS society [938/10]; UK Stem Cell Foundation; Medical Research Council [G0800679]; Center for Cancer Research; National Cancer Institute; Miltenyi Biotec FX P.A.M. is supported by the Italian MS Society (FISM; Ref. 2010/R/24), the UK MS society (Ref. 938/10), the UK MS Society and UK Stem Cell Foundation, and the Medical Research Council (Ref. G0800679). S.Z.P. is supported by the Center for Cancer Research, the intramural program of the National Cancer Institute.; Financial disclosure: Dr. van Laar has received speaker's fees from Miltenyi Biotec in 2010. NR 29 TC 15 Z9 15 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2012 VL 18 IS 1 SU 1 BP S177 EP S183 DI 10.1016/j.bbmt.2011.11.020 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 878EY UT WOS:000299239500030 PM 22226104 ER PT J AU Kitko, CL White, ES Baird, K AF Kitko, Carrie L. White, Eric S. Baird, Kristin TI Fibrotic and Sclerotic Manifestations of Chronic Graft-versus-Host Disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article ID IDIOPATHIC PULMONARY-FIBROSIS; CONSENSUS DEVELOPMENT PROJECT; STEM-CELL TRANSPLANTATION; WORKING GROUP-REPORT; BRONCHIOLITIS OBLITERANS SYNDROME; ADMINISTRATION DRUG APPROVAL; PLACEBO-CONTROLLED TRIAL; IMATINIB MESYLATE; CLINICAL-TRIALS; EXTRACELLULAR-MATRIX C1 [Kitko, Carrie L.] Univ Michigan, Div Pediat, Div Hematol Oncol, Blood & Marrow Transplant Program, Ann Arbor, MI 48109 USA. [White, Eric S.] Univ Michigan, Sch Med, Grad Program Cellular & Mol Biol, Ann Arbor, MI 48109 USA. [White, Eric S.] Grad Program Biomed Sci, Ann Arbor, MI USA. [Baird, Kristin] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kitko, CL (reprint author), Univ Michigan, Div Pediat, Div Hematol Oncol, Blood & Marrow Transplant Program, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM ckitko@med.umich.edu OI White, Eric/0000-0003-4060-8443 FU NHLBI NIH HHS [R01 HL085083, R01 HL085083-05] NR 47 TC 5 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2012 VL 18 IS 1 SU 1 BP S46 EP S52 DI 10.1016/j.bbmt.2011.10.021 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 878EY UT WOS:000299239500013 PM 22226112 ER PT J AU Shurin, S Krischer, J Groft, SC AF Shurin, Susan Krischer, Jeff Groft, Stephen C. TI Clinical Trials In BMT: Ensuring That Rare Diseases and Rarer Therapies are Well Done SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Editorial Material ID CHALLENGES; REGISTRY C1 [Shurin, Susan] NHLBI, Bethesda, MD 20892 USA. [Krischer, Jeff] Univ S Florida, Tampa, FL USA. [Groft, Stephen C.] NIH, Off Rare Dis, Rockville, MD USA. RP Shurin, S (reprint author), NHLBI, 31 Ctr Dr,5A48, Bethesda, MD 20892 USA. EM shurinsb@nhlbi.nih.gov NR 11 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2012 VL 18 IS 1 SU 1 BP S8 EP S11 DI 10.1016/j.bbmt.2011.10.030 PG 4 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 878EY UT WOS:000299239500003 PM 22226117 ER PT J AU Zatloukal, K Vaught, J AF Zatloukal, Kurt Vaught, Jim TI What Are the Next Steps to Overcoming Roadblocks to Transnational Biobank Collaboration? SO BIOPRESERVATION AND BIOBANKING LA English DT Editorial Material C1 [Zatloukal, Kurt] Med Univ Graz, Inst Pathol, A-8036 Graz, Austria. [Vaught, Jim] NCI, Off Biorepositories & Biospecimen Res, Bethesda, MD 20892 USA. RP Zatloukal, K (reprint author), Med Univ Graz, Inst Pathol, Auenbruggerpl 25, A-8036 Graz, Austria. EM kurt.zatloukal@medunigraz.at; vaughtj@mail.nih.gov NR 1 TC 1 Z9 1 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1947-5535 J9 BIOPRESERV BIOBANK JI Biopreserv. Biobank. PY 2012 VL 10 IS 1 BP 2 EP 3 DI 10.1089/bio.2012.1014 PG 2 WC Cell Biology; Chemistry, Applied; Medical Laboratory Technology SC Cell Biology; Chemistry; Medical Laboratory Technology GA 896BQ UT WOS:000300540800002 PM 24849747 ER PT J AU Shao, W Khin, S Kopp, WC AF Shao, Wen Khin, Sonny Kopp, William C. TI Characterization of Effect of Repeated Freeze and Thaw Cycles on Stability of Genomic DNA Using Pulsed Field Gel Electrophoresis SO BIOPRESERVATION AND BIOBANKING LA English DT Article ID HYDRODYNAMIC SHEAR; ESCHERICHIA-COLI; QUANTIFICATION; INJURY AB In this study, we systematically investigated the effects of repeated cycles of freeze/thaw on stability of genomic Deoxyribonucleic acid (DNA) samples as evaluated by changes in DNA size, concentration, and freeze/thaw protocols. The DNA was isolated using standard extraction procedures including phenol/chloroform and commercially available Gentra Puregene and Qiagen QIAmp kits. Changes in DNA were monitored over 18 cycles of freezing and thawing utilizing several freeze/thaw protocols. DNA samples from multiple subjects prepared from whole blood samples were examined by pulsed field gel electrophoresis (PFGE), and shown to have different average molecular sizes and size distribution patterns depending on the extraction method. Results of freeze/thaw experiments, analyzed by PFGE, showed progressive DNA degradation of the samples, with DNA sizes larger than 100 kb most sensitive to freeze/thaw degradation. Increasing the DNA concentration of stored samples from 10 mu g/mL to 100 mu g/mL had a somewhat protective effect on DNA stability. Variations in freeze/thaw protocols did not have a significant impact on DNA stability during repeated freeze/thaw cycles. At freeze/thaw cycle 18, average molecular size and size distribution of all DNA samples tested approached 25 kb, regardless of their initial average size and size distributions. This study provides insight on DNA degradation during freeze/thaw cycles and offers guidance to storage and handling of DNA samples. C1 [Shao, Wen; Khin, Sonny; Kopp, William C.] NCI, Appl Dev Res Directorate, SAIC Frederick, Frederick, MD 21701 USA. RP Shao, W (reprint author), NCI Frederick, Appl Dev Res Directorate, SAIC Frederick, POB 358, Clarksburg, MD 20871 USA. EM wenmd@yahoo.com FU National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does it mention trade names, commercial products, or organizations implying endorsement by the U.S. Government. NR 23 TC 7 Z9 7 U1 5 U2 14 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1947-5535 J9 BIOPRESERV BIOBANK JI Biopreserv. Biobank. PY 2012 VL 10 IS 1 BP 4 EP 11 DI 10.1089/bio.2011.0016 PG 8 WC Cell Biology; Chemistry, Applied; Medical Laboratory Technology SC Cell Biology; Chemistry; Medical Laboratory Technology GA 896BQ UT WOS:000300540800003 PM 24849748 ER PT J AU Pitt, KE AF Pitt, Karen E. TI Development of a Global Certification Program for Biorepository Technical Professionals SO BIOPRESERVATION AND BIOBANKING LA English DT Editorial Material C1 [Pitt, Karen E.] USN Hosp, NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20814 USA. [Pitt, Karen E.] ISBER Certificat Repository Technicians Task Forc, Santa Barbara, CA USA. RP Pitt, KE (reprint author), USN Hosp, NCI, Div Canc Epidemiol & Genet, 9650 Rockville Pike,Suite E133, Bethesda, MD 20814 USA. EM isber@asip.org NR 0 TC 4 Z9 4 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1947-5535 J9 BIOPRESERV BIOBANK JI Biopreserv. Biobank. PY 2012 VL 10 IS 1 BP 70 EP 71 DI 10.1089/bio.2011.1012 PG 2 WC Cell Biology; Chemistry, Applied; Medical Laboratory Technology SC Cell Biology; Chemistry; Medical Laboratory Technology GA 896BQ UT WOS:000300540800012 PM 24849756 ER PT J AU Bilusic, M Gulley, JL AF Bilusic, Marijo Gulley, James L. TI Endpoints, patient selection, and biomarkers in the design of clinical trials for cancer vaccines SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Review DE Cancer; Immunotherapy; Tumor growth kinetics; Tumor volume; Biomarkers; CIMT 2011 ID REFRACTORY PROSTATE-CANCER; REGULATORY T-CELLS; COLONY-STIMULATING FACTOR; DENDRITIC CELLS; IMMUNE-RESPONSES; TUMOR-IMMUNITY; FREE SURVIVAL; WHOLE-CELL; PHASE-III; IMMUNOTHERAPY AB Therapeutic cancer vaccines are an emerging and potentially effective treatment modality. Cancer vaccines are usually very well tolerated, with minimal toxicity compared with chemotherapy. Unlike conventional cytotoxic therapies, immunotherapy does not result in immediate tumor shrinkage but may alter growth rate and thus prolong survival. Multiple randomized controlled trials of various immunotherapeutic agents have shown a delayed separation in Kaplan-Meier survival curves, with no evidence of clinical benefit within the first 6-12 months of vaccine treatment. Overall survival benefit is seen in patients with lower disease burden who are not expected to die within those initial 6-12 months. The concept of improved overall survival without marked initial tumor reduction represents a significant shift from the current paradigms established by standard cytotoxic therapies. Future clinical studies of therapeutic vaccines should enroll patients with either lower tumor burden, more indolent disease or both, and must seek to identify early markers of clinical benefit that may correlate with survival. Until then, improved overall survival is the only clear, discriminatory endpoint for therapeutic vaccines as monotherapies. C1 [Bilusic, Marijo; Gulley, James L.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Bilusic, Marijo; Gulley, James L.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Gulley, JL (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA. EM gulleyj@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 FU Intramural NIH HHS [Z01 BC010666-03] NR 67 TC 22 Z9 22 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 EI 1432-0851 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD JAN PY 2012 VL 61 IS 1 BP 109 EP 117 DI 10.1007/s00262-011-1141-0 PG 9 WC Oncology; Immunology SC Oncology; Immunology GA 897OV UT WOS:000300662700012 PM 22120693 ER PT J AU Mazzone, L Vitiello, B AF Mazzone, Luigi Vitiello, Benedetto TI The Need to Develop More Sensitive Tools to Accurately Detect Clinical Response to Treatment in ADHD Reply SO CNS DRUGS LA English DT Letter ID ATOMOXETINE; DISORDER; CHILDREN C1 [Mazzone, Luigi] Childrens Hosp Bambino Gesu, Div Child Neurol & Psychiat, Dept Neurosci, Rome, Italy. [Vitiello, Benedetto] NIMH, Child & Adolescent Treatment & Prevent Intervent, Bethesda, MD 20892 USA. RP Mazzone, L (reprint author), Childrens Hosp Bambino Gesu, Div Child Neurol & Psychiat, Dept Neurosci, Rome, Italy. NR 5 TC 0 Z9 0 U1 0 U2 0 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PY 2012 VL 26 IS 2 BP 186 EP 187 PG 2 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 898OA UT WOS:000300750500008 ER PT J AU Gahl, WA Boerkoel, CF Boehm, M AF Gahl, William A. Boerkoel, Cornelius F. Boehm, Manfred TI The NIH Undiagnosed Diseases Program: bonding scientists and clinicians SO DISEASE MODELS & MECHANISMS LA English DT Editorial Material ID HEREDITARY SPASTIC PARAPLEGIA; M-AAA PROTEASE; I DEFICIENCY C1 [Gahl, William A.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA. [Gahl, William A.; Boerkoel, Cornelius F.] NIH, NIH Undiagnosed Dis Program, Bethesda, MD 20892 USA. [Boehm, Manfred] NHLBI, NIH, Bethesda, MD 20892 USA. RP Gahl, WA (reprint author), NHGRI, Off Clin Director, NIH, Bldg 10,Room 10C103,10 Ctr Dr,MSC 1851, Bethesda, MD 20892 USA. EM bgahl@helix.nih.gov NR 8 TC 11 Z9 11 U1 1 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 J9 DIS MODEL MECH JI Dis. Model. Mech. PD JAN PY 2012 VL 5 IS 1 BP 3 EP 5 DI 10.1242/dmm.009258 PG 3 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 897IG UT WOS:000300642200001 PM 22228787 ER PT S AU Kim, J Le, DX Thoma, GR AF Kim, Jongwoo Le, Daniel X. Thoma, George R. BE ViardGaudin, C Zanibbi, R TI Combining SVM Classifiers to Identify Investigator Name Zones in Biomedical Articles SO DOCUMENT RECOGNITION AND RETRIEVAL XIX SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Document Recognition and Retrieval XIX (DRR)/Electronic Imaging Symposium CY JAN 25-26, 2012 CL Burlingame, CA SP Soc Imaging Sci & Technol (IS&T), SPIE DE Investigator Names; MEDLINE; Support Vector Machine; labeling; text classification; bibliographic information AB This paper describes an automated system to label zones containing Investigator Names (IN) in biomedical articles, a key item in a MEDLINE (R) citation. The correct identification of these zones is necessary for the subsequent extraction of IN from these zones. A hierarchical classification model is proposed using two Support Vector Machine (SVM) classifiers. The first classifier is used to identify an IN zone with highest confidence, and the other classifier identifies the remaining IN zones. Eight sets of word lists are collected to train and test the classifiers, each set containing collections of words ranging from 100 to 1,200. Experiments based on a test set of 105 journal articles show a Precision of 0.88, 0.97 Recall, 0.92 F-Measure, and 0.99 Accuracy. C1 [Kim, Jongwoo; Le, Daniel X.; Thoma, George R.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kim, J (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM jongkim@mail.nih.gov NR 13 TC 1 Z9 1 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-81948-944-9 J9 PROC SPIE PY 2012 VL 8297 AR 829704 DI 10.1117/12.910517 PG 8 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic; Optics SC Computer Science; Engineering; Optics GA BYT89 UT WOS:000300251700003 ER PT J AU Taniya, T Tanaka, S Yamaguchi-Kabata, Y Hanaoka, H Yamasaki, C Maekawa, H Barrero, RA Lenhard, B Datta, MW Shimoyama, M Bumgarner, R Chakraborty, R Hopkinson, I Jia, LB Hide, W Auffray, C Minoshima, S Imanishi, T Gojobori, T AF Taniya, Takayuki Tanaka, Susumu Yamaguchi-Kabata, Yumi Hanaoka, Hideki Yamasaki, Chisato Maekawa, Harutoshi Barrero, Roberto A. Lenhard, Boris Datta, Milton W. Shimoyama, Mary Bumgarner, Roger Chakraborty, Ranajit Hopkinson, Ian Jia, Libin Hide, Winston Auffray, Charles Minoshima, Shinsei Imanishi, Tadashi Gojobori, Takashi TI A prioritization analysis of disease association by data-mining of functional annotation of human genes SO GENOMICS LA English DT Article DE Disease; Rheumatoid arthritis; Prostate cancer; Data-mining; Gene function; Discriminant analysis ID GENOME-WIDE ASSOCIATION; HUMAN PROSTATE-CANCER; RHEUMATOID-ARTHRITIS; MENDELIAN INHERITANCE; SUSCEPTIBILITY LOCUS; CANDIDATE GENES; GENETICS; NETWORK; IDENTIFICATION; INHIBITION AB Complex diseases result from contributions of multiple genes that act in concert through pathways. Here we present a method to prioritize novel candidates of disease-susceptibility genes depending on the biological similarities to the known disease-related genes. The extent of disease-susceptibility of a gene is prioritized by analyzing seven features of human genes captured in H-InvDB. Taking rheumatoid arthritis (RA) and prostate cancer (PC) as two examples, we evaluated the efficiency of our method. Highly scored genes obtained included TNFSF12 and OSM as candidate disease genes for RA and PC, respectively. Subsequent characterization of these genes based upon an extensive literature survey reinforced the validity of these highly scored genes as possible disease-susceptibility genes. Our approach, Prioritization ANalysis of Disease Association (PANDA), is an efficient and cost-effective method to narrow down a large set of genes into smaller subsets that are most likely to be involved in the disease pathogenesis. (C) 2011 Elsevier Inc. All rights reserved. C1 [Taniya, Takayuki; Yamasaki, Chisato; Maekawa, Harutoshi] Japan Biol Informat Consortium, Japan Biol Informat Res Ctr, Koto Ku, Tokyo 1350064, Japan. [Taniya, Takayuki; Yamaguchi-Kabata, Yumi; Yamasaki, Chisato; Imanishi, Tadashi; Gojobori, Takashi] Natl Inst Adv Ind Sci & Technol, Biol Informat Res Ctr, Koto Ku, Tokyo 1350064, Japan. [Tanaka, Susumu] Tokyo Metropolitan Inst Med Sci, Setagaya Ku, Tokyo 1568506, Japan. [Hanaoka, Hideki] Univ Tokyo, Plant Biotechnol Lab, Biotechnol Res Ctr, Bunkyo Ku, Tokyo 1138657, Japan. [Maekawa, Harutoshi] Cs Lab Co Ltd, Minato Ku, Tokyo 1010041, Japan. [Barrero, Roberto A.] Murdoch Univ, Ctr Comparat Genom, Murdoch, WA 6150, Australia. [Lenhard, Boris] Karolinska Inst, Ctr Genom & Bioinformat, SE-17177 Stockholm, Sweden. [Datta, Milton W.] Univ Minnesota, Sch Med, Dept Lab Med & Pathol, United Hosp, Minneapolis, MN 55455 USA. [Shimoyama, Mary] Med Coll Wisconsin, Rat Genome Database, Milwaukee, WI 53226 USA. [Shimoyama, Mary] Med Coll Wisconsin, Human & Mol Genet Ctr, Milwaukee, WI 53226 USA. [Bumgarner, Roger] Univ Washington, Dept Microbiol, Ctr Express Arrays, Seattle, WA 98195 USA. [Chakraborty, Ranajit] Univ N Texas Hlth Sci Ctr, Ctr Computat Genom, Inst Invest Genet, Ft Worth, TX 76107 USA. [Chakraborty, Ranajit] Univ N Texas Hlth Sci Ctr, Dept Forens & Invest Genet, Ft Worth, TX 76107 USA. [Hopkinson, Ian] Royal Free & Univ Coll Med Sch, British Heart Fdn Labs, London WC1E 6JJ, England. [Jia, Libin] NCI, NIH, Bethesda, MD 20892 USA. [Hide, Winston] Univ Western Cape, S African Natl Bioinforrnat Inst, ZA-7535 Bellville, South Africa. [Auffray, Charles] Univ Paris 06, Villejuif, France. [Auffray, Charles] CNRS, Array sIMAGE, LGN, UMR 7091, Villejuif, France. [Minoshima, Shinsei] Hamamatsu Univ Sch Med, Dept Med Photobiol, Med Photon Res Ctr, Higashi Ku, Hamamatsu, Shizuoka 4313192, Japan. [Gojobori, Takashi] Ctr Informat Biol, Natl Inst Genet, Mishima, Shizuoka 4118540, Japan. [Gojobori, Takashi] DNA Data Bank Japan, Mishima, Shizuoka 4118540, Japan. RP Imanishi, T (reprint author), Natl Inst Adv Ind Sci & Technol, Biol Informat Res Ctr, Koto Ku, 2-4-7 Aomi, Tokyo 1350064, Japan. EM t.imanishi@aist.go.jp; tgojobor@genes.nig.ac.jp RI Bumgarner, Roger/K-3531-2015; OI Bumgarner, Roger/0000-0002-8168-6985; Lenhard, Boris/0000-0002-1114-1509; Hide, Winston/0000-0002-8621-3271 FU Ministry of Economy, Trade and Industry of Japan (METI); Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT); Japan Biological Informatics Consortium (JBiC); National Institute of Advanced Industrial Science and Technology (AIST) FX We thank Drs. Peter Tonellato, Arek Kasprzyk, Teruyoshi Hishiki, Craig Gough, Makoto Shimada, and Naoki Nagata for their helpful discussion and comments on this study. We also thank all the members of the H-Invitational consortium and all the staff of JBIRC for construction of H-InvDB and the PANDA system. This work is financially supported by the Ministry of Economy, Trade and Industry of Japan (METI), the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT), the Japan Biological Informatics Consortium (JBiC), and National Institute of Advanced Industrial Science and Technology (AIST). NR 52 TC 3 Z9 3 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JAN PY 2012 VL 99 IS 1 BP 1 EP 9 DI 10.1016/j.ygeno.2011.10.002 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 879UC UT WOS:000299356700001 PM 22019378 ER PT J AU Patri, A Moorefield, CN Newkome, GR AF Patri, Anil Moorefield, Charles N. Newkome, George R. TI DENDRONIZED BI-2-QUINOLINE LIGANDS AND THEIR METAL COMPLEXES: DENDRON SYNTHESIS AND METALLOASSEMBLY SO HETEROCYCLES LA English DT Article DE Copper Complex; Biquinoline; Dendrimer; Dendron; Polyacid ID LIGHT-EMITTING-DIODES; TRIS(BIPYRIDINE) CORE DENDRIMERS; GREEN IRIDIUM DENDRIMERS; MOLECULAR RECOGNITION; BIS(2,2'/6',2''-TERPYRIDINE)RUTHENIUM(II) CONNECTIVITY; PHOSPHORESCENT DENDRIMERS; PHOTOPHYSICAL PROPERTIES; CASCADE POLYMERS; DENDRITIC WEDGES; CATALYSIS AB The synthesis of bis-biquinoline ligands possessing G1 and G2 Behera's amine-based dendrons with acid and ester termini was accomplished. Treatment with Cu(I) salts quantitatively generated the desired stable metal lodendrimers with a Cu(I) core. C1 [Patri, Anil] NCI, Nanotechnol Characterizat Lab, Frederick, MD 21702 USA. [Moorefield, Charles N.; Newkome, George R.] Univ Akron, Maurice Morton Inst Polymer Sci, Akron, OH 44325 USA. [Newkome, George R.] Univ Akron, Dept Polymer Sci, Akron, OH 44325 USA. [Newkome, George R.] Univ Akron, Dept Chem, Akron, OH 44325 USA. RP Patri, A (reprint author), NCI, Nanotechnol Characterizat Lab, Frederick, MD 21702 USA. EM newkome@uakron.edu RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU National Science Foundation [DMR-0705015, DMR-0812337]; Ohio Board of Regents FX We thank the National Science Foundation (Grant DMR-0705015 and DMR-0812337) for continued support and the Ohio Board of Regents. NR 66 TC 0 Z9 0 U1 0 U2 28 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0385-5414 J9 HETEROCYCLES JI Heterocycles PD JAN 1 PY 2012 VL 84 IS 2 BP 1023 EP 1032 DI 10.3987/COM-11-S(P)80 PG 10 WC Chemistry, Organic SC Chemistry GA 894YO UT WOS:000300463600020 ER PT J AU McLaughlin, HM Sakaguchi, R Giblin, W Wilson, TE Biesecker, L Lupski, JR Talbot, K Vance, JM Zuchner, S Lee, YC Kennerson, M Hou, YM Nicholson, G Antonellis, A AF McLaughlin, Heather M. Sakaguchi, Reiko Giblin, William Wilson, Thomas E. Biesecker, Leslie Lupski, James R. Talbot, Kevin Vance, Jeffery M. Zuechner, Stephan Lee, Yi-Chung Kennerson, Marina Hou, Ya-Ming Nicholson, Garth Antonellis, Anthony CA NISC Comparative Sequencing Progra TI A Recurrent Loss-of-Function Alanyl-tRNA Synthetase (AARS) Mutation in Patients with Charcot-Marie-Tooth Disease Type 2N (CMT2N) SO HUMAN MUTATION LA English DT Article ID SYMMETRIC POLYNEUROPATHY ROLE; PRACTICE PARAMETER EVALUATION; SPINAL MUSCULAR-ATROPHY; DNA METHYLATION; ELECTRODIAGNOSTIC MEDICINE; AMERICAN ASSOCIATION; PHYSICAL MEDICINE; CRYSTAL-STRUCTURE; NEUROPATHY; AMINOACYLATION C1 [McLaughlin, Heather M.; Giblin, William; Wilson, Thomas E.; Antonellis, Anthony] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA. [Sakaguchi, Reiko; Hou, Ya-Ming] Thomas Jefferson Univ, Dept Biochem & Mol Pharmacol, Philadelphia, PA 19107 USA. [NISC Comparative Sequencing Progra] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA. [Wilson, Thomas E.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. [Biesecker, Leslie] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Lupski, James R.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Lupski, James R.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Lupski, James R.] Texas Childrens Hosp, Houston, TX 77030 USA. [Talbot, Kevin] Univ Oxford, Dept Clin Neurol, Oxford, England. [Vance, Jeffery M.; Zuechner, Stephan] Univ Miami, Miller Sch Med, Hussman Inst Human Genom, Miami, FL 33136 USA. [Lee, Yi-Chung] Taipei Vet Gen Hosp, Dept Neurol, Neurol Inst, Taipei, Taiwan. [Lee, Yi-Chung] Natl Yang Ming Univ, Sch Med, Taipei, Taiwan. [Kennerson, Marina; Nicholson, Garth] Concord Hosp, Northcott Neurosci Lab, ANZAC Res Inst, Concord, NSW, Australia. [Kennerson, Marina; Nicholson, Garth] Concord Hosp, Mol Med Lab, Concord, NSW, Australia. [Kennerson, Marina; Nicholson, Garth] Univ Sydney, Fac Med, Camperdown, NSW, Australia. [Antonellis, Anthony] Univ Michigan, Sch Med, Dept Neurol, Ann Arbor, MI 48109 USA. RP Antonellis, A (reprint author), Univ Michigan, Sch Med, Dept Human Genet, 3710A Med Sci 2,1241 E Catherine St,SPC 5618, Ann Arbor, MI 48109 USA. EM antonell@umich.edu RI Kennerson, Marina/B-5058-2014; OI Hou, Ya-Ming/0000-0001-6546-2597; Lee, Yi-Chung/0000-0003-0102-164X FU National Institute of Neurological Diseases and Stroke [R00NS060983, U54NS065712, R01NS052767]; Muscular Dystrophy Association [157681]; National Human Genome Research Institute (NIH); Rackham Merit Fellowship; National Institutes of Health [T32 GM007544-32] FX Contract grant sponsors: National Institute of Neurological Diseases and Stroke (R00NS060983 to A. A., U54NS065712 to S.Z., and R01NS052767 to S.Z.); the Muscular Dystrophy Association (157681 to Y.-M.H.); the Intramural Research Program of the National Human Genome Research Institute (NIH); the Rackham Merit Fellowship (to H. M. M.); the National Institutes of Health Genetics Training Grant (T32 GM007544-32 to H.M.M.). NR 39 TC 24 Z9 25 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD JAN PY 2012 VL 33 IS 1 BP 244 EP 253 DI 10.1002/humu.21635 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 897ZY UT WOS:000300705300028 PM 22009580 ER PT J AU Dunn, K Locke, K Chheda, SG Bates, CK Karani, R AF Dunn, Kathel Locke, Kenneth Chheda, Shobhina G. Bates, Carol K. Karani, Reena TI Update in Medical Education 2010-2011 SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Review DE medical education; medical students; interns; residents; faculty C1 [Dunn, Kathel] Natl Lib Med, Bethesda, MD 20894 USA. [Locke, Kenneth] Univ Toronto, Dept Med, Div Gen Internal Med, Toronto, ON, Canada. [Chheda, Shobhina G.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA. [Bates, Carol K.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Karani, Reena] Mt Sinai Sch Med, Dept Med Educ, New York, NY USA. [Karani, Reena] Mt Sinai Sch Med, Dept Geriatr, New York, NY USA. [Karani, Reena] Mt Sinai Sch Med, Dept Med, New York, NY USA. RP Dunn, K (reprint author), Natl Lib Med, 8600 Rockville Pike,Bldg 38,2N-19, Bethesda, MD 20894 USA. EM Kathel.dunn@gmail.com OI Dunn, Kathel/0000-0002-6967-130X NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2012 VL 27 IS 1 BP 109 EP 112 DI 10.1007/s11606-011-1902-7 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 873LD UT WOS:000298883900019 PM 21979759 ER PT J AU Kretschmer, D Nikola, N Durr, M Otto, M Peschel, A AF Kretschmer, Dorothee Nikola, Nele Durr, Manuela Otto, Michael Peschel, Andreas TI The Virulence Regulator Agr Controls the Staphylococcal Capacity to Activate Human Neutrophils via the Formyl Peptide Receptor 2 SO JOURNAL OF INNATE IMMUNITY LA English DT Article DE Phenol-soluble modulins; Quorum-sensing system Agr; Staphylococci; Formyl peptide receptor 2 ID COMMUNITY-ASSOCIATED MRSA; PHENOL-SOLUBLE MODULINS; QUORUM-SENSING SYSTEM; CHEMOATTRACTANT RECEPTOR; GENE-EXPRESSION; AUREUS; EPIDERMIDIS; CHEMOTAXIS; INFECTION; PROTEIN AB The Agr quorum-sensing system represents the master regulator for staphylococcal virulence factors and is known to have a strong impact on the release of pathogen-associated molecular pattern (PAMP) molecules. Among the various staphylococcal PAMPs, phenol-soluble modulin (PSM) peptides have attracted increasing interest because they are crucial for staphylococcal virulence and have neutrophil-recruiting properties. The latter depend on recognition of PSMs by the neutrophil formyl peptide receptor 2 (FPR2/ALX), for which PSMs are highly efficient agonists. We demonstrate that Agr inactivation in Staphylococcus aureus or S. epidermidis leads to strongly reduced neutrophil responses, which is in agreement with the previously reported strict control of PSM expression by Agr. Agr had a distinct and profound impact on activation of FPR2/ALX but not of the related FPR1 receptor that senses bacterial formylated peptides. S. epidermidis PSMs had similar FPR2/ALX-activating properties but differed in their dependence on N-terminal formylation compared to S. aureus PSMs. Moreover, S. aureus and S. epidermidis PSMs upregulated the neutrophil complement receptor CD11b via FPR2/ALX stimulation in an Agr-dependent fashion. Hence, Agr controls the capacity of staphylococcal pathogens to activate FPR2/ALX-dependent neutrophil responses, underscoring the crucial role of FPR2/ALX and PSMs in staphylococcus-host interaction. Copyright (C) 2012 S\. Karger AG, Basel C1 [Kretschmer, Dorothee; Nikola, Nele; Durr, Manuela; Peschel, Andreas] Univ Tubingen, Cellular & Mol Microbiol Div, Interfac Inst Microbiol & Infect Med, DE-72076 Tubingen, Germany. [Otto, Michael] NIAID, Lab Human Bacterial Pathogenesis, US Natl Inst Hlth, Bethesda, MD 20892 USA. RP Peschel, A (reprint author), Univ Tubingen, Cellular & Mol Microbiol Div, Interfac Inst Microbiol & Infect Med, Elfriede Aulhorn Str 6, DE-72076 Tubingen, Germany. EM andreas.peschel@uni-tuebingen.de OI Otto, Michael/0000-0002-2222-4115 FU Medical Faculty, University of Tubingen; German Research Foundation [SFB685, TRR34]; German Ministry of Education and Research (SkinStaph, Menage); National Institute of Allergy and Infectious Diseases (NIAID), US National Institutes of Health FX We thank Francois Boulay for FPR1-, FPR2/ALX- and FPR3-transfected cell lines and Kok van Kessel and Jos van Strijp for CHIPS and FLIPr. This research was supported by grants from the Fortune program of the Medical Faculty, University of Tubingen (to D.K.), the German Research Foundation (SFB685, TRR34) and the German Ministry of Education and Research (SkinStaph, Menage) (to A.P.) and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), US National Institutes of Health (to M.O.). NR 56 TC 16 Z9 17 U1 2 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-811X J9 J INNATE IMMUN JI J. Innate Immun. PY 2012 VL 4 IS 2 BP 201 EP 212 DI 10.1159/000332142 PG 12 WC Immunology SC Immunology GA 898RB UT WOS:000300758400010 PM 22067547 ER PT J AU Romero, R Savasan, ZA Chaiworapongsa, T Berry, SM Kusanovic, JP Hassan, SS Yoon, BH Edwin, S Mazor, M AF Romero, Roberto Savasan, Zeynep Alpay Chaiworapongsa, Tinnakorn Berry, Stanley M. Pedro Kusanovic, Juan Hassan, Sonia S. Yoon, Bo Hyun Edwin, Samuel Mazor, Moshe TI Hematologic profile of the fetus with systemic inflammatory response syndrome SO JOURNAL OF PERINATAL MEDICINE LA English DT Article DE Cordocentesis; FIRS; hypoxia; infection; neutrophil; neutrophilia; nucleated red blood cells; neutropenia; preterm labor; preterm PROM; white blood cell count ID BLOOD-CELL COUNTS; TUMOR-NECROSIS-FACTOR; PRETERM PREMATURE RUPTURE; COLONY-STIMULATING FACTOR; FLUID MATRIX METALLOPROTEINASE-8; MIDTRIMESTER AMNIOTIC-FLUID; MONOCYTE CHEMOTACTIC PROTEIN-1; GESTATIONAL-AGE FETUSES; UMBILICAL-CORD PLASMA; WHITE-MATTER LESIONS AB Objective: The fetal inflammatory response syndrome (FIRS) is associated with impending onset of preterm labor/delivery, microbial invasion of the amniotic cavity and increased perinatal morbidity. FIRS has been defined by an elevated fetal plasma interleukin (IL)-6, a cytokine with potent effects on the differentiation and proliferation of hematopoietic precursors. The objective of this study was to characterize the hematologic profile of fetuses with FIRS. Study design: Fetal blood sampling was performed in patients with preterm prelabor rupture of membranes and preterm labor with intact membranes (n = 152). A fetal plasma IL-6 concentration >= 11 pg/mL was used to define FIRS. Hemoglobin concentration, platelet count, total white blood cell (WBC) count, differential count, and nucleated red blood cell (NRBC) count were obtained. Since blood cell count varies with gestational age, the observed values were corrected for fetal age by calculating a ratio between the observed and expected mean value for gestational age. Results: 1) The prevalence of FIRS was 28.9% (44/152); 2) fetuses with FIRS had a higher median corrected WBC and corrected neutrophil count than those without FIRS (WBC: median 1.4, range 0.3-5.6, vs. median 1.1, range 0.4-2.9, P=0.001; neutrophils: median 3.6, range 0.1-57.5, vs. median 1.8, range 0.2-13.9, P<0.001); 3) neutrophilia (defined as a neutrophil count >95th centile of gestational age) was significantly more common in fetuses with FIRS than in those without FIRS (71%, 30/42, vs. 35%, 37/105; P<0.001); 4) more than two-thirds of fetuses with FIRS had neutrophilia, whereas neutropenia was present in only 4.8% (2/42); 5) FIRS was not associated with detectable changes in hemoglobin concentration, platelet, lymphocyte, monocyte, basophil or eosinophil counts; and 6) fetuses with FIRS had a median corrected NRBC count higher than those without FIRS. However, the difference did not reach statistical significance (NRBC median 0.07, range 0-1.3, vs. median 0.04, range 0-2.3, P=0.06). Conclusion: The hematologic profile of the human fetus with FIRS is characterized by significant changes in the total WBC and neutrophil counts. The NRBC count in fetuses with FIRS tends to be higher than fetuses without FIRS. C1 [Romero, Roberto; Savasan, Zeynep Alpay; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA. [Savasan, Zeynep Alpay; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Hutzel Womens Hosp, Detroit, MI 48201 USA. [Berry, Stanley M.] William Beaumont Hosp, Royal Oak, MI 48072 USA. [Pedro Kusanovic, Juan] Pontificia Univ Catolica Chile, Dept Obstet & Gynecol, Santiago, Chile. [Pedro Kusanovic, Juan] Hosp Dr Sotero del Rio, Ctr Perinatal Res, Santiago, Chile. [Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Seoul, South Korea. [Edwin, Samuel] USARIID, Frederick, MD USA. [Mazor, Moshe] Ben Gurion Univ Negev, Dept Obstet & Gynecol, Soroka Univ Med Ctr, IL-84105 Beer Sheva, Israel. RP Romero, R (reprint author), NICHD, Perinatol Res Branch, NIH, DHHS, Box 4,3990 John R, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu RI Yoon, Bo Hyun/H-6344-2011 FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services FX This research was supported, in part, by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services. NR 199 TC 5 Z9 5 U1 0 U2 10 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0300-5577 J9 J PERINAT MED JI J. Perinat. Med. PY 2012 VL 40 IS 1 BP 19 EP 32 DI 10.1515/JPM.2011.100 PG 14 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 897LQ UT WOS:000300652600003 ER PT S AU Killian, JK Walker, RL Bilke, S Chen, YD Davis, S Cornelison, R Smith, WI Meltzer, PS AF Killian, J. Keith Walker, Robert L. Bilke, Sven Chen, Yidong Davis, Sean Cornelison, Robert Smith, William I. Meltzer, Paul S. BE Espina, V Liotta, LA TI Genome-Wide Methylation Profiling in Archival Formalin-Fixed Paraffin-Embedded Tissue Samples SO MOLECULAR PROFILING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Biomarker; DNA methylation; Epigenetics; FFPE; Pathology ID DNA METHYLATION; CANCER; ASSOCIATION AB New technologies allow for genome-scale measurement of DNA methylation. In an effort to increase the clinical utility of DNA methylation as a biomarkcr, we have adapted a commercial bisulfite epigenotyping assay for genome-wide methylation profiling in archival formalin-fixed paraffin-embedded pathology specimens. This chapter takes the reader step by step through a biomarker discovery experiment to identify phenotype-correlated DNA methylation signatures in routine pathology specimens. C1 [Killian, J. Keith; Walker, Robert L.; Bilke, Sven; Chen, Yidong; Davis, Sean; Cornelison, Robert; Meltzer, Paul S.] NCI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Smith, William I.] Suburban Hosp, Dept Pathol, Bethesda, MD USA. RP Killian, JK (reprint author), NCI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. OI Davis, Sean/0000-0002-8991-6458 NR 15 TC 3 Z9 3 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-215-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 823 BP 107 EP 118 DI 10.1007/978-1-60327-216-2_8 D2 10.1007/978-1-60327-216-2 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BYM14 UT WOS:000299299800008 PM 22081342 ER PT S AU Hewitt, SM AF Hewitt, Stephen M. BE Espina, V Liotta, LA TI Tissue Microarrays as a Tool in the Discovery and Validation of Predictive Biomarkers SO MOLECULAR PROFILING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Biomarker; FFPE; Immunohistochemistry; Pathology; Protein; RNA; Tissue microarray ID PARAFFIN-EMBEDDED TISSUE; BREAST-CANCER; EXPRESSION; PROTEIN; PHOSPHORYLATION; OVEREXPRESSION; ANTIGENICITY; POPULATION; PATTERNS; ONCOLOGY AB The tissue microarray (TMA) is the embodiment of high-throughput pathology. The platform combines tens to hundreds of tissue samples on a single microscope slide for interrogation with routine molecular pathology tools. TMAs have enabled the rapid and cost-effective screening of biomarkers for diagnostic, prognostic, and predictive utility. Most commonly applied to the field of oncology, the TM.A has accelerated the development of new biomarkers, and is emerging as an essential tool in the discovery and validation of tissue biomarkers for use in personalized medicine. This chapter provides an overview of TMA technology and highlights the advantages of using TMAs as tools toward rapid introduction of new biomarkers for clinical use. C1 NCI, Tissue Array Res Program, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Hewitt, SM (reprint author), NCI, Tissue Array Res Program, Pathol Lab, NIH, Bethesda, MD 20892 USA. OI Hewitt, Stephen/0000-0001-8283-1788 NR 43 TC 11 Z9 12 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-215-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 823 BP 201 EP 214 DI 10.1007/978-1-60327-216-2_13 D2 10.1007/978-1-60327-216-2 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BYM14 UT WOS:000299299800013 PM 22081347 ER PT J AU Jensen, RT Cadiot, G Brandi, ML de Herder, WW Kaltsas, G Komminoth, P Scoazec, JY Salazar, R Sauvanet, A Kianmanesh, R AF Jensen, Robert T. Cadiot, Guillaume Brandi, Maria L. de Herder, Wouter W. Kaltsas, Gregory Komminoth, Paul Scoazec, Jean-Yves Salazar, Ramon Sauvanet, Alain Kianmanesh, Reza CA Barcelona Consensus Conference TI ENETS Consensus Guidelines for the Management of Patients with Digestive Neuroendocrine Neoplasms: Functional Pancreatic Endocrine Tumor Syndromes SO NEUROENDOCRINOLOGY LA English DT Article ID ZOLLINGER-ELLISON-SYNDROME; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; PROTON PUMP INHIBITORS; CURATIVE GASTRINOMA RESECTION; INSTITUTES-OF-HEALTH; ISLET-CELL TUMORS; LONG-TERM; LIVER METASTASES; CUSHINGS-SYNDROME; MEDICAL-TREATMENT C1 [Jensen, Robert T.] NIH, Digest Dis Branch, Cell Biol Sect, Bethesda, MD 20892 USA. [Cadiot, Guillaume] CHU Reims, Hop Robert Debre, Serv Hepatogastroenterol, Reims, France. [Brandi, Maria L.] Univ Florence, Florence, Italy. [de Herder, Wouter W.] Erasmus MC Univ, Dept Endocrinol, Rotterdam, Netherlands. [Kaltsas, Gregory] Natl Univ Athens, Dept Pathophysiol, Athens, Greece. [Komminoth, Paul] Stadtspital Triemli, Inst Pathol, Zurich, Switzerland. [Scoazec, Jean-Yves; Sauvanet, Alain] Hop Edouard Herriot, Hosp Civils Lyon, Serv Cent Anat & Cytol Pathol, Lyon, France. [Salazar, Ramon] Inst Catala Oncol IDIBELL, Dept Oncol, Barcelona, Spain. [Kianmanesh, Reza] Louis Mourier Univ Hosp, Dept Surg, Colombes, France. RP Jensen, RT (reprint author), NIH, Digest Dis Branch, Cell Biol Sect, Bldg 10,Room 9C-103, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov RI Lopes, Jose Manuel/J-7428-2013; OI Lopes, Jose Manuel/0000-0001-8597-3474; Kloppel, Gunter/0000-0002-6688-086X; RINDI, Guido/0000-0003-2996-4404; Niederle, Bruno/0000-0001-8107-4068; Denecke, Timm/0000-0003-3313-3208; Perren, Aurel/0000-0002-6819-6092 NR 225 TC 156 Z9 171 U1 2 U2 13 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 EI 1423-0194 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2012 VL 95 IS 2 BP 98 EP 119 DI 10.1159/000335591 PG 22 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 897CQ UT WOS:000300619700004 PM 22261919 ER PT J AU Dickin, R Hall, CJ Taylor, LK Collings, AM Nussinov, R Bourne, PE AF Dickin, Rosemary Hall, Chris James Taylor, Laura K. Collings, Andrew M. Nussinov, Ruth Bourne, Philip E. TI A Review of 2011 for PLoS Computational Biology SO PLOS COMPUTATIONAL BIOLOGY LA English DT Editorial Material C1 [Dickin, Rosemary; Hall, Chris James; Taylor, Laura K.; Collings, Andrew M.] Publ Lib Sci, Cambridge, England. [Nussinov, Ruth] NCI, SAIC Frederick, Bethesda, MD 20892 USA. [Nussinov, Ruth] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. [Bourne, Philip E.] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA. [Bourne, Philip E.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA. RP Dickin, R (reprint author), Publ Lib Sci, Cambridge, England. EM pbourne@ucsd.edu OI Taylor, Laura/0000-0003-2820-4091 NR 8 TC 0 Z9 0 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-734X J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD JAN PY 2012 VL 8 IS 1 AR e1002387 DI 10.1371/journal.pcbi.1002387 PG 2 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 891LI UT WOS:000300218100034 ER PT J AU Tippin, BL Levine, AJ Materi, AM Song, WL Keku, TO Goodman, JE Sansbury, LB Das, S Dai, AH Kwong, AM Lin, AM Lin, JM Park, JM Patterson, RE Chlebowski, RT Garavito, RM Inoue, T Cho, W Lawson, JA Kapoor, S Kolonel, LN Le Marchand, L Haile, RW Sandler, RS Lin, HJ AF Tippin, Brigette L. Levine, A. Joan Materi, Alicia M. Song, Wen-Liang Keku, Temitope O. Goodman, Julie E. Sansbury, Leah B. Das, Sudipto Dai, Aihua Kwong, Alan M. Lin, Amy M. Lin, John M. Park, Jae Man Patterson, Ruth E. Chlebowski, Rowan T. Garavito, R. Michael Inoue, Tsuyoshi Cho, Wonhwa Lawson, John A. Kapoor, Shiv Kolonel, Laurence N. Le Marchand, Loic Haile, Robert W. Sandler, Robert S. Lin, Henry J. TI Hematopoietic prostaglandin D synthase (HPGDS): A high stability, Val187Ile isoenzyme common among African Americans and its relationship to risk for colorectal cancer SO PROSTAGLANDINS & OTHER LIPID MEDIATORS LA English DT Article DE Glutathione transferase; HPGDS; prostaglandin D-2; Colon cancer; PTGS2 ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; BASE-LINE CHARACTERISTICS; COLON-CANCER; D SYNTHETASE; EXPRESSION; CYCLOOXYGENASE-2; POLYMORPHISMS; BIOSYNTHESIS; PROTEIN; CELLS AB Intestinal tumors in Apc(Min/+) mice are suppressed by over-production of HPGDS, which is a glutathione transferase that forms prostaglandin D-2 (PGD(2)). We characterized naturally occurring HPGDS isoenzymes, to see if HPGDS variation is associated with human colorectal cancer risk We used DNA heteroduplex analysis and sequencing to identify HPGDS variants among healthy individuals. HPGDS isoenzymes were produced in bacteria, and their catalytic activities were tested. To determine in vivo effects, we conducted pooled case-control analyses to assess whether there is an association of the isoenzyme with colorectal cancer. Roughly 8% of African Americans and 2% of Caucasians had a highly stable Val187Ile isoenzyme (with isoleucine instead of valine at position 187). At 37 degrees C, the wild-type enzyme lost 15% of its activity in 1 h, whereas the Val187Ile form remained >95% active. At 50 degrees C, the half life of native HPGDS was 9 min, compared to 42 min for Val187Ile. The odds ratio for colorectal cancer among African Americans with Val187Ile was 1.10 (95% Cl, 0.75-1.62; 533 cases, 795 controls). Thus, the Val187Ile HPGDS isoenzyme common among African Americans is not associated with colorectal cancer risk. Other approaches will be needed to establish a role for HPGDS in occurrence of human intestinal tumors, as indicated by a mouse model. (C) 2011 Elsevier Inc. All rights reserved. C1 [Tippin, Brigette L.; Materi, Alicia M.; Dai, Aihua; Kwong, Alan M.; Lin, Amy M.; Lin, John M.; Park, Jae Man; Lin, Henry J.] Harbor UCLA Med Ctr, Div Med Genet, Torrance, CA 90509 USA. [Tippin, Brigette L.; Materi, Alicia M.; Dai, Aihua; Kwong, Alan M.; Lin, Amy M.; Lin, John M.; Park, Jae Man; Chlebowski, Rowan T.; Lin, Henry J.] Los Angeles Biomed Res Inst, Torrance, CA USA. [Chlebowski, Rowan T.] Harbor UCLA Med Ctr, Div Med Oncol & Hematol, Torrance, CA 90509 USA. [Levine, A. Joan; Haile, Robert W.] Univ So Calif, Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Song, Wen-Liang; Lawson, John A.; Kapoor, Shiv] Univ Penn, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. [Keku, Temitope O.] Univ N Carolina, Dept Med, Div Gastroenterol & Hepatol, Chapel Hill, NC USA. [Goodman, Julie E.] NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. [Sansbury, Leah B.; Sandler, Robert S.] Univ N Carolina, Sch Med, Ctr Gastrointestinal Biol & Dis, Div Gastroenterol & Hepatol, Chapel Hill, NC USA. [Das, Sudipto; Cho, Wonhwa] Univ Illinois, Dept Chem, Chicago, IL 60680 USA. [Patterson, Ruth E.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. [Garavito, R. Michael] Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. [Inoue, Tsuyoshi] Osaka Univ, Dept Chem Mat, Grad Sch Engn, Osaka, Japan. [Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA. RP Lin, HJ (reprint author), Harbor UCLA Med Ctr, Div Med Genet, Torrance, CA 90509 USA. EM hlin@labiomed.org FU National Institutes of Health [CA44684, CA51923, CA54281, CA66794, CA73403, CA91179, M01 RR00425]; National Heart, Lung, and Blood Institute, U.S. Department of Health and Human Services FX Human studies were approved by the Harbor-UCLA institutional review board. Dr. Curtis Harris kindly provided original data (related to reference [29]) that were used in our pooled analysis of the PTGS2 Val511Ala variant. Drs. Yoshihiro Urade and Kosuke Aritake (Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Osaka, Japan) assisted with the PGD2 synthesis assays. Dr. Florence Lin (Department of Mathematics, University of Southern California, Los Angeles) assisted with mathematical modeling of HPGDS enzyme levels. The work was supported by: National Institutes of Health grants CA44684 (R.S.S.), CA51923 (R.W.H.), CA54281 (L.N.K.), CA66794 (R.W.H.), CA73403 (H.J.L.), CA91179 (H.J.L.), and M01 RR00425 (the General Clinical Research Center at Harbor-UCLA Medical Center). The WHI program was funded by the National Heart, Lung, and Blood Institute, U.S. Department of Health and Human Services. Investigators are listed below. NR 49 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-8823 J9 PROSTAG OTH LIPID M JI Prostaglandins Other Lipid Mediat. PD JAN PY 2012 VL 97 IS 1-2 BP 22 EP 28 DI 10.1016/j.prostaglandins.2011.07.006 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 897MI UT WOS:000300654400003 PM 21821144 ER PT S AU Hartley, JL AF Hartley, James L. BE Hartley, JL TI Why Proteins in Mammalian Cells? SO PROTEIN EXPRESSION IN MAMMALIAN CELLS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Protein quality; Stable expression; Transient expression; Protein folding; Secreted proteins ID HIGH-EFFICIENCY TRANSFORMATION; HAMSTER OVARY CELLS; CHO-CELLS; THYMIDINE KINASE; GENE-DELIVERY; PLASMID DNA; MOUSE CELLS; EXPRESSION; BACULOVIRUS; POLYETHYLENIMINE AB Producing recombinant mammalian proteins in native or near-native conformation is fundamental to many aspects of biology. Unfortunately, it is also a task whose outcome is extremely unpredictable. A protein that has been shaped over millions of generations of evolution for expression at a level appropriate to a specific cell type or in a particular developmental stage, may be toxic to a new host. cell, or become insoluble (among many possible obstacles) when overexpressed in vitro. The object of this volume, "Protein Expression in Mammalian Cells," is to offer guidance for those who wish (or who have been forced by circumstance) to overexpress a mammalian protein in mammalian cells. C1 NCI, Prot Express Lab, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Hartley, JL (reprint author), NCI, Prot Express Lab, SAIC Frederick Inc, Frederick, MD 21701 USA. NR 57 TC 4 Z9 5 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-351-6 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 801 BP 1 EP 12 DI 10.1007/978-1-61779-352-3_1 D2 10.1007/978-1-61779-352-3 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BYM01 UT WOS:000299298500001 PM 21987243 ER PT S AU Hopkins, RF Wall, VE Esposito, D AF Hopkins, Ralph F. Wall, Vanessa E. Esposito, Dominic BE Hartley, JL TI Optimizing Transient Recombinant Protein Expression in Mammalian Cells SO PROTEIN EXPRESSION IN MAMMALIAN CELLS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Optimizing transient expression; Gateway cloning; Gateway Multisite; HEK293E; Polyethylenimine ID SITE-SPECIFIC RECOMBINATION; DNA CLONING; CULTURE; CLONES; GENE AB Transient gene expression (TGE) in mammalian cells has become a routine process for expressing recombinant proteins in cell lines such as human embryonic kidney 293 and Chinese hamster ovary cells. The rapidly increasing need for recombinant proteins requires further improvements in TGE technology. While a great deal of focus has been directed toward optimizing the secretion of antibodies and other naturally secreted targets, much less work has been done on ways to improve cytoplasmic expression in mammalian cells. The benefits to protein production in mammalian cells, particularly for eukaryotic proteins, should be very significant glycosylation and other posttranslational modifications will likely be native or near-native, solubility and protein folding would likely improve overexpression in heterologous hosts, and expression of proteins in their proper intracellular compartments is much more likely to occur. Improvements in this area have been slow, however, due to limited development of the cell culture processes needed for low-cost, higher-throughput expression in mammalian cells, and the relatively low diversity of DNA vectors for protein production in these systems. Here, we describe how the use of recombinational cloning, coupled with improvements in transfection protocols which increase speed and lower cost, can be combined to make mammalian cells much more amenable for routine recombinant protein expression. C1 [Hopkins, Ralph F.; Wall, Vanessa E.; Esposito, Dominic] NCI, Prot Express Lab, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Hopkins, RF (reprint author), NCI, Prot Express Lab, SAIC Frederick Inc, Frederick, MD 21701 USA. FU PHS HHS [HHSN261200800001E] NR 11 TC 9 Z9 12 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-351-6 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 801 BP 251 EP 268 DI 10.1007/978-1-61779-352-3_16 D2 10.1007/978-1-61779-352-3 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BYM01 UT WOS:000299298500016 PM 21987258 ER PT S AU Ma, WX Zhao, L Wong, WT AF Ma, Wenxin Zhao, Lian Wong, Wai T. BE LaVail, MM Ash, JD Anderson, RE Hollyfield, JG Grimm, C TI Microglia in the Outer Retina and Their Relevance to Pathogenesis of Age-Related Macular Degeneration SO RETINAL DEGENERATIVE DISEASES SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE Microglia; Retinal pigment epithelium; Age-related macular degeneration; Inflammation; Cell-cell interactions; Angiogenesis; Cytokines; Chemokines ID SUBRETINAL DRUSENOID DEPOSITS; RETICULAR PSEUDODRUSEN; PIGMENT-EPITHELIUM; MOUSE RETINA; INFLAMMATION; PREVALENCE; CELLS; ACCUMULATION; SYSTEM; BRAIN C1 [Ma, Wenxin; Zhao, Lian; Wong, Wai T.] NEI, Unit Neuron Glia Interact Retinal Dis, Bethesda, MD 20892 USA. RP Wong, WT (reprint author), NEI, Unit Neuron Glia Interact Retinal Dis, 6 Ctr Dr,Bldg 6,Room 215, Bethesda, MD 20892 USA. EM mawenxin@nei.nih.gov; zhaolia@nei.nih.gov; wongw@nei.nih.gov RI Wong, Wai/B-6118-2017 OI Wong, Wai/0000-0003-0681-4016 FU Intramural NIH HHS [Z01 EY000463-01] NR 30 TC 14 Z9 14 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-0630-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2012 VL 723 BP 37 EP 42 DI 10.1007/978-1-4614-0631-0_6 D2 10.1007/978-1-4614-0631-0 PG 6 WC Biology; Medicine, Research & Experimental; Ophthalmology SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine; Ophthalmology GA BYQ08 UT WOS:000299709700006 PM 22183313 ER PT S AU Ablonczy, Z Gutierrez, DB Grey, AC Schey, KL Crouch, RK AF Ablonczy, Zsolt Gutierrez, Danielle B. Grey, Angus C. Schey, Kevin L. Crouch, Rosalie K. BE LaVail, MM Ash, JD Anderson, RE Hollyfield, JG Grimm, C TI Molecule-Specific Imaging and Quantitation of A2E in the RPE SO RETINAL DEGENERATIVE DISEASES SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE A2E; Lipofuscin; Retinal pigment epithelium; Mass spectrometry; MALDI imaging; Quantitation; Stargardt disease; Age-related macular degeneration ID RETINAL-PIGMENT EPITHELIUM; LIPOFUSCIN; PRODUCTS C1 [Ablonczy, Zsolt; Crouch, Rosalie K.] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. [Gutierrez, Danielle B.] NEI, Retinal Cell & Mol Biol Lab, Bethesda, MD 20892 USA. [Grey, Angus C.] Univ Auckland, Dept Optometry & Vis Sci, Grafton 1023, New Zealand. [Schey, Kevin L.] Vanderbilt Univ, Dept Biochem, Nashville, TN 37240 USA. RP Ablonczy, Z (reprint author), Med Univ S Carolina, Dept Ophthalmol, 171 Ashley Ave, Charleston, SC 29425 USA. EM ablonczy@musc.edu; danielle.gutierrez@nih.gov; ac.grey@auckland.ac.nz; k.schey@Vanderbilt.edu; crouchrk@musc.edu RI Grey, Gus/J-7024-2015 OI Grey, Gus/0000-0002-1540-1080 FU NCRR NIH HHS [C06 RR015455]; NEI NIH HHS [R01 EY004939, R01 EY019065, R21 EY019728, R21 EY020661, EY020661, EY004939] NR 10 TC 9 Z9 9 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-0630-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2012 VL 723 BP 75 EP 81 DI 10.1007/978-1-4614-0631-0_11 D2 10.1007/978-1-4614-0631-0 PG 7 WC Biology; Medicine, Research & Experimental; Ophthalmology SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine; Ophthalmology GA BYQ08 UT WOS:000299709700011 PM 22183318 ER PT S AU Poliakov, E Gubin, A Laird, J Gentleman, S Salomon, RG Redmond, TM AF Poliakov, Eugenia Gubin, Alexander Laird, James Gentleman, Susan Salomon, Robert G. Redmond, T. Michael BE LaVail, MM Ash, JD Anderson, RE Hollyfield, JG Grimm, C TI The Mechanism of Fenretinide (4-HPR) Inhibition of beta-carotene Monooxygenase 1. New Suspect for the Visual Side Effects of Fenretinide SO RETINAL DEGENERATIVE DISEASES SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE (R)-carotene monooxygenase 1; BCMO1; beta-carotene; Fenretinide; 4-HPR; Noncompetitive inhibition; Retinoid ID RETINOL-BINDING-PROTEIN; PLASMA RETINOL; BREAST-CANCER; VITAMIN-A; REDUCTIONS; TRIAL; CYCLE C1 [Poliakov, Eugenia; Gubin, Alexander; Gentleman, Susan; Redmond, T. Michael] NEI, LRCMB, NIH, Bethesda, MD 20892 USA. [Laird, James; Salomon, Robert G.] Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA. RP Redmond, TM (reprint author), NEI, LRCMB, NIH, Bldg 6,6 Ctr Dr MSC0608, Bethesda, MD 20892 USA. EM poliakove@nei.nih.gov; gubina@csr.nih.gov; jx1122@case.edu; sgman@helix.nih.gov; rgs@case.edu; Redmond@helix.nih.gov OI Redmond, T. Michael/0000-0002-1813-5291 NR 21 TC 3 Z9 3 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-0630-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2012 VL 723 BP 167 EP 174 DI 10.1007/978-1-4614-0631-0_23 D2 10.1007/978-1-4614-0631-0 PG 8 WC Biology; Medicine, Research & Experimental; Ophthalmology SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine; Ophthalmology GA BYQ08 UT WOS:000299709700023 PM 22183330 ER PT S AU Strunnikova, N Zein, WM Silvin, C MacDonald, IM AF Strunnikova, Natalia Zein, Wadih M. Silvin, Chris MacDonald, Ian M. BE LaVail, MM Ash, JD Anderson, RE Hollyfield, JG Grimm, C TI Serum Biomarkers and Trafficking Defects in Peripheral Tissues Reflect the Severity of Retinopathy in Three Brothers Affected by Choroideremia SO RETINAL DEGENERATIVE DISEASES SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE CSNB; CSNB1A; CSNB2A; CANA1F; NYX; GRM6; TRMP1 ID MUTATIONS; DEGENERATION; DISEASE C1 [MacDonald, Ian M.] Univ Alberta, Dept Ophthalmol, Edmonton, AB, Canada. [Silvin, Chris] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Strunnikova, Natalia; Zein, Wadih M.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. RP MacDonald, IM (reprint author), Univ Alberta, Dept Ophthalmol, 10240 Kingsway Ave, Edmonton, AB, Canada. EM strunnikovan@nei.nih.gov; zeinw@nei.nih.gov; csilvin@mail.nih.gov; Ian.M.Macdonald@albertahealthservices.ca OI MacDonald, Ian/0000-0001-7472-8385 NR 11 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-0630-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2012 VL 723 BP 381 EP 387 DI 10.1007/978-1-4614-0631-0_49 D2 10.1007/978-1-4614-0631-0 PG 7 WC Biology; Medicine, Research & Experimental; Ophthalmology SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine; Ophthalmology GA BYQ08 UT WOS:000299709700049 PM 22183356 ER PT S AU Fischer, MD Huber, G Paquet-Durand, F Humphries, P Redmond, TM Grimm, C Seeliger, MW AF Fischer, M. Dominik Huber, Gesine Paquet-Durand, Francois Humphries, Peter Redmond, T. Michael Grimm, Christian Seeliger, Mathias W. BE LaVail, MM Ash, JD Anderson, RE Hollyfield, JG Grimm, C TI In Vivo Assessment of Rodent Retinal Structure Using Spectral Domain Optical Coherence Tomography SO RETINAL DEGENERATIVE DISEASES SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE Optical coherence tomography; Imaging; Mouse models; Retinal degeneration; Light damage; Rhodopsin; RPE65; Rd1 ID PHOTORECEPTOR DEGENERATION; MOUSE; MODELS C1 [Fischer, M. Dominik; Huber, Gesine; Seeliger, Mathias W.] Univ Tubingen, Inst Ophthalm Res, Div Ocular Neurodegenerat, Ctr Ophthalmol, D-72076 Tubingen, Germany. [Paquet-Durand, Francois] Univ Tubingen, Inst Ophthalm Res, Div Expt Ophthalmol, Ctr Ophthalmol, D-72076 Tubingen, Germany. [Humphries, Peter] Trinity Coll Dublin, Ocular Genet Unit, Dept Genet, Dublin 2, Ireland. [Redmond, T. Michael] NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Grimm, Christian] Univ Zurich, Dept Ophthalmol, Lab Retinal Cell Biol, Zurich, Switzerland. [Grimm, Christian] Univ Zurich, Ctr Integrat Human Physiol, Zurich, Switzerland. RP Fischer, MD (reprint author), Univ Tubingen, Inst Ophthalm Res, Div Ocular Neurodegenerat, Ctr Ophthalmol, Schleichstr 12-16, D-72076 Tubingen, Germany. EM Dominik.Fischer@med.uni-tuebingen.de; gesine.huber@med.uni-tuebingen.de; francois.paquet-durand@klinikum.uni-tuebingen.de; Pete.Humphries@tcd.ie; Redmond@helix.nih.gov; see@uni-tuebingen.de RI Paquet-Durand, Francois/G-6709-2015; OI Paquet-Durand, Francois/0000-0001-7355-5742; Redmond, T. Michael/0000-0002-1813-5291 NR 17 TC 7 Z9 7 U1 0 U2 9 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-0630-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2012 VL 723 BP 489 EP 494 DI 10.1007/978-1-4614-0631-0_61 D2 10.1007/978-1-4614-0631-0 PG 6 WC Biology; Medicine, Research & Experimental; Ophthalmology SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine; Ophthalmology GA BYQ08 UT WOS:000299709700061 PM 22183368 ER PT S AU Vijayasarathy, C Ziccardi, L Sieving, PA AF Vijayasarathy, Camasamudram Ziccardi, Lucia Sieving, Paul A. BE LaVail, MM Ash, JD Anderson, RE Hollyfield, JG Grimm, C TI Biology of Retinoschisin SO RETINAL DEGENERATIVE DISEASES SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE X-linked retinoschisis; Retinoschisin; Discoidin domain; Mutations; Retina; Photoreceptors; Bipolar cells; Synapse; Gene therapy ID X-LINKED RETINOSCHISIS; JUVENILE RETINOSCHISIS; BIPOLAR CELLS; GENE DELIVERY; MULLER CELLS; RS1; PROTEIN; PHOTORECEPTOR; MOUSE; EXPRESSION C1 [Sieving, Paul A.] NEI, NIH, Bethesda, MD 20892 USA. [Ziccardi, Lucia] Fdn GB Bietti IRCCS, Neurophthalmol Unit, I-300198 Rome, Italy. [Vijayasarathy, Camasamudram] Natl Inst Deafness & Other Commun Disorders, Sect Translat Res Retinal & Macular Degenerat, NIH, Bethesda, MD 20892 USA. RP Sieving, PA (reprint author), NEI, NIH, Bethesda, MD 20892 USA. EM camasamv@nidcd.nih.gov; lucia.ziccardi@nih.gov; paulsieving@nei.nih.gov FU Intramural NIH HHS [Z99 DC999999, ZIA DC000077-02] NR 37 TC 3 Z9 3 U1 1 U2 9 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-0630-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2012 VL 723 BP 513 EP 518 DI 10.1007/978-1-4614-0631-0_64 D2 10.1007/978-1-4614-0631-0 PG 6 WC Biology; Medicine, Research & Experimental; Ophthalmology SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine; Ophthalmology GA BYQ08 UT WOS:000299709700064 PM 22183371 ER PT S AU Hao, H AF Hao, Hong BE LaVail, MM Ash, JD Anderson, RE Hollyfield, JG Grimm, C TI Genome-Wide Occupancy Analysis by ChIP-chip and ChIP-Seq SO RETINAL DEGENERATIVE DISEASES SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE ChIP-chip; ChIP-Seq; Chromatin signature; Transcription; Enhancer; Histone; Transcription regulatory network; Photoreceptor; Development ID PREDICTIVE CHROMATIN SIGNATURES; TRANSCRIPTION FACTORS; DNA INTERACTIONS; RETINA; IMMUNOPRECIPITATION; PHOTORECEPTORS; EXPRESSION; PROMOTERS; ENHANCERS; LOCATION C1 NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA. RP Hao, H (reprint author), NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA. EM haoh@mail.nih.gov FU Intramural NIH HHS NR 27 TC 4 Z9 5 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-0630-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2012 VL 723 BP 753 EP 759 DI 10.1007/978-1-4614-0631-0_96 D2 10.1007/978-1-4614-0631-0 PG 7 WC Biology; Medicine, Research & Experimental; Ophthalmology SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine; Ophthalmology GA BYQ08 UT WOS:000299709700096 PM 22183403 ER PT S AU Subramanian, P Rapp, M Becerra, SP AF Subramanian, Preeti Rapp, Matthew Becerra, S. Patricia BE LaVail, MM Ash, JD Anderson, RE Hollyfield, JG Grimm, C TI Identification of Pigment Epithelium-Derived Factor Receptor (PEDF-R) Antibody Epitopes SO RETINAL DEGENERATIVE DISEASES SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE PEDF-R antibody; Epitope; PEDF; Phospholipase A(2); PNPLA2 ID INHIBITION; MEDIATOR; GROWTH C1 [Subramanian, Preeti; Becerra, S. Patricia] NEI, NIH, Bethesda, MD 20892 USA. [Rapp, Matthew] Univ Maryland Baltimore Cty, Baltimore, MD 21250 USA. RP Subramanian, P (reprint author), NEI, NIH, Bldg 6,Room 134,6 Ctr Dr,MSC 0608, Bethesda, MD 20892 USA. EM subramanianp@nei.nih.gov; rappm1@umbc.cdu; becerrap@nei.nih.gov FU Intramural NIH HHS [ZIA EY000306-16] NR 12 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-0630-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2012 VL 723 BP 799 EP 805 DI 10.1007/978-1-4614-0631-0_102 D2 10.1007/978-1-4614-0631-0 PG 7 WC Biology; Medicine, Research & Experimental; Ophthalmology SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine; Ophthalmology GA BYQ08 UT WOS:000299709700102 PM 22183409 ER PT S AU Cho, YW Hong, S Ge, K AF Cho, Young-Wook Hong, SunHwa Ge, Kai BE Vancura, A TI Affinity Purification of MLL3/MLL4 Histone H3K4 Methyltransferase Complex SO TRANSCRIPTIONAL REGULATION: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Histone H3K4 methyltransferase complex; MLL3; MLL4; PA1 ID SACCHAROMYCES-CEREVISIAE; LYSINE-4; DOMAIN; PROTEIN; SET1; IDENTIFICATION; GROWTH; MENIN AB Methylation on histone H3 lysine 4 (H3K4) correlates with actively transcribed genes. In mammalian cells, there exist multiple Sea-like histone H3K4 methyltransferase complexes, which have overlapping but distinct subunit compositions. Developing methods to isolate each of these histone H3K4 methyl-transferase complexes would help understand the molecular mechanisms by which histone H3K4 methylation regulates mammalian gene expression. In this chapter, we provide a one-step affinity purification protocol on isolation of the MLL3/MLL4 histone H3K4 methyltransferase complex using FLAG-tagged PA1, a unique subunit of the MLL3/MLL4 complex. C1 [Cho, Young-Wook; Hong, SunHwa; Ge, Kai] NIDDK, Nucl Receptor Biol Sect, NIH, Bethesda, MD 20892 USA. RP Cho, YW (reprint author), NIDDK, Nucl Receptor Biol Sect, NIH, Bethesda, MD 20892 USA. OI Ge, Kai/0000-0002-7442-5138 FU Intramural NIH HHS [ZIA DK075003-08, Z01 DK075003-04, Z01 DK075003-05, Z99 DK999999, ZIA DK075003-07, ZIA DK075003-09, ZIA DK075017-02, ZIA DK075017-03, ZIA DK075017-04]; NIDDK NIH HHS [ZIA DK075003-06, ZIA DK075017-01] NR 17 TC 7 Z9 7 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-375-2 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 809 BP 465 EP 472 DI 10.1007/978-1-61779-376-9_30 D2 10.1007/978-1-61779-376-9 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BYQ02 UT WOS:000299709100030 PM 22113294 ER PT S AU Fan, JS Chen, YC Watkins, T Dang, CV Gorospe, M Cheadle, C AF Fan, Jinshui Chen, Yu-Chi Watkins, Tonya Dang, Chi V. Gorospe, Myriam Cheadle, Chris BE Vancura, A TI Array-Based Nuclear Run-On Analysis SO TRANSCRIPTIONAL REGULATION: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Nascent RNA; Nuclear run-on; Biotin; Microarray; Posttranscriptional regulation ID MESSENGER-RNA DECAY; HUMAN B-CELLS; BINDING-SITES; TRANSCRIPTION; GENOME AB There is extensive evidence that posttranscriptional mechanisms of gene regulation, such as mRNA turnover, critically affect the patterns of expressed mRNAs. Conventional microarray analysis measures steady-state messenger RNA (mRNA) levels, which represents the dynamic balance between new transcription and mRNA degradation. Accordingly, only de novo transcription can accurately reflect the temporal and spatial events of transcriptional regulation. In this chapter, we describe a recently reported method to study transcription systematically. It involves the genome-wide labeling of nascent transcripts using nonradioactive modified nucleotides, their isolation for amplification, and their hybridization and analysis using commercial microarrays. C1 [Fan, Jinshui; Watkins, Tonya] Johns Hopkins Univ, Sch Med, Dept Med, MS Lowe Family Genom Core,Div Allergy & Clin Immu, Baltimore, MD 21205 USA. [Dang, Chi V.] Johns Hopkins Univ, Sch Med, Dept Med, Div Hematol, Baltimore, MD 21205 USA. [Dang, Chi V.] Johns Hopkins Univ, Sch Med, Dept Cell Biol, Div Hematol, Baltimore, MD 21205 USA. [Dang, Chi V.] Johns Hopkins Univ, Sch Med, Dept Oncol, Div Hematol, Baltimore, MD 21205 USA. [Dang, Chi V.] Johns Hopkins Univ, Sch Med, Dept Pathol, Div Hematol, Baltimore, MD 21205 USA. [Gorospe, Myriam] NIA, Lab Cellular & Mol Biol, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Fan, JS (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, MS Lowe Family Genom Core,Div Allergy & Clin Immu, Baltimore, MD 21205 USA. FU Intramural NIH HHS [ZIA AG000393-02] NR 11 TC 2 Z9 2 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-375-2 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 809 BP 505 EP 517 DI 10.1007/978-1-61779-376-9_33 D2 10.1007/978-1-61779-376-9 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BYQ02 UT WOS:000299709100033 PM 22113297 ER PT J AU Diamond, JS Lukasiewicz, PD AF Diamond, Jeffrey S. Lukasiewicz, Peter D. TI Amacrine cells: Seeing the forest and the trees INTRODUCTION SO VISUAL NEUROSCIENCE LA English DT Editorial Material C1 [Diamond, Jeffrey S.] NINDS, Synapt Physiol Sect, NIH, Bethesda, MD 20892 USA. [Lukasiewicz, Peter D.] Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA. RP Diamond, JS (reprint author), NINDS, Synapt Physiol Sect, NIH, Bethesda, MD 20892 USA. RI Diamond, Jeffrey/C-1835-2015 OI Diamond, Jeffrey/0000-0002-1770-2629 NR 0 TC 1 Z9 1 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0952-5238 J9 VISUAL NEUROSCI JI Visual Neurosci. PD JAN PY 2012 VL 29 IS 1 BP 1 EP 2 DI 10.1017/S0952523812000016 PG 2 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 895TM UT WOS:000300519300001 PM 22416288 ER PT J AU Kravitz, DJ Chan, AWY Baker, CI AF Kravitz, Dwight J. Chan, Annie W-Y Baker, Chris I. BE Kriegeskorte, N Kreiman, G TI Investigating High-Level Visual Representations: Objects, Bodies, and Scenes SO VISUAL POPULATION CODES: TOWARD A COMMON MULTIVARIATE FRAMEWORK FOR CELL RECORDING AND FUNCTIONAL IMAGING SE Computational Neuroscience-MIT LA English DT Article; Book Chapter ID INFERIOR TEMPORAL CORTEX; HUMAN EXTRASTRIATE CORTEX; MACAQUE INFEROTEMPORAL CORTEX; FUSIFORM FACE AREA; CEREBRAL-CORTEX; HUMAN BRAIN; BODY PARTS; NEURAL REPRESENTATIONS; DISTRIBUTED PATTERNS; MAGNETIC STIMULATION AB Human functional magnetic resonance imaging (fMRI) studies have revealed cortical regions selectively responsive to particular categories of visual stimuli (e. g., faces, body parts, objects, and scenes). However, it has been difficult to probe beyond this category selectivity to investigate more fine-grained representations, in part because traditional fMRI designs make implicit assumptions about the structure of those representations. Here, we take advantage of the flexibility of ungrouped event-related designs and the power of representational similarity analysis to directly investigate within-category representations of object, body parts, and scenes. This approach enables us to elucidate how the structure of these representations relates to categorization, individuation, and the complex relationship between the two. Responses from up to ninety-six conditions were analyzed using an iterative split-half correlation method allowing us to simultaneously investigate categorical structure (by grouping stimuli based on their response-pattern similarities) and individuation (by comparing the similarity between individual stimuli). First, we show that object-selective cortex contains distinct representations of the same objects in different positions. Second, we find that body-selective cortex contains distinct representations of different types of body parts. Further, those representations are strongest for body parts in their commonly experienced configuration. Finally, we show that scene-selective cortex contains strong representations of individual scenes and further categorizes scenes based on their expanse (open, closed the boundary of the scene). In each case, the flexibility afforded by condition-rich ungrouped-events design and representational similarity analysis allowed us to design data-driven experiments capable of revealing surprising and counterintuitive aspects of high-level representations. C1 [Kravitz, Dwight J.; Chan, Annie W-Y; Baker, Chris I.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RP Kravitz, DJ (reprint author), NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. NR 104 TC 0 Z9 0 U1 1 U2 6 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-26229-918-3 J9 COMPUT NEUROSCI-MIT JI Comput. Neurosci. MIT PY 2012 BP 357 EP 389 PG 33 WC Neurosciences SC Neurosciences & Neurology GA BYK14 UT WOS:000299078100016 ER PT J AU Ashcroft, GS Jeong, MJ Ashworth, JJ Hardman, M Jin, WW Moutsopoulos, N Wild, T McCartney-Francis, N Sim, D McGrady, G Song, XY Wahl, SM AF Ashcroft, Gillian S. Jeong, Moon-Jin Ashworth, Jason J. Hardman, Matthew Jin, Wenwen Moutsopoulos, Niki Wild, Teresa McCartney-Francis, Nancy Sim, Davis McGrady, George Song, Xiao-yu Wahl, Sharon M. TI Tumor necrosis factor-alpha (TNF-a) is a therapeutic target for impaired cutaneous wound healing SO WOUND REPAIR AND REGENERATION LA English DT Article ID LEUKOCYTE-PROTEASE-INHIBITOR; GENE-EXPRESSION; HUMAN SKIN; ACTIVATION; MACROPHAGES; SUPPRESSES; LIPOPOLYSACCHARIDE; METALLOPROTEINASES; INFLAMMATION; INDUCTION AB Impaired wound healing states lead to substantial morbidity and cost with treatment resulting in an expenditure of billions of dollars per annum in the US alone. Both chronic wounds and impaired acute wounds are characterized by excessive inflammation, enhanced proteolysis, and reduced matrix deposition. These confounding factors are exacerbated in the elderly, in part, as we report here, related to increased local and systemic tumor necrosis factor-alpha (TNF-a) levels. Moreover, we have used a secretory leukocyte protease inhibitor (SLPI) null mouse model of severely impaired wound healing and excessive inflammation, comparable to age-related delayed human healing, to demonstrate that topical application of anti-TNF-a neutralizing antibodies blunts leukocyte recruitment and NF?B activation, alters the balance between M1 and M2 macrophages, and accelerates wound healing. Following antagonism of TNF-a, matrix synthesis is enhanced, associated with suppression of both inflammatory parameters and NF?B binding activity. Our data suggest that inhibiting TNF-a is a critical event in reversing the severely impaired healing response associated with the absence of SLPI, and may be applicable to prophylaxis and/or treatment of impaired wound healing states in humans. C1 [Ashcroft, Gillian S.; Jeong, Moon-Jin; Jin, Wenwen; Moutsopoulos, Niki; Wild, Teresa; McCartney-Francis, Nancy; Sim, Davis; McGrady, George; Wahl, Sharon M.] NIDCR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. [Ashcroft, Gillian S.; Ashworth, Jason J.; Hardman, Matthew] Univ Manchester, Fac Life Sci, Manchester, Lancs, England. [Song, Xiao-yu] Centocor Inc, Res & Dev, Malvern, PA USA. [Jeong, Moon-Jin] Chosun Univ, Coll Dent, Kwangju, South Korea. RP Wahl, SM (reprint author), NIDCR, Oral Infect & Immun Branch, NIH, Bldg 30,Room 320,30 Convent Dr,MSC 4352, Bethesda, MD 20892 USA. EM smwahl@mail.nih.gov FU Wellcome Senior Fellowship in Clinical Science; NIH, National Institute of Dental and Craniofacial Research FX The authors are grateful to Calley Grace for editorial assistance, Azita Adli, Nancy Marinos, and Alec Waite for histological assistance and expertise with immunocytochemistry and Dr. S Vogel, U MD School of Medicine, Baltimore for Mac2 antibody. Gillian Ashcroft was funded under a Wellcome Senior Fellowship in Clinical Science. This research was supported in part by the Intramural Research Program of the NIH, National Institute of Dental and Craniofacial Research. NR 40 TC 44 Z9 47 U1 0 U2 17 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD JAN-FEB PY 2012 VL 20 IS 1 BP 38 EP 49 DI 10.1111/j.1524-475X.2011.00748.x PG 12 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 882GE UT WOS:000299551000050 PM 22151742 ER PT J AU Raju, TNK Bailit, J AF Raju, Tonse N. K. Bailit, Jennifer TI Patient Safety during Perinatal and Neonatal Care: Research, Education, and Clinical Care Issues Preface SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Editorial Material C1 [Raju, Tonse N. K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, Bethesda, MD 20892 USA. [Bailit, Jennifer] Case Western Univ, MetroHlth Med Ctr, Dept Obstet & Gynecol, Cleveland, OH USA. RP Raju, TNK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, 6100 Execut Blvd, Bethesda, MD 20892 USA. EM rajut@mail.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0735-1631 J9 AM J PERINAT JI Am. J. Perinatol. PD JAN PY 2012 VL 29 IS 1 BP 1 EP 2 DI 10.1055/s-0031-1301056 PG 2 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 891ZU UT WOS:000300256600001 PM 22270754 ER PT J AU Ispas, CR Crivat, G Andreescu, S AF Ispas, Cristina R. Crivat, Georgeta Andreescu, Silvana TI REVIEW: RECENT DEVELOPMENTS IN ENZYME-BASED BIOSENSORS FOR BIOMEDICAL ANALYSIS SO ANALYTICAL LETTERS LA English DT Review DE Bioanalysis; Biomedical; Electrochemical; Enzyme biosensors; Optical; Review ID RESONANCE ENERGY-TRANSFER; HIGHLY SENSITIVE DETECTION; GREEN FLUORESCENT PROTEIN; ON-A-CHIP; QUANTUM DOTS; IN-VIVO; GOLD NANOPARTICLES; DIRECT ELECTROCHEMISTRY; LACTATE-DEHYDROGENASE; GRAPHENE NANOSHEETS AB The need for simple, rapid, cost-effective, and portable screening methods has boosted the development of practical biosensors with applications in clinical monitoring, and diagnosis of disease. Compared with traditional analytical methods, enzyme-based bioanalytical devices have several distinct advantages such as high sensitivity and specificity, portability, cost-effectiveness, and the possibilities for miniaturization and mass production. Additionally, they can be developed for point-of-care diagnostic testing. This paper reviews recent advances in the development of enzyme biosensors, design characteristics, performances, and applications with a focus on electrochemical and optical sensors. Recent emerging technologies and innovative biosensing designs, such as nanosensors, paper based-sensors, lab-on-a-chip, biochips, and microfluidic devices are discussed. Specific applications in bioanalysis, clinical diagnosis, and pharmacology are discussed. C1 [Ispas, Cristina R.; Andreescu, Silvana] Clarkson Univ, Dept Chem & Biomol Sci, Potsdam, NY 13699 USA. [Crivat, Georgeta] Natl Inst Stand & Technol, Opt Technol Div, Gaithersburg, MD 20899 USA. [Crivat, Georgeta] NIH, Bethesda, MD 20892 USA. RP Andreescu, S (reprint author), Clarkson Univ, Dept Chem & Biomol Sci, Potsdam, NY 13699 USA. EM eandrees@clarkson.edu RI Ispas, Cristina/F-9300-2011; OI Andreescu, Silvana/0000-0003-3382-7939 FU NSF [0954919] FX This work was supported by NSF grant 0954919 to SA. NR 109 TC 50 Z9 51 U1 18 U2 172 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0003-2719 J9 ANAL LETT JI Anal. Lett. PY 2012 VL 45 IS 2-3 BP 168 EP 186 DI 10.1080/00032719.2011.633188 PG 19 WC Chemistry, Analytical SC Chemistry GA 894CV UT WOS:000300405500005 ER PT S AU Wang, YA Rouggly, L You, M Lubet, R AF Wang, Yian Rouggly, Lucina You, Ming Lubet, Ronald BE Conn, PM TI Animal Models of Lung Cancer: Characterization and Use for Chemoprevention Research SO ANIMAL MODELS OF MOLECULAR PATHOLOGY SE Progress in Molecular Biology and Translational Science LA English DT Review; Book Chapter ID SQUAMOUS-CELL CARCINOMA; PHASE IIB TRIAL; A/J MICE; K-RAS; BRONCHIAL EPITHELIUM; INTRAEPITHELIAL NEOPLASIA; N-NITROSODIETHYLAMINE; ADENOMA INDUCTION; TUMOR INDUCTION; POLYPHENON-E C1 [Wang, Yian; Rouggly, Lucina] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [You, Ming] Med Coll Wisconsin, Ctr Canc, Milwaukee, WI 53226 USA. [Lubet, Ronald] NCI, Chemoprevent Branch, Bethesda, MD 20892 USA. RP Wang, YA (reprint author), Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. NR 61 TC 11 Z9 11 U1 0 U2 6 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1877-1173 BN 978-0-12-394596-9 J9 PROG MOL BIOL TRANSL JI Prog. Molec. Biol. Transl. Sci. PY 2012 VL 105 BP 211 EP 226 DI 10.1010/B978-0-12-394596-9.00007-X PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BYN14 UT WOS:000299397700007 PM 22137433 ER PT J AU Henrich, CJ Thomas, CL Brooks, AD Booth, NL Lowery, EM Pompei, RJ McMahon, JB Sayers, TJ AF Henrich, Curtis J. Thomas, Cheryl L. Brooks, Alan D. Booth, Nancy Lynn Lowery, Evan M. Pompei, Richard J. McMahon, James B. Sayers, Thomas J. TI Effects of cucurbitacins on cell morphology are associated with sensitization of renal carcinoma cells to TRAIL-induced apoptosis SO APOPTOSIS LA English DT Article DE Cucurbitacins; TRAIL; TRAIL sensitizers; Apoptosis; STAT3; Cell morphology ID DEATH RECEPTORS; PANCREATIC-CANCER; SIGNALING PATHWAY; STAT3 ACTIVATION; DOWN-REGULATION; UP-REGULATION; THERAPY; CYTOTOXICITY; INFLAMMATION; INHIBITION AB Cucurbitacins B and D were among the compounds identified as sensitizers of cancer cells to TRAIL-mediated apoptosis in a high-throughput screen. Therefore a series of cucurbitacins was further investigated for TRAIL sensitization and possible mechanisms of action. A total of six cucurbitacins promoted TRAIL-induced apoptosis (B, I, E, C, D, and K) and one (P) was inactive. Sensitization of renal adenocarcinoma cells to TRAIL was apparent after as little as 1-4 h pretreatment and did not require continued presence of cucurbitacin. Active cucurbitacins induced caspase-8 activation only after subsequent TRAIL addition and caspase activation was required for apoptosis suggesting amplified proximal signaling from TRAIL death receptors. Cucurbitacin-sensitized TRAIL-induced cytotoxicity was inhibited by N-acetyl cysteine. Structure-activity relationship analysis in comparison to published studies suggests that TRAIL-sensitizing and general cytotoxic activities of cucurbitacins may be decoupled. Cucurbitacins are reported to be inhibitors of STAT3 activation. However, their TRAIL-sensitizing activity is STAT3-independent. Treatment of renal carcinoma cells with active cucurbitacins produced rapid and dramatic changes in cell morphology and cytoskeletal organization (also prevented by NAC). Therefore, cucurbitacins may be useful as tools for investigating the molecular mechanism(s) of action of TRAIL sensitizers, particularly with regard to temporal aspects of sensitization and modulation of TRAIL signaling by cell morphology, and could form the basis for future therapeutic development in combination with TRAIL death receptor agonists. C1 [Henrich, Curtis J.; Brooks, Alan D.; Sayers, Thomas J.] NCI Frederick, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Henrich, Curtis J.; Thomas, Cheryl L.; Booth, Nancy Lynn; McMahon, James B.] NCI Frederick, Mol Targets Lab, Frederick, MD 21702 USA. [Brooks, Alan D.; Lowery, Evan M.; Pompei, Richard J.; Sayers, Thomas J.] NCI Frederick, Expt Immunol Lab, Frederick, MD 21702 USA. [Brooks, Alan D.; Lowery, Evan M.; Pompei, Richard J.; Sayers, Thomas J.] NCI Frederick, Canc Inflammat Program, Frederick, MD 21702 USA. RP Henrich, CJ (reprint author), NCI Frederick, Basic Res Program, SAIC Frederick Inc, Bldg 538,Room 141, Frederick, MD 21702 USA. EM Curtis.Henrich2@nih.gov RI Sayers, Thomas/G-4859-2015 FU national Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX Thanks to Heidi Bokesh and Kirk Gustafson for performing and interpreting chemical analysis to confirm identities of the compounds obtained from the DTP repository. Thanks also to Anna Maciag for assistance with ROS assays and to Tommy Turbyville for help with actin staining and confocal microscopy. This project has been funded in whole or in part with Federal funds from the national Cancer Institute, National Institutes of Health, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. This research was supported (in part) by the Intramural Research Program of NIH, National Cancer Institute, Center for Cancer Research. NR 40 TC 4 Z9 4 U1 3 U2 9 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1360-8185 J9 APOPTOSIS JI Apoptosis PD JAN PY 2012 VL 17 IS 1 BP 79 EP 89 DI 10.1007/s10495-011-0652-7 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 891VN UT WOS:000300244900008 PM 21928090 ER PT J AU Graziotto, JJ Cao, K Collins, FS Krainc, D AF Graziotto, John J. Cao, Kan Collins, Francis S. Krainc, Dimitri TI Rapamycin activates autophagy in Hutchinson-Gilford progeria syndrome Implications for normal aging and age-dependent neurodegenerative disorders SO AUTOPHAGY LA English DT Editorial Material DE progerin; rapamycin; autophagy; aging; neurodegeneration; progeria ID GENETICALLY HETEROGENEOUS MICE; AGGREGATE-PRONE PROTEINS; EXTENDS LIFE-SPAN; MOUSE MODEL; DEFICIENT MICE; POLYGLUTAMINE EXPANSIONS; TELOMERE DYSFUNCTION; CELLULAR SENESCENCE; HUNTINGTONS-DISEASE; MUTANT HUNTINGTIN AB While rapamycin has been in use for years in transplant patients as an antirejection drug, more recently it has shown promise in treating diseases of aging, such as neurodegenerative disorders and atherosclerosis. We recently reported that rapamycin reverses the cellular phenotype of fibroblasts from children with the premature aging disease Hutchinson-Gilford progeria syndrome (HGPS). We found that the causative aberrant protein, progerin, was cleared through autophagic mechanisms when the cells were treated with rapamycin, suggesting a new potential treatment for HGPS. Recent evidence shows that progerin is also present in aged tissues of healthy individuals, suggesting that progerin may contribute to physiological aging. While it is intriguing to speculate that rapamycin may affect normal aging in humans, as it does in lower organisms, it will be important to identify safer analogs of rapamycin for chronic treatments in humans in order to minimize toxicity. In addition to its role in HGPS and normal aging, we discuss the potential of rapamycin for the treatment of age-dependent neurodegenerative diseases. C1 [Graziotto, John J.; Krainc, Dimitri] Harvard Univ, Sch Med, MassGen Inst Neurodegenerat Dis, Dept Neurol,Massachusetts Gen Hosp, Charlestown, MA USA. [Cao, Kan] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. [Collins, Francis S.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Krainc, D (reprint author), Harvard Univ, Sch Med, MassGen Inst Neurodegenerat Dis, Dept Neurol,Massachusetts Gen Hosp, Charlestown, MA USA. EM krainc@helix.mgh.harvard.edu FU NIA NIH HHS [R00 AG029761] NR 56 TC 25 Z9 30 U1 2 U2 11 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD JAN PY 2012 VL 8 IS 1 BP 147 EP 151 DI 10.4161/auto.8.1.18331 PG 5 WC Cell Biology SC Cell Biology GA 892ZR UT WOS:000300325000021 PM 22170152 ER PT S AU Zhang, YL Gildersleeve, JC AF Zhang, Yalong Gildersleeve, Jeffrey C. BE Chevolot, Y TI General Procedure for the Synthesis of Neoglycoproteins and Immobilization on Epoxide-Modified Glass Slides SO CARBOHYDRATE MICROARRAYS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE BSA-glycosides; Neoglycoprotein; Glycan array; Lectin inhibitors; Cancer biomarker ID SITE-SELECTIVE GLYCOSYLATION; PROTEINS; GLYCOPROTEINS; BSA AB Neoglycoproteins, such as BSA-glycosides, contain carbohydrates covalently attached to a protein carrier via nonnaturally occurring linkages. These conjugates have been used for decades to study carbohydrate-protein interactions and are frequently used as immunogens to raise antibodies to carbohydrate antigens. In fact, neoglycoproteins have been used extensively as vaccine antigens and several have obtained FDA approval. More recently, neoglycoproteins have been used in the construction of glycan arrays to produce "neoglycoprotein microarrays." In this chapter, two methods for preparing neoglycoproteins arc described along with methods to immobilize these conjugates on epoxide-coated glass microscope slides to produce arrays. C1 [Zhang, Yalong; Gildersleeve, Jeffrey C.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21701 USA. RP Zhang, YL (reprint author), NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21701 USA. RI Gildersleeve, Jeffrey/N-3392-2014 FU Intramural NIH HHS NR 20 TC 7 Z9 7 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-373-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 808 BP 155 EP 165 DI 10.1007/978-1-61779-373-8_11 D2 10.1007/978-1-61779-373-8 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BYN17 UT WOS:000299398000011 PM 22057524 ER PT J AU Truong, QA Massaro, JM Rogers, IS Mahabadi, AA Kriegel, MF Fox, CS O'Donnell, CJ Hoffmann, U AF Truong, Quynh A. Massaro, Joseph M. Rogers, Ian S. Mahabadi, Amir A. Kriegel, Matthias F. Fox, Caroline S. O'Donnell, Christopher J. Hoffmann, Udo TI Reference Values for Normal Pulmonary Artery Dimensions by Noncontrast Cardiac Computed Tomography The Framingham Heart Study SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE pulmonary artery; Framingham Heart Study; computed tomography ID HYPERTENSION; CT; DIAMETER; QUANTIFICATION; LUNG AB Background-Main pulmonary artery diameter (mPA) and ratio of mPA to ascending aorta diameter (ratio PA) derived from chest CT are commonly reported in clinical practice. We determined the age-and sex-specific distribution and normal reference values for mPA and ratio PA by CT in an asymptomatic community-based population. Methods and Results-In 3171 men and women (mean age, 51 +/- 10 years; 51% men) from the Framingham Heart Study, a noncontrast, ECG-gated, 8-slice cardiac multidetector CT was performed. We measured the mPA and transverse axial diameter of the ascending aorta at the level of the bifurcation of the right pulmonary artery and calculated the ratio PA. We defined the healthy referent cohort (n=706) as those without obesity, hypertension, current and past smokers, chronic obstructive pulmonary disease, history of pulmonary embolism, diabetics, cardiovascular disease, and heart valve surgery. The mean mPA diameter in the overall cohort was 25.1 +/- 2.8 mm and mean ratio PA was 0.77 +/- 0.09. The sex-specific 90th percentile cutoff value for mPA diameter was 28.9 mm in men and 26.9 mm in women and was associated with increase risk for self-reported dyspnea (adjusted odds ratio, 1.31; P=0.02). The 90th percentile cutoff value for ratio PA of the healthy referent group was 0.91, similar between sexes but decreased with increasing age (range, 0.82-0.94), though not associated with dyspnea. Conclusions-For simplicity, we established 29 mm in men and 27 mm in women as sex-specific normative reference values for mPA and 0.9 for ratio PA. (Circ Cardiovasc Imaging. 2012;5:147-154.) C1 [Truong, Quynh A.] Harvard Univ, Massachusetts Gen Hosp, Div Cardiol, Cardiac MR PET CT Program,Med Sch,Div Cardiol, Boston, MA 02114 USA. [Massaro, Joseph M.] Boston Univ, Dept Math, Boston, MA 02215 USA. [Rogers, Ian S.] Stanford Univ, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA. [Mahabadi, Amir A.] Univ Clin Essen, W German Heart Ctr, Dept Cardiol, Essen, Germany. [Fox, Caroline S.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. RP Truong, QA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Cardiol, Cardiac MR PET CT Program,Med Sch,Div Cardiol, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM qtruong@partners.org OI Massaro, Joseph/0000-0002-2682-4812 FU National Heart, Lung, and Blood Institute [N01-HC-25195]; National Institutes of Health [T32HL076136, K23HL098370, L30HL093896] FX The Framingham Heart Study is supported by the National Heart, Lung, and Blood Institute (N01-HC-25195). Drs Truong and Rogers received support from National Institutes of Health grant T32HL076136. Dr. Truong also received support from National Institutes of Health grant K23HL098370 and L30HL093896. NR 20 TC 46 Z9 49 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD JAN PY 2012 VL 5 IS 1 BP 147 EP 154 DI 10.1161/CIRCIMAGING.111.968610 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 894HG UT WOS:000300417100021 PM 22178898 ER PT J AU Maudsley, S Chadwick, W AF Maudsley, Stuart Chadwick, Wayne TI Progressive and Unconventional Pharmacotherapeutic Approaches to Alzheimer's Disease therapy SO CURRENT ALZHEIMER RESEARCH LA English DT Editorial Material ID NEURODEGENERATION; MICE; MENOPAUSE; DEMENTIA; AGENTS C1 [Maudsley, Stuart] NIA, Bethesda, MD 20892 USA. [Chadwick, Wayne] Takeda Pharmaceut, Deerfield, IL USA. RP Maudsley, S (reprint author), NIA, Bethesda, MD 20892 USA. NR 39 TC 3 Z9 3 U1 0 U2 5 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PD JAN PY 2012 VL 9 IS 1 BP 1 EP 4 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 892LY UT WOS:000300288900001 PM 22329648 ER PT J AU Cai, H Cong, WN Ji, SG Rothman, S Maudsley, S Martin, B AF Cai, Huan Cong, Wei-na Ji, Sunggoan Rothman, Sarah Maudsley, Stuart Martin, Bronwen TI Metabolic Dysfunction in Alzheimer's Disease and Related Neurodegenerative Disorders SO CURRENT ALZHEIMER RESEARCH LA English DT Article DE Neurodegenerative diseases; metabolic dysfunction; bodyweight; diabetes; glucose homeostasis; insulin; leptin; ghrelin; adiponectin; glucagon-like peptide 1; Alzheimer's disease; Huntington's disease; Parkinson's disease ID HIPPOCAMPAL SYNAPTIC PLASTICITY; TRANSGENIC MOUSE MODEL; BODY-MASS INDEX; CEREBRAL GLUCOSE-UTILIZATION; REVERSES INSULIN-RESISTANCE; AMYLOID PRECURSOR PROTEIN; DAILY ENERGY-EXPENDITURE; LONG-TERM POTENTIATION; NIGRA PARS-COMPACTA; HUNTINGTONS-DISEASE AB Alzheimer's disease and other related neurodegenerative diseases are highly debilitating disorders that affect millions of people worldwide. Efforts towards developing effective treatments for these disorders have shown limited efficacy at best, with no true cure to this day being present. Recent work, both clinical and experimental, indicates that many neurodegenerative disorders often display a coexisting metabolic dysfunction which may exacerbate neurological symptoms. It stands to reason therefore that metabolic pathways may themselves contain promising therapeutic targets for major neurodegenerative diseases. In this review, we provide an overview of some of the most recent evidence for metabolic dysregulation in Alzheimer's disease, Huntington's disease, and Parkinson's disease, and discuss several potential mechanisms that may underlie the potential relationships between metabolic dysfunction and etiology of nervous system degeneration. We also highlight some prominent signaling pathways involved in the link between peripheral metabolism and the central nervous system that are potential targets for future therapies, and we will review some of the clinical progress in this field. It is likely that in the near future, therapeutics with combinatorial neuroprotective and 'eumetabolic' activities may possess superior efficacies compared to less pluripotent remedies. C1 [Cai, Huan; Cong, Wei-na; Ji, Sunggoan; Martin, Bronwen] NIA, Metab Unit, Baltimore, MD 21224 USA. [Rothman, Sarah] NIA, Cellular & Mol Neurosci Sect, Baltimore, MD 21224 USA. [Maudsley, Stuart] NIA, Receptor Pharmacol Unit, Baltimore, MD 21224 USA. RP Martin, B (reprint author), NIA, Metab Unit, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. EM martinbro@mail.nih.gov RI Cai, Huan/B-6578-2016; Akbar, Afrah/C-2001-2016 OI Cai, Huan/0000-0001-7731-8891; FU National Institute on Aging, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. The authors have no conflicts of scientific interest with respect to the manuscript. NR 203 TC 59 Z9 61 U1 4 U2 20 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PD JAN PY 2012 VL 9 IS 1 BP 5 EP 17 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 892LY UT WOS:000300288900002 PM 22329649 ER PT J AU Stranahan, AM Martin, B Maudsley, S AF Stranahan, Alexis M. Martin, Bronwen Maudsley, Stuart TI Anti-Inflammatory Effects of Physical Activity in Relationship to Improved Cognitive Status in Humans and Mouse Models of Alzheimer's Disease SO CURRENT ALZHEIMER RESEARCH LA English DT Article DE Exercise; running; hippocampus; inflammation; Alzheimer's disease ID LONG-TERM POTENTIATION; TRANSGENIC MICE; HIPPOCAMPAL NEUROGENESIS; CARDIOVASCULAR FITNESS; NEUROTROPHIC FACTOR; VOLUNTARY EXERCISE; APOLIPOPROTEIN-E; TG2576 MOUSE; IN-VIVO; BRAIN AB Physical activity has been correlated with a reduced incidence of cognitive decline and Alzheimer's disease in human populations. Although data from intervention-based randomized trials is scarce, there is some indication that exercise may confer protection against age-related deficits in cognitive function. Data from animal models suggests that exercise, in the form of voluntary wheel running, is associated with reduced amyloid deposition and enhanced clearance of amyloid beta, the major constituent of plaques in Alzheimer's disease. Treadmill exercise has also been shown to ameliorate the accumulation of phosphorylated tau, an essential component of neurofibrillary tangles in Alzheimer's models. A common therapeutic theme arising from studies of exercise-induced neuroprotection in human populations and in animal models involves reduced inflammation in the central nervous system. In this respect, physical activity may promote neuronal resilience by reducing inflammation. C1 [Maudsley, Stuart] NIA, Biomed Res Ctr, Receptor Pharmacol Unit, Neurosci Lab,NIH, Baltimore, MD 21224 USA. [Martin, Bronwen] NIA, Metab Unit, Lab Clin Invest, NIH, Baltimore, MD 21224 USA. [Stranahan, Alexis M.] Johns Hopkins Univ, Dept Psychol & Brain Sci, Baltimore, MD USA. RP Maudsley, S (reprint author), NIA, Biomed Res Ctr, Receptor Pharmacol Unit, Neurosci Lab,NIH, Suite 100,Room 5C228,251 Bayview Blvd, Baltimore, MD 21224 USA. EM maudsleyst@mail.nih.gov FU Ford Foundation; National Institute on Aging FX This review was supported by a Ford Foundation Fellowship to A.M.S., and by the National Institute on Aging Intramural Research program (B.M. & S.M.). NR 45 TC 24 Z9 27 U1 1 U2 15 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PD JAN PY 2012 VL 9 IS 1 BP 86 EP 92 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 892LY UT WOS:000300288900006 PM 22329653 ER PT J AU Chadwick, W Mitchell, N Martin, B Maudsley, S AF Chadwick, Wayne Mitchell, Nicholas Martin, Bronwen Maudsley, Stuart TI Therapeutic Targeting of the Endoplasmic Reticulum in Alzheimer's Disease SO CURRENT ALZHEIMER RESEARCH LA English DT Article DE Endoplasmic; reticulum; Alzheimer's disease; amyloid; stress; calcium; protein synthesis; folding ID AMYLOID PRECURSOR PROTEIN; TRANSGENIC MOUSE MODEL; PROGRAMMED CELL-DEATH; APP GENE FAMILY; PRESENILIN-1 MUTATIONS; CORTICAL-NEURONS; BETA-PEPTIDE; SYNAPTIC PLASTICITY; PROAPOPTOTIC BAX; MESSENGER-RNAS AB The extensive prevalence of Alzheimer's disease (AD) places a tremendous burden physiologically, socially and economically upon those directly suffering and those caring for sufferers themselves. Considering the steady increases in numbers of patients diagnosed with Alzheimer's, the number of effective pharmacotherapeutic strategies to tackle the disease is still relatively few. As with many other neurodegenerative mechanisms, AD, is characterized by the continued presence and accumulation of cytotoxic protein aggregates, i.e. of beta-amyloid and the microtubule associated protein, tau. Therefore, one novel therapeutic avenue for the treatment of AD may be the actual targeting of factors that control protein synthesis, packaging and degradation. One of the prime cellular targets that, if effectively modulated, could accomplish this is the endoplasmic reticulum (ER). The ER can not only control cellular protein synthesis, trafficking and degradation but it is also closely associated with cytoprotective mechanisms, including calcium ion regulation and unfolded protein responses. This review will delineate some of the most important functional physiological features of the ER that, if effectively modulated, could result in beneficial amelioration or remediation of the negative cellular aspects of AD initiation and progression. While not a classical drug target, even with minimal levels of beneficial modulation, its multifactorial efficacy may amplify small effects resulting in significant therapeutic efficacy. C1 [Maudsley, Stuart] NIA, Receptor Pharmacol Unit, Biomed Res Ctr, Baltimore, MD 21224 USA. St Bonaventure Univ, Dept Biol, St Bonaventure, NY 14778 USA. NIA, Metab Unit, Baltimore, MD 21224 USA. RP Maudsley, S (reprint author), NIA, Receptor Pharmacol Unit, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM maudsleyst@mail.nih.gov FU National Institute on Aging, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. The authors have no conflicts of scientific interest with respect to the manuscript. NR 77 TC 13 Z9 13 U1 0 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PD JAN PY 2012 VL 9 IS 1 BP 110 EP 119 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 892LY UT WOS:000300288900009 PM 22329655 ER PT J AU Guo, MQ Huang, BX AF Guo, Ming-Quan Huang, Bill X. TI Liquid Chromatography and Mass Spectrometry (LC-MS) Based Strategies for Quantitative Phosphoproteomics SO CURRENT ANALYTICAL CHEMISTRY LA English DT Article DE Liquid chromatography; Mass spectrometry; Phosphoproteomics; Stable isotope labeling; Label-free quantification; Protein phosphorylation; Absolute quantification ID HYDROPHILIC INTERACTION CHROMATOGRAPHY; SITE-SPECIFIC PHOSPHORYLATION; ION AFFINITY-CHROMATOGRAPHY; MAMMALIAN 2-HYBRID ASSAYS; COMPLEX PROTEIN MIXTURES; TYROSINE PHOSPHORYLATION; ABSOLUTE QUANTIFICATION; SIGNALING NETWORKS; SACCHAROMYCES-CEREVISIAE; SHOTGUN PROTEOMICS AB Reversible protein phosphorylation is among the most widespread and important protein modifications in nature, regulating a vast number of key cellular signaling pathways, and deregulation of phosphorylation-mediated processes is often implicated in many human diseases including cancers. Large-scale qualitative and quantitative analysis of protein phosphorylation is thus essential for understanding these important cellular signaling pathways and their underlying mechanisms. This challenging task has been enabled by exciting progress in both effective phosphopeptide enrichment strategies and powerful liquid chromatography coupled to with mass spectrometry (LC-MS). This review will detail some of the most recent developments in LC-MS based phosphoproteomics with an emphasis on quantitative analysis of protein phosphorylation or quantitative phosphoproteomics. We discuss a variety of LC-MS based in vivo and in vitro stable-isotope labeling and label-free methods for global quantitative phosphoproteomics, and briefly introduce the progress in targeted quantitative phosphoproteomics while highlighting the application of some up-to-date popular techniques with corresponding representative workflows. For each strategy, the benefits and drawbacks are compared and highlighted in order to aid scientists in tailoring the most appropriate strategy under various circumstances for the global or targeted analysis of protein phosphorylation pertinent to any biological or biomedical questions in their own research. C1 [Guo, Ming-Quan] Univ So Calif, Keck Sch Med, Eli & Edythe Broad Ctr Regenerat Med, Alhambra, CA 91801 USA. [Huang, Bill X.] NIAAA, Lab Mol Signaling, NIH, Rockville, MD 20852 USA. RP Guo, MQ (reprint author), Univ So Calif, Keck Sch Med, Eli & Edythe Broad Ctr Regenerat Med, 2711 W Grand Ave,Suite C, Alhambra, CA 91801 USA. EM zhaoguo2000@gmail.com; bhuang@mail.nih.gov NR 178 TC 5 Z9 5 U1 1 U2 19 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1573-4110 J9 CURR ANAL CHEM JI Curr. Anal. Chem. PD JAN PY 2012 VL 8 IS 1 BP 3 EP 21 PG 19 WC Chemistry, Analytical SC Chemistry GA 893XM UT WOS:000300391000002 ER PT J AU Fuxe, K Borroto-Escuela, DO Marcellino, D Romero-Fernandez, W Frankowska, M Guidolin, D Filip, M Ferraro, L Woods, AS Tarakanov, A Ciruela, F Agnati, LF Tanganelli, S AF Fuxe, K. Borroto-Escuela, D. O. Marcellino, D. Romero-Fernandez, W. Frankowska, M. Guidolin, D. Filip, M. Ferraro, L. Woods, A. S. Tarakanov, A. Ciruela, F. Agnati, L. F. Tanganelli, S. TI GPCR Heteromers and their Allosteric Receptor-Receptor Interactions SO CURRENT MEDICINAL CHEMISTRY LA English DT Review DE Receptor mosaic; oligomers; allosteric modulation; GPCR; receptor recognition; receptor signaling; receptor interface; receptor trafficking; receptor G protein coupling; moonlighting; triplet homologies; adenosine receptor; dopamine receptors ID PROTEIN-COUPLED RECEPTORS; ADENOSINE A(2A) RECEPTORS; NUCLEUS-TRACTUS-SOLITARIUS; HIGHER-ORDER OLIGOMERS; PARKINSONS-DISEASE; NMDA RECEPTOR; ELECTROSTATIC INTERACTION; DOPAMINE-D-2 RECEPTORS; TRIPLET PUZZLE; BINDING-SITES AB The concept of intramembrane receptor-receptor interactions and evidence for their existences were introduced in the beginning of the 1980's, suggesting the existence of receptor heterodimerization. The discovery of GPCR heteromers and the receptor mosaic (higher order oligomers, more than two) has been related to the parallel development and application of a variety of resonance energy transfer techniques such as bioluminescence (BRET), fluorescence (FRET) and sequential energy transfer (SRET). The assembly of interacting GPCRs, heterodimers and receptor mosaic leads to changes in the agonist recognition, signaling, and trafficking of participating receptors via allosteric mechanisms, sometimes involving the appearance of cooperativity. The receptor interface in the GPCR heteromers is beginning to be characterized and the key role of electrostatic epitope-epitope interactions for the formation of the receptor heteromers will be discussed. Furthermore, a "guide-and-clasp" manner of receptor-receptor interactions has been proposed where the "adhesive guides" may be the triplet homologies. These interactions probably represent a general molecular mechanism for receptor-receptor interactions. It is proposed that changes in GPCR function (moonlighting) may develop through the intracellular loops and C-terminii of the GPCR heteromers as a result of dynamic allosteric interactions between different types of G proteins and other receptor interacting proteins in these domains of the receptors. The evidence for the existence of receptor heteromers opens up a new field for a better understanding of neurophysiology and neuropathology. Furthermore, novel therapeutic approaches could be possible based on the use of heteromers as targets for drug development based on their unique pharmacology. C1 [Fuxe, K.; Borroto-Escuela, D. O.; Marcellino, D.; Romero-Fernandez, W.] Karolinska Inst, Dept Neurosci, Stockholm, Sweden. [Frankowska, M.; Filip, M.] Polish Acad Sci, Inst Pharmacol, Dept Pharmacol, Lab Drug Addict Pharmacol, PL-31343 Krakow, Poland. [Guidolin, D.] Univ Padua, Dept Human Anat & Physiol, I-35100 Padua, Italy. [Ferraro, L.; Tanganelli, S.] Univ Ferrara, Dept Clin & Expt Med, Pharmacol Sect, I-44100 Ferrara, Italy. [Ferraro, L.; Tanganelli, S.] Univ Ferrara, LTTA Ctr, I-44100 Ferrara, Italy. [Woods, A. S.] NIDA IRP, Struct Biol Unit, Baltimore, MD USA. [Tarakanov, A.] Russian Acad Sci, St Petersburg Inst Informat & Automat, Moscow 117901, Russia. [Ciruela, F.] Univ Barcelona, Fac Med, Unitat Farmacol, E-08007 Barcelona, Spain. [Agnati, L. F.] Osped San Camillo, IRCCS, Venice, Italy. RP Fuxe, K (reprint author), Retziusvag 8, S-17177 Stockholm, Sweden. EM Kjell.Fuxe@ki.se RI Ferraro, Luca/F-9915-2015; Tanganelli, Sergio/I-7704-2015; Romero-Fernandez, Wilber/H-8106-2012; Zhang, Ning/F-1387-2014; Borroto-Escuela, Dasiel/F-3627-2014; Ciruela, Francisco/A-5096-2013 OI Ferraro, Luca/0000-0003-2390-6414; Tanganelli, Sergio/0000-0001-7576-3510; Marcellino, Daniel/0000-0002-4618-7267; Guidolin, Diego/0000-0003-2133-3552; Fuxe, Kjell/0000-0001-8491-4288; Romero-Fernandez, Wilber/0000-0001-9868-8074; Borroto-Escuela, Dasiel/0000-0002-5736-373X; Ciruela, Francisco/0000-0003-0832-3739 FU Swedish Research Council [04X-715]; Hjarnfonden, Torsten and Ragnar Soderberg; Telethon TV3's La Marato Foundation; M.M. Wallenberg Foundation; Karolinska Institutets Forskningsstiftelser; Ministerio de Ciencia e Innovacion [CSD2008-00005, SAF2008-01462]; Catalan Institution for Research and Advanced Studies; Ministry of Science and Higher Education, Warszawa, Poland [N N401 019635] FX This work was supported by: grants from the Swedish Research Council (04X-715), Hjarnfonden, Torsten and Ragnar Soderberg, Telethon TV3's La Marato Foundation 2008 and M.M. Wallenberg Foundation to KF, Karolinska Institutets Forskningsstiftelser 2010 and 2011 to D.O.B-E.; grants SAF2008-01462 and Consolider-Ingenio CSD2008-00005 from Ministerio de Ciencia e Innovacion and ICREA Academia-2010 from the Catalan Institution for Research and Advanced Studies to FC. A.O.T. has not received any support for this work; a grant from the Ministry of Science and Higher Education (no. N N401 019635), Warszawa, Poland. NR 59 TC 43 Z9 44 U1 4 U2 23 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PD JAN PY 2012 VL 19 IS 3 BP 356 EP 363 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 893XU UT WOS:000300391900004 PM 22335512 ER PT J AU Blum, K Gardner, E Oscar-Berman, M Gold, M AF Blum, Kenneth Gardner, Eliot Oscar-Berman, Marlene Gold, Mark TI "Liking" and "Wanting" Linked to Reward Deficiency Syndrome (RDS): Hypothesizing Differential Responsivity in Brain Reward Circuitry SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE Reward deficiency syndrome (RDS); neuroimaging; dopamine; "wanting" and "liking" ID INCENTIVE SALIENCE; DOPAMINE RELEASE; FOOD ADDICTION; ASSOCIATION; STRESS; TASTE; FMRI; SUPERSENSITIVITY; ACTIVATION; EXPERIENCE AB In an attempt to resolve controversy regarding the causal contributions of mesolimbic dopamine (DA) systems to reward, we evaluate the three main competing explanatory categories: "liking," "learning," and "wanting" [1]. That is, DA may mediate (a) the hedonic impact of reward (liking), (b) learned predictions about rewarding effects (learning), or (c) the pursuit of rewards by attributing incentive salience to reward-related stimuli (wanting). We evaluate these hypotheses, especially as they relate to the Reward Deficiency Syndrome (RDS), and we find that the incentive salience or "wanting" hypothesis of DA function is supported by a majority of the evidence. Neuroimaging studies have shown that drugs of abuse, palatable foods, and anticipated behaviors such as sex and gaming affect brain regions involving reward circuitry, and may not be unidirectional. Drugs of abuse enhance DA signaling and sensitize mesolimbic mechanisms that evolved to attribute incentive salience to rewards. Addictive drugs have in common that they are voluntarily self-administered, they enhance (directly or indirectly) dopaminergic synaptic function in the nucleus accumbens (NAC), and they stimulate the functioning of brain reward circuitry (producing the "high" that drug users seek). Although originally believed simply to encode the set point of hedonic tone, these circuits now are believed to be functionally more complex, also encoding attention, reward expectancy, disconfirmation of reward expectancy, and incentive motivation. Elevated stress levels, together with polymorphisms of dopaminergic genes and other neurotransmitter genetic variants, may have a cumulative effect on vulnerability to addiction. The RDS model of etiology holds very well for a variety of chemical and behavioral addictions. C1 [Blum, Kenneth; Gold, Mark] Univ Florida, Dept Psychiat, Gainesville, FL 32610 USA. [Blum, Kenneth; Gold, Mark] Univ Florida, McKnight Brain Inst, Gainesville, FL 32610 USA. [Gardner, Eliot] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD USA. [Oscar-Berman, Marlene] Dept Vet Affairs Healthcare Syst, Boston, MA USA. [Oscar-Berman, Marlene] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Blum, K (reprint author), Univ Florida, Dept Psychiat, Gainesville, FL 32610 USA. EM drd2gene@aol.com FU NIAAA [R01 AA07112, K05 AA 00219]; Medical Research Service of the US Department of Veterans Affairs FX Marlene Oscar Berman, Ph.D. is the recipient of grants from NIAAA (R01 AA07112, K05 AA 00219) and from the Medical Research Service of the US Department of Veterans Affairs. NR 57 TC 41 Z9 42 U1 10 U2 44 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD JAN PY 2012 VL 18 IS 1 BP 113 EP 118 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 892KD UT WOS:000300284200014 PM 22236117 ER PT J AU Lee, D Park, SJ Sung, KS Park, J Lee, SB Park, SY Lee, HJ Ahn, JW Choi, SJ Lee, SG Kim, SH Kim, DH Kim, J Kim, Y Choi, CY AF Lee, Deresa Park, Sang-Joon Sung, Ki Sa Park, Jikyoung Lee, Sean Bong Park, Sang-Yoon Lee, Hyo Jeong Ahn, Jang-Won Choi, So Jung Lee, Seok-Geun Kim, Sung-Hoon Kim, Duk-Hwan Kim, Jhingook Kim, Yongsok Choi, Cheol Yong TI Mdm2 associates with Ras effector NORE1 to induce the degradation of oncoprotein HIPK1 SO EMBO REPORTS LA English DT Article DE Novel Ras effector 1; RASSF5; homeodomain-interacting protein kinase 1; oncogene; tumorigenesis ID INTERACTING PROTEIN-KINASES; FAMILY; TRANSCRIPTION; ROLES AB The Ras effector NORE1 is frequently silenced in primary adenocarcinomas, although the significance of this silencing for tumorigenesis is unclear. Here we show that NORE1 induces polyubiquitination and proteasomal degradation of oncoprotein HIPK1 by facilitating its interaction with the Mdm2 E3 ubiquitin ligase. Endogenous HIPK1 is stabilized in Nore1-deficient mouse embryonic fibroblasts, and depletion of HIPK1 in NORE1-silenced lung adenocarcinoma cells inhibits anchorage-independent cell growth and tumour formation in nude mice. These findings indicate that the control of HIPK1 stability by Mdm2-NORE1 has a major effect on cell behaviour, and epigenetic inactivation of NORE1 enables adenocarcinoma formation in vivo through HIPK1 stabilization. C1 [Kim, Yongsok] NHLBI, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA. [Kim, Duk-Hwan] Samsung Biomed Res Inst, Ctr Genome Res, Seoul 135710, South Korea. [Choi, So Jung; Kim, Jhingook] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Thorac Surg, Seoul 135710, South Korea. [Park, Sang-Yoon; Lee, Hyo Jeong; Lee, Seok-Geun; Kim, Sung-Hoon] Kyung Hee Univ, Coll Oriental Med, Canc Prevent Mat Dev Res Ctr, Seoul 130701, South Korea. [Park, Jikyoung; Lee, Sean Bong] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [Park, Sang-Joon] Kyungpook Natl Univ, Dept Vet Med, Taegu 702701, South Korea. [Lee, Deresa; Sung, Ki Sa; Ahn, Jang-Won; Choi, Cheol Yong] Sungkyunkwan Univ, Dept Biol Sci, Suwon 440746, South Korea. RP Kim, Y (reprint author), NHLBI, Genet & Dev Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM yongsok@helix.nih.gov; choicy@skku.ac.kr RI Lee, Seok-Geun/B-3408-2011 OI Lee, Seok-Geun/0000-0002-0060-5777 FU Korea Science and Engineering Foundation (KOSEF) [KRF-2008-313-C00605]; National Research Foundation [2009-0085548]; Ministry of Education, Science and Technology [2009-0063466] FX This work was supported in part by a Korea Science and Engineering Foundation (KOSEF) grant (KRF-2008-313-C00605 and the Ubiquitome Research Program, 2011-00983 to C.Y.C.), and by a Mid-career Researcher Program through an National Research Foundation grant funded (no. 2009-0085548 to C.Y.C.). We also acknowledge support from the KOSEF grant funded by the Ministry of Education, Science and Technology (no. 2009-0063466 to S.-G.L. and S.-H.K.). NR 9 TC 11 Z9 13 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD JAN PY 2012 VL 13 IS 2 BP 163 EP 169 DI 10.1038/embor.2011.235 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 894DK UT WOS:000300407000015 PM 22173032 ER PT J AU McGuinn, LA Ghazarian, AA Ellison, GL Harvey, CE Kaefer, CM Reid, BC AF McGuinn, Laura A. Ghazarian, Armen A. Ellison, Gary L. Harvey, Chinonye E. Kaefer, Christine M. Reid, Britt C. TI Cancer and environment: Definitions and misconceptions SO ENVIRONMENTAL RESEARCH LA English DT Review DE Cancer; Environmental exposures; Environmental health risks; Epidemiology; Public health ID RISK-ASSESSMENT; EPIDEMIOLOGY; CAUSATION; FINLAND AB Background: Scientific evidence supports an association between environmental exposures and cancer. However, a reliable estimate for the proportion of cancers attributable to environmental factors is currently unavailable. This may be related to the varying definitions of the term "environment." The current review aims to determine how the reporting of the definition of the environment and of the estimates of environmentally attributable risks have changed over the past 50 years. Methods: A systematic literature search was performed to retrieve all relevant publications relating to the environment and cancer from January 1960 to December 2010 using PubMed, EMBASE, Scopus, and Web of Science. Definitions of the environment and environmentally attributable risks for cancer were extracted from each relevant publication. Results: The search resulted in 261 relevant publications. We found vast discrepancies in the definition of the environment, ranging from broad (including lifestyle factors, occupational exposures, pollutants, and other non-genetic factors) to narrow (including air, water, and soil pollutants). Reported environmentally attributable risk estimates ranged from 1% to 100%. Conclusions: Our findings emphasize the discrepancies in reporting environmental causation of cancer and the limits of inference in interpreting environmentally attributable risk estimates. Rather than achieving consensus on a single definition for the environment, we suggest the focus be on achieving transparency for any environmentally attributable risks. Published by Elsevier Inc. C1 [McGuinn, Laura A.; Ghazarian, Armen A.; Ellison, Gary L.; Harvey, Chinonye E.; Kaefer, Christine M.; Reid, Britt C.] NCI, Div Canc Control & Populat Sci, Epidemiol & Genom Res Program, Bethesda, MD 20892 USA. RP Reid, BC (reprint author), NCI, Div Canc Control & Populat Sci, Epidemiol & Genom Res Program, 6130 Execut Blvd,Rm 5134, Bethesda, MD 20892 USA. EM reidbr@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 35 TC 6 Z9 6 U1 2 U2 17 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD JAN PY 2012 VL 112 BP 230 EP 234 DI 10.1016/j.envres.2011.10.009 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 885TX UT WOS:000299804800031 PM 22099913 ER PT S AU Yan, JZ Burgess, SM AF Yan, Jizhou Burgess, Shawn M. BE Deplancke, B Gheldof, N TI Using a Yeast Inverse One-Hybrid System to Identify Functional Binding Sites of Transcription Factors SO GENE REGULATORY NETWORKS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Yeast; Inverse one-hybrid; DNA binding sites; Transcription factor; Protein-DNA interaction; Genome-wide screening ID TARGET GENES; DNA; CHROMOSOMES AB Binding of transcription factors to promoters is a necessary step to initiate transcription. From an evolutionary standpoint, the regulatory proteins and their binding sites are considered to have molecularly coevolved. We developed an efficient yeast strategy, an "inverse one-hybrid system", to identify binding targets of transcription factors globally in a genome of interest. The technique consists of a yeast strain expressing a transcription factor of interest mated to yeast containing a library of random genomic fragments cloned upstream of a reporter gene (URA3). Positive growth on media without uracil denotes a fragment being bound by the transcription factor, e.g., zebrafish FoxI1. The bound fragments in hundreds of positive clones are sequenced and retested for their binding activities using a colony PCR and sequencing strategy. The resulting tools allow For rapid and genomic-wide identification of transcriptional binding targets. C1 [Yan, Jizhou] Shanghai Ocean Univ, Inst Marine Biosyst & Neurosci, Dept Hydrobiol, Coll Fisheries & Life Sci, Lingang New City, Shanghai, Peoples R China. [Burgess, Shawn M.] NHGRI, NIH, Bethesda, MD 20892 USA. RP Yan, JZ (reprint author), Shanghai Ocean Univ, Inst Marine Biosyst & Neurosci, Dept Hydrobiol, Coll Fisheries & Life Sci, Lingang New City, Shanghai, Peoples R China. OI Burgess, Shawn/0000-0003-1147-0596 FU Intramural NIH HHS NR 8 TC 1 Z9 1 U1 0 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-291-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 786 BP 275 EP 290 DI 10.1007/978-1-61779-292-2_17 D2 10.1007/978-1-61779-292-2 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BYM15 UT WOS:000299299900017 PM 21938633 ER PT J AU Valent, P Akin, C Arock, M Brockow, K Butterfield, JH Carter, MC Castells, M Escribano, L Hartmann, K Lieberman, P Nedoszytko, B Orfao, A Schwartz, LB Sotlar, K Sperr, WR Triggiani, M Valenta, R Horny, HP Metcalfe, DD AF Valent, Peter Akin, Cem Arock, Michel Brockow, Knut Butterfield, Joseph H. Carter, Melody C. Castells, Mariana Escribano, Luis Hartmann, Karin Lieberman, Philip Nedoszytko, Boguslaw Orfao, Alberto Schwartz, Lawrence B. Sotlar, Karl Sperr, Wolfgang R. Triggiani, Massimo Valenta, Rudolf Horny, Hans-Peter Metcalfe, Dean D. TI Definitions, Criteria and Global Classification of Mast Cell Disorders with Special Reference to Mast Cell Activation Syndromes: A Consensus Proposal SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article DE Mast cells; Mast cell activation syndrome; Allergy; Anaphylaxis; Tryptase ID ACUTE MYELOID-LEUKEMIA; SYSTEMIC MASTOCYTOSIS; SERUM TRYPTASE; BONE-MARROW; HISTAMINE INTOLERANCE; PROSTAGLANDIN D-2; SPANISH NETWORK; ANAPHYLAXIS; MECHANISMS; DIAGNOSIS AB Activation of tissue mast cells (MCs) and their abnormal growth and accumulation in various organs are typically found in primary MC disorders also referred to as mastocytosis. However, increasing numbers of patients are now being informed that their clinical findings are due to MC activation (MCA) that is neither associated with mastocytosis nor with a defined allergic or inflammatory reaction. In other patients with MCA, MCs appear to be clonal cells, but criteria for diagnosing mastocytosis are not met. A working conference was organized in 2010 with the aim to define criteria for diagnosing MCA and related disorders, and to propose a global unifying classification of all MC disorders and pathologic MC reactions. This classification includes three types of 'MCA syndromes' (MCASs), namely primary MCAS, secondary MCAS and idiopathic MCAS. MCA is now defined by robust and generally applicable criteria, including (1) typical clinical symptoms, (2) a substantial transient increase in serum total tryptase level or an increase in other MC-derived mediators, such as histamine or prostaglandin D 2, or their urinary metabolites, and (3) a response of clinical symptoms to agents that attenuate the production or activities of MC mediators. These criteria should assist in the identification and diagnosis of patients with MCAS, and in avoiding misdiagnoses or overinterpretation of clinical symptoms in daily practice. Moreover, the MCAS concept should stimulate research in order to identify and exploit new molecular mechanisms and therapeutic targets. Copyright (C) 2011 S. Karger AG, Basel C1 [Valent, Peter; Sperr, Wolfgang R.] Med Univ Vienna, Div Hematol & Hemostaseol, Dept Internal Med 1, AT-1090 Vienna, Austria. [Valent, Peter] Ludwig Boltzmann Cluster Oncol, Vienna, Austria. [Akin, Cem; Castells, Mariana] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Arock, Michel] Ecole Normale Super, LBPA CNRS UMR8113, Cachan, France. [Brockow, Knut] Tech Univ Munich, Dept Dermatol & Allergy Biederstein, Munich, Germany. [Butterfield, Joseph H.] Mayo Clin, Div Allerg Dis, Rochester, MN USA. [Carter, Melody C.; Metcalfe, Dean D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Escribano, Luis] Hosp Virgen del Valle, Inst Estudios Mastocitosis Castilla La Mancha, Toledo, Spain. [Hartmann, Karin] Univ Cologne, Dept Dermatol, Cologne, Germany. [Lieberman, Philip] Univ Tennessee, Div Allergy & Immunol, Germantown, TN USA. [Nedoszytko, Boguslaw] Med Univ Gdansk, Dept Dermatol, Gdansk, Poland. [Orfao, Alberto] Univ Salamanca, IBMCC, Ctr Invest Canc, Serv Cent Citometria, E-37008 Salamanca, Spain. [Orfao, Alberto] Univ Salamanca, CSIC USAL, E-37008 Salamanca, Spain. [Orfao, Alberto] Univ Salamanca, Dept Med, E-37008 Salamanca, Spain. [Schwartz, Lawrence B.] Virginia Commonwealth Univ, Dept Internal Med, Div Rheumatol Allergy & Immunol, Richmond, VA USA. [Sotlar, Karl] Univ Munich, Inst Pathol, D-8000 Munich, Germany. [Triggiani, Massimo] Univ Naples Federico 2, Div Allergy & Clin Immunol, Naples, Italy. [Valenta, Rudolf] Med Univ Vienna, Ctr Physiol & Pathophysiol, Div Immunopathol, Vienna, Austria. [Horny, Hans-Peter] Inst Pathol, Ansbach, Germany. RP Valent, P (reprint author), Med Univ Vienna, Div Hematol & Hemostaseol, Dept Internal Med 1, Waehringer Guertel 18-20, AT-1090 Vienna, Austria. EM peter.valent@meduniwien.ac.at RI Hartmann, Karin/N-4865-2015; OI Hartmann, Karin/0000-0002-4595-8226; Akin, Cem/0000-0001-6301-4520 FU patients' organization in US; patients' organization in EU; NIH, NIAID; Ministerio de Sanidad y Asuntos Sociales [FIS PS09/00032]; Fondo de Investigacion Sanitaria de Castilla la Mancha [FISCAM 2007/36, FISCAM 2008/46]; Fonds zur Forderung der Wissenschaftlichen Forschung in Osterreich; Medical University of Vienna, Austria FX We would like to thank the following persons for providing support and assistance in logistic and administrative or technical issues of the conference: Kordula Krassel, Sabine Sonnleitner, Sabine Cerny-Reiterer, Emir Hadzijusufovic, Harald Herrmann and Friedrich Wimazal, who also contributed by voting. We would also like to thank the patients' organizations in the US and EU for their contributions and support in this project. This research was supported in part by the Intramural Research Program of the NIH, NIAID, by the Ministerio de Sanidad y Asuntos Sociales (FIS PS09/00032) Fondo de Investigacion Sanitaria de Castilla la Mancha (FISCAM 2007/36 and FISCAM 2008/46); the Fonds zur Forderung der Wissenschaftlichen Forschung in Osterreich, and a Mastocytosis Grant of the Medical University of Vienna, Austria. NR 58 TC 149 Z9 150 U1 3 U2 19 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PY 2012 VL 157 IS 3 BP 215 EP 225 DI 10.1159/000328760 PG 11 WC Allergy; Immunology SC Allergy; Immunology GA 894CY UT WOS:000300405800002 PM 22041891 ER PT J AU Rosel, D Khurana, T Majithia, A Huang, XL Bhandari, R Kimmel, AR AF Rosel, Daniel Khurana, Taruna Majithia, Amit Huang, Xiuli Bhandari, Ramanath Kimmel, Alan R. TI TOR complex 2 (TORC2) in Dictyostelium suppresses phagocytic nutrient capture independently of TORC1-mediated nutrient sensing SO JOURNAL OF CELL SCIENCE LA English DT Article DE Rapamycin; Raptor; Actin; FKBP12; 4E-BP; Dictyostelium ID RICTOR-MTOR COMPLEX; FISSION YEAST; MAMMALIAN TARGET; BINDING PARTNER; KINASE-ACTIVITY; PROTEIN-KINASE; SIGNAL RELAY; RAPAMYCIN; ACTIVATION; CHEMOTAXIS AB The TOR protein kinase functions in two distinct complexes, TOR complex 1 (TORC1) and 2 (TORC2). TORC1 is required for growth in response to growth factors, nutrients and the cellular energy state; TORC2 regulates AKT signaling, which can modulate cytoskeletal polarization. In its ecological niche, Dictyostelium engulf bacteria and yeast for nutrient capture. Despite the essential role of TORC1 in control of cellular growth, we show that nutrient particle capture (phagocytosis) in Dictyostelium is independent of TORC1-mediated nutrient sensing and growth regulation. However, loss of Dictyostelium TORC2 components Rictor/Pia, SIN1/RIP3 and Lst8 promotes nutrient particle uptake; inactivation of TORC2 leads to increased efficiency and speed of phagocytosis. In contrast to phagocytosis, we show that macropinocytosis, an AKT-dependent process for cellular uptake of fluid phase nutrients, is not regulated by either of the TOR complexes. The integrated and balanced regulation of TORC1 and TORC2 might be crucial in Dictyostelium to coordinate growth and energy needs with other essential TOR-regulated processes. C1 [Rosel, Daniel; Khurana, Taruna; Majithia, Amit; Huang, Xiuli; Bhandari, Ramanath; Kimmel, Alan R.] NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. RP Kimmel, AR (reprint author), NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. EM ark1@helix.nih.gov FU National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases; Czech Ministry of Education, Youth and Sport [LC06061] FX This research was supported by the Intramural Research Program of the National Institutes of Health; the National Institute of Diabetes and Digestive and Kidney Diseases; and by the Czech Ministry of Education, Youth and Sport [Research Center grant number LC06061]. A.M. is a Howard Hughes Medical Institute-National Institutes of Health Research Scholar. Deposited in PMC for release after 12 months. NR 55 TC 9 Z9 9 U1 1 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JAN 1 PY 2012 VL 125 IS 1 BP 37 EP 48 DI 10.1242/jcs.077040 PG 12 WC Cell Biology SC Cell Biology GA 893BB UT WOS:000300329100005 PM 22266904 ER PT J AU Toulmay, A Prinz, WA AF Toulmay, Alexandre Prinz, William A. TI A conserved membrane-binding domain targets proteins to organelle contact sites SO JOURNAL OF CELL SCIENCE LA English DT Article DE ERMES; Lipid-binding domain; Membrane contact sites; SMP domain ID NUCLEUS-VACUOLE JUNCTIONS; SACCHAROMYCES-CEREVISIAE; PLASMA-MEMBRANE; ENDOPLASMIC-RETICULUM; PIECEMEAL MICROAUTOPHAGY; C2 DOMAINS; H+-ATPASE; YEAST; ER; FAMILY AB Membrane contact sites (MCSs), where the membranes of two organelles are closely apposed, are regions where small molecules such as lipids or calcium are exchanged between organelles. We have identified a conserved membrane-binding domain found exclusively in proteins at MCSs in Saccharomyces cerevisiae. The synaptotagmin-like-mitochondrial-lipid binding protein (SMP) domain is conserved across species. We show that all seven proteins that contain this domain in yeast localize to one of three MCSs. Human proteins with SMP domains also localize to MCSs when expressed in yeast. The SMP domain binds membranes and is necessary for protein targeting to MCSs. Proteins containing this domain could be involved in lipid metabolism. This is the first protein domain found exclusively in proteins at MCSs. C1 [Toulmay, Alexandre; Prinz, William A.] NIDDK, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. RP Prinz, WA (reprint author), NIDDK, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. EM wprinz@helix.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases FX This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. NR 46 TC 67 Z9 67 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JAN 1 PY 2012 VL 125 IS 1 BP 49 EP 58 DI 10.1242/jcs.085118 PG 10 WC Cell Biology SC Cell Biology GA 893BB UT WOS:000300329100006 PM 22250200 ER PT J AU Cizza, G Rother, KI AF Cizza, Giovanni Rother, Kristina I. TI Cortisol Binding Globulin: More Than Just a Carrier? SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID TRANSCORTIN; MICE; POLYMORPHISM; ASSOCIATION; DEFICIENT; AFFINITY; FATIGUE; PROTEIN; VARIANT; PLASMA C1 [Cizza, Giovanni] NIDDKD, Sect Neuroendocrinol Obes, Ctr Clin, NIH,US Dept HHS, Bethesda, MD 20892 USA. [Rother, Kristina I.] NIDDKD, Sect Pediat Diabet & Metab, Ctr Clin, NIH,US Dept HHS, Bethesda, MD 20892 USA. RP Cizza, G (reprint author), Clin Res Ctr, Bldg 10,Room 6-3940, Bethesda, MD 20892 USA. EM cizzag@intra.niddk.nih.gov OI Mericq, Veronica/0000-0003-2287-0181 FU Intramural NIH HHS NR 17 TC 12 Z9 12 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2012 VL 97 IS 1 BP 77 EP 80 DI 10.1210/jc.2011-3090 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 893YM UT WOS:000300393800037 PM 22223768 ER PT J AU Hartman, TJ Mahabir, S Baer, DJ Stevens, RG Albert, PS Dorgan, JF Kesner, JS Meadows, JW Shields, R Taylor, PR AF Hartman, T. J. Mahabir, S. Baer, D. J. Stevens, R. G. Albert, P. S. Dorgan, J. F. Kesner, J. S. Meadows, J. W. Shields, R. Taylor, P. R. TI Moderate Alcohol Consumption and 24-Hour Urinary Levels of Melatonin in Postmenopausal Women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BREAST-CANCER RISK; NIGHT WORK; 6-SULFATOXYMELATONIN; ETHANOL; SECRETION; LIGHT AB Context: Low overnight urinary melatonin metabolite concentrations have been associated with increased risk for breast cancer among postmenopausal women. The Postmenopausal Women's Alcohol Study was a controlled feeding study to test the effects of low to moderate alcohol intake on potential risk factors for breast cancer including serum and urinary levels of hormones and other biomarkers. Previously, we observed significant increases in concentrations of serum estrone sulfate and dehydroepiandrosterone sulfate in participants after consumption of 15 or 30 g (one or two drinks) of alcohol per day. Objective: In the present analysis, we evaluated the relationship of alcohol consumption with 24-h urinary 6-sulfatoxymelatonin (6-SMT) concentration (micrograms per 24 h). Design and Participants: Healthy postmenopausal women(n = 51) consumed a controlled diet plus each of three treatments (a nonalcoholic placebo beverage or 15 or 30 g alcohol/d) during three 8-wk periods in random order under conditions of weight maintenance. Measures: 6-SMT was measured in 24-h urine samples that were collected at entry into the study (baseline) and at the midpoint (4 wk) and end (8 wk) of each of the three diet periods. Results: Concentration of 6-SMT was not significantly modified by the alcohol treatment after adjustment for body mass index, hours of sleep, daylight hours, and baseline level of 6-SMT. Conclusions: These results suggest that low to moderate daily alcohol consumption does not significantly affect 24-h urinary levels of melatonin among healthy postmenopausal women.(J Clin Endocrinol Metab 97: E65-E68, 2012) C1 [Hartman, T. J.] Penn State Univ, Chandlee Lab 110, Dept Nutr Sci, University Pk, PA 16802 USA. [Hartman, T. J.; Taylor, P. R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Mahabir, S.] NCI, Modifiable Risk Factors Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Baer, D. J.] USDA, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA. [Stevens, R. G.] Univ Connecticut, Ctr Hlth, Dept Community Med & Hlth Care, Farmington, CT 06032 USA. [Albert, P. S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Bethesda, MD 20892 USA. [Dorgan, J. F.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Kesner, J. S.; Meadows, J. W.] NIOSH, Reprod Hlth Assessment Team, Cincinnati, OH 45226 USA. [Shields, R.] Informat Management Serv Inc, Silver Spring, MD 20904 USA. RP Hartman, TJ (reprint author), Penn State Univ, Chandlee Lab 110, Dept Nutr Sci, University Pk, PA 16802 USA. EM tjh9@psu.edu FU National Institutes of Health, National Cancer Institute; Division of Cancer Epidemiology and Genetics and the Agricultural Research Service, U.S. Department of Agriculture FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, and the Division of Cancer Epidemiology and Genetics and the Agricultural Research Service, U.S. Department of Agriculture. NR 20 TC 4 Z9 4 U1 2 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2012 VL 97 IS 1 BP E65 EP E68 DI 10.1210/jc.2011-1904 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 893YM UT WOS:000300393800010 PM 22013099 ER PT J AU Ward, JM AF Ward, J. M. TI THE PERILS OF MOUSE PATHOLOGY SO JOURNAL OF COMPARATIVE PATHOLOGY LA English DT Meeting Abstract C1 [Ward, J. M.] NIAID, Immunopathol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9975 J9 J COMP PATHOL JI J. Comp. Pathol. PD JAN PY 2012 VL 146 IS 1 BP 51 EP 51 PG 1 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA 890JW UT WOS:000300141900029 ER PT J AU Ward, JM AF Ward, J. M. TI LYMPHOPROLIFERATIVE DISEASE IN MICE SO JOURNAL OF COMPARATIVE PATHOLOGY LA English DT Meeting Abstract C1 [Ward, J. M.] Global VetPathol, Montgomery Village, MD USA. [Ward, J. M.] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9975 J9 J COMP PATHOL JI J. Comp. Pathol. PD JAN PY 2012 VL 146 IS 1 BP 93 EP 93 PG 1 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA 890JW UT WOS:000300141900195 ER PT J AU Jett, JR AF Jett, James R. TI Status of Journal of Thoracic Oncology in 2011 SO JOURNAL OF THORACIC ONCOLOGY LA English DT Editorial Material C1 [Jett, James R.] NIH, Dept Med, Div Oncol, Denver, CO USA. RP Jett, JR (reprint author), NIH, Div Oncol J307A, 1400 Jackson St, Denver, CO 80206 USA. EM JETTJ@NJHealth.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JAN PY 2012 VL 7 IS 1 BP 1 EP 2 DI 10.1097/JTO.0b013e31823d4543 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 892SJ UT WOS:000300305600001 ER PT J AU Ichikawa-Tomikawa, N Ogawa, J Douet, V Xu, Z Kamikubo, Y Sakurai, T Kohsaka, S Chiba, H Hattori, N Yamada, Y Arikawa-Hirasawa, E AF Ichikawa-Tomikawa, Naoki Ogawa, Junko Douet, Vanessa Xu, Zhuo Kamikubo, Yuji Sakurai, Takashi Kohsaka, Shinichi Chiba, Hideki Hattori, Nobutaka Yamada, Yoshihiko Arikawa-Hirasawa, Eri TI Laminin alpha 1 is essential for mouse cerebellar development SO MATRIX BIOLOGY LA English DT Article DE Laminin alpha 1 chain; Meninges; Cerebellum ID CELL PRECURSOR PROLIFERATION; GRANULE NEURON MIGRATION; ASTROCYTIC GAP-JUNCTIONS; CENTRAL-NERVOUS-SYSTEM; BERGMANN GLIAL-CELLS; BASEMENT-MEMBRANE; EXTRACELLULAR-MATRIX; PURKINJE-CELLS; GROWTH-FACTOR; EXPRESSION AB Laminin alpha 1 (Lama1), which is a subunit of laminin-1 (laminin-111), a heterotrimeric ECM protein, is essential for embryonic development and promotes neurite outgrowth in culture. Because the deletion of Lama1 causes lethality at early embryonic stages in mice, the in vivo role of Lama1 in neural development and functions has not yet been possible to determine. In this study, we generated conditional Lama1 knockout (Lama1(CKO)) mice in the epiblast lineage using Sox2-Cre mice. These Lama1(CKO) mice survived, but displayed behavioral disorders and impaired formation of the cerebellum. Deficiency of Lama1 in the pial basement membrane of the meninges resulted in defects in the conformation of the meninges. During cerebellar development, Lama1 deficiency also caused a decrease in the proliferation and migration of granule cell precursors, disorganization of Bergmann glial fibers and endfeet, and a transient reduction in the activity of Akt. A marked reduction in numbers of dendritic processes in Purkinje cells was observed in Lama1(CKO) mice. Together, these results indicate that Lama1 is required for cerebellar development and functions. (C) 2011 Elsevier B.V. All rights reserved. C1 [Arikawa-Hirasawa, Eri] Juntendo Univ, Grad Sch Med, Res Inst Dis Old Age, Bunkyo Ku, Tokyo 1138421, Japan. [Kamikubo, Yuji; Sakurai, Takashi] Juntendo Univ, Grad Sch Med, Dept Pharmacol, Tokyo 1138421, Japan. [Hattori, Nobutaka; Arikawa-Hirasawa, Eri] Juntendo Univ, Grad Sch Med, Dept Neurol, Tokyo 1138421, Japan. [Ogawa, Junko; Kohsaka, Shinichi] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Tokyo, Japan. [Chiba, Hideki] Fukushima Med Univ, Dept Basic Pathol, Sch Med, Fukushima, Japan. [Yamada, Yoshihiko] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP Arikawa-Hirasawa, E (reprint author), Juntendo Univ, Grad Sch Med, Res Inst Dis Old Age, Bunkyo Ku, Bldg 10,Room 606,2-1-1 Hongo, Tokyo 1138421, Japan. EM ehirasaw@juntendo.ac.jp RI Ogawa, Junko/I-7619-2015; OI Kamikubo, Yuji/0000-0003-1985-5212 FU NIDCR, National Institutes of Health; Ministry of Education, Culture, Sports Science and Technology of Japan [17082008, 2230023] FX We thank Glenn Longenecker and Ashok B. Kulkarni for their help in creating the mutant mice, Takako Sasaki for the laminin alpha 1 antibody, and Hynda K. Kleinman for critical reading. This work was supported by the Intramural Program of the NIDCR, National Institutes of Health (Y.Y.) and grants from the Ministry of Education, Culture, Sports Science and Technology of Japan (17082008 and 2230023 to E.A-H.). NR 59 TC 15 Z9 15 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD JAN PY 2012 VL 31 IS 1 BP 17 EP 28 DI 10.1016/j.matbio.2011.09.002 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 892BX UT WOS:000300262800002 PM 21983115 ER PT J AU Norian, JM Owen, CM Taboas, J Korecki, C Tuan, R Malik, M Catherino, WH Segars, JH AF Norian, John M. Owen, Carter M. Taboas, Juan Korecki, Casey Tuan, Rocky Malik, Minnie Catherino, William H. Segars, James H. TI Characterization of tissue biomechanics and mechanical signaling in uterine leiomyoma SO MATRIX BIOLOGY LA English DT Article DE Mechanotransduction; RhoA; Leiomyoma; Mechanical properties; Extracellular matrix; AKAPI3; Myometrium; Uterine fibroids; Rho-kinase; ROCK ID ARTICULAR-CARTILAGE; EXTRACELLULAR-MATRIX; NORMAL MYOMETRIUM; TENSIONAL HOMEOSTASIS; MALIGNANT PHENOTYPE; HORMONE AGONIST; IN-VITRO; CELLS; STRESS; RHO AB Leiomyoma are common tumors arising within the uterus that feature excessive deposition of a stiff, disordered extracellular matrix (ECM). Mechanical stress is a critical determinant of excessive ECM deposition and increased mechanical stress has been shown to be involved in tumorigenesis. Here we tested the viscoelastic properties of leiomyoma and characterized dynamic and static mechanical signaling in leiomyoma cells using three approaches, including measurement of active RhoA. We found that the peak strain and pseudo-dynamic modulus of leiomyoma tissue was significantly increased relative to matched myometrium. In addition, leiomyoma cells demonstrated an attenuated response to applied cyclic uniaxial strain and to variation in substrate stiffness, relative to myometrial cells. However, on a flexible pronectin-coated silicone substrate, basal levels and lysophosphatidic acid-stimulated levels of activated RhoA were similar between leiomyoma and myometrial cells. In contrast, leiomyoma cells plated on a rigid polystyrene substrate had elevated levels of active RhoA, compared to myometrial cells. The results indicate that viscoelastic properties of the ECM of leiomyoma contribute significantly to the tumor's inherent stiffness and that leiomyoma cells have an attenuated sensitivity to mechanical cues. The findings suggest there may be a fundamental alteration in the communication between the external mechanical environment (extracellular forces) and reorganization of the actin cytoskeleton mediated by RhoA in leiomyoma cells. Additional research will be needed to elucidate the mechanism(s) responsible for the attenuated mechanical signaling in leiomyoma cells. Published by Elsevier B.V. C1 [Segars, James H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, CRC, NIH, Bethesda, MD 20892 USA. [Taboas, Juan; Tuan, Rocky] Univ Pittsburgh, Med Ctr, Dept Orthoped Surg, Pittsburgh, PA USA. [Taboas, Juan; Korecki, Casey; Tuan, Rocky] NIAMSD, Cartilage Biol & Orthoped Branch, NIH, Bethesda, MD 20892 USA. [Malik, Minnie; Catherino, William H.; Segars, James H.] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. RP Segars, JH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, CRC, NIH, Bldg 10,Room E1-3140,10 Ctr Dr, Bethesda, MD 20892 USA. EM segarsj@mail.nih.gov OI Owen, Carter Monique/0000-0002-5012-2706; Malik, Minnie/0000-0003-1129-6575 FU NICHD, NIH, Bethesda, MD [Z01-HD-008737-10]; NIH; Pfizer, Inc. FX This research was supported by Z01-HD-008737-10, Program in Reproductive and Adult Endocrinology, NICHD, NIH, Bethesda, MD and the Clinical Research Training Program (CRTP), a public-private partnership supported jointly by the NIH and Pfizer, Inc. (via a grant to the NIH Foundation from Pfizer Inc.). NR 57 TC 30 Z9 32 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD JAN PY 2012 VL 31 IS 1 BP 57 EP 65 DI 10.1016/j.matbio.2011.09.001 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 892BX UT WOS:000300262800006 PM 21983114 ER PT S AU Wong, RN Steenbergen, C Murphy, E AF Wong, Renee Steenbergen, Charles Murphy, Elizabeth BE Palmeira, CM Moreno, AJ TI Mitochondrial Permeability Transition Pore and Calcium Handling SO MITOCHONDRIAL BIOENERGETICS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Calcium; Mitochondria; Pore opening; Swelling; Uptake ID CA-2&-INDUCED MEMBRANE TRANSITION; REPERFUSION INJURY; CYCLOPHILIN-D; CELL-DEATH; RAT HEARTS; METABOLISM; MECHANISMS; IONS; CYCLOSPORINE; PROTECTION AB Opening of a large conductance channel in the inner mitochondrial membrane, known as the mitochondrial permeability transition (MPT) pore, has been shown to be a primary mediator of cell death in the heart subjected to ischemia-reperfusion injury. Inhibitors of the MPT have been shown to reduce cardiac ischemia-reperfusion injury. Furthermore, most cardioprotective strategies appear to reduce ischemic cell death either by reducing the triggers for the opening of the MPT, such as reducing calcium overload or reactive oxygen species, or by more direct inhibition of the MPT. This chapter focuses on key issues in the study of the MPT and provides some methods for measuring MPT opening in isolated mitochondria. C1 [Wong, Renee; Murphy, Elizabeth] NHLBI, Cardiac Physiol Sect, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. [Steenbergen, Charles] Johns Hopkins Med Sch, Dept Pathol, Bethesda, MD 20892 USA. RP Wong, RN (reprint author), NHLBI, Cardiac Physiol Sect, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. FU Intramural NIH HHS [ZIA HL002066-04]; NHLBI NIH HHS [R01 HL039752] NR 26 TC 20 Z9 21 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-381-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 810 BP 235 EP 242 DI 10.1007/978-1-61779-382-0_15 D2 10.1007/978-1-6177-382-0 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BYL99 UT WOS:000299298300015 PM 22057571 ER PT B AU Diamond, MS Pierson, TC Roehrig, JT AF Diamond, Michael S. Pierson, Theodore C. Roehrig, John T. BE Shi, PY TI Antibody Therapeutics Against Flaviviruses SO MOLECULAR VIROLOGY AND CONTROL OF FLAVIVIRUSES LA English DT Article; Book Chapter ID WEST-NILE-VIRUS; JAPANESE ENCEPHALITIS-VIRUS; TICK-BORNE ENCEPHALITIS; YELLOW-FEVER VIRUS; NONSTRUCTURAL PROTEIN NS1; HUMANIZED MONOCLONAL-ANTIBODY; LETHAL DENGUE INFECTION; TYPE-2 ENVELOPE PROTEIN; VIRAL MEMBRANE-FUSION; 17D VACCINE STRAIN AB Flaviviruses are a group of small RNA enveloped viruses that cause severe disease in humans worldwide. Recent advances in the structural biology of the flavivirus envelope proteins and virion have catalysed rapid progress towards understanding how the most potently inhibitory antibodies neutralize infection. These insights have identified factors that modulate the potency of neutralizing antibodies and provided insight into the design of novel antibody-based therapeutics against several members of the flavivirus genus. This chapter will discuss recent advances in the understanding of the mechanisms of antibody neutralization of flaviviruses, and review the progress towards development of antibody-based therapeutics against several different flaviviruses of global concern. C1 [Diamond, Michael S.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Diamond, Michael S.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. [Diamond, Michael S.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Diamond, Michael S.] Washington Univ, Sch Med, Midwest Reg Ctr Excellence Biodef & Emerging, St Louis, MO 63110 USA. [Roehrig, John T.] US Dept Hlth & Human Serv, Div Vector Borne Infect Dis, Ctr Dis Control & Prevent, Publ Hlth Serv, Ft Collins, CO USA. [Pierson, Theodore C.] NIH, Viral Pathogenesis Sect, Viral Dis Lab, Bethesda, MD 20892 USA. RP Diamond, MS (reprint author), Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. EM diamond@borcim.wustl.edu; piersontc@mail.nih.gov; jtr1@cdc.gov NR 223 TC 6 Z9 6 U1 0 U2 1 PU CAISTER ACADEMIC PRESS PI WYMONDHAM PA 32 HEWITTS LANE, WYMONDHAM NR 18 0JA, ENGLAND BN 978-1-904455-92-9 PY 2012 BP 231 EP 255 PG 25 WC Virology SC Virology GA BYM17 UT WOS:000299300400011 ER PT J AU Huang, CM Polk, TA Goh, JO Park, DC AF Huang, Chih-Mao Polk, Thad A. Goh, Joshua O. Park, Denise C. TI Both left and right posterior parietal activations contribute to compensatory processes in normal aging SO NEUROPSYCHOLOGIA LA English DT Article DE Age-related compensation; Event-related fMRI; Interference resolution; Posterior parietal cortex; Prefrontal cortex ID EVENT-RELATED FMRI; ADULT LIFE-SPAN; OLDER-ADULTS; WORKING-MEMORY; NUMERICAL STROOP; AGE-DIFFERENCES; BRAIN ACTIVITY; INTERFERENCE RESOLUTION; TASK; RECRUITMENT AB Older adults often exhibit greater brain activation in prefrontal cortex compared to younger adults, and there is some evidence that this increased activation compensates for age-related neural degradation that would otherwise adversely affect cognitive performance. Less is known about aging and compensatory recruitment in the parietal cortex. In this event-related functional magnetic resonance imaging study, we presented healthy young and old participants with two Stroop-like tasks (number magnitude and physical size). In young, the number magnitude task activated right parietal cortex and the physical size task activated left parietal cortex. In older adults, we observed contralateral parietal recruitment that depended on the task: in the number magnitude task older participants recruited left posterior parietal cortex (in addition to the right parietal activity observed in young) while in the physical size task they recruited right (in addition to left) posterior parietal cortex. In both cases, the additional parietal activity was associated with better performance suggesting that it played a compensatory role. Older adults also recruited left prefrontal cortex during both tasks and this common activation was also associated with better performance. The results provide evidence for task-specific compensatory recruitment in parietal cortex as well as task-independent compensatory recruitment in prefrontal cortex in normal aging. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Huang, Chih-Mao; Park, Denise C.] Univ Texas Dallas, Ctr Vital Longev, Dallas, TX 75235 USA. [Huang, Chih-Mao] Univ Illinois, Dept Psychol, Urbana, IL 61801 USA. [Polk, Thad A.] Univ Michigan, Dept Psychol, Ann Arbor, MI USA. [Goh, Joshua O.] NIA, Lab Behav Neurosci, Baltimore, MD 21224 USA. RP Huang, CM (reprint author), Univ Texas Dallas, Ctr Vital Longev, 1600 Viceroy Dr, Dallas, TX 75235 USA. EM chuang40@illinois.edu RI GOH, JOSHUA/C-8063-2016 OI GOH, JOSHUA/0000-0001-7808-5452 FU National Institute of Aging [R01AGO15047, R37AGO60625]; National Institute on Aging, NIH FX We gratefully acknowledge the members of the Center for Vital Longevity for valuable discussions regarding this project and paper. This work was supported by National Institute of Aging Grants R01AGO15047 and R37AGO60625 awarded to Denise C. Park and in part by the Intramural Research Program, National Institute on Aging, NIH. NR 55 TC 25 Z9 25 U1 0 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD JAN PY 2012 VL 50 IS 1 BP 55 EP 66 DI 10.1016/j.neuropsychologia.2011.10.022 PG 12 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 893WR UT WOS:000300388900007 PM 22063904 ER PT J AU Hudson, KL AF Hudson, Kathy L. TI Genomics, Health Care, and Society EDITORIAL COMMENT SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material AB Genetic tests are growing in number and in clinical relevance as a result of rapid advances in genomic technologies. The widespread availability of genomic data from individuals has raised concerns over privacy issues and controversy over possible misuse of genomic data. This review describes broad issues raised by genetic technologies and information and discusses evolving policies for regulating genetic and genomic research and integrating of genetics into clinical care. The storage of biologic specimens collected from patients has engendered long-standing controversy about patient consent to allow access to their samples or data for future research, typically unanticipated at the time of specimen collection. Recent proposed regulations by the Department of Health and Human Services address both patient consent and institutional review of the research use of biospecimens. The United States Congress enacted the Clinical Laboratory Improvement Amendments in 1988 to regulate medical-testing laboratories at a time when genetic testing of a patient's genome to diagnose a disease was not anticipated. Although the Food and Drug Administration has the legal authority to regulate laboratory-developed tests, including genetic tests, relatively few genetic tests have been regulated. To correct this oversight, the Food and Drug Administration intends to begin risk-based oversight of laboratory-developed genetic tests. Pharmacogenomic testing is a specific form of genetic testing in which the genetic profile of an individual can be used to predict the occurrence of toxicity as well as efficacy of specific drugs. Genomic research can also be used to identify promising targets for new and existing drugs. Other technologic advances that have provided great benefits yet also raised concerns, include the use of electronic medical records. Although well established in some large health care systems, the ease of transfer of information across electronic databases has raised concern for increased risk of unauthorized access and misuse of such information. The privacy rule in the Health Insurance Portability and Accountability Act did not explicitly provide privacy protections for genetic information. Genetic testing raises the potential for a new form of discrimination. The Genetic Information Nondiscrimination Act of 2008 (GINA) and additional proposed legislative changes require that Department of Health and Human Services amend the Health Insurance Portability and Accountability Act privacy rules to protect individual privacy and prevent discriminatory use of genomic data for underwriting in health insurance and for hiring decisions by employers. In the United States' criminal justice system, DNA has been collected and used as an aid in obtaining convictions, as well as to exonerate wrongly convicted individuals. The use of DNA in the law enforcement has raised concerns about privacy and a possible racially disproportional effect of using this evidence. A court ruling in 1980 that an engineered microorganism was patentable, led to a 30-year explosion in research and methods in biotechnology, especially in sequencing and genetic testing. There is considerable controversy on the patentability of engineered DNA and RNA sequences developed for diagnostic and therapeutic purposes. A number of US courts have issued additional rulings on this issue. The final court ruling on a current lawsuit could have major effects on innovation, investment, and access to patents, with major implications for research, the biotechnology industry, and medicine. The author of this report concludes that the current challenge is to foster innovation and discovery leading to improved clinical care by allowing broad access to genomic information, while developing policies that protect individual privacy and respect research participants and patients. C1 NIH, Bethesda, MD 20892 USA. RP Hudson, KL (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7828 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD JAN PY 2012 VL 67 IS 1 BP 24 EP 26 DI 10.1097/OGX.0b013e3182439ec9 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 891MD UT WOS:000300220300011 ER PT J AU Csokmay, JM Hill, MJ Chason, RJ Hennessy, S James, AN Cohen, J DeCherney, AH Segars, JH Payson, MD AF Csokmay, John M. Hill, Micah J. Chason, Rebecca J. Hennessy, Sasha James, Aidita N. Cohen, Jacques DeCherney, Alan H. Segars, James H. Payson, Mark D. TI Experience With a Patient-Friendly, Mandatory, Single-Blastocyst Transfer Policy: The Power of One EDITORIAL COMMENT SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material AB During in vitro fertilization, double embryo transfer not only increases the probability of live birth, but also increases the likelihood of multiple gestation and its inherent maternal and neonatal complications. Data from 2 meta-analyses suggest that single embryo transfer of cleavage-stage embryos reduces the likelihood of multiple births; however, live birth rates are also reduced. In a recent study, the implementation of a mandatory single-blastocyst transfer (mSBT) policy resulted in a 45% reduction in multiple gestations while maintaining good pregnancy rates. The present study tested the hypothesis that transfer of a single blastocyst in good prognosis patients during their first assisted reproductive technology (ART) cycle would reduce the risk of multiple gestations while maintaining high pregnancy rates. This retrospective analysis investigated outcomes before and after implementation of an mSBT policy/algorithm at a university-based ART center. The participants were women younger than 38 years undergoing their first ART cycle in 2009 or 2010 with at least 4 high-grade embryos on day 3 after oocyte retrieval. Patients from 2009 completing ART before initiation of the mandatory single embryo transfer policy were the "before" group, and patients completing ART under the new mSBT policy in 2010 were the "after" group. Baseline demographics were similar in both groups. The primary study outcome measures were multiple gestation and clinical pregnancy rates. Of the 136 patients who met study inclusion criteria, 62 were in the before group and 74 in the after group. Compared with the before group, the after group had fewer blastocysts transferred per patient (1.9 vs. 1.3, P < 0.001). There were no significant differences between groups in implantation rates (54.6% vs. 49.6%) or clinical pregnancies (67.7% vs. 63.5%). The rates of multiple gestations were markedly reduced after the policy was implemented (before group: 43.8% vs. after group: 14.6%, P < 0.001). More patients in the after group had >= 1 blastocyst cryopreserved than in the before group (52.8% vs. 30.6%, P = 0.01). These findings show that the mSBT algorithm maintains high pregnancy rates and improves the number of high-quality cryopreserved embryos, while markedly reducing the number of multiple gestations in good prognosis patients. C1 [Csokmay, John M.] Walter Reed Army Med Ctr, Washington, DC 20307 USA. NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. ART Inst Washington Inc, Washington, DC USA. Reprogenetics, Livingston, NJ USA. RP Csokmay, JM (reprint author), Walter Reed Army Med Ctr, Washington, DC 20307 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7828 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD JAN PY 2012 VL 67 IS 1 BP 31 EP 32 DI 10.1097/OGX.0b013e3182439f08 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 891MD UT WOS:000300220300014 ER PT J AU Zoppoli, G Solier, S Reinhold, WC Liu, H Connelly, JW Monks, A Shoemaker, RH Abaan, OD Davis, SR Meltzer, PS Doroshow, JH Pommier, Y AF Zoppoli, G. Solier, S. Reinhold, W. C. Liu, H. Connelly, J. W., Jr. Monks, A. Shoemaker, R. H. Abaan, O. D. Davis, S. R. Meltzer, P. S. Doroshow, J. H. Pommier, Y. TI CHEK2 genomic and proteomic analyses reveal genetic inactivation or endogenous activation across the 60 cell lines of the US National Cancer Institute SO ONCOGENE LA English DT Article DE Chk2; centrosome; H2AX; p53; BRCA1; Fanconi anemia ID DNA-DAMAGE RESPONSE; CHK2 PROTEIN-KINASE; LI-FRAUMENI-SYNDROME; TUMOR-SUPPRESSOR; BREAST-CANCER; THREONINE-68 PHOSPHORYLATION; CHECKPOINT PATHWAY; LUNG-CANCER; IN-VITRO; EXPRESSION AB CHEK2 encodes a serine/threonine kinase (Chk2) activated by ATM in response to DNA double-strand breaks. On the one hand, CHEK2 has been described as a tumor suppressor with proapoptotic, cell-cycle checkpoint and mitotic functions. On the other hand, Chk2 is also commonly activated (phosphorylated at T68) in cancers and precancerous lesions. Here, we report an extensive characterization of CHEK2 across the panel of 60 established cancer cell lines from the NCI Anticancer Screen (the NCI-60) using genomic and proteomic analyses, including exon-specific mRNA expression, DNA copy-number variation (CNV) by aCGH, exome sequencing, as well as western blot analyses for total and activated (pT68-Chk2) Chk2. We show that the high heterogeneity of Chk2 levels in cancer cells is primarily due to its inactivation (owing to low gene expression, alternative splicing, point mutations, copy-number alterations and premature truncation) or reduction of protein levels. Moreover, we observe that a significant percentage of cancer cells (12% of the NCI-60 and HeLa cells) show high endogenous Chk2 activation, which is always associated with p53 inactivation, and which is accompanied by downregulation of the Fanconi anemia and homologous recombination pathways. We also report the presence of activated Chk2 (pT68-Chk2) along with histone gamma-H2AX in centrosomes. Oncogene (2012) 31, 403-418; doi: 10.1038/onc.2011.283; published online 18 July 2011 C1 [Zoppoli, G.] Univ Genoa, Dept Internal Med DiMI, I-16132 Genoa, Italy. [Zoppoli, G.; Solier, S.; Reinhold, W. C.; Liu, H.; Doroshow, J. H.; Pommier, Y.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Liu, H.] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA. [Connelly, J. W., Jr.; Monks, A.] SAIC Frederick Inc, Lab Funct Genom, NCI Frederick, Frederick, MD USA. [Shoemaker, R. H.] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21701 USA. [Abaan, O. D.; Davis, S. R.; Meltzer, P. S.] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Doroshow, J. H.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. RP Zoppoli, G (reprint author), Univ Genoa, Dept Internal Med DiMI, Avancorpo 2 Piano,Vle Benedetto XV,Room 223,6, I-16132 Genoa, Italy. EM gabriele.zoppoli@unige.it; pommier@nih.gov RI Zoppoli, Gabriele/B-6935-2016; OI Zoppoli, Gabriele/0000-0003-3890-5588; Davis, Sean/0000-0002-8991-6458 FU Center for Cancer Research; National Cancer Institute; Division of Cancer Treatment and Diagnosis; National Cancer Institute (National Institutes of Health); AIRC MFAG [10570]; University of Genova (Genova, Italy) FX This work was supported by the Center for Cancer Research, Intramural Program of the National Cancer Institute, and by the Division of Cancer Treatment and Diagnosis, Extramural Program of the National Cancer Institute (National Institutes of Health), and by AIRC MFAG grant no. 10570 (GZ). GZ was also supported by a PhD fellowship grant (XXIII Ciclo) from the University of Genova (Genova, Italy). NR 84 TC 9 Z9 9 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN PY 2012 VL 31 IS 4 BP 403 EP 418 DI 10.1038/onc.2011.283 PG 16 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 891LU UT WOS:000300219300001 PM 21765476 ER PT S AU Gimenez-Alejandre, M Gros, A Alemany, R AF Gimenez-Alejandre, Marta Gros, Alena Alemany, Ramon BE Kirn, DH Liu, TC Thorne, SH TI Construction of Capsid-Modified Adenoviruses by Recombination in Yeast and Purification by Iodixanol-Gradient SO ONCOLYTIC VIRUSES: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Adenovirus; Detargeting; Homologous recombination; Iodixanol; Biodistribution ID GROWTH-FACTOR RECEPTOR; GENE-TRANSFER; IN-VIVO; BINDING SITE; FIBER SHAFT; LIVER; SYSTEM; HEXON; HEPATOTOXICITY; INFECTION AB Adenovirus represents a valuable tool for the treatment of cancer, but tumor targeting remains a pending issue. Most common procedures to modify adenovirus genome are time-consuming due to the requirement of multiple cloning steps, and the low efficacy of the recombination process. Here, we present a new method for homologous recombination in yeast to fast construct recombinant adenoviruses. Also, an alternative procedure to purify viral stocks, based on iodixanol gradient is described. Compared to classical methods, iodixanol is nontoxic to cells, which avoids desalting to use in vitro and in vivo. Moreover, viral stocks are more viable and it can be used for large-scale purifications. Finally, a protocol for analyzing blood persistence of modified vector in in vivo biodistribution is presented. C1 [Gimenez-Alejandre, Marta; Alemany, Ramon] Inst Catala Oncol IDIBELL, Lab Recerca Translac, Barcelona, Spain. [Gros, Alena] NCI, US Natl Inst Hlth, Bethesda, MD 20892 USA. RP Gimenez-Alejandre, M (reprint author), Inst Catala Oncol IDIBELL, Lab Recerca Translac, Barcelona, Spain. OI Gros, Alena/0000-0002-1207-1880 NR 22 TC 4 Z9 4 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-339-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 797 BP 21 EP 34 DI 10.1007/978-1-61779-340-0_2 D2 10.1007/978-1-61779-340-0 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BYN64 UT WOS:000299454500002 PM 21948466 ER PT J AU Fontelo, P Faustorilla, J Gavino, A Marcelo, A AF Fontelo, Paul Faustorilla, John Gavino, Alex Marcelo, Alvin TI Digital pathology - implementation challenges in low-resource countries SO ANALYTICAL CELLULAR PATHOLOGY LA English DT Article DE Digital pathology; virtual slide; virtual microscope; whole slide imaging; medical education; low-resource countries ID VIRTUAL MICROSCOPY; TELEPATHOLOGY; HISTOLOGY; CONSULTATION; EXPERIENCE; ACCURACY; PROJECT; ROUTINE; SLIDE AB Background: Medical education in pathology and histology in low-resource countries face many obstacles because of equipment cost and telecommunication deficiencies. Digital Pathology may provide solutions. We report student experience with virtual slides on a local network and a remote image server. Methods: Using an iPad tablet device, fifty 3rd and 4th year medical students viewed digital pathology slides from a Web server at the National Library of Medicine and a mirror server on the local network. Results: The quality of images from both servers was found to be satisfactory, but the local server was deemed faster and preferred by the participants in this study (p < 0.005). Conclusions: Virtual slides on a local network server may provide solutions to equipment and technical obstacles and could enhance student learning in developing countries. C1 [Fontelo, Paul; Gavino, Alex] Natl Lib Med, Bethesda, MA USA. [Faustorilla, John; Gavino, Alex; Marcelo, Alvin] Univ Philippines Manila, Natl Telehlth Ctr, Manila, Philippines. RP Fontelo, P (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM fontelo@nlm.nih.gov NR 27 TC 8 Z9 9 U1 2 U2 8 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 2210-7177 J9 ANAL CELL PATHOL JI Anal. Cell. Pathol. PY 2012 VL 35 IS 1 BP 31 EP 36 DI 10.3233/ACP-2011-0024 PG 6 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 889VF UT WOS:000300102100006 PM 22233702 ER PT J AU Huang, XL Swierczewska, M Choi, KY Zhu, L Bhirde, A Park, J Kim, K Xie, J Niu, G Lee, KC Lee, S Chen, XY AF Huang, Xinglu Swierczewska, Magdalena Choi, Ki Young Zhu, Lei Bhirde, Ashwinkumar Park, Jinwoo Kim, Kwangmeyung Xie, Jin Niu, Gang Lee, Kang Choon Lee, Seulki Chen, Xiaoyuan TI Multiplex Imaging of an Intracellular Proteolytic Cascade by using a Broad-Spectrum Nanoquencher SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE caspases; fluorescence; imaging agents; nanoparticles; proteolysis ID RESONANCE ENERGY-TRANSFER; IN-VIVO; APOPTOSIS; PROTEASES; PROBES; ACTIVATION; CELLS; NANOPARTICLES; CASPASES; PEPTIDE C1 [Huang, Xinglu; Swierczewska, Magdalena; Choi, Ki Young; Zhu, Lei; Bhirde, Ashwinkumar; Niu, Gang; Lee, Seulki; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Swierczewska, Magdalena] SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11790 USA. [Kim, Kwangmeyung] Korea Inst Sci & Technol, Ctr Theragnosis, Seoul, South Korea. [Xie, Jin] Univ Georgia, Dept Chem, Athens, GA 30602 USA. [Xie, Jin] Univ Georgia, Bioimaging Res Ctr, Athens, GA 30602 USA. [Lee, Kang Choon] Sungkyunkwan Univ, Coll Pharm, Seoul, South Korea. RP Lee, S (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. EM seulki.lee@nih.gov; shawn.chen@nih.gov RI Zhu, Lei/P-9786-2016; CHOI, KI YOUNG/Q-7177-2016 OI Zhu, Lei/0000-0002-1820-4795; FU NIBIB, NIH; NIH [K99/R00]; Henry M. Jackson Foundation; KIST (Korea) FX This work was supported by the Intramural Research Program of the NIBIB, NIH and partially supported by an NIH Pathway to Independence (K99/R00) Award, the Henry M. Jackson Foundation, and the Intramural Research Program of KIST (Korea). We thank Myung Sun Lee for illustrations. NR 34 TC 30 Z9 31 U1 1 U2 19 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2012 VL 51 IS 7 BP 1625 EP 1630 DI 10.1002/anie.201107795 PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA 887RJ UT WOS:000299946400022 PM 22213412 ER PT J AU Chu, EY Freeman, AF Jing, H Cowen, EW Davis, J Su, HC Holland, SM Turner, MLC AF Chu, Emily Y. Freeman, Alexandra F. Jing, Huie Cowen, Edward W. Davis, Joie Su, Helen C. Holland, Steven M. Turner, Maria L. Chanco TI Cutaneous Manifestations of DOCK8 Deficiency Syndrome SO ARCHIVES OF DERMATOLOGY LA English DT Article ID HYPER-IGE SYNDROME; STEM-CELL TRANSPLANTATION; CYTOKINESIS 8 DOCK8; CLINICAL-MANIFESTATIONS; MUTATIONS; IMMUNODEFICIENCY; CARCINOMA; GENE; DIFFERENTIATION; EXPRESSION AB Background: Mutations in the dedicator of cytokinesis 8 gene (DOCK8) cause a combined primary immunodeficiency syndrome that is characterized by elevated serum IgE levels, depressed IgM levels, eosinophilia, sinopulmonary infections, cutaneous viral infections, and lymphopenia. Many patients with DOCK8 deficiency were previously thought to have a variant of Job's syndrome. Distinguishing between DOCK8 deficiency and Job's syndrome, also referred to as autosomal dominant hyper-IgE syndrome, on the basis of clinical findings alone is challenging. The discovery of the DOCK8 mutation has made it possible to differentiate the cutaneous manifestations of these hyper-IgE syndromes. Observations: Twenty-one patients from 14 families with confirmed homozygous or compound heterozygous mutations in DOCKS were evaluated. Clinical findings included dermatitis, asthma, food and environmental allergies, recurrent sinopulmonary infections, staphylococcal skin abscesses, and severe cutaneous viral infections. Malignant neoplasms, including aggressive cutaneous T-cell lymphoma, anal and vulvar squamous cell carcinomas, and diffuse large B-cell lymphoma, developed in 5 patients during adolescence and young adulthood. Conclusions: DOCK8 deficiency and Job's syndrome share several clinical features, including elevated serum IgE levels, dermatitis, recurrent sinopulmonary infections, and cutaneous staphylococcal abscesses. However, the presence of recalcitrant, widespread cutaneous viral infections, asthma, and food and environmental allergies, as well as the absence of newborn rash and coarse facies, favors the clinical diagnosis of DOCK8 deficiency. Rates of malignancy and overall mortality in patients with DOCK8 deficiency were higher than in those with Job's syndrome, highlighting the value of distinguishing between these conditions and the importance of close monitoring for neoplasia. C1 [Freeman, Alexandra F.; Jing, Huie; Davis, Joie; Su, Helen C.; Holland, Steven M.] NIAID, Bethesda, MD 20892 USA. [Chu, Emily Y.; Cowen, Edward W.; Turner, Maria L. Chanco] NCI, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Chu, EY (reprint author), Hosp Univ Penn, Dept Dermatol, 2 Maloney,3600 Spruce St, Philadelphia, PA 19104 USA. EM emily.chu@uphs.upenn.edu RI Su, Helen/H-9541-2015 OI Su, Helen/0000-0002-5582-9110 FU National Institutes of Health; National Cancer Institute (Center for Cancer Research); National Institute of Allergy and Infectious Diseases FX This study was supported in part by the Intramural Research Programs of the National Institutes of Health; the National Cancer Institute (Center for Cancer Research) and the National Institute of Allergy and Infectious Diseases. NR 31 TC 44 Z9 44 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JAN PY 2012 VL 148 IS 1 BP 79 EP 84 DI 10.1001/archdermatol.2011.262 PG 6 WC Dermatology SC Dermatology GA 883SB UT WOS:000299653900014 PM 21931011 ER PT J AU Emera, D Romero, R Wagner, G AF Emera, Deena Romero, Roberto Wagner, Guenter TI The evolution of menstruation: A new model for genetic assimilation SO BIOESSAYS LA English DT Article DE genetic assimilation; maternal-fetal conflict; menstruation; molecular evolution ID HUMAN-ENDOMETRIUM; TROPHOBLAST INVASION; REPRODUCTIVE-CYCLE; PHENOTYPIC PLASTICITY; EMBRYO IMPLANTATION; EXPRESSION; PREGNANCY; UTERINE; CYCLOOXYGENASE-2; DECIDUALIZATION AB Why do humans menstruate while most mammals do not? Here, we present our answer to this long-debated question, arguing that (i) menstruation occurs as a mechanistic consequence of hormone-induced differentiation of the endometrium (referred to as spontaneous decidualization, or SD); (ii) SD evolved because of maternalfetal conflict; and (iii) SD evolved by genetic assimilation of the decidualization reaction, which is induced by the fetus in non-menstruating species. The idea that menstruation occurs as a consequence of SD has been proposed in the past, but here we present a novel hypothesis on how SD evolved. We argue that decidualization became genetically stabilized in menstruating lineages, allowing females to prepare for pregnancy without any signal from the fetus. We present three models for the evolution of SD by genetic assimilation, based on recent advances in our understanding of the mechanisms of endometrial differentiation and implantation. Testing these models will ultimately shed light on the evolutionary significance of menstruation, as well as on the etiology of human reproductive disorders like endometriosis and recurrent pregnancy loss. C1 [Emera, Deena; Wagner, Guenter] Yale Univ, Dept Ecol & Evolutionary Biol, New Haven, CT 06520 USA. [Emera, Deena; Wagner, Guenter] Yale Univ, Yale Syst Biol Inst, New Haven, CT USA. [Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. RP Emera, D (reprint author), Yale Univ, Dept Ecol & Evolutionary Biol, New Haven, CT 06520 USA. EM deena.emera@yale.edu FU NIH [N01-HD-2-3342]; John Templeton Foundation [12793]; Intramural Research Division of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS; Yale University FX Research in the Wagner lab on this topic was done in part under the NIH subcontract N01-HD-2-3342 and the John Templeton Foundation grant # 12793. This research was supported in part by the Intramural Research Division of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. Financial support by the Yale University Science Development Fund is gratefully acknowledged. NR 68 TC 26 Z9 26 U1 8 U2 41 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0265-9247 J9 BIOESSAYS JI Bioessays PD JAN PY 2012 VL 34 IS 1 BP 26 EP 35 DI 10.1002/bies.201100099 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 865GQ UT WOS:000298299500007 PM 22057551 ER PT J AU Manolio, TA Chanock, SJ AF Manolio, Teri A. Chanock, Stephen J. TI The riddle of intergenic disease-associated loci SO CELL CYCLE LA English DT News Item ID COMMON HUMAN DISORDERS; PROSTATE-CANCER; COLORECTAL-CANCER; 8Q24; RS6983267; SEQUENCE C1 [Manolio, Teri A.] NHGRI, Bethesda, MD 20892 USA. [Chanock, Stephen J.] NCI, NIH, Bethesda, MD 20892 USA. RP Manolio, TA (reprint author), NHGRI, Bethesda, MD 20892 USA. EM manolio@nih.gov NR 9 TC 0 Z9 0 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JAN 1 PY 2012 VL 11 IS 1 BP 15 EP 16 DI 10.4161/cc.11.1.18731 PG 2 WC Cell Biology SC Cell Biology GA 877FO UT WOS:000299162900009 PM 22193034 ER PT J AU Aravind, L Iyer, LM AF Aravind, L. Iyer, Lakshminarayan M. TI The HARE-HTH and associated domains Novel modules in the coordination of epigenetic DNA and protein modifications SO CELL CYCLE LA English DT Article DE DNA modifications; methylation; Tet2; nucleosomal spacing ISWI; restriction enzymes; polycomb repressive complex ID ACUTE MYELOID-LEUKEMIA; CHROMATIN-REMODELING COMPLEX; ADDITIONAL-SEX-COMBS; DE-NOVO METHYLATION; RNA-POLYMERASE; PHD FINGER; BACILLUS-SUBTILIS; MAMMALIAN DNA; TRANSCRIPTIONAL REGULATION; STRUCTURE PREDICTION AB Human ASXL proteins, orthologs of Drosophila Additional sex combs, have been implicated in conjunction with TET2 as a major target for mutations and translocations, leading to a wide range of myeloid leukemias, related myelodysplastic conditions (ASXL1 and ASXL2) and Bohring-Opitz syndrome, a developmental disorder (ASXL1). Using sensitive sequence and structure comparison methods, we show that most animal ASXL proteins contain a novel N-terminal domain that is also found in several other eukaryotic chromatin proteins, diverse restriction endonucleases and DNA glycosylases, the RNA polymerase delta subunit of Gram-positive bacteria and certain bacterial proteins that combine features of the RNA polymerase a-subunit and sigma factors. This domain adopts the winged helix-turn-helix fold (wHTH) and is predicted to bind DNA. Based on its domain architectural contexts, we present evidence that this domain might play an important role both in eukaryotes and bacteria in the recruitment of diverse effector activities, including the the deubiquitinase subunit of Polycomb repressive complexes, to DNA, depending on the state of epigenetic modifications such as 5-methylcytosine and its oxidized derivatives. In other eukaryotic chromatin proteins, wHTH domain is fused to a region with three conserved motifs, which are also found in diverse eukaryotic chromatin proteins, such as the animal BAZ/WAL proteins, plant HB1 and MBD9, yeast Itc1p and Ioc3, RSF1, CECR2 and NURF1. Based on the crystal structure of Ioc3, we establish that these motifs in conjunction with the DDT motif constitute a structural determinant that is central to nucleosomal repositioning by the ISWI clade of SWI2/SNF2 ATPases. We also show that the central domain of the ASXL proteins (ASXH domain) is conserved outside of animals in fungi and plants, where it is combined with other domains, suggesting that it might be an ancient module mediating interactions between chromatin-linked protein complexes and transcription factors and UCH37-like deubiquitnases via its conserved LXXLL motif. We present evidence that the C-terminal PHD finger of ASXL protein has peculiar structural modifications that might allow it to recognize internal modified lysines other than those from the N terminus of histone H3, making it the mediator of previously unexpected interactions in chromatin. C1 [Aravind, L.; Iyer, Lakshminarayan M.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM aravind@ncbi.nlm.nih.gov FU National Library of Medicine FX Work by the authors is supported by the intramural funds of the National Library of Medicine. NR 103 TC 33 Z9 36 U1 2 U2 8 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PD JAN 1 PY 2012 VL 11 IS 1 BP 119 EP 131 DI 10.4161/cc.11.1.18475 PG 13 WC Cell Biology SC Cell Biology GA 877FO UT WOS:000299162900024 PM 22186017 ER PT J AU Kaplan, RM AF Kaplan, Robert M. TI Economic decision models: Can they inform child welfare policy? SO CHILD ABUSE & NEGLECT LA English DT Editorial Material ID HEALTH C1 [Kaplan, Robert M.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. [Kaplan, Robert M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Kaplan, RM (reprint author), NIH, Off Behav & Social Sci Res, Off Director, 31 Ctr Dr,Room B1C19, Bethesda, MD 20892 USA. NR 16 TC 3 Z9 3 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2134 J9 CHILD ABUSE NEGLECT JI Child Abuse Negl. PD JAN PY 2012 VL 36 IS 1 BP 1 EP 3 DI 10.1016/j.chiabu.2011.06.007 PG 3 WC Family Studies; Psychology, Social; Social Work SC Family Studies; Psychology; Social Work GA 889KE UT WOS:000300071800001 PM 22265903 ER PT J AU Goodwin, R Giaccone, G Calvert, H Lobbezoo, M Eisenhauer, EA AF Goodwin, Rachel Giaccone, Giuseppe Calvert, Hilary Lobbezoo, Marinus Eisenhauer, Elizabeth A. CA Methodology Dev Innovative Canc TI Targeted agents: How to select the winners in preclinical and early clinical studies? SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Targeted cancer agents; Drug development ID ANTICANCER DRUG DEVELOPMENT; IN-VITRO; CANCER; MODELS; TUMOR; DISCOVERY; DESIGN AB There has been a significant shift within oncology drug development away from empiric screening of cytotoxic compounds to the era of genomics and molecularly targeted agents. The drug development process is evolving with greater emphasis on proof-of-mechanism studies in both preclinical and early clinical development. The Methodology for the Development of Innovative Cancer Therapies (MDICT) Task Force, established as a forum for academic and pharmaceutical leaders to discuss methodological issues in targeted anticancer therapy development, met in March 2010 to review what were the minimal data required to make appropriate decisions about moving new targeted cancer agents from late preclinical development into phase I and from phase I into phase II trials. A number of specific questions were posed, and responses to each developed through survey, literature review and discussion at the face to face meeting of the MDICT Task Force. Consensus emerged around the necessity to demonstrate proof-of-mechanism and obtain information on key pharmacokinetic aspects of drug behaviour in late preclinical and early clinical trials. However, controversy remains on the extent of in vivo anti-tumour efficacy required to support clinical development of targeted agents. A systematic review of the data in this area would be informative. Further, while objective response in phase! trials may be a favourable signal about the potential activity of a new agent, debate exists around the weight that should be placed on the observation of stable disease or functional imaging changes in driving drug development decisions in the absence of observing either responses or convincing pharmacodynamic data in phase I. MDICT made a number of recommendations that may aid in future development of targeted agents. (C) 2011 Published by Elsevier Ltd. C1 [Goodwin, Rachel; Eisenhauer, Elizabeth A.] Queens Univ, NCIC Clin Trials Grp, Kingston, ON K7L 3N6, Canada. [Giaccone, Giuseppe] NCI, Thorac Oncol Sect, Bethesda, MD 20892 USA. [Calvert, Hilary] UCL, London, England. [Lobbezoo, Marinus] NDDO Educ Fdn, Amsterdam, Netherlands. RP Eisenhauer, EA (reprint author), Queens Univ, NCIC Clin Trials Grp, 10 Stuart St, Kingston, ON K7L 3N6, Canada. EM eeisenhauer@ctg.queensu.ca RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 NR 14 TC 16 Z9 17 U1 0 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JAN PY 2012 VL 48 IS 2 BP 170 EP 178 DI 10.1016/j.ejca.2011.09.024 PG 9 WC Oncology SC Oncology GA 891EK UT WOS:000300199800002 PM 22093946 ER PT J AU Srikantan, S Gorospe, M AF Srikantan, Subramanya Gorospe, Myriam TI HuR function in disease SO FRONTIERS IN BIOSCIENCE-LANDMARK LA English DT Article DE RNA-binding protein; elav; post-transcriptional gene regulation; mRNA turnover; translational regulation ID RNA-BINDING PROTEIN; NECROSIS-FACTOR-ALPHA; STABILITY FACTOR HUR; AU-RICH ELEMENT; FACTOR MESSENGER-RNA; BREAST-CANCER CELLS; ELAV-LIKE PROTEIN; HUMAN-ANTIGEN-R; POSTTRANSCRIPTIONAL GENE-REGULATION; SMOOTH-MUSCLE-CELLS AB The cytoplasmic events that control mammalian gene expression, primarily mRNA stability and translation, potently influence the cellular response to internal and external signals. The ubiquitous RNA-binding protein (RBP) HuR is one of the best-studied regulators of cytoplasmic mRNA fate. Through its post-transcriptional influence on specific target mRNAs, HuR can alter the cellular response to proliferative, stress, apoptotic, differentiation, senescence, inflammatory and immune stimuli. In light of its central role in important cellular functions, HuR's role in diseases in which these responses are aberrant is increasingly appreciated. Here, we review the mechanisms that control HuR function, its influence on target mRNAs, and how impairment in HuR-governed gene expression programs impact upon different disease processes. We focus on HuR's well-recognized implication in cancer and chronic inflammation, and discuss emerging studies linking HuR to cardiovascular, neurological, and muscular pathologies. We also discuss the progress, potential, and challenges of targeting HuR therapeutically. C1 [Srikantan, Subramanya; Gorospe, Myriam] NIA, LMBI, IRP, NIH, Baltimore, MD 21224 USA. RP Gorospe, M (reprint author), NIA, LMBI, IRP, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov OI srikantan, subramanya/0000-0003-1810-6519 FU National Institute on Aging, NIH FX M. G. and S. S. are supported by the Intramural Research Program of the National Institute on Aging, NIH. NR 176 TC 102 Z9 102 U1 1 U2 13 PU FRONTIERS IN BIOSCIENCE INC PI IRVINE PA 16471 SCIENTIFIC WAY, IRVINE, CA 92618 USA SN 1093-9946 J9 FRONT BIOSCI-LANDMRK JI Front. Biosci. PD JAN 1 PY 2012 VL 17 BP 189 EP 205 DI 10.2741/3921 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 889BG UT WOS:000300047900011 PM 22201738 ER PT J AU Singh, A Winterbottom, E Daar, IO AF Singh, Arvinder Winterbottom, Emily Daar, Ira O. TI Eph/ephrin signaling in cell-cell and cell-substrate adhesion SO FRONTIERS IN BIOSCIENCE-LANDMARK LA English DT Article DE EphA; EphB; ephrin-A; ephrin-B; Adhesion; Repulsion; Metastasis; Morphogenesis; Cell Movement; Review ID RECEPTOR TYROSINE KINASE; XENOPUS-LAEVIS EMBRYOS; DENDRITIC SPINE MORPHOGENESIS; REGULATES INTEGRIN ACTIVITY; CRANIAL NEURAL CREST; GTP-BINDING PROTEIN; ACTIN STRESS FIBERS; EPH RECEPTORS; ENDOTHELIAL-CELLS; T-LYMPHOCYTES AB Cell-cell and cell-matrix adhesion are critical processes for the formation and maintenance of tissue patterns during development, as well as control of invasion and metastasis of cancer cells. Although great strides have been made regarding our understanding of the processes that play a role in cell adhesion and cell movement, the precise mechanisms by which diverse signaling events regulate cell and tissue architecture are poorly understood. One group of cell surface molecules, Eph receptor tyrosine kinases, and their membrane-bound ligands, ephrins, are key regulators in these processes. It is the ability of Eph/ephrin signaling pathways to regulate cell-cell adhesion and motility that establishes this family as a formidable system for regulating tissue separation and morphogenesis. Moreover, the de-regulation of this signaling system is linked to the promotion of more aggressive and metastatic tumors in humans. C1 [Daar, Ira O.] NCI, Dev Signal Tranduct Sect, Lab Cell & Dev Signaling, Frederick, MD 21702 USA. RP Daar, IO (reprint author), NCI, Dev Signal Tranduct Sect, Lab Cell & Dev Signaling, Bld 560,Room 22-3, Frederick, MD 21702 USA. EM daari@mail.nih.gov OI Daar, Ira/0000-0003-2657-526X NR 169 TC 16 Z9 17 U1 0 U2 11 PU FRONTIERS IN BIOSCIENCE INC PI IRVINE PA 16471 SCIENTIFIC WAY, IRVINE, CA 92618 USA SN 1093-9946 J9 FRONT BIOSCI-LANDMRK JI Front. Biosci. PD JAN 1 PY 2012 VL 17 BP 473 EP 497 DI 10.2741/3939 PG 25 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 889BX UT WOS:000300049600006 PM 22201756 ER PT J AU Ma, XF Adelstein, RS AF Ma, Xuefei Adelstein, Robert S. TI In vivo studies on nonmuscle myosin II expression and function in heart development SO FRONTIERS IN BIOSCIENCE-LANDMARK LA English DT Article DE Nonmuscle Mysoin II; Cardiac Myocyte; Cytokinesis; Karyokinesis; Intercalated Disc; Cardiomyopathy; Knockout Mice; Review ID HEAVY-CHAIN; CARDIAC-MUSCLE; CELL-ADHESION; STEM-CELLS; ABLATION; ACTIN; CYTOKINESIS; DEFECTS; ISOFORM; BRAIN AB Nonmuscle myosin II-B (NM II-B) plays an important role in cardiac development and function. Genetic ablation of NM II-B in mice results in both cellular and structural defects involving cardiac myocytes. These abnormalities include a ventricular septal defect, double outlet of the right ventricle, myocyte hypertrophy and premature onset of myocyte binucleation due to abnormalities in cytokinesis. The mice die by embryonic day (E) 14.5 due to defects in heart development. Conditional ablation of NM II-B in cardiac myocytes after E11.5 allows study of NM II-B function in adult myocytes. B-alpha MHC/B-alpha MHC mice are born with enlarged cardiac myocytes, some of which are multinucleated. Between 6-10 months of age they develop a cardiomyopathy. Many of these mice develop a marked widening of the intercalated discs. The loss of NM II-B from the intercalated discs primarily affects the adhesion junctions rather than the gap junctions and desmosomes. Interestingly, the loss of NM II-B results in a decrease in the actin binding protein mXin which also has been shown to cause disruption of the intercalated disc in addition to cardiac arrhythmias (Gustafson-Wagner et al. Am J Physiol Heart Circ Physiol. 2007, 293: H2680-92). Finally we review the evidence showing that ablation of NM II-C (which also localizes to the intercalated disc) in mouse hearts deficient in NM II-B expression results in destabilization of N-cadherin and beta-catenin in the intercalated disc. C1 [Ma, Xuefei; Adelstein, Robert S.] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Adelstein, RS (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bldg 10,Room 6C-103,10 Ctr Dr,MSC-1583, Bethesda, MD 20892 USA. EM adelster@mail.nih.gov OI Adelstein, Robert/0000-0002-8683-2144 FU Intramural NIH HHS [Z01 HL004228-13] NR 37 TC 6 Z9 7 U1 0 U2 4 PU FRONTIERS IN BIOSCIENCE INC PI IRVINE PA 16471 SCIENTIFIC WAY, IRVINE, CA 92618 USA SN 1093-9946 J9 FRONT BIOSCI-LANDMRK JI Front. Biosci. PD JAN 1 PY 2012 VL 17 BP 545 EP 555 DI 10.2741/3942 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 889BX UT WOS:000300049600009 PM 22201759 ER PT J AU Burroughs, AM Iyer, LM Aravind, L AF Burroughs, Alexander Maxwell Iyer, Lakshminarayan M. Aravind, L. TI The natural history of ubiquitin and ubiquitin-related domains SO FRONTIERS IN BIOSCIENCE-LANDMARK LA English DT Article DE Ubiquitin; Prokaryotic Ubiquitin Conjugation; Non-Ribosomal Peptide Ligases; Sumo; Rna Modification; Beta-Grasp Fold; Review ID PROTEIN CONJUGATION SYSTEM; TRANSFER-RNA SYNTHETASES; CASPASE-ACTIVATED DNASE; X-RAY CRYSTALLOGRAPHY; INITIATION-FACTOR IF3; NUCLEAR-PORE COMPLEX; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; SULFUR TRANSFER; DEUBIQUITINATING ENZYMES AB The ubiquitin (Ub) system is centered on conjugation and deconjugation of Ub and Ub-like (Ubls) proteins by a system of ligases and peptidases, respectively. Ub/Ubls contain the beta-grasp fold, also found in numerous proteins with biochemically distinct roles unrelated to the conventional Ub-system. The beta-GF underwent an early radiation spawning at least seven clades prior to the divergence of extant organisms from their last universal common ancestor, first emerging in the context of translation-related RNA-interactions and subsequently exploding to occupy various functional niches. Most beta-GF diversification occurred in prokaryotes, with the Ubl clade showing dramatic expansion in the eukaryotes. Diversification of Ubl families in eukaryotes played a major role in emergence of characteristic eukaryotic cellular sub-structures and systems. Recent comparative genomics studies indicate precursors of the eukaryotic Ub-system emerged in prokaryotes. The simplest of these combine an Ubl and an E1-like enzyme in metabolic pathways. Sampylation in archaea and Urmylation in eukaryotes appear to represent recruitment of such systems as simple protein-tagging apparatuses. However, other prokaryotic systems incorporated further components and mirror the eukaryotic condition in possessing an E2, a RING-type E3 or both of these components. Additionally, prokaryotes have evolved conjugation systems independent of Ub ligases, such as the Pup system. C1 [Iyer, Lakshminarayan M.; Aravind, L.] NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Burroughs, Alexander Maxwell] RIKEN Yokohama Inst, Omics Sci Ctr OSC, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan. RP Aravind, L (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM aravind@mail.nih.gov FU National Library of Medicine at the National Institutes of Health, USA FX Work by LMI and LA is supported by the intramural funds of the National Library of Medicine at the National Institutes of Health, USA. Supplementary material can be found at: ftp://ftp.ncbi.nih.gov/pub/aravind/UB/Ubls.html NR 146 TC 15 Z9 16 U1 0 U2 7 PU FRONTIERS IN BIOSCIENCE INC PI IRVINE PA 16471 SCIENTIFIC WAY, IRVINE, CA 92618 USA SN 1093-9946 J9 FRONT BIOSCI-LANDMRK JI Front. Biosci. PD JAN 1 PY 2012 VL 17 BP 1433 EP 1460 DI 10.2741/3996 PG 28 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 889DM UT WOS:000300053700016 PM 22201813 ER PT J AU Lowe, J Cha, H Lee, MO Mazur, SJ Appella, E Fornace, AJ AF Lowe, Julie Cha, Hyukjin Lee, Mi-Ok Mazur, Sharlyn J. Appella, Ettore Fornace, Albert J., Jr. TI Regulation of the Wip1 phosphatase and its effects on the stress response SO FRONTIERS IN BIOSCIENCE-LANDMARK LA English DT Article DE Wip1; PPM1D; Stress Signaling; DNA Damage Response; Review ID DNA-DAMAGE RESPONSE; MESENCHYMAL STEM-CELLS; NF-KAPPA-B; GENOME-WIDE ANALYSIS; BREAST-CANCER; TUMOR-SUPPRESSOR; P53-INDUCED PHOSPHATASE; SIGNALING PATHWAYS; P53-DEPENDENT APOPTOSIS; PROTEIN PHOSPHATASE AB Wip1 (PPM1D) is a stress responsive PP2C phosphatase that plays a key role in stress signaling. Although originally identified as a gene induced by p53 after genotoxic stress, we now know that Wip1 expression is additionally regulated by other mechanisms. Wip1 is not only a target of p53, but is also a target of other transcription factors, including Estrogen Receptor-alpha and NF-kappaB. Additionally, Wip1 expression is regulated by post-transcriptional mechanisms such as mRNA stabilization and alternative splicing. Upon induction, Wip1 dampens the stress response by dephosphorylating and inactivating proteins such as p53, p38 MAPK, and ATM, usually as part of a negative feedback loop. As a result, Wip1 functions to abrogate cell cycle checkpoints and inhibit senescence, apoptosis, DNA repair, and the production of inflammatory cytokines. Furthermore, Wip1 is overexpressed in several types of human cancers and has oncogenic functions. The regulation of Wip1, the role of Wip1 in stress signaling, and the cooperation of Wip1 with oncogenes in promoting tumorigenesis will be discussed in this review. C1 [Cha, Hyukjin; Fornace, Albert J., Jr.] Georgetown Univ, Dept Biochem & Mol & Cell Biol, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. [Lowe, Julie] Natl Inst Environm & Hlth Sci, Chromosome Stabil Grp, Mol Genet Lab, Res Triangle Pk, NC USA. [Cha, Hyukjin; Lee, Mi-Ok] Sogang Univ, Dept Life Sci, Seoul, South Korea. [Mazur, Sharlyn J.; Appella, Ettore] NCI, Cell Biol Lab, CCR, Bethesda, MD 20892 USA. [Fornace, Albert J., Jr.] Dankook Univ, Dept Nanobiomed Sci, Chungnam 330714, South Korea. [Fornace, Albert J., Jr.] Dankook Univ, WCU Res Ctr Nanobiomed Sci, Chungnam 330714, South Korea. RP Fornace, AJ (reprint author), Georgetown Univ, Dept Biochem & Mol & Cell Biol, Lombardi Comprehens Canc Ctr, Room E504 Res Bldg,3970 Reservoir Rd,NW, Washington, DC 20057 USA. EM af294@georgetown.edu OI Fornace, Albert/0000-0001-9695-085X FU NASA [NNJ06ZSA001N, NNX09AU95G]; World Class University; Ministry of Education, Science and Technology through the National Research Foundation of Korea [R31-10069]; NIEHS; NCI; Korea Science and Engineering Foundation (KOSEF) [201131076]; Priority Research Centers [2010-0028297] FX The authors would like to acknowledge support by NASA NNJ06ZSA001N (AJF), NNX09AU95G (AJF), World Class University program funded by the Ministry of Education, Science and Technology through the National Research Foundation of Korea(R31-10069) (AJF), the NIEHS (JL) and NCI (EA and SJM) intramural programs, and the Korea Science and Engineering Foundation (KOSEF) (201131076) (HC and MOL) and the Priority Research Centers Program (2010-0028297) (HC and MOL). NR 109 TC 39 Z9 40 U1 1 U2 24 PU FRONTIERS IN BIOSCIENCE INC PI IRVINE PA 16471 SCIENTIFIC WAY, IRVINE, CA 92618 USA SN 1093-9946 J9 FRONT BIOSCI-LANDMRK JI Front. Biosci. PD JAN 1 PY 2012 VL 17 BP 1480 EP 1498 DI 10.2741/3999 PG 19 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 889DM UT WOS:000300053700019 PM 22201816 ER PT J AU Phang, JM Liu, W AF Phang, James M. Liu, Wei TI Proline metabolism and cancer SO FRONTIERS IN BIOSCIENCE-LANDMARK LA English DT Article DE Apoptosis; Autophagy; Metabolic stress; Survival; Review ID PPAR-GAMMA; MATRIX METALLOPROTEINASES; GENE-EXPRESSION; TUMOR SUPPRESSORS; OXIDIZED LDL; OXIDASE; APOPTOSIS; STRESS; ACTIVATION; GENERATION AB Proline plays a special role in cancer metabolism. Proline oxidase (POX), a.k.a. proline dehydrogenase (PRODH), is among a few genes induced rapidly and robustly by P53, the tumor suppressor. Ectopic expression of POX under control of tet-off promoter initiated mitochondrial apoptosis. The mechanism activated by POX is mediated by its production of ROS. In immunodeficient mice, POX overexpression markedly retarded growth of xenograft tumors. In human tumors of the digestive tract and kidney, POX was markedly decreased, suggesting that the suppressive effect of POX was downregulated. This was not due to POX gene mutations or hypermethylation. Instead, a microRNA, miR-23b*, expressed at high levels in tumors, was a potent inhibitor of POX expression. Furthermore, antagomirs of miR-23b* reversed the downregulated expression of POX and its tumor-suppressive effect, thereby providing a therapeutic strategy. POX not only responds to genotoxic stress, but also to inflammatory and metabolic stress. Depending on microenvironmental and temporal factors, POX can mediate oppositely-directed responses-programmed cell death, on the one hand, and survival, on the other. C1 [Phang, James M.; Liu, Wei] NCI Frederick, Metab & Canc Susceptibil Sect, Comparat Carcinogenesis Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Phang, JM (reprint author), NCI Frederick, Metab & Canc Susceptibil Sect, Comparat Carcinogenesis Lab, Ctr Canc Res, Frederick, MD 21702 USA. EM phangj@mail.nih.gov RI liu, wei /E-7340-2012 FU NIH, National Cancer Institute, Center for Cancer Research; National Cancer Institute, NIH [HHSN27612080001] FX This review was adapted from the Keynote Address given at the 3rd International Symposium on Proline Metabolism held in Lincoln, Nebraska, November 7-9, 2010. Organizers of the meeting were Donald Becker, U. of Nebraska-Lincoln, and John Tanner, U. of Missouri-Columbia. The work was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This project also has been funded in part with Federal funds from the National Cancer Institute, NIH, under contract no. HHSN27612080001. The content of this review does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. government. We thank Dr. Anna Maciag for her reading of the manuscript. NR 64 TC 27 Z9 28 U1 1 U2 22 PU FRONTIERS IN BIOSCIENCE INC PI IRVINE PA 16471 SCIENTIFIC WAY, IRVINE, CA 92618 USA SN 1093-9946 J9 FRONT BIOSCI-LANDMRK JI Front. Biosci. PD JAN 1 PY 2012 VL 17 BP 1835 EP 1845 DI 10.2741/4022 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 889DT UT WOS:000300054400017 PM 22201839 ER PT J AU Panzarin, V Fusaro, A Monne, I Cappellozza, E Patarnello, P Bovo, G Capua, I Holmes, EC Cattoli, G AF Panzarin, Valentina Fusaro, Alice Monne, Isabella Cappellozza, Elisabetta Patarnello, Pierpaolo Bovo, Giuseppe Capua, Ilaria Holmes, Edward C. Cattoli, Giovanni TI Molecular epidemiology and evolutionary dynamics of betanodavirus in southern Europe SO INFECTION GENETICS AND EVOLUTION LA English DT Article DE Betanodavirus; Phylogeny; Evolution; Reassortment; Natural selection ID LATES-CALCARIFER BLOCH; COAT PROTEIN GENE; NERVOUS-NECROSIS-VIRUS; WILD MARINE FISH; PHYLOGENETIC ANALYSIS; DICENTRARCHUS-LABRAX; SEA-BASS; GENOMIC CLASSIFICATION; VIRAL ENCEPHALOPATHY; PISCINE NEUROPATHY AB Viral encephalopathy and retinopathy (VER) is one of the most devastating diseases for marine aquaculture, and similarly represents a threat to wild fish populations because of its high infectivity and broad host range. Betanodavirus, the causative agent of VER, is a small non-enveloped virus with a bipartite RNA genome comprising the RNA1 and RNA2 segments. We partially sequenced both RNA1 and RNA2 from 120 viral strains isolated from 2000 to 2009 in six different countries in Southern Europe. Phylogenetic analysis revealed the presence of the red-spotted grouper nervous necrosis virus (RGNNV) (n = 96) and striped jack nervous necrosis virus (SJNNV) (n = 1) genotypes in Southern Europe, with 23/120 samples classified as RGNNV/SJNNV reassortants. Viruses sampled from individual countries tended to cluster together suggesting a major geographic subdivision among betanodaviruses, although some phylogenetic evidence for viral gene flow was also obtained. Rates of nucleotide substitution were similar to those observed in a broad array of RNA viruses, and revealed a significantly higher evolutionary rate in the polymerase compared to the coat protein gene. This may reflect temperature adaptation of betanodaviruses, although a site-specific analysis of selection pressures identified relatively few selected sites in either gene. Overall, our analyses yielded novel data on the evolutionary dynamics and phylogeography of betanodaviruses and therein provides a more complete understanding of the distribution and evolution of different genotypes in Southern Europe. (C) 2011 Elsevier B.V. All rights reserved. C1 [Panzarin, Valentina; Fusaro, Alice; Monne, Isabella; Capua, Ilaria; Cattoli, Giovanni] Ist Zooprofilatt Sperimentale Venezie, Div Biomed Sci, Res & Innovat Dept, I-35020 Legnaro, PD, Italy. [Cappellozza, Elisabetta; Bovo, Giuseppe] Ist Zooprofilatt Sperimentale Venezie, OIE Reference Lab Viral Encephalopathy & Retinopa, Fish & Shellfish Pathol Dept, I-35020 Legnaro, PD, Italy. [Patarnello, Pierpaolo] Vet Fishpathologist Private Consultant, I-73100 Lecce, Italy. [Holmes, Edward C.] Penn State Univ, Mueller Lab, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Panzarin, V (reprint author), Ist Zooprofilatt Sperimentale Venezie, Div Biomed Sci, Res & Innovat Dept, Viale Univ 10, I-35020 Legnaro, PD, Italy. EM vpanzarin@izsvenezie.it OI Fusaro, Alice/0000-0002-8213-5472; Holmes, Edward/0000-0001-9596-3552 FU Italian Ministry of Health [RC IZSVe 02/06, RC IZSVe 07/10]; Italian Ministry of Agricultural, Food and Forestry Policies FX This study was supported by the Italian Ministry of Health (RC IZSVe 02/06, RC IZSVe 07/10) and the Italian Ministry of Agricultural, Food and Forestry Policies. The authors thank Erika Rampazzo and Rosita Quartesan for their technical support, and Dr. Paolo Antonetti and Dr. Carlos Zarza Araque for providing fish samples. NR 49 TC 33 Z9 34 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-1348 J9 INFECT GENET EVOL JI Infect. Genet. Evol. PD JAN PY 2012 VL 12 IS 1 BP 63 EP 70 DI 10.1016/j.meegid.2011.10.007 PG 8 WC Infectious Diseases SC Infectious Diseases GA 882YK UT WOS:000299599600008 PM 22036789 ER PT J AU Satou, N Ishihara, K Hiratsuka, M Tanaka, H Endo, Y Saito, S Iwakura, Y Leonard, WJ Hirasawa, N AF Satou, Nozomi Ishihara, Kenji Hiratsuka, Masahiro Tanaka, Hiroyuki Endo, Yasuo Saito, Saburo Iwakura, Yoichiro Leonard, Warren J. Hirasawa, Noriyasu TI Induction of Thymic Stromal Lymphopoietin Production by Xylene and Exacerbation of Picryl Chloride-Induced Allergic Inflammation in Mice SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article DE Allergic inflammation; Thymic stromal lymphopoietin; Xylene ID HUMAN EPITHELIAL-CELLS; DENDRITIC CELLS; OX40 LIGAND; MAST-CELLS; TSLP; EXPRESSION; DISEASE; SKIN; DERMATITIS; PATHWAY AB Background: Some chemical compounds in the environment worsen allergic inflammation. In this study, we examined whether organic solvents induce the production of thymic stromal lymphopoietin (TSLP) which elicits Th2-type immune responses. Methods: Organic solvents were painted on the earlobes of BALB/c mice. The expression of TSLP in the ear was determined by ELISA. Results: Xylene and toluene, but not chloroform or ethyl acetate, induced the expression of mRNA for TSLP in the earlobe tissue. Among the aromatic compounds, xylene, especially m-xylene, and trimethylbenzene caused apparent TSLP production. The level of TSLP in the xylene-treated earlobes reached a maximum at 24 h, and TSLP was expressed in epithelial tissues. Production of TSLP was unaffected in mast cell-deficient W/W-v mice but apparently diminished in TNF-alpha knockout mice and IL-4 receptor knockout mice. Repeated painting of xylene for 7 days induced an increase in the weight of cervical lymph nodes and expression of OX40 ligand, both of which were inhibited in TSLP receptor knockout mice. Xylene promoted the picryl chloride-induced thickening of the ear and IL-4 production, which were reversed in TSLP receptor knockout mice. Conclusion: Xylene induced TSLP production, resulting in an exacerbation of allergic inflammation. Thus, xylene might be a good tool for examining the roles of TSLP in eliciting allergy in experimental animals. Copyright (C) 2011 S. Karger AG, Basel C1 [Hirasawa, Noriyasu] Tohoku Univ, Grad Sch Pharmaceut Sci, Aoba Ku, Sendai, Miyagi 9808578, Japan. [Ishihara, Kenji] Ibaraki Univ, Fac Educ, Mito, Ibaraki, Japan. [Endo, Yasuo] Tohoku Univ, Grad Sch Dent, Sendai, Miyagi 9808578, Japan. [Tanaka, Hiroyuki] Gifu Pharmaceut Univ, Dept Bioact Mol, Gifu, Japan. [Saito, Saburo] Jikei Univ, Inst DNA Med, Sch Med, Dept Mol Immunol, Tokyo, Japan. [Iwakura, Yoichiro] Univ Tokyo, Inst Med Sci, Lab Anim Res Ctr, Tokyo 108, Japan. [Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Hirasawa, N (reprint author), Tohoku Univ, Grad Sch Pharmaceut Sci, Aoba Ku, 6-3 Aoba Aramaki, Sendai, Miyagi 9808578, Japan. EM hirasawa@mail.pharm.tohoku.ac.jp RI Iwakura, Yoichiro/E-5457-2011 OI Iwakura, Yoichiro/0000-0002-9934-5775 FU Long Range Research Initiative (LRI) by the Japan Chemical Industry Association (JCIA); Japan Society for the Promotion of Science [22659025]; Division of Intramural Research, National Heart, Lung, and Blood Institute, NIH FX This study was supported in part through a grant of the Long Range Research Initiative (LRI) by the Japan Chemical Industry Association (JCIA), Grant-in-Aid for Challenging Exploratory Research (22659025) from the Japan Society for the Promotion of Science, and by the Division of Intramural Research, National Heart, Lung, and Blood Institute, NIH. NR 25 TC 11 Z9 11 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PY 2012 VL 157 IS 2 BP 194 EP 201 DI 10.1159/000327545 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 890HJ UT WOS:000300135400010 PM 21986191 ER PT J AU Gerrish, A Russo, G Richards, A Moskvina, V Ivanov, D Harold, D Sims, R Abraham, R Hollingworth, P Chapman, J Hamshere, M Pahwa, JS Dowzell, K Williams, A Jones, N Thomas, C Stretton, A Morgan, AR Lovestone, S Powell, J Proitsi, P Lupton, MK Brayne, C Rubinsztein, DC Gill, M Lawlor, B Lynch, A Morgan, K Brown, KS Passmore, PA Craig, D McGuinness, B Todd, S Johnston, JA Holmes, C Mann, D Smith, AD Love, S Kehoe, PG Hardy, J Mead, S Fox, N Rossor, M Collinge, J Maier, W Jessen, F Kolsch, H Heun, R Schurmann, B van den Bussche, H Heuser, I Kornhuber, J Wiltfang, J Dichgans, M Frolich, L Hampel, H Hull, M Rujescu, D Goate, AM Kauwe, JSK Cruchaga, C Nowotny, P Morris, JC Mayo, K Livingston, G Bass, NJ Gurling, H McQuillin, A Gwilliam, R Deloukas, P Davies, G Harris, SE Starr, JM Deary, IJ Al-Chalabi, A Shaw, CE Tsolaki, M Singleton, AB Guerreiro, R Muhleisen, TW Noethen, MM Moebus, S Jockel, KH Klopp, N Wichmann, HE Carrasquillo, MM Pankratz, VS Younkin, SG Jones, L Holmans, PA O'Donovan, MC Owen, MJ Williams, J AF Gerrish, Amy Russo, Giancarlo Richards, Alexander Moskvina, Valentina Ivanov, Dobril Harold, Denise Sims, Rebecca Abraham, Richard Hollingworth, Paul Chapman, Jade Hamshere, Marian Pahwa, Jaspreet Singh Dowzell, Kimberley Williams, Amy Jones, Nicola Thomas, Charlene Stretton, Alexandra Morgan, Angharad R. Lovestone, Simon Powell, John Proitsi, Petroula Lupton, Michelle K. Brayne, Carol Rubinsztein, David C. Gill, Michael Lawlor, Brian Lynch, Aoibhinn Morgan, Kevin Brown, Kristelle S. Passmore, Peter A. Craig, David McGuinness, Bernadette Todd, Stephen Johnston, Janet A. Holmes, Clive Mann, David Smith, A. David Love, Seth Kehoe, Patrick G. Hardy, John Mead, Simon Fox, Nick Rossor, Martin Collinge, John Maier, Wolfgang Jessen, Frank Koelsch, Heike Heun, Reinhard Schuermann, Britta van den Bussche, Hendrik Heuser, Isabella Kornhuber, Johannes Wiltfang, Jens Dichgans, Martin Froelich, Lutz Hampel, Harald Huell, Michael Rujescu, Dan Goate, Alison M. Kauwe, John S. K. Cruchaga, Carlos Nowotny, Petra Morris, John C. Mayo, Kevin Livingston, Gill Bass, Nicholas J. Gurling, Hugh McQuillin, Andrew Gwilliam, Rhian Deloukas, Panagiotis Davies, Gail Harris, Sarah E. Starr, John M. Deary, Ian J. Al-Chalabi, Ammar Shaw, Christopher E. Tsolaki, Magda Singleton, Andrew B. Guerreiro, Rita Muehleisen, Thomas W. Noethen, Markus M. Moebus, Susanne Joeckel, Karl-Heinz Klopp, Norman Wichmann, H-Erich Carrasquillo, Minerva M. Pankratz, V. Shane Younkin, Steven G. Jones, Lesley Holmans, Peter A. O'Donovan, Michael C. Owen, Michael J. Williams, Julie TI The Role of Variation at A beta PP, PSEN1, PSEN2, and MAPT in Late Onset Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; amyloid-beta protein precursor; genetics; human; MAPT protein; PSEN1 protein; PSEN2 protein ID GENOME-WIDE ASSOCIATION; PROGRESSIVE SUPRANUCLEAR PALSY; COMMON VARIANTS; CORTICOBASAL DEGENERATION; IDENTIFIES VARIANTS; HAN CHINESE; TAU GENE; RISK; HAPLOTYPE; LOCUS AB Rare mutations in A beta PP, PSEN1, and PSEN2 cause uncommon early onset forms of Alzheimer's disease (AD), and common variants in MAPT are associated with risk of other neurodegenerative disorders. We sought to establish whether common genetic variation in these genes confer risk to the common form of AD which occurs later in life (> 65 years). We therefore tested single-nucleotide polymorphisms at these loci for association with late-onset AD (LOAD) in a large case-control sample consisting of 3,940 cases and 13,373 controls. Single-marker analysis did not identify any variants that reached genome-wide significance, a result which is supported by other recent genome-wide association studies. However, we did observe a significant association at the MAPT locus using a gene-wide approach (p = 0.009). We also observed suggestive association between AD and the marker rs9468, which defines the H1 haplotype, an extended haplotype that spans the MAPT gene and has previously been implicated in other neurodegenerative disorders including Parkinson's disease, progressive supranuclear palsy, and corticobasal degeneration. In summary common variants at A beta PP, PSEN1, and PSEN2 and MAPT are unlikely to make strong contributions to susceptibility for LOAD. However, the gene-wide effect observed at MAPT indicates a possible contribution to disease risk which requires further study. C1 [Gerrish, Amy; Russo, Giancarlo; Richards, Alexander; Moskvina, Valentina; Ivanov, Dobril; Harold, Denise; Sims, Rebecca; Abraham, Richard; Hollingworth, Paul; Chapman, Jade; Hamshere, Marian; Pahwa, Jaspreet Singh; Dowzell, Kimberley; Williams, Amy; Jones, Nicola; Thomas, Charlene; Stretton, Alexandra; Morgan, Angharad R.; Jones, Lesley; Holmans, Peter A.; O'Donovan, Michael C.; Owen, Michael J.; Williams, Julie] Cardiff Univ, MRC Ctr Neuropsychiat Genet & Genom, Dept Psychol Med & Neurol, Sch Med,Neurosci & Mental Hlth Res Inst, Cardiff CF14 4XN, S Glam, Wales. [Powell, John; Proitsi, Petroula; Lupton, Michelle K.] Kings Coll London, Inst Psychiat, Dept Neurosci, London WC2R 2LS, England. [Brayne, Carol] Univ Cambridge, Inst Publ Hlth, Cambridge, England. [Rubinsztein, David C.] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England. [Gill, Michael; Lawlor, Brian; Lynch, Aoibhinn] St James Hosp, Mercers Inst Res Aging, Dublin 8, Ireland. [Gill, Michael; Lawlor, Brian; Lynch, Aoibhinn] Trinity Coll Dublin, Dublin, Ireland. [Morgan, Kevin; Brown, Kristelle S.] Univ Nottingham, Queens Med Ctr, Sch Mol Med Sci, Human Genet Grp, Nottingham NG7 2RD, England. [Passmore, Peter A.; Craig, David; McGuinness, Bernadette; Todd, Stephen; Johnston, Janet A.] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Ctr Publ Hlth, Ageing Grp, Belfast BT7 1NN, Antrim, North Ireland. [Holmes, Clive] Univ Southampton, Sch Med, Div Clin Neurosci, Southampton, Hants, England. [Mann, David] Univ Manchester, Sch Community Based Med, Neurodegenerat & Mental Hlth Res Grp, Salford, Lancs, England. [Smith, A. David] Univ Oxford, John Radcliffe Hosp, Oxford Project Investigate Memory & Ageing, Oxford OX3 9DU, England. [Love, Seth; Kehoe, Patrick G.] Univ Bristol, Frenchay Hosp, Inst Clin Neurosci, Dementia Res Grp, Bristol, Avon, England. [Hardy, John] Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. [Hardy, John] Inst Neurol, Reta Lilla Weston Labs, London WC1N 3BG, England. [Mead, Simon; Collinge, John] UCL, Inst Neurol, MRC Prion Unit, London WC1E 6BT, England. [Mead, Simon; Collinge, John] UCL, Inst Neurol, Dept Neurodegenerat Dis, London WC1E 6BT, England. [Fox, Nick; Rossor, Martin] UCL Inst Neurol, Dept Neurodegenerat Dis, Dementia Res Ctr, London, England. [Maier, Wolfgang; Jessen, Frank; Koelsch, Heike; Heun, Reinhard; Schuermann, Britta] Univ Bonn, Dept Psychiat, Bonn, Germany. [Heun, Reinhard] Royal Derby Hosp, Radbourne Unit, Derby, England. [van den Bussche, Hendrik] Univ Med Ctr Hamburg Eppendorf, Inst Primary Med Care, Hamburg, Germany. [Heuser, Isabella] Charite, Dept Psychiat, Berlin, Germany. [Kornhuber, Johannes] Univ Erlangen Nurnberg, Dept Psychiat & Psychotherapy, Erlangen, Germany. [Wiltfang, Jens] Univ Duisburg Essen, Dept Psychiat & Psychotherapy, LVR Hosp Essen, Duisburg, Germany. [Dichgans, Martin] Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany. [Dichgans, Martin] Klinikum Univ Munchen, Dept Neurol, Munich, Germany. [Froelich, Lutz] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Geriatr Psychiat, D-6800 Mannheim, Germany. [Hampel, Harald] Goethe Univ Frankfurt, Dept Psychiat Psychosomat Med & Psychotherapy, Frankfurt, Germany. [Huell, Michael; Rujescu, Dan] Univ Munich, Dept Psychiat, D-8000 Munich, Germany. [Goate, Alison M.; Cruchaga, Carlos; Nowotny, Petra; Morris, John C.; Mayo, Kevin] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Goate, Alison M.; Cruchaga, Carlos; Nowotny, Petra; Morris, John C.; Mayo, Kevin] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Goate, Alison M.; Cruchaga, Carlos; Nowotny, Petra; Morris, John C.; Mayo, Kevin] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [Kauwe, John S. K.] Brigham Young Univ, Dept Biol, Provo, UT 84602 USA. [Livingston, Gill; Bass, Nicholas J.; Gurling, Hugh; McQuillin, Andrew] UCL, Mental Hlth Unit, London, England. [Gwilliam, Rhian; Deloukas, Panagiotis] Wellcome Trust Sanger Inst, Cambridge, England. [Davies, Gail; Harris, Sarah E.; Starr, John M.; Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland. [Davies, Gail; Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland. [Harris, Sarah E.] Univ Edinburgh, Mol Med Ctr, Edinburgh, Midlothian, Scotland. [Starr, John M.] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland. [Al-Chalabi, Ammar; Shaw, Christopher E.] Kings Coll London, Inst Psychiat, Dept Clin Neurosci, MRC Ctr Neurodegenerat Res, London WC2R 2LS, England. [Tsolaki, Magda] Aristotle Univ Thessaloniki, Dept Neurol 3, GR-54006 Thessaloniki, Greece. [Singleton, Andrew B.; Guerreiro, Rita] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany. [Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Inst Human Genet, Bonn, Germany. [Moebus, Susanne; Joeckel, Karl-Heinz] Univ Duisburg Essen, Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany. [Klopp, Norman; Wichmann, H-Erich] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol, Neuherberg, Germany. [Wichmann, H-Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Wichmann, H-Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany. [Carrasquillo, Minerva M.; Younkin, Steven G.] Mayo Clin, Coll Med, Dept Neurosci, Jacksonville, FL 32224 USA. [Pankratz, V. Shane] Mayo Clin & Mayo Fdn, Div Biomed Stat & Informat, Rochester, MN 55905 USA. RP Williams, J (reprint author), Cardiff Univ, MRC Ctr Neuropsychiat Genet & Genom, Dept Psychol Med & Neurol, Sch Med,Neurosci & Mental Hlth Res Inst, Henry Wellcome Bldg,Heath Pk, Cardiff CF14 4XN, S Glam, Wales. EM WilliamsJ@cardiff.ac.uk RI Kornhuber, Johannes/B-9613-2014; Fox, Nick/B-1319-2009; Holmans, Peter/F-4518-2015; Smith, Anthony/A-4233-2010; McQuillin, Andrew/C-1623-2008; Al-Chalabi, Ammar/E-5361-2010; Powell, John/G-4412-2011; Hull, Michael/F-2618-2012; Gurling, Hugh/A-5029-2010; Hardy, John/C-2451-2009; Love, Seth/E-6545-2012; Jessen, Frank/E-7655-2012; Guerreiro, Rita/A-1327-2011; Singleton, Andrew/C-3010-2009; Kauwe, John/B-2034-2009; Deloukas, Panos/B-2922-2013; Mead, Simon/E-9414-2011; Deary, Ian/C-6297-2009; Livingston, Gill/C-7081-2008 OI Kornhuber, Johannes/0000-0002-8096-3987; Fox, Nick/0000-0002-6660-657X; Holmans, Peter/0000-0003-0870-9412; Smith, Anthony/0000-0002-1095-6722; McQuillin, Andrew/0000-0003-1567-2240; O'Donovan, Michael/0000-0001-7073-2379; Gill, Michael/0000-0003-0206-5337; Wiltfang, Jens/0000-0003-1492-5330; Harold, Denise/0000-0001-5195-0143; Ivanov, Dobril/0000-0001-6271-6301; Al-Chalabi, Ammar/0000-0002-4924-7712; Powell, John/0000-0001-6124-439X; Kauwe, John/0000-0001-8641-2468; Deloukas, Panos/0000-0001-9251-070X; Mead, Simon/0000-0002-4326-1468; FU Wellcome Trust; Medical Research Council (MRC, UK); Alzheimer's Research UK (ARUK); Welsh Assembly Government; Alzheimer's Society; ARUK Ulster Garden Villages; Northern Ireland Research and Development Office; Royal College of Physicians-Dunhill Medical Trust; American Federation for Aging Research for the Paul Beeson Career Development Awards; Trinity College group; Bristol Research into Alzheimer's and Care of the Elderly; Oxford Project; Motor Neurone Disease Association; MRC; US National Institutes of Health (NIH); Barnes Jewish Foundation; Charles and Joanne Knight Alzheimer's Research Initiative; NIH; Palumbo Professorship in AD Research; Lundbeck SA; German Federal Ministry of Education and Research (BMBF); Competence Network Dementia and Competence Network Degenerative Dementia; Alfried Krupp von Bohlen und Halbach-Stiftung; Helmholtz Zentrum Munchen; German Research Center for Environmental Health; BMBF; German National Genome Research Network; Munich Center of Health Sciences; Heinz Nixdorf Foundation; US National Institute of Neurological Disorders and Stroke; National Institute on Aging; US National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; National Human Genome Research Institute; National Institute of Child Health and Human Development; Juvenile Diabetes Research Foundation International; UK's Biotechnology and Biological Sciences Research Council (BBSRC); BBSRC; Royal Society; Chief Scientist Office of the Scottish Government; EPSRC; ESRC FX We thank the individuals and families who took part in this research. Cardiff University was supported by the Wellcome Trust, Medical Research Council (MRC, UK), Alzheimer's Research UK (ARUK) and the Welsh Assembly Government. ARUK supported sample collections at the Institute of Psychiatry, the South West Dementia Bank and the Universities of Cambridge, Nottingham, Manchester and Belfast. The Belfast group acknowledges support from the Alzheimer's Society, ARUK Ulster Garden Villages, Northern Ireland Research and Development Office and the Royal College of Physicians-Dunhill Medical Trust. They also acknowledge the American Federation for Aging Research for the Paul Beeson Career Development Awards in Aging Research Programme for the Island of Ireland. The MRC and Mercer's Institute for Research on Ageing supported the Trinity College group. The South West Dementia Brain Bank acknowledges support from Bristol Research into Alzheimer's and Care of the Elderly. The Charles Wolfson Charitable Trust supported the Oxford Project to Investigate Memory and Ageing group. A. Al-Chalabi and C. Shaw thank the Motor Neurone Disease Association and MRC for support. D. C. R. is a Wellcome Trust Senior Clinical Research Fellow. Washington University was funded by US National Institutes of Health (NIH) grants, the Barnes Jewish Foundation and the Charles and Joanne Knight Alzheimer's Research Initiative. The Mayo GWAS was supported by NIH grants, the Robert and Clarice Smith and Abigail Van Buren AD Research Program, and the Palumbo Professorship in AD Research. Patient recruitment for the MRC Prion Unit/University College London Department of Neurodegenerative Disease collection was supported by the UCL Hospital/UCL Biomedical Centre. London and the South East Region (LASER)-AD was funded by Lundbeck SA. The Bonn groupwas supported by the German Federal Ministry of Education and Research (BMBF), Competence Network Dementia and Competence Network Degenerative Dementia, and by the Alfried Krupp von Bohlen und Halbach-Stiftung. The Kooperative gesundheitsforschung in der region Augsburg (KORA) F4 studies were financed by Helmholtz Zentrum Munchen, the German Research Center for Environmental Health, BMBF, the German National Genome Research Network and the Munich Center of Health Sciences. The Heinz Nixdorf Recall cohort was funded by the Heinz Nixdorf Foundation (G. Schmidt, chairman) and BMBF. Coriell Cell Repositories is supported by the US National Institute of Neurological Disorders and Stroke and the Intramural Research Program of the National Institute on Aging. We acknowledge use of DNA from the 1958 Birth Cohort collection and National Blood Service, funded by the MRC and the Wellcome Trust, which was genotyped by the Wellcome Trust Case Control Consortium and the Type-1 Diabetes Genetics Consortium, sponsored by the US National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Allergy and Infectious Diseases, National Human Genome Research Institute, National Institute of Child Health and Human Development and Juvenile Diabetes Research Foundation International. Genotyping of the Lothian Birth Cohort (LBC) 1921 and 1936 was supported by the UK's Biotechnology and Biological Sciences Research Council (BBSRC). Recruitment and phenotype collection in the Lothian Birth Cohort 1921 was supported by the BBSRC, The Royal Society, and The Chief Scientist Office of the Scottish Government.; Phenotype collection in the Lothian Birth Cohort 1936 was supported by Research Into Ageing (which continues as part of Age UK's TheDisconnected Mind project). The LBC work was undertaken in The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (G0700704/84698). Funding from the BBSRC, EPSRC, ESRC and MRC is gratefully acknowledged. We thank R. Brown, J. Landers, D. Warden, D. Lehmann, N. Leigh, J. Uphill, J. Beck, T. Campbell, S. Klier, G. Adamson, J. Wyatt, M. L. Perez, T. Meitinger, P. Lichtner, G. Eckstein, N. Graff-Radford, R. Petersen, D. Dickson, G. Fischer, H. Bickel, M. Hull, H. Jahn, H. Kaduszkiewicz, C. Luckhaus, S. Riedel-Heller, S. Wolf, S. Weyerer, the Helmholtz Zentrum Munchen genotyping staff and the NIMH AD Genetics Initiative. We thank Advanced Research Computing@Cardiff (ARCCA), which facilitated data analysis. NR 46 TC 29 Z9 29 U1 0 U2 14 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2012 VL 28 IS 2 BP 377 EP 387 DI 10.3233/JAD-2011-110824 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 888MV UT WOS:000300008800012 PM 22027014 ER PT J AU Gage, JC Sadorra, M LaMere, BJ Kail, R Aldrich, C Kinney, W Fetterman, B Lorey, T Schiffman, M Castleg, PE AF Gage, Julia C. Sadorra, Mark LaMere, Brandon J. Kail, Randi Aldrich, Carrie Kinney, Walter Fetterman, Barbara Lorey, Thomas Schiffman, Mark Castleg, Philip E. CA Pap Cohort Study Grp TI Comparison of the cobas Human Papillomavirus (HPV) Test with the Hybrid Capture 2 and Linear Array HPV DNA Tests SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID CERVICAL INTRAEPITHELIAL NEOPLASIA; CARCINOGENIC HUMAN-PAPILLOMAVIRUS; CLINICAL-PRACTICE; WOMEN; CYTOLOGY; CANCER; RISK; HYBRID-CAPTURE-2; PRECANCER; GRADE AB The cobas human papillomavirus (HPV) test (cobas) was recently approved by the U.S. Food and Drug Administration (FDA) and identifies HPV16 and HPV18 separately as well as detecting a pool of 11 HR-HPV genotypes (HPV31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -68) and also HPV66. We compared cobas, Linear Array (LA), and Hybrid Capture 2 (HC2) assays for detection of carcinogenic HPV DNA, and cobas and LA for detection of HPV16 and HPV18 DNA, among the first 1,852 women enrolled in the HPV Persistence and Progression Cohort (PaP Cohort) study. Specimens were tested by all 3 assays 1 year after an HC2-positive result. In 1,824 specimens with cobas results, cobas had an 85.9% agreement with HC2 and 91.0% agreement with LA for carcinogenic HPV detection. When results between cobas and HC2 disagreed, cobas tended to call more women HPV positive (P < 0.01). Categorizing cobas and LA results hierarchically according to cancer risk (HPV16, HPV18, other carcinogenic HPV genotypes, or carcinogen negative), there was a 90% agreement for all categories of HPV (n = 1,824). We found good agreement between the two U.S. FDA-approved HPV tests, with discrepancies between the two assays due to specific characteristics of the individual assays. Additional studies are needed to compare HC2 and cobas for detecting and predicting CIN3 to understand the clinical implications of the discrepant test results between the two tests. C1 [Gage, Julia C.; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Sadorra, Mark; Kail, Randi] Roche Mol Syst, Alameda, CA USA. [Aldrich, Carrie] Ventana Med Syst Inc, Tucson, AZ USA. [LaMere, Brandon J.] Kaiser Permanente Med Care Program, Womens Hlth Res Inst, Oakland, CA USA. [Kinney, Walter] Kaiser Permanente No Calif, Reg Lab, Berkeley, CA USA. [Fetterman, Barbara; Lorey, Thomas] Kaiser Permanente Med Care Program, Div Gynecol Oncol, Oakland, CA USA. [Castleg, Philip E.] Amer Soc Clin Pathologists, Washington, DC USA. RP Gage, JC (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. EM gagej@mail.nih.gov NR 16 TC 25 Z9 26 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JAN PY 2012 VL 50 IS 1 BP 61 EP 65 DI 10.1128/JCM.05989-11 PG 5 WC Microbiology SC Microbiology GA 888IH UT WOS:000299996600013 PM 22075592 ER PT J AU Kawamoto, EM Lima, LS Munhoz, CD Yshii, LM Kinoshita, PF Amaral, FG Pestana, RRF Orellana, AMM Cipolla-Neto, J Britto, LRG Avellar, MCW Rossoni, LV Scavone, C AF Kawamoto, E. M. Lima, L. S. Munhoz, C. D. Yshii, L. M. Kinoshita, P. F. Amaral, F. G. Pestana, R. R. F. Orellana, A. M. M. Cipolla-Neto, J. Britto, L. R. G. Avellar, M. C. W. Rossoni, L. V. Scavone, C. TI Influence of N-methyl-D-aspartate receptors on ouabain activation of nuclear factor-kappa B in the rat hippocampus SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE glutamate; NF-kappa B; Na; K-ATPase; N-methyl-D-aspartate; ouabain ID ENDOGENOUS CARDIOTONIC STEROIDS; GENERATES CALCIUM OSCILLATIONS; K+-ATPASE INHIBITOR; NA+/K+-ATPASE; ADRENOCORTICAL-CELLS; NMDA RECEPTOR; ADRENAL-GLAND; NITRIC-OXIDE; IN-VIVO; GLUTAMATE AB It has been shown that ouabain (OUA) can activate the Na,K-ATPase complex and mediate intracellular signaling in the central nervous system (CNS). Inflammatory stimulus increases glutamatergic transmission, especially at N-methyl-D-aspartate (NMDA) receptors, which are usually coupled to the activation of nitric oxide synthase (NOS). Nuclear factor-kappa B (NF-kappa B) activation modulates the expression of genes involved in development, plasticity, and inflammation. The present work investigated the effects of OUA on NF-kappa B binding activity in rat hippocampus and the influence of this OUA-Na,K-ATPase signaling cascade in NMDA-mediated NF-kappa B activation. The findings presented here are the first report indicating that intrahippocampal administration of OUA, in a concentration that did not alter Na,K-ATPase or NOS activity, induced an activation of NF-kappa B, leading to increases in brain-derived neurotrophic factor (Bdnf), inducible NOS (iNos), tumor necrosis factor-alpha (Tnf-alpha), and B-cell leukemia/lymphoma 2 (Bcl2) mRNA levels. This response was not linked to any significant signs of neurodegeneration as showed via Fluoro-Jade B and Nissl stain. Intrahippocampal administration of NMDA induced NF alpha B activation and increased NOS and alpha 2/3-Na,K-ATPase activities. NMDA treatment further increased OUA-induced NF-kappa B activation, which was partially blocked by MK-801, an antagonist of NMDA receptor. These results suggest that OUA-induced NF-kappa B activation is at least in part dependent on Na,K-ATPase modulatory action of NMDA receptor in hippocampus. The interaction of these signaling pathways could be associated with biological mechanisms that may underlie the basal homeostatic state linked to the inflammatory signaling cascade in the brain. (c) 2011 Wiley Periodicals, Inc. C1 [Kawamoto, E. M.; Lima, L. S.; Munhoz, C. D.; Yshii, L. M.; Kinoshita, P. F.; Orellana, A. M. M.; Scavone, C.] Univ Sao Paulo, Dept Pharmacol, Inst Biomed Sci, Mol Neuropharmacol Lab, BR-05508900 Sao Paulo, Brazil. [Kawamoto, E. M.] NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. [Amaral, F. G.; Pestana, R. R. F.; Cipolla-Neto, J.; Britto, L. R. G.; Rossoni, L. V.] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508900 Sao Paulo, Brazil. [Avellar, M. C. W.] Univ Fed Sao Paulo, Escola Paulista Med, Dept Pharmacol, Sect Expt Endocrinol, Sao Paulo, Brazil. RP Scavone, C (reprint author), Univ Sao Paulo, Dept Pharmacol, Inst Biomed Sci ICB 1, Avenida Prof Lineu Prestes 1524, BR-05508900 Sao Paulo, Brazil. EM cscavone@icb.usp.br RI Rossoni, Luciana/C-7226-2012; Munhoz, Carolina/I-2118-2012; Avellar, Maria Christina W./E-2865-2013; Fisiologia comparada, Inct/I-2427-2013; Cipolla-Neto, Jose/B-1619-2009; Munhoz, Carolina/N-7219-2014; Kawamoto, Elisa/E-3485-2012; YSHII, Lidia/I-6039-2013; OI Avellar, Maria Christina W./0000-0003-4392-7554; Cipolla-Neto, Jose/0000-0003-3748-3731; Munhoz, Carolina/0000-0002-8656-5234; Kawamoto, Elisa/0000-0001-8637-414X; YSHII, Lidia/0000-0002-1988-6855; Scavone, Cristoforo/0000-0002-1206-0882 FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESP [2003/08989-0]; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-CNPq [485953-2007-2]; Universidade de Sao Paulo FX Contract grant sponsor: Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESP; Contract grant number: 2003/08989-0 (to C.S.); Contract grant sponsor: Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-CNPq; Contract grant number: 485953-2007-2 (to E. M.K.).; E.M.K. and F.G.A. are supported by postdoctoral fellowships from FAPESP; L.M.Y., R.R.F.P., and A.M.M.O. are PhD students and research fellows from FAPESP and CAPES; P.F.K. is an undergraduate student fellow from FAPESP; and L.S.L. is supported by a grant from the Universidade de Sao Paulo. C.S., J.C.N, L.R.G.B., M.C.W.A. and L.V.R. are research fellow from CNPq. The authors declare that, except for income received from a primary employer, no financial support or compensation has been received from any individual or corporate entity over the past 34 years for research or professional service and that no personal financial holdings that could be perceived as constituting a potential conflict of interest. NR 82 TC 15 Z9 15 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JAN PY 2012 VL 90 IS 1 BP 213 EP 228 DI 10.1002/jnr.22745 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 860LZ UT WOS:000297951100019 PM 22006678 ER PT J AU Malek-Khosravi, S Rahimi, Z Rahimi, Z Jalilvand, F Parsian, A AF Malek-Khosravi, Shohreh Rahimi, Zohreh Rahimi, Ziba Jalilvand, Faranak Parsian, Abbas TI Thrombophilic mutations and susceptibility to preeclapmsia in Western Iran SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE Preeclampsia; Factor V Leiden; Prothrombin G20210A; Western Iran ID FACTOR-V-LEIDEN; REDUCTASE GENE VARIANTS; INHERITED THROMBOPHILIAS; PREGNANCY COMPLICATIONS; SEVERE PREECLAMPSIA; POLYMORPHISM; PROTHROMBIN; ASSOCIATION; POPULATION; WOMEN AB The aim of the present study was to investigate the frequency and the possible association between thrombophilic mutations of factor V Leiden (FVL) and prothrombin G20210A with preeclampsia among Kurdish population of Western Iran. We studied 198 women with preeclampsia including 128 women with mild and 70 women with severe forms and 101 healthy pregnant women with uncomplicated pregnancy. Among cases there were 23 women with early onset preeclampsia and 175 cases with late-onset preeclampsia. The sample was genotyped by polymerase chain reaction-restriction fragment-length polymorphism using Mnl I and Hind III for FVL and prothrombin G20210A, respectively. The frequency of heterozygous FVL mutation was 7.6% among all preeclamptic women (8.6% in mild and 5.7% in severe preeclamptic women) and 7.9% in controls (P > 0.05). However, the prevalence of heterozygous FVL were 10.5 and 3.9% among severe preeclamptic women with early onset and late-onset preeclampsia, respectively (P > 0.05). The prevalence of prothrombin G20210A were 1.6, 2.9, and 3% among women with mild preeclamsia, severe preeclampsia and controls, respectively (P > 0.05). The level of serum triglycerides (TG) was significantly higher among women with preeclampsia compared to healthy pregnant women that was not associated with the two thrombophilic mutations. Our results indicate that neither FVL nor prothrombin G20210A could be a risk factor for preeclampsia in our population. However, high prevalence of FVL in preeclamptic women with early onset compared to those with late-onset preeclampsia may suggest a role for this mutation in predisposition to early onset preeclampsia that need to be confirmed with larger sample size. C1 Kermanshah Univ Med Sci, Dept Biochem, Sch Med, Kermanshah, Iran. [Malek-Khosravi, Shohreh; Jalilvand, Faranak] Kermanshah Univ Med Sci, Dept Obstet & Gynecol, Sch Med, Kermanshah, Iran. [Rahimi, Zohreh; Rahimi, Ziba] Kermanshah Univ Med Sci, Med Biol Res Ctr, Kermanshah, Iran. [Parsian, Abbas] NIAAA, Div Neurosci & Behav, NIH, Rockville, MD 20852 USA. RP Rahimi, Z (reprint author), Kermanshah Univ Med Sci, Dept Biochem, Sch Med, Daneshgah Ave,POB 67148-69914, Kermanshah, Iran. EM zrahimi@kums.ac.ir; rahimizus@yahoo.com OI Rahimi, Zohreh/0000-0001-7589-3307 NR 35 TC 7 Z9 9 U1 2 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD JAN PY 2012 VL 33 IS 1 BP 109 EP 115 DI 10.1007/s11239-011-0653-y PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 885JR UT WOS:000299775700016 PM 22068545 ER PT J AU Beydoun, HA Beydoun, MA Wiggins, N Stadtmauer, L AF Beydoun, Hind A. Beydoun, May A. Wiggins, Natasha Stadtmauer, Laurel TI Relationship of obesity-related disturbances with LH/FSH ratio among post-menopausal women in the United States SO MATURITAS LA English DT Article DE Chronic inflammation; Follicular stimulating hormone; Insulin resistance; Luteinizing hormone; Obesity ID POLYCYSTIC-OVARY-SYNDROME; PROSTATE-SPECIFIC ANTIGEN; INSULIN-RESISTANCE; CHRONIC INFLAMMATION; NATIONAL-HEALTH; NONOBESE WOMEN; PATHOGENESIS; METFORMIN; DRUGS AB Objectives: Although luteinizing hormone to follicular stimulating hormone (LH/FSH) ratio is a controversial criterion for identifying a sub-group of infertile women with polycystic ovary syndrome (PCOS) and. abnormalities at the level of the hypothalamic-pituitary-ovarian axis, an elevated LH/FSH ratio is frequently observed in PCOS cases. Obesity and insulin resistance are highly prevalent among PCOS women. To date, no studies have examined the associations of LH/FSH ratio with these co-morbid conditions outside the context of pre- and peri-menopausal PCOS women. The objective of this study is to evaluate whether the LH/FSH ratio is associated with obesity, insulin resistance, metabolic disturbances and chronic inflammation among post-menopausal U.S. women, 35-60 years of age. Study design: Cross-sectional study of 693 women who participated in the 1999-2002 National Health and Nutrition Examination Survey. Main outcome measures: Body mass index, waist circumference, triglycerides, high-density lipoprotein (HDL) cholesterol, systolic and diastolic blood pressures, fasting glucose, metabolic syndrome, Homeostasis Model Assessment for Insulin Resistance and C-reactive protein (CRP). Results: Age- and hysterectomy-adjusted regression models suggest that CRP level is positively associated with LH/FSH ratio and LH/FSH > 1, high glucose level and LH/FSH > 2 are inversely related and HDL < 50 mg/dL is positively associated with both LH/FSH > 1 and LH/FSH > 2. Conclusions: In a nationally representative sample of post-menopausal women, markers of chronic inflammation and dyslipidemia which are characteristics of PCOS-associated morbidities were also significantly associated with LH/FSH ratio, meriting further investigation. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Beydoun, Hind A.] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23501 USA. [Beydoun, May A.] NIA, NIH, Intramural Res Program, Baltimore, MD 21224 USA. [Wiggins, Natasha] ORISE NMPHC, Portsmouth, VA USA. [Stadtmauer, Laurel] Eastern Virginia Med Sch, Jones Inst Reprod Med, Norfolk, VA 23501 USA. RP Beydoun, HA (reprint author), Eastern Virginia Med Sch, Grad Program Publ Hlth, POB 1980, Norfolk, VA 23501 USA. EM baydouha@evms.edu FU NIH, National Institute on Aging FX This research was partly supported by the Intramural Research Program of the NIH, National Institute on Aging. We would like to thank Dr. Melissa Kitner-Triolo and Dr. Alyssa Gamaldo for their thoughtful comments. NR 29 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-5122 J9 MATURITAS JI Maturitas PD JAN PY 2012 VL 71 IS 1 BP 55 EP 61 DI 10.1016/j.maturitas.2011.10.010 PG 7 WC Geriatrics & Gerontology; Obstetrics & Gynecology SC Geriatrics & Gerontology; Obstetrics & Gynecology GA 888CO UT WOS:000299981600012 PM 22088801 ER PT J AU Marugan, JJ Huang, WW Motabar, O Zheng, W Xiao, JB Patnaik, S Southall, N Westbroek, W Lea, WA Simeonov, A Goldin, E DeBernardi, MA Sidransky, E AF Marugan, Juan Jose Huang, Wenwei Motabar, Omid Zheng, Wei Xiao, Jingbo Patnaik, Samarjit Southall, Noel Westbroek, Wendy Lea, Wendy A. Simeonov, Anton Goldin, Ehud DeBernardi, Maria A. Sidransky, Ellen TI Non-iminosugar glucocerebrosidase small molecule chaperones SO MEDCHEMCOMM LA English DT Article ID LYSOSOMAL STORAGE DISORDERS; GAUCHER-DISEASE; PHARMACOLOGICAL CHAPERONES; SELECTIVITY; STRATEGIES; INHIBITORS; INCREASE; ENZYME AB Small molecule chaperones are a promising therapeutic approach for the Lysosomal Storage Disorders (LSDs). Here, we report the discovery of a new series of non-iminosugar glucocerebrosidase inhibitors with chaperone capacity, and describe their structure activity relationship (SAR), selectivity, cell activity and phamacokinetics. C1 [Marugan, Juan Jose; Huang, Wenwei; Zheng, Wei; Xiao, Jingbo; Patnaik, Samarjit; Southall, Noel; Lea, Wendy A.; Simeonov, Anton] NHGRI, NIH Chem Genom Ctr, NIH, Rockville, MD 20850 USA. [Motabar, Omid; Westbroek, Wendy; Goldin, Ehud; Sidransky, Ellen] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [DeBernardi, Maria A.] Johns Hopkins Univ, Microscopy Ctr, Rockville, MD 20850 USA. RP Marugan, JJ (reprint author), NHGRI, NIH Chem Genom Ctr, NIH, 9800 Med Ctr Dr, Rockville, MD 20850 USA. EM maruganj@mail.nih.gov RI Southall, Noel/H-8991-2012; OI Southall, Noel/0000-0003-4500-880X; Zheng, Wei/0000-0003-1034-0757 FU Molecular Libraries Initiative of the NIH Roadmap for Medical Research [U54MH084681]; National Human Genome Research Institute, National Institutes of Health FX We thank Xianlong Chu, Xin Chen, Ruihong Tao (Alputon Inc.) and the Alputon chemistry team for their participation in this project. We also thank Ms Allison Mandich for critical review of the manuscript. This research was supported by the Molecular Libraries Initiative of the NIH Roadmap for Medical Research (U54MH084681) and the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. NR 19 TC 11 Z9 12 U1 1 U2 11 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-2503 J9 MEDCHEMCOMM JI MedChemComm PD JAN PY 2012 VL 3 IS 1 BP 56 EP 60 DI 10.1039/c1md00200g PG 5 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 888AD UT WOS:000299975300009 PM 22606365 ER PT J AU Byun, JS Fufa, TD Wakano, C Fernandez, A Haggerty, CM Sung, MH Gardner, K AF Byun, Jung S. Fufa, Temesgen D. Wakano, Clay Fernandez, Alfonso Haggerty, Cynthia M. Sung, Myong-Hee Gardner, Kevin TI ELL facilitates RNA polymerase II pause site entry and release SO NATURE COMMUNICATIONS LA English DT Article ID TRANSCRIPTION ELONGATION-FACTORS; BROMODOMAIN PROTEIN BRD4; EMBRYONIC STEM-CELLS; MLL-FUSION PROTEINS; P-TEFB; POL-II; MEDIATOR COMPLEX; HIV-1 TAT; LEUKEMIA; INITIATION AB Transcription is a multi-stage process that coordinates several steps within the transcription cycle including chromatin reorganization, RNA polymerase II recruitment, initiation, promoter clearance and elongation. Recent advances have identified the super elongation complex, containing the eleven-nineteen lysine-rich leukaemia (ELL) protein, as a key regulator of transcriptional elongation. Here we show that ELL has a diverse and kinetically distinct role before its assembly into the super elongation complex by stabilizing Pol II recruitment/initiation and entry into the pause site. Loss of ELL destabilizes the pre-initiation complexes and results in disruption of early elongation and promoter proximal chromatin structure before recruitment of AFF4 and other super elongation complex components. These changes result in significantly reduced transcriptional activation of rapidly induced genes. Thus, ELL has an early and essential role during rapid high-amplitude gene expression that is required for both Pol II pause site entry and release. C1 [Byun, Jung S.; Fufa, Temesgen D.; Wakano, Clay; Fernandez, Alfonso; Haggerty, Cynthia M.; Sung, Myong-Hee; Gardner, Kevin] NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. RP Gardner, K (reprint author), NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. EM gardnerk@mail.nih.gov FU NIH, National Cancer Institute FX We thank K. Adelman and D. Gilmour for helpful discussions. This work was supported by the intramural research program of NIH, National Cancer Institute. NR 42 TC 19 Z9 21 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JAN PY 2012 VL 3 AR 633 DI 10.1038/ncomms1652 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 887IV UT WOS:000299921000031 PM 22252557 ER PT J AU Englund, EA Wang, DY Fujigaki, H Sakai, H Micklitsch, CM Ghirlando, R Martin-Manso, G Pendrak, ML Roberts, DD Durell, SR Appella, DH AF Englund, Ethan A. Wang, Deyun Fujigaki, Hidetsugu Sakai, Hiroyasu Micklitsch, Christopher M. Ghirlando, Rodolfo Martin-Manso, Gema Pendrak, Michael L. Roberts, David D. Durell, Stewart R. Appella, Daniel H. TI Programmable multivalent display of receptor ligands using peptide nucleic acid nanoscaffolds SO NATURE COMMUNICATIONS LA English DT Article ID ALPHA(V)BETA(3) INTEGRIN LIGANDS; EXTRACELLULAR SEGMENT; CRYSTAL-STRUCTURE; RGD PEPTIDES; BINDING; DNA; NANOPARTICLES; OLIGONUCLEOTIDES; ALPHA-V-BETA-3; THERAPEUTICS AB Multivalent effects dictate the binding affinity of multiple ligands on one molecular entity to receptors. Integrins are receptors that mediate cell attachment through multivalent binding to peptide sequences within the extracellular matrix, and overexpression promotes the metastasis of some cancers. Multivalent display of integrin antagonists enhances their efficacy, but current scaffolds have limited ranges and precision for the display of ligands. Here we present an approach to studying multivalent effects across wide ranges of ligand number, density, and three-dimensional arrangement. Using L-lysine gamma-substituted peptide nucleic acids, the multivalent effects of an integrin antagonist were examined over a range of 1-45 ligands. The optimal construct improves the inhibitory activity of the antagonist by two orders of magnitude against the binding of melanoma cells to the extracellular matrix in both in vitro and in vivo models. C1 [Englund, Ethan A.; Wang, Deyun; Micklitsch, Christopher M.; Appella, Daniel H.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Fujigaki, Hidetsugu; Sakai, Hiroyasu; Durell, Stewart R.] NCI, Cell Biol Lab, CCR, NIH, Bethesda, MD 20892 USA. [Ghirlando, Rodolfo] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Martin-Manso, Gema; Pendrak, Michael L.; Roberts, David D.] NCI, Pathol Lab, CCR, NIH, Bethesda, MD 20892 USA. RP Appella, DH (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM appellad@niddk.nih.gov RI Roberts, David/A-9699-2008; Martin Manso, Maria Gema/D-4612-2013 OI Roberts, David/0000-0002-2481-2981; FU NIDDK; NCI at NIH FX This work was supported by the Intramural Programs of the NIDDK and NCI at NIH. We thank Gail McMullen for assistance with mice, Sergio Coelho for assistance with photography, and George Leiman and Lisa Jenkins for helpful comments. We dedicate this paper to the memory of Dr. Ryan Monfeli. NR 45 TC 43 Z9 43 U1 2 U2 35 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JAN PY 2012 VL 3 AR 614 DI 10.1038/ncomms1629 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 887IV UT WOS:000299921000012 PM 22233624 ER PT J AU Hartmuller, VW Milner, JA AF Hartmuller, Virginia W. Milner, John A. TI Nutrition: What Do Cancer Survivors Need? SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Editorial Material ID PANCREATIC-CANCER; SUPPLEMENTATION; PREVENTION; EXERCISE; EFFICACY; IMPACT; DIET; ACID C1 [Hartmuller, Virginia W.] NCI, Nutrit Sci Res Grp, Canc Prevent Div, Rockville, MD 20892 USA. RP Hartmuller, VW (reprint author), NCI, Nutrit Sci Res Grp, Canc Prevent Div, 6130 Execut Blvd,Suite 3164 Execut Plaza N, Rockville, MD 20892 USA. EM hartmulv@mail.nih.gov NR 22 TC 3 Z9 3 U1 0 U2 3 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PD JAN PY 2012 VL 64 IS 1 BP 1 EP 3 DI 10.1080/01635581.2012.630553 PG 3 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 888WA UT WOS:000300034100001 PM 22172285 ER PT J AU Wang, D Zheng, W Wang, SM Wang, JB Wei, WQ Liang, H Qiao, YL Boffetta, P AF Wang, Ding Zheng, Wei Wang, Shao-Ming Wang, Jian-Bing Wei, Wen-Qiang Liang, Hao Qiao, You-Lin Boffetta, Paolo TI Estimation of Cancer Incidence and Mortality Attributable to Overweight, Obesity, and Physical Inactivity in China SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID BODY-MASS INDEX; COLORECTAL-CANCER; RISK; SHANGHAI; DISEASE; ADULTS; HEALTH; TRENDS; ASSOCIATION; PREVALENCE AB The objective was to provide an evidence-based, systematic assessment of the burden of cancer due to overweight/obesity and physical inactivity in China. This study evaluated the proportion of cancers of colon, rectum, pancreas, breast (postmenopausal), endometrium, and kidney attributable to overweight [30 kg/m(2) > body mass index (BMI) >= 25 kg/m(2))/obesity (BMI >= 30 kg/m(2)) and physical inactivity in China in 2005. Data of prevalence of overweight/obesity and lack of physical activity were derived from cross-sectional surveys among representative samples of Chinese population, and data of relative risks on cancers were derived from meta-analyses or large-scale studies from China and East Asian populations. The attributable fractions were calculated by combining both data of prevalence and relative risks. In China in 2005, 0.32% of cancer deaths and 0.65% of cancer cases were attributable to overweight and obesity combined. Lack of physical activity was responsible for 0.27% of cancer deaths and 0.39% of cancer cases. Future projections indicate that the contribution of overweight and obesity to the overall cancer burden will increase in the next decades. The largest increased attributable fractions will be for endometrial cancer. The increase in attributable fractions would be greater in men and in rural populations. Although the current burden of cancer associated with overweight/obesity and physical inactivity is still relatively small in China, it is expected to increase in the future. C1 [Wang, Ding; Wang, Shao-Ming; Wang, Jian-Bing; Wei, Wen-Qiang; Liang, Hao; Qiao, You-Lin] Chinese Acad Med Sci, Dept Canc Epidemiol, Inst Canc, Beijing 100021, Peoples R China. [Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Boffetta, Paolo] Int Prevent Res Inst, Lyon, France. [Wang, Jian-Bing] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Zheng, Wei] Vanderbilt Univ, Dept Med, Div Epidemiol, Vanderbilt Epidemiol Ctr, Nashville, TN USA. RP Qiao, YL (reprint author), Chinese Acad Med Sci, Dept Canc Epidemiol, Inst Canc, 17 S Panjiayuan Lane, Beijing 100021, Peoples R China. EM qiaoy@cicams.ac.cn RI Qiao, You-Lin/B-4139-2012 OI Qiao, You-Lin/0000-0001-6380-0871 FU International Agency for Research on Cancer (Lyon, France) [GEE/08/19] FX This study was conducted by Department of Cancer Epidemiology, Cancer Institute, Chinese Academy of Medical Sciences, Beijing, China. Funding of this research was supported by International Agency for Research on Cancer (Lyon, France) grant CRA No. GEE/08/19. All authors declare they have no conflicts of interest due to financial, academic, or personal relationships, which might bias their contribution to the study. NR 41 TC 22 Z9 22 U1 0 U2 19 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0163-5581 EI 1532-7914 J9 NUTR CANCER JI Nutr. Cancer PD JAN PY 2012 VL 64 IS 1 BP 48 EP 56 DI 10.1080/01635581.2012.630166 PG 9 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 888WA UT WOS:000300034100006 PM 22136606 ER PT J AU Shuch, B Bratslavsky, G Linehan, WM Srinivasan, R AF Shuch, Brian Bratslavsky, Gennady Linehan, W. Marston Srinivasan, Ramaprasad TI Sarcomatoid Renal Cell Carcinoma: A Comprehensive Review of the Biology and Current Treatment Strategies SO ONCOLOGIST LA English DT Article DE Sarcomatoid; Renal cell carcinoma; Kidney cancer ID LYMPH-NODE DISSECTION; TUMOR-SUPPRESSOR GENE; CYTOREDUCTIVE NEPHRECTOMY; RADICAL NEPHRECTOMY; IMMUNOHISTOCHEMICAL EXPRESSION; HEREDITARY LEIOMYOMATOSIS; SYSTEMIC THERAPY; TARGETED THERAPY; MUTATIONS; CANCER AB Recent advancements in the molecular characterization of renal cell carcinoma altered the classification system and now kidney cancer is divided into several distinct histologic subtypes. Although once a separate histologic category, sarcomatoid renal cell carcinoma is no longer considered a separate tumor type because it can occur with all histologic subtypes. Limited research on tumors with sarcomatoid change has led to minimal progress in the understanding and treatment of these tumors. Because the sarcomatoid variant of renal cell carcinoma can account for approximately one in six cases of advanced kidney cancer, we hope to familiarize clinicians with these tumors by describing the historic background, histologic features, molecular characterization, diagnosis, prognosis, treatment strategies, and active clinical trials of this aggressive type of tumor. The Oncologist 2012; 17: 46-54 C1 [Shuch, Brian; Bratslavsky, Gennady; Linehan, W. Marston; Srinivasan, Ramaprasad] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Srinivasan, R (reprint author), NCI, Urol Oncol Branch, NIH, 10 Ctr Dr,MSC1107,Bldg 10,CRC,Room 1-5940, Bethesda, MD 20892 USA. EM ramasrin@mail.nih.gov RI Inov Farmaceutica, Inct/K-2313-2013 FU GlaxoSmithKline; NIH, National Cancer Institute, Center for Cancer Research FX GlaxoSmithKline; This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. A special thanks goes to Maria Kwon and Sheldon Shuch for manuscript review and support. NR 67 TC 40 Z9 41 U1 0 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD JAN PY 2012 VL 17 IS 1 BP 46 EP 54 DI 10.1634/theoncologist.2011-0227 PG 9 WC Oncology SC Oncology GA 887UG UT WOS:000299955500008 PM 22234634 ER PT J AU Cippitelli, A Damadzic, R Singley, E Thorsell, A Ciccocioppo, R Eskay, RL Heilig, M AF Cippitelli, Andrea Damadzic, Ruslan Singley, Erick Thorsell, Annika Ciccocioppo, Roberto Eskay, Robert L. Heilig, Markus TI Pharmacological blockade of corticotropin-releasing hormone receptor 1 (CRH1R) reduces voluntary consumption of high alcohol concentrations in non-dependent Wistar rats SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE Intermittent; Alcohol; CRH1R; Intake; Withdrawal; Antalarmin ID PREFERRING MSP RATS; ELEVATED PLUS-MAZE; ANIMAL-MODELS; ETHANOL-CONSUMPTION; DEPENDENCE INDUCTION; INTERMITTENT ACCESS; 20-PERCENT ETHANOL; C57BL/6J MICE; LONG-EVANS; DRINKING AB Background: A dysregulation of the corticotropin-releasing hormone (CRH) system has been implicated in the development of excessive alcohol consumption and dependence. The aim of the present study was to evaluate whether the CRH system is also recruited when non-dependent Wistar rats escalate to high alcohol intake in the intermittent (alternate days) model of drinking. Methods: We compared intermittent and continuous access to 20% (v/v) alcohol in a two-bottle free choice drinking paradigm. Following a total of twenty 24-hour exposures for every experimental group, we assessed signs of alcohol withdrawal, including anxiety-like behavior and sensitivity to stress. The selective CRH1 receptor (CRH1R) antagonist antalarmin (0, 10, 20 mg/kg, i.p.) was tested on alcohol consumption. Results: Intermittent access to 20% alcohol led non-selected Wistar rats to escalate their voluntary intake to a high and stable level, whereas continuously exposed animals maintained a lower consumption. These groups did not differ in physical withdrawal signs. In addition, no differences were found when anxiogenic-like behavior was studied, neither under basal conditions or following restraint stress. Nevertheless, sensitivity to the treatment with the CRH1R antalarmin was observed since a reduction of 20% alcohol intake was found in both groups of animals regardless of the regimen of alcohol exposure. In addition, antalarmin was effective when injected to animals exposed to intermittent 10% (v/v) alcohol whereas it failed to suppress 10% continuous alcohol intake. Conclusions: Pharmacological blockade of CRH1R reduced alcohol drinking when sustained high levels of intake were achieved suggesting that the CRH system plays a key role when high doses of ethanol are consumed by non-dependent subjects. This supports the notion that CRH system not only maintains the dependent state but also engages the transition to dependence. Published by Elsevier Inc. C1 [Cippitelli, Andrea; Damadzic, Ruslan; Singley, Erick; Thorsell, Annika; Eskay, Robert L.; Heilig, Markus] NIAAA, LCTS, NIH, Bethesda, MD 20892 USA. [Ciccocioppo, Roberto] Univ Camerino, Sch Pharm, Pharmacol Unit, I-62032 Camerino, Italy. RP Cippitelli, A (reprint author), NIAAA, LCTS, NIH, 10 Ctr Dr,1-5330, Bethesda, MD 20892 USA. EM cippitellia@mail.nih.gov OI Heilig, Markus/0000-0003-2706-2482; Thorsell, Annika/0000-0003-3535-3845 FU Intramural NIH HHS [Z99 AA999999] NR 51 TC 28 Z9 28 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JAN PY 2012 VL 100 IS 3 BP 522 EP 529 DI 10.1016/j.pbb.2011.10.016 PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 889LI UT WOS:000300074800025 PM 22036774 ER PT J AU Wassermann, EM Zimmermann, T AF Wassermann, Eric M. Zimmermann, Trelawny TI Transcranial magnetic brain stimulation: Therapeutic promises and scientific gaps SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE Brain stimulation; Neuromodulation; Neurology; Psychiatry; Depression ID HUMAN MOTOR CORTEX; OBSESSIVE-COMPULSIVE DISORDER; RANDOMIZED CONTROLLED-TRIAL; POSTTRAUMATIC-STRESS-DISORDER; MAJOR DEPRESSIVE DISORDER; THETA-BURST-STIMULATION; SHAM-CONTROLLED TRIAL; DOUBLE-BLIND; PARKINSONS-DISEASE; PREFRONTAL CORTEX AB Since its commercial advent in 1985, transcranial magnetic stimulation (TMS), a technique for stimulating neurons in the cerebral cortex through the scalp, safely and with minimal discomfort, has captured the imaginations of scientists, clinicians and lay observers. Initially a laboratory tool for neurophysiologists studying the human motor system, TMS now has a growing list of applications in clinical and basic neuroscience. Although we understand many of its effects at the system level, detailed knowledge of its actions, particularly as a modulator of neural activity, has lagged, due mainly to the lack of suitable non-human models. Nevertheless, these gaps have not blocked the therapeutic application of TMS in brain disorders. Moderate success has been achieved in treating disorders such as depression, where the U.S. Food and Drug Administration has cleared a TMS system for therapeutic use. In addition, there are small, but promising, bodies of data on the treatment of schizophrenic auditory hallucinations, tinnitus, anxiety disorders, neurodegenerative diseases, hemiparesis, and pain syndromes. Some other nascent areas of study also exist. While the fate of TMS as a therapeutic modality depends on continued innovation and experimentation, economic and other factors may be decisive. Published by Elsevier Inc. C1 [Wassermann, Eric M.; Zimmermann, Trelawny] Natl Inst Neurol Disorders & Stroke, Behav Neurol Unit, NIH, Bethesda, MD USA. RP Wassermann, EM (reprint author), 10 Ctr DR MSC 1440, Bethesda, MD 20892 USA. EM eric.wassermann@nih.gov FU NINDS FX This work was supported by NINDS intramural funding. The authors thank Ms. D. Schoenberg for her skillful editing. NR 110 TC 74 Z9 79 U1 5 U2 28 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD JAN PY 2012 VL 133 IS 1 BP 98 EP 107 DI 10.1016/j.pharmthera.2011.09.003 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 888BU UT WOS:000299979600007 PM 21924290 ER PT J AU Lee, MG Ohana, E Park, HW Yang, D Muallem, S AF Lee, Min Goo Ohana, Ehud Park, Hyun Woo Yang, Dongki Muallem, Shmuel TI MOLECULAR MECHANISM OF PANCREATIC AND SALIVARY GLAND FLUID AND HCO3- SECRETION SO PHYSIOLOGICAL REVIEWS LA English DT Review ID TRANSMEMBRANE CONDUCTANCE REGULATOR; PAROTID ACINAR-CELLS; CYSTIC-FIBROSIS GENE; GUINEA-PIG PANCREAS; VASOACTIVE-INTESTINAL-PEPTIDE; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; SODIUM-BICARBONATE COTRANSPORTER; RAT SUBMANDIBULAR-GLAND; DUCT EPITHELIAL-CELLS; CA2+-ACTIVATED K+ CHANNELS AB Lee MG, Ohana E, Park HW, Yang D, Muallem S. Molecular Mechanism of Pancreatic and Salivary Gland Fluid and HCO3- Secretion. Physiol Rev 92: 39-74, 2012; doi: 10.1152/physrev.00011.2011.-Fluid and HCO3- secretion is a vital function of all epithelia and is required for the survival of the tissue. Aberrant fluid and HCO3- secretion is associated with many epithelial diseases, such as cystic fibrosis, pancreatitis, Sjogren's syndrome, and other epithelial inflammatory and autoimmune diseases. Significant progress has been made over the last 20 years in our understanding of epithelial fluid and HCO3- secretion, in particular by secretory glands. Fluid and HCO3- secretion by secretory glands is a two-step process. Acinar cells secrete isotonic fluid in which the major salt is NaCl. Subsequently, the duct modifies the volume and electrolyte composition of the fluid to absorb the Cl- and secrete HCO3-. The relative volume secreted by acinar and duct cells and modification of electrolyte composition of the secreted fluids varies among secretory glands to meet their physiological functions. In the pancreas, acinar cells secrete a small amount of NaCl-rich fluid, while the duct absorbs the Cl- and secretes HCO3- and the bulk of the fluid in the pancreatic juice. Fluid secretion appears to be driven by active HCO3- secretion. In the salivary glands, acinar cells secrete the bulk of the fluid in the saliva that is driven by active Cl- secretion and contains high concentrations of Na+ and Cl-. The salivary glands duct absorbs both the Na+ and Cl- and secretes K+ and HCO3-. In this review, we focus on the molecular mechanism of fluid and HCO3- secretion by the pancreas and salivary glands, to highlight the similarities of the fundamental mechanisms of acinar and duct cell functions, and to point out the differences to meet gland-specific secretions. C1 [Lee, Min Goo] Yonsei Univ, Coll Med, Dept Pharmacol, Seoul 120752, South Korea. Yonsei Univ, Coll Med, Brain Korea Project Med Sci 21, Seoul 120752, South Korea. [Muallem, Shmuel] Natl Inst Dent & Craniofacial Res, Epithelial Signaling & Transport Sect, Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. Gachon Univ Med & Sci, Grad Sch Med, Dept Physiol, Inchon, South Korea. RP Lee, MG (reprint author), Yonsei Univ, Coll Med, Dept Pharmacol, Seoul 120752, South Korea. EM mlee@yuhs.ac; shmuel.muallem@nih.gov RI Lee, Min Goo/D-5635-2012 OI Lee, Min Goo/0000-0001-7436-012X FU National Research Foundation of Korea [2010-0001670, 2010-0017752]; Ministry of Education, Science, and Technology, Korea; National Institutes of Health/National Institute of Dental and Craniofacial Research [Z1A DE000735-01] FX This work was supported by National Research Foundation of Korea Grants 2010-0001670 and 2010-0017752; the Ministry of Education, Science, and Technology, Korea (to M. G. Lee); and National Institutes of Health/National Institute of Dental and Craniofacial Research Intramural Research Fund Z1A DE000735-01 (to S. Muallem). NR 478 TC 99 Z9 103 U1 3 U2 25 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0031-9333 J9 PHYSIOL REV JI Physiol. Rev. PD JAN PY 2012 VL 92 IS 1 BP 39 EP 74 DI 10.1152/physrev.00011.2011 PG 36 WC Physiology SC Physiology GA 889BH UT WOS:000300048000002 PM 22298651 ER PT J AU Hay, J Kaphingst, KA Baser, R Li, Y Hensley-Alford, S McBride, CM AF Hay, J. Kaphingst, K. A. Baser, R. Li, Y. Hensley-Alford, S. McBride, C. M. TI Skin Cancer Concerns and Genetic Risk Information-Seeking in Primary Care SO PUBLIC HEALTH GENOMICS LA English DT Article DE Genetic information; Skin cancer concerns ID PUBLIC-HEALTH; MELANOMA INCIDENCE; UNITED-STATES; CLASSIFICATION; INTERVENTION; INDIVIDUALS; REGRESSION; BEHAVIORS; GENOMICS; DISEASE AB Background: Genomic testing for common genetic variants associated with skin cancer risk could enable personalized risk feedback to motivate skin cancer screening and sun protection. Methods: In a cross-sectional study, we investigated whether skin cancer cognitions and behavioral factors, sociodemographics, family factors, and health information-seeking were related to perceived importance of learning about how (a) genes and (b) health habits affect personal health risks using classification and regression trees (CART). Results: The sample (n = 1,772) was collected in a large health maintenance organization as part of the Multiplex Initiative, ranged in age from 25-40, was 53% female, 41% Caucasian, and 59% African-American. Most reported that they placed somewhat to very high importance on learning about how genes (79%) and health habits (88%) affect their health risks. Social influence actors were associated with information-seeking about genes and health habits. Awareness of family history was associated with importance of health habit, but not genetic, information-seeking. Conclusions: The investment of family and friends in health promotion may be a primary motivator for prioritizing information-seeking about how genes and health habits affect personal health risks and may contribute to the personal value, or personal utility, of risk information. Individuals who seek such risk information may be receptive to interventions aimed to maximize the social implications of healthy lifestyle change to reduce their health risks. Copyright (C) 2011 S. Karger AG, Basel C1 [Hay, J.; Baser, R.] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10022 USA. [Baser, R.; Li, Y.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10022 USA. [Kaphingst, K. A.] Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, St Louis, MO 63110 USA. [Hensley-Alford, S.] Henry Ford Hosp, Detroit, MI 48202 USA. [McBride, C. M.] NHGRI, Washington, DC USA. RP Hay, J (reprint author), Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, 641 Lexington Ave, New York, NY 10022 USA. EM hayj@mskcc.org FU National Institutes of Health [CA98106, CA133376, CA137532, HHSN268200782096C]; Weill Cornell Medical College [NIH UL1-RR024996]; National Human Genome Research Institute at the National Institutes of Health in Bethesda, Maryland (USA); National Cancer Institute [U19 CA 079689] FX Preparation of this manuscript was supported by National Institutes of Health grants CA98106, CA133376 and CA137532 to Jennifer Hay and Weill Cornell Medical College Clinical and Translational Science Award support for Yuelin Li (NIH UL1-RR024996). We also acknowledge the invaluable assistance of Susan Gall and Marcel Ramos in the preparation of this paper. This research was supported by the Intramural Research Program of the National Human Genome Research Institute at the National Institutes of Health in Bethesda, Maryland (USA). However, the proposed research was made possible by collaboration with the Cancer Research Network funded by the National Cancer Institute (U19 CA 079689). Additional resources were provided by the Cancer Research Network, Group Health Research Institute and Henry Ford Hospital. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University (HHSN268200782096C). We also thank the Multiplex steering committee members (Drs. Colleen McBride, Larry Brody, Andy Baxevanis, Robert Reid, Eric Larson, and Sharon Kardia) for their critical review of this paper. Our thanks also go to the study participants who were all members of the Henry Ford Health System. NR 46 TC 6 Z9 6 U1 0 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-4246 J9 PUBLIC HEALTH GENOM JI Pub. Health Genomics PY 2012 VL 15 IS 2 BP 57 EP 72 DI 10.1159/000330403 PG 16 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA 890AB UT WOS:000300116400001 PM 21921576 ER PT J AU Armstrong, K Liu, F Seymour, A Mazhani, L Littman-Quinn, R Fontelo, P Kovarik, C AF Armstrong, Kathleen Liu, Fang Seymour, Anne Mazhani, Loeto Littman-Quinn, Ryan Fontelo, Paul Kovarik, Carrie TI Evaluation of txt2MEDLINE and Development of Short Messaging Service-Optimized, Clinical Practice Guidelines in Botswana SO TELEMEDICINE AND E-HEALTH LA English DT Article DE telemedicine; distance learning; e-health AB Objective: Currently clinicians in sub-Saharan Africa have limited access to the Internet, whereas mobile phone access and use is extensive. The University of Pennsylvania in collaboration with the National Library of Medicine launched txt2MEDLINE, a short messaging service (SMS) query of PubMed/MEDLINE, and SMS-optimized clinical guidelines in Botswana. The objective of this project was to establish and evaluate the utility of these tools for clinicians in Botswana. Materials and Methods: A local server was established at the University of Botswana that allowed clinicians to send queries and receive results via local (in-country) SMS text messaging on any type of cellular phone. The queries sent via txt2MEDLINE were returned as abbreviated "the bottom line" summaries of abstracts. The 2007 Botswana Treatment Guide was converted into a format that can be queried by SMS. Various types of healthcare workers were recruited to use and evaluate these services. Results: Seventy-six healthcare workers attended training sessions for these services. In the preusage survey, most said they would use the services daily or weekly. During a 4-week trial period, use of these services dropped off dramatically. Participant feedback was collected and indicated that improvements in ease of use would increase the usage. Conclusions: This pilot project enables clinicians to query and receive PubMed abstract summaries and country-specific clinical guidelines using mobile phones. Feedback offers insight on how to improve this technology so that it can be adopted for long-term use. With further adjustments, these resources may provide an effective working model for other countries where limited Internet access impedes upon patient care. C1 [Kovarik, Carrie] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Armstrong, Kathleen] Univ Toronto, Dept Med, Sch Med, Toronto, ON, Canada. [Liu, Fang; Fontelo, Paul] Natl Lib Med, Bethesda, MD USA. [Seymour, Anne] Univ Penn, Biomed Lib, Philadelphia, PA 19104 USA. [Mazhani, Loeto] Univ Botswana, Dept Pediat, Sch Med, Gaborone, Botswana. [Littman-Quinn, Ryan; Kovarik, Carrie] Botswana UPenn Partnership, Philadelphia, PA USA. RP Kovarik, C (reprint author), Univ Penn, Dept Dermatol, 2 Maloney Bldg,3600 Spruce St, Philadelphia, PA 19104 USA. EM carrie.kovarik@uphs.upenn.edu RI Emchi, Karma/Q-1952-2016; OI Armstrong, Kathleen/0000-0001-9898-6725; Seymour, Anne/0000-0002-4285-7702 NR 6 TC 8 Z9 8 U1 2 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 J9 TELEMED E-HEALTH JI Telemed. e-Health PD JAN-FEB PY 2012 VL 18 IS 1 BP 14 EP 17 DI 10.1089/tmj.2011.0014 PG 4 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 888YN UT WOS:000300040700005 PM 22150636 ER PT J AU Crivat, G Taraska, JW AF Crivat, Georgeta Taraska, Justin W. TI Imaging proteins inside cells with fluorescent tags SO TRENDS IN BIOTECHNOLOGY LA English DT Review ID MOLECULES IN-VIVO; LIVING CELLS; MAMMALIAN-CELLS; LIVE CELLS; FUSION PROTEINS; BIOLOGICAL APPLICATIONS; TETRACYSTEINE MOTIF; ESCHERICHIA-COLI; MONOMERIC RED; FLASH AB Watching biological molecules provides clues to their function and regulation. Some of the most powerful methods of labeling proteins for imaging use genetically encoded fluorescent fusion tags. There are four standard genetic methods of covalently tagging a protein with a fluorescent probe for cellular imaging. These use (i) autofluorescent proteins, (ii) self-labeling enzymes, WO enzymes that catalyze the attachment of a probe to a target sequence, and (iv) biarsenical dyes that target tetracysteine motifs. Each of these techniques has advantages and disadvantages. In this review, we cover new developments in these methods and discuss practical considerations for their use in imaging proteins inside living cells. C1 [Taraska, Justin W.] NHLBI, Lab Mol & Cellular Imaging, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. [Crivat, Georgeta] Univ Maryland, Dept Entomol, College Pk, MD 20742 USA. [Crivat, Georgeta] Univ Maryland, Program Cell & Mol Biol, College Pk, MD 20742 USA. RP Taraska, JW (reprint author), NHLBI, Lab Mol & Cellular Imaging, Lab Mol Biophys, NIH, Bldg 10, Bethesda, MD 20892 USA. EM justin.taraska@nih.gov RI Taraska, Justin/H-8876-2016 OI Taraska, Justin/0000-0001-5355-9535 FU National Heart Lung and Blood Institute, National Institutes of Health; National Research Council (NRC) (NIST); National Institute of Allergy and Infectious Diseases, National Institutes of Health; NIST; National Institute for Biomedical Imaging and Bioengineering of the NIH FX We would like to thank M.W. Davidson (FSU) for helpful discussions and information presented at the 2011 analytical and quantitative light microscopy course (Marine Biological Lab, Woods Hole, MA). We would also like to thank J. Hwang (NIST), T. Wellems and F. Tokumasu (NIAID/NIH) for helpful discussions and for providing the image of ReAsH-labeled transgenic parasites and M.J. Schell (Uniformed Services University) for the ITPKA-tdTomato construct. We also thank J. Silver (NHLBI/NIH), G. Shtengel, H.F. Hess, and L.D. Lavis (Janelia Farm/HHMI) for helpful discussions. We thank F. Madani and A.O. Graslund (Stockholm University) for providing the NMR structure of the ReAsH bound peptide. J.W. Taraska is supported by the intramural research program at the National Heart Lung and Blood Institute, National Institutes of Health. G. Crivat was supported by a National Research Council Research Award (NRC) (NIST) and the National Institute of Allergy and Infectious Diseases, National Institutes of Health. Funding for the award was provided by NIST and the Intramural Program of the National Institute for Biomedical Imaging and Bioengineering of the NIH. NR 86 TC 62 Z9 62 U1 5 U2 90 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD JAN PY 2012 VL 30 IS 1 BP 8 EP 16 DI 10.1016/j.tibtech.2011.08.002 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 889MG UT WOS:000300077200002 PM 21924508 ER PT J AU Steel, JC Waldmann, TA Morris, JC AF Steel, Jason C. Waldmann, Thomas A. Morris, John C. TI Interleukin-15 biology and its therapeutic implications in cancer SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID CD8(+) T-CELLS; ACUTE LYMPHOBLASTIC-LEUKEMIA; RECEPTOR-ALPHA-CHAIN; ANTITUMOR-ACTIVITY; NATURAL-KILLER; TRANSGENIC MICE; IL-2 RECEPTOR; GROWTH-FACTOR; BETA-CHAIN; IN-VIVO AB Cancer immunotherapy is designed to stimulate the immune system to reject and destroy tumors. Recently, interleukin-15 (IL-15), a member of the four alpha-helix bundle family of cytokines, has emerged as a candidate immunomodulator for the treatment of cancer. IL-15 acts through its specific receptor, IL-15R alpha, which is expressed on antigen-presenting dendritic cells, monocytes and macrophages. IL-15 exhibits broad activity and induces the differentiation and proliferation of T, B and natural killer (NK) cells. It also enhances the cytolytic activity of CD8(+) T cells and induces long-lasting antigen-experienced CD8(+)CD44(hi) memory T cells. IL-15 stimulates differentiation and immunoglobulin synthesis by B cells and induces maturation of dendritic cells. It does not stimulate immunosuppressive T regulatory cells (Tregs). Thus, boosting IL-15 activity could enhance innate and specific immunity and fight tumors. Here we review aspects of IL-15 biology that make it a promising agent for anticancer therapy. We also discuss preclinical models in which IL-15 has demonstrated antitumor activity and highlight ongoing clinical trials of IL-15 in patients with cancer and HIV infection. C1 [Steel, Jason C.; Morris, John C.] Univ Cincinnati, Dept Internal Med, Div Hematol Oncol, Cincinnati, OH 45267 USA. [Waldmann, Thomas A.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Morris, JC (reprint author), Univ Cincinnati, Dept Internal Med, Div Hematol Oncol, Cincinnati, OH 45267 USA. EM morri2j7@ucmail.uc.edu RI Steel, Jason/D-1805-2013 OI Steel, Jason/0000-0003-3608-7542 FU Division of Hematology-Oncology, University of Cincinnati; Cancer Research, NCI, National Institutes of Health (NIH) FX This work is supported in part by the Division of Hematology-Oncology, University of Cincinnati and the Intramural Research Program of the Center for Cancer Research, NCI, National Institutes of Health (NIH). T.A.W. holds a U.S. government patent on monoclonal antibodies that target IL-2R/II-1.5R beta gamma and a patent application for expansion of natural killer and CD8 T cells with IL-15R/ligand activator complexes. NR 59 TC 112 Z9 116 U1 2 U2 22 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD JAN PY 2012 VL 33 IS 1 BP 35 EP 41 DI 10.1016/j.tips.2011.09.004 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 887ZP UT WOS:000299973900006 PM 22032984 ER PT J AU Leese, MP Jourdan, F Dohle, W Kimberley, MR Thomas, MP Bai, RL Hamel, E Ferrandis, E Potter, BVL AF Leese, Mathew P. Jourdan, Fabrice Dohle, Wolfgang Kimberley, Meriel R. Thomas, Mark P. Bai, Ruoli Hamel, Ernest Ferrandis, Eric Potter, Barry V. L. TI Steroidomimetic Tetrahydroisoquinolines for the Design of New Microtubule Disruptors SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Tetrahydroisoquinoline; microtubule disruptor; structure-activity relationship; steroidomimetic ID MULTITARGETED ANTITUMOR AGENTS; BREAST-CANCER CELLS; IN-VITRO; ANTICANCER ACTIVITY; DERIVATIVES; VIVO; SAR AB Structure-activity relationship translation offers an expeditious means for discovery of new active series. This approach was applied to discover tetrahydroisoquinoline (THIQ)-based steroidomimetic microtubule disruptors. The two A-ring elements of a three-point steroidal pharmacophore were incorporated into a THIQ-based A,B-ring mimic to which an H-bond acceptor was attached as the third motif Optimization of the representative 6c through conformational biasing delivered a 10-fold gain in activity and a new series of microtubule disruptors (e.g., 9c) with antiproliferative activity in the nanomolar range. The THIQ derivatives match, or surpass, the activities of the steroidal series and exhibit improved physicochemical properties. C1 [Leese, Mathew P.; Jourdan, Fabrice; Dohle, Wolfgang; Kimberley, Meriel R.; Thomas, Mark P.; Potter, Barry V. L.] Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England. [Bai, Ruoli; Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA. [Ferrandis, Eric] Inst Rech Henri Beaufour, IPSEN, F-91966 Les Ulis, France. RP Potter, BVL (reprint author), Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England. EM B.V.L.Potter@bath.ac.uk FU Sterix Ltd.; Ipsen group; Wellcome Trust [082837] FX This work was supported by Sterix Ltd., a member of the Ipsen group, by VIP awards and a Programme Grant (082837) from the Wellcome Trust. NR 20 TC 14 Z9 14 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-5875 J9 ACS MED CHEM LETT JI ACS Med. Chem. Lett. PD JAN PY 2012 VL 3 IS 1 BP 5 EP 9 DI 10.1021/ml200232c PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 882TP UT WOS:000299587100002 ER PT J AU Hyman, BT Phelps, CH Beach, TG Bigio, EH Cairns, NJ Carrillo, MC Dickson, DW Duyckaerts, C Frosch, MP Masliah, E Mirra, SS Nelson, PT Schneider, JA Thal, DR Thies, B Trojanowski, JQ Vinters, HV Montine, TJ AF Hyman, Bradley T. Phelps, Creighton H. Beach, Thomas G. Bigio, Eileen H. Cairns, Nigel J. Carrillo, Maria C. Dickson, Dennis W. Duyckaerts, Charles Frosch, Matthew P. Masliah, Eliezer Mirra, Suzanne S. Nelson, Peter T. Schneider, Julie A. Thal, Dietmar Rudolf Thies, Bill Trojanowski, John Q. Vinters, Harry V. Montine, Thomas J. TI National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Lewy body disease; Vascular brain injury; Neuropathology; Consensus guidelines ID CEREBRAL AMYLOID ANGIOPATHY; LEWY BODY DISEASE; A-BETA-DEPOSITION; FRONTOTEMPORAL LOBAR DEGENERATION; VASCULAR COGNITIVE IMPAIRMENT; BRAINNET EUROPE CONSORTIUM; MEDIAL TEMPORAL-LOBE; NEUROFIBRILLARY TANGLES; DIAGNOSTIC GUIDELINES; HIPPOCAMPAL SCLEROSIS AB A consensus panel from the United States and Europe was convened recently to update and revise the 1997 consensus guidelines for the neuropathologic evaluation of Alzheimer's disease (AD) and other diseases of brain that are common in the elderly. The new guidelines recognize the pre-clinical stage of AD, enhance the assessment of AD to include amyloid accumulation as well as neurofibrillary change and neuritic plaques, establish protocols for the neuropathologic assessment of Lewy body disease, vascular brain injury, hippocampal sclerosis, and TDP-43 inclusions, and recommend standard approaches for the workup of cases and their clinico-pathologic correlation. (C) 2012 The Alzheimer's Association. All rights reserved. C1 [Montine, Thomas J.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. [Hyman, Bradley T.] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. [Phelps, Creighton H.] NIA, Bethesda, MD 20892 USA. [Beach, Thomas G.] Banner Sun Hlth Res Inst, Civin Lab Neuropathol, Sun City, AZ USA. [Bigio, Eileen H.] Northwestern Univ, Dept Pathol, NW Alzheimer Dis Ctr, Feinberg Sch Med, Chicago, IL 60611 USA. [Cairns, Nigel J.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Cairns, Nigel J.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Carrillo, Maria C.; Thies, Bill] Alzheimers Assoc, Chicago, IL USA. [Dickson, Dennis W.] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. [Duyckaerts, Charles] Hop La Pitie Salpetriere, Serv Neuropathol Raymond Escourolle, Paris, France. [Frosch, Matthew P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, CS Kubik Lab Neuropathol, Boston, MA USA. [Masliah, Eliezer] Univ Calif San Diego, Sch Med, Dept Neurosci, La Jolla, CA 92093 USA. [Masliah, Eliezer] Univ Calif San Diego, Sch Med, Dept Pathol, La Jolla, CA 92093 USA. [Mirra, Suzanne S.] Suny Downstate Med Ctr, Dept Pathol, Brooklyn, NY 11203 USA. [Nelson, Peter T.] Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. [Schneider, Julie A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Schneider, Julie A.] Rush Univ, Med Ctr, Dept Pathol, Chicago, IL 60612 USA. [Schneider, Julie A.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Thal, Dietmar Rudolf] Univ Ulm, Inst Pathol, Neuropathol Lab, Ulm, Germany. [Trojanowski, John Q.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Inst Aging,Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA. [Vinters, Harry V.] Univ Calif Los Angeles, Dept Pathol & Lab Med Neuropathol, Los Angeles, CA USA. [Vinters, Harry V.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. RP Montine, TJ (reprint author), Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. EM tmontine@uw.edu OI Dickson, Dennis W/0000-0001-7189-7917 FU NIH [AG05134, AG05136, AG03991, AG05681, AG24904, AG28383, AG10161, AG17917, AG10124, AG13854, AG19610, NS62684, AG16570, AG15819, AG12435, AG05131, AG016976, AG18840]; AA, Arizona Department of Health Services (Arizona Alzheimer's Consortium) [211002]; Deutsche Forschungsgemeinschaft (DFG) [TH-624-4-1]; Alzheimer Forschung Initiative (AFT) [10810]; Nancy and Buster Alvord Endowment; Charles and Joanne Knight Alzheimer Research Initiative FX Support was provided by the NIH (AG05134, AG05136, AG03991, AG05681, AG24904, AG28383, AG10161, AG17917, AG10124, AG13854, AG19610, NS62684, AG16570, AG15819, AG12435, AG05131, AG016976, and AG18840) as well as the AA, Arizona Department of Health Services (contract 211002, Arizona Alzheimer's Consortium), Deutsche Forschungsgemeinschaft (DFG TH-624-4-1) and Alzheimer Forschung Initiative (AFT #10810), the Nancy and Buster Alvord Endowment, and the Charles and Joanne Knight Alzheimer Research Initiative. The authors extend their deepest thanks to Dr. Heiko Braak, Dr. Kelly Del Tredici, Dr. Nina Silverberg, Dr. Walter Kukull, Dr. Kathleen Montine, Dr. Cerise Elliott, and Ms. Sarah Monsell for their valuable input. NR 106 TC 401 Z9 412 U1 6 U2 50 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JAN PY 2012 VL 8 IS 1 BP 1 EP 13 DI 10.1016/j.jalz.2011.10.007 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA 882TN UT WOS:000299586900001 PM 22265587 ER PT J AU Wendler, D AF Wendler, David TI A New Justification for Pediatric Research Without the Potential for Clinical Benefit SO AMERICAN JOURNAL OF BIOETHICS LA English DT Article DE benefits; exploitation; interests; risks; pediatric research ID MINIMAL RISK; CHILDREN; ETHICS AB Pediatric research without the potential for clinical benefit is vital to improving pediatric medical care. This research also raises ethical concern and is regarded by courts and commentators as unethical. While at least 10 justifications have been proposed in response, all have fundamental limitations. This article describes and defends a new justification based on the fact that enrollment in clinical research offers children the opportunity to contribute to a valuable project. Contributing as children to valuable projects can benefit individuals in two ways. First, individualsmay come to "embrace" the contributions they made as children. Second, contributing to valuable projects can lead to a better overall life. Because these potential benefits can outweigh small research risks, they provide a justification for pediatric research without the potential for clinical benefit, when it poses low risks and has the potential to benefit others in important ways. C1 NIH Clin Ctr, Dept Bioeth, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIH Clin Ctr, Dept Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov NR 31 TC 15 Z9 15 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2012 VL 12 IS 1 BP 23 EP 31 DI 10.1080/15265161.2011.634482 PG 9 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 885PC UT WOS:000299790200009 PM 22220955 ER PT J AU Etemadi, A Abnet, CC Golozar, A Malekzadeh, R Dawsey, SM AF Etemadi, Arash Abnet, Christian C. Golozar, Asieh Malekzadeh, Reza Dawsey, Sanford M. TI Modeling the Risk of Esophageal Squamous Cell Carcinoma and Squamous Dysplasia in a High Risk Area in Iran SO ARCHIVES OF IRANIAN MEDICINE LA English DT Article DE Esophagus; risk modeling; squamous cell carcinoma; squamous dysplasia ID BARRETTS-ESOPHAGUS; CANCER; POPULATION; SYMPTOMS; CHINA AB Background: Identifying people at higher risk of having squamous dysplasia, the precursor lesion for esophageal squamous cell carcinoma (ESCC), would allow targeted endoscopic screening. Methods: We used multivariate logistic regression models to predict ESCC and dysplasia as outcomes. The ESCC model was based on data from the Golestan Case-Control Study (total n = 871; cases = 300), and the dysplasia model was based on data from a cohort of subjects from a gastroenterology clinic in Northeast Iran (total n = 724; cases = 26). In each of these analyses, we fit a model including all risk factors known in this region to be associated with ESCC. Individual risks were calculated using the linear combination of estimated regression coefficients and individual-specific values for covariates. We used cross-validation to determine the area under the curve (AUC) and to find the optimal cut points for each of the models. Results: The model had an area under the curve of 0.77 (95% Cl: 0.74-0.80) to predict ESCC with 74% sensitivity and 70.4% specificity for the optimum cut point. The area under the curve was 0.71 (95% Cl: 0.64-0.79) for dysplasia diagnosis, and the classification table optimized at 61.5% sensitivity and 69.5% specificity. In this population, the positive and negative predictive values for diagnosis of dysplasia were 6.8% and 97.8%, respectively. Conclusion: Our models were able to discriminate between ESCC oases and controls in about 77%, and between individuals with and without squamous dysplasia in about 70% of the cases. Using risk factors to predict individual risk of ESCC or squamous dysplasia still has limited application in clinical practice, but such models may be suitable for selecting high risk individuals in research studies, or increasing the pretest probability for other screening strategies. C1 [Etemadi, Arash; Golozar, Asieh; Malekzadeh, Reza] Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Ctr, Tehran, Iran. [Etemadi, Arash; Abnet, Christian C.; Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Etemadi, A (reprint author), 6120 Execut Blvd, Rockville, MD 20852 USA. EM arash.etemadi@nih.gov RI Abnet, Christian/C-4111-2015; Etemadi, Arash/C-1386-2016; OI Abnet, Christian/0000-0002-3008-7843; Etemadi, Arash/0000-0002-3458-1072; Malekzadeh, Reza/0000-0003-1043-3814 FU Intramural NIH HHS [Z99 CA999999] NR 24 TC 8 Z9 8 U1 0 U2 0 PU ACAD MEDICAL SCIENCES I R IRAN PI TEHRAN PA PO BOX 19395-5655, TEHRAN, 00000, IRAN SN 1029-2977 J9 ARCH IRAN MED JI Arch. Iran. Med. PD JAN PY 2012 VL 15 IS 1 BP 18 EP 21 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 883QL UT WOS:000299648700005 PM 22208438 ER PT J AU Riley, JD Amyot, F Pohida, T Pursley, R Ardeshipour, Y Kainerstorfer, JM Najafizadeh, L Chernomordik, V Smith, P Smirniotopoulos, J Wassermann, EM Gandjbakhche, AH AF Riley, Jason D. Amyot, Franck Pohida, Tom Pursley, Randall Ardeshipour, Yasaman Kainerstorfer, Jana M. Najafizadeh, Laleh Chernomordik, Victor Smith, Paul Smirniotopoulos, James Wassermann, Eric M. Gandjbakhche, Amir H. TI A hematoma detector-a practical application of instrumental motion as signal in near infra-red imaging SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID OPTICAL TOMOGRAPHY; BRAIN ACTIVATION; SPECTROSCOPY; TECHNOLOGY; TISSUE AB In this paper we discuss results based on using instrumental motion as a signal rather than treating it as noise in Near Infra-Red (NIR) imaging. As a practical application to demonstrate this approach we show the design of a novel NIR hematoma detection device. The proposed device is based on a simplified single source configuration with a dual separation detector array and uses motion as a signal for detecting changes in blood volume in the dural regions of the head. The rapid triage of hematomas in the emergency room will lead to improved use of more sophisticated/expensive imaging facilities such as CT/MRI units. We present simulation results demonstrating the viability of such a device and initial phantom results from a proof of principle device. The results demonstrate excellent localization of inclusions as well as good quantitative comparisons. (C) 2011 Optical Society of America C1 [Riley, Jason D.; Amyot, Franck; Ardeshipour, Yasaman; Kainerstorfer, Jana M.; Najafizadeh, Laleh; Chernomordik, Victor; Gandjbakhche, Amir H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Funct & Analyt Biophoton, NIH, Bethesda, MD 20892 USA. [Wassermann, Eric M.] NINDS, Behav Neurol Unit, NIH, Bethesda, MD 20892 USA. [Najafizadeh, Laleh] Henry Jackson Fdn, Ctr Neurosci & Regenerat Med, Rockville, MD 20852 USA. [Smirniotopoulos, James] Uniformed Serv Univ Hlth Sci, Imaging & Diagnost Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA. [Pohida, Tom; Pursley, Randall] NIH, Signal Proc & Instrumentat Sect, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. [Smith, Paul] Natl Inst Biomed Imaging & Bioengn, Biomed Instrumentat & Multiscale Imaging Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA. RP Riley, JD (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Funct & Analyt Biophoton, NIH, Bethesda, MD 20892 USA. EM amir@helix.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; Centre for Neuro Rehabilitative Medicine (Henry Jackson Foundation) FX We would like to acknowledge the contributions of Tim Mzorek of the Unit on Computer Support Services at the Eunice Kennedy Shriver National Institute of Child Health and Human Development in providing the rendering and visualization of the device design. We also acknowledge the funding of the intramural program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Centre for Neuro Rehabilitative Medicine (Henry Jackson Foundation). We would like to acknowledge Dr. Gibson and Professor Hebden of the Biomedical Optics Research Laboratory of the Department of Medical Physics at UCL for supplying the phantoms for the experimental study. NR 35 TC 4 Z9 4 U1 0 U2 1 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD JAN 1 PY 2012 VL 3 IS 1 BP 192 EP 205 PG 14 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 886WM UT WOS:000299884600017 PM 22254179 ER PT J AU DeCensi, A Dunn, BK Puntoni, M Gennari, A Ford, LG AF DeCensi, Andrea Dunn, Barbara K. Puntoni, Matteo Gennari, Alessandra Ford, Leslie G. TI Exemestane for Breast Cancer Prevention: A Critical Shift? SO CANCER DISCOVERY LA English DT Review ID STEROIDAL AROMATASE INHIBITOR; LOW-DOSE TAMOXIFEN; SURGICAL ADJUVANT BREAST; POSTMENOPAUSAL OSTEOPOROTIC WOMEN; REPLACEMENT THERAPY USERS; BONE-MINERAL DENSITY; BOWEL PROJECT P-1; BODY-MASS INDEX; ATAC TRIAL; CARDIOVASCULAR EVENTS AB The Mammary Prevention 3 (MAP.3) placebo-controlled randomized trial in 4,560 high-risk postmenopausal women showed a 65% reduction in invasive breast cancer with the use of exemestane at 35 months median follow-up. Few differences in adverse events were observed between the arms, suggesting a promising risk: benefit balance with exemestane for use in chemoprevention. Yet, the MAP. 3 design and implementation raise concerns regarding limited data maturity and not prospectively including key bone-related and other toxicities as study end points. Exemestane for prevention is juxtaposed against selective estrogen receptor modulators and the other aromatase inhibitors. Additional issues for prevention, including the influence of obesity, alternative dosing, and biomarker use in phase III trials, are addressed. Significance: The recently completed MAP. 3 trial of exemestane for breast cancer prevention offers a potential new standard for pharmaceutical risk reduction in high-risk postmenopausal women. In addition to describing key findings from the publication of MAP. 3 and related trials, our review undertakes a detailed analysis of the strengths and weaknesses of MAP. 3 as well as the implications for future prevention research. Cancer Discovery; 2(1); 25-40. (C) 2012 AACR. C1 [DeCensi, Andrea; Gennari, Alessandra] EO Osped Galliera, Div Med Oncol, Genoa, Italy. [Puntoni, Matteo] EO Osped Galliera, Off Sci Director, Genoa, Italy. [DeCensi, Andrea] European Inst Oncol, Div Canc Prevent & Genet, Milan, Italy. [Dunn, Barbara K.; Ford, Leslie G.] NCI, NIH, Canc Prevent Div, Bethesda, MD 20892 USA. RP DeCensi, A (reprint author), EO Osped Galliera, Div Med Oncol, Genoa, Italy. EM andrea.decensi@galliera.it RI Puntoni, Matteo/J-5440-2016 OI Puntoni, Matteo/0000-0002-7908-0626 FU Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD FX A. DeCensi's work was supported in part by a contract from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD. NR 80 TC 14 Z9 15 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD JAN PY 2012 VL 2 IS 1 BP 25 EP 40 DI 10.1158/2159-8290.CD-11-0248 PG 16 WC Oncology SC Oncology GA 883LR UT WOS:000299636100029 PM 22585166 ER PT J AU Roberts, NJ Jiao, YC Yu, J Kopelovich, L Petersen, GM Bondy, ML Gallinger, S Schwartz, AG Syngal, S Cote, ML Axilbund, J Schulick, R Ali, SZ Eshleman, JR Velculescu, VE Goggins, M Vogelstein, B Papadopoulos, N Hruban, RH Kinzler, KW Klein, AP AF Roberts, Nicholas J. Jiao, Yuchen Yu, Jun Kopelovich, Levy Petersen, Gloria M. Bondy, Melissa L. Gallinger, Steven Schwartz, Ann G. Syngal, Sapna Cote, Michele L. Axilbund, Jennifer Schulick, Richard Ali, Syed Z. Eshleman, James R. Velculescu, Victor E. Goggins, Michael Vogelstein, Bert Papadopoulos, Nickolas Hruban, Ralph H. Kinzler, Kenneth W. Klein, Alison P. TI ATM Mutations in Patients with Hereditary Pancreatic Cancer SO CANCER DISCOVERY LA English DT Article ID ATAXIA-TELANGIECTASIA; BREAST-CANCER; GENE; IDENTIFICATION; HETEROZYGOTES; PHENOTYPES; FAMILIES; TUMORS; ONSET AB Pancreatic cancers are the fourth most-common cause of cancer-related deaths in the Western world, with >200,000 cases reported in 2010. Although up to 10% of these cases occur in familial patterns, the hereditary basis for predisposition in the vast majority of affected families is unknown. We used next-generation sequencing, including whole-genome and whole-exome analyses, and identified heterozygous, constitutional, ataxia telangiectasia mutated (ATM) gene mutations in 2 kindreds with familial pancreatic cancer. Mutations segregated with disease in both kindreds and tumor analysis demonstrated LOH of the wild-type allele. By using sequence analysis of an additional 166 familial pancreatic cancer probands, we identified 4 additional patients with deleterious mutations in the ATM gene, whereas we identified no deleterious mutations in 190 spouse controls (P = 0.046). When we considered only the mostly severely affected families with 3 or more pancreatic cancer cases, 4 deleterious mutations were found in 87 families (P = 0.009). Our results indicate that inherited ATM mutations play an important role in familial pancreatic cancer predisposition. SIGNIFICANCE : The genes responsible for the majority of cases of familial pancreatic ductal adenocarcinoma are unknown. We here identify ATM as a predisposition gene for pancreatic ductal adenocarcinoma. Our results have important implications for the management of patients in affected families and illustrate the power of genome-wide sequencing to identify the basis of familial cancer syndromes. Cancer Discovery; 2(1): 41-6. (C) 2011 AACR. C1 [Yu, Jun; Axilbund, Jennifer; Ali, Syed Z.; Eshleman, James R.; Goggins, Michael; Hruban, Ralph H.; Klein, Alison P.] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Dept Pathol, Baltimore, MD 21231 USA. [Schulick, Richard] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Dept Surg, Baltimore, MD 21231 USA. [Goggins, Michael; Hruban, Ralph H.; Klein, Alison P.] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Dept Oncol, Baltimore, MD 21231 USA. [Yu, Jun; Goggins, Michael] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Dept Med, Baltimore, MD 21231 USA. [Roberts, Nicholas J.; Jiao, Yuchen; Velculescu, Victor E.; Vogelstein, Bert; Papadopoulos, Nickolas; Kinzler, Kenneth W.] Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr Canc Genet, Baltimore, MD USA. [Roberts, Nicholas J.; Jiao, Yuchen; Velculescu, Victor E.; Vogelstein, Bert; Papadopoulos, Nickolas; Kinzler, Kenneth W.] Johns Hopkins Kimmel Canc Ctr, Howard Hughes Med Inst, Baltimore, MD USA. [Klein, Alison P.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Kopelovich, Levy] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Petersen, Gloria M.] Mayo Clin, Div Epidemiol, Rochester, MN USA. [Bondy, Melissa L.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. [Gallinger, Steven] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Univ Hlth Network, Hepatobiliary Pancreat Surg Oncol Program, Toronto, ON M5G 1X5, Canada. [Schwartz, Ann G.; Cote, Michele L.] Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI USA. [Syngal, Sapna] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. RP Klein, AP (reprint author), Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Dept Pathol, 303 CRB2,1550 Orleans St, Baltimore, MD 21231 USA. EM rhruban@jhmi.edu; kinzlke@jhmi.edu; aklein1@jhmi.edu RI Papadopoulos, Nickolas/K-7272-2012; Gallinger, Steven/E-4575-2013 FU Lustgarten Foundation for Pancreatic Cancer Research; Virginia and D. K. Ludwig Fund for Cancer Research; Sol Goldman Pancreatic Cancer Research Center NIH [CA62924, CA057345, CA123483, CA121113, RO1CA97075]; Michael Rolfe Pancreatic Cancer Foundation; Stand Up To Cancer Dream Team; Entertainment Industry Foundation [SU2C-AACR-DT0509]; Stringer Foundation; Joseph L. Rabinowitz Fund for Pancreatic Cancer Research; Karp Family; H.H. & M. Metals, Inc.; Fund for Cancer Research; NCI [N01-PC-35145, NO1-CN-43302] FX This work was supported by the Lustgarten Foundation for Pancreatic Cancer Research; The Virginia and D. K. Ludwig Fund for Cancer Research; Sol Goldman Pancreatic Cancer Research Center NIH grants CA62924, CA057345, CA123483, CA121113, and RO1CA97075; the Michael Rolfe Pancreatic Cancer Foundation; V. E. Velculescu, R. H. Hruban, and K. W. Kinzler are supported by a Stand Up To Cancer Dream Team Translational Research Grant, a Program of the Entertainment Industry Foundation (SU2C-AACR-DT0509); The Stringer Foundation; The Joseph L. Rabinowitz Fund for Pancreatic Cancer Research; the family and friends of Dick Knox and Cliff Minor; The Karp Family; H.H. & M. Metals, Inc. Fund for Cancer Research; and NCI contracts N01-PC-35145 and NO1-CN-43302. NR 29 TC 136 Z9 139 U1 0 U2 15 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD JAN PY 2012 VL 2 IS 1 BP 41 EP 46 DI 10.1158/2159-8290.CD-11-0194 PG 6 WC Oncology SC Oncology GA 883LR UT WOS:000299636100030 PM 22585167 ER PT J AU Bornstein, MH Britto, PR Nonoyama-Tarumi, Y Ota, Y Petrovic, O Putnick, DL AF Bornstein, Marc H. Britto, Pia Rebello Nonoyama-Tarumi, Yuko Ota, Yumiko Petrovic, Oliver Putnick, Diane L. TI Child Development in Developing Countries: Introduction and Methods SO CHILD DEVELOPMENT LA English DT Article ID ECONOMIC-GROWTH; PSYCHOLOGY; WORLD; SCIENCE; RISK AB The Multiple Indicator Cluster Survey (MICS) is a nationally representative, internationally comparable household survey implemented to examine protective and risk factors of child development in developing countries around the world. This introduction describes the conceptual framework, nature of the MICS3, and general analytic plan of articles in this Special Section. The articles that follow describe the situations of children with successive foci on nutrition, parenting, discipline and violence, and the home environment. They address 2 common questions: How do developing and underresearched countries in the world vary with respect to these central indicators of childrens development? How do key indicators of national development relate to child development in each of these substantive areas? The Special Section concludes with policy implications from the international findings. C1 [Bornstein, Marc H.; Putnick, Diane L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. [Britto, Pia Rebello] Yale Univ, New Haven, CT 06520 USA. [Nonoyama-Tarumi, Yuko] Ochanomizu Univ, Tokyo, Japan. RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Suite 8030-6705,Rockledge Dr, Bethesda, MD 20892 USA. EM Marc_H_Bornstein@nih.gov OI Putnick, Diane/0000-0002-6323-749X FU Intramural NIH HHS [Z01 HD001119-20] NR 55 TC 30 Z9 31 U1 1 U2 16 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-3920 J9 CHILD DEV JI Child Dev. PD JAN-FEB PY 2012 VL 83 IS 1 BP 16 EP 31 DI 10.1111/j.1467-8624.2011.01671.x PG 16 WC Psychology, Educational; Psychology, Developmental SC Psychology GA 881EV UT WOS:000299465000002 PM 22277004 ER PT J AU Bornstein, MH Putnick, DL AF Bornstein, Marc H. Putnick, Diane L. TI Cognitive and Socioemotional Caregiving in Developing Countries SO CHILD DEVELOPMENT LA English DT Article ID PRESCHOOL-CHILDREN; MATERNAL SPEECH; YOUNG-CHILDREN; INFANT; MOTHERS; GROWTH; COMPETENCE; FAMILIES; COHORT; PLAY AB Enriching caregiving practices foster the course and outcome of child development. This study examined 2 developmentally significant domains of positive caregivingcognitive and socioemotionalin more than 127,000 families with under-5 year children from 28 developing countries. Mothers varied widely in cognitive and socioemotional caregiving and engaged in more socioemotional than cognitive activities. More than half of mothers played with their children and took them outside, but only a third or fewer read books and told stories to their children. The GDP of countries related to caregiving after controlling for life expectancy and education. The majority of mothers report that they do not leave their under-5s alone. Policy and intervention recommendations are elaborated. C1 [Bornstein, Marc H.; Putnick, Diane L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM Marc_H_Bornstein@nih.gov OI Putnick, Diane/0000-0002-6323-749X FU Intramural NIH HHS [Z01 HD001119-20] NR 106 TC 34 Z9 34 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-3920 J9 CHILD DEV JI Child Dev. PD JAN-FEB PY 2012 VL 83 IS 1 BP 46 EP 61 DI 10.1111/j.1467-8624.2011.01673.x PG 16 WC Psychology, Educational; Psychology, Developmental SC Psychology GA 881EV UT WOS:000299465000004 PM 22277006 ER PT J AU Bagci, U Bray, M Caban, J Yao, JH Mollura, DJ AF Bagci, Ulas Bray, Mike Caban, Jesus Yao, Jianhua Mollura, Daniel J. TI Computer-assisted detection of infectious lung diseases: A review SO COMPUTERIZED MEDICAL IMAGING AND GRAPHICS LA English DT Article DE Infectious diseases; Computer assisted detection; Texture analysis; Lung CT; Feature extraction; Tomography ID HIGH-RESOLUTION CT; INFLUENZA-A H1N1; ARTIFICIAL NEURAL-NETWORK; IMAGE FEATURE ANALYSIS; GROUND-GLASS OPACITY; CHEST RADIOGRAPHIC FINDINGS; AIDED DIAGNOSIS; TEXTURE CLASSIFICATION; INTERSTITIAL DISEASE; DIGITAL RADIOGRAPHY AB Respiratory tract infections are a leading cause of death and disability worldwide. Although radiology serves as a primary diagnostic method for assessing respiratory tract infections, visual analysis of chest radiographs and computed tomography (CT) scans is restricted by low specificity for causal infectious organisms and a limited capacity to assess severity and predict patient outcomes. These limitations suggest that computer-assisted detection (CAD) could make a valuable contribution to the management of respiratory tract infections by assisting in the early recognition of pulmonary parenchymal lesions, providing quantitative measures of disease severity and assessing the response to therapy. In this paper, we review the most common radiographic and CT features of respiratory tract infections, discuss the challenges of defining and measuring these disorders with CAD, and propose some strategies to address these challenges. Published by Elsevier Ltd. C1 [Bagci, Ulas; Mollura, Daniel J.] NIH, Ctr Infect Dis Imaging, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA. [Bray, Mike] NIAID, NIH, Bethesda, MD 20892 USA. [Caban, Jesus] NIH, Natl Lib Med, Bethesda, MD 20892 USA. [Yao, Jianhua] NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA. RP Bagci, U (reprint author), NIH, Ctr Infect Dis Imaging, Dept Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA. EM ulasbagci@gmail.com RI Bagci, Ulas/A-4225-2012; OI Bagci, Ulas/0000-0001-7379-6829 FU Imaging Sciences Training Program (ISTP); Center for Infectious Disease Imaging (CIDI); National Institute of Bio-imaging and Bioengineering at the National Institutes of Health FX This research is supported in part by the Imaging Sciences Training Program (ISTP), the Center for Infectious Disease Imaging (CIDI), and Intramural Research Program of the National Institute of Bio-imaging and Bioengineering at the National Institutes of Health. NR 125 TC 27 Z9 27 U1 0 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-6111 EI 1879-0771 J9 COMPUT MED IMAG GRAP JI Comput. Med. Imaging Graph. PD JAN PY 2012 VL 36 IS 1 BP 72 EP 84 DI 10.1016/j.compmedimag.2011.06.002 PG 13 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 882ZC UT WOS:000299601400008 PM 21723090 ER PT J AU Svikis, DS Keyser-Marcus, L Stitzer, M Rieckmann, T Safford, L Loeb, P Allen, T Luna-Anderson, C Back, SE Cohen, J DeBernardi, MA Dillard, B Forcehimes, A Jaffee, W Killeen, T Kolodner, K Levy, M Pallas, D Perl, HI Potter, JS Provost, S Reese, K Sampson, RR Sepulveda, A Snead, N Wong, CJ Zweben, J AF Svikis, Dace S. Keyser-Marcus, Lori Stitzer, Maxine Rieckmann, Traci Safford, Lauretta Loeb, Peter Allen, Tim Luna-Anderson, Carol Back, Sudie E. Cohen, Judith DeBernardi, Michael A. Dillard, Bruce Forcehimes, Alyssa Jaffee, William Killeen, Therese Kolodner, Ken Levy, Michael Pallas, Diane Perl, Harold I. Potter, Jennifer Sharpe Provost, Scott Reese, Karen Sampson, Royce R. Sepulveda, Allison Snead, Ned Wong, Conrad J. Zweben, Joan TI Randomized multi-site trial of the Job Seekers' Workshop in patients with substance use disorders SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Substance use disorders; Vocational rehabilitation; Treatment; Translational research; Employment ID DRUG-ABUSE TREATMENT; EX-HEROIN ADDICTS; VOCATIONAL-REHABILITATION; TREATMENT PROGRAMS; INCREASING EMPLOYMENT; METHADONE TREATMENT; TREATMENT CLIENTS; BASE-LINE; SERVICES; OUTCOMES AB Background: Unemployment is associated with negative outcomes both during and after drug abuse treatment. Interventions designed to increase rates of employment may also improve drug abuse treatment outcomes. The purpose of this multi-site clinical trial was to evaluate the Job Seekers' Workshop (JSW), a three session, manualized program designed to train patients in the skills needed to find and secure a job. Method: Study participants were recruited through the NIDA Clinical Trials Network (CTN) from six psychosocial counseling (n = 327) and five methadone maintenance (n = 301) drug treatment programs. Participants were randomly assigned to either standard care (program-specific services plus brochure with local employment resources) (SC) or standard care plus JSW. Three 4-h small group JSW sessions were offered weekly by trained JSW facilitators with ongoing fidelity monitoring. Results: JSW and SC participants had similar 12- and 24-week results for the primary outcome measure (i.e., obtaining a new taxed job or enrollment in a training program). Specifically, one-fifth of participants at 12 weeks (20.1-24.3%) and nearly one-third at 24 weeks (31.4-31.9%) had positive outcomes, with "obtaining a new taxed job" accounting for the majority of cases. JSW group participants did not have higher rates of employment/training than SC controls. Rates of job acquisition were modest for both groups, suggesting more intensive interventions may be needed. Alternate targets (e.g., enhancing patient motivation, training in job-specific skills) warrant further study as well. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Svikis, Dace S.] Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23298 USA. [Keyser-Marcus, Lori] Virginia Commonwealth Univ, Dept Psychiat, Inst Womens Hlth, Richmond, VA 23298 USA. [Stitzer, Maxine] Johns Hopkins Univ, Sch Med, Behav Pharmacol Res Unit, Baltimore, MD 21218 USA. [Rieckmann, Traci] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Svikis, Dace S.; Safford, Lauretta] Virginia Commonwealth Univ, Inst Drug & Alcohol Studies, Richmond, VA 23298 USA. [Loeb, Peter; Allen, Tim] Allen & Loeb Associates, San Francisco, CA USA. [Luna-Anderson, Carol; DeBernardi, Michael A.] Life Link, Santa Fe, NM USA. [Back, Sudie E.; Killeen, Therese; Sampson, Royce R.] Med Univ S Carolina, Clin Neurosci Div, Charleston, SC USA. [Cohen, Judith] E Bay Community Recovery Project, Oakland, CA USA. [Dillard, Bruce; Snead, Ned] Chesterfield Community Serv Board, Chesterfield, VA USA. [Forcehimes, Alyssa] Univ New Mexico, Ctr Alcoholism Subst Abuse & Addict, Albuquerque, NM 87131 USA. [Jaffee, William; Provost, Scott] Harvard Univ, Sch Med, McLean Hosp, Cambridge, MA 02138 USA. [Kolodner, Ken] Epidemiol & Stat Consulting, Baltimore, MD USA. [Pallas, Diane] Na Nizhoozhi Ctr Inc, Albuquerque, NM USA. [Perl, Harold I.] Natl Inst Drug Abuse, NIH, Bethesda, MD 20892 USA. [Potter, Jennifer Sharpe] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Reese, Karen] Man Alive Inc, Baltimore, MD USA. [Wong, Conrad J.] Eli Lilly & Co, Greenwood, IN USA. [Zweben, Joan] E Bay Community Recovery Project, Berkeley, CA USA. RP Svikis, DS (reprint author), Virginia Commonwealth Univ, Dept Psychol, Old City Hall,Room 350A,1001 E Broad St,POB 98034, Richmond, VA 23298 USA. EM dssvikis@vcu.edu RI Potter, Jennifer/C-6720-2008 OI Potter, Jennifer/0000-0002-7250-4422 FU National Institute of Drug Abuse Clinical Trials Network [U10 DA13034] FX This research was supported by grant U10 DA13034 National Institute of Drug Abuse Clinical Trials Network. The NIDA CTN provided oversight for study design, implementation and progress monitoring and analyses. The CTN Publications Committee has reviewed the manuscript and they approved submission of the paper for peer review and possible publication. NR 49 TC 15 Z9 15 U1 3 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JAN 1 PY 2012 VL 120 IS 1-3 BP 55 EP 64 DI 10.1016/j.drugalcdep.2011.06.024 PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 881PY UT WOS:000299499800009 PM 21802222 ER PT J AU Anderson, AL Li, SH Biswas, K McSherry, F Holmes, T Iturriaga, E Kahn, R Chiang, N Beresford, T Campbell, J Haning, W Mawhinney, J McCann, M Rawson, R Stock, C Weis, D Yu, E Elkashef, AM AF Anderson, Ann L. Li, Shou-Hua Biswas, Kousick McSherry, Frances Holmes, Tyson Iturriaga, Erin Kahn, Roberta Chiang, Nora Beresford, Thomas Campbell, Jan Haning, William Mawhinney, Joseph McCann, Michael Rawson, Richard Stock, Christopher Weis, Dennis Yu, Elmer Elkashef, Ahmed M. TI Modafinil for the treatment of methamphetamine dependence SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Methamphetamine; Substance-related disorders; Drug therapy; Modafinil; Medication adherence; Attention Deficit Hyperactivity Disorders ID PLACEBO-CONTROLLED TRIAL; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DOUBLE-BLIND; INDUCED WAKEFULNESS; COCAINE DEPENDENCE AB Aim: Modafinil was tested for efficacy in decreasing use in methamphetamine-dependent participants, compared to placebo. Methods: This was a randomized, double-blind, placebo-controlled study, with 12 weeks of treatment and a 4-week follow-up. Eight outpatient substance abuse treatment clinics participated in the study. There were 210 treatment-seekers randomized, who all had a DSM-IV diagnosis of methamphetamine dependence; 68 participants to placebo, 72 to modafinil 200 mg, and 70 to modafinil 400 mg, taken once daily on awakening. Participants came to the clinic three times per week for assessments, urine drug screens, and group psychotherapy. The primary outcome measure was a methamphetamine non-use week, which required all the week's qualitative urine drug screens to be negative for methamphetamine. Results: Regression analysis showed no significant difference between either modafinil group (200 or 400 mg) or placebo in change in weekly percentage having a methamphetamine non-use week over the 12-week treatment period (p=0.53). Similarly, a number of secondary outcomes did not show significant effects of modafinil. However, an ad-hoc analysis of medication compliance, by urinalysis for modafinil and its metabolite, did find a significant difference in maximum duration of abstinence (23 days vs. 10 days, p=0.003), between those having the top quartile of compliance (> 85% of urines were positive for modafinil, N=36), and the lower three quartiles of modafinil 200 and 400 mg groups (N=106). Conclusions: Although these data suggest that modafinil, plus group behavioral therapy, was not effective for decreasing methamphetamine use, the study is probably inconclusive because of inadequate compliance with taking medication. Published by Elsevier Ireland Ltd. C1 [Anderson, Ann L.] Natl Inst Drug Abuse, DPMC, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Bethesda, MD 20892 USA. [Biswas, Kousick; McSherry, Frances] VA Maryland Healthcare Ctr, Coop Studies Program, Perry Point, MD USA. [Holmes, Tyson] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Beresford, Thomas] VA Med Ctr, Psychiat Serv, Denver, CO USA. [Campbell, Jan] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Haning, William] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. [Mawhinney, Joseph] S Bay Treatment Ctr, San Diego, CA USA. [McCann, Michael] Matrix Inst Addict, Los Angeles, CA USA. [Rawson, Richard] UCLA Integrated Subst Abuse Program, Los Angeles, CA USA. [Stock, Christopher] VA Salt Lake City Healthcare Syst, Salt Lake City, UT USA. [Weis, Dennis] Iowa Lutheran Hosp, Des Moines, IA USA. [Yu, Elmer] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Anderson, AL (reprint author), Natl Inst Drug Abuse, DPMC, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, 6001 Execut Blvd,Rm 4149, Bethesda, MD 20892 USA. EM aa135m@nih.gov FU NIDA [Y1-DA-4006-01] FX Funding for this study was provided by NIDA Contract # Y1-DA-4006-01. The National Institute on Drug Abuse-NIH had a major role in study design, in the analysis and interpretation of data, and in the writing and submission of this manuscript for publication. NR 28 TC 44 Z9 45 U1 1 U2 11 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JAN 1 PY 2012 VL 120 IS 1-3 BP 135 EP 141 DI 10.1016/j.drugalcdep.2011.07.007 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 881PY UT WOS:000299499800019 PM 21840138 ER PT J AU Shannahan, JH Nyska, A Cesta, M Schladweiler, MCJ Vallant, BD Ward, WO Ghio, AJ Gavett, SH Kodavanti, UP AF Shannahan, Jonathan H. Nyska, Abraham Cesta, Mark Schladweiler, Mette C. J. Vallant, Beena D. Ward, William O. Ghio, Andrew J. Gavett, Stephen H. Kodavanti, Urmila P. TI Subchronic Pulmonary Pathology, Iron Overload, and Transcriptional Activity after Libby Amphibole Exposure in Rat Models of Cardiovascular Disease SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE cardiovascular disease; iron overload; Lilly amphibole; pulmonary pathology ID CHRYSOTILE ASBESTOS INHALATION; LARGE GENE LISTS; FERRUGINOUS BODIES; OXIDATIVE STRESS; LUNG; INFLAMMATION; EXPRESSION; CROCIDOLITE; ACTIVATION; TOXICITY AB BACKGROUND: Surface-available iron (Fe) is proposed to contribute to asbestos-induced toxicity through the production of reactive oxygen species. OBJECTIVE: Our goal was to evaluate the hypothesis that rat models of cardiovascular disease with coexistent Fe overload would be increasingly sensitive to Libby amphibole (LA)-induced subchronic lung injury. METHODS: Male healthy Wistar Kyoto (WKY), spontaneously hypertensive (SH), and SH heart failure (SHHF) rats were intratracheally instilled with 0.0, 0.25, or 1.0 mg LA (with saline as the vehicle). We examined bronchoalveolar lavage fluid (BALF) and histological lung sections after 1 week, 1 month, or 3 months for pulmonary biomarkers and pathology. SHHF rats were also assessed at 6 months for pathological changes. RESULTS: All animals developed concentration- and time-dependent interstitial fibrosis. Time-dependent Fe accumulation occurred in LA-laden macrophages in all strains but was exacerbated in SHHF rats. LA-exposed SHHF rats developed atypical hyperplastic lesions of bronchiolar epithelial cell origin at 3 and 6 months. Strain-related baseline differences existed in gene expression at 3 months, with persistent LA effects in WKY but not SH or SHHF rats. LA exposure altered genes for a number of pathways, including inflammation, immune regulation, and cell-cycle control. Cell-cycle control genes were inhibited after LA exposure in SH and SHHF but not WKY rats, whereas tumor suppressor genes were induced only in WKY rats. The inflammatory gene expression also was apparent only in WKY rats. CONCLUSION: These data show that in Fe-overload conditions, progressive Fe accumulation occurs in fiber-laden macrophages within LA-induced lesions. Fe overload does not appear to contribute to chronic inflammation, and its role in hyperplastic lesion development requires further examination. C1 [Schladweiler, Mette C. J.; Gavett, Stephen H.; Kodavanti, Urmila P.] US EPA, Cardiopulm & Immunotoxicol Branch, Environm Publ Hlth Div, Natl Hlth & Environm Effects Res Lab,Off Res & De, Res Triangle Pk, NC 27711 USA. [Shannahan, Jonathan H.] Univ N Carolina, Sch Med, Curriculum Toxicol, Chapel Hill, NC USA. [Nyska, Abraham] Tel Aviv Univ, Sackler Sch Med, Timrat, Israel. [Cesta, Mark] NIEHS, Cellular & Mol Pathol Branch, NIH, Res Triangle Pk, NC 27709 USA. [Ward, William O.] US EPA, Res Core Units, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA. [Ghio, Andrew J.] US EPA, Clin Res Branch, Environm Publ Hlth Div, Natl Hlth & Environm Effects Res Lab,Off Res & De, Chapel Hill, NC USA. RP Kodavanti, UP (reprint author), US EPA, Cardiopulm & Immunotoxicol Branch, Environm Publ Hlth Div, Natl Hlth & Environm Effects Res Lab,Off Res & De, B105-02, Res Triangle Pk, NC 27711 USA. EM Kodavanti.Urmila@epa.gov FU U.S. Environmental Protection Agency/University of North Carolina [CR833237]; Curriculum in Toxicology, University of North Carolina at Chapel Hill; National Institute of Environmental Health Sciences, National Institutes of Health FX This work was supported by U.S. Environmental Protection Agency/University of North Carolina Toxicology Research Program training agreement CR833237, with the Curriculum in Toxicology, University of North Carolina at Chapel Hill, and in part by the Intramural Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health. NR 30 TC 15 Z9 16 U1 0 U2 2 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JAN PY 2012 VL 120 IS 1 BP 85 EP 91 DI 10.1289/ehp.1103990 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 883RC UT WOS:000299650400030 PM 21979745 ER PT J AU Freeman, KS AF Freeman, Kris S. TI Remediating Soil Lead with Fish Bones SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 [Freeman, Kris S.] NIH, Bethesda, MD USA. NR 12 TC 4 Z9 4 U1 0 U2 2 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JAN PY 2012 VL 120 IS 1 BP A20 EP A21 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 883RC UT WOS:000299650400011 PM 22214821 ER PT J AU Lau, YS Machha, A Achike, FI Murugan, D Mustafa, MR AF Lau, Yeh-Siang Machha, Ajay Achike, Francis I. Murugan, Dharmani Mustafa, Mohd Rais TI The aporphine alkaloid boldine improves endothelial function in spontaneously hypertensive rats SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article DE boldine; blood pressure; endothelial function; hypertension; oxidative stress ID OXIDATIVE STRESS; IN-VIVO; NAD(P)H OXIDASE; PHOEBE-GRANDIS; NITRIC-OXIDE; ANTIOXIDANT; DYSFUNCTION; SUPEROXIDE; RELAXATION; MECHANISMS AB Boldine, a major aporphine alkaloid found in Chilean boldo tree, is a potent antioxidant. Oxidative stress plays a detrimental role in the pathogenesis of endothelial dysfunction in hypertension. In the present study, we investigated the effects of boldine on endothelial dysfunction in hypertension using spontaneously hypertensive rats (SHR), the most studied animal model of hypertension. SHR and their age-matched normotensive Wistar-Kyoto (WKY) rats were treated with boldine (20 mg/kg per day) or its vehicle, which served as control, for seven days. Control SHR displayed higher systolic blood pressure (SBP), reduced endothelium-dependent aortic relaxation to acetylcholine (ACh), marginally attenuated endothelium-independent aortic relaxation to sodium nitroprusside (SNP), increased aortic superoxide and peroxynitrite production, and enhanced p47(phox) protein expression as compared with control WKY rats. Boldine treatment significantly lowered SBP in SHR but not in WKY. Boldine treatment enhanced the maximal relaxation to ACh in SHR, but had no effect in WKY, whereas the sensitivity to ACh was increased in both SHR and WKY aortas. Boldine treatment enhanced sensitivity, but was without effect on maximal aortic relaxation responses, to SNP in both WKY and SHR aortas. In addition, boldine treatment lowered aortic superoxide and peroxynitrite production and downregulated p47(phox) protein expression in SHR aortas, but had no effect in the WKY control. These results show that boldine treatment exerts endothelial protective effects in hypertension, achieved, at least in part, through the inhibition of NADPH-mediated superoxide production. C1 [Lau, Yeh-Siang; Murugan, Dharmani; Mustafa, Mohd Rais] Univ Malaya, Fac Med, Dept Pharmacol, Ctr Nat Prod & Drug Discovery CENAR, Kuala Lumpur 50603, Malaysia. [Machha, Ajay] NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA. [Achike, Francis I.] Int Med Univ, Clin Sci Sect, Kuala Lumpur 57000, Malaysia. RP Mustafa, MR (reprint author), Univ Malaya, Fac Med, Dept Pharmacol, Ctr Nat Prod & Drug Discovery CENAR, Kuala Lumpur 50603, Malaysia. EM rais@um.edu.my RI MURUGAN, DHARMANI DEVI/B-8436-2010; Mustafa, Mohamed/B-1647-2009; Lau, Yeh Siang/D-2136-2016; Lau, Yee Ling/C-6996-2009 OI Mustafa, Mohamed/0000-0002-7864-5189; Lau, Yeh Siang/0000-0002-1770-3058; Lau, Yee Ling/0000-0002-2037-2165 FU University of Malaya (UM) [RG 140/09HTM]; Malaysian Society of Hypertension FX This study was funded by an University of Malaya Research Grant (UMRG) RG 140/09HTM and the Malaysian Society of Hypertension. NR 33 TC 7 Z9 8 U1 1 U2 5 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 1535-3702 J9 EXP BIOL MED JI Exp. Biol. Med. PD JAN PY 2012 VL 237 IS 1 BP 93 EP 98 DI 10.1258/ebm.2011.011145 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 886PF UT WOS:000299865600012 PM 22156043 ER PT J AU Benson, SC Lee, L Wei, WG Ni, F Olmos, JDJ Strom, KR Beeler, AB Cheng, KCC Inglese, J Kota, S Takahashi, V Strosberg, AD Connor, JH Bushkin, GG Snyder, JK AF Benson, Scott C. Lee, Lily Wei, Wanguo Ni, Feng Olmos, Julian David Janna Strom, Kyle R. Beeler, Aaron B. Cheng, Ken Chih-Chien Inglese, James Kota, Smitha Takahashi, Virginia Strosberg, A. Donny Connor, John H. Bushkin, G. Guy Snyder, John K. TI TRUNCATED ASPIDOSPERMA ALKALOID-LIKE SCAFFOLDS: UNIQUE STRUCTURES FOR THE DISCOVERY OF NEW, BIOACTIVE COMPOUNDS SO HETEROCYCLES LA English DT Review DE Anti-Viral Activity; Anti-Malarial Activity; Hepatitis C Virus; Tryptophan Dienophilicity; Tryptamine Dienophilicity ID DEMAND DIELS-ALDER; DIVERSITY-ORIENTED SYNTHESIS; HEPATITIS-C VIRUS; INTRAMOLECULAR DIELS-ALDER/1,3-DIPOLAR CYCLOADDITION; ASYMMETRIC TOTAL-SYNTHESIS; HETEROAROMATIC PI-SYSTEMS; CROSS-COUPLING REACTION; INTERMOLECULAR REACTIONS; RHODIUM CARBENOIDS; ALZHEIMERS-DISEASE AB Exploration into the dienophilicity of indole in inverse electron demand Diels-Alder reactions has led to the development of the triazatetracyclo[7.7.0.0(1,13).0(2,7)]hexadeca-2,4,6,10,12-pentaene and related scaffolds for diversification in the search for new, biologically active compounds. The libraries constructed from these core structures have lead to the discovery of new anti-viral and anti-malarial compounds. C1 [Benson, Scott C.; Lee, Lily; Wei, Wanguo; Ni, Feng; Olmos, Julian David Janna; Strom, Kyle R.; Beeler, Aaron B.; Snyder, John K.] Boston Univ, Dept Chem, Boston, MA 02215 USA. [Wei, Wanguo; Ni, Feng; Olmos, Julian David Janna; Strom, Kyle R.; Beeler, Aaron B.; Snyder, John K.] Boston Univ, Ctr Chem Methodol & Lib Dev, Boston, MA 02215 USA. [Cheng, Ken Chih-Chien; Inglese, James] NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. [Kota, Smitha; Takahashi, Virginia; Strosberg, A. Donny] Scripps Res Inst, Dept Infectol, Jupiter, FL 33458 USA. [Connor, John H.; Bushkin, G. Guy] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA. RP Snyder, JK (reprint author), Boston Univ, Dept Chem, 590 Commonwealth Ave, Boston, MA 02215 USA. OI Connor, John/0000-0002-8867-7256; Janna Olmos, Julian/0000-0002-4905-5235 FU National Science Foundation (NSF) [CHE-9501069]; NIGMS CMLD initiative [P50 GM067041]; Boston University FX We thank National Science Foundation (NSF CHE-9501069), the NIGMS CMLD initiative (P50 GM067041), and the Boston University Undergraduate Research Opportunities Program for financial support. We are also grateful to the NSF for the purchase of the NMR (CHE 0619339) and HRMS spectrometers (CHE 0443618) used in this work. NR 96 TC 3 Z9 3 U1 0 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0385-5414 J9 HETEROCYCLES JI Heterocycles PD JAN PY 2012 VL 84 IS 1 BP 135 EP 155 DI 10.3987/REV-11-SR(P)4 PG 21 WC Chemistry, Organic SC Chemistry GA 882UM UT WOS:000299589400006 ER PT J AU Mash, C Bornstein, MH AF Mash, Clay Bornstein, Marc H. TI 5-Month-Olds' Categorization of Novel Objects: Task and Measure Dependence SO INFANCY LA English DT Article ID INFANT CATEGORIZATION; PERCEPTUAL CATEGORIZATION; YOUNG INFANTS; FAMILIARIZATION; RECOGNITION; 3-MONTH-OLD; EXPERIENCE; COMPONENTS; ATTENTION; ATTRIBUTE AB To examine key parameters of the initial conditions in early category learning, two studies compared 5-month-olds object categorization between tasks involving previously unseen novel objects, and between measures within tasks. Infants in Experiment 1 participated in a visual familiarizationnovelty preference (VFNP) task with two-dimensional (2D) stimulus images. Infants provided no evidence of categorization by either their looking or their examining even though infants in previous research systematically categorized the same objects by examining when they could handle them directly. Infants in Experiment 2 participated in a VFNP task with 3D stimulus objects that allowed visual examination of objects 3D instantiation while denying manual contact with the objects. Under these conditions, infants demonstrated categorization by examining but not by looking. Focused examination appears to be a key component of young infants ability to form category representations of novel objects, and 3D instantiation appears to better engage such examining. C1 [Mash, Clay; Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, US Dept HHS, Rockville, MD USA. RP Mash, C (reprint author), NICHD, 6705 Rockledge Dr,Suite 8030, Bethesda, MD 20892 USA. EM mashc@mail.nih.gov FU Intramural NIH HHS [Z01 HD001119-20] NR 36 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1525-0008 J9 INFANCY JI Infancy PY 2012 VL 17 IS 2 BP 179 EP 197 DI 10.1111/j.1532-7078.2011.00076.x PG 19 WC Psychology, Developmental SC Psychology GA 886CV UT WOS:000299830000003 PM 23024609 ER PT J AU Koonin, EV AF Koonin, Eugene V. TI To the Editors of IUBMB Life: Correspondence Concerning an Alleged Erratum in a Review on the Genetic Code Response SO IUBMB LIFE LA English DT Letter RP Koonin, EV (reprint author), NIH, NCBI, NLM, Bldg 38A,Rm 5N503, Bethesda, MD 20892 USA. EM Koonin@ncbi.nlm.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PD JAN PY 2012 VL 64 IS 1 BP 108 EP 108 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 872WT UT WOS:000298842000014 ER PT J AU Best, M Gifford, AN Kim, SW Babst, B Piel, M Rosch, F Fowler, JS AF Best, Marcel Gifford, Andrew N. Kim, Sung Won Babst, Ben Piel, Markus Roesch, Frank Fowler, Joanna S. TI Rapid radiosynthesis of [11C] and [14C]azelaic, suberic, and sebacic acids for in vivo mechanistic studies of systemic acquired resistance in plants SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE azelaic acid; 1; 9-nonanedioic acid; systemic acquired resistance; plant signaling; plant hormone ID SIGNAL AB A recent report that the aliphatic dicarboxylic acid, azelaic acid (1,9-nonanedioic acid) but not related acids, suberic acid (1,8-octanedioic acid) or sebacic (1,10-decanedioic acid) acid induces systemic acquired resistance to invading pathogens in plants stimulated the development of a rapid method for labeling these dicarboxylic acids with 11C and 14C for in vivo mechanistic studies in whole plants. 11C-labeling was performed by reaction of ammonium [11C]cyanide with the corresponding bromonitrile precursor followed by hydrolysis with aqueous sodium hydroxide solution. Total synthesis time was 60 min. Median decay-corrected radiochemical yield for [11C]azelaic acid was 40% relative to trapped [11C]cyanide, and specific activity was 15 GBq/mu mol. Yields for [11C]suberic and sebacic acids were similar. The 14C-labeled version of azelaic acid was prepared from potassium [14C]cyanide in 45% overall radiochemical yield. Radiolabeling procedures were verified using 13C-labeling coupled with 13C-NMR and liquid chromatographymass spectrometry analysis. The 11C and 14C-labeled azelaic acid and related dicarboxylic acids are expected to be of value in understanding the mode-of-action, transport, and fate of this putative signaling molecule in plants. Copyright (C) 2011 John Wiley & Sons, Ltd. C1 [Best, Marcel; Gifford, Andrew N.; Babst, Ben; Fowler, Joanna S.] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. [Best, Marcel; Piel, Markus; Roesch, Frank] Johannes Gutenberg Univ Mainz, Inst Kernchem, D-55128 Mainz, Germany. [Kim, Sung Won] Natl Inst Alcohol & Alcoholism, NIH, Bethesda, MD 20892 USA. RP Gifford, AN (reprint author), Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. EM gifforda@bnl.gov RI Piel, Markus/L-8787-2016; OI Babst, Benjamin/0000-0001-5657-0633 FU US Department of Energy, Office of Biological and Environmental Research [DE-AC02-98CH10886]; National Institute on Alcohol Abuse and Alcoholism FX This work was supported by the US Department of Energy, Office of Biological and Environmental Research under contract DE-AC02-98CH10886. Additional support was from the National Institute on Alcohol Abuse and Alcoholism (S. W. K.). We thank Michael Schueller for the cyclotron operations, DohyunKim and David Alexoff for the help with the optimization of [11C]cyanide production, Lisa Muench for the assistance with 11C-labeling, Laura Reffert for measuring the 13C-NMR spectra, and Richard Ferrieri for the advice on the plant studies. NR 8 TC 6 Z9 6 U1 0 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JAN PY 2012 VL 55 IS 1 BP 39 EP 43 DI 10.1002/jlcr.1951 PG 5 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 882HZ UT WOS:000299555700007 ER PT J AU Tian, Y Schwieters, CD Opella, SJ Marassi, FM AF Tian, Ye Schwieters, Charles D. Opella, Stanley J. Marassi, Francesca M. TI AssignFit: A program for simultaneous assignment and structure refinement from solid-state NMR spectra SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE Resonance assignment; Orientation; Dipolar coupling; Chemical shift anisotropy; XPLOR-NIH; Membrane protein ID RESIDUAL DIPOLAR COUPLINGS; MEMBRANE PROTEIN OMPX; RESONANCE ASSIGNMENT; STRUCTURE PREDICTION; POWDER PATTERNS; LIPID-BILAYER; SPECTROSCOPY; ORIENTATION; MICELLES; TENSORS AB AssignFit is a computer program developed within the XPLOR-NIH package for the assignment of dipolar coupling (DC) and chemical shift anisotropy (CSA) restraints derived from the solid-state NMR spectra of protein samples with uniaxial order. The method is based on minimizing the difference between experimentally observed solid-state NMR spectra and the frequencies back calculated from a structural model. Starting with a structural model and a set of DC and CSA restraints grouped only by amino acid type, as would be obtained by selective isotopic labeling, AssignFit generates all of the possible assignment permutations and calculates the corresponding atomic coordinates oriented in the alignment frame, together with the associated set of NMR frequencies, which are then compared with the experimental data for best fit. Incorporation of AssignFit in a simulated annealing refinement cycle provides an approach for simultaneous assignment and structure refinement (SASR) of proteins from solid-state NMR orientation restraints. The methods are demonstrated with data from two integral membrane proteins, one a-helical and one beta-barrel, embedded in phospholipid bilayer membranes. (C) 2011 Elsevier Inc. All rights reserved. C1 [Tian, Ye; Marassi, Francesca M.] Sanford Burnham Med Res Inst, La Jolla, CA 92037 USA. [Tian, Ye; Opella, Stanley J.] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA. [Schwieters, Charles D.] NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Marassi, FM (reprint author), Sanford Burnham Med Res Inst, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM fmarassi@sanfordbumham.org FU National Institutes of Health [R21GM094727, P30CA030199]; NIH of the Center for Information Technology FX This research was supported by a Grant from the National Institutes of Health (R21GM094727). It utilized the Biotechnology Research Center for NMR Molecular Imaging of Proteins at UCSD (P41EB002031) and the NIH-supported NMR Facility at the Sanford Burnham Medical Research Institute (P30CA030199). C.D.S. was supported by the NIH Intramural Research Program of the Center for Information Technology. NR 51 TC 13 Z9 13 U1 2 U2 19 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD JAN PY 2012 VL 214 BP 42 EP 50 DI 10.1016/j.jmr.2011.10.002 PG 9 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 883SY UT WOS:000299656400006 PM 22036904 ER PT J AU Subramanian, S Devasahayam, N McMillan, A Matsumoto, S Munasinghe, JP Saito, K Mitchell, JB Chandramouli, GVR Krishna, MC AF Subramanian, Sankaran Devasahayam, Nallathamby McMillan, Alan Matsumoto, Shingo Munasinghe, Jeeva P. Saito, Keita Mitchell, James B. Chandramouli, Gadisetti V. R. Krishna, Murali C. TI Reporting of quantitative oxygen mapping in EPR imaging SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE EPR imaging; Intrinsic resolution; Digital resolution; Deconvolution; Oximetry ID TUMOR HYPOXIA; PHARMACOKINETICS; RESOLUTION; MRI AB Oxygen maps derived from electron paramagnetic resonance spectral-spatial imaging (EPRI) are based upon the relaxivity of molecular oxygen with paramagnetic spin probes. This technique can be combined with MRI to facilitate mapping of pO(2) values in specific anatomic locations with high precision. The co-registration procedure, which matches the physical and digital dimensions of EPR and MR images, may present the pO(2) map at the higher MRI resolution, exaggerating the spatial resolution of oxygen, making it difficult to precisely distinguish hypoxic regions from normoxic regions. The latter distinction is critical in monitoring the treatment of cancer by radiation and chemotherapy, since it is well-established that hypoxic regions are three or four times more resistant to treatment compared to normoxic regions. The aim of this article is to describe pO(2) maps based on the intrinsic resolution of EPRI. A spectral parameter that affects the intrinsic spatial resolution of EPRI is the full width at half maximum (FWHM) height of the gradient-free EPR absorption line in frequency-encoded imaging. In single point imaging too, the transverse relaxation times (T-2*) limit the resolution since the signal decays by exp(-t(p)/T-2*) where the delay time after excitation pulse, t(p), is related to the resolution. Although the spin densities of two point objects may be resolved at this separation, it is inadequate to evaluate quantitative changes of pO(2) levels since the linewidths are proportionately affected by pO(2). A spatial separation of at least twice this resolution is necessary to correctly identify a change in pO(2) level. In addition, the pO(2) values are blurred by uncertainties arising from spectral dimensions. Blurring due to noise and low resolution modulates the pO(2) levels at the boundaries of hypoxic and normoxic regions resulting in higher apparent pO(2) levels in hypoxic regions. Therefore, specification of intrinsic resolution and pO(2) uncertainties are necessary to interpret digitally processed pO(2) illustrations. Published by Elsevier Inc. C1 [Subramanian, Sankaran; Devasahayam, Nallathamby; Matsumoto, Shingo; Saito, Keita; Mitchell, James B.; Krishna, Murali C.] NCI, Radiat Biol Branch, CCR, NIH, Bethesda, MD 20892 USA. [McMillan, Alan] Univ Maryland, Dept Diagnost Radiol & Nucl Med, Sch Med, Baltimore, MD 21201 USA. [Munasinghe, Jeeva P.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA. [Chandramouli, Gadisetti V. R.] GenEpria Consulting Inc, Columbia, MD 21046 USA. RP Krishna, MC (reprint author), NCI, Radiat Biol Branch, CCR, NIH, Bethesda, MD 20892 USA. EM murali@helix.nih.gov FU Intramural NIH HHS [Z01 BC010476-05, ZIA BC010477-07, ZIA BC010476-08] NR 19 TC 7 Z9 7 U1 1 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD JAN PY 2012 VL 214 BP 244 EP 251 DI 10.1016/j.jmr.2011.11.013 PG 8 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 883SY UT WOS:000299656400030 PM 22188976 ER PT J AU Xiang, Y Shen, J AF Xiang, Yun Shen, Jun TI Spectral editing for in vivo C-13 magnetic resonance spectroscopy SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE In vivo C-13 MRS; Carboxylic/amide spectral region; Acetate metabolism; Spectral editing ID GAMMA-AMINOBUTYRIC-ACID; CEREBRAL METABOLISM; HUMAN BRAIN; 3 T; GLUTAMATE GLUTAMINE; 11.7 TESLA; RAT-BRAIN; RF POWER; NMR; MRS AB In vivo detection of carboxylic/amide carbons is a promising technique for studying cerebral metabolism and neurotransmission due to the very low RF power required for proton decoupling. In the carboxylic/amide region, however, there is severe spectral overlap between acetate Cl and glutamate C5, complicating studies that use acetate as an astroglia-specific substrate. There are no known in vivo MRS techniques that can spectrally resolve acetate Cl and glutamate C5 singlets. In this study, we propose to spectrally separate acetate Cl and glutamate C5 by a two-step J-editing technique after introducing homonuclear C-13-C-13 scalar coupling between carboxylic/amide carbons and aliphatic carbons. By infusing [1,2-C-13(2)]acetate instead of [1-C-13]acetate the acetate doublet can be spectrally edited because of the large separation between acetate C2 and glutamate C4 in the aliphatic region. This technique can be applied to studying acetate transport and metabolism in brain in the carboxylic/amide region without spectral interference. (C) 2011 Jun Shen. Published by Elsevier Inc. All rights reserved. C1 [Xiang, Yun; Shen, Jun] NIMH, Mol Imaging Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Xiang, Yun] Wuhan Med & Hlth Ctr Women & Children, Dept Lab Med, Wuhan, Peoples R China. RP Shen, J (reprint author), NIMH, Mol Imaging Branch, Intramural Res Program, NIH, Bldg 10,Rm 2D51A,9000 Rockville Pike, Bethesda, MD 20892 USA. EM shenj@intra.nimh.nih.gov FU National Institutes of Health, National Institute of Mental Health FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Mental Health. The authors thank Mr. Christopher Johnson for help. NR 26 TC 1 Z9 1 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD JAN PY 2012 VL 214 BP 252 EP 257 DI 10.1016/j.jmr.2011.11.012 PG 6 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 883SY UT WOS:000299656400031 PM 22172286 ER PT J AU Botelho, MB Andrade, BB AF Botelho, Marcelo B. Andrade, Bruno B. TI EFFECT OF CERVICAL SPINE MANIPULATIVE THERAPY ON JUDO ATHLETES' GRIP STRENGTH SO JOURNAL OF MANIPULATIVE AND PHYSIOLOGICAL THERAPEUTICS LA English DT Article DE Martial Arts; Manipulation, Spinal; Chiropractic; Athletic Performance ID LOW-BACK-PAIN; ARTERY DISSECTION; CHIROPRACTIC CARE; RISK-FACTORS; TRIAL; ACUPUNCTURE; RESPONSES AB Objective: The objective of this study was to perform an investigation evaluating if cervical spinal manipulative therapy (SMT) can increase grip strength on judo athletes in a top 10 national-ranked team. Methods: A single-blinded, prospective, comparative, pilot, randomized, clinical trial was performed with 18 athletes of both sexes from a judo team currently competing on a national level. The athletes were randomly assigned to 2 groups: chiropractic SMT and sham. Three interventions were performed on each of the athletes at different time points. Force measurements were obtained by a hydraulic dynamometer immediately before and after each intervention at the same period before training up to 3 weeks with at least 36 hours between interventions. Results: Analysis of grip strength data revealed a statistically significant increase in strength within the treatment group after the first intervention (6.95% right, 12.61% left) as compared with the second (11.53% right, 17.02% left) and the third interventions (10.53% right, 16.81% left). No statistically significant differences were found in grip strength comparison within the sham group. Overall differences in strength were consistently significant between the study groups (P = .0025). Conclusion: The present study suggests that the grip strength of national level judo athletes receiving chiropractic SMT improved compared to those receiving sham. (J Manipulative Physiol Ther 2012; 35:38-44) C1 [Andrade, Bruno B.] NIH, Bethesda, MD 20892 USA. RP Botelho, MB (reprint author), Av Oceanica,3731,Rio Vermelho, BR-41950000 Salvador, BA, Brazil. EM Quiropraxia@hotmail.com RI Andrade, Bruno/J-9111-2012 OI Andrade, Bruno/0000-0001-6833-3811 NR 29 TC 6 Z9 6 U1 4 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-4754 J9 J MANIP PHYSIOL THER JI J. Manip. Physiol. Ther. PD JAN PY 2012 VL 35 IS 1 BP 38 EP 44 DI 10.1016/j.jmpt.2011.09.005 PG 7 WC Health Care Sciences & Services; Integrative & Complementary Medicine; Rehabilitation SC Health Care Sciences & Services; Integrative & Complementary Medicine; Rehabilitation GA 885OQ UT WOS:000299788900005 PM 22079053 ER PT J AU Lee, HJ Lee, KH AF Lee, Hyun-Jung Lee, Kyu-Ho TI Identification of the Fur-Binding Site in Regulatory Region of the Vulnibactin-Receptor Gene in Vibrio vulnificus SO JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article DE Fur; vulnibactin-receptor gene; Vibrio vulnificus ID SIDEROPHORE; CHOLERAE; CLONING; PATHOGENESIS; EXPRESSION; VIRULENCE; HEME AB The Vibrio vulnificus vuuA gene, of which expression is repressed by a complex of iron and ferric uptake regulator (Fur), was characterized to localize the Fur-binding site in its upstream regulatory region. In silico analysis suggested the presence of two possible Fur-binding sites; one is a classical Fur-box and the other is a previously reported distinct Fur-binding site. Site-directed mutagenesis and DNase I protection assays revealed the binding site for the iron Fur complex, which includes an extended inverted repeat containing a homologous sequence to the classical Fur-box. C1 [Lee, Kyu-Ho] Sogang Univ, Dept Life Sci, Seoul 121742, South Korea. [Lee, Kyu-Ho] Sogang Univ, Interdisciplinary Program Integrated Biotechnol, Seoul 121742, South Korea. [Lee, Hyun-Jung] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Lee, KH (reprint author), Sogang Univ, Dept Life Sci, Seoul 121742, South Korea. EM kyuholee@sogang.ac.kr FU NRF, MEST, Republic of Korea [2009-0092822] FX This work was supported by the Mid-career Researcher Program through NRF (No. 2009-0092822), MEST, Republic of Korea. NR 18 TC 3 Z9 3 U1 0 U2 0 PU KOREAN SOC MICROBIOLOGY & BIOTECHNOLOGY PI SEOUL PA KOREA SCI TECHNOL CENTER #507, 635-4 YEOGSAM-DONG, KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1017-7825 J9 J MICROBIOL BIOTECHN JI J. Microbiol. Biotechnol. PD JAN PY 2012 VL 22 IS 1 BP 46 EP 49 DI 10.4014/jmb.1108.08042 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 884OC UT WOS:000299716400005 PM 22297218 ER PT J AU Racine, EF Laditka, SB Dmochowski, J Alavanja, MCR Lee, DC Hoppin, JA AF Racine, Elizabeth F. Laditka, Sarah B. Dmochowski, Jacek Alavanja, Michael C. R. Lee, Duck-chul Hoppin, Jane A. TI Farming Activities and Carrying and Lifting: The Agricultural Health Study SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH LA English DT Article DE occupational physical activity; muscle strengthening; resistance exercise ID OCCUPATIONAL PHYSICAL-ACTIVITY; ENERGY-EXPENDITURE; PROSTATE-CANCER; NATIONAL-HEALTH; FOLLOW-UP; RISK; MORTALITY; CANADA; COHORT; WOMEN AB Background: Heavy carrying and lifting (HCL) is a common activity among farmers that may be related to health. The aim of this study was to examine HCL as a proxy for occupational physical activity (PA) among farm residents. The secondary objective was to evaluate PA based on HCL. Methods: Data from 21,296 farmers and 30,951 spouses in the Agricultural Health Study examined the relationship between HCL and farm activities and individual/farm characteristics. HCL was categorized as >= 1 or < 1 hours per day. The association between HCL and farm activities (15 for farmers; 16 for spouses) and individual/farm characteristics was examined using adjusted logistic regression. To evaluate PA, we created a PA activity index using metabolic equivalents for HCL, and compared PA weekly averages with national guidelines. Results: In adjusted results, most farm activities were significantly associated with HCL. Based on HCL, farmers had a median of 1.5 hours and spouses 0.5 hours of vigorous or muscle-strengthening PA per day. Most farmers (94%) and about 60% of spouses meet or exceed 2008 national guidelines for vigorous or muscle-strengthening PA. Conclusion: Findings suggest the HCL measure may be useful as a PA metric in future studies of occupational PA among farm residents. C1 [Racine, Elizabeth F.; Laditka, Sarah B.] Univ N Carolina, Dept Publ Hlth Sci, Charlotte, NC 28223 USA. [Dmochowski, Jacek] Univ N Carolina, Dept Math & Stat, Charlotte, NC 28223 USA. [Alavanja, Michael C. R.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Lee, Duck-chul] Univ S Carolina, Dept Exercise Sci, Columbia, SC 29208 USA. [Hoppin, Jane A.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Racine, EF (reprint author), Univ N Carolina, Dept Publ Hlth Sci, Charlotte, NC 28223 USA. FU Intramural NIH HHS [ZIA ES049030-13]; NCI NIH HHS [Z01 CP010119, Z01-CP010119]; NIEHS NIH HHS [Z01 ES049030] NR 30 TC 5 Z9 5 U1 6 U2 9 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1543-3080 J9 J PHYS ACT HEALTH JI J. Phys. Act. Health PD JAN PY 2012 VL 9 IS 1 BP 39 EP 47 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 885SW UT WOS:000299802100006 PM 22232503 ER PT J AU Hearst, MO Sirard, JR Lytle, L Dengel, DR Berrigan, D AF Hearst, Mary O. Sirard, John R. Lytle, Leslie Dengel, Donald R. Berrigan, David TI Comparison of 3 Measures of Physical Activity and Associations With Blood Pressure, HDL, and Body Composition in a Sample of Adolescents SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH LA English DT Article DE accelerometer; modified activity questionnaire; 3DPAR ID METABOLIC SYNDROME; ENERGY-COST; HEART-RATE; VALIDITY; CHILDREN; YOUTH; ACCELEROMETRY; CHILDHOOD; SCHOOL; PEDOMETRY AB Background: The association of physical activity (PA), measured 3 ways, and biomarkers were compared in a sample of adolescents. Methods: PA data were collected on 2 cohorts of adolescents (N = 700) in the Twin Cities, Minnesota, 2007-2008. PA was measured using 2 survey questions [Modified Activity Questionnaire (MAQ)], the 3-Day Physical Activity Recall (3DPAR), and accelerometers. Biomarkers included systolic (SBP) and diastolic blood pressure (DBP), lipids, percent body fat (%BF), and body mass index (BMI) percentile. Bivariate relationships among PA measures and biomarkers were examined followed by generalized estimating equations for multivariate analysis. Results: The 3 measures were significantly correlated with each other (r = .22.36, P < .001). Controlling for study, puberty, age, and gender, all 3.PA measures were associated with %BF (MAQ = 1.93, P < .001; 3DPAR = 1.64, P < .001; accelerometer = 1.06, P = .001). The MAQ and accelerometers were negatively associated with BMI percentile. None of the 3 PA measures were significantly associated with SBP or lipids. The percentage of adolescents meeting the national PA recommendations varied by instrument. Conclusions: All 3 instruments demonstrated consistent findings when estimating associations with %BF, but were different for prevalence estimates. Researchers must carefully consider the intended use of PA data when choosing a measurement instrument. C1 [Hearst, Mary O.; Lytle, Leslie] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Sirard, John R.] Univ Virginia, Curry Sch Educ & Kinesiol, Charlottesville, VA USA. [Dengel, Donald R.] Univ Minnesota, Dept Kinesiol, Minneapolis, MN USA. [Berrigan, David] NCI, Bethesda, MD 20892 USA. RP Hearst, MO (reprint author), Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. RI Schmoelz, Camilie/D-1707-2012 OI Schmoelz, Camilie/0000-0003-2221-9954 FU NCI NIH HHS [U54 CA116849]; NHLBI NIH HHS [R01 HL085978] NR 39 TC 6 Z9 7 U1 2 U2 9 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1543-3080 J9 J PHYS ACT HEALTH JI J. Phys. Act. Health PD JAN PY 2012 VL 9 IS 1 BP 78 EP 85 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 885SW UT WOS:000299802100011 PM 22232509 ER PT J AU Ainsworth, BE Caspersen, CJ Matthews, CE Masse, LC Baranowski, T Zhu, WM AF Ainsworth, Barbara E. Caspersen, Carl J. Matthews, Charles E. Masse, Louise C. Baranowski, Tom Zhu, Weimo TI Recommendations to Improve the Accuracy of Estimates of Physical Activity Derived From Self Report SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH LA English DT Article DE survey; questionnaire; measurement error ID OLDER-ADULTS; ACTIVITY QUESTIONNAIRE; MEASUREMENT ERROR; UNITED-STATES; WOMEN; ACCELEROMETER; INTERVENTIONS; VALIDATION; COMPENDIUM; MEN AB Context: Assessment of physical activity using self-report has the potential for measurement error that can lead to incorrect inferences about physical activity behaviors and bias study results. Objective: To provide recommendations to improve the accuracy of physical activity derived from self report. Process: We provide an overview of presentations and a compilation of perspectives shared by the authors of this paper and workgroup members. Findings: We identified a conceptual framework for reducing errors using physical activity self-report questionnaires. The framework identifies 6 steps to reduce error: 1) identifying the need to measure physical activity, 2) selecting an instrument, 3) collecting data, 4) analyzing data, 5) developing a summary score, and 6) interpreting data. Underlying the first 4 steps are behavioral parameters of type, intensity, frequency, and duration of physical activities performed, activity domains, and the location where activities are performed. We identified ways to reduce measurement error at each step and made recommendations for practitioners, researchers, and organizational units to reduce error in questionnaire assessment of physical activity. Conclusions: Self-report measures of physical activity have a prominent role in research and practice settings. Measurement error may be reduced by applying the framework discussed in this paper. C1 [Ainsworth, Barbara E.] Arizona State Univ, Program Exercise & Wellness, Sch Nutr & Hlth Promot, Phoenix, AZ 85069 USA. [Caspersen, Carl J.] Ctr Dis Control & Prevent, Epidemiol & Stat Branch, Div Diabet Translat, Atlanta, GA USA. [Matthews, Charles E.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Masse, Louise C.] Univ British Columbia, Dept Pediat, Sch Populat & Publ Hlth, Vancouver, BC V6T 1W5, Canada. [Baranowski, Tom] Baylor Coll Med, Dept Pediat, Childrens Nutr Res Ctr, Houston, TX 77030 USA. [Zhu, Weimo] Univ Illinois, Dept Kinesiol & Community Hlth, Coll Appl Hlth Sci, Urbana, IL 61801 USA. RP Ainsworth, BE (reprint author), Arizona State Univ, Program Exercise & Wellness, Sch Nutr & Hlth Promot, Phoenix, AZ 85069 USA. RI Caspersen, Carl/B-2494-2009; matthews, Charles/E-8073-2015 OI matthews, Charles/0000-0001-8037-3103 FU Intramural NIH HHS [Z99 CA999999] NR 38 TC 48 Z9 49 U1 8 U2 26 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1543-3080 J9 J PHYS ACT HEALTH JI J. Phys. Act. Health PD JAN PY 2012 VL 9 SU 1 BP S76 EP S84 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 885FR UT WOS:000299764400010 PM 22287451 ER EF