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Find video protocols related to scientific articles indexed in Pubmed.
Longitudinal performance of an implantable vestibular prosthesis.
Hear. Res.
PUBLISHED: 05-20-2014
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Loss of vestibular function may be treatable with an implantable vestibular prosthesis that stimulates semicircular canal afferents with biphasic pulse trains. Several studies have demonstrated short-term activation of the vestibulo-ocular reflex (VOR) with electrical stimulation. Fewer long-term studies have been restricted to small numbers of animals and stimulation designed to produce adaptive changes in the electrically elicited response. This study is the first large consecutive series of implanted rhesus macaque to be studied longitudinally using brief stimuli designed to limit adaptive changes in response, so that the efficacy of electrical activation can be studied over time, across surgeries, canals and animals. The implantation of a vestibular prosthesis in animals with intact vestibular end organs produces variable responses to electrical stimulation across canals and animals, which change in threshold for electrical activation of eye movements and in elicited slow phase velocities over time. These thresholds are consistently lower, and the slow phase velocities higher, than those obtained in human subjects. The changes do not appear to be correlated with changes in electrode impedance. The variability in response suggests that empirically derived transfer functions may be required to optimize the response of individual canals to a vestibular prosthesis, and that this function may need to be remapped over time. This article is part of a Special Issue entitled .
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A global analysis of Y-chromosomal haplotype diversity for 23 STR loci.
Josephine Purps, Sabine Siegert, Sascha Willuweit, Marion Nagy, Cíntia Alves, Renato Salazar, Sheila M T Angustia, Lorna H Santos, Katja Anslinger, Birgit Bayer, Qasim Ayub, Wei Wei, Yali Xue, Chris Tyler-Smith, Miriam Baeta Bafalluy, Begoña Martínez-Jarreta, Balazs Egyed, Beate Balitzki, Sibylle Tschumi, David Ballard, Denise Syndercombe Court, Xinia Barrantes, Gerhard Bäßler, Tina Wiest, Burkhard Berger, Harald Niederstätter, Walther Parson, Carey Davis, Bruce Budowle, Helen Burri, Urs Borer, Christoph Koller, Elizeu F Carvalho, Patricia M Domingues, Wafaa Takash Chamoun, Michael D Coble, Carolyn R Hill, Daniel Corach, Mariela Caputo, Maria E D'Amato, Sean Davison, Ronny Decorte, Maarten H D Larmuseau, Claudio Ottoni, Olga Rickards, Di Lu, Chengtao Jiang, Tadeusz Dobosz, Anna Jonkisz, William E Frank, Ivana Furac, Christian Gehrig, Vincent Castella, Branka Gršković, Cordula Haas, Jana Wobst, Gavrilo Hadzic, Katja Drobnic, Katsuya Honda, Yiping Hou, Di Zhou, Yan Li, Shengping Hu, Shenglan Chen, Uta-Dorothee Immel, Rüdiger Lessig, Zlatko Jakovski, Tanja Ilievska, Anja E Klann, Cristina Cano García, Peter de Knijff, Thirsa Kraaijenbrink, Aikaterini Kondili, Penelope Miniati, Maria Vouropoulou, Lejla Kovacevic, Damir Marjanović, Iris Lindner, Issam Mansour, Mouayyad Al-Azem, Ansar El Andari, Miguel Marino, Sandra Furfuro, Laura Locarno, Pablo Martín, Gracia M Luque, Antônio Alonso, Luís Souto Miranda, Helena Moreira, Natsuko Mizuno, Yasuki Iwashima, Rodrigo S Moura Neto, Tatiana L S Nogueira, Rosane Silva, Marina Nastainczyk-Wulf, Jeanett Edelmann, Michael Köhl, Shengjie Nie, Xianping Wang, Baowen Cheng, Carolina Núñez, Marian Martínez de Pancorbo, Jill K Olofsson, Niels Morling, Valerio Onofri, Adriano Tagliabracci, Horolma Pamjav, Antónia Völgyi, Gusztav Barany, Ryszard Pawlowski, Agnieszka Maciejewska, Susi Pelotti, Witold Pepiński, Monica Abreu-Glowacka, Christopher Phillips, Jorge Cárdenas, Danel Rey-Gonzalez, Antonio Salas, Francesca Brisighelli, Cristian Capelli, Ulises Toscanini, Andrea Piccinini, Marilidia Piglionica, Stefania L Baldassarra, Rafal Ploski, Magdalena Konarzewska, Emila Jastrzebska, Carlo Robino, Antti Sajantila, Jukka U Palo, Evelyn Guevara, Jazelyn Salvador, Maria Corazon De Ungria, Jae Joseph Russell Rodriguez, Ulrike Schmidt, Nicola Schlauderer, Pekka Saukko, Peter M Schneider, Miriam Sirker, Kyoung-Jin Shin, Yu Na Oh, Iulia Skitsa, Alexandra Ampati, Tobi-Gail Smith, Lina Solis de Calvit, Vlastimil Stenzl, Thomas Capal, Andreas Tillmar, Helena Nilsson, Stefania Turrina, Domenico De Leo, Andrea Verzeletti, Venusia Cortellini, Jon H Wetton, Gareth M Gwynne, Mark A Jobling, Martin R Whittle, Denilce R Sumita, Paulina Wolanska-Nowak, Rita Y Y Yong, Michael Krawczak, Michael Nothnagel, Lutz Roewer.
Forensic Sci Int Genet
PUBLISHED: 03-28-2014
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In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129 different populations in 51 countries. These chromosomes were typed for 23 short-tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643) and using the PowerPlex Y23 System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic spectra of these markers were determined and a consistently high level of allelic diversity was observed. A considerable number of null, duplicate and off-ladder alleles were revealed. Standard single-locus and haplotype-based parameters were calculated and compared between subsets of Y-STR markers established for forensic casework. The PPY23 marker set provides substantially stronger discriminatory power than other available kits but at the same time reveals the same general patterns of population structure as other marker sets. A strong correlation was observed between the number of Y-STRs included in a marker set and some of the forensic parameters under study. Interestingly a weak but consistent trend toward smaller genetic distances resulting from larger numbers of markers became apparent.
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Melanoma incidence rates in active duty military personnel compared with a population-based registry in the United States, 2000-2007.
Mil Med
PUBLISHED: 03-06-2014
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This study was conducted to investigate whether incidence rates of malignant cutaneous melanoma in U.S. Department of Defense active duty military personnel differed from rates in the U.S. general population between 2000 and 2007.
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Short-Term Intra-Subject Variation in Exhaled Volatile Organic Compounds (VOCs) in COPD Patients and Healthy Controls and Its Effect on Disease Classification.
Metabolites
PUBLISHED: 02-26-2014
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Exhaled volatile organic compounds (VOCs) are of interest for their potential to diagnose disease non-invasively. However, most breath VOC studies have analyzed single breath samples from an individual and assumed them to be wholly consistent representative of the person. This provided the motivation for an investigation of the variability of breath profiles when three breath samples are taken over a short time period (two minute intervals between samples) for 118 stable patients with Chronic Obstructive Pulmonary Disease (COPD) and 63 healthy controls and analyzed by gas chromatography and mass spectroscopy (GC/MS). The extent of the variation in VOC levels differed between COPD and healthy subjects and the patterns of variation differed for isoprene versus the bulk of other VOCs. In addition, machine learning approaches were applied to the breath data to establish whether these samples differed in their ability to discriminate COPD from healthy states and whether aggregation of multiple samples, into single data sets, could offer improved discrimination. The three breath samples gave similar classification accuracy to one another when evaluated separately (66.5% to 68.3% subjects classified correctly depending on the breath repetition used). Combining multiple breath samples into single data sets gave better discrimination (73.4% subjects classified correctly). Although accuracy is not sufficient for COPD diagnosis in a clinical setting, enhanced sampling and analysis may improve accuracy further. Variability in samples, and short-term effects of practice or exertion, need to be considered in any breath testing program to improve reliability and optimize discrimination.
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"New turns from old STaRs": Enhancing the capabilities of forensic short tandem repeat analysis.
Electrophoresis
PUBLISHED: 02-26-2014
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The field of research and development of forensic STR genotyping remains active, innovative, and focused on continuous improvements. A series of recent developments including the introduction of a sixth dye have brought expanded STR multiplex sizes while maintaining sensitivity to typical forensic DNA. New supplementary kits complimenting the core STRs have also helped improve analysis of challenging identification cases such as distant pairwise relationships in deficient pedigrees. This article gives an overview of several recent key developments in forensic STR analysis: availability of expanded core STR kits and supplementary STRs, short-amplicon mini-STRs offering practical options for highly degraded DNA, Y-STR enhancements made from the identification of rapidly mutating loci, and enhanced analysis of genetic ancestry by analyzing 32-STR profiles with a Bayesian forensic classifier originally developed for SNP population data. As well as providing scope for genotyping larger numbers of STRs optimized for forensic applications, the launch of compact next-generation sequencing systems provides considerable potential for genotyping the sizeable proportion of nucleotide variation existing in forensic STRs, which currently escapes detection with CE.
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Toward male individualization with rapidly mutating y-chromosomal short tandem repeats.
Kaye N Ballantyne, Arwin Ralf, Rachid Aboukhalid, Niaz M Achakzai, Maria J Anjos, Qasim Ayub, Jože Balažic, Jack Ballantyne, David J Ballard, Burkhard Berger, Cecilia Bobillo, Mehdi Bouabdellah, Helen Burri, Tomas Capal, Stefano Caratti, Jorge Cárdenas, François Cartault, Elizeu F Carvalho, Mónica Carvalho, Baowen Cheng, Michael D Coble, David Comas, Daniel Corach, Maria E D'Amato, Sean Davison, Peter de Knijff, Maria Corazon A De Ungria, Ronny Decorte, Tadeusz Dobosz, Berit M Dupuy, Samir Elmrghni, Mateusz Gliwiński, Sara C Gomes, Laurens Grol, Cordula Haas, Erin Hanson, Jürgen Henke, Lotte Henke, Fabiola Herrera-Rodríguez, Carolyn R Hill, Gunilla Holmlund, Katsuya Honda, Uta-Dorothee Immel, Shota Inokuchi, Mark A Jobling, Mahmoud Kaddura, Jong S Kim, Soon H Kim, Wook Kim, Turi E King, Eva Klausriegler, Daniel Kling, Lejla Kovacevic, Leda Kovatsi, Paweł Krajewski, Sergey Kravchenko, Maarten H D Larmuseau, Eun Young Lee, Ruediger Lessig, Ludmila A Livshits, Damir Marjanović, Marek Minarik, Natsuko Mizuno, Helena Moreira, Niels Morling, Meeta Mukherjee, Patrick Munier, Javaregowda Nagaraju, Franz Neuhuber, Shengjie Nie, Premlaphat Nilasitsataporn, Takeki Nishi, Hye H Oh, Jill Olofsson, Valerio Onofri, Jukka U Palo, Horolma Pamjav, Walther Parson, Michal Petlach, Christopher Phillips, Rafal Ploski, Samayamantri P R Prasad, Dragan Primorac, Gludhug A Purnomo, Josephine Purps, Héctor Rangel-Villalobos, Krzysztof Rebała, Budsaba Rerkamnuaychoke, Danel Rey Gonzalez, Carlo Robino, Lutz Roewer, Alexandra Rosa, Antti Sajantila, Andrea Sala, Jazelyn M Salvador, Paula Sanz, Cornelia Schmitt, Anil K Sharma, Dayse A Silva, Kyoung-Jin Shin, Titia Sijen, Miriam Sirker, Daniela Siváková, Vedrana Skaro, Carlos Solano-Matamoros, Luis Souto, Vlastimil Stenzl, Herawati Sudoyo, Denise Syndercombe-Court, Adriano Tagliabracci, Duncan Taylor, Andreas Tillmar, Iosif S Tsybovsky, Chris Tyler-Smith, Kristiaan J van der Gaag, Daniel Vanek, Antónia Völgyi, Denise Ward, Patricia Willemse, Eric P H Yap, Rita Y Y Yong, Irena Zupanič Pajnič, Manfred Kayser.
Hum. Mutat.
PUBLISHED: 02-25-2014
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Relevant for various areas of human genetics, Y-chromosomal short tandem repeats (Y-STRs) are commonly used for testing close paternal relationships among individuals and populations, and for male lineage identification. However, even the widely used 17-loci Yfiler set cannot resolve individuals and populations completely. Here, 52 centers generated quality-controlled data of 13 rapidly mutating (RM) Y-STRs in 14,644 related and unrelated males from 111 worldwide populations. Strikingly, >99% of the 12,272 unrelated males were completely individualized. Haplotype diversity was extremely high (global: 0.9999985, regional: 0.99836-0.9999988). Haplotype sharing between populations was almost absent except for six (0.05%) of the 12,156 haplotypes. Haplotype sharing within populations was generally rare (0.8% nonunique haplotypes), significantly lower in urban (0.9%) than rural (2.1%) and highest in endogamous groups (14.3%). Analysis of molecular variance revealed 99.98% of variation within populations, 0.018% among populations within groups, and 0.002% among groups. Of the 2,372 newly and 156 previously typed male relative pairs, 29% were differentiated including 27% of the 2,378 father-son pairs. Relative to Yfiler, haplotype diversity was increased in 86% of the populations tested and overall male relative differentiation was raised by 23.5%. Our study demonstrates the value of RM Y-STRs in identifying and separating unrelated and related males and provides a reference database.
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Trends in new U.S. Marine Corps accessions during the recent conflicts in Iraq and Afghanistan.
Mil Med
PUBLISHED: 01-10-2014
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The objective of this study was to analyze trends in preservice characteristics among Marine Corps recruits during the recent operations in Iraq and Afghanistan. Recruits completed a confidential survey during their first week of training at the Marine Corps Recruit Depot in San Diego, California. Demographics, behaviors, and health information were analyzed for trends from 2001 to 2010 using the Cochran-Armitage trend test and F statistic. Data from 131,961 male recruits with a mean age of 19.8 years were analyzed. Overall, entry characteristics remained stable exhibiting only modest changes over the study period. Favorable trends included recent (2009-2010) improvements in body mass index and physical activity levels. Unfavorable trends included increases in smokeless tobacco and caffeine use, and angry outbursts. Although many recruit characteristics remained similar over the past decade, both favorable and unfavorable trends in sociobehavioral characteristics were noted. The ongoing assessment of preservice characteristics is important for detecting emerging trends over time. Findings may guide leadership's understanding of changes to help develop early-service trainings promoting a healthier force and potentially reducing future adverse outcomes.
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Health-related behaviors and effectiveness of trivalent inactivated versus live attenuated influenza vaccine in preventing influenza-like illness among young adults.
PLoS ONE
PUBLISHED: 01-01-2014
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Vaccination is the preferred preventive strategy against influenza. Though health behaviors are known to affect immunity and vaccine delivery modes utilize different immune processes, data regarding the preferred influenza vaccine type among adults endorsing specific health-related behaviors (alcohol use, tobacco use, and exercise level) are limited.
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Determinants of regioselective hydroxylation in the fungal polysaccharide monooxygenases.
J. Am. Chem. Soc.
PUBLISHED: 12-26-2013
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The ubiquitous fungal polysaccharide monooxygenases (PMOs) (also known as GH61 proteins, LPMOs, and AA9 proteins) are structurally related but have significant variation in sequence. A heterologous expression method in Neurospora crassa was developed as a step towards connecting regioselectivity of the chemistry to PMO phylogeny. Activity assays, as well as sequence and phylogenetic analyses, showed that the majority of fungal PMOs fall into three major groups with distinctive active site surface features. PMO1s and PMO2s hydroxylate glycosidic positions C1 and C4, respectively. PMO3s hydroxylate both C1 and C4. A subgroup of PMO3s (PMO3*) hydroxylate C1.Mutagenesis studies showed that an extra sub-domain of about 12 amino acids contribute to C4 oxidation in the PMO3 family.
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Postural responses to electrical stimulation of the vestibular end organs in human subjects.
Exp Brain Res
PUBLISHED: 03-26-2013
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A multichannel vestibular prosthesis that delivers electrical stimulation to the perilymph of individual semicircular canals is a potential new treatment modality for patients with vestibular deficiencies. Most research in this field has evaluated the efficacy of this approach by its ability to reproduce eye movements in response to head rotations. Our group has developed such a device and implanted it in four human subjects with intractable unilateral Menieres disease. This allows us to evaluate individual semicircular canal contribution to the control of balance and posture in human subjects. In this report, we demonstrate that electrical stimulation trains delivered to the perilymph of individual semicircular canals elicit postural responses specific to the particular canal stimulated, with some current spread to adjacent end organs. Modulation of stimulation current modulates the amplitude of the postural response. However, eye movements elicited by the same electrical stimuli were not consistent with postural responses in magnitude or direction in all subjects. Taken together, these findings support the feasibility of a vestibular prosthesis for the control of balance and illustrate new challenges for the development of this technology.
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TAK1 inhibition in the DFG-out conformation.
Chem Biol Drug Des
PUBLISHED: 03-14-2013
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The first example of an inhibitor of the kinase TAK1 that binds in the DFG-out conformation is disclosed. These preliminary studies used kinase-targeted screening and structure-based drug design to create a molecule with dual pharmacological inhibition of p38 and TAK1 that demonstrated significant activity in a cell-based, anti-inflammatory assay.
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An overview of STRUCTURE: applications, parameter settings, and supporting software.
Front Genet
PUBLISHED: 01-01-2013
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Objectives: We present an up-to-date review of STRUCTURE software: one of the most widely used population analysis tools that allows researchers to assess patterns of genetic structure in a set of samples. STRUCTURE can identify subsets of the whole sample by detecting allele frequency differences within the data and can assign individuals to those sub-populations based on analysis of likelihoods. The review covers STRUCTUREs most commonly used ancestry and frequency models, plus an overview of the main applications of the software in human genetics including case-control association studies (CCAS), population genetics, and forensic analysis. The review is accompanied by supplementary material providing a step-by-step guide to running STRUCTURE. Methods: With reference to a worked example, we explore the effects of changing the principal analysis parameters on STRUCTURE results when analyzing a uniform set of human genetic data. Use of the supporting software: CLUMPP and distruct is detailed and we provide an overview and worked example of STRAT software, applicable to CCAS. Conclusion: The guide offers a simplified view of how STRUCTURE, CLUMPP, distruct, and STRAT can be applied to provide researchers with an informed choice of parameter settings and supporting software when analyzing their own genetic data.
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Oxidative cleavage of cellulose by fungal copper-dependent polysaccharide monooxygenases.
J. Am. Chem. Soc.
PUBLISHED: 12-28-2011
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Fungal-derived, copper-dependent polysaccharide monooxygenases (PMOs), formerly known as GH61 proteins, have recently been shown to catalyze the O(2)-dependent oxidative cleavage of recalcitrant polysaccharides. Different PMOs isolated from Neurospora crassa were found to generate oxidized cellodextrins modified at the reducing or nonreducing ends upon incubation with cellulose and cellobiose dehydrogenase. Here we show that the nonreducing end product formed by an N. crassa PMO is a 4-ketoaldose. Together with isotope labeling experiments, further support is provided for a mechanism involving oxygen insertion and subsequent elimination to break glycosidic bonds in crystalline cellulose.
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Medical registrars in 2010: experience and expectations of the future consultant physicians of the UK.
Clin Med
PUBLISHED: 12-21-2011
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In 2010, 2,176 medical registrars in England (43%) responded to a survey of attitudes to current and future working conditions. Regarding current working, 88% were currently happy with their job with respect to their specialty but only 49% were happy with respect to acute medicine. Even if pay was increased, 59% would only want to work a 48-hour week or less. Regarding future jobs, 59% were worried about future job prospects with 91% exploring ways of extending their training. Only 36% would consider working away from their current location as a consultant, only 42% of those trained in acute medicine wish to take part in the acute take, 15% would consider a sub-consultant post and only 60% were looking forward to becoming a consultant. The findings of this survey show that medical registrars are very concerned about their future. From their perspective, clinical medicine in England is in poor health.
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Linking extinction-colonization dynamics to genetic structure in a salamander metapopulation.
Proc. Biol. Sci.
PUBLISHED: 11-23-2011
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Theory predicts that founder effects have a primary role in determining metapopulation genetic structure. However, ecological factors that affect extinction-colonization dynamics may also create spatial variation in the strength of genetic drift and migration. We tested the hypothesis that ecological factors underlying extinction-colonization dynamics influenced the genetic structure of a tiger salamander (Ambystoma tigrinum) metapopulation. We used empirical data on metapopulation dynamics to make a priori predictions about the effects of population age and ecological factors on genetic diversity and divergence among 41 populations. Metapopulation dynamics of A. tigrinum depended on wetland area, connectivity and presence of predatory fish. We found that newly colonized populations were more genetically differentiated than established populations, suggesting that founder effects influenced genetic structure. However, ecological drivers of metapopulation dynamics were more important than age in predicting genetic structure. Consistent with demographic predictions from metapopulation theory, genetic diversity and divergence depended on wetland area and connectivity. Divergence was greatest in small, isolated wetlands where genetic diversity was low. Our results show that ecological factors underlying metapopulation dynamics can be key determinants of spatial genetic structure, and that habitat area and isolation may mediate the contributions of drift and migration to divergence and evolution in local populations.
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Design and synthesis of inhaled p38 inhibitors for the treatment of chronic obstructive pulmonary disease.
J. Med. Chem.
PUBLISHED: 10-28-2011
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This paper describes the identification and optimization of a novel series of DFG-out binding p38 inhibitors as inhaled agents for the treatment of chronic obstructive pulmonary disease. Structure based drug design and "inhalation by design" principles have been applied to the optimization of the lead series exemplied by compound 1a. Analogues have been designed to be potent and selective for p38, with an emphasis on slow enzyme dissociation kinetics to deliver prolonged lung p38 inhibition. Pharmacokinetic properties were tuned with high intrinsic clearance and low oral bioavailability in mind, to minimize systemic exposure and reduce systemically driven adverse events. High CYP mediated clearance and glucuronidation were targeted to achieve high intrinsic clearance coupled with multiple routes of clearance to minimize drug-drug interactions. Furthermore, pharmaceutical properties such as stability, crystallinity, and solubility were considered to ensure compatibility with a dry powder inhaler. 1ab (PF-03715455) was subsequently identified as a clinical candidate from this series with efficacy and safety profiles confirming its potential as an inhaled agent for the treatment of COPD.
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Cellobiose dehydrogenase and a copper-dependent polysaccharide monooxygenase potentiate cellulose degradation by Neurospora crassa.
ACS Chem. Biol.
PUBLISHED: 10-25-2011
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The high cost of enzymes for saccharification of lignocellulosic biomass is a major barrier to the production of second generation biofuels. Using a combination of genetic and biochemical techniques, we report that filamentous fungi use oxidative enzymes to cleave glycosidic bonds in cellulose. Deletion of cdh-1, the gene encoding the major cellobiose dehydrogenase of Neurospora crassa, reduced cellulase activity substantially, and addition of purified cellobiose dehydrogenases from M. thermophila to the ?cdh-1 strain resulted in a 1.6- to 2.0-fold stimulation in cellulase activity. Addition of cellobiose dehydrogenase to a mixture of purified cellulases showed no stimulatory effect. We show that cellobiose dehydrogenase enhances cellulose degradation by coupling the oxidation of cellobiose to the reductive activation of copper-dependent polysaccharide monooxygenases (PMOs) that catalyze the insertion of oxygen into C-H bonds adjacent to the glycosidic linkage. Three of these PMOs were characterized and shown to have different regiospecifities resulting in oxidized products modified at either the reducing or nonreducing end of a glucan chain. In contrast to previous models where oxidative enzymes were thought to produce reactive oxygen species that randomly attacked the substrate, the data here support a direct, enzyme-catalyzed oxidation of cellulose. Cellobiose dehydrogenases and proteins related to the polysaccharide monooxygenases described here are found throughout both ascomycete and basidiomycete fungi, suggesting that this model for oxidative cellulose degradation may be widespread throughout the fungal kingdom. When added to mixtures of cellulases, these proteins enhance cellulose saccharification, suggesting that they could be used to reduce the cost of biofuel production.
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Quantitative proteomic approach for cellulose degradation by Neurospora crassa.
J. Proteome Res.
PUBLISHED: 08-01-2011
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Conversion of plant biomass to soluble sugars is the primary bottleneck associated with production of economically viable cellulosic fuels and chemicals. To better understand the biochemical route that filamentous fungi use to degrade plant biomass, we have taken a quantitative proteomics approach to characterizing the secretome of Neurospora crassa during growth on microcrystalline cellulose. Thirteen proteins were quantified in the N. crassa secretome using a combination of Absolute Quantification (AQUA) and Absolute SILAC to verify protein concentrations. Four of these enzymes including 2 cellobiohydrolases (CBH-1 and GH6-2), an endoglucanase (GH5-1), and a ?-glucosidase (GH3-4) were then chosen to reconstitute a defined cellulase mixture in vitro. These enzymes were assayed alone and in mixtures and the activity of the reconstituted set was then compared to the crude mixture of N. crassa secretome proteins. Results show that while these 4 proteins represent 63-65% of the total secretome by weight, they account for just 43% of the total activity on microcrystalline cellulose after 24 h of hydrolysis. This result and quantitative proteomic data on other less abundant proteins secreted by Neurospora suggest that proteins other than canonical fungal cellulases may play an important role in cellulose degradation by fungi.
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A prospective study of lupus and rheumatoid arthritis in relation to deployment in support of iraq and afghanistan: the millennium cohort study.
Autoimmune Dis
PUBLISHED: 06-13-2011
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The objective of this study was to prospectively assess the association between deployment in support of the operations in Iraq and Afghanistan and newly reported lupus and rheumatoid arthritis while also considering the effects of demographic, behavioral, and occupational characteristics. A total of 77,047 (2001-2003) and 31,110 (2004-2006) participants completed the baseline Millennium Cohort questionnaire and were resurveyed approximately every 3 years. Longitudinal analyses were used to assess the adjusted association between deployment to Iraq and Afghanistan with and without combat exposures and newly reported disease. After adjusting, deployment was not significantly associated with newly reported lupus compared with nondeployers. However, compared with nondeployers, deployers with and without combat exposures were significantly less likely to newly report rheumatoid arthritis. Women, non-Hispanic black, and Hispanic participants had a significantly elevated risk for both diseases. Overall, deployment was not associated with an increased risk of newly reported lupus or rheumatoid arthritis.
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ENGINES: exploring single nucleotide variation in entire human genomes.
BMC Bioinformatics
PUBLISHED: 04-19-2011
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Next generation ultra-sequencing technologies are starting to produce extensive quantities of data from entire human genome or exome sequences, and therefore new software is needed to present and analyse this vast amount of information. The 1000 Genomes project has recently released raw data for 629 complete genomes representing several human populations through their Phase I interim analysis and, although there are certain public tools available that allow exploration of these genomes, to date there is no tool that permits comprehensive population analysis of the variation catalogued by such data.
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Validation of a cost-efficient multi-purpose SNP panel for disease based research.
PLoS ONE
PUBLISHED: 04-13-2011
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Here we present convergent methodologies using theoretical calculations, empirical assessment on in-house and publicly available datasets as well as in silico simulations, that validate a panel of SNPs for a variety of necessary tasks in human genetics disease research before resources are committed to larger-scale genotyping studies on those samples. While large-scale well-funded human genetic studies routinely have up to a million SNP genotypes, samples in a human genetics laboratory that are not yet part of such studies may be productively utilized in pilot projects or as part of targeted follow-up work though such smaller scale applications require at least some genome-wide genotype data for quality control purposes such as DNA "barcoding" to detect swaps or contamination issues, determining familial relationships between samples and correcting biases due to population effects such as population stratification in pilot studies.
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The combined influence of oral contraceptives and human papillomavirus virus on cutaneous squamous cell carcinoma.
Clin Med Insights Oncol
PUBLISHED: 03-27-2011
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The vast majority of cutaneous squamous cell carcinoma (CSCC) will occur in those with fair complexion, tendency to burn, and high ultraviolet radiation (UVR) exposure. Organ transplant recipients also are an important population at great risk for CSCC. An association has been reported between oral contraceptive (OC) use, human papillomavirus virus (HPV) and cervical cancer, and there could be a similar association for CSCC. The cutaneous HPV ?-E6 protein, a close cousin of the transformative E6 protein underlying anogenital cancers, has been shown to inhibit apoptosis in response to UVR damage and stimulate morphologic transformation in rodent fibroblast cell lines. Furthermore, OC use has been shown to enhance HPV transcription and may contribute to CSCC risk through this pathway.
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Do frogs get their kicks on Route 66? Continental U.S. transect reveals spatial and temporal patterns of Batrachochytrium dendrobatidis infection.
PLoS ONE
PUBLISHED: 03-07-2011
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The chytrid fungus Batrachochytrium dendrobatidis (Bd) has been devastating amphibians globally. Two general scenarios have been proposed for the nature and spread of this pathogen: Bd is an epidemic, spreading as a wave and wiping out individuals, populations, and species in its path; and Bd is endemic, widespread throughout many geographic regions on every continent except Antarctica. To explore these hypotheses, we conducted a transcontinental transect of United States Department of Defense (DoD) installations along U.S. Highway 66 from California to central Illinois, and continuing eastward to the Atlantic Seaboard along U.S. Interstate 64 (in sum from Marine Corps Base Camp Pendleton in California to Naval Air Station Oceana in Virginia). We addressed the following questions: 1) Does Bd occur in amphibian populations on protected DoD environments? 2) Is there a temporal pattern to the presence of Bd? 3) Is there a spatial pattern to the presence of Bd? and 4) In these limited human-traffic areas, is Bd acting as an epidemic (i.e., with evidence of recent introduction and/or die-offs due to chytridiomycosis), or as an endemic (present without clinical signs of disease)? Bd was detected on 13 of the 15 bases sampled. Samples from 30 amphibian species were collected (10% of known United States species); half (15) tested Bd positive. There was a strong temporal (seasonal) component; in total, 78.5% of all positive samples came in the first (spring/early-summer) sampling period. There was also a strong spatial component--the eleven temperate DoD installations had higher prevalences of Bd infection (20.8%) than the four arid (<60 mm annual precipitation) bases (8.5%). These data support the conclusion that Bd is now widespread, and promote the idea that Bd can today be considered endemic across much of North America, extending from coast-to-coast, with the exception of remote pockets of naïve populations.
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Telemonitoring in patients with heart failure.
N. Engl. J. Med.
PUBLISHED: 11-16-2010
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Small studies suggest that telemonitoring may improve heart-failure outcomes, but its effect in a large trial has not been established.
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CADASIL can mimic multiple sclerosis.
J La State Med Soc
PUBLISHED: 07-30-2010
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Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) can be confused with multiple sclerosis (MS). We report a man with a father diagnosed with MS via magnetic resonance imaging (MRI). The index patient was subsequently diagnosed with MS after MRI for evaluation of migraine headaches. Genetic testing confirmed the CADASIL diagnosis. CADASIL is characterized by a history of migraine headaches, mid-adult onset of progressive cerebrovascular disease, diffuse white matter changes, and dementia. The mutation involves the Notch3 gene which changes a codon for arginine to cysteine at amino acid position 90.
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Racial disparities in health literacy and access to care among patients with heart failure.
J. Card. Fail.
PUBLISHED: 07-28-2010
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Previous work has shown that there is a higher frequency of hospitalizations among black heart failure patients relative to white heart failure patients. We sought to determine whether racial differences exist in health literacy and access to outpatient medical care, and to identify factors associated with these differences.
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Expression and characterization of the Neurospora crassa endoglucanase GH5-1.
Protein Expr. Purif.
PUBLISHED: 07-08-2010
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Filamentous fungi secrete a wide range of enzymes, including cellulases and hemicellulases, with potential applications in the production of lignocellulosic biofuels. Of the cellulolytic fungi, Hypocrea jecorina (anamorph Trichoderma reesei) is the best characterized in terms of cellulose degradation, but other cellulolytic fungi, such as the model filamentous fungus Neurospora crassa, can serve a crucial role in building our knowledge about the fungal response to biomass due to the many molecular and genetic tools available for this organism. Here we cloned and expressed GH5-1 (NCU00762), a secreted endoglucanase in N. crassa. The protein was produced using a ccg-1 promoter under conditions in which no other cellulases are present. Native GH5-1 (nGH5-1) and this recombinant GH5-1 (rGH5-1) were purified to gauge differences in glycosylation and activity; both rGH5-1 and nGH5-1 were similarly glycosylated, with an estimated molecular weight of 52kDa. On azo-carboxymethylcellulose, rGH5-1 activity was equal to that of nGH5-1, and on cellulose (Avicel) rGH5-1 was 20% more active. The activity of a GH5-1-GFP fusion protein (rGH5-1-GFP-6xHis) was similar to rGH5-1 and nGH5-1. To determine the binding pattern of catalytically active rGH5-1-GFP-6xHis to plant cell walls, Arabidopsis seedlings were incubated with rGH5-1-GFP-6xHis or Pontamine Fast Scarlet 4B (S4B), a cellulose-specific dye. Confocal microscopy showed that rGH5-1-GFP-6xHis bound in linear, longitudinal patterns on seedling roots, similar to S4B. The functional expression and characterization of rGH5-1 and its GFP fusion derivative set important precedents for further investigation of biomass degradation by filamentous fungi, especially N. crassa, with applications for characterization and manipulation of novel enzymes.
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Risk factors for posttraumatic stress disorder among deployed US male marines.
BMC Psychiatry
PUBLISHED: 06-25-2010
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Combat exposure has been reported as one of the strongest risk factors for postdeployment posttraumatic stress disorder (PTSD) among military service members. Determining the impact of specific deployment-related exposures on the risk of developing PTSD has not been fully explored. Our study objective was to explore the relationship between specific combat exposures and other life experiences with postdeployment PTSD.
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Association study of 44 candidate genes with depressive and anxiety symptoms in post-partum women.
J Psychiatr Res
PUBLISHED: 01-22-2010
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The post-partum period is a time of extreme vulnerability for a whole spectrum of psychiatric disorders. Delivery may be considered an important risk factor in genetically susceptible women. Five hundred and eight SNPs in 44 genes at candidate pathways putatively related to mood changes after delivery were genotyped in a multicenter cohort of 1804 women from Spain. Participants completed two scales at 2-3 days, 8 weeks, and 32 weeks post-partum, the Edinburgh Post-partum Depression Scale (EPDS) and the Spielberger State-Trait Anxiety Inventory (STAI). Those women who scored 9 or more on EPDS were evaluated for major depression using the Diagnostic Interview for Genetics Studies (DIGS) adapted for post-partum depression. Association with major depression was assessed using likelihood ratio tests under a codominant genotype model. Association with scale scores was tested using linear mixed models to take into account repeated measures over time. Two intronic SNPs, one at the serotonin transporter gene (SLC6A4) and another at dopa decarboxylase (DDC), were significantly associated to STAI anxiety scores after multiple testing correction (nominal P=0.0000513 and 0.000097, respectively). In addition, post hoc analysis at the unphased haplotype level using nominal significant SNPs revealed an association with a combination of three SNPs at protein kinase C, beta (PRKCB) with major depression, significant after multiple testing correction (nominal global P=0.0001596). In conclusion, we detected a role of SLC6A4 in mood changes after stressful events, and revealed new putative associations involving DDC and PRKCB. Therefore, these genes deserve further investigation to confirm these results.
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Discharge planning from hospital to home.
Cochrane Database Syst Rev
PUBLISHED: 01-22-2010
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Discharge planning is a routine feature of health systems in many countries. The aim of discharge planning is to reduce hospital length of stay and unplanned readmission to hospital, and improve the co-ordination of services following discharge from hospital.
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A new multiplex for human identification using insertion/deletion polymorphisms.
Electrophoresis
PUBLISHED: 10-29-2009
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Human identification is usually based on the study of STRs or SNPs depending on the particular characteristics of the investigation. However, other types of genetic variation such as insertion/deletion polymorphisms (indels) have considerable potential in the field of identification, since they can combine the desirable characteristics of both STRs and SNPs. In this study, a set of 38 non-coding bi-allelic autosomal indels reported to be polymorphic in African, European, and Asian populations were selected. We developed a sensitive genotyping assay, which is able to characterize all 38 bi-allelic markers using a single multiplex PCR and detected with standard CE analyzers. Amplicon length was designed to be shorter than 160 bp. Complete profiles were obtained using 0.3 ng of DNA, and full genotyping of degraded samples was possible in cases where standard STR typing had partially failed. A total of 306 individuals from Angola, Mozambique, Portugal, Macau, and Taiwan were studied and population data are presented. All indels were polymorphic in the three population groups studied and the random match probabilities of the set ranged in orders of magnitude from 10(-14) to 10(-15). Therefore, the indel-plex represents a valuable approach in human identification studies, especially in challenging DNA cases, as a more straightforward and efficient alternative to SNP typing.
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SNP databases.
Methods Mol. Biol.
PUBLISHED: 09-22-2009
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Researchers interested in obtaining detailed information on SNPs now work in a golden age of online database availability: never has so much data and such a wealth of information been freely accessible for such a substantial proportion of the 18 million single nucleotide polymorphism (SNP) loci currently characterized in the human genome. This chapter describes the major SNP databases available for human genetics studies. Tools and strategies are outlined that can help researchers properly formulate a database query to be able to access the most appropriate information needed for their research aims, including medical or population genetics analysis--an approach that is getting increased attention given the expanding scale of online SNP data.
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Ancestry analysis in the 11-M Madrid bomb attack investigation.
PLoS ONE
PUBLISHED: 07-08-2009
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The 11-M Madrid commuter train bombings of 2004 constituted the second biggest terrorist attack to occur in Europe after Lockerbie, while the subsequent investigation became the most complex and wide-ranging forensic case in Spain. Standard short tandem repeat (STR) profiling of 600 exhibits left certain key incriminatory samples unmatched to any of the apprehended suspects. A judicial order to perform analyses of unmatched samples to differentiate European and North African ancestry became a critical part of the investigation and was instigated to help refine the search for further suspects. Although mitochondrial DNA (mtDNA) and Y-chromosome markers routinely demonstrate informative geographic differentiation, the populations compared in this analysis were known to show a proportion of shared mtDNA and Y haplotypes as a result of recent gene-flow across the western Mediterranean, while any two loci can be unrepresentative of the ancestry of an individual as a whole. We based our principal analysis on a validated 34plex autosomal ancestry-informative-marker single nucleotide polymorphism (AIM-SNP) assay to make an assignment of ancestry for DNA from seven unmatched case samples including a handprint from a bag containing undetonated explosives together with personal items recovered from various locations in Madrid associated with the suspects. To assess marker informativeness before genotyping, we predicted the probable classification success for the 34plex assay with standard error estimators for a naïve Bayesian classifier using Moroccan and Spanish training sets (each n = 48). Once misclassification error was found to be sufficiently low, genotyping yielded seven near-complete profiles (33 of 34 AIM-SNPs) that in four cases gave probabilities providing a clear assignment of ancestry. One of the suspects predicted to be North African by AIM-SNP analysis of DNA from a toothbrush was identified late in the investigation as Algerian in origin. The results achieved illustrate the benefit of adding specialized marker sets to provide enhanced scope and power to an already highly effective system of DNA analysis for forensic identification.
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Identification, synthesis and SAR of amino substituted pyrido[3,2b]pyrazinones as potent and selective PDE5 inhibitors.
Bioorg. Med. Chem. Lett.
PUBLISHED: 05-08-2009
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A new class of potent and selective PDE5 inhibitors is disclosed. Guided by X-ray crystallographic data, optimization of an HTS lead led to the discovery of a series of 2-aryl, (N8)-alkyl substituted-6-aminosubstituted pyrido[3,2b]pyrazinones which show potent inhibition of the PDE5 enzyme. Synthetic details and some structure-activity relationships are also presented.
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Antibodies to squalene in US Navy Persian Gulf War veterans with chronic multisymptom illness.
Vaccine
PUBLISHED: 03-24-2009
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Since the end of the 1991 Gulf War, there have been reports of unexplained, multisymptom illnesses afflicting veterans who consistently report more symptoms than do nondeployed veterans. One of the many possible exposures suspected of causing chronic multisymptom illnesses Gulf War veterans is squalene, thought to be present in anthrax vaccine. We examined the relationship between squalene antibodies and chronic symptoms reported by Navy construction workers (Seabees), n=579. 30.2% were deployers, 7.4% were defined as ill, and 43.5% were positive for squalene antibodies. We found no association between squalene antibody status and chronic multisymptom illness (p=0.465). The etiology of Gulf War syndrome remains unknown, but should not include squalene antibody status.
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Viability of in-house datamarting approaches for population genetics analysis of SNP genotypes.
BMC Bioinformatics
PUBLISHED: 03-19-2009
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Databases containing very large amounts of SNP (Single Nucleotide Polymorphism) data are now freely available for researchers interested in medical and/or population genetics applications. While many of these SNP repositories have implemented data retrieval tools for general-purpose mining, these alone cannot cover the broad spectrum of needs of most medical and population genetics studies.
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Gene expression profiling of rat hippocampus following exposure to the acetylcholinesterase inhibitor soman.
Chem. Res. Toxicol.
PUBLISHED: 03-14-2009
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Soman (O-pinacolyl methylphosphonofluoridate) is a potent neurotoxicant. Acute exposure to soman causes acetylcholinesterase inhibition, resulting in excessive levels of acetylcholine. Excessive acetylcholine levels cause convulsions, seizures, and respiratory distress. The initial cholinergic crisis can be overcome by rapid anticholinergic therapeutic intervention, resulting in increased survival. However, conventional treatments do not protect the brain from seizure-related damage, and thus, neurodegeneration of soman-sensitive brain areas is a potential postexposure outcome. We performed gene expression profiling of the rat hippocampus following soman exposure to gain greater insight into the molecular pathogenesis of soman-induced neurodegeneration. Male Sprague-Dawley rats were pretreated with the oxime HI-6 (l-(((4-aminocarbonyl)pyridinio)methoxyl)methyl)-2-((hydroxyimino)methyl)-pyridinium dichloride; 125 mg/kg, ip) 30 min prior to challenge with soman (180 microg/kg, sc). One minute after soman challenge, animals were treated with atropine methyl nitrate (2.0 mg/kg, im). Hippocampi were harvested 1, 3, 6, 12, 24, 48, 72, 96, and 168 h after soman exposure and RNA extracted to generate microarray probes for gene expression profiling. Principal component analysis of the microarray data revealed a progressive alteration in gene expression profiles beginning 1 h postexposure and continuing through 24 h postexposure. At 48 h to 168 h postexposure, the gene expression profiles clustered nearer to controls but did not completely return to control profiles. On the basis of the principal component analysis, analysis of variance was used to identify the genes most significantly changed as a result of soman at each postexposure time point. To gain insight into the biological relevance of these gene expression changes, genes were rank ordered by p-value and categorized using gene ontology-based algorithms into biological functions, canonical pathways, and gene networks significantly affected by soman. Numerous signaling and inflammatory pathways were identified as perturbed by soman. These data provide important insights into the molecular pathways involved in soman-induced neuropathology and a basis for generating hypotheses about the mechanism of soman-induced neurodegeneration.
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Global gene expression in rat brain and liver after oral exposure to the explosive hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX).
Chem. Res. Toxicol.
PUBLISHED: 02-26-2009
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RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine) is a synthetic, high-impact, relatively stable explosive that has been in use since WWII. Exposure to RDX can occur in occupational settings (e.g., during manufacture) or through the inadvertent ingestion of contaminated environmental media such as groundwater. The toxicology of RDX is dominated by acute clonic-tonic seizures at high doses, which remit when exposure is removed and internal RDX levels decrease. Subchronic studies have revealed few other measurable toxic effects. The objective of this study was to examine the acute effects of RDX on the mammalian brain and liver using global gene expression analysis based on a predetermined maximum internal dose. Male Sprague-Dawley rats were given a single, oral, nonseizure-inducing dose of either 3 or 18 mg/kg RDX in a gel capsule. Effects on gene expression in the cerebral cortex and liver were assessed using Affymetrix Rat Genome 230 2.0 whole genome arrays at 0, 3.5, 24, and 48 h postexposure. RDX blood and brain tissue concentrations rapidly increased between 0 and 3.5 h, followed by decreases at 24 h to below the detection limit at 48 h. Pairwise comparison of high and low doses at each time point showed dramatic differential changes in gene expression at 3.5 h, the time of peak RDX in brain and blood. Using Gene Ontology, biological processes that affected neurotransmission were shown to be primarily down-regulated in the brain, the target organ of toxicity, while those that affected metabolism were up-regulated in the liver, the site of metabolism. Overall, these results demonstrate that a single oral dose of RDX is quickly absorbed and transported into the brain where processes related to neurotransmission are negatively affected, consistent with a potential excitotoxic response, whereas in the liver there was a positive effect on biological processes potentially associated with RDX metabolism.
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Dopamine modulates an mGluR5-mediated depolarization underlying prefrontal persistent activity.
Nat. Neurosci.
PUBLISHED: 01-25-2009
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The intrinsic properties of neurons that enable them to maintain depolarized, persistently activated states in the absence of sustained input are poorly understood. In short-term memory tasks, individual prefrontal cortical (PFC) neurons can maintain persistent action potential output during delay periods between informative cues and behavioral responses. Dopamine and drugs of abuse alter PFC function and working memory, possibly by modulating intrinsic neuronal properties. Here we used patch-clamp recording of layer 5 PFC pyramidal neurons to identify a postsynaptic depolarization that was evoked by action potential bursts and mediated by metabotropic glutamate receptor 5 (mGluR5). This depolarization occurred in the absence of recurrent synaptic activity and was reduced by a dopamine D1 receptor (D1R) protein kinase A pathway. After behavioral sensitization to cocaine, the depolarization was substantially diminished and D1R modulation was lost. We propose that burst-evoked intrinsic depolarization is a form of short-term cellular memory that is modulated by dopamine and cocaine experience.
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Longitudinal performance of a vestibular prosthesis as assessed by electrically evoked compound action potential recording.
Conf Proc IEEE Eng Med Biol Soc
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Electrical stimulation of the vestibular end organ with a vestibular prosthesis may provide an effective treatment for vestibular loss if the stimulation remains effective over a significant period of time after implantation of the device. To assess efficacy of electrical stimulation in an animal model, we implanted 3 rhesus monkeys with a vestibular prosthesis based on a cochlear implant. We then recorded vestibular electrically evoked compound action potentials (vECAPs) longitudinally in each of the implanted canals to see how the amplitude of the response changed over time. The results suggest that vECAPs, and therefore electrical activation of vestibular afferent fibers, can remain largely stable over time following implantation.
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Comparison of the effectiveness of trivalent inactivated influenza vaccine and live, attenuated influenza vaccine in preventing influenza-like illness among US military service members, 2006-2009.
Clin. Infect. Dis.
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Influenza is a significant cause of morbidity, and vaccination is the preferred preventive strategy. Data regarding the preferred influenza vaccine type among adults are limited.
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Evaluation of forensic and anthropological potential of D9S1120 in Mestizos and Amerindian populations from Mexico.
Croat. Med. J.
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To carry out a deeper forensic and anthropological evaluation of the short tandem repeat (STR) D9S1120 in five Mestizo populations and eight Amerindian groups from Mexico.
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Comparative analysis of the efficacy of continuous glucose monitoring and self-monitoring of blood glucose in type 1 diabetes mellitus.
J Diabetes Sci Technol
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Self-monitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM) have been proven effective in improving hemoglobin A1c (HbA1c) and in reducing hypoglycemia in patients with type 1 diabetes mellitus (T1DM). It is not clear, however, if CGM provides further efficacy and safety benefits beyond SMBG in the management of T1DM.
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SNPs as Supplements in Simple Kinship Analysis or as Core Markers in Distant Pairwise Relationship Tests: When Do SNPs Add Value or Replace Well-Established and Powerful STR Tests?
Transfus Med Hemother
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BACKGROUND: Genetic tests for kinship testing routinely reach likelihoods that provide virtual proof of the claimed relationship by typing microsatellites-commonly consisting of 12-15 standard forensic short tandem repeats (STRs). Single nucleotide polymorphisms (SNPs) have also been applied to kinship testing but these binary markers are required in greater numbers than multiple-allele STRs. However SNPs offer certain advantageous characteristics not found in STRs, including, much higher mutational stability, good performance typing highly degraded DNA, and the ability to be readily up-scaled to very high marker numbers reaching over a million loci. This article outlines kinship testing applications where SNPs markedly improve the genetic data obtained. In particular we explore the minimum number of SNPs that will be required to confirm pairwise relationship claims in deficient pedigrees that typify missing persons identification or war grave investigations where commonly few surviving relatives are available for comparison and the DNA is highly degraded. METHODS: We describe the application of SNPs alongside STRs when incomplete profiles or allelic instability in STRs create ambiguous results, we review the use of high density SNP arrays when the relationship claim is very distant, and we outline simulations of kinship analyses with STRs supplemented with SNPs in order to estimate the practical limit of pairwise relationships that can be differentiated from random unrelated pairs from the same population. RESULTS: The minimum number of SNPs for robust statistical inference of parent-offspring relationships through to those of second cousins (S-3-3) is estimated for both simple, single multiplex SNP sets and for subsets of million-SNP arrays. CONCLUSIONS: There is considerable scope for resolving ambiguous STR results and for improving the statistical power of kinship analysis by adding small-scale SNP sets but where the pedigree is deficient the pairwise relationships must be relatively close. For more distant relationships it is possible to reduce chip-based SNP arrays from the million+ markers down to ?7,000. However, such numbers indicate that current genotyping approaches will not be able to deliver sufficient data to resolve distant pairwise relationships from the limited DNA typical of the most challenging identification cases.
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The effects of exposure to documented open-air burn pits on respiratory health among deployers of the Millennium Cohort Study.
J. Occup. Environ. Med.
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To investigate respiratory illnesses and potential open-air burn pit exposure among Millennium Cohort participants who deployed to Iraq or Afghanistan.
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Prospective assessment of chronic multisymptom illness reporting possibly associated with open-air burn pit smoke exposure in Iraq.
J. Occup. Environ. Med.
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To investigate the relationship between chronic multisymptom illness (CMI) and possible exposure to an open-air burn pit at three selected bases among those deployed to operations in Iraq and Afghanistan.
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Evaluation of PRDM9 variation as a risk factor for recurrent genomic disorders and chromosomal non-disjunction.
Hum. Genet.
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Recent studies have identified PRDM9, a zinc finger (ZF) protein, as a key regulator of meiotic recombination. As both recurrent genomic disorders and chromosomal non-disjunction are known to be associated with specific unusual patterns of recombination, we hypothesized a possible link between PRDM9 ZF variation and susceptibility to microdeletion syndromes and/or trisomy. We sequenced the PRDM9 ZF domain in 271 parents of patients with de novo microdeletions of known parental origin (velocardiofacial syndrome, the 17q21.31 microdeletion syndrome, Prader-Willi/Angelman syndrome and Williams-Beuren syndrome), and in 61 parents of individuals with a supernumerary X chromosome. We compared PRDM9 ZF genotype frequencies between parents in whose germ line the de novo rearrangement occurred and their spouses. We observed a significantly increased frequency (p = 0.006) of PRDM9 variants in parents who transmitted de novo 7q11.23 deletions to their offspring. These data suggest that certain PRDM9 alleles may be associated with an increased susceptibility to recurrent 7q11.23 microdeletions that cause Williams-Beuren syndrome. However, as the majority of parents who transmitted a de novo microdeletion/supernumerary X chromosome to their offspring have the common AA genotype, we conclude that none of the rearrangements we have studied are dependent on specific non-A PRDM9 alleles.
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Patterning of antibodies using flexographic printing.
Langmuir
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Antibodies were patterned onto flexible plastic films using the flexographic printing process. An ink formulation was developed using high molecular weight polyvinyl alcohol in carbonate-bicarbonate buffer. In order to aid both antibody adhesion and the quality of definition in the printed features, a nitrocellulose coating was developed that was capable of being discretely patterned, thus increasing the signal-to-noise ratio of an antibody array. Printing antibody features such as dots, squares, text, and fine lines were reproduced effectively. Furthermore, this process could be easily adapted for printing of other biological materials, including, but not limited to, enzymes, DNA, proteins, aptamers, and cells.
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Newly reported lupus and rheumatoid arthritis in relation to deployment within proximity to a documented open-air burn pit in Iraq.
J. Occup. Environ. Med.
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To assess the relationship between possible exposure to smoke from documented open-air burn pits and newly reported lupus and rheumatoid arthritis among Millennium Cohort participants who have deployed in support of operations in Iraq and Afghanistan.
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Structural basis for substrate targeting and catalysis by fungal polysaccharide monooxygenases.
Structure
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The use of cellulases remains a major cost in the production of renewable fuels and chemicals from lignocellulosic biomass. Fungi secrete copper-dependent polysaccharide monooxygenases (PMOs) that oxidatively cleave crystalline cellulose and improve the effectiveness of cellulases. However, the means by which PMOs recognize and cleave their substrates in the plant cell wall remain unclear. Here, we present structures of Neurospora crassa PMO-2 and PMO-3 at 1.10 and 1.37 Å resolution, respectively. In the structures, dioxygen species are found in the active sites, consistent with the proposed cleavage mechanism. Structural and sequence comparisons between PMOs also reveal that the enzyme substrate-binding surfaces contain highly varied aromatic amino acid and glycosylation positions. The structures reported here provide evidence for a wide range of PMO substrate recognition patterns in the plant cell wall, including binding modes that traverse multiple glucan chains.
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Informational odds ratio: a useful measure of epidemiologic association in environment exposure studies.
Environ Health Insights
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The informational odds ratio (IOR) measures the post-exposure odds divided by the pre-exposure odds (ie, information gained after knowing exposure status). A desirable property of an adjusted ratio estimate is collapsibility (ie, the combined crude ratio will not change after adjusting for a variable that is not a confounder). Adjusted traditional odds ratios (TORs) are not collapsible. In contrast, Mantel-Haenszel adjusted IORs generally are collapsible. IORs are a useful measure of disease association in environmental case-referent studies, especially when the disease is common in the exposed and/or unexposed groups.
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Birth outcomes among military personnel after exposure to documented open-air burn pits before and during pregnancy.
J. Occup. Environ. Med.
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To examine birth outcomes in military women and men with potential exposure to documented open-air burn pits before and during pregnancy.
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Straightforward inference of ancestry and admixture proportions through ancestry-informative insertion deletion multiplexing.
PLoS ONE
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Ancestry-informative markers (AIMs) show high allele frequency divergence between different ancestral or geographically distant populations. These genetic markers are especially useful in inferring the likely ancestral origin of an individual or estimating the apportionment of ancestry components in admixed individuals or populations. The study of AIMs is of great interest in clinical genetics research, particularly to detect and correct for population substructure effects in case-control association studies, but also in population and forensic genetics studies. This work presents a set of 46 ancestry-informative insertion deletion polymorphisms selected to efficiently measure population admixture proportions of four different origins (African, European, East Asian and Native American). All markers are analyzed in short fragments (under 230 basepairs) through a single PCR followed by capillary electrophoresis (CE) allowing a very simple one tube PCR-to-CE approach. HGDP-CEPH diversity panel samples from the four groups, together with Oceanians, were genotyped to evaluate the efficiency of the assay in clustering populations from different continental origins and to establish reference databases. In addition, other populations from diverse geographic origins were tested using the HGDP-CEPH samples as reference data. The results revealed that the AIM-INDEL set developed is highly efficient at inferring the ancestry of individuals and provides good estimates of ancestry proportions at the population level. In conclusion, we have optimized the multiplexed genotyping of 46 AIM-INDELs in a simple and informative assay, enabling a more straightforward alternative to the commonly available AIM-SNP typing methods dependent on complex, multi-step protocols or implementation of large-scale genotyping technologies.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.