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Jun Itakura, Masayuki Kurosaki, Chitomi Hasebe, Yukio Osaki, Kouji Joko, Hitoshi Yagisawa, Shinya Sakita, Hiroaki Okushin, Takashi Satou, Hiroyuki Hisai, Takehiko Abe, Keiji Tsuji, Takashi Tamada, Haruhiko Kobashi, Akeri Mitsuda, Yasushi Ide, Chikara Ogawa, Syotaro Tsuruta, Kouichi Takaguchi, Miyako Murakawa, Yasuhiro Asahina, Nobuyuki Enomoto, Namiki Izumi
BACKGROUNDS & AIMS: We aimed to clarify the characteristics of resistance-associated substitutions (RASs) after treatment failure with NS5A inhibitor, daclatasvir (DCV) in combination with NS3/4A inhibitor, asunaprevir (ASV), in patients with chronic hepatitis C virus genotype 1b infection. METHODS: This is a nationwide multicenter study conducted by the Japanese Red Cross Liver Study Group. The sera were obtained from 68 patients with virological failure after 24 weeks of DCV/ASV treatment...
2016: PloS One
Sabrina J Merat, Richard Molenkamp, Koen Wagner, Sylvie M Koekkoek, Dorien van de Berg, Etsuko Yasuda, Martino Böhne, Yvonne B Claassen, Bart P Grady, Maria Prins, Arjen Q Bakker, Menno D de Jong, Hergen Spits, Janke Schinkel, Tim Beaumont
Hepatitis C virus (HCV) is world-wide a major cause of liver related morbidity and mortality. No vaccine is available to prevent HCV infection. To design an effective vaccine, understanding immunity against HCV is necessary. The memory B cell repertoire was characterized from an intravenous drug user who spontaneously cleared HCV infection 25 years ago. CD27+IgG+ memory B cells were immortalized using BCL6 and Bcl-xL. These immortalized B cells were used to study antibody-mediated immunity against the HCV E1E2 glycoproteins...
2016: PloS One
Daveena Meeks, Susan E Robinson, David Macleod, Eugene Oteng-Ntim
Pregnancy in women with Sickle Cell Disease (SCD) has been linked with an increased incidence of adverse foetal outcomes when compared to women without haemoglobinopathies (HbAA). There's a paucity of data into foetal outcomes for infants born to women with SCD. Customised growth charts have been demonstrated to be better than population-based growth charts at identifying unhealthy small babies. We analysed the mean birth weight and customised birth weight centiles of infants born to mothers with SCD versus mothers with HbAA genotype, to quantify the risk of having a smaller baby...
2016: PloS One
Amy B Wilfert, Katherine R Chao, Madhurima Kaushal, Sanjay Jain, Sebastian Zöllner, David R Adams, Donald F Conrad
Standard techniques from genetic epidemiology are ill-suited to formally assess the significance of variants identified from a single case. We developed a statistical inference framework for identifying unusual functional variation from a single exome or genome, what we refer to as the 'n-of-one' problem. Using this approach we assessed our ability to identify the causal genotypes in over 5 million simulated cases of Mendelian disease, identifying 39% of disease genotypes as the most damaging unit in a typical exome background...
October 24, 2016: Nature Genetics
María Muñoz-Amatriaín, Hamid Mirebrahim, Pei Xu, Steve I Wanamaker, MingCheng Luo, Hind Alhakami, Matthew Alpert, Ibrahim Atokple, Benoit Joseph Batieno, Ousmane Boukar, Serdar Bozdag, Ndiaga Cisse, Issa Drabo, Jeffrey D Ehlers, Andrew Farmer, Christian Fatokun, Yong Q Gu, Yi-Ning Guo, Bao-Lam Huynh, Scott A Jackson, Francis Kusi, Cynthia T Lawley, Mitchell R Lucas, Yaqin Ma, Michael P Timko, Jiajie Wu, Frank You, Philip A Roberts, Stefano Lonardi, Timothy J Close
Cowpea (Vigna unguiculata L. Walp.) is a legume crop that is resilient to hot and drought-prone climates, and a primary source of protein in sub-Saharan Africa and other parts of the developing world. However, genome resources for cowpea have lagged behind most other major crops. Here we describe foundational genome resources and their application to analysis of germplasm currently in use in West African breeding programs. Resources developed from the African cultivar IT97K-499-35 include a whole-genome shotgun (WGS) assembly, a bacterial artificial chromosome (BAC) physical map, and assembled sequences from 4,355 BACs...
October 24, 2016: Plant Journal: for Cell and Molecular Biology
Feng Su, Pamela K Green, Kristin Berry, George N Ioannou
: Black race and Hispanic ethnicity were associated with lower rates of sustained virologic response (SVR) to interferon (IFN)-based treatments for chronic hepatitis C virus (HCV) infection whereas Asian race was associated with higher SVR rates compared to white patients. We aimed to describe the association between race/ethnicity and effectiveness of new direct-acting antiviral (DAA) regimens in the Veterans Affairs (VA) healthcare system nationally. We identified 21,095 HCV-infected patients (11,029 [52%] white, 6,171 [29%] black, 1,187 [6%] Hispanic, 348 [2%] Asian/Pacific Islander/American Indian/Alaska Native [Asian/PI/AI/AN] and 2,360 [11%] declined/missing race or ethnicity) who initiated antiviral treatment with regimens containing sofosbuvir (SOF), simeprevir + sofosbuvir (SMV+SOF), ledipasvir/sofosbuvir (LDV/SOF) or paritaprevir/ombitasvir/ritonavir/dasabuvir (PrOD), during the 18-month period from 01/01/2014 to 06/30/2015...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
José Alcaraz-Quiles, Esther Titos, Mireia Casulleras, Marco Pavesi, Cristina López-Vicario, Bibiana Rius, Aritz Lopategi, Andrea de Gottardi, Ivo Graziadei, Henning Gronbaek, Pere Ginès, Mauro Bernardi, Vicente Arroyo, Joan Clària
: Acute-on-chronic liver failure (ACLF) in cirrhosis is an increasingly recognized syndrome characterized by acute decompensation, organ failure(s) and high short-term mortality. Recent findings suggest that an over-exuberant systemic inflammation plays a primary role in ACLF progression. In this study, we examined whether genetic factors shape systemic immune responses in patients with decompensated cirrhosis. Six single nucleotide polymorphisms (SNPs) in inflammation-related genes (IL-1β: rs1143623, IL-1ra: rs4251961, IL-10: rs1800871, SOCS3: rs4969170, NOD2: rs3135500 and CMKLR1: rs1878022) were genotyped in 279 cirrhotic patients with (n=178) and without (n=101) ACLF from the CANONIC study of the CLIF consortium...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Wenjun Jia, Xin Qi, Qi Li
BACKGROUND Atrial fibrillation (AF) is the most common sustained arrhythmia affected by multiple cardiovascular risk factors. It is reported that caveolin-1 gene (CAV1) rs3807989 polymorphism might be associated with AF risk. The goal of this meta-analysis was to confirm the association between CAV1 rs3807989 polymorphism and susceptibility to AF. MATERIAL AND METHODS We carried out a comprehensive literature search through the electronic databases PubMed, MEDLIN, and Web of Science. We performed a meta-analysis of all selected studies based on CAV1 rs3807989 polymorphism genotypes, including 3758 cases and 6126 controls...
October 24, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Lynnette R Ferguson, Matthew P G Barnett
For many years, there has been confusion about the role that nutrition plays in inflammatory bowel diseases (IBD). It is apparent that good dietary advice for one individual may prove inappropriate for another. As with many diseases, genome-wide association studies across large collaborative groups have been important in revealing the role of genetics in IBD, with more than 200 genes associated with susceptibility to the disease. These associations provide clues to explain the differences in nutrient requirements among individuals...
October 21, 2016: International Journal of Molecular Sciences
Hongbo Chen, Yinan Yao, Yifan Wang, Hua Zhou, Tianxiang Xu, Jing Liu, Guocheng Wang, Yongfeng Zhang, Xiang Chen, Qingwei Liu, Peng Huang, Rongbin Yu
BACKGROUND: HLA-DM gene, which is related to antigen processing and presentation and located in the non-classical class-II region of human leukocyte antigen (HLA) region, may play a crucial role in chronic hepatitis C virus (HCV) infection treatment outcomes. The study was conducted to evaluate the role of the variant of several single nucleotide polymorphisms (SNPs) in HLA-DM gene in HCV treatment outcomes. METHODS: We genotyped four SNPs from the candidate genes (HLA-DMA and DMB) in 336 patients who were treated with pegylated interferon-alpha and ribavirin (PEG IFN-α/RBV)...
October 20, 2016: International Journal of Environmental Research and Public Health
Jerome A Staal, Yanxin Pei, Brian R Rood
Brain tumors are the leading cause of cancer-related deaths in children, and medulloblastoma is the most prevalent malignant childhood/pediatric brain tumor. Providing effective treatment for these cancers, with minimal damage to the still-developing brain, remains one of the greatest challenges faced by clinicians. Understanding the diverse events driving tumor formation, maintenance, progression, and recurrence is necessary for identifying novel targeted therapeutics and improving survival of patients with this disease...
October 19, 2016: International Journal of Molecular Sciences
Ebrahiem M Babiker, Tyler Gordon, Shiaoman Chao, Matthew N Rouse, Maricelis Acevedo, Gina Brown-Guedira, Ruth Wanyera, John Michael Bonman
Wheat landrace PI 177906 has seedling resistance to stem rust caused by Puccinia graminis f. sp. tritici races TTKSK, TTKST, and BCCBC and field resistance to the Ug99 race group. Parents, 140 recombinant inbred lines, and 138 double haploid (DH) lines were evaluated for seedling resistance to races TTKSK and BCCBC. Parents and the DH population were evaluated for field resistance to Ug99 in Kenya. The 90K wheat SNP genotyping platform was used to genotype the parents and populations. Goodness-of-fit tests indicated that two dominant genes in PI 177906 conditioned seedling resistance to TTKSK...
October 24, 2016: Phytopathology
Yu Lei, Meinan Wang, Anmin Wan, Chongjing Xia, Deven R See, Min Zhang, Xianming Chen
Puccinia striiformis causes stripe rust on wheat, barley, and grasses. Natural population studies have indicated that somatic recombination plays a possible role in P. striiformis variation. To determine if somatic recombination can occur, susceptible wheat or barley plants were inoculated with mixed urediniospores of paired isolates of P. striiformis. Progeny isolates were selected by passing through a series of inoculations of wheat or barley genotypes. Potential recombinant isolates were compared with the parental isolates on the set of 18 wheat and/or 12 barley genotypes that are used to differentiate races of P...
October 24, 2016: Phytopathology
Alfred Chikweto, Ravindra N Sharma, Keshaw P Tiwari, Shiv K Verma, Rafael Calero-Bernal, Tiantian Jiang, Chunlei Su, Oliver C Kwok, Jitender P Dubey
The objectives of the present cross sectional study were to isolate and genotype Toxoplasma gondii in free-range chickens from Grenada, West Indies. Using the modified agglutination test, antibodies to T. gondii were found in 39 (26.9%) of 145 free-range chickens with titers of 25 in 7chickens; 50 in 6 chickens; 100 in 2 chickens; 200 or higher in 24 chickens. The hearts of the 39 seropositive chickens were bioassayed in mice; viable T. gondii was isolated from 20 and further propagated in cell culture. Genotyping of T...
October 24, 2016: Journal of Parasitology
Yanwen Wang, Yongfeng Yang, Yihan Zhu, Li Li, Fei Chen, Li Zhang
CONTEXT: Polymorphisms of IL-32 related closely to tumoregenesis. MATERIALS AND METHODS: Two IL-32 polymorphisms (rs12934561 and rs28372698) and mRNA expression were conducted by SNP genotype assay and real-time PCR in 423 lung cancer patients and 437 controls. RESULTS: T allele of rs28372698 associated significantly with poor prognosis in moderate and well differentiation lung cancer patients. TT genotype of rs12934561 related closely to poor survival status in squamous carcinoma...
October 24, 2016: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
Damjan Glavač, Martina Jarc-Vidmar, Katarina Vrabec, Metka Ravnik-Glavač, Ana Fakin, Marko Hawlina
PURPOSE: To determine the spectrum of BEST1 mutations and to study the phenotype in Slovenian families with Best vitelliform macular dystrophy (BVMD) to identify genotype-phenotype correlations. METHODS: Twenty patients from five families underwent the ophthalmological examination including electrooculogram (EOG; N = 17), fundus autofluorescence imaging (N = 16) and optical coherence tomography (N = 14). Mutational screening was performed by direct DNA sequencing of the BEST1 gene...
October 24, 2016: Acta Ophthalmologica
S Des Roches, R Sollmann, K Calhoun, A Rothstein, E B Rosenblum
Measuring links among genotype, phenotype, and survival in the wild has long been a focus of studies of adaptation. We conducted a four-year capture-recapture study to measure survival by genotype and phenotype in the Southwestern Fence Lizard (Sceloporus cowlesi) at the White Sands ecotone (transition area between white sands and dark soil habitats). We report several unanticipated findings. First, in contrast with previous work showing that cryptic blanched colouration in S. cowlesi from the heart of the dunes is associated with mutations in the melanocortin-1 receptor gene (Mc1r), ecotonal S...
October 24, 2016: Molecular Ecology
Pauline D Scanlan, Alex R Hall, Angus Buckling
Antagonistic coevolution between hosts and parasites can lead to local adaptation (LA), such that parasite fitness is greatest in sympatric hosts (or vice versa). The magnitude of LA typically increases with geographic distance, which is assumed to be because genetic (and hence phenotypic) distance increases with geographic distance. Here we explicitly test the relationships between parasite genetic and phenotypic distance and LA using isolates of coevolved viral parasites (lytic bacteriophage ϕ2) and the host bacterium Pseudomonas fluorescens SBW25...
October 24, 2016: Molecular Ecology
Rahul A Bharadwaj, Andrew E Jaffe, Qiang Chen, Amy Deep-Soboslay, Aaron L Goldman, Michelle I Mighdoll, John A Cotoia, Anna C Brandtjen, JooHeon Shin, Thomas M Hyde, Venkata S Mattay, Daniel R Weinberger, Joel E Kleinman
Posttraumatic stress disorder (PTSD) follows exposure to a traumatic event in susceptible individuals. Recently, genome-wide association studies have identified a number of genetic sequence variants that are associated with the risk of developing PTSD. To follow up on identifying the molecular mechanisms of these risk variants, we performed genotype to RNA sequencing-derived quantitative expression (whole gene, exon, and exon junction levels) analysis in the dorsolateral prefrontal cortex (DLPFC) of normal postmortem human brains...
October 24, 2016: Journal of Neuroscience Research
Handan Tan, Bolin Deng, Hongsong Yu, Yi Yang, Lin Ding, Qi Zhang, Jieying Qin, Aize Kijlstra, Rui Chen, Peizeng Yang
Interleukin-1 (IL-1) and the IL-1 receptor (IL-1R) family play an important role in the pathogenesis of inflammatory diseases. This study aimed to investigate the association between single nucleotide polymorphisms (SNP) of IL-1 and IL-1R family genes with Vogt-Koyanagi-Harada (VKH) and Behcet's disease (BD) in Han Chinese. The case-control study was divided into two stages and included 419 VKH cases, 1063 BD cases and 1872 healthy controls. The MassARRAY platform (Sequenom), iPLEX Gold Assay and TaqMan SNP assays were used to score genotypes of 24 SNPs...
October 24, 2016: Scientific Reports
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