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Sample records for aa genotype compared

  1. Comparative haematological parameters of HbAA and HbAS genotype children infected with Plasmodium falciparum malaria in Yemen.

    PubMed

    Albiti, Anisa H; Nsiah, Kwabena

    2014-04-01

    Sickle haemoglobin (HbS) is known to offer considerable protection against falciparum malaria. However, the mechanism of protection is not yet completely understood. In this study, we investigate how the presence of the sickle cell trait affects the haematological profile of AS persons with malaria, in comparison with similarly infected persons with HbAA. This study is based on the hypothesis that the sickle cell trait plays a protective role against malaria. Children from an endemic malaria transmission area in Yemen were enrolled in this study. Hematological parameters were estimated using manual methods, the percentage of parasite density on stained thin smear was calculated, haemoglobin genotypes were determined on paper electrophoresis, ferritin was measured using enzyme-linked immunosorbent assay, serum iron and TIBC were assayed using spectrophotometer, transferrin saturation index was calculated by dividing serum iron by TIBC and expressing the result as a percentage. Haematological parameters were compared in HbAA- and HbAS-infected children. Falciparum malaria parasitaemia was confirmed in the blood smears of 62 children, 44 (55.7%) of AA and 18 (37.5%) AS, so there was higher prevalence in HbAA children (P = 0.047). Parasite density was lower in HbAS- than HbAA-infected children (P = 0.003). Anaemia was prominent in malaria-infected children, with high proportions of moderate and severe forms in HbAA (P = 0.001). The mean levels of haemoglobin, packed cell volume, reticulocyte count, platelets count, lymphocytes, eosinophils, and serum iron were significantly lower while total leukocytes, immature granulocytes, monocytes, erythrocyte sedimentation rate, transferrin saturation, and serum ferritin were significantly higher in HbAA-infected children than HbAS-infected children. Infection with Plasmodium falciparum malaria caused more significant haematological alterations of HbAA children than HbAS. This study supports the observation that sickle cell trait

  2. HHEX_23 AA Genotype Exacerbates Effect of Diabetes on Dementia and Alzheimer Disease: A Population-Based Longitudinal Study

    PubMed Central

    Xu, Wei-Li; Pedersen, Nancy L.; Keller, Lina; Kalpouzos, Grégoria; Wang, Hui-Xin; Graff, Caroline; Winblad, Bengt; Bäckman, Lars; Fratiglioni, Laura

    2015-01-01

    Background Research has suggested that variations within the IDE/HHEX gene region may underlie the association of type 2 diabetes with Alzheimer disease (AD). We sought to explore whether IDE genes play a role in the association of diabetes with dementia, AD, and structural brain changes using data from two community-based cohorts of older adults and a subsample with structural MRI. Methods and Findings The first cohort, which included dementia-free adults aged ≥75 y (n = 970) at baseline, was followed for 9 y to detect incident dementia (n = 358) and AD (n = 271) cases. The second cohort (for replication), which included 2,060 dementia-free participants aged ≥60 y at baseline, was followed for 6 y to identify incident dementia (n = 166) and AD (n = 121) cases. A subsample (n = 338) of dementia-free participants from the second cohort underwent MRI. HHEX_23 and IDE_9 were genotyped, and diabetes (here including type 2 diabetes and prediabetes) was assessed. In the first cohort, diabetes led to an adjusted hazard ratio (HR) of 1.73 (95% CI 1.19–2.32) and 1.66 (95% CI 1.06–2.40) for dementia and AD, respectively, among all participants. Compared to people carrying the GG genotype without diabetes, AA genotype carriers with diabetes had an adjusted HR of 5.54 (95% CI 2.40–7.18) and 4.81 (95% CI 1.88–8.50) for dementia and AD, respectively. There was a significant interaction between HHEX_23-AA and diabetes on dementia (HR 4.79, 95% CI 1.63–8.90, p = 0.013) and AD (HR 3.55, 95% CI 1.45–9.91, p = 0.025) compared to the GG genotype without diabetes. In the second cohort, the HRs were 1.68 (95% CI 1.04–2.99) and 1.64 (1.02–2.33) for the diabetes–AD and dementia–AD associations, respectively, and 4.06 (95% CI 1.06–7.58, p = 0.039) and 3.29 (95% CI 1.02–8.33, p = 0.044) for the interactions, respectively. MRI data showed that HHEX_23-AA carriers with diabetes had significant structural brain changes compared to HHEX_23-GG carriers without

  3. Association of the AA genotype of the BCL2 (-938C>A) promoter polymorphism with better survival in ovarian cancer.

    PubMed

    Heubner, Martin; Wimberger, Pauline; Otterbach, Friedrich; Kasimir-Bauer, Sabine; Siffert, Winfried; Kimmig, Rainer; Nückel, Holger

    2009-01-01

    Bcl-2 plays a key role in the regulation of apoptosis. Recently, a novel regulatory single nucleotide polymorphism (-938C>A) in the inhibitory P2 BCL2 promoter was described. In this study we investigated its potential association with survival in epithelial ovarian cancer. Patients (n=110) with primary epithelial ovarian cancer were retrospectively genotyped by pyrosequencing. Genotype distribution was not significantly different between 110 ovarian cancer patients and 120 healthy controls, suggesting that genotypes of this polymorphism do not increase the susceptibility to ovarian cancer. Kaplan-Meier curves showed a significant association of the AA genotype with increased survival (p=0.002). Multivariate analysis revealed that the BCL2-938AC/CC genotype (hazard ratio 4.5; p=0.003) was an independent prognostic factor compared to other prognostic factors such as age, histological grade or tumor stage. The results suggest a role for the BCL2-938C>A polymorphism as a marker for survival in patients with epithelial ovarian cancer.

  4. The M694I/M694I genotype: A genetic risk factor of AA-amyloidosis in a group of Algerian patients with familial Mediterranean fever.

    PubMed

    Ait-Idir, Djouher; Djerdjouri, Bahia; Bouldjennet, Faiza; Taha, Rowaida Z; El-Shanti, Hatem; Sari-Hamidou, Rawda; Khellaf, Ghalia; Benmansour, Mustapha; Benabadji, Mohamed; Haddoum, Farid

    2017-03-01

    Familial Mediterranean fever (FMF, OMIM 249100) is the most common hereditary fever, resulting from mutations in MEFV. FMF is characterized by episodic febrile attacks and polyserositis. Renal AA-amyloidosis is a major complication, which often leads to end-stage renal disease in untreated patients. The data about the renal AA-amyloidosis secondary to FMF are scarce in North African countries and non-existent in Algeria. We aimed to investigate the MEFV mutations associated with this complication in an Algerian patient cohort. Molecular analysis included 28 unrelated Algerian FMF patients with ascertained amyloidosis, 23 of them were symptomatic and 5 were asymptomatic. For this study, a group of 20 FMF patients without renal amyloidosis were selected as controls according to their age, disease onset and disease duration. The mutations were detected by sequencing exon 10 of MEFV. A total of 87.5% (49/56) mutant alleles were identified in 27/28 analyzed patients; p.M694I was predominant and appeared with an allele frequency of 62.5%, followed by p.M694V (17.85%), p.M680I (5.35%) and p.I692Del (1.78%). Remarkably, only p.M694I mutation was observed among the asymptomatic patients. The M694I/M694I genotype, identified in 14/27 (52%) patients, was significantly associated with the development of amyloidosis compared to group of controls (p = 0.022). This study did not link the M694V/M694V genotype to the renal complication despite the fact that it has been observed only in the patients with amyloidosis (3/27; 11%) (p = 0.349). The association of other identified genotypes to this complication was statistically insignificant. The progression of amyloidosis led to end-stage renal disease in 14 patients with 6 deaths. This study shows that p.M694I homozygosity is a potential genetic risk factor for the development of renal AA-amyloidosis in Algerian FMF patients. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  5. Comparative proteomics lends insight into genotype-specific pathogenicity.

    PubMed

    Guarnieri, Michael T

    2013-09-01

    Comparative proteomic analyses have emerged as a powerful tool for the identification of unique biomarkers and mechanisms of pathogenesis. In this issue of Proteomics, Murugaiyan et al. utilize difference gel electrophoresis (DIGE) to examine differential protein expression between nonpathogenic and pathogenic genotypes of Prototheca zopfii, a causative agent in bovine enteritis and mastitis. Their findings provide insights into molecular mechanisms of infection and evolutionary adaptation of pathogenic genotypes, demonstrating the power of comparative proteomic analyses. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. TNFalpha and IL-10 gene polymorphisms in inflammatory bowel disease. Association of -1082 AA low producer IL-10 genotype with steroid dependency.

    PubMed

    Castro-Santos, Patricia; Suarez, Ana; López-Rivas, Laureano; Mozo, Lourdes; Gutierrez, Carmen

    2006-05-01

    An altered production of cytokines underlies inflammatory bowel disease (IBD) susceptibility. Various polymorphisms at the IL-10 and TNFalpha gene promoters control cytokine production levels. The influence of these polymorphisms on susceptibility to ulcerative colitis (UC) and Crohn's disease (CD) and their association with clinical features were analyzed. Genetic polymorphisms of TNFalpha (-308 G/A) and IL-10 (-1082 G/A, -812 C/T, and -592 C/A) were determined using the LightCycler system with hybridization probes matched with one sequence variant. The study population included 99 UC patients, 146 CD patients, and 343 matched controls. We did not find association between TNFalpha or IL-10 gene polymorphisms and UC or CD susceptibility, though a slight influence of -1082*G allele in UC appearance was observed. In a stratified analysis, a highly significant association between the -1082 AA IL-10 genotype and the steroid dependency was observed in IBD (p < 0.0001), contributing both UC (p = 0.004) and CD (p = 0.003) to this association. In contrast, TNFalpha genotypes did not influence steroid dependency in IBD. Further, the contribution of cytokine genotypes and of clinical features to the appearance of steroid-dependent status (dependent variable) was studied by multivariate analysis. The steroid-dependent phenotype correlated in UC with extensive disease (p = 0.010) and with the low producer -1082 AA IL-10 genotype (p = 0.002) and in CD with penetrating disease (p = 0.010), arthritis (p = 0.011), and the -1082 AA IL-10 genotype (p = 0.006). The main conclusion is that carriage of the -1082 AA IL-10 genotype (low producer) is a relevant risk factor for developing steroid-dependent IBD.

  7. The AA genotype of the regulatory BCL2 promoter polymorphism ( 938C>A) is associated with a favorable outcome in lymph node negative invasive breast cancer patients.

    PubMed

    Bachmann, Hagen S; Otterbach, Friedrich; Callies, Rainer; Nückel, Holger; Bau, Maja; Schmid, Kurt W; Siffert, Winfried; Kimmig, Rainer

    2007-10-01

    Expression of the antiapoptotic and antiproliferative protein Bcl-2 has been repeatedly shown to be associated with better clinical outcome in breast cancer. We recently showed a novel regulatory (-938C>A) single-nucleotide polymorphism (SNP) in the inhibitory P2 BCL2 gene promoter generating significantly different BCL2 promoter activities. Paraffin-embedded neoplastic and nonneoplastic tissues from 274 patients (161 still alive after a follow-up period of at least 80 months) with primary unilateral invasive breast carcinoma were investigated. Bcl-2 expression of tumor cells was shown by immunohistochemistry; nonneoplastic tissues were used for genotyping. Both the Bcl-2 expression and the (-938C>A) genotypes were correlated with the patients' survival. Kaplan-Meier curves revealed a significant association of the AA genotype with increased survival (P = 0.030) in lymph node-negative breast cancer patients, whereas no genotype effect could be observed in lymph node-positive cases. Ten-year survival rates were 88.6% for the AA genotype, 78.4% for the AC genotype, and 65.8% for the CC genotype. Multivariable Cox regression identified the BCL2 (-938CC) genotype as an independent prognostic factor for cancer-related death in lymph node-negative breast carcinoma patients (hazard ratio, 3.59; P = 0.032). Immunohistochemical Bcl-2 expression was significantly associated with the clinical outcome of lymph node-positive but not of lymph node-negative breast cancer patients. In lymph node-negative cases, the (-938C>A) SNP was both significantly related with the immunohistochemically determined level of Bcl-2 expression (P = 0.044) and the survival of patients with Bcl-2-expressing carcinomas (P = 0.006). These results suggest the (-938C>A) polymorphism as a survival prognosticator as well as indicator of a high-risk group within patients with lymph node-negative breast cancer.

  8. Advantages of continuous genotype values over genotype classes for GWAS in higher polyploids: a comparative study in hexaploid chrysanthemum.

    PubMed

    Grandke, Fabian; Singh, Priyanka; Heuven, Henri C M; de Haan, Jorn R; Metzler, Dirk

    2016-08-24

    Association studies are an essential part of modern plant breeding, but are limited for polyploid crops. The increased number of possible genotype classes complicates the differentiation between them. Available methods are limited with respect to the ploidy level or data producing technologies. While genotype classification is an established noise reduction step in diploids, it gains complexity with increasing ploidy levels. Eventually, the errors produced by misclassifications exceed the benefits of genotype classes. Alternatively, continuous genotype values can be used for association analysis in higher polyploids. We associated continuous genotypes to three different traits and compared the results to the output of the genotype caller SuperMASSA. Linear, Bayesian and partial least squares regression were applied, to determine if the use of continuous genotypes is limited to a specific method. A disease, a flowering and a growth trait with h (2) of 0.51, 0.78 and 0.91 were associated with a hexaploid chrysanthemum genotypes. The data set consisted of 55,825 probes and 228 samples. We were able to detect associating probes using continuous genotypes for multiple traits, using different regression methods. The identified probe sets were overlapping, but not identical between the methods. Baysian regression was the most restrictive method, resulting in ten probes for one trait and none for the others. Linear and partial least squares regression led to numerous associating probes. Association based on genotype classes resulted in similar values, but missed several significant probes. A simulation study was used to successfully validate the number of associating markers. Association of various phenotypic traits with continuous genotypes is successful with both uni- and multivariate regression methods. Genotype calling does not improve the association and shows no advantages in this study. Instead, use of continuous genotypes simplifies the analysis, saves

  9. Optimal haematocrit in subjects with normal haemoglobin genotype (HbAA), sickle cell trait (HbAS), and homozygous sickle cell disease (HbSS).

    PubMed

    Bowers, A S; Pepple, D J; Reid, H L

    2011-01-01

    The determination of an optimal haematocrit (H0) has important clinical implications if such a level can be attained, and more importantly, maintained. This is defined as a haematocrit level, above or below which oxygen delivery is deleteriously affected. This study is designed to determine an optimal haematocrit in normal (AA), sickle cell trait (AS) and sickle cell disease (SS) subjects. Twenty-seven apparently healthy subjects having normal haemoglobin genotype, 24 with sickle cell trait and 42 with homozygous sickle cell disease were recruited into the study. Whole blood viscosity (WBV) was measured by a Wells Brookfield Cone and Plate Viscometer at a shear rate of 230 sec-1. Haematocrit was determined by an AC.Tron Coulter Counter. The optimal haematocrit was calculated as the inverse of a constant, K, which was derived from the haematocrit and viscosity data. Our findings showed that the H0 varied significantly among the 3 haemoglobin genotypes, in the order AA vs SS and AS vs SS. Additionally, the data indicated an increased H0 in subjects with sickle cell trait, suggesting a possible impairment in oxygen delivery in these individuals.

  10. Influence of the Temperature and the Genotype of the HSP90AA1 Gene over Sperm Chromatin Stability in Manchega Rams

    PubMed Central

    Ramón, Manuel; Salces-Ortiz, Judit; González, Carmen; Pérez-Guzmán, M. Dolores; Garde, J. Julián; García-Álvarez, Olga; Maroto-Morales, Alejandro; Calvo, Jorge H.; Serrano, M. Magdalena

    2014-01-01

    The present study addresses the effect of heat stress on males' reproduction ability. For that, we have evaluated the sperm DNA fragmentation (DFI) by SCSA of ejaculates incubated at 37°C during 0, 24 and 48 hours after its collection, as a way to mimic the temperature circumstances to which spermatozoa will be subject to in the ewe uterus. The effects of temperature and temperature-humidity index (THI) from day 60 prior collection to the date of semen collection on DFI were examined. To better understand the causes determining the sensitivity of spermatozoa to heat, this study was conducted in 60 males with alternative genotypes for the SNP G/C−660 of the HSP90AA1 promoter, which encode for the Hsp90α protein. The Hsp90α protein predominates in the brain and testis, and its role in spermatogenesis has been described in several species. Ridge regression analyses showed that days 29 to 35 and 7 to 14 before sperm collection (bsc) were the most critical regarding the effect of heat stress over DFI values. Mixed model analyses revealed that DFI increases over a threshold of 30°C for maximum temperature and 22 for THI at days 29 to 35 and 7 to 14 bsc only in animals carrying the GG−660 genotype. The period 29–35 bsc coincide with the meiosis I process for which the effect of the Hsp90α has been described in mice. The period 7–14 bsc may correspond with later stages of the meiosis II and early stages of epididymal maturation in which the replacement of histones by protamines occurs. Because of GG−660 genotype has been associated to lower levels of HSP90AA1 expression, suboptimal amounts of HSP90AA1 mRNA in GG−660 animals under heat stress conditions make spermatozoa DNA more susceptible to be fragmented. Thus, selecting against the GG−660 genotype could decrease the DNA fragmentation and spermatozoa thermal susceptibility in the heat season, and its putative subsequent fertility gains. PMID:24465903

  11. The IL1B-511 Polymorphism (rs16944 AA Genotype) Is Increased in Aspirin-Exacerbated Respiratory Disease in Mexican Population.

    PubMed

    Falfán-Valencia, Ramcés; Pavón-Romero, Gandhi F; Camarena, Angel; García, María de la Luz; Galicia-Negrete, Gustavo; Negrete-García, María Cristina; Teran, Luis Manuel

    2012-01-01

    Aspirin exacerbated respiratory disease (AERD) is characterized by chronic hyperplastic rhinosinusitis, nasal polyposis, asthma, and aspirin sensitivity. The mechanisms which produce these manifestations of intolerance are not fully defined, current research focuses on cyclooxygenase 1 (COX-1) inhibition, metabolism of arachidonic acid, and the COX pathway to the lipoxygenase (LO) route, inducing increased synthesis of leukotrienes (LT). The biological plausibility of this model has led to the search for polymorphisms in genes responsible for proinflammatory cytokines synthesis, such as IL1B and IL8. We performed a genetic association study between IL8-251 (rs4073) and IL1B-511 (rs16944) polymorphisms in AERD, aspirin-tolerant asthma (ATA), and healthy control subjects. Using allelic discrimination by real-time PCR, we found statistically nonsignificant associations between AERD, ATA, and healthy control subjects for the GG and GA genotypes of IL1B (rs16944). Interestingly, the AA genotype showed an increased frequency in the AERD patients versus the ATA group (GF = 0.19 versus 0.07, p = 0.018, OR 2.98, and 95% CI 1.17-7.82). This is the first observation that IL1B polymorphisms are involved in AERD. Thus, future studies must investigate whether interleukin-1β is released in the airways of AERD patients and whether it relates to genetic polymorphisms in the IL1B gene.

  12. The IL1B-511 Polymorphism (rs16944 AA Genotype) Is Increased in Aspirin-Exacerbated Respiratory Disease in Mexican Population

    PubMed Central

    Falfán-Valencia, Ramcés; Pavón-Romero, Gandhi F.; Camarena, Angel; García, María de la Luz; Galicia-Negrete, Gustavo; Negrete-García, María Cristina; Teran, Luis Manuel

    2012-01-01

    Aspirin exacerbated respiratory disease (AERD) is characterized by chronic hyperplastic rhinosinusitis, nasal polyposis, asthma, and aspirin sensitivity. The mechanisms which produce these manifestations of intolerance are not fully defined, current research focuses on cyclooxygenase 1 (COX-1) inhibition, metabolism of arachidonic acid, and the COX pathway to the lipoxygenase (LO) route, inducing increased synthesis of leukotrienes (LT). The biological plausibility of this model has led to the search for polymorphisms in genes responsible for proinflammatory cytokines synthesis, such as IL1B and IL8. We performed a genetic association study between IL8-251 (rs4073) and IL1B-511 (rs16944) polymorphisms in AERD, aspirin-tolerant asthma (ATA), and healthy control subjects. Using allelic discrimination by real-time PCR, we found statistically nonsignificant associations between AERD, ATA, and healthy control subjects for the GG and GA genotypes of IL1B (rs16944). Interestingly, the AA genotype showed an increased frequency in the AERD patients versus the ATA group (GF = 0.19 versus 0.07, p = 0.018, OR 2.98, and 95% CI 1.17–7.82). This is the first observation that IL1B polymorphisms are involved in AERD. Thus, future studies must investigate whether interleukin-1β is released in the airways of AERD patients and whether it relates to genetic polymorphisms in the IL1B gene. PMID:22132000

  13. Comparative analysis of juice volatiles in selected mandarins, mandarin relatives and other citrus genotypes.

    PubMed

    Yu, Yuan; Bai, Jinhe; Chen, Chunxian; Plotto, Anne; Baldwin, Elizabeth A; Gmitter, Frederick G

    2018-02-01

    Citrus fruit flavor is an important attribute prioritized in variety improvement. The present study compared juice volatiles compositions from 13 selected citrus genotypes, including six mandarins (Citrus reticulata), three sour oranges (Citrus aurantium), one blood orange (Citrus sinensis), one lime (Citrus limonia), one Clementine (Citrus clementina) and one satsuma (Citrus unshiu). Large differences were observed with respect to volatile compositions among the citrus genotypes. 'Goutou' sour orange contained the greatest number of volatile compounds and the largest volatile production level. 'Ponkan' mandarin had the smallest number of volatiles and 'Owari' satsuma yielded the lowest volatile production level. 'Goutou' sour orange and 'Moro' blood orange were clearly distinguished from other citrus genotypes based on the analysis of volatile compositions, even though they were assigned into one single group with two other sour oranges by the molecular marker profiles. The clustering analysis based on the aroma volatile compositions was able to differentiate mandarin varieties and natural sub-groups, and was also supported by the molecular marker study. The gas chromatography-mass spectrometry analysis of citrus juice aroma volatiles can be used as a tool to distinguish citrus genotypes and assist in the assessment of future citrus breeding programs. The aroma volatile profiles of the different citrus genotypes and inter-relationships detected among volatile compounds and among citrus genotypes will provide fundamental information on the development of marker-assisted selection in citrus breeding. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  14. Comparative analysis of transcriptome in two wheat genotypes with contrasting levels of drought tolerance

    USDA-ARS?s Scientific Manuscript database

    Drought tolerance is a complex trait that is governed by multiple genes. To identify the potential candidate genes, comparative analysis of drought stress-responsive transcriptome between drought-tolerant (Triticum aestivum Cv. C306) and drought-sensitive (Triticum aestivum Cv. WL711) genotypes was ...

  15. Comparative analysis of juice volatiles in selected mandarins, mandarin relatives and other citrus genotypes

    USDA-ARS?s Scientific Manuscript database

    Citrus fruit flavor is an important attribute prioritized in variety improvement. The objectives of this study were to compare aroma volatiles in juice samples from 13 selected genotypes of mandarins and mandarin relatives, including six mandarins, three sour oranges, one satsuma, one clementine, on...

  16. Weldability of AA 5052 H32 aluminium alloy by TIG welding and FSW process - A comparative study

    NASA Astrophysics Data System (ADS)

    Shanavas, S.; Raja Dhas, J. Edwin

    2017-10-01

    Aluminium 5xxx series alloys are the strongest non-heat treatable aluminium alloy. Its application found in automotive components and body structures due to its good formability, good strength, high corrosion resistance, and weight savings. In the present work, the influence of Tungsten Inert Gas (TIG) welding parameters on the quality of weld on AA 5052 H32 aluminium alloy plates were analyzed and the mechanical characterization of the joint so produced was compared with Friction stir (FS) welded joint. The selected input variable parameters are welding current and inert gas flow rate. Other parameters such as welding speed and arc voltage were kept constant throughout the study, based on the response from several trial runs conducted. The quality of the weld is measured in terms of ultimate tensile strength. A double side V-butt joints were fabricated by double pass on one side to ensure maximum strength of TIG welded joints. Macro and microstructural examination were conducted for both welding process.

  17. MMP-8 genotypes influence the inflammatory response in human endotoxemia.

    PubMed

    Rella, Judith M; Jilma, Bernd; Fabry, Astrid; Kaynar, A Murat; Mayr, Florian B

    2014-04-01

    Clinical studies have reported associations between MMP-8 genotypes and clinical outcomes without exploring underlying mechanisms. This study aims to understand the influence of the rs1940475 SNP on downstream chemokine and cytokine response in human endotoxemia. Rs1940475 was genotyped in 44 healthy Caucasian males, who were challenged with an intravenous bolus of 2 ng/kg lipopolysaccharide (LPS). Plasma levels of tumor necrosis factor (TNF), interleukin (IL)-6, IL-8, and macrophage inflammatory protein (MIP)-1α were measured at baseline and 2, 4, 6, and 24 h after LPS infusion with high-sensitivity enzyme immunoassays. Peak TNF levels at 2 h after LPS infusion were significantly higher in subjects with AA genotype compared to subjects with AG or GG genotypes (185 pg/mL [IQR, 154-234] vs. 94 pg/mL [IQR, 65-125] vs. 107 pg/mL [IQR, 80-241], respectively; p = 0.03 between groups). Peak IL-6 levels were trend-wise higher in subjects with AA genotype compared to those with AG or GG genotypes (566 pg/mL [IQR, 294-644] vs. 278 pg/mL [IQR, 184-539] and 329 pg/mL [IQR, 240-492], respectively; p = 0.15 between groups). In contrast, peak MIP-1α at 2 h was highest in GG genotype carriers compared to those with AG or AA genotypes (602 pg/mL [IQR, 449-727] vs. 389 pg/mL [IQR, 375-490] and 510 pg/mL [425-813], respectively; p < 0.03 between groups). AA genotype carriers had highest peak TNF and IL-6 levels after LPS challenge, whereas peak MIP-1α levels were highest in GG carriers. This indicates that the rs1940475 SNP modifies the host response to inflammatory stimuli, which may in part explain previously shown associations with clinical outcomes.

  18. Variable salinity responses of 12 alfalfa genotypes and comparative expression analyses of salt-response genes

    PubMed Central

    Sandhu, Devinder; Cornacchione, Monica V.; Ferreira, Jorge F. S.; Suarez, Donald L.

    2017-01-01

    Twelve alfalfa genotypes that were selected for biomass under salinity, differences in Na and Cl concentrations in shoots and K/Na ratio were evaluated in this long-term salinity experiment. The selected plants were cloned to reduce genetic variability within each genotype. Salt tolerance (ST) index of the genotypes ranged from 0.39 to 1. The most salt-tolerant genotypes SISA14-1 (G03) and AZ-90ST (G10), the top performers for biomass, exhibited the least effect on shoot number and height. SISA14-1 (G03) accumulated low Na and Cl under salinity. Most genotypes exhibited a net reduction in shoot Ca, Mg, P, Fe, and Cu, while Mn and Zn increased under salinity. Salinity reduced foliar area and stomatal conductance; while net photosynthetic rate and transpiration were not affected. Interestingly, salinity increased chlorophyll and antioxidant capacity in most genotypes; however neither parameter correlated well to ST index. Salt-tolerant genotypes showed upregulation of the SOS1, SOS2, SOS3, HKT1, AKT1, NHX1, P5CS1, HSP90.7, HSP81.2, HSP71.1, HSPC025, OTS1, SGF29 and SAL1 genes. Gene expression analyses allowed us to classify genotypes based on their ability to regulate different components of the salt tolerance mechanism. Pyramiding different components of the salt tolerance mechanism may lead to superior salt-tolerant alfalfa genotypes. PMID:28225027

  19. Methylation of the oxytocin receptor gene in clinically depressed patients compared to controls: The role of OXTR rs53576 genotype.

    PubMed

    Reiner, I; Van IJzendoorn, M H; Bakermans-Kranenburg, M J; Bleich, S; Beutel, M; Frieling, H

    2015-06-01

    The emerging field of epigenetics provides a biological basis for gene-environment interactions relevant to depression. We focus on DNA methylation of exon 1 and 2 of the oxytocin receptor gene (OXTR) promoter. The research aims of the current study were to compare OXTR DNA methylation of depressed patients with healthy control subjects and to investigate possible influences of the OXTR rs53576 genotype. The sample of the present study consisted of 43 clinically depressed women recruited from a psychosomatic inpatient unit and 42 healthy, female control subjects - mean age 30 years (SD = 9). DNA methylation profiles of the OXTR gene were assessed from leukocyte DNA by means of bisulfite sequencing. Depressed female patients had decreased OXTR exon 1 DNA methylation compared to non-depressed women. The association between depression and methylation level was moderated by OXTR rs53576 genotype. Exon 2 methylation was associated with OXTR rs53576 genotype but not with depression. Our findings suggest exon-specific methylation mechanisms. Exon 1 methylation appears to be associated with depressive phenotypes whereas exon 2 methylation is influenced by genotype. Previously reported divergent associations between OXTR genotype and depression might be explained by varying exon 1 methylation. In order to further understand the etiology of depression, research on the interplay between genotype, environmental influences and exon-specific methylation patterns is needed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Comparative transcriptome profiling of potassium starvation responsiveness in two contrasting watermelon genotypes.

    PubMed

    Fan, Molin; Huang, Yuan; Zhong, Yaqin; Kong, Qiusheng; Xie, Junjun; Niu, Mengliang; Xu, Yong; Bie, Zhilong

    2014-02-01

    Potassium (K) is one of the essential nutrients for crops, and K⁺ deficiency highly restricts crop yield and quality. Watermelon [Citrullus lanatus (Thunb.) Matsum. & Nakai] is an economically important crop that often suffers from K⁺ deficiency. To elucidate the underlying tolerance mechanism of watermelon to K⁺ deficiency and to improve K efficiency of watermelon and other crops in the future, two watermelon genotypes, namely, YS and 8424, that exhibit contrasting K efficiencies were studied to compare their response mechanisms to K⁺ deficiency. YS was more tolerant of K⁺ deficiency and displayed less inhibited root growth than 8424. Roots of YS and 8424 seedlings with or without K⁺ supply were harvested at 6 and 120 h after treatment (HAT), and their transcriptomes were analyzed by Illumina RNA sequencing. Different regulation mechanisms of the root K⁺-uptake genes for short- and long-term stress were observed. Genes involved in jasmonic acid and reactive oxygen species production; Ca²⁺ and receptor-like kinase signaling; lignin biosynthesis; and other stress-related genes were repressed in YS, whereas a large number of such stress-related genes were induced in 8424 at 120 HAT. These results suggested that repressed defense and stress response can save energy for better root growth in YS, which can facilitate K⁺ uptake and increase K efficiency and tolerance to K⁺ deficiency. This study presents the first global root transcriptome in watermelon and provides new insights into the molecular mechanisms underlying tolerance to K⁺ deficiency of K-efficient watermelon genotypes.

  1. A SNP panel and online tool for checking genotype concordance through comparing QR codes.

    PubMed

    Du, Yonghong; Martin, Joshua S; McGee, John; Yang, Yuchen; Liu, Eric Yi; Sun, Yingrui; Geihs, Matthias; Kong, Xuejun; Zhou, Eric Lingfeng; Li, Yun; Huang, Jie

    2017-01-01

    In the current precision medicine era, more and more samples get genotyped and sequenced. Both researchers and commercial companies expend significant time and resources to reduce the error rate. However, it has been reported that there is a sample mix-up rate of between 0.1% and 1%, not to mention the possibly higher mix-up rate during the down-stream genetic reporting processes. Even on the low end of this estimate, this translates to a significant number of mislabeled samples, especially over the projected one billion people that will be sequenced within the next decade. Here, we first describe a method to identify a small set of Single nucleotide polymorphisms (SNPs) that can uniquely identify a personal genome, which utilizes allele frequencies of five major continental populations reported in the 1000 genomes project and the ExAC Consortium. To make this panel more informative, we added four SNPs that are commonly used to predict ABO blood type, and another two SNPs that are capable of predicting sex. We then implement a web interface (http://qrcme.tech), nicknamed QRC (for QR code based Concordance check), which is capable of extracting the relevant ID SNPs from a raw genetic data, coding its genotype as a quick response (QR) code, and comparing QR codes to report the concordance of underlying genetic datasets. The resulting 80 fingerprinting SNPs represent a significant decrease in complexity and the number of markers used for genetic data labelling and tracking. Our method and web tool is easily accessible to both researchers and the general public who consider the accuracy of complex genetic data as a prerequisite towards precision medicine.

  2. A SNP panel and online tool for checking genotype concordance through comparing QR codes

    PubMed Central

    Du, Yonghong; Martin, Joshua S.; McGee, John; Yang, Yuchen; Liu, Eric Yi; Sun, Yingrui; Geihs, Matthias; Kong, Xuejun; Zhou, Eric Lingfeng; Li, Yun

    2017-01-01

    In the current precision medicine era, more and more samples get genotyped and sequenced. Both researchers and commercial companies expend significant time and resources to reduce the error rate. However, it has been reported that there is a sample mix-up rate of between 0.1% and 1%, not to mention the possibly higher mix-up rate during the down-stream genetic reporting processes. Even on the low end of this estimate, this translates to a significant number of mislabeled samples, especially over the projected one billion people that will be sequenced within the next decade. Here, we first describe a method to identify a small set of Single nucleotide polymorphisms (SNPs) that can uniquely identify a personal genome, which utilizes allele frequencies of five major continental populations reported in the 1000 genomes project and the ExAC Consortium. To make this panel more informative, we added four SNPs that are commonly used to predict ABO blood type, and another two SNPs that are capable of predicting sex. We then implement a web interface (http://qrcme.tech), nicknamed QRC (for QR code based Concordance check), which is capable of extracting the relevant ID SNPs from a raw genetic data, coding its genotype as a quick response (QR) code, and comparing QR codes to report the concordance of underlying genetic datasets. The resulting 80 fingerprinting SNPs represent a significant decrease in complexity and the number of markers used for genetic data labelling and tracking. Our method and web tool is easily accessible to both researchers and the general public who consider the accuracy of complex genetic data as a prerequisite towards precision medicine. PMID:28926565

  3. Variable salinity responses of 12 alfalfa genotypes and comparative expression analyses of salt-response genes

    USDA-ARS?s Scientific Manuscript database

    Twelve alfalfa genotypes that were selected for biomass under salinity, differences in Na and Cl concentrations in shoots and K/Na ratio were evaluated in this long-term salinity experiment. The selected plants were cloned to reduce genetic variability within each genotype. Salt tolerance (ST) index...

  4. Comparative proteomic analysis of two pathogenic Tritrichomonas foetus genotypes: there is more to the proteome than meets the eye.

    PubMed

    Stroud, Leah J; Šlapeta, Jan; Padula, Matthew P; Druery, Dylan; Tsiotsioras, George; Coorssen, Jens R; Stack, Colin M

    2017-03-01

    Certain clinical isolates of Tritrichomonas foetus infect the urogenital tract of cattle while others infect the gastrointestinal tract of cats. Previous studies have identified subtle genetic differences between these isolates with the term "genotype" adopted to reflect host origin. The aim of this work was to seek evidence of host-specific adaptation and to clarify the relationship between T. foetus genotypes. To do this we characterised the proteomes of both genotypes using two-dimensional gel electrophoresis (2DE) coupled with LC-MS/MS. Our comparative analysis of the data revealed that both genotypes exhibited largely similar proteoform profiles; however differentiation was possible with 24 spots identified as having a four-fold or greater change. Deeper analysis using 2DE zymography and protease-specific fluorogenic substrates revealed marked differences in cysteine protease (CP) expression profiles between the two genotypes. These variances in CP activities could also account for the pathogenic and histopathological differences previously observed between T. foetus genotypes in cross-infection studies. Our findings highlight the importance of CPs as major determinants of parasite virulence and provide a foundation for future host-parasite interaction studies, with direct implications for the development of vaccines or drugs targeting T. foetus. Copyright © 2017 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

  5. Rating AAs.

    ERIC Educational Resources Information Center

    Carter, Susan J.

    2001-01-01

    Why alternative investments? In a word: performance. Many higher education endowment and foundation managers are making increasing commitments to alternative investments, or AAs, in order to obtain higher returns and broader diversification for their investment portfolios than public securities instruments can usually provide. Learn how to handle…

  6. Comparative transcriptome analysis during early fruit development between three seedy citrus genotypes and their seedless mutants

    USDA-ARS?s Scientific Manuscript database

    Identification of genes with differential transcript abundance (GDTA) in seedless mutants may enhance understanding of seedless citrus development. Transcriptome analysis was conducted at three time points during early fruit development (Phase 1) of three seedy citrus genotypes: Fallglo [Bower citru...

  7. Identification and comparative analysis of drought-associated microRNAs in two cowpea genotypes.

    PubMed

    Barrera-Figueroa, Blanca E; Gao, Lei; Diop, Ndeye N; Wu, Zhigang; Ehlers, Jeffrey D; Roberts, Philip A; Close, Timothy J; Zhu, Jian-Kang; Liu, Renyi

    2011-09-17

    Cowpea (Vigna unguiculata) is an important crop in arid and semi-arid regions and is a good model for studying drought tolerance. MicroRNAs (miRNAs) are known to play critical roles in plant stress responses, but drought-associated miRNAs have not been identified in cowpea. In addition, it is not understood how miRNAs might contribute to different capacities of drought tolerance in different cowpea genotypes. We generated deep sequencing small RNA reads from two cowpea genotypes (CB46, drought-sensitive, and IT93K503-1, drought-tolerant) that grew under well-watered and drought stress conditions. We mapped small RNA reads to cowpea genomic sequences and identified 157 miRNA genes that belong to 89 families. Among 44 drought-associated miRNAs, 30 were upregulated in drought condition and 14 were downregulated. Although miRNA expression was in general consistent in two genotypes, we found that nine miRNAs were predominantly or exclusively expressed in one of the two genotypes and that 11 miRNAs were drought-regulated in only one genotype, but not the other. These results suggest that miRNAs may play important roles in drought tolerance in cowpea and may be a key factor in determining the level of drought tolerance in different cowpea genotypes.

  8. Comparing simple root phenotyping methods on a core set of rice genotypes.

    PubMed

    Shrestha, R; Al-Shugeairy, Z; Al-Ogaidi, F; Munasinghe, M; Radermacher, M; Vandenhirtz, J; Price, A H

    2014-05-01

    Interest in belowground plant growth is increasing, especially in relation to arguments that shallow-rooted cultivars are efficient at exploiting soil phosphorus while deep-rooted ones will access water at depth. However, methods for assessing roots in large numbers of plants are diverse and direct comparisons of methods are rare. Three methods for measuring root growth traits were evaluated for utility in discriminating rice cultivars: soil-filled rhizotrons, hydroponics and soil-filled pots whose bottom was sealed with a non-woven fabric (a potential method for assessing root penetration ability). A set of 38 rice genotypes including the OryzaSNP set of 20 cultivars, additional parents of mapping populations and products of marker-assisted selection for root QTLs were assessed. A novel method of image analysis for assessing rooting angles from rhizotron photographs was employed. The non-woven fabric was the easiest yet least discriminatory method, while the rhizotron was highly discriminatory and allowed the most traits to be measured but required more than three times the labour of the other methods. The hydroponics was both easy and discriminatory, allowed temporal measurements, but is most likely to suffer from artefacts. Image analysis of rhizotrons compared favourably to manual methods for discriminating between cultivars. Previous observations that cultivars from the indica subpopulation have shallower rooting angles than aus or japonica cultivars were confirmed in the rhizotrons, and indica and temperate japonicas had lower maximum root lengths in rhizotrons and hydroponics. It is concluded that rhizotrons are the preferred method for root screening, particularly since root angles can be assessed. © 2013 German Botanical Society and The Royal Botanical Society of the Netherlands.

  9. Sustained virological response and its treatment predictors in hepatitis C virus genotype 4 compared to genotypes 1, 2, and 3: a meta-analysis.

    PubMed

    Yee, Brittany E; Nguyen, Nghia H; Zhang, Bing; Lin, Derek; Vutien, Philip; Wong, Carrie R; Lutchman, Glen A; Nguyen, Mindie H

    2015-01-01

    Pegylated interferon and ribavirin (PEG-IFN+RBV) may be more cost-effective than direct-acting antivirals in resource-limited settings. Current literature suggests sustained virological response (SVR) in hepatitis C virus genotype 4 (HCV-4) is similar to genotype 1 (HCV-1), but worse than 2 and 3 (HCV-2/3). However, few studies have compared treatment response between these groups and these have been limited by small sample sizes with heterogeneous designs. We performed a meta-analysis of SVR predictors in HCV-4 versus HCV-1, 2, and 3 patients treated with PEG-IFN+RBV. In November 2013, we searched for 'genotype 4' in MEDLINE/EMBASE databases and scientific conferences. We included original articles with ≥25 treatment-naïve HCV-4 and comparisons to HCV-1, 2, and/or 3 patients treated with PEG-IFN+RBV. Random effects modelling was used with heterogeneity defined by Cochrane Q-test (p value<0.10) and I(2) statistic (>50%). Five studies with 20 014 patients (899 HCV-4; 12 033 HCV-1; and 7082 HCV-2/3 patients) were included. SVR was 53% (CI 43% to 62%) for HCV-4, 44% (CI 40% to 47%) for HCV-1; and 73% (CI 58% to 84%) for HCV-2/3. SVR with EVR (early virological response) was 75% (CI 61% to 86%) in HCV-4; 64% (CI 46% to 79%) in HCV-1; and 85% (CI 71% to 93%) in HCV-2/3. SVR without EVR was 10% (CI 6% to 17%) for HCV-4; 13% (CI 12% to 15%) for HCV-1; and 23% (CI 16% to 33%) for HCV-2/3. SVR rates are similar in HCV-4 (∼50%) and HCV-1 (∼40%). Lack of EVR is a good stopping rule for HCV-4 and HCV-1 since only 10% subsequently achieve SVR. In HCV-4 patients with EVR, three-quarters can expect to achieve SVR with PEG-IFN+RBV.

  10. Comparative transcriptome profiling of resistant and susceptible rice genotypes in response to the seedborne pathogen Fusarium fujikuroi.

    PubMed

    Matić, Slavica; Bagnaresi, Paolo; Biselli, Chiara; Orru', Luigi; Amaral Carneiro, Greice; Siciliano, Ilenia; Valé, Giampiero; Gullino, Maria Lodovica; Spadaro, Davide

    2016-08-11

    Fusarium fujikuroi is the causal agent of bakanae, the most significant seed-borne disease of rice. Molecular mechanisms regulating defence responses of rice towards this fungus are not yet fully known. To identify transcriptional mechanisms underpinning rice resistance, a RNA-seq comparative transcriptome profiling was conducted on infected seedlings of selected rice genotypes at one and three weeks post germination (wpg). Twelve rice genotypes were screened against bakanae disease leading to the identification of Selenio and Dorella as the most resistant and susceptible cultivars, respectively. Transcriptional changes were more appreciable at 3 wpg, suggesting that this infection stage is essential to study the resistance mechanisms: 3,119 DEGs were found in Selenio and 5,095 in Dorella. PR1, germin-like proteins, glycoside hydrolases, MAP kinases, and WRKY transcriptional factors were up-regulated in the resistant genotype upon infection with F. fujikuroi. Up-regulation of chitinases and down-regulation of MAP kinases and WRKY transcriptional factors were observed in the susceptible genotype. Gene ontology (GO) enrichment analyses detected in Selenio GO terms specific to response to F. fujikuroi: 'response to chitin', 'jasmonic acid biosynthetic process', and 'plant-type hypersensitive response', while Dorella activated different mechanisms, such as 'response to salicylic acid stimulus' and 'gibberellin metabolic process', which was in agreement with the production of gibberellin A3 in Dorella plants. RNA-seq profiling was performed for the first time to analyse response of rice to F. fujikuroi infection. Our findings allowed the identification of genes activated in one- and three- week-old rice seedlings of two genotypes infected with F. fujikuroi. Furthermore, we found the pathways involved in bakanae resistance, such as response to chitin, JA-dependent signalling and hypersensitive response. Collectively, this provides important information to elucidate the

  11. Comparative study of the biological properties of Trypanosoma cruzi I genotypes in a murine experimental model.

    PubMed

    Cruz, Lissa; Vivas, Angie; Montilla, Marleny; Hernández, Carolina; Flórez, Carolina; Parra, Edgar; Ramírez, Juan David

    2015-01-01

    Chagas disease is an endemic zoonosis in Latin America and caused by the parasite Trypanosoma cruzi. This kinetoplastid displays remarkable genetic variability, allowing its classification into six Discrete Typing Units (DTUs) from TcI to TcVI. T. cruzi I presents the broadest geographical distribution in the continent and has been associated to severe forms of cardiomyopathies. Recently, a particular genotype associated to human infections has been reported and named as TcIDOM (previously named TcIa-b). This genotype shows to be clonal and adapted to the domestic cycle but so far no studies have determined the biological properties of domestic (TcIDOM) and sylvatic TcI strains (previously named TcIc-e). Hence, the aim of this study was to untangle the biological features of these genotypes in murine models. We infected ICR-CD1 mice with five TcI strains (two domestic, two sylvatic and one natural mixture) and determined the course of infection during 91 days (acute and chronic phase of the disease) in terms of parasitemia, tissue tropism, immune response (IgG titers) and tissue invasion by means of histopathology studies. Statistically significant differences were observed in terms of parasitemia curves and prepatent period between domestic (TcIDOM) and sylvatic strains. There were no differences in terms of IgG antibodies response across the mice infected with the five strains. Regarding the histopathology, our results indicate that domestic strains present higher parasitemias and low levels of histopathological damage. In contrast, sylvatic strains showed lower parasitemias and high levels of histopathological damage. These results highlight the sympatric and behavioral differences of domestic and sylvatic TcI strains; the clinical and epidemiological implications are herein discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Comparative Transcriptome Analysis of Resistant and Susceptible Common Bean Genotypes in Response to Soybean Cyst Nematode Infection

    PubMed Central

    Jain, Shalu; Chittem, Kishore; Brueggeman, Robert; Osorno, Juan M.; Richards, Jonathan; Nelson, Berlin D.

    2016-01-01

    Soybean cyst nematode (SCN; Heterodera glycines Ichinohe) reproduces on the roots of common bean (Phaseolus vulgaris L.) and can cause reductions in plant growth and seed yield. The molecular changes in common bean roots caused by SCN infection are unknown. Identification of genetic factors associated with SCN resistance could help in development of improved bean varieties with high SCN resistance. Gene expression profiling was conducted on common bean roots infected by SCN HG type 0 using next generation RNA sequencing technology. Two pinto bean genotypes, PI533561 and GTS-900, resistant and susceptible to SCN infection, respectively, were used as RNA sources eight days post inoculation. Total reads generated ranged between ~ 3.2 and 5.7 million per library and were mapped to the common bean reference genome. Approximately 70–90% of filtered RNA-seq reads uniquely mapped to the reference genome. In the inoculated roots of resistant genotype PI533561, a total of 353 genes were differentially expressed with 154 up-regulated genes and 199 down-regulated genes when compared to the transcriptome of non- inoculated roots. On the other hand, 990 genes were differentially expressed in SCN-inoculated roots of susceptible genotype GTS-900 with 406 up-regulated and 584 down-regulated genes when compared to non-inoculated roots. Genes encoding nucleotide-binding site leucine-rich repeat resistance (NLR) proteins, WRKY transcription factors, pathogenesis-related (PR) proteins and heat shock proteins involved in diverse biological processes were differentially expressed in both resistant and susceptible genotypes. Overall, suppression of the photosystem was observed in both the responses. Furthermore, RNA-seq results were validated through quantitative real time PCR. This is the first report describing genes/transcripts involved in SCN-common bean interaction and the results will have important implications for further characterization of SCN resistance genes in common bean

  13. Comparative Transcriptome Analysis of Resistant and Susceptible Common Bean Genotypes in Response to Soybean Cyst Nematode Infection.

    PubMed

    Jain, Shalu; Chittem, Kishore; Brueggeman, Robert; Osorno, Juan M; Richards, Jonathan; Nelson, Berlin D

    2016-01-01

    Soybean cyst nematode (SCN; Heterodera glycines Ichinohe) reproduces on the roots of common bean (Phaseolus vulgaris L.) and can cause reductions in plant growth and seed yield. The molecular changes in common bean roots caused by SCN infection are unknown. Identification of genetic factors associated with SCN resistance could help in development of improved bean varieties with high SCN resistance. Gene expression profiling was conducted on common bean roots infected by SCN HG type 0 using next generation RNA sequencing technology. Two pinto bean genotypes, PI533561 and GTS-900, resistant and susceptible to SCN infection, respectively, were used as RNA sources eight days post inoculation. Total reads generated ranged between ~ 3.2 and 5.7 million per library and were mapped to the common bean reference genome. Approximately 70-90% of filtered RNA-seq reads uniquely mapped to the reference genome. In the inoculated roots of resistant genotype PI533561, a total of 353 genes were differentially expressed with 154 up-regulated genes and 199 down-regulated genes when compared to the transcriptome of non- inoculated roots. On the other hand, 990 genes were differentially expressed in SCN-inoculated roots of susceptible genotype GTS-900 with 406 up-regulated and 584 down-regulated genes when compared to non-inoculated roots. Genes encoding nucleotide-binding site leucine-rich repeat resistance (NLR) proteins, WRKY transcription factors, pathogenesis-related (PR) proteins and heat shock proteins involved in diverse biological processes were differentially expressed in both resistant and susceptible genotypes. Overall, suppression of the photosystem was observed in both the responses. Furthermore, RNA-seq results were validated through quantitative real time PCR. This is the first report describing genes/transcripts involved in SCN-common bean interaction and the results will have important implications for further characterization of SCN resistance genes in common bean.

  14. [AA amyloidosis].

    PubMed

    Stojanovic, Katia Stankovic; Georgin-Lavialle, Sophie; Grateau, Gilles

    2017-06-01

    AA amyloidosis remains one of the three main types of systemic amyloidosis with AL and ATTR. Its incidence has been however decreasing recently in Western countries. Chronic inflammatory diseases are currently the first cause of AA amyloidosis, including rheumatoid arthritis, spondyloarthritis and autoinflammatory diseases. Castleman's disease is a specific cause of AA amyloidosis that can be cured by surgery. A chronic inflammatory response is required to develop amyloidosis. Other genetic and environmental factors are also involved. The first clinical manifestation is a chronic glomerular nephropathy, which can be detected by urine examination and serum creatinine measure. Immunohistochemistry is mandatory to confirm the clinical diagnosis of AA amyloidosis and to avoid misdiagnosis. Long-term prognosis remains poor on chronic dialysis in case of clinical gut involvement. Current treatment is based on the control of the inflammatory response. Specific treatment aimed at inhibiting amyloid formation targeting serum amyloid P component and heparan sulphate are currently evaluated. Copyright © 2017 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.

  15. Comparative phenotypic and genotypic analyses of Salmonella Rissen that originated from food animals in Thailand and United States.

    PubMed

    Pornsukarom, S; Patchanee, P; Erdman, M; Cray, P F; Wittum, T; Lee, J; Gebreyes, W A

    2015-03-01

    Salmonella enterica serovar Rissen has been recognized as one of the most common serovar among humans and pork production systems in different parts of the world, especially Asia. In the United States, this serovar caused outbreaks but its epidemiologic significance remains unknown. The objectives of this study were to compare the phenotypic (antimicrobial susceptibility) and genotypic attributes of Salmonella Rissen isolated in Thailand (Thai) and the United States (US). All the Thai isolates (n = 30) were recovered from swine faecal samples. The US isolates (n = 35) were recovered from swine faecal samples (n = 29), cattle (n = 2), chicken (n = 2), dog (n = 1) and a ready-to-eat product (n = 1). The antimicrobial susceptibility of isolates was determined using the Kirby-Bauer disk diffusion method with a panel of 12 antimicrobials. Pulse-field gel electrophoresis (PFGE) was used to determine the genotypic diversity of isolates. All Thai isolates showed multidrug resistance (MDR) with the most frequent antibiotic resistance shown against ampicillin (100%), sulfisoxazole (96.7%), tetracycline (93.3%), streptomycin (90%) and chloramphenicol (30%). About half of the isolates of USA origin were pan-susceptible and roughly 30% were resistant to only tetracycline (R-type: Te). Salmonella Rissen isolated from Thailand and the USA in this study were found to be clonally unrelated. Genotypic analyses indicated that isolates were clustered primarily based on the geographic origin implying the limited clonality among the strains. Clonal relatedness among different host species within the same geography (USA) was found. We found genotypic similarity in Thai and US isolates in few instances but with no epidemiological link. Further studies to assess propensity for increased inter-regional transmission and dissemination is warranted. © 2014 Blackwell Verlag GmbH.

  16. Comparing different post-mortem human samples as DNA sources for downstream genotyping and identification.

    PubMed

    Calacal, Gayvelline C; Apaga, Dame Loveliness T; Salvador, Jazelyn M; Jimenez, Joseph Andrew D; Lagat, Ludivino J; Villacorta, Renato Pio F; Lim, Maria Cecilia F; Fortun, Raquel D R; Datar, Francisco A; De Ungria, Maria Corazon A

    2015-11-01

    The capability of DNA laboratories to perform genotyping procedures from post-mortem remains, including those that had undergone putrefaction, continues to be a challenge in the Philippines, a country characterized by very humid and warm conditions all year round. These environmental conditions accelerate the decomposition of human remains that were recovered after a disaster and those that were left abandoned after a crime. When considerable tissue decomposition of human remains has taken place, there is no other option but to extract DNA from bone and/or teeth samples. Routinely, femur shafts are obtained from recovered bodies for human identification because the calcium matrix protects the DNA contained in the osteocytes. In the Philippines, there is difficulty in collecting femur samples after natural disasters or even human-made disasters, because these events are usually characterized by a large number of fatalities. Identification of casualties is further delayed by limitation in human and material resources. Hence, it is imperative to test other types of biological samples that are easier to collect, transport, process and store. We analyzed DNA that were obtained from body fluid, bone marrow, muscle tissue, clavicle, femur, metatarsal, patella, rib and vertebral samples from five recently deceased untreated male cadavers and seven male human remains that were embalmed, buried for ∼ 1 month and then exhumed. The bodies had undergone different environmental conditions and were in various stages of putrefaction. A DNA extraction method utilizing a detergent-washing step followed by an organic procedure was used. The utility of bone marrow and vitreous fluid including bone marrow and vitreous fluid that was transferred on FTA(®) cards and subjected to autosomal STR and Y-STR DNA typing were also evaluated. DNA yield was measured and the presence or absence of PCR inhibitors in DNA extracts was assessed using Plexor(®)HY. All samples were amplified using

  17. A comparative study of competitiveness between different genotypes of weedy rice (Oryza sativa) and cultivated rice.

    PubMed

    Dai, Lei; Dai, Weimin; Song, Xiaoling; Lu, Baorong; Qiang, Sheng

    2014-01-01

    Competition from weedy rice can cause serious yield losses to cultivated rice. However, key traits that facilitate competitiveness are still not well understood. To explore the mechanisms behind the strong growth and competitive ability, replacement series experiments were established with six genotypes of weedy rice from different regions and one cultivated rice cultivar. (1) Weedy rice from southern China had the greatest impact on growth and yield of cultivated rice throughout the entire growing season. Weedy rice from the northeast was very competitive during the early vegetative stage while the competitive effects of eastern weedy rice were more detrimental at later crop-growth stages. (2) As the proportion of weedy rice increased, plant height, tillers, above-ground biomass, and yield of cultivated rice significantly declined; the crop always being at disadvantage regardless of proportion. (3) Weedy biotypes with greater diversity as estimated by their Shannon indexes were more detrimental to the growth and yield of cultivated rice. Geographic origin (latitude) of weedy rice biotype, its mixture proportion under competition with the crop and its genetic diversity are determinant factors of the outcome of competition and the associated decline in the rice crop yield. © 2013 Society of Chemical Industry. © 2013 Society of Chemical Industry.

  18. Carcass measurements and meat quality characteristics of dairy suckling kids compared to an indigenous genotype.

    PubMed

    Ekiz, Bulent; Ozcan, Mustafa; Yilmaz, Alper; Tölü, Cemil; Savaş, Türker

    2010-06-01

    Effects of genotype on carcass measurements and meat quality were investigated by using 24 suckling kids from Turkish Saanen, Gokceada and Maltese breeds. Carcass quality characteristics of indigenous kids (Gokceada) were lower than those of dairy type (Turkish Saanen and Maltese) kids. Breed effect on ultimate meat pH, cooking loss, drip loss and Warner Bratzler shear force values were not significant. Meat samples from Turkish Saanen kids had higher redness (at 0, 1 and 24h) and yellowness (at 24h) values than Gokceada kids (P<0.05). Breed had no significant effect on sensory characteristics except flavour intensity. Flavour intensity scores given to meat samples of Maltese kids were higher than those of Turkish Saanen and Gokceada kids (P<0.01). In conclusion, dairy type breeds should be considered for meat production as well, with meat from Maltese kids potentially offering better colour and flavour intensity than that of Turkish Saanen kids. Copyright 2010 Elsevier Ltd. All rights reserved.

  19. HPV genotypes and cervical intraepithelial neoplasia in a multiethnic cohort in the southeastern USA.

    PubMed

    Vidal, Adriana C; Smith, Jennifer S; Valea, Fidel; Bentley, Rex; Gradison, Maggie; Yarnall, Kimberly S H; Ford, Anne; Overcash, Francine; Grant, Kathy; Murphy, Susan K; Hoyo, Cathrine

    2014-08-01

    For poorly understood reasons, invasive cervical cancer (ICC) incidence and mortality rates are higher in women of African descent. Oncogenic human papillomavirus (HPV) genotypes distribution may vary between European American (EA) and African-American (AA) women and may contribute to differences in ICC incidence. The current study aimed at disentangling differences in HPV distribution among AA and EA women. Five-hundred and seventy-two women were enrolled at the time of colposcopic evaluation following an abnormal liquid-based cytology screen. HPV infections were detected using HPV linear array, and chi-squared tests and linear regression models were used to compare HPV genotypes across racial/ethnic groups by CIN status. Of the 572 participants, 494 (86 %) had detectable HPV; 245 (43 %) had no CIN lesion, 239 (42 %) had CIN1, and 88 (15 %) had CIN2/3. Seventy-three percent of all women were infected with multiple HPV genotypes. After adjusting for race, age, parity, income, oral contraception use, and current smoking, AAs were two times less likely to harbor HPV 16/18 (OR 0.48, 95 % CI 0.21-0.94, p = 0.03) when all women were considered. This association remained unchanged when only women with CIN2/3 lesions were examined (OR 0.22, 95 % CI 0.05-0.95, p = 0.04). The most frequent high-risk HPV genotypes detected among EAs were 16, 18, 56, 39, and 66, while HPV genotypes 33, 35, 45, 58, and 68 were the most frequent ones detected in AAs. Our data suggest that while HPV 16/18 are the most common genotypes among EA women with CIN, AAs may harbor different genotypes.

  20. Comparative Susceptibility of Sheep of Different Origins, Breeds and PRNP Genotypes to Challenge with Bovine Spongiform Encephalopathy and Scrapie

    PubMed Central

    Houston, Fiona; Goldmann, Wilfred; Foster, James; González, Lorenzo; Jeffrey, Martin; Hunter, Nora

    2015-01-01

    Sheep are natural hosts of the prion disease, scrapie. They are also susceptible to experimental challenge with various scrapie strains and with bovine spongiform encephalopathy (BSE), which affects cattle and has been accidentally transmitted to a range of other species, including man. Incidence and incubation period of clinical disease in sheep following inoculation is controlled by the PRNP gene, which has different alleles defined on the basis of polymorphisms, particularly at codons 136, 154 and 171, although other codons are associated with survival time, and the exact responses of the sheep may be influenced by other breed-related differences. Here we report the results of a long term single study of experimental scrapie and BSE susceptibility of sheep of Cheviot, Poll Dorset and Suffolk breeds, originating from New Zealand and of a wide range of susceptible and resistant PRNP genotypes. Responses were compared with those of sheep from a closed Cheviot flock of UK origin (Roslin Cheviot flock). The unusually long observation period (6–8 years for most, but up to 12 years for others) allows us to draw robust conclusions about rates of survival of animals previously regarded as resistant to infection, particularly PRNP heterozygotes, and is the most comprehensive such study reported to date. BSE inoculation by an intracerebral route produced disease in all genotype groups with differing incubation periods, although M112T and L141F polymorphisms seemed to give some protection. Scrapie isolate SSBP/1, which has the shortest incubation period in sheep with at least one VRQ PRNP allele, also produced disease following sub-cutaneous inoculation in ARQ/ARQ animals of New Zealand origin, but ARQ/ARQ sheep from the Roslin flock survived the challenge. Our results demonstrate that the links between PRNP genotype and clinical prion disease in sheep are much less secure than previously thought, and may break down when, for example, a different breed of sheep is moved

  1. Towards Development of Clustering Applications for Large-Scale Comparative Genotyping and Kinship Analysis Using Y-Short Tandem Repeats.

    PubMed

    Seman, Ali; Sapawi, Azizian Mohd; Salleh, Mohd Zaki

    2015-06-01

    Y-chromosome short tandem repeats (Y-STRs) are genetic markers with practical applications in human identification. However, where mass identification is required (e.g., in the aftermath of disasters with significant fatalities), the efficiency of the process could be improved with new statistical approaches. Clustering applications are relatively new tools for large-scale comparative genotyping, and the k-Approximate Modal Haplotype (k-AMH), an efficient algorithm for clustering large-scale Y-STR data, represents a promising method for developing these tools. In this study we improved the k-AMH and produced three new algorithms: the Nk-AMH I (including a new initial cluster center selection), the Nk-AMH II (including a new dominant weighting value), and the Nk-AMH III (combining I and II). The Nk-AMH III was the superior algorithm, with mean clustering accuracy that increased in four out of six datasets and remained at 100% in the other two. Additionally, the Nk-AMH III achieved a 2% higher overall mean clustering accuracy score than the k-AMH, as well as optimal accuracy for all datasets (0.84-1.00). With inclusion of the two new methods, the Nk-AMH III produced an optimal solution for clustering Y-STR data; thus, the algorithm has potential for further development towards fully automatic clustering of any large-scale genotypic data.

  2. Comparative study on the mechanical and microstructural characterisation of AA 7075 nano and hybrid nanocomposites produced by stir and squeeze casting.

    PubMed

    Kannan, C; Ramanujam, R

    2017-07-01

    In this research work, a comparative evaluation on the mechanical and microstructural characteristics of aluminium based single and hybrid reinforced nanocomposites was carried out. The manufacture of a single reinforced nanocomposite was conducted with the distribution of 2 wt.% nano alumina particles (avg. particle size 30-50 nm) in the molten aluminium alloy of grade AA 7075; while the hybrid reinforced nanocomposites were produced with of 4 wt.% silicon carbide (avg. particle size 5-10 µm) and 2 wt.%, 4 wt.% nano alumina particles. Three numbers of single reinforced nanocomposites were manufactured through stir casting with reinforcements preheated to different temperatures viz. 400 °C, 500 °C, and 600 °C. The stir cast procedure was extended to fabricate two hybrid reinforced nanocomposites with reinforcements preheated to 500 °C prior to their inclusion. A single reinforced nanocomposite was also developed by squeeze casting with a pressure of 101 MPa. Mechanical and physical properties such as density, hardness, ultimate tensile strength, and impact strength were evaluated on all the developed composites. The microstructural observation was carried out using optical and scanning electron microscopy. On comparison with base alloy, an improvement of 63.7% and 81.1% in brinell hardness was observed for single and hybrid reinforced nanocomposites respectively. About 16% higher ultimate tensile strength was noticed with the squeeze cast single reinforced nanocomposite over the stir cast.

  3. Comparative Proteomic and Nutritional Composition Analysis of Independent Transgenic Pigeon Pea Seeds Harboring cry1AcF and cry2Aa Genes and Their Nontransgenic Counterparts.

    PubMed

    Mishra, Pragya; Singh, Shweta; Rathinam, Maniraj; Nandiganti, Muralimohan; Ram Kumar, Nikhil; Thangaraj, Arulprakash; Thimmegowda, Vinutha; Krishnan, Veda; Mishra, Vagish; Jain, Neha; Rai, Vandna; Pattanayak, Debasis; Sreevathsa, Rohini

    2017-02-22

    Safety assessment of genetically modified plants is an important aspect prior to deregulation. Demonstration of substantial equivalence of the transgenics compared to their nontransgenic counterparts can be performed using different techniques at various molecular levels. The present study is a first-ever comprehensive evaluation of pigeon pea transgenics harboring two independent cry genes, cry2Aa and cry1AcF. The absence of unintended effects in the transgenic seed components was demonstrated by proteome and nutritional composition profiling. Analysis revealed that no significant differences were found in the various nutritional compositional analyses performed. Additionally, 2-DGE-based proteome analysis of the transgenic and nontransgenic seed protein revealed that there were no major changes in the protein profile, although a minor fold change in the expression of a few proteins was observed. Furthermore, the study also demonstrated that neither the integration of T-DNA nor the expression of the cry genes resulted in the production of unintended effects in the form of new toxins or allergens.

  4. Aa Ah Nak

    ERIC Educational Resources Information Center

    Tha, Na Gya; Wus, Thay

    2017-01-01

    In this article, Aa Ah Nak, the authors' methodology presents not only various reflections but also diverse contradictions about the Aa Nii language as well as language revitalization. This article explores language foundation and how the Aa Nii language revitalization is inextricably linked to the genocide and resulting historic trauma pervasive…

  5. Comparative analysis of alfalfa (Medicago sativa L.) leaf transcriptomes reveals genotype-specific salt tolerance mechanisms.

    PubMed

    Lei, Yunting; Xu, Yuxing; Hettenhausen, Christian; Lu, Chengkai; Shen, Guojing; Zhang, Cuiping; Li, Jing; Song, Juan; Lin, Honghui; Wu, Jianqiang

    2018-02-15

    Soil salinity is an important factor affecting growth, development, and productivity of almost all land plants, including the forage crop alfalfa (Medicago sativa). However, little is known about how alfalfa responds and adapts to salt stress, particularly among different salt-tolerant cultivars. Among seven alfalfa cultivars, we found that Zhongmu-1 (ZM) is relatively salt-tolerant and Xingjiang Daye (XJ) is salt-sensitive. Compared to XJ, ZM showed slower growth under low-salt conditions, but exhibited stronger tolerance to salt stress. RNA-seq analysis revealed 2237 and 1125 differentially expressed genes (DEGs) between ZM and XJ in the presence and absence of salt stress, among which many genes are involved in stress-related pathways. After salt treatment, compared with the controls, the number of DEGs in XJ (19373) was about four times of that in ZM (4833). We also detected specific differential gene expression patterns: In response to salt stress, compared with XJ, ZM maintained relatively more stable expression levels of genes related to the ROS and Ca 2+ pathways, phytohormone biosynthesis, and Na + /K + transport. Notably, several salt resistance-associated genes always showed greater levels of expression in ZM than in XJ, including a transcription factor. Consistent with the suppression of plant growth resulting from salt stress, the expression of numerous photosynthesis- and growth hormone-related genes decreased more dramatically in XJ than in ZM. By contrast, the expression levels of photosynthetic genes were lower in ZM under low-salt conditions. Compared with XJ, ZM is a salt-tolerant alfalfa cultivar possessing specific regulatory mechanisms conferring exceptional salt tolerance, likely by maintaining high transcript levels of abiotic and biotic stress resistance-related genes. Our results suggest that maintaining this specific physiological status and/or plant adaptation to salt stress most likely arises by inhibition of plant growth in ZM through

  6. Comparative ultrastructure of fruit plastids in three genetically diverse genotypes of apple (Malus × domestica Borkh.) during development

    PubMed Central

    Schaeffer, Scott M.; Christian, Ryan; Castro-Velasquez, Nohely; Hyden, Brennan; Lynch-Holm, Valerie

    2017-01-01

    Plastids are the defining organelle for a plant cell and are critical for myriad metabolic functions. The role of leaf plastid, chloroplast, is extensively documented; however, fruit plastids—chromoplasts—are poorly understood, especially in the context of the diverse metabolic processes operating in these diverse plant organs. Recently, in a comparative study of the predicted plastid-targeted proteomes across seven plant species, we reported that each plant species is predicted to harbor a unique set of plastid-targeted proteins. However, the temporal and developmental context of these processes remains unknown. In this study, an ultrastructural analysis approach was used to characterize fruit plastids in the epidermal and collenchymal cell layers at 11 developmental timepoints in three genotypes of apple (Malus × domestica Borkh.): chlorophyll-predominant ‘Granny Smith’, carotenoid-predominant ‘Golden Delicious’, and anthocyanin-predominant ‘Top Red Delicious’. Plastids transitioned from a proplastid-like plastid to a chromoplast-like plastid in epidermis cells, while in the collenchyma cells, they transitioned from a chloroplast-like plastid to a chloro-chromo-amyloplast plastid. Plastids in the collenchyma cells of the three genotypes demonstrated a diverse array of structures and features. This study enabled the identification of discrete developmental stages during which specific functions are most likely being performed by the plastids as indicated by accumulation of plastoglobuli, starch granules, and other sub-organeller structures. Information regarding the metabolically active developmental stages is expected to facilitate biologically relevant omics studies to unravel the complex biochemistry of plastids in perennial non-model systems. PMID:28698906

  7. Comparative 454 pyrosequencing of transcripts from two olive genotypes during fruit development

    PubMed Central

    Alagna, Fiammetta; D'Agostino, Nunzio; Torchia, Laura; Servili, Maurizio; Rao, Rosa; Pietrella, Marco; Giuliano, Giovanni; Chiusano, Maria Luisa; Baldoni, Luciana; Perrotta, Gaetano

    2009-01-01

    Background Despite its primary economic importance, genomic information on olive tree is still lacking. 454 pyrosequencing was used to enrich the very few sequence data currently available for the Olea europaea species and to identify genes involved in expression of fruit quality traits. Results Fruits of Coratina, a widely cultivated variety characterized by a very high phenolic content, and Tendellone, an oleuropein-lacking natural variant, were used as starting material for monitoring the transcriptome. Four different cDNA libraries were sequenced, respectively at the beginning and at the end of drupe development. A total of 261,485 reads were obtained, for an output of about 58 Mb. Raw sequence data were processed using a four step pipeline procedure and data were stored in a relational database with a web interface. Conclusion Massively parallel sequencing of different fruit cDNA collections has provided large scale information about the structure and putative function of gene transcripts accumulated during fruit development. Comparative transcript profiling allowed the identification of differentially expressed genes with potential relevance in regulating the fruit metabolism and phenolic content during ripening. PMID:19709400

  8. Resistance of different stocks and transferrin genotypes of coho salmon, Oncorhynchus kisutch, and steelhead trout, Salmo gairdneri, to bacterial kidney disease and vibriosis

    USGS Publications Warehouse

    Winter , Gary W.; Schreck, Carl B.; McIntyre, John D.

    1979-01-01

    Juvenile coho salmon and steelhead trout ofdifferentstocks and three transferrin genotypes(AA, AC, and CCl, all reared in identical or similar environments, were experimentally infected with Corynebacterium sp., the causative agent ofbacterial kidney disease, or with Vibrio anguillarum, the causative agent of vibriosis. Mortality due to the pathogens was compared among stocks within a species and among transferrin genotypes within a stock to determine whetherthere was a geneticbasis for resistance to disease. Differences in resistance to bacterial kidney disease among coho salmon stocks had a genetic basis. Stock susceptibility to vibriosis was strongly influenced by environmental factors. Coho salmon orsteelhead trout of one stock may be resistant to one disease but susceptible to another. The importance of transferrin genotype of coho salmon in resistance to bacterial kidney disease was stock specific; in stocks that showed differential resistance of genotypes, the AA was the most susceptible. No differencesin resistance to vibriosis were observed among transferrin genotypes.

  9. A Large Maize (Zea mays L.) SNP Genotyping Array: Development and Germplasm Genotyping, and Genetic Mapping to Compare with the B73 Reference Genome

    PubMed Central

    Ganal, Martin W.; Durstewitz, Gregor; Polley, Andreas; Bérard, Aurélie; Buckler, Edward S.; Charcosset, Alain; Clarke, Joseph D.; Graner, Eva-Maria; Hansen, Mark; Joets, Johann; Le Paslier, Marie-Christine; McMullen, Michael D.; Montalent, Pierre; Rose, Mark; Schön, Chris-Carolin; Sun, Qi; Walter, Hildrun; Martin, Olivier C.; Falque, Matthieu

    2011-01-01

    SNP genotyping arrays have been useful for many applications that require a large number of molecular markers such as high-density genetic mapping, genome-wide association studies (GWAS), and genomic selection. We report the establishment of a large maize SNP array and its use for diversity analysis and high density linkage mapping. The markers, taken from more than 800,000 SNPs, were selected to be preferentially located in genes and evenly distributed across the genome. The array was tested with a set of maize germplasm including North American and European inbred lines, parent/F1 combinations, and distantly related teosinte material. A total of 49,585 markers, including 33,417 within 17,520 different genes and 16,168 outside genes, were of good quality for genotyping, with an average failure rate of 4% and rates up to 8% in specific germplasm. To demonstrate this array's use in genetic mapping and for the independent validation of the B73 sequence assembly, two intermated maize recombinant inbred line populations – IBM (B73×Mo17) and LHRF (F2×F252) – were genotyped to establish two high density linkage maps with 20,913 and 14,524 markers respectively. 172 mapped markers were absent in the current B73 assembly and their placement can be used for future improvements of the B73 reference sequence. Colinearity of the genetic and physical maps was mostly conserved with some exceptions that suggest errors in the B73 assembly. Five major regions containing non-colinearities were identified on chromosomes 2, 3, 6, 7 and 9, and are supported by both independent genetic maps. Four additional non-colinear regions were found on the LHRF map only; they may be due to a lower density of IBM markers in those regions or to true structural rearrangements between lines. Given the array's high quality, it will be a valuable resource for maize genetics and many aspects of maize breeding. PMID:22174790

  10. Determination of the full-genome sequence of hepatitis E virus (HEV) SAAS-FX17 and use as a reference to identify putative HEV genotype 4 virulence determinants.

    PubMed

    Zhu, Yumin; Yu, Xiaoming; Huang, Fenfen; Yu, Ruisong; Dong, Shijuan; Si, Fusheng; Zhang, Yuanshu; Li, Zhen

    2012-11-08

    Four major genotypes of hepatitis E virus (HEV), the causative agent of hepatitis E, have so far been recognized. While genotypes 3 and 4 are both zoonotic, the disease symptoms caused by the latter tend to be more severe. To examine if specific nucleotide/amino acid variations between genotypes 3 and 4 play a role in determining the severity of hepatitis E disease, the complete genome of one swine HEV genotype 4 isolate, SAAS-FX17, was determined and compared with other genotype 4 and genotype 3 genomes to identify putative HEV genotype 4 virulence determinants. A total of 42 conformable nt/aa variations between genotype 3 and 4 HEVs were detected, of which 19 were proposed to be potential disease severity determinants for genotype 4 strains. One potential determinant was located in each of the 5'-UTR and 3'-UTR, 3 and 12 within ORF1 and ORF2 respectively, and 2 in the junction region.

  11. Genetic polymorphisms within exon 3 of heat shock protein 90AA1 gene and its association with heat tolerance traits in Sahiwal cows

    PubMed Central

    Kumar, Rakesh; Gupta, I. D.; Verma, Archana; Verma, Nishant; Vineeth, M. R.

    2015-01-01

    Aim: The present study was undertaken to identify novel single nucleotide polymorphism (SNP) in Exon 3 of HSP90AA1 gene and to analyze their association with respiration rate (RR) and rectal temperature (RT) in Sahiwal cows. Materials and Methods: The present study was carried out in Sahiwal cows (n=100) with the objectives to identify novel SNP in exon 3 of HSP90AA1 gene and to explore the association with heat tolerance traits. CLUSTAL-W multiple sequence analysis was used to identify novel SNPs in exon 3 of HSP90AA1 gene in Sahiwal cows. Gene and genotype frequencies of different genotypes were estimated by standard procedure POPGENE version 1.32 (University of Alberta, Canada). The significant effect of SNP variants on physiological parameters, e.g. RR and RT were analyzed using the General Linear model procedure of SAS Version 9.2. Results: The polymerase chain reaction product with the amplicon size of 450 bp was successfully amplified, covering exon 3 region of HSP90AA1 gene in Sahiwal cows. On the basis of comparative sequence analysis of Sahiwal samples (n=100), transitional mutations were detected at locus A1209G as compared to Bos taurus (NCBI GenBank AC_000178.1). After chromatogram analysis, three genotypes AA, AG, and GG with respective frequencies of 0.23, 0.50, and 0.27 ascertained. RR and RT were recorded once during probable extreme hours in winter, spring, and summer seasons. It was revealed that significant difference (p<0.01) among genetic variants of HSP90AA1 gene with heat tolerance trait was found in Sahiwal cattle. The homozygotic animals with AA genotype had lower heat tolerance coefficient (HTC) (1.78±0.04a), as compared to both AG and GG genotypes (1.85±0.03b and 1.91±0.02c), respectively. The gene and genotype frequencies for the locus A1209G were ascertained. Conclusions: Novel SNP was found at the A1209G position showed all possible three genotypes (homozygous and heterozygous). Temperature humidity index has a highly significant

  12. Comparative transcriptional profiling of two wheat genotypes, with contrasting levels of minerals in grains, shows expression differences during grain filling.

    PubMed

    Singh, Sudhir P; Jeet, Raja; Kumar, Jitendra; Shukla, Vishnu; Srivastava, Rakesh; Mantri, Shrikant S; Tuli, Rakesh

    2014-01-01

    Wheat is one of the most important cereal crops in the world. To identify the candidate genes for mineral accumulation, it is important to examine differential transcriptome between wheat genotypes, with contrasting levels of minerals in grains. A transcriptional comparison of developing grains was carried out between two wheat genotypes- Triticum aestivum Cv. WL711 (low grain mineral), and T. aestivum L. IITR26 (high grain mineral), using Affymetrix GeneChip Wheat Genome Array. The study identified a total of 580 probe sets as differentially expressed (with log2 fold change of ≥2 at p≤0.01) between the two genotypes, during grain filling. Transcripts with significant differences in induction or repression between the two genotypes included genes related to metal homeostasis, metal tolerance, lignin and flavonoid biosynthesis, amino acid and protein transport, vacuolar-sorting receptor, aquaporins, and stress responses. Meta-analysis revealed spatial and temporal signatures of a majority of the differentially regulated transcripts.

  13. Comparative Transcriptional Profiling of Two Wheat Genotypes, with Contrasting Levels of Minerals in Grains, Shows Expression Differences during Grain Filling

    PubMed Central

    Singh, Sudhir P.; Jeet, Raja; Kumar, Jitendra; Shukla, Vishnu; Srivastava, Rakesh; Mantri, Shrikant S.; Tuli, Rakesh

    2014-01-01

    Wheat is one of the most important cereal crops in the world. To identify the candidate genes for mineral accumulation, it is important to examine differential transcriptome between wheat genotypes, with contrasting levels of minerals in grains. A transcriptional comparison of developing grains was carried out between two wheat genotypes- Triticum aestivum Cv. WL711 (low grain mineral), and T. aestivum L. IITR26 (high grain mineral), using Affymetrix GeneChip Wheat Genome Array. The study identified a total of 580 probe sets as differentially expressed (with log2 fold change of ≥2 at p≤0.01) between the two genotypes, during grain filling. Transcripts with significant differences in induction or repression between the two genotypes included genes related to metal homeostasis, metal tolerance, lignin and flavonoid biosynthesis, amino acid and protein transport, vacuolar-sorting receptor, aquaporins, and stress responses. Meta-analysis revealed spatial and temporal signatures of a majority of the differentially regulated transcripts. PMID:25364903

  14. Comparative shoot proteome analysis of two potato (Solanum tuberosum L.) genotypes contrasting in nitrogen deficiency responses in vitro.

    PubMed

    Meise, Philipp; Jozefowicz, Anna Maria; Uptmoor, Ralf; Mock, Hans-Peter; Ordon, Frank; Schum, Annegret

    2017-08-23

    Aiming at a better understanding of the physiological and biochemical background of nitrogen use efficiency, alterations in the shoot proteome under N-deficiency were investigated in two contrasting potato genotypes grown in vitro with 60 and 7.5mM N, respectively. A gel based proteomic approach was applied to identify candidate proteins associated with genotype specific responses to N-deficiency. 21% of the detected proteins differed in abundance between the two genotypes. Between control and N-deficiency conditions 19.5% were differentially accumulated in the sensitive and 15% in the tolerant genotype. 93% of the highly N-deficiency responsive proteins were identified by MALDI TOF/TOF mass spectrometry. The major part was associated with photosynthesis, carbohydrate metabolism, stress response and regulation. Differential accumulation of enzymes involved in the Calvin cycle and glycolysis suggest activation of alternative carbohydrate pathways. In the tolerant genotype, increased abundance under N-deficiency was also found for enzymes involved in chlorophyll synthesis and stability of enzymes, which increase photosynthetic carbon fixation efficiency. Out of a total of 106 differentially abundant proteins, only eight were detected in both genotypes. Our findings suggest that mutually responsive proteins reflect universal stress responses while adaptation to N-deficiency in metabolic pathways is more genotype specific. Nitrogen losses from arable farm land considerably contribute to environmental pollution. In potato, this is a special problem due cultivation on light soils, irrigation and the shallow root system. Therefore, breeding of cultivars with improved nitrogen use efficiency and stable yields under reduced N fertilization is an important issue. Knowledge of genotype dependent adaptation to N-deficiency at the proteome level can help to understand regulation of N efficiency and development of N-efficient cultivars. Copyright © 2017 Elsevier B.V. All rights

  15. [Effectiveness of human papillomavirus genotyping for detection of high-grade anal intraepithelial neoplasia compared to anal cytology].

    PubMed

    Padilla-España, Laura; Repiso-Jiménez, Juan Bosco; Fernández-Sánchez, Fernando; Pereda, Teresa; Rivas-Ruiz, Francisco; Fernández-Morano, Teresa; de la Torre-Lima, Javier; Palma, Fermín; Redondo, Maximino; de Troya-Martín, Magdalena

    2016-01-01

    The incidence of high-grade anal intraepithelial neoplasia (HGAIN) -with an aetiological based on high-risk types of human papillomavirus- is increasing in some high-risk groups. Screening for HGAIN includes routine anal cytology and, more recently, HPV genotyping. The main objective of this study was to determine the sensitivity and specificity of anal cytology and HPV genotyping for the detection of HGAIN. This is a study to determine the correlation of cytological and microbiological findings with anal biopsy findings in a cohort of patients at high risk of developing AIN referred to the department of sexually transmitted infections of the Hospital Costa del Sol, Spain, between January 2008 and December 2014. Of the 151 patients subjected to screening, a total of 92 patients, all of them with the result of three screening test (anal cytology, genotyping and biopsy) were included in the study. Just under two-thirds (62%) of them were HIV-positive. The sensitivity and specificity of anal cytology to detect HGAIN were 52.8 and 85.7%, respectively (k: 0.328), and 78 and 62.8% to detect two or more HPV oncogenic genotypes (k: 0.417). The detection of oncogenic HPV genotypes allowed the identification of 23 new cases of HGAIN that had been underdiagnosed with anal cytology, with 14 cases containing at least three high-risk genotypes. Anal cytology did not show enough sensitivity in HGAIN screening. HPV genotyping has shown to be a useful tool to detect HGAIN cases, although it could lead to an over-diagnosis as a solitary screening procedure. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  16. Comparative analysis of miRNAs of two rapeseed genotypes in response to acetohydroxyacid synthase-inhibiting herbicides by high-throughput sequencing.

    PubMed

    Hu, Maolong; Pu, Huiming; Gao, Jianqin; Long, Weihua; Chen, Feng; Zhang, Wei; Zhou, Xiaoyin; Peng, Qi; Chen, Song; Zhang, Jiefu

    2017-01-01

    Acetohydroxyacid synthase (AHAS), also called acetolactate synthase, is a key enzyme involved in the first step of the biosynthesis of the branched-chain amino acids valine, isoleucine and leucine. Acetohydroxyacid synthase-inhibiting herbicides (AHAS herbicides) are five chemical families of herbicides that inhibit AHAS enzymes, including imidazolinones (IMI), sulfonylureas (SU), pyrimidinylthiobenzoates, triazolinones and triazolopyrimidines. Five AHAS genes have been identified in rapeseed, but little information is available regarding the role of miRNAs in response to AHAS herbicides. In this study, an AHAS herbicides tolerant genotype and a sensitive genotype were used for miRNA comparative analysis. A total of 20 small RNA libraries were obtained of these two genotypes at three time points (0h, 24 h and 48 h) after spraying SU and IMI herbicides with two replicates. We identified 940 conserved miRNAs and 1515 novel candidate miRNAs in Brassica napus using high-throughput sequencing methods combined with computing analysis. A total of 3284 genes were predicted to be targets of these miRNAs, and their functions were shown using GO, KOG and KEGG annotations. The differentiation expression results of miRNAs showed almost twice as many differentiated miRNAs were found in tolerant genotype M342 (309 miRNAs) after SU herbicide application than in sensitive genotype N131 (164 miRNAs). In additiond 177 and 296 miRNAs defined as differentiated in sensitive genotype and tolerant genotype in response to SU herbicides. The miR398 family was observed to be associated with AHAS herbicide tolerance because their expression increased in the tolerant genotype but decreased in the sensitive genotype. Moreover, 50 novel miRNAs from 39 precursors were predicted. There were 8 conserved miRNAs, 4 novel miRNAs and 3 target genes were validated by quantitative real-time PCR experiment. This study not only provides novel insights into the miRNA content of AHAS herbicides tolerant

  17. Comparative analysis of miRNAs of two rapeseed genotypes in response to acetohydroxyacid synthase-inhibiting herbicides by high-throughput sequencing

    PubMed Central

    Hu, Maolong; Pu, Huiming; Gao, Jianqin; Long, Weihua; Chen, Feng; Zhang, Wei; Zhou, Xiaoyin; Peng, Qi; Chen, Song; Zhang, Jiefu

    2017-01-01

    Acetohydroxyacid synthase (AHAS), also called acetolactate synthase, is a key enzyme involved in the first step of the biosynthesis of the branched-chain amino acids valine, isoleucine and leucine. Acetohydroxyacid synthase-inhibiting herbicides (AHAS herbicides) are five chemical families of herbicides that inhibit AHAS enzymes, including imidazolinones (IMI), sulfonylureas (SU), pyrimidinylthiobenzoates, triazolinones and triazolopyrimidines. Five AHAS genes have been identified in rapeseed, but little information is available regarding the role of miRNAs in response to AHAS herbicides. In this study, an AHAS herbicides tolerant genotype and a sensitive genotype were used for miRNA comparative analysis. A total of 20 small RNA libraries were obtained of these two genotypes at three time points (0h, 24 h and 48 h) after spraying SU and IMI herbicides with two replicates. We identified 940 conserved miRNAs and 1515 novel candidate miRNAs in Brassica napus using high-throughput sequencing methods combined with computing analysis. A total of 3284 genes were predicted to be targets of these miRNAs, and their functions were shown using GO, KOG and KEGG annotations. The differentiation expression results of miRNAs showed almost twice as many differentiated miRNAs were found in tolerant genotype M342 (309 miRNAs) after SU herbicide application than in sensitive genotype N131 (164 miRNAs). In additiond 177 and 296 miRNAs defined as differentiated in sensitive genotype and tolerant genotype in response to SU herbicides. The miR398 family was observed to be associated with AHAS herbicide tolerance because their expression increased in the tolerant genotype but decreased in the sensitive genotype. Moreover, 50 novel miRNAs from 39 precursors were predicted. There were 8 conserved miRNAs, 4 novel miRNAs and 3 target genes were validated by quantitative real-time PCR experiment. This study not only provides novel insights into the miRNA content of AHAS herbicides tolerant

  18. Pharmacogenomics of platinum-based chemotherapy response in NSCLC: a genotyping study and a pooled analysis

    PubMed Central

    Chen, Juan; Wang, Zhan; Zou, Ting; Cui, Jiajia; Yin, Jiye; Zheng, Wei; Jiang, Wuzhong; Zhou, Honghao; Liu, Zhaoqian

    2016-01-01

    Published data showed inconsistent results about associations of extensively studied polymorphisms with platinum-based chemotherapy response. Our study aimed to provide reliable conclusions of these associations by detecting genotypes of the SNPs in a larger sample size and summarizing a comprehensive pooled analysis. 13 SNPs in 8 genes were genotyped in 1024 NSCLC patients by SequenomMassARRAY. 39 published studies and our study were included in meta-analysis. Patients with GA or GG genotypes of XRCC1 G1196 had better response than AA genotype carriers (Genotyping study: OR = 0.72, 95%CI: 0.53-0.96, P = 0.028; Meta-analysis: OR = 0.74, 95%CI: 0.62-0.89, P = 0.001). Patients carrying CT or TT genotypes of XRCC1 C580T could be more sensitive to platinum-based chemotherapy compared to patients with CC genotype (OR = 0.54, 95%CI: 0.37-0.80, P = 0.002). CC genotype of XRCC3 C18067T carriers showed more resistance to platinum-based chemotherapy when compared to those with CT or TT genotypes (OR = 0.69, 95%CI: 0.52-0.91, P = 0.009). Our study indicated that XRCC1 G1196A/C580T and XRCC3 C18067T should be paid attention for personalized platinum-based chemotherapy in NSCLC patients. PMID:27248474

  19. Comparative genotyping of Clostridium thermocellum strains isolated from biogas plants: genetic markers and characterization of cellulolytic potential.

    PubMed

    Koeck, Daniela E; Zverlov, Vladimir V; Liebl, Wolfgang; Schwarz, Wolfgang H

    2014-07-01

    Clostridium thermocellum is among the most prevalent of known anaerobic cellulolytic bacteria. In this study, genetic and phenotypic variations among C. thermocellum strains isolated from different biogas plants were determined and different genotyping methods were evaluated on these isolates. At least two C. thermocellum strains were isolated independently from each of nine different biogas plants via enrichment on cellulose. Various DNA-based genotyping methods such as ribotyping, RAPD (Random Amplified Polymorphic DNA) and VNTR (Variable Number of Tandem Repeats) were applied to these isolates. One novel approach - the amplification of unknown target sequences between copies of a previously discovered Random Inserted Mobile Element (RIME) - was also tested. The genotyping method with the highest discriminatory power was found to be the amplification of the sequences between the insertion elements, where isolates from each biogas plant yielded a different band pattern. Cellulolytic potentials, optimal growth conditions and substrate spectra of all isolates were characterized to help identify phenotypic variations. Irrespective of the genotyping method used, the isolates from each individual biogas plant always exhibited identical patterns. This is suggestive of a single C. thermocellum strain exhibiting dominance in each biogas plant. The genotypic groups reflect the results of the physiological characterization of the isolates like substrate diversity and cellulase activity. Conversely, strains isolated across a range of biogas plants differed in their genotyping results and physiological properties. Both strains isolated from one biogas plant had the best specific cellulose-degrading properties and might therefore achieve superior substrate utilization yields in biogas fermenters. Copyright © 2014 Elsevier GmbH. All rights reserved.

  20. Comparing triage algorithms using HPV DNA genotyping, HPV E7 mRNA detection and cytology in high-risk HPV DNA-positive women.

    PubMed

    Luttmer, Roosmarijn; Berkhof, Johannes; Dijkstra, Maaike G; van Kemenade, Folkert J; Snijders, Peter J F; Heideman, Daniëlle A M; Meijer, Chris J L M

    2015-06-01

    High-risk human papillomavirus (hrHPV) DNA positive women require triage testing to identify those with high-grade cervical intraepithelial neoplasia or cancer (≥CIN2). Comparing three triage algorithms (1) E7 mRNA testing following HPV16/18/31/33/45/52/58 genotyping (E7 mRNA test), (2) HPV16/18 DNA genotyping and (3) cytology, for ≥CIN2 detection in hrHPV DNA-positive women. hrHPV DNA-positive women aged 18-63 years visiting gynecology outpatient clinics were included in a prospective observational cohort study. From these women a cervical scrape and colposcopy-directed biopsies were obtained. Cervical scrapes were evaluated by cytology, HPV DNA genotyping by bead-based multiplex genotyping of GP5+6+-PCR-products, and presence of HPV16/18/31/33/45/52/58 E7 mRNA using nucleic acid sequence-based amplification (NASBA) in DNA positive women for respective HPV types. Sensitivities and specificities for ≥CIN2 were compared between E7 mRNA test and HPV16/18 DNA genotyping in the total group (n=348), and E7 mRNA test and cytology in a subgroup of women referred for non-cervix-related gynecological complaints (n=133). Sensitivity for ≥CIN2 of the E7 mRNA test was slightly higher than that of HPV16/18 DNA genotyping (66.9% versus 60.9%; ratio 1.10, 95% CI: 1.0002-1.21), at similar specificity (54.8% versus 52.3%; ratio 1.05, 95% CI: 0.93-1.18). Neither sensitivity nor specificity of the E7 mRNA test differed significantly from that of cytology (sensitivity: 68.8% versus 75.0%; ratio 0.92, 95% CI: 0.72-1.17; specificity: 59.4% versus 65.3%; ratio 0.91, 95% CI: 0.75-1.10). For detection of ≥CIN2 in hrHPV DNA-positive women, an algorithm including E7 mRNA testing following HPV16/18/31/33/45/52/58 DNA genotyping performs similar to HPV16/18 DNA genotyping or cytology. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. High prevalence of Cryptosporidium bovis and the deer-like genotype in calves compared to mature cows in beef cow-calf operations.

    PubMed

    Feltus, Dawn C; Giddings, Catherine W; Khaitsa, Margaret L; McEvoy, John M

    2008-02-14

    Recent studies have identified the novel, host adapted Cryptosporidium bovis and the deer-like genotype in dairy cattle from farms in the United States, China, India and Europe. This novel species and genotype appear to be more prevalent in older, post-weaned dairy cattle than previously thought. However, little information is available on their prevalence in beef cow-calf operations. In the present study, we determined the prevalence of Cryptosporidium species in 98 calves (6-8 months old) and 114 cows (>2 years old) in seven beef cow-calf herds in western North Dakota. DNA was extracted from fecal samples and Cryptosporidium spp. were identified by amplification of the 18S rRNA gene followed by sequencing or RFLP analysis. All seven herds tested positive for Cryptosporidium. Overall, 43/212 (20.3%) animals were positive. Only five of these positives were from cows. C. bovis, the deer-like genotype and C. andersoni were identified in 9.4, 6.6 and 1.4% of animals sampled, respectively. C. parvum was not identified in any of the positive samples. C. bovis, the deer-like genotype and C. andersoni were detected in 6/7, 5/7 and 2/7 herds, respectively. C. bovis and the deer-like genotype were primarily detected in calves, while C. andersoni was only detected in cows. Six isolates could not be typed. These results show a relatively high prevalence of C. bovis and the deer-like genotype in 6-8-month-old beef calves compared to cows older than 2 years in the seven herds studied.

  2. Comparative Transcriptome Analysis Reveals a Preformed Defense System in Apple Root of a Resistant Genotype of G.935 in the Absence of Pathogen

    PubMed Central

    Shao, Jonathan; Zhou, Zhe; Davis, Robert E.

    2017-01-01

    Two apple rootstock genotypes G.935 and B.9 were recently demonstrated to exhibit distinct resistance responses following infection by Pythium ultimum. As part of an effort to elucidate the genetic regulation of apple root resistance to soilborne pathogens, preinoculation transcriptome variations in roots of these two apple rootstock genotypes are hypothesized to contribute to the observed disease resistance phenotypes. Results from current comparative transcriptome analysis demonstrated elevated transcript abundance for many genes which function in a system-wide defense response in the root tissue of the resistant genotype of G.935 in comparison with susceptible B.9. Based on the functional annotation, these differentially expressed genes encode proteins that function in several tiers of defense responses, such as pattern recognition receptors for pathogen detection and subsequent signal transduction, defense hormone biosynthesis and signaling, transcription factors with known roles in defense activation, enzymes of secondary metabolism, and various classes of resistance proteins. The data set suggested a more poised status, which is ready to defend pathogen infection, in the root tissues of resistant genotype of G.935, compared to the susceptible B.9. The significance of preformed defense in the absence of a pathogen toward overall resistance phenotypes in apple root and the potential fitness cost due to the overactivated defense system were discussed. PMID:28465679

  3. AAS 227: Day 1

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-01-01

    The mission was featured on the front pages of 450 newspapers worldwide on every single continent (including Antartica!)New Horizons reached the Moon in9 HOURSafter launch (compared to the ~3 days it took the Apollo missions)The mission controllers were aiming for a 100km window of space all the way from EarthThere was a window of ~400seconds which the probe had to arrive within the probe arrived90 seconds early! Putting tardy astronomers everywhere to shame.Charon was the only satellite of Pluto known at the time of the mission proposalThe canyon found on Charon is not only bigger than the Grand Canyon but bigger than Mariner Valley on Mars which is already4000 km (2500 mi) long and reaches depths of up to 7 km (4 mi)!Charons surface. Tectonic feature runs about 1500 km, around 10 km deep. Eat it, Mars. #aas227 pic.twitter.com/blewwJaXEn Danny Barringer (@HeavyFe_H) January 5, 2016The mountains ringing the Sputnik Planum (aka the heart of Pluto) are over 4km high and are snow capped with methane icePlutos mountain ranges. Means surface nitrogen layer is thin, probably water ice according to @AlanStern. #aas227 pic.twitter.com/0yyHZvpBOE Danny Barringer (@HeavyFe_H) January 5, 2016Plutos atmosphere has a dozendistincthaze layers but how they arecreated is a mystery#aas227 hazes on Pluto wow pic.twitter.com/VPx99ZhPj1 Lisa StorrieLombardi (@lisajsl) January 5, 2016Alan also spoke about the future of New Horizons there is a new mission proposal for a fly by of a Kuiper Belt object 2014MU69 in Jan 2019 which should give us a better understanding of this icy frontier at the edge ofthe Solar System. As a parting gift Alan playedthemost gorgeously detailed fly over video of Plutos surface that had all in the room melting into their flip flops. Its safe to say that the whole room is now Pluto-curious and wondering whether a change of discipline is in order!Press Conference: Black Holes and Exoplanets (by Susanna Kohler)This morning marked the first press conference of the meeting

  4. Longitudinal study of experimental induction of AA amyloidosis in mice seeded with homologous and heterologous AA fibrils.

    PubMed

    Muhammad, Naeem; Murakami, Tomoaki; Inoshima, Yasuo; Ishiguro, Naotaka

    2016-09-01

    To investigate pathogenesis and kinetics of experimentally induced murine AA amyloidosis seeded with homologous (murine) and heterologous (bovine) AA fibrils. Experimental AA amyloidosis was induced by administration of inflammatory stimulus and preformed AA fibrils to a total of 111 female C57/Black mice. In this longitudinal study, heterologous (bovine) as well as homologous (murine) AA fibrils were injected intraperitoneally to mice in various combinations. Re-stimulation was done at 120 or 300 days post first inoculation. To analyze the intensity of amyloid depositions in mice organs, immunohistochemical techniques and image J software were used. Assessment of cytokines level in sera was done using a Mouse Th1/Th2/Th17 Cytokine CBA Kit. Incidence and severity of AA amyloidosis were quite low in mice inoculated with heterologous bovine AA fibrils than homologous murine one. Homologous AA fibrils administration at first and second inoculation caused maximum amount of amyloid depositions and severe systemic form of amyloidosis. Increase in the level of pro-inflammatory cytokine IL-6 was observed after first inoculation, while second inoculation caused a further increase in the level of anti-inflammatory cytokine IL-10. AA amyloidosis can be induced by heterologous as well as homologous AA fibrils. Severity of AA amyloidosis induced with homologous AA fibrils is higher compared to heterologous AA fibrils.

  5. High-resolution mapping of genotype-phenotype relationships in cridu chat syndrome using array comparative genomic hybridization

    SciTech Connect

    Zhang, Xiaoxiao; Snijders, Antoine; Segraves, Richard

    2007-07-03

    We have used array comparative genomic hybridization to map DNA copy-number changes in 94 patients with cri du chat syndrome who had been carefully evaluated for the presence of the characteristic cry, speech delay, facial dysmorphology, and level of mental retardation (MR). Most subjects had simple deletions involving 5p (67 terminal and 12 interstitial). Genotype-phenotype correlations localized the region associated with the cry to 1.5 Mb in distal 5p15.31, between bacterial artificial chromosomes (BACs) containing markers D5S2054 and D5S676; speech delay to 3.2 Mb in 5p15.32-15.33, between BACs containing D5S417 and D5S635; and the region associated with facial dysmorphology tomore » 2.4 Mb in 5p15.2-15.31, between BACs containing D5S208 and D5S2887. These results overlap and refine those reported in previous publications. MR depended approximately on the 5p deletion size and location, but there were many cases in which the retardation was disproportionately severe, given the 5p deletion. All 15 of these cases, approximately two-thirds of the severely retarded patients, were found to have copy-number aberrations in addition to the 5p deletion. Restriction of consideration to patients with only 5p deletions clarified the effect of such deletions and suggested the presence of three regions, MRI-III, with differing effect on retardation. Deletions including MRI, a 1.2-Mb region overlapping the previously defined cri du chat critical region but not including MRII and MRIII, produced a moderate level of retardation. Deletions restricted to MRII, located just proximal to MRI, produced a milder level of retardation, whereas deletions restricted to the still-more proximal MRIII produced no discernible phenotype. However, MR increased as deletions that included MRI extended progressively into MRII and MRIII, and MR became profound when all three regions were deleted.« less

  6. Non-invasive fetal RHD genotyping for RhD negative women stratified into RHD gene deletion or variant groups: comparative accuracy using two blood collection tube types.

    PubMed

    Hyland, Catherine A; Millard, Glenda M; O'Brien, Helen; Schoeman, Elizna M; Lopez, Genghis H; McGowan, Eunike C; Tremellen, Anne; Puddephatt, Rachel; Gaerty, Kirsten; Flower, Robert L; Hyett, Jonathan A; Gardener, Glenn J

    2017-12-01

    Non-invasive fetal RHD genotyping in Australia to reduce anti-D usage will need to accommodate both prolonged sample transport times and a diverse population demographic harbouring a range of RHD blood group gene variants. We compared RHD genotyping accuracy using two blood sample collection tube types for RhD negative women stratified into deleted RHD gene haplotype and RHD gene variant cohorts. Maternal blood samples were collected into EDTA and cell-free (cf)DNA stabilising (BCT) tubes from two sites, one interstate. Automated DNA extraction and polymerase chain reaction (PCR) were used to amplify RHD exons 5 and 10 and CCR5. Automated analysis flagged maternal RHD variants, which were classified by genotyping. Time between sample collection and processing ranged from 2.9 to 187.5 hours. cfDNA levels increased with time for EDTA (range 0.03-138 ng/μL) but not BCT samples (0.01-3.24 ng/μL). For the 'deleted' cohort (n=647) all fetal RHD genotyping outcomes were concordant, excepting for one unexplained false negative EDTA sample. Matched against cord RhD serology, negative predictive values using BCT and EDTA tubes were 100% and 99.6%, respectively. Positive predictive values were 99.7% for both types. Overall 37.2% of subjects carried an RhD negative baby. The 'variant' cohort (n=15) included one novel RHD and eight hybrid or African pseudogene variants. Review for fetal RHD specific signals, based on one exon, showed three EDTA samples discordant to BCT, attributed to high maternal cfDNA levels arising from prolonged transport times. For the deleted haplotype cohort, fetal RHD genotyping accuracy was comparable for samples collected in EDTA and BCT tubes despite higher cfDNA levels in the EDTA tubes. Capacity to predict fetal RHD genotype for maternal carriers of hybrid or pseudogene RHD variants requires stringent control of cfDNA levels. We conclude that fetal RHD genotyping is feasible in the Australian environment to avoid unnecessary anti

  7. AAS 227: Day 3

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-01-01

    many orbits has made it a powerhouse for learning about the temperatures, atmospheres, and orbits of exoplanets. The list of examples that Fazio provided included the first global temperature map of an exoplanet (HD 189733b), the detection of the closest transiting exoplanet (HD 219134b), and the measurement of thermal emission from a super-Earth (55 Cnc e). Spitzers large distance from the Earth (specifically, the ground-based telescopes on Earth) even allowed astronomers to observe an exoplanet via gravitational microlensing using a special technique called space-based parallax.Spitzer has also been extremely useful for observing everything from Solar System scales (such as the enormous infrared dust ring around Saturn) to galactic structures. Comparing images of galaxies observed at visible wavelengths with Spitzer images of the same galaxies at infrared wavelengths has allowed us to probe the structure and composition of galaxies at a new level.Astronomers have also used Spitzer to explore the evolution of stars. Thanks to its infrared detectors, Spitzer can look through large clouds of dust that are opaque at visible wavelengths, and observe young stellar objects in their birth environments. Cosmologists can use Spitzer to study the early universe and the formation of galaxies over twelve billion years ago. Fazio used all of these examples and more to demonstrate that Spitzer has truly changed our understanding of the universe.Climate Change for Astronomers (Meredith Rawls)Every astronomer at #aas227 wants to learn about climate change! WOW this room is ridiculously full. pic.twitter.com/ud9an0gLJG Meredith Rawls (@merrdiff) January 7, 2016The second half of the session was a presentation by Doug Duncan featuring an activity from his 101-level college course. He uses climate change as a way to teach critical thinking and scientific reasoning. Members of the audience were walked through an exercise that included interpreting plots of changing surface temperatures

  8. [Comparative studies of serological typing and HLA-A, B antigen genotyping with PCR using sequence-specific primers].

    PubMed

    Wu, Da-lin; Ling, Han-xin; Tang, Hao

    2004-11-01

    To evaluate the accuracy of PCR with sequence-specific primers (PCR-SSP) for HLA-I genotyping and analyze the causes of the errors occurring in the genotyping. DNA samples and were obtained from 34 clinical patients, and serological typing with monoclonal antibody (mAb) and HLA-A and, B antigen genotyping with PCR-SSP were performed. HLA-A and, B alleles were successfully typed in 34 clinical samples by mAb and PCR-SSP. No false positive or false negative results were found, and the erroneous and missed diagnosis rates were obviously higher in serological detection, being 23.5% for HLA-A and 26.5% for HLA-B. Error or confusion was more likely to occur in the antigens of A2 and A68, A32 and A33, B5, B60 and B61. DNA typing for HLA-I class (A, B antigens) by PCR-SSP has high resolution, high specificity, and good reproducibility, which is more suitable for clinical application than serological typing. PCR-SSP may accurately detect the alleles that are easily missed or mistaken in serological typing.

  9. Negative Affect, Relapse, and Alcoholics Anonymous (AA): Does AA Work by Reducing Anger?*

    PubMed Central

    Kelly, John F.; Stout, Robert L.; Tonigan, J. Scott; Magill, Molly; Pagano, Maria E.

    2010-01-01

    Objective: Anger and other indices of negative affect have been implicated in a stress-induced pathway to relapse. The Alcoholics Anonymous (AA) literature states that reduction of anger is critical to recovery, yet this proposed mechanism has rarely been investigated. Using lagged, controlled hierarchical linear modeling analyses, this study investigated whether AA attendance mobilized changes in anger and whether such changes explained AA-related benefit. Method: Alcohol-dependent adults (N = 1,706) receiving treatment as part of a clinical trial were assessed at intake and at 3, 6, 9, 12, and 15 months. Results: Findings revealed substantially elevated levels of anger compared with the general population (98th percentile) that decreased over 15-month follow-up but remained high (89th percentile). AA attendance was associated with better drinking outcomes, and higher levels of anger were associated with heavier drinking. However, AA attendance was unrelated to changes in anger. Conclusions: Although support was not found for anger as a mediator, there was strong convergence between AA's explicit emphasis on anger and the present findings: Anger appears to be a serious, enduring problem related to relapse and heavy alcohol consumption. Methodological factors may have contributed to the lack of association between AA and anger, but results suggest that AA attendance alone may be insufficient to alleviate the suffering and alcohol-related risks specifically associated with anger. PMID:20409438

  10. Genotypic to expression profiling of bovine calcium channel, voltage-dependent, alpha-2/delta subunit 1 gene, and their association with bovine mastitis among Frieswal (HFX Sahiwal) crossbred cattle of Indian origin.

    PubMed

    Deb, Rajib; Singh, Umesh; Kumar, Sushil; Kumar, Arun; Singh, Rani; Sengar, Gyanendra; Mann, Sandeep; Sharma, Arjava

    2014-04-03

    Calcium channel, voltage-dependent, alpha-2/delta subunit 1 (CACNA2D1) gene is considered to be an important noncytokine candidate gene influencing mastitis. Scanty of reports are available until today regarding the role play of CACNA2D1 gene on the susceptibility of bovine mastitis. We interrogated the CACNA2D1 G519663A [A>G] SNP by PCR-RFLP among two hundreds Frieswal (HF X Sahiwal) crossbred cattle of Indian origin. Genotypic frequency of AA (51.5, n=101) was comparatively higher than AG (35, n=70) and GG (14.5, n=29). Association of Somatic cell score (SCS) with genotypes revealed that, GG genotypes showing lesser count (less susceptible to mastitis) compare to AA and AG. Relative expression of CACNA2D1 transcript (in milk samples) was significantly higher among GG than AG and AA. Further we have also isolated blood sample from the all groups and PBMCs were cultured from each blood sample as per the standard protocol. They were treated with Calcium channel blocker and the expression level of the CACNA2D1 gene was evaluated by Real Time PCR. Results show that expression level decline in each genotypic group after treatment and expression level of GG are again significantly higher than AA and AG. Thus, it may be concluded that GG genotypic animals are favorable for selecting disease resistant breeds.

  11. Comparative analysis of caffeoylquinic acids and lignans in roots and seeds among various burdock (Arctium lappa) genotypes with high antioxidant activity.

    PubMed

    Liu, Jingyi; Cai, Yi-Zhong; Wong, Ricky Ngok Shun; Lee, Calvin Kai-Fai; Tang, Sydney Chi Wai; Sze, Stephen Cho Wing; Tong, Yao; Zhang, Yanbo

    2012-04-25

    Caffeoylquinic acids and lignans in the crude extracts of both roots and seeds from different burdock ( Arctium lappa L.) genotypes were simultaneously characterized and systematically compared by LC-MS and matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight mass spectrometry (MALDI-QIT-TOF MS), and their antioxidant activities were also investigated. A total of 14 lignans were identified in burdock seeds and 12 caffeoylquinic acids in burdock roots. High levels of caffeoylquinic acids were also detected in burdock seeds, but only trace amounts of lignans were found in burdock roots. Burdock seeds contained higher concentrations of lignans and caffeoylquinic acids than burdock roots. Quantitative analysis of caffeoylquinic acids and lignans in roots and seeds of various burdock genotypes was reported for the first time. Great variations in contents of both individual and total phenolic compounds as well as antioxidant activities were found among different genotypes. Burdock as a root vegetable or medicinal plants possessed considerably stronger antioxidant activity than common vegetables and fruits.

  12. AAS Career Services

    NASA Astrophysics Data System (ADS)

    Marvel, Kevin B.

    2012-08-01

    The American Astronomical Society provides substantial programs in the area of Career Services.Motivated by the Society's mission to enhance and share humanity's understanding of the Universe, the AAS provides a central resource for advertising positions, interviewing opportunities at its annual winter meeting and information, workshops and networks to enable astronomers to find employment.The programs of the Society in this area are overseen by an active committee on employment and the AAS Council itself.Additional resources that help characterize the field, its growth and facts about employment such as salaries and type of jobs available are regularly summarized and reported on by the American Institute of Physics.

  13. AAS Oral History Project

    NASA Astrophysics Data System (ADS)

    Buxner, Sanlyn; Holbrook, Jarita; AAS Oral History Team

    2016-06-01

    Now in its fourth year, the AAS Oral History Project has interviewed over 80 astronomers from all over the world. Led by the AAS Historical Astronomy Division (HAD) and partially funded by the American Institute of Physics Niels Bohr Library and ongoing support from the AAS, volunteers have collected oral histories from astronomers at professional meetings starting in 2015, including AAS, DPS, and the IAU general assembly. Each interview lasts one and a half to two hours and focuses on interviewees’ personal and professional lives. Questions include those about one’s family, childhood, strong influences on one’s scientific career, career path, successes and challenges, perspectives on how astronomy is changing as a field, and advice to the next generation. Each interview is audio recorded and transcribed, the content of which is checked with each interviewee. Once complete, interview transcripts are posted online as part of a larger oral history library at https://www.aip.org/history-programs/niels-bohr-library/oral-histories. Future analysis will reveal a rich story of astronomers and will help the community address issues of diversity, controversies, and the changing landscape of science. We are still recruiting individuals to be interviewed from all stages of career from undergraduate students to retired and emeritus astronomers. Contact Jarita Holbrook to schedule an interview or to find out more information about the project (astroholbrook@gmail.com). Also, contact Jarita Holbrook if you would like to become an interviewer for the project.

  14. The impact of the catechol-O-methyltransferase genotype on vascular function and blood pressure after acute green tea ingestion.

    PubMed

    Miller, Rosalind J; Jackson, Kim G; Dadd, Tony; Mayes, Andrew E; Brown, A Louise; Lovegrove, Julie A; Minihane, Anne M

    2012-06-01

    Evidence for the benefits of green tea catechins on vascular function is inconsistent, with genotype potentially contributing to the heterogeneity in response. Here, the impact of the catechol-O-methyltransferase (COMT) genotype on vascular function and blood pressure (BP) after green tea extract ingestion are reported. Fifty subjects (n = 25 of the proposed low-activity [AA] and of the high-activity [GG] COMT rs4680 genotype), completed a randomized, double-blind, crossover study. Peripheral arterial tonometry, digital volume pulse (DVP), and BP were assessed at baseline and 90 min after 1.06 g of green tea extract or placebo. A 5.5 h and subsequent 18.5 h urine collection was performed to assess green tea catechin excretion. A genotype × treatment interaction was observed for DVP reflection index (p = 0.014), with green tea extract in the AA COMT group attenuating the increase observed with placebo. A tendency for a greater increase in diastolic BP was evident at 90 min after the green tea extract compared to placebo (p = 0.07). A genotypic effect was observed for urinary methylated epigallocatechin during the first 5.5 h, with the GG COMT group demonstrating a greater concentration (p = 0.049). Differences in small vessel tone according to COMT genotype were evident after acute green tea extract. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Comparative Analysis of Anther Transcriptome Profiles of Two Different Rice Male Sterile Lines Genotypes under Cold Stress.

    PubMed

    Bai, Bin; Wu, Jun; Sheng, Wen-Tao; Zhou, Bo; Zhou, Li-Jie; Zhuang, Wen; Yao, Dong-Ping; Deng, Qi-Yun

    2015-05-18

    Rice is highly sensitive to cold stress during reproductive developmental stages, and little is known about the mechanisms of cold responses in rice anther. Using the HiSeq™ 2000 sequencing platform, the anther transcriptome of photo thermo sensitive genic male sterile lines (PTGMS) rice Y58S and P64S (Pei'ai64S) were analyzed at the fertility sensitive stage under cold stress. Approximately 243 million clean reads were obtained from four libraries and aligned against the oryza indica genome and 1497 and 5652 differentially expressed genes (DEGs) were identified in P64S and Y58S, respectively. Both gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted for these DEGs. Functional classification of DEGs was also carried out. The DEGs common to both genotypes were mainly involved in signal transduction, metabolism, transport, and transcriptional regulation. Most of the DEGs were unique for each comparison group. We observed that there were more differentially expressed MYB (Myeloblastosis) and zinc finger family transcription factors and signal transduction components such as calmodulin/calcium dependent protein kinases in the Y58S comparison group. It was also found that ribosome-related DEGs may play key roles in cold stress signal transduction. These results presented here would be particularly useful for further studies on investigating the molecular mechanisms of rice responses to cold stress.

  16. Comparative Analysis of Anther Transcriptome Profiles of Two Different Rice Male Sterile Lines Genotypes under Cold Stress

    PubMed Central

    Bai, Bin; Wu, Jun; Sheng, Wen-Tao; Zhou, Bo; Zhou, Li-Jie; Zhuang, Wen; Yao, Dong-Ping; Deng, Qi-Yun

    2015-01-01

    Rice is highly sensitive to cold stress during reproductive developmental stages, and little is known about the mechanisms of cold responses in rice anther. Using the HiSeq™ 2000 sequencing platform, the anther transcriptome of photo thermo sensitive genic male sterile lines (PTGMS) rice Y58S and P64S (Pei’ai64S) were analyzed at the fertility sensitive stage under cold stress. Approximately 243 million clean reads were obtained from four libraries and aligned against the oryza indica genome and 1497 and 5652 differentially expressed genes (DEGs) were identified in P64S and Y58S, respectively. Both gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted for these DEGs. Functional classification of DEGs was also carried out. The DEGs common to both genotypes were mainly involved in signal transduction, metabolism, transport, and transcriptional regulation. Most of the DEGs were unique for each comparison group. We observed that there were more differentially expressed MYB (Myeloblastosis) and zinc finger family transcription factors and signal transduction components such as calmodulin/calcium dependent protein kinases in the Y58S comparison group. It was also found that ribosome-related DEGs may play key roles in cold stress signal transduction. These results presented here would be particularly useful for further studies on investigating the molecular mechanisms of rice responses to cold stress. PMID:25993302

  17. The Microjet of AA Tau

    NASA Astrophysics Data System (ADS)

    Cox, A. W.; Hilton, G. M.; Williger, G. M.; Grady, C. A.; Woodgate, B.

    2005-12-01

    The microjet of AA Tau A.W. Cox (Atholton High School, Columbia MD), G.M. Hilton (SSAI and GSFC), G.M. Williger (JHU and U. Louisville), C.A. Grady (Eureka Scientific and GSFC) B.Woodgate (NASA's GSFC) AA Tau is a classical T Tauri star with a spatially resolved disk viewed at approximately 70 degrees from pole-on. Photo-polarimetric variability of the star has been interpreted as being caused by the stellar magnetic field being inclined at 30 degrees with respect to the stellar rotation axis, producing a warp in the inner disk. Under these conditions, any jet should be less collimated than typical of T Tauri microjets, and should show signs of the jet axis precessing around the stellar rotation axis. When compared with the microjets imaged in the HST/STIS coronagraphic imaging survey, the AA Tau jet has an opening half-angle of approximately 10-15 degrees rather than the 3-5 degrees typical of the other T Tauri stars which have been coronagraphically imaged by HST/STIS. Using the HST data with ultra-narrowband imagery and long slit spectroscopy obtained with the Goddard Fabry-Perot and the Dual Imaging Spectrograph at the Apache Point Observatory 3.5m telescope, we derive the jet inclination, knot ejection epochs, and ejection frequency. We also compare the jet opening angle with model predictions. Apache Point Observatory observations with the Goddard Fabry-Perot were made through a grant of Director's Discretionary Time. Apache Point Observatory is operated by the Astrophysical Research Consortium. The GFP was supported under NASA RTOP 51-188-01-22 to GSFC. Grady is supported under NASA contract NNH05CD30C to Eureka Scientific.

  18. Cluster-distinguishing genotypic and phenotypic diversity of carbapenem-resistant Gram-negative bacteria in solid-organ transplantation patients: a comparative study.

    PubMed

    Karampatakis, Theodoros; Geladari, Anastasia; Politi, Lida; Antachopoulos, Charalampos; Iosifidis, Elias; Tsiatsiou, Olga; Karyoti, Aggeliki; Papanikolaou, Vasileios; Tsakris, Athanassios; Roilides, Emmanuel

    2017-07-31

    Solid-organ transplant recipients may display high rates of colonization and/or infection by multidrug-resistant bacteria. We analysed and compared the phenotypic and genotypic diversity of carbapenem-resistant (CR) strains of Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii isolated from patients in the Solid Organ Transplantation department of our hospital. Between March 2012 and August 2013, 56 CR strains from various biological fluids underwent antimicrobial susceptibility testing with VITEK 2, molecular analysis by PCR amplification and genotypic analysis with pulsed-field gel electrophoresis (PFGE). They were clustered according to antimicrobial drug susceptibility and genotypic profiles. Diversity analyses were performed by calculating Simpson's diversity index and applying computed rarefaction curves.Results/Key findings. Among K. pneumoniae, KP-producers predominated (57.1 %). VIM and OXA-23 carbapenemases prevailed among P. aeruginosa and A. baumannii (89.4 and 88.9 %, respectively). KPC-producing K. pneumoniae and OXA-23 A. baumannii were assigned in single PFGE pulsotypes. VIM-producing P. aeruginosa generated multiple pulsotypes. CR K. pneumoniae strains displayed phenotypic diversity in tigecycline, colistin (CS), amikacin (AMK), gentamicin (GEN) and co-trimoxazole (SXT) (16 clusters); P. aeruginosa displayed phenotypic diversity in cefepime (FEP), ceftazidime, aztreonam, piperacillin, piperacillin-tazobactam, AMK, GEN and CS (9 clusters); and A. baumannii displayed phenotypic diversity in AMK, GEN, SXT, FEP, tobramycin and rifampicin (8 clusters). The Simpson diversity indices for the interpretative phenotype and PFGE analysis were 0.89 and 0.6, respectively, for K. pneumoniae strains (P<0.001); 0.77 and 0.6 for P. aeruginosa (P=0.22); and 0.86 and 0.19 for A. baumannii (P=0.004). The presence of different antimicrobial susceptibility profiles does not preclude the possibility that two CR K. pneumoniae or A. baumannii

  19. Analytical Validation of a Personalized Medicine APOL1 Genotyping Assay for Nondiabetic Chronic Kidney Disease Risk Assessment.

    PubMed

    Zhang, Jinglan; Fedick, Anastasia; Wasserman, Stephanie; Zhao, Geping; Edelmann, Lisa; Bottinger, Erwin P; Kornreich, Ruth; Scott, Stuart A

    2016-03-01

    The incidence of chronic kidney disease (CKD) varies by ancestry, with African Americans (AA) having a threefold to fourfold higher rate than whites. Notably, two APOL1 alleles, termed G1 [c.(1072A>G; 1200T>G)] and G2 (c.1212_1217del6), are strongly associated with higher rates of nondiabetic CKD and an increased risk for hypertensive end-stage renal disease. This has prompted the opportunity to implement APOL1 testing to identify at-risk patients and modify other risk factors to reduce the progression of CKD to end-stage renal disease. We developed an APOL1 genotyping assay using multiplex allele-specific primer extension, and validated using 58 positive and negative controls. Genotyping results were completely concordant with Sanger sequencing, and both triplicate interrun and intrarun genotyping results were completely concordant. Multiethnic APOL1 allele frequencies were also determined by genotyping 7059 AA, Hispanic, and Asian individuals from the New York City metropolitan area. The AA, Hispanic, and Asian APOL1 G1 and G2 allele frequencies were 0.22 and 0.13, 0.037 and 0.025, and 0.013 and 0.004, respectively. Notably, approximately 14% of the AA population carried two risk alleles and are at increased risk for CKD, compared with <1% of the Hispanic and Asian populations. This novel APOL1 genotyping assay is robust and highly accurate, and represents one of the first personalized medicine clinical genetic tests for disease risk prediction. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  20. Comparative Analysis of Muscle Transcriptome between Pig Genotypes Identifies Genes and Regulatory Mechanisms Associated to Growth, Fatness and Metabolism

    PubMed Central

    Ayuso, Miriam; Fernández, Almudena; Núñez, Yolanda; Benítez, Rita; Isabel, Beatriz; Barragán, Carmen; Fernández, Ana Isabel; Rey, Ana Isabel; Medrano, Juan F.; Cánovas, Ángela; González-Bulnes, Antonio; López-Bote, Clemente; Ovilo, Cristina

    2015-01-01

    Iberian ham production includes both purebred (IB) and Duroc-crossbred (IBxDU) Iberian pigs, which show important differences in meat quality and production traits, such as muscle growth and fatness. This experiment was conducted to investigate gene expression differences, transcriptional regulation and genetic polymorphisms that could be associated with the observed phenotypic differences between IB and IBxDU pigs. Nine IB and 10 IBxDU pigs were slaughtered at birth. Morphometric measures and blood samples were obtained and samples from Biceps femoris muscle were employed for compositional and transcriptome analysis by RNA-Seq technology. Phenotypic differences were evident at this early age, including greater body size and weight in IBxDU and greater Biceps femoris intramuscular fat and plasma cholesterol content in IB newborns. We detected 149 differentially expressed genes between IB and IBxDU neonates (p < 0.01 and Fold-Change > 1. 5). Several were related to adipose and muscle tissues development (DLK1, FGF21 or UBC). The functional interpretation of the transcriptomic differences revealed enrichment of functions and pathways related to lipid metabolism in IB and to cellular and muscle growth in IBxDU pigs. Protein catabolism, cholesterol biosynthesis and immune system were functions enriched in both genotypes. We identified transcription factors potentially affecting the observed gene expression differences. Some of them have known functions on adipogenesis (CEBPA, EGRs), lipid metabolism (PPARGC1B) and myogenesis (FOXOs, MEF2D, MYOD1), which suggest a key role in the meat quality differences existing between IB and IBxDU hams. We also identified several polymorphisms showing differential segregation between IB and IBxDU pigs. Among them, non-synonymous variants were detected in several transcription factors as PPARGC1B and TRIM63 genes, which could be associated to altered gene function. Taken together, these results provide information about candidate

  1. Comparative evaluation of p5+14 with SAP and peptide p5 by dual-energy SPECT imaging of mice with AA amyloidosis.

    PubMed

    Martin, Emily B; Williams, Angela; Richey, Tina; Stuckey, Alan; Heidel, R Eric; Kennel, Stephen J; Wall, Jonathan S

    2016-03-03

    Amyloidosis is a protein-misfolding disorder characterized by the extracellular deposition of amyloid, a complex matrix composed of protein fibrils, hyper-sulphated glycosaminoglycans and serum amyloid P component (SAP). Accumulation of amyloid in visceral organs results in the destruction of tissue architecture leading to organ dysfunction and failure. Early differential diagnosis and disease monitoring are critical for improving patient outcomes; thus, whole body amyloid imaging would be beneficial in this regard. Non-invasive molecular imaging of systemic amyloid is performed in Europe by using iodine-123-labelled SAP; however, this tracer is not available in the US. Therefore, we evaluated synthetic, poly-basic peptides, designated p5 and p5+14, as alternative radiotracers for detecting systemic amyloidosis. Herein, we perform a comparative effectiveness evaluation of radiolabelled peptide p5+14 with p5 and SAP, in amyloid-laden mice, using dual-energy SPECT imaging and tissue biodistribution measurements. All three radiotracers selectively bound amyloid in vivo; however, p5+14 was significantly more effective as compared to p5 in certain organs. Moreover, SAP bound principally to hepatosplenic amyloid, whereas p5+14 was broadly distributed in numerous amyloid-laden anatomic sites, including the spleen, liver, pancreas, intestines and heart. These data support clinical validation of p5+14 as an amyloid radiotracer for patients in the US.

  2. Complementary and alternative medicine (CAM) use by african american (AA) and caucasian american (CA) older adults in a rural setting: a descriptive, comparative study

    PubMed Central

    Cuellar, Norma; Aycock, Teresa; Cahill, Bridgett; Ford, Julie

    2003-01-01

    Background The use of CAM is at an all time high. There is very little research that compares the use of CAM in elders by ethnicity in rural settings. The purpose of the study was to determine if there was a difference between African American and Caucasian American rural elders on use of CAM and self-reported satisfaction with CAM. Methods The design was a descriptive, comparative study of 183 elders who reported the number of CAM used and satisfaction with CAM. A convenience sample was recruited through community service organizations in the state of Mississippi. The availability of elders through the support groups, sampling bias, subject effect, and self-report were limitations of the study. Results The commonest examples of CAM used by rural elders were prayer, vitamins, exercise, meditation, herbs, chiropractic medicine, glucosamine, and music therapy. Significant findings on SES and marital status were calculated. Differences on ethnicity and demographic variables were significant for age, education, and the use of glucosamine. Conclusions Health care providers must be aware that elders are using CAM and are satisfied with their use. Identifying different uses of CAM by ethnicity is important for health care practitioners, impacting how health care is provided. PMID:14622445

  3. Complementary and alternative medicine (CAM) use by African American (AA) and Caucasian American (CA) older adults in a rural setting: a descriptive, comparative study.

    PubMed

    Cuellar, Norma; Aycock, Teresa; Cahill, Bridgett; Ford, Julie

    2003-11-18

    The use of CAM is at an all time high. There is very little research that compares the use of CAM in elders by ethnicity in rural settings. The purpose of the study was to determine if there was a difference between African American and Caucasian American rural elders on use of CAM and self-reported satisfaction with CAM. The design was a descriptive, comparative study of 183 elders who reported the number of CAM used and satisfaction with CAM. A convenience sample was recruited through community service organizations in the state of Mississippi. The availability of elders through the support groups, sampling bias, subject effect, and self-report were limitations of the study. The commonest examples of CAM used by rural elders were prayer, vitamins, exercise, meditation, herbs, chiropractic medicine, glucosamine, and music therapy. Significant findings on SES and marital status were calculated. Differences on ethnicity and demographic variables were significant for age, education, and the use of glucosamine. Health care providers must be aware that elders are using CAM and are satisfied with their use. Identifying different uses of CAM by ethnicity is important for health care practitioners, impacting how health care is provided.

  4. Comparative ultrastructure of fruit plastids in three genetically diverse genotypes of apple (Malus × domestica Borkh.) during development.

    PubMed

    Schaeffer, Scott M; Christian, Ryan; Castro-Velasquez, Nohely; Hyden, Brennan; Lynch-Holm, Valerie; Dhingra, Amit

    2017-10-01

    Comparative ultrastructural developmental time-course analysis has identified discrete stages at which the fruit plastids undergo structural and consequently functional transitions to facilitate subsequent development-guided understanding of the complex plastid biology. Plastids are the defining organelle for a plant cell and are critical for myriad metabolic functions. The role of leaf plastid, chloroplast, is extensively documented; however, fruit plastids-chromoplasts-are poorly understood, especially in the context of the diverse metabolic processes operating in these diverse plant organs. Recently, in a comparative study of the predicted plastid-targeted proteomes across seven plant species, we reported that each plant species is predicted to harbor a unique set of plastid-targeted proteins. However, the temporal and developmental context of these processes remains unknown. In this study, an ultrastructural analysis approach was used to characterize fruit plastids in the epidermal and collenchymal cell layers at 11 developmental timepoints in three genotypes of apple (Malus × domestica Borkh.): chlorophyll-predominant 'Granny Smith', carotenoid-predominant 'Golden Delicious', and anthocyanin-predominant 'Top Red Delicious'. Plastids transitioned from a proplastid-like plastid to a chromoplast-like plastid in epidermis cells, while in the collenchyma cells, they transitioned from a chloroplast-like plastid to a chloro-chromo-amyloplast plastid. Plastids in the collenchyma cells of the three genotypes demonstrated a diverse array of structures and features. This study enabled the identification of discrete developmental stages during which specific functions are most likely being performed by the plastids as indicated by accumulation of plastoglobuli, starch granules, and other sub-organeller structures. Information regarding the metabolically active developmental stages is expected to facilitate biologically relevant omics studies to unravel the complex

  5. The influence of CYP1A2 genotype in the blood pressure response to caffeine ingestion is affected by physical activity status and caffeine consumption level.

    PubMed

    Soares, Rogerio Nogueira; Schneider, Augusto; Valle, Sandra Costa; Schenkel, Paulo Cavalheiro

    2018-03-06

    This study aimed to investigate whether the influence of CYP1A2 genotype in the blood pressure (BP) response to caffeine ingestion was affected by physical activity status and habitual caffeine consumption. Thirty-seven participants (19-50 years old) took place in the study and were categorized according to i) genotype: CYP1A2 (AA) "fast metabolizer", and CYP1A2 (AC) "slow metabolizer"; ii) physical activity level: sedentary (S) and physically active (A); and iii) caffeine consumption level: non-habitual caffeine consumer (NC) and habitual heavy caffeine consumer (C). All groups had BP assessed before (basal) and 1 hourh after (post) caffeine ingestion (6 mg·kg -1 ). It was observed that AC genotype individuals had increased basal-DBP and post-caffeine SBP when compared to AA individuals. Additionally, acute caffeine ingestion increased SBP only in the AC group. It was also found that physical activity only modulated the BP responses to acute caffeine ingestion in AC individuals. Furthermore, the results indicated that the habitual heavy caffeine consumers AC individuals had increased basal-DBP when compared to the AA ones. Our results suggest that the influence of CYP1A2 genotype in the basal and post-caffeine BP response to caffeine ingestion is modified by physical activity status and caffeine consumption level. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Clinical severity of pediatric respiratory illness with enterovirus D68 compared with rhinovirus or other enterovirus genotypes.

    PubMed

    Mertz, Dominik; Alawfi, Abdulsalam; Pernica, Jeffrey M; Rutherford, Candy; Luinstra, Kathy; Smieja, Marek

    2015-11-17

    Enterovirus D68 (EV-D68) resulted in a reported increase in the number of children needing hospital or critical care admission because of respiratory insufficiency during 2014. It remains unclear, however, whether EV-D68 infections were more severe than rhinovirus or non-EV-D68 enterovirus infections. We evaluated consecutive children presenting to a pediatric hospital between Aug. 1 and Oct. 31, 2014, with positive nasopharyngeal swabs for rhinovirus or enterovirus that were sent automatically for EV-D68 testing. We compared characteristics and outcomes of patients with EV-D68 with those with rhinovirus or non-EV-D68 enterovirus in a matched cohort study. A total of 93/297 (31.3%) of rhinovirus or enterovirus samples tested positive for EV-D68, and it was possible to compare 87 matched pairs. Children with EV-D68 infection were more likely to have difficulty breathing (odds ratio [OR] 3.00, 95% confidence interval [CI] 1.47-6.14). There was no significant difference in admission to the critical care unit or death among children with EV-D68 infection compared with those with other rhinovirus or enterovirus infections (adjusted OR 1.47, 95% CI 0.61-3.52). Children with EV-D68 infection were more often admitted to hospital, but not significantly so (adjusted OR 2.29, 95% CI 0.96-5.46). Enterovirus D68 seems to be a more virulent pulmonary pathogen than rhinovirus or non-EV-D68 enterovirus, but we did not find a significant difference in death or need for critical care. © 2015 Canadian Medical Association or its licensors.

  7. Phenotype–genotype correlation in Hirschsprung disease is illuminated by comparative analysis of the RET protein sequence

    PubMed Central

    Kashuk, Carl S.; Stone, Eric A.; Grice, Elizabeth A.; Portnoy, Matthew E.; Green, Eric D.; Sidow, Arend; Chakravarti, Aravinda; McCallion, Andrew S.

    2005-01-01

    The ability to discriminate between deleterious and neutral amino acid substitutions in the genes of patients remains a significant challenge in human genetics. The increasing availability of genomic sequence data from multiple vertebrate species allows inclusion of sequence conservation and physicochemical properties of residues to be used for functional prediction. In this study, the RET receptor tyrosine kinase serves as a model disease gene in which a broad spectrum (≥116) of disease-associated mutations has been identified among patients with Hirschsprung disease and multiple endocrine neoplasia type 2. We report the alignment of the human RET protein sequence with the orthologous sequences of 12 non-human vertebrates (eight mammalian, one avian, and three teleost species), their comparative analysis, the evolutionary topology of the RET protein, and predicted tolerance for all published missense mutations. We show that, although evolutionary conservation alone provides significant information to predict the effect of a RET mutation, a model that combines comparative sequence data with analysis of physiochemical properties in a quantitative framework provides far greater accuracy. Although the ability to discern the impact of a mutation is imperfect, our analyses permit substantial discrimination between predicted functional classes of RET mutations and disease severity even for a multigenic disease such as Hirschsprung disease. PMID:15956201

  8. Genotyping-by-sequencing highlights original diversity patterns within a European collection of 1191 maize flint lines, as compared to the maize USDA genebank.

    PubMed

    Gouesnard, Brigitte; Negro, Sandra; Laffray, Amélie; Glaubitz, Jeff; Melchinger, Albrecht; Revilla, Pedro; Moreno-Gonzalez, Jesus; Madur, Delphine; Combes, Valérie; Tollon-Cordet, Christine; Laborde, Jacques; Kermarrec, Dominique; Bauland, Cyril; Moreau, Laurence; Charcosset, Alain; Nicolas, Stéphane

    2017-10-01

    Genotyping by sequencing is suitable for analysis of global diversity in maize. We showed the distinctiveness of flint maize inbred lines of interest to enrich the diversity of breeding programs. Genotyping-by-sequencing (GBS) is a highly cost-effective procedure that permits the analysis of large collections of inbred lines. We used it to characterize diversity in 1191 maize flint inbred lines from the INRA collection, the European Cornfed association panel, and lines recently derived from landraces. We analyzed the properties of GBS data obtained with different imputation methods, through comparison with a 50 K SNP array. We identified seven ancestral groups within the Flint collection (dent, Northern flint, Italy, Pyrenees-Galicia, Argentina, Lacaune, Popcorn) in agreement with breeding knowledge. Analysis highlighted many crosses between different origins and the improvement of flint germplasm with dent germplasm. We performed association studies on different agronomic traits, revealing SNPs associated with cob color, kernel color, and male flowering time variation. We compared the diversity of both our collection and the USDA collection which has been previously analyzed by GBS. The population structure of the 4001 inbred lines confirmed the influence of the historical inbred lines (B73, A632, Oh43, Mo17, W182E, PH207, and Wf9) within the dent group. It showed distinctly different tropical and popcorn groups, a sweet-Northern flint group and a flint group sub-structured in Italian and European flint (Pyrenees-Galicia and Lacaune) groups. Interestingly, we identified several selective sweeps between dent, flint, and tropical inbred lines that co-localized with SNPs associated with flowering time variation. The joint analysis of collections by GBS offers opportunities for a global diversity analysis of maize inbred lines.

  9. Effect of the Microstructure on Diffusion Bonded AA5083, AA6082 and AA7075 Aluminium Alloys

    NASA Astrophysics Data System (ADS)

    Venugopal, S.; Mahendran, G.

    2018-05-01

    Rolled plates of aluminium alloys AA5083, AA6082 and AA7075 of 5 mm thickness are joined by diffusion bonding at varied parameters. The microstructure evolution of AA5083, AA6082 and AA7075 aluminium alloys is characterized by Transmission Electron Microscopy (TEM). Metallurgical investigations and mechanical tests are also performed to correlate the results of the TEM investigations with the mechanical properties of the produced diffusion bonded joints. It is observed that the bonding and shear strength of the alloys increase with the increase in bonding temperature, due to the diffusion of micro-constituents in the interface. High temperature enhances the uniform distribution of secondary phase particles and reduces pore formation/defects in the bonded joints.

  10. AAS 227: Day 2

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-01-01

    Editors Note:This week were at the 227th AAS Meeting in Kissimmee, FL. Along with several fellow authors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting at the end of each day. Follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.Welcome to Day 2 of the winter American Astronomical Society (AAS) meeting in Kissimmee! Several of us are attending the conference this year, and we will report highlights from each day here on astrobites. If youd like to see more timely updates during the day, we encourage you to follow @astrobites on twitter or search the #aas227 hashtag.Plenary Session: Black Hole Physics with the Event Horizon Telescope (by Susanna Kohler)If anyone needed motivation to wake up early this morning, they got it in the form of Feryal Ozel (University of Arizona) enthralling us all with exciting pictures, videos, and words about black holes and the Event Horizon Telescope. Ozel spoke to a packed room (at 8:30am!) about where the project currently stands, and where its heading in the future.The EHT has pretty much the coolest goal ever: actually image the event horizons of black holes in our universe. The problem is that the largest black hole we can look at (Sgr A*, in the center of our galaxy) has an event horizon size of 50 as. For this kind of resolution roughly equivalent to trying to image a DVD on the Moon! wed need an Earth-sized telescope. EHT has solved this problem by linking telescopes around the world, creating one giant, mm-wavelength effective telescope with a baseline the size of Earth.Besides producing awesome images, the EHT will be able to test properties of black-hole spacetime, the no-hair theorem, and general relativity (GR) in new regimes.Ozel walked us through some of the theory prep work we need to do now in order to get the most science out of the EHT, including devising new

  11. African Ancestry Influences CCR5 –2459G>A Genotype-Associated Virologic Success of Highly Active Antiretroviral Therapy

    PubMed Central

    Cheruvu, Vinay K.; Igo, Robert P.; Jurevic, Richard J.; Serre, David; Zimmerman, Peter A.; Rodriguez, Benigno; Mehlotra, Rajeev K.

    2014-01-01

    Introduction In a North American, HIV-positive, highly active antiretroviral therapy (HAART)-treated, adherent cohort of self-identified white and black patients, we previously observed that chemokine (C-C motif) receptor 5 (CCR5) –2459G>A genotype had a strong association with time to achieve virologic success (TVLS) in black but not in white patients. Methods Using 128 genome-wide ancestry informative markers, we performed a quantitative assessment of ancestry in these patients (n = 310) to determine (1) whether CCR5 –2459G>A genotype is still associated with TVLS of HAART when ancestry, not self-identified race, is considered and (2) whether this association is influenced by varying African ancestry. Results We found that the interaction between CCR5 –2459G>A genotype and African ancestry (≤0.125 vs. ≥0.425 and <0.71 vs. ≥0.71) was significantly associated with TVLS (GG compared with AA, P = 0.044 and 0.018, respectively). Furthermore, the association between CCR5 –2459G>A genotype and TVLS was stronger in patients with African ancestry ≥0.71 than in patients with African ancestry ≥0.452, in both Kaplan-Meier (log-rank P = 0.039 and 0.057, respectively, for AA, GA, and GG) and Cox proportional hazards regression (relative hazard for GG compared with AA 2.59 [95% CI, 1.27–5.22; P = 0.01] and 2.26 [95% CI, 1.18–4.32; P = 0.01], respectively) analyses. Conclusions We observed that the association between CCR5 –2459G>A genotype and TVLS of HAART increased with stronger African ancestry. Understanding the genomic mechanisms by which African ancestry influences this association is critical, and requires further studies. PMID:24714069

  12. Contribution of Matrix Metalloproteinase-7 Genotypes to the Risk of Non-solid Tumor, Childhood Leukemia.

    PubMed

    Pei, Jen-Sheng; Chou, An-Kuo; Hsu, Pei-Chen; Tsai, Chia-Wen; Chang, Wen-Shin; Wu, Meng-Feng; Wu, Ming-Hsien; Hsia, Te-Chun; Cheng, Shun-Ping; Bau, DA-Tian

    2017-12-01

    The matrix metalloproteinases (MMPs) are important in inflammation and carcinogenesis, and the genotypic role of MMP7 has never been examined in leukemia to date. Therefore, in this study we aimed to evaluate the contribution of the genotypic variants in the promoter region of MMP7 (A-181G and C-153T) to childhood acute lymphoblastic leukemia (ALL) risk in Taiwan. In this case-control study, 266 patients with childhood ALL and 266 non-cancer controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism methodology. The distribution of AA, AG and GG for MMP7 promoter A-181G genotype was 83.5, 12.0 and 4.5% in the childhood ALL group and 89.8%, 9.4 and 0.8% in the non-cancer control group, respectively (p for trend=0.0134), significantly differentially distributed between childhood ALL and control groups. The comparisons in allelic frequency distribution also support the findings that G appears to be the risky allele in childhood ALL. In genotype and gender interaction analysis, it was found that boys carrying the MMP7 A-181G GG and AG+GG genotypes had 9.05- and 2.45-fold odds ratios (ORs) (p=0.0135 and 0.0142, respectively) for childhood ALL compared to those carrying wild-type AA genotype. But these differences were not found in girls. Analysis of genotype interaction with age of onset age showed those aged less than 3.5 years at onset carrying the GG or AG+GG genotypes also had elevated ORs of 8.79- and 2.04-fold (p=0.0150 and 0.0413, respectively) for childhood ALL, but there was no such difference for those having an age at onset of 3.5 years or more. Our results indicate that the MMP7 A-181G genotype interacts with age and gender and may serve as an early and predictive biomarker for childhood ALL. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  13. Anal Cytology and Human Papillomavirus Genotyping in Women With a History of Lower Genital Tract Neoplasia Compared With Low-Risk Women.

    PubMed

    Robison, Katina; Cronin, Beth; Bregar, Amy; Luis, Christine; DiSilvestro, Paul; Schechter, Steven; Pisharodi, Latha; Raker, Christina; Clark, Melissa

    2015-12-01

    To compare the prevalence of abnormal anal cytology and high-risk human papillomavirus (HPV) among women with a history of HPV-related genital neoplasia with women without a history of HPV-related genital neoplasia. A cross-sectional cohort study was performed from December 2012 to February 2014. Women were recruited from outpatient clinics at an academic medical center. Women with a history of high-grade cervical, vulvar, or vaginal cytology, dysplasia, or cancer were considered the high-risk group. Women with no history of high-grade anogenital dysplasia or cancer were considered the low-risk group. Human immunodeficiency virus-positive women were excluded. Anal cytology and HPV genotyping were performed. Women with abnormal anal cytology were referred for high-resolution anoscopy. There were 190 women in the high-risk group and 83 in the low-risk group. The high-risk group was slightly older: 57 years compared with 47 years (P=.045); 21.7% of low-risk women had abnormal anal cytology compared with 41.2% of high-risk women (P=.006). High-risk HPV was detected in the anal canal of 1.2% of the low-risk group compared with 20.8% of the high-risk group (P<.001). Among women who underwent anoscopy, no anal dysplasia was detected in the low-risk group, whereas 13.4% in the high-risk group had anal dysplasia with 4.2% having anal intraepithelial neoplasia 2 or greater (P<.001). Human immunodeficiency virus-negative women with a history of lower genital tract neoplasia are more likely to have positive anal cytology, anal high-risk HPV, and anal intraepithelial neoplasia. Anal cancer screening should be considered for these high-risk women. II.

  14. Compressed Genotyping

    PubMed Central

    Erlich, Yaniv; Gordon, Assaf; Brand, Michael; Hannon, Gregory J.; Mitra, Partha P.

    2011-01-01

    Over the past three decades we have steadily increased our knowledge on the genetic basis of many severe disorders. Nevertheless, there are still great challenges in applying this knowledge routinely in the clinic, mainly due to the relatively tedious and expensive process of genotyping. Since the genetic variations that underlie the disorders are relatively rare in the population, they can be thought of as a sparse signal. Using methods and ideas from compressed sensing and group testing, we have developed a cost-effective genotyping protocol to detect carriers for severe genetic disorders. In particular, we have adapted our scheme to a recently developed class of high throughput DNA sequencing technologies. The mathematical framework presented here has some important distinctions from the ’traditional’ compressed sensing and group testing frameworks in order to address biological and technical constraints of our setting. PMID:21451737

  15. AAS 228: Day 1 morning

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-06-01

    Jeffrey Coughlin and colleagues to improve our ability to automatically detect and confirm exoplanet candidates with the traditional transit technique. They have developed a robotic technique called DAVE (Discovery And Vetting of K2 Exoplanets), which does an impressive job of eliminating false positive eclipse signals. To complement K2 observations of exoplanet transits, astrobites alumna Courtney Dressing presented a method which incorporates observations from the infrared Spitzer Space Telescope to better refine planet properties such as radius. @AstroDressing: Spitzer lets us refine Kepler planet radii, orbits, and even masses in prep for the Webb. #aas228 pic.twitter.com/qAUHeUSMYa Meredith Rawls (@merrdiff) June 13, 2016One of the challenges of K2 compared to Kepler is noise introduced by the spacecrafts less precise ability to point. Derek Buzasi implored us to not consider any one pipeline that removes this jitter as necessarily best, but rather to try several and recognize that different science goals will need different approaches to data processing.There isnt one best K2 pipeline! Depends strongly on your science goals. Buzasi begs us not to rank them. #aas228 pic.twitter.com/ykl89WqKNk Meredith Rawls (@merrdiff) June 13, 2016Jeffrey Van Cleve showed examples of what can be accomplished when K2 data is appropriately processed: just like Kepler, K2 can use asteroseismology to see the ringing oscillations of acoustic waves inside evolved stars. More gorgeous asteroseismology coming out of K2! Thanks to K2P2 pipelines handling of calibrated pixels. #aas228 pic.twitter.com/dGY6DcZHlV Meredith Rawls (@merrdiff) June 13, 2016Finally, several speakers including Buzasi presented their work on stellar astrophysics with K2. In addition to stellar activity and asteroseismology, presenters discussed spots and flares on cool brown dwarfs (John Gizis) and using eclipses together with stellar models to measure distances to star clusters (Keivan Stassun). Not a bad roundup for

  16. Influence of Genotype on Structural Atrial Abnormalities and Atrial Fibrillation or Flutter in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy.

    PubMed

    Bourfiss, Mimount; Te Riele, Anneline S J M; Mast, Thomas P; Cramer, Maarten J; VAN DER Heijden, Jeroen F; VAN Veen, Toon A B; Loh, Peter; Dooijes, Dennis; Hauer, Richard N W; Velthuis, Birgitta K

    2016-12-01

    Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is associated with desmosomal mutations. Although desmosomal disruption affects both ventricles and atria, little is known about atrial involvement in ARVD/C. To describe the extent and clinical significance of structural atrial involvement and atrial arrhythmias (AA) in ARVD/C stratified by genotype. We included 71 patients who met ARVD/C Task Force Criteria and underwent cardiac magnetic resonance (CMR) imaging and molecular genetic analysis. Indexed atrial end-diastolic volume and area-length-ejection-fraction (ALEF) were evaluated on CMR and compared to controls with idiopathic right ventricular outflow tract tachycardia (n = 40). The primary outcome was occurrence of AA (atrial fibrillation or atrial flutter) during follow-up, recorded by 12-lead ECG, Holter monitoring or implantable cardioverter defibrillator (ICD) interrogation. Patients harbored a desmosomal plakophilin-2 (PKP2) (n = 37) or nondesmosomal phospholamban (PLN) (n = 14) mutation. In 20 subjects, no pathogenic mutation was identified. Compared to controls, right atrial (RA) volumes were reduced in PKP2 (P = 0.002) and comparable in PLN (P = 0.441) mutation carriers. In patients with no mutation identified, RA (P = 0.011) and left atrial (P = 0.034) volumes were increased. Bi-atrial ALEF showed no significant difference between the groups. AA were experienced by 27% of patients and occurred equally among PKP2 (30%) and no mutation identified patients (30%), but less among PLN mutation carriers (14%). Genotype influences atrial volume and occurrence of AA in ARVD/C. While the incidence of AA is similar in PKP2 mutation carriers and patients with no mutation identified, PKP2 mutation carriers have significantly smaller atria. This suggests a different arrhythmogenic mechanism. © 2016 Wiley Periodicals, Inc.

  17. High-density genotyping of the A.E. Watkins Collection of hexaploid landraces identifies a large molecular diversity compared to elite bread wheat.

    PubMed

    Winfield, Mark O; Allen, Alexandra M; Wilkinson, Paul A; Burridge, Amanda J; Barker, Gary L A; Coghill, Jane; Waterfall, Christy; Wingen, Luzie U; Griffiths, Simon; Edwards, Keith J

    2018-01-01

    The importance of wheat as a food crop makes it a major target for agricultural improvements. As one of the most widely grown cereal grains, together with maize and rice, wheat is the leading provider of calories in the global diet, constituting 29% of global cereal production in 2015. In the last few decades, however, yields have plateaued, suggesting that the green revolution, at least for wheat, might have run its course and that new sources of genetic variation are urgently required. The overall aim of our work was to identify novel variation that may then be used to enable the breeding process. As landraces are a potential source of such diversity, here we have characterized the A.E. Watkins Collection alongside a collection of elite accessions using two complementary high-density and high-throughput genotyping platforms. While our results show the importance of using the appropriate SNP collection to compare diverse accessions, they also show that the Watkins Collection contains a substantial amount of novel genetic diversity which has either not been captured in current breeding programmes or which has been lost through previous selection pressures. As a consequence of our analysis, we have identified a number of accessions which carry an array of novel alleles along with a number of interesting chromosome rearrangements which confirm the variable nature of the wheat genome. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  18. Comparative pathogenomic characterization of a non-invasive serotype M71 strain Streptococcus pyogenes NS53 reveals incongruent phenotypic implications from distinct genotypic markers.

    PubMed

    Bao, Yun-Juan; Li, Yang; Liang, Zhong; Agrahari, Garima; Lee, Shaun W; Ploplis, Victoria A; Castellino, Francis J

    2017-07-31

    The strains serotyped as M71 from group A Streptococcus are common causes of pharyngeal and skin diseases worldwide. Here we characterize the genome of a unique non-invasive M71 human isolate, NS53. The genome does not contain structural rearrangements or large-scale gene gains/losses, but encodes a full set of non-truncated known virulence factors, thus providing an ideal reference for comparative studies. However, the NS53 genome showed incongruent phenotypic implications from distinct genotypic markers. NS53 is characterized as an emm pattern D and FCT (fibronectin-collagen-T antigen) type-3 strain, typical of skin tropic strains, but is phylogenetically close to emm pattern E strains with preference for both skin and pharyngeal infections. We propose that this incongruence could result from recombination within the emm gene locus, or, alternatively, selection has been against those genetic alterations. Combined with the inability to select for CovS switching, a process is indicated whereby NS53 has been pre-adapted to specific host niches selecting against variations in CovS and many other genes. This may allow the strain to attain successful colonization and long-term survival. A balance between genetic variations and fitness may exist for this bacterium to form a stabilized genome optimized for survival in specific host environments. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. AAS 228: Day 4

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-06-01

    Editors Note: Lastweek we were at the 228th AAS Meeting in San Diego, CA. Here is a final post aboutselectedevents on the last day of the meeting, written by authors fromastrobites.com, a grad-student collaborative project with which we recently announced a new partnership! Starting in July,keep an eye out for astrobites postsat AAS Nova in between Highlights(i.e., on Tuesdays and Thursdays).Were excited to be working together to bring you more recent astronomy research from AAS journals!Extrasolar Planets: Detection (by Leonardo dos Santos)Thursdays first session on exoplanets was about detecting these distant worlds, and the opening talk was given by Robert Siverd (Las Cumbres Observatory). He describes the NRES, a network of spectrographs that will look for exoplanets using the radial velocity method. One of the coolest aspects of this instrument is that it will feature an on the fly scheduling system that will perform observations as efficiently as possible. The spectrograph is still being tested, but a unit will be deployed at CTIO later this year.@lcogt contracted by @NASA_TESS for follow up of their candidates. #aas228 Jessie Christiansen (@aussiastronomer) June 16, 2016Measuring the depths of transits and eclipses in Spitzer has been problematic in the past, since the Spitzer instrument IRAC (InfraRed Array Camera) has a non-uniform response in its detectors pixels. But, as reported by James Ingalls (Spitzer Science Center, Caltech), observers are circumventing this issue by using what they call the staring mode (avoiding large pointing jumps) and an algorithm to pick sweet spot pixels. Moreover, the results from the IRAC Data Challenge are helping to better understand its behavior. Giuseppe Morello (University College London), on the other hand, explained how his research group gets rid of instrumental effects from IRAC using machine learning. This method removes systematics from exoplanet transit data no matter if the noise source is from an instrument or

  20. Characterization of the radical-scavenging reaction of 2-O-substituted ascorbic acid derivatives, AA-2G, AA-2P, and AA-2S: a kinetic and stoichiometric study.

    PubMed

    Takebayashi, Jun; Tai, Akihiro; Gohda, Eiichi; Yamamoto, Itaru

    2006-04-01

    The aim of this study was to characterize the antioxidant activity of three ascorbic acid (AA) derivatives O-substituted at the C-2 position of AA: ascorbic acid 2-glucoside (AA-2G), ascorbic acid 2-phosphate (AA-2P), and ascorbic acid 2-sulfate (AA-2S). The radical-scavenging activities of these AA derivatives and some common low molecular-weight antioxidants such as uric acid or glutathione against 1,1-diphenyl-picrylhydrazyl (DPPH) radical, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS+), or galvinoxyl radical were kinetically and stoichiometrically evaluated under pH-controlled conditions. Those AA derivatives slowly and continuously reacted with DPPH radical and ABTS+, but not with galvinoxyl radical. They effectively reacted with DPPH radical under acidic conditions and with ABTS+ under neutral conditions. In contrast, AA immediately quenched all species of radicals tested at all pH values investigated. The reactivity of Trolox, a water-soluble vitamin E analogue, was comparable to that of AA in terms of kinetics and stoichiometrics. Uric acid and glutathione exhibited long-lasting radical-scavenging activity against these radicals under certain pH conditions. The radical-scavenging profiles of AA derivatives were closer to those of uric acid and glutathione rather than to that of AA. The number of radicals scavenged by one molecule of AA derivatives, uric acid, or glutathione was equal to or greater than that by AA or Trolox under the appropriate conditions. These data suggest the potential usage of AA derivatives as radical scavengers.

  1. CK-MM and ACE genotypes and physiological prediction of the creatine kinase response to exercise.

    PubMed

    Heled, Yuval; Bloom, Michael S; Wu, T John; Stephens, Quiona; Deuster, Patricia A

    2007-08-01

    Exertional rhabdomyolysis (ERB) is a syndrome of severe skeletal muscle breakdown. Blood levels of creatine kinase (CK) are widely used as a marker to reflect muscle breakdown. Some individuals exhibit extreme increases in blood CK after exercise and have been characterized as high responders (HR), but no clinical definition of HR exists and reasons for the HR phenomenon are not understood. This study investigated possible associations between the magnitude of the CK response to exercise and polymorphisms of two genes: muscle-specific creatine kinase (CK-MM) NcoI and angiotensin-converting enzyme (ACE) I/D. An exercise test for defining HR was also investigated. Participants (n = 88) underwent an exercise test that included stepping up and down two stairs for 5 min followed by 15 squats while wearing a backpack weighted at 30% of their body weight. CK levels were measured before, immediately after, and 48 and 72 h after the test. Nine participants (10.2%) were defined as HR. Participants with the CK-MM NcoI AA genotype had a sixfold higher risk of being HR compared with GG and AG genotypes (P = 0.031). No significant differences were found for the ACE I/D polymorphism. Percent body fat was an independent predictor of being a HR. We conclude that the CK-MM AA genotype and percent body fat may be part of the constellation of mechanisms that explain susceptibility to ERB. A physiological test that may assist in predicting ERB is also presented.

  2. AAS 227: Day 4

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-01-01

    Editors Note:This week were at the 227th AAS Meeting in Kissimmee, FL. Along with several fellow authors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting at the end of each day. Follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.Welcome to Day 4 of the winter American Astronomical Society (AAS) meeting in Kissimmee! Several of us are attending the conference this year, and we will report highlights from each day here on astrobites. If youd like to see more timely updates during the day, we encourage you to follow @astrobites on twitter or search the #aas227 hashtag.Helen B. Warner Prize: Origins of Structure in Planetary Systems (by Erika Nesvold)Another excellent prize lecture started off todays sessions. The Helen B. Warner Prize is awarded for achievement in observational or theoretical astrophysics by a young researcher (no more than eight years after their Ph.D.). This years Warner Prize was presented to Ruth Murray-Clay of UC Santa Barbara. For her award lecture, Murray-Clay told us all about planetary system architecture: the number, masses, and orbits of planets in a given system.Ruth Murray-Clay [photo from http://web.physics.ucsb.edu/ ~murray/biocv.html]The underlying question motivating this type of research is: How rare is the Solar System? In other words, how likely is it that a given planetary system will have rocky planets close to their star, gas giants farther out, and ice giants at the outer reaches of the system? Answering this question will help us solve the physics problem of how and where planets form, and will also help us on our search for other planets like Earth.The data on exoplanet population from transit and radial velocity observations and from direct imaging tell us that our Solar System is not common (many systems we observe have much more eccentric gas giants), but that doesnt

  3. Effect of nitrogen fertilisation on the amino acid digestibility of different triticale genotypes in caecectomised laying hens.

    PubMed

    Siegert, Wolfgang; Boguhn, Jeannette; Maurer, Hans Peter; Weiss, Jochen; Zuber, Tobias; Möhring, Jens; Rodehutscord, Markus

    2017-01-01

    The influence of nitrogen fertilisation and genotype on the amino acid (AA) digestibility of triticale grain was investigated in caecectomised laying hens. Three genotypes, Grenado, EAW6002 and Lasko, were cultivated with and without nitrogen fertilisation at the end of the heading stage. The six triticale variants as well as a basal diet were each used to feed seven laying hens in a 7 × 7 Latin square design. Nitrogen fertilisation influenced the digestibility of Cys, Glu, Phe and Ser in some triticale genotypes and reduced Ala, Ile, Lys, Met and Val digestibility in all genotypes (P < 0.05). Nitrogen fertilisation increased the concentration of all AAs in the grain. Consequently, the concentration of digestible AAs in the grains was increased for most AAs upon nitrogen fertilisation. Overall, Lys had the lowest digestibility, whereas that of Glu and Pro was the highest. For the triticale genotypes, the level of AA digestibility was highest for EAW6002 followed by Lasko and Grenado, with significant differences (P < 0.05) between genotypes for some but not all AAs. The results indicated that the accuracy of the digestible AA supply for hen feeding might benefit from considering fertilisation and genotype-specific digestibility data in feed formulation. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  4. Comparative genotypic and phenotypic analysis of human peripheral blood monocytes and surrogate monocyte-like cell lines commonly used in metabolic disease research.

    PubMed

    Riddy, Darren M; Goy, Emily; Delerive, Philippe; Summers, Roger J; Sexton, Patrick M; Langmead, Christopher J

    2018-01-01

    Monocyte-like cell lines (MCLCs), including THP-1, HL-60 and U-937 cells, are used routinely as surrogates for isolated human peripheral blood mononuclear cells (PBMCs). To systematically evaluate these immortalised cells and PBMCs as model systems to study inflammation relevant to the pathogenesis of type II diabetes and immuno-metabolism, we compared mRNA expression of inflammation-relevant genes, cell surface expression of cluster of differentiation (CD) markers, and chemotactic responses to inflammatory stimuli. Messenger RNA expression analysis suggested most genes were present at similar levels across all undifferentiated cells, though notably, IDO1, which encodes for indoleamine 2,3-dioxygenase and catabolises tryptophan to kynureninase (shown to be elevated in serum from diabetic patients), was not expressed in any PMA-treated MCLC, but present in GM-CSF-treated PBMCs. There was little overall difference in the pattern of expression of CD markers across all cells, though absolute expression levels varied considerably and the correlation between MCLCs and PBMCs was improved upon MCLC differentiation. Functionally, THP-1 and PBMCs migrated in response to chemoattractants in a transwell assay, with varying sensitivity to MCP-1, MIP-1α and LTB-4. However, despite similar gene and CD expression profiles, U-937 cells were functionally impaired as no migration was observed to any chemoattractant. Our analysis reveals that the MCLCs examined only partly replicate the genotypic and phenotypic properties of human PBMCs. To overcome such issues a universal differentiation protocol should be implemented for these cell lines, similar to those already used with isolated monocytes. Although not perfect, in our hands the THP-1 cells represent the closest, simplified surrogate model of PBMCs for study of inflammatory cell migration.

  5. Comparative analysis of DNA methylation polymorphism in drought sensitive (HPKC2) and tolerant (HPK4) genotypes of horse Gram (Macrotyloma uniflorum).

    PubMed

    Bhardwaj, Jyoti; Mahajan, Monika; Yadav, Sudesh Kumar

    2013-08-01

    DNA methylation is known as an epigenetic modification that affects gene expression in plants. Variation in CpG methylation behavior was studied in two natural horse gram (Macrotyloma uniflorum [Lam.] Verdc.) genotypes, HPKC2 (drought-sensitive) and HPK4 (drought-tolerant). The methylation pattern in both genotypes was studied through methylation-sensitive amplified polymorphism. The results revealed that methylation was higher in HPKC2 (10.1%) than in HPK4 (8.6%). Sequencing demonstrated sequence homology with the DRE binding factor (cbf1), the POZ/BTB protein, and the Ty1-copia retrotransposon among some of the polymorphic fragments showing alteration in methylation behavior. Differences in DNA methylation patterns could explain the differential drought tolerance and the epigenetic signature of these two horse gram genotypes.

  6. Barley yellow dwarf virus Infection Leads to Higher Chemical Defense Signals and Lower Electrophysiological Reactions in Susceptible Compared to Tolerant Barley Genotypes.

    PubMed

    Paulmann, Maria K; Kunert, Grit; Zimmermann, Matthias R; Theis, Nina; Ludwig, Anatoli; Meichsner, Doreen; Oelmüller, Ralf; Gershenzon, Jonathan; Habekuss, Antje; Ordon, Frank; Furch, Alexandra C U; Will, Torsten

    2018-01-01

    Barley yellow dwarf virus (BYDV) is a phloem limited virus that is persistently transmitted by aphids. Due to huge yield losses in agriculture, the virus is of high economic relevance. Since the control of the virus itself is not possible, tolerant barley genotypes are considered as the most effective approach to avoid yield losses. Although several genes and quantitative trait loci are known and used in barley breeding for virus tolerance, little is known about molecular and physiological backgrounds of this trait. Therefore, we compared the anatomy and early defense responses of a virus susceptible to those of a virus-tolerant cultivar. One of the very early defense responses is the transmission of electrophysiological reactions. Electrophysiological reactions to BYDV infection might differ between susceptible and tolerant cultivars, since BYDV causes disintegration of sieve elements in susceptible cultivars. The structure of vascular bundles, xylem vessels and sieve elements was examined using microscopy. All three were significantly decreased in size in infected susceptible plants where the virus causes disintegration of sieve elements. This could be associated with an uncontrolled ion exchange between the sieve-element lumen and apoplast. Further, a reduced electrophysiological isolation would negatively affect the propagation of electrophysiological reactions. To test the influence of BYDV infection on electrophysiological reactions, electropotential waves (EPWs) induced by leaf-tip burning were recorded using aphids as bioelectrodes. EPWs in infected susceptible plants disappeared already after 10 cm in contrast to those in healthy susceptible or infected tolerant or healthy tolerant plants. Another early plant defense reaction is an increase in reactive oxygen species (ROS). Using a fluorescent dye, we found a significant increase in ROS content in infected susceptible plants but not in infected tolerant plants. Similar results were found for the

  7. Barley yellow dwarf virus Infection Leads to Higher Chemical Defense Signals and Lower Electrophysiological Reactions in Susceptible Compared to Tolerant Barley Genotypes

    PubMed Central

    Paulmann, Maria K.; Kunert, Grit; Zimmermann, Matthias R.; Theis, Nina; Ludwig, Anatoli; Meichsner, Doreen; Oelmüller, Ralf; Gershenzon, Jonathan; Habekuss, Antje; Ordon, Frank; Furch, Alexandra C. U.; Will, Torsten

    2018-01-01

    Barley yellow dwarf virus (BYDV) is a phloem limited virus that is persistently transmitted by aphids. Due to huge yield losses in agriculture, the virus is of high economic relevance. Since the control of the virus itself is not possible, tolerant barley genotypes are considered as the most effective approach to avoid yield losses. Although several genes and quantitative trait loci are known and used in barley breeding for virus tolerance, little is known about molecular and physiological backgrounds of this trait. Therefore, we compared the anatomy and early defense responses of a virus susceptible to those of a virus-tolerant cultivar. One of the very early defense responses is the transmission of electrophysiological reactions. Electrophysiological reactions to BYDV infection might differ between susceptible and tolerant cultivars, since BYDV causes disintegration of sieve elements in susceptible cultivars. The structure of vascular bundles, xylem vessels and sieve elements was examined using microscopy. All three were significantly decreased in size in infected susceptible plants where the virus causes disintegration of sieve elements. This could be associated with an uncontrolled ion exchange between the sieve-element lumen and apoplast. Further, a reduced electrophysiological isolation would negatively affect the propagation of electrophysiological reactions. To test the influence of BYDV infection on electrophysiological reactions, electropotential waves (EPWs) induced by leaf-tip burning were recorded using aphids as bioelectrodes. EPWs in infected susceptible plants disappeared already after 10 cm in contrast to those in healthy susceptible or infected tolerant or healthy tolerant plants. Another early plant defense reaction is an increase in reactive oxygen species (ROS). Using a fluorescent dye, we found a significant increase in ROS content in infected susceptible plants but not in infected tolerant plants. Similar results were found for the

  8. A Randomized Study of Peginterferon Lambda-1a Compared to Peginterferon Alfa-2a in Combination with Ribavirin and Telaprevir in Patients with Genotype-1 Chronic Hepatitis C.

    PubMed

    Flisiak, Robert; Shiffman, Mitchell; Arenas, Juan; Cheinquer, Hugo; Nikitin, Igor; Dong, Yuping; Rana, Khurram; Srinivasan, Subasree

    2016-01-01

    A randomized, double-blind, multinational, phase 3 study was conducted comparing the efficacy and safety of peginterferon lambda-1a (Lambda)/ribavirin (RBV)/telaprevir (TVR) vs. peginterferon alfa-2a (Alfa)/RBV/TVR in patients with chronic hepatitis C virus (HCV) genotype-1 (GT-1) infection. Patients (treatment-naïve or relapsers on prior Alfa/RBV treatment) were randomly assigned in a 2:1 ratio to receive Lambda/RBV/TVR or Alfa/RBV/TVR. Total duration of treatment was either 24 or 48 weeks (response-guided treatment), with TVR administered for the first 12 weeks. The primary endpoint was the proportion of patients who achieved a sustained virologic response at post treatment week 12 (SVR12), which was tested for noninferiority of Lambda/RBV/TVR. A total of 838 patients were enrolled, and 617 were treated; 411 and 206 patients received Lambda/RBV/TVR and Alfa/RBV/TVR, respectively. The majority of patients were treatment-naïve, with HCV GT-1b and a high baseline viral load (≥800,000 IU/mL). Less than 10% of patients had cirrhosis (Lambda, 7.5%; Alfa, 6.8%). Lambda/RBV/TVR did not meet the criterion for noninferiority (lower bound of the treatment difference interval was -12.3%); the SVR12 in all patients (modified intent-to-treat) was 76.2% in the Lambda arm and 82.0% in the Alfa arm. Overall, the frequency of adverse events in each arm was comparable (Lambda, 91.7%; Alfa, 97.1%). As expected based on the safety profile of the 2 interferons, there were more hepatobiliary events observed in the Lambda arm and more hematologic events in the Alfa arm. In this comparison of Lambda/RBV/TVR and Alfa/RBV/TVR in patients who were treatment-naïve or had relapsed on prior Alfa/RBV treatment, Lambda failed to demonstrate noninferiority based on SVR12 results. Treatment with Lambda/RBV/TVR was associated with a higher incidence of relapse. More patients discontinued Lambda/RBV/TVR treatment during the first 4 weeks of study treatment, mainly due to hepatobiliary

  9. Fat mass- and obesity-associated genotype, dietary intakes and anthropometric measures in European adults: the Food4Me study.

    PubMed

    Livingstone, Katherine M; Celis-Morales, Carlos; Navas-Carretero, Santiago; San-Cristobal, Rodrigo; Forster, Hannah; O'Donovan, Clare B; Woolhead, Clara; Marsaux, Cyril F M; Macready, Anna L; Fallaize, Rosalind; Kolossa, Silvia; Tsirigoti, Lydia; Lambrinou, Christina P; Moschonis, George; Godlewska, Magdalena; Surwiłło, Agnieszka; Drevon, Christian A; Manios, Yannis; Traczyk, Iwona; Gibney, Eileen R; Brennan, Lorraine; Walsh, Marianne C; Lovegrove, Julie A; Martinez, J Alfredo; Saris, Wim H M; Daniel, Hannelore; Gibney, Mike; Mathers, John C

    2016-02-14

    The interplay between the fat mass- and obesity-associated (FTO) gene variants and diet has been implicated in the development of obesity. The aim of the present analysis was to investigate associations between FTO genotype, dietary intakes and anthropometrics among European adults. Participants in the Food4Me randomised controlled trial were genotyped for FTO genotype (rs9939609) and their dietary intakes, and diet quality scores (Healthy Eating Index and PREDIMED-based Mediterranean diet score) were estimated from FFQ. Relationships between FTO genotype, diet and anthropometrics (weight, waist circumference (WC) and BMI) were evaluated at baseline. European adults with the FTO risk genotype had greater WC (AA v. TT: +1·4 cm; P=0·003) and BMI (+0·9 kg/m2; P=0·001) than individuals with no risk alleles. Subjects with the lowest fried food consumption and two copies of the FTO risk variant had on average 1·4 kg/m2 greater BMI (Ptrend=0·028) and 3·1 cm greater WC (Ptrend=0·045) compared with individuals with no copies of the risk allele and with the lowest fried food consumption. However, there was no evidence of interactions between FTO genotype and dietary intakes on BMI and WC, and thus further research is required to confirm or refute these findings.

  10. Low Lignin (Brown Mid-rib) Sorghum Genotypes Restrict Growth of Fusarium Spp. as Compared with Near-Isogenic Wild-Type Sorghum

    USDA-ARS?s Scientific Manuscript database

    To increase usability of sorghum for bioenergy and forages, two different brown midrib (bmr) genes, bmr-6 and bmr-12, were backcrossed into five elite backgrounds, resulting in reduced lignin near-isogenic genotypes. Field-grown grain from bmr-6 and bmr-12 plants had significantly reduced colonizati...

  11. HBV Genotypic Variability in Cuba

    PubMed Central

    Loureiro, Carmen L.; Aguilar, Julio C.; Aguiar, Jorge; Muzio, Verena; Pentón, Eduardo; Garcia, Daymir; Guillen, Gerardo; Pujol, Flor H.

    2015-01-01

    The genetic diversity of HBV in human population is often a reflection of its genetic admixture. The aim of this study was to explore the genotypic diversity of HBV in Cuba. The S genomic region of Cuban HBV isolates was sequenced and for selected isolates the complete genome or precore-core sequence was analyzed. The most frequent genotype was A (167/250, 67%), mainly A2 (149, 60%) but also A1 and one A4. A total of 77 isolates were classified as genotype D (31%), with co-circulation of several subgenotypes (56 D4, 2 D1, 5 D2, 7 D3/6 and 7 D7). Three isolates belonged to genotype E, two to H and one to B3. Complete genome sequence analysis of selected isolates confirmed the phylogenetic analysis performed with the S region. Mutations or polymorphisms in precore region were more common among genotype D compared to genotype A isolates. The HBV genotypic distribution in this Caribbean island correlates with the Y lineage genetic background of the population, where a European and African origin prevails. HBV genotypes E, B3 and H isolates might represent more recent introductions. PMID:25742179

  12. Racial Differences in CYP3A4 Genotype and Survival Among Men Treated on Radiation Therapy Oncology Group (RTOG) 9202: A Phase III Randomized Trial

    SciTech Connect

    Roach, Mack; Silvio, Michelle de; Rebbick, Timothy

    2007-09-01

    Purpose: Inherited genotypes may explain the inferior outcomes of African American (AA) men with prostate cancer. To understand how variation in CYP3A4 correlated with outcomes, a retrospective examination of the CYP3A4*1B genotype was performed on men treated with Radiation Therapy Oncology Group (RTOG) 92-02. Methods and Materials: From 1,514 cases, we evaluated 56 (28.4%) of 197 AA and 54 (4.3%) of 1,274 European American (EA) patients. All patients received goserelin and flutamide for 2 months before and during RT (STAD-RT) {+-} 24 months of goserelin (long-term androgen deprivation plus radiation [LTAD-RT]). Events studied included overall survival and biochemical progression usingmore » American Society for Therapeutic Radiology and Oncology consensus guidelines. Results: There were no differences in outcome in patients in with or without CYP3A4 data. There was an association between race and CYP3A4 polymorphisms with 75% of EAs having the Wild Type compared to only 25% of AA men (p <0.0001). There was no association between CYP3A4 classification or race and survival or progression. Conclusions: The samples analyzed support previously reported observations about the distribution of CYP3A4*1B genotype by race, but race was not associated with poorer outcome. However, patient numbers were limited, and selection bias cannot be completely ruled out.« less

  13. AAS 228: Day 3 morning

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-06-01

    Editors Note:This week were at the 228th AAS Meeting in San Diego, CA. Along with a team ofauthors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting twiceeach day. Follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.Plenary Session 2015 Newton Lacy Pierce Prize Lecture: The Elephant in the Room: Effects of Distant, Massive Companions on Planetary System Architectures (by Leonardo dos Santos)The first session on Wednesday at 228th AAS Meeting was the Newton Lacy Pierce Prize Lecture by Heather Knutson (California Institute of Technology). This talk featured a broad range of research efforts on exoplanets, with the main focus on how we study the composition of their atmospheres, and how multi-body interactions carve the structure of the planetary systems we observe.One of her first points is the well-known idea that the Solar System is an oddball, compared to the exoplanet systems we have found so far: most of these systems contain hot Jupiters and mini-Neptunes at very close-in orbits around their host stars. Moreover, even when studying their transmission spectra, it is difficult to know the exact composition of their atmospheres.Knutson: it is difficult to constrain atmospheric composition of exoplanets (H-poor or H-rich+clouds?) #aas228pic.twitter.com/LdyN4o9RC7 astrobites (@astrobites) June 15, 2016The main proposal on how these systems formed is the migration scenario. In order to validate this idea, Dr. Knutson and her group The Friends of Hot Jupiters study systems with close-in gas giants and their frequency of binary companions, which are supposed to be the main culprits causing gas-giant migration. They found that approximately half of the observed systems have long-distance companions, providing strong validation of the migration scenario. Moreover, Dr. Knutson speculates that wide binaries have more

  14. Prevalence of IL-28B and ITPA genotypes in Chinese Han population infected persistently with hepatitis C virus genotype 6 or HCV-1.

    PubMed

    Zhang, Xiao-Hong; Cai, Qing-Xian; Hong, Chun-Xia; Lin, Chao-Shuang; Zhao, Zhi-Xin

    2013-07-01

    The geographic distribution, demographics, epidemiology, host factors, and clinical characteristics of persistent HCV-6 infection in China need further characterization. This multicenter study enrolled 63 patients with persistent HCV-6 infection and 63 patients with persistent HCV-1 infection as controls. Blood biochemistry, quantitation of HCV RNA levels, and identification of host IL-28B genotypes (rs12979860, rs8099917, and rs12980275) and ITPA genotype (rs1127354) were performed to estimate potential variability in host factors that may affect response to treatment. The mean HCV-6 RNA level (3.8E6 IU/ml) was significantly higher than that in patients infected with HCV-1 (1.7E6 IU/ml; P < 0.001). Patients persistently infected with HCV-6 had a high prevalence of IL-28B rs12979860 CC genotype (92.1%), rs8099917 TT genotype (93.7%), and rs12980275 AA genotype (90.5%). Their prevalence in patients infected with HCV-1 was only modestly lower (82.5%, 84.1%, and 82.5%, respectively; P > 0.05). The inosine triphosphate pyrophosphatase (ITPA) SNP rs1127354 CC genotype was present in 66.7% of patients infected with HCV-6, comparable to that of patients infected with HCV-1 (65.1%; P > 0.05). There were no differences in the liver function, proportion of hepatic cirrhosis patients or patients with increased serum glucose between these two groups. Persistent HCV-6 infection in Chinese Han is found mainly in the southern China. Chinese Han with chronic HCV-1 or HCV-6 infection have IL-28B genotypes, suggesting responsiveness to interferon-based pharmacotherapy. Most patients (67%) possess the ITPA genotype associated with susceptibility to ribavirin-induced hemolysis. The routes of transmission for HCV-6 genotype were more diversified than HCV-1 genotype. The outbreak of HCV-6 infection through blood transfusion progressed faster than HCV-1. Copyright © 2013 Wiley Periodicals, Inc.

  15. Tracing QTLs for Leaf Blast Resistance and Agronomic Performance of Finger Millet (Eleusine coracana (L.) Gaertn.) Genotypes through Association Mapping and in silico Comparative Genomics Analyses.

    PubMed

    Ramakrishnan, M; Antony Ceasar, S; Duraipandiyan, V; Vinod, K K; Kalpana, Krishnan; Al-Dhabi, N A; Ignacimuthu, S

    2016-01-01

    Finger millet is one of the small millets with high nutritive value. This crop is vulnerable to blast disease caused by Pyricularia grisea, which occurs annually during rainy and winter seasons. Leaf blast occurs at early crop stage and is highly damaging. Mapping of resistance genes and other quantitative trait loci (QTLs) for agronomic performance can be of great use for improving finger millet genotypes. Evaluation of one hundred and twenty-eight finger millet genotypes in natural field conditions revealed that leaf blast caused severe setback on agronomic performance for susceptible genotypes, most significant traits being plant height and root length. Plant height was reduced under disease severity while root length was increased. Among the genotypes, IE4795 showed superior response in terms of both disease resistance and better agronomic performance. A total of seven unambiguous QTLs were found to be associated with various agronomic traits including leaf blast resistance by association mapping analysis. The markers, UGEP101 and UGEP95, were strongly associated with blast resistance. UGEP98 was associated with tiller number and UGEP9 was associated with root length and seed yield. Cross species validation of markers revealed that 12 candidate genes were associated with 8 QTLs in the genomes of grass species such as rice, foxtail millet, maize, Brachypodium stacei, B. distachyon, Panicum hallii and switchgrass. Several candidate genes were found proximal to orthologous sequences of the identified QTLs such as 1,4-β-glucanase for leaf blast resistance, cytokinin dehydrogenase (CKX) for tiller production, calmodulin (CaM) binding protein for seed yield and pectin methylesterase inhibitor (PMEI) for root growth and development. Most of these QTLs and their putatively associated candidate genes are reported for first time in finger millet. On validation, these novel QTLs may be utilized in future for marker assisted breeding for the development of fungal

  16. Tracing QTLs for Leaf Blast Resistance and Agronomic Performance of Finger Millet (Eleusine coracana (L.) Gaertn.) Genotypes through Association Mapping and in silico Comparative Genomics Analyses

    PubMed Central

    Ramakrishnan, M.; Antony Ceasar, S.; Duraipandiyan, V.; Vinod, K. K.; Kalpana, Krishnan; Al-Dhabi, N. A.; Ignacimuthu, S.

    2016-01-01

    Finger millet is one of the small millets with high nutritive value. This crop is vulnerable to blast disease caused by Pyricularia grisea, which occurs annually during rainy and winter seasons. Leaf blast occurs at early crop stage and is highly damaging. Mapping of resistance genes and other quantitative trait loci (QTLs) for agronomic performance can be of great use for improving finger millet genotypes. Evaluation of one hundred and twenty-eight finger millet genotypes in natural field conditions revealed that leaf blast caused severe setback on agronomic performance for susceptible genotypes, most significant traits being plant height and root length. Plant height was reduced under disease severity while root length was increased. Among the genotypes, IE4795 showed superior response in terms of both disease resistance and better agronomic performance. A total of seven unambiguous QTLs were found to be associated with various agronomic traits including leaf blast resistance by association mapping analysis. The markers, UGEP101 and UGEP95, were strongly associated with blast resistance. UGEP98 was associated with tiller number and UGEP9 was associated with root length and seed yield. Cross species validation of markers revealed that 12 candidate genes were associated with 8 QTLs in the genomes of grass species such as rice, foxtail millet, maize, Brachypodium stacei, B. distachyon, Panicum hallii and switchgrass. Several candidate genes were found proximal to orthologous sequences of the identified QTLs such as 1,4-β-glucanase for leaf blast resistance, cytokinin dehydrogenase (CKX) for tiller production, calmodulin (CaM) binding protein for seed yield and pectin methylesterase inhibitor (PMEI) for root growth and development. Most of these QTLs and their putatively associated candidate genes are reported for first time in finger millet. On validation, these novel QTLs may be utilized in future for marker assisted breeding for the development of fungal

  17. Comparing human papillomavirus prevalences in women with normal cytology or invasive cervical cancer to rank genotypes according to their oncogenic potential: a meta-analysis of observational studies

    PubMed Central

    2013-01-01

    Background Mucosal human papillomavirus (HPV) infection is a necessary cause of cervical cancer. Vaccine and non-vaccine genotype prevalences may change after vaccine introduction. Therefore, it appears essential to rank HPV genotypes according to their oncogenic potential for invasive cervical cancer, independently of their respective prevalences. Methods We performed meta-analyses of published observational studies and estimated pooled odds ratios with random-effects models for 32 HPV genotypes, using HPV-16 as the reference. Results Twenty-seven studies yielded 9,252 HPV-infected women: 2,902 diagnosed with invasive cervical cancer and 6,350 with normal cytology. Expressed as (odds ratio [95% confidence interval]), HPV-18 (0.63 [0.51, 0.78]) ranked closest to HPV-16, while other genotypes showed continuously decreasing relative oncogenic potentials: HPV-45 (0.35 [0.22, 0.55]), HPV-69 (0.28 [0.09, 0.92]), HPV-58 (0.24 [0.15, 0.38]), HPV-31 (0.22 [0.14, 0.35]), HPV-33 (0.22 [0.12, 0.38]), HPV-34 (0.21 [0.06, 0.80]), HPV-67 (0.21 [0.06, 0.67]), HPV-39 (0.17 [0.09, 0.30]), HPV-59 (0.17 [0.09, 0.31]), HPV-73 (0.16 [0.06, 0.41]), and HPV-52 (0.16 [0.11, 0.23]). Conclusions Our results support the markedly higher oncogenic potentials of HPV-16 and -18, followed by HPV-31, -33, -39, -45, -52, -58 and -59, and highlight the need for further investigation of HPV-34, -67, -69 and -73. Overall, these findings could have important implications for the prevention of cervical cancer. PMID:23941096

  18. A Comparative Study of Proteolytic Mechanisms during Leaf Senescence of Four Genotypes of Winter Oilseed Rape Highlighted Relevant Physiological and Molecular Traits for NRE Improvement

    PubMed Central

    Girondé, Alexandra; Poret, Marine; Etienne, Philippe; Trouverie, Jacques; Bouchereau, Alain; Le Cahérec, Françoise; Leport, Laurent; Niogret, Marie-Françoise; Avice, Jean-Christophe

    2015-01-01

    Winter oilseed rape is characterized by a low N use efficiency related to a weak leaf N remobilization efficiency (NRE) at vegetative stages. By investigating the natural genotypic variability of leaf NRE, our goal was to characterize the relevant physiological traits and the main protease classes associated with an efficient proteolysis and high leaf NRE in response to ample or restricted nitrate supply. The degradation rate of soluble proteins and D1 protein (a thylakoid-bound protein) were correlated to N remobilization, except for the genotype Samouraï which showed a low NRE despite high levels of proteolysis. Under restricted nitrate conditions, high levels of soluble protein degradation were associated with serine, cysteine and aspartic proteases at acidic pH. Low leaf NRE was related to a weak proteolysis of both soluble and thylakoid-bound proteins. The results obtained on the genotype Samouraï suggest that the timing between the onset of proteolysis and abscission could be a determinant. The specific involvement of acidic proteases suggests that autophagy and/or senescence-associated vacuoles are implicated in N remobilization under low N conditions. The data revealed that the rate of D1 degradation could be a relevant indicator of leaf NRE and might be used as a tool for plant breeding. PMID:27135221

  19. Amino acid digestibility of different rye genotypes in caecectomised laying hens.

    PubMed

    Zuber, Tobias; Miedaner, Thomas; Rosenfelder, Pia; Rodehutscord, Markus

    2016-12-01

    This study investigated the variability of amino acid (AA) digestibility of rye grains in laying hens. Relationships between AA digestibility and physical properties (thousand seed weight, test weight, falling number, and extract viscoelasticity), chemical composition (proximate nutrients, non-starch polysaccharides, AA, minerals, and inositol phosphates), gross energy concentration, and in vitro solubility of nitrogen (N) of the grains were also examined. Twenty rye genotypes were grown under standardised agronomic and environmental conditions as part of a collaborative research project known as "GrainUp". Each genotype was added to a basal diet at 500 g/kg at the expense of maize starch to produce 20 rye diets. The experimental design comprised four Latin Squares (6 × 6) distributed over two runs, resulting in 12 experimental periods. Caecectomised laying hens (LSL-Classic) were individually kept in metabolism cages. Excreta were collected quantitatively for 4 d, and AA digestibility of the rye genotypes was determined using a regression approach. The digestibility of AA was generally low but varied significantly among the 20 rye genotypes, especially for Lys (digestibility range 35-59%), Met (57-75%), Thr (34-54%), and Trp (36-71%). Nevertheless, physical and chemical characteristics as well as the in vitro solubility of N correlated in only a few cases with AA digestibility. Multiple linear regression was used to calculate equations to predict AA digestibility based on the analysed characteristics. However, their explanatory power, as judged by the adjusted R(2), was not sufficiently precise for practical application (below 0.6 for most AA). In conclusion, the AA digestibility of rye grain is generally low and varies significantly between crop genotypes. Equations based on its physical and chemical characteristics are not sufficiently precise to be useful for feed formulation.

  20. The Contribution of Matrix Metalloproteinase-7 Promoter Genotypes in Breast Cancer in Taiwan.

    PubMed

    Chou, An-Kuo; Hsiao, Chieh-Lun; Shih, Tzu-Ching; Wang, Hwei-Chung; Tsai, Chia-Wen; Chang, Wen-Shin; Liu, Liang-Chih; Way, Tzong-DER; Chung, Jing-Gung; Bau, DA-Tian

    2017-09-01

    The matrix metalloproteinase (MMP) family of enzymes are in charge of degradation of various components of the extracellular matrix and their functional genetic polymorphisms may be associated with cancer susceptibility. The functional polymorphisms in the promoter region of MMP7 (A-181G and C-153T) have been reported to influence the binding capacity of nuclear proteins and may contribute to genetic susceptibility to cancer. In this study, we focused on investigating the contribution of the genotypes of MMP7 (A-181G and C-153T) to breast cancer in Taiwan. These two polymorphisms were genotyped in 1,232 patients with breast cancer and 1,232 controls by polymerase chain reaction-restriction fragment length polymorphism methodology. The odds ratios (ORs) after adjusting for age, family history of cancer, smoking and alcohol drinking status for those carrying AG and GG genotypes at MMP7 promoter A-181G were 1.22 (95%CI=0.91-1.63, p=0.2235) and 2.84 (95%CI=1.64-7.48, p=0.0007) respectively, compared to those carrying the wild-type AA genotype. Supporting this finding, the adjusted OR for those carrying the G allele at MMP7 promoter A-181G was 1.57 (95%CI=1.29-1.93, p=0.0008), compared to those carrying the wild-type A allele. There was no polymorphic genotype at MMP7 C-153T found among any of the investigated individuals. Our findings suggest that the MMP7 A-181G polymorphisms may play a role in determining personal cancer susceptibility and GG genotype at MMP7 A-181G may serve as a biomarker for early detection and prediction of breast cancer in Taiwanese. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  1. Significant association between ERCC2 and MTHR polymorphisms and breast cancer susceptibility in Moroccan population: genotype and haplotype analysis in a case-control study.

    PubMed

    Hardi, Hanaa; Melki, Rahma; Boughaleb, Zouhour; El Harroudi, Tijani; Aissaoui, Souria; Boukhatem, Noureddine

    2018-03-15

    Genetic determinants of breast cancer (BC) remained largely unknown in the majority of Moroccan patients. The purpose of this study was to explore the association of ERCC2 and MTHFR polymorphisms with genetic susceptibility to breast cancer in Moroccan population. We genotyped ERCC2 polymorphisms (rs1799793 (G934A) and rs13181 (A2251C)) and MTHFR polymorphisms (rs1801133 (C677T) and rs1801131 (A1298C)) using TaqMan SNP Genotyping Assays. Genotypes were compared in 151 BC cases and 156 population-matched controls. Allelic, genotypic and haplotype associations with the risk and clinicopathological features of BC were assessed using logistic regression analyses. ERCC2-rs1799793-AA genotype was associated with high risk of BC compared to wild type genotype (recessive model: OR: 2.90, 95% CI: 1.34-6.26, p = 0.0069) even after Bonferroni correction (p < 0,0125). MTHFR rs1801133-TT genotype was associated with increased risk of BC (recessive model, OR: 2.49, 95% CI: 1.17-5.29, p = 0.017) but the association turned insignificant after Bonferroni correction. For the rest of SNPs, no statistical associations to BC risk were detected. Significant association with clinical features was detected for MTHFR-rs1801133-TC genotype with early age at diagnosis and familial BC. Following Bonferroni correction, only association with familial BC remained significant. MTHFR-rs1801131-CC genotype was associated with sporadic BC. ERCC2-rs1799793-AA genotype correlated with ER+ and PR+ breast cancer. ERCC2-rs13181-CA genotype was significantly associated large tumors (T ≥ 3) in BC patients. None of these associations passed Bonferroni correction. Haplotype analysis showed that ERCC2 A-C haplotype was significantly associated with increased BC risk (OR: 3.71, 95% CI: 1.7-8.12, p = 0.0002 and p = 0.0008 before and after Bonferroni correction, respectively) and positive expression of ER and PR in BC patients. ERCC2 G-C haplotype was correlated with PR negative and

  2. Geographical distribution of HCV genotypes in Mexico.

    PubMed

    Sánchez-Avila, Juan Francisco; González, Elizabeth; Vázquez, Victoria; Suárez, Susana; Uribe, Misael

    2007-01-01

    Chronic hepatitis C (CHC) is the second cause of endstage liver disease in our country and one of the main indications of liver transplantation. Hepatitis C virus (HCV) genotype is the principal prognostic factor and the determinant of the therapeutic scheme. In our country few data exist regarding the prevalence of HCV infection and genotype distribution in the Mexican Republic has not been determined. The aim of this study was to characterize the prevalence of the different HCV genotypes and to explore their geographical distribution. Mexican patients with hepatitis C infection, detected throughout the country between 2003 and 2006, were included. All samples were analyzed by a central laboratory and Hepatitis C genotype was identified by Line Immuno Probe Assay in PCR positive samples (Versant Line Probe Assay Quest Diagnostics Nichols Institute, San Juan Capistrano CA). Data were analyzed according to the four geographical areas in Mexico. One thousand three hundred and ninety CHC patients were included. The most frequent genotype detected was genotype 1 (69%) followed by genotype 2 (21.4%) and genotype 3 (9.2%). Genotype 4 and 5 were infrequent. There was no subject infected with genotype 6. Genotype 1 and 2 exhibit very similar distribution in all geographical areas. Genotype 3 infected patients were more frequent in the North region (52%) compared with other areas:center-western (30%), center (17%), South-South east (1%) (p < 0.001). The most prevalent HCV genotype in Mexico is genotype 1. Geographical distribution of HCV genotypes in the four geographical areas in Mexico is not homogenous with a greater frequency of genotype3 in the north region. This difference could be related to the global changes of risk factors for HCV infection.

  3. A genotype-directed comparative effectiveness trial of Bucindolol and metoprolol succinate for prevention of symptomatic atrial fibrillation/atrial flutter in patients with heart failure: Rationale and design of the GENETIC-AF trial.

    PubMed

    Piccini, Jonathan P; Connolly, Stuart J; Abraham, William T; Healey, Jeff S; Steinberg, Benjamin A; Al-Khalidi, Hussein R; Dignacco, Patricia; van Veldhuisen, Dirk J; Sauer, William H; White, Michel; Wilton, Stephen B; Anand, Inder S; Dufton, Christopher; Marshall, Debra A; Aleong, Ryan G; Davis, Gordon W; Clark, Richard L; Emery, Laura L; Bristow, Michael R

    2018-05-01

    Few therapies are available for the safe and effective treatment of atrial fibrillation (AF) in patients with heart failure. Bucindolol is a non-selective beta-blocker with mild vasodilator activity previously found to have accentuated antiarrhythmic effects and increased efficacy for preventing heart failure events in patients homozygous for the major allele of the ADRB1 Arg389Gly polymorphism (ADRB1 Arg389Arg genotype). The safety and efficacy of bucindolol for the prevention of AF or atrial flutter (AFL) in these patients has not been proven in randomized trials. The Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Metoprolol Succinate for Prevention of Symptomatic Atrial Fibrillation/Atrial Flutter in Patients with Heart Failure (GENETIC-AF) trial is a multicenter, randomized, double-blinded "seamless" phase 2B/3 trial of bucindolol hydrochloride versus metoprolol succinate, for the prevention of symptomatic AF/AFL in patients with reduced ejection fraction heart failure (HFrEF). Patients with pre-existing HFrEF and recent history of symptomatic AF are eligible for enrollment and genotype screening, and if they are ADRB1 Arg389Arg, eligible for randomization. A total of approximately 200 patients will comprise the phase 2B component and if pre-trial assumptions are met, 620 patients will be randomized at approximately 135 sites to form the Phase 3 population. The primary endpoint is the time to recurrence of symptomatic AF/AFL or mortality over a 24-week follow-up period, and the trial will continue until 330 primary endpoints have occurred. GENETIC-AF is the first randomized trial of pharmacogenetic guided rhythm control, and will test the safety and efficacy of bucindolol compared with metoprolol succinate for the prevention of recurrent symptomatic AF/AFL in patients with HFrEF and an ADRB1 Arg389Arg genotype. (ClinicalTrials.govNCT01970501). Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Comparative genome-wide mapping versus extreme pool-genotyping and development of diagnostic SNP markers linked to QTL for adult plant resistance to stripe rust in common wheat.

    PubMed

    Wu, Jianhui; Huang, Shuo; Zeng, Qingdong; Liu, Shengjie; Wang, Qilin; Mu, Jingmei; Yu, Shizhou; Han, Dejun; Kang, Zhensheng

    2018-06-16

    A major stripe rust resistance QTL on chromosome 4BL was localized to a 4.5-Mb interval using comparative QTL mapping methods and validated in 276 wheat genotypes by haplotype analysis. CYMMIT-derived wheat line P10103 was previously identified to have adult plant resistance (APR) to stripe rust in the greenhouse and field. The conventional approach for QTL mapping in common wheat is laborious. Here, we performed QTL detection of APR using a combination of genome-wide scanning and extreme pool-genotyping. SNP-based genetic maps were constructed using the Wheat55 K SNP array to genotype a recombinant inbred line (RIL) population derived from the cross Mingxian 169 × P10103. Five stable QTL were detected across multiple environments. A fter comparing SNP profiles from contrasting, extreme DNA pools of RILs six putative QTL were located to approximate chromosome positions. A major QTL on chromosome 4B was identified in F 2:4 contrasting pools from cross Zhengmai 9023 × P10103. A consensus QTL (LOD = 26-40, PVE = 42-55%), named QYr.nwafu-4BL, was defined and localized to a 4.5-Mb interval flanked by SNP markers AX-110963704 and AX-110519862 in chromosome arm 4BL. Based on stripe rust response, marker genotypes, pedigree analysis and mapping data, QYr.nwafu-4BL is likely to be a new APR QTL. The applicability of the SNP-based markers flanking QYr.nwafu-4BL was validated on a diversity panel of 276 wheat lines. The additional minor QTL on chromosomes 4A, 5A, 5B and 6A enhanced the level of resistance conferred by QYr.nwafu-4BL. Marker-assisted pyramiding of QYr.nwafu-4BL and other favorable minor QTL in new wheat cultivars should improve the level of APR to stripe rust.

  5. Diagnostic accuracy of high-risk HPV DNA genotyping for primary cervical cancer screening and triage of HPV-positive women, compared to cytology: preliminary results of the PIPAVIR study.

    PubMed

    Chatzistamatiou, Kimon; Moysiadis, Theodoros; Angelis, Eleftherios; Kaufmann, Andreas; Skenderi, Alkmini; Jansen-Duerr, Pidder; Lekka, Irini; Kilintzis, Vasilis; Angelidou, Stamatia; Katsiki, Evangelia; Hagemann, Ingke; Tsertanidou, Athena; Koch, Isabel; Boecher, Oliver; Soutschek, Erwin; Maglaveras, Nikolaos; Agorastos, Theodoros

    2017-05-01

    The purpose of the presented PIPAVIR (persistent infections with human papillomaviruses; http://www.pipavir.com ) subanalysis is to assess the performance of high-risk (hr) HPV-DNA genotyping as a method of primary cervical cancer screening and triage of HPV positive women to colposcopy compared to liquid-based cytology (LBC) in an urban female population. Women, aged 30-60, provided cervicovaginal samples at the Family-Planning Centre, Hippokratio Hospital of Thessaloniki, Greece, and the Department of Gynecology and Obstetrics in Mare Klinikum, Kiel, Germany. Cytology and HPV genotyping was performed using LBC and HPV Multiplex Genotyping (MPG), respectively. Women positive for cytology [atypical squamous cells of undetermined significance (ASC-US) or worse] or hrHPV were referred for colposcopy. Among 1723/1762 women included in the final analysis, hrHPV and HPV16/18 prevalence was 17.7 and 9.6%, respectively. Cytology was ASCUS or worse in 7.6%. Cervical Intraepithelial Neoplasia grade 2 or worse (CIN2+) was detected in 28 women (1.6%). Sensitivity of cytology (ASCUS or worse) and HPV DNA testing for the detection of CIN2+ was 50.0 and 100%, and specificity was 94.49 and 85.49%, respectively. The screening approach according to which only women positive for HPV16/18 and for hrHPV(non16/18) with ASCUS or worse were referred to colposcopy presented 78.57% sensitivity and 13.17% positive predictive value (PPV). HPV testing represents a more sensitive methodology for primary cervical cancer screening compared to cytology. For triage of HPV positive women to colposcopy, partial HPV genotyping offers better sensitivity than cytology, at the cost of higher number of colposcopies.

  6. Role and mechanism of AT1-AA in the pathogenesis of HELLP syndrome.

    PubMed

    Bu, Shurui; Wang, Yuxian; Sun, Shuqing; Zheng, Yanqian; Jin, Zhu; Zhi, Jianming

    2018-01-10

    HELLP syndrome remains a leading cause of maternal and neonatal mortality and morbidity worldwide, which symptoms include hemolysis, elevated liver enzymes and low platelet count. The objective of this study was to determine whether HELLP is associated with AT1-AA. The positive rate and titer of AT1-AA in plasma from pregnant women were determined, and the correlation of AT1-AA titer with the grade of HELLP was analyzed. A HELLP rat model established by intravenous injection of AT1-AA. Our experimental results show the AT1-AA titer and positive rate were significantly higher in HELLP group, and AT1-AA titer were positively correlated with the level of TNF-α and ET-1 in plasma and the grade of HELLP syndrome. The results of animal experiments showed that the typical features of HELLP in the pregnant rats after AT1-AA injection. The levels of TNF-α and ET-1 in plasma and liver tissue were significantly increased in AT1-AA-treated rats compared with control rats. The HELLP syndrome induced by AT1-AA was attenuated markedly after administration of losartan. These data support the hypothesis that one the potential pathway that AT1-AA induce damage to capillary endothelial cells and liver during pregnancy is through activation of TNF-α and ET-1.

  7. Cost-Effectiveness and Efficacy of spa, SCCmec, and PVL Genotyping of Methicillin-Resistant Staphylococcus aureus as Compared to Pulsed-Field Gel Electrophoresis

    PubMed Central

    Li, Vincent; Chui, Linda; Louie, Lisa; Simor, Andrew; Golding, George R.; Louie, Marie

    2013-01-01

    Pulsed-field gel electrophoresis (PFGE) is a valuable molecular typing assay used for methicillin-resistant Staphylococcus aureus (MRSA) surveillance and genotyping. However, there are several limitations associated with PFGE. In Alberta, Canada, the significant increase in the number of MRSA isolates submitted to the Provincial Laboratory for Public Health (ProvLab) for PFGE typing led to the need for an alternative genotyping method. In this study, we describe the transition from PFGE to Staphylococcus protein A (spa), Staphylococcal cassette chromosome (SCCmec), and Panton-Valentine leukocidin (PVL) typing. A total of 1915 clinical MRSA isolates collected from 2005 to 2009 were used to develop and validate an algorithm for assigning PFGE epidemic types using spa, SCCmec, and PVL typing and the resulting data was used to populate a new Alberta MRSA typing database. An additional 12620 clinical MRSA isolates collected from 2010 to 2012 as part of ongoing routine molecular testing at ProvLab were characterized using the new typing algorithm and the Alberta MRSA typing database. Switching to spa, SCCmec, and PVL from PFGE typing substantially reduced hands-on and turn-around times while maintaining historical PFGE epidemic type designations. This led to an approximate $77,000 reduction in costs from 2010 to 2012. PFGE typing is still required for a small subset of MRSA isolates that have spa types that are rare, novel, or associated with more than one PFGE epidemic type. PMID:24244440

  8. Identification and comparative analysis of the microRNA transcriptome in roots of two contrasting tobacco genotypes in response to cadmium stress

    NASA Astrophysics Data System (ADS)

    He, Xiaoyan; Zheng, Weite; Cao, Fangbin; Wu, Feibo

    2016-09-01

    Tobacco (Nicotiana tabacum L.) is more acclimated to cadmium (Cd) uptake and preferentially enriches Cd in leaves than other crops. MicroRNAs (miRNAs) play crucial roles in regulating expression of various stress response genes in plants. However, genome-wide expression of miRNAs and their target genes in response to Cd stress in tobacco are still unknown. Here, miRNA high-throughput sequencing technology was performed using two contrasting tobacco genotypes Guiyan 1 and Yunyan 2 of Cd-sensitive and tolerance. Comprehensive analysis of miRNA expression profiles in control and Cd treated plants identified 72 known (27 families) and 14 novel differentially expressed miRNAs in the two genotypes. Among them, 28 known (14 families) and 5 novel miRNAs were considered as Cd tolerance associated miRNAs, which mainly involved in cell growth, ion homeostasis, stress defense, antioxidant and hormone signaling. Finally, a hypothetical model of Cd tolerance mechanism in Yunyan 2 was presented. Our findings suggest that some miRNAs and their target genes and pathways may play critical roles in Cd tolerance.

  9. Mendel: a simple excel workbook to compare the observed and expected distributions of genotypes/phenotypes in transgenic and knockout mouse crosses involving up to three unlinked loci by means of a χ2 test.

    PubMed

    Montoliu, Lluís

    2012-06-01

    The analysis of transgenic and knockout mice always involves the establishment of matings with individuals carrying different loci, segregating independently, whose presence is expected among the progeny, according to a Mendelian distribution. The appearance of distorted inheritance ratios suggests the existence of unexpected lethal or sub-lethal phenotypes associated with some genotypes. These situations are common in a number of cases, including: testing transgenic founder mice for germ-line transmission of their transgenes; setting up heterozygous crosses to obtain homozygous individuals, both for transgenic and knockout mice; establishing matings between floxed mouse lines and suitable cre transgenic mouse lines, etc. The Pearson's χ(2) test can be used to assess the significance of the observed frequencies of genotypes/phenotypes in relation to the expected values, in order to determine whether the observed cases fit the expected distribution. Here, I describe a simple Excel workbook to compare the observed and expected distributions of genotypes/phenotypes in transgenic and knockout mouse crosses involving up to three unlinked loci by means of a χ(2) test. The file is freely available for download from my laboratory's web page at: http://www.cnb.csic.es/~montoliu/Mendel.xls .

  10. Correlation between Waardenburg syndrome phenotype and genotype in a population of individuals with identified PAX3 mutations.

    PubMed

    DeStefano, A L; Cupples, L A; Arnos, K S; Asher, J H; Baldwin, C T; Blanton, S; Carey, M L; da Silva, E O; Friedman, T B; Greenberg, J; Lalwani, A K; Milunsky, A; Nance, W E; Pandya, A; Ramesar, R S; Read, A P; Tassabejhi, M; Wilcox, E R; Farrer, L A

    1998-05-01

    Waardenburg syndrome (WS) type 1 is an autosomal dominant disorder characterized by sensorineural hearing loss, pigmentary abnormalities of the eye, hair, and skin, and dystopia canthorum. The phenotype is variable and affected individuals may exhibit only one or a combination of several of the associated features. To assess the relationship between phenotype and gene defect, clinical and genotype data on 48 families (271 WS individuals) collected by members of the Waardenburg Consortium were pooled. Forty-two unique mutations in the PAX3 gene, previously identified in these families, were grouped in five mutation categories: amino acid (AA) substitution in the paired domain, AA substitution in the homeodomain, deletion of the Ser-Thr-Pro-rich region, deletion of the homeodomain and the Ser-Thr-Pro-rich region, and deletion of the entire gene. These mutation classes are based on the structure of the PAX3 gene and were chosen to group mutations predicted to have similar defects in the gene product. Association between mutation class and the presence of hearing loss, eye pigment abnormality, skin hypopigmentation, or white forelock was evaluated using generalized estimating equations, which allowed for incorporation of a correlation structure that accounts for potential similarity among members of the same family. Odds for the presence of eye pigment abnormality, white forelock, and skin hypopigmentation were 2, 8, and 5 times greater, respectively, for individuals with deletions of the homeodomain and the Pro-Ser-Thr-rich region compared to individuals with an AA substitution in the homeodomain. Odds ratios that differ significantly from 1.0 for these traits may indicate that the gene products resulting from different classes of mutations act differently in the expression of WS. Although a suggestive association was detected for hearing loss with an odds ratio of 2.6 for AA substitution in the paired domain compared with AA substitution in the homeodomain, this odds

  11. Nicotine N-glucuronidation relative to N-oxidation and C-oxidation and UGT2B10 genotype in five ethnic/racial groups

    PubMed Central

    Murphy, Sharon E.; Park, Sung-Shim L.; Thompson, Elizabeth F.; Wilkens, Lynne R.; Patel, Yesha; Stram, Daniel O.; Le Marchand, Loic

    2014-01-01

    Nicotine metabolism influences smoking behavior and differences in metabolism probably contribute to ethnic variability in lung cancer risk. We report here on the proportion of nicotine metabolism by cytochrome P450 2A6-catalyzed C-oxidation, UDP-glucuronosyl transferase 2B10 (UGT2B10)-catalyzed N-glucuronidation and flavin monooxygenase 3-catalyzed N-oxidation in five ethnic/racial groups and the role of UGT2B10 genotype on the metabolic patterns observed. Nicotine and its metabolites were quantified in urine from African American (AA, n = 364), Native Hawaiian (NH, n = 311), White (n = 437), Latino (LA, n = 453) and Japanese American (JA, n = 674) smokers. Total nicotine equivalents, the sum of nicotine and six metabolites, and nicotine metabolism phenotypes were calculated. The relationship of UGT2B10 genotype to nicotine metabolic pathways was determined for each group; geometric means were computed and adjusted for age, sex, creatinine, and body mass index. Nicotine metabolism patterns were unique across the groups, C-oxidation was lowest in JA and NH (P < 0.0001), and N-glucuronidation lowest in AA (P < 0.0001). There was no difference in C-oxidation among Whites and AA and LA. Nicotine and cotinine glucuronide ratios were 2- and 3-fold lower in AA compared with Whites. Two UGT variants, a missense mutation (Asp67Tyr, rs61750900) and a splice variant (rs116294140) accounted for 33% of the variation in glucuronidation. In AA, the splice variant accounted for the majority of the reduced nicotine glucuronidation. UGT2B10 variant allele carriers had increased levels of C-oxidation (P = 0.0099). Our data indicate that the relative importance of nicotine metabolic pathways varies by ethnicity, and all pathways should be considered when characterizing the role of nicotine metabolism on smoking behavior and cancer risk. PMID:25233931

  12. Seizure variables and their relationship to genotype and functional abilities in the CDKL5 disorder.

    PubMed

    Fehr, Stephanie; Wong, Kingsley; Chin, Richard; Williams, Simon; de Klerk, Nick; Forbes, David; Krishnaraj, Rahul; Christodoulou, John; Downs, Jenny; Leonard, Helen

    2016-11-22

    To investigate seizure outcomes and their relationships to genotype and functional abilities in individuals with the cyclin-dependent kinase-like-5 (CDKL5) disorder. Using the International CDKL5 Disorder Database, we identified 172 cases with a pathogenic CDKL5 mutation. We categorized individual mutations into 4 groups based on predicted structural and functional consequences. Negative binomial regression was used to model the linear association between current seizure rate and mutation group, current level of assistance required to walk 10 steps, and the highest level of expressive communication used to convey refusal or request. All but 3 (169/172) patients had a history of epilepsy. The median age at seizure onset was 6 weeks (range 1 week-1.5 years) and the median seizure rate at ascertainment was 2 per day (range 0-20 per day). After adjusting for walking ability and confounders including use or otherwise of polytherapy, seizure rate was lower in those with truncating mutations between aa172 and aa781 compared to those with no functional protein (incidence rate ratio [IRR] 0.57; 95% confidence interval [CI] 0.35-0.93). Ability to walk and use of spoken language were associated with lower rates of current seizures when compared to those with the least ability after adjusting for genotype (walking: IRR 0.62; 95% CI 0.39-0.99, communication: IRR 0.48; 95% CI 0.23-1.02). At a median age at questionnaire completion of 5 years, those previously treated with corticosteroids had more frequent seizures than those who have never been treated, whether or not there was a history of infantile spasms. Epilepsy is pervasive but not mandatory for the CDKL5 disorder. Genotype and functional abilities were related to seizure frequency, which appears refractory to antiepileptic drugs. © 2016 American Academy of Neurology.

  13. Constitutive behavior of as-cast AA1050, AA3104, and AA5182

    NASA Astrophysics Data System (ADS)

    van Haaften, W. M.; Magnin, B.; Kool, W. H.; Katgerman, L.

    2002-07-01

    Recent thermomechanical modeling to calculate the stress field in industrially direct-chill (DC) cast-aluminum slabs has been successful, but lack of material data limits the accuracy of these calculations. Therefore, the constitutive behavior of three aluminum alloys (AA1050, AA3104, and AA5182) was determined in the as-cast condition using tensile tests at low strain rates and from room temperature to solidus temperature. The parameters of two constitutive equations, the extended Ludwik equation and a combination of the Sellars-Tegart equation with a hardening law, were determined. In order to study the effect of recovery, the constitutive behavior after prestraining at higher temperatures was also investigated. To evaluate the quantified constitutive equations, tensile tests were performed simulating the deformation and cooling history experienced by the material during casting. It is concluded that both constitutive equations perform well, but the combined hardening-Sellars-Tegart (HST) equation has temperature-independent parameters, which makes it easier to implement in a DC casting model. Further, the deformation history of the ingot should be taken into account for accurate stress calculations.

  14. Resting-State Brain and the FTO Obesity Risk Allele: Default Mode, Sensorimotor, and Salience Network Connectivity Underlying Different Somatosensory Integration and Reward Processing between Genotypes.

    PubMed

    Olivo, Gaia; Wiemerslage, Lyle; Nilsson, Emil K; Solstrand Dahlberg, Linda; Larsen, Anna L; Olaya Búcaro, Marcela; Gustafsson, Veronica P; Titova, Olga E; Bandstein, Marcus; Larsson, Elna-Marie; Benedict, Christian; Brooks, Samantha J; Schiöth, Helgi B

    2016-01-01

    Single-nucleotide polymorphisms (SNPs) of the fat mass and obesity associated (FTO) gene are linked to obesity, but how these SNPs influence resting-state neural activation is unknown. Few brain-imaging studies have investigated the influence of obesity-related SNPs on neural activity, and no study has investigated resting-state connectivity patterns. We tested connectivity within three, main resting-state networks: default mode (DMN), sensorimotor (SMN), and salience network (SN) in 30 male participants, grouped based on genotype for the rs9939609 FTO SNP, as well as punishment and reward sensitivity measured by the Behavioral Inhibition (BIS) and Behavioral Activation System (BAS) questionnaires. Because obesity is associated with anomalies in both systems, we calculated a BIS/BAS ratio (BBr) accounting for features of both scores. A prominence of BIS over BAS (higher BBr) resulted in increased connectivity in frontal and paralimbic regions. These alterations were more evident in the obesity-associated AA genotype, where a high BBr was also associated with increased SN connectivity in dopaminergic circuitries, and in a subnetwork involved in somatosensory integration regarding food. Participants with AA genotype and high BBr, compared to corresponding participants in the TT genotype, also showed greater DMN connectivity in regions involved in the processing of food cues, and in the SMN for regions involved in visceral perception and reward-based learning. These findings suggest that neural connectivity patterns influence the sensitivity toward punishment and reward more closely in the AA carriers, predisposing them to developing obesity. Our work explains a complex interaction between genetics, neural patterns, and behavioral measures in determining the risk for obesity and may help develop individually-tailored strategies for obesity prevention.

  15. Resting-State Brain and the FTO Obesity Risk Allele: Default Mode, Sensorimotor, and Salience Network Connectivity Underlying Different Somatosensory Integration and Reward Processing between Genotypes

    PubMed Central

    Olivo, Gaia; Wiemerslage, Lyle; Nilsson, Emil K.; Solstrand Dahlberg, Linda; Larsen, Anna L.; Olaya Búcaro, Marcela; Gustafsson, Veronica P.; Titova, Olga E.; Bandstein, Marcus; Larsson, Elna-Marie; Benedict, Christian; Brooks, Samantha J.; Schiöth, Helgi B.

    2016-01-01

    Single-nucleotide polymorphisms (SNPs) of the fat mass and obesity associated (FTO) gene are linked to obesity, but how these SNPs influence resting-state neural activation is unknown. Few brain-imaging studies have investigated the influence of obesity-related SNPs on neural activity, and no study has investigated resting-state connectivity patterns. We tested connectivity within three, main resting-state networks: default mode (DMN), sensorimotor (SMN), and salience network (SN) in 30 male participants, grouped based on genotype for the rs9939609 FTO SNP, as well as punishment and reward sensitivity measured by the Behavioral Inhibition (BIS) and Behavioral Activation System (BAS) questionnaires. Because obesity is associated with anomalies in both systems, we calculated a BIS/BAS ratio (BBr) accounting for features of both scores. A prominence of BIS over BAS (higher BBr) resulted in increased connectivity in frontal and paralimbic regions. These alterations were more evident in the obesity-associated AA genotype, where a high BBr was also associated with increased SN connectivity in dopaminergic circuitries, and in a subnetwork involved in somatosensory integration regarding food. Participants with AA genotype and high BBr, compared to corresponding participants in the TT genotype, also showed greater DMN connectivity in regions involved in the processing of food cues, and in the SMN for regions involved in visceral perception and reward-based learning. These findings suggest that neural connectivity patterns influence the sensitivity toward punishment and reward more closely in the AA carriers, predisposing them to developing obesity. Our work explains a complex interaction between genetics, neural patterns, and behavioral measures in determining the risk for obesity and may help develop individually-tailored strategies for obesity prevention. PMID:26924971

  16. Laboratory Astrophysics Division of The AAS (LAD)

    NASA Astrophysics Data System (ADS)

    Salama, Farid; Drake, R. P.; Federman, S. R.; Haxton, W. C.; Savin, D. W.

    2012-10-01

    The purpose of the Laboratory Astrophysics Division (LAD) is to advance our understanding of the Universe through the promotion of fundamental theoretical and experimental research into the underlying processes that drive the Cosmos. LAD represents all areas of astrophysics and planetary sciences. The first new AAS Division in more than 30 years, the LAD traces its history back to the recommendation from the scientific community via the White Paper from the 2006 NASA-sponsored Laboratory Astrophysics Workshop. This recommendation was endorsed by the Astronomy and Astrophysics Advisory Committee (AAAC), which advises the National Science Foundation (NSF), the National Aeronautics and Space Administration (NASA), and the U.S. Department of Energy (DOE) on selected issues within the fields of astronomy and astrophysics that are of mutual interest and concern to the agencies. In January 2007, at the 209th AAS meeting, the AAS Council set up a Steering Committee to formulate Bylaws for a Working Group on Laboratory Astrophysics (WGLA). The AAS Council formally established the WGLA with a five-year mandate in May 2007, at the 210th AAS meeting. From 2008 through 2012, the WGLA annually sponsored Meetings in-a-Meeting at the AAS Summer Meetings. In May 2011, at the 218th AAS meeting, the AAS Council voted to convert the WGLA, at the end of its mandate, into a Division of the AAS and requested draft Bylaws from the Steering Committee. In January 2012, at the 219th AAS Meeting, the AAS Council formally approved the Bylaws and the creation of the LAD. The inaugural gathering and the first business meeting of the LAD were held at the 220th AAS meeting in Anchorage in June 2012. You can learn more about LAD by visiting its website at http://lad.aas.org/ and by subscribing to its mailing list.

  17. Laboratory Astrophysics Division of the AAS (LAD)

    NASA Technical Reports Server (NTRS)

    Salama, Farid; Drake, R. P.; Federman, S. R.; Haxton, W. C.; Savin, D. W.

    2012-01-01

    The purpose of the Laboratory Astrophysics Division (LAD) is to advance our understanding of the Universe through the promotion of fundamental theoretical and experimental research into the underlying processes that drive the Cosmos. LAD represents all areas of astrophysics and planetary sciences. The first new AAS Division in more than 30 years, the LAD traces its history back to the recommendation from the scientific community via the White Paper from the 2006 NASA-sponsored Laboratory Astrophysics Workshop. This recommendation was endorsed by the Astronomy and Astrophysics Advisory Committee (AAAC), which advises the National Science Foundation (NSF), the National Aeronautics and Space Administration (NASA), and the U.S. Department of Energy (DOE) on selected issues within the fields of astronomy and astrophysics that are of mutual interest and concern to the agencies. In January 2007, at the 209th AAS meeting, the AAS Council set up a Steering Committee to formulate Bylaws for a Working Group on Laboratory Astrophysics (WGLA). The AAS Council formally established the WGLA with a five-year mandate in May 2007, at the 210th AAS meeting. From 2008 through 2012, the WGLA annually sponsored Meetings in-a-Meeting at the AAS Summer Meetings. In May 2011, at the 218th AAS meeting, the AAS Council voted to convert the WGLA, at the end of its mandate, into a Division of the AAS and requested draft Bylaws from the Steering Committee. In January 2012, at the 219th AAS Meeting, the AAS Council formally approved the Bylaws and the creation of the LAD. The inaugural gathering and the first business meeting of the LAD were held at the 220th AAS meeting in Anchorage in June 2012. You can learn more about LAD by visiting its website at http://lad.aas.org/ and by subscribing to its mailing list.

  18. Hot tearing studies in AA5182

    NASA Astrophysics Data System (ADS)

    van Haaften, W. M.; Kool, W. H.; Katgerman, L.

    2002-10-01

    One of the major problems during direct chill (DC) casting is hot tearing. These tears initiate during solidification of the alloy and may run through the entire ingot. To study the hot tearing mechanism, tensile tests were carried out in semisolid state and at low strain rates, and crack propagation was studied in situ by scanning electron microscopy (SEM). These experimentally induced cracks were compared with hot tears developed in an AA5182 ingot during a casting trial in an industrial research facility. Similarities in the microstructure of the tensile test specimens and the hot tears indicate that hot tearing can be simulated by performing tensile tests at semisolid temperatures. The experimental data were compared with existing hot tearing models and it was concluded that the latter are restricted to relatively high liquid fractions because they do not take into account the existence of solid bridges in the crack.

  19. Japanese population structure, based on SNP genotypes from 7003 individuals compared to other ethnic groups: effects on population-based association studies.

    PubMed

    Yamaguchi-Kabata, Yumi; Nakazono, Kazuyuki; Takahashi, Atsushi; Saito, Susumu; Hosono, Naoya; Kubo, Michiaki; Nakamura, Yusuke; Kamatani, Naoyuki

    2008-10-01

    Because population stratification can cause spurious associations in case-control studies, understanding the population structure is important. Here, we examined Japanese population structure by "Eigenanalysis," using the genotypes for 140,387 SNPs in 7003 Japanese individuals, along with 60 European, 60 African, and 90 East-Asian individuals, in the HapMap project. Most Japanese individuals fell into two main clusters, Hondo and Ryukyu; the Hondo cluster includes most of the individuals from the main islands in Japan, and the Ryukyu cluster includes most of the individuals from Okinawa. The SNPs with the greatest frequency differences between the Hondo and Ryukyu clusters were found in the HLA region in chromosome 6. The nonsynonymous SNPs with the greatest frequency differences between the Hondo and Ryukyu clusters were the Val/Ala polymorphism (rs3827760) in the EDAR gene, associated with hair thickness, and the Gly/Ala polymorphism (rs17822931) in the ABCC11 gene, associated with ear-wax type. Genetic differentiation was observed, even among different regions in Honshu Island, the largest island of Japan. Simulation studies showed that the inclusion of different proportions of individuals from different regions of Japan in case and control groups can lead to an inflated rate of false-positive results when the sample sizes are large.

  20. Polymorphisms in the HSP90AA1 5' flanking region are associated with scrapie incubation period in sheep.

    PubMed

    Marcos-Carcavilla, Ane; Moreno, Carole; Serrano, Magdalena; Laurent, Pascal; Cribiu, Edmond P; Andréoletti, Olivier; Ruesche, Julien; Weisbecker, Jean-Louis; Calvo, Jorge H; Moazami-Goudarzi, Katayoun

    2010-07-01

    Susceptibility to scrapie is mainly controlled by point mutations at the PRNP locus. However, additional quantitative trait loci (QTL) have been identified across the genome including a region in OAR18. The gene which encodes the inducible form of the cytoplasmic Hsp90 chaperone (HSP90AA1) maps within this region and seems to be associated with the resistance/susceptibility to scrapie in sheep. Here, we have analyzed several polymorphisms which were previously described in the ovine HSP90AA1 5' flanking region and in intron 10 in two naturally scrapie infected Romanov sheep populations. First, we have studied 58 ARQ/VRQ animals pertaining to the sire family where the QTL influencing scrapie incubation period in OAR18 was detected. We have found a significant association between polymorphisms localized at -660 and -528 in the HSP90AA1 5' flanking region and the scrapie incubation period. These two polymorphisms have also been studied in a second sample constituted by 62 VRQ/VRQ sheep showing an extreme incubation period. Results are concordant with the first dataset. Finally, we have studied the HSP90AA1 expression in scrapie and control animals (N = 41) with different HSP90AA1 genotypes by real time PCR on blood samples. The HSP90AA1 expression rate was equivalent in CC(-600)AA(-528) and CG(-600)AG(-528) scrapie resistant animals (ARR/ARR) and was higher in their CC(-600)AA(-528) than in their CG(-600)AG(-528) scrapie susceptible counterparts (VRQ/VRQ). Our results support the hypothesis that the ovine HSP90AA1 gene acts as a modulator of scrapie susceptibility, contributing to the observed differences in the incubation period of scrapie infected animals with the same PRNP genotype.

  1. AAS 228: Day 2 afternoon

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-06-01

    Editors Note:This week were at the 228th AAS Meeting in San Diego, CA. Along with a team ofauthors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting twiceeach day. Follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.The Limits of Scientific Cosmology: Setting the Stage: Accepted Facts, and Testing Limitations in Theory and Data (by Gourav Khullar)With a stellar lineup of speakers to talk about current and future prospects of cosmology and its limits (or lack thereof), the first session kicked off with talks by Risa Wechsler, Joseph Silk, and Sean Carroll (his talk on Multiverses is described below, by Nathan Sanders). Risa set the stage with an elaborate description of the current accepted facts in the era of precision cosmology including the standard model of concordance cosmology, described by seven parameters and an accepted Lambda-CDM paradigm (with a cosmological constant and cold dark matter). The talk stressed on the fact that all these parameters are understood to a percent order precision, which is a remarkable deviation from the time in 1990s when according to Risa, Alan Guth never thought that any of these numbers could be measured precisely!Risa Wechsler describing our current constraints on what Dark Matter could constitute.Joseph Silk discussing limits on cosmological parameters.The CMB measurements, Big Bang Nucleosynthesis estimates and galaxy clustering statistics all contribute to locking down the description of our universe. She emphasized on the tensions between different probes to measure expansion rate H0 of the universe, and small scale predictions of cold dark matter simulations, but she is hopeful that these shall be resolved eventually. Joe Silk followed this up with his interpretation of trying to understand our place in the universe and placing limits on different parameters and

  2. Co-expression of AaPMT and AaTRI effectively enhances the yields of tropane alkaloids in Anisodus acutangulus hairy roots

    PubMed Central

    2011-01-01

    Background Tropane alkaloids (TA) including anisodamine, anisodine, hyoscyamine and scopolamine are a group of important anticholinergic drugs with rapidly increasing market demand, so it is significant to improve TA production by biotechnological approaches. Putrescine N-methyltransferase (PMT) was considered as the first rate-limiting upstream enzyme while tropinone reductase I (TRI) was an important branch-controlling enzyme involved in TA biosynthesis. However, there is no report on simultaneous introduction of PMT and TRI genes into any TA-producing plant including Anisodus acutangulus (A. acutangulus), which is a Solanaceous perennial plant that is endemic to China and is an attractive resource plant for production of TA. Results In this study, 21 AaPMT and AaTRI double gene transformed lines (PT lines), 9 AaPMT single gene transformed lines (P lines) and 5 AaTRI single gene transformed lines (T lines) were generated. RT-PCR and real-time fluorescence quantitative analysis results revealed that total AaPMT (AaPMT T) and total AaTRI (AaTRI T) gene transcripts in transgenic PT, P and T lines showed higher expression levels than native AaPMT (AaPMT E) and AaTRI (AaTRI E) gene transcripts. As compared to the control and single gene transformed lines (P or T lines), PT transgenic hairy root lines produced significantly higher levels of TA. The highest yield of TA was detected as 8.104 mg/g dw in line PT18, which was 8.66, 4.04, and 3.11-times higher than those of the control (0.935 mg/g dw), P3 (highest in P lines, 2.004 mg/g dw) and T12 (highest in T lines, 2.604 mg/g dw), respectively. All the tested samples were found to possess strong radical scavenging capacity, which were similar to control. Conclusion In the present study, the co-expression of AaPMT and AaTRI genes in A. acutangulus hairy roots significantly improved the yields of TA and showed higher antioxidant activity than control because of higher total TA content, which is the first report on

  3. Low Cotinine Glucuronidation Results in Higher Serum and Saliva Cotinine in African American Compared to White Smokers.

    PubMed

    Murphy, Sharon E; Sipe, Christopher J; Choi, Kwangsoo; Raddatz, Leah M; Koopmeiners, Joseph S; Donny, Eric C; Hatsukami, Dorothy K

    2017-07-01

    Background: Tobacco exposure is often quantified by serum or saliva concentrations of the primary nicotine metabolite, cotinine. However, average cotinine concentrations are higher in African Americans (AA) compared with Whites with similar smoking levels. Cotinine is metabolized by UGT2B10 and CYP2A6, and low UGT2B10 activity is common in AA, due to the prevalence of a UGT2B10 splice variant. Methods: UGT2B10 activity was phenotyped in 1,446 smokers (34% AA) by measuring the percentage of cotinine excreted as a glucuronide. Urinary total nicotine equivalents (TNE), the sum of nicotine and 6 metabolites, were determined to quantify smoking dose, and cotinine and 3'-hydroxycotinine were quantified in saliva (study 1) or serum (study 2). Results: Ninety-seven smokers (78% AA) were null for UGT2B10 activity, and the saliva and serum cotinine levels, after adjustment for TNE and cigarettes per day (CPD), were 68% and 48% higher in these smokers compared with nonnull smokers ( P < 0.001). After adjustment for TNE and CPD, salivary cotinine was 35% higher, and serum cotinine 24% higher in AA versus White smokers, but with additional adjustment for UGT2B10 activity, there were no significant differences in saliva and serum cotinine concentrations between these two groups. Conclusions: UGT2B10 activity significantly influences plasma cotinine levels, and higher cotinine concentrations in AA versus White smokers (after adjustment for smoking dose) result from lower levels of UGT2B10-catalyzed cotinine glucuronidation by AA. Impact: UGT2B10 activity or genotype should be considered when using cotinine as a tobacco exposure biomarker, particularly in populations such as AA with high frequencies of UGT2B10 nonfunctional variants. Cancer Epidemiol Biomarkers Prev; 26(7); 1093-9. ©2017 AACR . ©2017 American Association for Cancer Research.

  4. Randomized clinical trial comparing high versus standard dose of ribavirin plus peginterferon alfa-2a in hepatitis C genotype 3 and high viral load. Dargen-3 study.

    PubMed

    Fernández-Rodríguez, Conrado M; Morillas, Rosa María; Masnou, Helena; Navarro, José María; Bárcena, Rafael; González, José Manuel; Martín-Martín, Leticia; Poyato, Antonio; Miquel-Planas, Mireia; Jorquera, Francisco; Casanovas, Teresa; Salmerón, Javier; Calleja, José Luis; Solà, Ricard; Alonso, Sonia; Planas, Ramón; Romero-Gomez, Manuel

    2014-01-01

    Less than half of patients with chronic hepatitis C genotype 3 (G3) and high viral load (HVL) without a rapid virological response (RVR) achieve a sustained virological response (SVR) when treated with peginterferon plus ribavirin (RBV). To assess the impact of high doses of RBV on SVR in patients with G3 and HVL. Ninety-seven patients were randomized to receive peginterferon α-2a+RBV 800 mg/day (A; n=42) or peginterferon α-2a+RBV 1600 mg/day+epoetin β 400 IU/kg/week SC (B; n=55). Patients allocated to group B who achieved RVR continued on RBV (800mg/day) for a further 20 weeks (B1; n=42) while non-RVR patients received a higher dose of RBV (1600 mg/day)+epoetin β (B2; n=13). RVR was observed in 64.3% of patients in A and in 76.4% in B (p=0.259). Intention-to-treat (ITT) analysis showed SVR rates of 64.3% (A) and 61.8% (B), with a reduction of -2.5% (-21.8% to 16.9%) (p=0.835). The SVR rate was 61.9% in arm B1 and 61.5% in arm B2. No serious adverse events were reported, and the rate of moderate adverse events was < 5%. G3 patients with high viral load without RVR did not obtain a benefit from a higher dose of RBV. Higher doses of RBV plus epoetin β were safe and well tolerated (Clin Trials Gov NCT00830609). Copyright © 2013 Elsevier España, S.L. and AEEH y AEG. All rights reserved.

  5. A network meta-analysis to compare simeprevir with boceprevir and telaprevir in combination with peginterferon-α and ribavirin in patients infected with genotype 1 Hepatitis C virus.

    PubMed

    Taieb, Vanessa; Pacou, Maud; Ho, Sophia; Pettré, Ségolène; Van Sanden, Suzy; Pisini, Marta; Ustianowski, Andrew; Mehnert, Angelika

    2015-01-01

    To conduct a network meta-analysis (NMA) to assess the relative efficacy and safety of simeprevir, a second generation oral protease inhibitor (PI), compared to telaprevir and boceprevir in combination with pegylated interferon-α and ribavirin (PR) in patients with chronic hepatitis C. A systematic literature review and NMA of randomized controlled trials involving anti-virals added to PR were conducted. Electronic database searches and hand searches were conducted to identify relevant publications. Outcomes of interest included sustained virologic response (SVR), incidence of adverse events (AEs), and discontinuation due to AEs. Networks were based on treatment-, dose-, and duration-specific nodes. Sub-group analyses were conducted to investigate heterogeneity, based on Metavir scores, sub-genotypes 1a/1b, and prior response. A total of 15 publications were considered for the base case of the meta-analysis. Simeprevir was associated with higher SVR rates than PR alone. Compared to telaprevir and boceprevir, SVR rates tended to be higher for simeprevir, with odds ratios ranging from 1.27 [0.81-2.00] to 2.61 [1.44-4.74] in treatment-naïve and from 1.04 [0.78-1.38] to 1.74 [0.84-3.61] in treatment-experienced patients, respectively. In terms of safety, the risks of anemia and discontinuations due to AEs were lower for simeprevir compared to PR alone, telaprevir, and boceprevir. The risk of rash was lower for simeprevir compared to telaprevir, and similar compared to PR alone and boceprevir. This NMA in genotype 1 HCV patients suggests a similar or better efficacy and tolerability profile for simeprevir compared to telaprevir and boceprevir.

  6. AAS 228: Day 2 morning

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-06-01

    tendency to prefer sugars and proteins that are one chirality only, but it is unknown whether this is a universal preference or a quirk of Earth-based life. Carroll and McGuires new detection in a star-forming cloud of material near the center of the Milky Way does not distinguish whether the propylene oxide is left- or right-handed, but it does show that the cosmos is capable of producing complex molecules that are essential to biology. In the future, they hope to use polarized light to directly measure chirality.Next, Joel Green from STScI presented how a young star surrounded by a bright protoplanetary disk, FU Orionis, has changed since a bright outburst in 1936. Since then, it has consumed some 80 Jupiters worth of material! By comparing observations of the disks brightness taken twelve years apart, Green showed that the hottest inner regions of the disk have faded significantly while the cooler regions farther out have not. In other words, the star has consumed the hot parts of the disk closest to it and altered the chemical composition in the disk that remains. This is likely what our own Sun experienced as a young star, and has implications for planet formation because the chemical composition of the disk affects what materials are available for forming planets. Green hopes that future observations with the Webb telescope will complement existing Spitzer and SOFIA data.A gluttonous star may hold clues to #planet formation: https://t.co/bTcFJM3xcY#aas228pic.twitter.com/nDWLF3bXVN NASA PlanetQuest (@PlanetQuest) June 14, 2016

  7. AAS 228: Day 3 afternoon

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-06-01

    Editors Note:This week were at the 228th AAS Meeting in San Diego, CA. Along with a team ofauthors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting twiceeach day. Follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.Wikipedia Year of Science Editathon (by Meredith Rawls)Whats your first go-to source for an unfamiliar topic on the internet? If you said Wikipedia, youre not alone. For many people, Wikipedia is the primary source of information about astronomy and science. However, many Wikipedia articles about science topics are incomplete or missing, and women are underrepresented among scientists with biographies.To address this, the AAS Astronomy Education Board teamed up with the Wiki Education Foundation to host an edit-a-thon as part of the Wikipedia Year of Science. More than forty attendees spent the better part of three hours working through tutorials, creating new articles, and editing existing ones. The session was generously sponsored by the Simons Foundation.The Year of Science initiative seeks to bring Wikipedia editing skills to the classroom and help new editors find sustainable ways to contribute to Wikipedia in the long term. Anybody can create a free account and start editing!As a first-time Wikipedia contributor, I took the time to go through nearly all the tutorial exercises and familiarize myself with the process of editing a page. I decided to flesh out one section in an existing page about asteroseismology. Others created biography pages from scratch or selected various astronomical topics to write about. To me, the editing process felt like a cross between writing a blog post and a journal article, in a hack day type environment. Working through the tutorial and some examples renewed my empathy for learners who are tackling a new skill set for the first time. A full summary of our

  8. AAS Statistics and the 60% Cohort

    NASA Astrophysics Data System (ADS)

    Marvel, K. B.

    2004-05-01

    I will present the latest statistics available describing the gender of the AAS membership including an update on the so-called 60% cohort (that group of AAS members from the ages of 18 to 25 who are 60% women and 40% men). The AAS membership has changed significantly in the past 30 years from an overall female membership percentage of about 10% to a level around 30% today. This trend is accelerating and indicates the ongoing inclusion of women in the physical sciences, especially astronomy. By the year 2030, the AAS membership should reach gender parity if the present trend continues.

  9. Phenolic profiles and their contribution to the antioxidant activity of selected chickpea genotypes from Mexico and ICRISAT collections.

    PubMed

    Quintero-Soto, Maria F; Saracho-Peña, Ana G; Chavez-Ontiveros, Jeanett; Garzon-Tiznado, Jose A; Pineda-Hidalgo, Karen V; Delgado-Vargas, Francisco; Lopez-Valenzuela, Jose A

    2018-06-01

    Chickpea (Cicer arietinum L.) genotypes, nine kabuli from Mexico and 9 desi from other countries, were investigated for their phenolic profiles and antioxidant activity (AA). Phenolics in methanol extracts (ME) were analyzed by ultra-performance liquid chromatography coupled to diode array detection and mass spectrometry (UPLC-DAD-MS), whereas the AA was measured as Trolox equivalents (TE) by ABTS, DPPH and FRAP methods. Twenty phenolic compounds were identified in the ME and their levels showed a great variability among the chickpea genotypes. Phenolic acids and flavonoids were the most abundant compounds in kabuli and desi genotypes, respectively. The AA values (μmol TE/ 100 g dw) by ABTS (278-2417), DPPH (52-1650), and FRAP (41-1181) were mainly associated with the content of sinapic acid hexoside, gallic acid, myricetin, quercetin, catechin, and isorhamnetin, suggesting they are the main compounds responsible for the AA. The sum of the AA obtained for standards of these compounds evaluated at the concentration found in the extracts accounted for 34.3, 69.8, and 47.0% of the AA in the extract by ABTS, DPPH, and FRAP, respectively. In the AA by DPPH, most of the mixtures of these compounds resulted in synergistic interactions. Three desi genotypes with black seeds (ICC 4418, ICC 6306, and ICC 3761) showed the highest AA and flavonoids content, whereas the most promising kabuli genotypes were Surutato 77, Bco. Sin. 92, and Blanoro that showed the highest values of phenolic acids. These genotypes represent good sources of antioxidants for the improvement of nutraceutical properties in chickpea.

  10. Predicting Hot Deformation of AA5182 Sheet

    NASA Astrophysics Data System (ADS)

    Lee, John T.; Carpenter, Alexander J.; Jodlowski, Jakub P.; Taleff, Eric M.

    Aluminum 5000-series alloy sheet materials exhibit substantial ductilities at hot and warm temperatures, even when grain size is not particularly fine. The relatively high strain-rate sensitivity exhibited by these non-superplastic materials, when deforming under solute-drag creep, is a primary contributor to large tensile ductilities. This active deformation mechanism influences both plastic flow and microstructure evolution across conditions of interest for hot- and warm-forming. Data are presented from uniaxial tensile and biaxial bulge tests of AA5182 sheet material at elevated temperatures. These data are used to construct a material constitutive model for plastic flow, which is applied in finite-element-method (FEM) simulations of plastic deformation under multiaxial stress states. Simulation results are directly compared against experimental data to explore the usefulness of this constitutive model. The effects of temperature and stress state on plastic response and microstructure evolution are discussed.

  11. Comparison of ``AA`` nickel metal hydride cells with ``AA`` Ni-Cd cells

    SciTech Connect

    Alminauskas, V.; Johnson, W.

    1996-12-31

    This paper compares ``AA`` size nickel metal hydride (Ni-HM) cells with comparable ``AA;; nickel cadmium (Ni-Cd) cells both of which were obtained in 1993. The Ni-MH cells were found to be a suitable substitute for conventional Ni-Cd cells. Both these cell types have similar voltages and discharge characteristics. The Ni-MH cells, though had nearly twice the capacity as comparable Ni-Cd cells. There was no significant difference in self discharge between the two types of cells. The Ni-MH cells also performed as well as Ni-Cd cells at rates lower than 5 amperes and at temperatures higher than 0 C (32 F).more » The most interesting finding is that the Ni-MH cells showed an irreversible decay of the discharge voltage with each cycle which was more noticeable during pulses. Eventually the Ni-MH packs fail, not because of loss of capacity, but because of low voltage during the pulse.« less

  12. Safe fetal platelet genotyping: new developments.

    PubMed

    Le Toriellec, Emilie; Chenet, Christophe; Kaplan, Cecile

    2013-08-01

    Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is due to maternal alloimmunization against fetal platelet (PLT) antigens. Antenatal management strategies have been developed to avoid complications such as intracranial hemorrhage. The aim of this study was to set up two reliable, noninvasive fetal genotyping assays to determine the fetal risk in pregnancies in which the father is heterozygous for the offending antigen. This study focused on human PLT antigen (HPA)-1, the most frequently implicated antigen in FNAIT in Caucasians. Two assays based on cell-free fetal DNA extracted from maternal blood samples and on real-time polymerase chain reaction (QPCR) were developed: an allele-specific QPCR specifically targeting the polymorphic sequence in HPA-1 and the study of the variation in the high-resolution melting curve of amplicons containing the polymorphic region. All results from the 49 samples obtained from 29 pregnant women were consistent with expectations. Six women were compatible with their fetuses (three HPA-1aa women and three HPA-1bb women), 41 HPA-1bb women were incompatible with their fetuses, as were two HPA-1aa women. Two fetal PLT genotyping assays on maternal blood samples proved to be reliable as of 15 weeks of gestation, thereby avoiding invasive techniques such as amniocentesis. © 2012 American Association of Blood Banks.

  13. Simultaneous genotyping of HPA-17w to -21w by PCR-SSP in Chinese Cantonese.

    PubMed

    Zhou, Haojie; Ding, Haoqiang; Chen, Yangkai; Li, Xiaofan; Ye, Xin; Nie, Yongmei

    2015-01-01

    Studies have reported the polymorphism of human platelet antigen (HPA)-17w, -18w, -19w, -20w, and -21w. However, the distribution of these five antigens in Chinese Cantonese is still unknown. In this study, we designed new sequence-specific primers for HPA-19w to -21w and used published primers for HPA-17w and -18w to develop a polymerase chain reaction with the sequence-specific primers (PCR-SSP) method for simultaneously genotyping HPA-17w to -21w. A total of 820 unrelated Cantonese apheresis platelet donors in Guangzhou were involved in this study. Among the five HPAs, complete a/a homozygosity was observed for HPA-17w to -20w with an allele frequency of 1.0000. For HPA-21w, nine individuals (9/820, 1.10%) were found to be HPA-21a/bw heterozygous and the allele frequencies of HPA-21a and HPA-21bw were 0.9945 (1631/1640) and 0.0055 (9/1640), respectively. The reliability of the PCR-SSP method was determined by comparing with the genotyping results by DNA sequencing, and no inconsistencies were observed between the two methods. This study provides a reliable PCR-SSP method for simultaneously genotyping HPA-17w to -21w and could improve HPA-matched platelet transfusion in Chinese Cantonese.

  14. Genotyping of β-Lactoglobulin gene by PCR-RFLP in Sahiwal and Tharparkar cattle breeds

    PubMed Central

    Rachagani, Satyanarayana; Gupta, Ishwar Dayal; Gupta, Neelam; Gupta, SC

    2006-01-01

    Genotype frequencies of AA were the lowest compared to that of BB genotype in Sahiwal cattle while AB genotypes were more frequent in Tharparkar cattle. The frequency of A allele was found to be lower than that of B allele in both the breeds studied. These results further confirm that Bos indicus cattle are predominantly of β-Lactoglobulin B type than Bos taurus breeds. PMID:16725039

  15. Contribution of DNA Repair Xeroderma Pigmentosum Group D Genotype to Gastric Cancer Risk in Taiwan.

    PubMed

    Ji, Hong-Xue; Chang, Wen-Shin; Tsai, Chia-Wen; Wang, Ju-Yu; Huang, Nai-Kuei; Lee, An-Sheng; Shen, Ming-Yi; Chen, Wei-Yu; Chiang, Yao-Chang; Shih, Tzu-Ching; Hsu, Chin-Mu; Bau, Da-Tian

    2015-09-01

    It has been proposed that genetic variations of DNA repair genes confer susceptibility to cancer, and the DNA repair gene xeroderma pigmentosum group D (XPD), the caretaker of genome stability, is thought to play a major role in the nucleotide excision repair system. We investigated three genotypes of XPD, at promoter -114 (rs3810366), and codon 312 (rs1799793), 751 (rs13181), and their associated with gastric cancer susceptibility in a Taiwanese population. In the present study, 121 patients with gastric cancer and 363 gender- and age-matched healthy controls were recruited and genotyped for XPD by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) methodology, and the association of XPD genotype with gastric cancer risk was investigated. We found a significant difference in the distribution of A allele-bearing XPD codon 312 genotypes [odds ratio (OR)=1.64, 95% confidence interval (CI)=1.20-2.25, p=0.0019], but not in XPD codon 751 or promoter -114 sites, between the gastric cancer and control groups. Those who had G/A or A/A at XPD codon 312 had a 1.83-fold (95% CI=1.14-2.95, p=0.0159) and 1.87-fold (95% CI=1.04-3.34, p=0.0378) increased risk of gastric cancer compared to those with G/G. The risk for G/A and A/A genotypes had synergistic effects with alcohol drinking (OR=11.27, 95% CI=3.72-34.17, p=0.0001), cigarette smoking (OR=23.20, 95% CI=6.24-86.23, p=0.0001) and Helicobacter pylori infection (OR=5.38, 95% CI=2.76-10.52, p=0.0001) on gastric cancer susceptibility. Our findings suggest that the A allele of XPD codon 312 may contribute to gastric carcinogenesis and may be useful for early detection and prevention of gastric cancer. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  16. Race moderates the association of Catechol-O-methyltransferase genotype and posttraumatic stress disorder in preschool children.

    PubMed

    Humphreys, Kathryn L; Scheeringa, Michael S; Drury, Stacy S

    2014-10-01

    The present study sought to replicate previous findings of an association between the Catechol-O-methyltransferase (COMT) val158met polymorphism with posttraumatic stress disorder (PTSD) and symptomatology in a novel age group, preschool children. COMT genotype was determined in a sample of 171 3-6-year-old trauma-exposed children. PTSD was assessed with a semistructured interview. Accounting for sex, trauma type, and age, genotype was examined in relation to categorical and continuous measures of PTSD both controlling for race and within the two largest racial categories (African American [AA] and European American [EA]). Race significantly moderated the association between genotype and PTSD. Specifically, the genotype associated with increased PTSD symptoms in one racial group had the opposite association in the other racial group. For AA children the met/met genotype was associated with more PTSD symptoms. However, for EA children, val allele carriers had more PTSD symptoms. Whereas every AA child with the met/met genotype met criteria for PTSD, none of the EA children with the met/met genotype did. This genetic association with COMT genotype, in both races but in opposite directions, was most associated with increased arousal symptoms. These findings replicate previous findings in participants of African descent, highlight the moderating effect of race on the association between COMT genotype and PTSD, and provide direct evidence that consideration of population stratification within gene-by-environment studies is valuable to prevent false negative findings.

  17. Race Moderates the Association of Catechol-O-methyltransferase Genotype and Posttraumatic Stress Disorder in Preschool Children

    PubMed Central

    Humphreys, Kathryn L.; Scheeringa, Michael S.

    2014-01-01

    Abstract Objective: The present study sought to replicate previous findings of an association between the Catechol-O-methyltransferase (COMT) val158met polymorphism with posttraumatic stress disorder (PTSD) and symptomatology in a novel age group, preschool children. Methods: COMT genotype was determined in a sample of 171 3–6-year-old trauma-exposed children. PTSD was assessed with a semistructured interview. Accounting for sex, trauma type, and age, genotype was examined in relation to categorical and continuous measures of PTSD both controlling for race and within the two largest racial categories (African American [AA] and European American [EA]). Results: Race significantly moderated the association between genotype and PTSD. Specifically, the genotype associated with increased PTSD symptoms in one racial group had the opposite association in the other racial group. For AA children the met/met genotype was associated with more PTSD symptoms. However, for EA children, val allele carriers had more PTSD symptoms. Whereas every AA child with the met/met genotype met criteria for PTSD, none of the EA children with the met/met genotype did. This genetic association with COMT genotype, in both races but in opposite directions, was most associated with increased arousal symptoms. Conclusions: These findings replicate previous findings in participants of African descent, highlight the moderating effect of race on the association between COMT genotype and PTSD, and provide direct evidence that consideration of population stratification within gene-by-environment studies is valuable to prevent false negative findings. PMID:25329975

  18. Impact of IL-10 (-1082) promoter-single nucleotide polymorphism on the outcome of hepatitis C virus genotype 4 infection.

    PubMed

    Helal, Soheir F; Gomaa, Howayda E; Thabet, Eman H; Younan, Mariam A; Helmy, Neveen A

    2014-01-01

    Immunoregulatory cytokines may influence the hepatitis C virus (HCV) infection outcome. This study aimed to determine the genotypic and allelic frequencies of the interleukin (IL)-10 (-1082) G/A polymorphism, and its association with chronicity or resolution of HCV genotype 4 infection in Egypt. The frequencies of different dimorphic polymorphisms based on single nucleotide substitution in chronic HCV patients (50) and resolved HCV patients (50) were: IL-10 (-1082) G/G 22 (44%) and 18 (36%), G/A 19 (38%) and 24 (48%), and A/A 9 (18%), and 8 (16%), respectively. In the sustained virologic response (SVR) (36) and spontaneously resolved subjects (14) groups, the frequencies were: IL-10 (-1082) G/G 11 (30.6%) and 7 (50%) G/A 18 (50%) and 6 (42.9%), A/A 7 (19.4%) and 1 (7.1%), respectively. An association between male gender and chronic hepatitis C outcome (P value 0.041) was found. However, no significant gender difference was found when we compared females versus males with elevated alanine transaminase (ALT) levels in the chronic HCV patient group (P value = 1). No significant difference in the frequency of IL-10 single nucleotide polymorphism (SNP) at position 1082 was found between chronic and resolved HCV subjects.

  19. Isolation of midgut escape mutants of two American genotype dengue 2 viruses from Aedes aegypti

    PubMed Central

    2013-01-01

    Background Several studies have shown that American genotype dengue 2 viruses (DENV2) have reduced viral fitness in the mosquito vector, Aedes aegypti, compared to other DENV2 genotypes. Diminished replication efficiency or inability to efficiently traverse membrane barriers encompassing organs such as the midgut or salivary glands are considered major factors negatively impacting viral fitness in the mosquito. Results We analyzed the vector competence of Ae. aegypti for two American DENV2 strains, QR94 and PR159 originating from Mexico and Puerto-Rico, respectively. Both strains infected mosquito midguts following acquisition of infectious bloodmeals. However, DENV2-QR94 and DENV2-PR159 poorly disseminated from the midgut at 7 or 14 days post-bloodmeal (pbm). We detected one virus isolate, EM33, among 31 DENV2-QR94 infected mosquitoes, and one isolate, EM41, among 121 DENV2-PR159 infected mosquitoes, generating high virus titers in mosquito carcasses at 7 days pbm. In oral challenge experiments, EM33 and EM41 showed midgut dissemination rates of 40-50%. Replication efficiency of EM41 in secondary mosquito tissue was similar to that of a dissemination-competent control strain, whereas the replication efficiency of EM33 was significantly lower than that of the control virus. The genome sequence of DENV2-QR94 encoded seven unique amino acids (aa), which were not found in 100 of the most closely related DENV2 strains. EM33 had one additional aa change, E202K, in the E protein. DENV2-PR159 encoded four unique aa residues, one of them E202K, whereas EM41 had two additional aa substitutions, Q77E in the E protein and E93D in NS3. Conclusions Our results indicate that the midgut of Ae. aegypti acts as a selective sieve for DENV2 in which genetically distinct, dissemination-competent virus variants are rapidly selected from the viral quasispecies to be transmitted to vertebrates. PMID:23937713

  20. Proteomics insight into the biological safety of transgenic modification of rice as compared with conventional genetic breeding and spontaneous genotypic variation.

    PubMed

    Gong, Chun Yan; Li, Qi; Yu, Hua Tao; Wang, Zizhang; Wang, Tai

    2012-05-04

    The potential of unintended effects caused by transgenic events is a key issue in the commercialization of genetically modified (GM) crops. To investigate whether transgenic events cause unintended effects, we used comparative proteomics approaches to evaluate proteome differences in seeds from 2 sets of GM indica rice, herbicide-resistant Bar68-1 carrying bar and insect-resistant 2036-1a carrying cry1Ac/sck, and their respective controls D68 and MH86, as well as indica variety MH63, a parental line for breeding MH86, and japonica variety ZH10. This experimental design allowed for comparing proteome difference caused by transgenes, conventional genetic breeding, and natural genetic variation. Proteomics analysis revealed the maximum numbers of differentially expressed proteins between indica and japonica cultivars, second among indica varieties with relative small difference between MH86 and MH63, and the minimum between GM rice and respective control, thus indicating GM events do not substantially alter proteome profiles as compared with conventional genetic breeding and natural genetic variation. Mass spectrometry analysis revealed 234 proteins differentially expressed in the 6 materials, and these proteins were involved in different cellular and metabolic processes with a prominent skew toward metabolism (31.2%), protein synthesis and destination (25.2%), and defense response (22.4%). In these seed proteomes, proteins implicated in the 3 prominent biological processes showed significantly different composite expression patterns and were major factors differentiating japonica and indica cultivars, as well as indica varieties. Thus, metabolism, protein synthesis and destination, and defense response in seeds are important in differentiating rice cultivars and varieties.

  1. Methylenetetrahydrofolate reductase and thymidylate synthase genotypes and risk of acute graft-versus-host disease following hematopoietic cell transplantation for chronic myelogenous leukemia.

    PubMed

    Robien, Kim; Bigler, Jeannette; Yasui, Yutaka; Potter, John D; Martin, Paul; Storb, Rainer; Ulrich, Cornelia M

    2006-09-01

    Methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) play key roles in intracellular folate metabolism. Polymorphisms in these enzymes have been shown to modify toxicity of methotrexate (MTX) after hematopoietic cell transplantation. In this study, we evaluated the risk of acute graft-versus-host disease (GVHD) associated with genetic variation in recipient and donor MTHFR and TS genotypes to assess whether genotype alters the efficacy of MTX in acute GVHD prophylaxis. Data on the transplantation course were abstracted from medical records for 304 adults who received allogeneic hematopoietic cell transplants. MTHFR (C677T and A1298C) and TS (enhancer-region 28-base pair repeat, TSER, and 1494del6) genotypes were determined using polymerase chain reaction/restriction fragment length polymorphism and TaqMan assays. Multivariable logistic regression was used to assess the associations between genotypes and risk of acute GVHD. Compared with recipients with the wild-type MTHFR 677CC genotype, those with the variant 677T allele showed a decreased risk of detectable acute GVHD (677CT: odds ratio, 0.8; 95% confidence interval, 0.4-1.6; 677TT: odds ratio, 0.4; 95% confidence interval, 0.2-0.8; P for trend = .01). The variant MTHFR 1298C allele in recipients was associated with an increased risk of acute GVHD compared with the wild-type MTHFR 1298AA genotype (1298AC: odds ratio, 2.0; 95% confidence interval, 1.1-3.9; 1298CC: odds ratio, 3.6; 95% confidence interval, 1.0-12.7; P for trend < .01). No association with risk of acute GVHD was observed for donor MTHFR genotypes or for recipient or donor TS genotypes, with the exception of an increase in acute GVHD among recipients whose donors had the TSER 3R/2R genotype (odds ratio, 3.0; 95% confidence interval, 1.3-7.2). These findings indicate that host, but not donor, MTHFR genotypes modify the risk of acute GVHD in recipients receiving MTX, in a manner consistent with our previously reported associations

  2. Comparing sex steroid levels during the annual cycles of rainbow trout (Oncorhynchus mykiss) diploid female (XX) and triploid female (XXX) genotypic sex.

    PubMed

    Espinosa, E; Josa, A; Gil, L; Malo, C; Mitjana, O

    2013-02-01

    In this study, the annual cycle of the gonadal steroids testosterone (T), 11-ketotestosterone (11-KT), 17β-estradiol (E2) and 17α, 20β-dihydroxy-4-pregnen-3-one (DHP) was determined using radioimmunoassay and then compared for two populations of rainbow trout, XX diploid females (n = 40) and XXX triploid females (n = 15). In females, E2 and DHP levels were found to be significantly related to body weight (r = 0.22513; p < 0.0001 and r = 0.15831; p > 0.001, respectively). In this group, E2 concentrations peaked in November (25.05 ng/ml), while maximum DHP levels, only measurable from October to April, were attained in February (64.14 ng/ml). No significant differences in hormone ranges related to egg output ability were observed. Finally, sex steroid concentrations were low in the triploid female XXX fish compared to the female XX population. Nevertheless, maximum T (33.85 ng/ml) and 11-KT (32.35 ng/ml) levels were recorded in January, for XXX. The levels for these two hormones are relatively high and are also significantly associated (r = 0.8430; p < 0.0001). Diploid females showed significantly higher levels of E2 than triploids over the 12-month study period. The female triploid fish produced the lowest steroid hormone levels, such that these would be the most suitable for human consumption. © 2012 Blackwell Verlag GmbH.

  3. Water limitation and rootstock genotype interact to alter grape berry metabolism through transcriptome reprogramming

    PubMed Central

    Berdeja, Mariam; Nicolas, Philippe; Kappel, Christian; Dai, Zhan Wu; Hilbert, Ghislaine; Peccoux, Anthony; Lafontaine, Magali; Ollat, Nathalie; Gomès, Eric; Delrot, Serge

    2015-01-01

    Grapevine is a perennial crop often cultivated by grafting a scion cultivar on a suitable rootstock. Rootstocks influence scions, particularly with regard to water uptake and vigor. Therefore, one of the possibilities to adapt viticulture to the extended drought stress periods is to select rootstocks conferring increased tolerance to drought. However, the molecular mechanisms associated with the ability of rootstock/scion combination to influence grape berry metabolism under drought stress are still poorly understood. The transcriptomic changes induced by drought stress in grape berries (cv. Pinot noir) from vines grafted on either 110R (drought-tolerant) or 125AA (drought-sensitive) rootstock were compared. The experiments were conducted in the vineyard for two years and two grape berry developmental stages (50% and 100% veraison). The genome-wide microarray approach showed that water stress strongly impacts gene expression in the berries, through ontology categories that cover cell wall metabolism, primary and secondary metabolism, signaling, stress, and hormones, and that some of these effects strongly depend on the rootstock genotype. Indeed, under drought stress, berries from vines grafted on 110R displayed a different transcriptional response compared to 125AA-concerning genes related to jasmonate (JA), phenylpropanoid metabolism, and pathogenesis-related proteins. The data also suggest a link between JA and secondary metabolism in water-stressed berries. Overall, genes related to secondary metabolism and JA are more induced and/or less repressed by drought stress in the berries grafted on the drought-sensitive rootstock 125AA. These rootstock-dependent gene expression changes are relevant for berry composition and sensory properties. PMID:26504567

  4. Distribution of HBV genotypes in Poland.

    PubMed

    Świderska, Magdalena; Pawłowska, Małgorzata; Mazur, Włodzimierz; Tomasiewicz, Krzysztof; Simon, Krzysztof; Piekarska, Anna; Wawrzynowicz-Syczewska, Marta; Jaroszewicz, Jerzy; Rajewski, Paweł; Zasik, Ewelina; Murias-Bryłowska, Elżbieta; Pniewska, Anna; Halota, Waldemar; Flisiak, Robert

    2015-05-01

    To identify distribution of HBV genotypes in particular regions of Poland. The study included 270 treatment-naïve, HBV-infected individuals, enrolled in 7 centers of Poland. HBV genotyping was performed in 243 of them with the INNO-LiPA HBV Genotyping assay (Innogenetics). Genotype A present in 2/3 patients was demonstrated as the most predominant in Poland. It was followed by D (20%), H (5%) and mixed A + D (5%). Remaining patients were infected with genotype F, mixed D + G, A + C or D + F. Analysis of distribution demonstrated regional differences, with a higher rate of genotype D prevalence (about 30%) in the eastern (Białystok and Lublin) and south-western (Wrocław) parts compared to other regions, where the prevalence rate was below 15%. The highest prevalence of genotype A (exceeding 80%) was observed in central Poland (Bydgoszcz, Łódź). The presented data reveal the current distribution of HBV genotypes across Poland, which is the first and the largest such epidemiological analysis.

  5. Analyses of Genotypes and Phenotypes of Ten Chinese Patients with Wolf-Hirschhorn Syndrome by Multiplex Ligation-dependent Probe Amplification and Array Comparative Genomic Hybridization

    PubMed Central

    Yang, Wen-Xu; Pan, Hong; Li, Lin; Wu, Hai-Rong; Wang, Song-Tao; Bao, Xin-Hua; Jiang, Yu-Wu; Qi, Yu

    2016-01-01

    Background: Wolf-Hirschhorn syndrome (WHS) is a contiguous gene syndrome that is typically caused by a deletion of the distal portion of the short arm of chromosome 4. However, there are few reports about the features of Chinese WHS patients. This study aimed to characterize the clinical and molecular cytogenetic features of Chinese WHS patients using the combination of multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (array CGH). Methods: Clinical information was collected from ten patients with WHS. Genomic DNA was extracted from the peripheral blood of the patients. The deletions were analyzed by MLPA and array CGH. Results: All patients exhibited the core clinical symptoms of WHS, including severe growth delay, a Greek warrior helmet facial appearance, differing degrees of intellectual disability, and epilepsy or electroencephalogram anomalies. The 4p deletions ranged from 2.62 Mb to 17.25 Mb in size and included LETM1, WHSC1, and FGFR3. Conclusions: The combined use of MLPA and array CGH is an effective and specific means to diagnose WHS and allows for the precise identification of the breakpoints and sizes of deletions. The deletion of genes in the WHS candidate region is closely correlated with the core WHS phenotype. PMID:26960370

  6. Human Monoclonal Antibodies to a Novel Cluster of Conformational Epitopes on HCV E2 with Resistance to Neutralization Escape in a Genotype 2a Isolate

    PubMed Central

    Keck, Zhen-yong; Xia, Jinming; Wang, Yong; Wang, Wenyan; Krey, Thomas; Prentoe, Jannick; Carlsen, Thomas; Li, Angela Ying-Jian; Patel, Arvind H.; Lemon, Stanley M.; Bukh, Jens; Rey, Felix A.; Foung, Steven K. H.

    2012-01-01

    The majority of broadly neutralizing antibodies to hepatitis C virus (HCV) are against conformational epitopes on the E2 glycoprotein. Many of them recognize overlapping epitopes in a cluster, designated as antigenic domain B, that contains residues G530 and D535. To gain information on other regions that will be relevant for vaccine design, we employed yeast surface display of antibodies that bound to genotype 1a H77C E2 mutant proteins containing a substitution either at Y632A (to avoid selecting non-neutralizing antibodies) or D535A. A panel of nine human monoclonal antibodies (HMAbs) was isolated and designated as HC-84-related antibodies. Each HMAb neutralized cell culture infectious HCV (HCVcc) with genotypes 1–6 envelope proteins with varying profiles, and each inhibited E2 binding to the viral receptor CD81. Five of these antibodies neutralized representative genotypes 1–6 HCVcc. Epitope mapping identified a cluster of overlapping epitopes that included nine contact residues in two E2 regions encompassing aa418–446 and aa611–616. Effect on virus entry was measured using H77C HCV retroviral pseudoparticles, HCVpp, bearing an alanine substitution at each of the contact residues. Seven of ten mutant HCVpp showed over 90% reduction compared to wild-type HCVpp and two others showed approximately 80% reduction. Interestingly, four of these antibodies bound to a linear E2 synthetic peptide encompassing aa434–446. This region on E2 has been proposed to elicit non-neutralizing antibodies in humans that interfere with neutralizing antibodies directed at an adjacent E2 region from aa410–425. The isolation of four HC-84 HMAbs binding to the peptide, aa434–446, proves that some antibodies to this region are to highly conserved epitopes mediating broad virus neutralization. Indeed, when HCVcc were passaged in the presence of each of these antibodies, virus escape was not observed. Thus, the cluster of HC-84 epitopes, designated as antigenic domain D, is

  7. Comparative Genotypic and Phenotypic Analysis of Cronobacter Species Cultured from Four Powdered Infant Formula Production Facilities: Indication of Pathoadaptation along the Food Chain

    PubMed Central

    Yan, Qiongqiong; Wang, Juan; Gangiredla, Jayanthi; Cao, Yu; Martins, Marta; Gopinath, Gopal R.; Stephan, Roger; Lampel, Keith; Tall, Ben D.

    2015-01-01

    Cronobacter species are opportunistic pathogens commonly found in the environment. Among the seven Cronobacter species, Cronobacter sakazakii sequence type 4 (ST-4) is predominantly associated with recorded cases of infantile meningitis. This study reports on a 26-month powdered infant formula (PIF) surveillance program in four production facilities located in distinct geographic regions. The objective was to identify the ST(s) in PIF production environments and to investigate the phenotypic features that support their survival. Of all 168 Cronobacter isolates, 133 were recovered from a PIF production environment, 31 were of clinical origin, and 4 were laboratory type strains. Sequence type 1 (n = 84 isolates; 63.9%) was the dominant type in PIF production environments. The majority of these isolates clustered with an indistinguishable pulsotype and persisted for at least an 18-month period. Moreover, DNA microarray results identified two phylogenetic lineages among ST-4 strains tested. Thereafter, the ST-1 and -4 isolates were phenotypically compared. Differences were noted based on the phenotypes expressed by these isolates. The ST-1 PIF isolates produced stronger biofilms at both 28°C and 37°C, while the ST-4 clinical isolates exhibited greater swimming activity and increased binding to Congo red dye. Given the fact that PIF is a low-moisture environment and that the clinical environment provides for an interaction between the pathogen and its host, these differences may be consistent with a form of pathoadaptation. These findings help to extend our current understanding of the epidemiology and ecology of Cronobacter species in PIF production environments. PMID:25911470

  8. AAS 228: Day 1 afternoon

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-06-01

    Editors Note:This week were at the 228th AAS Meeting in San Diego, CA. Along with a team ofauthors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting twiceeach day. Follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.Plenary Session: From Space Archeology to Serving the World Today: A 20-year Journey from the Jungles of Guatemala to a Network of Satellite Remote Sensing Facilities Around the World(by Michael Zevin)In the conferences second plenary session, NASAs Daniel Irwin turned the eyes of the conference back to Earth by highlighting the huge impact that NASA missions play in protecting and developing our own planet.Daniel Irwin: using satellite imagery to detect differences in vegetation and find ancient Mayan cities. #aas228 pic.twitter.com/9LFPQdCHTM astrobites (@astrobites) June 13, 2016Irwin came to be involved in NASA through his work mapping Guatemalan jungles, where he would spend 22 days at a time exploring the treacherous jungles on foot armed with a 1st generation GPS, a compass, and a machete. A colleague introduced Irwin to the satellite imagery thathe was exploring, demonstratinghow these images are a strong complement to field work. The sharing of this satellite data with nearby villages helped to show the encroachment of agriculture and the necessity of connecting space to the village. Satellite imagery also played a role in archeological endeavors, uncovering dozens of Mayan cities that have been buried for over a millennia by vegetation, and it provided evidence that the fall of the Mayan civilization may have been due to massive deforestation that ledto drought.Glacial retreat in Chile imaged by ISERV.Irwin displayed the constellation of NASAs Earth-monitoring satellites that have played an integral role in conserving our planet and alerting the world of natural disasters. He also showed

  9. Comparison between genotyping by sequencing and SNP-chip genotyping in QTL mapping in wheat

    USDA-ARS?s Scientific Manuscript database

    Array- or chip-based single nucleotide polymorphism (SNP) markers are widely used in genomic studies because of their abundance in a genome and cost less per data point compared to older marker technologies. Genotyping by sequencing (GBS), a relatively newer approach of genotyping, suggests equal or...

  10. Comparative Genotypes, Staphylococcal Cassette Chromosome mec (SCCmec) Genes and Antimicrobial Resistance amongst Staphylococcus epidermidis and Staphylococcus haemolyticus Isolates from Infections in Humans and Companion Animals.

    PubMed

    McManus, Brenda A; Coleman, David C; Deasy, Emily C; Brennan, Gráinne I; O' Connell, Brian; Monecke, Stefan; Ehricht, Ralf; Leggett, Bernadette; Leonard, Nola; Shore, Anna C

    2015-01-01

    This study compares the characteristics of Staphylococcus epidermidis (SE) and Staphylococcus haemolyticus (SH) isolates from epidemiologically unrelated infections in humans (Hu) (28 SE-Hu; 8 SH-Hu) and companion animals (CpA) (12 SE-CpA; 13 SH-CpA). All isolates underwent antimicrobial susceptibility testing, multilocus sequence typing and DNA microarray profiling to detect antimicrobial resistance and SCCmec-associated genes. All methicillin-resistant (MR) isolates (33/40 SE, 20/21 SH) underwent dru and mecA allele typing. Isolates were predominantly assigned to sequence types (STs) within a single clonal complex (CC2, SE, 84.8%; CC1, SH, 95.2%). SCCmec IV predominated among MRSE with ST2-MRSE-IVc common to both Hu (40.9%) and CpA (54.5%). Identical mecA alleles and nontypeable dru types (dts) were identified in one ST2-MRSE-IVc Hu and CpA isolate, however, all mecA alleles and 2/4 dts detected among 18 ST2-MRSE-IVc isolates were closely related, sharing >96.5% DNA sequence homology. Although only one ST-SCCmec type combination (ST1 with a non-typeable [NT] SCCmec NT9 [class C mec and ccrB4]) was common to four MRSH-Hu and one MRSH-CpA, all MRSH isolates were closely related based on similar STs, SCCmec genes (V/VT or components thereof), mecA alleles and dts. Overall, 39.6% of MR isolates harbored NT SCCmec elements, and ACME was more common amongst MRSE and CpA isolates. Multidrug resistance (MDR) was detected among 96.7% of isolates but they differed in the prevalence of specific macrolide, aminoglycoside and trimethoprim resistance genes amongst SE and SH isolates. Ciprofloxacin, rifampicin, chloramphenicol [fexA, cat-pC221], tetracycline [tet(K)], aminoglycosides [aadD, aphA3] and fusidic acid [fusB] resistance was significantly more common amongst CpA isolates. SE and SH isolates causing infections in Hu and CpA hosts belong predominantly to STs within a single lineage, harboring similar but variable SCCmec genes, mecA alleles and dts. Host and

  11. Comparative Genotypes, Staphylococcal Cassette Chromosome mec (SCCmec) Genes and Antimicrobial Resistance amongst Staphylococcus epidermidis and Staphylococcus haemolyticus Isolates from Infections in Humans and Companion Animals

    PubMed Central

    McManus, Brenda A.; Coleman, David C.; Deasy, Emily C.; Brennan, Gráinne I.; O’ Connell, Brian; Monecke, Stefan; Ehricht, Ralf; Leggett, Bernadette; Leonard, Nola; Shore, Anna C.

    2015-01-01

    This study compares the characteristics of Staphylococcus epidermidis (SE) and Staphylococcus haemolyticus (SH) isolates from epidemiologically unrelated infections in humans (Hu) (28 SE-Hu; 8 SH-Hu) and companion animals (CpA) (12 SE-CpA; 13 SH-CpA). All isolates underwent antimicrobial susceptibility testing, multilocus sequence typing and DNA microarray profiling to detect antimicrobial resistance and SCCmec-associated genes. All methicillin-resistant (MR) isolates (33/40 SE, 20/21 SH) underwent dru and mecA allele typing. Isolates were predominantly assigned to sequence types (STs) within a single clonal complex (CC2, SE, 84.8%; CC1, SH, 95.2%). SCCmec IV predominated among MRSE with ST2-MRSE-IVc common to both Hu (40.9%) and CpA (54.5%). Identical mecA alleles and nontypeable dru types (dts) were identified in one ST2-MRSE-IVc Hu and CpA isolate, however, all mecA alleles and 2/4 dts detected among 18 ST2-MRSE-IVc isolates were closely related, sharing >96.5% DNA sequence homology. Although only one ST-SCCmec type combination (ST1 with a non-typeable [NT] SCCmec NT9 [class C mec and ccrB4]) was common to four MRSH-Hu and one MRSH-CpA, all MRSH isolates were closely related based on similar STs, SCCmec genes (V/VT or components thereof), mecA alleles and dts. Overall, 39.6% of MR isolates harbored NT SCCmec elements, and ACME was more common amongst MRSE and CpA isolates. Multidrug resistance (MDR) was detected among 96.7% of isolates but they differed in the prevalence of specific macrolide, aminoglycoside and trimethoprim resistance genes amongst SE and SH isolates. Ciprofloxacin, rifampicin, chloramphenicol [fexA, cat-pC221], tetracycline [tet(K)], aminoglycosides [aadD, aphA3] and fusidic acid [fusB] resistance was significantly more common amongst CpA isolates. SE and SH isolates causing infections in Hu and CpA hosts belong predominantly to STs within a single lineage, harboring similar but variable SCCmec genes, mecA alleles and dts. Host and

  12. Antioxidant Bioactive Compounds Changes in Fruit of Quince Genotypes Over Cold Storage.

    PubMed

    Moradi, Samira; Koushesh Saba, Mahmoud; Mozafari, Ali Akbar; Abdollahi, Hamid

    2016-07-01

    Quince fruit has many benefits to human health and is excellent source of bioactive compounds. The fruit of 15 quince genotypes stored at 2 °C for 5 mo to study fruit quality changes during cold storage. Fruit were sampled monthly and stored at 20 °C for 24 h. Fruit ascorbic acid (AA), total phenol (TP), and total flavonoid (TF) concentrations, total antioxidant activity (TAA), flesh browning (FB) incidence, polyphenol oxidase (PPO), peroxidase (POX), and superoxide dismutase (SOD) activities were measured during storage. A high variation in bioactive compounds was observed across genotypes. The range of 26.8 to 44.4 mg/100 g FW for AA, 86.7% to 98.2% for TAA, 157.7 to 380.7 mg GAE 100(-1) g FW for TP, and 5.3 to 10.7 mg/100 g FW for TF were observed across genotypes at harvest time. The overall AA, TAA, TP, TF, and SOD decreased while PPO and POX increased during storage. FB was first observed after 4 mo and increased thereafter while the FB index was different across genotypes. Higher bioactive content may prevent or reduce FB index so that a negative correlation was found between FB and AA, TAA, TP, TF, and SOD. © 2016 Institute of Food Technologists®

  13. Combined genotype and haplotype distributions of MTHFR C677T and A1298C polymorphisms

    PubMed Central

    Fan, Shujun; Yang, Boyi; Zhi, Xueyuan; Wang, Yanxun; Zheng, Quanmei; Sun, Guifan

    2016-01-01

    Abstract Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms are, independently and/or in combination, associated with many disorders. However, data on the combined genotype and haplotype distributions of the 2 polymorphisms in Chinese population were limited. We recruited 13,473 adult women from 9 Chinese provinces, collected buccal cell samples, and determined genotypes, to estimate the combined genotype and haplotype distributions of the MTHFR C677T and A1298C polymorphisms. In the total sample, the 6 common combined genotypes were CT/AA (29.5%), TT/AA (21.9%), CC/AA (15.4%), CC/AC (14.9%), CT/AC (13.7%), and CC/CC (3.4%); the 3 frequent haplotypes were 677T-1298A (43.6%), 677C-1298A (37.9%), and 677C-1298C (17.6%). Importantly, we observed that there were 51 (0.4%) individuals with the CT/CC genotype, 92 (0.7%) with the TT/AC genotype, 17 (0.1%) with the TT/CC genotype, and that the frequency of the 677T-1298C haplotype was 0.9%. In addition, the prevalence of some combined genotypes and haplotypes varied among populations residing in different areas and even showed apparent geographical gradients. Further linkage disequilibrium analysis showed that the D’ and r2 values were 0.883 and 0.143, respectively. In summary, the findings of our study provide further strong evidence that the MTHFR C677T and A1298C polymorphisms are usually in trans and occasionally in cis configurations. The frequencies of mutant genotype combinations were relatively higher in Chinese population than other populations, and showed geographical variations. These baseline data would be useful for future related studies and for developing health management programs. PMID:27902594

  14. Donor KIR B Genotype Improves Progression-Free Survival of Non-Hodgkin Lymphoma Patients Receiving Unrelated Donor Transplantation.

    PubMed

    Bachanova, Veronika; Weisdorf, Daniel J; Wang, Tao; Marsh, Steven G E; Trachtenberg, Elizabeth; Haagenson, Michael D; Spellman, Stephen R; Ladner, Martha; Guethlein, Lisbeth A; Parham, Peter; Miller, Jeffrey S; Cooley, Sarah A

    2016-09-01

    Donor killer immunoglobulin-like receptor (KIR) genotypes are associated with relapse protection and survival after allotransplantation for acute myelogenous leukemia. We examined the possibility of a similar effect in a cohort of 614 non-Hodgkin lymphoma (NHL) patients receiving unrelated donor (URD) T cell-replete marrow or peripheral blood grafts. Sixty-four percent (n = 396) of donor-recipient pairs were 10/10 allele HLA matched and 26% were 9/10 allele matched. Seventy percent of donors had KIR B/x genotype; the others had KIR A/A genotype. NHL patients receiving 10/10 HLA-matched URD grafts with KIR B/x donors experienced significantly lower relapse at 5 years (26%; 95% confidence interval [CI], 21% to 32% versus 37%; 95% CI, 27% to 46%; P = .05) compared with KIR A/A donors, resulting in improved 5-year progression-free survival (PFS) (35%; 95% CI, 26% to 44% versus 22%; 95% CI, 11% to 35%; P = .007). In multivariate analysis, use of KIR B/x donors was associated with significantly reduced relapse risk (relative risk [RR], .63, P = .02) and improved PFS (RR, .71, P = .008). The relapse protection afforded by KIR B/x donors was not observed in HLA-mismatched transplantations and was not specific to any particular KIR-B gene. Selecting 10/10 HLA-matched and KIR B/x donors should benefit patients with NHL receiving URD allogeneic transplantation. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  15. Endothelin-1, oxidative stress and endogenous ANGII: mechanisms of AT1-AA-enhanced Renal and Blood Pressure Response during pregnancy

    PubMed Central

    Brewer, Justin; Liu, Ruisheng; Lu, Yan; Scott, Jeremy; Wallace, Kedra; Wallukat, Gerd; Moseley, Janae; Herse, Florian; Dechend, Ralf; Martin, James N.; LaMarca, Babbette

    2013-01-01

    Hypertension during preeclampsia is associated with increased maternal vascular sensitivity to angiotensin II (ANGII). This study was designed to determine mechanisms whereby agonistic autoantibodies to the ANGII type I receptor (AT1-AA) enhance blood pressure (MAP) and renal vascular sensitivity to ANGII during pregnancy. First, we examined MAP and renal artery resistance index (RARI) in response to chronic administration of ANGII or AT1-AA or AT1-AA+ANGII in pregnant rats compared to control pregnant rats. In order to examine mechanisms of heightened sensitivity in response to AT1-AA during pregnancy we examined the role of endogenous ANGII in AT1-AA infused pregnant rats, Endothelin-1 and oxidative stress in AT1-AA+ANGII treated rats. Chronic ANGII increased MAP from 95 +/−2 in NP rats to 115 +/−2 mmHg. Chronic AT1-AA increased MAP to 118+/−1 mmHg in NP rats which further increased to 123+/−2 with AT1-AA+ANGII. Increasing ANGII from (10−11-10−8) decreased Af-Art diameter 15-20% but sharply decreased Af-Art diameter 60% in AT1-AA pretreated vessels. RARI increased from 0.67 in NP rats to 0.70 with AT1-AA infusion, which was exacerbated to 0.74 in AT1-AA + ANGII infused rats. AT1-AA-induced hypertension decreased with Enalapril but was not attenuated. Both tissue ET-1 and ROS increased with AT1-AA+ANGII compared to AT1-AA alone and blockade of either of these pathways had significant effects on MAP or RARI. These data support the hypothesis that AT1-AA, via activation of ET-1 and oxidative stress and interaction with endogenous ANGII, are important mechanisms whereby MAP and renal vascular responses are enhanced during preeclampsia. PMID:24041954

  16. Genotype 3 is the predominant hepatitis C genotype in a multi-ethnic Asian population in Malaysia.

    PubMed

    Ho, Shiaw-Hooi; Ng, Kee-Peng; Kaur, Harvinder; Goh, Khean-Lee

    2015-06-01

    Genotypes of hepatitis C virus (HCV) are distributed differently across the world. There is a paucity of such data in a multi-ethnic Asian population like Malaysia. The objectives of this study were to determine the distribution of HCV genotypes between major ethnic groups and to ascertain their association with basic demographic variables like age and gender. This was a cross-sectional prospective study conducted from September 2007 to September 2013. Consecutive patients who were detected to have anti-HCV antibodies in the University of Malaya Medical Centre were included and tested for the presence of HCV RNA using Roche Cobas Amplicor Analyzer and HCV genotype using Roche single Linear Array HCV Genotyping strip. Five hundred and ninety-six subjects were found to have positive anti-HCV antibodies during this period of time. However, only 396 (66.4%) were HCV RNA positive and included in the final analysis. Our results showed that HCV genotype 3 was the predominant genotype with overall frequency of 61.9% followed by genotypes 1 (35.9%), 2 (1.8%) and 6 (0.5%). There was a slightly higher prevalence of HCV genotype 3 among the Malays when compared to the Chinese (P=0.043). No other statistical significant differences were observed in the distribution of HCV genotypes among the major ethnic groups. There was also no association between the predominant genotypes and basic demographic variables. In a multi-ethnic Asian society in Malaysia, genotype 3 is the predominant genotype among all the major ethnic groups with genotype 1 as the second commonest genotype. Both genotypes 2 and 6 are uncommon. Neither genotype 4 nor 5 was detected. There is no identification of HCV genotype according to ethnic origin, age and gender.

  17. Methylenetetrahydrofolate reductase A1298C genotypes are associated with the risks of acute lymphoblastic leukaemia and chronic myelogenous leukaemia in the Korean population.

    PubMed

    Hur, M; Park, J Y; Cho, H C; Lee, K M; Shin, H Y; Cho, H I

    2006-06-01

    Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme involved in folate metabolism, DNA methylation and synthesis. We investigated the association between MTHFR polymorphisms and the risks of acute and chronic leukaemias. MTHFR C677T and A1298C were genotyped in 396 Korean individuals using multiplex polymerase chain reaction/restriction fragment-length polymorphism. They were acute lymphoblastic leukaemia (ALL, n = 89), acute myeloid leukaemia (AML, n = 55), biphenotypic acute leukaemia (n = 12), chronic myelogenous leukaemia (CML, n = 40), and normal controls (n = 200). C677T genotypes were not associated with the risk of each disease. A1298C variants, however, significantly decreased the risks of ALL and CML compared with 1298AA. Odds ratios and 95% confidence intervals of 1298AC and 1298AC + CC were 0.53 (0.31-0.93) and 0.54 (0.31-0.93) in ALL, and 0.34 (0.14-0.80) and 0.40 (0.18-0.89) in CML, respectively, compared with 1298AA. These findings demonstrate that the development of ALL and CML is more dependent on folate status, and more susceptible to DNA instability than that of AML. In addition, A1298C rather than C677T may be a more important genetic risk modifier in leukaemogenesis at least in the Korean population.

  18. Selection and characterization of resistance to the Vip3Aa20 protein from Bacillus thuringiensis in Spodoptera frugiperda.

    PubMed

    Bernardi, Oderlei; Bernardi, Daniel; Horikoshi, Renato J; Okuma, Daniela M; Miraldo, Leonardo L; Fatoretto, Julio; Medeiros, Fernanda Cl; Burd, Tony; Omoto, Celso

    2016-09-01

    Spodoptera frugiperda is one the main target pests of maize events expressing Vip3Aa20 protein from Bacillus thuringiensis (Bt) in Brazil. In this study, we selected a resistant strain of S. frugiperda on Bt maize expressing Vip3Aa20 protein and characterized the inheritance and fitness costs of the resistance. The resistance ratio of the Vip3Aa20-resistant strain of S. frugiperda was >3200-fold. Neonates of the Vip3Aa20-resistant strain were able to survive and emerge as fertile adults on Vip3Aa20 maize, while larvae from susceptible and heterozygous strains did not survive. The inheritance of Vip3Aa20 resistance was autosomal recessive and monogenic. Life history studies to investigate fitness cost revealed an 11% reduction in the survival rate until adult stage and a ∼50% lower reproductive rate of the Vip3Aa20-resistant strain compared with susceptible and heterozygous strains. This is the first characterization of S. frugiperda resistance to Vip3Aa protein. Our results provide useful information for resistance management programs designed to prevent or delay resistance evolution to Vip3Aa proteins in S. frugiperda. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  19. Whole body gamma radiation and marrow sensitivity: A comparative study between adult rats of eight different strains

    SciTech Connect

    Smith, G.S.; Elshafie, M.S.; Abdelrahman, H.G.

    1996-10-01

    Rats of Fischer-344 strain is quite resistant to whole-body gamma radiation. There is a genetic difference in rat hemoglobin (Hb) {beta}-chain structure, with alternate alleles, A and B, at a single locus. This study was designed to find out whether marrow sensitivity due to sublethal gamma exposure in age matched adult rats is entirely strain specific or a combination of both strain and Hb genotype specific. Eight strains of rats comprising of Hb genotypes AA and BB were studied. Several hematological parameters reflecting marrow evaluation were analyzed and compared. The data to be presented indicate that there is a partialmore » but distinct relationship between radiosensitivity and Hb genotypes.« less

  20. Signaling Pathways Related to Protein Synthesis and Amino Acid Concentration in Pig Skeletal Muscles Depend on the Dietary Protein Level, Genotype and Developmental Stages

    PubMed Central

    Liu, Yingying; Li, Fengna; Kong, Xiangfeng; Tan, Bie; Li, Yinghui; Duan, Yehui; Blachier, François; Hu, Chien-An A.; Yin, Yulong

    2015-01-01

    Muscle growth is regulated by the homeostatic balance of the biosynthesis and degradation of muscle proteins. To elucidate the molecular interactions among diet, pig genotype, and physiological stage, we examined the effect of dietary protein concentration, pig genotype, and physiological stages on amino acid (AA) pools, protein deposition, and related signaling pathways in different types of skeletal muscles. The study used 48 Landrace pigs and 48 pure-bred Bama mini-pigs assigned to each of 2 dietary treatments: lower/GB (Chinese conventional diet)- or higher/NRC (National Research Council)-protein diet. Diets were fed from 5 weeks of age to respective market weights of each genotype. Samples of biceps femoris muscle (BFM, type I) and longissimus dorsi muscle (LDM, type II) were collected at nursery, growing, and finishing phases according to the physiological stage of each genotype, to determine the AA concentrations, mRNA levels for growth-related genes in muscles, and protein abundances of mechanistic target of rapamycin (mTOR) signaling pathway. Our data showed that the concentrations of most AAs in LDM and BFM of pigs increased (P<0.05) gradually with increasing age. Bama mini-pigs had generally higher (P<0.05) muscle concentrations of flavor-related AA, including Met, Phe, Tyr, Pro, and Ser, compared with Landrace pigs. The mRNA levels for myogenic determining factor, myogenin, myocyte-specific enhancer binding factor 2 A, and myostatin of Bama mini-pigs were higher (P<0.05) than those of Landrace pigs, while total and phosphorylated protein levels for protein kinase B, mTOR, and p70 ribosomal protein S6 kinases (p70S6K), and ratios of p-mTOR/mTOR, p-AKT/AKT, and p-p70S6K/p70S6K were lower (P<0.05). There was a significant pig genotype-dependent effect of dietary protein on the levels for mTOR and p70S6K. When compared with the higher protein-NRC diet, the lower protein-GB diet increased (P<0.05) the levels for mTOR and p70S6K in Bama mini-pigs, but

  1. Comparative phenotypic and genotypic analysis of Edwardsiella spp. isolates from different hosts and geographic origins, with an emphasis on isolates formerly classified as E. tarda and an evaluation of diagnostic methods

    USDA-ARS?s Scientific Manuscript database

    Aims: Conventional phenotypic and genotypic analyses for the differentiation of phenotypically ambiguous Edwardsiella congeners was evaluated and historical E. tarda designations were linked to current taxonomic nomenclature. Methods and Results: Forty-seven Edwardsiella spp. isolates recovered over...

  2. Obesity is a significant susceptibility factor for idiopathic AA amyloidosis.

    PubMed

    Blank, Norbert; Hegenbart, Ute; Dietrich, Sascha; Brune, Maik; Beimler, Jörg; Röcken, Christoph; Müller-Tidow, Carsten; Lorenz, Hanns-Martin; Schönland, Stefan O

    2018-03-01

    To investigate obesity as susceptibility factor in patients with idiopathic AA amyloidosis. Clinical, biochemical and genetic data were obtained from 146 patients with AA amyloidosis. Control groups comprised 40 patients with long-standing inflammatory diseases without AA amyloidosis and 56 controls without any inflammatory disease. Patients with AA amyloidosis had either familial Mediterranean fever (FMF) or long-standing rheumatic diseases as underlying inflammatory disease (n = 111, median age 46 years). However, in a significant proportion of patients with AA amyloidosis no primary disease was identified (idiopathic AA; n = 37, median age 60 years). Patients with idiopathic AA amyloidosis were more obese and older than patients with AA amyloidosis secondary to FMF or rheumatic diseases. Serum leptin levels correlated with the body mass index (BMI) in all types of AA amyloidosis. Elevated leptin levels of more than 30 µg/l were detected in 18% of FMF/rheumatic + AA amyloidosis and in 40% of patients with idiopathic AA amyloidosis (p = .018). Finally, the SAA1 polymorphism was confirmed as a susceptibility factor for AA amyloidosis irrespective of the type of the disease. Obesity, age and the SAA1 polymorphism are susceptibility factors for idiopathic AA amyloidosis. Recent advances in treatment of FMF and rheumatic disorders will decrease the incidence of AA amyloidosis due to these diseases. Idiopathic AA, however, might be an emerging problem in the ageing and increasingly obese population.

  3. Microstructure and hardness performance of AA6061 aluminium composite using friction stir processing

    NASA Astrophysics Data System (ADS)

    Marini, C. D.; Fatchurrohman, N.

    2018-04-01

    Rice husk ash (RHA) is an industrial waste that has become a potential reinforced material for aluminium matrix composite (AMCs) due to low cost and abundantly available resources. Friction stir processing (FSP) has been introduced as a method to modify surface properties of the metal and alloy including theirs composite as well. The present work reports the production and characterization of AA6061 and AA6061/5 vol% RHA using FSP using parameters rotation speed 1000 rpm and traversed speed 25 mm/min. The microstructure was studied using optical microscopy (OM). A homogenous dispersion of RHA particles was obtained in the composite. No agglomeration or segregation was observed. The produced composite exhibited a fine grain structure. An improvement in hardness profile was observed as AA6061/5 vol% RHA improves in hardness compared to FSPed of AA6061 without reinforcement.

  4. Genotype imputation in the domestic dog

    PubMed Central

    Meurs, K. M.

    2016-01-01

    Application of imputation methods to accurately predict a dense array of SNP genotypes in the dog could provide an important supplement to current analyses of array-based genotyping data. Here, we developed a reference panel of 4,885,283 SNPs in 83 dogs across 15 breeds using whole genome sequencing. We used this panel to predict the genotypes of 268 dogs across three breeds with 84,193 SNP array-derived genotypes as inputs. We then (1) performed breed clustering of the actual and imputed data; (2) evaluated several reference panel breed combinations to determine an optimal reference panel composition; and (3) compared the accuracy of two commonly used software algorithms (Beagle and IMPUTE2). Breed clustering was well preserved in the imputation process across eigenvalues representing 75 % of the variation in the imputed data. Using Beagle with a target panel from a single breed, genotype concordance was highest using a multi-breed reference panel (92.4 %) compared to a breed-specific reference panel (87.0 %) or a reference panel containing no breeds overlapping with the target panel (74.9 %). This finding was confirmed using target panels derived from two other breeds. Additionally, using the multi-breed reference panel, genotype concordance was slightly higher with IMPUTE2 (94.1 %) compared to Beagle; Pearson correlation coefficients were slightly higher for both software packages (0.946 for Beagle, 0.961 for IMPUTE2). Our findings demonstrate that genotype imputation from SNP array-derived data to whole genome-level genotypes is both feasible and accurate in the dog with appropriate breed overlap between the target and reference panels. PMID:27129452

  5. MDCT evaluation of acute aortic syndrome (AAS)

    PubMed Central

    Rossi, Giovanni; Lassandro, Francesco; Rea, Gaetano; Marino, Maurizio; Muto, Maurizio; Molino, Antonio; Scaglione, Mariano

    2016-01-01

    Non-traumatic acute thoracic aortic syndromes (AAS) describe a spectrum of life-threatening aortic pathologies with significant implications on diagnosis, therapy and management. There is a common pathway for the various manifestations of AAS that eventually leads to a breakdown of the aortic intima and media. Improvements in biology and health policy and diffusion of technology into the community resulted in an associated decrease in mortality and morbidity related to aortic therapeutic interventions. Hybrid procedures, branched and fenestrated endografts, and percutaneous aortic valves have emerged as potent and viable alternatives to traditional surgeries. In this context, current state-of-the art multidetector CT (MDCT) is actually the gold standard in the emergency setting because of its intrinsic diagnostic value. Management of acute aortic disease has changed with the increasing realization that endovascular therapies may offer distinct advantages in these situations. This article provides a summary of AAS, focusing especially on the MDCT technique, typical and atypical findings and common pitfalls of AAS, as well as recent concepts regarding the subtypes of AAS, consisting of aortic dissection, intramural haematoma, penetrating atherosclerotic ulcer and unstable aortic aneurysm or contained aortic rupture. MDCT findings will be related to pathophysiology, timing and management options to achieve a definite and timely diagnostic and therapeutic definition. In the present article, we review the aetiology, pathophysiology, clinical presentation, outcomes and therapeutic approaches to acute aortic syndromes. PMID:27033344

  6. Antibodies Targeting Novel Neutralizing Epitopes of Hepatitis C Virus Glycoprotein Preclude Genotype 2 Virus Infection

    PubMed Central

    Rao, Huiying; Jiang, Dong; Wang, Jianghua; Xie, Xingwang; Wei, Lai

    2015-01-01

    Currently, there is no effective vaccine to prevent hepatitis C virus (HCV) infection, partly due to our insufficient understanding of the virus glycoprotein immunology. Most neutralizing antibodies (nAbs) were identified using glycoprotein immunogens, such as recombinant E1E2, HCV pseudoparticles or cell culture derived HCV. However, the fact that in the HCV acute infection phase, only a small proportion of patients are self-resolved accompanied with the emergence of nAbs, indicates the limited immunogenicity of glycoprotein itself to induce effective antibodies against a highly evolved virus. Secondly, in previous reports, the immunogen sequence was mostly the genotype of the 1a H77 strain. Rarely, other genotypes/subtypes have been studied, although theoretically one genotype/subtype immunogen is able to induce cross-genotype neutralizing antibodies. To overcome these drawbacks and find potential novel neutralizing epitopes, 57 overlapping peptides encompassing the full-length glycoprotein E1E2 of subtype 1b were synthesized to immunize BALB/c mice, and the neutralizing reactive of the induced antisera against HCVpp genotypes 1–6 was determined. We defined a domain comprising amino acids (aa) 192–221, 232–251, 262–281 and 292–331 of E1, and 421–543, 564–583, 594–618 and 634–673 of E2, as the neutralizing regions of HCV glycoprotein. Peptides PUHI26 (aa 444–463) and PUHI45 (aa 604–618)-induced antisera displayed the most potent broad neutralizing reactive. Two monoclonal antibodies recognizing the PUHI26 and PUHI45 epitopes efficiently precluded genotype 2 viral (HCVcc JFH and J6 strains) infection, but they did not neutralize other genotypes. Our study mapped a neutralizing epitope region of HCV glycoprotein using a novel immunization strategy, and identified two monoclonal antibodies effective in preventing genotype 2 virus infection. PMID:26406225

  7. Homocysteine induced cardiovascular events: a consequence of long term anabolic‐androgenic steroid (AAS) abuse

    PubMed Central

    Graham, M R; Grace, F M; Boobier, W; Hullin, D; Kicman, A; Cowan, D; Davies, B; Baker, J S

    2006-01-01

    Objectives The long term effects (>20 years) of anabolic‐androgenic steroid (AAS) use on plasma concentrations of homocysteine (HCY), folate, testosterone, sex hormone binding globulin (SHBG), free androgen index, urea, creatinine, haematocrit (HCT), vitamin B12, and urinary testosterone/epitestosterone (T/E) ratio, were examined in a cohort of self‐prescribing bodybuilders. Methods Subjects (n = 40) were divided into four distinct groups: (1) AAS users still using AAS (SU; n = 10); (2) AAS users abstinent from AAS administration for 3 months (SA; n = 10); (3) non‐drug using bodybuilding controls (BC; n = 10); and (4) sedentary male controls (SC; n = 10). Results HCY levels were significantly higher in SU compared with BC and SC (p<0.01), and with SA (p<0.05). Fat free mass was significantly higher in both groups of AAS users (p<0.01). Daily energy intake (kJ) and daily protein intake (g/day) were significantly higher in SU and SA (p<0.05) compared with BC and SC, but were unlikely to be responsible for the observed HCY increases. HCT concentrations were significantly higher in the SU group (p<0.01). A significant linear inverse relationship was observed in the SU group between SHBG and HCY (r = −0.828, p<0.01), indicating a possible influence of the sex hormones in determining HCY levels. Conclusions With mounting evidence linking AAS to adverse effects on some clotting factors, the significantly higher levels of HCY and HCT observed in the SU group suggest long term AAS users have increased risk of future thromboembolic events. PMID:16488899

  8. PON1-192 phenotype and genotype assessments in 918 subjects of the Stanislas cohort study.

    PubMed

    Vincent-Viry, Monique; Sass, Catherine; Bastien, Sabine; Aguillon, Dominique; Siest, Gérard; Visvikis, Sophie

    2003-04-01

    This study describes the factors of variation of the enzymes related to the PON1-192 phenotype assessment, i.e., basal paraoxonase, salt-stimulated paraoxonase and arylesterase activities, and compares the PON1-192 phenotype to the PON1-192 genotype assessments in supposedly healthy subjects issued from the Stanislas cohort study. The studied population included 918 subjects, i.e., 221 families including 441 adults and 477 children aged 4 to 58 years. Potential determinants such as age, gender, body mass index, alcohol and tobacco consumption, and oral contraceptive intake have been studied. The PON ratio (salt-stimulated paraoxonase/arylesterase) was trimodally distributed and the cut-off values used to differentiate the two homozygous (AA and BB phenotypes) from the heterozygous (AB phenotype) subjects were 3.0 and 7.0 in this study. In males, basal paraoxonase and salt-stimulated paraoxonase activities were not affected by alcohol consumption and current smoking, but basal paraoxonase activity was decreased by 15% by current smoking and was increased by 15% by oral contraceptive intake in females as was the salt-stimulated paraoxonase activity. The level of discordance between phenotype and genotype assessments was 7.2% (66/918). Most of the discrepancies were observed between the BB and AB phenotypes (4.25%).

  9. Impact of IL-10 (−1082) Promoter–Single Nucleotide Polymorphism on the Outcome of Hepatitis C Virus Genotype 4 Infection

    PubMed Central

    Helal, Soheir F.; Gomaa, Howayda E.; Thabet, Eman H.; Younan, Mariam A.; Helmy, Neveen A.

    2014-01-01

    Immunoregulatory cytokines may influence the hepatitis C virus (HCV) infection outcome. This study aimed to determine the genotypic and allelic frequencies of the interleukin (IL)-10 (−1082) G/A polymorphism, and its association with chronicity or resolution of HCV genotype 4 infection in Egypt. The frequencies of different dimorphic polymorphisms based on single nucleotide substitution in chronic HCV patients (50) and resolved HCV patients (50) were: IL-10 (−1082) G/G 22 (44%) and 18 (36%), G/A 19 (38%) and 24 (48%), and A/A 9 (18%), and 8 (16%), respectively. In the sustained virologic response (SVR) (36) and spontaneously resolved subjects (14) groups, the frequencies were: IL-10 (−1082) G/G 11 (30.6%) and 7 (50%) G/A 18 (50%) and 6 (42.9%), A/A 7 (19.4%) and 1 (7.1%), respectively. An association between male gender and chronic hepatitis C outcome (P value 0.041) was found. However, no significant gender difference was found when we compared females versus males with elevated alanine transaminase (ALT) levels in the chronic HCV patient group (P value = 1). CONCLUSION No significant difference in the frequency of IL-10 single nucleotide polymorphism (SNP) at position 1082 was found between chronic and resolved HCV subjects. PMID:24833945

  10. Comparison of calculated and experimentally determined SID of CP and AA in complex diets differing in AA contents for grower finisher pigs.

    PubMed

    Büsing, K; Berk, A; Müller, S; Kieckhäven, S; Krüger, K; Zeyner, A

    2017-10-01

    In practice, the content of standardized ileal digestible AA in complex feeds for pigs is calculated on the basis of tabulated values for individual feedstuffs. It comes into question, however, whether this truly reflects an accurate content based upon the estimate made for the individual feedstuffs. The objective of this study was to compare standardized ileal digestibility (SID) of crude protein (CP) and selected AA in complex feeds for grower and finisher pigs either calculated or experimentally determined. Six diets with increasing AA levels were prepared for grower (BW from 30 to 70 kg) and finisher (BW from 70 to 120 kg) feed. Crystalline L-lys, DL-met and L-thr were added to both diets, L-trp and L-val only to the grower feed. SID of both CP and AA was calculated from feed tables and experimentally determined in six adult minipigs (MINILEWE) with ileorectal anastomosis. With increasing AA levels, experimentally determined SID of supplemented AA increased (p < 0.05), but SID of CP (p ≥ 0.05) was not affected. In both grower and finisher feed, calculated and experimentally determined SID of CP, Met, Cys, Trp, Ile and Tyr differed by more than 2% units, but those of Lys and His only in the finisher feed. Yet this effect was not directly consistent. The margin of error following estimation of SID of AA via tabulated values for individual feedstuffs, however, seems to be acceptable for practical use. Journal of Animal Physiology and Animal Nutrition © 2017 Blackwell Verlag GmbH.

  11. Detection of AA76, a Common Form of Amyloid A Protein, as a Way of Diagnosing AA Amyloidosis.

    PubMed

    Sato, Junji; Okuda, Yasuaki; Kuroda, Takeshi; Yamada, Toshiyuki

    2016-01-01

    Reactive amyloid deposits consist of amyloid A (AA) proteins, the degradation products of serum amyloid A (SAA). Since the most common species of AA is the amino terminal portion produced by cleavage between residues 76 and 77 of SAA (AA76), the presence of AA76 in tissues could be a consequence of AA amyloid deposition. This study assessed the diagnostic significance of the detection of AA76 for AA amyloidosis using two different approaches. Biopsy specimens (n=130 from 54 subjects) from gastroduodenal mucosa or abdominal fat (n=9 from 9 subjects) of patients who had already been diagnosed with or were suspected of having AA amyloidosis were used. Fixed mucosal sections were subjected to immunohistochemistry using a newly developed antibody recognizing the carboxyl terminal end of AA76 (anti-AA76). The non-fixed materials from gastroduodenal mucosa or abdominal fat were subjected to immunoblotting for detection of the size of AA76. Among the gastroduodenal specimens (n=115) from already diagnosed patients, the positive rates of Congo red staining, immunohistochemistry using anti-AA76, and immunoblotting were 68.4%, 73.0%, and 92.2%, respectively. The anti-AA76 did not stain the supposed SAA in the blood or leakage, which was stained by anti-SAA antibody. AA76 was not detected either by immunohistochemistry or by immunoblot in the materials from patients in whom AA amyloidosis had been ruled out. In the abdominal fat, the immunoblot detected AA76 in 8 materials from 8 already diagnosed patients and did not in 1 patient whose gastroduodenal mucosa was negative. In conclusion, the detection of AA76 may alter the ability to diagnose AA amyloidosis. In immunohistochemistry for fixed specimens, the new anti-AA76 antibody can improve the specificity. Immunoblot for non-fixed materials, which can considerably improve the sensitivity, should be beneficial for small materials like abdominal fat. © 2016 by the Association of Clinical Scientists, Inc.

  12. New Measles Genotype, Uganda

    PubMed Central

    Muwonge, Apollo; Nanyunja, Miriam; Bwogi, Josephine; Lowe, Luis; Liffick, Stephanie L.; Bellini, William J.; Sylvester, Sempala

    2005-01-01

    We report the first genetic characterization of wildtype measles viruses from Uganda. Thirty-six virus isolates from outbreaks in 6 districts were analyzed from 2000 to 2002. Analyses of sequences of the nucleoprotein (N) and hemagglutinin (H) genes showed that the Ugandan isolates were all closely related, and phylogenetic analysis indicated that these viruses were members of a unique group within clade D. Sequences of the Ugandan viruses were not closely related to any of the World Health Organization reference sequences representing the 22 currently recognized genotypes. The minimum nucleotide divergence between the Ugandan viruses and the most closely related reference strain, genotype D2, was 3.1% for the N gene and 2.6% for the H gene. Therefore, Ugandan viruses should be considered a new, proposed genotype (d10). This new sequence information will expand the utility of molecular epidemiologic techniques for describing measles transmission patterns in eastern Africa. PMID:16318690

  13. Dual roles for CoAA and its counterbalancing isoform CoAM in human kidney cell tumorigenesis

    PubMed Central

    Kang, Yun Kyoung; Schiff, Rachel; Ko, Lan; Wang, Tao; Tsai, Sophia Y.; Tsai, Ming-Jer; W. O’Malley, Bert

    2008-01-01

    Co-Activator Activator (CoAA) has been reported to be a coactivator that regulates steroid receptor-mediated transcription and alternative RNA splicing. Herein we show that CoAA is a dual-function coregulator that inhibits G1/S transition in human kidney cells and suppresses anchorage independent growth and xenograft tumor formation. Suppression occurs in part by downregulating c-myc and its downstream effectors ccnd1 and skp2, and causing accumulation of p27/Kip1 protein. In this cellular setting, CoAA directly represses the proto-oncogene, c-myc by recruiting HDAC3 protein and decreasing both the acetylation of histone H3 and the presence of RNA polymerase II on the c-myc promoter. Interestingly, a splicing isoform of CoAA, Coactivator Modulator (CoAM), antagonizes CoAA-induced G1/S transition and growth inhibition by negatively regulating the mRNA levels of the endogenous CoAA isoform. In addition, we found that expression of CoAA protein is significantly decreased in human renal cell carcinoma as compared to normal kidney. Our study presents evidence that CoAA is a potential tumor suppressor in renal carcinoma and that CoAM is a counterbalancing splice-isoform. This is so far the only example of a nuclear receptor coregulator involved in suppression of kidney cancer, and suggests potentially significant new roles for coregulators in renal cancer biology. PMID:18829545

  14. Feasibility of the UV/AA process as a pretreatment approach for bioremediation of dye-laden wastewater.

    PubMed

    Yang, Minghui; Wu, Bingdang; Li, Qiuhao; Xiong, Xiaofeng; Zhang, Haoran; Tian, Yu; Xie, Jiawen; Huang, Ping; Tan, Suo; Wang, Guodong; Zhang, Li; Zhang, Shujuan

    2018-03-01

    Biodegradability and toxicity are two important indexes in considering the feasibility of a chemical process for environmental remediation. The acetylacetone (AA) mediated photochemical process has been proven as an efficient approach for dye decolorization. Both AA and its photochemical degradation products had a high bioavailability. However, the biocompatibility and ecotoxicology of the UV/AA treated solutions are unclear yet. In the present work, we evaluated the biocompatibility and toxicity of the UV/AA treated solutions at both biochemical and organismal levels. The biodegradability of the treated solution was evaluated with the ratio of 5-d biological oxygen demand (BOD 5 ) to chemical oxygen demand (COD) and a 28-d activated sludge assay (Zahn-Wellens tests). The UV/AA process significantly improved the biodegradability of the tested dye solutions. Toxicity was assessed with responses of microorganisms (microbes in activated sludge and Daphnia magna) and plants (bok choy, rice seed, and Arabidopsis thaliana) to the treated solutions, which showed that the toxicity of the UV/AA treated solutions was lower or comparable to that of the UV/H 2 O 2 counterparts. The results are helpful for us to determine whether the UV/AA process is applicable to certain wastewaters and how the UV/AA process could be effectively combined into a sequential chemical-biological water treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Plant genotypic diversity reduces the rate of consumer resource utilization

    PubMed Central

    McArt, Scott H.; Thaler, Jennifer S.

    2013-01-01

    While plant species diversity can reduce herbivore densities and herbivory, little is known regarding how plant genotypic diversity alters resource utilization by herbivores. Here, we show that an invasive folivore—the Japanese beetle (Popillia japonica)—increases 28 per cent in abundance, but consumes 24 per cent less foliage in genotypic polycultures compared with monocultures of the common evening primrose (Oenothera biennis). We found strong complementarity for reduced herbivore damage among plant genotypes growing in polycultures and a weak dominance effect of particularly resistant genotypes. Sequential feeding by P. japonica on different genotypes from polycultures resulted in reduced consumption compared with feeding on different plants of the same genotype from monocultures. Thus, diet mixing among plant genotypes reduced herbivore consumption efficiency. Despite positive complementarity driving an increase in fruit production in polycultures, we observed a trade-off between complementarity for increased plant productivity and resistance to herbivory, suggesting costs in the complementary use of resources by plant genotypes may manifest across trophic levels. These results elucidate mechanisms for how plant genotypic diversity simultaneously alters resource utilization by both producers and consumers, and show that population genotypic diversity can increase the resistance of a native plant to an invasive herbivore. PMID:23658201

  16. Plant genotypic diversity reduces the rate of consumer resource utilization.

    PubMed

    McArt, Scott H; Thaler, Jennifer S

    2013-07-07

    While plant species diversity can reduce herbivore densities and herbivory, little is known regarding how plant genotypic diversity alters resource utilization by herbivores. Here, we show that an invasive folivore--the Japanese beetle (Popillia japonica)--increases 28 per cent in abundance, but consumes 24 per cent less foliage in genotypic polycultures compared with monocultures of the common evening primrose (Oenothera biennis). We found strong complementarity for reduced herbivore damage among plant genotypes growing in polycultures and a weak dominance effect of particularly resistant genotypes. Sequential feeding by P. japonica on different genotypes from polycultures resulted in reduced consumption compared with feeding on different plants of the same genotype from monocultures. Thus, diet mixing among plant genotypes reduced herbivore consumption efficiency. Despite positive complementarity driving an increase in fruit production in polycultures, we observed a trade-off between complementarity for increased plant productivity and resistance to herbivory, suggesting costs in the complementary use of resources by plant genotypes may manifest across trophic levels. These results elucidate mechanisms for how plant genotypic diversity simultaneously alters resource utilization by both producers and consumers, and show that population genotypic diversity can increase the resistance of a native plant to an invasive herbivore.

  17. Sequence variability of the respiratory syncytial virus (RSV) fusion gene among contemporary and historical genotypes of RSV/A and RSV/B

    PubMed Central

    Hause, Anne M.; Henke, David M.; Avadhanula, Vasanthi; Shaw, Chad A.; Tapia, Lorena I.

    2017-01-01

    Background The fusion (F) protein of RSV is the major vaccine target. This protein undergoes a conformational change from pre-fusion to post-fusion. Both conformations share antigenic sites II and IV. Pre-fusion F has unique antigenic sites p27, ø, α2α3β3β4, and MPE8; whereas, post-fusion F has unique antigenic site I. Our objective was to determine the antigenic variability for RSV/A and RSV/B isolates from contemporary and historical genotypes compared to a historical RSV/A strain. Methods The F sequences of isolates from GenBank, Houston, and Chile (N = 1,090) were used for this analysis. Sequences were compared pair-wise to a reference sequence, a historical RSV/A Long strain. Variability (calculated as %) was defined as changes at each amino acid (aa) position when compared to the reference sequence. Only aa at antigenic sites with variability ≥5% were reported. Results A total of 1,090 sequences (822 RSV/A and 268 RSV/B) were analyzed. When compared to the reference F, those domains with the greatest number of non-synonymous changes included the signal peptide, p27, heptad repeat domain 2, antigenic site ø, and the transmembrane domain. RSV/A subgroup had 7 aa changes in the antigenic sites: site I (N = 1), II (N = 1), p27 (N = 4), α2α3β3β4(AM14) (N = 1), ranging in frequency from 7–91%. In comparison, RSV/B had 19 aa changes in antigenic sites: I (N = 3), II (N = 1), p27 (N = 9), ø (N = 4), α2α3β3β4(AM14) (N = 1), and MPE8 (N = 1), ranging in frequency from 79–100%. Discussion Although antigenic sites of RSV F are generally well conserved, differences are observed when comparing the two subgroups to the reference RSV/A Long strain. Further, these discrepancies are accented in the antigenic sites in pre-fusion F of RSV/B isolates, often occurring with a frequency of 100%. This could be of importance if a monovalent F protein from the historical GA1 genotype of RSV/A is used for vaccine development. PMID:28414749

  18. Sequence variability of the respiratory syncytial virus (RSV) fusion gene among contemporary and historical genotypes of RSV/A and RSV/B.

    PubMed

    Hause, Anne M; Henke, David M; Avadhanula, Vasanthi; Shaw, Chad A; Tapia, Lorena I; Piedra, Pedro A

    2017-01-01

    The fusion (F) protein of RSV is the major vaccine target. This protein undergoes a conformational change from pre-fusion to post-fusion. Both conformations share antigenic sites II and IV. Pre-fusion F has unique antigenic sites p27, ø, α2α3β3β4, and MPE8; whereas, post-fusion F has unique antigenic site I. Our objective was to determine the antigenic variability for RSV/A and RSV/B isolates from contemporary and historical genotypes compared to a historical RSV/A strain. The F sequences of isolates from GenBank, Houston, and Chile (N = 1,090) were used for this analysis. Sequences were compared pair-wise to a reference sequence, a historical RSV/A Long strain. Variability (calculated as %) was defined as changes at each amino acid (aa) position when compared to the reference sequence. Only aa at antigenic sites with variability ≥5% were reported. A total of 1,090 sequences (822 RSV/A and 268 RSV/B) were analyzed. When compared to the reference F, those domains with the greatest number of non-synonymous changes included the signal peptide, p27, heptad repeat domain 2, antigenic site ø, and the transmembrane domain. RSV/A subgroup had 7 aa changes in the antigenic sites: site I (N = 1), II (N = 1), p27 (N = 4), α2α3β3β4(AM14) (N = 1), ranging in frequency from 7-91%. In comparison, RSV/B had 19 aa changes in antigenic sites: I (N = 3), II (N = 1), p27 (N = 9), ø (N = 4), α2α3β3β4(AM14) (N = 1), and MPE8 (N = 1), ranging in frequency from 79-100%. Although antigenic sites of RSV F are generally well conserved, differences are observed when comparing the two subgroups to the reference RSV/A Long strain. Further, these discrepancies are accented in the antigenic sites in pre-fusion F of RSV/B isolates, often occurring with a frequency of 100%. This could be of importance if a monovalent F protein from the historical GA1 genotype of RSV/A is used for vaccine development.

  19. APOL1 Genotype and Kidney Transplantation Outcomes From Deceased African American Donors.

    PubMed

    Freedman, Barry I; Pastan, Stephen O; Israni, Ajay K; Schladt, David; Julian, Bruce A; Gautreaux, Michael D; Hauptfeld, Vera; Bray, Robert A; Gebel, Howard M; Kirk, Allan D; Gaston, Robert S; Rogers, Jeffrey; Farney, Alan C; Orlando, Giuseppe; Stratta, Robert J; Mohan, Sumit; Ma, Lijun; Langefeld, Carl D; Bowden, Donald W; Hicks, Pamela J; Palmer, Nicholette D; Palanisamy, Amudha; Reeves-Daniel, Amber M; Brown, W Mark; Divers, Jasmin

    2016-01-01

    Two apolipoprotein L1 gene (APOL1) renal-risk variants in donors and African American (AA) recipient race are associated with worse allograft survival in deceased-donor kidney transplantation (DDKT) from AA donors. To detect other factors impacting allograft survival from deceased AA kidney donors, APOL1 renal-risk variants were genotyped in additional AA kidney donors. The APOL1 genotypes were linked to outcomes in 478 newly analyzed DDKTs in the Scientific Registry of Transplant Recipients. Multivariate analyses accounting for recipient age, sex, race, panel-reactive antibody level, HLA match, cold ischemia time, donor age, and expanded criteria donation were performed. These 478 transplantations and 675 DDKTs from a prior report were jointly analyzed. Fully adjusted analyses limited to the new 478 DDKTs replicated shorter renal allograft survival in recipients of APOL1 2-renal-risk-variant kidneys (hazard ratio [HR], 2.00; P = 0.03). Combined analysis of 1153 DDKTs from AA donors revealed donor APOL1 high-risk genotype (HR, 2.05; P = 3 × 10), older donor age (HR, 1.18; P = 0.05), and younger recipient age (HR, 0.70; P = 0.001) adversely impacted allograft survival. Although prolonged allograft survival was seen in many recipients of APOL1 2-renal-risk-variant kidneys, follow-up serum creatinine concentrations were higher than that in recipients of 0/1 APOL1 renal-risk-variant kidneys. A competing risk analysis revealed that APOL1 impacted renal allograft survival, but not recipient survival. Interactions between donor age and APOL1 genotype on renal allograft survival were nonsignificant. Shorter renal allograft survival is reproducibly observed after DDKT from APOL1 2-renal-risk-variant donors. Younger recipient age and older donor age have independent adverse effects on renal allograft survival.

  20. Somatic effects of AAS abuse: A 30-years follow-up study of male former power sports athletes.

    PubMed

    Lindqvist Bagge, A S; Rosén, T; Fahlke, C; Ehrnborg, C; Eriksson, B O; Moberg, T; Thiblin, I

    2017-09-01

    The aim of the present study was to investigate the association between somatic health and former abuse of AAS in former elite male athletes 30 years after the end of their active sports career. Retrospective follow-up study. N=996 former elite male athletes were sent a questionnaire concerning sociodemographic variables, previous and past sport activity and lifetime prevalence of seeking professional help for health problems. N=683 (68.6%) answered the questionnaire. The lifetime prevalence of AAS-abuse was 21% (n=143), while 79% (n=540) did not admit having ever used AAS. Former AAS-abuse was associated with tendon ruptures (p=0.01), depression (p=0.001), anxiety (p=0.01) and lower prevalence of prostate hypertrophy (p=0.01) and decreased libido (p=0.01). Former advanced AAS-abusers had higher anxiety (p=0.004) compared to the former less advanced AAS-abusers. Moreover, former advanced AAS-abusers, compared to AAS-naïves, reported more psychiatric problems (p=0.002), depression (p=0.003) and anxiety (p=0.00). A former AAS-abuse seems to be associated with some somatic and mental health problem, although a former less advanced AAS-abuse is related to lower incidence of prostate hypertrophy. The results raise the question whether some of these associations might be dose- and frequency dependent. These findings should however be seen as hypothesis generating and further studies are needed. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  1. Axiom turkey genotyping array

    USDA-ARS?s Scientific Manuscript database

    The Axiom®Turkey Genotyping Array interrogates 643,845 probesets on the array, covering 643,845 SNPs. The array development was led by Dr. Julie Long of the USDA-ARS Beltsville Agricultural Research Center under a public-private partnership with Hendrix Genetics, Aviagen, and Affymetrix. The Turk...

  2. Novel types of COMP mutations and genotype-phenotype association in pseudoachondroplasia and multiple epiphyseal dysplasia.

    PubMed

    Mabuchi, Akihiko; Manabe, Noriyo; Haga, Nobuhiko; Kitoh, Hiroshi; Ikeda, Toshiyuki; Kawaji, Hiroyuki; Tamai, Kazuya; Hamada, Junichiro; Nakamura, Shigeru; Brunetti-Pierri, Nicola; Kimizuka, Mamori; Takatori, Yoshio; Nakamura, Kozo; Nishimura, Gen; Ohashi, Hirofumi; Ikegawa, Shiro

    2003-01-01

    Mutations in the gene encoding cartilage oligomeric matrix protein ( COMP) cause two skeletal dysplasias, pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED). More than 40 mutations have been identified; however, genotype-phenotype relationships are not well delineated. Further, mutations other than in-frame insertion/deletions and substitutions have not been found, and currently known mutations are clustered within relatively small regions. Here we report the identification of nine novel and three recurrent COMP mutations in PSACH and MED patients. These include two novel types of mutations; the first, a gross deletion spanning an exon-intron junction, causes an exon deletion. The second, a frameshift mutation that results in a truncation of the C-terminal domain, is the first known truncating mutation in the COMP gene. The remaining mutations, other than a novel exon 18 mutation, affected highly conserved aspartate or cysteine residues in the calmodulin-like repeat (CLR) region. Genotype-phenotype analysis revealed a correlation between the position and type of mutations and the severity of short stature. Mutations in the seventh CLR produced more severe short stature compared with mutations elsewhere in the CLRs ( P=0.0003) and elsewhere in the COMP gene ( P=0.0007). Patients carrying mutations within the five-aspartates repeat (aa 469-473) in the seventh CLR were extremely short (below -6 SD). Patients with deletion mutations were significantly shorter than those with substitution mutations ( P=0.0024). These findings expand the mutation spectrum of the COMP gene and highlight genotype-phenotype relationships, facilitating improved genetic diagnosis and analysis of COMP function in humans.

  3. High proportion of subgroup A' (genotype A) among Brazilian isolates of Hepatitis B virus.

    PubMed

    Araujo, N M; Mello, F C A; Yoshida, C F T; Niel, C; Gomes, S A

    2004-07-01

    Hepatitis B virus (HBV) genotype A has been divided recently into two subgroups, designated A-A' (genotype A excluding A') and A'. Isolates belonging to subgroup A' have been identified in Africa. A new genotyping method, based on PCR amplification of the pre-S/S genome region and subsequent restriction fragment length polymorphism (RFLP) analysis, was developed, that established a correlation between RFLP subtypes and subgroups within genotype A. To investigate the occurrence of subgroup A' in South America, 119 Brazilian HBV isolates were analyzed. Ninety-three (78%) of them belonged to genotype A, with three predominating RFLP subtypes: 44 (37%) isolates were classified as AI, 30 (25%) were AII, and 18 (15%) were AIII. Pre-S/S nucleotide sequences of 15 genotype A isolates were determined. Phylogenetic analysis performed with these 15 and an additional 41 sequences revealed that isolates AI and AII clustered in subgroup A', whereas isolates AIII were classified into subgroup A-A'. The correlation RFLP subtypes-subgroups was confirmed by the presence of amino acid residues specific for subgroup A' in the surface antigens and polymerase of isolates AI and AII. The high proportion (63%) of isolates from subgroup A' suggested an African origin for a large number of Brazilian HBVs.

  4. Association of genotypes and haplotypes of multi-drug transporter genes ABCB1 and ABCG2 with clinical response to imatinib mesylate in chronic myeloid leukemia patients.

    PubMed

    Au, Anthony; Aziz Baba, Abdul; Goh, Ai Sim; Wahid Fadilah, S Abdul; Teh, Alan; Rosline, Hassan; Ankathil, Ravindran

    2014-04-01

    The introduction and success of imatinib mesylate (IM) has become a paradigm shift in chronic myeloid leukemia (CML) treatment. However, the high efficacy of IM has been hampered by the issue of clinical resistance that might due to pharmacogenetic variability. In the current study, the contribution of three common single nucleotide polymorphisms (SNPs) of ABCB1 (T1236C, G2677T/A and C3435T) and two SNPs of ABCG2 (G34A and C421A) genes in mediating resistance and/or good response among 215 CML patients on IM therapy were investigated. Among these patients, the frequency distribution of ABCG2 421 CC, CA and AA genotypes were significantly different between IM good response and resistant groups (P=0.01). Resistance was significantly associated with patients who had homozygous ABCB1 1236 CC genotype with OR 2.79 (95%CI: 1.217-6.374, P=0.01). For ABCB1 G2677T/A polymorphism, a better complete cytogenetic remission was observed for patients with variant TT/AT/AA genotype, compared to other genotype groups (OR=0.48, 95%CI: 0.239-0.957, P=0.03). Haplotype analysis revealed that ABCB1 haplotypes (C1236G2677C3435) was statistically linked to higher risk to IM resistance (25.8% vs. 17.4%, P=0.04), while ABCG2 diplotype A34A421 was significantly correlated with IM good response (9.1% vs. 3.9%, P=0.03). In addition, genotypic variant in ABCG2 421C>A was associated with a major molecular response (MMR) (OR=2.20, 95%CI: 1.273-3.811, P=0.004), whereas ABCB1 2677G>T/A variant was associated with a significantly lower molecular response (OR=0.49, 95%CI: 0.248-0.974, P=0.04). However, there was no significant correlation of these SNPs with IM intolerance and IM induced hepatotoxicity. Our results suggest the usefulness of genotyping of these single nucleotide polymorphisms in predicting IM response among CML patients. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  5. [Risk control of traditional Chinese medicines containing aristolochis acids (AAs) based on influencing factors of content of AAs].

    PubMed

    Tian, Jing-Zhuo; Liang, Ai-Hua; Liu, Jing; Zhang, Bo-Li

    2017-12-01

    Aristolochic acids (AAs) widely exist in such plants as Aristolochia and Asarum. The renal toxicity of AAs as well as its carcinogenicity to urinary system have been widely known. In 2003 and 2004, China prohibited the use of Aristolochiae Radix, Aristolochiae Manshuriensis Caulis and Aristolochiae Fangchi Radix, and required administering other AAs-containing medicines in accordance with the regulations for prescription drugs. In this paper, we retrieved literatures on the content determination of AAs in recent 10 years in China. It suggested that the AAs content is lower in Asarum herb, especially in its roots and rhizomes, and most of which do not show detectable amount of AA-I. Some of traditional Chinese medicines show fairly small amount of detectable AA-I. The AAs content in Aristolochia herb (including Fructus Aristolochiae, kaempfer dutchmanspipe root) is relatively high; however, there are fewer literatures for studying the content determination of AAs in Chinese patent medicines. There were many factors affecting AAs content, including the parts used, origins, processing methods, extraction process. It suggested that we should pay attention to the toxicity of Chinese medicines containing AAs and use these decoction pieces and traditional Chinese medicines cautiously. In addition, basic studies for the origins, processing methods and extraction process of Chinese patent medicines containing AAs, as well as supervision and detection of AAs content in traditional Chinese medicinal materials, decoction pieces and Chinese patent medicines shall be strengthened for reducing medication risk and guaranteeing clinical medication safety. Copyright© by the Chinese Pharmaceutical Association.

  6. ABCB1 haplotype and OPRM1 118A > G genotype interaction in methadone maintenance treatment pharmacogenetics

    PubMed Central

    Barratt, Daniel T; Coller, Janet K; Hallinan, Richard; Byrne, Andrew; White, Jason M; Foster, David JR; Somogyi, Andrew A

    2012-01-01

    Background: Genetic variability in ABCB1, encoding the P-glycoprotein efflux transporter, has been linked to altered methadone maintenance treatment dose requirements. However, subsequent studies have indicated that additional environmental or genetic factors may confound ABCB1 pharmacogenetics in different methadone maintenance treatment settings. There is evidence that genetic variability in OPRM1, encoding the mu opioid receptor, and ABCB1 may interact to affect morphine response in opposite ways. This study aimed to examine whether a similar gene-gene interaction occurs for methadone in methadone maintenance treatment. Methods: Opioid-dependent subjects (n = 119) maintained on methadone (15–300 mg/day) were genotyped for five single nucleotide polymorphisms of ABCB1 (61A > G; 1199G > A; 1236C > T; 2677G > T; 3435C > T), as well as for the OPRM1 118A > G single nucleotide polymorphism. Subjects’ methadone doses and trough plasma (R)-methadone concentrations (Ctrough) were compared between ABCB1 haplotypes (with and without controlling for OPRM1 genotype), and between OPRM1 genotypes (with and without controlling for ABCB1 haplotype). Results: Among wild-type OPRM1 subjects, an ABCB1 variant haplotype group (subjects with a wild-type and 61A:1199G:1236C:2677T:3435T haplotype combination, or homozygous for the 61A:1199G:1236C:2677T:3435T haplotype) had significantly lower doses (median ± standard deviation 35 ± 5 versus 180 ± 65 mg/day, P < 0.01) and Ctrough (78 ± 22 versus 177 ± 97 ng/mL, P < 0.05) than ABCB1 wild-type subjects. Among subjects with the most common ABCB1 haplotype combination (wild-type with 61A:1199G:1236T:2677T:3435T), the OPRM1 118 A/G genotype was associated with a significantly higher Ctrough than 118 A/A (250 ± 126 versus 108 ± 36 ng/mL, P = 0.016). No ABCB1 haplotype group or OPRM1 genotype was associated with dose or Ctrough without taking into account confounding genetic variability at the other locus. Therefore, two

  7. Genotyping of Coxiella burnetii from domestic ruminants in northern Spain.

    PubMed

    Astobiza, Ianire; Tilburg, Jeroen J H C; Piñero, Alvaro; Hurtado, Ana; García-Pérez, Ana L; Nabuurs-Franssen, Marrigje H; Klaassen, Corné H W

    2012-12-10

    Information on the genotypic diversity of Coxiella burnetii isolates from infected domestic ruminants in Spain is limited. The aim of this study was to identify the C. burnetii genotypes infecting livestock in Northern Spain and compare them to other European genotypes. A commercial real-time PCR targeting the IS1111a insertion element was used to detect the presence of C. burnetii DNA in domestic ruminants from Spain. Genotypes were determined by a 6-loci Multiple Locus Variable number tandem repeat analysis (MLVA) panel and Multispacer Sequence Typing (MST). A total of 45 samples from 4 goat herds (placentas, N = 4), 12 dairy cattle herds (vaginal mucus, individual milk, bulk tank milk, aerosols, N = 20) and 5 sheep flocks (placenta, vaginal swabs, faeces, air samples, dust, N = 21) were included in the study. Samples from goats and sheep were obtained from herds which had suffered abortions suspected to be caused by C. burnetii, whereas cattle samples were obtained from animals with reproductive problems compatible with C. burnetii infection, or consisted of bulk tank milk (BTM) samples from a Q fever surveillance programme. C. burnetii genotypes identified in ruminants from Spain were compared to those detected in other countries. Three MLVA genotypes were found in 4 goat farms, 7 MLVA genotypes were identified in 12 cattle herds and 4 MLVA genotypes were identified in 5 sheep flocks. Clustering of the MLVA genotypes using the minimum spanning tree method showed a high degree of genetic similarity between most MLVA genotypes. Overall 11 different MLVA genotypes were obtained corresponding to 4 different MST genotypes: MST genotype 13, identified in goat, sheep and cattle from Spain; MST genotype 18, only identified in goats; and, MST genotypes 8 and 20, identified in small ruminants and cattle, respectively. All these genotypes had been previously identified in animal and human clinical samples from several European countries, but some of the MLVA

  8. Genotyping of Coxiella burnetii from domestic ruminants and human in Hungary: indication of various genotypes.

    PubMed

    Sulyok, Kinga M; Kreizinger, Zsuzsa; Hornstra, Heidie M; Pearson, Talima; Szigeti, Alexandra; Dán, Ádám; Balla, Eszter; Keim, Paul S; Gyuranecz, Miklós

    2014-05-07

    Information about the genotypic characteristic of Coxiella burnetii from Hungary is lacking. The aim of this study is to describe the genetic diversity of C. burnetii in Hungary and compare genotypes with those found elsewhere. A total of 12 samples: (cattle, n = 6, sheep, n = 5 and human, n = 1) collected from across Hungary were studied by a 10-loci multispacer sequence typing (MST) and 6-loci multiple-locus variable-number of tandem repeat analysis (MLVA). Phylogenetic relationships among MST genotypes show how these Hungarian samples are related to others collected around the world. Three MST genotypes were identified: sequence type (ST) 20 has also been identified in ruminants from other European countries and the USA, ST28 was previously identified in Kazakhstan, and the proposed ST37 is novel. All MST genotypes yielded different MLVA genotypes and three different MLVA genotypes were identified within ST20 samples alone. Two novel MLVA types 0-9-5-5-6-2 (AG) and 0-8-4-5-6-2 (AF) (Ms23-Ms24-Ms27-Ms28-Ms33-Ms34) were defined in the ovine materials correlated with ST28 and ST37. Samples from different parts of the phylogenetic tree were associated with different hosts, suggesting host-specific adaptations. Even with the limited number of samples analysed, this study revealed high genetic diversity among C. burnetii in Hungary. Understanding the background genetic diversity will be essential in identifying and controlling outbreaks.

  9. 7 CFR 51.596 - U.S. Grade AA.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false U.S. Grade AA. 51.596 Section 51.596 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Consumer Standards for Celery Stalks Grades § 51.596 U.S. Grade AA. U.S. Grade AA shall consist of stalks...

  10. 7 CFR 51.596 - U.S. Grade AA.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 2 2012-01-01 2012-01-01 false U.S. Grade AA. 51.596 Section 51.596 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Consumer Standards for Celery Stalks Grades § 51.596 U.S. Grade AA. U.S. Grade AA shall consist of stalks...

  11. 7 CFR 51.596 - U.S. Grade AA.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 2 2013-01-01 2013-01-01 false U.S. Grade AA. 51.596 Section 51.596 Agriculture..., CERTIFICATION, AND STANDARDS) United States Consumer Standards for Celery Stalks Grades § 51.596 U.S. Grade AA. U.S. Grade AA shall consist of stalks of celery of similar varietal characteristics, which are well...

  12. 7 CFR 51.596 - U.S. Grade AA.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 2 2014-01-01 2014-01-01 false U.S. Grade AA. 51.596 Section 51.596 Agriculture..., CERTIFICATION, AND STANDARDS) United States Consumer Standards for Celery Stalks Grades § 51.596 U.S. Grade AA. U.S. Grade AA shall consist of stalks of celery of similar varietal characteristics, which are well...

  13. Variability in amino acid digestibility of triticale grain from diverse genotypes as studied in cecectomized laying hens.

    PubMed

    Zuber, T; Maurer, H P; Möhring, J; Nautscher, N; Siegert, W; Rosenfelder, P; Rodehutscord, M

    2016-12-01

    Triticale, an anthropogenic hybrid grain, is increasing in importance as a feed grain for laying hens. However, our limited knowledge of its nutritional qualities and their impact on hen performance prevents optimization of its use. The present study investigated the digestibility of amino acids ( AA: ) in triticale grain in laying hens, and additionally examined relationships between AA digestibility and chemical and physical characteristics of the grain. Twenty genotypes of triticale were grown under standardized agronomic and environmental conditions and were characterized according to their physical properties (thousand-seed weight, test weight, falling number, extract viscoelasticity), chemical composition (proximate nutrients, non-starch polysaccharides, AA, minerals, inositol phosphates) and gross energy concentration. Additionally, the in vitro solubility of nitrogen was determined. The animal trial comprised 4 Latin Squares (6 × 6) distributed among 2 subsequent runs. Twelve cecectomized LSL-Classic hens were individually housed in metabolism cages and either fed a basal diet containing 500 g/kg cornstarch or one of 20 triticale diets, each replacing the cornstarch with one triticale genotype, for 8 d. During the last 4 d, feed intake was recorded and excreta were collected quantitatively. Amino acid digestibility of the triticale genotypes was calculated by linear regression. The digestibility of all AA differed significantly between the 20 genotypes, including Lys (digestibility range 68 to 80%), Met (77 to 86%), Thr (68 to 78%) and Trp (74 to 83%). However, AA digestibility only correlated with characteristics of the grain in few cases, without a consistent pattern among AA. Equations to predict AA digestibility based on the grain's physical and chemical characteristics were calculated by multiple linear regression. The explanatory power (adjusted R 2 ;) of these prediction equations was below 0.7 for most AA and thus not sufficiently precise to be

  14. Development of a Laboratory Project to Determine Human ABO Genotypes--Limitations Lead to Further Student Explorations

    ERIC Educational Resources Information Center

    Salerno, Theresa A.

    2009-01-01

    A multiplex allele-specific PCR analysis was developed to identify six "common" genotypes: AA, AO, BB, BO, OO, and AB. This project included a pre-laboratory exercise that provided active learning experiences and developed critical thinking skills. This laboratory resulted in many successful analyses, which were verified by student knowledge of…

  15. 40 CFR Table Aa-1 to Subpart Aa of... - Kraft Pulping Liquor Emissions Factors for Biomass-Based CO2, CH4, and N2O

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 22 2013-07-01 2013-07-01 false Kraft Pulping Liquor Emissions Factors for Biomass-Based CO2, CH4, and N2O AA Table AA-1 to Subpart AA of Part 98 Protection of Environment... Paper Manufacturing Pt. 98, Subpt. AA, Table AA-1 Table AA-1 to Subpart AA of Part 98—Kraft Pulping...

  16. 40 CFR Table Aa-1 to Subpart Aa of... - Kraft Pulping Liquor Emissions Factors for Biomass-Based CO2, CH4, and N2O

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 21 2011-07-01 2011-07-01 false Kraft Pulping Liquor Emissions Factors for Biomass-Based CO2, CH4, and N2O AA Table AA-1 to Subpart AA of Part 98 Protection of Environment... Paper Manufacturing Pt. 98, Subpt. AA, Table AA-1 Table AA-1 to Subpart AA of Part 98—Kraft Pulping...

  17. 40 CFR Table Aa-2 to Subpart Aa of... - Kraft Lime Kiln and Calciner Emissions Factors for CH4 and N2O

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 21 2014-07-01 2014-07-01 false Kraft Lime Kiln and Calciner Emissions Factors for CH4 and N2O AA Table AA-2 to Subpart AA of Part 98 Protection of Environment ENVIRONMENTAL... Manufacturing Pt. 98, Subpt. AA, Table AA -2 Table AA-2 to Subpart AA of Part 98—Kraft Lime Kiln and Calciner...

  18. 40 CFR Table Aa-1 to Subpart Aa of... - Kraft Pulping Liquor Emissions Factors for Biomass-Based CO2, CH4, and N2O

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Kraft Pulping Liquor Emissions Factors for Biomass-Based CO2, CH4, and N2O AA Table AA-1 to Subpart AA of Part 98 Protection of Environment... Paper Manufacturing Pt. 98, Subpt. AA, Table AA-1 Table AA-1 to Subpart AA of Part 98—Kraft Pulping...

  19. 40 CFR Table Aa-1 to Subpart Aa of... - Kraft Pulping Liquor Emissions Factors for Biomass-Based CO2, CH4, and N2O

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 21 2014-07-01 2014-07-01 false Kraft Pulping Liquor Emissions Factors for Biomass-Based CO2, CH4, and N2O AA Table AA-1 to Subpart AA of Part 98 Protection of Environment... Paper Manufacturing Pt. 98, Subpt. AA, Table AA-1 Table AA-1 to Subpart AA of Part 98—Kraft Pulping...

  20. Constant amplitude and post-overload fatigue crack growth behavior in PM aluminum alloy AA 8009

    NASA Technical Reports Server (NTRS)

    Reynolds, A. P.

    1991-01-01

    A recently developed, rapidly solidified, powder metallurgy, dispersion strengthened aluminum alloy, AA 8009, was fatigue tested at room temperature in lab air. Constant amplitude/constant delta kappa and single spike overload conditions were examined. High fatigue crack growth rates and low crack closure levels compared to typical ingot metallurgy aluminum alloys were observed. It was proposed that minimal crack roughness, crack path deflection, and limited slip reversibility, resulting from ultra-fine microstructure, were responsible for the relatively poor da/dN-delta kappa performance of AA 8009 as compared to that of typical IM aluminum alloys.

  1. Constant amplitude and post-overload fatigue crack growth behavior in PM aluminum alloy AA 8009

    NASA Technical Reports Server (NTRS)

    Reynolds, A. P.

    1992-01-01

    A recently developed, rapidly solidified, powder metallurgy, dispersion strengthened aluminum alloy, AA 8009, was fatigue tested at room temperature in lab air. Constant amplitude/constant delta kappa and single spike overload conditions were examined. High fatigue crack growth rates and low crack closure levels compared to typical ingot metallurgy aluminum alloys were observed. It was proposed that minimal crack roughness, crack path delection, and limited slip reversibility, resulting from ultra-fine microstructure, were responsible for the relatively poor da/dN-delta kappa performance of AA 8009 as compared to that of typical IM aluminum alloys.

  2. Increased Virulence and Competitive Advantage of a/α Over a/a or α/α Offspring Conserves the Mating System of Candida albicans

    PubMed Central

    Lockhart, Shawn R.; Wu, Wei; Radke, Joshua B.; Zhao, Rui; Soll, David R.

    2005-01-01

    The majority of Candida albicans strains in nature are a/α and must undergo homozygosis to a/a or α/α to mate. Here we have used a mouse model for systemic infection to test the hypothesis that a/α strains predominate in nature because they have a competitive advantage over a/a and α/α offspring in colonizing hosts. Single-strain injection experiments revealed that a/α strains were far more virulent than either their a/a or α/α offspring. When equal numbers of parent a/α and offspring a/a or α/α cells were co-injected, a/α always exhibited a competitive advantage at the time of extreme host morbidity or death. When equal numbers of an engineered a/a/α2 strain and its isogenic a/a parent strain were co-injected, the a/a/α2 strain exhibited a competitive advantage at the time of host morbidity or death, suggesting that the genotype of the mating-type (MTL) locus, not associated genes on chromosome 5, provides a competitive advantage. We therefore propose that heterozygosity at the MTL locus not only represses white-opaque switching and genes involved in the mating process, but also affects virulence, providing a competitive advantage to the a/α genotype that conserves the mating system of C. albicans in nature. PMID:15695357

  3. Increased virulence and competitive advantage of a/alpha over a/a or alpha/alpha offspring conserves the mating system of Candida albicans.

    PubMed

    Lockhart, Shawn R; Wu, Wei; Radke, Joshua B; Zhao, Rui; Soll, David R

    2005-04-01

    The majority of Candida albicans strains in nature are a/alpha and must undergo homozygosis to a/a or alpha/alpha to mate. Here we have used a mouse model for systemic infection to test the hypothesis that a/alpha strains predominate in nature because they have a competitive advantage over a/a and alpha/alpha offspring in colonizing hosts. Single-strain injection experiments revealed that a/alpha strains were far more virulent than either their a/a or alpha/alpha offspring. When equal numbers of parent a/alpha and offspring a/a or alpha/alpha cells were co-injected, a/alpha always exhibited a competitive advantage at the time of extreme host morbidity or death. When equal numbers of an engineered a/a/alpha2 strain and its isogenic a/a parent strain were co-injected, the a/a/alpha2 strain exhibited a competitive advantage at the time of host morbidity or death, suggesting that the genotype of the mating-type (MTL) locus, not associated genes on chromosome 5, provides a competitive advantage. We therefore propose that heterozygosity at the MTL locus not only represses white-opaque switching and genes involved in the mating process, but also affects virulence, providing a competitive advantage to the a/alpha genotype that conserves the mating system of C. albicans in nature.

  4. Human T-cell leukemia virus type I Tax genotype analysis in Okinawa, the southernmost and remotest islands of Japan: Different distributions compared with mainland Japan and the potential value for the prognosis of aggressive adult T-cell leukemia/lymphoma.

    PubMed

    Sakihama, Shugo; Saito, Mineki; Kuba-Miyara, Megumi; Tomoyose, Takeaki; Taira, Naoya; Miyagi, Takashi; Hayashi, Masaki; Kinjo, Shigeko; Nakachi, Sawako; Tedokon, Iori; Nishi, Yukiko; Tamaki, Keita; Morichika, Kazuho; Uchihara, Jun-Nosuke; Morishima, Satoko; Karube, Ken-Nosuke; Tanaka, Yuetsu; Masuzaki, Hiroaki; Fukushima, Takuya

    2017-10-01

    Okinawa, comprising remote islands off the mainland of Japan, is an endemic area of human T-cell leukemia virus type I (HTLV-1), the causative virus of adult T-cell leukemia-lymphoma (ATL) and HTLV-1-associated myelopathy (HAM). We investigated the tax genotype of HTLV-1 among 29 HTLV-1 carriers, 74 ATL patients, and 33 HAM patients in Okinawa. The genotype distribution-60 (44%) taxA cases and 76 (56%) taxB cases-differed from that of a previous report from Kagoshima Prefecture in mainland Japan (taxA, 10%; taxB, 90%). A comparison of the clinical outcomes of 45 patients (taxA, 14; taxB, 31) with aggressive ATL revealed that the overall response and 1-year overall survival rates for taxA (50% and 35%, respectively) were lower than those for taxB (71% and 49%, respectively). In a multivariate analysis of two prognostic indices for aggressive ATL, Japan Clinical Oncology Group-Prognostic Index and Prognostic Index for acute and lymphoma ATL, with respect to age, performance status, corrected calcium, soluble interleukin-2 receptor, and tax genotype, the estimated hazard ratio of taxA compared with taxB was 2.68 (95% confidence interval, 0.87-8.25; P=0.086). Our results suggest that the tax genotype has clinical value as a prognostic factor for aggressive ATL. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Experimental Investigation on Friction Stir Welding of Cryorolled AA2219 Aluminum Alloy Joints

    NASA Astrophysics Data System (ADS)

    Babu, K. Kamal; Panneerselvam, K.; Sathiya, P.; Haq, A. Noorul; Sundarrajan, S.; Mastanaiah, P.; Murthy, C. V. Srinivasa

    2017-07-01

    In this paper, experimental investigation on cryorolled aluminum AA2219-T87 plate by using friction stir welding (FSW) process is carried out. AA2219-T87 plates with a size of 200×100×22.4 mm were rolled and reduced to 12.2mm thickness (more than 45% of reduction in total thickness of the base material) at cryogenic temperature (operating temperature range -90--30∘C). The cryorolled (CR) plates have reduced grain size, improved hardness and increased corrosion resistance property compared with the uncryorolled AA2219-T87 plates. FSW joints of cryorolled AA2219-T87 plates were prepared using cylindrical threaded FSW tool pin profile. Mechanical and metallurgical behaviors of friction stir welded joints were analyzed and the effects of the FSW process parameters are discussed in this paper. The variation of microhardness in the FSW joint regions were correlated with the microstructure of FSW joints. Cryorolled plate and FSW joints were tested for corrosion resistance using potentiodynamic polarization test. FSW joints shows better result during the corrosion resistance analysis compared to base AA2219-T87. The X-ray diffraction (XRD) test results showed that fine α-Al grains with eutectic phase (Al2Cu) were present in the weld nugget (WN). The large clusters of strengthening precipitates were reduced in size and merged with the weld nugget portion.

  6. Treatment of AA amyloidosis in rheumatoid arthritis.

    PubMed

    Balakrishnan, C; Sule, A; Mittal, G; Gaitonde, S; Pathan, E; Rajadhyaksha, S; Deshpande, R B; Gurmeet, M; Samant, R; Joshi, V R

    2002-07-01

    Four patients of rheumatoid arthritis (RA) with biopsy confirmed AA amyloidosis were treated with chlorambucil. All had established but uncontrolled RA with a persistently raised ESR. Moderate (> 1 gm, < 3.5 gm/d) to nephrotic range (> 3.5 gm/d) proteinuria and a relatively well preserved renal function was noted in three patients. One patient had deranged renal function and required dialysis. On chlorambucil, there was complete recovery, partial improvement and no improvement in one patient each. The fourth patient required haemodialysis, did not tolerate chlorambucil and succumbed to the illness. Therapy with chlorambucil can benefit some patients of RA with AA amyloidosis. Leucopenia is the most important dose limiting side effect.

  7. Structure of AA5056 after friction drilling

    NASA Astrophysics Data System (ADS)

    Eliseev, A. A.; Kalashnikova, T. A.; Fortuna, S. V.

    2017-12-01

    Here we present data on the structure of AA5056 alloy after friction drilling to unveil potentials of the process for use in model experiments on friction stir welding. Our analysis of the average size and volume content of precipitates shows that their content decreases immediately beneath the friction surface and that the structure of this zone is the same as the structure of stirring zones formed in friction stir welding. The data suggest that both processes provide similar metal structures.

  8. The Effectiveness of the AAS REU Program

    NASA Astrophysics Data System (ADS)

    Hemenway, M. K.; Boyce, P. B.; Milkey, R. W.

    1996-05-01

    In an attempt to address the particular needs of astronomy faculty and undergraduate students, in 1991 the Education Office of the American Astronomical Society approached the National Science Foundation with a unique proposal for funding through the Research Experiences for Undergraduates program. The goals of the AAS program were to "slow the hemorrhage of students out of science...", extend the REU program to non-NSF-funded scientists, to reach under-represented women and minority students particularly in small educational institutions, and to encourage research scientists there to mentor students. As this grant has now expired, the AAS has surveyed the 44 mentors and their students to assess the program's effect on the mentor and the mentor's career; the educational institution; and the student's education and career choices. More than half the mentors responded by the abstract deadline. The program clearly had an effect upon the individuals involved. The greatest effect (in 85% of the cases) was to develop more interest in the mentor's research project both among the students and among the mentor's faculty colleagues. The mentors rated the grant to be a medium or strong factor in their student's decision to pursue graduate study, which 90% of them did. All but one of the AAS-REU students attended an AAS meeting and 3/4 of those gave a paper on their project research. Over 90% of the mentors felt that the research experience strongly promoted a greater interest in science, a greater understanding of science and a desire to continue in science. According to the mentors, this was a very positive and beneficial program for the students as well as for themselves.

  9. Administrator Bolden Delivers Speech at AAS

    NASA Image and Video Library

    2010-01-05

    NASA Administrator Charles Bolden speaks at the 215th meeting of the American Astronomical Society (AAS) in Washington on Tuesday, Jan. 5, 2009. Throughout the meeting, NASA research and mission highlights will be presented from missions that include Kepler, the Spitzer Space Telescope, the Hubble Space Telescope, and the newly launched Wide-field Infrared Survey Explorer, or WISE. Photo Credit: (NASA/Bill Ingalls)

  10. AAS Oral History Project - Seeking Planetary Scientist

    NASA Astrophysics Data System (ADS)

    Buxner, Sanlyn; Holbrook, Jarita

    2016-10-01

    Now in its fourth year, the AAS Oral History Project has interviewed over 100 space scientists from all over the world. Led by the AAS Historical Astronomy Division (HAD) and partially funded by the American Institute of Physics Niels Bohr Library and ongoing support from the AAS, volunteers have collected oral histories from space scientists at professional meetings starting in 2015, including AAS, DPS, and the IAU general assembly. Each interview lasts one and a half to two hours and focuses on interviewees' personal and professional lives. Questions include those about one's family, childhood, strong influences on one's scientific career, career path, successes and challenges, perspectives on how astronomy is changing as a field, and advice to the next generation. Each interview is audio recorded and transcribed, the content of which is checked with each interviewee. Once complete, interview transcripts are posted online as part of a larger oral history library at https://www.aip.org/history-programs/niels-bohr-library/oral-histories. We will present preliminary analysis of those interviewed including characterizing career status, age range, nationality, and primary field. Additionally, we will discuss trends beginning to emerge in analysis of participants' responses about data driven science and advice to the next generation. Future analysis will reveal a rich story of space scientists and will help the community address issues of diversity, controversies, and the changing landscape of science. We are actively recruiting individuals to be interviewed at this meeting from all stages of career from undergraduate students to retired and emeritus astronomers. We are especially interested in interviewing 40+E members of DPS. Contact Sanlyn Buxner to schedule an interview or to find out more information about the project (buxner@psi.edu). Contact Jarita Holbrook if you would like to become an interviewer for the project (astroholbrook@gmail.com).

  11. Ethanol-reinforced responding by AA and ANA rats following the sucrose-substitution initiation procedure.

    PubMed

    Files, F J; Denning, C E; Hyytia, P; Kiianmaa, K; Samson, H H

    1997-06-01

    Ethanol-reinforced responding was initiated in male AA and ANA rats using the sucrose-substitution procedure. Before the initiation procedure, a homecage, two-bottle preference test was conducted. The rats were then trained to respond on an Fixed-Ratio 1 schedule with sucrose reinforcement. Over sessions, ethanol was added gradually to the sucrose solution as the concentration of sucrose was reduced until 10% ethanol (v/v) alone functioned as the reinforcer for lever pressing. The schedule of reinforcement was then increased to Fixed-Ratio 4. Next, the ethanol concentration presented as the reinforcer was increased over weeks to 15%, 20%, 30%, and then returned to 10%. A second homecage test was then performed. The results showed that the AA and ANA lines differed significantly on preference and intake (g/kg) during the homecage preference tests. There was a significant increase in preference during the second homecage test. During sucrose substitution, initial large differences in responding were observed between the lines. When the ethanol concentration was increased, intake (grams per kilogram) increased for the AA line but not for the ANA line. These effects were a function of no change in responding by the AA rats as concentration was increased and a decrease in responding by the ANA rats at the higher concentrations (20% and 30%). Taken together, data indicate that ethanol can function as a positive reinforcer for the behavior of AA and ANA rats. Even though 10% ethanol functioned as a reinforcer similarly for the two lines, ethanol intake in the AA line was significantly greater at the higher concentrations of ethanol, suggesting that ethanol functioned as a qualitatively different reinforcer for the AA rats, compared with the ANA rats.

  12. AaCAT1 of the Yellow Fever Mosquito, Aedes aegypti

    PubMed Central

    Hansen, Immo A.; Boudko, Dmitri Y.; Shiao, Shin-Hong; Voronov, Dmitri A.; Meleshkevitch, Ella A.; Drake, Lisa L.; Aguirre, Sarah E.; Fox, Jeffrey M.; Attardo, Geoffrey M.; Raikhel, Alexander S.

    2011-01-01

    Insect yolk protein precursor gene expression is regulated by nutritional and endocrine signals. A surge of amino acids in the hemolymph of blood-fed female mosquitoes activates a nutrient signaling system in the fat bodies, which subsequently derepresses yolk protein precursor genes and makes them responsive to activation by steroid hormones. Orphan transporters of the SLC7 family were identified as essential upstream components of the nutrient signaling system in the fat body of fruit flies and the yellow fever mosquito, Aedes aegypti. However, the transport function of these proteins was unknown. We report expression and functional characterization of AaCAT1, cloned from the fat body of A. aegypti. Expression of AaCAT1 transcript and protein undergoes dynamic changes during postembryonic development of the mosquito. Transcript expression was especially high in the third and fourth larval stages; however, the AaCAT1 protein was detected only in pupa and adult stages. Functional expression and analysis of AaCAT1 in Xenopus oocytes revealed that it acts as a sodium-independent cationic amino acid transporter, with unique selectivity to l-histidine at neutral pH (K0.5l-His = 0.34 ± 0.07 mm, pH 7.2). Acidification to pH 6.2 dramatically increases AaCAT1-specific His+-induced current. RNAi-mediated silencing of AaCAT1 reduces egg yield of subsequent ovipositions. Our data show that AaCAT1 has notable differences in its transport mechanism when compared with related mammalian cationic amino acid transporters. It may execute histidine-specific transport and signaling in mosquito tissues. PMID:21262963

  13. AA9int: SNP Interaction Pattern Search Using Non-Hierarchical Additive Model Set.

    PubMed

    Lin, Hui-Yi; Huang, Po-Yu; Chen, Dung-Tsa; Tung, Heng-Yuan; Sellers, Thomas A; Pow-Sang, Julio; Eeles, Rosalind; Easton, Doug; Kote-Jarai, Zsofia; Amin Al Olama, Ali; Benlloch, Sara; Muir, Kenneth; Giles, Graham G; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher A; Schleutker, Johanna; Nordestgaard, Børge G; Travis, Ruth C; Hamdy, Freddie; Neal, David E; Pashayan, Nora; Khaw, Kay-Tee; Stanford, Janet L; Blot, William J; Thibodeau, Stephen N; Maier, Christiane; Kibel, Adam S; Cybulski, Cezary; Cannon-Albright, Lisa; Brenner, Hermann; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R; Pandha, Hardev; Lu, Yong-Jie; Park, Jong Y

    2018-06-07

    The use of single nucleotide polymorphism (SNP) interactions to predict complex diseases is getting more attention during the past decade, but related statistical methods are still immature. We previously proposed the SNP Interaction Pattern Identifier (SIPI) approach to evaluate 45 SNP interaction patterns/patterns. SIPI is statistically powerful but suffers from a large computation burden. For large-scale studies, it is necessary to use a powerful and computation-efficient method. The objective of this study is to develop an evidence-based mini-version of SIPI as the screening tool or solitary use and to evaluate the impact of inheritance mode and model structure on detecting SNP-SNP interactions. We tested two candidate approaches: the 'Five-Full' and 'AA9int' method. The Five-Full approach is composed of the five full interaction models considering three inheritance modes (additive, dominant and recessive). The AA9int approach is composed of nine interaction models by considering non-hierarchical model structure and the additive mode. Our simulation results show that AA9int has similar statistical power compared to SIPI and is superior to the Five-Full approach, and the impact of the non-hierarchical model structure is greater than that of the inheritance mode in detecting SNP-SNP interactions. In summary, it is recommended that AA9int is a powerful tool to be used either alone or as the screening stage of a two-stage approach (AA9int+SIPI) for detecting SNP-SNP interactions in large-scale studies. The 'AA9int' and 'parAA9int' functions (standard and parallel computing version) are added in the SIPI R package, which is freely available at https://linhuiyi.github.io/LinHY_Software/. hlin1@lsuhsc.edu. Supplementary data are available at Bioinformatics online.

  14. AAS Publishing News: Astronomical Software Citation Workshop

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2015-07-01

    Do you write code for your research? Use astronomical software? Do you wish there were a better way of citing, sharing, archiving, or discovering software for astronomy research? You're not alone! In April 2015, AAS's publishing team joined other leaders in the astronomical software community in a meeting funded by the Sloan Foundation, with the purpose of discussing these issues and potential solutions. In attendance were representatives from academic astronomy, publishing, libraries, for-profit software sharing platforms, telescope facilities, and grantmaking institutions. The goal of the group was to establish “protocols, policies, and platforms for astronomical software citation, sharing, and archiving,” in the hopes of encouraging a set of normalized standards across the field. The AAS is now collaborating with leaders at GitHub to write grant proposals for a project to develop strategies for software discoverability and citation, in astronomy and beyond. If this topic interests you, you can find more details in this document released by the group after the meeting: http://astronomy-software-index.github.io/2015-workshop/ The group hopes to move this project forward with input and support from the broader community. Please share the above document, discuss it on social media using the hashtag #astroware (so that your conversations can be found!), or send private comments to julie.steffen@aas.org.

  15. Introducing the AAS Astronomy Ambassadors Program

    NASA Astrophysics Data System (ADS)

    Gurton, S.; Fienberg, R. T.; Fraknoi, A.; Prather, E. E.

    2013-04-01

    Newly established by the American Astronomical Society (AAS), the Astronomy Ambassadors program is designed to support early-career AAS members with training in resources and techniques for effective outreach to students and/or the public. A pilot Astronomy Ambassadors workshop will be held at the January 2013 AAS meeting. Workshop participants will learn to communicate effectively with public and school audiences; find outreach opportunities and establish ongoing partnerships with local schools, science centers, museums, parks, and/or community centers; reach audiences with personal stories, hands-on activities, and jargon-free language; identify strategies and techniques to improve their presentation skills; gain access to a menu of outreach resources that work in a variety of settings; and become part of an active community of astronomers who do outreach. Applications are welcome from advanced undergraduates (those doing research and committed to continuing in astronomy), graduate students, and postdocs and new faculty in their first two years after receipt of the PhD. We especially encourage applications from members of groups that are presently underrepresented in science.

  16. Presence of human non-polio enterovirus and parechovirus genotypes in an Amsterdam hospital in 2007 to 2011 compared to national and international published surveillance data: a comprehensive review.

    PubMed

    Janes, V A; Minnaar, R; Koen, G; van Eijk, H; Dijkman-de Haan, K; Pajkrt, D; Wolthers, K C; Benschop, K S

    2014-11-20

    Enteroviruses (EV) and human parechoviruses (HPeV) are endemic worldwide. These infections are a constant cause of hospitalisation and severe disease, predominantly in young children and infants. Coordinated monitoring and surveillance are crucial to control these infections. We have monitored EV and HPeV epidemiology in Amsterdam from 2007 to 2011 with real-time RT-PCR and direct genotyping, facilitating highly sensitive surveillance. Moreover, we conducted a literature survey of existing surveillance data for comparison. Only 14 studies were identified. While HPeV1 was most frequently detected in Amsterdam, EV-B viruses dominated nationally and internationally. Furthermore, the top 10 strains detected differed yearly and per study. However, detection and typing methods were too varied to allow direct comparison and comprehension of the worldwide distribution and circulation patterns of the different genotypes. This limited a direct response to anticipate peaks. Uniform European monitoring programmes are essential to aid prediction of outbreaks and disease management.

  17. Sugarcane Genotype Selection for Sand Soils in Florida

    USDA-ARS?s Scientific Manuscript database

    Selection of high yielding sugarcane (Saccharum spp.) genotypes for organic (muck) soils in Florida has been more successful than for sand soils. The purpose of this study was to compare the performance of 31 sugarcane genotypes on sand soils with and without mill mud added at the rate of 1510 cubic...

  18. FTO genotype is associated with exercise training-induced changes in body composition

    PubMed Central

    Rankinen, Tuomo; Rice, Treva; Teran-Garcia, Margarita; Rao, D.C.; Bouchard, Claude

    2010-01-01

    The fat mass and obesity associated (FTO) gene is the first obesity-susceptibility gene identified by genome-wide association scans and confirmed in several follow-up studies. Homozygotes for the risk allele (A/A) have 1.67 times greater risk of obesity than those who do not have the allele. However, it is not known if regular exercise-induced changes in body composition are influenced by the FTO genotype. The purpose of our study was to test if the FTO genotype is associated with exercise-induced changes in adiposity. Body composition was derived from underwater weighing before and after a 20-week endurance training program in 481 previously sedentary white subjects of the HERITAGE Family Study. FTO SNP rs8050136 was genotyped using Illumina GoldenGate assay. In the sedentary state, the A/A homozygotes were significantly heavier and fatter than the heterozygotes and the C/C homozygotes in men (p=0.004) but not in women (p=0.331; gene-by-sex interaction p=0.0053). The FTO genotype was associated with body fat responses to regular exercise (p<0.005; adjusted for age, sex, and baseline value of response trait): carriers of the C-allele showed three times greater fat mass and %body fat losses than the A/A homozygotes. The FTO genotype explained 2% of the variance in adiposity changes. Our data suggest that the FTO obesity-susceptibility genotype influences the body fat responses to regular exercise. Resistance to exercise-induced reduction in total adiposity may represent one mechanism by which the FTO A allele promotes overweight and obesity. PMID:19543202

  19. The AAS Visiting Professor Programs: Three Anniversaries

    NASA Astrophysics Data System (ADS)

    Philip, A. G. Davis

    2003-05-01

    The AAS Program of Visiting Professors was started in 1958 with three astronomers as lecturers. They were Paul Merrill (Mt. Wilson and Palomar Observatories), Seth Nicholson (Mt. Wilson and Palomar Observatories) and Harlow Shapley (Harvard College Observatory). The program was run by a Committee on Visiting Professors from 1958 through 1963. The program was funded by grants from the National Science Foundation. The Executive Officer of the AAS, Paul Routley headed the program from the 1963 - 64 academic year through the 1968 - 69 academic year. Larry Fredrick headed the program for 1969 - 70 and then Hank Gurin headed it through 1973 -74, the last year of the program. At the end of this summer meeting, the combined Visiting Professors Program and the Shapley Program will be starting their 47th year. The Shapley Visiting Lectureships in Astronomy Program was started in the 1974 - 75 academic year under the leadership of Hank Gurin. The original funding came from the Perkin Fund and a three year grant from the Research Corporation. In 1975 the Shapley Endowment fund was set up to help pay the expenses of the program. In 1976 there was support from the Slipher fund which lasted through the 1978 - 79 academic year. From 1979 to the present the program is financed by the Shapley Endowment Fund and by the contributions made by institutions which host the visits. In the fall of 1998 the fee that Institutions pay to the AAS in support of their Shapley visits was reduced from 300 to 250 to make it easier for them to apply for visits. Members of the AAS have made contributions to the program over the years and we are very appreciative of this support. In 1974 there were 42 lecturers in the program, of whom four are still active giving lectures (George Carruthers, Larry Fredrick, Arlo Landolt and Davis Philip). After the summer meeting, the Shapley Program will be embarking on its 30th year. Now there are 82 astronomers in the program and we get from 40 to 60 requests a year

  20. Comparative evaluation of the identification of rapidly growing non-tuberculous mycobacteria by mass spectrometry (MALDI-TOF MS), GenoType Mycobacterium CM/AS assay and partial sequencing of the rpoβ gene with phylogenetic analysis as a reference method.

    PubMed

    Costa-Alcalde, José Javier; Barbeito-Castiñeiras, Gema; González-Alba, José María; Aguilera, Antonio; Galán, Juan Carlos; Pérez-Del-Molino, María Luisa

    2018-06-02

    The American Thoracic Society and the Infectious Diseases Society of America recommend that clinically significant non-tuberculous mycobacteria (NTM) should be identified to the species level in order to determine their clinical significance. The aim of this study was to evaluate identification of rapidly growing NTM (RGM) isolated from clinical samples by using MALDI-TOF MS and a commercial molecular system. The results were compared with identification using a reference method. We included 46 clinical isolates of RGM and identified them using the commercial molecular system GenoType ® CM/AS (Hain, Lifescience, Germany), MALDI-TOF MS (Bruker) and, as reference method, partial rpoβ gene sequencing followed by BLAST and phylogenetic analysis with the 1093 sequences available in the GeneBank. The degree of agreement between GenoType ® and MALDI-TOF MS and the reference method, partial rpoβ sequencing, was 27/43 (62.8%) and 38/43 cases (88.3%) respectively. For all the samples correctly classified by GenoType ® , we obtained the same result with MALDI-TOF MS (27/27). However, MALDI-TOF MS also correctly identified 68.75% (11/16) of the samples that GenoType ® had misclassified (p=0.005). MALDI-TOF MS classified significantly better than GenoType ® . When a MALDI-TOF MS score >1.85 was achieved, MALDI-TOF MS and partial rpoβ gene sequencing were equivalent. GenoType ® was not able to distinguish between species belonging to the M. fortuitum complex. MALDI-TOF MS methodology is simple, rapid and associated with lower consumable costs than GenoType ® . The partial rpoβ sequencing methods with BLAST and phylogenetic analysis were not able to identify some RGM unequivocally. Therefore, sequencing of additional regions would be indicated in these cases. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  1. 40 CFR Appendix A to Subpart Aa of... - Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart AA

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... (40 CFR Part 63, Subpart A) to Subpart AA A Appendix A to Subpart AA of Part 63 Protection of... Hazardous Air Pollutants From Phosphoric Acid Manufacturing Plants Pt. 63, Subpt. AA, App. A Appendix A to Subpart AA of Part 63—Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart AA 40 CFR...

  2. 40 CFR Appendix A to Subpart Aa of... - Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart AA

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (40 CFR Part 63, Subpart A) to Subpart AA A Appendix A to Subpart AA of Part 63 Protection of... Hazardous Air Pollutants From Phosphoric Acid Manufacturing Plants Pt. 63, Subpt. AA, App. A Appendix A to Subpart AA of Part 63—Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart AA 40 CFR...

  3. Variation in PPP3CC Genotype Is Associated with Long-Term Recovery after Severe Brain Injury.

    PubMed

    Osier, Nicole D; Bales, James W; Pugh, Bunny; Shin, Samuel; Wyrobek, Julie; Puccio, Ava M; Okonkwo, David O; Ren, Dianxu; Alexander, Sheila; Conley, Yvette P; Dixon, C Edward

    2017-01-01

    After experimental traumatic brain injury (TBI), calcineurin is upregulated; blocking calcineurin is associated with improved outcomes. In humans, variation in the calcineurin A-gamma gene (PPP3CC) has been associated with neuropsychiatric disorders, though any role in TBI recovery remains unknown. This study examines associations between PPP3CC genotype and mortality, as well as gross functional status assessed at admission using the Glasgow Coma Scale (GCS) and at 3, 6, and 12 months after severe TBI using the Glasgow Outcome Score (GOS). The following tagging single nucleotide polymorphisms (tSNPs) in PPP3CC were genotyped: rs2443504, rs2461491, rs2469749, and rs10108011. The rs2443504 AA genotype was univariately associated with GCS (p = 0.022), GOS at 3, 6, and 12 months (p = 0.002, p = 0.034, and p = 0.004, respectively), and mortality (p = 0.007). In multivariate analysis controlling for age, sex, and GCS, the AA genotype of rs2443504 was associated with GOS at 3 (p = 0.02), and 12 months (p = 0.01), with a trend toward significance at 6 months (p = 0.05); the AA genotype also was associated with mortality in the multivariate model (p = 0.04). Further work is warranted to better understand the role of calcineurin, as well as the genes encoding it and their relevance to outcomes after brain injury.

  4. [Distribution and clinical significance of HBV genotypes in patients with HBV infection in 30 regions of China].

    PubMed

    Zhang, Ai-min; Wang, Hui-fen; Wang, Hai-bin; Su, Hai-bin; Xin, Shao-jie; Hu, Jin-hua; You, Shao-li

    2011-04-01

    To explore the distribution and clinical significance of HBV genotypes in patients with HBV infection in China. Serum samples were collected from 2922 patients with HBV infection. HBV genotyping was performed with type-specific primers polymerase chain reaction, and the virological and biochemical markers were detected, which differences in the genotypes distribution between various regions and liver function and virological markers between various HBV genotyping were analyzed. The genotype B, C, B + C, D of 2922 patients with HBV infection accounted for 15.9%, 83.5%, 0.41%, 0.21% respectively. In Northern China, genotype C was most prevalent, accounting for 90% of all cases, while it was less common in Southern China; genotype C was present in Zhejiang and Jiangsu provinces, but genotype B was comparatively more common in Guangdong, Hunan, Hubei, and Jiangxi provinces. B, C genotype HBV infection patients in the sex difference was not statistically significant; B genotypes compared with C genotype HBV infection patients, the average age of is less (P < 0.001); HBeAg positive rate of C genotype HBV infection patients are higher than that of B genotype (P = 0.023); Viral load of genotype C HBV infection patients is higher than that of genotype B (P = 0.038); Cholinesterase and Albumin levels of genotype C HBV infection patients are lower than that of genotype B (P values were 0.016, <0.001). There were HBV genotype B, C, B + C and D in Chinese patients with HBV infection, with genotype B and C being the major ones. Mainly in northern regions of genotype C, C genotype significantly reduced the southern region, some of the southern region dominated by B genotype. Genotype C HBV infection patients are older, and their HBeAg-positive rate is higher, and their liver damage is more severe, but their viral load is less.

  5. Transient thermal analysis during friction stir welding between AA2014-T6 and pure copper

    NASA Astrophysics Data System (ADS)

    Gadhavi, A. R.; Ghetiya, N. D.; Patel, K. M.

    2018-04-01

    AA2xxx-Cu alloys showed larger applications in the defence sectors and in aerospace industries due to high strength to weight ratio and toughness. FSW in a butt joint configuration was carried out between AA2014-T6 and pure Copper placing AA2014 on AS and Cu on RS. Temperature profiles were observed by inserting K-type thermocouples in the mid-thickness at various locations of the plate. A sharp decrease in temperature profiles was observed on Copper side due to its higher thermal conductivity. A thermal numerical model was prepared in ANSYS to compare the simulated temperature profiles with the experimental temperature profiles and both the temperature profiles were found to be in good agreement.

  6. Compression Behavior and Energy Absorption of Aluminum Alloy AA6061 Tubes with Multiple Holes

    NASA Astrophysics Data System (ADS)

    Simhachalam, Bade; Lakshmana Rao, C.; Srinivas, Krishna

    2014-05-01

    In this article, compression behavior and energy absorption of aluminum alloy AA6061 tubes are investigated both experimentally and numerically. Static and dynamic simulations are done using LS-Dyna Software for AA6061 tubes. True stress-plastic strain curves from the tensile test are used in the static and dynamic simulations of AA6061 tubes. The energy absorption values between experimental compression results and numeral simulation are found to be in good agreement. Dynamic simulations are done with drop velocity of up to 10 m/s to understand the inertia effects on energy absorption. The deformed modes from the numerical simulation are compared between tubes with and without holes in static and dynamic conditions.

  7. Comparison of preliminary results from Airborne Aster Simulator (AAS) with TIMS data

    NASA Technical Reports Server (NTRS)

    Kannari, Yoshiaki; Mills, Franklin; Watanabe, Hiroshi; Ezaka, Teruya; Narita, Tatsuhiko; Chang, Sheng-Huei

    1992-01-01

    The Japanese Advanced Spaceborne Thermal Emission and Reflection radiometer (ASTER), being developed for a NASA EOS-A satellite, will have 3 VNIR, 6 SWIR, and 5 TIR (8-12 micron) bands. An Airborne ASTER Simulator (AAS) was developed for Japan Resources Observation System Organization (JAROS) by the Geophysical Environmental Research Group (GER) Corp. to research surface temperature and emission features in the MWIR/TIR, to simulate ASTER's TIR bands, and to study further possibility of MWIR/TIR bands. ASTER Simulator has 1 VNIR, 3 MWIR (3-5 microns), and 20 (currently 24) TIR bands. Data was collected over 3 sites - Cuprite, Nevada; Long Valley/Mono Lake, California; and Death Valley, California - with simultaneous ground truth measurements. Preliminary data collected by AAS for Cuprite, Nevada is presented and AAS data is compared with Thermal Infrared Multispectral Scanner (TIMS) data.

  8. Simultaneous Genotype Calling and Haplotype Phasing Improves Genotype Accuracy and Reduces False-Positive Associations for Genome-wide Association Studies

    PubMed Central

    Browning, Brian L.; Yu, Zhaoxia

    2009-01-01

    We present a novel method for simultaneous genotype calling and haplotype-phase inference. Our method employs the computationally efficient BEAGLE haplotype-frequency model, which can be applied to large-scale studies with millions of markers and thousands of samples. We compare genotype calls made with our method to genotype calls made with the BIRDSEED, CHIAMO, GenCall, and ILLUMINUS genotype-calling methods, using genotype data from the Illumina 550K and Affymetrix 500K arrays. We show that our method has higher genotype-call accuracy and yields fewer uncalled genotypes than competing methods. We perform single-marker analysis of data from the Wellcome Trust Case Control Consortium bipolar disorder and type 2 diabetes studies. For bipolar disorder, the genotype calls in the original study yield 25 markers with apparent false-positive association with bipolar disorder at a p < 10−7 significance level, whereas genotype calls made with our method yield no associated markers at this significance threshold. Conversely, for markers with replicated association with type 2 diabetes, there is good concordance between genotype calls used in the original study and calls made by our method. Results from single-marker and haplotypic analysis of our method's genotype calls for the bipolar disorder study indicate that our method is highly effective at eliminating genotyping artifacts that cause false-positive associations in genome-wide association studies. Our new genotype-calling methods are implemented in the BEAGLE and BEAGLECALL software packages. PMID:19931040

  9. Determination of germanium by AAS in chloride-containing matrices.

    PubMed

    Anwari, M A; Abbasi, H U; Volkan, M; Ataman, O Y

    1996-06-01

    Interference effects of NaCl on the ET-AAS determination of Ge have been studied. The use of several matrix modifiers to alleviate this problem such as Ni and Zn perchlorates and nitrates, nitric acid, ammonium nitrate are reported. The stabilizing effect of Zn and Ni perchlorates allows the use of high pretreatment temperatures. NaCl is thus thermally volatilized from the atomizer by employing pretreatment temperatures higher than 1500 degrees C resulting in an improved sensitivity. Germanium levels in zinc plant slag samples, have been determined and compared to those obtained for the same samples spiked with NaCl with platform and wall atomization using nickel perchlorate as a matrix modifier. The results were compared with those from a hydride generation system equipped with a liquid nitrogen trap. The recoveries for germanium have been almost complete and amount to 99% for the original slag samples and 80% for 15% (w/w) NaCl containing spiked samples.

  10. Cholesterol, APOE genotype, and Alzheimer disease

    PubMed Central

    Hall, K.; Murrell, J.; Ogunniyi, A.; Deeg, M.; Baiyewu, O.; Gao, S.; Gureje, O.; Dickens, J.; Evans, R.; Smith-Gamble, V.; Unverzagt, F.W.; Shen, J.; Hendrie, H.

    2010-01-01

    Objective To examine the relationship between cholesterol and other lipids, APOE genotype, and risk of Alzheimer disease (AD) in a population-based study of elderly Yoruba living in Ibadan, Nigeria. Methods Blood samples and clinical data were collected from Yoruba study participants aged 70 years and older (N = 1,075) as part of the Indianapolis-Ibadan Dementia Project, a longitudinal epidemiologic study of AD. Cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride levels were measured in fasting blood samples. DNA was extracted and APOE was genotyped. Diagnoses of AD were made by consensus using National Institute of Neurologic Disorders/Stroke-Alzheimer's Disease and Related Disorders Association criteria. Results Logistic regression models showed interaction after adjusting for age and gender between APOE-ε4 genotype and biomarkers in the risk of AD cholesterol*genotype (p = 0.022), LDL*genotype (p = 0.018), and triglyceride*genotype (p = 0.036). Increasing levels of cholesterol and LDL were associated with increased risk of AD in individuals without the APOE-ε4 allele, but not in those with APOE-ε4. There was no significant association between levels of triglycerides and AD risk in those without APOE-ε4. Conclusions There was a significant interaction between cholesterol, APOE-ε4, and the risk of Alzheimer disease (AD) in the Yoruba, a population that has lower cholesterol levels and lower incidence rates of AD compared to African Americans. APOE status needs to be considered when assessing the relationship between lipid levels and AD risk in population studies. PMID:16434658

  11. Abnormal scintigraphic evolution in AA hepatic amyloidosis

    SciTech Connect

    Lomena, F.; Rosello, R.; Pons, F.

    1988-03-01

    A patient with AA amyloidosis secondary to ankylosing spondylitis showed intense liver uptake of Tc-99m MDP on bone imaging. The biopsy showed hepatic amyloid deposition. A repeat bone scan with Tc-99m MDP 1 year later was negative, although the clinical signs and liver function tests of the patient had not changed. A mechanism might exist, other than the affinity of amyloid to calcium, which would explain the extraosseous uptake of pyrophosphates and diphosphonates in organs and soft tissues affected by systemic amyloidosis.

  12. Vitamin D supplementation reduces some AT1-AA-induced downstream targets implicated in preeclampsia including hypertension

    PubMed Central

    Faulkner, Jessica L.; Amaral, Lorena M.; Cornelius, Denise C.; Cunningham, Mark W.; Ibrahim, Tarek; Heep, Autumn; Campbell, Nathan; Usry, Nathan; Wallace, Kedra; Herse, Florian; Dechend, Ralf

    2017-01-01

    Autoantibodies to the ANG II type I receptor (AT1-AA) are associated with preeclampsia (PE). We found that vitamin D supplementation reduced AT1-AA and blood pressure (MAP) in the RUPP rat model of PE. However, it was undetermined whether the decrease in AT1-AA was the mechanism whereby vitamin D lowered MAP or if it were through factors downstream of AT1-AA. Uterine artery resistance index, placental ET-1, and soluble FMS-like tyrosine kinase-1 are increased with AT1-AA-induced hypertension and are considered markers of PE in pregnant women. Therefore, we hypothesized that vitamin D would reduce PE factors during AT1-AA-induced hypertension and could lower blood pressure in a model of hypertension during pregnancy without PE features. Either ANG II (50 ng·kg−1·day) or AT1-AA (1:40) was infused from gestational day (GD) 12–19. vitamin D2 (VD2, 270 IU/day) or vitamin D3 (VD3, 15 IU/day) was administered orally from GD14–GD18. MAP (mmHg) increased in AT1-AA (121 ± 4) and ANG II (113 ± 1)-infused pregnant rats compared with normal pregnant rats (NP) (101 ± 2) but was lower in AT1-AA+VD2 (105 ± 2), AT1-AA+VD3 (109 ± 2), ANG II+VD2 (104 ± 4), and ANG II+VD3 (104 ± 3). VD2 and/or VD3 improved PE features associated with AT1-AA during pregnancy, while ANG II did not induce such features, supporting the hypothesis that AT1-AA induces PE features during pregnancy, and these are improved with vitamin D. In this study, we demonstrate that vitamin D improved many factors associated with PE and reduced blood pressure in a hypertensive model without PE features, indicating that vitamin D could be beneficial for various hypertensive disorders of pregnancy. PMID:27903510

  13. Vitamin D supplementation reduces some AT1-AA-induced downstream targets implicated in preeclampsia including hypertension.

    PubMed

    Faulkner, Jessica L; Amaral, Lorena M; Cornelius, Denise C; Cunningham, Mark W; Ibrahim, Tarek; Heep, Autumn; Campbell, Nathan; Usry, Nathan; Wallace, Kedra; Herse, Florian; Dechend, Ralf; LaMarca, Babbette

    2017-01-01

    Autoantibodies to the ANG II type I receptor (AT 1 -AA) are associated with preeclampsia (PE). We found that vitamin D supplementation reduced AT 1 -AA and blood pressure (MAP) in the RUPP rat model of PE. However, it was undetermined whether the decrease in AT 1 -AA was the mechanism whereby vitamin D lowered MAP or if it were through factors downstream of AT 1 -AA. Uterine artery resistance index, placental ET-1, and soluble FMS-like tyrosine kinase-1 are increased with AT 1 -AA-induced hypertension and are considered markers of PE in pregnant women. Therefore, we hypothesized that vitamin D would reduce PE factors during AT 1 -AA-induced hypertension and could lower blood pressure in a model of hypertension during pregnancy without PE features. Either ANG II (50 ng·kg -1 ·day) or AT 1 -AA (1:40) was infused from gestational day (GD) 12-19. vitamin D 2 (VD2, 270 IU/day) or vitamin D 3 (VD3, 15 IU/day) was administered orally from GD14-GD18. MAP (mmHg) increased in AT 1 -AA (121 ± 4) and ANG II (113 ± 1)-infused pregnant rats compared with normal pregnant rats (NP) (101 ± 2) but was lower in AT 1 -AA+VD2 (105 ± 2), AT 1 -AA+VD3 (109 ± 2), ANG II+VD2 (104 ± 4), and ANG II+VD3 (104 ± 3). VD2 and/or VD3 improved PE features associated with AT 1 -AA during pregnancy, while ANG II did not induce such features, supporting the hypothesis that AT 1 -AA induces PE features during pregnancy, and these are improved with vitamin D. In this study, we demonstrate that vitamin D improved many factors associated with PE and reduced blood pressure in a hypertensive model without PE features, indicating that vitamin D could be beneficial for various hypertensive disorders of pregnancy. Copyright © 2017 the American Physiological Society.

  14. Role of the 2 adenine (g.11293_11294insAA) insertion polymorphism in the 3' untranslated region of the factor VII (FVII) gene: molecular characterization of a patient with severe FVII deficiency.

    PubMed

    Peyvandi, F; Garagiola, I; Palla, R; Marziliano, N; Mannucci, P M

    2005-11-01

    Polymorphic variants in the gene encoding factor VII (F7) affect the plasma levels of this coagulation protein and modify the clinical phenotype of FVII deficiency in some patients. In this study we report the in vitro functional analysis of a novel polymorphic variant located in the 3' untranslated region of F7: g.11293_11294insAA. To determine whether this variant regulates FVII expression, we initially compared an expression vector containing FVII cDNA with g.11293_11294insAA with the FVII wild-type (WT) construct. The kinetics of mRNA production showed that the insertion decreases the steady-state FVII mRNA levels. To assess whether the insertion influences the phenotype of FVII-deficient patients, we evaluated its effect on the expression of FVII in a patient with severe FVII deficiency (undetectable FVII activity and antigen) carrying two additional homozygous missense variations (p.Arg277Cys and p.Arg353Gln). The two substitutions alone reduced the expression of FVII activity and antigen in vitro, but with the insertion polymorphism in our expression vector the patient's phenotype of undetectable plasma FVII was recapitulated. The insertion polymorphism in the 3' untranslated region of F7 is another modifier of FVII expression that might explain the poor genotype-phenotype correlation in some FVII-deficient patients. Copyright 2005 Wiley-Liss, Inc.

  15. Microstructural features of friction stir welded dissimilar Aluminium alloys AA2219-AA7475

    NASA Astrophysics Data System (ADS)

    Zaman Khan, Noor; Ubaid, Mohammed; Siddiquee, Arshad Noor; Khan, Zahid A.; Al-Ahmari, Abdulrahman; Chen, Xizhang; Haider Abidi, Mustufa

    2018-05-01

    High strength, good corrosion resistance, light weight make aluminium alloys a material of choice in many industrial sectors like aerospace, marine etc. Problems associated with welding of these alloys by fusion welding processes restricted their use in various industries. Friction stir welding (FSW), a clean solid-state joining process, easily overcomes various difficulties encountered during conventional fusion welding processes. In the present work, the effect of rotational speed (710 rpm, 900 rpm and 1120 rpm) on micro-hardness distribution and microstructure of FSWed dissimilar aluminium alloy joints were analyzed. Plates of AA7475-T761 and AA2219-O having thickness of 2.5 mm were welded by fixing AA7475 on retreating side (RS) and AA2219 on advancing side (AS). Welded joints were characterized by Vickers micro-hardness testing, scanning electron microscopy (SEM) and optical microscopy (OM). Results revealed that rotational speed significantly affects the micro-hardness due to increase in grain size, coarsening and dissolution of strengthening precipitates and re-precipitation. Higher micro-hardness values were observed in stir zone due to grain refinement and re-precipitation. Minimum micro-hardness value was observed at the TMAZ/HAZ of advancing side due to thermal softening.

  16. NR3C1 polymorphisms in Brazilians of Caucasian, African, and Asian ancestry: glucocorticoid sensitivity and genotype association.

    PubMed

    Souza, Manoel Carlos L A; Martins, Clarissa S; Silva-Junior, Ivan M; Chriguer, Rosangela S; Bueno, Ana C; Antonini, Sonir R; Silva, Wilson Araújo; Zago, Marco A; Moreira, Ayrton C; Castro, Margaret de

    2014-02-01

    The Brazilian population has heterogeneous ethnicity. No previous study evaluated NR3C1 polymorphisms in a Brazilian healthy population. We assessed NR3C1 polymorphisms in Brazilians of Caucasian, African and Asian ancestry (n = 380). In a subgroup (n = 40), we compared the genotypes to glucocorticoid (GC) sensitivity, which was previously evaluated by plasma (PF) and salivary (SF) cortisol after dexamethasone (DEX) suppression tests, GC receptor binding affinity (K d ), and DEX-50% inhibition (IC 50 ) of concanavalin-A-stimulated mononuclear cell proliferation. p.N363S (rs6195), p.ER22/23EK (rs6189-6190), and BclI (rs41423247) allelic discrimination was performed by Real-Time PCR (Polymerase Chain Reaction). Exons 3 to 9 and exon/intron boundaries were amplified by PCR and sequenced. Genotypic frequencies (%) were: rs6195 (n = 380; AA:96.6/AG:3.14/GG:0.26), rs6189-6190 (n = 264; GG:99.6/GA:0.4), rs41423247 (n = 264; CC:57.9/CG:34.1/GG:8.0), rs6188 (n = 155; GG:69.6/GT:25.7/TT:4.7), rs258751 (n = 150; CC:88.0/CT:10.7/TT:1.3), rs6196 (n = 176; TT:77.2/TC:20.4/CC:2.4), rs67300719 (n = 137; CC:99.3/CT:0.7), and rs72542757 (n = 137; CC:99.3/CG:0.7). The rs67300719 and rs72542757 were found only in Asian descendants, in whom p.N363S and p.ER22/23EK were absent. The p.ER22/23EK was observed exclusively in Caucasian descendants. Hardy-Weinberg equilibrium was observed, except in the Asian for rs6188 and rs258751, and in the African for p.N363S. The K d , IC 50 , baseline and after DEX PF or SF did not differ between genotype groups. However, the mean DEX dose that suppressed PF or SF differed among the BclI genotypes (P = 0.03). DEX dose was higher in GG- (0.7 ± 0.2 mg) compared to GC- (0.47 ± 0.2 mg) and CC-carriers (0.47 ± 0.1 mg). The genotypic frequencies of NR3C1 polymorphisms in Brazilians are similar to worldwide populations. Additionally, the BclI polymorphism was associated with altered pituitary-adrenal axis GC sensitivity.

  17. Clinical and epidemiological characteristics of Korean patients with hepatitis C virus genotype 6

    PubMed Central

    Seong, Mun Hyuk; Kil, Ho; Kim, Jong Yeop; Lee, Sang Soo; Jang, Eun Sun; Kim, Jin-Wook; Kim, Young Seok; Bae, Si Hyun; Lee, Youn Jae; Lee, Han Chu; Yun, Haesun; Kang, Byung Hak; Kim, Kisang

    2013-01-01

    Background/Aims The distribution of hepatitis C virus (HCV) genotypes varies geographically. In Korea, genotypes 1 and 2 comprise more than 90% of HCV infections, while genotype 6 is very rare. This study compared the clinical and epidemiological characteristics of patients with genotype 6 HCV infection with those infected with HCV genotypes 1 and 2. Methods This was a prospective, multicenter HCV cohort study that enrolled 1,173 adult patients, of which 930 underwent HCV genotype analysis, and only 9 (1.0%) were found to be infected with genotype 6 HCV. The clinical and epidemiological parameters of the genotypes were compared. Results The patients with genotype 6 HCV had a mean age of 41.5 years, 77.8% were male, and they had no distinct laboratory features. A sustained virologic response (SVR) was observed in four (67%) of six patients who received antiviral therapy. Risk factors such as the presence of a tattoo (n=6, 66.7%), more than three sexual partners (n=3, 33.3%), and injection drug use (n=3, 33.3%) were more common among genotype 6 patients than among genotypes 1 or 2. Conclusions The epidemiology and treatment response of patients infected with genotype 6 HCV differed significantly from those with genotypes 1 or 2, warranting continuous monitoring. PMID:23593609

  18. Heroin Use Is Associated with AA-Type Kidney Amyloidosis in the Pacific Northwest.

    PubMed

    Sharma, Arjun; Govindan, Priyanka; Toukatly, Mirna; Healy, Jack; Henry, Connor; Senter, Steve; Najafian, Behzad; Kestenbaum, Bryan

    2018-06-15

    AA-type kidney amyloidosis is classically associated with chronic autoimmune or inflammatory disorders. However, some urban centers have reported a high prevalence of injection drug use among patients with kidney AA amyloidosis. Previous reports lack control groups to quantify associations and most predate the opioid epidemic in the United States. We conducted a case-control study of 38 patients with biopsy-confirmed kidney AA amyloidosis and 72 matched control individuals without this condition from two large hospital systems in Seattle, Washington. We ascertained the pattern and duration of heroin use by medical chart review and determined associations using logistic regression. Among case patients, 95% had a prior history of heroin use, 87% had skin abscesses, and 76% and 27% had evidence of muscling and skin popping, respectively. After adjustment for age, race, sex, site, and year of biopsy, any heroin use (past or current) was associated with an estimated 170-times higher risk of kidney AA amyloidosis compared with no heroin use (95% confidence interval, 28 to 1018 times higher; P <0.001). Chronic autoimmune disorders were uncommon among case patients in this study. The median time to ESKD among patients with AA amyloidosis was 2.4 years (interquartile range, 0.5-7.5 years). Injection heroin use is strongly associated with kidney AA amyloidosis in the Pacific Northwest. Unique aspects of heroin use, in particular geographic regions or frequent associated soft-tissue infections, may be an important cause of this progressive kidney disease. Copyright © 2018 by the American Society of Nephrology.

  19. Scorpion neurotoxin AaIT-expressing Beauveria bassiana enhances the virulence against Aedes albopictus mosquitoes.

    PubMed

    Deng, Sheng-Qun; Cai, Qun-Di; Deng, Ming-Zhi; Huang, Qiang; Peng, Hong-Juan

    2017-12-01

    To improve the insecticidal efficacy of this entomopathogen Beauveria bassiana, the fungus was genetically modified to express an insect-specific scorpion neurotoxin AaIT. The virulence of the recombinant B. bassiana strain (Bb-AaIT) against Aedes albopictus adults (which occurs via penetration through the cuticle during spore germination or by conidia ingestion), and the larvae (by conidia ingestion) was measured with bioassays. The median lethal concentration (LC 50 ) of Bb-AaIT against A. albopictus larvae was 313.3-fold lower on day 4 and 11.3-fold lower on day 10 than that of the wild type (WT). Through conidia feeding or body contact, Bb-AaIT killed 50% of adult female mosquitoes at 3.9- or 1.9-fold reduced concentrations on day 4 and at 2.1- or 2.4-fold reduced concentrations on day 10. Compared with the results for the WT, the median lethal time (LT 50 ) of Bb-AaIT was reduced by 28.6% at 1 × 10 7 conidia ml -1 and 34.3% at 1 × 10 6 conidia ml -1 in the larvae bioassay by conidia ingestion, while it decreased 32.3% at 1 × 10 7 conidia ml -1 by conidia ingestion and 24.2% at 1 × 10 8 conidia ml -1 by penetrating through the cuticle in the adult bioassay. All the differences were significant. Our findings indicated that Bb-AaIT had higher virulence and faster action than the WT in killing the larval and adult mosquitoes, and therefore, it is valuable for development as a commercial mosquito pesticide.

  20. Discovery of novel variants in genotyping arrays improves genotype retention and reduces ascertainment bias

    PubMed Central

    2012-01-01

    Background High-density genotyping arrays that measure hybridization of genomic DNA fragments to allele-specific oligonucleotide probes are widely used to genotype single nucleotide polymorphisms (SNPs) in genetic studies, including human genome-wide association studies. Hybridization intensities are converted to genotype calls by clustering algorithms that assign each sample to a genotype class at each SNP. Data for SNP probes that do not conform to the expected pattern of clustering are often discarded, contributing to ascertainment bias and resulting in lost information - as much as 50% in a recent genome-wide association study in dogs. Results We identified atypical patterns of hybridization intensities that were highly reproducible and demonstrated that these patterns represent genetic variants that were not accounted for in the design of the array platform. We characterized variable intensity oligonucleotide (VINO) probes that display such patterns and are found in all hybridization-based genotyping platforms, including those developed for human, dog, cattle, and mouse. When recognized and properly interpreted, VINOs recovered a substantial fraction of discarded probes and counteracted SNP ascertainment bias. We developed software (MouseDivGeno) that identifies VINOs and improves the accuracy of genotype calling. MouseDivGeno produced highly concordant genotype calls when compared with other methods but it uniquely identified more than 786000 VINOs in 351 mouse samples. We used whole-genome sequence from 14 mouse strains to confirm the presence of novel variants explaining 28000 VINOs in those strains. We also identified VINOs in human HapMap 3 samples, many of which were specific to an African population. Incorporating VINOs in phylogenetic analyses substantially improved the accuracy of a Mus species tree and local haplotype assignment in laboratory mouse strains. Conclusion The problems of ascertainment bias and missing information due to genotyping errors

  1. Hepatitis delta genotypes in chronic delta infection in the northeast of Spain (Catalonia).

    PubMed

    Cotrina, M; Buti, M; Jardi, R; Quer, J; Rodriguez, F; Pascual, C; Esteban, R; Guardia, J

    1998-06-01

    Based on genetic analysis of variants obtained around the world, three genotypes of the hepatitis delta virus have been defined. Hepatitis delta virus variants have been associated with different disease patterns and geographic distributions. To determine the prevalence of hepatitis delta virus genotypes in the northeast of Spain (Catalonia) and the correlation with transmission routes and clinical disease, we studied the nucleotide divergence of the consensus sequence of HDV RNA obtained from 33 patients with chronic delta hepatitis (24 were intravenous drug users and nine had no risk factors), and four patients with acute self-limited delta infection. Serum HDV RNA was amplified by the polymerase chain reaction technique and a fragment of 350 nucleotides (nt 910 to 1259) was directly sequenced. Genetic analysis of the nucleotide consensus sequence obtained showed a high degree of conservation among sequences (93% of mean). Comparison of these sequences with those derived from different geographic areas and pertaining to genotypes I, II and III, showed a mean sequence identity of 92% with genotype I, 73% with genotype II and 61% with genotype III. At the amino acid level (aa 115 to 214), the mean identity was 87% with genotype I, 63% with genotype II and 56% with genotype III. Conserved regions included the RNA editing domain, the carboxyl terminal 19 amino acids of the hepatitis delta antigen and the polyadenylation signal of the viral mRNA. Hepatitis delta virus isolates in the northeast of Spain are exclusively genotype I, independently of the transmission route and the type of infection. No hepatitis delta virus subgenotypes were found, suggesting that the origin of hepatitis delta virus infection in our geographical area is homogeneous.

  2. Activity of vegetative insecticidal proteins Vip3Aa58 and Vip3Aa59 of Bacillus thuringiensis against lepidopteran pests.

    PubMed

    Baranek, Jakub; Kaznowski, Adam; Konecka, Edyta; Naimov, Samir

    2015-09-01

    Vegetative insecticidal proteins (Vips) secreted by some isolates of Bacillus thuringiensis show activity against insects and are regarded as insecticides against pests. A number of B. thuringiensis strains harbouring vip3A genes were isolated from different sources and identified by using a PCR based approach. The isolates with the highest insecticidal activity were indicated in screening tests, and their vip genes were cloned and sequenced. The analysis revealed two polymorphic Vip protein forms, which were classified as Vip3Aa58 and Vip3Aa59. After expression of the vip genes, the proteins were isolated and characterized. The activity of both toxins was estimated against economically important lepidopteran pests of woodlands (Dendrolimus pini), orchards (Cydia pomonella) and field crops (Spodoptera exigua). Vip3Aa58 and Vip3Aa59 were highly toxic and their potency surpassed those of many Cry proteins used in commercial bioinsecticides. Vip3Aa59 revealed similar larvicidal activity as Vip3Aa58 against S. exigua and C. pomonella. Despite 98% similarity of amino acid sequences of both proteins, Vip3Aa59 was significantly more active against D. pini. Additionally the effect of proteolytic activation of Vip58Aa and Vip3Aa59 on toxicity of D. pini and S. exigua was studied. Both Vip3Aa proteins did not show any activity against Tenebrio molitor (Coleoptera) larvae. The results suggest that the Vip3Aa58 and Vip3Aa59 toxins might be useful for controlling populations of insect pests of crops and forests. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Systemic AA amyloidosis in island foxes (Urocyon littoralis): Severity and risk factors

    PubMed Central

    Gaffney, Patricia M.; Witte, Carmel; Clifford, Deana L.; Imai, Denise M.; O’Brien, Timothy D.; Trejo, Margarita; Liberta, Falk; Annamalai, Karthikeyan; Fändrich, Marcus; Masliah, Eliezer; Munson, Linda; Sigurdson, Christina J.

    2016-01-01

    Systemic amyloid A (AA) amyloidosis is highly prevalent (34%) in endangered island foxes (Urocyon littoralis) and poses a risk to species recovery. Although elevated serum amyloid A from prolonged or recurrent inflammation predisposes to AA amyloidosis, additional risk factors are poorly understood. Here we define the severity of glomerular and medullary renal amyloid and identify risk factors for AA amyloidosis in 321 island foxes necropsied from 1987 through 2010. In affected kidneys, amyloid more commonly accumulated in the medullary interstitium than in the glomeruli [98% (78/80) versus 56% (45/80), respectively, p < 0.0001], and medullary deposition was more commonly severe [19% (20/105)] as compared to glomeruli [7% (7/105), p = 0.01]. Univariate odds ratios (ORs) of severe renal AA amyloidosis were greater for short- and long-term captive foxes compared to free-ranging (OR=3.2, 3.7, respectively, overall p = 0.05) and females compared to males (OR = 2.9, p = 0.05). Multivariable logistic regression revealed independent risk factors for amyloid development were increasing age class (OR = 3.8, p < 0.0001), San Clemente Island subspecies compared to San Nicolas Island subspecies (OR = 5.3, p = 0.0003), captivity (OR = 5.1, p = 0.0001), and nephritis (OR = 2.3, p = 0.01). The increased risk associated with the San Clemente subspecies or captivity suggests roles for genetic as well as exogenous risk factors in the development of AA amyloidosis. PMID:26419399

  4. Analysis for genotyping Duffy blood group in inhabitants of Sudan, the Fourth Cataract of the Nile

    PubMed Central

    2012-01-01

    Background Genetic polymophisms of the Duffy antigen receptor for the chemokines (DARC) gene successfully protected against blood stage infection by Plasmodium vivax infection. The Fy (a-, b-) phenotype is predominant among African populations, particularly those originating from West Africa, and it is rare among non-African populations. The aim of this study was to analyse the frequency of four Duffy blood groups based on SNPs (T-33C, G125A, G298A and C5411T) in two local tribes of Sudanese Arabs, the Shagia and Manasir, which are both from the region of the Fourth Nile cataract in Sudan. Methods An analysis of polymorphisms was performed on 217 individuals (126 representatives of the Shagia tribe and 91 of the Manasir). Real-time PCR and TaqMan Genotyping Assays were used to study the prevalence of alleles and genotypes. Results The analysis of allelic and genotype frequency in the T-33C polymorphisms demonstrated a significant dominance of the C allele and CC genotype (OR = 0.53 [0.32-0.88]; p = 0.02) in both tribes. The G125A polymorphism is associated with phenotype Fy(a-, b-) and was identified in 83% of Shagia and 77% of Manasir. With regard to G298A polymorphisms, the genotype frequencies were different between the tribes (p = 0,002) and no single AA homozygote was found. Based on four SNPs examined, 20 combinations of genotypes for the Shagia and Manasir tribes were determined. The genotype CC/AA/GG/CT occurred most often in Shagia tribe (45.9%) but was rare in the Manasir tribe (6.6%) (p < 0.001 Shagia versus Manasir). The FY*AES allele was identified in both analysed tribes. The presence of individuals with the FY*A/FY*A genotype was demonstrated only in the Shagia tribe. Conclusion This is probably the first report showing genotypically Duffy-negative people who carry both FY*BES and FY*AES. The identification of the FY*AES allele in both tribes may be due to admixture of the non-African genetic background. Taken as a whole, allele and genotype

  5. Safety and efficacy of an 8-week regimen of grazoprevir plus ruzasvir plus uprifosbuvir compared with grazoprevir plus elbasvir plus uprifosbuvir in participants without cirrhosis infected with hepatitis C virus genotypes 1, 2, or 3 (C-CREST-1 and C-CREST-2, part A): two randomised, phase 2, open-label trials.

    PubMed

    Gane, Edward J; Pianko, Stephen; Roberts, Stuart K; Thompson, Alexander J; Zeuzem, Stefan; Zuckerman, Eli; Ben-Ari, Ziv; Foster, Graham R; Agarwal, Kosh; Laursen, Alex L; Gerstoft, Jan; Gao, Wei; Huang, Hsueh-Cheng; Fitzgerald, Brian; Fernsler, Doreen; Li, Jerry J; Grandhi, Anjana; Liu, Hong; Su, Feng-Hsiu; Wan, Shuyan; Zeng, Zhen; Chen, Huei-Ling; Dutko, Frank J; Nguyen, Bach-Yen T; Wahl, Janice; Robertson, Michael N; Barr, Eliav; Yeh, Wendy W; Plank, Rebeca M; Butterton, Joan R; Esteban, Rafael

    2017-11-01

    New hepatitis C virus (HCV) therapies with pan-genotypic efficacy are needed. The goals of part A of C-CREST-1 and C-CREST-2 were to compare the efficacies of two doses (300 mg or 450 mg once daily) of uprifosbuvir (MK-3682; NS5B inhibitor) in an 8-week regimen combined with grazoprevir (NS3/4A inhibitor; 100 mg once daily) and an NS5A inhibitor, either elbasvir (50 mg once daily) or ruzasvir (MK-8408; 60 mg once daily), and to evaluate the safety and tolerability of these combination regimens in individuals infected with genotypes 1, 2, or 3. Part A of these phase 2, randomised, multicentre, open-label, clinical trials enrolled participants from 11 countries, aged 18 years or older, chronically infected with HCV genotypes 1, 2, or 3, with HCV RNA of at least 10 000 IU/mL, without evidence of cirrhosis, who had not received previous treatment for HCV infection. Within each HCV genotype, participants were randomly assigned (1:1:1:1) with a block size of 4, to open-label treatment to one of four treatment groups: grazoprevir (100 mg/day) plus ruzasvir (60 mg/day) plus uprifosbuvir (300 mg/day); grazoprevir (100 mg/day) plus ruzasvir (60 mg/day) plus uprifosbuvir (450 mg/day); grazoprevir (100 mg/day) plus elbasvir (50 mg/day) plus uprifosbuvir (300 mg/day); or grazoprevir (100 mg/day) plus elbasvir (50 mg/day) plus uprifosbuvir (450 mg/day), according to a computer-generated allocation schedule. Randomisation was centrally implemented using an interactive voice response system and integrated web response system. The primary endpoint was the proportion of participants achieving sustained virological response at 12 weeks (SVR12; HCV RNA less than the lower limit of quantitation at 12 weeks after the end of all study therapy) in the per-protocol analysis set, which included all participants who were randomised and received at least one dose of study drug. The trials are registered with ClinicalTrials.gov, numbers NCT02332707 and NCT02332720. 241 participants were

  6. Neurotrophin 3 genotype and emotional adverse effects of osmotic-release oral system methylphenidate (OROS-MPH) in children with attention-deficit/hyperactivity disorder.

    PubMed

    Park, Subin; Kim, Bung-Nyun; Kim, Jae-Won; Shin, Min-Sup; Cho, Soo-Churl; Kim, Ji-Hoon; Son, Jung-Woo; Shin, Yun-Mi; Chung, Un-Sun; Han, Doug-Hyun

    2014-03-01

    Neurotrophin 3 (NTF3) has been studied in relation to the pathophysiology of attention-deficit/hyperactivity disorder (ADHD) and mood disorders as well as psychostimulant action. We hypothesized that the risk of an emotional side effect to methylphenidate (MPH) treatment may be associated with NTF3 genotypes. Ninety-six medication-naïve children with ADHD (mean age 8.70, standard deviation 1.41 years, 79 males) were genotyped and treated with MPH. At baseline, which was prior to MPH treatment, and after two weeks of medication, investigators asked children and their parents or caregivers about adverse events using a symptom rating scale. ADHD subjects with the A/A genotype at the NTF3 rs6332 polymorphism showed the highest 'Emotionality' and 'Over-focus/euphoria' factor scores, followed by those with the G/A genotype and those with the G/G genotype (p=0.042 and p=0.045, respectively). ADHD subjects with the A/A genotype at the NTF3 rs6332 polymorphism showed the highest 'Proneness to crying' and 'Nail biting' item scores, followed by those with the G/A genotype and those with the G/G genotype (p=0.047 and p=0.017, respectively). These data provide preliminary evidence that genetic variation in the NTF3 gene is related to susceptibility to emotional side effects in response to MPH treatment in Korean children with ADHD.

  7. Indirect comparison of the antiviral efficacy of peginterferon alpha 2a plus ribavirin used with or without simeprevir in genotype 4 hepatitis C virus infection, where common comparator study arms are lacking: a special application of the matching adjusted indirect comparison methodology.

    PubMed

    Van Sanden, Suzy; Pisini, Marta; Duchesne, Inge; Mehnert, Angelika; Belsey, Jonathan

    2016-01-01

    The need to assess relative efficacy in the absence of comparative clinical trials is a problem that is often encountered in economic modeling. The use of matching adjusted indirect comparison (MAIC) in this situation has been suggested. We present the results of a MAIC used to evaluate the incremental benefit offered by adding simeprevir (SMV) to standard therapy in the treatment of patients infected with genotype 4 hepatitis C virus (HCV). Individual patient data for a single arm study evaluating the use of SMV with peginterferon alfa 2a + ribavirin (PR) in genotype 4 HCV were available (RESTORE study). A systematic literature review was used to identify studies of PR alone used in the same patient group. By applying the inclusion criteria for each study in turn to the RESTORE dataset and then applying the published MAIC covariate matching algorithm, a series of pseudosamples from RESTORE were generated. After assessment of the matching outcomes, the best matched comparisons were used to derive estimates of efficacy for SMV + PR in patients equivalent to those participating in the PR trial. Five potential comparator studies were identified. After applying the matching process, two emerged as offering the greatest equivalence with the generated RESTORE pseudosamples and were used to estimate SMV + PR efficacy, expressed as the percentage of patients achieving sustained viral response (SVR). In one comparison, SVR in the SMV + PR group was 85% versus 63% for PR alone. In the second comparison, the corresponding SVRs were 77% and 44% respectively. After matching for varying baseline characteristics, both comparisons of RESTORE versus studies of PR alone yielded a benefit for SMV + PR vs PR alone in genotype 4 HCV-infected patients. The incremental gain in SVR associated with use of SMV ranged from 22% to 33%. In the absence of direct comparative studies, the MAIC gives a better perspective than simple comparison of absolute SVR from individual

  8. AN EVALUATION OF CRYPTOSPORIDIUM PARVUM GENOTYPING

    EPA Science Inventory

    We evaluated the specificity and sensitivity of 11 previously described species differentiation and genotyping PCR protocols for detection of Cryptosporidium parasites. Genomic DNA from three species of Crytosporidium parasites (genotype 1 and genotype 2 of C. parvum, C. muris, a...

  9. Genotype Specification Language.

    PubMed

    Wilson, Erin H; Sagawa, Shiori; Weis, James W; Schubert, Max G; Bissell, Michael; Hawthorne, Brian; Reeves, Christopher D; Dean, Jed; Platt, Darren

    2016-06-17

    We describe here the Genotype Specification Language (GSL), a language that facilitates the rapid design of large and complex DNA constructs used to engineer genomes. The GSL compiler implements a high-level language based on traditional genetic notation, as well as a set of low-level DNA manipulation primitives. The language allows facile incorporation of parts from a library of cloned DNA constructs and from the "natural" library of parts in fully sequenced and annotated genomes. GSL was designed to engage genetic engineers in their native language while providing a framework for higher level abstract tooling. To this end we define four language levels, Level 0 (literal DNA sequence) through Level 3, with increasing abstraction of part selection and construction paths. GSL targets an intermediate language based on DNA slices that translates efficiently into a wide range of final output formats, such as FASTA and GenBank, and includes formats that specify instructions and materials such as oligonucleotide primers to allow the physical construction of the GSL designs by individual strain engineers or an automated DNA assembly core facility.

  10. Inhibitory effect of propolis on the development of AA amyloidosis.

    PubMed

    Harata, Daichi; Tsuchiya, Yuya; Miyoshi, Tomoyuki; Yanai, Tokuma; Suzuki, Kazuhiko; Murakami, Tomoaki

    2018-04-01

    In the several types of amyloidoses, participation of oxidative stresses in the pathogenesis and the effect of antioxidants on amyloidosis have been reported. Meanwhile, the relationship between oxidative stresses and pathogenesis of amyloid A (AA) amyloidosis is still unclear. In this study, we used an antioxidant, Brazilian propolis, to investigate the inhibitory effects on AA amyloidosis. The results showed that AA deposition was inhibited by administration of propolis. Increased expression of antioxidant markers was detected in molecular biological examinations of mice treated with propolis. Although serum amyloid A (SAA) levels were strongly correlated with the immunoreactive area of AA deposits in the control group, the correlation was weaker in the propolis-treated groups. In addition, there were no changes in SAA levels between the control group and the propolis-treated groups. The results indicate that propolis, an antioxidant, may induce inhibitory effects against AA amyloidosis.

  11. Changes of seed weight, fatty acid composition, oil and protein contents from different peanut FAD2 genotypes at different seed developmental and maturation stages

    USDA-ARS?s Scientific Manuscript database

    The level of oleic acid in peanut seed is one of the most important factors in determining seed quality and is controlled by two pairs of homeologous genes Fatty Acid Desaturase 2A and 2B (FAD2A and FAD2B). The genotypes of eight F8 breeding lines were determined as AABB, aaBB, AAbb, and aabb by rea...

  12. Echinococcus granulosus genotypes in Iran

    PubMed Central

    Sharafi, Seyedeh Maryam; Rostami-Nejad, Mohammad; Moazeni, Mohammad; Yousefi, Morteza; Saneie, Behnam; Hosseini-Safa, Ahmad

    2014-01-01

    Hydatidosis, caused by Echinococcus granulosus is one of the most important zoonotic diseases, throughout most parts of the world. Hydatidosis is endemic in Iran and responsible for approximately 1% of admission to surgical wards. There are extensive genetic variations within E. granulosus and 10 different genotypes (G1–G10) within this parasite have been reported. Identification of strains is important for improvement of control and prevention of the disease. No new review article presented the situation of Echinococcus granulosus genotypes in Iran in the recent years; therefore in this paper we reviewed the different studies regarding Echinococcus granulosus genotypes in Iran. PMID:24834298

  13. Vip3Aa induces apoptosis in cultured Spodoptera frugiperda (Sf9) cells.

    PubMed

    Jiang, Kun; Mei, Si-Qi; Wang, Ting-Ting; Pan, Jin-Hua; Chen, Yue-Hua; Cai, Jun

    2016-09-15

    The vegetative insecticidal proteins (Vip) secreted by many Bacillus thuringiensis strains during their vegetative growth stage are regarded as second generation insecticidal proteins, as they share no sequence or structural homology with known crystal insecticidal proteins (Cry) and have a broad insecticidal spectrum. Compared with insecticidal crystal proteins (ICPs), the insecticidal mechanisms of Vips have been little studied. Here we investigated the mechanism responsible for Vip3Aa toxicity in cultured insect cells. Using, flow cytometry analyzes, TUNEL staining and DNA fragmentation assays, we show that Vip3Aa can induce apoptosis in Spodoptera frugiperda (Sf9) cells and cause cells to arrest at the G2/M phase. We also show that Vip3Aa can disrupt mitochondrial membrane potential (ΔΨm), leading to the activation of Sf-caspase-1, suggesting that a mitochondrial mediated and caspase dependent pathway may be involved in Vip3Aa-induced apoptosis in Sf9 cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. States' Flexibility Waiver Plans for Alternate Assessments Based on Alternate Achievement Standards (AA-AAS). Synthesis Report 96

    ERIC Educational Resources Information Center

    Lazarus, Sheryl S.; Edwards, Lynn M.; Thurlow, Martha L.; Hodgson, Jennifer R.

    2014-01-01

    All states have alternate assessments based on alternate achievement standards (AA-AAS) for students with the most significant cognitive disabilities. For accountability purposes, the Elementary and Secondary Education Act (ESEA) allows up to 1% of students to be counted as proficient with this assessment option. In 2011 the U.S. Department of…

  15. Myeloperoxidase genotype, fruit and vegetable consumption, and breast cancer risk.

    PubMed

    Ahn, Jiyoung; Gammon, Marilie D; Santella, Regina M; Gaudet, Mia M; Britton, Julie A; Teitelbaum, Susan L; Terry, Mary Beth; Neugut, Alfred I; Josephy, P David; Ambrosone, Christine B

    2004-10-15

    Myeloperoxidase (MPO), an antimicrobial enzyme in the breast, generates reactive oxygen species (ROS) endogenously. An MPO G463A polymorphism exists in the promoter region, with the variant A allele conferring lower transcription activity than the common G allele. Because oxidative stress may play a role in breast carcinogenesis, we evaluated MPO genotypes in relation to breast cancer risk among 1,011 cases and 1,067 controls from the Long Island Breast Cancer Study Project (1996-1997). We also assessed the potential modifying effects of dietary antioxidants and hormonally related risk factors on these relationships. Women over 20 years with incident breast cancer who were residents of Nassau and Suffolk Counties, NY, were identified as potential cases. Population-based controls were frequency matched by 5-year age groups. Genotyping was performed with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) technology, and suspected breast cancer risk factors and usual dietary intake were assessed during an in-person interview. Unconditional logistic regression was used to estimate odds ratios and 95% confidence intervals. Having at least one A allele was associated with an overall 13% reduction in breast cancer risk. When consumption of fruits and vegetables and specific dietary antioxidants were dichotomized at the median, inverse associations with either GA or AA genotypes were most pronounced among women who consumed higher amounts of total fruits and vegetables (odds ratio, 0.75; 95% confidence interval, 0.58-0.97); this association was not noted among the low-consumption group (P for interaction = 0.04). Relationships were strongest among premenopausal women. Results from this first study of MPO genotypes and breast cancer risk indicate that MPO variants, related to reduced generation of ROS, are associated with decreased breast cancer risk, and emphasize the importance of fruit and vegetable consumption in reduction of breast

  16. The cytochrome P450 2AA gene cluster in zebrafish (Danio rerio): Expression of CYP2AA1 and CYP2AA2 and response to phenobarbital-type inducers

    SciTech Connect

    Kubota, Akira; Bainy, Afonso C.D.; Departamento de Bioquímica, CCB, Universidade Federal de Santa Catarina, Florianopolis, SC 88040-900

    2013-10-01

    The cytochrome P450 (CYP) 2 gene family is the largest and most diverse CYP gene family in vertebrates. In zebrafish, we have identified 10 genes in a new subfamily, CYP2AA, which does not show orthology to any human or other mammalian CYP genes. Here we report evolutionary and structural relationships of the 10 CYP2AA genes and expression of the first two genes, CYP2AA1 and CYP2AA2. Parsimony reconstruction of the tandem duplication pattern for the CYP2AA cluster suggests that CYP2AA1, CYP2AA2 and CYP2AA3 likely arose in the earlier duplication events and thus are most diverged in function from the other CYP2AAs.more » On the other hand, CYP2AA8 and CYP2AA9 are genes that arose in the latest duplication event, implying functional similarity between these two CYPs. A molecular model of CYP2AA1 showing the sequence conservation across the CYP2AA cluster reveals that the regions with the highest variability within the cluster map onto CYP2AA1 near the substrate access channels, suggesting differing substrate specificities. Zebrafish CYP2AA1 transcript was expressed predominantly in the intestine, while CYP2AA2 was most highly expressed in the kidney, suggesting differing roles in physiology. In the liver CYP2AA2 expression but not that of CYP2AA1, was increased by 1,4-bis [2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP) and, to a lesser extent, by phenobarbital (PB). In contrast, pregnenolone 16α-carbonitrile (PCN) increased CYP2AA1 expression, but not CYP2AA2 in the liver. The results identify a CYP2 subfamily in zebrafish that includes genes apparently induced by PB-type chemicals and PXR agonists, the first concrete in vivo evidence for a PB-type response in fish. - Highlights: • A tandemly duplicated cluster of ten CYP2AA genes was described in zebrafish. • Parsimony and duplication analyses suggest pathways to CYP2AA diversity. • Homology models reveal amino acid positions possibly related to functional diversity. • The CYP2AA locus does not share

  17. Dopaminergic and Serotonergic Genotypes and the Subjective Experiences of Hypnosis.

    PubMed

    Katonai, E R; Szekely, Anna; Vereczkei, A; Sasvari-Szekely, Maria; Bányai, Éva I; Varga, Katalin

    2017-01-01

    Hypnotizability is related to the Val 158 Met polymorphism of the COMT gene. The authors' aim was to find associations between candidate genes and subjective dimensions of hypnosis; 136 subjects participated in hypnosis and noninvasive DNA sampling. The phenomenological dimensions were tapped by the Archaic Involvement Measure (AIM), the Phenomenology of Consciousness Inventory (PCI), and the Dyadic Interactional Harmony Questionnaire (DIH). The main results were that the "Need of dependence" subscale of AIM was associated with the COMT genotypes. The GG subgroup showed higher scores, whereas AA had below average scores on the majority of the subjective measures. An association between the 5-HTTLPR polymorphism and the intimacy scores on the DIH was also evident. The effects are discussed in the social-psychobiological model of hypnosis.

  18. Warfarin sensitivity genotyping: a review of the literature and summary of patient experience.

    PubMed

    Moyer, Thomas P; O'Kane, Dennis J; Baudhuin, Linnea M; Wiley, Carmen L; Fortini, Alexandre; Fisher, Pamela K; Dupras, Denise M; Chaudhry, Rajeev; Thapa, Prabin; Zinsmeister, Alan R; Heit, John A

    2009-12-01

    The antithrombotic benefits of warfarin are countered by a narrow therapeutic index that contributes to excessive bleeding or cerebrovascular clotting and stroke in some patients. This article reviews the current literature describing warfarin sensitivity genotyping and compares the results of that review to the findings of our study in 189 patients at Mayo Clinic conducted between June 2001 and April 2003. For the review of the literature, we identified relevant peer-reviewed articles by searching the Web of Knowledge using key word warfarin-related adverse event. For the 189 Mayo Clinic patients initiating warfarin therapy to achieve a target international normalized ratio (INR) in the range of 2.0 to 3.5, we analyzed the CYP2C9 (cytochrome P450 2C9) and VKORC1 (vitamin K epoxide reductase complex, subunit 1) genetic loci to study the relationship among the initial warfarin dose, steady-state dose, time to achieve steady-state dose, variations in INR, and allelic variance. Results were compared with those previously reported in the literature for 637 patients. The relationships between allelic variants and warfarin sensitivity found in our study of Mayo Clinic patients are fundamentally the same as in those reported by others. The Mayo Clinic population is predominantly white and shows considerable allelic variability in CYP2C9 and VKORC1. Certain of these alleles are associated with increased sensitivity to warfarin. Polymorphisms in CYP2C9 and VKORC1 have a considerable effect on warfarin dose in white people. A correlation between steady-state warfarin dose and allelic variants of CYP2C9 and VKORC1 has been demonstrated by many previous reports and is reconfirmed in this report. The allelic variants found to most affect warfarin sensitivity are CYP2C9*1*1-VKORC1BB (less warfarin sensitivity than typical); CYP2C9*1*1-VKORC1AA (considerable variance in INR throughout initiation); CYP2C9*1*2-VKORC1AB (more sensitivity to warfarin than typical); CYP2C9*1*3-VKORC1

  19. Profile of renal AA amyloidosis in older and younger individuals: a single-centre experience.

    PubMed

    Erdogmus, Siyar; Kendi Celebi, Zeynep; Akturk, Serkan; Kumru, Gizem; Duman, Neval; Ates, Kenan; Erturk, Sehsuvar; Nergizoglu, Gokhan; Kutlay, Sim; Sengul, Sule; Keven, Kenan

    2018-05-18

    In epidemiological studies of amyloid A (AA) amyloidosis from Turkey, the most frequently cause was familial Mediterranean fever (FMF) and it occurs generally in young age population. However, there are no sufficient data regarding aetiology, clinical presentation and prognosis of renal AA amyloidosis in advanced age patients. In this study, we aimed to investigate demographic, clinical presentation, aetiology and outcomes of adults aged 60 years or older patients with biopsy-proven renal AA amyloidosis. This is a retrospective study involving 53 patients who were diagnosed with AA amyloidosis by kidney biopsy from 2006 to 2016. In all patients, kidney biopsies were performed due to asymptomatic proteinuria, nephrotic syndrome and/or renal insufficiency. The patients were separated into two groups on the basis of age (group I: ≥60 years and group II: <60 years). Outcomes of patients in terms of the requirement of renal replacement therapy and mortality were recorded. In patients with group I, the causes of AA amyloidosis were as follows: FMF 16 (50%), bronchiectasis 7 (23%), chronic osteomyelitis 2 (6%), inflammatory bowel disease 2 (6%), rheumatoid arthritis 2 (6%), ankylosing spondylitis 1 (3%) and unknown aetiology 2 (6%). The underlying disorders of AA amyloidosis in group II patients were as follows: FMF 17 (81%), Behcet's disease 1 (5%) and unknown aetiology 3 (14%). No statistically significant differences were detected between two groups with regard to systolic and diastolic blood pressures, albumin, proteinuria and lipids. The combination of chronic kidney disease and nephrotic syndrome was the most common clinical presentation in group I (73%) and group II (43%) (p = .05). Compared to the group II, estimated glomerular filtration rate was significantly lower in group I at the time of kidney biopsy (p = .003). At 12-month follow-up, 61% of the group I and 33% of the group II developed end-stage kidney disease requiring dialysis, while 11% of the

  20. Dynamic Response of AA2519 Aluminum Alloy under High Strain Rates

    NASA Astrophysics Data System (ADS)

    Olasumboye, Adewale Taiwo

    Like others in the AA2000 series, AA2519 is a heat-treatable Al-Cu alloy. Its excellent ballistic properties and stress corrosion cracking resistance, combined with other properties, qualify it as a prime candidate for armored vehicle and aircraft applications. However, available data on its high strain-rate response remains limited. In this study, AA2519 aluminum alloy was investigated in three different temper conditions: T4, T6, and T8, to determine the effects of heat treatment on the microstructure and dynamic deformation behavior of the material at high strain rates ranging within 1000 ≤ epsilon ≤ 4000 s-1. Split Hopkinson pressure bar integrated with digital image correlation system was used for mechanical response characterization. Optical microscopy and scanning electron microscopy were used to assess the microstructure of the material after following standard metallographic specimen preparation techniques. Results showed heterogeneous deformation in the three temper conditions. It was observed that dynamic behavior in each condition was dependent on strength properties due to the aging type controlling the strengthening precipitates produced and initial microstructure. At 1500 s -1, AA2519-T6 exhibited peak dynamic yield strength and flow stress of 509 and 667 MPa respectively, which are comparable with what were observed in T8 condition at higher rate of 3500 s-1 but AA2519-T4 showed the least strength and flow stress properties. Early stress collapse, dynamic strain aging, and higher susceptibility to shear band formation and fracture were observed in the T6 condition within the selected range of high strain rates. The alloy's general mode of damage evolution was by dispersoid particle nucleation, shearing and cracking.

  1. Bone Morphogenic Protein 4-Smad-Induced Upregulation of Platelet-Derived Growth Factor AA Impairs Endothelial Function.

    PubMed

    Hu, Weining; Zhang, Yang; Wang, Li; Lau, Chi Wai; Xu, Jian; Luo, Jiang-Yun; Gou, Lingshan; Yao, Xiaoqiang; Chen, Zhen-Yu; Ma, Ronald Ching Wan; Tian, Xiao Yu; Huang, Yu

    2016-03-01

    Bone morphogenic protein 4 (BMP4) is an important mediator of endothelial dysfunction in cardio-metabolic diseases, whereas platelet-derived growth factors (PDGFs) are major angiogenic and proinflammatory mediator, although the functional link between these 2 factors is unknown. The present study investigated whether PDGF mediates BMP4-induced endothelial dysfunction in diabetes mellitus. We generated Ad-Bmp4 to overexpress Bmp4 and Ad-Pdgfa-shRNA to knockdown Pdgfa in mice through tail intravenous injection. SMAD4-shRNA lentivirus, SMAD1-shRNA, and SMAD5 shRNA adenovirus were used for knockdown in human and mouse endothelial cells. We found that PDGF-AA impaired endothelium-dependent vasodilation in aortas and mesenteric resistance arteries. BMP4 upregulated PDGF-AA in human and mouse endothelial cells, which was abolished by BMP4 antagonist noggin or knockdown of SMAD1/5 or SMAD4. BMP4-impared relaxation in mouse aorta was also ameliorated by PDGF-AA neutralizing antibody. Tail injection of Ad-Pdgfa-shRNA ameliorates endothelial dysfunction induced by Bmp4 overexpression (Ad-Bmp4) in vivo. Serum PDGF-AA was elevated in both diabetic patients and diabetic db/db mice compared with nondiabetic controls. Pdgfa-shRNA or Bmp4-shRNA adenovirus reduced serum PDGF-AA concentration in db/db mice. PDGF-AA neutralizing antibody or tail injection with Pdgfa-shRNA adenovirus improved endothelial function in aortas and mesenteric resistance arteries from db/db mice. The effect of PDGF-AA on endothelial function in mouse aorta was also inhibited by Ad-Pdgfra-shRNA to inhibit PDGFRα. The present study provides novel evidences to show that PDGF-AA impairs endothelium-dependent vasodilation and PDGF-AA mediates BMP4-induced adverse effect on endothelial cell function through SMAD1/5- and SMAD4-dependent mechanisms. Inhibition of PGDF-AA ameliorates vascular dysfunction in diabetic mice. © 2016 American Heart Association, Inc.

  2. HLA genotyping by next-generation sequencing of complementary DNA.

    PubMed

    Segawa, Hidenobu; Kukita, Yoji; Kato, Kikuya

    2017-11-28

    Genotyping of the human leucocyte antigen (HLA) is indispensable for various medical treatments. However, unambiguous genotyping is technically challenging due to high polymorphism of the corresponding genomic region. Next-generation sequencing is changing the landscape of genotyping. In addition to high throughput of data, its additional advantage is that DNA templates are derived from single molecules, which is a strong merit for the phasing problem. Although most currently developed technologies use genomic DNA, use of cDNA could enable genotyping with reduced costs in data production and analysis. We thus developed an HLA genotyping system based on next-generation sequencing of cDNA. Each HLA gene was divided into 3 or 4 target regions subjected to PCR amplification and subsequent sequencing with Ion Torrent PGM. The sequence data were then subjected to an automated analysis. The principle of the analysis was to construct candidate sequences generated from all possible combinations of variable bases and arrange them in decreasing order of the number of reads. Upon collecting candidate sequences from all target regions, 2 haplotypes were usually assigned. Cases not assigned 2 haplotypes were forwarded to 4 additional processes: selection of candidate sequences applying more stringent criteria, removal of artificial haplotypes, selection of candidate sequences with a relaxed threshold for sequence matching, and countermeasure for incomplete sequences in the HLA database. The genotyping system was evaluated using 30 samples; the overall accuracy was 97.0% at the field 3 level and 98.3% at the G group level. With one sample, genotyping of DPB1 was not completed due to short read size. We then developed a method for complete sequencing of individual molecules of the DPB1 gene, using the molecular barcode technology. The performance of the automatic genotyping system was comparable to that of systems developed in previous studies. Thus, next-generation sequencing of

  3. The fatty acid amide hydrolase (FAAH) gene variant rs324420 AA/AC is not associated with weight loss in a 1-year lifestyle intervention for obese children and adolescents.

    PubMed

    Knoll, N; Volckmar, A-L; Pütter, C; Scherag, A; Kleber, M; Hebebrand, J; Hinney, A; Reinehr, T

    2012-01-01

    Adult obese carriers of the A allele of SNP rs324420 in the fatty acid amide hydrolase (FAAH) gene lose more weight and improve associated phenotypes better than non-carriers during an intervention. We aimed to replicate this finding in obese children and adolescents undergoing a one year lifestyle intervention (Obeldicks program). A total of 453 overweight and obese children and adolescents (10.8±2.6 years, BMI-SDS 2.4±0.5; 55% girls) were genotyped for rs324420 (C/A) by restriction fragment length polymorphism (RFLP) analysis. Participants were prescribed a balanced diet, containing 55 En% carbohydrates, 30 En% fat, and 15 En% proteins. Moreover, they took part in an exercise therapy once a week. Blood was taken at baseline and after 1 year of intervention. Anthropometric (height, weight, BMI, and BMI-SDS) and plasma parameters (total cholesterol, LDL-cholesterol, HDL-cholesterol, triacylglycerides, glucose, insulin, and HOMA) as well as blood pressure were measured. Both mean BMI and BMI-SDS improved significantly. The mean systolic blood pressure was also lowered and concentrations of HDL-cholesterol increased significantly. However, none of the measured changes were associated with FAAH rs324420 AA/AC genotype. We did not detect evidence for an association of FAAH genotypes with weight reduction in overweight and obese children and adolescents. Hence, the previous finding in adults could not be confirmed. As the length (1 year as compared to 3 months) and mode of treatment (hypocaloric diet in adults vs. physical activity plus balanced meals) of the interventions varied, these parameters might have influenced the inconsistent results. © Georg Thieme Verlag KG Stuttgart · New York.

  4. Molecular characterization of subgenotype A1 (subgroup Aa) of hepatitis B virus.

    PubMed

    Kramvis, Anna; Kew, Michael C

    2007-07-01

    Subgenotypes of hepatitis B virus (HBV) were first recognized after a unique segment of genotype A was identified when sequencing the preS2/S region of southern African HBV isolates. Originally named subgroup A', subsequently called subgroup Aa (for Africa) or subgenotype A1, this subgenotype is found in South Africa, Malawi, Uganda, Tanzania, Somalia, Yemen, India, Nepal, the Philippines and Brazil. The relatively higher mean nucleotide divergence of subgenotype A1 suggests that it has been endemic and has a long evolutionary history in the populations where it prevails. Distinctive sequence characteristics could account for the high hepatitis B e-antigen (HBeAg) negativity and low HBV DNA levels in carriers of this subgenotype. Substitutions or mutations can reduce HBeAg expression at three levels: (i) 1762T1764A atthe transcriptional level; (ii) substitutions at nt 1809-1812 at the translational level; and (iii) 1862T at the post-translational level. Co-existence of 1762T1764A and nt 1809-1812 mutations reduces HBeAg expression in an additive manner. In addition, subgenotype A1 has unique sequence alterations in the transcriptional regulatory elements and the polymerase coding region. The distinct sequence characteristics of subgenotype A1 may contribute to the 4.5-fold increased risk of heptocellular carcinoma in HBV carriers infected with genotype A, which is entirely attributable to subgenotype A1.

  5. Mechanisms of Behavior Change in Alcoholics Anonymous: Does AA lead to better alcohol use outcomes by reducing depression symptoms?

    PubMed Central

    Kelly, John F.; Stout, Robert L.; Magill, Molly; Tonigan, J. Scott; Pagano, Maria E.

    2009-01-01

    Rationale Indices of negative affect, such as depression, have been implicated in stress-induced pathways to alcohol relapse. Empirically-supported continuing care resources, such as Alcoholics Anonymous (AA), emphasize reducing negative affect to reduce relapse risk, but little research has been conducted to examine putative affective mechanisms of AA’s effects. Method Using lagged, controlled, hierarchical linear modeling and mediational analyses this study investigated whether AA participation mobilized changes in depression symptoms and whether such changes explained subsequent reductions in alcohol use. Alcohol dependent adults (N = 1,706), receiving treatment as part of a clinical trial, were assessed at intake, 3, 6, 9, 12, and 15 months. Results Findings revealed elevated levels of depression compared to the general population, which decreased during treatment and then remained stable over follow-up. Greater AA attendance was associated with better subsequent alcohol use outcomes and decreased depression. Greater depression was associated with heavier and more frequent drinking. Lagged, mediation analyses revealed that the effects of AA on alcohol use was partially mediated by reductions in depression symptoms. However, this salutary effect on depression itself appeared to be explained by AA’s proximal effect on reducing concurrent drinking. Conclusions AA attendance was both concurrently and predictively associated with improved alcohol outcomes. Although AA attendance was additionally associated with subsequent improvements in depression, it did not predict such improvements over and above concurrent alcohol use. AA appears to lead both to improvements in alcohol use and psychological and emotional well-being, which, in turn, may reinforce further abstinence and recovery-related change. PMID:20102345

  6. Genotype Imputation with Millions of Reference Samples.

    PubMed

    Browning, Brian L; Browning, Sharon R

    2016-01-07

    We present a genotype imputation method that scales to millions of reference samples. The imputation method, based on the Li and Stephens model and implemented in Beagle v.4.1, is parallelized and memory efficient, making it well suited to multi-core computer processors. It achieves fast, accurate, and memory-efficient genotype imputation by restricting the probability model to markers that are genotyped in the target samples and by performing linear interpolation to impute ungenotyped variants. We compare Beagle v.4.1 with Impute2 and Minimac3 by using 1000 Genomes Project data, UK10K Project data, and simulated data. All three methods have similar accuracy but different memory requirements and different computation times. When imputing 10 Mb of sequence data from 50,000 reference samples, Beagle's throughput was more than 100× greater than Impute2's throughput on our computer servers. When imputing 10 Mb of sequence data from 200,000 reference samples in VCF format, Minimac3 consumed 26× more memory per computational thread and 15× more CPU time than Beagle. We demonstrate that Beagle v.4.1 scales to much larger reference panels by performing imputation from a simulated reference panel having 5 million samples and a mean marker density of one marker per four base pairs. Copyright © 2016 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  7. Genotype Imputation with Millions of Reference Samples

    PubMed Central

    Browning, Brian L.; Browning, Sharon R.

    2016-01-01

    We present a genotype imputation method that scales to millions of reference samples. The imputation method, based on the Li and Stephens model and implemented in Beagle v.4.1, is parallelized and memory efficient, making it well suited to multi-core computer processors. It achieves fast, accurate, and memory-efficient genotype imputation by restricting the probability model to markers that are genotyped in the target samples and by performing linear interpolation to impute ungenotyped variants. We compare Beagle v.4.1 with Impute2 and Minimac3 by using 1000 Genomes Project data, UK10K Project data, and simulated data. All three methods have similar accuracy but different memory requirements and different computation times. When imputing 10 Mb of sequence data from 50,000 reference samples, Beagle’s throughput was more than 100× greater than Impute2’s throughput on our computer servers. When imputing 10 Mb of sequence data from 200,000 reference samples in VCF format, Minimac3 consumed 26× more memory per computational thread and 15× more CPU time than Beagle. We demonstrate that Beagle v.4.1 scales to much larger reference panels by performing imputation from a simulated reference panel having 5 million samples and a mean marker density of one marker per four base pairs. PMID:26748515

  8. Determination of elements in ayurvedic medicinal plants by AAS

    SciTech Connect

    Teerthe, Santoshkumar S.; Kerur, B. R., E-mail: kerurbrk@yahoo.com

    India has a rich country for the uses of Ayurvedic medicinal plants for treatment and also the north- Karnataka boasts an unparallel diversity of medicinal plants. The present study attempts to estimate and compare the level of trace and heavy metals in some selected leaves and root samples of Ayurvedic medicinal plants such as Mg, Al, K, Cr, Mn, Fe, Cu, Zn, and Cd. The samples are collected from different places of North-Karnataka regions and sample solutions prepared as the ratio of 1:25:25+950ml=1000ppm.the trace and heavy elemental concentration was estimated using Atomic Absorption Spectrometric (AAS) Method. The average concentrations ofmore » Mg, Mn, Fe and Zn, are ranging from 2ppm to 5250.2ppm and potassium (K) has more concentration as compare to all other. The other elements likes Al, Cr, Cu, and Cd were also estimed and presented in the table. Therefore, these medicinal plants are rich in some essential minerals, especially K, Mg, Mn, Fe and Zn which are essential for human health.« less

  9. A&A Painting and Restoration Co., Inc. Information Sheet

    EPA Pesticide Factsheets

    A&A Painting and Restoration Co., Inc. (the Company) is located in Great Mills, Maryland. The settlement involves renovation activities conducted at properties constructed prior to 1978, located in Drayden, Maryland.

  10. View northwest, wharf, A portion AA, detail showing timber groin ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View northwest, wharf, A portion AA, detail showing timber groin - U.S. Coast Guard Sandy Hook Station, Western Docking Structure, West of intersection of Canfield Road & Hartshorne Drive, Highlands, Monmouth County, NJ

  11. SECTION AA, AXONOMETRIC Dyess Air Force Base, Atlas F ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    SECTION A-A, AXONOMETRIC - Dyess Air Force Base, Atlas F Missle Site S-8, Launch Control Center (LCC), Approximately 3 miles east of Winters, 500 feet southwest of Highway 17700, northwest of Launch Facility, Winters, Runnels County, TX

  12. Section AA through main entrance gates & west stairs. San ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Section AA through main entrance gates & west stairs. San Bernardino Valley Union Junior College, Science Building. Also includes plans and sections of boys' and girls' toilets. Howard E. Jones, Architect, San Bernardino, California. Sheet 5, job no. 311. Scales 1/4 inch to the foot (section AA) and 1/2 inch to the foot (toilet rooms). February 15, 1927. - San Bernardino Valley College, Life Science Building, 701 South Mount Vernon Avenue, San Bernardino, San Bernardino County, CA

  13. Characteristics of AA amyloidosis patients in San Francisco.

    PubMed

    Lejmi, Hiba; Jen, Kuang-Yu; Olson, Jean L; James, Sam H; Sam, Ramin

    2016-04-01

    AA amyloidosis due to subcutaneous injection of drugs of abuse has been described in the USA, but all the existing literature is from more than 20 years ago. There is more recent literature from Europe. We have observed a high incidence of AA amyloidosis in the county hospital in San Francisco. Here, we describe 24 patients who had kidney biopsy-proven AA amyloidosis from our hospital from 1998 to 2013. All the patients were thought to have AA amyloidosis from skin popping of illicit drugs after having exhausted the intravenous route. These patients with biopsy-proven AA amyloidosis were analysed further. All patients were found to have hepatitis C infection, hypertension was not common, most had advanced kidney failure, and acidosis was common as was tubulointerstitial involvement on the kidney biopsy. Other organ involvement included hepatomegaly and splenomegaly in a number of patients; direct myocardial involvement was not seen, but pulmonary hypertension, history of deep vein thrombosis and pulmonary embolism were common. The prognosis of these patients was poor. The mortality rate approached 50% 1 year after biopsy, and most of the patient needed dialysis shortly after diagnosis. Cessation of drug use seemed beneficial but rarely achievable. AA amyloidosis from skin popping is common in San Francisco. Most patients with renal involvement end up on dialysis, and mortality rates are exceedingly high. © 2015 Asian Pacific Society of Nephrology.

  14. Transgenic plants expressing the AaIT/GNA fusion protein show increased resistance and toxicity to both chewing and sucking pests.

    PubMed

    Liu, Shu-Min; Li, Jie; Zhu, Jin-Qi; Wang, Xiao-Wei; Wang, Cheng-Shu; Liu, Shu-Sheng; Chen, Xue-Xin; Li, Sheng

    2016-04-01

    The adoption of pest-resistant transgenic plants to reduce yield losses and decrease pesticide use has been successful. To achieve the goal of controlling both chewing and sucking pests in a given transgenic plant, we generated transgenic tobacco, Arabidopsis, and rice plants expressing the fusion protein, AaIT/GNA, in which an insecticidal scorpion venom neurotoxin (Androctonus australis toxin, AaIT) is fused to snowdrop lectin (Galanthus nivalis agglutinin, GNA). Compared with transgenic tobacco and Arabidopsis plants expressing AaIT or GNA, transgenic plants expressing AaIT/GNA exhibited increased resistance and toxicity to one chewing pest, the cotton bollworm, Helicoverpa armigera. Transgenic tobacco and rice plants expressing AaIT/GNA showed increased resistance and toxicity to two sucking pests, the whitefly, Bemisia tabaci, and the rice brown planthopper, Nilaparvata lugens, respectively. Moreover, in the field, transgenic rice plants expressing AaIT/GNA exhibited a significant improvement in grain yield when infested with N. lugens. This study shows that expressing the AaIT/GNA fusion protein in transgenic plants can be a useful approach for controlling pests, particularly sucking pests which are not susceptible to the toxin in Bt crops. © 2015 Institute of Zoology, Chinese Academy of Sciences.

  15. Effects of simulated ice on the performance of price type-AA current meter rotors

    USGS Publications Warehouse

    Fulford, Janice M.

    1994-01-01

    Slush ice readily adheres to the standard metal rotor of the winter Price type-AA current meter and affects the ability of the meter to measure the flow velocity accurately. Tests conducted at the U.S. Geological Survey Hydraulics Laboratory at Stennis Space Center, Mississippi, attempt to quantify the effects of slush ice on the performance of standard Price type-AA meter metal rotors. Test data obtained for rotors filled with simulated slush are compared with data for solid-cup polymer and standard hollow-cup metal rotors. Partial filling of the cups only marginally affects rotor performance at velocities greater than 15.24 centimeters per second. However, when cups are filled or over-filled with simulated slush, rotor performance is noticeably affected. Errors associated with slush over-filling and filling of cups are also significant when flows are angled vertically.

  16. AAS and spectrophotometric methods for the determination metoprolol tartrate in tablets

    NASA Astrophysics Data System (ADS)

    Alpdoğan, Güzin; Sungur, Sidika

    1999-11-01

    Sensitive and specific atomic adsorption spectroscopy (AAS) and spectrophotometric methods have been developed for the determination of beta adrenergic blocking drug, metoprolol tartrate.The method is based on the formation of Cu(II) dithiocarbamate complex by derivatization of the secondary amino group of metoprolol with CS 2 and CuCl 2 in the presence of ammonia.The copper-bis(dithiocarbamate) complex was extracted into chloroform and the concentration of metoprolol tartrate was determined directly by spectrophotometric and indirectly by AAS measurement of copper.The two methods developed were applied to the assay of metoprolol tartrate in commercial tablet formulations.The methods were compared statistically with each other and with the high performance liquid chromatography (HPLC) method of USPXXII using t- and F-tests.

  17. Work capacity and anticipation in A.A. Ukhtomsky's concept of dominance

    NASA Astrophysics Data System (ADS)

    Pavlova, L. P.

    2015-08-01

    This paper presents the results of theoretical and experimental investigations of human activity and anticipation based on A.A. Ukhtomsky's concept of brain dominance - a non-equilibrium system-forming factor in living systems. Facts on the stages of dominance formation are presented in relation to the creative abilities of the human brain and the role of fatigue as a "lever" for increasing systems' work capacity on the basis of "trace exaltation". Individually, specific features of dominantogenesis are compared with variations in behavioural types. On the basis of chronotopic EEG analysis, we delineate cortical dominants that underlie individual specifics of cognitive processes. The relation is shown between anticipation and the "expansion of dominants" - the broadening of "distal perception" in time and space, as framed by A.A. Ukhtomsky.

  18. Comparison of soil pollution concentrations determined using AAS and portable XRF techniques.

    PubMed

    Radu, Tanja; Diamond, Dermot

    2009-11-15

    Past mining activities in the area of Silvermines, Ireland, have resulted in heavily polluted soils. The possibility of spreading pollution to the surrounding areas through dust blow-offs poses a potential threat for the local communities. Conventional environmental soil and dust analysis techniques are very slow and laborious and consequently there is a need for fast and accurate analytical methods, which can provide real-time in situ pollution mapping. Laboratory-based aqua regia acid digestion of the soil samples collected in the area followed by the atomic absorption spectrophotometry (AAS) analysis confirmed very high pollution, especially by Pb, As, Cu, and Zn. In parallel, samples were analyzed using portable X-ray fluorescence radioisotope and miniature tube powered (XRF) NITON instruments and their performance was compared. Overall, the portable XRF instrument gave excellent correlation with the laboratory-based reference AAS method.

  19. Transforming microbial genotyping: a robotic pipeline for genotyping bacterial strains.

    PubMed

    O'Farrell, Brian; Haase, Jana K; Velayudhan, Vimalkumar; Murphy, Ronan A; Achtman, Mark

    2012-01-01

    Microbial genotyping increasingly deals with large numbers of samples, and data are commonly evaluated by unstructured approaches, such as spread-sheets. The efficiency, reliability and throughput of genotyping would benefit from the automation of manual manipulations within the context of sophisticated data storage. We developed a medium- throughput genotyping pipeline for MultiLocus Sequence Typing (MLST) of bacterial pathogens. This pipeline was implemented through a combination of four automated liquid handling systems, a Laboratory Information Management System (LIMS) consisting of a variety of dedicated commercial operating systems and programs, including a Sample Management System, plus numerous Python scripts. All tubes and microwell racks were bar-coded and their locations and status were recorded in the LIMS. We also created a hierarchical set of items that could be used to represent bacterial species, their products and experiments. The LIMS allowed reliable, semi-automated, traceable bacterial genotyping from initial single colony isolation and sub-cultivation through DNA extraction and normalization to PCRs, sequencing and MLST sequence trace evaluation. We also describe robotic sequencing to facilitate cherrypicking of sequence dropouts. This pipeline is user-friendly, with a throughput of 96 strains within 10 working days at a total cost of < €25 per strain. Since developing this pipeline, >200,000 items were processed by two to three people. Our sophisticated automated pipeline can be implemented by a small microbiology group without extensive external support, and provides a general framework for semi-automated bacterial genotyping of large numbers of samples at low cost.

  20. Transforming Microbial Genotyping: A Robotic Pipeline for Genotyping Bacterial Strains

    PubMed Central

    Velayudhan, Vimalkumar; Murphy, Ronan A.; Achtman, Mark

    2012-01-01

    Microbial genotyping increasingly deals with large numbers of samples, and data are commonly evaluated by unstructured approaches, such as spread-sheets. The efficiency, reliability and throughput of genotyping would benefit from the automation of manual manipulations within the context of sophisticated data storage. We developed a medium- throughput genotyping pipeline for MultiLocus Sequence Typing (MLST) of bacterial pathogens. This pipeline was implemented through a combination of four automated liquid handling systems, a Laboratory Information Management System (LIMS) consisting of a variety of dedicated commercial operating systems and programs, including a Sample Management System, plus numerous Python scripts. All tubes and microwell racks were bar-coded and their locations and status were recorded in the LIMS. We also created a hierarchical set of items that could be used to represent bacterial species, their products and experiments. The LIMS allowed reliable, semi-automated, traceable bacterial genotyping from initial single colony isolation and sub-cultivation through DNA extraction and normalization to PCRs, sequencing and MLST sequence trace evaluation. We also describe robotic sequencing to facilitate cherrypicking of sequence dropouts. This pipeline is user-friendly, with a throughput of 96 strains within 10 working days at a total cost of < €25 per strain. Since developing this pipeline, >200,000 items were processed by two to three people. Our sophisticated automated pipeline can be implemented by a small microbiology group without extensive external support, and provides a general framework for semi-automated bacterial genotyping of large numbers of samples at low cost. PMID:23144721

  1. Transcriptome profiling of the intoxication response of Tenebrio molitor larvae to Bacillus thuringiensis Cry3Aa protoxin.

    PubMed

    Oppert, Brenda; Dowd, Scot E; Bouffard, Pascal; Li, Lewyn; Conesa, Ana; Lorenzen, Marcé D; Toutges, Michelle; Marshall, Jeremy; Huestis, Diana L; Fabrick, Jeff; Oppert, Cris; Jurat-Fuentes, Juan Luis

    2012-01-01

    Bacillus thuringiensis (Bt) crystal (Cry) proteins are effective against a select number of insect pests, but improvements are needed to increase efficacy and decrease time to mortality for coleopteran pests. To gain insight into the Bt intoxication process in Coleoptera, we performed RNA-Seq on cDNA generated from the guts of Tenebrio molitor larvae that consumed either a control diet or a diet containing Cry3Aa protoxin. Approximately 134,090 and 124,287 sequence reads from the control and Cry3Aa-treated groups were assembled into 1,318 and 1,140 contigs, respectively. Enrichment analyses indicated that functions associated with mitochondrial respiration, signalling, maintenance of cell structure, membrane integrity, protein recycling/synthesis, and glycosyl hydrolases were significantly increased in Cry3Aa-treated larvae, whereas functions associated with many metabolic processes were reduced, especially glycolysis, tricarboxylic acid cycle, and fatty acid synthesis. Microarray analysis was used to evaluate temporal changes in gene expression after 6, 12 or 24 h of Cry3Aa exposure. Overall, microarray analysis indicated that transcripts related to allergens, chitin-binding proteins, glycosyl hydrolases, and tubulins were induced, and those related to immunity and metabolism were repressed in Cry3Aa-intoxicated larvae. The 24 h microarray data validated most of the RNA-Seq data. Of the three intoxication intervals, larvae demonstrated more differential expression of transcripts after 12 h exposure to Cry3Aa. Gene expression examined by three different methods in control vs. Cry3Aa-treated larvae at the 24 h time point indicated that transcripts encoding proteins with chitin-binding domain 3 were the most differentially expressed in Cry3Aa-intoxicated larvae. Overall, the data suggest that T. molitor larvae mount a complex response to Cry3Aa during the initial 24 h of intoxication. Data from this study represent the largest genetic sequence dataset for T. molitor

  2. Transcriptome Profiling of the Intoxication Response of Tenebrio molitor Larvae to Bacillus thuringiensis Cry3Aa Protoxin

    PubMed Central

    Oppert, Brenda; Dowd, Scot E.; Bouffard, Pascal; Li, Lewyn; Conesa, Ana; Lorenzen, Marcé D.; Toutges, Michelle; Marshall, Jeremy; Huestis, Diana L.; Fabrick, Jeff; Oppert, Cris; Jurat-Fuentes, Juan Luis

    2012-01-01

    Bacillus thuringiensis (Bt) crystal (Cry) proteins are effective against a select number of insect pests, but improvements are needed to increase efficacy and decrease time to mortality for coleopteran pests. To gain insight into the Bt intoxication process in Coleoptera, we performed RNA-Seq on cDNA generated from the guts of Tenebrio molitor larvae that consumed either a control diet or a diet containing Cry3Aa protoxin. Approximately 134,090 and 124,287 sequence reads from the control and Cry3Aa-treated groups were assembled into 1,318 and 1,140 contigs, respectively. Enrichment analyses indicated that functions associated with mitochondrial respiration, signalling, maintenance of cell structure, membrane integrity, protein recycling/synthesis, and glycosyl hydrolases were significantly increased in Cry3Aa-treated larvae, whereas functions associated with many metabolic processes were reduced, especially glycolysis, tricarboxylic acid cycle, and fatty acid synthesis. Microarray analysis was used to evaluate temporal changes in gene expression after 6, 12 or 24 h of Cry3Aa exposure. Overall, microarray analysis indicated that transcripts related to allergens, chitin-binding proteins, glycosyl hydrolases, and tubulins were induced, and those related to immunity and metabolism were repressed in Cry3Aa-intoxicated larvae. The 24 h microarray data validated most of the RNA-Seq data. Of the three intoxication intervals, larvae demonstrated more differential expression of transcripts after 12 h exposure to Cry3Aa. Gene expression examined by three different methods in control vs. Cry3Aa-treated larvae at the 24 h time point indicated that transcripts encoding proteins with chitin-binding domain 3 were the most differentially expressed in Cry3Aa-intoxicated larvae. Overall, the data suggest that T. molitor larvae mount a complex response to Cry3Aa during the initial 24 h of intoxication. Data from this study represent the largest genetic sequence dataset for T. molitor

  3. BK polyomavirus genotypes Ia and Ib1 exhibit different biological properties in renal transplant recipients.

    PubMed

    Varella, Rafael B; Zalona, Ana Carolina J; Diaz, Nuria C; Zalis, Mariano G; Santoro-Lopes, Guilherme

    2018-01-02

    BK polyomavirus (BKV) is an opportunist agent associated with nephropathy (BKVAN) in 1-10% of kidney transplant recipients. BKV is classified into genotypes or subgroups according to minor nucleotidic variations with unknown biological implications. Studies assessing the possible association between genotypes and the risk of BKVAN in kidney transplant patients have presented conflicting results. In these studies, genotype Ia, which is highly prevalent in Brazil, was less frequently found and, thus, comparative data on the biological properties of this genotype are lacking. In this study, BKV Ia and Ib1 genotypes were compared according to their viral load, genetic evolution (VP1 and NCCR) - in a cohort of renal transplant recipients. The patients infected with Ia (13/23; 56.5%) genotype exhibited higher viral loads in urine [>1.4 log over Ib1 (10/23; 43.5%); p=0.025]. In addition, genotype Ia was associated with diverse mutations at VP1 loops and sites under positive selection outside loops, which were totally absent in Ib1. Although the number of viremic patients was similar, the three patients who had BK nephropathy (BKVAN) were infected with Ia genotype. NCCR architecture (ww or rr) were not distinctive between Ia and Ib1 genotypes. Ia genotype, which is rare in other published BKV cohorts, presented some diverse biological properties in transplanted recipients in comparison to Ib1. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Strategies for genotype imputation in composite beef cattle.

    PubMed

    Chud, Tatiane C S; Ventura, Ricardo V; Schenkel, Flavio S; Carvalheiro, Roberto; Buzanskas, Marcos E; Rosa, Jaqueline O; Mudadu, Maurício de Alvarenga; da Silva, Marcos Vinicius G B; Mokry, Fabiana B; Marcondes, Cintia R; Regitano, Luciana C A; Munari, Danísio P

    2015-08-07

    Genotype imputation has been used to increase genomic information, allow more animals in genome-wide analyses, and reduce genotyping costs. In Brazilian beef cattle production, many animals are resulting from crossbreeding and such an event may alter linkage disequilibrium patterns. Thus, the challenge is to obtain accurately imputed genotypes in crossbred animals. The objective of this study was to evaluate the best fitting and most accurate imputation strategy on the MA genetic group (the progeny of a Charolais sire mated with crossbred Canchim X Zebu cows) and Canchim cattle. The data set contained 400 animals (born between 1999 and 2005) genotyped with the Illumina BovineHD panel. Imputation accuracy of genotypes from the Illumina-Bovine3K (3K), Illumina-BovineLD (6K), GeneSeek-Genomic-Profiler (GGP) BeefLD (GGP9K), GGP-IndicusLD (GGP20Ki), Illumina-BovineSNP50 (50K), GGP-IndicusHD (GGP75Ki), and GGP-BeefHD (GGP80K) to Illumina-BovineHD (HD) SNP panels were investigated. Seven scenarios for reference and target populations were tested; the animals were grouped according with birth year (S1), genetic groups (S2 and S3), genetic groups and birth year (S4 and S5), gender (S6), and gender and birth year (S7). Analyses were performed using FImpute and BEAGLE software and computation run-time was recorded. Genotype imputation accuracy was measured by concordance rate (CR) and allelic R square (R(2)). The highest imputation accuracy scenario consisted of a reference population with males and females and a target population with young females. Among the SNP panels in the tested scenarios, from the 50K, GGP75Ki and GGP80K were the most adequate to impute to HD in Canchim cattle. FImpute reduced computation run-time to impute genotypes from 20 to 100 times when compared to BEAGLE. The genotyping panels possessing at least 50 thousands markers are suitable for genotype imputation to HD with acceptable accuracy. The FImpute algorithm demonstrated a higher efficiency of

  5. Interleukin-6 genotypes and serum levels in Chinese Hui population

    PubMed Central

    Gao, Shu-Ping; Liang, Shu; Pan, Min; Sun, Rong-Liang; Chen, Chu; Luan, Hong; Jiang, Min-Hui

    2014-01-01

    Interleukin-6 (IL-6) is a key pro-inflammatory cytokine involved in different physiologic and pathophysiologic processes, and circulating levels of IL-6 differ greatly between individuals. The Chinese Hui is one of the largest ethnic minorities, little is known about the distribution of IL-6 genetic variations and their effects on serum levels in Hui population. The aim of the present study is to determine the prevalence of -174G/C (rs1800795), -597G/A (rs1800797), and -634C/G (rs1800796) polymorphisms in the IL-6 gene promoter region and their association with IL-6 serum levels in the Ningxia Hui population. A total of 96 Hui subjects, (57 men and 39 women; mean age 49.65 ± 19.73 years) unrelated nationality residents in Ningxia Hui Autonomous Region were enrolled. Genotyping of the three polymorphisms were performed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) combined with gel electrophoresis and then confirmed by direct sequencing. The -174G/C (97.92% GG, 2.08% GC, and 0% CC) and -597G/A (98.96% GG, 1.04% GA, and 0% AA) polymorphisms were rare. The frequencies of -634C/G genotypes CC, CG, and GG were found to be 54.17%, 40.62%, and 5.21%, respectively in total studied subjects, the derived allele frequencies for the C and G alleles were 74.48% and 25.52%. Increased IL-6 levels were correlated with the IL-6 -634G allele carriers (CG+GG genotypes). The results suggest that IL-6 -174G/C and -597G/A are rare but -634C/G is common in the Ningxia Hui population, and the -634G allele is associated with circulating levels of IL-6. PMID:25356148

  6. Genotypic distribution of hepatitis C virus in voluntary blood donors of northern Thailand.

    PubMed

    Jutavijittum, Prapan; Jiviriyawat, Yupa; Yousukh, Amnat; Pantip, Chansom; Maneekarn, Niwat; Toriyama, Kan

    2009-05-01

    The purpose of this study was to determine the prevalence and distribution of HCV genotypes among voluntary blood donors in northern Thailand. From 1998 to 2000, 167 serum samples which tested positive for anti-HCV antibodies in the screening of voluntary blood donors from 5 provinces in northern Thailand were selected for genotyping. Viral RNA was extracted from the sera. The core-E1 region of the HCV-RNA genome was amplified using a OneStep RT-PCR kit. The core-E1 amplicon was sequenced and the HCV genotype was assigned by comparing with the reference sequences available in the GenBank database. Of 167 anti-HCV positive serum samples, 126 (75.4%) contained HCV RNA as detected by PCR. HCV genotype 3 was the most predominant genotype (39.6%), of which 33.3% belonged to genotype 3a and 6.3% to 3b. Genotype 6 was detected in 31%, and genotype 1 was detected in 27.8%. Of the genotype 1 isolates, 14.3% were la, 12.7% were 1b, and 0.8% were 1c. Two HCV isolates detected in the present study were untypeable. About 75% of anti-HCV positive blood donors had chronic HCV infection. In northern Thailand, genotype 3a was the most predominant genotype, while genotype 6, 1a and 1b were also commonly found. The genotypic distribution of HCV isolates from various regions of Thailand were more or less similar. Nevertheless, in this study, the prevalence of HCV genotype 6 (31%) was higher than previously reported by others (8-18%). Phylogenetic analysis of the HCV isolates detected in the present study was also performed.

  7. Outcomes From AAS Hack Day at the 227th AAS Meeting

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-01-01

    Editors Note:This is a final post from the 227th AAS Meeting in Kissimmee, FL. This special summary of AAS Hack Day, a meeting of AAS members to collaboratively work on various small projects, was written by Meredith Rawls (@Merrdiff) and was originally posted on astrobites.com.As the 227thAmerican Astronomical Society meeting drew to a close (see highlights from Day 1, Day 2, Day 3, and Day 4), a group of at least 50 attendees spent Day 4working on small projects fondly called hacks. Thanks to sponsorship from LSST and Northrup Grumman, the industrious hackers werewell-caffeinated and fed so we could devote time and energy toworking in groups on one-day projects.TheHack Day beganat 10am with pitches. Anybody with a project idea was welcome to briefly speak and try to convince others to work with them. Only someideas panned out, but the enthusiasm was palpable. Its not every day you get a full room of astronomers and affiliates eager to spend hours working on fun and useful projects to benefit the community.#hackAAS is getting underway! #aas227 pic.twitter.com/yX7jlOnSCK James R A Davenport (@jradavenport) January 8, 2016Here is a rundown of what we accomplished. Pretty impressive for a single day! Many thanks to fellow astrobiter Erika Nesvold (now at Carnegie DTM; @erikanesvold) whose hack was live-documenting all the other hacks. Her tweets as @astrobites appeared with the #hackaas hashtag, and her notes made this recap post infinitely easier to write.Interested in joining the fun? Sign up for Hack Day at the 2017 JanuaryAAS meeting (its free with meeting registration), and consider applying for the .Astronomy conference this summer.Towards Optimal Session Scheduling:Adrian Price-Whelan (Columbia), David Hogg (NYU), and Scott Idem (AAS) began writing a program to take all submitted abstracts to a conference like AAS and sort them using keywords to avoid scheduling similar talks in parallel sessions. Its impossible to make everyone happy, but minimizing conflicts

  8. Microstructure Evolution during Dissimilar Friction Stir Welding of AA7003-T4 and AA6060-T4.

    PubMed

    Dong, Jialiang; Zhang, Datong; Zhang, Weiwen; Zhang, Wen; Qiu, Cheng

    2018-02-27

    In this work, the dissimilar joint of AA7003-T4 and 6060-T4 alloy has been produced by friction stir welding (FSW). The microstructure was examined by optical microscope (OM), electron back scattered diffraction (EBSD), transmission electron microscopy (TEM), and the mechanical properties of the joint were investigated. It is demonstrated that sound dissimilar joint can be produced through FSW. In the nugget; precipitations dissolve into the matrix and η' reprecipitate subsequently; and the elongated aluminum grains are replaced by fine and equiaxed grains due to dynamic recrystallization (DRX). In the heat affected zone (HAZ), coarse β' and η precipitates are formed and the aluminum grains are coarser as compared to the base materials. In the thermo-mechanical affected zone (TMAZ), equiaxed and elongated grains coexist due to incomplete DRX. The ultimate tensile strength of the dissimilar joint is 159.2 MPa and its elongation is 10.4%. The weak area exists in the HAZ of 6060 alloy, which is placed in the retreating side during FSW. The correlations between the microstucture and mechanical properties of the dissimilar joint are discussed.

  9. Microstructure Evolution during Dissimilar Friction Stir Welding of AA7003-T4 and AA6060-T4

    PubMed Central

    Dong, Jialiang; Zhang, Datong; Zhang, Weiwen; Zhang, Wen; Qiu, Cheng

    2018-01-01

    In this work, the dissimilar joint of AA7003-T4 and 6060-T4 alloy has been produced by friction stir welding (FSW). The microstructure was examined by optical microscope (OM), electron back scattered diffraction (EBSD), transmission electron microscopy (TEM), and the mechanical properties of the joint were investigated. It is demonstrated that sound dissimilar joint can be produced through FSW. In the nugget; precipitations dissolve into the matrix and η′ reprecipitate subsequently; and the elongated aluminum grains are replaced by fine and equiaxed grains due to dynamic recrystallization (DRX). In the heat affected zone (HAZ), coarse β′ and η precipitates are formed and the aluminum grains are coarser as compared to the base materials. In the thermo-mechanical affected zone (TMAZ), equiaxed and elongated grains coexist due to incomplete DRX. The ultimate tensile strength of the dissimilar joint is 159.2 MPa and its elongation is 10.4%. The weak area exists in the HAZ of 6060 alloy, which is placed in the retreating side during FSW. The correlations between the microstucture and mechanical properties of the dissimilar joint are discussed. PMID:29495463

  10. Association of Matrix Metalloproteinase-7 Genotypes to the Risk of Oral Cancer in Taiwan.

    PubMed

    Shih, Liang-Chun; Li, Ching-Hao; Sun, Kuo-Ting; Chen, Liang-Yu; Hsu, Che-Lun; Hung, Yi-Wen; Wu, Cheng-Nan; Hsia, Te-Chun; Shen, Te-Chun; Chang, Wen-Shin; Shih, Tzu-Ching; Tsai, Chia-Wen; Bau, DA-Tian

    2018-04-01

    Matrix metalloproteinases (MMPs) play a critical role in inflammation and carcinogenesis, and the expression of mRNA MMP7 in oral squamous cell carcinoma tissues was higher than in the oral lichen planus or normal oral mucosa. However, the genotypic role of MMP7 has never been examined in oral cancer. Therefore, in the current study we aimed to examine the contribution of genotypic variants in the promoter region of MMP7 (A-181G and C-153T) to oral cancer risk in Taiwan. In this hospital-based case-control study, 788 patients with oral cancer and 956 gender-and age-matched healthy controls were genotyped for MMP7 A-181G and C-153T via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. The distribution pattern of AA, AG and GG for MMP7 promoter A-181G genotype was 88.2, 10.4 and 1.4% in the oral cancer patient group and 89.0, 9.3 and 1.7% in the healthy control group, respectively (p for trend=0.6779), non-significantly differentially distributed between the two groups. There is no polymorphic genotype for MMP7 C-153T among Taiwanese. The comparisons in allelic frequency distribution also support the findings that G allele may not be the risk determinant allele for oral cancer. There is no interaction between the genotypes of MMP7 with age, gender, smoking, alcohol or betel quid consumption on oral cancer risk. Our results indicate that the MMP7 promoter genotypes only play an indirect role in determining the personal susceptibility to oral cancer in Taiwan. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  11. Computational strategies for alternative single-step Bayesian regression models with large numbers of genotyped and non-genotyped animals.

    PubMed

    Fernando, Rohan L; Cheng, Hao; Golden, Bruce L; Garrick, Dorian J

    2016-12-08

    Two types of models have been used for single-step genomic prediction and genome-wide association studies that include phenotypes from both genotyped animals and their non-genotyped relatives. The two types are breeding value models (BVM) that fit breeding values explicitly and marker effects models (MEM) that express the breeding values in terms of the effects of observed or imputed genotypes. MEM can accommodate a wider class of analyses, including variable selection or mixture model analyses. The order of the equations that need to be solved and the inverses required in their construction vary widely, and thus the computational effort required depends upon the size of the pedigree, the number of genotyped animals and the number of loci. We present computational strategies to avoid storing large, dense blocks of the MME that involve imputed genotypes. Furthermore, we present a hybrid model that fits a MEM for animals with observed genotypes and a BVM for those without genotypes. The hybrid model is computationally attractive for pedigree files containing millions of animals with a large proportion of those being genotyped. We demonstrate the practicality on both the original MEM and the hybrid model using real data with 6,179,960 animals in the pedigree with 4,934,101 phenotypes and 31,453 animals genotyped at 40,214 informative loci. To complete a single-trait analysis on a desk-top computer with four graphics cards required about 3 h using the hybrid model to obtain both preconditioned conjugate gradient solutions and 42,000 Markov chain Monte-Carlo (MCMC) samples of breeding values, which allowed making inferences from posterior means, variances and covariances. The MCMC sampling required one quarter of the effort when the hybrid model was used compared to the published MEM. We present a hybrid model that fits a MEM for animals with genotypes and a BVM for those without genotypes. Its practicality and considerable reduction in computing effort was

  12. Folate supplementation in schizophrenia: a possible role for MTHFR genotype.

    PubMed

    Hill, Michele; Shannahan, Kelsey; Jasinski, Sarah; Macklin, Eric A; Raeke, Lisa; Roffman, Joshua L; Goff, Donald C

    2011-04-01

    Folate deficiency and the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism have been linked to negative symptoms in schizophrenia both independently and synergistically. This study examined the effect of folate supplementation on negative symptoms overall and in relation to MTHFR 677C>T genotype. Forty-six stable adult schizophrenia outpatients were enrolled and 32 were randomised, double-blind, in a parallel-group, twelve week add-on trial of folate 2mg/d or matching placebo. The primary outcome measure was change from baseline to week 12 on the modified SANS total score using a mixed-model analysis. In addition, we measured the effect of MTHFR genotype on treatment effects and on changes in serum folate by grouping participants with T/T genotype together with C/T genotype and comparing their interactions to patients with C/C genotype. Twenty-eight participants completed the trial. Folate supplementation did not significantly affect negative symptoms compared to placebo across the entire cohort. However, there was a significant genotype×treatment effect on negative symptoms (F=7.13, df=1,39, p=0.01). In addition, MTHFR status significantly moderated the relationship between change in serum folate and change in negative symptoms: among participants with at least one copy of the T allele negative symptoms were more likely to improve with increased serum folate (p=0.03). We did not detect a therapeutic benefit of folate supplementation in a sample of patients with residual negative symptoms. However, a possible association between genotypes associated with reduced MTHFR activity and benefit from folate supplementation should be investigated further. Copyright © 2010 Elsevier B.V. All rights reserved.

  13. Epidemiological manifestations of hepatitis C virus genotypes and its association with potential risk factors among Libyan patients.

    PubMed

    Elasifer, Hana A; Agnnyia, Yossif M; Al-Alagi, Basher A; Daw, Mohamed A

    2010-11-13

    The information on hepatitis C virus genotypes and subtypes among Libyan population and its association with various risk factors is not known. The objectives of this study were to determine the epidemiological manifestations of HCV genotypes among Libyan patients and their association with certain potential risk factors. A total of 1240 of HCV infected patients registered at Tripoli Medical Centre were studied in five years period from January 2005 to October 2009. The information were reviewed and the data were collected. A sample from each patient (785 male; 455 female) was analysed for genotyping and sub-typing using specific genotyping assay. The information was correlated with the risk factors studied and the statistical data were analyzed using SPSS version 11.5. Off the total patients studied, four different genotypes were reported, including genotypes 1, 2, 3, and 4. Genotype4 was the commonest (35.7%), followed by genotype1 (32.6%). According to subtypes 28% were unclassified genotype 4, 14.6% were genotype 1b and some patients infected with more than one subtype (2.3% genotype 4c/d, 1% genotype 2a/c). Genotypes 1 was the commonest among males, while genotype 4 among females. According to the risk factors studied, Genotype1 and genotype 4 were found with most of the risk factors. Though they were particularly evident surgical intervention, dental procedures and blood transfusion while genotype 1 was only followed by genotype 3 mainly which mainly associated with certain risk groups such as intravenous drug abusers. Here in we report on a detailed description of HCV genotype among Libyans. The most common genotype was type 4 followed by genotype 1, other genotypes were also reported at a low rate. The distribution of such genotypes were also variable according to gender and age. The commonly prevalent genotypes found to be attributable to the medical -related transmission of HCV, such as blood, surgery and dental procedures when compared with other risk

  14. Epidemiological manifestations of hepatitis C virus genotypes and its association with potential risk factors among Libyan patients

    PubMed Central

    2010-01-01

    Background The information on hepatitis C virus genotypes and subtypes among Libyan population and its association with various risk factors is not known. The objectives of this study were to determine the epidemiological manifestations of HCV genotypes among Libyan patients and their association with certain potential risk factors. Methods A total of 1240 of HCV infected patients registered at Tripoli Medical Centre were studied in five years period from January 2005 to October 2009. The information were reviewed and the data were collected. A sample from each patient (785 male; 455 female) was analysed for genotyping and sub-typing using specific genotyping assay. The information was correlated with the risk factors studied and the statistical data were analyzed using SPSS version 11.5. Results Off the total patients studied, four different genotypes were reported, including genotypes 1, 2, 3, and 4. Genotype4 was the commonest (35.7%), followed by genotype1 (32.6%). According to subtypes 28% were unclassified genotype 4, 14.6% were genotype 1b and some patients infected with more than one subtype (2.3% genotype 4c/d, 1% genotype 2a/c). Genotypes 1 was the commonest among males, while genotype 4 among females. According to the risk factors studied, Genotype1 and genotype 4 were found with most of the risk factors. Though they were particularly evident surgical intervention, dental procedures and blood transfusion while genotype 1 was only followed by genotype 3 mainly which mainly associated with certain risk groups such as intravenous drug abusers. Conclusion Here in we report on a detailed description of HCV genotype among Libyans. The most common genotype was type 4 followed by genotype 1, other genotypes were also reported at a low rate. The distribution of such genotypes were also variable according to gender and age. The commonly prevalent genotypes found to be attributable to the medical -related transmission of HCV, such as blood, surgery and dental

  15. The Pasadena Recommendations: Five Years After AAS Endorsement

    NASA Astrophysics Data System (ADS)

    Knezek, Patricia; Frattare, L.; Ulvestad, J.

    2010-01-01

    It has been five years since the AAS Council unanimously endorsed the document, known as "Equity Now: The Pasadena Recommendations for Gender Equality in Astronomy," in January 2005. This document was the main product of the conference entitled "Women in Astronomy II: Ten Years After” (WIA II), held in June 2003 in Pasadena, CA. Participants of that 2003 meeting assessed the progress for women in science, offering insights into causes of the slower advancement of women, and discussed strategies to accelerate the achievement of equality. These insights and strategies were then incorporated into the "Pasadena Recommendations" by the CSWA. It was subsequently released to the entire AAS community for review and comments prior to its endorsement by the AAS. We will discuss the Recommendations and their impact since the endorsement by the AAS, including the process that is in place for organizations and departments to formally endorse the Pasadena Recommendations, thus making an organizational commitment to their implementation (see http://www.aas.org/cswa/pasadena_endorse.html).

  16. Dihydrocodeine Overdoses in a Neonate and in a 14-year-old Girl Who Were Both Genotyped as Cytochrome P450 2D6*1/*10-*36: Comparing Developmental Ages and Drug Monitoring Data With the Results of Pharmacokinetic Modeling.

    PubMed

    Shimizu, Makiko; Kondo, Tatsuki; Fukuoka, Tetsuya; Tanaka, Toshihiro; Yamazaki, Hiroshi

    2018-04-01

    A high activity of cytochrome P450 2D6 (CYP2D6) reportedly leads to toxicity of dihydrocodeine/codeine by increasing toxic potential of their metabolite dihydromorphine/morphine, which are further metabolized to highly active dihydromorphine 6-O-glucuronide and the less active morphine 3-O-glucorinide but rapidly excreted into urine as water-soluble forms. A case of acute respiratory depression after administration of prescribed dihydrocodeine phosphate (2.0 mg/d divided twice a day for 2 days) to a 1-month-old baby boy genotyped as CYP2D6*1/*10-*36 is described. The case is compared with that of a 14-year-old girl, also genotyped as CYP2D6*1/*10-*36, presenting in an agitated state after an overdose (37 mg) of dihydrocodeine phosphate taken as simultaneous ingestion of multiple over-the-counter tablets. In contrast to the rapid clearance of dihydrocodeine from blood in the 14-year-old girl (apparent half-life of 3 hours), the 1-month-old baby boy still had high serum concentrations of dihydrocodeine (400 nmol/L) and dihydromorphine (1.9 nmol/L) 21 hours after the last oral administration of dihydrocodeine-containing cough mixture. The rapid clearance in the 14-year-old girl was mainly attributed to dihydrocodeine glucuronidation and partly attributed to dihydromorphine formation, as determined by liquid chromatography-tandem mass spectrometry analyses. However, the conjugation ratios of dihydrocodeine and dihydromorphine in the neonate were low in comparison with those in the 14-year-old girl and with those measured in 3-, 6-, and 13-year-old control subjects, resulting from the poorly developed glucuronidation potential of the neonate. The current observations suggest that the CYP2D6*1/*10-*36 genotype seen in the 2 Japanese patients may not significantly contribute to the likelihood of dihydrocodeine overdose but highlight the importance of considering age when prescribing dihydrocodeine.

  17. Corrosion Properties of Cryorolled AA2219 Friction Stir Welded Joints Using Different Tool Pin Profiles

    NASA Astrophysics Data System (ADS)

    Kamal Babu, K.; Panneerselvam, K.; Sathiya, P.; Noorul Haq, A.; Sundarrajan, S.; Mastanaiah, P.; Srinivasa Murthy, C. V.

    The purpose of this paper is to present the corrosion behavior of the Cryorolled (CR) material and its Friction Stir Welded joints. Due to the thermal cycles of Friction Stir Welding (FSW) process, the corrosion behavior of the material gets affected. Here, the cryorolling process was carried out on AA2219 alloy and CR material was joined by FSW process using four different pin tool profiles such as cylindrical, threaded cylindrical, square and hexagonal pin. The FSW joints were analyzed by corrosion resistance with the help of potentiodynamic polarization test with 3.5% NaCl solution. From the analysis, it is found that CR AA2219 material exhibits good corrosion resistance compared to the base AA2219 material, and also a hexagonal pin profile FSW joint exhibits high corrosion resistance. Among the weld joints created by four different tools, the lowest corrosion resistance was found in the cylindrical pin tool FSW welds. Further, the corroded samples were investigated through metallurgical investigations like OM, Transmission Electron Microscopy (TEM), Energy-Dispersive X-ray Spectroscopy (EDX) and X-Ray Diffraction (XRD). It was found that the amount of dissolution of Al2Cu precipitate was present in the weld nugget. The amount of dissolution of Al2Cu precipitate is higher in the weld nugget produced by hexagonal pin tool. This is due to the enhancement of the corrosion resistance.

  18. Theory-based pharmacokinetics and pharmacodynamics of S- and R-warfarin and effects on international normalized ratio: influence of body size, composition and genotype in cardiac surgery patients.

    PubMed

    Xue, Ling; Holford, Nick; Ding, Xiao-Liang; Shen, Zhen-Ya; Huang, Chen-Rong; Zhang, Hua; Zhang, Jing-Jing; Guo, Zhe-Ning; Xie, Cheng; Zhou, Ling; Chen, Zhi-Yao; Liu, Lin-Sheng; Miao, Li-Yan

    2017-04-01

    The aims of this study are to apply a theory-based mechanistic model to describe the pharmacokinetics (PK) and pharmacodynamics (PD) of S- and R-warfarin. Clinical data were obtained from 264 patients. Total concentrations for S- and R-warfarin were measured by ultra-high performance liquid tandem mass spectrometry. Genotypes were measured using pyrosequencing. A sequential population PK parameter with data method was used to describe the international normalized ratio (INR) time course. Data were analyzed with NONMEM. Model evaluation was based on parameter plausibility and prediction-corrected visual predictive checks. Warfarin PK was described using a one-compartment model. CYP2C9 *1/*3 genotype had reduced clearance for S-warfarin, but increased clearance for R-warfarin. The in vitro parameters for the relationship between prothrombin complex activity (PCA) and INR were markedly different (A = 0.560, B = 0.386) from the theory-based values (A = 1, B = 0). There was a small difference between healthy subjects and patients. A sigmoid E max PD model inhibiting PCA synthesis as a function of S-warfarin concentration predicted INR. Small R-warfarin effects was described by competitive antagonism of S-warfarin inhibition. Patients with VKORC1 AA and CYP4F2 CC or CT genotypes had lower C50 for S-warfarin. A theory-based PKPD model describes warfarin concentrations and clinical response. Expected PK and PD genotype effects were confirmed. The role of predicted fat free mass with theory-based allometric scaling of PK parameters was identified. R-warfarin had a minor effect compared with S-warfarin on PCA synthesis. INR is predictable from 1/PCA in vivo. © 2016 The British Pharmacological Society.

  19. Theory‐based pharmacokinetics and pharmacodynamics of S‐ and R‐warfarin and effects on international normalized ratio: influence of body size, composition and genotype in cardiac surgery patients

    PubMed Central

    Xue, Ling; Holford, Nick; Ding, Xiao‐liang; Shen, Zhen‐ya; Huang, Chen‐rong; Zhang, Hua; Zhang, Jing‐jing; Guo, Zhe‐ning; Xie, Cheng; Zhou, Ling; Chen, Zhi‐yao; Liu, Lin‐sheng

    2016-01-01

    Aims The aims of this study are to apply a theory‐based mechanistic model to describe the pharmacokinetics (PK) and pharmacodynamics (PD) of S‐ and R‐warfarin. Methods Clinical data were obtained from 264 patients. Total concentrations for S‐ and R‐warfarin were measured by ultra‐high performance liquid tandem mass spectrometry. Genotypes were measured using pyrosequencing. A sequential population PK parameter with data method was used to describe the international normalized ratio (INR) time course. Data were analyzed with NONMEM. Model evaluation was based on parameter plausibility and prediction‐corrected visual predictive checks. Results Warfarin PK was described using a one‐compartment model. CYP2C9 *1/*3 genotype had reduced clearance for S‐warfarin, but increased clearance for R‐warfarin. The in vitro parameters for the relationship between prothrombin complex activity (PCA) and INR were markedly different (A = 0.560, B = 0.386) from the theory‐based values (A = 1, B = 0). There was a small difference between healthy subjects and patients. A sigmoid Emax PD model inhibiting PCA synthesis as a function of S‐warfarin concentration predicted INR. Small R‐warfarin effects was described by competitive antagonism of S‐warfarin inhibition. Patients with VKORC1 AA and CYP4F2 CC or CT genotypes had lower C50 for S‐warfarin. Conclusion A theory‐based PKPD model describes warfarin concentrations and clinical response. Expected PK and PD genotype effects were confirmed. The role of predicted fat free mass with theory‐based allometric scaling of PK parameters was identified. R‐warfarin had a minor effect compared with S‐warfarin on PCA synthesis. INR is predictable from 1/PCA in vivo. PMID:27763679

  20. Genotypic and Phenotypic Characterization of Chikungunya Virus of Different Genotypes from Malaysia

    PubMed Central

    Sam, I-Ching; Loong, Shih-Keng; Michael, Jasmine Chandramathi; Chua, Chong-Long; Wan Sulaiman, Wan Yusoff; Vythilingam, Indra; Chan, Shie-Yien; Chiam, Chun-Wei; Yeong, Yze-Shiuan; AbuBakar, Sazaly; Chan, Yoke-Fun

    2012-01-01

    Background Mosquito-borne Chikungunya virus (CHIKV) has recently re-emerged globally. The epidemic East/Central/South African (ECSA) strains have spread for the first time to Asia, which previously only had endemic Asian strains. In Malaysia, the ECSA strain caused an extensive nationwide outbreak in 2008, while the Asian strains only caused limited outbreaks prior to this. To gain insight into these observed epidemiological differences, we compared genotypic and phenotypic characteristics of CHIKV of Asian and ECSA genotypes isolated in Malaysia. Methods and Findings CHIKV of Asian and ECSA genotypes were isolated from patients during outbreaks in Bagan Panchor in 2006, and Johor in 2008. Sequencing of the CHIKV strains revealed 96.8% amino acid similarity, including an unusual 7 residue deletion in the nsP3 protein of the Asian strain. CHIKV replication in cells and Aedes mosquitoes was measured by virus titration. There were no differences in mammalian cell lines. The ECSA strain reached significantly higher titres in Ae. albopictus cells (C6/36). Both CHIKV strains infected Ae. albopictus mosquitoes at a higher rate than Ae. aegypti, but when compared to each other, the ECSA strain had much higher midgut infection and replication, and salivary gland dissemination, while the Asian strain infected Ae. aegypti at higher rates. Conclusions The greater ability of the ECSA strain to replicate in Ae. albopictus may explain why it spread far more quickly and extensively in humans in Malaysia than the Asian strain ever did, particularly in rural areas where Ae. albopictus predominates. Intergenotypic genetic differences were found at E1, E2, and nsP3 sites previously reported to be determinants of host adaptability in alphaviruses. Transmission of CHIKV in humans is influenced by virus strain and vector species, which has implications for regions with more than one circulating CHIKV genotype and Aedes species. PMID:23209750

  1. Genotypic and phenotypic characterization of Chikungunya virus of different genotypes from Malaysia.

    PubMed

    Sam, I-Ching; Loong, Shih-Keng; Michael, Jasmine Chandramathi; Chua, Chong-Long; Wan Sulaiman, Wan Yusoff; Vythilingam, Indra; Chan, Shie-Yien; Chiam, Chun-Wei; Yeong, Yze-Shiuan; AbuBakar, Sazaly; Chan, Yoke-Fun

    2012-01-01

    Mosquito-borne Chikungunya virus (CHIKV) has recently re-emerged globally. The epidemic East/Central/South African (ECSA) strains have spread for the first time to Asia, which previously only had endemic Asian strains. In Malaysia, the ECSA strain caused an extensive nationwide outbreak in 2008, while the Asian strains only caused limited outbreaks prior to this. To gain insight into these observed epidemiological differences, we compared genotypic and phenotypic characteristics of CHIKV of Asian and ECSA genotypes isolated in Malaysia. CHIKV of Asian and ECSA genotypes were isolated from patients during outbreaks in Bagan Panchor in 2006, and Johor in 2008. Sequencing of the CHIKV strains revealed 96.8% amino acid similarity, including an unusual 7 residue deletion in the nsP3 protein of the Asian strain. CHIKV replication in cells and Aedes mosquitoes was measured by virus titration. There were no differences in mammalian cell lines. The ECSA strain reached significantly higher titres in Ae. albopictus cells (C6/36). Both CHIKV strains infected Ae. albopictus mosquitoes at a higher rate than Ae. aegypti, but when compared to each other, the ECSA strain had much higher midgut infection and replication, and salivary gland dissemination, while the Asian strain infected Ae. aegypti at higher rates. The greater ability of the ECSA strain to replicate in Ae. albopictus may explain why it spread far more quickly and extensively in humans in Malaysia than the Asian strain ever did, particularly in rural areas where Ae. albopictus predominates. Intergenotypic genetic differences were found at E1, E2, and nsP3 sites previously reported to be determinants of host adaptability in alphaviruses. Transmission of CHIKV in humans is influenced by virus strain and vector species, which has implications for regions with more than one circulating CHIKV genotype and Aedes species.

  2. Mineral Composition of Organically Grown Wheat Genotypes: Contribution to Daily Minerals Intake

    PubMed Central

    Hussain, Abrar; Larsson, Hans; Kuktaite, Ramune; Johansson, Eva

    2010-01-01

    In this study, 321 winter and spring wheat genotypes were analysed for twelve nutritionally important minerals (B, Cu, Fe, Se, Mg, Zn, Ca, Mn, Mo, P, S and K). Some of the genotypes used were from multiple locations and years, resulting in a total number of 493 samples. Investigated genotypes were divided into six genotype groups i.e., selections, old landraces, primitive wheat, spelt, old cultivars and cultivars. For some of the investigated minerals higher concentrations were observed in selections, primitive wheat, and old cultivars as compared to more modern wheat material, e.g., cultivars and spelt wheat. Location was found to have a significant effect on mineral concentration for all genotype groups, although for primitive wheat, genotype had a higher impact than location. Spring wheat was observed to have significantly higher values for B, Cu, Fe, Zn, Ca, S and K as compared to winter wheat. Higher levels of several minerals were observed in the present study, as compared to previous studies carried out in inorganic systems, indicating that organic conditions with suitable genotypes may enhance mineral concentration in wheat grain. This study also showed that a very high mineral concentration, close to daily requirements, can be produced by growing specific primitive wheat genotypes in an organic farming system. Thus, by selecting genotypes for further breeding, nutritional value of the wheat flour for human consumption can be improved. PMID:20948934

  3. Representativeness of Tuberculosis Genotyping Surveillance in the United States, 2009-2010.

    PubMed

    Shak, Emma B; France, Anne Marie; Cowan, Lauren; Starks, Angela M; Grant, Juliana

    2015-01-01

    Genotyping of Mycobacterium tuberculosis isolates contributes to tuberculosis (TB) control through detection of possible outbreaks. However, 20% of U.S. cases do not have an isolate for testing, and 10% of cases with isolates do not have a genotype reported. TB outbreaks in populations with incomplete genotyping data might be missed by genotyping-based outbreak detection. Therefore, we assessed the representativeness of TB genotyping data by comparing characteristics of cases reported during January 1, 2009-December 31, 2010, that had a genotype result with those cases that did not. Of 22,476 cases, 14,922 (66%) had a genotype result. Cases without genotype results were more likely to be patients <19 years of age, with unknown HIV status, of female sex, U.S.-born, and with no recent history of homelessness or substance abuse. Although cases with a genotype result are largely representative of all reported U.S. TB cases, outbreak detection methods that rely solely on genotyping data may underestimate TB transmission among certain groups.

  4. Representativeness of Tuberculosis Genotyping Surveillance in the United States, 2009–2010

    PubMed Central

    Shak, Emma B.; Cowan, Lauren; Starks, Angela M.; Grant, Juliana

    2015-01-01

    Genotyping of Mycobacterium tuberculosis isolates contributes to tuberculosis (TB) control through detection of possible outbreaks. However, 20% of U.S. cases do not have an isolate for testing, and 10% of cases with isolates do not have a genotype reported. TB outbreaks in populations with incomplete genotyping data might be missed by genotyping-based outbreak detection. Therefore, we assessed the representativeness of TB genotyping data by comparing characteristics of cases reported during January 1, 2009–December 31, 2010, that had a genotype result with those cases that did not. Of 22,476 cases, 14,922 (66%) had a genotype result. Cases without genotype results were more likely to be patients <19 years of age, with unknown HIV status, of female sex, U.S.-born, and with no recent history of homelessness or substance abuse. Although cases with a genotype result are largely representative of all reported U.S. TB cases, outbreak detection methods that rely solely on genotyping data may underestimate TB transmission among certain groups. PMID:26556930

  5. Genotypes of Coxiella burnetii in wildlife: disentangling the molecular epidemiology of a multi-host pathogen.

    PubMed

    González-Barrio, David; Jado, Isabel; Fernández-de-Mera, Isabel G; Del Rocio Fernández-Santos, María; Rodríguez-Vargas, Manuela; García-Amil, Cristina; Beltrán-Beck, Beatriz; Anda, Pedro; Ruiz-Fons, Francisco

    2016-06-23

    Evidences point to a relevant role of wildlife in the ecology of Coxiella burnetii worldwide. The lack of information on C. burnetii genotypes in wildlife prevents tracing-back clinical animal and human Q fever cases with potential wildlife origin. To compare C. burnetii genotypes circulating in wildlife, livestock and humans, 107 samples from red deer, European wild rabbit, racoon, small mammals, goat and sheep were genotyped by polymerase chain reaction and reverse line blot hybridization. Genomic groups I, II, VI and VII were found in wildlife and groups I, II, III and IV in domestic ruminants. Livestock genotypes clustered mainly with genotypes reported previously in livestock. Genotyping confirmed previous findings that suggest that C. burnetii may display host specificity since most genotypes of sympatric deer and rabbits clustered in separate groups. Wildlife genotypes clustered with genotypes from ticks and from acute hepatitis human Q fever cases, suggesting that particular C. burnetii genotypes circulating in a wildlife-tick cycle may occasionally jump into humans through tick bites or exposure to wildlife. This finding could be behind the reported geographic variation in the clinical presentation of acute Q fever in humans in Spain: atypical pneumonia in the north and hepatitis in the south. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  6. Incidence of hepatocellular carcinoma according to hepatitis B virus genotype in Alaska Native people.

    PubMed

    Ching, Lance K; Gounder, Prabhu P; Bulkow, Lisa; Spradling, Philip R; Bruce, Michael G; Negus, Susan; Snowball, Mary; McMahon, Brian J

    2016-10-01

    Most regions of the world have ≤3 co-circulating hepatitis B virus (HBV) genotypes, which limits direct comparisons of hepatocellular carcinoma (HCC) risk among HBV-infected persons by genotype. We evaluated HCC incidence by HBV genotype in a cohort of Alaska Native (AN) persons where five HBV genotypes (A, B, C, D, F) have been identified. Our cohort comprised AN persons with chronic HBV infection identified during 1983-2012 who consented to participate in this study. Cohort persons were offered annual hepatitis B e antigen (HBeAg) testing and semi-annual HCC screening. We developed a logistic regression model to compare HCC risk by genotype, adjusting for age, sex, region and HBeAg status. Among the 1235 consenting study participants, 711 (57.6%) were male, 510 (41.3%) were HBeAg positive at cohort entry and 43 (3.5%) developed HCC. The HBV genotype was known for 1142 (92.5%) persons (13.5% A, 3.9% B, 6.7% C, 56.9% D, 19.0% F). The HCC incidence/1000 person-years of follow-up for genotypes A, B, C, D and F was 1.3, 0, 5.5, 0.4 and 4.2 respectively. Compared with persons with HBV genotype B/D infection, the HCC risk was higher for persons with genotypes A [adjusted odds ratio (aOR): 3.9, 95% confidence interval (CI): 1.14-13.74], C (aOR: 16.3, 95% CI: 5.20-51.11) and F (aOR: 13.9, 95% CI: 5.30-36.69). HBV genotype is independently associated with HCC risk. AN persons with genotypes A, C and F are at higher risk compared with genotypes B or D. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  7. Incidence of Hepatocellular Carcinoma According to Hepatitis B Virus Genotype in Alaska Native People

    PubMed Central

    Ching, Lance K.; Gounder, Prabhu P.; Bulkow, Lisa; Spradling, Philip R.; Bruce, Michael; Negus, Susan; Snowball, Mary; McMahon, Brian J.

    2016-01-01

    Background & Aims Most regions of the world have <3 co-circulating hepatitis B virus (HBV) genotypes, which limits direct comparisons of hepatocellular carcinoma (HCC) risk among HBV-infected persons by genotype. We evaluated HCC incidence by HBV genotype in a cohort of Alaska Native (AN) persons where 5 HBV genotypes (A, B, C, D, F) have been identified. Methods Our cohort comprised AN persons with chronic HBV infection identified during 1983–2012 who consented to participate in the study. Cohort persons were offered annual hepatitis B e antigen (HBeAg) testing and semiannual HCC screening. We developed a logistic regression model to compare HCC risk by genotype, adjusting for age, sex, region, and HBeAg status. Results Among the 1,235 consenting study participants, 711 (57.6%) were male, 510 (41.3%) were HBeAg positive at cohort entry, and 43 (3.5%) developed HCC. The HBV genotype was known for 1,142 (92.5%) persons (13.5% A, 3.9% B, 6.7% C, 56.9% D, 19.0% F). The HCC incidence/1,000 person-years of follow-up for genotypes A, B, C, D, and F was 1.3, 0, 5.5, 0.4, and 4.2, respectively. Compared with persons with HBV genotype B/D infection, the HCC risk was higher for persons with genotypes A (adjusted odds ratio [aOR]: 3.9, 95% CI: 1.14–13.74), C (aOR: 16.3, 95% CI: 5.20–51.11), and F (aOR: 13.9, 95% CI: 5.30–36.69). Conclusion HBV genotype is independently associated with HCC risk. AN persons with genotypes A, C, and F are at higher risk compared with genotypes B or D. PMID:27009849

  8. Fecal transmission of AA amyloidosis in the cheetah contributes to high incidence of disease

    PubMed Central

    Zhang, Beiru; Une, Yumi; Fu, Xiaoying; Yan, Jingmin; Ge, FengXia; Yao, Junjie; Sawashita, Jinko; Mori, Masayuki; Tomozawa, Hiroshi; Kametani, Fuyuki; Higuchi, Keiichi

    2008-01-01

    AA amyloidosis is one of the principal causes of morbidity and mortality in captive cheetahs (Acinonyx jubatus), which are in danger of extinction, but little is known about the underlying mechanisms. Given the transmissible characteristics of AA amyloidosis, transmission between captive cheetahs may be a possible mechanism involved in the high incidence of AA amyloidosis. In this study of animals with AA amyloidosis, we found that cheetah feces contained AA amyloid fibrils that were different from those of the liver with regard to molecular weight and shape and had greater transmissibility. The infectious activity of fecal AA amyloid fibrils was reduced or abolished by the protein denaturants 6 M guanidine·HCl and formic acid or by AA immunodepletion. Thus, we propose that feces are a vehicle of transmission that may accelerate AA amyloidosis in captive cheetah populations. These results provide a pathogenesis for AA amyloidosis and suggest possible measures for rescuing cheetahs from extinction. PMID:18474855

  9. Multiple HPV genotype infection impact on invasive cervical cancer presentation and survival

    PubMed Central

    Martins, Toni Ricardo; Mendoza Lopez, Rossana V.; Sadalla, José Carlos; de Carvalho, João Paulo Mancusi; Baracat, Edmund Chada

    2017-01-01

    Background Invasive cervical cancer (ICC) is the third most common malignant neoplasm affecting Brazilian women. Little is known about the impact of specific HPV genotypes in the prognosis of ICC. We hypothesized that HPV genotype would impact ICC clinical presentation and survival. Methods Women diagnosed with ICC at the Instituto do Câncer do Estado de São Paulo (ICESP) between May 2008 and June 2012 were included in the study and were followed until December 2015. HPV genotype was detected from formalin-fixed paraffin-embedded (FFPE) tumor tissue samples using Onclarity™ system (BD Viper™ LT automated system). Results 292 patients aged 50±14 years were analyzed. HPVDNA was detected in 84% of patients. The HPV genotypes studied were: HPV16 (64%), HPV18 (10%), HPV33-58 (7%), HPV45 (5%), HPV31 (4%) and other high-risk HPV genotypes (11%). HPV genotypes showed different distributions regarding histological type and clinical stage. Patients were followed for 35±21 months. The overall survival at 5 years after diagnosis of cervical cancer was 54%. Age, clinical staging, histological type and multiple HPV genotypes infection detected in the same tumor specimen were associated with poorer overall survival on multivariate Cox proportional hazard analysis (p<0.05). No specific HPV genotype affected survival. Conclusion Multiple HPV genotype infection was associated with poorer ICC survival in our study, compared with single genotype infection. HPV genotyping from FFPE tumor tissue using an automated assay such as the Onclarity BD™ assay provides a simpler alternative for routine clinical use. Impact This is the largest study employing an automated HPV genotyping assay using FFPE of ICC. Multiple HPV genotype infection adversely influenced survival. PMID:28829791

  10. Measurements of experimental precision for trials with cowpea (Vigna unguiculata L. Walp.) genotypes.

    PubMed

    Teodoro, P E; Torres, F E; Santos, A D; Corrêa, A M; Nascimento, M; Barroso, L M A; Ceccon, G

    2016-05-09

    The aim of this study was to evaluate the suitability of statistics as experimental precision degree measures for trials with cowpea (Vigna unguiculata L. Walp.) genotypes. Cowpea genotype yields were evaluated in 29 trials conducted in Brazil between 2005 and 2012. The genotypes were evaluated with a randomized block design with four replications. Ten statistics that were estimated for each trial were compared using descriptive statistics, Pearson correlations, and path analysis. According to the class limits established, selective accuracy and F-test values for genotype, heritability, and the coefficient of determination adequately estimated the degree of experimental precision. Using these statistics, 86.21% of the trials had adequate experimental precision. Selective accuracy and the F-test values for genotype, heritability, and the coefficient of determination were directly related to each other, and were more suitable than the coefficient of variation and the least significant difference (by the Tukey test) to evaluate experimental precision in trials with cowpea genotypes.

  11. Immunogenicity of mumps virus vaccine candidates matching circulating genotypes in the United States and China.

    PubMed

    Zengel, James; Phan, Shannon I; Pickar, Adrian; Xu, Pei; He, Biao

    2017-07-13

    Mumps virus (MuV) causes acute infection in humans with characteristic swelling of the parotid gland. While vaccination has greatly reduced the incidence of MuV infection, there have been multiple large outbreaks of mumps virus (MuV) in highly vaccinated populations. The most common vaccine strain, Jeryl Lynn, belongs to genotype A, which is no longer a circulating genotype. We have developed two vaccine candidates that match the circulating genotypes in the United States (genotype G) and China (genotype F). We found that there was a significant decrease in the ability of the Jeryl Lynn vaccine to produce neutralizing antibody responses to non-matched viruses, when compared to either of our vaccine candidates. Our data suggests that an updated vaccine may allow for better immunity against the circulating MuV genotypes G and F. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Epidemiology and Genetic Characterization of Hepatitis A Virus Genotype IIA▿

    PubMed Central

    Desbois, Delphine; Couturier, Elisabeth; Mackiewicz, Vincent; Graube, Arielle; Letort, Marie-José; Dussaix, Elisabeth; Roque-Afonso, Anne-Marie

    2010-01-01

    Three hepatitis A virus (HAV) genotypes, I, II, and III, divided into subtypes A and B, infect humans. Genotype I is the most frequently reported, while genotype II is hardly ever isolated, and its genetic diversity is unknown. From 2002 to 2007, a French epidemiological survey of HAV identified 6 IIA isolates, mostly from patients who did not travel abroad. The possible African origin of IIA strains was investigated by screening the 2008 mandatory notification records of HAV infection: 171 HAV strains from travelers to West Africa and Morocco were identified. Genotyping was performed by sequencing of the VP1/2A junction in 68 available sera. Entire P1 and 5′ untranslated regions of IIA strains were compared to reference sequences of other genotypes. The screening retrieved 5 imported IIA isolates. An additional autochthonous case and 2 more African cases were identified in 2008 and 2009, respectively. A total of 14 IIA isolates (8 African and 6 autochthonous) were analyzed. IIA sequences presented lower nucleotide and amino acid variability than other genotypes. The highest variability was observed in the N-terminal region of VP1, while for other genotypes the highest variability was observed at the VP1/2A junction. Phylogenetic analysis identified 2 clusters, one gathering all African and two autochthonous cases and a second including only autochthonous isolates. In conclusion, most IIA strains isolated in France are imported by travelers returning from West Africa. However, the unexplained contamination mode of autochthonous cases suggests another, still to be discovered geographical origin or a French reservoir to be explored. PMID:20592136

  13. Comparing alcohol affordability in 65 cities worldwide.

    PubMed

    Kan, Ming-Yue; Lau, Maggie

    2013-01-01

    To develop a measure of alcohol affordability (AA) and compare the AA of 65 cities worldwide. In this paper, AA is defined as the proportion of median daily income needed to buy a certain quantity of certain alcoholic beverages. The income data and the price of alcoholic beverages were drawn from the Union Bank of Switzerland survey and the Economist Intelligence Unit respectively. A large majority of cities (87.7%, n = 57) had a high level of AA. The top 20 ranking was occupied by European and American cities with Tokyo in the Western Pacific region being the exception. All cities belonging to high-income countries had high levels of AA. However, two cities with low-level AA came from low-middle-income countries instead of low-income countries. The findings have shown that alcohol consumption is highly affordable in many cities. If price policy is being considered as policy instrument of alcohol control, it is in urgent need of price adjustments. More specifically, the new emerging economies play a significant role in the world alcohol control movement because of their bright economic performance with huge population size. Further studies on AA, especially periodical monitoring and its impacts on alcohol consumption and alcohol related health problems, should be conducted so as to facilitate the formulation and evaluation price measure of alcohol control. © 2012 Australasian Professional Society on Alcohol and other Drugs.

  14. Carbon Dots and 9AA as a Binary Matrix for the Detection of Small Molecules by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Chen, Yongli; Gao, Dan; Bai, Hangrui; Liu, Hongxia; Lin, Shuo; Jiang, Yuyang

    2016-07-01

    Application of matrix-assisted laser-desorption/ionization mass spectrometry (MALDI MS) to analyze small molecules have some limitations, due to the inhomogeneous analyte/matrix co-crystallization and interference of matrix-related peaks in low m/z region. In this work, carbon dots (CDs) were for the first time applied as a binary matrix with 9-Aminoacridine (9AA) in MALDI MS for small molecules analysis. By 9AA/CDs assisted desorption/ionization (D/I) process, a wide range of small molecules, including nucleosides, amino acids, oligosaccharides, peptides, and anticancer drugs with a higher sensitivity were demonstrated in the positive ion mode. A detection limit down to 5 fmol was achieved for cytidine. 9AA/CDs matrix also exhibited excellent reproducibility compared with 9AA matrix. Moreover, by exploring the ionization mechanism of the matrix, the influence factors might be attributed to the four parts: (1) the strong UV absorption of 9AA/CDs due to their π-conjugated network; (2) the carboxyl groups modified on the CDs surface act as protonation sites for proton transfer in positive ion mode; (3) the thin layer crystal of 9AA/CDs could reach a high surface temperature more easily and lower transfer energy for LDI MS; (4) CDs could serve as a matrix additive to suppress 9AA ionization. Furthermore, this matrix was allowed for the analysis of glucose as well as nucleosides in human urine, and the level of cytidine was quantified with a linear range of 0.05-5 mM (R2 > 0.99). Therefore, the 9AA/CDs matrix was proven to be an effective MALDI matrix for the analysis of small molecules with improved sensitivity and reproducibility. This work provides an alternative solution for small molecules detection that can be further used in complex samples analysis.

  15. Proteolysis of serum amyloid A and AA amyloid proteins by cysteine proteases: cathepsin B generates AA amyloid proteins and cathepsin L may prevent their formation

    PubMed Central

    Rocken, C; Menard, R; Buhling, F; Vockler, S; Raynes, J; Stix, B; Kruger, S; Roessner, A; Kahne, T

    2005-01-01

    Background: AA amyloidosis develops in patients with chronic inflammatory diseases. The AA amyloid proteins are proteolytic fragments obtained from serum amyloid A (SAA). Previous studies have provided evidence that endosomes or lysosomes might be involved in the processing of SAA, and contribute to the pathology of AA amyloidosis. Objective: To investigate the anatomical distribution of cathepsin (Cath) B and CathL in AA amyloidosis and their ability to process SAA and AA amyloid proteins. Methods and results: CathB and CathL were found immunohistochemically in every patient with AA amyloidosis and displayed a spatial relationship with amyloid in all the cases studied. Both degraded SAA and AA amyloid proteins in vitro. With the help of mass spectrometry 27 fragments were identified after incubation of SAA with CathB, nine of which resembled AA amyloid proteins, and seven fragments after incubation with CathL. CathL did not generate AA amyloid-like peptides. When native human AA amyloid proteins were used as a substrate 26 fragments were identified after incubation with CathB and 18 after incubation with CathL. Conclusion: The two most abundant and ubiquitously expressed lysosomal proteases can cleave SAA and AA amyloid proteins. CathB generates nine AA amyloid-like proteins by its carboxypeptidase activity, whereas CathL may prevent the formation of AA amyloid proteins by endoproteolytic activity within the N-terminal region of SAA. This is particularly interesting, because AA amyloidosis is a systemic disease affecting many organs and tissue types, almost all of which express CathB and CathL. PMID:15897303

  16. Experimental transmission of AA amyloidosis by injecting the AA amyloid protein into interleukin-1 receptor antagonist knockout (IL-1raKO) mice.

    PubMed

    Watanabe, K; Uchida, K; Chambers, J K; Tei, M; Shoji, A; Ushio, N; Nakayama, H

    2015-05-01

    The incidence of AA amyloidosis is high in humans with rheumatoid arthritis and several animal species, including cats and cattle with prolonged inflammation. AA amyloidosis can be experimentally induced in mice using severe inflammatory stimuli and a coinjection of AA amyloid; however, difficulties have been associated with transmitting AA amyloidosis to a different animal species, and this has been attributed to the "species barrier." The interleukin-1 receptor antagonist knockout (IL-1raKO) mouse, a rodent model of human rheumatoid arthritis, has been used in the transmission of AA amyloid. When IL-1raKO and BALB/c mice were intraperitoneally injected with mouse AA amyloid together with a subcutaneous pretreatment of 2% AgNO3, all mice from both strains that were injected with crude or purified murine AA amyloid developed AA amyloidosis. However, the amyloid index, which was determined by the intensity of AA amyloid deposition, was significantly higher in IL-1raKO mice than in BALB/c mice. When IL-1raKO and BALB/c mice were injected with crude or purified bovine AA amyloid together with the pretreatment, 83% (5/6 cases) and 38% (3/8 cases) of IL-1raKO mice and 17% (1/6 cases) and 0% (0/6 cases) of BALB/c mice, respectively, developed AA amyloidosis. Similarly, when IL-1raKO and BALB/c mice were injected with crude or purified feline AA amyloid, 33% (2/6 cases) and 88% (7/8 cases) of IL-1raKO mice and 0% (0/6 cases) and 29% (2/6 cases) of BALB/c mice, respectively, developed AA amyloidosis. These results indicated that IL-1raKO mice are a useful animal model for investigating AA amyloidogenesis. © The Author(s) 2014.

  17. The division of labor: genotypic versus phenotypic specialization.

    PubMed

    Wahl, L M

    2002-07-01

    A model of the division of labor in simple evolving systems is explored to compare two strategies evident in natural populations: phenotypic specialization (such as differentiation by regulated gene expression) and genotypic specialization (such as co-infection by complementary covirus populations). While genotypic specialization is vulnerable to the chance extinction of an essential specialist type and to parasitism, phenotypic specialization is able to overcome these hurdles. When simple spatial effects are included, phenotypic specialization has further benefits, protecting against destructive dynamic patterns. Many of the advantages of phenotypic specialization, however, can only be realized when a high degree of relatedness within groups is ensured.

  18. New Hepatitis E Virus Genotype in Camels, the Middle East

    PubMed Central

    Lau, Susanna K.P.; Teng, Jade L.L.; Tsang, Alan K. L.; Joseph, Marina; Wong, Emily Y.M.; Tang, Ying; Sivakumar, Saritha; Xie, Jun; Bai, Ru; Wernery, Renate; Wernery, Ulrich; Yuen, Kwok-Yung

    2014-01-01

    In a molecular epidemiology study of hepatitis E virus (HEV) in dromedaries in Dubai, United Arab Emirates, HEV was detected in fecal samples from 3 camels. Complete genome sequencing of 2 strains showed >20% overall nucleotide difference to known HEVs. Comparative genomic and phylogenetic analyses revealed a previously unrecognized HEV genotype. PMID:24856611

  19. SUGARCANE GENOTYPE SELECTION ON A SAND SOIL WITH AND WITHOUT ADDED MILL MUD

    USDA-ARS?s Scientific Manuscript database

    Long-term results for identifying high yielding sugarcane Saccharum spp.) cultivars have been better for Histosols (muck soils) than sand soils in Florida. We examined whether genotype selection could be improved by comparing genotypes on a sand soil with and without added mill mud (in Florida, mill...

  20. Reliability increases from combining 50,000- and 777,000-marker genotypes from four countries

    USDA-ARS?s Scientific Manuscript database

    Genomic predictions were compared on U.S. scale after combining 50,000 (50K) and 777,000 (HD) marker genotypes across countries. The genotyped Holsteins included 161,341 animals with five marker densities including 1,510 with HD. Imputation was more accurate with FImpute than with findhap across the...

  1. Cow genotyping strategies for genomic selection in small dairy cattle population

    USDA-ARS?s Scientific Manuscript database

    This study compares how different cow genotyping strategies increase the accuracy of genomic estimated breeding values (EBV) in dairy cattle breeds with low numbers. In these breeds there are few sires with progeny records and genotyping cows can improve the accuracy of genomic EBV. The Guernsey bre...

  2. A real time genotyping PCR assay for polyomavirus BK.

    PubMed

    Gard, Lilli; Niesters, Hubert G M; Riezebos-Brilman, Annelies

    2015-09-01

    Polyomavirus BK (BKV) may cause nephropathy in renal transplant recipients and hemorrhagic cystitis in bone marrow recipients. We developed real-time PCRs (RT-PCR) to determine easily and rapidly the different BKV genotypes (BKGT) (I-IV). On the VP1 gene a duplex of RT-PCRs was developed and validated to differentiate the four main BKGT. 212 BKV positive samples (21 plasma, 191 urine) were tested with these specific PCRs. Of these 212 samples, 55 PCR results were additionally confirmed by sequencing a VP1 gene fragment (nucleotide 1630-1956). For every genotype, a highly specific, precise and internally controlled assay was developed with a limit of detection of log 3 copies per ml. In 18 (8.5%) of these samples genotyping was not successful due to a low viral load. By sequence analysis, the genotype of 46 out of 55 and 2 out of 4 samples with double infection could be confirmed. This study describes RT-PCRs for detection of the main BKGT. It proved to be rapid, cheap and sensitive compared to sequencing. Double infections can also be detected. This method will be of value to investigate the role of BKV infection in relation to the genotype. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Methods for MHC genotyping in non-model vertebrates.

    PubMed

    Babik, W

    2010-03-01

    Genes of the major histocompatibility complex (MHC) are considered a paradigm of adaptive evolution at the molecular level and as such are frequently investigated by evolutionary biologists and ecologists. Accurate genotyping is essential for understanding of the role that MHC variation plays in natural populations, but may be extremely challenging. Here, I discuss the DNA-based methods currently used for genotyping MHC in non-model vertebrates, as well as techniques likely to find widespread use in the future. I also highlight the aspects of MHC structure that are relevant for genotyping, and detail the challenges posed by the complex genomic organization and high sequence variation of MHC loci. Special emphasis is placed on designing appropriate PCR primers, accounting for artefacts and the problem of genotyping alleles from multiple, co-amplifying loci, a strategy which is frequently necessary due to the structure of the MHC. The suitability of typing techniques is compared in various research situations, strategies for efficient genotyping are discussed and areas of likely progress in future are identified. This review addresses the well established typing methods such as the Single Strand Conformation Polymorphism (SSCP), Denaturing Gradient Gel Electrophoresis (DGGE), Reference Strand Conformational Analysis (RSCA) and cloning of PCR products. In addition, it includes the intriguing possibility of direct amplicon sequencing followed by the computational inference of alleles and also next generation sequencing (NGS) technologies; the latter technique may, in the future, find widespread use in typing complex multilocus MHC systems. © 2009 Blackwell Publishing Ltd.

  4. ACE DD genotype: a predisposing factor for abdominal aortic aneurysm.

    PubMed

    Fatini, C; Pratesi, G; Sofi, F; Gensini, F; Sticchi, E; Lari, B; Pulli, R; Dorigo, W; Azas, L; Pratesi, C; Gensini, G F; Abbate, R

    2005-03-01

    To examine the role of polymorphisms in angiotensin converting enzyme (ACE, I/D) and angiotensin II receptor (AT1R, A1166C) in the development of abdominal aortic aneurysm (AAA). We investigated 250 consecutive patients, 217 males and 33 females (median age 72, range 50-83), undergone AAA elective repair and 250 healthy controls, comparable for sex and age. ACE and AT1R polymorphisms were studied by PCR-RFLP analysis. The genotype distribution was in Hardy-Weinberg equilibrium for all polymorphisms. The genotype distribution and allele frequency of ACE I/D, but not AT1R A1166C polymorphism were significantly different between patients and controls (ACE I/D: p=0.0002 and p<0.0001, respectively, and AT1R A1166C: p=0.6 and p=0.4, respectively). An association between the ACE DD genotype and the predisposition to AAA was found (OR DD vs. ID+II=1.9 95% CI 1.3-2.9, p<0.0001). Multivariate analysis adjusted for age, sex, traditional vascular risk factors and other atherosclerotic localizations, showed ACE DD genotype to be independently related to the disease (OR DD vs. ID+II=2.4, 95% CI 1.3-4.2 p=0.003). Our findings document that ACE DD genotype represents a susceptibility factor for AAA.

  5. Bardoxolone methyl (BARD) ameliorates aristolochic acid (AA)-induced acute kidney injury through Nrf2 pathway.

    PubMed

    Wu, Juan; Liu, Xinhui; Fan, Jinjin; Chen, Wenfang; Wang, Juan; Zeng, Youjia; Feng, Xiaorang; Yu, Xueqing; Yang, Xiao

    2014-04-06

    Bardoxolone methyl (BARD) is an antioxidant modulator that acts through induction of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. This study aimed to investigate the role of BARD in protecting kidneys from aristolochic acid (AA)-induced acute kidney injury (AKI). Male C57BL/6 mice received intraperitoneal (i.p.) injections of aristolochic acid I (AAI) (5mg/kg/day) for 5 days to produce acute AA nephropathy (AAN) model. BARD (10mg/kg/day, i.p.) was applied for 7 consecutive days, starting 2 days prior to AAI administration. The mice in the AA group showed AKI as evidenced by worsening kidney function evaluated by blood urea nitrogen (BUN) and serum creatinine (SCr) levels, and severe tubulointerstitial injury marked by massive tubule necrosis in kidney tissues. BARD significantly reduced BUN and SCr levels which were elevated by AAI. Additionally, AAI-induced histopathological renal damage was ameliorated by BARD. Furthermore, the expression of Nrf2 was reduced, and its repressor Kelch-like ECH-associated protein 1 (Keap1) was increased significantly, whereas heme oxygenase-1 (HO-1) was upregulated and NAD(P)H quinone oxidoreductase-1 (NQO1) was barely increased in the cytoplasm of tubules in kidneys after treatment with AAI. BARD significantly upregulated renal Nrf2, NQO1 and HO-1 expression and downregulated Keap1 expression compared with those in the AA group. Moreover, it was found that Nrf2 was expressed both in the cytoplasm and nuclear of glomeruli and tubules, whereas NQO1 and HO-1 were localized in the cytoplasm of tubules only. In conclusion, AA-induced acute renal injury was associated with impaired Nrf2 activation and expression of its downstream target genes in renal tissues. BARD prevented renal damage induced by AAI, and this renoprotective effect may be exerted by activating the Nrf2 signaling pathway and increasing expression of the downstream target genes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. Evaluation of the Abbott realtime HCV genotype II RUO (GT II) assay with reference to 5'UTR, core and NS5B sequencing.

    PubMed

    Mallory, Melanie A; Lucic, Danijela X; Sears, Mitchell T; Cloherty, Gavin A; Hillyard, David R

    2014-05-01

    HCV genotyping is a critical tool for guiding initiation of therapy and selecting the most appropriate treatment regimen. To evaluate the concordance between the Abbott GT II assay and genotyping by sequencing subregions of the HCV 5'UTR, core and NS5B. The Abbott assay was used to genotype 127 routine patient specimens and 35 patient specimens with unusual subtypes and mixed infection. Abbott results were compared to genotyping by 5'UTR, core and NS5B sequencing. Sequences were genotyped using the NCBI non-redundant database and the online genotyping tool COMET. Among routine specimens, core/NS5B sequencing identified 93 genotype 1s, 13 genotype 2s, 15 genotype 3s, three genotype 4s, two genotype 6s and one recombinant specimen. Genotype calls by 5'UTR, core, NS5B sequencing and the Abbott assay were 97.6% concordant. Core/NS5B sequencing identified two discrepant samples as genotype 6 (subtypes 6l and 6u) while Abbott and 5'UTR sequencing identified these samples as genotype 1 with no subtype. The Abbott assay subtyped 91.4% of genotype 1 specimens. Among the 35 rare specimens, the Abbott assay inaccurately genotyped 3k, 6e, 6o, 6q and one genotype 4 variant; gave indeterminate results for 3g, 3h, 4r, 6m, 6n, and 6q specimens; and agreed with core/NS5B sequencing for mixed specimens. The Abbott assay is an automated HCV genotyping method with improved accuracy over 5'UTR sequencing. Samples identified by the Abbott assay as genotype 1 with no subtype may be rare subtypes of other genotypes and thus require confirmation by another method. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. View northeast, wharf A, portion AA, details showing earlier piers ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View northeast, wharf A, portion AA, details showing earlier piers and braces sloping toward water, reused charred plates for existing decking - U.S. Coast Guard Sandy Hook Station, Western Docking Structure, West of intersection of Canfield Road & Hartshorne Drive, Highlands, Monmouth County, NJ

  8. Systemic AA amyloidosis in the red fox (Vulpes vulpes).

    PubMed

    Rising, Anna; Cederlund, Ella; Palmberg, Carina; Uhlhorn, Henrik; Gaunitz, Stefan; Nordling, Kerstin; Ågren, Erik; Ihse, Elisabet; Westermark, Gunilla T; Tjernberg, Lars; Jörnvall, Hans; Johansson, Jan; Westermark, Per

    2017-11-01

    Amyloid A (AA) amyloidosis occurs spontaneously in many mammals and birds, but the prevalence varies considerably among different species, and even among subgroups of the same species. The Blue fox and the Gray fox seem to be resistant to the development of AA amyloidosis, while Island foxes have a high prevalence of the disease. Herein, we report on the identification of AA amyloidosis in the Red fox (Vulpes vulpes). Edman degradation and tandem MS analysis of proteolyzed amyloid protein revealed that the amyloid partly was composed of full-length SAA. Its amino acid sequence was determined and found to consist of 111 amino acid residues. Based on inter-species sequence comparisons we found four residue exchanges (Ser31, Lys63, Leu71, Lys72) between the Red and Blue fox SAAs. Lys63 seems unique to the Red fox SAA. We found no obvious explanation to how these exchanges might correlate with the reported differences in SAA amyloidogenicity. Furthermore, in contrast to fibrils from many other mammalian species, the isolated amyloid fibrils from Red fox did not seed AA amyloidosis in a mouse model. © 2017 The Protein Society.

  9. 32. SECTIONS AA, BB, CC, DD, AND EE WASTE CALCINATION ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    32. SECTIONS A-A, B-B, C-C, D-D, AND E-E WASTE CALCINATION FACILITY SHOWING RELATIONSHIPS OF DIFFERENT FLOOR LEVELS TO ONE ANOTHER. INEEL DRAWING NUMBER 200-0633-00-287-106353. FLUOR NUMBER 5775-CPP-633-A-3. - Idaho National Engineering Laboratory, Old Waste Calcining Facility, Scoville, Butte County, ID

  10. PAI-1 gain-of-function genotype, factors increasing PAI-1 levels, and airway obstruction: The GALA II Cohort.

    PubMed

    Sherenian, M G; Cho, S H; Levin, A; Min, J-Y; Oh, S S; Hu, D; Galanter, J; Sen, S; Huntsman, S; Eng, C; Rodriguez-Santana, J R; Serebrisky, D; Avila, P C; Kalhan, R; Smith, L J; Borrell, L N; Seibold, M A; Keoki Williams, L; Burchard, E G; Kumar, R

    2017-09-01

    PAI-1 gain-of-function variants promote airway fibrosis and are associated with asthma and with worse lung function in subjects with asthma. We sought to determine whether the association of a gain-of-function polymorphism in plasminogen activator inhibitor-1 (PAI-1) with airway obstruction is modified by asthma status, and whether any genotype effect persists after accounting for common exposures that increase PAI-1 level. We studied 2070 Latino children (8-21y) with genotypic and pulmonary function data from the GALA II cohort. We estimated the relationship of the PAI-1 risk allele with FEV1/FVC by multivariate linear regression, stratified by asthma status. We examined the association of the polymorphism with asthma and airway obstruction within asthmatics via multivariate logistic regression. We replicated associations in the SAPPHIRE cohort of African Americans (n=1056). Secondary analysis included the effect of the at-risk polymorphism on postbronchodilator lung function. There was an interaction between asthma status and the PAI-1 polymorphism on FEV 1 /FVC (P=.03). The gain-of-function variants, genotypes (AA/AG), were associated with lower FEV 1 /FVC in subjects with asthma (β=-1.25, CI: -2.14,-0.35, P=.006), but not in controls. Subjects with asthma and the AA/AG genotypes had a 5% decrease in FEV 1 /FVC (P<.001). In asthmatics, the risk genotype (AA/AG) was associated with a 39% increase in risk of clinically relevant airway obstruction (OR=1.39, CI: 1.01, 1.92, P=.04). These associations persisted after exclusion of factors that increase PAI-1 including tobacco exposure and obesity. The decrease in the FEV 1 /FVC ratio associated with the risk genotype was modified by asthma status. The genotype increased the odds of airway obstruction by 75% within asthmatics only. As exposures known to increase PAI-1 levels did not mitigate this association, PAI-1 may contribute to airway obstruction in the context of chronic asthmatic airway inflammation. © 2017

  11. Identification of three genotypes of sugarcane yellow leaf virus causing yellow leaf disease from India and their molecular characterization.

    PubMed

    Viswanathan, R; Balamuralikrishnan, M; Karuppaiah, R

    2008-12-01

    Sugarcane yellow leaf virus (SCYLV) that causes yellow leaf disease (YLD) in sugarcane (recently reported in India) belongs to Polerovirus. Detailed studies were conducted to characterize the virus based on partial open reading frames (ORFs) 1 and 2 and complete ORFs 3 and 4 sequences in their genome. Reverse-transcriptase polymerase chain reaction (RT-PCR) was performed on 48 sugarcane leaf samples to detect the virus using a specific set of primers. Of the 48 samples, 36 samples (field samples with and without foliar symptoms) including 10 meristem culture derived plants were found to be positive to SCYLV infection. Additionally, an aphid colony collected from symptomatic sugarcane in the field was also found to be SCYLV positive. The amplicons from 22 samples were cloned, sequenced and acronymed as SCYLV-CB isolates. The nucleotide (nt) and amino acid (aa) sequence comparison showed a significant variation between SCYLV-CB and the database sequences at nt (3.7-5.1%) and aa (3.2-5.3%) sequence level in the CP coding region. However, the database sequences comprising isolates of three reported genotypes, viz., BRA, PER and REU, were observed with least nt and aa sequence dissimilarities (0.0-1.6%). The phylogenetic analyses of the overlapping ORFs (ORF 3 and ORF 4) of SCYLV encoding CP and MP determined in this study and additional sequences of 26 other isolates including an Indian isolate (SCYLV-IND) available from GenBank were distributed in four phylogenetic clusters. The SCYLV-CB isolates from this study lineated in two clusters (C1 and C2) and all the other isolates from the worldwide locations into another two clusters (C3 and C4). The sequence variation of the isolates in this study with the database isolates, even in the least variable region of the SCYLV genome, showed that the population existing in India is significantly different from rest of the world. Further, comparison of partial sequences encoding for ORFs 1 and 2 revealed that YLD in sugarcane in

  12. Rotavirus genotypes associated with acute diarrhea in Egyptian infants.

    PubMed

    Ahmed, Salwa F; Mansour, Adel M; Klena, John D; Husain, Tupur S; Hassan, Khaled A; Mohamed, Farag; Steele, Duncan

    2014-01-01

    Before the introduction of rotavirus vaccine in Egypt, information on the burden of disease and the circulating rotavirus genotypes is critical to monitor vaccine effectiveness. A cohort of 348 Egyptian children was followed from birth to 2 years of age with twice-weekly home visits to detect diarrheal illness. VP7 and VP4 genes were genotyped by reverse-transcription polymerase chain reaction and DNA sequencing. Forty percentage of children had rotavirus-associated diarrhea at least once by their second birthday. One hundred and twelve children experienced a single rotavirus diarrheal episodes (RDE) at a median age of 9 months; while 27 infants had their second RDE at a median age of 15 months and 1 infant had 3 RDE at the age of 2, 16 and 22 months. Of the 169 RDE, 82% could be assigned a G-type, while 58% had been identified a P-type. The most prevalent genotype was G2 (32%), followed by G1 (24%) and G9 (19%). G2P[4] rotavirus episodes were significantly associated with fever (P = 0.03) and vomiting (P = 0.06) when compared with other genotypes. G2 strains were the predominant genotype causing 50% of the second RDE while G9 represented 25% of the second RDE. Genotypes identified are similar to those detected globally except for absence of G4. Our finding that 75% of the second RDE were due to G2 and G9 indicates a possible reduction in natural protection afforded by these types compared with G1, where 90% of G1 cases did not experience a second xposure, indicating greater protection against recurrent symptomatic infection.

  13. Associations between Oxytocin Receptor (OXTR) Genotype and Elementary School Children's Likability, Dis-likability and Friendship among Classroom Peers: A Longitudinal Study.

    PubMed

    He, Jin; Buil, J Marieke; Koot, Hans M; van Lier, Pol A C

    2018-04-27

    The single nucleotide polymorphism rs53576 of the oxytocin receptor (OXTR) gene is involved in forming and maintaining relationships in various social contexts. However, this has not been studied in the childhood peer context. The present study followed 359 children (51.6% girls) from age 9 to 12 to explore associations between OXTR rs53576 genotype (i.e., AA, AG or GG genotype) and three indicators of children's relationships with peers: likability and dis-likability among, and friendship with, classroom peers. Our results showed that OXTR rs53576 was associated with likability among boys, but not with dis-likability and friendship or among girls. Boys with an A and a G allele (i.e., AG genotype) became increasingly more liked by their peers across the four-year studied period than those with two A alleles or two G alleles (i.e., AA and GG genotype). This study indicates that OXTR rs53576 genotype might influence children's peer relationships, particularly their likeability among peers. Associations between OXTR rs53576 and peer relationships may differ depending on children's sex and the specific type of peer-relationship under scrutiny.

  14. Erythrocyte polyunsaturated fatty acid composition is associated with depression and FADS genotype in Caucasians.

    PubMed

    Cribb, Lachlan; Murphy, Jenifer; Froud, Amy; Oliver, Georgina; Bousman, Chad A; Ng, Chee H; Sarris, Jerome

    2017-05-29

    Polyunsaturated fatty acids (PUFAs) play an important role in the pathophysiology of major depressive disorder (MDD), related, in part, to their role in inflammatory systems. The enzymes δ-5 and δ-6 desaturase are the rate-limiting steps in the metabolism of PUFAs and are encoded in the genes fatty acid desaturase (FADS) 1 and 2, respectively. Single nucleotide polymorphisms (SNPs) and haplotypes within the FADS gene cluster have been shown to influence PUFA composition. The objective of this study was to determine whether key omega-3 (n-3) and omega-6 (n-6) fatty acids may be associated with depression, and to explore the role of FADS genotype in PUFA variation. Four erythrocyte long chain (LC) fatty acids (linoleic acid [LA], α-linolenic acid [ALA], arachidonic acid [AA] and Eicosapentaenoic acid [EPA]), as well as six SNPs (rs174537, rs174547, rs174570, rs174575, rs498793 and rs3834458) within the FADS gene cluster were measured in a sample of 207 participants (154 with MDD versus 53 non-depressed controls). The precursor LC-PUFAs LA and ALA appeared to be negatively associated with depression (P < 0.001 and P < 0.01, respectively), while AA:LA (surrogate measure of desaturase activity) was positively associated with depression (P < 0.01). No significant differences were noted in erythrocyte EPA, AA or AA:EPA between groups. Minor alleles of each SNP (excluding rs498793) were associated with variation in desaturase activity and LA. Both rs174537 and rs174547 were associated with ALA. No genotype was associated with EPA or AA. Minor alleles of rs174537 and rs174547 were significantly associated with lower odds of MDD (although significance was lost after correction for multiple comparisons). Precursor LC-PUFAs, LA and ALA, appear to be associated with MDD and potentially modulated by genetic variation in the FADS gene cluster. These results provide support for the consideration of PUFA composition, diet and FADS genetic variation in the

  15. CC genotype of anti-apoptotic gene BCL-2 (-938 C/A) is an independent prognostic marker of unfavorable clinical outcome in patients with non-small-cell lung cancer.

    PubMed

    Javid, J; Mir, R; Mirza, M; Imtiyaz, A; Prasant, Y; Mariyam, Z; Julka, P K; Mohan, A; Lone, M; Ray, P C; Saxena, A

    2015-04-01

    B cell lymphoma 2 (BCL-2) gene is a well-known regulator of apoptosis and a key element in cancer development and progression. A regulatory (-938C>A, rs2279115) single-nucleotide polymorphism in the inhibitory P2 BCL-2 gene promoter generates significantly different BCL-2 promoter activities and has been associated with different clinical outcomes in various malignancies. The aim of the present study was to analyze the possible influence of the (-938C>A) SNP on the risk and survival of Indian patients suffering from NSCLC. A hospital-based case-control study of 155 age- and sex-matched patients diagnosed with NSCLC and 155 cancer-free controls was conducted and genotyped by performing PIRA-PCR to elucidate the putative association between clinical outcome and genotypes of BCL-2 (-938C>A, rs2279115). The association of the polymorphism with the survival of NSCLC patients was analyzed by Kaplan-Meier curves. In Indian NSCLC, patients increased risk of developing NSCLC was found to be associated with BCL-2 (-938) CC genotype, [OR 3.68 (1.92-6.79), RR 1.87 (1.35-2.57) and RD 31.03 (16.79-45.27) p 0.00006 for CC and OR 2.08 (1.18-3.66), RR 1.36 (1.08-1.71) and RD 17.74 (4.68-30.81) p 0.01 for AC genotype]. Patients homozygous for C allele exhibited a significant poor overall survival compared with patients displaying AC + CC or AC or AA genotype [median survival (months) 8 vs. 11 vs. 14 vs. 35.5 (p < 0.0001)]. In addition, significant associations were observed between TNM stage, histological type, distant metastases status, family history of any cancer, gender and age group of NSCLC patients with BCL-2 (-938C>A) polymorphism. Genetic polymorphism in the inhibitory P2 promoter region of anti-apoptotic BCL-2 genes contributes to the risk of developing non-small-cell lung cancer in Indian population. BCL-2 (-938CC) genotype was an independent adverse prognostic factor for patients with NSCLC.

  16. Breakfast with glycomacropeptide compared with amino acids suppresses plasma ghrelin levels in individuals with phenylketonuria

    PubMed Central

    MacLeod, Erin L.; Clayton, Murray K.; van Calcar, Sandra C.; Ney, Denise M.

    2010-01-01

    Phenylketonuria (PKU) requires a lifelong low-phenylalanine (phe) diet where protein needs are met by consumption of a phe-free amino acid (AA) formula; complaints of persistent hunger are common. Foods made with glycomacropeptide (GMP), an intact protein that contains minimal phe and may promote satiety, provide an alternative to AA formula. The objective was to assess the ability of a GMP breakfast to promote satiety and affect plasma concentrations of AAs, insulin, and the appetite stimulating hormone ghrelin in those with PKU, when compared to an AA-based breakfast. Eleven PKU subjects (8 adults and 3 boys ages 11–14) served as their own controls in an inpatient metabolic study with two 4-day treatments: an AA-based diet followed by a diet replacing all AA formula with GMP foods. Plasma concentrations of AAs, insulin and ghrelin were obtained before and/or 180 minutes after breakfast. Satiety was assessed using a visual analog scale before, immediately after and 180 minutes after breakfast. Postprandial ghrelin concentration was significantly lower (p=0.03) with GMP compared to an AA-based breakfast, with no difference in fasting ghrelin. Lower postprandial ghrelin concentrations were associated with greater feelings of fullness 180 minutes after breakfast suggesting greater satiety with GMP compared to AAs. Postprandial concentrations of insulin and total plasma AAs were higher after a GMP breakfast compared to an AA-based breakfast consistent with slower absorption of AAs from GMP. These results show sustained ghrelin suppression, and suggest greater satiety with ingestion of a meal containing GMP compared with AAs. PMID:20466571

  17. A Status Report on the AAS Astronomy Ambassadors Program

    NASA Astrophysics Data System (ADS)

    Fienberg, Richard Tresch; Fraknoi, Andrew; Gurton, Suzanne; Hurst, Anna; Schatz, Dennis L.

    2014-06-01

    The American Astronomical Society, in partnership with the Astronomical Society of the Pacific (ASP), has launched a series of professional-development workshops and a community of practice designed to improve early-career astronomers’ ability to communicate effectively with students and the public. Called AAS Astronomy Ambassadors, the program provides training and mentoring for young astronomers, from advanced undergraduates to beginning faculty; it also provides them access to resources and a network of contacts within the astronomy education and public outreach (EPO) community. Ambassadors are provided with a library of outreach activities and resource materials suitable for a range of venues and audiences. For much of this library we are using resources developed by organizations such as the ASP, the Pacific Science Center, and the Center for Astronomy Education for other outreach programs, though some resources have been created by one of us (AF) specifically for this program. After a period of evaluation and revision, the program’s “Menu of Outreach Opportunities for Science Education” (MOOSE) is now posted on the AAS website at http://aas.org/outreach/moose-menu-outreach-opportunities-science-education.The first two Astronomy Ambassadors workshops were held at AAS meetings in January 2013 and January 2014; each served 30 young astronomers chosen from about twice that many applicants. Web-based follow-up activities are being provided through a website at the ASP designed to keep cohorts of educators trained in their programs in touch with one another. The AAS is exploring ways to fund additional workshops at future winter meetings; suggestions are most welcome. Meanwhile, the Astronomy Ambassadors trained to date have logged more than 150 outreach events, reaching many thousands of children and adults across the U.S. and Canada.

  18. AA amyloidosis: Mount Sinai experience, 1997-2012.

    PubMed

    Bunker, Daniel; Gorevic, Peter

    2012-01-01

    AA amyloidosis is a systemic disease characterized by the extracellular deposition of amyloid fibrils derived from the acute-phase reactant serum amyloid A protein. It is typically a consequence of chronic inflammatory conditions like rheumatoid arthritis or Crohn's disease, although more patients are being identified who have more unusual causes or no known inflammatory stimulus. We performed a retrospective chart review of all patients with AA amyloidosis seen at Mount Sinai during the period of 1997-2012. Particular attention was paid to the patients' underlying diseases, extent of organ involvement, levels of inflammatory markers and proinflammatory cytokines, presence of pyrin gene mutations, and outcomes. Forty-three patients were seen at Mount Sinai with AA amyloidosis during this period. The most common underlying diseases were rheumatoid arthritis (21%) and Crohn's disease (16%), though 21% of patients were considered to have idiopathic AA amyloid after an extensive search found no underlying inflammatory disease. Almost all patients (95%) had renal involvement based on biopsy or clinical criteria, with 19 patients (44%) eventually requiring dialysis and 5 (12%) undergoing renal transplantation. Inflammatory markers were elevated in most patients; however, interleukin-6 was the only consistently elevated cytokine. Three patients (of 9 tested) were found to be positive for the E148Q pyrin gene mutation. Our study confirms the increasing number of patients being seen with idiopathic AA amyloidosis. More research is needed to determine if these patients have an underlying genetic susceptibility encoded in pyrin or other genes. Our study also confirms the dominance of renal disease in this population. The elevated levels of interleukin-6, in comparison with other cytokines, could represent a therapeutic target. © 2012 Mount Sinai School of Medicine.

  19. Birth of correctly genotyped calves after multiplex marker detection from bovine embryo microblade biopsies.

    PubMed

    Peippo, Jaana; Viitala, Sirja; Virta, Jouni; Räty, Mervi; Tammiranta, Niina; Lamminen, Terttu; Aro, Johanna; Myllymäki, Hannu; Vilkki, Johanna

    2007-11-01

    We report a method for multiplex genotyping of bovine embryo microblade biopsies. We have tested the reliability of the method and the viability of the embryos in vitro and in vivo. Two polymorphic gene markers (GHR F279Y and PRLR S18N) associated with milk production traits and one marker for sex diagnosis (ZFX/ZFY) were genotyped simultaneously with a method that combines nested PCR and allelic discrimination. To test the accuracy of genotyping, in the first experiment the genotypes of 134 biopsies from in vitro produced embryos were compared to genotypes determined from the corresponding embryos after biopsy. The method proved to be highly accurate as only in three cases (two for PRLR S18N and one for GHR F279Y) out of 395 genotypes the genotype was in disagreement between the two samples. The viability of similarly biopsied embryos was tested in parallel: after 24-hr culture 94.6% of embryos recovered in vitro. In the second experiment, a total of 150 in vivo-produced embryos were biopsied on Day 7 and genotyped. After the genotyping results were obtained on Day 8, female embryos were selected for transfer. From a total of 57 selected embryos 43 were transferred individually and 14 as pairs. After single embryo transfers, 19 recipients became pregnant and after embryo transfers in pairs one became pregnant. The success of genotyping was tested with the genotypes of donors and bulls and also from the hair samples of born calves. All calves were females and of the same genotypes determined from the biopsy. (c) 2007 Wiley-Liss, Inc.

  20. Allelopathic interference of alfalfa (Medicago sativa L.) genotypes to annual ryegrass (Lolium rigidum).

    PubMed

    Zubair, Hasan Muhammad; Pratley, James E; Sandral, G A; Humphries, A

    2017-07-01

    Alfalfa (Medicago sativa L.) genotypes at varying densities were investigated for allelopathic impact using annual ryegrass (Lolium rigidum) as the target species in a laboratory bioassay. Three densities (15, 30, and 50 seedlings/beaker) and 40 alfalfa genotypes were evaluated by the equal compartment agar method (ECAM). Alfalfa genotypes displayed a range of allelopathic interference in ryegrass seedlings, reducing root length from 5 to 65%. The growth of ryegrass decreased in response to increasing density of alfalfa seedlings. At the lowest density, Q75 and Titan9 were the least allelopathic genotypes. An overall inhibition index was calculated to rank each alfalfa genotype. Reduction in seed germination of annual ryegrass occurred in the presence of several alfalfa genotypes including Force 10, Haymaster7 and SARDI Five. A comprehensive metabolomic analysis using Quadruple Time of Flight (Q-TOF), was conducted to compare six alfalfa genotypes. Variation in chemical compounds was found between alfalfa root extracts and exudates and also between genotypes. Further individual compound assessments and quantitative study at greater chemical concentrations are needed to clarify the allelopathic activity. Considerable genetic variation exists among alfalfa genotypes for allelopathic activity creating the opportunity for its use in weed suppression through selection.

  1. Molecular characterisation and prevalence of a new genotype of Cyprinid herpesvirus 2 in mainland China.

    PubMed

    Li, Lijuan; Luo, Yangzhi; Gao, Zexia; Huang, Jian; Zheng, Xianghai; Nie, Huihui; Zhang, Junmei; Lin, Li; Yuan, Junfa

    2015-06-01

    Cyprinid herpesvirus 2 (CyHV-2, species Cyprinid herpesvirus 2) has been confirmed as a causative agent of the acute haematopoietic necrosis disease outbreak in farmed goldfish (Carassius auratus L.) and gibel carp (Carassius auratus gibelio Bloch). In this study, we present the genomic characteristics of a variant CyHV-2 strain (SY-C1) isolated from farmed gibel carp in mainland China and its comparative genomics analysis with the CyHV-2 reference strain ST-J1. Overall, the full-length genome of SY-C1 shares 98.8% homology with that of ST-J1. Sequence comparisons between SY-C1 and ST-J1 indicate that the variations include single-nucleotide mutations, insertions, deletions, and rearrangements, which suggested that SY-C1 is different from ST-J1 and represents a new genotype. Therefore, we propose that the identified CyHV-2 can be divided into 2 different genotypes and be named China genotype (C genotype) and Japan genotype (J genotype) according to their isolation loci. Furthermore, epidemiological surveys indicate that the dominant genotype of CyHV-2 circulating in mainland China is closer to the China genotype than the Japan genotype.

  2. Minimum Information about a Genotyping Experiment (MIGEN)

    PubMed Central

    Huang, Jie; Mirel, Daniel; Pugh, Elizabeth; Xing, Chao; Robinson, Peter N.; Pertsemlidis, Alexander; Ding, LiangHao; Kozlitina, Julia; Maher, Joseph; Rios, Jonathan; Story, Michael; Marthandan, Nishanth; Scheuermann, Richard H.

    2011-01-01

    Genotyping experiments are widely used in clinical and basic research laboratories to identify associations between genetic variations and normal/abnormal phenotypes. Genotyping assay techniques vary from single genomic regions that are interrogated using PCR reactions to high throughput assays examining genome-wide sequence and structural variation. The resulting genotype data may include millions of markers of thousands of individuals, requiring various statistical, modeling or other data analysis methodologies to interpret the results. To date, there are no standards for reporting genotyping experiments. Here we present the Minimum Information about a Genotyping Experiment (MIGen) standard, defining the minimum information required for reporting genotyping experiments. MIGen standard covers experimental design, subject description, genotyping procedure, quality control and data analysis. MIGen is a registered project under MIBBI (Minimum Information for Biological and Biomedical Investigations) and is being developed by an interdisciplinary group of experts in basic biomedical science, clinical science, biostatistics and bioinformatics. To accommodate the wide variety of techniques and methodologies applied in current and future genotyping experiment, MIGen leverages foundational concepts from the Ontology for Biomedical Investigations (OBI) for the description of the various types of planned processes and implements a hierarchical document structure. The adoption of MIGen by the research community will facilitate consistent genotyping data interpretation and independent data validation. MIGen can also serve as a framework for the development of data models for capturing and storing genotyping results and experiment metadata in a structured way, to facilitate the exchange of metadata. PMID:22180825

  3. Decoding noises in HIV computational genotyping.

    PubMed

    Jia, MingRui; Shaw, Timothy; Zhang, Xing; Liu, Dong; Shen, Ye; Ezeamama, Amara E; Yang, Chunfu; Zhang, Ming

    2017-11-01

    Lack of a consistent and reliable genotyping system can critically impede HIV genomic research on pathogenesis, fitness, virulence, drug resistance, and genomic-based healthcare and treatment. At present, mis-genotyping, i.e., background noises in molecular genotyping, and its impact on epidemic surveillance is unknown. For the first time, we present a comprehensive assessment of HIV genotyping quality. HIV sequence data were retrieved from worldwide published records, and subjected to a systematic genotyping assessment pipeline. Results showed that mis-genotyped cases occurred at 4.6% globally, with some regional and high-risk population heterogeneities. Results also revealed a consistent mis-genotyping pattern in gp120 in all studied populations except the group of men who have sex with men. Our study also suggests novel virus diversities in the mis-genotyped cases. Finally, this study reemphasizes the importance of implementing a standardized genotyping pipeline to avoid genotyping disparity and to advance our understanding of virus evolution in various epidemiological settings. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. CSI 2264: Probing the inner disks of AA Tauri-like systems in NGC 2264

    NASA Astrophysics Data System (ADS)

    McGinnis, P. T.; Alencar, S. H. P.; Guimarães, M. M.; Sousa, A. P.; Stauffer, J.; Bouvier, J.; Rebull, L.; Fonseca, N. N. J.; Venuti, L.; Hillenbrand, L.; Cody, A. M.; Teixeira, P. S.; Aigrain, S.; Favata, F.; Fűrész, G.; Vrba, F. J.; Flaccomio, E.; Turner, N. J.; Gameiro, J. F.; Dougados, C.; Herbst, W.; Morales-Calderón, M.; Micela, G.

    2015-05-01

    Context. The classical T Tauri star (CTTS) AA Tau has presented photometric variability that was attributed to an inner disk warp, caused by the interaction between the inner disk and an inclined magnetosphere. Previous studies of the young cluster NGC 2264 have shown that similar photometric behavior is common among CTTS. Aims: The goal of this work is to investigate the main causes of the observed photometric variability of CTTS in NGC 2264 that present AA Tau-like light curves, and verify if an inner disk warp could be responsible for their observed variability. Methods: In order to understand the mechanism causing these stars' photometric behavior, we investigate veiling variability in their spectra and u - r color variations and estimate parameters of the inner disk warp using an occultation model proposed for AA Tau. We also compare infrared Spitzer IRAC and optical CoRoT light curves to analyze the dust responsible for the occultations. Results: AA Tau-like variability proved to be transient on a timescale of a few years. We ascribe this variability to stable accretion regimes and aperiodic variability to unstable accretion regimes and show that a transition, and even coexistence, between the two is common. We find evidence of hot spots associated with occultations, indicating that the occulting structures could be located at the base of accretion columns. We find average values of warp maximum height of 0.23 times its radial location, consistent with AA Tau, with variations of on average 11% between rotation cycles. We also show that extinction laws in the inner disk indicate the presence of grains larger than interstellar grains. Conclusions: The inner disk warp scenario is consistent with observations for all but one star with AA Tau-like variability in our sample. AA Tau-like systems are fairly common, comprising 14% of CTTS observed in NGC 2264, though this number increases to 35% among systems of mass 0.7 M⊙ ≲ M ≲ 2.0 M⊙. Assuming random

  5. The 9aaTAD Transactivation Domains: From Gal4 to p53.

    PubMed

    Piskacek, Martin; Havelka, Marek; Rezacova, Martina; Knight, Andrea

    2016-01-01

    The family of the Nine amino acid Transactivation Domain, 9aaTAD family, comprises currently over 40 members. The 9aaTAD domains are universally recognized by the transcriptional machinery from yeast to man. We had identified the 9aaTAD domains in the p53, Msn2, Pdr1 and B42 activators by our prediction algorithm. In this study, their competence to activate transcription as small peptides was proven. Not surprisingly, we elicited immense 9aaTAD divergence in hundreds of identified orthologs and numerous examples of the 9aaTAD species' convergence. We found unforeseen similarity of the mammalian p53 with yeast Gal4 9aaTAD domains. Furthermore, we identified artificial 9aaTAD domains generated accidentally by others. From an evolutionary perspective, the observed easiness to generate 9aaTAD transactivation domains indicates the natural advantage for spontaneous generation of transcription factors from DNA binding precursors.

  6. Dynamic Response and Microstructure Evolution of AA2219-T4 and AA2219-T6 Aluminum Alloys

    NASA Astrophysics Data System (ADS)

    Olasumboye, A.; Owolabi, G.; Odeshi, A.; Zeytinci, A.; Yilmaz, N.

    2018-02-01

    In this study, the dynamic deformation behavior of AA2219 aluminum alloy was investigated in two different temper conditions: T4 and T6, with a view to determining the effect of heat treatment on the microstructure and flow behavior of the material under high strain rates. Split Hopkinson pressure bar experiment was used in determining the dynamic response of the alloy while a digital image correlation system was employed in visualizing and tracking the surface deformation of the specimens. Optical microscopy and scanning electron microscopy were used to assess the microstructure of the material after following standard metallographic specimen preparation techniques. The results obtained showed heterogeneous deformation of the alloy in the two temper conditions. It was observed that the dynamic mechanical behavior of each sample preparation was dependent on its strength properties due to aging type, which in turn controls the metamorphosis of the strengthening precipitates and the initial microstructure. At the maximum strain rate of 3500 s-1, transformed bands leading to crack nucleation was observed in the AA2219-T4 aluminum alloy while AA2219-T6 had fractured at the same strain rate. The modes of crack formation and growth in the two alloys were found to be similar: nucleation, growth and coalescence of voids. However, shear band bifurcation phenomenon was observed only in the AA2219-T6 alloy.

  7. Dynamic Response and Microstructure Evolution of AA2219-T4 and AA2219-T6 Aluminum Alloys

    NASA Astrophysics Data System (ADS)

    Olasumboye, A.; Owolabi, G.; Odeshi, A.; Zeytinci, A.; Yilmaz, N.

    2018-06-01

    In this study, the dynamic deformation behavior of AA2219 aluminum alloy was investigated in two different temper conditions: T4 and T6, with a view to determining the effect of heat treatment on the microstructure and flow behavior of the material under high strain rates. Split Hopkinson pressure bar experiment was used in determining the dynamic response of the alloy while a digital image correlation system was employed in visualizing and tracking the surface deformation of the specimens. Optical microscopy and scanning electron microscopy were used to assess the microstructure of the material after following standard metallographic specimen preparation techniques. The results obtained showed heterogeneous deformation of the alloy in the two temper conditions. It was observed that the dynamic mechanical behavior of each sample preparation was dependent on its strength properties due to aging type, which in turn controls the metamorphosis of the strengthening precipitates and the initial microstructure. At the maximum strain rate of 3500 s-1, transformed bands leading to crack nucleation was observed in the AA2219-T4 aluminum alloy while AA2219-T6 had fractured at the same strain rate. The modes of crack formation and growth in the two alloys were found to be similar: nucleation, growth and coalescence of voids. However, shear band bifurcation phenomenon was observed only in the AA2219-T6 alloy.

  8. Comprehensive Analysis and Characterization of Linear Antigenic Domains on HN Protein from Genotype VII Newcastle Disease Virus Using Yeast Surface Display System

    PubMed Central

    Li, Tao; Wang, Gaoling; Shi, Bingtian; Liu, Peixin; Si, Wei; Wang, Bin; Jiang, Li; Zhou, Lunjiang; Xiu, Jinsheng; Liu, Henggui

    2015-01-01

    Circulation of genotype VII Newcastle disease virus (NDV) has posed a great threat for the poultry industry worldwide. Antibodies against Hemagglutinin-neuraminidase (HN), a membrane protein of NDV with critical roles in NDV infection, have been reported to provide chickens protection from NDV infection. In this study, we comprehensively analyzed the in vivo antibody responses against the linear antigenic domains of the HN protein from genotype VII NDV using a yeast surface display system. The results revealed four distinct regions of HN, P1 (1-52aa), P2 (53-192aa), P3 (193-302aa) and P4 (303-571aa), respectively, according to their antigenic potency. Analysis by FACS and ELISA assay indicated P2 to be the dominant linear antigenic domain, with the immunogenic potency to protect the majority of chickens from NDV challenge. In contrast, the P1, P3 and P4 domains showed weak antigenicity in vivo and could not protect chickens from NDV challenge. These results provide important insight into the characteristic of humoral immune responses elicited by HN of NDV in vivo. PMID:26121247

  9. Inhibiting CD146 by its Monoclonal Antibody AA98 Improves Radiosensitivity of Cervical Cancer Cells.

    PubMed

    Cheng, Huawen

    2016-09-20

    BACKGROUND Cervical cancer is one of the major causes of cancer death of females worldwide. Radiotherapy is considered effective for cervical cancer treatment, but the low radiosensitivity found in some cases severely affects therapeutic outcomes. This study aimed to reveal the role of CD146, an important adhesion molecule facilitating tumor angiogenesis, in regulating radiosensitivity of cervical cancer cells. MATERIAL AND METHODS CD146 protein expression was compared in normal cells, cervical cancer cells with lower radiosensitivity, and cervical cancer cells with higher sensitivity from cervical squamous cell carcinoma patients. Anti-CD146 monoclonal antibody AA98 was used to inhibit CD146 in human cervical cancer SiHa cells with relatively low radiosensitivity, and then the cell survival and apoptosis changes after radiation were detected by colony formation assay and flow cytometry. RESULTS CD146 protein was significantly up-regulated in cervical cancer cells (P<0.001), especially in cancer cells with lower radiosensitivity. The SiHa cells treated with AA98 showed more obvious inhibition in cell survival (P<0.05) and promotion in cell apoptosis (P<0.01) after radiation, compared to the untreated cells. More dramatic changes in apoptotic factors Caspase 3 and Bcl-XL were also detected in AA98-treated cells. CONCLUSIONS These results indicate that inhibiting CD146 improves the effect of radiation in suppressing SiHa cells. This study shows the potential of CD146 as a target for increasing radiosensitivity of cervical cancer cells, which might allow improvement in treatment outcome in cervical cancer. Further studies are necessary for understanding the detailed mechanism of CD146 in regulating radiosensitivity.

  10. Displaying Now-Understanding: The Finnish Change-of-State Token "aa"

    ERIC Educational Resources Information Center

    Koivisto, Aino

    2015-01-01

    This article discusses the use of the Finnish change-of-state token "aa" that has previously not been identified. The central claim is that even though "aa" indicates a cognitive shift experienced by the speaker, it does not function as a receipt of new information. Instead, the token "aa" indicates that the speaker…

  11. An Analysis of the Rise and Fall of the AA-MAS Policy

    ERIC Educational Resources Information Center

    Lazarus, Sheryl S.; Thurlow, Martha L.; Ysseldyke, James E.; Edwards, Lynn M.

    2015-01-01

    In 2005, to address concerns about students who might fall in the "gap" between the regular assessment and the alternate assessment based on alternate achievement standards (AA-AAS), the U.S. Department of Education announced that states could develop alternate assessments based on modified achievement standards (AA-MAS). This article…

  12. An Existential Approach: An Alternative to the AA Model of Recovery

    ERIC Educational Resources Information Center

    Rogers, Maria A.; Cobia, Debra

    2008-01-01

    Alcoholics Anonymous (AA) is the most widely used organization for the treatment of alcoholism. AA's philosophy has changed how many people view themselves and their substance use. The majority of substance abuse programs in the United States use the 12 steps, either by making them the basis of their treatment program, or by introducing AA to…

  13. Hepatitis C genotype distribution in patient and blood donor samples in South Africa for the period 2008-2012.

    PubMed

    Prabdial-Sing, N; Chirwa, T; Thaver, J; Smuts, H; Vermeulen, M; Suchard, M; Puren, A J

    2016-11-01

    There are limited molecular epidemiological studies of hepatitis C at a national level in South Africa. The introduction of newer treatment modalities for hepatitis C requires knowledge of the genotypes as these may have different prognostic and therapeutic implications. This retrospective study describes genotype distributions of patients attending specialist clinics and a blood donor group studied during the period 2008-2012 in South Africa. Residual samples from diagnostic viral load testing from specialist clinics in South Africa (n=941) and from the South African National Blood Service (n=294) were analysed quantitatively by real-time PCR and genotyped using the Versant line probe assay or sequencing. Genotype 1 was predominant in blood donors (34%), whilst genotype 5a was prevalent in patients (36%). In the blood donor group, genotype 4 was detected for the first time. Genotype 2 was rare in the patient group and not detected in blood donors. Genotype 1 was the predominant genotype in the younger age groups (less than 30 years), whereas genotype 5a was found at higher proportions in the older age groups for both the patient and blood donor groups, comprising more than 60% of genotypes in those older than 50 years. Genotypes 1 and 5 were at highest proportions across all provinces compared to other genotypes. In blood donors, genotype 1 was predominant among Caucasians (43%) and genotype 5a among Blacks (54%). Such information is required for planning the impact on the health sector with regard to newly emerging therapies for hepatitis C and burden of disease. © 2016 John Wiley & Sons Ltd.

  14. Measles virus genotypes circulating in India, 2011-2015.

    PubMed

    Vaidya, Sunil R; Chowdhury, Deepika T

    2017-05-01

    The Government of India is accepted to participate in the measles elimination and rubella control goal 2020, hence genetic characterization of measles viruses (MeV) becomes essential. At National Reference Laboratory (National Institute of Virology, Pune), the throat swabs/urine specimens (n = 380) or PCR products (n = 219) obtained from the suspected measles cases were referred for the molecular testing and subsequently, MeV nucleoprotein (N) gene sequencing/genotyping. In addition, 2,449 suspected measles cases, mainly from the Maharashtra state were referred for the laboratory diagnosis. A detailed study was performed on N gene sequences obtained during last two decades. Indian MeV sequences obtained during 2011-2015 were compared with 1996-2010 sequences and genetic divergence was studied. Circulation of measles genotypes B3 (n = 3), D4 (n = 49), and D8 (n = 351) strains were observed in 19 States and three Union Territories of India. In addition, 64 measles viruses were isolated from 253 throat swab or urine specimens obtained from the suspected measles cases. During 2011-2015, 67.9% (1,663/2,449) suspected measles cases were laboratory confirmed. Molecular studies showed circulation of measles genotype B3 in India along with prominently circulating genotypes D4 and D8 except D7 strains. The genetic diversion within Indian B3, D4, and D8 genotypes was 0.3%, 1.1%, and 2.1%, respectively. The genetic divergence of Indian B3, D4, and D8 measles strains with the WHO reference sequences was 2.5%, 2.6%, and 1.8%, respectively. It is crucial data for national immunization program. More measles/rubella genotyping studies are necessary to track transmission and to support measles elimination and rubella control. J. Med. Virol. 89:753-758, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. AA amyloidosis complicating the hereditary periodic fever syndromes.

    PubMed

    Lane, Thirusha; Loeffler, Jutta M; Rowczenio, Dorota M; Gilbertson, Janet A; Bybee, Alison; Russell, Tonia L; Gillmore, Julian D; Wechalekar, Ashutosh D; Hawkins, Philip N; Lachmann, Helen J

    2013-04-01

    AA amyloidosis is a life-threatening complication of the hereditary periodic fever syndromes (HPFS), which are otherwise often compatible with normal life expectancy. This study was undertaken to determine the characteristics, presentation, natural history, and response to treatment in 46 patients who had been referred for evaluation at the UK National Amyloidosis Centre. Disease activity was monitored by serial measurement of serum amyloid A. Renal function was assessed by measurement of serum creatinine and albumin levels, the estimated glomerular filtration rate, and proteinuria from 24-hour urine collections. The amyloid load was measured by serum amyloid P scintigraphy. Twenty-four patients had familial Mediterranean fever, 12 patients had tumor necrosis factor receptor-associated periodic syndrome, 6 patients had cryopyrin-associated periodic syndromes, and 4 patients had mevalonate kinase deficiency. The median age at onset of HPFS was 5 years; median age at presentation with AA amyloidosis was 38 years. Diagnosis of an HPFS had not been considered prior to presentation with AA amyloidosis in 23 patients (50%). Eleven patients (24%) had end-stage renal failure (ESRF) at presentation; of these, 3 had received transplants prior to referral. A further 13 patients developed ESRF over the followup period, with 10 undergoing renal transplantation. The median time to progression to ESRF from onset of AA amyloidosis was 3.3 years (interquartile range [IQR] 2-8), with a median time to transplant of 4 years (IQR 3-6). Eleven patients (24%) died. The median survival in the entire cohort was 19 years from diagnosis of AA amyloidosis. Of the 37 patients who were treated successfully, or in whom at least partial suppression of the underlying HPFS was achieved, 17 (46%) showed amyloid regression, 14 (38%) showed a stable amyloid load, and 2 (5%) showed increased amyloid deposition over the followup period. AA amyloidosis remains a challenging and serious late complication

  16. Heterogeneous recombination among Hepatitis B virus genotypes.

    PubMed

    Castelhano, Nadine; Araujo, Natalia M; Arenas, Miguel

    2017-10-01

    The rapid evolution of Hepatitis B virus (HBV) through both evolutionary forces, mutation and recombination, allows this virus to generate a large variety of adapted variants at both intra and inter-host levels. It can, for instance, generate drug resistance or the diverse viral genotypes that currently exist in the HBV epidemics. Concerning the latter, it is known that recombination played a major role in the emergence and genetic diversification of novel genotypes. In this regard, the quantification of viral recombination in each genotype can provide relevant information to devise expectations about the evolutionary trends of the epidemic. Here we measured the amount of this evolutionary force by estimating global and local recombination rates in >4700 HBV complete genome sequences corresponding to nine (A to I) HBV genotypes. Counterintuitively, we found that genotype E presents extremely high levels of recombination, followed by genotypes B and C. On the other hand, genotype G presents the lowest level, where recombination is almost negligible. We discuss these findings in the light of known characteristics of these genotypes. Additionally, we present a phylogenetic network to depict the evolutionary history of the studied HBV genotypes. This network clearly classified all genotypes into specific groups and indicated that diverse pairs of genotypes are derived from a common ancestor (i.e., C-I, D-E and, F-H) although still the origin of this virus presented large uncertainty. Altogether we conclude that the amount of observed recombination is heterogeneous among HBV genotypes and that this heterogeneity can influence on the future expansion of the epidemic. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Effect of hereditary haemochromatosis genotypes and iron overload on other trace elements.

    PubMed

    Beckett, Jeffrey M; Ball, Madeleine J

    2013-02-01

    Hereditary haemochromatosis is a common genetic disorder involving dysregulation of iron absorption. There is some evidence to suggest that abnormal iron absorption and metabolism may influence the status of other important trace elements. In this study, the effect of abnormal HFE genotypes and associated iron overload on the status of other trace elements was examined. Dietary data and blood samples were collected from 199 subjects (mean age = 55.4 years; range = 21-81 years). Dietary intakes, serum selenium, copper and zinc concentrations and related antioxidant enzymes (glutathione peroxidase and superoxide dismutase) in subjects with normal HFE genotype (n = 118) were compared to those with abnormal HFE genotype, with both normal iron status (n = 42) and iron overload (n = 39). For most dietary and biochemical variables measured, there were no significant differences between study groups. Red cell GPx was significantly higher in male subjects with normal genotypes and normal iron status compared to those with abnormal genotypes and normal iron status (P = 0.03) or iron overload (P = 0.001). Red cell GPx was also highest in normal women and significantly lower in the abnormal genotype and normal iron group (P = 0.016), but not in the iron overload group (P = 0.078). Although it may not be possible to exclude a small effect between the genotype groups on RBC GPx, overall, haemochromatosis genotypes or iron overload did not appear to have a significant effect on selenium, copper or zinc status.

  18. Similar predictions of etravirine sensitivity regardless of genotypic testing method used: comparison of available scoring systems.

    PubMed

    Vingerhoets, Johan; Nijs, Steven; Tambuyzer, Lotke; Hoogstoel, Annemie; Anderson, David; Picchio, Gaston

    2012-01-01

    The aims of this study were to compare various genotypic scoring systems commonly used to predict virological outcome to etravirine, and examine their concordance with etravirine phenotypic susceptibility. Six etravirine genotypic scoring systems were assessed: Tibotec 2010 (based on 20 mutations; TBT 20), Monogram, Stanford HIVdb, ANRS, Rega (based on 37, 30, 27 and 49 mutations, respectively) and virco(®)TYPE HIV-1 (predicted fold change based on genotype). Samples from treatment-experienced patients who participated in the DUET trials and with both genotypic and phenotypic data (n=403) were assessed using each scoring system. Results were retrospectively correlated with virological response in DUET. κ coefficients were calculated to estimate the degree of correlation between the different scoring systems. Correlation between the five scoring systems and the TBT 20 system was approximately 90%. Virological response by etravirine susceptibility was comparable regardless of which scoring system was utilized, with 70-74% of DUET patients determined as susceptible to etravirine by the different scoring systems achieving plasma viral load <50 HIV-1 RNA copies/ml. In samples classed as phenotypically susceptible to etravirine (fold change in 50% effective concentration ≤3), correlations with genotypic score were consistently high across scoring systems (≥70%). In general, the etravirine genotypic scoring systems produced similar results, and genotype-phenotype concordance was high. As such, phenotypic interpretations, and in their absence all genotypic scoring systems investigated, may be used to reliably predict the activity of etravirine.

  19. 40 CFR Table Aa-2 to Subpart Aa of... - Kraft Lime Kiln and Calciner Emissions Factors for Fossil Fuel-Based CH4 and N2O

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Kraft Lime Kiln and Calciner Emissions Factors for Fossil Fuel-Based CH4 and N2O AA Table AA-2 to Subpart AA of Part 98 Protection of Environment... and Calciner Emissions Factors for Fossil Fuel-Based CH4 and N2O Fuel Fossil fuel-based emissions...

  20. 40 CFR Table Aa-2 to Subpart Aa of... - Kraft Lime Kiln and Calciner Emissions Factors for Fossil Fuel-Based CH4 and N2O

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 21 2011-07-01 2011-07-01 false Kraft Lime Kiln and Calciner Emissions Factors for Fossil Fuel-Based CH4 and N2O AA Table AA-2 to Subpart AA of Part 98 Protection of Environment... and Calciner Emissions Factors for Fossil Fuel-Based CH4 and N2O Fuel Fossil fuel-based emissions...

  1. 40 CFR Table Aa-2 to Subpart Aa of... - Kraft Lime Kiln and Calciner Emissions Factors for Fossil Fuel-Based CH4 and N2O

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 22 2013-07-01 2013-07-01 false Kraft Lime Kiln and Calciner Emissions Factors for Fossil Fuel-Based CH4 and N2O AA Table AA-2 to Subpart AA of Part 98 Protection of Environment... and Calciner Emissions Factors for Fossil Fuel-Based CH4 and N2O Fuel Fossil fuel-based emissions...

  2. Hepatitis C virus genotypes in Myanmar.

    PubMed

    Win, Nan Nwe; Kanda, Tatsuo; Nakamoto, Shingo; Yokosuka, Osamu; Shirasawa, Hiroshi

    2016-07-21

    Myanmar is adjacent to India, Bangladesh, Thailand, Laos and China. In Myanmar, the prevalence of hepatitis C virus (HCV) infection is 2%, and HCV infection accounts for 25% of hepatocellular carcinoma. In this study, we reviewed the prevalence of HCV genotypes in Myanmar. HCV genotypes 1, 3 and 6 were observed in volunteer blood donors in and around the Myanmar city of Yangon. Although there are several reports of HCV genotype 6 and its variants in Myanmar, the distribution of the HCV genotypes has not been well documented in areas other than Yangon. Previous studies showed that treatment with peginterferon and a weight-based dose of ribavirin for 24 or 48 wk could lead to an 80%-100% sustained virological response (SVR) rates in Myanmar. Current interferon-free treatments could lead to higher SVR rates (90%-95%) in patients infected with almost all HCV genotypes other than HCV genotype 3. In an era of heavy reliance on direct-acting antivirals against HCV, there is an increasing need to measure HCV genotypes, and this need will also increase specifically in Myanmar. Current available information of HCV genotypes were mostly from Yangon and other countries than Myanmar. The prevalence of HCV genotypes in Myanmar should be determined.

  3. Hepatitis C virus genotypes in Myanmar

    PubMed Central

    Win, Nan Nwe; Kanda, Tatsuo; Nakamoto, Shingo; Yokosuka, Osamu; Shirasawa, Hiroshi

    2016-01-01

    Myanmar is adjacent to India, Bangladesh, Thailand, Laos and China. In Myanmar, the prevalence of hepatitis C virus (HCV) infection is 2%, and HCV infection accounts for 25% of hepatocellular carcinoma. In this study, we reviewed the prevalence of HCV genotypes in Myanmar. HCV genotypes 1, 3 and 6 were observed in volunteer blood donors in and around the Myanmar city of Yangon. Although there are several reports of HCV genotype 6 and its variants in Myanmar, the distribution of the HCV genotypes has not been well documented in areas other than Yangon. Previous studies showed that treatment with peginterferon and a weight-based dose of ribavirin for 24 or 48 wk could lead to an 80%-100% sustained virological response (SVR) rates in Myanmar. Current interferon-free treatments could lead to higher SVR rates (90%-95%) in patients infected with almost all HCV genotypes other than HCV genotype 3. In an era of heavy reliance on direct-acting antivirals against HCV, there is an increasing need to measure HCV genotypes, and this need will also increase specifically in Myanmar. Current available information of HCV genotypes were mostly from Yangon and other countries than Myanmar. The prevalence of HCV genotypes in Myanmar should be determined. PMID:27468202

  4. Global perspective on the natural history of chronic hepatitis B: role of hepatitis B virus genotypes A to J.

    PubMed

    Liu, Chun-Jen; Kao, Jia-Horng

    2013-05-01

    Clinical outcomes of chronic hepatitis B virus (HBV) infection vary widely. In addition to host factors, several viral factors including HBV genotype, viral load, specific viral mutations and quantitative HBsAg levels, have been associated with disease outcomes. Among viral factors, HBV genotype correlates with not only the clinical outcomes, but also with the response to interferon treatment. Currently, 10 HBV genotypes have been identified. Compared with genotype A and B cases, patients with genotypes C and D have lower rates and usually delayed onset of spontaneous HBeAg seroconversion. HBV-genotype C has a higher frequency of basal core promoter (BCP) A1762T/G1764A mutation and preS deletion, and a higher viral load than genotype B. Similarly, genotype D has a higher prevalence of BCP A1762T/G1764A mutation than genotype A. These observations suggest pathogenic differences between HBV genotypes. Genotyping of HBV can help practicing physicians identify chronic hepatitis B patients at risk of disease progression. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  5. DEVELOPMENTAL AND WITHDRAWAL EFFECTS OF ADOLESCENT AAS EXPOSURE ON THE GLUTAMATERGIC SYSTEM IN HAMSTERS

    PubMed Central

    Carrillo, Maria; Ricci, Lesley A.; Melloni, Richard H.

    2011-01-01

    In the Syrian hamster (Mesocricetus auratus) glutamate activity has been implicated in the modulation of adolescent anabolic-androgenic steroid (AAS)-induced aggression. The current study investigated the time course of adolescent AAS-induced neurodevelopmental and withdrawal effects on the glutamatergic system and examined whether these changes paralleled those of adolescent AAS-induced aggression. Glutamate activity in brain areas comprising the aggression circuit in hamsters and aggression were examined following 1, 2, 3 and 4 weeks of AAS treatment or 1, 2, 3 and 4 weeks following the cessation of AAS exposure. In these studies glutamate activity was examined using vesicular glutamate transporter 2 (VGLUT2). The onset of aggression was observed following 2 weeks exposure to AAS and continued to increase showing maximal aggression levels after 4 weeks of AAS treatment. This aggressive phenotype was detected after 2 weeks of withdrawal from AAS. The time-course of AAS-induced changes in latero anterior hypothalamus (LAH)-VGLUT2 closely paralleled increases in aggression. Increases in LAH-VGLUT2 were first detected in animals exposed to AAS for 2 weeks and were maintained up to 3 weeks following the cessation of AAS treatment. AAS treatment also produced developmental and long-term alterations in VGLUT2 expression within other aggression areas. However, AAS-induced changes in glutamate activity within these regions did not coincide with changes in aggression. Together, these data indicate that adolescent AAS treatment leads to alterations in the glutamatergic system in brain areas implicated in aggression control, yet only alterations in LAH-glutamate parallel the time course of AAS-induced changes in the aggressive phenotype. PMID:21500881

  6. Amyloid fibril protein AA in Papua New Guinean amyloidosis.

    PubMed Central

    Anders, R F; Price, M A; Wilkey, I S; Husby, G; Takitaki, F; Natvig, J B; McAdam, K P

    1976-01-01

    In this study of protein composition of amyloid fibrils isolated from eight patients representative of the spectrum of amyloidosis found in Papua New Guinea has been investigated. All fibril preparations, including three from patients with amyloidosis secondary to lepromatous leprosy and one from an unusual juvenile case of primary amyloidosis, contained the non-immunogobulin amyloid protein, protein AA. However, only 44% of thirty-six amyloid patients had detectable levels of the protein AA-related serum component, protein SAA. Alkali-degraded material from each of the fibril preparations failed to react in double immunodiffusion test with antiserum to the amyloid-related light chain VgammaV, but evidence was found for this immunoglobulin light chain-specificity in the serum of one patient. Images FIG. 1 PMID:820500

  7. Amyloid fibril protein AA in Papua New Guinean amyloidosis.

    PubMed

    Anders, R F; Price, M A; Wilkey, I S; Husby, G; Takitaki, F; Natvig, J B; McAdam, K P

    1976-04-01

    In this study of protein composition of amyloid fibrils isolated from eight patients representative of the spectrum of amyloidosis found in Papua New Guinea has been investigated. All fibril preparations, including three from patients with amyloidosis secondary to lepromatous leprosy and one from an unusual juvenile case of primary amyloidosis, contained the non-immunogobulin amyloid protein, protein AA. However, only 44% of thirty-six amyloid patients had detectable levels of the protein AA-related serum component, protein SAA. Alkali-degraded material from each of the fibril preparations failed to react in double immunodiffusion test with antiserum to the amyloid-related light chain VgammaV, but evidence was found for this immunoglobulin light chain-specificity in the serum of one patient.

  8. Characterization of amyloid in equine recurrent uveitis as AA amyloid.

    PubMed

    Ostevik, L; de Souza, G A; Wien, T N; Gunnes, G; Sørby, R

    2014-01-01

    Two horses with chronic uveitis and histological lesions consistent with equine recurrent uveitis (ERU) were examined. Microscopical findings in the ciliary body included deposits of amyloid lining the non-pigmented epithelium, intracytoplasmic, rod-shaped, eosinophilic inclusions and intraepithelial infiltration of T lymphocytes. Ultrastructural examination of the ciliary body of one horse confirmed the presence of abundant extracellular deposits of non-branching fibrils (9-11 nm in diameter) consistent with amyloid. Immunohistochemistry revealed strong positive labelling for AA amyloid and mass spectrometry showed the amyloid to consist primarily of serum amyloid A1 in both cases. The findings suggest that localized, intraocular AA amyloidosis may occur in horses with ERU. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Evaluation of the Abbott Real Time HCV genotype II assay for Hepatitis C virus genotyping.

    PubMed

    Sariguzel, Fatma Mutlu; Berk, Elife; Gokahmetoglu, Selma; Ercal, Baris Derya; Celik, Ilhami

    2015-01-01

    The determination of HCV genotypes and subtypes is very important for the selection of antiviral therapy and epidemiological studies. The aim of this study was to evaluate the performance of Abbott Real Time HCV Genotype II assay in HCV genotyping of HCV infected patients in Kayseri, Turkey. One hundred patients with chronic hepatitis C admitted to our hospital were evaluated between June 2012 and December 2012, HCV RNA levels were determined by the COBAS® AmpliPrep/COBAS® TaqMan® 48 HCV test. HCV genotyping was investigated by the Abbott Real Time HCV Genotype II assay. With the exception of genotype 1, subtypes of HCV genotypes could not be determined by Abbott assay. Sequencing analysis was used as the reference method. Genotypes 1, 2, 3 and 4 were observed in 70, 4, 2 and 24 of the 100 patients, respectively, by two methods. The concordance between the two systems to determine HCV major genotypes was 100%. Of 70 patients with genotype 1, 66 showed infection with subtype 1b and 4 with subtype 1a by Abbott Real Time HCV Genotype II assay. Using sequence analysis, 61 showed infection with subtype 1b and 9 with subtype 1a. In determining of HCV genotype 1 subtypes, the difference between the two methods was not statistically significant (P>0.05). HCV genotype 4 and 3 samples were found to be subtype 4d and 3a, respectively, by sequence analysis. There were four patients with genotype 2. Sequence analysis revealed that two of these patients had type 2a and the other two had type 2b. The Abbott Real Time HCV Genotype II assay yielded results consistent with sequence analysis. However, further optimization of the Abbott Real Time HCV Genotype II assay for subtype identification of HCV is required.

  10. Kidney biopsy in AA amyloidosis: impact of histopathology on prognosis.

    PubMed

    Kendi Celebi, Zeynep; Kiremitci, Saba; Ozturk, Bengi; Akturk, Serkan; Erdogmus, Siyar; Duman, Neval; Ates, Kenan; Erturk, Sehsuvar; Nergizoglu, Gokhan; Kutlay, Sim; Sengul, Sule; Ensari, Arzu; Keven, Kenan

    2017-09-01

    In AA amyloidosis, while kidney biopsy is widely considered for diagnosis by clinicians, there is no evidence that the detailed investigation of renal histopathology can be utilized for the prognosis and clinical outcomes. In this study, we aimed to obtain whether histopathologic findings in kidney biopsy of AA amyloidosis might have prognostic and clinical value. This is a retrospective cohort study that included 38 patients who were diagnosed with AA amyloidosis by kidney biopsy between 2005 and 2013.The kidney biopsy specimens of patients were evaluated and graded for several characteristics of histopathological lesions and their relationship with renal outcomes. Segmental amyloid deposition in the kidney biopsy was seen in 29%, global amyloid deposition in 71, diffuse involvement of glomeruli in 84.2%, focal involvement in 7%, glomerular enlargement in 53%, tubular atrophy in 75% and interstitial fibrosis in 78% of patients. Histopathologically, glomerular enlargement, interstitial fibrosis, tubular atrophy, interstitial inflammation and global amyloid deposition were significantly associated with lower estimated glomerular filtration rate (eGFR) (p = .02, p < .001, p = .001, p = .009, p = .002, respectively) in univariate analysis. In multivariate analysis, tubular atrophy was the only predictor of eGFR (p = .019 B = -20.573). In the follow-up at an average of 27 months, 18 patients developed end-stage renal disease (ESRD). Among them, global amyloid deposition was the only risk factor for the development of ESRD (p = .01, OR = 18.750, %95 CI= 2.021-173.942). This is the first study showing that the histopathological findings in kidney biopsy of AA amyloidosis might have a prognostic and clinical value for renal outcomes.

  11. My First AAS Meeting: Bloomington and ANN Arbor, June 1950

    NASA Astrophysics Data System (ADS)

    Osterbrock, D. E.

    1999-05-01

    I attended my first AAS meeting at the end of my first year as a graduate student at Yerkes Observatory, in the summer of 1950. Yerkes was the home base of the astronomy faculty, staff, and graduate students of the University of Chicago, and a large contingent went to this meeting at nearby Indiana University, and then on to the symposium immediately following it at the University of Michigan. In this paper I will describe these meetings so as to bring out the differences between this typical AAS meeting nearly half a century ago, and one today, as well as their similarities. Briefly, the main differences resulted from the fact that astronomy was much smaller then, and less well funded. Membership in the AAS, attendance at its 1950 meeting, and the number of papers presented were all smaller by factors of roughly ten than now. Most astronomers paid their own expenses to meetings, or were only reimbursed for part of them by their universities. Hence most meetings were held on university campuses. There were no registration fees, and the receptions, picnics, and outings were provided by the ``host" institution, which treated the visiting astronomers as its guests. The AAS had no paid staff. There were no parallel sessions nor poster papers. Members submitted only titles for their papers, most of them on stars; fewer on planets, asteroids and meteors; and fewer still on interstellar matter, gaseous nebulae, galaxies, or cosmology. Research papers were the most important part of the meeting, but ``teachers' sessions," the equivalent of the education sessions of today, were part of the program too. Seeing old friends and meeting new ones were an important, unscheduled part of the meeting. This paper will provide a narrative of these meetings, illustrated by photographs of groups, scenes, and astronomers.

  12. Microstructure Stability During Creep of Friction Stir Welded AA2024-T3 Alloy

    NASA Astrophysics Data System (ADS)

    Regev, Michael; Rashkovsky, Tal; Cabibbo, Marcello; Spigarelli, Stefano

    2018-01-01

    The poor weldability of the AA2024 aluminum alloy limits its use in industrial applications. Because friction stir welding (FSW) is a non-fusion welding process, it seems to be a promising solution for welding this alloy. In the current study, FSW was applied to butt weld AA2024-T3 aluminum alloy plates. Creep tests were conducted at 250 and at 315 °C on both the parent material and the friction stir welded specimens. The microstructures of the welded and non-welded AA2024-T3 specimens before and after the creep tests were studied and compared. A comprehensive transmission electron microscopy study together with a high-resolution scanning electron microscopy study and energy-dispersive x-ray spectroscopy analysis was conducted to investigate the microstructure stability. The parent material seems to contain two kinds of Cu-rich precipitates—coarse precipitates of a few microns each and uniformly dispersed fine nanosized precipitates. Unlike the parent material, the crept specimens were found to contain the two kinds of precipitates mentioned above together with platelet-like precipitates. In addition, extensive decoration of the grain boundaries with precipitates was clearly observed in the crept specimens. Controlled aging experiments for up to 280 h at the relevant temperatures were conducted on both the parent material and the welded specimens in order to isolate the contribution of exposure to high temperatures to the microstructure changes. TEM study showed the development of dislocation networks into a cellular dislocation structure in the case of the parent metal. Changes in the dislocation structure as a function of the creep strain and the FSW process were recorded. A detailed creep data analysis was conducted, taking into account the instability of the microstructure.

  13. Insights into the Structure of the Vip3Aa Insecticidal Protein by Protease Digestion Analysis

    PubMed Central

    Bel, Yolanda; Banyuls, Núria; Chakroun, Maissa; Escriche, Baltasar; Ferré, Juan

    2017-01-01

    Vip3 proteins are secretable proteins from Bacillus thuringiensis whose mode of action is still poorly understood. In this study, the activation process for Vip3 proteins was closely examined in order to better understand the Vip3Aa protein stability and to shed light on its structure. The Vip3Aa protoxin (of 89 kDa) was treated with trypsin at concentrations from 1:100 to 120:100 (trypsin:Vip3A, w:w). If the action of trypsin was not properly neutralized, the results of SDS-PAGE analysis (as well as those with Agrotis ipsilon midgut juice) equivocally indicated that the protoxin could be completely processed. However, when the proteolytic reaction was efficiently stopped, it was revealed that the protoxin was only cleaved at a primary cleavage site, regardless of the amount of trypsin used. The 66 kDa and the 19 kDa peptides generated by the proteases co-eluted after gel filtration chromatography, indicating that they remain together after cleavage. The 66 kDa fragment was found to be extremely resistant to proteases. The trypsin treatment of the protoxin in the presence of SDS revealed the presence of secondary cleavage sites at S-509, and presumably at T-466 and V-372, rendering C-terminal fragments of approximately 29, 32, and 42 kDa, respectively. The fact that the predicted secondary structure of the Vip3Aa protein shows a cluster of beta sheets in the C-terminal region of the protein might be the reason behind the higher stability to proteases compared to the rest of the protein, which is mainly composed of alpha helices. PMID:28387713

  14. GALEX Distributes Local Galactic Treasures at AAS

    NASA Technical Reports Server (NTRS)

    2006-01-01

    [figure removed for brevity, see original site] GALEX Poster

    From sparkling blue rings to dazzling golden disks, Galaxy Evolution Explorer (Galex) scientists are handing out a collection of their finest galactic treasures at the January 2006 American Astronomical Society meeting in Washington, D.C.

    Mined from the mission's Survey of Nearby Galaxies data, these cosmic gems were collected with the telescope's sensitive ultraviolet instruments. The gallery of galaxies has been made into a poster for meeting attendees visiting the mission's booth. Organized from far-ultraviolet to near-ultraviolet bright galaxies, this poster encapsulates the heart of the mission to study how galaxies and star formation rates have changed over the past 10 billion years.

    Events in space take millions or billions of years to unfold, which means that astronomers can't watch individual galaxies and stars age over time. Luckily, because the physics of light travel dictates that the farther away an object is from Earth, the longer it takes for its light to travel to us, the universe can be thought of as a time machine. By building telescopes sensitive enough to capture objects that are 10 billion light-years away, astronomers can essentially see an object the way it looked 10 billion years ago. Galex astronomers are using this phenomenon to their advantage by taking snapshots of different galaxies at various distances in space. By comparing portraits of numerous objects at various times in the universe's history, the team can begin to piece together the life cycle of stars and galaxies.

    For the poster, Galex scientists organized 196 different nearby galaxies in bins of increasing ultraviolet color. By placing the various snapshots side by side, astronomers can see how galaxies age differently. When viewed in ultraviolet, active star-forming regions in galaxies can be seen as glittering blue structures, while a soft, golden glow indicates the presence of older stars

  15. CETP genotypes and HDL-cholesterol phenotypes in the HERITAGE Family Study.

    PubMed

    Spielmann, Nadine; Leon, Arthur S; Rao, D C; Rice, Treva; Skinner, James S; Bouchard, Claude; Rankinen, Tuomo

    2007-09-19

    Associations between cholesteryl ester transfer protein (CETP) polymorphisms and high-density lipoprotein cholesterol (HDL-c) levels before and after 20 wk of endurance training were investigated in the HERITAGE Family Study. Plasma HDL-c, HDL(2)-c, HDL(3)-c, and apolipoprotein (apo)A1 levels were measured, and 13 CETP single nucleotide polymorphisms (SNPs) were genotyped in 265 blacks and 486 whites. Three haplotypes defined by SNPs at the -1337, -971, and -629 sites were strongly associated with baseline HDL-c levels in whites. Both C-1337T and C-629A were associated with baseline HDL-c (P < 0.001) and apoA1 (P < 0.01) when tested separately. However, only C-629A remained significant in a combined model. G-971A was not associated with HDL phenotypes, but showed significant interactions with C-629A (P = 0.002) on baseline traits. Genotype-by-sex interactions were observed at the -629 locus for HDL(3)-c (P = 0.004) and apoA1 (P = 0.02) training responses in whites. In women, the -629 A/A homozygotes showed greater increases in HDL(3)-c (P = 0.02) and apoA1 (P = 0.02) levels than the other genotypes. Finally, apolipoprotein E (APOE) genotype and the CETP C-629A locus contributed independently and in additive fashion to the HDL traits, explaining 6.0-8.8% of the variance. The CETP -1337T and -629A alleles are associated with higher baseline HDL-c and apoA1 levels. The beneficial effects of endurance training on plasma HDL(3)-c and apoA1 levels are evident in white women homozygous for the -629A allele. The CETP and APOE genotypes account for up to 9% of the variance in HDL-c phenotypes in the HERITAGE Family Study.

  16. Four-point-bend fatigue of AA 2026 aluminum alloys

    NASA Astrophysics Data System (ADS)

    Li, J. X.; Zhai, T.; Garratt, M. D.; Bray, G. H.

    2005-09-01

    High-cycle fatigue tests were carried out on a newly developed high-strength AA 2026 Al alloy, which was in the form of extrusion bars with square and rectangular cross sections, using a self-aligning four-point-bend rig at room temperature, 15 Hz, and R = 0.1, in lab air. The fatigue strength of the square and rectangular bars was measured to be 85 and 90 pct of their yield strength, respectively, more than twice that of the predecessor to the 2026 alloy (the AA 2024 Al alloy). Fatigue cracks were found to be always initiated at large Θ' (Al7Cu2(Fe,Mn)) particles and to propagate predominantly in a crystallographic mode in the AA 2026 alloy. The fatigue fractographies of the square and rectangular extrusion bars were found to be markedly different, due to their different grain structures (fibril and layered, respectively). Fracture steps on the crack face were found in both of these extrusion bars. Since the 2026 alloy was purer in terms of Fe and Si content, it contained much less coarse particles than in a 2024 alloy. This partially accounted for the superior fatigue strength of the 2026 alloy.

  17. The trajectory and atmospheric impact of asteroid 2014 AA

    NASA Astrophysics Data System (ADS)

    Farnocchia, Davide; Chesley, Steven R.; Brown, Peter G.; Chodas, Paul W.

    2016-08-01

    Near-Earth asteroid 2014 AA entered the Earth's atmosphere on 2014 January 2, only 21 h after being discovered by the Catalina Sky Survey. In this paper we compute the trajectory of 2014 AA by combining the available optical astrometry, seven ground-based observations over 69 min, and the International Monitoring System detection of the atmospheric impact infrasonic airwaves in a least-squares orbit estimation filter. The combination of these two sources of observations results in a tremendous improvement in the orbit uncertainties. The impact time is 3:05 UT with a 1σ uncertainty of 6 min, while the impact location corresponds to a west longitude of 44.2° and a latitude of 13.1° with a 1σ uncertainty of 140 km. The minimum impact energy estimated from the infrasound data and the impact velocity result in an estimated minimum mass of 22.6 t. By propagating the trajectory of 2014 AA backwards we find that the only window for finding precovery observations is for the three days before its discovery.

  18. Characterizing the Constitutive Properties of AA7075 for Hot Forming

    NASA Astrophysics Data System (ADS)

    Omer, K.; Kim, S.; Butcher, C.; Worswick, M.

    2017-09-01

    The work presented herein investigates the constitutive properties of AA7075 as it undergoes a hot stamping/die quenching process. Tensile specimens were solutionized inside a heated furnace set to 470°C. Once solutionized, the samples were quenched to an intermediate temperature using a vortex air chiller at a minimum rate of 52°C/s. Tensile tests were conducted at steady state temperatures of 470, 400, 300, 200, 115 and 25°C. This solutionizing and subsequent quenching process replicated the temperature cycle and quench rates representative of a die quenching operation. The results of the tensile test were analyzed with digital imaging correlation using an area reduction approach. The area reduction approach approximated the cross-sectional area of the tensile specimen as it necked. The approach allowed for the true stress-strain response to be calculated well past the initial necking point. The resulting true stress-strain curves showed that the AA7075 samples experienced almost no hardening at 470°C. As steady state temperature decreased, the rate of hardening as well as overall material strength increased. The true stress strain curves were fit to a modified version of the extended Voce constitutive model. The resulting fits can be used in a finite element model to predict the behaviour of an AA7075 blank during a die quenching operation.

  19. Long-term biases in geomagnetic K and aa indices

    USGS Publications Warehouse

    Love, J.J.

    2011-01-01

    Analysis is made of the geomagnetic-activity aa index and its source K-index data from groups of ground-based observatories in Britain, and Australia, 1868.0-2009.0, solar cycles 11-23. The K data show persistent biases, especially for high (low) K-activity levels at British (Australian) observatories. From examination of multiple subsets of the K data we infer that the biases are not predominantly the result of changes in observatory location, localized induced magnetotelluric currents, changes in magnetometer technology, or the modernization of K-value estimation methods. Instead, the biases appear to be artifacts of the latitude-dependent scaling used to assign K values to particular local levels of geomagnetic activity. The biases are not effectively removed by weighting factors used to estimate aa. We show that long-term averages of the aa index, such as annual averages, are dominated by medium-level geomagnetic activity levels having K values of 3 and 4. ?? 2011 Author(s).

  20. Comparison of Lipoprotein Electrophoresis and Apolipoprotein E Genotyping in Investigating Dysbetalipoproteinemia.

    PubMed

    Ahmed, Farhan; El-Kadiki, Alia; Gibbons, Stephen

    2017-06-01

    Dysbetalipoproteinemia is often associated with apolipoprotein E2E2 homozygosity; however, lipoprotein electrophoresis may also be used to assist in the diagnosis. The aim of this study was to compare apolipoprotein E (apo E) genotyping and lipoprotein electrophoresis in investigating dysbetalipoproteinemia. Data were collected over a three-year period from a lipid clinic in a tertiary referral centre and reviewed for apo E genotyping and lipoprotein electrophoresis. Sixty-two patients had both apo E genotyping and lipoprotein electrophoresis. Of these, 16 patients showed broad beta band on electrophoresis. However, only 3 of them had apo E2E2 homozygosity on genotyping. Lipoprotein electrophoresis and apo E genotyping results showed poor concordance. This was primarily due to visual interpretation error of lipoprotein electrophoresis which may over diagnose dysbetalipoproteinemia.

  1. Genotype imputation efficiency in Nelore Cattle

    USDA-ARS?s Scientific Manuscript database

    Genotype imputation efficiency in Nelore cattle was evaluated in different scenarios of lower density (LD) chips, imputation methods and sets of animals to have their genotypes imputed. Twelve commercial and virtual custom LD chips with densities varying from 7K to 75K SNPs were tested. Customized L...

  2. Effects of CD36 Genotype on Oral Perception of Oleic Acid Supplemented Safflower Oil Emulsions in Two Ethnic Groups: A Preliminary Study.

    PubMed

    Burgess, Brenda; Melis, Melania; Scoular, Katelyn; Driver, Michael; Schaich, Karen M; Keller, Kathleen L; Tomassini Barbarossa, Iole; Tepper, Beverly J

    2018-05-01

    Previous studies demonstrate humans can detect fatty acids via specialized sensors on the tongue, such as the CD36 receptor. Genetic variation at the common single nucleotide polymorphism rs1761667 of CD36 has been shown to differentially impact the perception of fatty acids, but comparative data among different ethnic groups are lacking. In a small cohort of Caucasian and East Asian young adults, we investigated if: (1) participants could detect oleic acid (C18:1) added to safflower oil emulsions at a constant ratio of 3% (w/v); (2) supplementation of oleic acid to safflower oil emulsions enhanced perception of fattiness and creaminess; and (3) variation at rs1761667 influenced oleic acid detection and fat taste perception. In a 3-alternate forced choice test, 62% of participants detected 2.9 ± 0.7 mM oleic acid (or 0.08% w/v) in a 2.8% safflower oil emulsion. Supplementation of oleic acid did not enhance fattiness and creaminess perception for the cohort as a whole, though East Asians carrying the GG genotype perceived more overall fattiness and creaminess than their AA genotype counterparts (P < 0.001). No differences were observed for the Caucasians. These preliminary findings indicate that free oleic acid can be detected in an oil-in-water emulsion at concentrations found in commercial oils, but it does not increase fattiness or creaminess perception. Additionally, variation at rs1761667 may have ethnic-specific effects on fat taste perception. © 2018 The Authors Journal of Food Science published by Wiley Periodicals, Inc. on behalf of Institute of Food Technologists.

  3. Deletion Genotypes Reduce Occlusion Body Potency but Increase Occlusion Body Production in a Colombian Spodoptera frugiperda Nucleopolyhedrovirus Population

    PubMed Central

    Barrera, Gloria; Williams, Trevor; Villamizar, Laura; Caballero, Primitivo; Simón, Oihane

    2013-01-01

    A Colombian field isolate (SfCOL-wt) of Spodoptera frugiperda multiple nucleopolyhedrovirus (SfMNPV) is a mixture of different genotypes. To evaluate the insecticidal properties of the different genotypic variants, 83 plaque purified virus were characterized. Ten distinct genotypes were identified (named A through J). SfCOL-A was the most prevalent (71±2%; mean ± SE) showing a PstI restriction profile indistinguishable to that of SfCOL-wt. The remaining nine genotypes presented genomic deletions of 3.8 - 21.8 Kb located mainly between nucleotides 11,436 and 33,883 in the reference genome SfMNPV-B, affecting the region between open reading frames (ORFs) sf20 and sf33. The insecticidal activity of each genotype from SfCOL-wt and several mixtures of genotypes was compared to that of SfCOL-wt. The potency of SfCOL-A occlusion bodies (OBs) was 4.4-fold higher than SfCOL-wt OBs, whereas the speed of kill of SfCOL-A was similar to that of SfCOL-wt. Deletion genotype OBs were similarly or less potent than SfCOL-wt but six deletion genotypes were faster killing than SfCOL-wt. The potency of genotype mixtures co-occluded within OBs were consistently reduced in two-genotype mixtures involving equal proportions of SfCOL-A and one of three deletion genotypes (SfCOL-C, -D or -F). Speed of kill and OB production were improved only when the certain genotype mixtures were co-occluded, although OB production was higher in the SfCOL-wt isolate than in any of the component genotypes, or mixtures thereof. Deleted genotypes reduced OB potency but increased OB production of the SfCOL-wt population, which is structured to maximize the production of OBs in each infected host. PMID:24116220

  4. Geographic distribution and characteristics of genotype A hepatitis B virus infection in acute and chronic hepatitis B patients in Japan.

    PubMed

    Ito, Kiyoaki; Yotsuyanagi, Hiroshi; Sugiyama, Masaya; Yatsuhashi, Hiroshi; Karino, Yoshiyasu; Takikawa, Yasuhiro; Saito, Takafumi; Arase, Yasuji; Imazeki, Fumio; Kurosaki, Masayuki; Umemura, Takeji; Ichida, Takafumi; Toyoda, Hidenori; Yoneda, Masashi; Tanaka, Yasuhito; Mita, Eiji; Yamamoto, Kazuhide; Michitaka, Kojiro; Maeshiro, Tatsuji; Tanuma, Junko; Korenaga, Masaaki; Murata, Kazumoto; Masaki, Naohiko; Koike, Kazuhiko; Mizokami, Masashi

    2016-01-01

    The prevalence of sexually transmitted acute infections of the genotype A hepatitis B virus (HBV) has been increasing in Japan. Genotype A HBV is associated with an increased risk of HBV progression to chronic infection after acute hepatitis B (AHB) in adults. A nationwide survey was conducted to evaluate the geographic distribution, clinical, and virologic characteristics of genotype A AHB and chronic hepatitis B (CHB) in Japan. Five hundred seventy AHB patients were recruited between 2005 and 2010, and 3682 CHB patients were recruited between 2010 and 2011. HBV genotypes were determined for 552 and 3619 AHB and CHB patients, respectively. Clinical characteristics were compared among different genotypes in AHB and CHB patients. Genomic characteristics of HBV genotype A were examined by molecular evolutionary analysis. Hepatitis B virus genotype A was the predominant genotype for AHB between 2005 and 2010. Phylogenetic analysis showed that all strains in the AHB patients with genotype A were classified into subtype Ae. Among CHB patients, the occurrence of genotype A was 4.1%, and genotype A was spreading in young adults. In genotype A CHB patients, early stage liver diseases were predominant, although liver diseases progressed to cirrhosis or hepatocellular carcinoma in some patients. The distribution of HBV genotypes is quite different between AHB and CHB in Japanese patients. Genotype A infection is spreading in young adults of Japanese CHB patients. Sequences derived from Japanese AHB patients were identical to or closely resembled the sequences derived from other Japanese AHB patients. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  5. Pneumocystis jirovecii multilocus genotyping profiles in patients from Portugal and Spain.

    PubMed

    Esteves, F; Montes-Cano, M A; de la Horra, C; Costa, M C; Calderón, E J; Antunes, F; Matos, O

    2008-04-01

    Pneumonia caused by the opportunistic organism Pneumocystis jirovecii is a clinically important infection affecting AIDS and other immunocompromised patients. The present study aimed to compare and characterise the frequency pattern of DNA sequences from the P. jirovecii mitochondrial large-subunit rRNA (mtLSU rRNA) gene, the dihydropteroate synthase (DHPS) gene and the internal transcribed spacer (ITS) regions of the nuclear rRNA operon in specimens from Lisbon (Portugal) and Seville (Spain). Total DNA was extracted and used for specific molecular sequence analysis of the three loci. In both populations, mtLSU rRNA gene analysis revealed an overall prevalence of genotype 1. In the Portuguese population, genotype 2 was the second most common, followed by genotype 3. Inversely, in the Spanish population, genotype 3 was the second most common, followed by genotype 2. The DHPS wild-type sequence was the genotype observed most frequently in both populations, and the DHPS genotype frequency pattern was identical to distribution patterns revealed in other European studies. ITS types showed a significant diversity in both populations because of the high sequence variability in these genomic regions. The most prevalent ITS type in the Portuguese population was Eg, followed by Cg. In contrast to other European studies, Bi was the most common ITS type in the Spanish samples, followed by Eg. A statistically significant association between mtLSU rRNA genotype 1 and ITS type Eg was revealed.

  6. Phylogeny and evolution of Newcastle disease virus genotypes isolated in Asia during 2008-2011.

    PubMed

    Ebrahimi, Mohammad Majid; Shahsavandi, Shahla; Moazenijula, Gholamreza; Shamsara, Mahdi

    2012-08-01

    The full-length fusion (F) genes of 51 Newcastle disease (ND) strains isolated from chickens in Asia during the period 2008-2011 were genetically analyzed. Phylogenetic analysis showed that genotype VII of NDV still predominant in the domestic poultry of Asia. The sub-genotype VIIb circulated in the Iran and Indian sub-continent countries, whereas VIId sub-genotype existed in Far East countries. The non-synonymous to synonymous substitutions ratio was calculated 0.27 for VIId sub-genotype and 0.51 for VIIb sub-genotype indicates purifying/stabilizing selection which resulted in a low evolution rate in F gene of VIIb sub-genotype. There is evidence of localized positive selection when comparing these sub-genotypes protein sequences. Five codons in F gene of ND viruses had a posterior probability >90% using the Bayesian method, indicating these sites were under positive selection. To identify sites under positive selection; amino acid substitution classified depends on their radicalism and neutrality. The results indicate that although most positions were under purifying selection and can be eliminated, a few positions located in sub-genotype specific regions were subject to positive selection.

  7. Through-thickness recrystallization characteristics of a laminated AA3xxx–AA6xxx aluminum alloy system

    SciTech Connect

    Liao, L.H., E-mail: l2liao@uwaterloo.ca; Jin, H.; Gallerneault, M.

    2015-03-15

    The through-thickness annealing behavior of a laminated AA3xxx–AA6xxx alloy system at 300 °C has been studied by scanning electron microscopy, electron backscatter diffraction analysis, electron probe micro-analysis, differential scanning calorimetry, and hardness measurement. Results show that the recrystallization process starts at the interface region between the AA3xxx (clad) and AA6xxx (core) layers. Subsequently, the recrystallization process front progresses into the core layer, while the clad layer is the last region to recrystallize. It is also found that precipitation precedes recrystallization in the entire laminate at the investigated temperature. The preferential onset of recrystallization at the interface region is attributed tomore » the net driving pressure being the highest in this region. The factors that lead to such enhanced net driving pressure are (a) deformation incompatibility between the two alloy layers, (b) lower solute content of the interface, which also leads to lower volume fraction of precipitates, and (c) an accelerated rate of precipitate coarsening due to the presence of a higher density of dislocations. The gradual progress of recrystallization from the interface towards the core layer is dictated by precipitate coarsening and the dependence of its rate on the density of deformation-induced dislocations. The lower driving pressure due to lower work hardening capacity, high solute drag pressure due to Mn, and additional Zener drag from precipitates that form due to solute redistribution during annealing explain the late initiation of recrystallization in the clad layer. - Highlights: • The through-thickness recrystallization of a laminated system is investigated. • The early onset of recrystallization at the interface is discussed. • The effects of precipitation and coarsening on recrystallization are analyzed.« less

  8. Laboratory study on the behaviour of spent AA household alkaline batteries in incineration

    SciTech Connect

    Almeida, Manuel F.; Xara, Susana M.; Delgado, Julanda

    2009-01-15

    The quantitative evaluation of emissions from incineration is essential when Life Cycle Assessment (LCA) studies consider this process as an end-of-life solution for some wastes. Thus, the objective of this work is to quantify the main gaseous emissions produced when spent AA alkaline batteries are incinerated. With this aim, batteries were kept for 1 h at 1273 K in a refractory steel tube hold in a horizontal electric furnace with temperature control. At one end of the refractory steel tube, a constant air flow input assures the presence of oxygen in the atmosphere and guides the gaseous emissions to amore » filter system followed by a set of two bubbler flasks having an aqueous solution of 10% (v/v) nitric acid. After each set of experiments, sulphur, chlorides and metals (As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Sb, Tl and Zn) were analyzed in both the solutions obtained from the steel tube washing and from the bubblers. Sulphur, chlorides and metals were quantified, respectively, using barium sulfate gravimetry, the Volhard method and atomic absorption spectrometry (AAS). The emissions of zinc, the most emitted metal, represent about 6.5% of the zinc content in the batteries. Emissions of manganese (whose oxide is the main component of the cathode) and iron (from the cathode collector) are negligible when compared with their amount in AA alkaline batteries. Mercury is the metal with higher volatility in the composition of the batteries and was collected even in the second bubbler flask. The amount of chlorides collected corresponds to about 36% of the chlorine in the battery sleeve that is made from PVC. A considerable part of the HCl formed in PVC plastic sleeve incineration is neutralized with KOH, zinc and manganese oxides and, thus, it is not totally released in the gas. Some of the emissions are predictable through a thermodynamic data analysis at temperatures in the range of 1200-1300 K taking into account the composition of the batteries. This analysis

  9. LinkImpute: Fast and Accurate Genotype Imputation for Nonmodel Organisms

    PubMed Central

    Money, Daniel; Gardner, Kyle; Migicovsky, Zoë; Schwaninger, Heidi; Zhong, Gan-Yuan; Myles, Sean

    2015-01-01

    Obtaining genome-wide genotype data from a set of individuals is the first step in many genomic studies, including genome-wide association and genomic selection. All genotyping methods suffer from some level of missing data, and genotype imputation can be used to fill in the missing data and improve the power of downstream analyses. Model organisms like human and cattle benefit from high-quality reference genomes and panels of reference genotypes that aid in imputation accuracy. In nonmodel organisms, however, genetic and physical maps often are either of poor quality or are completely absent, and there are no panels of reference genotypes available. There is therefore a need for imputation methods designed specifically for nonmodel organisms in which genomic resources are poorly developed and marker order is unreliable or unknown. Here we introduce LinkImpute, a software package based on a k-nearest neighbor genotype imputation method, LD-kNNi, which is designed for unordered markers. No physical or genetic maps are required, and it is designed to work on unphased genotype data from heterozygous species. It exploits the fact that markers useful for imputation often are not physically close to the missing genotype but rather distributed throughout the genome. Using genotyping-by-sequencing data from diverse and heterozygous accessions of apples, grapes, and maize, we compare LD-kNNi with several genotype imputation methods and show that LD-kNNi is fast, comparable in accuracy to the best-existing methods, and exhibits the least bias in allele frequency estimates. PMID:26377960

  10. LinkImpute: Fast and Accurate Genotype Imputation for Nonmodel Organisms.

    PubMed

    Money, Daniel; Gardner, Kyle; Migicovsky, Zoë; Schwaninger, Heidi; Zhong, Gan-Yuan; Myles, Sean

    2015-09-15

    Obtaining genome-wide genotype data from a set of individuals is the first step in many genomic studies, including genome-wide association and genomic selection. All genotyping methods suffer from some level of missing data, and genotype imputation can be used to fill in the missing data and improve the power of downstream analyses. Model organisms like human and cattle benefit from high-quality reference genomes and panels of reference genotypes that aid in imputation accuracy. In nonmodel organisms, however, genetic and physical maps often are either of poor quality or are completely absent, and there are no panels of reference genotypes available. There is therefore a need for imputation methods designed specifically for nonmodel organisms in which genomic resources are poorly developed and marker order is unreliable or unknown. Here we introduce LinkImpute, a software package based on a k-nearest neighbor genotype imputation method, LD-kNNi, which is designed for unordered markers. No physical or genetic maps are required, and it is designed to work on unphased genotype data from heterozygous species. It exploits the fact that markers useful for imputation often are not physically close to the missing genotype but rather distributed throughout the genome. Using genotyping-by-sequencing data from diverse and heterozygous accessions of apples, grapes, and maize, we compare LD-kNNi with several genotype imputation methods and show that LD-kNNi is fast, comparable in accuracy to the best-existing methods, and exhibits the least bias in allele frequency estimates. Copyright © 2015 Money et al.

  11. [A review for recent advances in AA amyloid research and therapeutic approach to AA amyloidosis complicating rheumatoid arthritis].

    PubMed

    Tamura, Hiroaki; Hasegawa, Kiminori

    2009-02-01

    AA amyloidosis is a life threatening clinical complication of chronic inflammatory diseases such as rheumatoid arthritis. It has been demonstrated biochemically that amyloidosis resulted from abnormal folding of proteins, which are deposited as insoluble fibrils in extracellular tissue, leading to the disruption of their normal function. In this regard, amyloidosis has been recognized as a conformation disorder. Interestingly, genetic polymorphisms of amyloid precursor protein (SAA) have been reported to associate with increased risk for AA amyloidosis. Also recent biochemical research revealed that SAA is synthesized under the influence of the proinflammatory cytokines, such as IL-6, TNF-alpha, IL-1. Additionally, it was suggested that amyloid deposits in extracellular tissue could reflect to the serum level of SAA in the reversible fashion, leading to the hypothesis that the control of the SAA synthesis could be beneficial to the treatment of amyloidosis. In this context, anti-cytokine therapies may be most effective. Especially the inhibition of IL-6 is critical to suppression of SAA production, so treatment with a humanized monoclonal antibody against human IL-6 receptor may not only ameliorate RA disease activity but also pave the way for the treatment of AA amyloidosis.

  12. Dependence of deodorant usage on ABCC11 genotype: scope for personalized genetics in personal hygiene.

    PubMed

    Rodriguez, Santiago; Steer, Colin D; Farrow, Alexandra; Golding, Jean; Day, Ian N M

    2013-07-01

    Earwax type and axillary odor are genetically determined by rs17822931, a single-nucleotide polymorphism (SNP) located in the ABCC11 gene. The literature has been concerned with the Mendelian trait of earwax, although axillary odor is also Mendelian. Ethnic diversity in rs17822931 exists, with higher frequency of allele A in east Asians. Influence on deodorant usage has not been investigated. In this work, we present a detailed analysis of the rs17822931 effect on deodorant usage in a large (N∼17,000 individuals) population cohort (the Avon Longitudinal Study of Parents and Children (ALSPAC)). We found strong evidence (P=3.7 × 10(-20)) indicating differential deodorant usage according to the rs17822931 genotype. AA homozygotes were almost 5-fold overrepresented in categories of never using deodorant or using it infrequently. However, 77.8% of white European genotypically nonodorous individuals still used deodorant, and 4.7% genotypically odorous individuals did not. We provide evidence of a behavioral effect associated with rs17822931. This effect has a biological basis that can result in a change in the family's environment if an aerosol deodorant is used. It also indicates potential cost saving to the nonodorous and scope for personalized genetics usage in personal hygiene choices, with consequent reduction of inappropriate chemical exposures for some.

  13. Genotype-based dosage of acenocoumarol in highly-sensitive geriatric patients.

    PubMed

    Lozano, Roberto; Franco, María-Esther; López, Luis; Moneva, Juan-José; Carrasco, Vicente; Pérez-Layo, Maria-Angeles

    2015-03-01

    Our aim was to determinate the acenocoumarol dose requirement in highly sensitive geriatric patients, based on a minimum of genotype (VKORC1 and CYP2C9) data. We used a Gaussian kernel density estimation test to identify patients highly sensitive to the drug and PHARMACHIP®-Cuma test (Progenika Biopharma, SA, Grifols, Spain) to determine the CYP2C9 and VKORC1 genotype. All highly sensitive geriatric patients were taking ≤5.6 mg/week of acenocoumarol (AC), and 86% of these patients presented the following genotypes: CYP2C9*1/*3 or CYP2C9*1/*2 plus VKORC1 A/G, CYP2C9*3/*3, or VKORC1 A/A. VKORC1 A and CYP2C9*2 and/or *3 allelic variants extremely influence on AC dose requirement of highly sensitive geriatric patients. These patients display acenocoumarol dose requirement of ≤5.6 mg/week.

  14. Dependence of Deodorant Usage on ABCC11 Genotype: Scope for Personalized Genetics in Personal Hygiene

    PubMed Central

    Rodriguez, Santiago; Steer, Colin D; Farrow, Alexandra; Golding, Jean; Day, Ian N M

    2013-01-01

    Earwax type and axillary odor are genetically determined by rs17822931, a single-nucleotide polymorphism (SNP) located in the ABCC11 gene. The literature has been concerned with the Mendelian trait of earwax, although axillary odor is also Mendelian. Ethnic diversity in rs17822931 exists, with higher frequency of allele A in east Asians. Influence on deodorant usage has not been investigated. In this work, we present a detailed analysis of the rs17822931 effect on deodorant usage in a large (N∼17,000 individuals) population cohort (the Avon Longitudinal Study of Parents and Children (ALSPAC)). We found strong evidence (P=3.7 × 10−20) indicating differential deodorant usage according to the rs17822931 genotype. AA homozygotes were almost 5-fold overrepresented in categories of never using deodorant or using it infrequently. However, 77.8% of white European genotypically nonodorous individuals still used deodorant, and 4.7% genotypically odorous individuals did not. We provide evidence of a behavioral effect associated with rs17822931. This effect has a biological basis that can result in a change in the family's environment if an aerosol deodorant is used. It also indicates potential cost saving to the nonodorous and scope for personalized genetics usage in personal hygiene choices, with consequent reduction of inappropriate chemical exposures for some. PMID:23325016

  15. Cytogenetic evidence of mixed disomic and polysomic inheritance in an allotetraploid (AABB) Musa genotype.

    PubMed

    Jeridi, Mouna; Perrier, Xavier; Rodier-Goud, Marguerite; Ferchichi, Ali; D'Hont, Angélique; Bakry, Frédéric

    2012-12-01

    Edible bananas originated mainly from two wild species, Musa acuminata Colla (AA) and Musa balbisiana Colla (BB), and triploid cultivars with an AAA, AAB or ABB genome are the most widely used. In the present study, chromosome pairing affinities are investigated in a sterile AB Indian variety and in its fertile colchicine-induced allotetraploid (AABB) derivative to determine the inheritance pattern of the tetraploid genotype. The potential implications of interspecific recombination and chromosomal composition of diploid gametes for Musa improvement are presented. The pairing of different chromosome sets at diploid and tetraploid levels was investigated through a combination of conventional cytogenetic and genomic in-situ hybridization (GISH) analyses of meiotic chromosomes, leading to a likelihood model of the pairing behaviour. GISH analysis of mitotic chromosomes was also conducted to reveal the chromosome constitution of hybrids derived from crosses involving the allotetraploid genotype. Analysis of chromosome associations at both ploidy levels suggested that the newly formed allotetraploid behaves as a 'segmental allotetraploid' with three chromosome sets in a tetrasomic pattern, three sets in a likely disomic pattern and the five remaining sets in an intermediate pattern. Balanced and unbalanced diploid gametes were detected in progenies, with the chromosome constitution appearing to be more homogenous in pollen than in ovules. Colchicine-induced allotetraploids in Musa provide access to the genetic background of natural AB varieties. The segmental inheritance pattern exhibited by the AABB allotetraploid genotype implies chromosome exchanges between M. acuminata and M. balbisiana species and opens new horizons for reciprocal transfer of valuable alleles.

  16. Hepatitis C Genotypes in Libya: Correlation with Patients' Characteristics, Level of Viremia, and Degree of Liver Fibrosis.

    PubMed

    Elzuoki, Abdel-Naser; Elzouki, Islam; Albarassi, Sabah; Gammo, Mohamed; Burwaiss, Abdalla

    2017-09-01

    Our study sought to determine the distribution of hepatitis C virus (HCV)-genotypes among patients attending two tertiary care hospitals in Benghazi and Tripoli, Libya, and correlate this with patient's characteristics, viral load, and degree of fibrosis. We conducted a retrospective study of 286 HCV-RNA positive Libyan patients referred from different health care facilities in east and west Libya for specific HCV treatment. HCV genotyping was carried out by gene amplification. Liver histology was graded by Metavir score according to the stage of fibrosis. HCV genotypes 1, 2, 3, and 4 were found in 24.1%, 10.8%, 3.4%, and 61.5% of the patients, respectively. Genotype 4 was detected more frequently in patients from east Libya (Benghazi) compared to west Libya (Tripoli) (75.9% vs. 41.6%, p = 0.245). Genotype 1 was more frequent in patients from west Libya compared to east Libya (34.1% vs. 16.8%, p = 0.657). There was a significant correlation between HCV genotype distribution and viral load. Patients with genotype 4 exhibited a higher degree of liver fibrosis ( p < 0.001). HCV genotype 4 is the predominant genotype in Libya followed by genotype 1. However, as we go from the east to the west of the country, genotype 1 increases. Genotype 4 was associated with higher level of viremia and higher stage of liver fibrosis. It is important to note that both genotypes 1 and 4 are associated with a poor response to pegylated interferon and ribavirin combination therapy. The findings emphasize the need to develop improved strategies in Libya for the successful treatment of HCV infection with novel newly available antiviral drugs.

  17. Apolipoprotein A-II induces acute-phase response associated AA amyloidosis in mice through conformational changes of plasma lipoprotein structure.

    PubMed

    Yang, Mu; Liu, Yingye; Dai, Jian; Li, Lin; Ding, Xin; Xu, Zhe; Mori, Masayuki; Miyahara, Hiroki; Sawashita, Jinko; Higuchi, Keiichi

    2018-04-04

    During acute-phase response (APR), there is a dramatic increase in serum amyloid A (SAA) in plasma high density lipoproteins (HDL). Elevated SAA leads to reactive AA amyloidosis in animals and humans. Herein, we employed apolipoprotein A-II (ApoA-II) deficient (Apoa2 -/- ) and transgenic (Apoa2Tg) mice to investigate the potential roles of ApoA-II in lipoprotein particle formation and progression of AA amyloidosis during APR. AA amyloid deposition was suppressed in Apoa2 -/- mice compared with wild type (WT) mice. During APR, Apoa2 -/- mice exhibited significant suppression of serum SAA levels and hepatic Saa1 and Saa2 mRNA levels. Pathological investigation showed Apoa2 -/- mice had less tissue damage and less inflammatory cell infiltration during APR. Total lipoproteins were markedly decreased in Apoa2 -/- mice, while the ratio of HDL to low density lipoprotein (LDL) was also decreased. Both WT and Apoa2 -/- mice showed increases in LDL and very large HDL during APR. SAA was distributed more widely in lipoprotein particles ranging from chylomicrons to very small HDL in Apoa2 -/- mice. Our observations uncovered the critical roles of ApoA-II in inflammation, serum lipoprotein stability and AA amyloidosis morbidity, and prompt consideration of therapies for AA and other amyloidoses, whose precursor proteins are associated with circulating HDL particles.

  18. Relationship between patient-reported outcomes and clinical outcomes in metastatic castration-resistant prostate cancer: post hoc analysis of COU-AA-301 and COU-AA-302.

    PubMed

    Cella, D; Traina, S; Li, T; Johnson, K; Ho, K F; Molina, A; Shore, N D

    2018-02-01

    Patient-reported outcomes (PROs) are used to assess benefit-risk in drug development. The relationship between PROs and clinical outcomes is not well understood. We aim to elucidate the relationships between changes in PRO measures and clinical outcomes in metastatic castration-resistant prostate cancer (mCRPC). We investigated relationships between changes in self-reported fatigue, pain, functional well-being (FWB), physical well-being (PWB) and prostate cancer-specific symptoms with overall survival (OS) and radiographic progression-free survival (rPFS) after 6 and 12 months of treatment in COU-AA-301 (N = 1195) or COU-AA-302 (N = 1088). Eligible COU-AA-301 patients had progressed after docetaxel and had Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 2. Eligible COU-AA-302 patients had no prior chemotherapy and ECOG PS 0 or 1. Patients were treated with abiraterone acetate (1000 mg/day) plus prednisone (10 mg/day) or prednisone alone daily. Association between self-reported fatigue, pain and functional status, and OS and/or rPFS, using pooled data regardless of treatment, was assessed. Cox proportional hazard regression modeled time to death or radiographic progression. In COU-AA-301 patients, PRO improvements were associated with longer OS and longer time to radiographic progression versus worsening or stable PROs (P < 0.0001). In multivariate models, all except pain intensity remained associated with OS. Pain intensity, PWB and FWB improvements remained associated with rPFS. In COU-AA-302 patients, worsening PROs were associated with higher likelihood of radiographic progression (P ≤ 0.025) compared with improved or stable PROs. In multivariate models, worsening PWB remained associated with worse rPFS. The 12-month analysis confirmed the 6-month results. PROs are significantly associated with clinically relevant time-to-event efficacy outcomes in clinical trials and may complement and help predict traditional

  19. 76 FR 6794 - 30-Day Submission Period for Requests for ONC-Approved Accreditor (ONC-AA) Status

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-08

    ... Accreditor (ONC-AA) Status AGENCY: Office of the National Coordinator for Health Information Technology... submission of requests for ONC-Approved Accreditor (ONC-AA) status. Authority: 42 U.S.C. 300jj-11. DATES: The... for ONC-AA status may be submitted. The 30-day period for submission of requests for ONC-AA status...

  20. Development of 2024 AA-Yttrium composites by Spark Plasma Sintering

    NASA Astrophysics Data System (ADS)

    Vidyasagar, CH S.; Karunakar, D. B.

    2018-04-01

    The method of fabrication of MMNCs is quite a challenge, which includes advanced processing techniques like Spark Plasma Sintering (SPS), etc. The objective of the present work is to fabricate aluminium based MMNCs with the addition of small amounts of yttrium using Spark Plasma Sintering and to evaluate their mechanical and microstructure properties. Samples of 2024 AA with yttrium ranging from 0.1% to 0.5 wt% are fabricated by Spark Plasma Sintering (SPS). Hardness of the samples is determined using Vickers hardness testing machine. The metallurgical characterization of the samples is evaluated by Optical Microscopy (OM), Field Emission Scanning Electron Microscopy (FE-SEM). Unreinforced 2024 AA sample is also fabricated as a benchmark to compare its properties with those of the composite developed. It is found that the yttrium addition increases the above mentioned properties by altering the precipitation kinetics and intermetallic formation to some extent and then decreases gradually when yttrium wt% increases beyond 0.3 wt%. High density (˂ 99.75) is achieved in the samples and highest hardness achieved is 114 Hv, fabricated by spark plasma sintering and uniform distribution of yttrium is observed.

  1. 12-Step Therapy and Women with and without Social Phobia: A Study of the Effectiveness of 12-Step Therapy to Facilitate AA Engagement

    PubMed Central

    Tonigan, J. Scott; Book, Sarah W.; Pagano, Maria E.; Randall, Patrick K.; Smith, Joshua P.; Randall, Carrie L.

    2011-01-01

    Alcoholism treatment often encourages involvement in Alcoholics Anonymous (AA). Little provision is made for women with social phobia (SP), who have been reported to have worse outcomes in twelve-step-facilitation (TSF) relative to cognitive behavioral therapy. This study examined whether SP moderated the effects of gender for these women in TSF. 133 SP alcoholics assigned to TSF (35 females and 98 males) in Project MATCH were compared to a non-SP control group. SP women drank earlier and more intensely than non-SP women and all males, had equivalent AA attendance and completion of Step 5, and were less likely to acquire a sponsor during TSF. PMID:21423569

  2. Epigenomics and bolting tolerance in sugar beet genotypes.

    PubMed

    Hébrard, Claire; Peterson, Daniel G; Willems, Glenda; Delaunay, Alain; Jesson, Béline; Lefèbvre, Marc; Barnes, Steve; Maury, Stéphane

    2016-01-01

    In sugar beet (Beta vulgaris altissima), bolting tolerance is an essential agronomic trait reflecting the bolting response of genotypes after vernalization. Genes involved in induction of sugar beet bolting have now been identified, and evidence suggests that epigenetic factors are involved in their control. Indeed, the time course and amplitude of DNA methylation variations in the shoot apical meristem have been shown to be critical in inducing sugar beet bolting, and a few functional targets of DNA methylation during vernalization have been identified. However, molecular mechanisms controlling bolting tolerance levels among genotypes are still poorly understood. Here, gene expression and DNA methylation profiles were compared in shoot apical meristems of three bolting-resistant and three bolting-sensitive genotypes after vernalization. Using Cot fractionation followed by 454 sequencing of the isolated low-copy DNA, 6231 contigs were obtained that were used along with public sugar beet DNA sequences to design custom Agilent microarrays for expression (56k) and methylation (244k) analyses. A total of 169 differentially expressed genes and 111 differentially methylated regions were identified between resistant and sensitive vernalized genotypes. Fourteen sequences were both differentially expressed and differentially methylated, with a negative correlation between their methylation and expression levels. Genes involved in cold perception, phytohormone signalling, and flowering induction were over-represented and collectively represent an integrative gene network from environmental perception to bolting induction. Altogether, the data suggest that the genotype-dependent control of DNA methylation and expression of an integrative gene network participate in bolting tolerance in sugar beet, opening up perspectives for crop improvement. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  3. Eicosapentaenoic acid to arachidonic acid (EPA/AA) ratio as an associated factor of high risk plaque on coronary computed tomography in patients without coronary artery disease.

    PubMed

    Nagahara, Yasuomi; Motoyama, Sadako; Sarai, Masayoshi; Ito, Hajime; Kawai, Hideki; Takakuwa, Yoko; Miyagi, Meiko; Shibata, Daisuke; Takahashi, Hiroshi; Naruse, Hiroyuki; Ishii, Junichi; Ozaki, Yukio

    2016-07-01

    Coronary computed tomography angiography (CCTA)-verified high risk plaque (HRP) characteristics including positive remodeling and low attenuation plaque have been associated with acute coronary syndromes. Several studies reported that the n-3 polyunsaturated fatty acids have been associated with cardiovascular events. However, the relationship between serum eicosapentaenoic acid to arachidonic acid (EPA/AA) ratio and CCTA-verified HRP in patients without known coronary artery disease (CAD) is unclear. We aimed at investigating the relation between EPA/AA and CCTA-verified HRP in patients without known CAD. We included 193 patients undergoing CCTA without known CAD (65.5 ± 12.0 years, 55.0% male). No patient has been treated with EPA. The relation of coronary risk factors, lipid profile, high-sensitivity C-reactive protein, coronary artery calcification score (CACS), number of vessel disease, plaque burden, and EPA/AA with the presence of HRP was evaluated by logistic regression analysis. Incremental value of EPA/AA to predict HRP was also analyzed by C-index, NRI, and IDI. A Cox proportional hazards model was used to estimate the time to cardiovascular event. HRP was observed in 37 (19%) patients. Multivariable logistic regression analysis revealed that current smoking (OR 2.58; p=0.046), number of vessel disease (OR 1.87; p=0.031), and EPA/AA ratio (OR 0.65; p=0.0006) were independent associated factors of HRP on CCTA. Although the addition of EPA/AA to the baseline model did not significantly improve C-index, both NRI (0.60, p=0.0049) and IDI (0.054, p=0.0072) were significantly improved. Patients with HRP had significantly higher rate of events compared with patients without HRP (14% vs. 3%, Logrank p=0.0004). On multivariable Cox hazard analysis, baseline EPA/AA ratio was an independent predictor (HR 0.57, p=0.047). Low EPA/AA was an associated factor of HRP on CCTA in patients without CAD. In addition to conventional coronary risk factors and CACS, EPA/AA

  4. Treatment switch guided by HIV-1 genotyping in Brazil.

    PubMed

    Tupinambás, Unaí; Ribeiro, Flávia Andrade; Aleixo, Agdemir; Greco, Dirceu

    2006-04-01

    We assessed the performance of HIV-1 genotyping tests in rescue therapy. Patients were divided into two groups: group 1 (genotyped), included those switching to new antiretroviral drugs based on HIV-1 genotyping data, and group 2 (standard of care -SOC), comprised those in rescue therapy who had not used this test. This was an open and non-randomized study, with 74 patients, followed up for a mean period of 12 months, from February 2002 to May 2003. The groups differed in the duration of antiretroviral use, experience with diverse drug classes (non-nucleoside reverse transcriptase inhibitors and protease inhibitors) and viral load <2.6 log10 copies/mL at any time during treatment. In 23 patients (group 1), the switch in antiretroviral (ARV) regimen was based on genotyping data; this test was not used for 51 patients (group 2). Two CD4 + lymphocyte counts and viral load counts were made for each patient during the study. Data from the pharmacy where patients received antiretroviral agents, medical charts, and direct interviews with patients to assess compliance to treatment, were analyzed. In the genotyped group, the average drop in viral load was 2.8 log10, compared with a 1.5 log10 difference in group 2; the difference was significant in the first assessment performed six months after switching (p=0.001). Considering the patients with viral load < 2.6 log10 (400 copies/mL) after switching, the patients in group 1 had a better performance in the first assessment (73.9% versus 31.1% in groups 1 and 2, respectively); this difference was significant (p=0.001). In multivariate analysis, the variables associated with a greater drop in viral load in the first assessment were the patients whose switching was based on genotyping (group 1), those with a past history of viral load < 2.6 log10 and correct use of antiretroviral agents. In conclusion, the genotyping test and adherence were found to be independent factors for success in the management of patients who failed

  5. Adverse effects of doping with anabolic androgenic steroids (AAS) in competitive athletics, recreational sports and bodybuilding.

    PubMed

    Vorona, Elena; Nieschlag, Eberhard

    2018-02-19

    Despite the fact that sports organizations and legislators have introduced various mechanisms to discourage athletes from using performance and appearance enhancing substances a high percentage of athletes admits to their unabated application. In competitive athletics, bodybuilding and in recreational sports anabolic androgenic steroids (AAS) continue to be the substances most abused. This review summarizes the side effects of AAS abuse on organs and system functions in both sexes. High doses of AAS cause a significant increase of erythrocytes und haemoglobin concentration, which may lead to thromboembolism, intracardiac thrombosis and stroke. Long-term AAS abusers have a higher incidence of arrhythmias, atherosclerosis, concentric left-ventricular myocardial hypertrophy with impaired diastolic function and also sudden cardiac death. Changes of liver function and structure, up to hepatocellular carcinoma, have been described, mainly in cases of chronic misuse of 17α-alkylated AAS. Sleeplessness, increased irritability, depressive mood status are often observed in AAS abuse. In former AAS abusers depression, anxiety and melancholy may persist for many years. Due to negative feedback in the regulation of the hypothalamic-pituitary-gonadal axis AAS can cause reversible suppression of spermatogenesis up to azoospermia. In women the changes most often caused by AAS abuse are hirsutism, irreversible deepening of voice, dysmenorrhoea, secondary amenorrhoea with anovulation and infertility. AAS abuse notwithstanding, under clinical conditions testosterone remains the most important hormone for substitution therapy of male hypogonadism.

  6. Generation of recombinant European bat lyssavirus type 1 and inter-genotypic compatibility of lyssavirus genotype 1 and 5 antigenome promoters.

    PubMed

    Orbanz, Jeannette; Finke, Stefan

    2010-10-01

    Bat lyssaviruses (Fam. Rhabdoviridae) represent a source for the infection of terrestial mammals and the development of rabies disease. Molecular differences in the replication of bat and non-bat lyssaviruses and their contribution to pathogenicity, however, are unknown. One reason for this is the lack of reverse genetics systems for bat-restricted lyssaviruses. To investigate bat lyssavirus replication and host adaptation, we developed a reverse genetics system for European bat lyssavirus type 1 (EBLV-1; genotype 5). This was achieved by co-transfection of HEK-293T cells with a full-length EBLV-1 genome cDNA and expression plasmids for EBLV-1 proteins, resulting in recombinant EBLV-1 (rEBLV-1). Replication of rEBLV-1 was comparable to that of parental virus, showing that rEBLV-1 is a valid tool to investigate EBLV-1 replication functions. In a first approach, we tested whether the terminal promoter sequences of EBLV-1 are genotype-specific. Although genotype 1 (rabies virus) minigenomes were successfully amplified by EBLV-1 helper virus, in the context of the complete virus, only the antigenome promoter (AGP) sequence of EBLV-1 was replaceable, as indicated by comparable replication of rEBLV-1 and the chimeric virus. These analyses demonstrate that the terminal AGPs of genotype 1 and genotype 5 lyssaviruses are compatible with those of the heterologous genotype.

  7. The Complete Genome Phylogeny of Geographically Distinct Dengue Virus Serotype 2 Isolates (1944-2013) Supports Further Groupings within the Cosmopolitan Genotype

    PubMed Central

    Ali, Akhtar; Ali, Ijaz

    2015-01-01

    Dengue virus serotype 2 (DENV-2) isolates have been implicated in deadly outbreaks of dengue fever (DF) and dengue hemorrhagic fever (DHF) in several regions of the world. Phylogenetic analysis of DENV-2 isolates collected from particular countries has been performed using partial or individual genes but only a few studies have examined complete whole-genome sequences collected worldwide. Herein, 50 complete genome sequences of DENV-2 isolates, reported over the past 70 years from 19 different countries, were downloaded from GenBank. Phylogenetic analysis was conducted and evolutionary distances of the 50 DENV-2 isolates were determined using maximum likelihood (ML) trees or Bayesian phylogenetic analysis created from complete genome nucleotide (nt) and amino acid (aa) sequences or individual gene sequences. The results showed that all DENV-2 isolates fell into seven main groups containing five previously defined genotypes. A Cosmopolitan genotype showed further division into three groups (C-I, C-II, and C-III) with the C-I group containing two subgroups (C-IA and C-IB). Comparison of the aa sequences showed specific mutations among the various groups of DENV-2 isolates. A maximum number of aa mutations was observed in the NS5 gene, followed by the NS2A, NS3 and NS1 genes, while the smallest number of aa substitutions was recorded in the capsid gene, followed by the PrM/M, NS4A, and NS4B genes. Maximum evolutionary distances were found in the NS2A gene, followed by the NS4A and NS4B genes. Based on these results, we propose that genotyping of DENV-2 isolates in future studies should be performed on entire genome sequences in order to gain a complete understanding of the evolution of various isolates reported from different geographical locations around the world. PMID:26414178

  8. Genotypic gain with simultaneous selection of production, nutrition, and culinary traits in cowpea crosses and backcrosses using mixed models.

    PubMed

    Oliveira, D G; Rocha, M M; Damasceno-Silva, K J; Sá, F V; Lima, L R L; Resende, M D V

    2017-08-17

    The aim of this study was to estimate the genotypic gain with simultaneous selection of production, nutrition, and culinary traits in cowpea crosses and backcrosses and to compare different selection indexes. Eleven cowpea populations were evaluated in a randomized complete block design with four replications. Fourteen traits were evaluated, and the following parameters were estimated: genotypic variation coefficient, genotypic determination coefficient, experimental quality indicator and selection reliability, estimated genotypic values ​​- BLUE, genotypic correlation coefficient among traits, and genotypic gain with simultaneous selection of all traits. The genotypic gain was estimated based on tree selection indexes: classical, multiplicative, and the sum of ranks. The genotypic variation coefficient was higher than the environmental variation coefficient for the number of days to start flowering, plant type, the weight of one hundred grains, grain index, and protein concentration. The majority of the traits presented genotypic determination coefficient from medium to high magnitude. The identification of increases in the production components is associated with decreases in protein concentration, and the increase in precocity leads to decreases in protein concentration and cooking time. The index based on the sum of ranks was the best alternative for simultaneous selection of traits in the cowpea segregating populations resulting from the crosses and backcrosses evaluated, with emphasis on the F 4 BC 12 , F 4 C 21 , and F 4 C 12 populations, which had the highest genotypic gains.

  9. Beta-2 adrenoceptor genotype and progress in term and late preterm active labor

    PubMed Central

    MILLER, Russell S.; SMILEY, Richard M.; DANIEL, Danette; WENG, Chunhua; EMALA, Charles W.; BLOUIN, Jean-Louis; FLOOD, Pamela D.

    2011-01-01

    OBJECTIVE To evaluate whether beta-2 adrenoceptor genotype at a functional polymorphic site encoding for amino acid residue 16 influences rate of cervical dilatation in term and late preterm active labor. STUDY DESIGN Subjects that underwent vaginal delivery at 34 or greater weeks gestational age between May, 2006, and August, 2007, were identified. Each subject had provided venous blood from which DNA was extracted for beta-2 adrenoceptor genotyping. Digital cervical examinations with paired examination times were collected from intrapartum records. Rate of cervical dilatation in active labor was determined using linear regression and rates were compared between genotype groups. RESULTS Among 401 subjects with satisfactory genotype and intrapartum data, overall rate of active labor was 0.76+/−0.01 cm/hr. When labor was compared by genotype, homozygous Arg/Arg16 subjects progressed at a slower rate (0.64+/−0.03 cm/hr) than all other pooled genotypes (0.8+/−0.02 cm/hr). CONCLUSION Homozygous beta-2 adrenoceptor genotype encoding for Arg/Arg16 was associated with slower progress in active labor. PMID:21600547

  10. Detection and genotyping of human papilloma virus in cervical cancer specimens from Saudi patients.

    PubMed

    Al-Badawi, Ismail A; Al-Suwaine, Abdulrahman; Al-Aker, Murad; Asaad, Lina; Alaidan, Alwaleed; Tulbah, Asma; Fe Bohol, Marie; Munkarah, Adnan R

    2011-07-01

    To determine the rates and types of human papilloma virus (HPV) infection in cervical cancer specimens from Saudi patients. One hundred specimens were randomly selected and retrieved from the achieved samples stored in the pathology department accessioned under the diagnosis of cervical cancer and carcinoma in situ between the years 1997 and 2007. Human papilloma virus in the clinical samples was detected using polymerase chain reaction amplification methods. Two primer systems are commonly used: the MY09-MY11 primers and the GP5+-GP6+ that amplify a wide range of HPV genotypes. Human papilloma virus isolates were genotyped using DNA sequencing and reverse line blot hybridization assay to identify the high-risk HPV genotypes. Ninety cases fulfilled the diagnostic criteria and were analyzed. The rate of HPV genotype detection among cervical cancer samples was 95.5%. The most common HPV genotype detected by both methods was HPV-16 (63.4%), followed by HPV-18 (11.1%), HPV-45 (4.5%), HPV-33 (3.3%), and HPV-31, HPV-52, HPV-53, HPV-58, HPV-59, and HPV-66 with 2.2% prevalence rate each. Prevalence of HPV genotypes among patients with cervical cancer in Saudi Arabia is comparable to the international rates. The use of the reverse line blot hybridization assay genotyping method could be useful for classifying oncogenic HPV-positive women. It is relatively inexpensive and reliable and can be performed in routine practice or epidemiological study