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  • Genetics Society of America (GSA)  (2)
  • BMJ Publishing  (1)
  • Oxford University Press  (1)
  • The American Association of Immunologists (AAI)  (1)
  • 2015-2019  (5)
  • 1
    Publication Date: 2018-02-09
    Description: The Hulunbuir short-tailed sheep ( Ovis aries ) is a breed native to China, in which the short-tail phenotype is the result of artificial and natural selection favoring a specific set of genetic mutations. Here, we analyzed the genetic differences between short-tail and normal-tail phenotypes at the genomic level. Selection signals were identified in genome-wide sequences. From 16 sheep, we identified 72,101,346 single nucleotide polymorphisms. Selection signals were detected based on the fixation index and heterozygosity. Seven genomic regions under putative selection were identified, and these regions contained nine genes. Among these genes, T was the strongest candidate as T is related to vertebral development. In T , a nonsynonymous mutation at c.G334T resulted in p.G112W substitution. We inferred that the c.G334T mutation in T leads to functional changes in Brachyury—encoded by this gene—resulting in the short-tail phenotype. Our findings provide a valuable insight into the development of the short-tail phenotype in sheep and other short-tailed animals.
    Electronic ISSN: 2160-1836
    Topics: Biology
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  • 2
    Publication Date: 2018-01-28
    Description: Objectives This study aimed to assess the relationship between infection with multiple human papillomavirus (HPV) types and abnormal anal cytology in HIV-infected men. Design An observational, cross-sectional study. Setting A regional referral hospital in Taiwan. Participants In total, 714 HIV-infected men were enrolled between March 2011 and June 2016. Thin preparation anal Pap smears were interpreted according to the 2001 Bethesda System. Thirty-seven types of HPV were detected by reverse line blotting, including 13 oncogenic types and 24 non-oncogenic types. Outcome measures The relationship between anal HPV infection and abnormal anal cytology in people of Asian ethnicity and the coverage efficacy in HPV-vaccinated HIV-infected men. Results On anal cytology, 175 (24.5%) subjects had atypical squamous cells of undetermined significance (ASCUS) or higher grades of dysplasia, including 87 (49.7%) with ASCUS, 73 (41.7%) with low-grade squamous intraepithelial lesions (LSILs) and 15 (8.6%) with high-grade squamous intraepithelial lesions (HSILs). A higher proportion of subjects with those without LSIL/HSIL (93.1% vs 67.3%, P〈0.0001) had multiple HPV types. The odds of having LSIL/HSIL increased with an increasing number of HPV types: the ORs ranged from 1 for no HPV types to 6.96 (95% CI 2.38 to 20.37) for more than five types (P trend 〈0.0001). Multivariate logistic regression analysis showed a significant association between LSIL/HSIL and the number of HPV genotypes present (OR 1.20; 95% CI 1.02 to 1.42, P〈0.05). HPV types covered by the nonavalent HPV vaccine (types 6/11/16/18/31/33/45/52/58) were detected in 70.1% of the patients in this study. Conclusions The odds of having anal LSIL/HSIL are approximately seventimes greater in HIV-infected men with than withoutsix or more types of HPV. Multiple HPV types in HIV-infected patients deserves aggressive follow-up, and HPV vaccination programme require scaling up.
    Keywords: Oncology, Open access
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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  • 3
    Publication Date: 2018-06-01
    Description: Recombination often differs markedly between males and females. Here we present the first analysis of sex-specific recombination in Gasterosteus sticklebacks. Using whole-genome sequencing of 15 crosses between G. aculeatus and G. nipponicus , we localized 698 crossovers with a median resolution of 2.3 kb. We also used a bioinformatic approach to infer historical sex-averaged recombination patterns for both species. Recombination is greater in females than males on all chromosomes, and overall map length is 1.64 times longer in females. The locations of crossovers differ strikingly between sexes. Crossovers cluster toward chromosome ends in males, but are distributed more evenly across chromosomes in females. Suppression of recombination near the centromeres in males causes crossovers to cluster at the ends of long arms in acrocentric chromosomes, and greatly reduces crossing over on short arms. The effect of centromeres on recombination is much weaker in females. Genomic differentiation between G. aculeatus and G. nipponicus is strongly correlated with recombination rate, and patterns of differentiation along chromosomes are strongly influenced by male-specific telomere and centromere effects. We found no evidence for fine-scale correlations between recombination and local gene content in either sex. We discuss hypotheses for the origin of sexual dimorphism in recombination and its consequences for sexually antagonistic selection and sex chromosome evolution.
    Electronic ISSN: 2160-1836
    Topics: Biology
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  • 4
    Publication Date: 2018-03-06
    Description: Background Mouse models of glioblastoma (GBM), the most aggressive primary brain tumor, are critical for understanding GBM pathology and can contribute to the preclinical evaluation of therapeutic agents. Platelet-derived growth factor (PDGF) signaling has been implicated in the development and pathogenesis of GBM, specifically the proneural subtype. Although multiple mouse models of PDGF-driven glioma have been described, they require transgenic mice engineered to activate PDGF signaling and/or impair tumor suppressor genes and typically represent lower-grade glioma. Methods We designed recombinant lentiviruses expressing both PDGFB and a short hairpin RNA targeting Cdkn2a to induce gliomagenesis following stereotactic injection into the dentate gyrus of adult immunocompetent mice. We engineered these viruses to coexpress CreERT2 with PDGFB , allowing for deletion of floxed genes specifically in transduced cells, and designed another version of this recombinant lentivirus in which enhanced green fluorescent protein was coexpressed with PDGFB and CreERT2 to visualize transduced cells. Results The dentate gyrus of injected mice showed hypercellularity one week post-injection and subsequently developed bona fide tumors with the pathologic hallmarks of GBM leading to a median survival of 77 days post-injection. Transcriptomic analysis of these tumors revealed a proneural gene expression signature. Conclusion Informed by the genetic alterations observed in human GBM, we engineered a novel mouse model of proneural GBM. While reflecting many of the advantages of transgenic mice, this model allows for the facile in vivo testing of gene function in tumor cells and makes possible the rapid production of large numbers of immunocompetent tumor-bearing mice for preclinical testing of therapeutics.
    Print ISSN: 1522-8517
    Electronic ISSN: 1523-5866
    Topics: Medicine
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  • 5
    Publication Date: 2018-10-23
    Description: Enterovirus D68 (EV-D68) belongs to the picornavirus family and was first isolated in CA, USA, in 1962. EV-D68 can cause severe cranial nerve system damage such as flaccid paralysis and acute respiratory diseases such as pneumonia. There are currently no efficient therapeutic methods or effective prophylactics. In this study, we isolated the mAb A6-1 from an EV-D68–infected rhesus macaque ( Macaca mulatta ) and found that the Ab provided effective protection in EV-D68 intranasally infected suckling mice. We observed that A6-1 bound to the DE loop of EV-D68 VP1 and interfered with the interaction between the EV-D68 virus and α2,6-linked sialic acids of the host cell. The production of A6-1 and its Ab properties present a bridging study for EV-D68 vaccine design and provide a tool for analyzing the process by which Abs can inhibit EV-D68 infection.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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