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摘要： Prenatal growth is influenced by bidirectional exchange between the fetal and maternal systems that programme birth weight and postnatal phenotype. Fetal fluids are essential but unexplored areas for prenatal growth. This study examined allantoic and amniotic fluids and maternal blood in a Bos taurus, Bos indicus bovine model to provide fundamental information that is lacking regarding (i) changes in clinico-chemical parameters of maternal blood in early and midgestation and their relationships with placental-embryo/fetal weights (ii) differences in clinico-chemical parameters of allantoic and amniotic fluids of bovine concepti in early and midgestation, (iii) effects of genetics and sex on clinico-chemical parameters of fetal fluids and their relationships with feto-placental phenotype, and (iv) the effects of conceptus sex and genetics on maternal blood parameters. Purebred and reciprocal cross Bos taurus, (Bt) and Bos taurus indicus, (Bi) concepti were recovered in early gestation (Day 48, n = 60), and midgestation (Day 153, n = 72), (term ~ 280 days). Fetal fluids and maternal blood were sampled and analysed for clinico-chemical parameters. Insulin-like growth factors and thyroid hormones were assessed in maternal blood. Effects of genetics and sex on the measured parameters were determined using general linear models, and relationships with feto-placental phenotype assessed by linear regression. Breed effects on maternal electrolytes, metabolites and enzymes and their relationships with placental-embryo/fetal weights provide evidence of differences in maternal mineral metabolism, liver and kidney functions that influence conceptus growth. Stage- and genetic-specific differences were seen in clinico-chemical parameters of fetal fluids, which likely reflect differences in feto-placental phenotype. Greater maternal genome effects on fetal fluid in early gestation reflect the significance of placenta and maternal environment and represent maternal-offspring coadapt

摘要： Susceptibility to viral infection, development of immunity, response to treatment and patient clinical outcomes are all under the control of heritable factors in the host. In the context of the current SARS-Cov-2 pandemic, this review considers existing immunogenetic knowledge of virus-immune system interactions. A major focus is to highlight areas in which work is required in order to improve understanding of antiviral immune responses and to move towards improved patient management.

关键词： Kawasaki disease   Coronary artery aneurysms   Genome-wide association studies   Single-nucleotide polymorphism  

摘要： Kawasaki disease (KD) is a medium vessel vasculitis that affects young children. Despite extensive research over the last 50 years, the etiology of KD remains an enigma. Seasonal change in wind patterns was shown to have correlation with the epidemics of KD in Japan. Occurrence of disease in epidemiological clusters, seasonal variation, and a very low risk of recurrence suggest that KD is triggered by an infectious agent. The identification of oligoclonal IgA response in the affected tissues suggests an antigen-driven inflammation. The recent identification of a viral antigen in the cytoplasm of bronchial ciliated epithelium also favors infection as the main trigger for KD. Pointers that suggest a genetic basis of KD include a high disease prevalence in North-East Asian populations, a high risk among siblings, and familial occurrence of cases. Dysregulated innate and adaptive immune responses are evident in the acute stages of KD. In addition to the coronary wall inflammation, endothelial dysfunction and impaired vascular remodeling contribute to the development of coronary artery abnormalities (CAAs) and thrombosis. Genetic aberrations in certain intracellular signaling pathways involving immune effector functions are found to be associated with increased susceptibility to KD and development of coronary artery abnormalities (CAAs). Several susceptible genes have been identified through genome-wide association studies (GWAS) and linkage studies (GWLS). The genes that are studied in KD can be classified under 4 major groups-enhanced T cell activation (ITPKC,ORAI1,STIM1), dysregulated B cell signaling (CD40,BLK,FCGR2A), decreased apoptosis (CASP3), and altered transforming growth factor beta signaling (TGFB2,TGFBR2,MMP,SMAD). The review aims to highlight the role of several genetic risk factors that are linked with the increased susceptibility to KD.

摘要： Antimicrobial use (AMU) in livestock has come under growing criticism. There is increasing pressure to optimize AMU in food-producing animals, which will likely entail restrictions and voluntary reductions of their use, as well as implementation of protocols promoting antimicrobial stewardship. In this thesis, 1) methods were compared for obtaining AMU data on dairy farms, 2) factors associated with the prevalence of antimicrobial resistance (AMR) in non-aureus staphylococci (NAS) isolated from intramammary infections were studied, 3) treatment strategies for non-severe clinical mastitis (CM) in dairy cattle were contrasted, and 4) effects of restricted antimicrobial use in food-producing animals towards the prevalence of AMR genes (ARGs) were evaluated. Chapter 2 confirmed that treatment records accurately quantified AMU in well-managed dairy herds. Yet, their widespread adoption into AMU surveillance cannot be recommended, due to an underestimation of AMU in herds with elevated bulk tank somatic cell count. In regard to AMR, Chapter 3 demonstrated that resistance against tetracycline, penicillin and erythromycin in NAS was common in Canadian dairy herds. In Chapter 4, factors associated with AMR were further explored. An association between AMR in NAS and AMU was present when penicillins, 3 rd generation cephalosporins or macrolides were administered systemically, whereas intramammary use of antimicrobials were not associated with AMR. As antimicrobials classified as critically important antimicrobials (CIAs) for humans were associated with AMR, in Chapter 5 a systematic review was done to assess whether CIAs and non-CIAs had comparable efficacy to treat non-severe bovine CM caused by the most prevalent bacteria causing mastitis worldwide. No protocol including the use of CIAs had superior bacteriological cure rates of non- severe CM than protocols relying on non-CIAs. Therefore, no adverse effects in terms of animal health should be expected by ceasing use of CIA

关键词： 师范认证   产出导向   遗传学   课程建设  

摘要： 当前师范认证背景下，以产出为导向的人才培养体系对生物学课程教学提出了新期待、新要求。本文通过对当前师范院校遗传学课程建设及教学过程中存在问题的探讨，提出在以产出为导向的前提下，遗传学课程体系需要更为系统，课程内容应更加贴合中学教育，教学方式应多样化，评价体制需多元化等建议，上述建议将为高校师范专业认证及课程建设提供一定的参考。

摘要： Knowing the predisposing genetic risk factors of drug efficacy and adverse reactions has the potential to help personalize treatment towards the desired outcome. Biobanked genetic data coupled with Electronic health records (EHRs) is a valuable resource for different pharmacogenomics research directions that help to determine the entire spectrum of genetic variants influencing drug response. Discovered and validated actionable genetic markers can be implemented in the clinical setting to detect the individuals in need of dosing adjustments for safer, more effective, cost-saving treatments. The main conclusions drawn from this thesis are as follows: • Studies of adverse events (ADE) that are extracted from EHRs and linked with the genetic information of individuals sets a framework for the validation and discovery of potential genetic risk factors for the incidence of ADEs. • EHRs enable the rapid collection of a large number of cases with ADEs, such as hypersensitivity due to penicillin. A strongly significant and replicated association of penicillin allergy with the MHC class I molecule HLA-B*55:01 suggest its role in creating predisposition a hypersensitivity reaction. Further signals of the tag-SNP for the association, which overlapped with regulatory annotations in T cells and correlated with lymphocyte levels, proposes the HLA-B*55:01 alllele's role in T-cell-mediated, delayed type of penicillin allergy. • Genetic variants in the SOST gene that encodes sclerostin have been associated with a higher bone mineral density and lower fracture risk, which lead to the development of romosozumab, a first-in-class sclerostin inhibitor for the treatment of osteoporosis. However, variants mimicking the therapeutic inhibition of sclerostin indicate an association with the increased risk of cardiovascular disease in large-scale biobanks, supporting the evidence of adverse cardiovascular effects reported in clinical trials of romosozumab. This demonstrates the potential value

摘要： Statistical machine learning has played a key role in many areas, such as biology, health sciences, finance and genetics. Important tasks in computational genetics include disease prediction, capturing shapes within images, computation of genetic sharing between pairs of individuals, genome-wide association studies and image clustering. This thesis develops several learning methods to address these computational genetics problems. Firstly, motivated by the need for fast computation of genetic sharing among pairs of individuals, we propose the fastest algorithms for computing the kinship coefficient of a set of individuals with a known large pedigree. {Moreover, we consider the possibility that the founders of the known pedigree may themselves be inbred and compute the appropriate inbreeding-adjusted kinship coefficients, which has not been addressed in literature.} Secondly, motivated by an imaging genetics study of the Alzheimer's Disease Neuroimaging Initiative, we develop a Bayesian bivariate spatial group lasso model for multivariate regression analysis applicable to exam the influence of genetic variation on brain structure and accommodate the correlation structures typically seen in structural brain imaging data. We develop a mean-field variational Bayes algorithm and a Gibbs sampling algorithm to fit the model. We also incorporate Bayesian false discovery rate procedures to select SNPs. The new spatial model demonstrates superior performance over a standard model in our application. Thirdly, we propose the Random Tessellation Process (RTP) to model complex genetic data structures to predict disease status. The RTP is a multi-dimensional partitioning tree with non-axis aligned cuts. We develop a sequential Monte Carlo (SMC) algorithm for inference. Our process is self-consistent and can relax axis-aligned constraints, allowing complex inter-dimensional dependence to be captured. Fourthly, we propose the Random Tessellation with Splines (RTS) to acquire complex

关键词： 动物遗传学   在线开放课程   传统课程  

摘要： 在线开放课程在国内发展近10年,今年受新冠肺炎疫情影响,对在线开放课程需求明显。文章以在线开放课程“动物遗传学”为例,从其发展过程、与传统教学模式下的对比以及教学效果等多个方面分析当前形势下开展“动物遗传学”在线开放课程的可行性和必要性。