Drawing inferences about the coancestry coefficient

The coancestry coefficient, also known as the population structure parameter, is of great interest in population genetics. It can be thought of as the intraclass correlation of pairs of alleles within populations and it can serve as a measure of genetic distance between populations. For a general class of evolutionary models it determines the distribution of allele frequencies among populations. Under more restrictive models it can be regarded as the probability of identity by descent of any pair of alleles at a locus within a random mating population. In this paper we review estimation procedures that use the method of moments or are maximum likelihood under the assumption of normally distributed allele frequencies. We then consider the problem of testing hypotheses about this parameter. In addition to parametric and non-parametric bootstrap tests we present an asymptotically-distributed chi-square test. This test reduces to the contingency-table test for equal sample sizes across populations. Our new test appears to be more powerful than previous tests, especially for loci with multiple alleles. We apply our methods to HapMap SNP data to confirm that the coancestry coefficient for humans is strictly positive.     

CGI-58在动物脂类代谢中的作用

细胞中脂滴(Lipid droplets, LDs)表面存在多个调控脂肪储存和分解的蛋白, 这些蛋白对机体的脂肪代谢起着很重要的调控作用。CGI-58(Comparative gene identification-58)分布在LDs表面, 属于α/β水解酶折叠家族, 是脂肪甘油三酯脂肪酶(Adipose triglyceride lipase, ATGL)和依赖酰基辅酶A溶血磷脂酸酰基转移酶(Lysophosphatidic acid acyltransferase, LPAAT)的激活剂。在脂肪分解过程中, CGI-58结合PAT蛋白家族成员之一的脂滴包被蛋白(Perlipin)和ATGL, 促进脂肪分解, 同时CGI-58对ATGL的激活功能受脂滴包被蛋白家族成员间蛋白质与蛋白质相互作用的影响。文章结合国内外研究热点, 针对CGI-58在动物脂类代谢中的作用进行了综述。     

Developing environmental performance indicators for food and beverage processors in the USA

Despite consumer and regulatory focus on the quality of final food and beverage (F&B) products, little attention is given to the release and management of toxic chemicals by F&B processors. This study develops five plant-level indicators of environmental performance specific to toxic chemicals. Our findings suggest that (i) only few F&B processors invest in toxic chemical prevention activities; (ii) the major toxic chemical management strategy is treatment rather than recycling or energy recovery; (iii) F&B processors, on average, have improved their toxic chemical management rates between 2001 and 2012; and (iv) there is evidence for homogeneous performance across similar producers in the F&B processing industry but there is no evidence for the role of socio-economic characteristics of surrounding communities on the environmental performance of F&B processors.     

A protein-kinase, IFN-inducible double-stranded RNA dependent inhibitor and repressor of p58 (PRKRIR) enhances type I IFN-mediated antiviral response through the stability control of RIG-I protein

The cellular RIG-I-like receptor (RLR) senses pathogenic RNA molecular patterns and transmits signals for type I interferon (IFN) production. It acts as a center for antiviral responses, and large numbers of RIG-I (retinoic acid inducible gene-I) interacting proteins are identified as signaling regulators. In the present study, we report PRKRIR, a negative regulator of PKR inhibitor, as a novel RIG-I interacting protein. In HEK293FT cells, PRKRIR synergistically enhances type I IFN production mediated by a signal activated- or constitutively active form of RIG-I. The C-terminal domain of the PRKRIR was required for physical interaction and the signal augmentation. The PRKRIR blocks poly-ubiquitination and protein degradation of RIG-I, thereby increasing cellular levels of RIG-I proteins. Furthermore, overexpression of PRKRIR, along with a signal activated- or constitutively active form of RIG-I, efficiently inhibits virus replication in the infected host. In conclusion, PRKRIR provides a novel positive regulator controlling the RIG-I-IFN production system through protein stability control.     

The effect of gastric inhibitory polypeptide on intestinal glucose absorption and intestinal motility in mice

Holocarboxylase synthetase (HLCS) catalyzes the covalent binding of biotin to both carboxylases in extranuclear structures and histones in cell nuclei, thereby mediating important roles in intermediary metabolism, gene regulation, and genome stability. HLCS has three putative translational start sites (methionine-1, -7, and -58), but lacks a strong nuclear localization sequence that would explain its participation in epigenetic events in the cell nucleus. Recent evidence suggests that small quantities of HLCS with a start site in methionine-58 (HLCS58) might be able to enter the nuclear compartment. We generated the following novel insights into HLCS biology. First, we generated a novel HLCS fusion protein vector to demonstrate that methionine-58 is a functional translation start site in human cells. Second, we used confocal microscopy and western blots to demonstrate that HLCS58 enters the cell nucleus in meaningful quantities, and that full-length HLCS localizes predominantly in the cytoplasm but may also enter the nucleus. Third, we produced recombinant HLCS58 to demonstrate its biological activity toward catalyzing the biotinylation of both carboxylases and histones. Collectively, these observations are consistent with roles of HLCS58 and full-length HLCS in nuclear events. We conclude this report by proposing a novel role for HLCS in epigenetic events, mediated by physical interactions between HLCS and other chromatin proteins as part of a larger multiprotein complex that mediates gene repression.     

Golgi 58K-like protein in pollens and pollen tubes ofLilium davidii

In animal cells, Golgi apparatus is located near the microtubule organizing center (MTOC) and its position is determined partly by 58K protein. By sodium dodecyl-sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immuno-blotting methods, a 58K-like protein has been found in pollen grains and pollen tubes of Lilium davidii. Its molecular weight is very similar to that of the 58K protein of animal cells. By immunofluorescence labeling, under a confocal laser scanning microscope (CLSM), the animal 58K antibody revealed a punctate staining in pollen grains and pollen tubes, which is consistent with the distribution of Golgi apparatus in plant cells. In addition, immuno-gold labeling and transmission electron microscopy showed that the 58K-like protein bound mainly to the membrane of vesicles-like structure near Golgi apparatus. This is the first demonstration of the 58K-like protein in plant cells.     

Lipid droplet proteins and metabolic diseases

Lipid droplets (LDs) are ubiquitous cellular organelles for lipid storage which are composed of a neutral lipid core bounded by a protein decorated phospholipid monolayer. Although lipid storage is their most obvious function, LDs are far from inert as they participate in maintaining lipid homeostasis through lipid synthesis, metabolism, and transportation. Furthermore, they are involved in cell signaling and other molecular events closely associated with human disease such as dyslipidemia, obesity, lipodystrophy, diabetes, fatty liver, atherosclerosis, and others. The last decade has seen a great increase in the attention paid to LD biology. Regardless, many fundamental features of LD biology remain obscure. In this review, we will discuss key aspects of LD biology including their biogenesis, growth and regression. We will also summarize the current knowledge about the role LDs play in human disease, especially from the perspective of the dynamics of the associated proteins. This article is part of a Special issue entitled Cardiac adaptations to obesity, diabetes and insulin resistance, edited by Professors Jan F.C. Glatz, Jason R.B. Dyck and Christine Des Rosiers.     

人乳头瘤病毒(HPV)58型DNA疫苗免疫原性的初步分析

为了检测HPV 58型不同L1基因的DNA疫苗的免疫原性,以pcDNA3.1为载体分别构建含HFV 58型不同L1基因的DNA疫苗,命名为L1h、L1h△c、L1S、L1SM和L1wt.用免疫印迹法检测各DNA疫苗的体外表达情况;各重组质粒与pcDNA3.1-h58L2和pcDNA3.1-GFP共转染293FT细胞,检测其形成假病毒的能力;并将各DNA疫苗肌肉注射免疫小鼠,利用假病毒中和实验检测中和抗体水平,用ELISPOT检测细胞免疫情况.结果显示,本实验成功构建了五种DNA疫苗,L1h△c的体外表达量最高,L1S和L1SM的表达量次之,L1wt没有表达;重组质粒L1S能够形成假病毒,而其他四种重组质粒均不能形成假病毒.L1S和L1h均可在小鼠体内诱导中和抗体,但L1S诱导的中和抗体的平均滴度为1:6 400,明显高于L1h诱导的中和抗体水平(平均滴度为1:48),而其他疫苗在小鼠体内未产生中和抗体.对五种疫苗均未检测出特异性的细胞免疫反应.结果提示,体外能够组装成假病毒的DNA疫苗在免疫动物后可诱导高滴度的中和抗体,为今后DNA疫苗的筛选提供参考.