A variant in IL6ST with a selective IL-11 signaling defect in human and mouse

The GP130 cytokine receptor subunit encoded by IL6ST is the shared receptor for ten cytokines of the IL-6 family. We describe a homozygous non-synonymous variant in IL6 ST(p.R281 Q) in a patient with craniosynostosis and retained deciduous teeth. We characterize the impact of the variant on cytokine signaling in vitro using transfected cell lines as well as primary patient-derived cells and support these findings using a mouse model with the corresponding genome-edited variant Il6 st p.R279 Q. We show that human GP130 p.R281 Q is associated with selective loss of IL-11 signaling without affecting IL-6, IL-27, OSM, LIF, CT1, CLC, and CNTF signaling. In mice Il6 st p.R279 Q lowers litter size and causes facial synostosis and teeth abnormalities. The effect on IL-11 signaling caused by the GP130 variant shows incomplete penetrance but phenocopies aspects of IL11 RA deficiency in humans and mice. Our data show that a genetic variant in a pleiotropic cytokine receptor can have remarkably selective defects.

中国和英国子宫内膜异位症患者的发病相关因素分析

目的研究子宫内膜异位症发病的相关因素及其在中国和英国患者之间可能的差异。方法采用病例对照研究方法,选取英国牛津John Radcliffe Hospital收治的子宫内膜异位症患者387例和非子宫内膜异位症患者199例、广州中医药大学第一附属医院收治的子宫内膜异位症患者101例和非子宫内膜异位症患者50例分别为病例组和对照组。通过标准化的WERF EPHect调查问卷,收集4组人群的身高、体质量、体质量指数、婚姻状况、工作状况、月经情况、生育情况、手术原因等临床资料并进行统计分析。结果多因素Logistic回归分析结果显示,英国患者中体质量指数、因痛经进行手术、怀孕史、既往子宫内膜异位症手术次数、工作情况等均与子宫内膜异位症的发生相关(P<0.05),而中国患者中痛经史与子宫内膜异位症的发生相关(P<0.05)。结论痛经可能是中国和英国子宫内膜异位症患者最主要的相关因素;同时,子宫内膜异位症发生的相关因素在中国和英国患者之间可能存在差异。

Identification of Genetic Variants Underlying Anxiety and Multiple Sclerosis in Heterogeneous Stock Rats

Identifying genetic variants that contribute to phenotypic variation is expected to provide insights into the etiology of complex traits. Here we show how combining genetic mapping in an outbred population of rats with sequence data from the progenitors of the population made it possible to identify causal variants and genes for a large number of phenotypes. We identified 355 genomic loci contributing to 122 measures relevant to six models of disease, including fear-related behaviors and experimental autoimmune encephalomyelitis. At 35 of those loci we identified the responsible gene, and in some cases, the responsible variant.

I3:A Self-organising Learning Workflow for Intuitive Integrative Interpretation of Complex Genetic Data

We propose a computational workflow(I3)for intuitive integrative interpretation of complex genetic data mainly building on the self-organising principle.We illustrate the use in interpreting genetics of gene expression and understanding genetic regulators of protein phenotypes,particularly in conjunction with information from human population genetics and/or evolutionary history of human genes.We reveal that loss-of-function intolerant genes tend to be depleted of tissue-sharing genetics of gene expression in brains,and if highly expressed,have broad effects on the protein phenotypes studied.We suggest that this workflow presents a general solution to the challenge of complex genetic data interpretation.I3 is available at http://suprahex.r-forge.r-project.org/I3.html.

1型糖尿病患儿的筛查 值得深思和进一步研究

1921年胰岛素的发现,使糖尿病成为一种慢性疾病,患者不再被判"死刑"。100年后胰岛素仍然是1型糖尿病唯一的治疗手段。但是,新策略的出现正在为患儿的生活提供一条不同的道路。

Single probes and resonant four-wave-mixing enabling novel correlative light electron microscopy workflow

Correlative light electron microscopy prefers single probes with stable performance in both optical and electron microscopy.Now researchers have shown how to harness gold nanoparticles featuring exceptional photostability and four-wave-mixing nonlinearity to realize a new correlation imaging approach.