Systematic documentation and analysis of human genetic variation in hemoglobinopathies using the microattribution approach

We developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to hemoglobinopathies and thalassemia and implemented microattribution to encourage submission of unpublished observations of genetic variation to these public repositories. A total of 1,941 unique genetic variants in 37 genes, encoding globins and other erythroid proteins, are currently documented in these databases, with reciprocal attribution of microcitations to data contributors. Our project provides the first example of implementing microattribution to incentivise submission of all known genetic variation in a defined system. It has demonstrably increased the reporting of human variants, leading to a comprehensive online resource for systematically describing human genetic variation in the globin genes and other genes contributing to hemoglobinopathies and thalassemias. The principles established here will serve as a model for other systems and for the analysis of other common and/or complex human genetic diseases.     

Mutations in lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome

3MC syndrome has been proposed as a unifying term encompassing the overlapping Carnevale, Mingarelli, Malpuech and Michels syndromes. These rare autosomal recessive disorders exhibit a spectrum of developmental features, including characteristic facial dysmorphism, cleft lip and/or palate, craniosynostosis, learning disability and genital, limb and vesicorenal anomalies. Here we studied 11 families with 3MC syndrome and identified two mutated genes, COLEC11 and MASP1, both of which encode proteins in the lectin complement pathway (collectin kidney 1 (CL-K1) and MASP-1 and MASP-3, respectively). CL-K1 is highly expressed in embryonic murine craniofacial cartilage, heart, bronchi, kidney and vertebral bodies. Zebrafish morphants for either gene develop pigmentary defects and severe craniofacial abnormalities. Finally, we show that CL-K1 serves as a guidance cue for neural crest cell migration. Together, these findings demonstrate a role for complement pathway factors in fundamental developmental processes and in the etiology of 3MC syndrome.     

The stress kinase MKK7 couples oncogenic stress to p53 stability and tumor suppression

Most preneoplastic lesions are quiescent and do not progress to form overt tumors. It has been proposed that oncogenic stress activates the DNA damage response and the key tumor suppressor p53, which prohibits tumor growth. However, the molecular pathways by which cells sense a premalignant state in vivo are largely unknown. Here we report that tissue-specific inactivation of the stress signaling kinase MKK7 in KRas(G12D)-driven lung carcinomas and NeuT-driven mammary tumors markedly accelerates tumor onset and reduces overall survival. Mechanistically, MKK7 acts through the kinases JNK1 and JNK2, and this signaling pathway directly couples oncogenic and genotoxic stress to the stability of p53, which is required for cell cycle arrest and suppression of epithelial cancers. These results show that MKK7 functions as a major tumor suppressor in lung and mammary cancer in mouse and identify MKK7 as a vital molecular sensor to set a cellular anti-cancer barrier.     

Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis

Hajdu-Cheney syndrome is a rare autosomal dominant skeletal disorder with facial anomalies, osteoporosis and acro-osteolysis. We sequenced the exomes of six unrelated individuals with this syndrome and identified heterozygous nonsense and frameshift mutations in NOTCH2 in five of them. All mutations cluster to the last coding exon of the gene, suggesting that the mutant mRNA products escape nonsense-mediated decay and that the resulting truncated NOTCH2 proteins act in a gain-of-function manner.     

The long and winding road from correlation to causation

Follow-up studies of a Crohn's disease risk locus encompassing IRGM have revealed unexpected complexity. A new study shows that a synonymous variant in the IRGM coding region alters a binding site for miR-196 and modulates IRGM-dependent autophagy, adding to the list of possible mechanisms by which this locus influences disease risk.     

近10年江西省自然灾害应急响应的时空分布特征

基于2008-2017年江西省历次启动自然灾害救助应急响应的统计数据,分析研究了江西省自然灾害救助应急响应的时空分布变化规律和特征。结果表明:1)江西省是一个自然灾害多发频发的省份,近10 a启动救助应急响应58次,平均每年要应对近6次重大自然灾害;2)洪涝灾害是江西省自然灾害的主要灾种,近10a针对洪涝灾害启动响应42次、占总数的72%。启动响应依据指标最多的是紧急转移安置人口、其次是因灾死亡人口;3)启动应急响应时间基本在5-8月份,6月份又是最多的月份,表明重特大自然灾害主要发生在5-8月份;4)启动救助应急响应总次数呈现出北部多、南部少的地域分布特征。     

吃哪些鱼会安全

禽流感爆发之后,鱼类又一次被看作是"最安全"的食物。吃鱼真的安全么?生活在水中的鱼类,其肉质健康与否往往和水质的好坏息息相关。以食用的安全性来排序,由高至低应为:海水鱼、淡化养殖海水鱼、淡水鱼。不久前,上海市松江区部分水域出现大量死鱼。经有关部门检测,很可能是因大规模批量放生的鱼不适应温差所致。但是经过这一事件,对食用水产品安全性的担忧又重新进入了我们的视线。到底有哪些鱼类和其他水产品是安全的,又有哪些可能带来疾病隐患?     

Fe/Cr(001)超晶格层间耦合和自旋极化的第一性原理计算

采用基于密度泛函理论的平面波赝势法对Fe／Cr（001）起晶格的层间耦合和自旋极化进行了系统地研究．结果表明：理想Fe／Cr超晶格的层间耦合随反铁磁Cr层层数的增加呈短周期性振荡；在较稳定的结构中，整个Cr层都以较大的磁矩被极化，且极化程度受铁磁层原子数的影响较大．     

Function and evolution of nodulation genes in legumes

Root nodule (RN) symbiosis has a unique feature in which symbiotic bacteria fix atmospheric nitrogen. The symbiosis is established with a limited species of land plants, including legumes. How RN symbiosis evolved is still a mystery, but recent findings on legumes genes that are necessary for RN symbiosis may give us a clue.