ATM protein kinase: the linchpin of cellular defenses to stress

ATM is the most significant molecule involved in monitoring the genomic integrity of the cell. Any damage done to DNA relentlessly challenges the cellular machinery involved in recognition, processing and repair of these insults. ATM kinase is activated early to detect and signal lesions in DNA, arrest the cell cycle, establish DNA repair signaling and faithfully restore the damaged chromatin. ATM activation plays an important role as a barrier to tumorigenesis, metabolic syndrome and neurodegeneration. Therefore, studies of ATM-dependent DNA damage signaling pathways hold promise for treatment of a variety of debilitating diseases through the development of new therapeutics capable of modulating cellular responses to stress. In this review, we have tried to untangle the complex web of ATM signaling pathways with the purpose of pinpointing multiple roles of ATM underlying the complex phenotypes observed in AT patients.     

Recessive LAMC3 mutations cause malformations of occipital cortical development

The biological basis for regional and inter-species differences in cerebral cortical morphology is poorly understood. We focused on consanguineous Turkish families with a single affected member with complex bilateral occipital cortical gyration abnormalities. By using whole-exome sequencing, we initially identified a homozygous 2-bp deletion in LAMC3, the laminin γ3 gene, leading to an immediate premature termination codon. In two other affected individuals with nearly identical phenotypes, we identified a homozygous nonsense mutation and a compound heterozygous mutation. In human but not mouse fetal brain, LAMC3 is enriched in postmitotic cortical plate neurons, localizing primarily to the somatodendritic compartment. LAMC3 expression peaks between late gestation and late infancy, paralleling the expression of molecules that are important in dendritogenesis and synapse formation. The discovery of the molecular basis of this unusual occipital malformation furthers our understanding of the complex biology underlying the formation of cortical gyrations.     

DNMT3A mutations in acute myeloid leukemia

New studies reveal that 20% of individuals with acute myeloid leukemia harbor somatic mutations in DNMT3A (encoding DNA methyltransferase 3A). Although these leukemias have some gene expression and DNA methylation changes, a direct link between mutant DNMT3A, epigenetic changes and pathogenesis remains to be established.     

Multiple newly identified loci associated with prostate cancer susceptibility

Prostate cancer is the most common cancer affecting males in developed countries. It shows consistent evidence of familial aggregation, but the causes of this aggregation are mostly unknown. To identify common alleles associated with prostate cancer risk, we conducted a genome-wide association study (GWAS) using blood DNA samples from 1,854 individuals with clinically detected prostate cancer diagnosed at 相似文献   

The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm

Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD) and type 2 diabetes (T2D), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) = 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.     

悬空轨枕对轨道结构动力响应的影响

首先建立了带有悬空轨枕的铁路轨道数学模型,在此基础上推导了车—轨系统运动方程,其中考虑了轮轨非线性接触力引起的非线性问题,然后利用逐步积分法解方程重点分析了悬空轨枕对轨道各个组成部分动力响应的影响,结果表明如果在悬空部分存在轨道不平顺,会引起很大的轨枕加速度和轮轨接触力     

洋葱性状的回归分析

本文就洋葱鳞茎的颈粗、横径、纵径、生物产量、叶数与鳞茎鲜重进行了回归分析,结果表明:洋葱鳞茎的横径、纵径、单株生物产量与洋葱鲜重之间的回归关系显著,横径的作用大于纵径。     

连载二洋兰

4.卡特兰属的古塔塔C.guttata（同种异名C.leopoldii） 卡特兰属中蛔古塔塔C.guttata（同种异名C.leopoldii）是卡特兰属中双叶小花系种类，原生于巴西东海岸低地至海拔400米左右的地区。古塔塔guttata的语意是[泪斑]，是因花瓣上有似泪花斑点，而被除数定为种名。南半球的巴西是在1-2月开花，北半球是在7月左右开花。花数可有6-15朵，花虽不很大，植株可高达1.5米，是卡特兰中植株最高的种类。花期长，有芳香味，花的色彩也很多。     

Do prostaglandins mediate the somatostatin preventive effect on gastric lesion?

Summary The inhibition of endogenous prostaglandin synthesis by indomethacin treatment blocks the somatostatin preventive effect on the gastric lesions induced in a stress model and has no preventive effect on an intragastric distension model.     

Enhancement of drug activity by chymotrypsin. Penicillin penetration into granulomatous lesions and inflammatory fluids

Résumé L'enzyme chymotrypsine protéolytique rehausse sensiblement la pénétration de la pénicilline G par voie intra-musculaire dans le sérum, les tissus granulomateux et le fluide péritonéal enflammé des rats.