Microsatellite instability in gastric cancer: molecular bases,clinical perspectives,and new treatment approaches

Gastric cancer is one of the most aggressive malignancies, with limited treatment options in both locally advanced and metastatic setting, resulting in poor prognosis. Based on genomic characterization, stomach tumour has recently been described as a heterogeneous disease composed by different subtypes, each of them with peculiar molecular aspects and specific clinical behaviour. With an incidence of 22% among all western gastric tumour cases, stomach cancer with microsatellite instability was identified as one of these subgroups. Retrospective studies and limited prospective trials reported differences between gastric cancers with microsatellite stability and those with instability, mainly concerning clinical and pathological features, but also in regard to immunological microenvironment, correlation with prognostic value, and responses to treatment. In particular, gastric cancer with microsatellite instability constitutes a small but relevant subgroup associated with older age, female sex, distal stomach location, and lower number of lymph-node metastases. Emerging data attribute to microsatellite instability status a favourable prognostic meaning, whereas the poor outcomes reported after perioperative chemotherapy administration suggest a detrimental role of cytotoxic drugs in this gastric cancer subgroup. The strong immunogenicity and the widespread expression of immune-checkpoint ligands make microsatellite instability subtype more vulnerable to immunotherapeutic approach, e.g., with anti-PD-L1 and anti-CTLA4 antibodies. Since gastric cancer with microsatellite instability shows specific features and clinical behaviour not overlapping with microsatellite stable disease, microsatellite instability test might be suitable for inclusion in a diagnostic setting for all tumour stages to guarantee the most targeted and effective treatment to every patient.     

Revision of the West Palaearctic species of Rhoptromeris Förster, 1869 (Hymenoptera: Figitidae: Eucoilinae)

The West Palearctic species of Rhoptromeris are revised. A total of 11 species are recognised as valid in this region, including four newly described species: Rhoptromeris dichromata sp. nov., Rhoptromeris koponeni sp. nov., Rhoptromeris leptocornis sp. nov. and Rhoptromeris macaronesiensis sp. nov. Eucoila luteicornis Ionescu, 1959 is synonymised with Rhoptromeris heptoma (Hartig, 1840) syn. nov. A checklist of the Holarctic Rhoptromeris is presented and an identification key to the West Palearctic species is provided. www.zoobank.org/urn:lsid:zoobank.org:pub:8164332C-93E2-4E3F-A408-F5FF5DFB366E     

我国巨型机发展概述

系统地总结和介绍了我国高性能计算机，包括“银河”系列巨型机、“曙光”系列巨型机、“神威”系列巨型机、“深腾”系列巨型机以及“深超”系列巨型机的开发研制以及应用情况。     

The influence of chronic nicotine treatment on stress-induced gastric ulceration and emptying rate in rats.

Ten-day treatment with nicotine (5, 25 or 50 micrograms/ml drinking water) dose-dependently intensified gastric ulceration induced by cold-restraint, and emptying rate. Stomach contractions produced by graded doses of bethanechol i.v. were elevated further by nicotine treatment. It is suggested that chronic nicotine administration produces hypersensitivity of the gastric muscarinic receptors; stomach hypermotility contributes to the ulcer-worsening action of the alkaloid.     

林肯羊与陕北地方绵羊杂交后代产肉性能研究

林肯羊和陕北地方土种绵羊杂交后代,不但能提高当地绵羊的产毛量和羊毛品质,而且能显著地提高产肉量和肉品质,经济效益十分显著。     

森林生物技术走出实验室举步艰难

新的、高密度树木种植正在给林业生物技术带来迅速的变化。但是如果不能克服生态风险和经济障碍．这些新的方法或许永远也无法使用——     

传染病医院污水处理工艺选择案例

文章通过对临汾市传染病医院拟建的传染病区污水的来源、排放量、污染物的分析,结合污水处理原则,提出了具体的污水处理工艺。并根据污染物去除率预测了污染物浓度,与污染物排放标准进行对比分析,结果表明所选工艺处理后的污染物浓度能够达标,污水处理工艺是可行的。     

视觉文化及其教育价值反思

在语言文字文化之后出现的现代视觉文化以其突出的媒介特性对整个文化的特性产生了深刻的影响，文字文本的传统优势地位受到影像文本的挤占，这一变化促进了教育的向前发展，也对教育产生了许多负面影响。解决这一两难问题的策略就是使视觉文化与传统语言文字文化有相结合，各取所长，共同推动教育的繁荣和发展，而且只有当我们的教育工作者、学生以及社会各界对视觉文化有正确的认识，才能令视觉文化朝正确的方向发展，推进教育的进步，而不是等它给我们的教育带来严重恶果时才来思考是谁惹的祸。     

The Shwachman-Bodian-Diamond syndrome protein mediates translational activation of ribosomes in yeast

The autosomal recessive disorder Shwachman-Diamond syndrome, characterized by bone marrow failure and leukemia predisposition, is caused by deficiency of the highly conserved Shwachman-Bodian-Diamond syndrome (SBDS) protein. Here, we identify the function of the yeast SBDS ortholog Sdo1, showing that it is critical for the release and recycling of the nucleolar shuttling factor Tif6 from pre-60S ribosomes, a key step in 60S maturation and translational activation of ribosomes. Using genome-wide synthetic genetic array mapping, we identified multiple TIF6 gain-of-function alleles that suppressed the pre-60S nuclear export defects and cytoplasmic mislocalization of Tif6 observed in sdo1Delta cells. Sdo1 appears to function within a pathway containing elongation factor-like 1, and together they control translational activation of ribosomes. Thus, our data link defective late 60S ribosomal subunit maturation to an inherited bone marrow failure syndrome associated with leukemia predisposition.     

Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL

Resequencing genes provides the opportunity to assess the full spectrum of variants that influence complex traits. Here we report the first application of resequencing to a large population (n = 3,551) to examine the role of the adipokine ANGPTL4 in lipid metabolism. Nonsynonymous variants in ANGPTL4 were more prevalent in individuals with triglyceride levels in the lowest quartile than in individuals with levels in the highest quartile (P = 0.016). One variant (E40K), present in approximately 3% of European Americans, was associated with significantly lower plasma levels of triglyceride and higher levels of high-density lipoprotein cholesterol in European Americans from the Atherosclerosis Risk in Communities Study and in Danes from the Copenhagen City Heart Study. The ratio of nonsynonymous to synonymous variants was higher in European Americans than in African Americans (4:1 versus 1.3:1), suggesting population-specific relaxation of purifying selection. Thus, resequencing of ANGPTL4 in a multiethnic population allowed analysis of the phenotypic effects of both rare and common variants while taking advantage of genetic variation arising from ethnic differences in population history.