Structural variation in two human genomes mapped at single-nucleotide resolution by whole genome de novo assembly

Here we use whole-genome de novo assembly of second-generation sequencing reads to map structural variation (SV) in an Asian genome and an African genome. Our approach identifies small- and intermediate-size homozygous variants (1-50 kb) including insertions, deletions, inversions and their precise breakpoints, and in contrast to other methods, can resolve complex rearrangements. In total, we identified 277,243 SVs ranging in length from 1-23 kb. Validation using computational and experimental methods suggests that we achieve overall <6% false-positive rate and <10% false-negative rate in genomic regions that can be assembled, which outperforms other methods. Analysis of the SVs in the genomes of 106 individuals sequenced as part of the 1000 Genomes Project suggests that SVs account for a greater fraction of the diversity between individuals than do single-nucleotide polymorphisms (SNPs). These findings demonstrate that whole-genome de novo assembly is a feasible approach to deriving more comprehensive maps of genetic variation.     

金匮肾气丸和男宝胶囊对肾阳虚证雄性大鼠生殖能力影响的干预研究

目的:研究金匮肾气丸和男宝胶囊对肾阳虚证雄性大鼠生殖能力的影响及作用机理.方法:用成年雄性SD大鼠80只随机分成4组:空白对照组(正常组)、金匮肾气丸组、男宝胶囊组、模型组.除正常组外,其他组大鼠用氢化可的松注射液制造肾阳虚模型.正常组和模型组用等体积蒸馏水灌胃,治疗组用相应剂量的药物灌胃,持续给药30d.检测各组大鼠左侧睾丸、脾脏、胸腺质量,测血清睾丸酮(T)、促黄体生成激素(LH)、促卵泡生成激素(FSH)水平,精子密度、精子活率改变情况.结果:模型组左侧睾丸、脾脏、胸腺质量低于正常组、金匮肾气丸组和男宝胶囊组(P.∞.05 o模型组血清T、LH、FSH水平低于正常组、金匮肾气丸组和男宝胶囊组(P＜0.05).模型组精子密度、精子活率低于正常组、金匮肾气丸组和男宝胶囊组(P＜0.05).结论:金匮肾气丸和男宝胶囊对肾阳虚证雄性大鼠生殖能力有较好的治疗作用.     

内蒙古赛罕乌拉国家级自然保护区猞猁食物构成初步分析

猞猁(Lynxlynx)是内蒙古赛罕乌拉国家级自然保护区内的顶级捕食者,在维持该地区生态平衡和调节猎物数量上具有重要地位。分析猞猁粪便样品残留物不仅能明确其猎物构成,了解与同域分布其他捕食者的关系,还能为制定物种保护措施和栖息地管理策略提供科学参考。本研究在2006至2008年间利用样线法在该区域收集到35份猞猁粪便样品。通过相对出现频率法对粪样进行食性分析,发现猞猁的主要食物组成以蒙古兔(Lepus tolai,30.85%)和植物(28.72%)较多;年度(χ~2=18.696,P <0.001)和季节性(χ~2=74.695,P <0.001)食物构成均存在显著差异。结果表明,蒙古兔在猞猁的食物组成中占最重要地位;猞猁的食物构成与季节有关,寒冷季节捕食大型猎物,而温暖季节捕食的小型猎物更常见。     

MORC4 is a novel breast cancer oncogene regulated by miR-193b-3p

A better understanding of breast cancer pathogenesis would contribute to improved diagnosis and therapy and potentially decreased mortality rates. Here, we found that the MORC family CW-type zinc finger 4 (MORC4) overexpression in breast cancer tissues is associated with poor survival, and the short-interfering RNA knockdown of MORC4 suppresses the growth of breast cancer cells by promoting apoptosis. To investigate the mechanisms associated with MORC4 upregulation, microRNAs potentially targeting MORC4 were analyzed, with miR-193b-3p identified as the regulator and a negative correlation between miR-193b-3p and MORC4 expression determined in both breast cancer cell lines and tissues. Further analysis verified that MORC4 silencing did not affect miR-193b-3p expression, although altered miR-193b-3p expression attenuated MORC4 protein levels. Moreover, dual-luciferase reporter assays verified miR-193b-3p binding to the 3′ untranslated region of MORC4. Furthermore, restoration of miR-193b-3p expression in breast cancer cells led to decreased growth and activation of apoptosis, which was consistent with results associated with MORC4 silencing in breast cancer cells. These results identified MORC4 as differentially expressed in breast cancer cells and tissues and its downregulation by miR-193b-3p, as well as its roles in regulating the growth of breast cancer cells via regulation of apoptosis. Our findings offer novel insights into potential mechanisms associated with breast cancer pathogenesis.     

Quality,bioactivity study,and preclinical acute toxicity,safety pharmacology evaluation of PEGylated recombinant human endostatin (M2ES)

Endostar, a potent endogenous antiangiogenic factor, is wildly used in clinics. However, it was easily degraded by enzymes and rapidly cleared by the kidneys. To overcome these shortcomings, PEGylated recombinant human endostatin was developed. In this study, the purity of M₂ES was evaluated by silver stain and reversed‐phase high‐performance liquid chromatography. Ultraviolet spectrum was used to examine the structural of M₂ES and endostar. The bioactivity and antitumor efficacy of M₂ES were evaluated using an in vitro endothelial cell migration model and athymic nude mouse xenograft model of a heterogeneous lung adenocarcinoma, respectively. A preclinical study was performed to evaluate the acute toxicity and safety pharmacology in rhesus monkeys. The purity of M₂ES was more than 98%; PEG modification has no effect on endostatin structure. Compared with the control group, M₂ES dramatically retards endothelial cell migration and tumor growth. After intravenous (IV) infusions of M₂ES at a dose level of three and 75 mg/kg in rhesus monkeys, there was no observable serious adverse event in both acute toxicity and safety pharmacology study. On the basis of the quality and bioactivity study data of M₂ES and the absence of serious side effect in rhesus monkeys, M₂ES was authorized to initiate a phase I clinical trial.     

一种新型一体化防护服的抗荷性能

目的:探讨一种新型一体化防护服(IPS)的抗荷性能.方法:在离心机上首先测定10名受试者的基础 Gz耐力,然后受试者穿IPS充气,测此时的松弛耐力,两者之差即为IPS的抗荷性能.结果:受试者穿IPS时的松弛耐力明显高于基础耐力(P＜0.01),其抗荷性能达到(2.38±0.38)G.结论:IPS的抗荷性能较好,可满足我国高性能战斗机的需要.     

抗HIV-1 gp160独特型阳性抗体的序列分析及表达

为了确定从噬菌体抗体文库中筛选出的抗体的属性和方便目的基因的表达及其产物的纯化,对两株具有“１Ｆ７”独特型的抗ＨＩＶ－１ｇｐ１６０抗体基因进行了序列分析并构建了可溶性表达载体．发现３Ｂ株含有完整的Ｆａｂ段,１Ｄ株只有重链Ｆｄ段．序列测定表明两株克隆的Ｆｄ段基因完全相同,其可变区ＶＨ属于ＶＨⅠ亚群,而３Ｂ株的“轻链”序列与已知的人的κ和λ轻链无同源性．用从另外的Ｆａｂ抗体文库中筛选出来的３株抗乙肝表面抗原抗体的轻链与３Ｂ的重链重组,并选择一个ＨＩＶ－１ｇｐ１６０特异性较好的重组抗体株,命名为３Ｂｓ．构建了１Ｄ株与３Ｂｓ株的可溶性表达载体,免疫印迹实验证实了具有“１Ｆ７”独特型的抗ｇｐ１６０独特型阳性抗体的表达．     

Preparation of lignosulfonate‐based nanofiltration membranes with improved water desalination performance

Pulping and papermaking generate large amounts of waste in the form of lignosulfonates which have limited valorized applications so far. Herein, we report a novel lignosulfonate‐based nanofiltration membrane, prepared by using polyethylenimine (PEI) and sodium lignosulfonate (SL) via a layer‐by‐layer (LbL) self‐assembly. As a low‐cost and renewable natural polyelectrolyte, SL is selected to replace the synthetic polyelectrolyte commonly used in the conventional LbL fabrication for composite membranes. The prepared LbL (PEI/SL)₇ membranes were crosslinked by glutaraldehyde (GA) to obtain (PEI/SL)₇‐GA membranes with compact selective layer. We characterized (PEI/SL)₇ and (PEI/SL)₇‐GA membranes to study the chemical compositions, morphologies, and surface hydrophilicity. To improve the nanofiltration performances of the (PEI/SL)₇‐GA membranes for water desalination, we investigated the effects of the crosslinking time, GA concentration and the NaCl supporting electrolyte on membrane structure and performance. The optimized (PEI/SL)₇‐GA membrane exhibited a permeating flux up to 39.6 L/(m²·h) and a rejection of 91.7% for the MgSO₄ aqueous solution 2.0 g/L concentration, showing its promising potential for water desalination. This study provides a new approach to applying the underdeveloped lignin‐based biomass as green membrane materials for water treatment.     

Hydrogen sulphide reduces hyperhomocysteinaemia-induced endothelial ER stress by sulfhydrating protein disulphide isomerase to attenuate atherosclerosis

Hyperhomocysteinaemia (HHcy)-impaired endothelial dysfunction including endoplasmic reticulum (ER) stress plays a crucial role in atherogenesis. Hydrogen sulphide (H₂S), a metabolic production of Hcy and gasotransmitter, exhibits preventing cardiovascular damages induced by HHcy by reducing ER stress, but the underlying mechanism is unclear. Here, we made an atherosclerosis with HHcy mice model by ApoE knockout mice and feeding Pagien diet and drinking L-methionine water. H₂S donors NaHS and GYY4137 treatment lowered plaque area and ER stress in this model. Protein disulphide isomerase (PDI), a modulation protein folding key enzyme, was up-regulated in plaque and reduced by H₂S treatment. In cultured human aortic endothelial cells, Hcy dose and time dependently elevated PDI expression, but inhibited its activity, and which were rescued by H₂S. H₂S and its endogenous generation key enzyme-cystathionine γ lyase induced a new post-translational modification-sulfhydration of PDI. Sulfhydrated PDI enhanced its activity, and two cysteine-terminal CXXC domain of PDI was identified by site mutation. HHcy lowered PDI sulfhydration association ER stress, and H₂S rescued it but this effect was blocked by cysteine site mutation. Conclusively, we demonstrated that H₂S sulfhydrated PDI and enhanced its activity, reducing HHcy-induced endothelial ER stress to attenuate atherosclerosis development.