In Silico Modeling of Shear-Stress-Induced Nitric Oxide Production in Endothelial Cells through Systems Biology

Nitric oxide (NO) produced by vascular endothelial cells is a potent vasodilator and an antiinflammatory mediator. Regulating production of endothelial-derived NO is a complex undertaking, involving multiple signaling and genetic pathways that are activated by diverse humoral and biomechanical stimuli. To gain a thorough understanding of the rich diversity of responses observed experimentally, it is necessary to account for an ensemble of these pathways acting simultaneously. In this article, we have assembled four quantitative molecular pathways previously proposed for shear-stress-induced NO production. In these pathways, endothelial NO synthase is activated 1), via calcium release, 2), via phosphorylation reactions, and 3), via enhanced protein expression. To these activation pathways, we have added a fourth, a pathway describing actual NO production from endothelial NO synthase and its various protein partners. These pathways were combined and simulated using CytoSolve, a computational environment for combining independent pathway calculations. The integrated model is able to describe the experimentally observed change in NO production with time after the application of fluid shear stress. This model can also be used to predict the specific effects on the system after interventional pharmacological or genetic changes. Importantly, this model reflects the up-to-date understanding of the NO system, providing a platform upon which information can be aggregated in an additive way.     

Deep Whole-Genome Sequencing of 100 Southeast Asian Malays

Whole-genome sequencing across multiple samples in a population provides an unprecedented opportunity for comprehensively characterizing the polymorphic variants in the population. Although the 1000 Genomes Project (1KGP) has offered brief insights into the value of population-level sequencing, the low coverage has compromised the ability to confidently detect rare and low-frequency variants. In addition, the composition of populations in the 1KGP is not complete, despite the fact that the study design has been extended to more than 2,500 samples from more than 20 population groups. The Malays are one of the Austronesian groups predominantly present in Southeast Asia and Oceania, and the Singapore Sequencing Malay Project (SSMP) aims to perform deep whole-genome sequencing of 100 healthy Malays. By sequencing at a minimum of 30× coverage, we have illustrated the higher sensitivity at detecting low-frequency and rare variants and the ability to investigate the presence of hotspots of functional mutations. Compared to the low-pass sequencing in the 1KGP, the deeper coverage allows more functional variants to be identified for each person. A comparison of the fidelity of genotype imputation of Malays indicated that a population-specific reference panel, such as the SSMP, outperforms a cosmopolitan panel with larger number of individuals for common SNPs. For lower-frequency (<5%) markers, a larger number of individuals might have to be whole-genome sequenced so that the accuracy currently afforded by the 1KGP can be achieved. The SSMP data are expected to be the benchmark for evaluating the value of deep population-level sequencing versus low-pass sequencing, especially in populations that are poorly represented in population-genetics studies.     

Synergistic activation of lipopolysaccharide-stimulated glial cells by propofol

Despite the extensive use of propofol in general anesthetic procedures, the effects of propofol on glial cell were not completely understood. In lipopolysaccharide (LPS)-stimulated rat primary astrocytes and BV2 microglial cell lines, co-treatment of propofol synergistically induced inflammatory activation as evidenced by the increased production of NO, ROS and expression of iNOS, MMP-9 and several cytokines. Propofol augmented the activation of JNK and p38 MAPKs induced by LPS and the synergistic activation of glial cells by propofol was prevented by pretreatment of JNK and p38 inhibitors. When we treated BV2 cell culture supernatants treated with LPS plus propofol on cultured rat primary neuron, it induced a significant neuronal cell death. The results suggest that the repeated use of propofol in immunologically challenged situation may induce glial activation in brain.     

黄土高原沟壑区森林带不同植物群落土壤氮素含量及其转化

为了探讨在黄土高原退耕还林还草过程中植物群落对土壤氮素含量及形态分布的影响,本文选择退耕历史较长的黄土高原沟壑区——安塞县洞子沟流域8种典型植物群落下0-10cm和10-20cm的土壤为对象,测定了土壤中有机氮、矿化氮、微生物量氮、硝态氮和铵态氮的含量。结果表明,从草本群落到乔灌草群落,土壤各形态氮素含量均增加,整体表现为乔灌草群落>灌草群落>草本群落。然而人工刺槐林的土壤氮素水平远低于自然恢复的乔灌草群落,甚至低于灌草群落。0-10cm 土层各形态氮素均高于10-20cm 土层。硝态氮对植物群落的变化最为敏感,可作为土壤氮素水平的敏感指标。土壤有机质、pH、容重与氮素含量极显著相关,各种氮素间极显著正相关。各种氮素占总氮的比例对总氮的变化有着不同的响应,有机氮、可矿化氮和微生物量氮占总氮的比例相对稳定,硝态氮占总氮的比例随总氮含量的增加而增加,铵态氮占总氮的比例随总氮含量的增加而降低。     

黄土丘陵区不同植被土壤氮素转化微生物生理群特征及差异

采用最大或然计数法(most probable number, MPN)对黄土高原洞子沟流域不同植被恢复阶段土壤氮素微生物生理群(氨化细菌、亚硝化细菌、反硝化细菌)数量分布特征进行了测定,结果表明:1)土壤氨化细菌、亚硝化细菌和反硝化细菌数量随植被恢复而增加,三者最大值分别为最小值的74、4和31倍,其中氨化细菌和反硝化细菌的数量在铁杆蒿群落最低,辽东栎群落最高,亚硝化细菌数量在丁香群落最低,辽东栎群落最高;2)植被恢复对各氮素生理群影响不同,对氨化细菌影响最大,其次分别为反硝化细菌和亚硝化细菌;3)各氮素生理群数量差异较大,氨化细菌>反硝化细菌>亚硝化细菌。研究区氨化细菌占总数的75%-80%,反硝化细菌占20%-25%时,生态系统最为稳定;4)土壤理化性质与各功能菌关系紧密,其中,土壤容重和硝态氮含量与微生物数量相关性最大,全钾、矿化氮和微生物量氮也表现出很大的相关性。     

黄土丘陵沟壑区不同植被区土壤生态化学计量特征

以黄土丘陵沟壑区3个植被区(森林区、森林草原区、草原区)不同坡向土壤作为研究对象,对土壤有机C、全N、全P、全K含量及其化学计量特征进行了研究.结果表明,不同植被区、坡向和土层土壤养分含量及其化学计量特征均有明显不同.土壤有机C、全N变异性较大,全P、全K变异性较小.表层土壤养分含量显著高于底层土壤;同一土层之间有机C、全N含量变异性较大,全P、全K含量变异性较小.不同坡向之间养分含量不同,阴坡最大,阳坡最小.土壤养分含量受植被类型及植被盖度的影响,森林区＞草原区＞森林草原区.土壤C/N、C/P、C/K、N/P、N/K比都较稳定,C/N比的变化范围为5.65-12.57,平均值为9.44; C/P比的变化范围为3.62-17.32,平均值为8.15;C/K比的变化范围为0.10-0.55,平均值为0.26;N/P比的变化范围为0.43-1.38,平均值为0.86; N/K比的变化范围为0.01-0.05,平均值为0.03;P/K比值较稳定,为0.03.土壤有机C和全N极显著正相关,全N和全P极显著正相关.     

太子参红外指纹图谱的双指标序列分析

本文采用傅里叶变换红外光谱仪测定了四大种植主产区(安徽、江苏、福建、贵州)的栽培品及河南的野生品,共13个批次太子参甲醇提取物,获得不同产地太子参栽培品的FTIR指纹图谱,并对指纹图谱进行了相似度的计算,同时结合(共有峰率,变异峰率)双指标序列分析方法,对不同产地太子参的FTIR光谱进行了研究。结果表明,该方法所建立的太子参FTIR指纹图谱能够区分栽培品和野生品的差异,双指标序列分析法能够为产区间和产区内太子参品质差异提供参考,两种分析方法结合可为该药材的质量分析、评价与控制提供依据。     

单纯疱疹病毒1型引起的发热出疹性疾病需要与手足口病进行鉴别

对2008年在甘肃省发生的一起疑似手足口病(HFMD)的发热出疹性疾病的流行进行病原体的实验室检测,明确引起这起传染病流行的病原体。从4名发热出疹患者采集的8份临床标本中(每个患者采集咽拭子和疱疹液标本),首先将临床标本接种到RD和HEp-2细胞上进行病毒分离,对病毒分离阳性的标本提取病毒核酸,然后使用荧光定量-逆转录-聚合酶链式反应(RT-PCR)进行人肠道病毒(HEV)核酸的检测。对HEV检测结果阴性的标本采用序列非依赖的单引物扩增技术(SISPA)进行"未知病原体"的鉴定。分离到的6株病毒均鉴定为单纯疱疹病毒I型(HSV-1),结合分析这起流行中患者的临床表现、流行病学调查结果以及实验室检测结果,表明HSV-1是引起这起发热出疹性疾病流行的病原体。6株HSV-1的gG区核苷酸和氨基酸水平上差异都较小,同源性分别高达98.8%和97.9%,说明这起疫情是由同一个病毒传播链引起的。HSV-1等病毒引起的发热出疹性疾病需要与HFMD进行鉴别诊断,由于仅从临床症状和流行病学资料上判断引起发热出疹性疾病的病原体是非常困难的,因此,必须依赖于实验室的诊断。     

4019例妇科门诊不同症状患者阴道微生态状况分析

目的探讨妇科门诊不同症状患者的阴道微生态状况。方法回顾性分析2011年11月至2012年9月西安交通大学医学院第一附属医院妇科门诊因不同症状就诊患者的阴道微生态评价（菌群的密集度、多样性、优势菌、病原菌、AV评分、Nugent评分及五项菌群功能及炎症反应指标）检测结果。结果4019例被检查者平均年龄为33．56岁。其中阴道微生态正常占n70％（28／4019）;阴道微生态失调者占99．30％（3991／4019）;后者包括未明确感染的阴道微生态失调患者占66．36％（2667／4019）;明确感染的阴道微生态失调患者占32．94％（1324／4019）;其中外阴阴道假丝酵母菌病（vulvovaginal candidiasis,VVC）患者占24．33％（978／4019）;需氧菌陛阴道炎（aerobic vaginitis,AV）患者占3．11％（125／4019）;细菌性阴道病（bacterial vaginosis,BV）患者占3．14％（126／4019）;滴虫阴道炎（trichomonas vaginitis,TV）患者占5．15％（207／4019）;混合感染患者占8．31％（110／1324）。优势菌群异常患者占54．32％（2183／4019）。结论妇科门诊中未明确感染的阴道微生态失调患者构成比最高;在明确感染的患者中外阴阴道假丝酵母菌病构成比最高;因此阴道微生态评价成为阴道感染性疾病诊断首选检测方法,在临床诊疗实践中具有重要意义。