Polymorphism of SARS-CoV Genomes

In this work, severe acute respiratory syndrome associated coronavirus (SARS-CoV) genome BJ202 (AY864806) was completely sequenced. The genome was directly accessed from the stool sample of a patient in Beijing. Comparative genomics methods were used to analyze the sequence variations of 116 SARS-CoV genomes (including BJ202) available in the NCBI Gen-Bank. With the genome sequence of GZ02 as the reference, there were 41 polymorphic sites identified in BJ202 and a total of 278 polymorphic sites present in at least two of the 116 genomes. The distribution of the polymorphic sites was biased over the whole genome. Nearly half of the variations (50.4%, 140/278) clustered in the one third of the whole genome at the 3′ end (19.0 kb-29.7 kb). Regions encoding Orf10-11, Orf3/4, E, M and S protein had the highest mutation rates. A total of 15 PCR products (about 6.0 kb of the genome) including 11 fragments containing 12 known polymorphic sites and 4 fragments without identified polymorphic sites were cloned and sequenced. Results showed that 3 unique polymorphic sites of BJ202 (positions 13 804, 15 031 and 20 792) along with 3 other polymorphic sites (26 428, 26 477 and 27 243) all contained 2 kinds of nucleotides. It is interesting to find that position 18379 which has not been identified to be polymorphic in any of the other 115 published SARS-CoV genomes is actually a polymorphic site. The nucleotide composition of this site is A (8) to G (6). Among 116 SARS-CoV genomes, 18 types of deletions and 2 insertions were identified. Most of them were related to a 300 bp region (27 700-28 000) which encodes parts of the putative ORF9 and ORF10-11. A phylogenetic tree illustrating the divergence of whole BJ202 genome from 115 other completely sequenced SARS-CoVs was also constructed. BJ202 was phylogeneticly closer to BJ01 and LLJ-2004.     

Otterlace软件在猪全基因组序列人工注释分析中的应用

2009年11月,美、英等国科学家宣布首次绘制出家猪的基因组草图。近两年,随着全基因组序列陆续释放,越来越多的测序片段得到正确拼接组装,从全基因组水平上对猪功能基因进行注释分析显得尤为迫切。文章以丝切蛋白1(Cofilin 1,CFL1)基因的注释过程为例,介绍了运用Sanger研究所开发的Otterlace软件对猪全基因组的免疫基因序列进行人工分析与注释。通过详细说明Zmap、Blixem和Dotter 3个注释工具的使用方法,并给出了注释过程的主要步骤,以期对Otterlace的应用起一个抛砖引玉的作用。运用Otterlace软件对243个免疫相关基因进行分析,其中180个基因得到完整或部分注释,这为后续深入开展这些基因的功能研究奠定了基础。     

Cost Effectiveness of Different Treatment Strategies in the Treatment of Patients with Moderate to Severe Rheumatoid Arthritis in China

Background

To analyse the cost-effectiveness of traditional disease-modifying anti-rheumatic drugs (tDMARDs) compared to biological therapies from the perspective of Chinese society.

Methodology/Principal Findings

A mathematical model was developed by incorporating the clinical trial data and Chinese unit costs and treatment sequences from a lifetime perspective. Hypothetical cohorts with moderate to severe RA were simulated. The primary outcome measure–quality-adjusted life years (QALYs)–was derived from disease severity (HAQ scores). Primary analysis included drug costs, monitoring costs, and other costs. Probabilistic and one-way sensitivity analyses were performed. Treatment sequences that included TNF antagonists and rituximab produced a greater number of QALYs than tDMARDs alone or TNF antagonists plus DMARDs. In comparison with tDMARDs, the incremental cost-effectiveness ratios (ICERs) for etanercept, infliximab, and adalimumab without rituximab were $77,357.7, $26,562.4 and $57,838.4 per QALY and $66,422.9, $28,780.6 and $50,937.6 per QALY, for etanercept, infliximab, and adalimumab with rituximab. No biotherapy was cost-effective under the willingness to pay threshold when the threshold was 3 times the per capita GDP of China. When 3 times the per capita GDP of Shanghai used as the threshold, infliximab and rituximab could yield nearly 90% cost-effective simulations in probabilistic sensitivity analysis.

Conclusions/Significance

tDMARD was the most cost-effective option in the Chinese healthcare setting. In some relatively developed regions in China, infliximab and rituximab may be a favorable cost-effective alternative for moderate to severe RA.     

退耕还林(草)过程中陕北地区NDVI时空变异及其驱动因子的地理探测

地表植被作为生态环境变化的敏感因子,对维持区域生态稳定性具有重要作用.基于退耕还林(草)生态工程实施过程中2000-2019年陕北地区的MODIS NDVI数据,结合地形、地貌、气候、土壤和植被等环境因子,探究NDVI时空变异特征,并运用地理探测器模型对植被NDVI影响因子及其影响程度进行探测,最终确定主要环境因子对N...     

不同生态区云南黄连居群的染色体核型比较

采用根尖压片和卡宝品红染色法,对分布于高黎贡山的东、西坡不同生态带的8个云南黄连居群进行染色体核型比较分析。结果表明,8个居群染色体数目均为2n=2x=18,核型基本一致,除东坡一个居群为3A型外,其余均为2A型;总体上同一生态区域内各居群的核型表现出较大的相似性,但不同生态区域的居群间却存在较大的差异,主要为近端部和端部着丝点染色体的有无及数目在东西坡居群间存在较大变化;东坡居群的不对称程度均较西坡高。     

全反式维甲酸通过γ-氨基丁酸途径促进小鼠胚胎腭板间充质细胞的凋亡

维甲酸(RA)是一种能够诱导腭裂发生的致畸物．研究显示γ-氨基丁酸(GABA)在腭板的发育过程中发挥重要作用．而GABA是否参与了RA诱导的腭裂发生还不清楚．本研究以小鼠胚胎腭板间充质细胞(MEPM)为研究对象,观察全反式维甲酸(atRA)(0.2、0.67、2.0和 6.7 μmol/L)对MEPM细胞增殖和凋亡的影响,并探讨GABA信号通路在其中的可能作用．结果显示,atRA(2.0 μmol/L和6.7 μmol/L)显著性抑制了MEPM的增殖,并促进了细胞凋亡．atRA(0.67、2.0和 6.7 μmol/L)显著性降低了GABA合成的关键酶谷氨酸脱羧酶(GAD67)mRNA和蛋白质的表达,但对γ-氨基丁酸A型受体-β3(GABAAR-β3)mRNA和蛋白质的表达没有影响．1.0 μmol/L的GABA逆转了atRA(6.7 μmol/L)对MEPM细胞增殖和凋亡的影响．以上结果表明,atRA通过下调GAD67的表达,减少GABA的产生,抑制MEPM的增殖和促进MEPM的凋亡,从而可能影响腭板的发育,诱导腭裂形成．     

纳板河流域土地利用变化对土壤有机碳及微生物生物量碳和氮的影响

与其他地区相比,热带森林的土地利用变化对碳循环的影响尤其显著。本文采用野外调查取样和室内分析相结合的方法,研究了纳板河流域自然林转变为旱地、水稻田、橡胶林、茶园后土壤有机碳(SOC)、土壤微生物生物量碳(SMBC)和微生物生物量氮(SMBN)的变化。结果表明:自然林转变为其他土地利用类型后,SOC、SMBC、SMBN均显著下降,水稻田的SOC和SMBC下降幅度最大。赤红壤的SOC和SMBC、SMBN均显著高于砖红壤。相关性分析表明:SOC与SMBC、SMBN、土壤含水量呈显著或极显著正相关,与土壤容重、pH呈极显著负相关;SMBN与SOC、SMBC呈极显著正相关,与土壤容重呈显著负相关;微生物商与pH呈极显著正相关。     

山楂酸减少L02细胞脂质累积作用的研究(英文)

非酒精性脂肪性肝在发达国家和发展中国家中是一种常见的肝脏疾病。引起非酒精性脂肪性肝病的最常见原因有肥胖、糖尿病和高胆固醇。尽管非酒精性脂肪性肝病的发病率日益升高,事实上至今尚未发现可以用于治疗的药物。山楂酸是一种五环三萜化合物,已报道具有多种药理特性,包括抗炎、抗氧化以及免疫调节作用。我们的前期研究表明,山楂酸能够抑制高脂饲料诱导大鼠非酒精性脂肪性肝病的生成。本研究中,我们将探讨山楂酸体外对肝细胞(LO2)脂质累积的抑制作用。结果表明,山楂酸可抑制游离脂肪酸(FFA)诱导的LO2细胞脂质累积,进一步研究表明,山楂酸可抑制LO2细胞的SCAP mRNA水平和蛋白水平的表达。     

中国东部亚热带地区树轮δ13C方位变化的谐波分析

对浙江天目山2株柳杉(Cryptomeria fortunei Hooibrenk ex Otto et Dietr,分别简称为CF-1,CF-3)及南京紫金山8株马尾松(Pinus massoniana Lamb.,分别简称为PM-1-PM-4,PM-7-PM-10)树轮δ¹³C平均值方位序列及2株柳杉树轮δ¹³C方位平均值年序列进行了谐波分析。分析结果及相关性检验表明,树轮δ¹³C值的方位变化有很强的谐波特征。第1次谐波与第2次谐波分量的方差贡献率占原序列总方差的百分比,除PM-8与PM-10低于70%外,其余均在70％以上,其中,CF-1与PM-9分别达到了93%和96.5％。第1次与第2次(或第3次)谐波的拟合序列与原序列的相关性极高,相关系数均在0.8以上,都通过了0.05的显著性检验,而且,两次谐波的拟合度均比较高,均在75％以上,拟合效果较好。分析结果表明,用2π与π(PM-1与PM-7为2π/3)两个主要谐波周期就可以较好地拟合各树轮δ¹³C序列的方位变化。初相位值的计算结果显示,第1、2次谐波的初相位值存在明显差异,这表明:不同树体2次谐波振幅的峰值出现的方位区域不同,即以2π及以π(PM-1与PM-7为2π/3)为周期的树轮δ¹³C方位变化的极大值并不出现在固定方位区。所以,两次谐波叠加的结果使树轮δ¹³C极值出现的方位区域更复杂。对天目山2株柳杉树轮δ¹³C各方位均值年序列的分析结果表明,2树轮δ¹³C极值均存在明显的年际漂移,其极大值出现频率较高的方位随树木生长坡向而发生转移。两树轮相比,多数年份其δ¹³C的主极大值出现的方位区基本发生45°的方位转移。而主、次极大值叠加的结果却使δ¹³C极值出现的方位基本发生90°的转移,这种极值转移的方向及转移度数与2株树所在坡向的变化和坡向变化度数正好相一致。