应用基因工程技术生产IL-11和IL-12

目前武汉大学生命科学学院科研人员针对人体失血和免疫功能下降,应用基因工程技术生产出了人白细胞介素-11(即IL-11)和人白细胞介素-12(即IL-12)。 1 IL-11为人体自然产生的细胞生长因子,能增加血小板,提高凝血速度,防止伤口出血不止,在临床上用来治疗低血小板症,还能辅助治疗癌症,主要用于化疗。克隆于载体,通过大肠杆菌充分表达,经分离、纯化和精制,生产出质量很高的医用成药,故疗效很好。 2 IL-12这是目前在细胞素中发现对人体免疫活性细胞诱导和调节最强、范围最广的一种。其研制技术是将IL-12的两种不同来源的基因克隆于昆虫病毒载体,在昆虫细胞内表达,经分离纯化成工程蛋白,再制备成医药产品。它能诱导干扰素的产生,激活T细胞和NK细胞产生肿瘤坏死因子,能抗利什曼原虫、疟原虫、结核杆菌、血吸虫、肿瘤和病毒及其各相应的疾病,故美国基因研究所和惠施-阿耶斯特制药公司将它用于治疗艾滋病和肿瘤病,效果很好。秦春圃     

Senescence—like changes induced by expression of p21^Waf1／Cip1 in NIH3T3 cell line

P21^Waf1/Cip1 is a potent cyclin-dependent kinase inhibitor.As a downstream mediator of P53,P21^Waf1/Cip1 involves in cell cycle arrest,differentiation and apoptosis.Previous studies in human cells provided evidence for a link between P21^Waf1/Cip1 and cellular senescence.While in murine cells,the role of P21^Waf1/Cip1 is indefinite.We explored this issue using NIH3T3 cells with inducible P21^Waf1/Cip1 expression.Induc-tion of P21^Waf1/Cip1 triggered G1 growth arrest, and NIH3T3-p21 cells exhibited morphologic features,such as enlarged and flattened cellular shape,specific to the senescence phenotype.We also showed that P21^Waf1/Cip1-transduced NIH3T3 cells expressed β-galactosidase activity at pH6.0 ,which is known to be a marker of senescence.Our results suggest that P21^Waf1/Cip1 can also induce senescence-like changes in murine cells.     

Gene Regulatory Networks in the Genomics Era

<正>The precise regulation of gene expression is critical to the normal development and biological function of all organisms. Dysregulation of gene expression during early development can result in a spectrum of failures ranging from minor defects to the termination of development. In adult life, dysregulation ncan lead to     

重组定点突变巴曲酶酶学性质研究

目的对重组定点突变巴曲酶的酶学性质进行研究,为开发成临床用药奠定基础。方法测定不同的温度、pH缓冲液和金属离子等条件对重组定点突变巴曲酶活性的影响。结果重组定点突变巴曲酶的最适pH值在6．5～7．5之间。该酶在50℃以下活力保持90％以上,但当温度超过60℃时,该酶已完全失活。Ca^2＋和Na^＋离子对酶的稳定性无明显影响,而Mg^2＋、K^＋、Mn^2＋离子则表现为激活作用,Zn^2、＋Cu^2＋、Fe^2＋、Co^＋离子则表现为明显的抑制作用。结论重组定点突变巴曲酶在中性条件下比较稳定,它不耐高温,金属离子对其活性有一定的影响。     

A head-to-head comparison of four artemisinin-based combinations for treating uncomplicated malaria in African children: a randomized trial

Background

Artemisinin-based combination therapies (ACTs) are the mainstay for the management of uncomplicated malaria cases. However, up-to-date data able to assist sub-Saharan African countries formulating appropriate antimalarial drug policies are scarce.

Methods and Findings

Between 9 July 2007 and 19 June 2009, a randomized, non-inferiority (10% difference threshold in efficacy at day 28) clinical trial was carried out at 12 sites in seven sub-Saharan African countries. Each site compared three of four ACTs, namely amodiaquine-artesunate (ASAQ), dihydroartemisinin-piperaquine (DHAPQ), artemether-lumefantrine (AL), or chlorproguanil-dapsone-artesunate (CD+A). Overall, 4,116 children 6–59 mo old with uncomplicated Plasmodium falciparum malaria were treated (1,226 with AL, 1,002 with ASAQ, 413 with CD+A, and 1,475 with DHAPQ), actively followed up until day 28, and then passively followed up for the next 6 mo. At day 28, for the PCR-adjusted efficacy, non-inferiority was established for three pair-wise comparisons: DHAPQ (97.3%) versus AL (95.5%) (odds ratio [OR]: 0.59, 95% CI: 0.37–0.94); DHAPQ (97.6%) versus ASAQ (96.8%) (OR: 0.74, 95% CI: 0.41–1.34), and ASAQ (97.1%) versus AL (94.4%) (OR: 0.50, 95% CI: 0.28–0.92). For the PCR-unadjusted efficacy, AL was significantly less efficacious than DHAPQ (72.7% versus 89.5%) (OR: 0.27, 95% CI: 0.21–0.34) and ASAQ (66.2% versus 80.4%) (OR: 0.40, 95% CI: 0.30–0.53), while DHAPQ (92.2%) had higher efficacy than ASAQ (80.8%) but non-inferiority could not be excluded (OR: 0.35, 95% CI: 0.26–0.48). CD+A was significantly less efficacious than the other three treatments. Day 63 results were similar to those observed at day 28.

Conclusions

This large head-to-head comparison of most currently available ACTs in sub-Saharan Africa showed that AL, ASAQ, and DHAPQ had excellent efficacy, up to day 63 post-treatment. The risk of recurrent infections was significantly lower for DHAPQ, followed by ASAQ and then AL, supporting the recent recommendation of considering DHAPQ as a valid option for the treatment of uncomplicated P. falciparum malaria.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00393679","term_id":"NCT00393679"}}NCT00393679; Pan African Clinical Trials Registry PACTR2009010000911750 Please see later in the article for the Editors'' Summary     

Improving the evidence base for decision making during a pandemic: the example of 2009 influenza A/H1N1

This article synthesizes and extends discussions held during an international meeting on "Surveillance for Decision Making: The Example of 2009 Pandemic Influenza A/H1N1," held at the Center for Communicable Disease Dynamics (CCDD), Harvard School of Public Health, on June 14 and 15, 2010. The meeting involved local, national, and global health authorities and academics representing 7 countries on 4 continents. We define the needs for surveillance in terms of the key decisions that must be made in response to a pandemic: how large a response to mount and which control measures to implement, for whom, and when. In doing so, we specify the quantitative evidence required to make informed decisions. We then describe the sources of surveillance and other population-based data that can presently--or in the future--form the basis for such evidence, and the interpretive tools needed to process raw surveillance data. We describe other inputs to decision making besides epidemiologic and surveillance data, and we conclude with key lessons of the 2009 pandemic for designing and planning surveillance in the future.     

Nationwide molecular surveillance of pandemic H1N1 influenza A virus genomes: Canada, 2009

Background

In April 2009, a novel triple-reassortant swine influenza A H1N1 virus (“A/H1N1pdm”; also known as SOIV) was detected and spread globally as the first influenza pandemic of the 21^st century. Sequencing has since been conducted at an unprecedented rate globally in order to monitor the diversification of this emergent virus and to track mutations that may affect virus behavior.

Methodology/Principal Findings

By Sanger sequencing, we determined consensus whole-genome sequences for A/H1N1pdm viruses sampled nationwide in Canada over 33 weeks during the 2009 first and second pandemic waves. A total of 235 virus genomes sampled from unique subjects were analyzed, providing insight into the temporal and spatial trajectory of A/H1N1pdm lineages within Canada. Three clades (2, 3, and 7) were identifiable within the first two weeks of A/H1N1pdm appearance, with clades 5 and 6 appearing thereafter; further diversification was not apparent. Only two viral sites displayed evidence of adaptive evolution, located in hemagglutinin (HA) corresponding to D222 in the HA receptor-binding site, and to E374 at HA2-subunit position 47. Among the Canadian sampled viruses, we observed notable genetic diversity (1.47×10⁻³ amino acid substitutions per site) in the gene encoding PB1, particularly within the viral genomic RNA (vRNA)-binding domain (residues 493–757). This genome data set supports the conclusion that A/H1N1pdm is evolving but not excessively relative to other H1N1 influenza A viruses. Entropy analysis was used to investigate whether any mutated A/H1N1pdm protein residues were associated with infection severity; however no virus genotypes were observed to trend with infection severity. One virus that harboured heterozygote coding mutations, including PB2 D567D/G, was attributed to a severe and potentially mixed infection; yet the functional significance of this PB2 mutation remains unknown.

Conclusions/Significance

These findings contribute to enhanced understanding of Influenza A/H1N1pdm viral dynamics.     

黄脊竹蝗对不同发酵天数人尿的行为反应

黄脊竹蝗(Ceracris kiangsu)是我国南方地区重要的竹子害虫,为了深入理解黄脊竹蝗的趋尿行为,测定了黄脊竹蝗对不同发酵天数人尿的行为反应.结果表明,人尿的发酵天数对黄脊竹蝗的趋尿行为有显著影响,发酵对人尿引诱竹蝗有明显的增效作用.与发酵时间分别为l、4、7、15和60 d的人尿相比,黄脊竹蝗显著趋向于发酵30 d的人尿,取食经发酵30 d的人尿处理滤纸的面积最大(3494.9±345.4) mm2,访问次数最多(43.7±5.2)次,单次停留时间也最长(360.5 ±39.8)s.林间诱杀的结果与行为生测的结果一致,发酵30 d的人尿每天诱杀的黄脊竹蝗数量最多,达到(507±139)头.诱杀及录像试验结果表明,发生趋尿行为的仅为黄脊竹蝗雌虫.     

沟垄全覆盖种植方式对旱地玉米生长及水分利用效率的影响

2008-2010年在渭北旱塬区,以沟不覆盖为对照(CK),研究垄上覆地膜沟内分别覆普通地膜(PP)、生物降解膜(PB)、玉米秸秆(PS)和液体地膜(PL)4种沟垄全覆盖种植模式对土壤水温、玉米生长、产量及水分利用效率的影响.结果表明,在玉米生长前期,PP、PB和PS处理可明显提高0-200 cm土壤蓄水量;生育中期,PS处理蓄水保墒效果最为显著;生育后期,各沟垄全覆盖处理与对照的土壤蓄水量无显著差异;整个生育期PL处理与CK的土壤蓄水量差异不显著.PP和PB处理3a玉米生育期5-25 cm平均土壤温度分别较CK增高1.6℃和1.3℃,PS处理降低1.9℃,而PL处理与CK无显著差异.PP和PB的增温保水效应使玉米株高、叶面积及地上生物量均高于CK;PS处理的降温效应促进玉米中后期生长,其株高、叶面积及地上生物量均高于CK;PL处理对玉米各生长指标影响不显著.与CK相比,PP、PB和PS处理3a平均的籽粒产量分别提高13.0％、13.8％和15.0％,水分利用效率分别提高9.8％、10.2％和11.6％.可见,垄覆地膜沟覆地膜、生物降解膜或秸秆的沟垄全覆盖种植可明显改善土壤的水温状况,促进玉米生长,从而显著提高作物产量和水分利用效率,对渭北旱塬区春玉米丰产栽培具有重要指导意义.