Modeling the epidemiological history of plague in Central Asia: Palaeoclimatic forcing on a disease system over the past millennium

Background

Human cases of plague (Yersinia pestis) infection originate, ultimately, in the bacterium's wildlife host populations. The epidemiological dynamics of the wildlife reservoir therefore determine the abundance, distribution and evolution of the pathogen, which in turn shape the frequency, distribution and virulence of human cases. Earlier studies have shown clear evidence of climatic forcing on contemporary plague abundance in rodents and humans.

Results

We find that high-resolution palaeoclimatic indices correlate with plague prevalence and population density in a major plague host species, the great gerbil (Rhombomys opimus), over 1949-1995. Climate-driven models trained on these data predict independent data on human plague cases in early 20th-century Kazakhstan from 1904-1948, suggesting a consistent impact of climate on large-scale wildlife reservoir dynamics influencing human epidemics. Extending the models further back in time, we also find correspondence between their predictions and qualitative records of plague epidemics over the past 1500 years.

Conclusions

Central Asian climate fluctuations appear to have had significant influences on regional human plague frequency in the first part of the 20th century, and probably over the past 1500 years. This first attempt at ecoepidemiological reconstruction of historical disease activity may shed some light on how long-term plague epidemiology interacts with human activity. As plague activity in Central Asia seems to have followed climate fluctuations over the past centuries, we may expect global warming to have an impact upon future plague epidemiology, probably sustaining or increasing plague activity in the region, at least in the rodent reservoirs, in the coming decades. See commentary: http://www.biomedcentral.com/1741-7007/8/108     

Discovery of small-molecule HIV-1 fusion and integrase inhibitors oleuropein and hydroxytyrosol: part II. integrase inhibition

We report molecular modeling and functional confirmation of Ole and HT binding to HIV-1 integrase. Docking simulations identified two binding regions for Ole within the integrase active site. Region I encompasses the conserved D64-D116-E152 motif, while region II involves the flexible loop region formed by amino acid residues 140-149. HT, on the other hand, binds to region II. Both Ole and HT exhibit favorable interactions with important amino acid residues through strong H-bonding and van der Waals contacts, predicting integrase inhibition. To test and confirm modeling predictions, we examined the effect of Ole and HT on HIV-1 integrase activities including 3'-processing, strand transfer, and disintegration. Ole and HT exhibit dose-dependent inhibition on all three activities, with EC(50)s in the nanomolar range. These studies demonstrate that molecular modeling of target-ligand interaction coupled with structural-activity analysis should facilitate the design and identification of innovative integrase inhibitors and other therapeutics.     

Connexins are mechanosensitive

Connexins form gap junction channels that provide a hydrophilic path between cell interiors. Some connexins, particularly the lens connexins, Cx46 and Cx50 and their orthologs, can form functional hemichannels in nonjunctional membranes. These hemichannels are a nonselective conduit to the extracellular medium and may jeopardize cell survival. The physiological function of hemichannels has remained elusive, but it has been postulated that hemichannels are involved in ATP-release caused by mechanical stimulation. Here we show with single-channel and whole cell electrophysiological studies that Cx46 hemichannels are mechanosensitive, like other families of ion channels and membrane-bound enzymes. The hemichannel response to mechanical stress is bipolar. At negative potentials stress opens the channel, and at positive potentials stress closes it. Physiologically, Cx46 hemichannels may assist accommodation of the ocular lens by providing a transient path for volume flow as the lens changes shape. mechanical stress; lens     

膜上tRNA结合蛋白的分离与初步鉴定

用ＴｒｉｔｏｎＸ－１１４分相法分离啤酒酵母的膜总蛋白,经过酵母ｔＲＮＡ分子交联的Ｓｅｐｈａｒｏｓｅ４Ｂ亲和层析,用０－０．８ｍｏｌ／Ｌ（ＮＨ４０２ＳＯ４梯度缓冲液洗脱ｔＲＮＡ结合的蛋白质。凝胶阻滞电泳实验室鉴定出两种主要的与ｔＲＮＡ分子特异性结合的蛋白质。     

吸血蝙蝠食性特化及其研究现状

翼手目动物（蝙蝠）的食性多样性丰富,其食物包括昆虫、鱼类、两栖动物、爬行动物、鸟类、哺乳动物、植物果实、花、花粉、花蜜、叶片和血液等。其中,大约70%的蝙蝠主要以昆虫为食,而以血液为食的吸血蝙蝠只有3种,它们是哺乳动物中唯一的仅以血液为食的动物类群。因此,吸血蝙蝠是研究动物食性演化的重要模式动物。本文综述了吸血蝙蝠在形态学、生理学、行为学、感觉系统和肠道微生物等方面的研究,指出了吸血蝙蝠食性特化的适应性特征。随着普通吸血蝠高质量基因组的公布,我们将有机会探究食性相关基因在吸血蝙蝠中的功能改变,阐明动物食性转变的分子机理。本文将为吸血蝙蝠和其它动物食性转变的研究提供有益的参考。     

神经元营养因子对大鼠隔—海马通路损伤的影响

为评价神经生长因子(NGF)、混合型神经节苷脂(GM)和单唾液酸神经节苷脂(GM1)对中枢胆碱能神经损伤早期的影响,在大鼠单侧隔-海马通路部分损伤后即时经脑室分别注入上述三种神经元营养因子,7d后取两侧海马分别测定乙酰胆碱(ACh)、胆碱乙酰基转移酶(ChAT)和胆碱酯酶(ChE)。损伤对照组(脑室注入盐水)术侧海马ACh含量保留率为对侧的20.3％,ChAT活力为50％,ChE活力为48.3％。给予NGF、GM或GM1的实验组,ACh含量保留率分别为34.9％,35.3％和47.7％;ChAT活力为77.4％,78.4％和69.2％;而ChE活力的保留率未见明显改变。这些神经元营养因子显著增加了大鼠隔-海马通路损伤后海马内ACh含量和ChAT活力,说明它们减轻了损伤侧海马胆碱能神经纤维的破坏,具有明显的损伤早期保护作用。     

运用红外相机对太行山猕猴国家级自然保护区（济源）鸟兽多样性的调查

河南太行山猕猴国家级自然保护区（济源）内野生动物种类非常丰富,但已多年未进行过野生动物本底资源调查。于2015年1月至7月,在保护区4个林场内设置了51个2km×2km网格,采用红外相机技术对保护区内兽类和地栖性鸟类资源进行调查。经过6,014个捕获日的调查,共记录到野生兽类5目13科17种,鸟类6目12科28种,其中东北刺猬（Erinaceus amurensis）、红腹锦鸡（Chrysolophus pictus）、灰林鸮（Strix aluco）、宝兴歌鸫（Turdus mupinensis）、虎斑地鸫（Zoothera dauma）、紫啸鸫（Myophonus caeruleus）、普通（Sitta europaea）、黄腹山雀（Parus venustulus）、斑胸钩嘴鹛（Pomatorhinus gravivox）、画眉（Garrulax canorus）等10个种类为保护区新记录种。首次在该保护区拍摄到国家Ⅰ级重点保护动物——豹（Panthera pardus）和林麝（Moschus berezovskii）,以及国家Ⅱ级重点保护动物猕猴（Macaques mulatta）、黄喉貂（Martes flavigula）、勺鸡（Pucrasia macrolopha）、红腹锦鸡和灰林鸮。兽类以猪獾（Arctonyx collaris）的相对丰富度指数最高为4.57;鸟类以红腹锦鸡的相对丰富度指数最高为2.03。调查结果显示保护区仍保存较为完整的大中型兽类群落,但顶级捕食者数量稀少,应加大对其栖息地及猎物的保护恢复力度。此外,相机拍摄到大量放牧活动照片,说明当地人为干扰严重,应加强管理。本次调查初步掌握了太行山猕猴国家级自然保护区（济源）内兽类和地栖性鸟类的资源现状,为保护区开展红外相机野生动物长期监测积累了基础资料。     

Docosahexaenoic Acid Induces Apoptosis in MCF-7 Cells In Vitro and In Vivo via Reactive Oxygen Species Formation and Caspase 8 Activation

Background

The present study sought to further investigate the in vitro and in vivo anticancer effects of a representative omega-3 fatty acid, docosahexaenoic acid (DHA), with a focus on assessing the induction of oxidative stress and apoptosis as an important mechanism for its anticancer actions.

Methodology/Principal Findings

In vitro studies showed that DHA strongly reduces the viability and DNA synthesis of MCF-7 human breast cancer cells in culture, and also promotes cell death via apoptosis. Mechanistically, accumulation of reactive oxygen species and activation of caspase 8 contribute critically to the induction of apoptotic cell death. Co-presence of antioxidants or selective inhibition or knockdown of caspase 8 each effectively abrogates the cytotoxic effect of DHA. Using athymic nude mice as an in vivo model, we found that feeding animals the 5% fish oil-supplemented diet for 6 weeks significantly reduces the growth of MCF-7 human breast cancer cells in vivo through inhibition of cancer cell proliferation as well as promotion of cell death. Using 3-nitrotyrosine as a parameter, we confirmed that the fish oil-supplemented diet significantly increases oxidative stress in tumor cells in vivo. Analysis of fatty acid content in plasma and tissues showed that feeding animals a 5% fish oil diet increases the levels of DHA and eicosapentaenoic acid in both normal and tumorous mammary tissues by 329% and 300%, respectively.

Conclusions/Significance

DHA can strongly induce apoptosis in human MCF-7 breast cancer cells both in vitro and in vivo. The induction of apoptosis in these cells is selectively mediated via caspase 8 activation. These observations call for further studies to assess the effectiveness of fish oil as a dietary supplement in the prevention and treatment of human breast cancer.