Epithelial-cell-intrinsic IKK-beta expression regulates intestinal immune homeostasis

Intestinal epithelial cells (IECs) provide a primary physical barrier against commensal and pathogenic microorganisms in the gastrointestinal (GI) tract, but the influence of IECs on the development and regulation of immunity to infection is unknown. Here we show that IEC-intrinsic IkappaB kinase (IKK)-beta-dependent gene expression is a critical regulator of responses of dendritic cells and CD4+ T cells in the GI tract. Mice with an IEC-specific deletion of IKK-beta show a reduced expression of the epithelial-cell-restricted cytokine thymic stromal lymphopoietin in the intestine and, after infection with the gut-dwelling parasite Trichuris, fail to develop a pathogen-specific CD4+ T helper type 2 (T(H)2) response and are unable to eradicate infection. Further, these animals show exacerbated production of dendritic-cell-derived interleukin-12/23p40 and tumour necrosis factor-alpha, increased levels of CD4+ T-cell-derived interferon-gamma and interleukin-17, and develop severe intestinal inflammation. Blockade of proinflammatory cytokines during Trichuris infection ablates the requirement for IKK-beta in IECs to promote CD4+ T(H)2 cell-dependent immunity, identifying an essential function for IECs in tissue-specific conditioning of dendritic cells and limiting type 1 cytokine production in the GI tract. These results indicate that the balance of IKK-beta-dependent gene expression in the intestinal epithelium is crucial in intestinal immune homeostasis by promoting mucosal immunity and limiting chronic inflammation.     

全球性挑战:可持续发展如何实现?

<正>气候变化问题政府间专门小组(IPCC)报告称,过去一年二氧化碳排放量的增速比2000～2004年间最糟糕的年份还要快。政府如不采取新的行动,那么到2030年,温室气体排放量将比2000年增加25%～90%。目前,海洋和森林对碳的吸收能量为每年大约30～35亿吨,人类活动每年增加碳量70亿吨。人类的消费大于自然界再生或吸收"生态脚印"能力的25%。     

喀什市城市生态环境质量评价研究

 以1997~2008期间12a的生态环境时间序列数据为数据源,建立了喀什市生态环境质量综合评价指标体系,运用层次分析法确定了各生态因子的权重,得出了影响因子的重要性排序并计算出了生态环境质量综合指数,最终对喀什市生态环境质量进行了评价.研究表明:喀什市生态环境质量综合指数呈现波动性的变化特征,2002年前后的变化状况有区别,2002年以前生态环境综合指数比较低,而且总体上呈现下降趋势,表明生态环境综合质量以下降趋势为主;2002年以后指数既有上升也有下降趋势,但指数比2002年以前的高,表明生态环境质量有所好转,但总的趋势并不理想.生态环境质量评价结果显示,喀什市生态环境综合质量整体上比较差,生态环境形势不乐观,因此喀什市必须要采取措施,加强生态环境建设方面的工作力度.     

和田茴香籽中黄酮类化合物提取工艺研究

采用正交设计法对新疆和田茴香籽中的黄酮类化合物提取工艺参数进行优化.结果表明:最佳提取工艺为70 ml 60％乙醇在70℃下提取2.5h.本实验采用分光光度法,以芦丁标准品测定新疆和田茴香籽提取物中总黄酮的含量,总黄酮含量为1.58％.该工艺稳定、简便、快速,可作为检测茴香籽提取物中黄酮含量的一种手段.     

Cell-to-cell spread of HIV permits ongoing replication despite antiretroviral therapy

Latency and ongoing replication have both been proposed to explain the drug-insensitive human immunodeficiency virus (HIV) reservoir maintained during antiretroviral therapy. Here we explore a novel mechanism for ongoing HIV replication in the face of antiretroviral drugs. We propose a model whereby multiple infections per cell lead to reduced sensitivity to drugs without requiring drug-resistant mutations, and experimentally validate the model using multiple infections per cell by cell-free HIV in the presence of the drug tenofovir. We then examine the drug sensitivity of cell-to-cell spread of HIV, a mode of HIV transmission that can lead to multiple infection events per target cell. Infections originating from cell-free virus decrease strongly in the presence of antiretrovirals tenofovir and efavirenz whereas infections involving cell-to-cell spread are markedly less sensitive to the drugs. The reduction in sensitivity is sufficient to keep multiple rounds of infection from terminating in the presence of drugs. We examine replication from cell-to-cell spread in the presence of clinical drug concentrations using a stochastic infection model and find that replication is intermittent, without substantial accumulation of mutations. If cell-to-cell spread has the same properties in vivo, it may have adverse consequences for the immune system, lead to therapy failure in individuals with risk factors, and potentially contribute to viral persistence and hence be a barrier to curing HIV infection.     

Genome sequence and analysis of the tuber crop potato

Potato (Solanum tuberosum L.) is the world's most important non-grain food crop and is central to global food security. It is clonally propagated, highly heterozygous, autotetraploid, and suffers acute inbreeding depression. Here we use a homozygous doubled-monoploid potato clone to sequence and assemble 86% of the 844-megabase genome. We predict 39,031 protein-coding genes and present evidence for at least two genome duplication events indicative of a palaeopolyploid origin. As the first genome sequence of an asterid, the potato genome reveals 2,642 genes specific to this large angiosperm clade. We also sequenced a heterozygous diploid clone and show that gene presence/absence variants and other potentially deleterious mutations occur frequently and are a likely cause of inbreeding depression. Gene family expansion, tissue-specific expression and recruitment of genes to new pathways contributed to the evolution of tuber development. The potato genome sequence provides a platform for genetic improvement of this vital crop.     

Complement factor H binds malondialdehyde epitopes and protects from oxidative stress

Oxidative stress and enhanced lipid peroxidation are linked to many chronic inflammatory diseases, including age-related macular degeneration (AMD). AMD is the leading cause of blindness in Western societies, but its aetiology remains largely unknown. Malondialdehyde (MDA) is a common lipid peroxidation product that accumulates in many pathophysiological processes, including AMD. Here we identify complement factor H (CFH) as a major MDA-binding protein that can block both the uptake of MDA-modified proteins by macrophages and MDA-induced proinflammatory effects in vivo in mice. The CFH polymorphism H402, which is strongly associated with AMD, markedly reduces the ability of CFH to bind MDA, indicating a causal link to disease aetiology. Our findings provide important mechanistic insights into innate immune responses to oxidative stress, which may be exploited in the prevention of and therapy for AMD and other chronic inflammatory diseases.     

East Antarctic rifting triggers uplift of the Gamburtsev Mountains

The Gamburtsev Subglacial Mountains are the least understood tectonic feature on Earth, because they are completely hidden beneath the East Antarctic Ice Sheet. Their high elevation and youthful Alpine topography, combined with their location on the East Antarctic craton, creates a paradox that has puzzled researchers since the mountains were discovered in 1958. The preservation of Alpine topography in the Gamburtsevs may reflect extremely low long-term erosion rates beneath the ice sheet, but the mountains' origin remains problematic. Here we present the first comprehensive view of the crustal architecture and uplift mechanisms for the Gamburtsevs, derived from radar, gravity and magnetic data. The geophysical data define a 2,500-km-long rift system in East Antarctica surrounding the Gamburtsevs, and a thick crustal root beneath the range. We propose that the root formed during the Proterozoic assembly of interior East Antarctica (possibly about 1 Gyr ago), was preserved as in some old orogens and was rejuvenated during much later Permian (roughly 250 Myr ago) and Cretaceous (roughly 100 Myr ago) rifting. Much like East Africa, the interior of East Antarctica is a mosaic of Precambrian provinces affected by rifting processes. Our models show that the combination of rift-flank uplift, root buoyancy and the isostatic response to fluvial and glacial erosion explains the high elevation and relief of the Gamburtsevs. The evolution of the Gamburtsevs demonstrates that rifting and preserved orogenic roots can produce broad regions of high topography in continental interiors without significantly modifying the underlying Precambrian lithosphere.