Cellular and genetic mechanisms of self tolerance and autoimmunity

The mammalian immune system has an extraordinary potential for making receptors that sense and neutralize any chemical entity entering the body. Inevitably, some of these receptors recognize components of our own body, and so cellular mechanisms have evolved to control the activity of these 'forbidden' receptors and achieve immunological self tolerance. Many of the genes and proteins involved are conserved between humans and other mammals. This provides the bridge between clinical studies and mechanisms defined in experimental animals to understand how sets of gene products coordinate self-tolerance mechanisms and how defects in these controls lead to autoimmune disease.     

模拟结果为什么比实际更暖:简化气候模型结果（英文）

设计了一个非专业人士能够使用、最简化的气候敏感模型,用来研究人类活动所导致的全球变暖的幅度问题.在1990年的第一次IPCC评估报告中,IPCC对其报告中预测的未来全球变暖幅度很有信心,但是随后的观测结果显示全球的变暖幅度只有预测的一半.而自2001年起,全球变暖出现停滞,但是仅仅考虑到二氧化碳浓度的增加,很少有模型能够模拟出这一变化.在已出版的IPCC第五次评估报告的草稿中,IPCC大幅度削减了近期变暖的幅度,并以专家评估代替了模型预测.但是报告中关于未来气候长期变化的预测仍被保留.如果把IPCC模型的总反馈从1.9 W m–2 K–1调整到1.5 W m–2 K–1,气候敏感模型中模拟的温度将从3.2 K降至2.2 K.同时由于反馈很可能是净负反馈,更合适的估计应该是1.0 K.1.0 K是一个能够实现的增幅,21世纪的实际变暖将会小于1 K.即使燃烧所有可开采的化石燃料也不会使全球变暖的幅度超过2.2 K,这一增加幅度也将趋于平稳.本文认为解决IPCC第四、五次报告中评估方法的差异非常关键.一旦这些差异得到解决,人类活动导致的全球变暖在22世纪以及几个世纪以后的平稳态将有可能不会超过IPCC当前模型预测的1/3~1/2.     

Acquisition of a multifunctional IgA+ plasma cell phenotype in the gut

The largest mucosal surface in the body is in the gastrointestinal tract, a location that is heavily colonized by microbes that are normally harmless. A key mechanism required for maintaining a homeostatic balance between this microbial burden and the lymphocytes that densely populate the gastrointestinal tract is the production and transepithelial transport of poly-reactive IgA (ref. 1). Within the mucosal tissues, B cells respond to cytokines, sometimes in the absence of T-cell help, undergo class switch recombination of their immunoglobulin receptor to IgA, and differentiate to become plasma cells. However, IgA-secreting plasma cells probably have additional attributes that are needed for coping with the tremendous bacterial load in the gastrointestinal tract. Here we report that mouse IgA(+) plasma cells also produce the antimicrobial mediators tumour-necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS), and express many molecules that are commonly associated with monocyte/granulocytic cell types. The development of iNOS-producing IgA(+) plasma cells can be recapitulated in vitro in the presence of gut stroma, and the acquisition of this multifunctional phenotype in vivo and in vitro relies on microbial co-stimulation. Deletion of TNF-α and iNOS in B-lineage cells resulted in a reduction in IgA production, altered diversification of the gut microbiota and poor clearance of a gut-tropic pathogen. These findings reveal a novel adaptation to maintaining homeostasis in the gut, and extend the repertoire of protective responses exhibited by some B-lineage cells.     

Optimal nitrogen-to-phosphorus stoichiometry of phytoplankton

Redfield noted the similarity between the average nitrogen-to-phosphorus ratio in plankton (N:P = 16 by atoms) and in deep oceanic waters (N:P = 15; refs 1, 2). He argued that this was neither a coincidence, nor the result of the plankton adapting to the oceanic stoichiometry, but rather that phytoplankton adjust the N:P stoichiometry of the ocean to meet their requirements through nitrogen fixation, an idea supported by recent modelling studies. But what determines the N:P requirements of phytoplankton? Here we use a stoichiometrically explicit model of phytoplankton physiology and resource competition to derive from first principles the optimal phytoplankton stoichiometry under diverse ecological scenarios. Competitive equilibrium favours greater allocation to P-poor resource-acquisition machinery and therefore a higher N:P ratio; exponential growth favours greater allocation to P-rich assembly machinery and therefore a lower N:P ratio. P-limited environments favour slightly less allocation to assembly than N-limited or light-limited environments. The model predicts that optimal N:P ratios will vary from 8.2 to 45.0, depending on the ecological conditions. Our results show that the canonical Redfield N:P ratio of 16 is not a universal biochemical optimum, but instead represents an average of species-specific N:P ratios.     

The interface between silicon and a high-k oxide

The ability of the semiconductor industry to continue scaling microelectronic devices to ever smaller dimensions (a trend known as Moore's Law) is limited by quantum mechanical effects: as the thickness of conventional silicon dioxide (SiO(2)) gate insulators is reduced to just a few atomic layers, electrons can tunnel directly through the films. Continued device scaling will therefore probably require the replacement of the insulator with high-dielectric-constant (high-k) oxides, to increase its thickness, thus preventing tunnelling currents while retaining the electronic properties of an ultrathin SiO(2) film. Ultimately, such insulators will require an atomically defined interface with silicon without an interfacial SiO(2) layer for optimal performance. Following the first reports of epitaxial growth of AO and ABO(3) compounds on silicon, the formation of an atomically abrupt crystalline interface between strontium titanate and silicon was demonstrated. However, the atomic structure proposed for this interface is questionable because it requires silicon atoms that have coordinations rarely found elsewhere in nature. Here we describe first-principles calculations of the formation of the interface between silicon and strontium titanate and its atomic structure. Our study shows that atomic control of the interfacial structure by altering the chemical environment can dramatically improve the electronic properties of the interface to meet technological requirements. The interface structure and its chemistry may provide guidance for the selection process of other high-k gate oxides and for controlling their growth.