ERAAP customizes peptides for MHC class I molecules in the endoplasmic reticulum

The ability of killer T cells carrying the CD8 antigen to detect tumours or intracellular pathogens requires an extensive display of antigenic peptides by major histocompatibility complex (MHC) class I molecules on the surface of potential target cells. These peptides are derived from almost all intracellular proteins and reveal the presence of foreign pathogens and mutations. How cells produce thousands of distinct peptides cleaved to the precise lengths required for binding different MHC class I molecules remains unknown. The peptides are cleaved from endogenously synthesized proteins by the proteasome in the cytoplasm and then trimmed by an unknown aminopeptidase in the endoplasmic reticulum (ER). Here we identify ERAAP, the aminopeptidase associated with antigen processing in the ER. ERAAP has a broad substrate specificity, and its expression is strongly upregulated by interferon-gamma. Reducing the expression of ERAAP through RNA interference prevents the trimming of peptides for MHC class I molecules in the ER and greatly reduces the expression of MHC class I molecules on the cell surface. Thus, ERAAP is the missing link between the products of cytosolic processing and the final peptides presented by MHC class I molecules on the cell surface.     

不同声学边界长空间内声场传播的相干模型

由于长空间的特殊空间尺寸,基于传统室内声学理论所假设的扩散声场分布规律和混响规律在长空间不完全适用.基于几何声学的虚源法可以对长空间的声场的传播进行研究.然而,虚源法建模忽略了长空间中声线在边界多次反射产生的干涉效应.在虚源法的基础上,通过对虚源之间的相干求和,考虑了多次反射形成的无限个虚源之间的干涉效应,并且将各不相同的边界阻抗率加入到模型中,实现了一种预测矩形长空间中声场的传播的复虚源模型.实验所用长空间的墙壁分别是密度板和吸声材料,以模拟不同的阻抗边界.实验采用衰减系数逾量描述数值模拟和实际测量的结果.实验证明了所提理论模型的有效性,所提理论模型的预测结果可以较好地模拟出不同边界长空间声场的衰减趋势,反映出不同频率的声波在长空间中的传播趋势,比基于声线法的软件ODEON的结果更接近实验结果.     

Carbon dioxide-sensing in organisms and its implications for human disease

The capacity of organisms to sense changes in the levels of internal and external gases and to respond accordingly is central to a range of physiologic and pathophysiologic processes. Carbon dioxide, a primary product of oxidative metabolism is one such gas that can be sensed by both prokaryotic and eukaryotic cells and in response to altered levels, elicit the activation of multiple adaptive pathways. The outcomes of activating CO₂-sensitive pathways in various species include increased virulence of fungal and bacterial pathogens, prey-seeking behavior in insects as well as taste perception, lung function, and the control of immunity in mammals. In this review, we discuss what is known about the mechanisms underpinning CO₂ sensing across a range of species and consider the implications of this for physiology, disease progression, and the possibility of developing new therapeutics for inflammatory and infectious disease.     

Three Criteria for Consensus Conferences

Consensus conferences are social techniques which involve bringing together a group of scientific experts, and sometimes also non-experts, in order to increase the public role in science and related policy, to amalgamate diverse and often contradictory evidence for a hypothesis of interest, and to achieve scientific consensus or at least the appearance of consensus among scientists. For consensus conferences that set out to amalgamate evidence, I propose three desiderata: Inclusivity (the consideration of all available evidence), Constraint (the achievement of some agreement of intersubjective assessments of the hypothesis of interest), and Evidential Complexity (the evaluation of available evidence based on a plurality of relevant evidential criteria). Two examples suggest that consensus conferences can readily satisfy Inclusivity and Evidential Complexity, but consensus conferences do not as easily satisfy Constraint. I end by discussing the relation between social inclusivity and the three desiderata.     

Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis

Atopic dermatitis (AD) is a commonly occurring chronic skin disease with high heritability. Apart from filaggrin (FLG), the genes influencing atopic dermatitis are largely unknown. We conducted a genome-wide association meta-analysis of 5,606 affected individuals and 20,565 controls from 16 population-based cohorts and then examined the ten most strongly associated new susceptibility loci in an additional 5,419 affected individuals and 19,833 controls from 14 studies. Three SNPs reached genome-wide significance in the discovery and replication cohorts combined, including rs479844 upstream of OVOL1 (odds ratio (OR) = 0.88, P = 1.1 × 10(-13)) and rs2164983 near ACTL9 (OR = 1.16, P = 7.1 × 10(-9)), both of which are near genes that have been implicated in epidermal proliferation and differentiation, as well as rs2897442 in KIF3A within the cytokine cluster at 5q31.1 (OR = 1.11, P = 3.8 × 10(-8)). We also replicated association with the FLG locus and with two recently identified association signals at 11q13.5 (rs7927894; P = 0.008) and 20q13.33 (rs6010620; P = 0.002). Our results underline the importance of both epidermal barrier function and immune dysregulation in atopic dermatitis pathogenesis.     

技术的源与流:四川夹江造纸匠群体中的行业崇拜、祖先与知识的传播

四川夹江的造纸业者认为他们的技艺是由先师蔡伦以及最初在夹江定居的祖先们创立起来的,造纸技术是祖先留给他们的生计财源.基于这种认识,夹江造纸业者认为造纸技术是社群共有的财产,属于先师和祖先的所有徒子徒孙及后代,而不是属于某一家或某一作坊.根据访谈以及当地石碑碑文的内容,探讨对先祖的感恩和义务是如何对造纸术的产生和流通产生影响的.     

KIF5C, a kinesin motor involved in apical trafficking of MDCK cells

Polarized traffic in epithelial cells depends on well-organized pathways that direct secretory cargo to the apical or basolateral plasma membrane. In MDCK cells, apical trafficking can be further divided into a lipid raft-dependent and a raft-independent route, which separate biosynthetic cargo in a post-Golgi endosomal compartment. We have now identified KIF5C as a kinesin motor for apical trafficking of both raft-associated sucrase isomaltase and raft-independent neurotrophin receptor. KIF5C was identified by mass spectrometry in vesicle enriched fractions and on immunoisolated post-Golgi vesicles carrying apical cargo. The amount of vesicle-associated KIF5C was highest on material isolated directly after trans-Golgi network release and declined thereafter. Altogether, our data suggest that KIF5C is involved in the passage of apical cargo molecules to a post-Golgi endosomal compartment, where further segregation into distinct vesicle populations proceeds.