Cross-talk and decision making in MAP kinase pathways

Cells must respond specifically to different environmental stimuli in order to survive. The signal transduction pathways involved in sensing these stimuli often share the same or homologous proteins. Despite potential cross-wiring, cells show specificity of response. We show, through modeling, that the physiological response of such pathways exposed to simultaneous and temporally ordered inputs can demonstrate system-level mechanisms by which pathways achieve specificity. We apply these results to the hyperosmolar and pheromone mitogen-activated protein (MAP) kinase pathways in the yeast Saccharomyces cerevisiae. These two pathways specifically sense osmolar and pheromone signals, despite sharing a MAPKKK, Ste11, and having homologous MAPKs (Fus3 and Hog1). We show that in a single cell, the pathways are bistable over a range of inputs, and the cell responds to only one stimulus even when exposed to both. Our results imply that these pathways achieve specificity by filtering out spurious cross-talk through mutual inhibition. The variability between cells allows for heterogeneity of the decisions.     

A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis

Toll-like receptors (TLRs) and members of their signaling pathway are important in the initiation of the innate immune response to a wide variety of pathogens. The adaptor protein Mal (also known as TIRAP), encoded by TIRAP (MIM 606252), mediates downstream signaling of TLR2 and TLR4 (refs. 4-6). We report a case-control study of 6,106 individuals from the UK, Vietnam and several African countries with invasive pneumococcal disease, bacteremia, malaria and tuberculosis. We genotyped 33 SNPs, including rs8177374, which encodes a leucine substitution at Ser180 of Mal. We found that heterozygous carriage of this variant associated independently with all four infectious diseases in the different study populations. Combining the study groups, we found substantial support for a protective effect of S180L heterozygosity against these infectious diseases (N = 6,106; overall P = 9.6 x 10(-8)). We found that the Mal S180L variant attenuated TLR2 signal transduction.     

基因工程为何必须坚持进行下去

今天的基因生物学充满了活力。它在有关细胞、酵母菌等单细胞生物以至复杂的人脑的生命科学中所占的份量与年俱增。这种奇妙的生物学热,在我最初踏人遗传学界时是完全无法想象的。1948年的生物学全是描述性的,处于科学标杆的最低部位,标杆的顶端是物理学。那时,爱因斯坦关于质．能互变的划时代理论已转化成为原子的巨大威力。如果不加约束的话,用它制成的武器完全可以摧毁人类文明的全部建筑物。因此,叙年代后期的物理学家们在因其使原子变成对社会有用之物而受人尊敬的同时,又担心他们发明的玩意儿一旦落入邪恶之手时,会干出何等蠢…     

The algorithmic turn in conservation biology: Characterizing progress in ethically-driven sciences

As a discipline distinct from ecology, conservation biology emerged in the 1980s as a rigorous science focused on protecting biodiversity. Two algorithmic breakthroughs in information processing made this possible: place-prioritization algorithms and geographical information systems. They provided defensible, data-driven methods for designing reserves to conserve biodiversity that obviated the need for largely intuitive and highly problematic appeals to ecological theory at the time. But the scientific basis of these achievements and whether they constitute genuine scientific progress has been criticized. We counter by pointing out important inaccuracies about the science and rejecting the apparent theory-first focus. More broadly, the case study reveals significant limitations of the predominant epistemic-semantic conceptions of scientific progress and the considerable merits of pragmatic, practically-oriented accounts.     

Deformation of the lowermost mantle from seismic anisotropy

The lowermost part of the Earth's mantle-known as D″-shows significant seismic anisotropy, the variation of seismic wave speed with direction. This is probably due to deformation-induced alignment of MgSiO(3)-post-perovskite (ppv), which is believed to be the main mineral phase present in the region. If this is the case, then previous measurements of D″ anisotropy, which are generally made in one direction only, are insufficient to distinguish candidate mechanisms of slip in ppv because the mineral is orthorhombic. Here we measure anisotropy in D″ beneath North and Central America, where material from subducting oceanic slabs impinges on the core-mantle boundary, using shallow as well as deep earthquakes to increase the azimuthal coverage in D″. We make more than 700 individual measurements of shear wave splitting in D″ in three regions from two different azimuths in each case. We show that the previously assumed case of vertical transverse isotropy (where wave speed shows no azimuthal variation) is not possible, and that more complicated mechanisms must be involved. We test the fit of different MgSiO(3)-ppv deformation mechanisms to our results and find that shear on (001) is most consistent with observations and the expected shear above the core-mantle boundary beneath subduction zones. With new models of mantle flow, or improved experimental determination of the dominant ppv slip systems, this method will allow us to map deformation at the core-mantle boundary and link processes in D″, such as plume initiation, to the rest of the mantle.     

面向语义检索应用的本体模型结构设计

为提高语义检索过程中术语关系自动判别的效果,引入本体理论,对本体的结构设计及推理机理展开研究。提出基于6元组的本体模型结构,采用描述逻辑作为表达工具,实现了对原子术语、复合术语、实例、实例描述、属性分配以及公理的语义描述。依据Gruber设计原则,从明确性和客观性、一致性、最大单向可扩展性、最小编码偏好和最小本体承诺5方面对本体结构进行评价。从语义检索的需求出发,提出面向术语和面向实例的两种推理类型,以及转换机制和判定算法。将语义检索抽象成信息请求与答复过程,提出4类信息搜索策略,并对语义检索系统的实现进行展望。     

论清朝前期对新疆南疆地区实行民族隔离政策的危害

清朝统一新疆以后,为巩固西北边防,抵御沙俄侵略,稳定社会秩序,维护国家统一,采取了一些具有地方特色的民族政策。在南疆实行的民族隔离政策则对新疆的发展埋下了一定的政治隐患。     

延续50年的公众科学素质提升实践——美国化学会的“种子计划”

 "种子计划"是美国化学会（American Chemical Society，ACS）（以下简称化学会）一项50年的计划，旨在推动科学素质的发展，尤其是美国科学素质的发展。ACS曾经邀请我到华盛顿会见他们的首席执行官（CEO），由此我参与了此项计划。"种子计划"是一个非常具有突破性意义的项目。它给受资助者提供可以在夏季进入高校或科研机构实验室的机会，帮助其进行化学方面的研究工作。我还在西北大学见到了一些在"种子计划"受益的学生，其中一位已经是副教授了，还有一位跟我谈到了他自种子计划受益的经历。