Common nonsynonymous variants in PCSK1 confer risk of obesity

Mutations in PCSK1 cause monogenic obesity. To assess the contribution of PCSK1 to polygenic obesity risk, we genotyped tag SNPs in a total of 13,659 individuals of European ancestry from eight independent case-control or family-based cohorts. The nonsynonymous variants rs6232, encoding N221D, and rs6234-rs6235, encoding the Q665E-S690T pair, were consistently associated with obesity in adults and children (P = 7.27 x 10(-8) and P = 2.31 x 10(-12), respectively). Functional analysis showed a significant impairment of the N221D-mutant PC1/3 protein catalytic activity.     

FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity

Naturally occurring variation in gene copy number is increasingly recognized as a heritable source of susceptibility to genetically complex diseases. Here we report strong association between FCGR3B copy number and risk of systemic lupus erythematosus (P = 2.7 x 10(-8)), microscopic polyangiitis (P = 2.9 x 10(-4)) and Wegener's granulomatosis in two independent cohorts from the UK (P = 3 x 10(-3)) and France (P = 1.1 x 10(-4)). We did not observe this association in the organ-specific Graves' disease or Addison's disease. Our findings suggest that low FCGR3B copy number, and in particular complete FCGR3B deficiency, has a key role in the development of systemic autoimmunity.     

Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders

SHANK3 (also known as ProSAP2) regulates the structural organization of dendritic spines and is a binding partner of neuroligins; genes encoding neuroligins are mutated in autism and Asperger syndrome. Here, we report that a mutation of a single copy of SHANK3 on chromosome 22q13 can result in language and/or social communication disorders. These mutations concern only a small number of individuals, but they shed light on one gene dosage-sensitive synaptic pathway that is involved in autism spectrum disorders.     

Realizability and the varieties of explanation

What realization is has been convincingly presented in relation to the way we determine what counts as the realizers of realized properties. The way we explain a fact of realization includes a reference to what realization should be; therefore it informs in turn our understanding of the nature of realization. Conceptions of explanation are thereby included in the views of realization as a metaphysical property.Recently, several major views of realization such as Polger and Shapiro's or Gillett and Aizawa's, however competing, have relied on the neo-mechanicist theory of explanations (e.g,. Darden and Caver 2013), currently popular among philosophers of science. However, it has also been increasingly argued that some explanations are not mechanistic (e.g., Batterman 2009).Using an account given in Huneman (2017), I argue that within those explanations the fact that some mathematical properties are instantiated is explanatory, and that this defines a specific explanatory type called “structural explanation”, whose subtypes could be: optimality explanations (usually found in economics), topological explanations, etc. This paper thereby argues that all subtypes of structural explanation define several kinds of realizability, which are not equivalent to the usual notion of realization tied to mechanistic explanations, onto which many of the philosophical investigations are focused. Then it draws some consequences concerning the notion of multiple realizability.     

"If You Don't Know How to Fix it, Please Stop Breaking it!" The Precautionary Principle and Climate Change

Taking precautions to prevent harm. Whether principe de précaution, Vorsorgeprinzip, føre-var prinsippet, or försiktighetsprincip, etc., the precautionary principle embodies the idea that public and private interests should act to prevent harm. Furthermore, the precautionary principle suggests that action should be taken to limit, regulate, or prevent potentially dangerous undertakings even in the absence of absolute scientific proof. Such measures also naturally entail taking economic costs into account. With the environmental disasters of the 1980s, the precautionary principle established itself as an operational concept. On the eve of the 1997 Climate Summit in Kyoto, precaution, as the precautionary principle is often referred to, has now become a key legal principle in environmental law, in general, and in current international climate negotiations, in particular, attempts to understand why. It examines in turn the natural affinity between the precautionary principle and climate change, reviews a series of issues which the principle raises, and discusses avenues which it opens paper, climate change fulfills the theoretical requirements set for the application of the precautionary principle. It comes as no surprise that the actual application of the precautionary principle in the context of climate change raises high political stakes. As a result, climate change science, in particular, and science, in general, is under the fire of politically-motivated scientific skeptics. Thus, by way of the counter-measures which must be put into effect, the precautionary principle calls for a greater sense of responsibility on the part of scientists and the public at large. Specifically, from scientists, it demands perseverance in rigor, excellence in communication, and committment to education. However, even if special efforts are made to implement the precautionary principle in the context of climate change, the success of climate change mitigation will constitute no test of the validity, the usefulness, or the efficiency of the precautionary principle. Indeed, the degree to which climate change mitigation succeeds only provides a measure of our kind's ability to manage responsibly the global commons which we inherited from our ancestors and which our generation enjoys, the global commons which we will pass on to today's children and to generations to come.     

太阳中心探秘

于1995年12月2日发射升空的“太阳及日光层天体探测”卫星（soho）朝着太阳中心作了一次令人惊异的旅行。太阳黑点下究竟蕴藏着什么？为什么围绕着太阳的日冕之内层温度远比其表面高？太阳风是怎么形成的？太阳磁场是一种什么现象？这些是人们想通过Soho号卫星收集到的最新资料来加以解决的问题。揭开太阳的面纱欧洲人研制的太阳探测器——Soho号卫星配备着极为完备的测量仪。科学家们通过先进的卫星得以探查太阳内部最深处，太阳黑子底下的秘密特被人类揭开。对太阳作深入细致探测已经开始。为推断出太阳内部究竟发生着什么，天文学家们一…