Phospholipid flippases attenuate LPS-induced TLR4 signaling by mediating endocytic retrieval of Toll-like receptor 4

P4-ATPases are lipid flippases that catalyze the transport of phospholipids to create membrane phospholipid asymmetry and to initiate the biogenesis of transport vesicles. Here we show, for the first time, that lipid flippases are essential to dampen the inflammatory response and to mediate the endotoxin-induced endocytic retrieval of Toll-like receptor 4 (TLR4) in human macrophages. Depletion of CDC50A, the β-subunit that is crucial for the activity of multiple P4-ATPases, resulted in endotoxin-induced hypersecretion of proinflammatory cytokines, enhanced MAP kinase signaling and constitutive NF-κB activation. In addition, CDC50A-depleted THP-1 macrophages displayed reduced tolerance to endotoxin. Moreover, endotoxin-induced internalization of TLR4 was strongly reduced and coincided with impaired endosomal MyD88-independent signaling. The phenotype of CDC50A-depleted cells was also induced by separate knockdown of two P4-ATPases, namely ATP8B1 and ATP11A. We conclude that lipid flippases are novel elements of the innate immune response that are essential to attenuate the inflammatory response, possibly by mediating endotoxin-induced internalization of TLR4.     

An unusual silver celestial planisphere in the Whipple Museum

An unusual silver celestial planisphere is held in the collection of the Whipple Museum of the History of Science (Wh.1762); little information about this object is recorded in the museum’s documentation. A comparison of this silver example with celestial planispheres printed on paper, coupled with the consideration of other aspects of the lives and work of the cartographers and instrument-makers involved in producing such objects, suggests some possibilities regarding its production. Through this individual case study, I aim to demonstrate that the careful examination of an individual instrument, coupled with an understanding of the class of instruments to which it belongs and the milieu in which it was produced, can result in a deeper understanding of any given artefact, its circumstances of design and manufacture, and its intended use and users.     

Zur Frage der Natur der Ablagerungen in den Gichtknoten

Summary A gout-tophus, which we examined by X-rays and micro-crystallographic methods was definitely proved to be a deposit of monosodiumurate-monohydrate in the form of crystals which could just be detected under the microscope.     

Measurements on the electrical resistivity of thin nickel films

Résumé Dans une publication antérieure, nous avions signalé que le coefficient de température de la résistance électrique des films en nickel était négatif en dessous d'une certaine épaisseur critique (40 mµ). Au-dessus de 40 mµ, la courbe «Résistance en fonction de la température» présentait un minimum aux basses températures. A la suite de nouvelles expériences, nous avons constaté que ce phénomène est accompagné d'une déviation de la loi d'Ohm: la résistance diminue quand le courant de mesure augmente. Nous avons pu conclure que ces deux particularités ne sont qu'indirectement provoquées par la minceur des films. La cause principale est leur état de cristallisation imparfaite. En effet, après avoir subi un échauffement à 150° C pendant plusieurs heures, le coefficient de température négatif change de signe (le minimum disparaît) et la loi d'Ohm est respectée.

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Research-fellow of the Belgian «Fonds National de la Recherche Scientifique»     

Die Nobelpreise für Medizin-Physiologie,Chemie und Physik

Ohne Zusammenfassung     

数据挖掘分类问题的贪婪粗糙集约简算法

基于贪婪算法和粗糙集方法,给出了一种处理数据挖掘分类问题的属性约简算法:贪婪粗糙集约简算法GRSR;在测试中得出的约简集为原始集的1/3,表明了它是一个有效的算法·其想法是:从初始约简集为空集开始,选择使分类质量最大的属性,将它加入约简集;再从余下的属性中选择使分类质量最大的属性并加入约简集,重复直至找到满意的约简集·     

连续梁桥的减隔震设计

在对桥梁减隔震原理进行分析的基础上,依据连续梁桥在地震作用时受力的特点,对连续桥梁的固定支座进行了减隔震设计,将原来的固定支座改为相对固定.对该桥在地震荷载作用下的抗震性能分析表明,采取减隔震措施后,固定墩的受力情况得到明显改善,主梁的纵向位移以及梁、墩的相对位移虽有所增大,但即使在8°的地震荷载作用下,位移幅度仍在支座允许的位移范围内.     

N′,N″-三(对甲苯磺酰)-三氨乙基胺(L)的合成和抗肿瘤活性研究

合成了一个三齿配体,并对其抗肿瘤活性进行了测试.