SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx

The primate lentivirus auxiliary protein Vpx counteracts an unknown restriction factor that renders human dendritic and myeloid cells largely refractory to HIV-1 infection. Here we identify SAMHD1 as this restriction factor. SAMHD1 is a protein involved in Aicardi-Goutières syndrome, a genetic encephalopathy with symptoms mimicking congenital viral infection, that has been proposed to act as a negative regulator of the interferon response. We show that Vpx induces proteasomal degradation of SAMHD1. Silencing of SAMHD1 in non-permissive cell lines alleviates HIV-1 restriction and is associated with a significant accumulation of viral DNA in infected cells. Concurrently, overexpression of SAMHD1 in sensitive cells inhibits HIV-1 infection. The putative phosphohydrolase activity of SAMHD1 is probably required for HIV-1 restriction. Vpx-mediated relief of restriction is abolished in SAMHD1-negative cells. Finally, silencing of SAMHD1 markedly increases the susceptibility of monocytic-derived dendritic cells to infection. Our results demonstrate that SAMHD1 is an antiretroviral protein expressed in cells of the myeloid lineage that inhibits an early step of the viral life cycle.     

Dynamic molecular processes mediate cellular mechanotransduction

Cellular responses to mechanical forces are crucial in embryonic development and adult physiology, and are involved in numerous diseases, including atherosclerosis, hypertension, osteoporosis, muscular dystrophy, myopathies and cancer. These responses are mediated by load-bearing subcellular structures, such as the plasma membrane, cell-adhesion complexes and the cytoskeleton. Recent work has demonstrated that these structures are dynamic, undergoing assembly, disassembly and movement, even when ostensibly stable. An emerging insight is that transduction of forces into biochemical signals occurs within the context of these processes. This framework helps to explain how forces of varying strengths or dynamic characteristics regulate distinct signalling pathways.     

Mapping and sequencing of structural variation from eight human genomes

Genetic variation among individual humans occurs on many different scales, ranging from gross alterations in the human karyotype to single nucleotide changes. Here we explore variation on an intermediate scale--particularly insertions, deletions and inversions affecting from a few thousand to a few million base pairs. We employed a clone-based method to interrogate this intermediate structural variation in eight individuals of diverse geographic ancestry. Our analysis provides a comprehensive overview of the normal pattern of structural variation present in these genomes, refining the location of 1,695 structural variants. We find that 50% were seen in more than one individual and that nearly half lay outside regions of the genome previously described as structurally variant. We discover 525 new insertion sequences that are not present in the human reference genome and show that many of these are variable in copy number between individuals. Complete sequencing of 261 structural variants reveals considerable locus complexity and provides insights into the different mutational processes that have shaped the human genome. These data provide the first high-resolution sequence map of human structural variation--a standard for genotyping platforms and a prelude to future individual genome sequencing projects.     

新传染病:它们来自何方

传染病在近25年来常常是头条新闻.1980年代艾滋病开始出现,现在已成为遍及全球的最致命的传染病.1990年代,在欧洲,也可以说是在世界各地,疯牛病危机对经济造成了破坏.新千年伊始,一种潜在的灾难性的流行性疾病SARS,本可以尽早控制,却因禽流感而雪上加霜.     

Adrenal relationships to aggressiveness in isolated female mice

Résumé Lorsque des souris femelles soumises à l'isolement sont groupées selon leur tempérament belliquex et non-belliqueux, on observe une augmentation de l'activité médullossurrénalienne chez les animaux isolés belliquex. Au contraire, les souris isolées non-belliqueuses ont montré des taux de catécholamines inférieurs et une secrétion cortico-surrénale nettement augmentée.

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Submitted byRalph Schwartz to the faculty of Richard L. Connelly College, Long Island University in partial fulfillment of the requirements for the Degree of Masters of Science.     

Plasticity of functional epithelial polarity

The fundamental characteristics that allow vectorial transport across an epithelial cell are the differential sorting and insertion of transport proteins either in the apical or the basolateral plasma membrane, and the preferential association of endocytosis and exocytosis with one or the other pole of the cell. Asymmetrical cellular structure and function, being manifestations of terminal differentiation, might be expected to be predetermined and invariant. Here we show that the polarity of transepithelial H+ transport, endocytosis and exocytosis in kidney can be reversed by environmental stimuli. The HCO3- secreting cell in the cortical collecting tubule is found to be an intercalated cell possessing a Cl-/HCO3- exchanger in the apical membrane and proton pumps in endocytic vesicles that fuse with the basolateral membrane; the H+-secreting cell in the medullary collecting tubule has these transport functions on the opposite membranes. Further, the HCO3- -secreting cell can be induced to change its functional polarity to that of the H+-secreting cell by acid-loading the animal.