排序方式: 共有66条查询结果,搜索用时 27 毫秒
41.
Dendritic cells have a unique function in the immune response owing to their ability to stimulate immunologically naive T lymphocytes. In response to microbial and inflammatory stimuli, dendritic cells enhance their capacity for antigen presentation by a process of terminal differentiation, termed maturation. The conversion of immature to mature dendritic cells is accompanied by a marked cellular reorganization, including the redistribution of major histocompatibility complex class II molecules (MHC II) from late endosomal and lysosomal compartments to the plasma membrane and the downregulation of some forms of endocytosis, which has been thought to slow the clearance of MHC II from the surface. The relative extent to which these or other mechanisms contribute to the regulation of surface MHC II remains unclear, however. Here we find that the MHC II beta-chain cytoplasmic tail is ubiquitinated in mouse immature dendritic cells. Although only partly required for the sequestration of MHC II in multivesicular bodies, this modification is essential for endocytosis. Notably, ubiquitination of MHC II ceased upon maturation, resulting in the accumulation of MHC II at the cell surface. Dendritic cells thus exhibit a unique ability to regulate MHC II surface expression by selectively controlling MHC II ubiquitination. 相似文献
42.
MA Deardorff M Bando R Nakato E Watrin T Itoh M Minamino K Saitoh M Komata Y Katou D Clark KE Cole E De Baere C Decroos N Di Donato S Ernst LJ Francey Y Gyftodimou K Hirashima M Hullings Y Ishikawa C Jaulin M Kaur T Kiyono PM Lombardi L Magnaghi-Jaulin GR Mortier N Nozaki MB Petersen H Seimiya VM Siu Y Suzuki K Takagaki JJ Wilde PJ Willems C Prigent G Gillessen-Kaesbach DW Christianson FJ Kaiser LG Jackson T Hirota ID Krantz K Shirahige 《Nature》2012,489(7415):313-317
43.
A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response 总被引:1,自引:0,他引:1
L Kruidenier CW Chung Z Cheng J Liddle K Che G Joberty M Bantscheff C Bountra A Bridges H Diallo D Eberhard S Hutchinson E Jones R Katso M Leveridge PK Mander J Mosley C Ramirez-Molina P Rowland CJ Schofield RJ Sheppard JE Smith C Swales R Tanner P Thomas A Tumber G Drewes U Oppermann DJ Patel K Lee DM Wilson 《Nature》2012,488(7411):404-408
44.
Jäger S Cimermancic P Gulbahce N Johnson JR McGovern KE Clarke SC Shales M Mercenne G Pache L Li K Hernandez H Jang GM Roth SL Akiva E Marlett J Stephens M D'Orso I Fernandes J Fahey M Mahon C O'Donoghue AJ Todorovic A Morris JH Maltby DA Alber T Cagney G Bushman FD Young JA Chanda SK Sundquist WI Kortemme T Hernandez RD Craik CS Burlingame A Sali A Frankel AD Krogan NJ 《Nature》2012,481(7381):365-370
Human immunodeficiency virus (HIV) has a small genome and therefore relies heavily on the host cellular machinery to replicate. Identifying which host proteins and complexes come into physical contact with the viral proteins is crucial for a comprehensive understanding of how HIV rewires the host's cellular machinery during the course of infection. Here we report the use of affinity tagging and purification mass spectrometry to determine systematically the physical interactions of all 18 HIV-1 proteins and polyproteins with host proteins in two different human cell lines (HEK293 and Jurkat). Using a quantitative scoring system that we call MiST, we identified with high confidence 497 HIV-human protein-protein interactions involving 435 individual human proteins, with ~40% of the interactions being identified in both cell types. We found that the host proteins hijacked by HIV, especially those found interacting in both cell types, are highly conserved across primates. We uncovered a number of host complexes targeted by viral proteins, including the finding that HIV protease cleaves eIF3d, a subunit of eukaryotic translation initiation factor 3. This host protein is one of eleven identified in this analysis that act to inhibit HIV replication. This data set facilitates a more comprehensive and detailed understanding of how the host machinery is manipulated during the course of HIV infection. 相似文献
45.
Walter F Decarli R Carilli C Bertoldi F Cox P Da Cunha E Daddi E Dickinson M Downes D Elbaz D Ellis R Hodge J Neri R Riechers DA Weiss A Bell E Dannerbauer H Krips M Krumholz M Lentati L Maiolino R Menten K Rix HW Robertson B Spinrad H Stark DP Stern D 《Nature》2012,486(7402):233-236
The Hubble Deep Field provides one of the deepest multiwavelength views of the distant Universe and has led to the detection of thousands of galaxies seen throughout cosmic time. An early map of the Hubble Deep Field at a wavelength of 850?micrometres, which is sensitive to dust emission powered by star formation, revealed the brightest source in the field, dubbed HDF?850.1 (ref. 2). For more than a decade, and despite significant efforts, no counterpart was found at shorter wavelengths, and it was not possible to determine its redshift, size or mass. Here we report a redshift of z = 5.183 for HDF?850.1, from a millimetre-wave molecular line scan. This places HDF?850.1 in a galaxy overdensity at z?≈?5.2, corresponding to a cosmic age of only 1.1?billion years after the Big Bang. This redshift is significantly higher than earlier estimates and higher than those of most of the hundreds of submillimetre-bright galaxies identified so far. The source has a star-formation rate of 850 solar masses per year and is spatially resolved on scales of 5 kiloparsecs, with an implied dynamical mass of about 1.3?×?10(11) solar masses, a significant fraction of which is present in the form of molecular gas. Despite our accurate determination of redshift and position, a counterpart emitting starlight remains elusive. 相似文献
46.
Remobilization of southern African desert dune systems by twenty-first century global warming 总被引:3,自引:0,他引:3
Although desert dunes cover 5 per cent of the global land surface and 30 per cent of Africa, the potential impacts of twenty-first century global warming on desert dune systems are not well understood. The inactive Sahel and southern African dune systems, which developed in multiple arid phases since the last interglacial period, are used today by pastoral and agricultural systems that could be disrupted if climate change alters twenty-first century dune dynamics. Empirical data and model simulations have established that the interplay between dune surface erodibility (determined by vegetation cover and moisture availability) and atmospheric erosivity (determined by wind energy) is critical for dunefield dynamics. This relationship between erodibility and erosivity is susceptible to climate-change impacts. Here we use simulations with three global climate models and a range of emission scenarios to assess the potential future activity of three Kalahari dunefields. We determine monthly values of dune activity by modifying and improving an established dune mobility index so that it can account for global climate model data outputs. We find that, regardless of the emission scenario used, significantly enhanced dune activity is simulated in the southern dunefield by 2039, and in the eastern and northern dunefields by 2069. By 2099 all dunefields are highly dynamic, from northern South Africa to Angola and Zambia. Our results suggest that dunefields are likely to be reactivated (the sand will become significantly exposed and move) as a consequence of twenty-first century climate warming. 相似文献
47.
LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription 总被引:4,自引:0,他引:4
Metzger E Wissmann M Yin N Müller JM Schneider R Peters AH Günther T Buettner R Schüle R 《Nature》2005,437(7057):436-439
48.
Positional cloning of a quantitative trait locus on chromosome 13q14 that influences immunoglobulin E levels and asthma 总被引:20,自引:0,他引:20
49.
Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family 总被引:23,自引:0,他引:23
Schlingmann KP Weber S Peters M Niemann Nejsum L Vitzthum H Klingel K Kratz M Haddad E Ristoff E Dinour D Syrrou M Nielsen S Sassen M Waldegger S Seyberth HW Konrad M 《Nature genetics》2002,31(2):166-170
Magnesium is an essential ion involved in many biochemical and physiological processes. Homeostasis of magnesium levels is tightly regulated and depends on the balance between intestinal absorption and renal excretion. However, little is known about specific proteins mediating transepithelial magnesium transport. Using a positional candidate gene approach, we identified mutations in TRPM6 (also known as CHAK2), encoding TRPM6, in autosomal-recessive hypomagnesemia with secondary hypocalcemia (HSH, OMIM 602014), previously mapped to chromosome 9q22 (ref. 3). The TRPM6 protein is a new member of the long transient receptor potential channel (TRPM) family and is highly similar to TRPM7 (also known as TRP-PLIK), a bifunctional protein that combines calcium- and magnesium-permeable cation channel properties with protein kinase activity. TRPM6 is expressed in intestinal epithelia and kidney tubules. These findings indicate that TRPM6 is crucial for magnesium homeostasis and implicate a TRPM family member in human disease. 相似文献
50.
Signalling by means of toll-like receptors (TLRs) is essential for the development of innate and adaptive immune responses. UNC93B1, essential for signalling of TLR3, TLR7 and TLR9 in both humans and mice, physically interacts with these TLRs in the endoplasmic reticulum (ER). Here we show that the function of the polytopic membrane protein UNC93B1 is to deliver the nucleotide-sensing receptors TLR7 and TLR9 from the ER to endolysosomes. In dendritic cells of 3d mice, which express an UNC93B1 missense mutant (H412R) incapable of TLR binding, neither TLR7 nor TLR9 exits the ER. Furthermore, the trafficking and signalling defects of the nucleotide-sensing TLRs in 3d dendritic cells are corrected by expression of wild-type UNC93B1. However, UNC93B1 is dispensable for ligand recognition and signal initiation by TLRs. To our knowledge, UNC93B1 is the first protein to be identified as a molecule specifically involved in trafficking of nucleotide-sensing TLRs. By inhibiting the interaction between UNC93B1 and TLRs it should be possible to achieve specific regulation of the nucleotide-sensing TLRs without compromising signalling via the cell-surface-disposed TLRs. 相似文献