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81.
Stable messenger RNA in nucleated erythrocytes 总被引:1,自引:0,他引:1
82.
C. A. Baile F. Anne Scott J. Mayer 《Cellular and molecular life sciences : CMLS》1967,23(12):1033-1034
Résumé Par des lésions bilatérales hypothalamiques on a rendu des rats aphagiques et adipsiques. Durant la période de convalescence, on a injecté dans le ventricule latéral du pentotal de sodium (ce qui normalement fait manger les animaux) et une solution saline hypertonique (qui normalement les fait boire). On a trouvé qu'après les lésions les rats ne réagissent que lorsqu'ils sont redevenus capables de manger et de boire spontanément.
This work was supported in part by a grant from the National Institute of Neurological Diseases and Blindness, No. NB 01941, of the National Institutes of Health, U.S. Public Health Service, Bethesda, Maryland; by a grant from the National Science Foundation, No. GB-4594, Washington, D.C.; and the Fund for Research and Teaching of the Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts. 相似文献
This work was supported in part by a grant from the National Institute of Neurological Diseases and Blindness, No. NB 01941, of the National Institutes of Health, U.S. Public Health Service, Bethesda, Maryland; by a grant from the National Science Foundation, No. GB-4594, Washington, D.C.; and the Fund for Research and Teaching of the Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts. 相似文献
83.
Illing PT Vivian JP Dudek NL Kostenko L Chen Z Bharadwaj M Miles JJ Kjer-Nielsen L Gras S Williamson NA Burrows SR Purcell AW Rossjohn J McCluskey J 《Nature》2012,486(7404):554-558
Human leukocyte antigens (HLAs) are highly polymorphic proteins that initiate immunity by presenting pathogen-derived peptides to T?cells. HLA polymorphisms mostly map to the antigen-binding cleft, thereby diversifying the repertoire of self-derived and pathogen-derived peptide antigens selected by different HLA allotypes. A growing number of immunologically based drug reactions, including abacavir hypersensitivity syndrome (AHS) and carbamazepine-induced Stevens-Johnson syndrome (SJS), are associated with specific HLA alleles. However, little is known about the underlying mechanisms of these associations, including AHS, a prototypical HLA-associated drug reaction occurring exclusively in individuals with the common histocompatibility allele HLA-B*57:01, and with a relative risk of more than 1,000 (refs?6, 7). We show that unmodified abacavir binds non-covalently to HLA-B*57:01, lying across the bottom of the antigen-binding cleft and reaching into the F-pocket, where a carboxy-terminal tryptophan typically anchors peptides bound to HLA-B*57:01. Abacavir binds with exquisite specificity to HLA-B*57:01, changing the shape and chemistry of the antigen-binding cleft, thereby altering the repertoire of endogenous peptides that can bind HLA-B*57:01. In this way, abacavir guides the selection of new endogenous peptides, inducing a marked alteration in 'immunological self'. The resultant peptide-centric 'altered self' activates abacavir-specific T-cells, thereby driving polyclonal CD8 T-cell activation and a systemic reaction manifesting as AHS. We also show that carbamazepine, a widely used anti-epileptic drug associated with hypersensitivity reactions in HLA-B*15:02 individuals, binds to this allotype, producing alterations in the repertoire of presented self peptides. Our findings simultaneously highlight the importance of HLA polymorphism in the evolution of pharmacogenomics and provide a general mechanism for some of the growing number of HLA-linked hypersensitivities that involve small-molecule drugs. 相似文献
84.
Scott MC Chen CC Mecklenburg M Zhu C Xu R Ercius P Dahmen U Regan BC Miao J 《Nature》2012,483(7390):444-447
Transmission electron microscopy is a powerful imaging tool that has found broad application in materials science, nanoscience and biology. With the introduction of aberration-corrected electron lenses, both the spatial resolution and the image quality in transmission electron microscopy have been significantly improved and resolution below 0.5??ngstr?ms has been demonstrated. To reveal the three-dimensional (3D) structure of thin samples, electron tomography is the method of choice, with cubic-nanometre resolution currently achievable. Discrete tomography has recently been used to generate a 3D atomic reconstruction of a silver nanoparticle two to three nanometres in diameter, but this statistical method assumes prior knowledge of the particle's lattice structure and requires that the atoms fit rigidly on that lattice. Here we report the experimental demonstration of a general electron tomography method that achieves atomic-scale resolution without initial assumptions about the sample structure. By combining a novel projection alignment and tomographic reconstruction method with scanning transmission electron microscopy, we have determined the 3D structure of an approximately ten-nanometre gold nanoparticle at 2.4-?ngstr?m resolution. Although we cannot definitively locate all of the atoms inside the nanoparticle, individual atoms are observed in some regions of the particle and several grains are identified in three dimensions. The 3D surface morphology and internal lattice structure revealed are consistent with a distorted icosahedral multiply twinned particle. We anticipate that this general method can be applied not only to determine the 3D structure of nanomaterials at atomic-scale resolution, but also to improve the spatial resolution and image quality in other tomography fields. 相似文献
85.
Chromatin-modifying enzymes as modulators of reprogramming 总被引:2,自引:0,他引:2
Onder TT Kara N Cherry A Sinha AU Zhu N Bernt KM Cahan P Marcarci BO Unternaehrer J Gupta PB Lander ES Armstrong SA Daley GQ 《Nature》2012,483(7391):598-602
86.
Almost all species are subject to continuous attack by parasites and pathogens. Because parasites and pathogens tend to have shorter generation times and often experience stronger selection due to interaction than their victims do, it is frequently argued that they should evolve more rapidly and thus maintain an advantage in the evolutionary race between defence and counter-defence. This prediction generates an apparent paradox: how do victim species survive and even thrive in the face of a continuous onslaught of more rapidly evolving enemies? One potential explanation is that defence is physiologically, mechanically or behaviourally easier than attack, so that evolution is less constrained for victims than for parasites or pathogens. Another possible explanation is that parasites and pathogens have enemies themselves and that victim species persist because parasites and pathogens are regulated from the top down and thus generally have only modest demographic impacts on victim populations. Here we explore a third possibility: that victim species are not as evolutionarily impotent as conventional wisdom holds, but instead have unique evolutionary advantages that help to level the playing field. We use quantitative genetic analysis and individual-based simulations to show that victims can achieve such an advantage when coevolution involves multiple traits in both the host and the parasite. 相似文献
87.
S Neph J Vierstra AB Stergachis AP Reynolds E Haugen B Vernot RE Thurman S John R Sandstrom AK Johnson MT Maurano R Humbert E Rynes H Wang S Vong K Lee D Bates M Diegel V Roach D Dunn J Neri A Schafer RS Hansen T Kutyavin E Giste M Weaver T Canfield P Sabo M Zhang G Balasundaram R Byron MJ MacCoss JM Akey MA Bender M Groudine R Kaul JA Stamatoyannopoulos 《Nature》2012,489(7414):83-90
88.
Ridgway J Zhang G Wu Y Stawicki S Liang WC Chanthery Y Kowalski J Watts RJ Callahan C Kasman I Singh M Chien M Tan C Hongo JA de Sauvage F Plowman G Yan M 《Nature》2006,444(7122):1083-1087
Haploinsufficiency of Dll4, a vascular-specific Notch ligand, has shown that it is essential for embryonic vascular development and arteriogenesis. Mechanistically, it is unclear how the Dll4-mediated Notch pathway contributes to complex vascular processes that demand meticulous coordination of multiple signalling pathways. Here we show that Dll4-mediated Notch signalling has a unique role in regulating endothelial cell proliferation and differentiation. Neutralizing Dll4 with a Dll4-selective antibody rendered endothelial cells hyperproliferative, and caused defective cell fate specification or differentiation both in vitro and in vivo. In addition, blocking Dll4 inhibited tumour growth in several tumour models. Remarkably, antibodies against Dll4 and antibodies against vascular endothelial growth factor (VEGF) had paradoxically distinct effects on tumour vasculature. Our data also indicate that Dll4-mediated Notch signalling is crucial during active vascularization, but less important for normal vessel maintenance. Furthermore, unlike blocking Notch signalling globally, neutralizing Dll4 had no discernable impact on intestinal goblet cell differentiation, supporting the idea that Dll4-mediated Notch signalling is largely restricted to the vascular compartment. Therefore, targeting Dll4 might represent a broadly efficacious and well-tolerated approach for the treatment of solid tumours. 相似文献
89.
90.
Marchis F Hestroffer D Descamps P Berthier J Bouchez AH Campbell RD Chin JC van Dam MA Hartman SK Johansson EM Lafon RE Le Mignant D de Pater I Stomski PJ Summers DM Vachier F Wizinovich PL Wong MH 《Nature》2006,439(7076):565-567
The Trojan population consists of two swarms of asteroids following the same orbit as Jupiter and located at the L4 and L5 stable Lagrange points of the Jupiter-Sun system (leading and following Jupiter by 60 degrees ). The asteroid 617 Patroclus is the only known binary Trojan. The orbit of this double system was hitherto unknown. Here we report that the components, separated by 680 km, move around the system's centre of mass, describing a roughly circular orbit. Using this orbital information, combined with thermal measurements to estimate the size of the components, we derive a very low density of 0.8(- 0.1)+0.2 g cm(-3). The components of 617 Patroclus are therefore very porous or composed mostly of water ice, suggesting that they could have been formed in the outer part of the Solar System. 相似文献