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排序方式: 共有433条查询结果,搜索用时 0 毫秒
41.
Léveillard T Mohand-Saïd S Lorentz O Hicks D Fintz AC Clérin E Simonutti M Forster V Cavusoglu N Chalmel F Dollé P Poch O Lambrou G Sahel JA 《Nature genetics》2004,36(7):755-759
Retinitis pigmentosa is an untreatable, inherited retinal disease that leads to blindness. The disease initiates with the loss of night vision due to rod photoreceptor degeneration, followed by irreversible, progressive loss of cone photoreceptor. Cone loss is responsible for the main visual handicap, as cones are essential for day and high-acuity vision. Their loss is indirect, as most genes associated with retinitis pigmentosa are not expressed by these cells. We previously showed that factors secreted from rods are essential for cone viability. Here we identified one such trophic factor by expression cloning and named it rod-derived cone viability factor (RdCVF). RdCVF is a truncated thioredoxin-like protein specifically expressed by photoreceptors. The identification of this protein offers new treatment possibilities for retinitis pigmentosa. 相似文献
42.
Maturation trends indicative of rapid evolution preceded the collapse of northern cod 总被引:1,自引:0,他引:1
Northern cod, comprising populations of Atlantic cod (Gadus morhua) off southern Labrador and eastern Newfoundland, supported major fisheries for hundreds of years. But in the late 1980s and early 1990s, northern cod underwent one of the worst collapses in the history of fisheries. The Canadian government closed the directed fishing for northern cod in July 1992, but even after a decade-long offshore moratorium, population sizes remain historically low. Here we show that, up until the moratorium, the life history of northern cod continually shifted towards maturation at earlier ages and smaller sizes. Because confounding effects of mortality changes and growth-mediated phenotypic plasticity are accounted for in our analyses, this finding strongly suggests fisheries-induced evolution of maturation patterns in the direction predicted by theory. We propose that fisheries managers could use the method described here as a tool to provide warning signals about changes in life history before more overt evidence of population decline becomes manifest. 相似文献
43.
Vetter DE Li C Zhao L Contarino A Liberman MC Smith GW Marchuk Y Koob GF Heinemann SF Vale W Lee KF 《Nature genetics》2002,31(4):363-369
Urocortin is a member of the corticotropin-releasing hormone peptide family and is found in many discrete brain regions. The distinct expression pattern of urocortin suggests that it influences such behaviors as feeding, anxiety and auditory processing. To better define the physiological roles of urocortin, we have generated mice carrying a null mutation of the urocortin gene. Urocortin-deficient mice have normal basal feeding behavior and stress responses, but show heightened anxiety-like behaviors in the elevated plus maze and open-field tests. In addition, hearing is impaired in the mutant mice at the level of the inner ear, suggesting that urocortin is involved in the normal development of cochlear sensory-cell function. These results provide the first example of a function for any peptidergic system in hearing. 相似文献
44.
Ostertag EM DeBerardinis RJ Goodier JL Zhang Y Yang N Gerton GL Kazazian HH 《Nature genetics》2002,32(4):655-660
The L1 retrotransposon has had an immense impact on the size and structure of the human genome through a variety of mechanisms, including insertional mutagenesis. To study retrotransposition in a living organism, we created a mouse model of human L1 retrotransposition. Here we show that L1 elements can retrotranspose in male germ cells, and that expression of a human L1 element under the control of its endogenous promoter is restricted to testis and ovary. In the mouse line with the highest level of L1 expression, we found two de novo L1 insertions in 135 offspring. Both insertions were structurally indistinguishable from natural endogenous insertions. This suggests that an individual L1 element can have substantial mutagenic potential. In addition to providing a valuable in vivo model of retrotransposition in mammals, these mice are an important step in the development of a new random mutagenesis system. 相似文献
45.
Low host specificity of herbivorous insects in a tropical forest 总被引:20,自引:0,他引:20
Two decades of research have not established whether tropical insect herbivores are dominated by specialists or generalists. This impedes our understanding of species coexistence in diverse rainforest communities. Host specificity and species richness of tropical insects are also key parameters in mapping global patterns of biodiversity. Here we analyse data for over 900 herbivorous species feeding on 51 plant species in New Guinea and show that most herbivorous species feed on several closely related plant species. Because species-rich genera are dominant in tropical floras, monophagous herbivores are probably rare in tropical forests. Furthermore, even between phylogenetically distant hosts, herbivore communities typically shared a third of their species. These results do not support the classical view that the coexistence of herbivorous species in the tropics is a consequence of finely divided plant resources; non-equilibrium models of tropical diversity should instead be considered. Low host specificity of tropical herbivores reduces global estimates of arthropod diversity from 31 million (ref. 1) to 4 6 million species. This finding agrees with estimates based on taxonomic collections, reconciling an order of magnitude discrepancy between extrapolations of global diversity based on ecological samples of tropical communities with those based on sampling regional faunas. 相似文献
46.
47.
Antibody neutralization and escape by HIV-1 总被引:62,自引:0,他引:62
Wei X Decker JM Wang S Hui H Kappes JC Wu X Salazar-Gonzalez JF Salazar MG Kilby JM Saag MS Komarova NL Nowak MA Hahn BH Kwong PD Shaw GM 《Nature》2003,422(6929):307-312
Neutralizing antibodies (Nab) are a principal component of an effective human immune response to many pathogens, yet their role in HIV-1 infection is unclear. To gain a better understanding of this role, we examined plasma from patients with acute HIV infection. Here we report the detection of autologous Nab as early as 52 days after detection of HIV-specific antibodies. The viral inhibitory activity of Nab resulted in complete replacement of neutralization-sensitive virus by successive populations of resistant virus. Escape virus contained mutations in the env gene that were unexpectedly sparse, did not map generally to known neutralization epitopes, and involved primarily changes in N-linked glycosylation. This pattern of escape, and the exceptional density of HIV-1 envelope glycosylation generally, led us to postulate an evolving 'glycan shield' mechanism of neutralization escape whereby selected changes in glycan packing prevent Nab binding but not receptor binding. Direct support for this model was obtained by mutational substitution showing that Nab-selected alterations in glycosylation conferred escape from both autologous antibody and epitope-specific monoclonal antibodies. The evolving glycan shield thus represents a new mechanism contributing to HIV-1 persistence in the face of an evolving antibody repertoire. 相似文献
48.
Lamarre D Anderson PC Bailey M Beaulieu P Bolger G Bonneau P Bös M Cameron DR Cartier M Cordingley MG Faucher AM Goudreau N Kawai SH Kukolj G Lagacé L LaPlante SR Narjes H Poupart MA Rancourt J Sentjens RE St George R Simoneau B Steinmann G Thibeault D Tsantrizos YS Weldon SM Yong CL Llinàs-Brunet M 《Nature》2003,426(6963):186-189
Hepatitis C virus (HCV) infection is a serious cause of chronic liver disease worldwide with more than 170 million infected individuals at risk of developing significant morbidity and mortality. Current interferon-based therapies are suboptimal especially in patients infected with HCV genotype 1, and they are poorly tolerated, highlighting the unmet medical need for new therapeutics. The HCV-encoded NS3 protease is essential for viral replication and has long been considered an attractive target for therapeutic intervention in HCV-infected patients. Here we identify a class of specific and potent NS3 protease inhibitors and report the evaluation of BILN 2061, a small molecule inhibitor biologically available through oral ingestion and the first of its class in human trials. Administration of BILN 2061 to patients infected with HCV genotype 1 for 2 days resulted in an impressive reduction of HCV RNA plasma levels, and established proof-of-concept in humans for an HCV NS3 protease inhibitor. Our results further illustrate the potential of the viral-enzyme-targeted drug discovery approach for the development of new HCV therapeutics. 相似文献
49.
CYLD is a deubiquitinating enzyme that negatively regulates NF-kappaB activation by TNFR family members 总被引:1,自引:0,他引:1
Trompouki E Hatzivassiliou E Tsichritzis T Farmer H Ashworth A Mosialos G 《Nature》2003,424(6950):793-796
50.