排序方式: 共有48条查询结果,搜索用时 15 毫秒
21.
Walker LM Huber M Doores KJ Falkowska E Pejchal R Julien JP Wang SK Ramos A Chan-Hui PY Moyle M Mitcham JL Hammond PW Olsen OA Phung P Fling S Wong CH Phogat S Wrin T Simek MD;Protocol G Principal Investigators Koff WC Wilson IA Burton DR Poignard P 《Nature》2011,477(7365):466-470
Broadly neutralizing antibodies against highly variable viral pathogens are much sought after to treat or protect against global circulating viruses. Here we probed the neutralizing antibody repertoires of four human immunodeficiency virus (HIV)-infected donors with remarkably broad and potent neutralizing responses and rescued 17 new monoclonal antibodies that neutralize broadly across clades. Many of the new monoclonal antibodies are almost tenfold more potent than the recently described PG9, PG16 and VRC01 broadly neutralizing monoclonal antibodies and 100-fold more potent than the original prototype HIV broadly neutralizing monoclonal antibodies. The monoclonal antibodies largely recapitulate the neutralization breadth found in the corresponding donor serum and many recognize novel epitopes on envelope (Env) glycoprotein gp120, illuminating new targets for vaccine design. Analysis of neutralization by the full complement of anti-HIV broadly neutralizing monoclonal antibodies now available reveals that certain combinations of antibodies should offer markedly more favourable coverage of the enormous diversity of global circulating viruses than others and these combinations might be sought in active or passive immunization regimes. Overall, the isolation of multiple HIV broadly neutralizing monoclonal antibodies from several donors that, in aggregate, provide broad coverage at low concentrations is a highly positive indicator for the eventual design of an effective antibody-based HIV vaccine. 相似文献
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Schmitt-John T Drepper C Mussmann A Hahn P Kuhlmann M Thiel C Hafner M Lengeling A Heimann P Jones JM Meisler MH Jockusch H 《Nature genetics》2005,37(11):1213-1215
Vacuolar-vesicular protein sorting (Vps) factors are involved in vesicular trafficking in eukaryotic cells. We identified the missense mutation L967Q in Vps54 in the wobbler mouse, an animal model of amyotrophic lateral sclerosis, and also characterized a lethal allele, Vps54(beta-geo). Motoneuron survival and spermiogenesis are severely compromised in the wobbler mouse, indicating that Vps54 has an essential role in these processes. 相似文献
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The mass and chemical composition of a star are the primary determinants of its basic physical properties-radius, temperature and luminosity-and how those properties evolve with time. Accordingly, two stars born at the same time, from the same natal material and with the same mass, are 'identical twins,' and as such might be expected to possess identical physical attributes. We have discovered in the Orion nebula a pair of stellar twins in a newborn binary star system. Each star in the binary has a mass of 0.41 +/- 0.01 solar masses, identical to within 2 per cent. Here we report that these twin stars have surface temperatures differing by approximately 300 K ( approximately 10 per cent) and luminosities differing by approximately 50 per cent, both at high confidence level. Preliminary results indicate that the stars' radii also differ, by 5-10 per cent. These surprising dissimilarities suggest that one of the twins may have been delayed by several hundred thousand years in its formation relative to its sibling. Such a delay could only have been detected in a very young, definitively equal-mass binary system. Our findings reveal cosmic limits on the age synchronization of young binary stars, often used as tests for the age calibrations of star-formation models. 相似文献
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Smith UM Consugar M Tee LJ McKee BM Maina EN Whelan S Morgan NV Goranson E Gissen P Lilliquist S Aligianis IA Ward CJ Pasha S Punyashthiti R Malik Sharif S Batman PA Bennett CP Woods CG McKeown C Bucourt M Miller CA Cox P Algazali L Trembath RC Torres VE Attie-Bitach T Kelly DA Maher ER Gattone VH Harris PC Johnson CA 《Nature genetics》2006,38(2):191-196
Meckel-Gruber syndrome is a severe autosomal, recessively inherited disorder characterized by bilateral renal cystic dysplasia, developmental defects of the central nervous system (most commonly occipital encephalocele), hepatic ductal dysplasia and cysts and polydactyly. MKS is genetically heterogeneous, with three loci mapped: MKS1, 17q21-24 (ref. 4); MKS2, 11q13 (ref. 5) and MKS3 (ref. 6). We have refined MKS3 mapping to a 12.67-Mb interval (8q21.13-q22.1) that is syntenic to the Wpk locus in rat, which is a model with polycystic kidney disease, agenesis of the corpus callosum and hydrocephalus. Positional cloning of the Wpk gene suggested a MKS3 candidate gene, TMEM67, for which we identified pathogenic mutations for five MKS3-linked consanguineous families. MKS3 is a previously uncharacterized, evolutionarily conserved gene that is expressed at moderate levels in fetal brain, liver and kidney but has widespread, low levels of expression. It encodes a 995-amino acid seven-transmembrane receptor protein of unknown function that we have called meckelin. 相似文献
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MicroRNAs can generate thresholds in target gene expression 总被引:2,自引:0,他引:2
Mukherji S Ebert MS Zheng GX Tsang JS Sharp PA van Oudenaarden A 《Nature genetics》2011,43(9):854-859
MicroRNAs (miRNAs) are short, highly conserved noncoding RNA molecules that repress gene expression in a sequence-dependent manner. We performed single-cell measurements using quantitative fluorescence microscopy and flow cytometry to monitor a target gene's protein expression in the presence and absence of regulation by miRNA. We find that although the average level of repression is modest, in agreement with previous population-based measurements, the repression among individual cells varies dramatically. In particular, we show that regulation by miRNAs establishes a threshold level of target mRNA below which protein production is highly repressed. Near this threshold, protein expression responds sensitively to target mRNA input, consistent with a mathematical model of molecular titration. These results show that miRNAs can act both as a switch and as a fine-tuner of gene expression. 相似文献
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Higgins GC Devenish RJ Beart PM Nagley P 《Cellular and molecular life sciences : CMLS》2011,68(22):3725-3740
Primary neurons undergo insult-dependent programmed cell death. We examined autophagy as a process contributing to cell death
in cortical neurons after treatment with either hydrogen peroxide (H2O2) or staurosporine. Although caspase-9 activation and cleavage of procaspase-3 were significant following staurosporine treatment,
neither was observed following H2O2 treatment, indicating a non-apoptotic death. Autophagic activity increased rapidly with H2O2, but slowly with staurosporine, as quantified by processing of endogenous LC3. Autophagic induction by both stressors increased
the abundance of fluorescent puncta formed by GFP-LC3, which could be blocked by 3-methyladenine. Significantly, such inhibition
of autophagy blocked cell death induced by H2O2 but not staurosporine. Suppression of Atg7 inhibited cell death by H2O2, but not staurosporine, whereas suppression of Beclin 1 prevented cell death by both treatments, suggesting it has a complex
role regulating both apoptosis and autophagy. We conclude that autophagic mechanisms are activated in an insult-dependent
manner and that H2O2 induces autophagic cell death. 相似文献
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Although there has been considerable progress in the development of engineering principles for synthetic biology, a substantial challenge is the construction of robust circuits in a noisy cellular environment. Such an environment leads to considerable intercellular variability in circuit behaviour, which can hinder functionality at the colony level. Here we engineer the synchronization of thousands of oscillating colony 'biopixels' over centimetre-length scales through the use of synergistic intercellular coupling involving quorum sensing within a colony and gas-phase redox signalling between colonies. We use this platform to construct a liquid crystal display (LCD)-like macroscopic clock that can be used to sense arsenic via modulation of the oscillatory period. Given the repertoire of sensing capabilities of bacteria such as Escherichia coli, the ability to coordinate their behaviour over large length scales sets the stage for the construction of low cost genetic biosensors that are capable of detecting heavy metals and pathogens in the field. 相似文献