排序方式: 共有57条查询结果,搜索用时 15 毫秒
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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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Julien Pollack 《Systemic Practice and Action Research》2006,19(4):383-398
This paper is written from the perspective of a practitioner-researcher coming to terms with methodologically or theoretically pluralist practice. Common depictions of the relationship between the hard and soft paradigms are discussed, including the influence of the problem of paradigmatic incommensurability. The consequences of different ways in which this relationship is depicted are examined, in light of various perspectives on the relationship of Critical Systems Thinking to these paradigms. Alternative models of this relationship are provided, followed by discussion of how these models can be extended to combinations of other paradigms in different contexts. 相似文献
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Defining the core Arabidopsis thaliana root microbiome 总被引:9,自引:0,他引:9
DS Lundberg SL Lebeis SH Paredes S Yourstone J Gehring S Malfatti J Tremblay A Engelbrektson V Kunin TG del Rio RC Edgar T Eickhorst RE Ley P Hugenholtz SG Tringe JL Dangl 《Nature》2012,488(7409):86-90
Land plants associate with a root microbiota distinct from the complex microbial community present in surrounding soil. The microbiota colonizing the rhizosphere (immediately surrounding the root) and the endophytic compartment (within the root) contribute to plant growth, productivity, carbon sequestration and phytoremediation. Colonization of the root occurs despite a sophisticated plant immune system, suggesting finely tuned discrimination of mutualists and commensals from pathogens. Genetic principles governing the derivation of host-specific endophyte communities from soil communities are poorly understood. Here we report the pyrosequencing of the bacterial 16S ribosomal RNA gene of more than 600 Arabidopsis thaliana plants to test the hypotheses that the root rhizosphere and endophytic compartment microbiota of plants grown under controlled conditions in natural soils are sufficiently dependent on the host to remain consistent across different soil types and developmental stages, and sufficiently dependent on host genotype to vary between inbred Arabidopsis accessions. We describe different bacterial communities in two geochemically distinct bulk soils and in rhizosphere and endophytic compartments prepared from roots grown in these soils. The communities in each compartment are strongly influenced by soil type. Endophytic compartments from both soils feature overlapping, low-complexity communities that are markedly enriched in Actinobacteria and specific families from other phyla, notably Proteobacteria. Some bacteria vary quantitatively between plants of different developmental stage and genotype. Our rigorous definition of an endophytic compartment microbiome should facilitate controlled dissection of plant-microbe interactions derived from complex soil communities. 相似文献
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The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein 总被引:22,自引:0,他引:22
Gottar M Gobert V Michel T Belvin M Duyk G Hoffmann JA Ferrandon D Royet J 《Nature》2002,416(6881):640-644
The antimicrobial defence of Drosophila relies largely on the challenge-induced synthesis of an array of potent antimicrobial peptides by the fat body. The defence against Gram-positive bacteria and natural fungal infections is mediated by the Toll signalling pathway, whereas defence against Gram-negative bacteria is dependent on the Immune deficiency (IMD) pathway. Loss-of-function mutations in either pathway reduce the resistance to corresponding infections. The link between microbial infections and activation of these two pathways has remained elusive. The Toll pathway is activated by Gram-positive bacteria through a circulating Peptidoglycan recognition protein (PGRP-SA). PGRPs appear to be highly conserved from insects to mammals, and the Drosophila genome contains 13 members. Here we report a mutation in a gene coding for a putative transmembrane protein, PGRP-LC, which reduces survival to Gram-negative sepsis but has no effect on the response to Gram-positive bacteria or natural fungal infections. By genetic epistasis, we demonstrate that PGRP-LC acts upstream of the imd gene. The data on PGRP-SA with respect to the response to Gram-positive infections, together with the present report, indicate that the PGRP family has a principal role in sensing microbial infections in Drosophila. 相似文献
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Doiron-Leyraud N Proust C LeBoeuf D Levallois J Bonnemaison JB Liang R Bonn DA Hardy WN Taillefer L 《Nature》2007,447(7144):565-568
Despite twenty years of research, the phase diagram of high-transition-temperature superconductors remains enigmatic. A central issue is the origin of the differences in the physical properties of these copper oxides doped to opposite sides of the superconducting region. In the overdoped regime, the material behaves as a reasonably conventional metal, with a large Fermi surface. The underdoped regime, however, is highly anomalous and appears to have no coherent Fermi surface, but only disconnected 'Fermi arcs'. The fundamental question, then, is whether underdoped copper oxides have a Fermi surface, and if so, whether it is topologically different from that seen in the overdoped regime. Here we report the observation of quantum oscillations in the electrical resistance of the oxygen-ordered copper oxide YBa2Cu3O6.5, establishing the existence of a well-defined Fermi surface in the ground state of underdoped copper oxides, once superconductivity is suppressed by a magnetic field. The low oscillation frequency reveals a Fermi surface made of small pockets, in contrast to the large cylinder characteristic of the overdoped regime. Two possible interpretations are discussed: either a small pocket is part of the band structure specific to YBa2Cu3O6.5 or small pockets arise from a topological change at a critical point in the phase diagram. Our understanding of high-transition-temperature (high-T(c)) superconductors will depend critically on which of these two interpretations proves to be correct. 相似文献
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Gleyzes S Kuhr S Guerlin C Bernu J Deléglise S Busk Hoff U Brune M Raimond JM Haroche S 《Nature》2007,446(7133):297-300
A microscopic quantum system under continuous observation exhibits at random times sudden jumps between its states. The detection of this quantum feature requires a quantum non-demolition (QND) measurement repeated many times during the system's evolution. Whereas quantum jumps of trapped massive particles (electrons, ions or molecules) have been observed, this has proved more challenging for light quanta. Standard photodetectors absorb light and are thus unable to detect the same photon twice. It is therefore necessary to use a transparent counter that can 'see' photons without destroying them. Moreover, the light needs to be stored for durations much longer than the QND detection time. Here we report an experiment in which we fulfil these challenging conditions and observe quantum jumps in the photon number. Microwave photons are stored in a superconducting cavity for times up to half a second, and are repeatedly probed by a stream of non-absorbing atoms. An atom interferometer measures the atomic dipole phase shift induced by the non-resonant cavity field, so that the final atom state reveals directly the presence of a single photon in the cavity. Sequences of hundreds of atoms, highly correlated in the same state, are interrupted by sudden state switchings. These telegraphic signals record the birth, life and death of individual photons. Applying a similar QND procedure to mesoscopic fields with tens of photons should open new perspectives for the exploration of the quantum-to-classical boundary. 相似文献
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Diego Sbardella Grazia R. Tundo Andrea Coletta Julien Marcoux Efthymia Ioanna Koufogeorgou Chiara Ciaccio Anna M. Santoro Danilo Milardi Giuseppe Grasso Paola Cozza Marie-Pierre Bousquet-Dubouch Stefano Marini Massimo Coletta 《Cellular and molecular life sciences : CMLS》2018,75(18):3441-3456
The interaction of insulin-degrading enzyme (IDE) with the main intracellular proteasome assemblies (i.e, 30S, 26S and 20S) was analyzed by enzymatic activity, mass spectrometry and native gel electrophoresis. IDE was mainly detected in association with assemblies with at least one free 20S end and biochemical investigations suggest that IDE competes with the 19S in vitro. IDE directly binds the 20S and affects its proteolytic activities in a bimodal fashion, very similar in human and yeast 20S, inhibiting at (IDE)?≤?30 nM and activating at (IDE)?≥?30 nM. Only an activating effect is observed in a yeast mutant locked in the “open” conformation (i.e., the α-3ΔN 20S), envisaging a possible role of IDE as modulator of the 20S “open”–”closed” allosteric equilibrium. Protein–protein docking in silico proposes that the interaction between IDE and the 20S could involve the C-term helix of the 20S α-3 subunit which regulates the gate opening of the 20S. 相似文献