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151.
A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins 总被引:2,自引:0,他引:2
Corti D Voss J Gamblin SJ Codoni G Macagno A Jarrossay D Vachieri SG Pinna D Minola A Vanzetta F Silacci C Fernandez-Rodriguez BM Agatic G Bianchi S Giacchetto-Sasselli I Calder L Sallusto F Collins P Haire LF Temperton N Langedijk JP Skehel JJ Lanzavecchia A 《Science (New York, N.Y.)》2011,333(6044):850-856
The isolation of broadly neutralizing antibodies against influenza A viruses has been a long-sought goal for therapeutic approaches and vaccine design. Using a single-cell culture method for screening large numbers of human plasma cells, we isolated a neutralizing monoclonal antibody that recognized the hemagglutinin (HA) glycoprotein of all 16 subtypes and neutralized both group 1 and group 2 influenza A viruses. Passive transfer of this antibody conferred protection to mice and ferrets. Complexes with HAs from the group 1 H1 and the group 2 H3 subtypes analyzed by x-ray crystallography showed that the antibody bound to a conserved epitope in the F subdomain. This antibody may be used for passive protection and to inform vaccine design because of its broad specificity and neutralization potency. 相似文献
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153.
Endocannabinoid hydrolysis generates brain prostaglandins that promote neuroinflammation 总被引:2,自引:0,他引:2
Nomura DK Morrison BE Blankman JL Long JZ Kinsey SG Marcondes MC Ward AM Hahn YK Lichtman AH Conti B Cravatt BF 《Science (New York, N.Y.)》2011,334(6057):809-813
Phospholipase A(2)(PLA(2)) enzymes are considered the primary source of arachidonic acid for cyclooxygenase (COX)-mediated biosynthesis of prostaglandins. Here, we show that a distinct pathway exists in brain, where monoacylglycerol lipase (MAGL) hydrolyzes the endocannabinoid 2-arachidonoylglycerol to generate a major arachidonate precursor pool for neuroinflammatory prostaglandins. MAGL-disrupted animals show neuroprotection in a parkinsonian mouse model. These animals are spared the hemorrhaging caused by COX inhibitors in the gut, where prostaglandins are instead regulated by cytosolic PLA(2). These findings identify MAGL as a distinct metabolic node that couples endocannabinoid to prostaglandin signaling networks in the nervous system and suggest that inhibition of this enzyme may be a new and potentially safer way to suppress the proinflammatory cascades that underlie neurodegenerative disorders. 相似文献
154.
Morrow EM Yoo SY Flavell SW Kim TK Lin Y Hill RS Mukaddes NM Balkhy S Gascon G Hashmi A Al-Saad S Ware J Joseph RM Greenblatt R Gleason D Ertelt JA Apse KA Bodell A Partlow JN Barry B Yao H Markianos K Ferland RJ Greenberg ME Walsh CA 《Science (New York, N.Y.)》2008,321(5886):218-223
To find inherited causes of autism-spectrum disorders, we studied families in which parents share ancestors, enhancing the role of inherited factors. We mapped several loci, some containing large, inherited, homozygous deletions that are likely mutations. The largest deletions implicated genes, including PCDH10 (protocadherin 10) and DIA1 (deleted in autism1, or c3orf58), whose level of expression changes in response to neuronal activity, a marker of genes involved in synaptic changes that underlie learning. A subset of genes, including NHE9 (Na+/H+ exchanger 9), showed additional potential mutations in patients with unrelated parents. Our findings highlight the utility of "homozygosity mapping" in heterogeneous disorders like autism but also suggest that defective regulation of gene expression after neural activity may be a mechanism common to seemingly diverse autism mutations. 相似文献
155.
Boly M Garrido MI Gosseries O Bruno MA Boveroux P Schnakers C Massimini M Litvak V Laureys S Friston K 《Science (New York, N.Y.)》2011,332(6031):858-862
Frontoparietal cortex is involved in the explicit processing (awareness) of stimuli. Frontoparietal activation has also been found in studies of subliminal stimulus processing. We hypothesized that an impairment of top-down processes, involved in recurrent neuronal message-passing and the generation of long-latency electrophysiological responses, might provide a more reliable correlate of consciousness in severely brain-damaged patients, than frontoparietal responses. We measured effective connectivity during a mismatch negativity paradigm and found that the only significant difference between patients in a vegetative state and controls was an impairment of backward connectivity from frontal to temporal cortices. This result emphasizes the importance of top-down projections in recurrent processing that involve high-order associative cortices for conscious perception. 相似文献
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157.
Chen X Dam MA Ono K Mal A Shen H Nutt SR Sheran K Wudl F 《Science (New York, N.Y.)》2002,295(5560):1698-1702
We have developed a transparent organic polymeric material that can repeatedly mend or "re-mend" itself under mild conditions. The material is a tough solid at room temperature and below with mechanical properties equaling those of commercial epoxy resins. At temperatures above 120 degrees C, approximately 30% (as determined by solid-state nuclear magnetic resonance spectroscopy) of "intermonomer" linkages disconnect but then reconnect upon cooling, This process is fully reversible and can be used to restore a fractured part of the polymer multiple times, and it does not require additional ingredients such as a catalyst, additional monomer, or special surface treatment of the fractured interface. 相似文献
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Atlas R Campbell P Cozzarelli NR Curfman G Enquist L Fink G Flanagin A Fletcher J George E Hammes G Heyman D Inglesby T Kaplan S Kennedy D Krug J Levinson R Marcus E Metzger H Morse SS O'Brien A Onderdonk A Poste G Renault B Rich R Rosengard A Salzburg S Scanlan M Shenk T Tabor H Varmus H Wimmer E Yamamoto K;Journal Editors Authors Group 《Science (New York, N.Y.)》2003,299(5610):1149