排序方式: 共有58条查询结果,搜索用时 15 毫秒
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Hohmann AG Suplita RL Bolton NM Neely MH Fegley D Mangieri R Krey JF Walker JM Holmes PV Crystal JD Duranti A Tontini A Mor M Tarzia G Piomelli D 《Nature》2005,435(7045):1108-1112
Acute stress suppresses pain by activating brain pathways that engage opioid or non-opioid mechanisms. Here we show that an opioid-independent form of this phenomenon, termed stress-induced analgesia, is mediated by the release of endogenous marijuana-like (cannabinoid) compounds in the brain. Blockade of cannabinoid CB(1) receptors in the periaqueductal grey matter of the midbrain prevents non-opioid stress-induced analgesia. In this region, stress elicits the rapid formation of two endogenous cannabinoids, the lipids 2-arachidonoylglycerol (2-AG) and anandamide. A newly developed inhibitor of the 2-AG-deactivating enzyme, monoacylglycerol lipase, selectively increases 2-AG concentrations and, when injected into the periaqueductal grey matter, enhances stress-induced analgesia in a CB1-dependent manner. Inhibitors of the anandamide-deactivating enzyme fatty-acid amide hydrolase, which selectively elevate anandamide concentrations, exert similar effects. Our results indicate that the coordinated release of 2-AG and anandamide in the periaqueductal grey matter might mediate opioid-independent stress-induced analgesia. These studies also identify monoacylglycerol lipase as a previously unrecognized therapeutic target. 相似文献
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Walton R Kimber M Rockett K Trafford C Kwiatkowski D Sirugo G 《Nature genetics》2005,37(9):915-6; author reply 916
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Wain LV Verwoert GC O'Reilly PF Shi G Johnson T Johnson AD Bochud M Rice KM Henneman P Smith AV Ehret GB Amin N Larson MG Mooser V Hadley D Dörr M Bis JC Aspelund T Esko T Janssens AC Zhao JH Heath S Laan M Fu J Pistis G Luan J Arora P Lucas G Pirastu N Pichler I Jackson AU Webster RJ Zhang F Peden JF Schmidt H Tanaka T Campbell H Igl W Milaneschi Y Hottenga JJ Vitart V Chasman DI Trompet S Bragg-Gresham JL Alizadeh BZ Chambers JC Guo X Lehtimäki T Kühnel B Lopez LM Polašek O Boban M Nelson CP 《Nature genetics》2011,43(10):1005-1011
Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP. 相似文献
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Valente EM Silhavy JL Brancati F Barrano G Krishnaswami SR Castori M Lancaster MA Boltshauser E Boccone L Al-Gazali L Fazzi E Signorini S Louie CM Bellacchio E;International Joubert Syndrome Related Disorders Study Group Bertini E Dallapiccola B Gleeson JG 《Nature genetics》2006,38(6):623-625
Joubert syndrome-related disorders (JSRD) are a group of syndromes sharing the neuroradiological features of cerebellar vermis hypoplasia and a peculiar brainstem malformation known as the 'molar tooth sign'. We identified mutations in the CEP290 gene in five families with variable neurological, retinal and renal manifestations. CEP290 expression was detected mostly in proliferating cerebellar granule neuron populations and showed centrosome and ciliary localization, linking JSRDs to other human ciliopathies. 相似文献
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A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis 总被引:1,自引:0,他引:1
Khor CC Chapman SJ Vannberg FO Dunne A Murphy C Ling EY Frodsham AJ Walley AJ Kyrieleis O Khan A Aucan C Segal S Moore CE Knox K Campbell SJ Lienhardt C Scott A Aaby P Sow OY Grignani RT Sillah J Sirugo G Peshu N Williams TN Maitland K Davies RJ Kwiatkowski DP Day NP Yala D Crook DW Marsh K Berkley JA O'Neill LA Hill AV 《Nature genetics》2007,39(4):523-528
Toll-like receptors (TLRs) and members of their signaling pathway are important in the initiation of the innate immune response to a wide variety of pathogens. The adaptor protein Mal (also known as TIRAP), encoded by TIRAP (MIM 606252), mediates downstream signaling of TLR2 and TLR4 (refs. 4-6). We report a case-control study of 6,106 individuals from the UK, Vietnam and several African countries with invasive pneumococcal disease, bacteremia, malaria and tuberculosis. We genotyped 33 SNPs, including rs8177374, which encodes a leucine substitution at Ser180 of Mal. We found that heterozygous carriage of this variant associated independently with all four infectious diseases in the different study populations. Combining the study groups, we found substantial support for a protective effect of S180L heterozygosity against these infectious diseases (N = 6,106; overall P = 9.6 x 10(-8)). We found that the Mal S180L variant attenuated TLR2 signal transduction. 相似文献
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Federica Corallini Paola Secchiero Antonio Paolo Beltrami Daniela Cesselli Elisa Puppato Roberto Ferrari Carlo Alberto Beltrami Giorgio Zauli 《Cellular and molecular life sciences : CMLS》2010,67(8):1307-1314
The number of circulating mesenchymal stem cells (MSC), analyzed after acute myocardial infarction (AMI), was lower in AMI
patients who developed heart failure (HF) in the follow-up. Conversely, the circulating levels of tumor necrosis factor (TNF)-α,
and osteoprotegerin (OPG) were higher in AMI patients who developed HF with respect to the patients who did not develop HF.
In vitro exposure to TNF-α enhanced the migration of MSC in response to TNF-related apoptosis-inducing ligand (TRAIL) and
significantly increased the release of OPG by endothelial cells. On the contrary, OPG dose-dependently neutralized the in
vitro pro-migratory activity of TRAIL. Thus, TNF-α exhibits opposite effects on MSC migration driven by TRAIL: it is capable
of potentiating MSC migration as well as of inhibiting MSC migration as an indirect consequence of OPG induction, which might
result in a suboptimal recruitment of circulating MSC after AMI in those patients who develop HF in the follow-up. 相似文献