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排序方式: 共有141条查询结果,搜索用时 46 毫秒
91.
David C. Blakemore Justin S. Bryans Pauline Carnell Nicola E.A. Chessum Mark J. Field Natasha Kinsella Jack K. Kinsora Simon A. Osborne Sophie C. Williams 《Bioorganic & medicinal chemistry letters》2010,20(1):362-365
A range of 3-alkylated five-membered ring derivatives of Gabapentin were synthesized and several were found to have good levels of potency against the α2δ calcium subunit of a voltage-gated calcium channel. Two compounds were profiled in in vivo models of pain and anxiety. 相似文献
92.
93.
Alexandra I.F. Blakemore David Meyre Jerome Delplanque Vincent Vatin Cecile Lecoeur Michel Marre Jean Tichet Beverley Balkau Philippe Froguel Andrew J. Walley 《Obesity (Silver Spring, Md.)》2009,17(8):1549-1553
Visfatin was recently reported as a novel adipokine encoded by the NAMPT (PBEF1) gene. This study was aimed at investigation of the possibility that single‐nucleotide polymorphisms (SNPs) in the visfatin gene are associated with either obesity or type 2 diabetes (T2D). A set of eight “tag‐SNPs” were selected and ABI SNPlex assays designed for genotyping purposes. A total of 1,709 severely obese subjects were typed (896 class III obese adults and 813 children) together with 2,367 T2D individuals and 2,850 controls. For quantitative trait analysis, an additional 2,362 subjects were typed for rs10487818 from a general population sample. One rare SNP, rs10487818, located in intron 4 of NAMPT was associated with severe obesity, with a minor allele frequency of 1.6% in controls, 0.4% in the class III obese adults and, remarkably, 0% in the severely obese children. A highly significant association was observed for the presence or absence of the rare allele, i.e., (A,A) vs. (A,T + T,T) genotypes, in children (P = 6 × 10?9) and in adults (P = 8 × 10?5). No other significant (P < 0.05) association was observed with obesity or T2D for this or any other SNP. No association with BMI or waist‐to‐hip ratio was observed in a general population sample (n = 5,212). This is one of the first rare SNPs shown to be protective against a common polygenic disease and provides further evidence that rare alleles of strong effect can contribute to complex diseases such as severe obesity. 相似文献
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95.
In 1970 the Boulder Committee described the basic principles of the development of the CNS, derived from observations on the human embryonic cerebrum. Since then, numerous studies have significantly advanced our knowledge of the timing, sequence and complexity of developmental events, and revealed important inter-species differences. We review current data on the development of the human cerebral cortex and update the classical model of how the structure that makes us human is formed. 相似文献
96.
The epithelial integrin alphavbeta6 is a receptor for foot-and-mouth disease virus 总被引:2,自引:0,他引:2
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Field isolates of foot-and-mouth disease virus (FMDV) have been shown to use the RGD-dependent integrin alphavbeta3 as a cellular receptor on cultured cells. However, several other RGD-dependent integrins may have the potential to act as receptors for FMDV in vivo. Of these, alphavbeta6 is a likely candidate for use as a receptor by FMDV as it is expressed on epithelial cells, which correlates with the tissue tropism of the virus. In this report, we show that human colon carcinoma cells (SW480) that are normally nonpermissive for FMDV become susceptible to infection as a result of transfection with the integrin beta6 subunit and expression of alphavbeta6 at the cell surface. Integrin alphavbeta6 is the major site for virus attachment on the beta6-transfected cells, and binding to alphavbeta6 serves to increase the rate of virus entry into these cells. In addition, we show that virus binding and infection of the beta6-transfected cells is mediated through an RGD-dependent interaction that is specifically inhibited by a monoclonal antibody (10D5) that recognizes alphavbeta6. These studies establish a role for alphavbeta6 as a cellular receptor for FMDV. 相似文献
97.
98.
Abnormalities in the awareness and control of action 总被引:19,自引:0,他引:19
Frith CD Blakemore SJ Wolpert DM 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2000,355(1404):1771-1788
Much of the functioning of the motor system occurs without awareness. Nevertheless, we are aware of some aspects of the current state of the system and we can prepare and make movements in the imagination. These mental representations of the actual and possible states of the system are based on two sources: sensory signals from skin and muscles, and the stream of motor commands that have been issued to the system. Damage to the neural substrates of the motor system can lead to abnormalities in the awareness of action as well as defects in the control of action. We provide a framework for understanding how these various abnormalities of awareness can arise. Patients with phantom limbs or with anosognosia experience the illusion that they can move their limbs. We suggest that these representations of movement are based on streams of motor commands rather than sensory signals. Patients with utilization behaviour or with delusions of control can no longer properly link their intentions to their actions. In these cases the impairment lies in the representation of intended movements. The location of the neural damage associated with these disorders suggests that representations of the current and predicted state of the motor system are in parietal cortex, while representations of intended actions are found in prefrontal and premotor cortex. 相似文献
99.
The structure and function of a foot-and-mouth disease virus-oligosaccharide receptor complex. 总被引:23,自引:1,他引:22
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E E Fry S M Lea T Jackson J W Newman F M Ellard W E Blakemore R Abu-Ghazaleh A Samuel A M King D I Stuart 《The EMBO journal》1999,18(3):543-554
Heparan sulfate has an important role in cell entry by foot-and-mouth disease virus (FMDV). We find that subtype O1 FMDV binds this glycosaminoglycan with a high affinity by immobilizing a specific highly abundant motif of sulfated sugars. The binding site is a shallow depression on the virion surface, located at the junction of the three major capsid proteins, VP1, VP2 and VP3. Two pre-formed sulfate-binding sites control receptor specificity. Residue 56 of VP3, an arginine in this virus, is critical to this recognition, forming a key component of both sites. This residue is a histidine in field isolates of the virus, switching to an arginine in adaptation to tissue culture, forming the high affinity heparan sulfate-binding site. We postulate that this site is a conserved feature of FMDVs, such that in the infected animal there is a biological advantage to low affinity, or more selective, interactions with glycosaminoglycan receptors. 相似文献
100.
Dissecting the roles of VP0 cleavage and RNA packaging in picornavirus capsid stabilization: the structure of empty capsids of foot-and-mouth disease virus. 总被引:2,自引:1,他引:1
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S Curry E Fry W Blakemore R Abu-Ghazaleh T Jackson A King S Lea J Newman D Stuart 《Journal of virology》1997,71(12):9743-9752
Empty capsids of foot-and-mouth disease virus (FMDV) type A22 Iraq 24/64, whose structure has been solved by X-ray crystallography, are unusual for picornaviruses since they contain VP2 and VP4, the cleavage products of the protein precursor VP0. Both the N terminus of VP1 and the C terminus of VP4, which pack together close to the icosahedral threefold symmetry axis where three pentamers associate, are more disordered in the empty capsid than they are in the RNA-containing virus. The ordering of these termini in the presence of RNA strengthens interactions within a single protomer and between protomers belonging to different pentamers. The disorder in the FMDV empty capsid forms a subset of that seen in the poliovirus empty capsid, which has VP0 intact. Thus, VP0 cleavage confers stability on the picornavirus capsid over and above that attributable to RNA encapsidation. In both FMDV and poliovirus empty capsids, the internal disordering uncovers a conserved histidine which has been proposed to be involved in the cleavage of VP0. A comparison of the putative active sites in FMDV and poliovirus suggests a structural explanation for the sequence specificity of the cleavage reaction. 相似文献