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排序方式: 共有100条查询结果,搜索用时 171 毫秒
41.
Talavera K Yasumatsu K Voets T Droogmans G Shigemura N Ninomiya Y Margolskee RF Nilius B 《Nature》2005,438(7070):1022-1025
TRPM5, a cation channel of the TRP superfamily, is highly expressed in taste buds of the tongue, where it has a key role in the perception of sweet, umami and bitter tastes. Activation of TRPM5 occurs downstream of the activation of G-protein-coupled taste receptors and is proposed to generate a depolarizing potential in the taste receptor cells. Factors that modulate TRPM5 activity are therefore expected to influence taste. Here we show that TRPM5 is a highly temperature-sensitive, heat-activated channel: inward TRPM5 currents increase steeply at temperatures between 15 and 35 degrees C. TRPM4, a close homologue of TRPM5, shows similar temperature sensitivity. Heat activation is due to a temperature-dependent shift of the activation curve, in analogy to other thermosensitive TRP channels. Moreover, we show that increasing temperature between 15 and 35 degrees C markedly enhances the gustatory nerve response to sweet compounds in wild-type but not in Trpm5 knockout mice. The strong temperature sensitivity of TRPM5 may underlie known effects of temperature on perceived taste in humans, including enhanced sweetness perception at high temperatures and 'thermal taste', the phenomenon whereby heating or cooling of the tongue evoke sensations of taste in the absence of tastants. 相似文献
42.
Laurence Meyer Christine Patte-Mensah Omar Taleb Ayikoe Guy Mensah-Nyagan 《Cellular and molecular life sciences : CMLS》2010,67(17):3017-3034
Painful neuropathy is a major side-effect limiting cancer chemotherapy. Therefore, novel strategies are required to suppress
the neuropathic effects of anticancer drugs without altering their chemotherapeutic effectiveness. By combining biochemical,
neuroanatomical/neurochemical, electrophysiological and behavioral methods, we demonstrated that progesterone-derived neurosteroids
including 5α-dihydroprogesterone and 3α,5α-tetrahydroprogesterone suppressed neuropathic symptoms evoked in naive rats by
vincristine. Neurosteroids counteracted vincristine-induced alterations in peripheral nerves including 2′,3′-cyclic nucleotide
3′-phosphodiesterase, neurofilament-200 kDa and intraepidermal nerve fiber repression, nerve conduction velocity, and pain
transmission abnormalities (allodynia/hyperalgesia). In skin-tumor rats generated with carcinosarcoma-cells, vincristine,
which suppressed the skin tumor and restored normal blood concentration of vascular endothelial growth factor (VEGF), reproduced
neuropathic side-effects. Administered alone, neurosteroids did not affect the tumor and VEGF level. Combined with vincristine,
neurosteroids preserved vincristine anti-tumor action but counteracted vincristine-induced neural side-effects. Together,
these results provide valuable insight into the cellular and functional mechanisms underlying anticancer drug-induced neuropathy
and suggest a neurosteroid-based strategy to eradicate painful neuropathy. 相似文献
43.
Stimulated platelets use serotonin to enhance their retention of procoagulant proteins on the cell surface. 总被引:17,自引:0,他引:17
George L Dale Paul Friese Peter Batar Stephen F Hamilton Guy L Reed Kenneth W Jackson Kenneth J Clemetson Lorenzo Alberio 《Nature》2002,415(6868):175-179
Activated platelets bind numerous adhesive and procoagulant proteins by receptor-mediated processes. Although there is little evidence to suggest that these processes are heterogeneous in platelets, we previously found that platelets co-stimulated with collagen and thrombin express functional alpha-granule factor V only on a subpopulation of cells. Here we show that these cells, referred to as 'COAT-platelets', bind additional alpha-granule proteins, including fibrinogen, von Willebrand factor, thrombospondin, fibronectin and alpha2-antiplasmin. These proteins are all transglutaminase substrates, and inhibitors of transglutaminase prevent the production of COAT-platelets. A synthetic transglutaminase substrate (CP15) also binds to COAT-platelets, and analysis by high performance liquid chromatography/mass spectrometry shows that a product is formed with a relative molecular mass (Mr) equal to CP15 plus 176. Serotonin, an abundant component of platelet-dense granules, has an Mr of 176, and fibrinogen isolated from COAT-platelets contains covalently linked serotonin. Synthetic bovine serum albumin-(serotonin)6 binds selectively to COAT-platelets and also inhibits the retention of procoagulant proteins on COAT-platelets. These data indicate that COAT-platelets use serotonin conjugation to augment the retention of procoagulant proteins on their cell surface through an as yet unidentified serotonin receptor. 相似文献
44.
Grbić M Van Leeuwen T Clark RM Rombauts S Rouzé P Grbić V Osborne EJ Dermauw W Ngoc PC Ortego F Hernández-Crespo P Diaz I Martinez M Navajas M Sucena É Magalhães S Nagy L Pace RM Djuranović S Smagghe G Iga M Christiaens O Veenstra JA Ewer J Villalobos RM Hutter JL Hudson SD Velez M Yi SV Zeng J Pires-daSilva A Roch F Cazaux M Navarro M Zhurov V Acevedo G Bjelica A Fawcett JA Bonnet E Martens C Baele G Wissler L Sanchez-Rodriguez A Tirry L Blais C Demeestere K Henz SR Gregory TR Mathieu J 《Nature》2011,479(7374):487-492
45.
Architecture of the Mediator head module 总被引:1,自引:0,他引:1
Imasaki T Calero G Cai G Tsai KL Yamada K Cardelli F Erdjument-Bromage H Tempst P Berger I Kornberg GL Asturias FJ Kornberg RD Takagi Y 《Nature》2011,475(7355):240-243
46.
Yvon-Durocher G Caffrey JM Cescatti A Dossena M del Giorgio P Gasol JM Montoya JM Pumpanen J Staehr PA Trimmer M Woodward G Allen AP 《Nature》2012,487(7408):472-476
Ecosystem respiration is the biotic conversion of organic carbon to carbon dioxide by all of the organisms in an ecosystem, including both consumers and primary producers. Respiration exhibits an exponential temperature dependence at the subcellular and individual levels, but at the ecosystem level respiration can be modified by many variables including community abundance and biomass, which vary substantially among ecosystems. Despite its importance for predicting the responses of the biosphere to climate change, it is as yet unknown whether the temperature dependence of ecosystem respiration varies systematically between aquatic and terrestrial environments. Here we use the largest database of respiratory measurements yet compiled to show that the sensitivity of ecosystem respiration to seasonal changes in temperature is remarkably similar for diverse environments encompassing lakes, rivers, estuaries, the open ocean and forested and non-forested terrestrial ecosystems, with an average activation energy similar to that of the respiratory complex (approximately 0.65?electronvolts (eV)). By contrast, annual ecosystem respiration shows a substantially greater temperature dependence across aquatic (approximately 0.65?eV) versus terrestrial ecosystems (approximately 0.32?eV) that span broad geographic gradients in temperature. Using a model derived from metabolic theory, these findings can be reconciled by similarities in the biochemical kinetics of metabolism at the subcellular level, and fundamental differences in the importance of other variables besides temperature—such as primary productivity and allochthonous carbon inputs—on the structure of aquatic and terrestrial biota at the community level. 相似文献
47.
Summary Locust ocellar retinal cells are innervated by giant second order cells, 2 mm long, which show discrete zones of integration along their course, including a major zone in the axonal length of the neuron. The complex synaptic arrangements which exist between higher-order afferent and efferent cells and these second order cells along their course suggests that transmission takes place by the electrotonic spread of slow potentials. The size and accessibility of these visual interneurons offers a unique preparation for examining mechanisms of graded synaptic transmission. 相似文献
48.
Brunet M Guy F Pilbeam D Mackaye HT Likius A Ahounta D Beauvilain A Blondel C Bocherens H Boisserie JR De Bonis L Coppens Y Dejax J Denys C Duringer P Eisenmann V Fanone G Fronty P Geraads D Lehmann T Lihoreau F Louchart A Mahamat A Merceron G Mouchelin G Otero O Pelaez Campomanes P Ponce De Leon M Rage JC Sapanet M Schuster M Sudre J Tassy P Valentin X Vignaud P Viriot L Zazzo A Zollikofer C 《Nature》2002,418(6894):145-151
The search for the earliest fossil evidence of the human lineage has been concentrated in East Africa. Here we report the discovery of six hominid specimens from Chad, central Africa, 2,500 km from the East African Rift Valley. The fossils include a nearly complete cranium and fragmentary lower jaws. The associated fauna suggest the fossils are between 6 and 7 million years old. The fossils display a unique mosaic of primitive and derived characters, and constitute a new genus and species of hominid. The distance from the Rift Valley, and the great antiquity of the fossils, suggest that the earliest members of the hominid clade were more widely distributed than has been thought, and that the divergence between the human and chimpanzee lineages was earlier than indicated by most molecular studies. 相似文献
49.
Rescue of a deficiency in ATP synthesis by transfer of MTATP6, a mitochondrial DNA-encoded gene, to the nucleus 总被引:8,自引:0,他引:8
A T-->G transversion at nt 8993 in mitochondrial DNA of MTATP6 (encoding ATPase 6 of complex V of the respiratory chain) causes impaired mitochondrial ATP synthesis in two related mitochondrial disorders: neuropathy, ataxia and retinitis pigmentosa and maternally inherited Leigh syndrome. To overcome the biochemical defect, we expressed wildtype ATPase 6 protein allotopically from nucleus-transfected constructs encoding an amino-terminal mitochondrial targeting signal appended to a recoded ATPase 6 gene (made compatible with the universal genetic code) that also contained a carboxy-terminal FLAG epitope tag. After transfection of human cells, the precursor polypeptide was expressed, imported into and processed within mitochondria, and incorporated into complex V. Allotopic expression of stably transfected constructs in cytoplasmic hybrids (cybrids) homoplasmic with respect to the 8993T-->G mutation showed a significantly improved recovery after growth in selective medium as well as a significant increase in ATP synthesis. This is the first successful demonstration of allotopic expression of an mtDNA-encoded polypeptide in mammalian cells and could form the basis of a genetic approach to treat a number of human mitochondrial disorders. 相似文献
50.
Genetics of gene expression surveyed in maize,mouse and man 总被引:111,自引:0,他引:111
Schadt EE Monks SA Drake TA Lusis AJ Che N Colinayo V Ruff TG Milligan SB Lamb JR Cavet G Linsley PS Mao M Stoughton RB Friend SH 《Nature》2003,422(6929):297-302