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53.
Thomson Reuters Pfizer 《科学观察》2013,(1):8-12
随着《美国孤儿药法案》的颁布以及世界多个国家相类似法案的出台,刺激了世界范围的孤儿药研究,为制药公司针对罕见病治疗的药物开发提供了潜在的利益刺激。该报告对孤儿药开发和商业运作的经济和投资进行了分析。表明尽管孤儿药比传统主流药物针对的人群小得多,但高昂的治疗费用及各种具有诱惑力的开发动力,如政府的鼓励、临床试验规模小且时间短、独占期长及审核成功率高等,让顶级孤儿药同非孤儿药一样具有生命力。 相似文献
54.
An N-methylaspartate receptor-mediated synapse in rat cerebral cortex: a site of action of ketamine? 总被引:5,自引:0,他引:5
It has been proposed that three major receptor subtypes subserve the putative transmitter role of glutamate and aspartate in the mammalian central nervous system. One subtype is classified by the specific agonist N-methylaspartate (NMA) and the specific antagonist 4-amino-2-phosphonovaleric acid. It has been shown recently that excitation of neurones by NMA is also selectively reduced by dissociative anaesthetics such as ketamine and phencyclidine and by sigma opiates, drugs of abuse with common psychotomimetic properties. Responses to NMA have an unusual voltage relation which may result from a voltage-dependent block of the activated channel by physiological concentrations of magnesium. No synaptic potential with properties similar to those of responses to NMA, however, has yet been reported. We describe here an excitatory postsynaptic potential (e.p.s.p.) evoked by electrical stimulation of the white matter and recorded intracellularly from pyramidal cells in slices of rat somatosensory cortex. This e.p.s.p. has the appropriate voltage relation and sensitivity to Mg2+ and ketamine to be an NMA receptor-mediated synapse and a potential central site for the psychotomimetic actions of ketamine. 相似文献
55.
Post-embedding staining with ferritin labelled antibodies 总被引:4,自引:0,他引:4
56.
Elimination of 5 mu particles from the human lung 总被引:7,自引:0,他引:7
57.
Features of the physical environment surrounding an ancestral organism can be inferred by reconstructing sequences of ancient proteins made by those organisms, resurrecting these proteins in the laboratory, and measuring their properties. Here, we resurrect candidate sequences for elongation factors of the Tu family (EF-Tu) found at ancient nodes in the bacterial evolutionary tree, and measure their activities as a function of temperature. The ancient EF-Tu proteins have temperature optima of 55-65 degrees C. This value seems to be robust with respect to uncertainties in the ancestral reconstruction. This suggests that the ancient bacteria that hosted these particular genes were thermophiles, and neither hyperthermophiles nor mesophiles. This conclusion can be compared and contrasted with inferences drawn from an analysis of the lengths of branches in trees joining proteins from contemporary bacteria, the distribution of thermophily in derived bacterial lineages, the inferred G + C content of ancient ribosomal RNA, and the geological record combined with assumptions concerning molecular clocks. The study illustrates the use of experimental palaeobiochemistry and assumptions about deep phylogenetic relationships between bacteria to explore the character of ancient life. 相似文献
58.
Understanding how larvae from extant hydrothermal vent fields colonize neighbouring regions of the mid-ocean ridge system remains a major challenge in oceanic research. Among the factors considered important in the recruitment of deep-sea larvae are metabolic lifespan, the connectivity of the seafloor topography, and the characteristics of the currents. Here we use current velocity measurements from Endeavour ridge to examine the role of topographically constrained circulation on larval transport along-ridge. We show that the dominant tidal and wind-generated currents in the region are strongly attenuated within the rift valley that splits the ridge crest, and that hydrothermal plumes rising from vent fields in the valley drive a steady near-bottom inflow within the valley. Extrapolation of these findings suggests that the suppression of oscillatory currents within rift valleys of mid-ocean ridges shields larvae from cross-axis dispersal into the inhospitable deep ocean. This effect, augmented by plume-driven circulation within rift valleys having active hydrothermal venting, helps retain larvae near their source. Larvae are then exported preferentially down-ridge during regional flow events that intermittently over-ride the currents within the valley. 相似文献
59.
Evidence of undiscovered cell regulatory mechanisms: phosphoproteins and protein kinases in mitochondria 总被引:3,自引:0,他引:3
Thomson M 《Cellular and molecular life sciences : CMLS》2002,59(2):213-219
The finding that mitochondria contain substrates for protein kinases lead to the discovery that protein kinases are located
in the mitochondria of certain tissues and species. These include pyruvate dyhydrogenase kinase, branched-chain α-ketoacid dehydrogenase kinase, protein kinase A, protein kinase Cδ, stress-activated kinase and A-Raf as well as unidentified kinases. Recent evidence suggests that mitochondrial protein kinases
may be involved in physiological processes such as apoptosis and steroidogenesis. Additionally, the novel finding of low-molecular-weight
GTP-binding proteins in mitochondria suggests the possibility that these may interact with mitochondrial protein kinases to
regulate the activity of mitochondrial effector proteins. The fact that there are components of cellular regulatory systems
in mitochondria indicates the exciting possibility of undiscovered systems regulating mitochondrial physiology.
Received 19 June 2001; received after revision 7 August 2001; accepted 8 August 2001 相似文献
60.
Massive gene decay in the leprosy bacillus 总被引:73,自引:0,他引:73
Cole ST Eiglmeier K Parkhill J James KD Thomson NR Wheeler PR Honoré N Garnier T Churcher C Harris D Mungall K Basham D Brown D Chillingworth T Connor R Davies RM Devlin K Duthoy S Feltwell T Fraser A Hamlin N Holroyd S Hornsby T Jagels K Lacroix C Maclean J Moule S Murphy L Oliver K Quail MA Rajandream MA Rutherford KM Rutter S Seeger K Simon S Simmonds M Skelton J Squares R Squares S Stevens K Taylor K Whitehead S Woodward JR Barrell BG 《Nature》2001,409(6823):1007-1011
Leprosy, a chronic human neurological disease, results from infection with the obligate intracellular pathogen Mycobacterium leprae, a close relative of the tubercle bacillus. Mycobacterium leprae has the longest doubling time of all known bacteria and has thwarted every effort at culture in the laboratory. Comparing the 3.27-megabase (Mb) genome sequence of an armadillo-derived Indian isolate of the leprosy bacillus with that of Mycobacterium tuberculosis (4.41 Mb) provides clear explanations for these properties and reveals an extreme case of reductive evolution. Less than half of the genome contains functional genes but pseudogenes, with intact counterparts in M. tuberculosis, abound. Genome downsizing and the current mosaic arrangement appear to have resulted from extensive recombination events between dispersed repetitive sequences. Gene deletion and decay have eliminated many important metabolic activities including siderophore production, part of the oxidative and most of the microaerophilic and anaerobic respiratory chains, and numerous catabolic systems and their regulatory circuits. 相似文献