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961.
Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence 总被引:46,自引:0,他引:46
Ohtani N Zebedee Z Huot TJ Stinson JA Sugimoto M Ohashi Y Sharrocks AD Peters G Hara E 《Nature》2001,409(6823):1067-1070
962.
The habitat and nature of early life 总被引:21,自引:0,他引:21
Earth is over 4,500 million years old. Massive bombardment of the planet took place for the first 500-700 million years, and the largest impacts would have been capable of sterilizing the planet. Probably until 4,000 million years ago or later, occasional impacts might have heated the ocean over 100 degrees C. Life on Earth dates from before about 3,800 million years ago, and is likely to have gone through one or more hot-ocean 'bottlenecks'. Only hyperthermophiles (organisms optimally living in water at 80-110 degrees C) would have survived. It is possible that early life diversified near hydrothermal vents, but hypotheses that life first occupied other pre-bottleneck habitats are tenable (including transfer from Mars on ejecta from impacts there). Early hyperthermophile life, probably near hydrothermal systems, may have been non-photosynthetic, and many housekeeping proteins and biochemical processes may have an original hydrothermal heritage. The development of anoxygenic and then oxygenic photosynthesis would have allowed life to escape the hydrothermal setting. By about 3,500 million years ago, most of the principal biochemical pathways that sustain the modern biosphere had evolved, and were global in scope. 相似文献
963.
Gomis-Rüth FX Moncalián G Pérez-Luque R González A Cabezón E de la Cruz F Coll M 《Nature》2001,409(6820):637-641
The transfer of DNA across membranes and between cells is a central biological process; however, its molecular mechanism remains unknown. In prokaryotes, trans-membrane passage by bacterial conjugation, is the main route for horizontal gene transfer. It is the means for rapid acquisition of new genetic information, including antibiotic resistance by pathogens. Trans-kingdom gene transfer from bacteria to plants or fungi and even bacterial sporulation are special cases of conjugation. An integral membrane DNA-binding protein, called TrwB in the Escherichia coli R388 conjugative system, is essential for the conjugation process. This large multimeric protein is responsible for recruiting the relaxosome DNA-protein complex, and participates in the transfer of a single DNA strand during cell mating. Here we report the three-dimensional structure of a soluble variant of TrwB. The molecule consists of two domains: a nucleotide-binding domain of alpha/beta topology, reminiscent of RecA and DNA ring helicases, and an all-alpha domain. Six equivalent protein monomers associate to form an almost spherical quaternary structure that is strikingly similar to F1-ATPase. A central channel, 20 A in width, traverses the hexamer. 相似文献
964.
Genome sequence of enterohaemorrhagic Escherichia coli O157:H7 总被引:31,自引:0,他引:31
Perna NT Plunkett G Burland V Mau B Glasner JD Rose DJ Mayhew GF Evans PS Gregor J Kirkpatrick HA Pósfai G Hackett J Klink S Boutin A Shao Y Miller L Grotbeck EJ Davis NW Lim A Dimalanta ET Potamousis KD Apodaca J Anantharaman TS Lin J Yen G Schwartz DC Welch RA Blattner FR 《Nature》2001,409(6819):529-533
The bacterium Escherichia coli O157:H7 is a worldwide threat to public health and has been implicated in many outbreaks of haemorrhagic colitis, some of which included fatalities caused by haemolytic uraemic syndrome. Close to 75,000 cases of O157:H7 infection are now estimated to occur annually in the United States. The severity of disease, the lack of effective treatment and the potential for large-scale outbreaks from contaminated food supplies have propelled intensive research on the pathogenesis and detection of E. coli O157:H7 (ref. 4). Here we have sequenced the genome of E. coli O157:H7 to identify candidate genes responsible for pathogenesis, to develop better methods of strain detection and to advance our understanding of the evolution of E. coli, through comparison with the genome of the non-pathogenic laboratory strain E. coli K-12 (ref. 5). We find that lateral gene transfer is far more extensive than previously anticipated. In fact, 1,387 new genes encoded in strain-specific clusters of diverse sizes were found in O157:H7. These include candidate virulence factors, alternative metabolic capacities, several prophages and other new functions--all of which could be targets for surveillance. 相似文献
965.
966.
The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene is mutated in recessive hereditary inclusion body myopathy 总被引:9,自引:0,他引:9
Eisenberg I Avidan N Potikha T Hochner H Chen M Olender T Barash M Shemesh M Sadeh M Grabov-Nardini G Shmilevich I Friedmann A Karpati G Bradley WG Baumbach L Lancet D Asher EB Beckmann JS Argov Z Mitrani-Rosenbaum S 《Nature genetics》2001,29(1):83-87
Hereditary inclusion body myopathy (HIBM; OMIM 600737) is a unique group of neuromuscular disorders characterized by adult onset, slowly progressive distal and proximal weakness and a typical muscle pathology including rimmed vacuoles and filamentous inclusions. The autosomal recessive form described in Jews of Persian descent is the HIBM prototype. This myopathy affects mainly leg muscles, but with an unusual distribution that spares the quadriceps. This particular pattern of weakness distribution, termed quadriceps-sparing myopathy (QSM), was later found in Jews originating from other Middle Eastern countries as well as in non-Jews. We previously localized the gene causing HIBM in Middle Eastern Jews on chromosome 9p12-13 (ref. 5) within a genomic interval of about 700 kb (ref. 6). Haplotype analysis around the HIBM gene region of 104 affected people from 47 Middle Eastern families indicates one unique ancestral founder chromosome in this community. By contrast, single non-Jewish families from India, Georgia (USA) and the Bahamas, with QSM and linkage to the same 9p12-13 region, show three distinct haplotypes. After excluding other potential candidate genes, we eventually identified mutations in the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) gene in the HIBM families: all patients from Middle Eastern descent shared a single homozygous missense mutation, whereas distinct compound heterozygotes were identified in affected individuals of families of other ethnic origins. Our findings indicate that GNE is the gene responsible for recessive HIBM. 相似文献
967.
Frequently, crop plants do not take up adequate amounts of iron from the soil, leading to chlorosis, poor yield and decreased nutritional quality. Extremely limited soil bioavailability of iron has led plants to evolve two distinct uptake strategies: chelation, which is used by the world's principal grain crops; and reduction, which is used by other plant groups. The chelation strategy involves extrusion of low-molecular-mass secondary amino acids (mugineic acids) known as 'phytosiderophores' which chelate sparingly soluble iron. The Fe(III)-phytosiderophore complex is then taken up by an unknown transporter at the root surface. The maize yellow stripe1 (ys1) mutant is deficient in Fe(III)-phytosiderophore uptake, therefore YS1 has been suggested to be the Fe(III)-phytosiderophore transporter. Here we show that ys1 is a membrane protein that mediates iron uptake. Expression of YS1 in a yeast iron uptake mutant restores growth specifically on Fe(III)-phytosiderophore media. Under iron-deficient conditions, ys1 messenger RNA levels increase in both roots and shoots. Cloning of ys1 is an important step in understanding iron uptake in grasses, and has implications for mechanisms controlling iron homeostasis in all plants. 相似文献
968.
Role for a bidentate ribonuclease in the initiation step of RNA interference 总被引:344,自引:0,他引:344
969.
Neuropeptide Y functions as a neuroproliferative factor 总被引:8,自引:0,他引:8
Neuropeptide Y (NPY) has a number of functions in mammalian physiology. Here we identify a role for NPY in promoting proliferation of postnatal neuronal precursor cells. NPY is synthesized in the postnatal olfactory epithelium by sustentacular cells, previously proposed to function only in structural support. Mice with a targeted deletion of NPY contain half as many dividing olfactory neuronal precursor cells as do controls. Furthermore, NPY-deficient mice develop significantly fewer olfactory neurons by adulthood. NPY acts on multipotent neuronal precursor or basal cells to activate rapidly and transiently the extracellular signal-regulated kinase (ERK)1/2 subgroup of mitogen-activated protein kinases. The NPY Y1 receptor subtype appears to mediate this effect. The ability of NPY to induce neuronal precursor proliferation is mediated by protein kinase C (PKC), indicating an upstream PKC-dependent activation of ERK1/2. These results indicate that NPY may regulate neuronal precursor proliferation in the adult mammal. 相似文献
970.
Insulin-stimulated GLUT4 translocation requires the CAP-dependent activation of TC10 总被引:35,自引:0,他引:35
Chiang SH Baumann CA Kanzaki M Thurmond DC Watson RT Neudauer CL Macara IG Pessin JE Saltiel AR 《Nature》2001,410(6831):944-948
The stimulation of glucose uptake by insulin in muscle and adipose tissue requires translocation of the GLUT4 glucose transporter protein from intracellular storage sites to the cell surface. Although the cellular dynamics of GLUT4 vesicle trafficking are well described, the signalling pathways that link the insulin receptor to GLUT4 translocation remain poorly understood. Activation of phosphatidylinositol-3-OH kinase (PI(3)K) is required for this trafficking event, but it is not sufficient to produce GLUT4 translocation. We previously described a pathway involving the insulin-stimulated tyrosine phosphorylation of Cbl, which is recruited to the insulin receptor by the adapter protein CAP. On phosphorylation, Cbl is translocated to lipid rafts. Blocking this step completely inhibits the stimulation of GLUT4 translocation by insulin. Here we show that phosphorylated Cbl recruits the CrkII-C3G complex to lipid rafts, where C3G specifically activates the small GTP-binding protein TC10. This process is independent of PI(3)K, but requires the translocation of Cbl, Crk and C3G to the lipid raft. The activation of TC10 is essential for insulin-stimulated glucose uptake and GLUT4 translocation. The TC10 pathway functions in parallel with PI(3)K to stimulate fully GLUT4 translocation in response to insulin. 相似文献