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821.
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
822.
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
823.
Chaudhari P Lacey J Doyle J Galligan E Lien SC Callegari A Hougham G Lang ND Andry PS John R Yang KH Lu M Cai C Speidell J Purushothaman S Ritsko J Samant M Stöhr J Nakagawa Y Katoh Y Saitoh Y Sakai K Satoh H Odahara S Nakano H Nakagaki J Shiota Y 《Nature》2001,411(6833):56-59
The technique used to align liquid crystals-rubbing the surface of a substrate on which a liquid crystal is subsequently deposited-has been perfected by the multibillion-dollar liquid-crystal display industry. However, it is widely recognized that a non-contact alignment technique would be highly desirable for future generations of large, high-resolution liquid-crystal displays. A number of alternative alignment techniques have been reported, but none of these have so far been implemented in large-scale manufacturing. Here, we report a non-contact alignment process, which uses low-energy ion beams impinging at a glancing angle on amorphous inorganic films, such as diamond-like carbon. Using this approach, we have produced both laptop and desktop displays in pilot-line manufacturing, and found that displays of higher quality and reliability could be made at a lower cost than the rubbing technique. The mechanism of alignment is explained by adopting a random network model of atomic arrangement in the inorganic films. Order is induced by exposure to an ion beam because unfavourably oriented rings of atoms are selectively destroyed. The planes of the remaining rings are predominantly parallel to the direction of the ion beam. 相似文献
824.
The Ph1 locus is needed to ensure specific somatic and meiotic centromere association 总被引:3,自引:0,他引:3
The correct pairing and segregation of chromosomes during meiosis is essential for genetic stability and subsequent fertility. This is more difficult to achieve in polyploid species, such as wheat, because they possess more than one diploid set of similar chromosomes. In wheat, the Ph1 locus ensures correct homologue pairing and recombination. Although clustering of telomeres into a bouquet early in meiosis has been suggested to facilitate homologue pairing, centromeres associate in pairs in polyploid cereals early during floral development. We can now extend this observation to root development. Here we show that the Ph1 locus acts both meiotically and somatically by reducing non-homologous centromere associations. This has the effect of promoting true homologous association when centromeres are induced to associate. In fact, non-homologously associated centromeres separate at the beginning of meiosis in the presence, but not the absence, of Ph1. This permits the correction of homologue association during the telomere-bouquet stage in meiosis. We conclude that the Ph1 locus is not responsible for the induction of centromere association, but rather for its specificity. 相似文献
825.
Phagocytosis and clearance of apoptotic cells is mediated by MER 总被引:43,自引:0,他引:43
Scott RS McMahon EJ Pop SM Reap EA Caricchio R Cohen PL Earp HS Matsushima GK 《Nature》2001,411(6834):207-211
Apoptosis is fundamental to the development and maintenance of animal tissues and the immune system. Rapid clearance of apoptotic cells by macrophages is important to inhibit inflammation and autoimmune responses against intracellular antigens. Here we report a new function for Mer, a member of the Axl/Mer/Tyro3 receptor tyrosine kinase family. mer(kd) mice with a cytoplasmic truncation of Mer had macrophages deficient in the clearance of apoptotic thymocytes. This was corrected in chimaeric mice reconstituted with bone marrow from wild-type animals. Primary macrophages isolated from mer(kd) mice showed that the phagocytic deficiency was restricted to apoptotic cells and was independent of Fc receptor-mediated phagocytosis or ingestion of other particles. The inability to clear apoptotic cells adequately may be linked to an increased number of nuclear autoantibodies in mer(kd) mice. Thus, the Mer receptor tyrosine kinase seems to be critical for the engulfment and efficient clearance of apoptotic cells. This has implications for inflammation and autoimmune diseases such as systemic lupus erythematosus. 相似文献
826.
827.
Molecular hydrogen (H2) is an important component of galaxies because it fuels star formation and the accretion of gas onto active galactic nuclei (AGN), the two processes that can generate the large infrared luminosities of gas-rich galaxies. Observations of spectral-line emission from the tracer molecule carbon monoxide (CO) are used to probe the properties of this gas. But the lines that have been studied in the local Universe-mostly the lower rotational transitions of J = 1 --> 0 and J = 2 --> 1-have hitherto been unobservable in high-redshift galaxies. Instead, higher transitions have been used, although the densities and temperatures required to excite these higher transitions may not be reached by much of the gas. As a result, past observations may have underestimated the total amount of molecular gas by a substantial amount. Here we report the discovery of large amounts of low-excitation molecular gas around the infrared-luminous quasar APM08279+5255 at redshift z = 3.91, using the two lowest excitation lines of 12 CO (J = 1 --> 0 and J = 2 --> 1). The maps confirm the presence of hot and dense gas near the nucleus, and reveal an extended reservoir of molecular gas with low excitation that is 10 to 100 times more massive than the gas traced by the higher-excitation observations. This raises the possibility that significant amounts of low-excitation molecular gas may exist in the environments of high-redshift (z > 3) galaxies. 相似文献
828.
ICOS is essential for effective T-helper-cell responses 总被引:60,自引:0,他引:60
Tafuri A Shahinian A Bladt F Yoshinaga SK Jordana M Wakeham A Boucher LM Bouchard D Chan VS Duncan G Odermatt B Ho A Itie A Horan T Whoriskey JS Pawson T Penninger JM Ohashi PS Mak TW 《Nature》2001,409(6816):105-109
The outcome of T-cell responses after T-cell encounter with specific antigens is modulated by co-stimulatory signals, which are required for both lymphocyte activation and development of adaptive immunity. ICOS, an inducible co-stimulator with homology to CD28, is expressed on activated, but not resting T cells, and shows T-cell co-stimulatory function in vitro. ICOS binds specifically to its counter-receptor B7RP-1 (refs 5,6,7), but not to B7-1 or B7-2. Here we provide in vivo genetic evidence that ICOS delivers a co-stimulatory signal that is essential both for efficient interaction between T and B cells and for normal antibody responses to T-cell-dependent antigens. To determine the physiological function of ICOS, we generated and characterized gene-targeted ICOS-deficient mice. In vivo, a lack of ICOS results in severely deficient T-cell-dependent B-cell responses. Germinal centre formation is impaired and immunoglobulin class switching, including production of allergy-mediating IgE, is defective. ICOS-deficient T cells primed in in vivo and restimulated in vitro with specific antigen produce only low levels of interleukin-4, but remain fully competent to produce interferon-gamma. 相似文献
829.
Palaeovegetation. Diversity of temperate plants in east Asia 总被引:3,自引:0,他引:3
The exceptionally broad species diversity of vascular plant genera in east Asian temperate forests, compared with their sister taxa in North America, has been attributed to the greater climatic diversity of east Asia, combined with opportunities for allopatric speciation afforded by repeated fragmentation and coalescence of populations through Late Cenozoic ice-age cycles. According to Qian and Ricklefs, these opportunities occurred in east Asia because temperate forests extended across the continental shelf to link populations in China, Korea and Japan during glacial periods, whereas higher sea levels during interglacial periods isolated these regions and warmer temperatures restricted temperate taxa to disjunct refuges. However, palaeovegetation data from east Asia show that temperate forests were considerably less extensive than today during the Last Glacial Maximum, calling into question the coalescence of tree populations required by the hypothesis of Qian and Ricklefs. 相似文献
830.
An agrin minigene rescues dystrophic symptoms in a mouse model for congenital muscular dystrophy 总被引:21,自引:0,他引:21
Moll J Barzaghi P Lin S Bezakova G Lochmüller H Engvall E Müller U Ruegg MA 《Nature》2001,413(6853):302-307
Congenital muscular dystrophy is a heterogeneous and severe, progressive muscle-wasting disease that frequently leads to death in early childhood. Most cases of congenital muscular dystrophy are caused by mutations in LAMA2, the gene encoding the alpha2 chain of the main laminin isoforms expressed by muscle fibres. Muscle fibre deterioration in this disease is thought to be caused by the failure to form the primary laminin scaffold, which is necessary for basement membrane structure, and the missing interaction between muscle basement membrane and the dystrophin-glycoprotein complex (DGC) or the integrins. With the aim to restore muscle function in a mouse model for this disease, we have designed a minigene of agrin, a protein known for its role in the formation of the neuromuscular junction. Here we show that this mini-agrin-which binds to basement membrane and to alpha-dystroglycan, a member of the DGC-amends muscle pathology by a mechanism that includes agrin-mediated stabilization of alpha-dystroglycan and the laminin alpha5 chain. Our data provides in vivo evidence that a non-homologous protein in combination with rational protein design can be used to devise therapeutic tools that may restore muscle function in human muscular dystrophies. 相似文献