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61.
Vetter DE Li C Zhao L Contarino A Liberman MC Smith GW Marchuk Y Koob GF Heinemann SF Vale W Lee KF 《Nature genetics》2002,31(4):363-369
Urocortin is a member of the corticotropin-releasing hormone peptide family and is found in many discrete brain regions. The distinct expression pattern of urocortin suggests that it influences such behaviors as feeding, anxiety and auditory processing. To better define the physiological roles of urocortin, we have generated mice carrying a null mutation of the urocortin gene. Urocortin-deficient mice have normal basal feeding behavior and stress responses, but show heightened anxiety-like behaviors in the elevated plus maze and open-field tests. In addition, hearing is impaired in the mutant mice at the level of the inner ear, suggesting that urocortin is involved in the normal development of cochlear sensory-cell function. These results provide the first example of a function for any peptidergic system in hearing. 相似文献
62.
Crumbs, the Drosophila homologue of human CRB1/RP12, is essential for photoreceptor morphogenesis 总被引:3,自引:0,他引:3
The apical transmembrane protein Crumbs is a central regulator of epithelial apical-basal polarity in Drosophila. Loss-of-function mutations in the human homologue of Crumbs, CRB1 (RP12), cause recessive retinal dystrophies, including retinitis pigmentosa. Here we show that Crumbs and CRB1 localize to corresponding subdomains of the photoreceptor apical plasma membrane: the stalk of the Drosophila photoreceptor and the inner segment of mammalian photoreceptors. These subdomains support the morphogenesis and orientation of the photosensitive membrane organelles: rhabdomeres and outer segments, respectively. Drosophila Crumbs is required to maintain zonula adherens integrity during the rapid apical membrane expansion that builds the rhabdomere. Crumbs also regulates stalk development by stabilizing the membrane-associated spectrin cytoskeleton, a function mechanistically distinct from its role in epithelial apical-basal polarity. We propose that Crumbs is a central component of a molecular scaffold that controls zonula adherens assembly and defines the stalk as an apical membrane subdomain. Defects in such scaffolds may contribute to human CRB1-related retinal dystrophies. 相似文献
63.
Entangled polymer solutions and melts exhibit elastic, solid-like resistance to quick deformations and a viscous, fluid-like response to slow deformations. This viscoelastic behaviour reflects the dynamics of individual polymer chains driven by brownian motion: since individual chains can only move in a snake-like fashion through the mesh of surrounding polymer molecules, their diffusive transport, described by reptation, is so slow that the relaxation of suddenly imposed stress is delayed. Entangled polymer solutions and melts therefore elastically resist deforming motions that occur faster than the stress relaxation time. Here we show that the protein myosin II permits active control over the viscoelastic behaviour of actin filament solutions. We find that when each actin filament in a polymerized actin solution interacts with at least one myosin minifilament, the stress relaxation time of the polymer solution is significantly shortened. We attribute this effect to myosin's action as a 'molecular motor', which allows it to interact with randomly oriented actin filaments and push them through the solution, thus enhancing longitudinal filament motion. By superseding reptation with sliding motion, the molecular motors thus overcome a fundamental principle of complex fluids: that only depolymerization makes an entangled, isotropic polymer solution fluid for quick deformations. 相似文献
64.
65.
Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice 总被引:23,自引:0,他引:23
66.
67.
This study uses information from the Millennium Cohort Study to examine the characteristics of families where children are born within a marriage, within a cohabiting union or outside of a co-residential partnership. For this latter group, for the first time in a national data set, an assessment can be made of the 'strength' of the parent's relationship at the time of the birth. We show that the context of childbearing varies with respect to geography, ethnicity, age, parity and educational status of the mother, and that the socioeconomic wellbeing of families varies according to the partnership status of their parents. A closer look at the non-partnered parents shows that the extent to which the fathers were involved with the mother of the child around the time the baby was born was related to the presence of the father at the birth of the child and whether his name was recorded on the child's birth certificate; as well as to subsequent behaviour, such as, whether they moved in with the mother, saw their children on a regular basis or contributed money to the child's maintenance. 相似文献
68.
69.
Many natural habitats exist on privately owned land outside protected areas, but few governments can afford to enforce or subsidize conservation of this biodiversity. Even in some developed countries, conservation subsidy schemes have only achieved limited success. Fortunately, some landowners may be willing to accept management costs in return for other benefits, although this remains controversial when it involves the killing of charismatic species. For example, participants in British field sports, such as fox hunting and game-bird shooting, may voluntarily conserve important habitats that are required by quarry species. Here we report results from a multidisciplinary study that addressed this issue by focusing on three sites across central England. We found that landowners participating in field sports maintained the most established woodland and planted more new woodland and hedgerows than those who did not, despite the equal availability of subsidies. Therefore, voluntary habitat management appears to be important for biodiversity conservation in Britain. Current debates on the future of field sports in Britain, and similar activities globally, may benefit from considering their utility as incentives to conserve additional habitat on private land. 相似文献
70.
Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing 总被引:26,自引:0,他引:26
Yu G Nishimura M Arawaka S Levitan D Zhang L Tandon A Song YQ Rogaeva E Chen F Kawarai T Supala A Levesque L Yu H Yang DS Holmes E Milman P Liang Y Zhang DM Xu DH Sato C Rogaev E Smith M Janus C Zhang Y Aebersold R Farrer LS Sorbi S Bruni A Fraser P St George-Hyslop P 《Nature》2000,407(6800):48-54
Nicastrin, a transmembrane glycoprotein, forms high molecular weight complexes with presenilin 1 and presenilin 2. Suppression of nicastrin expression in Caenorhabditis elegans embryos induces a subset of notch/glp-1 phenotypes similar to those induced by simultaneous null mutations in both presenilin homologues of C. elegans (sel-12 and hop-1). Nicastrin also binds carboxy-terminal derivatives of beta-amyloid precursor protein (betaAPP), and modulates the production of the amyloid beta-peptide (A beta) from these derivatives. Missense mutations in a conserved hydrophilic domain of nicastrin increase A beta42 and A beta40 peptide secretion. Deletions in this domain inhibit A beta production. Nicastrin and presenilins are therefore likely to be functional components of a multimeric complex necessary for the intramembranous proteolysis of proteins such as Notch/GLP-1 and betaAPP. 相似文献