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71.
Fas, also known as CD95 or APO-1, is a member of the tumor necrosis factor/nerve growth factor superfamily. Although best characterized in terms of its apoptotic function, recent studies have identified several other cellular responses emanating from Fas. These responses include migration, invasion, inflammation, and proliferation. In this review, we focus on the diverse cellular outcomes of Fas signaling and the molecular switches identified to date that regulate its pro- and anti-apoptotic functions. Such switches occur at different levels of signal transduction, ranging from the receptor through to cross-talk with other signaling pathways. Factors identified to date including other extracellular signals, proteins recruited to the death-inducing signaling complex, and the availability of different intracellular components of signal transduction pathways. The success of therapeutically targeting Fas will require a better understanding of these pathways, as well as the regulatory mechanisms that determine cellular outcome following receptor activation.  相似文献   
72.
73.
Estimates of site potential for ponderosa pine based on measured site indexes in 416 stands are compared between seven habitat types and one community type. No significant differences in mean site index are found between the habitat types studied. The habitat types are classified into high or moderate site potential classes based on mean site indexes.  相似文献   
74.
Vernal pools are seasonal pools occurring in Mediterranean-type climates within which grow concentric zones of vegetation. We studied two vernal pools that lie within an Artemisia tridentata/Festuca idahoensis shrub-steppe landscape in the Channeled Scabland of eastern Washington to determine the relationship between vegetation zonation and soil characteristics. Abundant plant species in the pools include Elymus cinereus, Poa scabrella, Lomatium grayi, Allium geyeri, Eleocharis palustris, Epilobium minutum, Myosurus aristatis, Deschampsia danthonioides, and Psilocarphus oregonus . We surveyed topography, measured plant species frequency and cover to describe the vegetation zones, and used Sorenson's index of percent to similarity to verify our designation of plant zones as communities. In one pool we described soil profiles and sampled soils throughout the growing season according to plant communities. We analyzed soils for pH; electrical conductivity; sodium, calcium, and magnesium ions; sodium absorption ratio; particle size; organic carbon; and water matric potential. ANOVA tests of soil characteristics and topography among plant communities showed that only differences in topography are statistically significant. There are, however, trends in particle size, some soil chemical parameters, and soil moisture potential among plant communities along the topographic gradient. Electrical conductivity decreased with increasing dryness of the soil through spring and summer. Seasonal changes in soil moisture potential showed that shallower soils in the centers of pools were wetter during the wet season and drier during the dry season than are deeper soils. These changes in moisture may be the most important influence on vegetation distribution within the vernal pools.  相似文献   
75.
We report genetic microsatellite data from analysis of 71 American black bears ( Ursus americanus ) from the East Tavaputs Plateau in eastern Utah. Heterozygosity was 52.9%, which is lower than other mainland North American populations and possibly reflects low recruitment into the study area. We used a combination of known pedigrees (mother/cubs), relatedness estimates, and paternity estimation using CERVUS to infer single and possible multiple paternity within litters, breeding by pairs over consecutive years, and the possibility of a single male successfully breeding with multiple females in a single year. Estimates of inbreeding effective population size indicate the East Tavaputs Plateau population is part of a larger black bear population.  相似文献   
76.
Résumé Des sections de muscle lisse d'aorte de lapin ou d'artère fémorale de chien répondent à une stimulation de champ (AC) par une contraction due en partie à la libération de catécholamines, contraction pouvant être relâchée sous l'effet de divers médicaments. D'autre part, l'AC manifeste une action au niveau de la membrane excitable et au-delà de cette membrane. Il en a peut-être aussi sur le couplage excitation-contraction. L'AC offre une méthode unique pour l'étude des agents susceptibles d'avoir une action vaso-dilatatrice.  相似文献   
77.
Ovarian carcinomas with mutations in the tumour suppressor BRCA2 are particularly sensitive to platinum compounds. However, such carcinomas ultimately develop cisplatin resistance. The mechanism of that resistance is largely unknown. Here we show that acquired resistance to cisplatin can be mediated by secondary intragenic mutations in BRCA2 that restore the wild-type BRCA2 reading frame. First, in a cisplatin-resistant BRCA2-mutated breast-cancer cell line, HCC1428, a secondary genetic change in BRCA2 rescued BRCA2 function. Second, cisplatin selection of a BRCA2-mutated pancreatic cancer cell line, Capan-1 (refs 3, 4), led to five different secondary mutations that restored the wild-type BRCA2 reading frame. All clones with secondary mutations were resistant both to cisplatin and to a poly(ADP-ribose) polymerase (PARP) inhibitor (AG14361). Finally, we evaluated recurrent cancers from patients whose primary BRCA2-mutated ovarian carcinomas were treated with cisplatin. The recurrent tumour that acquired cisplatin resistance had undergone reversion of its BRCA2 mutation. Our results suggest that secondary mutations that restore the wild-type BRCA2 reading frame may be a major clinical mediator of acquired resistance to platinum-based chemotherapy.  相似文献   
78.
Hair cells of the inner ear are mechanosensors that transduce mechanical forces arising from sound waves and head movement into electrochemical signals to provide our sense of hearing and balance. Each hair cell contains at the apical surface a bundle of stereocilia. Mechanoelectrical transduction takes place close to the tips of stereocilia in proximity to extracellular tip-link filaments that connect the stereocilia and are thought to gate the mechanoelectrical transduction channel. Recent reports on the composition, properties and function of tip links are conflicting. Here we demonstrate that two cadherins that are linked to inherited forms of deafness in humans interact to form tip links. Immunohistochemical studies using rodent hair cells show that cadherin 23 (CDH23) and protocadherin 15 (PCDH15) localize to the upper and lower part of tip links, respectively. The amino termini of the two cadherins co-localize on tip-link filaments. Biochemical experiments show that CDH23 homodimers interact in trans with PCDH15 homodimers to form a filament with structural similarity to tip links. Ions that affect tip-link integrity and a mutation in PCDH15 that causes a recessive form of deafness disrupt interactions between CDH23 and PCDH15. Our studies define the molecular composition of tip links and provide a conceptual base for exploring the mechanisms of sensory impairment associated with mutations in CDH23 and PCDH15.  相似文献   
79.
Tumorigenesis is a multi-step process that requires activation of oncogenes and inactivation of tumour suppressor genes. Mouse models of human cancers have recently demonstrated that continuous expression of a dominantly acting oncogene (for example, Hras, Kras and Myc) is often required for tumour maintenance; this phenotype is referred to as oncogene addiction. This concept has received clinical validation by the development of active anticancer drugs that specifically inhibit the function of oncoproteins such as BCR-ABL, c-KIT and EGFR. Identifying additional gene mutations that are required for tumour maintenance may therefore yield clinically useful targets for new cancer therapies. Although loss of p53 function is a common feature of human cancers, it is not known whether sustained inactivation of this or other tumour suppressor pathways is required for tumour maintenance. To explore this issue, we developed a Cre-loxP-based strategy to temporally control tumour suppressor gene expression in vivo. Here we show that restoring endogenous p53 expression leads to regression of autochthonous lymphomas and sarcomas in mice without affecting normal tissues. The mechanism responsible for tumour regression is dependent on the tumour type, with the main consequence of p53 restoration being apoptosis in lymphomas and suppression of cell growth with features of cellular senescence in sarcomas. These results support efforts to treat human cancers by way of pharmacological reactivation of p53.  相似文献   
80.
Amyotrophic lateral sclerosis (ALS) is a late-onset neurodegenerative disorder resulting from motor neuron death. Approximately 10% of cases are familial (FALS), typically with a dominant inheritance mode. Despite numerous advances in recent years, nearly 50% of FALS cases have unknown genetic aetiology. Here we show that mutations within the profilin 1 (PFN1) gene can cause FALS. PFN1 is crucial for the conversion of monomeric (G)-actin to filamentous (F)-actin. Exome sequencing of two large ALS families showed different mutations within the PFN1 gene. Further sequence analysis identified 4 mutations in 7 out of 274 FALS cases. Cells expressing PFN1 mutants contain ubiquitinated, insoluble aggregates that in many cases contain the ALS-associated protein TDP-43. PFN1 mutants also display decreased bound actin levels and can inhibit axon outgrowth. Furthermore, primary motor neurons expressing mutant PFN1 display smaller growth cones with a reduced F/G-actin ratio. These observations further document that cytoskeletal pathway alterations contribute to ALS pathogenesis.  相似文献   
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