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排序方式: 共有255条查询结果,搜索用时 31 毫秒
51.
Bernadette Earley Mary Glennon Brian E. Leonard Jean-Louis Junien 《Neurochemistry international》1995,26(6):559-570
The distribution patterns of M1 and M2 muscarinic receptor subtypes following TMT and JO 1784 administration in the male Sprague-Dawley rat were investigated. In the present study, JO 1784 was injected in doses of 1, 4 and 16 mg/kg i.p. for one week prior to the single injection of TMT (8 mg/kg i.p.) and subsequently for 33 days. The effects of JO 1784 on the density of muscarinic receptor sub-types (M1 and M2) in the control and trimethyltin (TMT) treated rats were then evaluated. The topographic distribution and changes in muscarinic (M1 and M2) receptor densities were determined by means of autoradiography using [3H]quinuclidinylbenzilate (QNB). Both sub-types of muscarinic receptors contributed to the observed decrease in total muscarinic receptor binding in TMT-treated rats. In control rats, JO 1784 alone decreased M1 receptor density in the amygdaloid nuclei, basal ganglia, cortex and hippocampus and decreased M2 receptor density in the amygdaloid nuclei, basal ganglia, cortex, hippocampus, hypothalamus and septal regions. In TMT treated rats, chronic JO 1784 administration has a “neuroprotective effect” on both M1 and M2 receptors subtypes. Thus, following chronic administration of JO 1784 to TMT treated rats, both increases and decreases in M1 receptor density were observed relative to TMT animals. A significant increase in M1 receptor density was found in the cortex, olfactory regions, septum, thalamus and basal forebrain nuclei. In the hippocampus (CA2 and CA3), a significant decrease in M1 receptor density was observed. In TMT-treated rats, JO 1784 produced a significant increase in M2 receptor density in several brain regions with the most marked effects occurring in the amygdaloid nuclei, basal ganglia, cortex, hippocampus and hypothalamus. The ability of the selective sigma ligand, JO 1784, to attenuate the loss of muscarinic receptors in TMT treated rats could be of importance in the development of novel neuroprotective drugs. 相似文献
52.
ALS/FTD‐associated FUS activates GSK‐3β to disrupt the VAPB–PTPIP51 interaction and ER–mitochondria associations 下载免费PDF全文
Patricia Gomez‐Suaga Jacqueline C Mitchell Dawn HW Lau Emma H Gray Rosa M Sancho Gema Vizcay‐Barrena Kurt J De Vos Christopher E Shaw Diane P Hanger Wendy Noble Christopher CJ Miller 《EMBO reports》2016,17(9):1326-1342
Defective FUS metabolism is strongly associated with amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD), but the mechanisms linking FUS to disease are not properly understood. However, many of the functions disrupted in ALS/FTD are regulated by signalling between the endoplasmic reticulum (ER) and mitochondria. This signalling is facilitated by close physical associations between the two organelles that are mediated by binding of the integral ER protein VAPB to the outer mitochondrial membrane protein PTPIP51, which act as molecular scaffolds to tether the two organelles. Here, we show that FUS disrupts the VAPB–PTPIP51 interaction and ER–mitochondria associations. These disruptions are accompanied by perturbation of Ca2+ uptake by mitochondria following its release from ER stores, which is a physiological read‐out of ER–mitochondria contacts. We also demonstrate that mitochondrial ATP production is impaired in FUS‐expressing cells; mitochondrial ATP production is linked to Ca2+ levels. Finally, we demonstrate that the FUS‐induced reductions to ER–mitochondria associations and are linked to activation of glycogen synthase kinase‐3β (GSK‐3β), a kinase already strongly associated with ALS/FTD. 相似文献
53.
Lidocaine block of cardiac sodium channels was studied in voltage-clamped rabbit purkinje fibers at drug concentrations ranging from 1 mM down to effective antiarrhythmic doses (5-20 μM). Dose-response curves indicated that lidocaine blocks the channel by binding one-to-one, with a voltage-dependent K(d). The half-blocking concentration varied from more than 300 μM, at a negative holding potential where inactivation was completely removed, to approximately 10 μM, at a depolarized holding potential where inactivation was nearly complete. Lidocaine block showed prominent use dependence with trains of depolarizing pulses from a negative holding potential. During the interval between pulses, repriming of I (Na) displayed two exponential components, a normally recovering component (τless than 0.2 s), and a lidocaine-induced, slowly recovering fraction (τ approximately 1-2 s at pH 7.0). Raising the lidocaine concentration magnified the slowly recovering fraction without changing its time course; after a long depolarization, this fraction was one-half at approximately 10 μM lidocaine, just as expected if it corresponded to drug-bound, inactivated channels. At less than or equal to 20 μM lidocaine, the slowly recovering fraction grew exponentially to a steady level as the preceding depolarization was prolonged; the time course was the same for strong or weak depolarizations, that is, with or without significant activation of I(Na). This argues that use dependence at therapeutic levels reflects block of inactivated channels, rather than block of open channels. Overall, these results provide direct evidence for the “modulated-receptor hypothesis” of Hille (1977) and Hondeghem and Katzung (1977). Unlike tetrodotoxin, lidocaine shows similar interactions with Na channels of heart, nerve, and skeletal muscle. 相似文献
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56.
Ryan L. Earley Yuying Hsu & Larry L. Wolf 《Ethology : formerly Zeitschrift fur Tierpsychologie》2000,106(8):743-761
Aggression plays an important role in animal contests, but the extent to which aggression correlates with dominance has been a topic of much debate. The relationship between aggression and dominance ability in the hermaphroditic fish, Rivulus marmoratus , was investigated using three standard protocols, the mirror test (Mi), model test (Mo), and standard opponent test (So). In each, display latency, attack latency, and biting frequency were quantified for a test individual towards its opponent. The general rank-order for eliciting strength of the three different stimuli was Mi > So > Mo. The relationships between the individual indices from the standard tests and three dyadic contest variables, initiator of display, initiator of attack, and winner, were analysed in contests between previously tested pairs to ascertain how well the standard protocols predicted dyadic contest behaviour/outcome. Display and attack latencies in the standard tests did not predict the level of analogous combat behaviour. Biting frequency differences between individuals in a pair in the So and Mo tests as well as display latency differences in the Mi test contributed to predictions of contest outcome. The individual that scored higher, relative to its opponent, won a significantly greater proportion of the bouts. These findings demonstrate the importance of relative differences in aggression in determining dominance. However, the predictive value of standard test behaviour is test-specific and, based on the available literature, depends on both the species used and the context in which they are employed. 相似文献
57.
Mickael Mazurek Daniel J Prendiville Mark A Crowe Isabelle Veissier Bernadette Earley 《BMC veterinary research》2010,6(1):55
Background
Beef suckler farms (194 farms throughout 13 counties) were assessed once with housed cattle and once with cattle at grass using an animal welfare index (AWI). Twenty-three of the 194 farms were revisited a year later and re-evaluated using the AWI and the Tier-Gerechtheits-Index 35L/2000 (TGI35L/2000). Thirty-three indicators were collected in five categories: locomotion (5 indicators); social interactions (between animals) (7), flooring (5), environment (7) and Stockpersonship (9). Three indicators relating to the size of the farm were also collected. 相似文献58.
59.
Pontes O Lawrence RJ Silva M Preuss S Costa-Nunes P Earley K Neves N Viegas W Pikaard CS 《PloS one》2007,2(11):e1157
Nucleolar dominance is an epigenetic phenomenon in plant and animal genetic hybrids that describes the expression of 45S ribosomal RNA genes (rRNA genes) inherited from only one progenitor due to the silencing of the other progenitor's rRNA genes. rRNA genes are tandemly arrayed at nucleolus organizer regions (NORs) that span millions of basepairs, thus gene silencing in nucleolar dominance occurs on a scale second only to X-chromosome inactivation in female mammals. In Arabidopsis suecica, the allotetraploid hybrid of A. thaliana and A. arenosa, the A. thaliana -derived rRNA genes are subjected to nucleolar dominance and are silenced via repressive chromatin modifications. However, the developmental stage at which nucleolar dominance is established in A. suecica is currently unknown. We show that nucleolar dominance is not apparent in seedling cotyledons formed during embryogenesis but becomes progressively established during early postembryonic development in tissues derived from both the shoot and root apical meristems. The progressive silencing of A. thaliana rRNA genes correlates with the transition of A. thaliana NORs from a decondensed euchromatic state associated with histone H3 that is trimethylated on lysine 4 (H3K4me3) to a highly condensed heterochromatic state in which the NORs are associated with H3K9me2 and 5-methylcytosine-enriched chromocenters. In RNAi-lines in which the histone deacetylases HDA6 and HDT1 are knocked down, the developmentally regulated condensation and inactivation of A. thaliana NORs is disrupted. Collectively, these data demonstrate that HDA6 and HDT1 function in the postembryonic establishment of nucleolar dominance, a process which recurs in each generation. 相似文献
60.
Corrine J Porter Jacqueline M Matthews Joel P Mackay Sharon E Pursglove Jason W Schmidberger Peter J Leedman Stephanie C Pero David N Krag Matthew CJ Wilce Jacqueline A Wilce 《BMC structural biology》2007,7(1):1-15