排序方式: 共有73条查询结果,搜索用时 15 毫秒
41.
Achintya K. Bandyopadhyaya Brad D. Manion Ann Benz Amanda Taylor Nigam P. Rath Alex S. Evers Charles F. Zorumski Steven Mennerick Douglas F. Covey 《Bioorganic & medicinal chemistry letters》2010,20(22):6680-6684
Alphaxalone, a neuroactive steroid containing a 17β-acetyl group, has potent anesthetic activity in humans. This pharmacological activity is attributed to this steroid’s enhancement of γ-amino butyric acid-mediated chloride currents at γ-amino butyric acid type A receptors. The conversion of alphaxalone into Δ16-alphaxalone produces an analogue that lacks anesthetic activity in humans and that has greatly diminished receptor actions. By contrast, the corresponding 17β-carbonitrile analogue of alphaxalone and the Δ16-17-carbonitrile analogue both have potent anesthetic and receptor actions. The differential effect of the Δ16-double bond on the actions of alphaxalone and the 17β-carbonitrile analogue is accounted for by a differential effect on the orientation of the 17-acetyl and 17-carbonitrile substituents. 相似文献
42.
43.
Alana C. Conti James W. Maas Jr Krista L. Moulder Xiaoping Jiang Bhumy A. Dave Steven Mennerick Louis J. Muglia 《PloS one》2009,4(5)
Background
Although ethanol exerts widespread action in the brain, only recently has progress been made in understanding the specific events occurring at the synapse during ethanol exposure. Mice deficient in the calcium-stimulated adenylyl cyclases, AC1 and AC8 (DKO), demonstrate increased sedation duration and impaired phosphorylation by protein kinase A (PKA) following acute ethanol treatment. While not direct targets for ethanol, we hypothesize that these cyclases initiate a homeostatic presynaptic response by PKA to reactivate neurons from ethanol-mediated inhibition.Methodology/Principal Findings
Here, we have used phosphoproteomic techniques and identified several presynaptic proteins that are phosphorylated in the brains of wild type mice (WT) after ethanol exposure, including synapsin, a known PKA target. Phosphorylation of synapsins I and II, as well as phosphorylation of non-PKA targets, such as, eukaryotic elongation factor-2 (eEF-2) and dynamin is significantly impaired in the brains of DKO mice. This deficit is primarily driven by AC1, as AC1-deficient, but not AC8-deficient mice also demonstrate significant reductions in phosphorylation of synapsin and eEF-2 in cortical and hippocampal tissues. DKO mice have a reduced pool of functional recycling vesicles and fewer active terminals as measured by FM1-43 uptake compared to WT controls, which may be a contributing factor to the impaired presynaptic response to ethanol treatment.Conclusions/Significance
These data demonstrate that calcium-stimulated AC-dependent PKA activation in the presynaptic terminal, primarily driven by AC1, is a critical event in the reactivation of neurons following ethanol-induced activity blockade. 相似文献44.
To examine persisting effects of depolarizing rises in extracellular potassium concentration ([K+](o)) on synapses, we depolarized cells to simulate ischemia-like rises in [K+](o). Elevated [K+](o) for 1-16 hr severely depressed glutamate signaling, while mildly depressing GABA transmission. The glutamate-specific changes were plastic over several hours and involved a decrease in the size of the pool of releasable vesicles. Rather than a reduction of the number of vesicles per release site, the change involved functional elimination of release sites. This change was clearly dissociable from a second effect, depressed probability of transmitter release, which was common to both glutamate and GABA transmission. Thus, while other recent evidence links alteration of the releasable pool size with changes in p(r), our results suggest the two can be independently manipulated. Selective depression of glutamate release may provide an adaptive mechanism by which neurons limit excitotoxicity. 相似文献
45.
Darbandi-Tonkabon R Hastings WR Zeng CM Akk G Manion BD Bracamontes JR Steinbach JH Mennerick SJ Covey DF Evers AS 《The Journal of biological chemistry》2003,278(15):13196-13206
Neuroactive steroids modulate the function of gamma-aminobutyric acid, type A (GABA(A)) receptors in the central nervous system by an unknown mechanism. In this study we have used a novel neuroactive steroid analogue, 3 alpha,5 beta-6-azi-3-hydroxypregnan-20-one (6-AziP), as a photoaffinity labeling reagent to identify neuroactive steroid binding sites in rat brain. 6-AziP is an effective modulator of GABA(A) receptors as evidenced by its ability to inhibit binding of [(35)S]t-butylbicyclophosphorothionate to rat brain membranes and to potentiate GABA-elicited currents in Xenopus oocytes and human endothelial kidney 293 cells expressing GABA(A) receptor subunits (alpha(1)beta(2)gamma(2)). [(3)H]6-AziP produced time- and concentration-dependent photolabeling of protein bands of approximately 35 and 60 kDa in rat brain membranes. The 35-kDa band was half-maximally labeled at a [(3)H]6-AziP concentration of 1.9 microM, whereas the 60-kDa band was labeled at higher concentrations. The photolabeled 35-kDa protein was isolated from rat brain by two-dimensional PAGE and identified as voltage-dependent anion channel-1 (VDAC-1) by both matrix-assisted laser desorption ionization time-of-flight and ESI-tandem mass spectrometry. Monoclonal antibody directed against the N terminus of VDAC-1 immunoprecipitated labeled 35-kDa protein from a lysate of rat brain membranes, confirming that VDAC-1 is the species labeled by [(3)H]6-AziP. The beta(2) and beta(3) subunits of the GABA(A) receptor were co-immunoprecipitated by the VDAC-1 antibody suggesting a physical association between VDAC-1 and GABA(A) receptors in rat brain membranes. These data suggest that neuroactive steroid effects on the GABA(A) receptor may be mediated by binding to an accessory protein, VDAC-1. 相似文献
46.
An opercular tag for marking adult milkfish ( Chanos chanos Forsskal) and seabass ( Lates calcarifer Bloch) is described. High tag retention and relatively low mortality rates were observed in adult fish handled two to ten times during 14-to 60-day tests. The features and advantages of the tag for marking large-sized fish in short-term studies are discussed.
Eine preiswerte Markierung für Kurzzeitstudien des Milchfisches (Chanos chanos Forsskal) und der Centropomidae (Lates calcarifer Bloch)
Eine Kiemendeckel-Markierung für adulte Milchfische (Chanos chanos Forsskal) und Centropomidae (Lates calcacifer Bloch) wird beschrieben. Sie zeichnet sich durch gute Haltbarkeit aus und verursacht relativ geringe Mortalität bei adulten Fischen, die in Versuchen von 14 bis 60 Tage Dauer 2-bis 10mal untersucht wurden. Die Eigenschaften und Vorteile dieser Markierung für große Fische in Kurzzeitstudien werden diskutiert.
Un marquage économique pour des études de courte durée du chanidé (Chanos chanos Forsskal) et du centropomidé (Lates calcarifer Bloch)
Un marquage d'opercule pour les chanidés (Chanos chanos Forsskal) et les centropomidés (Lates calcarifer Bloch) adultes est décrit. Une bonne conservation et une mortalité relativement basse ont été observées chez des poissons adultes examinés 2 à 10 fois pendant des expériences d'une durée de 14 à 60 jours. Les caractéristiques et les avantages du marquage de poissons de grande taille pendant des expériences d'une courte durée sont discutés. 相似文献
Zusammenfassung
Eine preiswerte Markierung für Kurzzeitstudien des Milchfisches (Chanos chanos Forsskal) und der Centropomidae (Lates calcarifer Bloch)
Eine Kiemendeckel-Markierung für adulte Milchfische (Chanos chanos Forsskal) und Centropomidae (Lates calcacifer Bloch) wird beschrieben. Sie zeichnet sich durch gute Haltbarkeit aus und verursacht relativ geringe Mortalität bei adulten Fischen, die in Versuchen von 14 bis 60 Tage Dauer 2-bis 10mal untersucht wurden. Die Eigenschaften und Vorteile dieser Markierung für große Fische in Kurzzeitstudien werden diskutiert.
Résumé
Un marquage économique pour des études de courte durée du chanidé (Chanos chanos Forsskal) et du centropomidé (Lates calcarifer Bloch)
Un marquage d'opercule pour les chanidés (Chanos chanos Forsskal) et les centropomidés (Lates calcarifer Bloch) adultes est décrit. Une bonne conservation et une mortalité relativement basse ont été observées chez des poissons adultes examinés 2 à 10 fois pendant des expériences d'une durée de 14 à 60 jours. Les caractéristiques et les avantages du marquage de poissons de grande taille pendant des expériences d'une courte durée sont discutés. 相似文献
47.
The harbor seal (Phoca vitulina) has the most extensive distribution of any
phocid seal species. An analysis of population structure in this species
across its European range was made using 7 phocid derived microsatellites
in a sample of 1,029 individuals from 12 separate geographic areas. Despite
the species potential for long-distance movement, significant genetic
differentiation between areas was observed using an unbiased estimator of
RST. Six distinct population units were identified: Ireland-Scotland,
English east coast, Waddensea, western Scandinavia
(Norway-Kattegat-Skagerrak-west Baltic), east Baltic, and Iceland. Little
local substructuring is present along coastlines with a continuous
distribution of breeding animals, but differentiation does increase with
geographic distance. The degree of differentiation is greater over
equivalent distances where the distribution is discontinuous, such as along
coasts where breeding colonies are separated by large distances or by
stretches of open sea. Patterns of population differentiation derived from
microsatellites are very similar to those obtained from previous
mitochondrial DNA analysis and suggest that philopatry in harbor seals
operates over 300-500 km. In Europe, harbor seals have experienced a
complex demographic history and patterns of population structure are likely
to have been affected by natural environmental influences such as
Pleistocene glaciations and epizootics. Comparison of Nm values from an
unbiased estimator of RST, GST, and theta are consistent and, in some
cases, may indicate populations where conditions deviate from the
expectations of the RST model.
相似文献
48.
A molecular and evolutionary study of the beta-globin gene family of the Australian marsupial Sminthopsis crassicaudata 总被引:1,自引:0,他引:1
Cooper SJ; Murphy R; Dolman G; Hussey D; Hope RM 《Molecular biology and evolution》1996,13(7):1012-1022
Beta-globin gene families in eutherians (placental mammals) consist of a
set of four or more developmentally regulated genes which are closely
linked and, in general, arranged in the order 5'-embryonic/fetal genes-
adult genes-3'. This cluster of genes is proposed to have arisen by tandem
duplication of ancestral beta-globin genes, with the first duplication
occurring 200 to 155 MYBP just prior to a period in mammalian evolution
when eutherians and marsupials diverged from a common ancestor. In this
paper we trace the evolutionary history of the beta-globin gene family back
to the origins of these mammals by molecular characterization of the
beta-globin gene family of the Australian marsupial Sminthopsis
crassicaudata. Using Southern and restriction analysis of total genomic DNA
and bacteriophage clones of beta-like globin genes, we provide evidence
that just two functional beta-like globin genes exist in this marsupial,
including one embryonic- expressed gene (S.c-epsilon) and one
adult-expressed gene (S.c-beta), linked in the order 5'-epsilon-beta-3'.
The entire DNA sequence of the adult beta-globin gene is reported and shown
to be orthologous to the adult beta-globin genes of the North American
marsupial Didelphis virginiana and eutherian mammals. These results,
together with results from a phylogenetic analysis of mammalian beta-like
globin genes, confirm the hypothesis that a two-gene cluster, containing an
embryonic- and an adult-expressed beta-like globin gene, existed in the
most recent common ancester of marsupials and eutherians. Northern analysis
of total RNA isolated from embryos and neonatals indicates that a switch
from embryonic to adult gene expression occurs at the time of birth,
coinciding with the transfer of the marsupial from a uterus to a pouch
environment.
相似文献
49.
Domains of receptor mobility and endocytosis in the membranes of neonatal human erythrocytes in the membranes of neonatal human erythrocytes and reticulocytes are deficient in spectrin
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It has previously shown (Schekman, R., and S.J. Singer, Proc. Natl. Acad. Sci. U.S.A. 73:4075-4079) that receptors in the membranes of neonatal human erythrocytes show a restricted degree of lateral mobility, whereas in adult human erythrocytes the receptors are essentially immobile. This restricted mobility is exhibited, for example, when concanavalin A (Con A) induces a limited clustering of its receptors in the neonatal erythrocyte membrane, resulting in the formation of invaginations and endocytic vesicles. This does not happen with adult cells. By the use of indirect immunoferritin labeling of ultrathin frozen sections of Con A-treated neonatal blood cells, we now show that the invaginations and endocytotic vesicles do not stain for spectrin, whereas the adjacent unperturbed membrane is heavily stained. The reticulocytes in the neonatal cell population undergo substantially more Con A-induced invagination and endocytosis than do the erythrocytes. These results lend strong support to the hypothesis that specialized discrete domains exist, or are induced, in the membranes of these neonatal cells, in which receptors are laterally mobile, whereas in the remaining (and predominant) part of the membrane the receptors are immobile. Such mobile domains are characterized by an absence of spectrin. During the maturation of the neonatal reticulocyte to erythrocyte, it is proposed that these domains are in large part, but not completely, eliminated. 相似文献
50.