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31.
Annie Arguello XiaoYong Yang Daniel Vogt Amelia Stanco John L. R. Rubenstein Benjamin N. R. Cheyette 《PloS one》2013,8(6)
Synaptogenesis has been extensively studied along with dendritic spine development in glutamatergic pyramidal neurons, however synapse development in cortical interneurons, which are largely aspiny, is comparatively less well understood. Dact1, one of 3 paralogous Dact (Dapper/Frodo) family members in mammals, is a scaffold protein implicated in both the Wnt/β-catenin and the Wnt/Planar Cell Polarity pathways. We show here that Dact1 is expressed in immature cortical interneurons. Although Dact1 is first expressed in interneuron precursors during proliferative and migratory stages, constitutive Dact1 mutant mice have no major defects in numbers or migration of these neurons. However, cultured cortical interneurons derived from these mice have reduced numbers of excitatory synapses on their dendrites. We selectively eliminated Dact1 from mouse cortical interneurons using a conditional knock-out strategy with a Dlx-I12b enhancer-Cre allele, and thereby demonstrate a cell-autonomous role for Dact1 during postsynaptic development. Confirming this cell-autonomous role, we show that synapse numbers in Dact1 deficient cortical interneurons are rescued by virally-mediated re-expression of Dact1 specifically targeted to these cells. Synapse numbers in these neurons are also rescued by similarly targeted expression of the Dact1 binding partner Dishevelled-1, and partially rescued by expression of Disrupted in Schizophrenia-1, a synaptic protein genetically implicated in susceptibility to several major mental illnesses. In sum, our results support a novel cell-autonomous postsynaptic role for Dact1, in cooperation with Dishevelled-1 and possibly Disrupted in Schizophrenia-1, in the formation of synapses on cortical interneuron dendrites. 相似文献
32.
Ca2+ channel antagonist actions in bladder smooth muscle: comparative pharmacologic and [3H]nitrendipine binding studies 总被引:2,自引:0,他引:2
F B Yousif G T Bolger A Ruzycky D J Triggle 《Canadian journal of physiology and pharmacology》1985,63(5):453-462
The actions of a series of 15 Ca2+ channel antagonists including D-600, nifedipine, and diltiazem were examined against K+ depolarization and muscarinic receptor induced responses in guinea pig bladder smooth muscle. Responses of bladder are very dependent upon extracellular Ca2+ and sensitive to the Ca2+ channel antagonists, the tonic component more than the phasic component of response. Regardless of stimulant, K+ or methylfurmethide (MF), or component of response, the same rank order of antagonist activities is expressed, suggestive of a single structure-activity relationship and the existence of a single category of binding site which may, however, exist in several affinity states. High affinity binding of [3H]nitrendipine (KD = 1.1 X 10(-10) M) occurs in bladder membranes, and similar high affinity binding was found in microsomal preparations from other smooth muscles including guinea pig and rat lung, rat vas deferens, uterus, and stomach. [3H]nitrendipine binding in the bladder was sensitive to displacement by other 1,4-dihydropyridines, paralleling their pharmacologic activities and showing excellent agreement with binding data previously obtained for guinea pig ileal smooth muscle. Comparison of pharmacologic data for inhibition of K+- and MF-induced responses by a common series of Ca2+ channel antagonists in bladder and ileum revealed excellent correlations. Neither pharmacologic nor binding studies suggest significant differences in Ca2+ channel antagonist properties in smooth muscle from bladder and intestine. 相似文献
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34.
Nonintegrative transformation in the filamentous fungus Podospora anserina: stabilization of a linear vector by the chromosomal ends of Tetrahymena thermophila. 总被引:3,自引:0,他引:3
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The effect of the chromosomal ends of Tetrahymena thermophila on the stability of linear transforming molecules in the filamentous fungus Podospora anserina was tested. A derivative of an integrative vector for this fungus has been constructed, so that after linearization, the ends of the plasmid are the telomeric sequences of T. thermophila. After transformation, this linear molecule was maintained as an extrachromosomal plasmid with no integrated copies in about 50% of the transformants. Under selective conditions, there was approximately one linear molecule per 5 to 10 nuclei, and these extrachromosomal molecules were rapidly lost under nonselective conditions. The circular plasmid carrying an inverted repeat of T. thermophila telomeres could be linearized and processed in vivo. 相似文献
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36.
An earlier report (1) of an adverse effect of high doses of oxytocin on human memory included results of studies on women receiving oxytocin as part of the treatment to induce 2nd trimester therapeutic abortion. These women served as their own controls. We have now been able to study a group of women who have been treated in all ways like the original group, with the exception that they did not receive oxytocin. The results from this external control corroborate the finding that oxytocin affected memory. 相似文献
37.
T B Hargreave 《BMJ (Clinical research ed.)》1982,284(6333):1948-1949
38.
Ryanodine was found to initially inhibit calcium uptake by cardiac sarcoplasmic reticulum. This initial depression was followed by a later marked stimulation of calcium uptake. These effects were noted when calcium uptake was measured in the presence or absence of oxalate. The requirement for preincubation with ryanodine was highly dependent on ryanodine concentration and temperature. The mechanism of action of ryanodine clearly was not an effect on oxalate entry or calcium oxalate precipitation because the effects were also observed in the absence of oxalate. Ryanodine also had no effect on passive calcium efflux from actively loaded vesicles. Because ryanodine had no effect on Ca2+-ATPase activity under defined conditions of an ATP-regenerating system and no calcium gradient, we suggest ryanodine does not change the stoichiometry of the pump. Our results are consistent with the hypothesis that ryanodine closes a calcium channel in a subpopulation of the vesicles. 相似文献
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40.
Summary A stream-breeding race of small-mouthed salamanders (Ambystoma texanum) in central Kentucky produces ova that are twice as large as those of a pond-breeding race found nearby. Embryos of stream-breeders also hatch at a more advanced developmental stage than those of pond-breeders. Morphological evidence indicates that stream-breeders were derived from pond-breeding stock. Assuming that differences between stream and pond-breeders reflect evolutionary change, and that the ancestral pond stock that invaded streams was similar to extant pond-breeders, we examined three hypotheses that might explain changes in ovum size and stage at hatching following the invasion of streams. (1) Larger ovum size evolved indirectly as a consequence of selection for rapid development which minimizes mortality risk from stream drying. (2) Increased ovum (hatchling) size and stage at hatching of stream-breeders are adaptations to resist stream current. (3) Increased ovum (hatchling) size and stage at hatching are adaptations to reduce predation on hatchlings from stream invertebrates. The results of field and laboratory studies only support hypotheses (2) and (3). Hatchlings that were relatively large or at a more advanced developmental stage had slower drift rates and were less vulnerable to predation by Phagocata gracilis, a flatworm abundant in streams in central Kentucky. Developmental and growth parameters were not correlated significantly with ovum size in populations of either geographic race. Differences in degree of parental care among races also cannot explain variation in ovum size since both races abandon their eggs immediately after oviposition. 相似文献