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71.
Padgett CL Lalive AL Tan KR Terunuma M Munoz MB Pangalos MN Martínez-Hernández J Watanabe M Moss SJ Luján R Lüscher C Slesinger PA 《Neuron》2012,73(5):978-989
Psychostimulants induce neuroadaptations in excitatory and fast inhibitory transmission in the ventral tegmental area (VTA). Mechanisms underlying drug-evoked synaptic plasticity of slow inhibitory transmission mediated by GABA(B) receptors and G protein-gated inwardly rectifying potassium (GIRK/Kir(3)) channels, however, are poorly understood. Here, we show that 1 day after methamphetamine (METH) or cocaine exposure both synaptically evoked and baclofen-activated GABA(B)R-GIRK currents were significantly depressed in VTA GABA neurons and remained depressed for 7 days. Presynaptic inhibition mediated by GABA(B)Rs on GABA terminals was also weakened. Quantitative immunoelectron microscopy revealed internalization of GABA(B1) and GIRK2, which occurred coincident with dephosphorylation of serine 783 (S783) in GABA(B2), a site implicated in regulating GABA(B)R surface expression. Inhibition of protein phosphatases recovered GABA(B)R-GIRK currents in VTA GABA neurons of METH-injected mice. This psychostimulant-evoked impairment in GABA(B)R signaling removes an intrinsic brake on GABA neuron spiking, which may augment GABA transmission in the mesocorticolimbic system. 相似文献
72.
73.
A procedure to remove protease activities from Bacillus subtilis sporulating cells and their crude extracts. 总被引:6,自引:0,他引:6
A simple procedure was developed to remove both extracellular and intracellular proteases associated with aporulating Bacillus subtilis cells. Cells are washed four times with 1 m KCl before breakage and their crude extracts are treated with 2 mm diisopropylfluorophosphate before passage through a hemoglobin-Sepharose affinity column. RNA polymerase in crude B. subtilis extracts treated by this procedure was stable, functionally and structurally, for more than 1 month at 4°C. This process for removing all proteases should work essentially with any crude extracts containing proteolytic activities. 相似文献
74.
The inhibition of neutrophil granule enzyme secretion and chemotaxis by pertussis toxin 总被引:19,自引:2,他引:19 下载免费PDF全文
E L Becker J C Kermode P H Naccache R Yassin M L Marsh J J Munoz R I Sha'afi 《The Journal of cell biology》1985,100(5):1641-1646
Pertussis toxin treatment of rabbit peritoneal neutrophils causes a concentration-dependent inhibition of granule enzyme secretion induced by formylmethionyl-leucyl-phenylalanine, C5a, and leukotriene B4. It also inhibits chemotaxis induced by formylmethionyl-leucyl-phenylalanine. The same toxin treatment, however, has no effect on granule enzyme secretion induced by the calcium ionophore A23187 or phorbol 12-myristate 13-acetate. Moreover, pertussis toxin treatment does not affect either the number or affinity of the formylpeptide receptors on the neutrophil nor does it have any effect on the unstimulated levels of cyclic AMP (cAMP) or the transient rise in cAMP induced by chemotactic factor stimulation in these cells. We hypothesize that pertussis toxin, as in other cells, interacts with a GTP binding regulatory protein identical with or analogous to either Ni or transducin which mediates the receptor-induced inhibition or activation of a target protein or proteins required in neutrophil activation. The nature of the target protein is unknown, but it is not the catalytic unit of adenylate cyclase. The target protein acts after binding of chemotactic factor to its receptor in the sequence that leads to the receptor-induced rise in intracellular Ca2+. It does not affect the responses elicited by the direct introduction of calcium into the cells or the activity of protein kinase C. 相似文献
75.
Marius Peacock J. Munoz George L. Tallent Richard A. Ormsbee 《Journal of bacteriology》1968,95(5):1580-1586
Passive cutaneous anaphylaxis (PCA) was produced in guinea pigs sensitized with guinea pig Coxiella burneti phase I–II antiserum and challenged with dimethylsulfoxide- or trichloroacetic acid-soluble extracts from phase I cells. The PCA reaction could not be induced by whole or mechanically disrupted phase I or phase II C. burneti cells or by extracted cells or extracts of phase II cells. The antibody responsible for PCA was in the 7Sγ1 (fast γ) globulin. Sensitization of the skin by 7Sγ1 antibody could be blocked nonspecifically by 7Sγ1 globulin from normal serum or from phase II antiserum. The 7Sγ2 (slow γ) globulin antibody inhibited the reaction specifically. Some antiserum pools containing high agglutinin and complement-fixing titers to phase I C. burneti cells failed to initiate the PCA reaction, perhaps due to an imbalanced ratio of γ1 to γ2 specific globulins or to an imbalance in the ratio of specific to nonspecific γ1 globulins. Agglutinins to phase I cells were found in both γ1 and γ2 antibody globulins. Complement-fixing antibodies were found in the γ2 globulin fraction. 相似文献
76.
Thirty litters of C57BL 6J mice were administered intraperitoneally one of four doses (0, 500, 750, and 1,000 mg/kg maternal weight) of acetazolamide on day 9 of gestation. The fetuses were removed on day 18 and fixed, stained, cleared, and examined for the pattern of malformations. The forelimb postaxial limb deficiency was the most common abnormality, but forelimb postaxial polydactyly and a postaxial deficiency in the hindlimb were also observed. Males were significantly more likely to be malformed than females at all doses, in contrast to the predominance of females observed in rat fetuses exposed to acetazolamide (Scott et al.: Teratology 6:239-240, '73). The occurrence of limb malformations did not correlate with maternal weight loss, the birth weight of the fetus, or the position of the fetus in the uterus. A "litter effect" was demonstrated in that there was a nonuniform distribution of litters with different proportions of malformed fetuses. 相似文献
77.
78.
White S. R.; Blake J. S.; Murphy T. M.; Mack M. M.; Munoz N. M.; Leff A. R. 《Journal of applied physiology》1989,66(4):1852-1859
We studied the sympathetic neural response on airways to hypotensive stimuli in 19 swine in vivo. The effects of pharmacologically induced hypotension with nitroprusside (NTP) and hypotension elicited by intravenous compound 48/80 (48/80), a mast cell degranulating agent, were compared after equivalent reductions in mean arterial blood pressure (MAP). Reduction of the MAP to 60% of base line with NTP in six swine caused an increase in plasma epinephrine (E) from 60 +/- 28 to 705 +/- 276 pg/ml (P = 0.032) and plasma norepinephrine (NE) from 270 +/- 46 to 796 +/- 131 pg/ml (P = 0.032). Comparable reduction in MAP elicited with 48/80 in six other swine caused a substantially greater increase in both plasma E (9,581 +/- 4,147 pg/ml; P = 0.012 vs. NTP group) and plasma NE (2,239 +/- 637 pg/ml; P = 0.041 vs. NTP group). Catecholamine secretion attenuated mediator-induced changes in lung resistance (RL). In animals receiving 48/80, RL increased from 2.97 +/- 0.31 to 7.44 +/- 0.56 cmH2O.l-1.s. In animals having ganglionic blockade with 7.5 mg/kg iv hexamethonium and beta-adrenergic blockade with propranolol (4.0 mg/kg iv followed by 40 micrograms/kg-1.min-1), comparable doses of 48/80 caused an increase in RL to 18.6 +/- 4.55 cmH2O.l-1.s (P less than 0.04 vs. swine receiving neither hexamethonium nor propranolol).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
79.
In diploid species, many multiparental populations have been developed to increase genetic diversity and quantitative trait loci (QTL) mapping resolution. In these populations, haplotype reconstruction has been used as a standard practice to increase the power of QTL detection in comparison with the marker-based association analysis. However, such software tools for polyploid species are few and limited to a single biparental F1 population. In this study, a statistical framework for haplotype reconstruction has been developed and implemented in the software PolyOrigin for connected tetraploid F1 populations with shared parents, regardless of the number of parents or mating design. Given a genetic or physical map of markers, PolyOrigin first phases parental genotypes, then refines the input marker map, and finally reconstructs offspring haplotypes. PolyOrigin can utilize single nucleotide polymorphism (SNP) data coming from arrays or from sequence-based genotyping; in the latter case, bi-allelic read counts can be used (and are preferred) as input data to minimize the influence of genotype calling errors at low depth. With extensive simulation we show that PolyOrigin is robust to the errors in the input genotypic data and marker map. It works well for various population designs with offspring per parent and for sequences with read depth as low as 10x. PolyOrigin was further evaluated using an autotetraploid potato dataset with a 3 × 3 half-diallel mating design. In conclusion, PolyOrigin opens up exciting new possibilities for haplotype analysis in tetraploid breeding populations. 相似文献
80.
Salman A. Rahman Sheila K. West Harran Mkocha Beatriz Munoz Travis C. Porco Jeremy D. Keenan Thomas M. Lietman 《PLoS neglected tropical diseases》2015,9(3)
BackgroundMathematical models predict an exponential distribution of infection prevalence across communities where a disease is disappearing. Trachoma control programs offer an opportunity to test this hypothesis, as the World Health Organization has targeted trachoma for elimination as a public health concern by the year 2020. Local programs may benefit if a single survey could reveal whether infection was headed towards elimination. Using data from a previously-published 2009 survey, we test the hypothesis that Chlamydia trachomatis prevalence across 75 Tanzanian communities where trachoma had been documented to be disappearing is exponentially distributed.Methods/FindingsWe fit multiple continuous distributions to the Tanzanian data and found the exponential gave the best approximation. Model selection by Akaike Information Criteria (AICc) suggested the exponential distribution had the most parsimonious fit to the data. Those distributions which do not include the exponential as a special or limiting case had much lower likelihoods of fitting the observed data. 95% confidence intervals for shape parameter estimates of those distributions which do include the exponential as a special or limiting case were consistent with the exponential. Lastly, goodness-of-fit testing was unable to reject the hypothesis that the prevalence data came from an exponential distribution.ConclusionsModels correctly predict that infection prevalence across communities where a disease is disappearing is best described by an exponential distribution. In Tanzanian communities where local control efforts had reduced the clinical signs of trachoma by 80% over 10 years, an exponential distribution gave the best fit to prevalence data. An exponential distribution has a relatively heavy tail, thus occasional high-prevalence communities are to be expected even when infection is disappearing. A single cross-sectional survey may be able to reveal whether elimination efforts are on-track. 相似文献