72 resultados para specific states of schizophrenia
Resumo:
Full-length transient receptor potential (TRP) cation channel TRPC4alpha and shorter TRPC4beta lacking 84 amino acids in the cytosolic C terminus are expressed in smooth muscle and endothelial cells where they regulate membrane potential and Ca(2+) influx. In common with other "classical" TRPCs, TRPC4 is activated by G(q)/phospholipase C-coupled receptors, but the underlying mechanism remains elusive. Little is also known about any isoform-specific channel regulation. Here we show that TRPC4alpha but not TRPC4beta was strongly inhibited by intracellularly applied phosphatidylinositol 4,5-bisphosphate (PIP(2)). In contrast, several other phosphoinositides (PI), including PI(3,4)P(2), PI(3,5)P(2), and PI(3,4,5)P(3), had no effect or even potentiated TRPC4alpha indicating that PIP(2) inhibits TRPC4alpha in a highly selective manner. We show that PIP(2) binds to the C terminus of TRPC4alpha but not that of TRPC4beta in vitro. Its inhibitory action was dependent on the association of TRPC4alpha with actin cytoskeleton as it was prevented by cytochalasin D treatment or by the deletion of the C-terminal PDZ-binding motif (Thr-Thr-Arg-Leu) that links TRPC4 to F-actin through the sodium-hydrogen exchanger regulatory factor and ezrin. PIP(2) breakdown appears to be a required step in TRPC4alpha channel activation as PIP(2) depletion alone was insufficient for channel opening, which additionally required Ca(2+) and pertussis toxin-sensitive G(i/o) proteins. Thus, TRPC4 channels integrate a variety of G-protein-dependent stimuli, including a PIP(2)/cytoskeleton dependence reminiscent of the TRPC4-like muscarinic agonist-activated cation channels in ileal myocytes.
Resumo:
The rat stomach is rich in endocrine cells. The acid-producing (oxyntic) mucosa contains ECL cells, A-like cells, and somatostatin (D) cells, and the antrum harbours gastrin (G) cells, enterochromaffin (EC) cells and D cells. Although chromogranin A (CgA) occurs in all these cells, its processing appears to differ from one cell type to another. Eleven antisera generated to different regions of rat CgA, two antisera generated to a human (h) CgA sequences, and one to a bovine Ib) CgA sequence, respectively, were employed together with antisera directed towards cell-specific markers such as gastrin (G cells), serotonin (EC cells), histidine decarboxylsae (ECL cells) and somatostatin (D cells) to characterize the expression of CgA and CgA-derived peptides in the various endocrine cell populations of the rat stomach. In the oxyntic mucosa, antisera raised against CgA(291-319) and CGA(316-321) immunostained D cells exclusively, whereas antisera raised against bCgA(82-91) and CgA(121-128) immunostained A-like cells and D cells. Antisera raised against CgA(318-349) and CgA(437-448) immunostained ECL cells and A-like cells, but not D cells. In the antrum, antisera against CgA(291-319) immunostained D cells, and antisera against CgA(351-356) immunostained G cells. Our observations suggest that each individual endocrine cell type in the rat stomach generates a unique mixture of CgA-derived peptides, probably reflecting cell-specific differences in the post-translational processing of CgA and its peptide products. A panel of antisera that recognize specific domains of CgA may help to identify individual endocrine cell populations.
Resumo:
The dynamics of adsorption and oxidation of CO on Ru(0001) electrode in sulfuric acid solution have been studied using in situ FTIR spectroscopy under potential control and at open circuit, the latter at 20 and 55 degrees C. The in situ IR data show clearly that the bisulfate anion adsorbs on the Ru(0001) surface over the potential range from -200 mV to 350 mV (vs. Ag/AgCl) at 20 degrees C in the absence and presence of adsorbed CO; however, increasing the temperature to 55 degrees C and/ or increasing the concentration of dissolved O-2 reduces the bisulfate adsorption. The formation of surface (hydro-) oxide at higher potentials replaces the bisulfate adsorbates. Both linear (COL) and three-fold hollow bonded CO (COH) adsorbates were produced following CO adsorption at Ru(0001) in H2SO4, as was observed in our previous studies in HClO4. However, the amount of adsorbed CO observed in H2SO4 was ca. 10% less than that in HClO4; in addition, the COL and COH frequencies were higher in H2SO4, and the onset potential for COads oxidation 25 mV lower. These new results are interpreted in terms of a model in which the adsorbed bisulfate weakens the CO adlayer, allowing the active Ru oxide layer to form at lower potentials. Significantly different results were observed at open circuit in H2SO4 compared both to the data under potential control and to our earlier data in HClO4, and these observations were rationalized in terms of the adsorbed HSO4- anions (pre-adsorbed at -200 mV) inhibiting the oxidation of the surface at open circuit (after stepping from the initial potential of -200 mV), as the latter was no longer driven by the imposed electrochemical potential but via chemical oxidation by trace dissolved O-2. Results from experiments at open circuit at 55 degrees C and using oxygen-saturated H2SO4 supported this model. The difference in Ru surface chemistry between imposed electrochemical control and chemical control has potential implications with respect to fuel cell electrocatalysis.
Resumo:
Published ab-initio and pseudopotential calculations for the dialkali halide systems suggest that the preferred co-linear geometry is for the metal to approach the metal end of the alkali halide. Here, ab-initio calculations on the Li2F system reveal that the well depth on the halide side in this radical is much deeper and is a local saddle-point associated with the ionic non-linear global minima. Although many features of the pseudopotential surfaces are confirmed, significant differences are apparent including the existence of a linear excited state instead of a triangular one, a considerably deeper global minimum some 50% lower in energy and a close approach between the X2A1 and the states, with the minimum 87 kJ mol-1 below the ground state asymptote. All the results can be rationalised as the avoided crossings between a long range, covalent potential dominant within the LiLiF geometry and an ionic state that forms the global minimum. Calculations on the 3rd 2A' potential indicate that even for Li + LiF collisions at ultracold temperatures the collision dynamics could involve as many as three electronic states.
Resumo:
We report the first experimental generation and characterization of a six-photon Dicke state. The produced state shows a fidelity of F=0.56 +/- 0.02 with respect to an ideal Dicke state and violates a witness detecting genuine six-qubit entanglement by 4 standard deviations. We confirm characteristic Dicke properties of our resource and demonstrate its versatility by projecting out four- and five-photon Dicke states, as well as four-photon Greenberger-Horne-Zeilinger and W states. We also show that Dicke states have interesting applications in multiparty quantum networking protocols such as open-destination teleportation, telecloning, and quantum secret sharing.
Resumo:
Paraoxonase 1 (PON1) has been suggested as a plausible candidate gene for human longevity due to its modulation of cardiovascular disease risk, by preventing oxidation of atherogenic low-density lipoprotein. The role of the PON1 192 Q/R polymorphism has been analyzed for association with survival at old age in several populations, albeit with controversial results. To reconcile the conflicting evidence, we performed a large association study with two samples of 2357 Germans and 1025 French, respectively. We combined our results with those from seven previous studies in the largest and most comprehensive meta-analysis on PON1 192 Q/R and longevity to-date, to include a total of 9580 individuals. No significant association of PON1 192 Q/R with longevity was observed, for either R allele or carriership. This finding relied on very large sample sizes, is supported by different analysis methods and is therefore considered very robust. Moreover, we have investigated a potential interaction of PON1 192 Q/R with APOE epsilon4 using data from four populations. Whereas a significant result was found in the German sample, this could not be confirmed in the other examined groups. Our large-scale meta-analysis provided no evidence that the PON1 192 Q/R polymorphism is associated with longevity, but this does not exclude the possibility of population-specific effects due to the influence of, and interaction between, different genetic and/or environmental factors (e.g. diet).
Resumo:
Evolving RNA interference (RNAi) platforms are providing opportunities to probe gene function in parasitic helminths using reverse genetics. Although relatively robust methods for the application of RNAi in parasitic flatworms have been established, reports of successful RNAi are confined to three genera and there are no known reports of the application of RNAi to the class Cestoda. Here we report the successful application of RNAi to a cestode. Our target species was the common ruminant tapeworm, Moniezia expansa which can significantly impact the health/productivity of cattle, sheep and goats. Initial efforts aimed to silence the neuronally expressed neuropeptide F gene (Me-npf-1), which encodes one of the most abundant neuropeptides in flatworms and a homologue of vertebrate neuropeptide Y (NPY). Double stranded (ds)RNAs, delivered by electroporation and soaking (4-8 h), failed to trigger consistent Me-npf-1 transcript knock-down in adult worms; small interfering RNAs (siRNAs) were also ineffective. Identical approaches resulted in significant and consistent transcript knock-down of actin transcript (71 +/- 4%) following soaking in Me-act-1 dsRNA. Similar successes were seen with hydrophobic lipid-binding protein (Me-lbp-1), with a dsRNA inducing significant target transcript reduction (72 +/- 5%). To confirm the validity of the observed transcript knock-downs we further investigated Me-act-1 RNAi worms for associated changes in protein levels, morphology and phenotype. Me-act-1 RNAi worms displayed significant reductions in both filamentous actin immunostaining (62 +/- 3%) and the amount of actin detected in Western blots (54 +/- 13%). Morphologically, Me-act-1 RNAi worms displayed profound tegumental disruption/blebbing. Further, muscle tension recordings from Me-act-1 RNAi worms revealed a significant reduction in both the number of worms contracting in response to praziquantel (20 +/- 12%) and in their contractile ability. These data demonstrate, to our knowledge for the first time, a functional RNAi pathway in a cestode and show that the robust knock-down of abundant gene transcripts is achievable using long dsRNAs following short exposure times. (C) 2009 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.