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121.
Vibeke Secher Dam Donna MB Boedtkjer Christian Aalkjaer Vladimir Matchkov 《Channels (Austin, Tex.)》2014,8(4):361-369
The presence of Ca2+-activated Cl– currents (ICl(Ca)) in vascular smooth muscle cells (VSMCs) is well established. ICl(Ca) are supposedly important for arterial contraction by linking changes in [Ca2+]i and membrane depolarization. Bestrophins and some members of the TMEM16 protein family were recently associated with ICl(Ca). Two distinct ICl(Ca) are characterized in VSMCs; the cGMP-dependent ICl(Ca) dependent upon bestrophin expression and the ‘classical’ Ca2+-activated Cl– current, which is bestrophin-independent. Interestingly, TMEM16A is essential for both the cGMP-dependent and the classical ICl(Ca). Furthermore, TMEM16A has a role in arterial contraction while bestrophins do not. TMEM16A’s role in the contractile response cannot be explained however only by a simple suppression of the depolarization by Cl– channels. It is suggested that TMEM16A expression modulates voltage-gated Ca2+ influx in a voltage-independent manner and recent studies also demonstrate a complex role of TMEM16A in modulating other membrane proteins. 相似文献
122.
123.
Barrueto Cid Luis Pedro Machado Adriane C.M.G. Carvalheira Sílvia B.R.C. Brasileiro Ana Cristina M. 《Plant Cell, Tissue and Organ Culture》1999,56(1):17-23
Hypocotyls, cotyledons, cotyledonary nodes and primary leaves were used as explants to establish a regeneration protocol for Eucalyptus grandis × E. urophylla. These seedling-derived explants were incubated on a modified MS medium (SP medium), supplemented with 2.0 M TDZ. After 1 month, the calluses obtained were transferred to SP medium containing different concentrations of BA and NAA or zeatin and NAA. Shoots were induced from these calluses at a high frequency. Shoot elongation was then stimulated on SP medium supplemented with BA, NAA and GA3 for 20 to 30 days. For rooting, 50 mm long shoots were cultivated on root induction medium containing IBA (2.5 M) for different periods and then transferred to the same medium but without auxin, for 30 days. Plantlets were then successfully transplanted to greenhouse conditions. 相似文献
124.
This study examined the application of previously characterized microparticles composed of hyaluronan (HA) and chitosan hydroglutamate (CH) as well as novel microparticles consisting of both polymers (HA/CH) to improve the nasal delivery of a model drug. The rabbit bioavailabilities of gentamicin incorporated in HA, CH, and HA/CH microparticles were increased 23-, 31-, and 42-fold, respectively, compared with the control intranasal solution of gentamicin, indicating that all test microparticles were retained for longer periods on the nasal mucosa of the rabbits as supported by previous in vitro dissolution as well as frog palate mucoadhesion studies, thereby improving drug absorption. The higher bioavailabilities of CH-based formulations (CH and HA/CH) suggest the penetration-enhancing effects of CH may also be partially responsible for the improvement. A model was developed, based on a glass impinger device, to deliver dry powder formulations reproducibly onto the surface of cultured cell monolayers. In vitro permeability and fluorescence microscopy studies on the tight junctions of the 16HBE14o- cell lines further confirmed the ability of CH-based formulations to enhance penetration. Furthermore, the in vitro absorption profile from cell culture studies was consistent with those determined from in vivo studies. The complementary effect from the mucoadhesive nature of HA coupled with the penetration-enhancing effects of CH makes the novel HA/CH formulation a promising nasal delivery system. 相似文献
125.
MB Malipatil 《Australian Journal of Entomology》2005,44(2):122-131
Abstract Two new species of Nysius Dallas, N. orarius sp. n. and N. tasmaniensis sp. n. are described from New South Wales and Tasmania (Australia), respectively. A new monotypic genus, Reticulatonysius , with type-species R. queenslandensis sp. n. is described from Queensland, and its systematic relationship with other orsilline genera is discussed. 相似文献
126.
Fernández-Acero T Rodríguez-Escudero I Vicente F Monteiro MC Tormo JR Cantizani J Molina M Cid VJ 《Journal of biomolecular screening》2012,17(8):1018-1029
The phosphatidylinositol 3-kinase (PI3K) pathway couples receptor-mediated signaling to essential cellular functions by generating the lipid second messenger phosphatidylinositol-3,4,5-trisphosphate. This pathway is implicated in multiple aspects of oncogenesis. A low-cost bioassay that readily measures PI3K inhibition in vivo would serve as a valuable tool for research in this field. Using heterologous expression, we have previously reconstituted the PI3K pathway in the model organism Saccharomyces cerevisiae. On the basis of the fact that the overproduction of PI3K is toxic in yeast, we tested the ability of commercial PI3K inhibitors to rescue cell growth. All compounds tested counteracted the PI3K-induced toxicity. Among them, 15e and PI-103 were the most active. Strategies to raise the intracellular drug concentration, specifically the use of 0.003% sodium dodecyl sulfate and the elimination of the Snq2 detoxification pump, optimized the bioassay by enhancing its sensitivity. The humanized yeast-based assay was then tested on a pilot scale for high-throughput screening (HTS) purposes using a collection of natural products of microbial origin. From 9600 extracts tested, 0.6% led to a recovery of yeast growth reproducibly, selectively, and in a dose-dependent manner. Cumulatively, we show that the developed PI3K inhibition bioassay is robust and applicable to large-scale HTS. 相似文献
127.
Ana Márquez Roser Solans José Hernández-Rodríguez Maria C. Cid Santos Casta?eda Marc Ramentol Luis Rodriguez-Rodriguez Javier Narváez Ricardo Blanco Norberto Ortego-Centeno Spanish GCA Consortium ?yvind Palm Andreas P. Diamantopoulos Niko Braun Frank Moosig Torsten Witte Lorenzo Beretta Claudio Lunardi Marco A. Cimmino Augusto Vaglio Carlo Salvarani Miguel A. González-Gay Javier Martín 《PloS one》2014,9(11)
Introduction
Increased expression of IL-33 and its receptor ST2, encoded by the IL1RL1 gene, has been detected in the inflamed arteries of giant cell arteritis (GCA) patients. The aim of the present study was to investigate for the first time the potential influence of the IL33 and IL1RL1 loci on GCA predisposition.Methods
A total of 1,363 biopsy-proven GCA patients and 3,908 healthy controls from four European cohorts (Spain, Italy, Germany and Norway) were combined in a meta-analysis. Six genetic variants: rs3939286, rs7025417 and rs7044343, within the IL33 gene, and rs2058660, rs2310173 and rs13015714, within the IL1RL1 gene, previously associated with immune-related diseases, were genotyped using predesigned TaqMan assays.Results
A consistent association between the rs7025417 polymorphism and GCA was evident in the overall meta-analysis, under both allele (PMH = 0.041, OR = 0.88, CI 95% 0.78–0.99) and recessive (PMH = 3.40E-03, OR = 0.53, CI 95% 0.35–0.80) models. No statistically significant differences between allele or genotype frequencies for the other IL33 and IL1RL1 genetic variants were detected in this pooled analysis.Conclusions
Our results clearly evidenced the implication of the IL33 rs7025417 polymorphism in the genetic network underlying GCA. 相似文献128.
Luz M. Suárez Elena Cid Beatriz Gal Marion Inostroza Jorge R. Brotons-Mas Daniel Gómez-Domínguez Liset Menéndez de la Prida José M. Solís 《PloS one》2012,7(10)
Seizures have profound impact on synaptic function and plasticity. While kainic acid is a popular method to induce seizures and to potentially affect synaptic plasticity, it can also produce physiological-like oscillations and trigger some forms of long-term potentiation (LTP). Here, we examine whether induction of LTP is altered in hippocampal slices prepared from rats with different sensitivity to develop status epilepticus (SE) by systemic injection of kainic acid. Rats were treated with multiple low doses of kainic acid (5 mg/kg; i.p.) to develop SE in a majority of animals (72–85% rats). A group of rats were resistant to develop SE (15–28%) after several accumulated doses. Animals were subsequently tested using chronic recordings and object recognition tasks before brain slices were prepared for histological studies and to examine basic features of hippocampal synaptic function and plasticity, including input/output curves, paired-pulse facilitation and theta-burst induced LTP. Consistent with previous reports in kindling and pilocapine models, LTP was reduced in rats that developed SE after kainic acid injection. These animals exhibited signs of hippocampal sclerosis and developed spontaneous seizures. In contrast, resistant rats did not become epileptic and had no signs of cell loss and mossy fiber sprouting. In slices from resistant rats, theta-burst stimulation induced LTP of higher magnitude when compared with control and epileptic rats. Variations on LTP magnitude correlate with animals’ performance in a hippocampal-dependent spatial memory task. Our results suggest dissociable long-term effects of treatment with kainic acid on synaptic function and plasticity depending on its epileptogenic efficiency. 相似文献
129.
Sandra Villanueva Johanna Burgos Karen I. López-Cayuqueo Ka-Man Venus Lai David M. Valenzuela L. Pablo Cid Francisco V. Sepúlveda 《PloS one》2015,10(9)
Kir7.1 is an inwardly rectifying K+ channel of the Kir superfamily encoded by the kcnj13 gene. Kir7.1 is present in epithelial tissues where it colocalizes with the Na+/K+-pump probably serving to recycle K+ taken up by the pump. Human mutations affecting Kir7.1 are associated with retinal degeneration diseases. We generated a mouse lacking Kir7.1 by ablation of the Kcnj13 gene. Homozygous mutant null mice die hours after birth and show cleft palate and moderate retardation in lung development. Kir7.1 is expressed in the epithelium covering the palatal processes at the time at which palate sealing takes place and our results suggest it might play an essential role in late palatogenesis. Our work also reveals a second unexpected role in the development and the physiology of the respiratory system, where Kir7.1 is expressed in epithelial cells all along the respiratory tree. 相似文献
130.
Serine/threonine protein phosphatase 1 (PP1) regulates multiple cellular processes. Protein phosphorylation-dephosphorylation is largely altered during ischemia and subsequent reperfusion. The brain is particularly vulnerable to stress resulting from ischemia-reperfusion (IR), however, the acquisition of ischemic tolerance (IT) protects against IR stress. We studied PP1 complexes in response to IR stress and IT in brain using proteomic characterization of PP1 complexes in animal models of IR and IT. PP1alpha and PP1gamma were immunoprecipitated and resolved by 2-D. DIGE analysis detected 14 different PP1-interacting proteins that exhibited significant changes in their association with PP1alpha or PP1gamma. These proteins were identified by MALDI-TOF MS. Seven had the PP1-binding RVxF motif. IR altered the interaction of heat shock cognate 71 kDa-protein, creatine kinase B, and dopamine- and cAMP-regulated phosphoprotein 32 kDa (DARPP32) with both PP1alpha and PP1gamma, and the interaction of phosphodiesterase-6B, transitional ER ATPase, lamin-A, glucose-regulated 78 kDa-protein, dihydropyrimidinase-related protein-2, gamma-enolase, neurofilament-L, and ubiquitin ligase SIAH2 with PP1gamma. IT prevented most of the IR-induced effects. This study identifies novel PP1alpha- and PP1gamma-interacting proteins and reveals an in vivo modularity of PP1 holoenzymes in response to physiological ischemic stress. It supports a potential role of PP1 in IR stress and as a target of the endogenous protective mechanisms induced by IT. 相似文献