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811.
In humans, KCNQ2/3 channels form an M-current that regulates neuronal excitability, with mutations in these channels causing benign neonatal familial convulsions. The M-current is important in mechanisms of neural plasticity underlying associative memory and in the response to ethanol, with KCNQ controlling the release of dopamine after ethanol exposure. We show that dKCNQ is broadly expressed in the nervous system, with targeted reduction in neuronal KCNQ increasing neural excitability and KCNQ overexpression decreasing excitability and calcium signalling, consistent with KCNQ regulating the resting membrane potential and neural release as in mammalian neurons. We show that the single KCNQ channel in Drosophila (dKCNQ) has similar electrophysiological properties to neuronal KCNQ2/3, including conserved acute sensitivity to ethanol block, with the fly channel (IC50 = 19.8 mM) being more sensitive than its mammalian ortholog (IC50 = 42.1 mM). This suggests that the role of KCNQ in alcohol behaviour can be determined for the first time by using Drosophila. We present evidence that loss of KCNQ function in Drosophila increased sensitivity and tolerance to the sedative effects of ethanol. Acute activation of dopaminergic neurons by heat-activated TRP channel or KCNQ-RNAi expression produced ethanol hypersensitivity, suggesting that both act via a common mechanism involving membrane depolarisation and increased dopamine signalling leading to ethanol sedation. 相似文献
812.
813.
Luciana L. Porfirio Rebecca M. B. Harris Edward C. Lefroy Sonia Hugh Susan F. Gould Greg Lee Nathaniel L. Bindoff Brendan Mackey 《PloS one》2014,9(11)
Choice of variables, climate models and emissions scenarios all influence the results of species distribution models under future climatic conditions. However, an overview of applied studies suggests that the uncertainty associated with these factors is not always appropriately incorporated or even considered. We examine the effects of choice of variables, climate models and emissions scenarios can have on future species distribution models using two endangered species: one a short-lived invertebrate species (Ptunarra Brown Butterfly), and the other a long-lived paleo-endemic tree species (King Billy Pine). We show the range in projected distributions that result from different variable selection, climate models and emissions scenarios. The extent to which results are affected by these choices depends on the characteristics of the species modelled, but they all have the potential to substantially alter conclusions about the impacts of climate change. We discuss implications for conservation planning and management, and provide recommendations to conservation practitioners on variable selection and accommodating uncertainty when using future climate projections in species distribution models. 相似文献
814.
Laura M. Ketelboeter Vishwakanth Y. Potharla Sonia L. Bardy 《Current microbiology》2014,69(3):343-348
Pyomelanin is a brown/black extracellular pigment with antioxidant and iron acquisition properties that is produced by a number of different bacteria. Production of pyomelanin in Pseudomonas aeruginosa contributes to increased resistance to oxidative stress and persistence in chronic infections. We demonstrate that pyomelanin production can be inhibited by 2-[2-nitro-4-(trifluoromethyl) benzoyl]-1,3-cyclohexanedione (NTBC). This treatment increases sensitivity of pyomelanogenic P. aeruginosa strains to oxidative stress, without altering the growth rate or resistance to aminoglycosides. As such, NTBC has potential to function as an anti-virulence factor in treating pyomelanogenic bacterial infections. 相似文献
815.
Sonia Hernández-Tiedra Gemma Fabriàs David Dávila Íñigo J. Salanueva Josefina Casas L. Ruth Montes 《Autophagy》2016,12(11):2213-2229
Autophagy is considered primarily a cell survival process, although it can also lead to cell death. However, the factors that dictate the shift between these 2 opposite outcomes remain largely unknown. In this work, we used Δ9-tetrahydrocannabinol (THC, the main active component of marijuana, a compound that triggers autophagy-mediated cancer cell death) and nutrient deprivation (an autophagic stimulus that triggers cytoprotective autophagy) to investigate the precise molecular mechanisms responsible for the activation of cytotoxic autophagy in cancer cells. By using a wide array of experimental approaches we show that THC (but not nutrient deprivation) increases the dihydroceramide:ceramide ratio in the endoplasmic reticulum of glioma cells, and this alteration is directed to autophagosomes and autolysosomes to promote lysosomal membrane permeabilization, cathepsin release and the subsequent activation of apoptotic cell death. These findings pave the way to clarify the regulatory mechanisms that determine the selective activation of autophagy-mediated cancer cell death. 相似文献
816.
Virginols A–C are three new withanolides containing an epoxylactol at the side chain. They were isolated from the aerial parts of Physalis virginiana Miller. Structures of these compounds were determined by analyses of their spectroscopic data, including 1D and 2D NMR. The structure of virginol A was confirmed by X-ray diffraction analysis. The anti-inflammatory activity of virginols was evaluated in the TPA-induced ear mouse edema model. 相似文献
817.
818.
Vernica A. Segarra Clara Primus Graciela A. Unguez Ashanti Edwards Candice Etson Sonia C. Flores Catherine Fry Ashley N. Guillory Susan L. Ingram Mark Lawson Richard McGee Stephanie Paxson Laura Phelan Kirsta Suggs Leticia R. Vega Elizabeth Vuong J. Christopher Havran Alfredo Leon Michael D. Burton J. Luis Lujan Marina Ramirez-Alvarado 《Molecular biology of the cell》2020,31(23):2495
Scientific societies aiming to foster inclusion of scientists from underrepresented (UR) backgrounds among their membership often delegate primary responsibility for this goal to a diversity-focused committee. The National Science Foundation has funded the creation of the Alliance to Catalyze Change for Equity in STEM Success (ACCESS), a meta-organization bringing together representatives from several such STEM society committees to serve as a hub for a growing community of practice. Our goal is to coordinate efforts to advance inclusive practices by sharing experiences and making synergistic discoveries about what works. ACCESS has analyzed the approaches by which member societies have sought to ensure inclusivity through selection of annual meeting speakers. Here we discuss how inclusive speaker selection fosters better scientific environments for all and identify challenges and promising practices for societies striving to maximize inclusivity of speakers in their scientific programming. 相似文献
819.
Giovanni Tossetta Sonia Fantone Stefano R. Giannubilo Elena Marinelli Busilacchi Andrea Ciavattini Mario Castellucci Nicoletta Di Simone Monica Mattioli-Belmonte Daniela Marzioni 《Journal of cellular physiology》2019,234(5):6091-6098
Pre-eclampsia (PE) is a multisystem disorder commonly diagnosed in the latter half of pregnancy and it is a leading cause of intrauterine fetal growth retardation (IUGR). The aim of this study was to investigate the localization and the role of SPARC, secreted protein acidic, and rich in cysteine, in PE and PE–IUGR placentas in comparison with normal placentas. SPARC was mainly expressed in the villous and extravillous cytotrophoblastic cells in first trimester, whereas in PE, PE–IUGR and at term placentas, SPARC immunostaining was visible in both cytotrophoblastic cells and syncytiotrophoblast. SPARC expression significantly decreased in normal placenta from first to third trimester and a further significant reduction was demonstrated in PE and PE–IUGR. The latter downregulation of SPARC depends on hypoxic condition as shown by in vitro models. In conclusion, SPARC can play a pivotal role in PE and PE–IUGR onset and it should be considered as a key molecule for future investigations in such pathologies. 相似文献
820.