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排序方式: 共有321条查询结果,搜索用时 15 毫秒
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Juan A. Godoy Macarena S. Arrázola Daniela Ordenes Carmen Silva-Alvarez Nady Braidy Nibaldo C. Inestrosa 《The Journal of biological chemistry》2014,289(52):36179-36193
The Wnt signaling pathway plays an important role in developmental processes, including embryonic patterning, cell specification, and cell polarity. Wnt components participate in the development of the central nervous system, and growing evidence indicates that this pathway also regulates the function of the adult nervous system. In this study, we report that Wnt-5a, a noncanonical Wnt ligand, is a potent activator of mitochondrial dynamics and induces acute fission and fusion events in the mitochondria of rat hippocampal neurons. The effect of Wnt-5a was inhibited in the presence of sFRP, a Wnt scavenger. Similarly, the canonical Wnt-3a ligand had no effect on mitochondrial fission-fusion events, suggesting that this effect is specific for Wnt-5a alone. We also show that the Wnt-5a effects on mitochondrial dynamics occur with an increase in both intracellular and mitochondrial calcium (Ca2+), which was correlated with an increased phosphorylation of Drp1(Ser-616) and a decrease of Ser-637 phosphorylation, both indicators of mitochondrial dynamics. Electron microscope analysis of hippocampal tissues in the CA1 region showed an increase in the number of mitochondria present in the postsynaptic region, and this finding correlated with a change in mitochondrial morphology. We conclude that Wnt-5a/Ca2+ signaling regulates the mitochondrial fission-fusion process in hippocampal neurons, a feature that might help to further understand the role of Wnt-related pathologies, including neurodegenerative diseases associated with mitochondrial dysfunction, and represents a potentially important link between impaired metabolic function and degenerative disorders. 相似文献
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Our understanding of the evolutionary consequences of mutation relies heavily on estimates of the rate and fitness effect of spontaneous mutations generated by mutation accumulation (MA) experiments. We performed a classic MA experiment in which frequent sampling of MA lines was combined with whole genome resequencing to develop a high-resolution picture of the effect of spontaneous mutations in a hypermutator (ΔmutS) strain of the bacterium Pseudomonas aeruginosa. After ∼644 generations of mutation accumulation, MA lines had accumulated an average of 118 mutations, and we found that average fitness across all lines decayed linearly over time. Detailed analyses of the dynamics of fitness change in individual lines revealed that a large fraction of the total decay in fitness (42.3%) was attributable to the fixation of rare, highly deleterious mutations (comprising only 0.5% of fixed mutations). Furthermore, we found that at least 0.64% of mutations were beneficial and probably fixed due to positive selection. The majority of mutations that fixed (82.4%) were base substitutions and we failed to find any signatures of selection on nonsynonymous or intergenic mutations. Short indels made up a much smaller fraction of the mutations that were fixed (17.4%), but we found evidence of strong selection against indels that caused frameshift mutations in coding regions. These results help to quantify the amount of natural selection present in microbial MA experiments and demonstrate that changes in fitness are strongly influenced by rare mutations of large effect. 相似文献
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Juan Antonio Surez‐Cuenca Rogelio Robledo‐Nolasco Marco Antonio Alcntara‐Melndez Luis Javier Díaz Hernndez Eduardo Vera‐Gmez Alejandro Hernndez‐Patricio Karla Susana Snchez‐Díaz Juan Ariel Buendía‐Gutirrez Alejandra Contreras‐Ramos Atzin Su Ruíz‐Hernndez Rebeca Prez‐Cabeza de Vaca Paul Mondragn‐Tern 《Journal of cellular and molecular medicine》2019,23(7):4844-4849
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A Pilot Study Identifying a Set of microRNAs As Precise Diagnostic Biomarkers of Acute Kidney Injury
Elia Aguado-Fraile Edurne Ramos Elisa Conde Macarena Rodríguez Laura Martín-Gómez Aurora Lietor ángel Candela Belen Ponte Fernando Lia?o María Laura García-Bermejo 《PloS one》2015,10(6)
In the last decade, Acute Kidney Injury (AKI) diagnosis and therapy have not notably improved probably due to delay in the diagnosis, among other issues. Precocity and accuracy should be critical parameters in novel AKI biomarker discovery. microRNAs are key regulators of cell responses to many stimuli and they can be secreted to the extracellular environment. Therefore, they can be detected in body fluids and are emerging as novel disease biomarkers. We aimed to identify and validate serum miRNAs useful for AKI diagnosis and management. Using qRT-PCR arrays in serum samples, we determined miRNAs differentially expressed between AKI patients and healthy controls. Statistical and target prediction analysis allowed us to identify a panel of 10 serum miRNAs. This set was further validated, by qRT-PCR, in two independent cohorts of patients with relevant morbi-mortality related to AKI: Intensive Care Units (ICU) and Cardiac Surgery (CS). Statistical correlations with patient clinical parameter were performed. Our results demonstrated that the 10 selected miRNAs (miR-101-3p, miR-127-3p, miR-210-3p, miR-126-3p, miR-26b-5p, miR-29a-3p, miR-146a-5p, miR-27a-3p, miR-93-3p and miR-10a-5p) were diagnostic biomarkers of AKI in ICU patients, exhibiting areas under the curve close to 1 in ROC analysis. Outstandingly, serum miRNAs estimated before CS predicted AKI development later on, thus becoming biomarkers to predict AKI predisposition. Moreover, after surgery, the expression of the miRNAs was modulated days before serum creatinine increased, demonstrating early diagnostic value. In summary, we have identified a set of serum miRNAs as AKI biomarkers useful in clinical practice, since they demonstrate early detection and high diagnostic value and they recognize patients at risk. 相似文献
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Michel Guipponi Federico A. Santoni Vincent Setola Corinne Gehrig Maud Rotharmel Macarena Cuenca Olivier Guillin Dimitris Dikeos Georgios Georgantopoulos George Papadimitriou Logos Curtis Alexandre Méary Franck Schürhoff Stéphane Jamain Dimitri Avramopoulos Marion Leboyer Dan Rujescu Ann Pulver Dominique Campion David P. Siderovski Stylianos E. Antonarakis 《PloS one》2015,10(10)
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Reproductive isolation between two populations of Aglaoctenus lagotis,a funnel‐web wolf spider 下载免费PDF全文
Macarena González Alfredo V. Peretti Fernando G. Costa 《Biological journal of the Linnean Society. Linnean Society of London》2015,114(3):646-658
Aglaoctenus lagotis (Lycosidae: Sosippinae) is a spider that, in contrast to the predominant wandering habit of the family, constructs funnel webs. The species is widely distributed throughout the Neotropics and is credited with high levels of intraspecific variation. Here, we evaluate whether reproductive isolating barriers operate between some populations of A. lagotis. We used heterotypic encounters between individuals from two distant localities: southern Uruguay (SU) and Central Argentina (CA). Additionally, we used spiders from an intermediate locality, western Uruguay (WU), where both forms of the species overlap (SU.WU was used to describe individuals from WU reminiscent of those from SU; and CA.WU was used to describe individuals from WU reminiscent of those from CA). No copulations occurred between SU and CA individuals, whereas a single and atypical copulation occurred between SU.WU and CA.WU individuals. Attacks (only by females on males) were rare. In tests of choice based on silk cues, SU males did not prefer homotypic cues but almost did not court CA females, whereas CA males preferred homotypic cues but usually courted heterotypic females. These findings, with a previously reported temporal asynchrony between populations, suggest the occurrence of reproductive isolation between both spider forms and a speciation process favoured by the wide distribution and plasticity of the species. © 2015 The Linnean Society of London, Biological Journal of the Linnean Society, 2015, 114 , 646–658. 相似文献
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Adel I. Aziziyeh Timothy T. Li Cynthia Pape Macarena Pampillo Peter Chidiac Fred Possmayer Andy V. Babwah Moshmi Bhattacharya 《Cellular signalling》2009,21(7):1207-1217
Lysophosphatidic acid (LPA) is a major constituent of blood and is involved in a variety of physiological and pathophysiological processes. LPA signals via the ubiquitously expressed G protein-coupled receptors (GPCRs), LPA1 and LPA2 that are specific for LPA. However, in large, the molecular mechanisms that regulate the signalling of these receptors are unknown. We show that the small GTPase RalA associates with both LPA1 and LPA2 in human embryonic kidney (HEK 293) cells and that stimulation of LPA1 receptors with LPA triggers the activation of RalA. While RalA was not found to play a role in the endocytosis of LPA receptors, we reveal that LPA1 receptor stimulation promoted Ral-dependent phospholipase C activity. Furthermore, we found that GRK2 is required for the desensitization of LPA1 and LPA2 and have identified a novel interaction between RalA and GRK2, which is promoted by LPA1 receptor activity. Taken together, these results establish RalA and GRK2 as key regulators of LPA receptor signalling and demonstrate for the first time that LPA1 activity facilitates the formation of a novel protein complex between these two proteins. 相似文献