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The mitochondrial H+-ATP synthase is a primary hub of cellular homeostasis by providing the energy required to sustain cellular activity and regulating the production of signaling molecules that reprogram nuclear activity needed for adaption to changing cues. Herein, we summarize findings regarding the regulation of the activity of the H+-ATP synthase by its physiological inhibitor, the ATPase inhibitory factor 1 (IF1) and their functional role in cellular homeostasis. First, we outline the structure and the main molecular mechanisms that regulate the activity of the enzyme. Next, we describe the molecular biology of IF1 and summarize the regulation of IF1 expression and activity as an inhibitor of the H+-ATP synthase emphasizing the role of IF1 as a main driver of energy rewiring and cellular signaling in cancer. Findings in transgenic mice in vivo indicate that the overexpression of IF1 is sufficient to reprogram energy metabolism to an enhanced glycolysis and activate reactive oxygen species (ROS)-dependent signaling pathways that promote cell survival. These findings are placed in the context of mitohormesis, a program in which a mild mitochondrial stress triggers adaptive cytoprotective mechanisms that improve lifespan. In this regard, we emphasize the role played by the H+-ATP synthase in modulating signaling pathways that activate the mitohormetic response, namely ATP, ROS and target of rapamycin (TOR). Overall, we aim to highlight the relevant role of the H+-ATP synthase and of IF1 in cellular physiology and the need of additional studies to decipher their contributions to aging and age-related diseases.  相似文献   
53.
We look into the interaction of Google's search queries and several aspects of international equity markets. Using a novel methodology for selecting words and a vector autoregressive modeling approach, we study whether the search queries of finance‐related words can have an impact on returns, volatility of returns and traded volume in four different English‐speaking countries. We identify several words whose search frequency is associated with changes in the dependent variables. In particular, we find that increases in search queries including the word stock predict increased volatility and decreased index returns over the next week. On top of that, we investigate the performance of a market‐timing strategy based on the search frequency of this word and benchmark it against random words from the Word‐Net database and a naive buy‐and‐hold strategy. The results of this empirical application are positive and particularly stronger during the global crisis of 2009. Copyright © 2016 John Wiley & Sons, Ltd.  相似文献   
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The embryonic development of the squid Loligo vulgaris was observed from 183 egg masses collected from special devices deployed throughout Cabrera National Park (Baleares Islands, western Mediterranean Sea). Sequence alignment analysis of the cytochrome oxidase I gene revealed that all embryos belonged to L. vulgaris. In total, 549 egg capsules were examined. Viable egg capsules (n = 420) were classified into one of five maturation stages according to the primary external features. The length of the viable egg capsules varied between 40 and 170 mm, and increased with embryonic development. The non-viable capsules (n = 129) were categorized into four groups: I (Ginger root), non-viable II and III, and empty egg capsule (IV). The percentage of non-viable capsules (i.e. grades I, II and III) was 92.25%. Empty capsules accounted for 7.75% of the total non-viable egg capsules. Embryonic development was classified into a second scale of eight stages. Egg capsule stage and embryonic stage were significantly related (n = 420; p < 0.001), facilitating the determination of the embryo developmental phase based on the outward appearance of the egg capsules. The embryo development stage based on the external features of the egg capsules might constitute an innovative tool for in situ embryological data collection. This new method is neither time consuming nor invasive, and could be helpful in fishing cruises, for scuba diving visual census in natural habitats and for laboratory culture. Slight variability in the developmental embryonic stages within egg capsules from the same egg mass was identified. The origin of this asynchrony is discussed. Chronological appearance of organs was similar to that of the six loliginid species previously examined. However, some developmental changes in the timing or rate of events (heterochronies) were observed: Hoyle’s organ was formed earlier in L. vulgaris and the appearance of ventral chromatophores was slightly delayed (2 days) compared with the other species considered.  相似文献   
56.
In spiders, temperature is considered an important environmental variable for microhabitat selection. In this study, we evaluated the effect of temperature and rock size on the presence of the sand recluse spider Sicarius thomisoides and the degree of selectivity in different locations. This species is a large spider that lives under rocks in desert and semi-desert climates and is particularly active during the summer. In Chile, these spiders can be found at both coastal and inland locations under different thermal conditions, where usually the temperatures are lower near the coast. If large-scale climatic conditions are important for this species, they may be expected to select lower rock temperatures on the coast than at inland locations. In addition, we would expect that the spiders would choose larger rocks in inland compared to coast locations, which reduce the effect of high temperatures. We found that the probability of finding individuals of this species increased according to rock temperature and rock size in the field. Our results suggest that S. thomisoides prefers larger and warmer rocks to shelter under during the day, this selectivity being similar at both coastal and inland locations. Thus, this species tends to select rocks with the same thermal and structural conditions, independent of the climatic conditions.  相似文献   
57.
Clustering techniques are based upon a dissimilarity or distance measure between objects and clusters. This paper focuses on the simplex space, whose elements??compositions??are subject to non-negativity and constant-sum constraints. Any data analysis involving compositions should fulfill two main principles: scale invariance and subcompositional coherence. Among fuzzy clustering methods, the FCM algorithm is broadly applied in a variety of fields, but it is not well-behaved when dealing with compositions. Here, the adequacy of different dissimilarities in the simplex, together with the behavior of the common log-ratio transformations, is discussed in the basis of compositional principles. As a result, a well-founded strategy for FCM clustering of compositions is suggested. Theoretical findings are accompanied by numerical evidence, and a detailed account of our proposal is provided. Finally, a case study is illustrated using a nutritional data set known in the clustering literature.  相似文献   
58.
We offer a framework to represent the roles of empirical and theoretical factors in theory construction, and examine a case study to illustrate how the framework can be used to illuminate central features of scientific reasoning. The case study provides an extension of French and Ladyman's (1997) analysis of Fritz and Heinz London's model of superconductivity to accommodate the role of the analogy between superconductivity and diamagnetic phenomena in the development of the model between 1935 and 1937. We focus on this case since it allows us to separate the roles of empirical and theoretical factors, and so provides an example of the utility of the approach that we have adopted. We conclude the paper by drawing on the particular framework here developed to address a range of concerns.  相似文献   
59.
Genome-wide association studies (GWAS) are a standard approach for studying the genetics of natural variation. A major concern in GWAS is the need to account for the complicated dependence structure of the data, both between loci as well as between individuals. Mixed models have emerged as a general and flexible approach for correcting for population structure in GWAS. Here, we extend this linear mixed-model approach to carry out GWAS of correlated phenotypes, deriving a fully parameterized multi-trait mixed model (MTMM) that considers both the within-trait and between-trait variance components simultaneously for multiple traits. We apply this to data from a human cohort for correlated blood lipid traits from the Northern Finland Birth Cohort 1966 and show greatly increased power to detect pleiotropic loci that affect more than one blood lipid trait. We also apply this approach to an Arabidopsis thaliana data set for flowering measurements in two different locations, identifying loci whose effect depends on the environment.  相似文献   
60.
Superconductivity in CaCuO2 as a result of field-effect doping.   总被引:2,自引:0,他引:2  
Understanding the doping mechanisms in the simplest superconducting copper oxide-the infinite-layer compound ACuO2 (where A is an alkaline earth metal)-is an excellent way of investigating the pairing mechanism in high-transition-temperature (high-Tc) superconductors more generally. Gate-induced modulation of the carrier concentration to obtain superconductivity is a powerful means of achieving such understanding: it minimizes the effects of potential scattering by impurities, and of structural modifications arising from chemical dopants. Here we report the transport properties of thin films of the infinite-layer compound CaCuO2 using field-effect doping. At high hole- and electron-doping levels, superconductivity is induced in the nominally insulating material. Maximum values of Tc of 89 K and 34 K are observed respectively for hole- and electron-type doping of around 0.15 charge carriers per CuO2. We can explore the whole doping diagram of the CuO2 plane while changing only a single electric parameter, the gate voltage.  相似文献   
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