1,721,280 research outputs found

    Increase in nuclear phosphatidylinositol 3-kinase activity and phosphatidylinositol (3,4,5) trisphosphate synthesis precede PKC-zeta translocation to the nucleus of NGF-treated PC12 cells.

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    We and others have previously demonstrated the existence of an autonomous nuclear polyphosphoinositide cycle that generates second messengers such as diacylglycerol (DAG), capable of attracting to the nucleus specific protein kinase C (PKC) isoforms (Neri et al. (1998) J. Biol. Chem. 273, 29738-29744). Recently, however, nuclei have also been shown to contain the enzymes responsible for the synthesis of the non-canonical 3-phosphorylated inositides. To clarify a possible role of this peculiar class of inositol lipids we have examined the question of whether nerve growth factor (NGF) induces PKC-zeta nuclear translocation in PC12 cells and whether this translocation is dependent on nuclear phosphatidylinositol 3-kinase (PI 3-K) activity and its product, phosphatidylinositol 3,4, 5-trisphosphate [PtdIns(3,4,5)P(3)]. NGF increased both the amount and the enzyme activity of immunoprecipitable PI 3-K in PC12 cell nuclei. Activation of the enzyme, but not its translocation, was blocked by PI 3-K inhibitors wortmannin and LY294002. Treatment of PC12 cells for 9 min with NGF led to an increase in the nuclear levels of PtdIns(3,4,5)P(3). Maximal translocation of PKC-zeta from the cytoplasm to the nucleus (as evaluated by immunoblotting, enzyme activity, and confocal microscopy) occurred after 12 min of exposure to NGF and was completely abrogated by either wortmannin or LY294002. In contrast, these two inhibitors did not block nuclear translocation of the conventional, DAG-sensitive, PKC-alpha. On the other hand, the specific phosphatidylinositol phospholipase C inhibitor, 1-O-octadeyl-2-O-methyl-sn-glycero-3-phosphocholine, was unable to abrogate nuclear translocation of the DAG-insensitive PKC-zeta. These data suggest that a nuclear increase in PI 3-K activity and PtdIns(3,4,5)P(3) production are necessary for the subsequent nuclear translocation of PKC-zeta. Furthermore, they point to the likelihood that PKC-zeta is a putative nuclear downstream target of PI 3-K during NGF-promoted neural differentiation.-Neri, L. M., Martelli, A. M., Borgatti, P., Colamussi, M. L., Marchisio, M., Capitani, S. Increase in nuclear phosphatidylinositol 3-kinase activity and phosphatidylinositol (3,4, 5) trisphosphate synthesis precede PKC-zeta translocation to the nucleus of NGF-treated PC12 cells

    Nuclear protein kinase C isoforms and apoptosis

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    The process of apoptosis is regulated at multiple levels through phosphorylation by several different protein kinases. The protein kinase C (PKC) family of isozymes have been shown to exert both inhibitory and stimulatory influences on apoptosis. During the apoptotic process phosphorylative events are known to occur also at the nuclear level. Evidence suggests that PKC isoforms play a key role in some steps that lead to nuclear disassembly during the execution phase of apoptosis. This review highlights the recent progress made in determining the roles played by individual PKC nuclear isoforms in the control of apoptosis

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Sperm aneuploidies and low progressive motility

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    BACKGROUND: Patients with poor semen quality show increased sperm disomy and diploidy rates. Oligozoospermia and teratozoospermia are known to influence sperm aneuploidy, but there is still a debate about whether aneuploidies are associated with reduced motility. METHODS: Ejaculates from a large group of patients were examined by light microscopy to evaluate sperm concentration, motility and morphology, and by fluorescence in-situ hybridization (FISH) to analyse the presence of aneuploidies. Statistical analysis was performed to compare differences and to evaluate the relationship between sperm aneuploidy rate and semen quality. RESULTS: Five groups were established following the motility parameter, and total aneuploidy rates were statistically significantly higher in the groups where motility was <30% compared to the controls. A homogeneous group of men with asthenozoospermia showed higher FISH values compared to control data, although the difference was not statistically significant. Motility and sperm morphology were each found to be statistically related to aneuploidy using a multiple linear regression analysis, whereas sperm concentration was only related to aneuploidy by the equation of a hyperbolic curve. CONCLUSIONS: In conclusion, biological and statistical data from the present research support the idea that the presence of aneuploidies could also be associated with reduced sperm motility

    Necrosis in human spermatozoa. II. Ultrastructural features and FISH study in semen from patients with recovered uro-genital infections

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    Inflammation of the male genital tract is a potential cause of male sterility. The quality of spermatozoa from ten patients with recovered uro-genital infections was examined by transmission electron microscopy (TEM); fluorescence in situ hybridization (FISH) was performed on sperm nuclei in six out of ten patients to investigate the frequency of aneuploidies. TEM analysis demonstrated the presence of a high percentage of necrosis in all patients, whereas apoptosis was present in only five of them. Meiotic segregation was altered in all analysed semen samples. Recovery from infections does not seem to coincide with improved sperm quality, probably because a persistent inflammatory state demonstrated by a high percentage of sperm necrosis sometimes associated with the presence of white blood cells (WBC) in the seminal plasma, is present. The effects of infections of the male genital tract could proceed in the absence of microbial agents due to immunological mechanisms involving the pattern of chemical products typical of inflammation. Our results suggest that the presence of necrosis, sometimes associated with apoptosis, could be considered to be an indicator of male genital tract inflammation. However, further studies are necessary to test the correlation between biochemical parameters and ultrastructural and molecular markers of inflammation
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