1,720,994 research outputs found

    Nek2 localises to the distal portion of the mother centriole/basal body and is required for timely cilium disassembly at the G2/M transition

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    The NIMA-related kinase Nek2 promotes centrosome separation at the G2/M transition and, consistent with this role, is known to be concentrated at the proximal ends of centrioles. Here, we show by immunofluorescence microscopy that Nek2 also localises to the distal portion of the mother centriole. Its accumulation at this site is cell cycle-dependent and appears to peak in late G2. These findings are consistent with previous data implicating Nek2 in promoting reorganisation of centrosome-anchored microtubules at the G2/M transition, given that microtubules are anchored at the subdistal appendages of the mother centriole in interphase. In addition, we report that siRNA-mediated depletion of Nek2 compromises the ability of cells to resorb primary cilia before the onset of mitosis, while overexpression of catalytically active Nek2A reduces ciliation and cilium length in serum-starved cells. Based on these findings, we propose that Nek2 has a role in promoting cilium disassembly at the onset of mitosis. We also present evidence that recruitment of Nek2 to the proximal ends of centrioles is dependent on one of its substrates, the centrosome cohesion protein C-Nap

    Cloning, structural organization and chromosomal localization of the mouse Aquaporin-8 water channel gene (Aqp8)

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    The gene encoding the mouse Aquaporin-8 water channel protein (Aqp8) was cloned and its genomic structure was defined. Aqp8 consists of six exons with boundaries at amino acids 1-4, 5-87, 88-129, 130-201, 202-246 and 247-261 which partially correspond to those of other known aquaporin genes. All splice sites conform to the GT-AG rule except the first one which is CT-CC. Primer extension and RNase protection analyses using mouse liver RNA demonstrated three initiation transcription sites located 385, 156 and 146 bp upstream from the translational start codon. No defined TATA box was found in the 5'-flanking region where numerous CAAT motifs and one GATA box were identified. Fluorescence in situ hybridization localized the Aqp8 locus to mouse chromosome 7F3. The 7F region is syntenic with human chromosomes 11, 16 and 10. These results (i) reveal marked structural distinction between the Aqp8 gene and the other known mammalian aquaporin genes, (ii) may now permit the molecular characterization of Aqp8 expression and (iii) represent a fundamental step for the construction of a target vector to generate transgenic Aqp8 knockout mice

    Chromosomal localization, genomic organization and evolution of the genes encoding human phosphatidylinositol transfer protein membrane-associated (PITPNM) 1, 2 and 3

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    Eukaryotic proteins containing a phosphatidylinositol transfer (PITP) domain can be divided into two groups, one consisting of small soluble 35-kDa proteins and the other those that are membrane-associated and show sequence similarities to the Drosophila retinal degeneration B (rdgB) protein. The rdgB protein consists of four domains, an amino terminal PITP domain, a Ca(2+)-binding domain, a transmembrane domain and a carboxyl terminal domain that interacts with the protein tyrosine kinase PYK2. Three mammalian phosphatidylinositol transfer protein membrane-associated genes (PITPNM1, 2 and 3) with homology to Drosophila rdgB have previously been described and shown to be expressed in the mammalian retina. These findings and the demonstration that the rdgB gene plays a critical role in the invertebrate phototransduction pathway have led to the mammalian genes being considered as candidate genes for human eye diseases. In order to facilitate the analysis of these genes we have used radiation hybrid mapping and fluorescence in situ hybridization to localize the PITPNM2 and 3 genes to human chromosomes 12p24 and 17p13 respectively and hybrid mapping to confirm the localization of PITPNM1 to chromosome 11q13. We have also determined the genomic organization of both the soluble and membrane-associated Drosophila and human PITP domain-containing genes. Phylogenetic analysis indicates that the two groups arose by gene duplication that occurred very early in animal evolution

    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

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    Influence of hypoxia on the epithelial-pathogen interactions in the lung: implications for respiratory disease

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    Under normal physiological conditions, the lung remains an oxygen rich environment. However, prominent regions of hypoxia are a common feature of infected and inflamed tissues and many chronic inflammatory respiratory diseases are associated with mucosal and systemic hypoxia. The airway epithelium represents a key interface with the external environment and is the first line of defense against potentially harmful agents including respiratory pathogens. The protective arsenal of the airway epithelium is provided in the form of physical barriers, and the production of an array of antimicrobial host defense molecules, proinflammatory cytokines and chemokines, in response to activation by receptors. Dysregulation of the airway epithelial innate immune response is associated with a compromised immunity and chronic inflammation of the lung. An increasing body of evidence indicates a distinct role for hypoxia in the dysfunction of the airway epithelium and in the responses of both innate immunity and of respiratory pathogens. Here we review the current evidence around the role of tissue hypoxia in modulating the host-pathogen interaction at the airway epithelium. Furthermore, we highlight the work needed to delineate the role of tissue hypoxia in the pathophysiology of chronic inflammatory lung diseases such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease in addition to novel respiratory diseases such as COVID-19. Elucidating the molecular mechanisms underlying the epithelial-pathogen interactions in the setting of hypoxia will enable better understanding of persistent infections and complex disease processes in chronic inflammatory lung diseases and may aid the identification of novel therapeutic targets and strategies
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