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    Effect of proprotein convertase subtilisin kexin type 9 (PCSK9) on smooth muscle cell proliferation and migration

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    Proprotein convertase subtilisin kexin type 9 (PCSK9) is an important regulator of hepatic low-density lipoprotein (LDL)-cholesterol levels. Although PCSK9 is mainly of hepatic origin, extrahepatic tissues significantly contribute to PCSK9 production. On these basis, we have previously shown that PCSK9 is expressed in cultured smooth muscle cells (SMCs) and it is detectable in human carotid atherosclerotic plaques. The aim of the present study was to investigate the role of PCSK9 on SMC proliferation, migration and differentiation. SMCs were isolated from PCSK9-/- mice (PCSK9null cells) and the expression of PCSK9 reconstituted by retroviral vector encoding for PCSK9-FLAG tag (PCSK9rec cells). The proliferation rate of PCSK9null cells and PCSK9rec was then determined by cell counting in response to 10%FCS to up of 6 days. The calculated doubling time of PCSK9null cells was significantly higher than that of PCSK9rec (41.2±1.9 h vs 32.2±3.1 h, respectively; p=0.01). Under these experimental conditions, PCSK9rec cells expressed lower levels of LDLR, determined by western blot analysis, while the mRNA levels were 10 fold higher. The reconstitution of PCSK9 expression in SMCs also determined a significant induction of the contractile phenotypic markers of SMCs, such as SM22 (15.5±4.4 fold p<0.01), -actin (3.1±1.1 fold; p=0.05) and KLF4 (2.9±0.5 fold p<0.01). The migratory capacity of both cell lines were also investigated by Boyden chamber chemotaxis assay in response to PDGF-BB (5÷20 ng/ml). Although the number of migrated cells were higher in PCSK9rec cells, either under basal or stimulated conditions, the entity of the chemotactic response (expressed as fold of induction vs basal condition) was not significantly different between the two cell lines. Taken together our data indicate that PCSK9 promotes the SMC proliferation and migration. A possible direct role for PCSK9 on SMC accumulation in atherogenesis is suggested

    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

    PCSK9 deficient mice are protected from neointima formation in carotid artery injury model

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    Proprotein convertase subtilisin kexin type 9 (PCSK9) is an important regulator of hepatic low-density lipoprotein (LDL)-cholesterol levels. We have previously shown that PCSK9 is expressed in cultured smooth muscle cells (SMCs) and it is detectable in human carotid atherosclerotic plaques. The aim of the present study was to compare the vascular changes induced by periadventitial placement of a non-occlusive constrictive silicone collar for 9 weeks around the common carotid artery of WT and PCSK9 deficient mice. Collared carotids of the PCSK9-/- mice (n=6 per group) showed a less marked intimal thickening compared WT mice (19055±10158 μm2 vs. 34989±12823 μm2; *P0.05) , a decreased intimal media ratio (2.54±1.67 vs. 0.82±0.70 *P<0.05) and higher lumen area (11821±7980 μm2 vs. 18830±8816 μm2). Carotid lesions of WT mice had an elevated content of SMCs (21.0±7.56% vs. 10.7±1.97% P<0.05) and collagen (18.38±7.90% vs. 10.45±9.11%; **P<0.01) and no difference in macrophage content was detected between the two groups. Cultured SMCs isolated from WT mice showed lower levels of the contractile markers smooth muscle α-actin (-94±6%; ***P<0.001 ) and calponin (-74±18%; ***P<0.001 ), and increased Col1a1 mRNA levels (2.30±0.3 fold ***P<0.001) after stimulation with PDGF-BB. Finally, the proliferation rate of PCSK9-/- SMCs was significantly lower compared to PCSK9-/- SMCs reconstituted with PCSK9 encoding plasmid (doubling time 41.2±1.9 h vs. 32.2±3.1 h; ***P=0.01). Taken together, the present results suggest a favorable action of PCSK9 on neointima formation in response to perivascular carotid, probably facilitating the phenotypic switch of medial SMCs and their proliferation

    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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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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