1,720,996 research outputs found
Functional studies of human K+ channels KCNH1 and KCNK4 and their role in human pathogenesis
Full text linkPotassium (K+) channels constitute the most diversified class of ion channels with regard to structure and gating characteristics. They contribute to the maintenance and stabilization of the resting potential and are key players in regulating cell excitability and functions in response to multiple signals (Tian et al., 2014). In recent years, the aberrant function of some of these channels has been documented to affect development and underlie syndromic disorders (Bauer et al., 2018).
KCNH1 (MIM 603305) is a member of the EAG (ether-à-go-go) family of voltage-gated K+ channels (Cázares-Ordoñez and Pardo, 2017). Recent studies have demonstrated that gain-of-function mutations in KCHN1 are implicated in Zimmermann-Laband syndromes (ZLS; MIM 135500;Kortüm et al., 2015) and other forms of developmental deficits that include mental retardation and epilepsy (Simons et al., 2015;Bramswig et al., 2015; Mégarbané et al., 2016; Fukai et al., 2016). These findings suggest that KCNH1 might be important for cognitive development in human. Recently, gain-of-function mutations in KCNK4 (MIM 605720), encoding a two-pore-domain K+ channel (K2P), have been reported in subjects with a phenotype of facial dysmorphism, hypertrichosis, epilepsy, developmental delay/ID, and gingival overgrowth (FHEIG syndrome, MIM 618381; Bauer et al., 2018). The clinical features of the KCNK4-related condition are reminiscent of ZLS (Kortüm et al., 2015), providing evidence for a channelopathy caused by hyperactivation of K+ channels, including KCNH1 and KCNK4. Some ion channels are bifunctional proteins contributing to several cell functions (Hegle et al., 2006). To date, only electrophysiology experiments were performed to explore the mechanism involving KCNH1 and KCNK4 in ZLS and FHEIG related developmental processes (Kortüm et al., 2015; Simons et al.,2015; Bauer et al., 2018).
Based on these considerations, major aims of my PhD project were to better characterize the cell role of KCNH1 and KCNK4 channels and to explore the functional impact of the KCNH1-ZLS and KCNK4-FHEIG mutations using cellular and molecular biology approaches, including Immunofluorescence, Western Blot and Real-Time Quantitative PCR. To this aim, we used cell lines, control fibroblasts and primary skin fibroblasts derived from ZLS-patients carrying mutations in KCNH1 (p.Arg330Gln and p.Leu352Val) and from FHEIG-patients carrying mutations in KCNK4 (p.Ala172Glu and p.Ala244Pro). We demonstrated impaired proliferation of KCNH1 and KCNK4 mutant fibroblasts, confirming the role of KCNH1 as a regulator of cell cycle of non-transformed cells and highlight a new function for KCNK4 in regulation of cell proliferation. We also found a significant increase of cilia number and a cilium-related pathway, i.e. SHH pathway, activation in all the mutant fibroblasts, thus suggesting functional role of KCNH1 and KCNK4 in cilia regulation. Moreover, confocal microscopy analysis revealed defects in cilia morphology in fibroblasts from ZLS patients. Confocal analysis refined also the reported KCNH1 localization in the cilium (Sánchez et al., 2016) to be concentrated at the centrosome and ciliary pocket regions for both wild-type and mutant fibroblasts. Finally, immunofluorescence analysis conducted in
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wild-type fibroblasts and cells lines disclosed a nucleolar localization of KCNK4 channels, possibly indicating unrevealed roles of KCNK4.
In summary, we demonstrated that KCNH1 and KCNK4 may have specific ion channel-independent function converging on some share cellular pathways whose alteration might affect development processes. Overall, these findings highlight the importance to characterize the intracellular role of K+ to shed light on the mechanisms of pathogenesis of ZLS and ZLS related developmental processes
TELLUS. Ground deformations and their effects in the near-Earth space
No full textThis report will describe the activities carried out by the TELLUS team during 2004. They are continuing those concerning ground aseismic creep strain events, observed by the TELLUS tilt network; the ESPERIA space mission project planned and designed for studying Earth near-Earth space interactions; the construction of the particle detector ARINA to be installed on board the Russian satellite RESURS-DK1, which launch is scheduled for next autumn 2005 within the PAMELA mission. ARINA is part of the ESPERIA payload, another one being the LAZIO-EGLE magnetic andparticle instruments to be tested in space on board the InternationalSpace Station and used for collecting particle and magnetic data. Thesetwo instruments have been built during 2004 within a collaborationbetween the Universities Roma Tre, Perugia and Roma Tor Vergata, andrelated INFN branches, with the Lazio Region and Polytechnic of Moscow(MEPhI). LAZIO-EGLE thermal, vibration and electromagnetic emission testshave been performed in laboratory both in Italy and in Russia. Launch isscheduled for February 2005. During 2003, on the basis of an ITT of theEuropean Space Agency (ESA), the TELLUS team also submitted assub-contractor (the prime one being Alenia-Laben S.p.A.) the ARETUSAproposal for a General Study with title "Techniques and SpaceborneConcepts for the Study of Earth-Quake Precursors and Analysis ofAssociated Atmospheric Effects". Both these two activities concerning theARETUSA proposal and the construction of the EGLE space magnetometer willbe described in the present annual report
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
MRI in diagnosis of osteoid osteoma of the proximal femur: a potentially deviating aspect. Description of a clinical case.
No full textDispelling the Myths Behind First-author Citation Counts
Full text linkWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe 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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