1,720,980 research outputs found
Analysis of role of AKTIP at different stages of cell division
AKTIP is a recently discovered non-shelterin telomeric protein, whose deficiency generates telomere fragility by impinging on replication (Burla et al., 2015). As previusly described, AKTIP interacts with lamins and its downregulation triggers a premature aging phenotype both at cellular level and at organismal level (in a mouse model knocked down for its murine homologue Ft1) recalling those of progeroid patients with mutations in LMNA gene (Burla et al., 2016; La Torre et. al., 2018). Another AKTIP peculiarity is its intracellular distribution: in interphases cells AKTIP is located, as discrete foci, both in the cytoplasm and in the nucleus, where it is especially enriched at nuclear envelope. In mitosis AKTIP is located at spindle matrix in metaphase and then it is enriched in anaphase at the bridge structure connecting the two newly formed cells, called midbody (Burla et al., 2015; 2016). Given these premises, this work aims at thouroughly investigating the AKTIP role and distribution at these two important cellular compartments. Concerning AKTIP at nuclear periphery we focused our attention on its relationship with lamins both in physiological and pathological conditions. Using Structure Illumination Microscopy (SIM) (Schermelleh et al., 2010) we demonstrated that AKTIP is localized at nuclear rim in a close proximity with A-type lamins and that it is mislocated in cells from LMNA-mutations associated progeroid patients suggesting that this mislocalization at nuclear rim could contribute to the HGPS phenotype. For AKTIP at midbody we described by SIM that AKTIP forms a super-molecular structure, with a shape of a ring, around microtubules at the center of the intercellular bridge where the endosomal sorting complex required for transport (ESCRT) complex is recruited and acts to finalize abscission (Elia et al., 2011; Karasmanis et al., 2019). ESCRTs are protein complexes involved in membrane remodeling acting through their highly regulated sequential recruitment at target membrane in collaboration with associated proteins (Gatta and Carlton, 2019). We also showed that AKTIP ring is in spatial proximity with ESCRT-III subunits, and functionally, AKTIP reduction impinges on ESCRT-III IST1 recruitment at the midbody and causes abscission defects, including longer abscission time and multinucleation. The collected data and AKTIP intracellular distribution suggest that AKTIP could act as an ESCRT protein. This hypothesis is further supported by the structural and bioinformatics similarity with TSG101 and by the identification of putative partners belonging to different ESCRTs involving pathways through a proteins interactions screening. We found that AKTIP interactes with an ESCRT-I member, the VPS28 subunit. Since VPS28 bridges the ESCRT-I to the ESCRT-II complex (Carlton and Martin-Serrano; 2007), these data make hypothesize a sequential pathway in which AKTIP is connected to ESCRT-II and then to ESCRT-III via VPS28. In summary, these data taken together indicate AKTIP as a new candidate factor associated with the ESCRT complex functioning at nuclear envelope and in cytokinesis
Work ability index in a cohort of railway construction workers
Working conditions and work load can have a significant effect on work ability, due not only to their direct impact on health and well-being, but also to the possibility they let to maintain job and competence at acceptable levels with normal ageing. In this perspective a cohort of 377 manual workers, aged between 21 and 67 years, engaged in a railway tunnel digging have been examined. They were miners, carpenters, maintenance workers, dumper drivers and clerks/storekeepers. In the whole cohort, the Work Ability Index resulted excellent in 23.6%, good in 47.2%, moderate in 24.4%, and poor in 4.8% of the workers (12.2% in those over 55 years). The mean WAI progressively decreases from the youngest to the oldest decade (from 41.5 in subjects under 25 years to 36.0 in subjects over 55 years), and passing from day-work (39.7) to semi-continuous three-shift work (39.2) and continuous 3-shift work (37.7). Miners and carpenters showed the highest percentages of poor-moderate WAI (31.6% and 35.1% respectively); these latter show also a steeper decrement over the years. Compared to other working groups of industrial and service sectors, the railway construction workers show the lower mean WAI scores at all age groups and the most pronounced decrease over decades
Going Beyond Counting First Authors in Author Co-citation Analysis
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
“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
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
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
Phosphatidylinositol 3-kinase is required for the induction of ornithine decarboxylase in leukemia cells stimulated to growth.
The involvement of phosphatidylinositol 3-kinase (PI3K) in the induction of ornithine decarboxylase (ODC) was investigated by using specific PI3K inhibitors. In difluoromethylornithine-resistant L1210 cells stimulated to growth from quiescence, treatment with LY294002 inhibited cell growth and provoked a complete block of the induction of ODC activity (IC50 approximately 2 microM) and ODC protein. Some reduction in the accumulation of ODC mRNA was also observed, whereas ODC turnover was not affected significantly. Wortmannin, another specific inhibitor of PI3K, structurally unrelated to LY294002, also inhibited ODC induction with an IC50 of about 10 nM. These results indicate that PI3K activity is required for the induction of ODC, possibly affecting both ODC mRNA level and translation. Since p70 S6 kinase (p70S6K) is considered an important mediator of PI3K action in several experimental systems, the effect of rapamycin, which can lead to selective inhibition of p70S6K, was also investigated. Rapamycin inhibited p70S6K activity and produced ODC inhibiting effects similar to those elicited by LY294002. However, LY294002 and wortmannin at concentrations which inhibited almost completely PI3K activity did not decrease p70S6K activity, suggesting that p70S6K does not mediate the PI3K effects on ODC, but may lie on a separate pathway in this experimental model
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