1,277 research outputs found

    The centrosomal kinase NEK2 is a novel splicing factor kinase involved in cell survival

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    NEK2 is a serine/threonine kinase that promotes centrosome splitting and ensures correct chromosome segregation during the G2/M phase of the cell cycle, through phosphorylation of specific substrates. Aberrant expression and activity of NEK2 in cancer cells lead to dysregulation of the centrosome cycle and aneuploidy. Thus, a tight regulation of NEK2 function is needed during cell cycle progression. In this study, we found that NEK2 localizes in the nucleus of cancer cells derived from several tissues. In particular, NEK2 co-localizes in splicing speckles with SRSF1 and SRSF2. Moreover, NEK2 interacts with several splicing factors and phosphorylates some of them, including the oncogenic SRSF1 protein. Overexpression of NEK2 induces phosphorylation of endogenous SR proteins and affects the splicing activity of SRSF1 toward reporter minigenes and endogenous targets, independently of SRPK1. Conversely, knockdown of NEK2, like that of SRSF1, induces expression of pro-apoptotic variants from SRSF1-target genes and sensitizes cells to apoptosis. Our results identify NEK2 as a novel splicing factor kinase and suggest that part of its oncogenic activity may be ascribed to its ability to modulate alternative splicing, a key step in gene expression regulation that is frequently altered in cancer cells

    miRNAs in the vitreous humor of patients affected by idiopathic epiretinal membrane and macular hole

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    The aim of the present study was to assess the expression of miRNAs in the Vitreous Humor (VH) of patients with Macular Hole (MH) and Epiretinal Membrane (ERM) compared to a control group. assays. Finally, we created a biological network of differentially expressed miRNA targets and their nearest neighbors. assays of the VH of patients affected by MH and ERM, with respect to controls, showed that the most differentially expressed were miR-19b (FC -9.13, p:<0.00004), mir-24 (FC -7.52, p:<0.004) and miR-142-3p (FC -5.32, p:<0.011). Our network data showed that deregulation of differentially expressed miRNAs induces an alteration of several pathways associated with genes involved in both MH and ERM.The present study suggests that disregulation of miR-19b, miR-24 and miR-142-3p, might be related to the alterations that characterize patients affected by MH and ERM

    Pulse processing routines for neutron time-of-flight data

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    A pulse shape analysis framework is described, which was developed for n_TOF-Phase3, the third phase in the operation of the n_TOF facility at CERN. The most notable feature of this new framework is the adoption of generic pulse shape analysis routines, characterized by a minimal number of explicit assumptions about the nature of pulses. The aim of these routines is to be applicable to a wide variety of detectors, thus facilitating the introduction of the new detectors or types of detectors into the analysis framework. The operational details of the routines are suited to the specific requirements of particular detectors by adjusting the set of external input parameters. Pulse recognition, baseline calculation and the pulse shape fitting procedure are described. Special emphasis is put on their computational efficiency, since the most basic implementations of these conceptually simple methods are often computationally inefficient.Comment: 13 pages, 10 figures, 5 table

    Regional Development of Glioblastoma: The Anatomical Conundrum of Cancer Biology and Its SurgicalImplication

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    Glioblastoma (GBM) are among the most common malignant central nervous system (CNS) cancers, they are relatively rare. This evidence suggests that the CNS microenvironment is naturally equipped to control proliferative cells, although, rarely, failure of this system can lead to cancer development. Moreover, the adult CNS is innately non-permissive to glioma cell invasion. Thus, glioma etiology remains largely unknown. In this review, we analyze the anatomical and biological basis of gliomagenesis considering neural stem cells, the spatiotemporal diversity of astrocytes, microglia, neurons and glutamate transporters, extracellular matrix and the peritumoral environment. The precise understanding of subpopulations constituting GBM, particularly astrocytes, is not limited to glioma stem cells (GSC) and could help in the understanding of tumor pathophysiology. The anatomical fingerprint is essential for non-invasive assessment of patients' prognosis and correct surgical/radiotherapy planning

    Increased adiposity appraised with cun-bae is highly predictive of incident hypertension. The sun project

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    Overweight and obesity are growing worldwide and strongly associated with hypertension. The Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) index is proposed as an optimal indicator of body fatness. We aimed to investigate the association of body fat as captured by the CUN-BAE index with incident hypertension in a Mediterranean population. We assessed 15,950 participants of the SUN (Seguimiento Universidad de Navarra) prospective cohort (63.7% women) initially free of hypertension. Participants completed follow-up questionnaires biennially. A validated 136-item food-frequency questionnaire was administered at baseline. We used Cox models adjusted for multiple confounders. Among 12.3 years of median follow-up (interquartile range: 8.3, 15.0 years), 2160 participants reported having received a diagnosis of hypertension. We observed a strong direct association between progressively higher the CUN-BAE index at baseline and incident hypertension during follow-up in multivariable-adjusted models for men and women, even after further adjustment for BMI ≥ 30 kg/m2, showing a significant association also in non-obese participants. For each 2-unit increase in the CUN-BAE index, hypertension risk increased by 27% and 29% in men and women, respectively. The results remained significant when considering longitudinal repeated measures of changes in body fat assessed with the CUN-BAE index among the different biennial follow-up questionnaires. Our results emphasize the importance of reducing and maintaining a low body fat to prevent hypertension

    Healthy Aging and Dietary Patterns

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    A number of factors contribute to the complex process of aging, which finally define whether someone will or not develop age-associated chronic diseases in late life. These determinants comprise genetic susceptibility as well as various behavioral, environmental, and dietary factors, all of which have been shown to influence specific pathways regulating the aging process and the extension of life, which makes longevity a multidimensional phenomenon. Although a “miraculous elixir” or a “nutrition pill” are not plausible, researchers agree on the notion that nutritional factors have major impact on the risk of age-associated chronic non-communicable diseases and mortality. In recent years nutrition research in relation to health outcomes has considerably changed from focusing exclusively on single nutrients to considering combinations of foods rather than nutrients in isolation. Although research on specific nutrients is scientifically valid providing crucial evidence on the mechanisms by which nutrition impacts health, the recent switch targeting the multifaceted synergistic interplay among nutrients, other dietary constituents, and whole foods, has promoted emerging interest on the actions of total dietary patterns. This narrative review aims to describe some specific dietary patterns with evidence of associations with reduction in the incidence of chronic diseases allowing older adults to live a long-lasting and healthier life, and confirming the powerful impact nutrition can exert on healthy aging. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

    Performance evaluation of SiPMĘĽs for low threshold gamma detection

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    In the context of the on-line monitoring of short and medium term for radioactive waste repository, a new system has been planned. Such system makes use a new kind of detector, named Silicon Photomultiplier, coupled to scintillating fibres to be positioned around each waste drum in shape of fine grid. The purpose of this design is evaluate the variations of the radioactivity distribution by counting the gamma radiation
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