554 research outputs found

    MicroRNAs in pulmonary arterial remodeling

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    Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH

    The miRNA biogenesis factors, p72/DDX17 and KHSRP regulate the protein level of Ago2 in human cells

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    © 2016 Elsevier B.V. MicroRNAs (miRNAs) are short (21–23 nt long) RNAs that post-transcriptionally regulate gene expression in plants and animals. They are key regulators in all biological processes. In mammalian cells miRNAs are loaded into one of the four members of the Argonaute (Ago) protein family to form the RNA-induced silencing complex (RISC). RISCs inhibit the translation of mRNAs that share sequence complementarity with their loaded miRNAs. miRNA processing and miRNA-mediated gene regulation are highly regulated processes and involve many RNA-binding proteins as auxiliary factors. Here we show that the two RNA-binding proteins, p72 and KHSRP, both with known roles in promoting miRNA biogenesis, regulate the protein level of human Ago2 in transformed human cells. We determined that p72 and KHSRP influence Ago2 stability by regulating miRNA levels in the cell and that loss of p72/KHSRP results in a decrease of unloaded Ago2

    Modelling Long-Period Variables -- II. Fundamental mode pulsation in the nonlinear regime

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    Long-period variability in luminous red giants has several promising applications, all of which require models able to accurately predict pulsation periods. Linear pulsation models have proven successful in reproducing the observed periods of overtone modes in evolved red giants, but they fail to accurately predict their fundamental mode periods. Here, we use a 1D hydrodynamic code to investigate the long-period variability of M-type asymptotic giant branch stars in the nonlinear regime. We examine the period and stability of low-order radial pulsation modes as a function of mass and radius, and find overtone mode periods in complete agreement with predictions from linear pulsation models. In contrast, nonlinear models predict an earlier onset of dominant fundamental mode pulsation, and shorter periods at large radii. Both features lead to a substantially better agreement with observations, that we verify against OGLE and Gaia data for the Magellanic Clouds. We provide simple analytic relations describing the nonlinear fundamental mode period-mass-radius relation. Differences with respect to linear predictions originate from the readjustment of the envelope structure induced by large-amplitude pulsation. We investigate the impact of turbulent viscosity on linear and nonlinear pulsation, and probe possible effects of varying metallicity and carbon abundance.Comment: 18 pages, 17 figures; accepted for publication in MNRA

    Concorrenza nel settore del trasporto aereo e dei servizi aeroportuali

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    L’abuso di posizione dominante delle compagnie aeree. Competizione e cooperazione tra compagnie aeree. La cessione degli slots come rimedio alla posizione dominante delle compagnie aeree. Abuso di posizione dominante del gestore aeroportuale.L’abuso di posizione dominante delle compagnie aeree. Competizione e cooperazione tra compagnie aeree. La cessione degli slots come rimedio alla posizione dominante delle compagnie aeree. Abuso di posizione dominante del gestore aeroportuale.LUISS PhD Thesi

    Efficacy of a computerized cognitive training application on cognition and depressive symptomatology in a group of healthy older adults: a randomized controlled trial

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    [Abstract] Objective. The purpose of this study was to evaluate the efficacy of a multimedia and interactive cognitive program on cognition and depressive symptomatology in healthy older adults. Methods. Adults aged ≥65 years were randomly assigned to two groups: the experimental group in which the participants received a computerized cognitive training application; and the control group in which the participants received no intervention during the protocol. Performance on the mini-mental state examination (MMSE) and the short-form of the geriatric depression scale (GDS-SF) were analysed using a three-way repeated-measure analysis of variance. Results. To determine cognition after the training, the cognitive program was used and the results were assessed using the MMSE, indicating that the significant time effects within the groups reflected the score for cognitive assessment that was significantly better after the intervention in the experimental group. No significant differences were observed with regard to the depressive symptomatology or between the groups according to sex or educational level on the two dimensions previously established (cognition and depressive symptomatology). Conclusion. The development of technological applications for intervention in older adults is increasing. Based on the established objective, we can conclude that the computerized intervention may constitute a good alternative to enhance the cognitive status in older people
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