89 research outputs found

    Accumulation of poly(A) RNA in nuclear granules enriched in Sam68 in motor neurons from the SMNA7 mouse model of SMA

    Get PDF
    Spinal muscular atrophy (SMA) is a severe motor neuron (MN) disease caused by the deletion or mutation of the survival motor neuron 1 (SMN1) gene, which results in reduced levels of the SMN protein and the selective degeneration of lower MNs. The best-known function of SMN is the biogenesis of spliceosomal snRNPs, the major components of the pre-mRNA splicing machinery. Therefore, SMN deficiency in SMA leads to widespread splicing abnormalities. We used the SMN?7 mouse model of SMA to investigate the cellular reorganization of polyadenylated mRNAs associated with the splicing dysfunction in MNs. We demonstrate that SMN deficiency induced the abnormal nuclear accumulation in euchromatin domains of poly(A) RNA granules (PARGs) enriched in the splicing regulator Sam68. However, these granules lacked other RNA-binding proteins, such as TDP43, PABPN1, hnRNPA12B, REF and Y14, which are essential for mRNA processing and nuclear export. These effects were accompanied by changes in the alternative splicing of the Sam68-dependent Bcl-x and Nrnx1 genes, as well as changes in the relative accumulation of the intron-containing Chat, Chodl, Myh9 and Myh14 mRNAs, which are all important for MN functions. PARG-containing MNs were observed at presymptomatic SMA stage, increasing their number during the symptomatic stage. Moreover, the massive accumulations of poly(A) RNA granules in MNs was accompanied by the cytoplasmic depletion of polyadenylated mRNAs for their translation. We suggest that the SMN-dependent abnormal accumulation of polyadenylated mRNAs and Sam68 in PARGs reflects a severe dysfunction of both mRNA processing and translation, which could contribute to SMA pathogenesis.This work was supported by grants from: “Dirección General de Investigación” of Spain (BFU2014-54754-P and SAF2015-70801-R, cofinanced by FEDER) and “Instituto de Investigación Marqués de Valdecilla-IDIVAL (NVAL17/22). Dr. Tapia is the recipient of a grant from SMA Europe and FundAME (Spain)

    Public–private research collaborations: longitudinal field-level analysis of determinants, frequency, and impact

    No full text
    This study on public–private research collaboration measures the variation over time of the propensity of academics to collaborate with colleagues from private companies. It also investigates the change in weights of the main drivers underlying the academics’ propensity to collaborate, and whether the type profile of the collaborating academics changes. To do this, the study applies an inferential model on a dataset of professors working in Italian universities in consecutive periods, 2010–2013 and 2014–2017. The results, obtained at overall and field levels, support the formulation of policies aimed at fostering public–private research collaborations, and should be taken into account in postassessment of their effectiveness

    Do the propensity and drivers of academics' engagement in research collaboration with industry vary over time?

    No full text
    This study is about public-private research collaboration. In particular, we want to measure how the propensity of academics to collaborate with their colleagues from private firms varies over time and whether the typical profile of such academics change. Furthermore, we investigate the change of the weights of main drivers underlying the academics' propensity to collaborate with industry. In order to achieve such goals, we apply an inferential model on a dataset of professors working in Italian universities in two subsequent periods, 2010-2013 and 2014-2017. Results can be useful for supporting the definition of policies aimed at fostering public-private research collaborations, and should be taken into account when assessing their effectiveness afterwards

    The geographic proximity effect on domestic cross-sector vis-Ă -vis intra-sector research collaborations

    No full text
    Geographic proximity is acknowledged to be a key factor in research collaborations. Specifically, it can work as a possible substitute for institutional proximity. The present study investigates the relevance of the “proximity” effect for different types of national research collaborations. We apply a bibliometric approach based on the Italian 2010–2017 scientific production indexed in the Web of Science. On such dataset, we apply statistical tools for analyzing if and to what extent geographical distance between co-authors in the byline of a publication varies across collaboration types, scientific disciplines, and along time. Results can inform policies aimed at effectively stimulating cross-sector collaborations, and also bear direct practical implications for research performance assessments

    Wrinkling analysis of solar-photon sails

    No full text
    This paper regards small/midsize square sails on which a field of wrinkles appears owing to the necessary sail-membrane operations before and during the deployment. We collected a large amount of data in our laboratory. Many ten thousands of measurements had been statistically processed for characterizing some sail’s sampled membranes consisting of aluminized-polyimide layers ð2:5 þ 0:1Þlm thin, and loaded at vertices. Such samples have exhibited area and orientation alterations, as a whole, which can affect the propulsive acceleration of a sailcraft. Wrinkled-sail orientation has been given a thrust-specialized meaning for trajectory computation. Threedimensional heliocentric minimum-time orbit transfer between Earth and Mercury orbits had been investigated. This had resulted in wrinkled-sail sailcraft moving on trajectories remarkably different from those ones of the corresponding ideal unwrinkled-sail sailcraft. Nevertheless, at least in the current framework, the most important result is that sail-wrinkled sailcraft’s interplanetary trajectories could be optimized without resorting to stochastic differential equations
    • …
    corecore