MPI-dot2dot: A Parallel Tool to Find DNA Tandem Repeats on Multicore Clusters

Financiado para publicación en acceso aberto: Universidade da Coruña/CISUG[Abstract] Tandem Repeats (TRs) are segments that occur several times in a DNA sequence, and each copy is adjacent to other. In the last few years, TRs have gained significant attention as they are thought to be related with certain human diseases. Therefore, identifying and classifying TRs have become a highly important task in bioinformatics in order to analyze their disorders and relationships with illnesses. Dot2dot, a tool recently developed to find TRs, provides more accurate results than the previous state-of-the-art, but it requires a long execution time even when using multiple threads. This work presents MPI-dot2dot, a novel version of this tool that combines MPI and OpenMP so that it can be executed in a cluster of multicore nodes and thus reduces its execution time. The performance of this new parallel implementation has been tested using different real datasets. Depending on the characteristics of the input genomes, it is able to obtain the same biological results as Dot2dot but more than 100 times faster on a 16-node multicore cluster (384 cores). MPI-dot2dot is publicly available to download from https://sourceforge.net/projects/mpi-dot2dot.This work was supported by the Ministry of Science and Innovation of Spain (PID2019-104184RB-I00 / AEI / 10.13039/501100011033), and by Xunta de Galicia and FEDER funds (Centro de Investigación de Galicia accreditation 2019-2022 and Consolidation Program of Competitive Reference Groups, under Grants ED431G 2019/01 and ED431C 2021/30, respectively). The authors would like to thank the Galician Supercomputing Center (CESGA) for providing access to the Finis Terrae II supercomputer. Open Access funding provided thanks to the CRUE-CSIC agreement with Springer NatureXunta de Galicia; ED431G 2019/01Xunta de Galicia; ED431C 2021/3

Risk Factors and treatment needs of batterer intervention program participants with substance abuse problems

The aim of the present study was to identify the main risk factors and treatment needs of batterer intervention program (BIP) participants with alcohol and drug abuse problems (ADAPs), beyond issues strictly related to their substance abuse, taking into account four sets of variables: sociodemographic (i.e., age, educational level, income, employment, and immigrant status); personality disorders and psychological adjustment (i.e., clinical symptomatology, personality disorders, anger, impulsivity, and self-esteem); social-relational variables (i.e., community support, intimate support, stressful life events, and perceived social rejection); and violence-related variables (i.e., family violence exposure, perceived severity of intimate partner violence against women [IPVAW], ambivalent sexism, risk of future violence, physical and psychological intimate partner violence, motivation to change, and stage of change). The study was based on a sample of 1,039 male IPVAW offenders court-mandated to a community-based BIP. Results from comparisons between BIP participants with and without ADAPs were interpreted in terms of effect sizes to highlight the most salient differences. Differences with moderate effect sizes were found for clinical symptomatology, anger trait, anxiety disorder, depressive disorder, stressful life events, motivation to change and stage of change. Differences with large effect sizes were found for impulsivity, antisocial disorder, borderline disorder, and aggressive disorder. Several intervention strategies are proposed to guide and adjust interventions to risk factors and treatment needs of BIP participants with ADAPs

Mip6 binds directly to the Mex67 UBA domain to maintain low levels of Msn2/4 stress dependent mRNAs

Abstract del trabajo presentado en 12ª Reunión de la Red Española de Levaduras. El Escorial, Madrid.11-13 de diciembre de 2019Pág. 44 del libro de abstracts que se adjunta. RNA-binding proteins (RBPs) participate in all steps of gene expression, underscoring their potential as regulators of RNA homeostasis. We structurally and functionally characterize Mip6, a four-RNA recognition motif (RRM)-containing RBP, as a functional and physical interactor of the export factor Mex67. Mip6-RRM4 directly interacts with the ubiquitin-associated (UBA) domain of Mex67 through a loop containing tryptophan 442. Mip6 shuttles between the nucleus and the cytoplasm in a Mex67-dependent manner and concentrates in cytoplasmic foci under stress. Photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation experiments show preferential binding of Mip6 to mRNAs regulated by the stress-response Msn2/4 transcription factors. Consistent with this binding, MIP6 deletion affects their export and expression levels. Additionally, Mip6 interacts physically and/or functionally with proteins with a role in mRNA metabolism and transcription such as Rrp6, Xrn1, Sgf73, and Rpb1. These results reveal a novel role for Mip6 in the homeostasis of Msn2/4-dependent transcripts through its direct interaction with the Mex67 UBA domain

The yeast prefoldin-like URI-orthologue Bud27 associates with the RSC nucleosome remodeler and modulates transcription

Bud27, the yeast orthologue of human URI/RMP, is a member of the prefoldin-like family of ATPindependent molecular chaperones. It has recently been shown to mediate the assembly of the three RNA polymerases in an Rpb5-dependent manner. In this work, we present evidence of Bud27 modulating RNA pol II transcription elongation. We show that Bud27 associates with RNA pol II phosphorylated forms (CTD-Ser5P and CTD-Ser2P), and that its absence affects RNA pol II occupancy of transcribed genes. We also reveal that Bud27 associatesin vivo with the Sth1 component of the chromatin remodeling complex RSC and mediates its association with RNA pol II. Our data suggest that Bud27, in addition of contributing to Rpb5 folding within the RNA polymerases, also participates in the correct assembly of other chromatin-associated protein complexes, such as RSC, thereby modulating their activit

Camelids in the south of the Iberian Peninsula in Roman and medieval times. Osteological evidence from the city of Cordoba (Spain)

This paper presents the results obtained concerning the possible presence of camelids in the city of Cordoba (Spain) in Roman and medieval times, after the review of all the faunal assemblages corresponding to these historical periods deposited in the Provincial Archaeological Museum of the city. This research has allowed the recovery and contextualization of nine dromedary bone remains corresponding to nine individuals, four of which have been dated by C. A stable isotope analysis has also been carried out which indicates the possible arrival of these animals from other provinces of the empire in Roman times and from North Africa in medieval times. Besides, we carried out a bibliographical update of all bone remains found in the Iberian Peninsula for the periods analyzed, concluding that the main use of them was for transporting and manufacturing different tools.This study have been funded through the Andalusian Regional Government’s I + D + i-FEDER Andalucía 2014-2020 program. C.A.M.E.L. Historical contextualization, Diet, Morphology, Genetic Study, and Lineage through the bone remains of camels recovered in archaeological sites in the southern Iberian Peninsula (Ref. 1380946-F) and Ministry of Science and Innovation of Spain through European Regional [SUMHAL, LIFEWATCH-2019-09-CSIC-13, POPE 2014-2020]. Both Dr. José A. Riquelme Cantal and Dr. Juan Manuel Garrido Anguita are the principal investigators leading the projects that have funded this research. Funding for open access charge: Universidad de Córdoba /CBUA

The association of the RSC remodeler complex with chromatin is influenced by the prefoldin-like Bud27 and determines nucleosome positioning and polyadenylation sites usage in Saccharomyces cerevisiae

The tripartite interaction between the chromatin remodeler complex RSC, RNA polymerase subunit Rpb5 and prefoldin-like Bud27 is necessary for proper RNA pol II elongation. Indeed lack of Bud27 alters this association and affects transcription elongation. This work investigates the consequences of lack of Bud27 on the chromatin association of RSC and RNA pol II, and on nucleosome positioning. Our results demonstrate that RSC binds chromatin in gene bodies and lack of Bud27 alters this association, mainly around polyA sites. This alteration impacts chromatin organization and leads to the accumulation of RNA pol II molecules around polyA sites, likely due to pausing or arrest. Our data suggest that RSC is necessary to maintain chromatin organization around those sites, and any alteration of this organization results in the widespread use of alternative polyA sites. Finally, we also find a similar molecular phenotype that occurs upon TOR inhibition with rapamycin, which suggests that alternative polyadenylation observed upon TOR inhibition is likely Bud27-dependent.Peer reviewe

Protein Kinase C δ Regulates the Depletion of Actin at the Immunological Synapse Required for Polarized Exosome Secretion by T Cells

Multivesicular bodies (MVB) are endocytic compartments that enclose intraluminal vesicles (ILVs) formed by inward budding from the limiting membrane of endosomes. In T lymphocytes, ILVs are secreted as Fas ligand-bearing, pro-apoptotic exosomes following T cell receptor (TCR)-induced fusion of MVB with the plasma membrane at the immune synapse (IS). In this study we show that protein kinase C δ (PKCδ), a novel PKC isotype activated by diacylglycerol (DAG), regulates TCR-controlled MVB polarization toward the IS and exosome secretion. Concomitantly, we demonstrate that PKCδ-interfered T lymphocytes are defective in activation-induced cell death. Using a DAG sensor based on the C1 DAG-binding domain of PKCδ and a GFP-PKCδ chimera, we reveal that T lymphocyte activation enhances DAG levels at the MVB endomembranes which mediates the association of PKCδ to MVB. Spatiotemporal reorganization of F-actin at the IS is inhibited in PKCδ-interfered T lymphocytes. Therefore, we propose PKCδ as a DAG effector that regulates the actin reorganization necessary for MVB traffic and exosome secretion

Adipose tissue concentrations of persistent organic pollutants and total cancer risk in an adult cohort from Southern Spain: Preliminary data from year 9 of the follow-up

There is an increasing trend in the incidence of cancer worldwide, and it has been accepted that environmental factors account for an important proportion of the global burden. The present paper reports preliminary findings on the influence of the historical exposure to a group of persistent organic pollutants on total cancer risk, at year 9 in the follow-up of a cohort from Southern Spain. A cohort of 368 participants (median age 51 years) was recruited in 2003. Their historical exposure was estimated by analyzing residues of persistent organic pollutants in adipose tissue. Estimation of cancer incidence was based on data from a population-based cancer registry. Statistical analyses were performed using multivariable Cox-regression models. In males, PCB 153 concentrations were positively associated with total cancer risk, with an adjusted hazard ratio (95% confidence interval) of 1.20 (1.01–1.41) for an increment of 100 ng/g lipid. Our preliminary findings suggest a potential relationship between the historical exposure to persistent organic pollutants and the risk of cancer in men. However, these results should be interpreted with caution and require verification during the future follow-up of this cohort.This study was supported in part by research grants from the Spanish Ministry of Health (FIS 02/974, EUS2008-03574), CIBER de Epidemiología; Junta de Andalucía (01/264, P09-CTS-5488 Project of Excellence, PI-0675-2010, and PI-0513-2012), and the Instituto de Salud Carlos III (FIS PI11/0610)

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true