Role of H4K16 acetylation in 53BP1 recruitment to double-strand break sites in in vitro aged cells

Increased frequency of DNA double strand breaks (DSBs) with aging suggests an age-associated decline in DSB repair efficiency, which is also influenced by the epigenetic landscape. H4 acetylation at lysine 16 (H4K16Ac) has been related to DSB repair since deacetylation of this mark is required for efficient 53BP1 recruitment to DSBs. Although age-associated changes in H4K16Ac levels have been studied, their contribution to age-related DSB accumulation remains unknown. In vitro aged Human Dermal Fibroblasts (HDFs) display lower levels of H4K16A that correlate with reduced recruitment of 53BP1 to basal DSBs. Following DNA damage induction, early passage (EP) cells suffered from a transient H4K16 deacetylation that allowed proper 53BP1 recruitment to DSBs. In contrast, to reach this specific and optimum level, aged cells responded by increasing their overall lower H4K16Ac levels. Induced hyperacetylation of late passage (LP) cells using trichostatin A increased H4K16Ac levels but did not ameliorate 53BP1 recruitment. Instead, deacetylation induced by MOF silencing reduced H4K16Ac levels and compromised 53BP1 recruitment in both EP and LP cells. Age-associated decrease of H4K16Ac levels contributes to the repair defect displayed by in vitro aged cells. H4K16Ac responds to DNA damage in order to reach a specific, optimum level that allows proper 53BP1 recruitment. This response may be compromised with age, as LP cells depart from lower H4K16Ac levels. Variations in H4K16Ac following the activation of the DNA damage response and aging point at this histone mark as a key mediator between DNA repair and age-associated chromatin alterations

Identification of reference genes for RT-qPCR data normalisation in aging studies

Aging is associated with changes in gene expression levels that affect cellular functions and predispose to age-related diseases. The use of candidate genes whose expression remains stable during aging is required to correctly address the age-associated variations in expression levels. Reverse transcription quantitative-polymerase chain reaction (RT-qPCR) has become a powerful approach for sensitive gene expression analysis. Reliable RT-qPCR assays rely on the normalisation of the results to stable reference genes. Taken these data together, here we evaluated the expression stability of eight frequently used reference genes in three aging models: oncogene-induced senescence (015), in vitro and in vivo aging. Using NormFinder and geNorm algorithms, we identified that the most stable reference gene pairs were PUM1 and TBP in 015, GUSB and PUM1 for in vitro aging and GUSB and OAZ1 for in vivo aging. To validate these candidates, we used them to normalise the expression data of CDKN1A, APOD and TFRC genes, whose expression is known to be affected during 015, in vitro and in vivo aging. This study demonstrates that accurate normalisation of RT-qPCR data is crucial in aging research and provides a specific subset of stable reference genes for future aging studies

Plan de negocios para la microempresa “Mix sabores”, ubicada en el municipio de Jinotepe, departamento de Carazo durante el segundo semestre del año 2020

La presente investigación se desarrolló en la ciudad de Jinotepe, departamento de Carazo durante el II periodo del año 2020, donde participaron estudiantes universitarios, licenciados, y adultos mayores, tomándose como referencia la población económicamente activa del casco urbano de la ciudad. La finalidad de la investigación consistió en elaborar un plan de negocio en la ciudad de Jinotepe. Para ello se elaboró estrategias publicitarias, mediante un estudio de mercado se proyectó, determino y cuantifico la demanda del producto. Por consiguiente se desarrolló la estructura legal y operativa del negocio y finalmente se determinó la rentabilidad del negocio. El presente estudio se justificó por cuando posee valor teórico, utilidad práctica, relevancia social en base a los beneficios que genera. El estudio se sustenta bajo criterios médicos en cuanto al cuido de la salud alimentaria. Metodológicamente el trabajo investigativo aborda los criterios del estudio descriptivo – exploratorios con la utilización de un diseño investigativo de campo donde la población estuvo conformada por 14,028 de los cuales se retomó una muestra de 3.55% tomando un tamaño muestral de 355. La técnica que se empleo fue la observaciones la cual se aplicó en una encuesta diseñada por un cuestionario de 24 preguntas cerradas. El procesamiento de datos permitió determinar los gustos y preferencias del producto determinando la fiabilidad del negocio que conllevo a las siguientes conclusiones: a) Determinación del mercado meta, mediante el estudio de mercado b) Valoración del punto de equilibrio múltiple para los 4 batidos demostrando que genera un punto medio de C$ 191,698.93 córdobas cubriendo la totalidad de sus costos donde la empresa no gana ni pierda, c) Rendimiento satisfactorio en la evaluación de indicadores financiero como el Valor Actual Neto la Tasa Interna de Retorno y la Rentabilidad

Identification of reference genes for RT-qPCR data normalisation in aging studies

Aging is associated with changes in gene expression levels that affect cellular functions and predispose to age-related diseases. The use of candidate genes whose expression remains stable during aging is required to correctly address the age-associated variations in expression levels. Reverse transcription quantitative-polymerase chain reaction (RT-qPCR) has become a powerful approach for sensitive gene expression analysis. Reliable RT-qPCR assays rely on the normalisation of the results to stable reference genes. Taken these data together, here we evaluated the expression stability of eight frequently used reference genes in three aging models: oncogene-induced senescence (OIS), in vitro and in vivo aging. Using NormFinder and geNorm algorithms, we identified that the most stable reference gene pairs were PUM1 and TBP in OIS, GUSB and PUM1 for in vitro aging and GUSB and OAZ1 for in vivo aging. To validate these candidates, we used them to normalise the expression data of CDKN1A, APOD and TFRC genes, whose expression is known to be affected during OIS, in vitro and in vivo aging. This study demonstrates that accurate normalisation of RT-qPCR data is crucial in aging research and provides a specific subset of stable reference genes for future aging studies

Relaciones interdisciplinarias entre Educación para la Salud y Literatura Universal

Es poco frecuente que se utilice la obra literaria para reflexionar acerca de los estilos de vida saludables de los hombres, ya que eso no es un objetivo de esta rama artística; sin embargo, el análisis literario puede servir para valorar elementos que van más allá de los que estudia la Teoría de la Literatura, como por ejemplo, la educación para la salud. Teniendo en cuenta que el establecimiento de relaciones interdisciplinarias constituye un imperativo actual derivado del desarrollo científico y la educación debe incorporarlo al proceso de enseñanza, el objetivo de este trabajo es describir las relaciones interdisciplinarias que se pueden establecer entre la Literatura Universal y la Educación para la Salud, en las especialidades de Enseñanza Técnica y Profesional insertadas en las Universidades de Ciencias Médicas de Cuba, que reciben la asignatura Español-Literatura. De esta manera se da cumplimiento, además, al Programa Director de Promoción y Educación para la Salud previsto por los Ministerios de Educación y de Salud en Cuba. Se abordaron las siguientes temáticas: higiene colectiva y personal y educación sexual, a través de una selección de fragmentos de obras de diferentes países y épocas, desde la cultura grecolatina hasta el siglo XIX; se presentan guías didácticas que posibilitan enriquecer y profundizar el estudio de la obra más allá de una perspectiva exclusivamente literaria, con lo que se contribuye a incrementar la educación para la salud y a reforzar los vínculos interdisciplinarios. Puede ser utilizado por profesores de la especialidad o de cualquier otra asignatura que aborde estos temas

Control de calidad para el diagnóstico de helmintos en la provincia Villa Clara, Cuba: 2016-2019

Helminthic diseases are a major public health problem. Laboratory diagnosis is of vital importance, which must be supported by a quality assurance system. The objective of the study was to carry out an external evaluation of the laboratories that make up the health care network in order to compare the results of the external quality control in the diagnosis of helminths of the governing laboratory, the Provincial Center of Hygiene, Epidemiology and Microbiology, with the participants in Villa Clara province, Cuba. A descriptive and transversal study was carried out, with a discretional sampling of intentional type by criteria. A total of 2,857 stool samples from 36 laboratories were processed from March 2016 to March 2019 by the Willis - Molloyʹs high-density solution method. In 98.6% of the diagnoses there was concordance of results and no concordance in 1% (29), in addition to 7 (0.2%) discrepant and 4 (0.1%) polyparasitized. Of 93 identified helminths, Enterobius vermicularis (Linnaeus, 1758) was present most frequently with 32, Ascaris lumbricoides (Linnaeus, 1758) with 27 and Necator/Ancylostoma with 8, for 82.8%; of the seven discrepant, two were diagnosed as Necator/Ancylostoma (participants)/ were Strongyloides stercoralis (Bavay, 1876) (rector). The participating laboratories were considered to have high quality assurance, because of the almost absolute predominance of concordant samples. The low presence of intestinal helminths in the samples received was confirmed. There are some difficulties in the identification of intestinal helminth eggs and/or larvae.Las enfermedades producidas por helmintos constituyen un importante problema de salud pública. El diagnóstico de laboratorio es de vital importancia, el cual debe estar avalado por un sistema de garantía de la calidad. El objetivo del estudio fue realizar una investigación relacionada con la evaluación externa a los laboratorios que componen la red asistencial para comparar los resultados del control de calidad externo en el diagnóstico de helmintos del laboratorio rector, el Centro Provincial de Higiene, Epidemiología y Microbiología con los participantes de la provincia Villa Clara, Cuba. Se realizó un estudio descriptivo y transversal, con un muestreo discrecional de tipo intencional por criterios. Fueron procesadas 2 857 muestras de heces fecales de 36 laboratorios, desde marzo del 2016 a marzo del 2019, por el método de solución de alta densidad de Willis-Molloy. En el 98,6% de los diagnósticos hubo concordancia de resultados y no concordancia en el 1% (29), además de 7 (0,2%) discrepante y 4 (0,1%) poliparasitados. De 93 helmintos identificados estuvieron presentes con mayor frecuencia Enterobius vermicularis (Linnaeus, 1758) con 32, Ascaris lumbricoides (Linnaeus, 1758) con 27 y Necator/Ancylostoma con 8, para el 82,8%; de los siete discrepantes, dos fueron diagnosticados como Necator/Ancylostoma (participantes)/ eran Strongyloides stercoralis (Bavay, 1876) (rector). Se consideró que los laboratorios participantes tienen una garantía de la calidad alta, por el predominio casi absoluto de muestras concordantes. Se confirmó la baja presencia de helmintos intestinales en las muestras recibidas. Existen algunas dificultades en la identificación de huevos y/o larvas de helmintos intestinales

Ética Profesional y Responsabilidad Social Universitaria

este libro compila reflexiones y experiencias en responsabilidad social y ética profesional desde instituciones de Educación Superior. La responsabilidad social universitaria, como ámbito de investigación y de desarrollo conceptual y metodológico es transversal a las universidades, tanto desde el punto de vista organizacional, como desde el misional e investigativo. Quienes impulsen la responsabilidad social, requieren de ética profesional, que debe ser la clave para la construcción de principios que guíen a empresarios, políticos, gestores sociales, investigadores, entre otros, para lograr consensuar el a veces difícil equilibrio entre el bien común y el desarrollo personal

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

MUSiC : a model-unspecific search for new physics in proton-proton collisions at root s=13TeV

Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.Peer reviewe

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe