Suchergebnisse
Filter
4 Ergebnisse
Sortierung:
Cardiac GRK2 protein levels show sexual dimorphism during aging and are regulated by ovarian hormones
Cardiovascular disease (CVD) risk shows a clear sexual dimorphism with age, with a lower incidence in young women compared to age‐matched men. However, this protection is lost after menopause. We demonstrate that sex‐biased sensitivity to the development of CVD with age runs in parallel with changes in G protein‐coupled receptor kinase 2 (GRK2) protein levels in the murine heart and that mitochondrial fusion markers, related to mitochondrial functionality and cardiac health, inversely correlate with GRK2. Young female mice display lower amounts of cardiac GRK2 protein compared to age‐matched males, whereas GRK2 is upregulated with age specifically in female hearts. Such an increase in GRK2 seems to be specific to the cardiac muscle since a different pattern is found in the skeletal muscles of aging females. Changes in the cardiac GRK2 protein do not seem to rely on transcriptional modulation since adrbk1 mRNA does not change with age and no differences are found between sexes. Global changes in proteasomal or autophagic machinery (known regulators of GRK2 dosage) do not seem to correlate with the observed GRK2 dynamics. Interestingly, cardiac GRK2 upregulation in aging females is recapitulated by ovariectomy and can be partially reversed by estrogen supplementation, while this does not occur in the skeletal muscle. Our data indicate an unforeseen role for ovarian hormones in the regulation of GRK2 protein levels in the cardiac muscle which correlates with the sex‐dependent dynamics of CVD risk, and might have interesting therapeutic applications, particularly for post‐menopausal women ; We acknowledge support by the Agencia Estatal de Investigación (MINECO/FEDER), Spain (grant SAF2017-84125-R to FM and CM and grant SAF2016-80384 R to ILL and AMP); the CIBER de Enfermedades Cardiovasculares (CIBERCV, Instituto de Salud Carlos III) Spain (grant CB16/11/00278 to F.M., co-funded with European FEDER contribution), and the Programa de Actividades en Biomedicina de la Comunidad de Madrid (B2017/BMD-3671-INFLAMUNE to FM). MR M-C was funded by a grant from Balearic Islands Government (FPI/1888/2016), after being selected in the framework of an operating program co-financed by the European Social Fund
BASE
PUBLIC UNIVERSITIES OF LATIN AMERICA. A VISION FROM THE ENTREPRENEURSHIP ; LAS UNIVERSIDADES PÚBLICAS DE LATINOAMÉRICA. UNA VISIÓN DESDE EL EMPRENDIMIENTO
In Latin American countries, the current problems in the labor market are a product of the changes and situations that have been producing results, which have been accumulated in turn provoking the current crisis. In the last three decades there have been demographic changes, political ups and downs, technological transformations, financial crises that have led to personal and corporate bankruptcies, changes in insertion into the world economy, among others. This paper aims to explain some elements about the role of entrepreneurship in Latin American universities. It is concluded that universities seek young people to create new ways to undertake and innovate to change the current reality, because universities have the potential to create technological parks that are physical spaces that allow to interact to the most innovative companies and also has a Social responsibility in the training of their students, so they must incorporate in addition to the knowledge related to their professional disciplines the social and ethical values so that their professional practice is a contribution for the development of their community. ; En los países latinoamericanos, los problemas actuales en el mercado laboral son producto de los cambios y situaciones que han ido arrojando resultados, que se han ido a su vez acumulando provocando la crisis actual. En las últimas tres décadas se han suscitados cambios demográficos, vaivenes políticos, transformaciones tecnológicas, crisis financieras que a su vez han provocado quiebras a nivel personal y empresarial, cambios en la inserción a la economía mundial, entre otros. El presente trabajo tiene como objetivo explicar algunos elementos sobre el rol de los emprendimientos desde las universidades latinoamericanas. Se concluye que las universidades buscan que los jóvenes creen nuevas formas de emprender e innovar para cambiar la realidad actual, debido a que las universidades tienen el potencial de crear parques tecnológicos que son espacios físicos que permiten interactuar a las empresas más innovadoras y además tiene una responsabilidad social en la formación de sus estudiantes, por lo cual debe incorporar además de los conocimientos relacionados con sus disciplinas profesionales los valores sociales y éticos para que su ejercicio profesional sea un aporte para el desarrollo de su comunidad.
BASE
Association of variants in the SPTLC1 gene with juvenile amyotrophic lateral sclerosis
Importance Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation. Objective To identify the genetic variants associated with juvenile ALS. Design, Setting, and Participants In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism. Main Outcomes and Measures De novo variants present only in the index case and not in unaffected family members. Results Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway. Conclusions and Relevance These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.
BASE