EFFECTS OF ATAXIA TELANGIECTASIA-MUTATED KINASE (ATM) DEFICIENCY ON CARDIAC REMODELING IN RESPONSE TO WESTERN-TYPE DIET (WD) PRIOR TO AND FOLLOWING MYOCARDIAL INFARCTION

Cardiovascular diseases are the leading cause of mortality worldwide. Ataxia telangiectasia mutated kinase (ATM) is a checkpoint protein involved in cell cycle regulation. It is activated in response to genotoxic mediators such as double-stranded DNA damage or oxidative damage. Mutations in the ATM gene result in a multisystemic disease called ataxia-telangiectasia (A-T). Independently, a Western-type Diet (WD) and ATM protein deficiency are linked with heart disease, exacerbated cardiac remodeling, and myocardial infarction (MI). Our laboratory has previously shown that in male mice, the consumption of a WD during ATM deficiency is associated with the exacerbation of cardiac remodeling. This study investigated the effect of ATM deficiency on WD-induced cardiac remodeling parameters before and 1-day post-MI in a sex-specific manner using female and male mice. Age-matched wild-type (WT) and ATM heterozygous knockout (hKO) mice were fed with normal-chow (NC) or WD for 14 weeks. MI was induced by ligation of the left anterior descending coronary artery (LAD) with a 7-0 polypropylene suture. After the study period, 14 weeks post-WD feeding and 1-day post-MI, the heart was removed through an opening in the diaphragm region. Heart sections were stained with Masson\u27s trichrome to quantify fibrosis, TUNEL-stained to quantify apoptosis, infarct size, and infarct thickness, and wheat germ agglutinin-stained to quantify myocyte hypertrophy. In WT female mice, WD increased myocardial fibrosis, myocyte hypertrophy, and apoptosis at baseline compared to NC. However, in hKO-WD female mice, apoptosis was significantly lower, and hypertrophy was significantly higher than in WT-NC female mice at baseline. Intriguingly, no significant difference in apoptosis, infarct size, and infarct thickness was observed in both genotypes and genders 1-day post-MI. Thus, our data suggest that 1) ATM deficiency plays a cardioprotective role in female mice responding to WD, as it reduces apoptosis and increases hypertrophy at baseline, and 2) sex-specific cardioprotective effects of ATM deficiency in female mice were not observed 1-day post-MI in response to WD

Deficiency of Ataxia Telangiectasia-mutated Kinase (ATM) Preserves Heart Function by Affecting Cardiac Remodeling in Response to Western-type Diet (WD) in Female Mice

WD and deficiency of ATM protein independently associates with heart disease. Previous work demonstrated that WD in male ATM deficient mice induces accelerated body weight gain and heart dysfunction (Am J Physiol Heart Circ Physiol. 2021;320:H2324-H2338). Conversely, WD in female ATM deficient mice attenuates weight gain and preserves heart function (unpublished). Here, we investigated the mechanism by which ATM deficiency preserves heart function in female mice. Female wild-type (WT) and ATM heterozygous knockout (hKO) mice, aged 6 weeks, were fed with normal chow (NC) or WD for 14 weeks. Heart sections were stained with Masson’s trichrome to quantify fibrosis, TUNEL-stained to quantify apoptosis, and WGA-stained to quantify myocyte hypertrophy. Data were analyzed using ANOVA followed by Student-Newman-Keuls test. WD significantly increased fibrosis in WT-WD mice, while no increase in fibrosis was observed in hKO-WD. WD significantly increased apoptosis (myocytes and non-myocytes) in both genotypes. Myocyte hypertrophy was increased only in WT-WD. Interestingly, the increase in apoptosis was significantly lower in hKO-WD, while the increase in hypertrophy was significantly higher in hKO-WD vs WT-WD.Thus, ATM deficiency preserves heart function in female mice with decreased myocardial fibrosis and apoptosis, and increased myocyte hypertrophy in response to WD

Incorporacion del adulto mayor a redes urbanas

121 p.El mundo que hoy vivimos, avanza a pasos agigantados en temas tecnológicos y de ciencia, donde no quedan atrás temas como el crecimiento de las ciudades que habitamos, globalización de nuestro entorno, avances tecnológicos que nos generan una mejor calidad de vida y el crecimiento poblacional. Sin embargo, este último nos lleva rápidamente a posibilitarlo como el envejecimiento de nuestra población. Hoy en día, en nuestro país el cambio demográfico ha sido notable, por ende es necesaria la creación de políticas que adopten estos cambios de acuerdo a las necesidades y posibilidades existentes. Hoy se considera que del total de la población nacional un 11,4% corresponde a adultos mayores en Chile, sector etario que va en un progresivo aumento a futuro. De este modo la intervención social, política, cultural, y de gobierno deben centrarse en la integración de los adultos mayores a nuestra sociedad.La integración de las personas mayores en un lejano próximo no solo se reduce a la implementación de recursos en temas previsionales o de salud, sino en infraestructura necesaria para su desarrollo cotidiano. Hoy en día los adultos mayores no tienen lugares donde realizar actividades que no sean de forma temporal, lo que limita que puedan desenvolverse en nuestras ciudades y frente a otros grupos etarios. Es por esta razón que la implementación de la ciudad como una plataforma de actividades para el desarrollo de las personas mayores es una posibilidad de integración a la sociedad y a su entorno. Por lo cual la propuesta además contempla problemáticas pos-terremoto (27 febrero 2010) y del mismo modo temáticas de movilidad y habitabilidad, configurando un proyecto a escala ciudad, aportando desde el barrio desarrollo e integración para las personas mayores

Covid-19: Better contact tracing could help save lives and the economy

The rates of daily infections are rising significantly. In order to save lives and to keep the UK economy open, improvements to the UK contact tracing system are urgently needed. Woolliscroft et al. outlined how the UK contact tracing system could be improved. Detailed evaluation of the Sheffield based community contact tracing pilot project offers additional insights. [1,2] An independent group of mainly retired NHS staff called Sheffield Community Contact Tracers (SCCT) conducted a pilot contact tracing project from April to May 2020 before the national system was introduced. The project was assessed to determine the feasibility and impact of a volunteer staffed community contact tracing approach. The assessment found that contact tracing was enhanced by: trust, local knowledge, interviewer skills and expertise, cooperation from employers, and contact in a timely manner

Industrial Clusters in England

Research trialling a big data approach to identifying industry clusters, with case studies from each of the sectors studied

Burst-Like Subcutaneous Electrical Stimulation Induces BDNF-Mediated, Cyclotraxin B-Sensitive Central Sensitization in Rat Spinal Cord

Intrathecal administration of brain derived neurotrophic factor (BDNF) induces long-term potentiation (LTP) and generates long-lasting central sensitization in spinal cord thus mimicking chronic pain, but the relevance of these observations to chronic pain mechanisms is uncertain. Since C-fiber activation by a high-frequency subcutaneous electrical stimulation (SES) protocol causes spinal release of BDNF and induces spinal cord LTP, we propose that application of such protocol would be a sufficient condition for generating long-lasting BDNF-mediated central sensitization. Results showed that application of burst-like SES to rat toes produced (i) rapid induction of hyperalgesia that lasted for more than 3 weeks, (ii) early increase of C-reflex activity followed by increased wind-up scores lasting for more than 1 week, and (iii) early increase followed by late decrease in BDNF protein levels and phosphorylated TrkB that lasted for more than 1 week. These changes were prevented by the TrkB antagonist cyclotraxin-B administered shortly before SES, while hyperalgesia was reversed by cyclotraxin-B administered 3 days after SES. Results suggest that mechanisms underlying central sensitization first involve BDNF release of probably neuronal origin, followed by brief increased expression of likely glial BDNF and pTrkB that could switch early phase sensitization into late one

Patents Go to The Market? University-Industry Technology Transfer from a Brazilian Perspective

The purpose of this paper is to explore the TT between university-industry from a Brazilian perspective, with special reference on the university Intellectual Property – IP and TT legal instruments. The methodology was designed on a quantitative approach aiming to provide a better understanding of the problem. Secondary data collection was performed through documentary analysis that aims to identify and quantify the variables related to patents, licensing and TT agreements. Later, data are grouped, classified and treated, which allowed inference and interpretation. The results show that the TT between university-industry is in an embryonic stage in Brazil, even if occurred a considerable increase of IP required over the last few years. In this context, it is possible to affirm that the academic research outcomes are not being absorbed in an effective way by the industries, and, as a consequence, just an insignificant percentage of the patents go to the market