Targeted expression of the human uncoupling protein 2 (hUCP2) to adult neurons extends life span in the fly

SummaryThe oxidative stress hypothesis of aging predicts that a reduction in the generation of mitochondrial reactive oxygen species (ROS) will decrease oxidative damage and extend life span. Increasing mitochondrial proton leak-dependent state 4 respiration by increasing mitochondrial uncoupling is an intervention postulated to decrease mitochondrial ROS production. When human UCP2 (hUCP2) is targeted to the mitochondria of adult fly neurons, we find an increase in state 4 respiration, a decrease in ROS production, a decrease in oxidative damage, heightened resistance to the free radical generator paraquat, and an extension in life span without compromising fertility or physical activity. Our results demonstrate that neuronal-specific expression of hUCP2 in adult flies decreases cellular oxidative damage and is sufficient to extend life span

Roles of the developmental regulator unc-62/homothorax in limiting longevity in Caenorhabditis elegans

This is an open-access article distributed under the terms of the Creative Commons Attribution License.The normal aging process is associated with stereotyped changes in gene expression, but the regulators responsible for these age-dependent changes are poorly understood. Using a novel genomics approach, we identified HOX co-factor unc-62 (Homothorax) as a developmental regulator that binds proximal to age-regulated genes and modulates lifespan. Although unc-62 is expressed in diverse tissues, its functions in the intestine play a particularly important role in modulating lifespan, as intestine-specific knockdown of unc-62 by RNAi increases lifespan. An alternatively-spliced, tissue-specific isoform of unc-62 is expressed exclusively in the intestine and declines with age. Through analysis of the downstream consequences of unc-62 knockdown, we identify multiple effects linked to aging. First, unc-62 RNAi decreases the expression of yolk proteins (vitellogenins) that aggregate in the body cavity in old age. Second, unc-62 RNAi results in a broad increase in expression of intestinal genes that typically decrease expression with age, suggesting that unc-62 activity balances intestinal resource allocation between yolk protein expression and fertility on the one hand and somatic functions on the other. Finally, in old age, the intestine shows increased expression of several aberrant genes; these UNC-62 targets are expressed predominantly in neuronal cells in developing animals, but surprisingly show increased expression in the intestine of old animals. Intestinal expression of some of these genes during aging is detrimental for longevity; notably, increased expression of insulin ins-7 limits lifespan by repressing activity of insulin pathway response factor DAF-16/FOXO in aged animals. These results illustrate how unc-62 regulation of intestinal gene expression is responsible for limiting lifespan during the normal aging process.ELVN has been supported by the Stanford Genome Training Program and the Smith Fellowship (Stanford Graduate Fellowships program). Research in the laboratory of SKK is supported by the NHGRI, NIGMS, NIA, and the Glenn Foundation. Some strains were provided by the Caenorhabditis Genetics Center, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440).Peer Reviewe

Influence of fiber content and annealing on the thermal properties of a bamboo fiber reinforced biocomposite material

In the present investigation, the effects of fiber content (20, 30 and 40 wt%) and annealing heat treatment on the thermal properties of the biocomposite material formed by an isotactic polypropylene polymeric matrix (iPP) reinforced with short bamboo fibers (PP/BF) were studied. The coupling agent was iPP with grafting of maleic anhydride molecules (MAPP). The Differential Scanning Calorimetry (DSC) technique was used to determine the melting temperature (Tm), crystallization temperature (Tc), and degree of crystallinity (Xc) of the biocomposites. The melting temperature of pure PP was not significantly affected by the presence of bamboo fibers. However, the degree of crystallinity of PP increased with fiber content. The annealing heat treatment caused an increase in the Tm of pure PP and PP/BF. The composite with 20 wt% fiber content (PP/20F) annealed achieved the highest Xc (37,47 %). The Tc of polypropylene increased with the presence of fibers, and the PP/20F composite reached the highest value (115 °C). Also, the study of the Tm of the biocomposites in amorphous state was carried out, and it was observed that the sample with a fiber content of 30 wt% presented an endothermic peak at a temperature of approximately 168 °C.En la presente investigación se estudiaron los efectos del contenido de fibra (20, 30 y 40 wt %) y el tratamiento térmico de recocido sobre las propiedades térmicas del material biocompuesto formado por una matriz polimérica de polipropileno isotáctico (iPP) reforzada con fibras cortas de bambú (PP/FB). El agente de acople fue iPP con injertos de moléculas de anhídrido maleico (MAPP). Se empleó la técnica de calorimetría diferencial de barrido (DSC) para determinar la temperatura de fusión (Tm), la temperatura de cristalización (Tc) y el grado de cristalinidad (Xc) de los biocompuestos. La temperatura de fusión del PP puro no se afectó de manera significativa por la presencia de las fibras de bambú; sin embargo, el grado de cristalinidad del PP aumentó con el contenido de fibra. El tratamiento térmico de recocido provocó un aumento de la Tm del PP puro y del PP/FB. El compuesto con 20 wt% de contenido de fibra (PP/20F) recocido alcanzó el mayor Xc (37,47 %). La Tc del polipropileno aumentó con la presencia de las fibras, y el compuesto PP/20F alcanzó el mayor valor (115 °C). También, se realizó el estudio de la Tm de los biocompuestos en estado amorfo, y se obtuvo que la muestra con un contenido de fibra de 30 wt% presentó un pico endotérmico a una temperatura aproximada de 168 °C

Advantageous Fungi against Parasites Transmitted through Soil

Although many fungal specimens are responsible for human and/or animal infection, other species are advantageous for preventing the infection by soil-transmitted zoonotic parasites. Infection occurs by the accidental ingestion of parasitic stages (cysts, oocysts, eggs, and larvae), their active penetration through the skin or through direct contact. Numerous species of helminths develop an external phase in the soil where the infective stages are attained, thus mammals become infected when grazing, drinking, or accidentally. Ectoparasites as ticks perform also in the soil the phase from egg to larva. Different soil saprophytic fungi that turn into predatory agents when parasitic stages are near have been isolated and described. These species are capable of destroying the pathogens or irreversibly decreasing their viability, providing thus a very interesting and sustainable tool to reduce environmental contamination by pathogenic agents. In the last year, a profound knowledge on the most appropriate fungal species, together with the proper way to disseminate them, has been acquired

Wind and turbulence relationship with NO2 in an urban environment: a fine-scale observational analysis

It is well known that meteorology plays an important role in the diurnal evolution of pollutants, especially those variables related to atmospheric dispersion. Most studies typically relate the concentration of some pollutants with wind speed from conventional anemometers; however, the use of turbulence variables is less common, in part because the needed instruments are not so typical in standard air-quality stations. In this work, we compare the wind-NO2 relationship with the turbulence-NO2 one using observational data from two field campaigns developed in Madrid (winter and summer). The turbulence data comes from two sonic anemometers deployed at different locations: one close to the street and the other at the top of a nearby tall building. The results indicate that the turbulent variables correlate better with the pollutant concentration than the wind speed when using data from the street sonic, while the contrary is found when using the terrace sonic. These data are also used to perform a fine-scale analysis of the turbulent diffusion-NO2 behaviour during a very-stable period in winter, when the turbulence typically shows a decrease in the evening transition, causing the highestNO2 concentrations. Conversely, under these conditions, the formation of thermally-driven winds is also favoured later in the night, which favours the pollutant dispersion and cleaning of the air. The important role of these dynamical processes on the NO2 evolution highlights the importance of the correct understanding of small-scale atmospheric processes to understand their relationship with the concentration of pollutants

Variable Pathogenicity Determines Individual Lifespan in Caenorhabditis elegans

A common property of aging in all animals is that chronologically and genetically identical individuals age at different rates. To unveil mechanisms that influence aging variability, we identified markers of remaining lifespan for Caenorhabditis elegans. In transgenic lines, we expressed fluorescent reporter constructs from promoters of C. elegans genes whose expression change with age. The expression levels of aging markers in individual worms from a young synchronous population correlated with their remaining lifespan. We identified eight aging markers, with the superoxide dismutase gene sod-3 expression being the best single predictor of remaining lifespan. Correlation with remaining lifespan became stronger if expression from two aging markers was monitored simultaneously, accounting for up to 49% of the variation in individual lifespan. Visualizing the physiological age of chronologically-identical individuals allowed us to show that a major source of lifespan variability is different pathogenicity from individual to individual and that the mechanism involves variable activation of the insulin-signaling pathway

Endoscopic Submucosal Dissection. Sociedad Española de Endoscopia Digestiva (SEED) clinical guideline

The reason to write this guideline is to familiarize Spanish endoscopists and gastroenterologists not only with the general indications of the procedure and possible complications but also the dedicated tools

Mutational spectrum of GNAL, THAP1 and TOR1A genes in isolated dystonia: study in a population from Spain and systematic literature review

[Objective] We aimed to investigate the prevalence of TOR1A, GNAL and THAP1 variants as the cause of dystonia in a cohort of Spanish patients with isolated dystonia and in the literature.[Methods] A population of 2028 subjects (including 1053 patients with different subtypes of isolated dystonia and 975 healthy controls) from southern and central Spain was included. The genes TOR1A, THAP1 and GNAL were screened using a combination of high-resolution melting analysis and direct DNA resequencing. In addition, an extensive literature search to identify original articles (published before 10 August 2020) reporting mutations in TOR1A, THAP1 or GNAL associated to dystonia was performed.[Results] Pathogenic or likely pathogenic variants in TOR1A, THAP1 and GNAL were identified in 0.48%, 0.57% and 0.29% of our patients, respectively. Five patients carried the variation p.Glu303del in TOR1A. A very rare variant in GNAL (p.Ser238Asn) was found as a putative risk factor for dystonia. In the literature, variations in TOR1A, THAP1 and GNAL accounted for about 6%, 1.8% and 1.1% of published dystonia patients, respectively.[Conclusions] There is a different genetic contribution to dystonia of these three genes in our patients (about 1.3% of patients) and in the literature (about 3.6% of patients), probably due the high proportion of adult-onset cases in our cohort. As regards age at onset, site of dystonia onset, and final distribution, in our population there is a clear differentiation between DYT-TOR1A and DYT-GNAL, with DYT-THAP1 likely to be an intermediate phenotype.This work was supported by the Carlos III Health Institute-European Regional Development Fund (ISCIII-FEDER) [PI14/01823, PI16/01575, PI18/01898, PI19/01576], the Andalusian Regional Ministry of Economics, Innovation, Science and Employment [CVI-02526, CTS-7685], the Andalusian Regional Ministry of Health and Welfare [PI-0741-2010, PI-0471-2013, PE-0210-2018, PI-0459-2018, PE-0186-2019], and the Alicia Koplowitz and Mutua Madrileña Foundations. Pilar Gómez-Garre was supported by the "Miguel Servet" program [MSII14/00018] (from ISCIII-FEDER) and “Nicolás Monardes” program [C-0048-2017] (from the Andalusian Regional Ministry of Health). Silvia Jesús was supported by the "Juan Rodés" program [B-0007-2019] and Daniel Macías-García by the “Río Hortega” program [CM18/00142] (both from ISCIII-FEDER). María Teresa Periñán was supported by the Spanish Ministry of Education [FPU16/05061]. Cristina Tejera was supported by VPPI-US from the University of Seville.Peer reviewe

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe