MicroRNA expression patterns in post-natal mouse skeletal muscle development

BACKGROUND: MiRNAs are essential regulators of skeletal muscle development and homeostasis. To date, the role and regulation of miRNAs in myogenesis have been mostly studied in tissue culture and during embryogenesis. However, little information relating to miRNA regulation during early post-natal skeletal muscle growth in mammals is available. Using a high-throughput miRNA qPCR-based array, followed by stringent statistical and bioinformatics analysis, we describe the expression pattern and putative role of 768 miRNAs in the quadriceps muscle of mice aged 2 days, 2 weeks, 4 weeks and 12 weeks. RESULTS: Forty-six percent of all measured miRNAs were expressed in mouse quadriceps muscle during the first 12 weeks of life. We report unprecedented changes in miRNA expression levels over time. The expression of a majority of miRNAs significantly decreased with post-natal muscle maturation in vivo. MiRNA clustering identified 2 subsets of miRNAs that are potentially involved in cell proliferation and differentiation, mainly via the regulation of non-muscle specific targets. CONCLUSION: Collective miRNA expression in mouse quadriceps muscle is subjected to substantial levels of regulation during the first 12 weeks of age. This study identified a new suite of highly conserved miRNAs that are predicted to influence early muscle development. As such it provides novel knowledge pertaining to post-natal myogenesis and muscle regeneration in mammals

Effects of breaking up sitting on adolescents\u27 postprandial glucose after consuming meals varying in energy: a cross-over randomised trial

ObjectivesTo explore the impact of uninterrupted sitting versus sitting with resistance-type activity breaks on adolescents’ postprandial glucose responses while consuming a diet varying in energy.DesignCross-over randomised trial.MethodsThirteen healthy participants (16.4 ± 1.3 years) completed a four-treatment cross-over trial: (1) uninterrupted sitting + high-energy diet; (2) sitting with breaks + high-energy diet; (3) uninterrupted sitting + standard-energy diet; and (4) sitting with breaks + standard-energy diet. For all four conditions, two identical meals were consumed; at 0 h and 3 h. A continuous glucose monitoring system (CGM) recorded interstitial glucose concentrations every five minutes. Linear mixed models examined differences in glucose positive incremental area under the curve (iAUC) and total AUC between the sitting and diet conditions for the first meal, second meal and entire trial period.ResultsCompared to the uninterrupted sitting conditions, the breaks condition elicited a 36.0 mmol/L/h (95%CI 6.6–65.5) and 35.9 mmol/L/h (95%CI 6.6–65.5) lower iAUC response after the first and second meal, respectively, but not for the entire trial period or for total AUC. Compared to the standard-energy diet, the high-energy diet elicited a 55.0 mmol/L/h (95%CI 25.8–84.2) and 75.7 mmol/L/h (95%CI 8.6–142.7) higher iAUC response after the first meal and entire trial, respectively. Similar response to the high-energy diet were observed for total AUC.ConclusionsAccording to iAUC, interrupting sitting had a significant effect on lowering postprandial glucose for both dietary conditions, however, it was not significant when examining total AUC. Larger studies are needed to confirm these findings

Controlo químico de infestantes

Uma planta é considerada infestante quando nasce espontaneamente num local e momento indesejados, podendo interferir negativamente com a cultura instalada. As infestantes competem com as culturas para o espaço, a luz, água e nutrientes, podendo atrasar e prejudicar as operações de colheita, depreciar o produto final e assegurarem a reinfestação nas culturas seguintes. Dado o modo de propagação diferenciado das diversas espécies de infestantes, com as anuais a propagarem-se por semente e as perenes ou vivazes a assegurarem a sua propagação através de órgãos vegetativos (rizomas, bolbos, tubérculos, etc.), assim, também o seu controlo quer químico, quer mecânico terá que ser diferenciado, ou seja, para controlar infestantes anuais será suficiente destruir a sua parte aérea, enquanto para controlar infestantes perenes teremos que destruir os seus órgãos reprodutivos. O controlo de infestantes poderá ser químico, através da utilização de herbicidas, ou mecânico pela utilização de alfaias agrícolas, tais como a charrua de aivecas, a charrua de discos, a grade de discos, o escarificador e a fresa. Quando a técnica utilizada na instalação das culturas é a sementeira directa, o controlo das infestantes terá que ser obrigatoriamente químico, enquanto se o recurso à mobilização do solo for a técnica mais utilizada (sistema de mobilização tradicional ou sistema de mobilização reduzida), o controlo das infestantes tanto poderá ser químico como mecânico. Neste trabalho iremos abordar apenas, o controlo químico de infestantes

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks : The GR@ACE project

Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. Results: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. Discussion: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Representaciones de los jóvenes en torno a la salud: un estudio exploratorio de perfiles

Área de Salud, Economía y Socieda

Adolescents and health. Group-building based on representations of health and disease

Área de Salud, Economía y Socieda

The influence of an essential fatty acid deficient-diet on the reproductive performance of female rats

Several parameters of the reproductive function were studied in albino rats of the Wistar strain fed an essential fatty acid-deficient (EFAD) diet, a linoleic acid-sufficient (EFAS) diet or a commercial diet (CD). The frequency of irregular estrous cycles, with an increased incidence of prolonged diestrus, was significantly higher in EFAD and EFAS groups than in the CD group. There were no significant differences between EFAD and EFAS rats in any of the estrous cycle parameters studied. The EFAD rats showed the following changes in reproductive performance in respect to EFAS and CD dams: prolonged period of gestation, reduced litter size and increased pup mortality during delivery and the first 48 neonatal hours. From this time to weaning, EFAD and EFAS pups had a similar rate of mortality and were different in this respect from the CD group. These results support previous reports indicating that linoleic acid is essential to the maintenance of normal pregnancy and the survival of newborn rats. Nevertheless, we cannot conclude that impairment of the estrous cycle and sucking mortality until weaning were primarily due to the absence of linoleic acid in the maternal diet. The possible role of alpha-linolenic acid in the reproductive is discussed

Intelligence studies on argentinian babies: The Argentine scale of sensory motor intelligence

El objetivo de este trabajo es presentar una prueba que permite evaluar el comportamiento de nuestros lactantes en el área del desarrollo cognoscitivo. Se distinguen dos grandes períodos en el desarrollo de la inteligencia: antes y después de la constitución de la función simbólica (o semiótica), apareciendo ésta última entre los 16 y 20 meses. El primer período se denomina inteligencia sensorio-motriz. La inteligencia sensorio-motriz es la capacidad de resolver los problemas a partir de actividades en las que intervienen sobre todo la percepción, las actitudes, el tono y los movimientos sin evocaciones simbólicas, es decir antes de la aparición del lenguaje verbal. Se elaboró la Escala Argentina de Inteligencia Sensorio motriz (EAIS) para bebés de 6 a 24 meses. Dicha Escala fue construida con 323 bebés argentinos con el objetivo de conocer el nivel de desarrollo mental en el período preverbal, obtener valores estándares de referencia de la población argentina y contribuir con un instrumento útil y eficaz para el diagnóstico del desarrollo intelectual de bebés de 6 a 24 meses de edad en la detección de trastornos en el área cognitiva. Dada la vulnerabilidad del bebé, su dependencia con los adultos, la complejidad de los procesos de maduración y desarrollo y la determinación del medio ambiente, utilizar pruebas adaptadas o construidas con bebés argentinos nos permite contar con instrumentos propios para la evaluación de nuestra población y enriquecer la perspectiva bio-sico-social de la primera infancia. Palabras clave: inteligencia sensoriomotriz, desarrollo cognoscitivo.The purpose of this work is to present a test, which allows the assessment of the behavior of our infants within the cognoscitive development area. There are two main periods in the development of intelligence: before and after the constitution of the symbolic (or semiotic) function, which appears within the age of 16 and 20 months old. The first period is called sensory-motor intelligence. The sensory motor intelligence is the ability to solve problems through activities that involve perception, attitudes, tone and movements without symbolic evocations -that is, before the verbal language appears. The Argentine Scale of Sensory Motor Intelligence (EAIS) was created for babies aged from 6 to 24 months old. The scale was developed with 323 Argentine babies in order to determine the level of mental development during the non-verbal period, obtain standard figures of reference of the Argentine population, contribute with a useful as well as effective tool to diagnose the intellectual development of Argentine babies aged from 6 to 24 months old, and detect cognitive disorders. Given the vulnerability of infants, their dependence on adults, the complexity of maturity and development processes, and the environment, the use of tests adapted or built with Argentine babies allow us to obtain standard reference values of the Argentine population to assess the intellectual development in 6 to 24 month old babies and diagnose cognitive disorders.Fil: Oiberman, Alicia Juana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Centro Interdisciplinario de Investigaciones en Psicología Matemática y Experimental Dr. Horacio J. A. Rimoldi; ArgentinaFil: Orellana, Liliana C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Centro Interdisciplinario de Investigaciones en Psicología Matemática y Experimental Dr. Horacio J. A. Rimoldi; ArgentinaFil: Mansilla, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Centro Interdisciplinario de Investigaciones en Psicología Matemática y Experimental Dr. Horacio J. A. Rimoldi; Argentin