Analysis of LINE1 Retrotransposons in Huntington’s Disease

Transposable elements (TEs) are mobile genetic elements that made up about half the human genome. Among them, the autonomous non-LTR retrotransposon long interspersed nuclear element-1 (L1) is the only currently active TE in mammals and covers about 17% of the mammalian genome. L1s exert their function as structural elements in the genome, as transcribed RNAs to influence chromatin structure and as retrotransposed elements to shape genomic variation in somatic cells. L1s activity has been shown altered in several diseases of the nervous system. Huntington disease (HD) is a dominantly inherited neurodegenerative disorder caused by an expansion of a CAG repeat in the HTT gene which leads to a gradual loss of neurons most prominently in the striatum and, to a lesser extent, in cortical brain regions. The length of the expanded CAG tract is related to age at disease onset, with longer repeats leading to earlier onset. Here we carried out bioinformatic analysis of public RNA-seq data of a panel of HD mouse models showing that a decrease of L1 RNA expression recapitulates two hallmarks of the disease: it correlates to CAG repeat length and it occurs in the striatum, the site of neurodegeneration. Results were then experimentally validated in HttQ111 knock-in mice. The expression of L1-encoded proteins was independent from L1 RNA levels and differentially regulated in time and tissues. The pattern of expression L1 RNAs in human HD post-mortem brains showed similarity to mouse models of the disease. This work suggests the need for further study of L1s in HD and adds support to the current hypothesis that dysregulation of TEs may be involved in neurodegenerative diseases

Effects of 12-week combined training versus high intensity interval training on cardiorespiratory fitness, body composition and fat metabolism in obese male adults

Background: /Objectives: A weekly combination of a high volume of moderate-intensity continuous training (MICT) with a low volume of high-intensity interval training (HIIT) provides important improvements in body composition and physical capacities in individuals with obesity. However, previous studies did not determine the weekly proportions of HIIT and MICT a priori. This study aimed to investigate changes in body composition, physical capacities and the fat oxidation rate in obese male adults by comparing a combination of MICT and HIIT, called combined training (COMB), with HIIT for a 12-week period. Methods: Thirty-four obese male adults (mean age: 39.4 ± 7.0 y; mean body mass index [BMI] 34.0 ± 4.2 kg m−2) participated in this study (n = 18 for COMB, n = 16 HIIT), attending ∼ 36 training sessions. The COMB group performed 3 repetitions of 2 min at 95% of peak oxygen uptake (V'O2 peak) (e.g., HIIT ≤20%), followed by 30 min at 60% of VO2 peak (e.g., MICT ≥80%). The HIIT group performed 5–7 repetitions of 2 min at 95% of VO2 peak. At baseline (PRE) and at the end of the training period (POST), body composition, VO2 peak, and the fat oxidation rate were measured. The two training programs were equivalent in caloric expenditure. Results: At POST, body mass (BM) and fat mass (FM) decreased by a mean of 3.09 ± 3.21 kg and 3.90 ± 2.40 kg, respectively (P < 0.05), in both groups and V'O2 peak increased in both groups by a mean of 0.47 ± 0.34 L min−1 (P < 0.05). The maximal fat oxidation rate increased similarly in both groups from 0.32 ± 0.05 to 0.36 ± 0.06 g min−1 (P < 0.05). Conclusion: COMB training represents a viable alternative to HIIT to improve anthropometric characteristics, physical capacities and fat oxidation in obese male adults

Quantitative and Qualitative tools for a physical education program that increases inclusion of children with disabilities

Aim: New technologies in PE provide children with the opportunity (a) to improve motor learning and self-efficacy, (b) model and stucture new prospective of the educational process (Clapham et al.,2015). The purpose of this study is to evalute and compare (a) the development of motor coordination of primary school\u2019s children in relation to BMI, (b) effects of strategies that utilize interactive video game technology (T0 vs T1), (c) enjoyment and physical selfefficacy between EG and CG. Methods: The study has been conducted in a primary school of Puglia, Italy. The sample includes 65 children, separated into two groups in relation to sex and BMI: EG (M: 22, age,10.09 \ub1 0.30; F:19, age 10.10 \ub1 0.31) and CG (M: 12, age, 10 \ub1 0.42; F: 12, age 10 \ub1 0.0). The experimental program consists of 10 lessons, using specialised interactive video game technology to point out unusual motor responses. For the CG has been used teaching styles of production. The following tests have been proposed before and after the intervention: MOBAK 5 (Hermann and Seelig 2016), PSP_C (physical self-efficacy) and PACES (enjoyment). Results: Besides the descriptive statistics (M \ub1 DS), T-test was used in order to highlights significative differences between T0-T1, indipendently from sex differences. The significance value was set at p\0.05. Data analysis revealed significative differences between EG for boys and girls about (a) Control Object and Self-Movement (p\0.05); (b) and physical self efficacy scale (p\0.05). Conclusions: The use of modern technologies and different teaching styles in PE promote motor learning and self-efficacy in children. The trail of new and different instruments are needed to enhance educational environments and develop intrinsic motivation to motor activities. References 1. Clapham, E.D. et al. (2015). The Physical Educator. 72,1, 102\u2013116. 2. Hermann, C. & Seelig, H. (2016). Sportwissenschaft

A Simplified Thermal Model to Control the Energy Fluxes and to Improve the Performance of Buildings

Abstract The article describes an accurate and suitable simplified tool aimed at evaluating, controlling and managing heat energy fluxes in buildings. The focus is the development of a Resistance-Capacitance (RC) thermal model able to represent the envelope thermal inertia on an hourly time basis. The single RC module simulates the thermal response of a single opaque or transparent element of the envelope. Each module consists of 3 Resistances and 2 Capacitances and is connected to the other modules by thermal nodes and coupled to an air internal temperature node in order to obtain a realistic exemplification of the specific boundary conditions and gains distribution in the conditioned space. The differential balance equations in each node have been solved with an explicit numerical method using Modelica simulation tool. A monitoring campaign was carried out on an outdoor test cell in order to observe the real thermal dynamic behaviour and the real hourly energy needs. The results of the model have been compared with the experimental collected data. The results are presented in terms of temperatures and heating power hourly profiles and cumulative daily energy needs. Finally the Bland-Altmann plot has been used to verify the accuracy and the shortcomings of the proposed thermal model

Pharmacological characterization of a new Ca2+ sensitizer

The benzimidazole molecule was modified to synthesize a Ca(2+) sensitizer devoid of additional effects associated with Ca(2+) overload. Newly synthesized compounds, termed 1, 2, 3, 4, and 5, were evaluated in spontaneously beating and electrically driven atria from reserpine-treated guinea pigs. Compound 3 resulted as the most effective positive inotropic agent, and experiments were performed to study its mechanism of action. In spontaneously beating atria, the inotropic effect of 3 was concentration-dependent (3.0 microM-0.3 mM). Compound 3 was more potent and more active than the structurally related Ca(2+) sensitizers sulmazole and caffeine, but unlike them it did not increase the heart rate. In electrically driven atria, the inotropic activity of 3 was well preserved and it was not inhibited by propranolol, prazosin, ranitidine, pyrilamine, carbachol, adenosine deaminase, or ruthenium red. At high concentrations (0.1-1.0 mM) 3 inhibited phosphodiesterase-III, whereas it did not affect Na(+)/K(+)-ATPase, sarcolemmal Ca(2+)-ATPase, Na(+)/Ca(2+) exchange carrier, or sarcoplasmic reticulum Ca(2+) pump activities of guinea pig heart. In skinned fibers obtained from guinea pig papillary muscle and skeletal soleus muscle, compound 3 (0.1 mM, 1 mM) shifted the pCa/tension relation curve to the left, with no effect on maximal tension and no signs of toxicity. Compound 3 did not influence the basal or raised tone of guinea pig isolated aorta rings, whose cells do not contain the contractile protein troponin. The present results indicate that the inotropic effect of compound 3 seems to be primarily sustained by sensitization of the contractile proteins to Ca(2+)

A randomized, placebo-controlled, phase II study of obeticholic acid for primary sclerosing cholangitis

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