Mitochondrial dynamics and quality control in Huntington's disease

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by polyglutamine expansion mutations in the huntingtin protein. Despite its ubiquitous distribution, expression of mutant huntingtin (mHtt) is particularly detrimental to medium spiny neurons within the striatum. Mitochondrial dysfunction has been associated with HD pathogenesis. Here we review the current evidence for mHtt-induced abnormalities in mitochondrial dynamics and quality control, with a particular focus on brain and neuronal data pertaining to striatal vulnerability. We address mHtt effects on mitochondrial biogenesis, protein import, complex assembly, fission and fusion, mitochondrial transport, and on the degradation of damaged mitochondria via autophagy (mitophagy). For an integrated perspective on potentially converging pathogenic mechanisms, we also address impaired autophagosomal transport and abnormal mHtt proteostasis in HD

Numerical analysis of the in-plane behaviour of three-leaf stone masonry panels consolidated with grout injection

This paper presents the calibration procedures of a numerical model based on the results of uniaxial and shear-compression tests on three-leaf stone masonry panels in scale 1:1 and 2:3, both in original and injected conditions. The stone masonry panels were simulated considering a macro-scale approach, where a nonlinear continuum damage model with distinct scalar damage parameters for tension and compression, implemented in the finite element software Cast3 M, was used to simulate the walls behaviour. The main goal of this paper is, first to calibrate, based on the obtained experimental results and using a phenomenological calibration strategy, a single set of parameters that represent a macroscopic constitutive law, by type of masonry, which is able to describe the different experimental tests. Afterwards, a parametric study was performed using the calibrated material laws, with the scope of assessing the influence of vertical pre-compression, slenderness and material strength on failure mechanisms and on different performance parameters such as the maximum load and displacement capacity (drift at ultimate state and drift at maximum load), for each type of masonry condition

Mechanical study of PLA-PCL fibers during in vitro degradation

The aliphatic polyesters are widely used in biomedical applications since they are susceptible to hydrolytic and/or enzymatic chain cleavage, leading to alpha-hydroxyacids, generally metabolized in the human body. This is particularly useful for many biomedical applications, especially, for temporary mechanical supports in regenerative medical devices. Ideally, the degradation should be compatible with the tissue recovering. In this work, the evolution of mechanical properties during degradation is discussed based on experimental data. The decrease of tensile strength of PLA-PCL fibers follows the same trend as the decrease of molecular weight, and so it can also be modeled using a first order equation. For each degradation stage, hyperelastic models such as Neo-Hookean, Mooney-Rivlin and second reduced order, allow a reasonable approximation of the material behavior. Based on this knowledge, constitutive models that describe the mechanical behavior during degradation are proposed and experimentally validated. The proposed theoretical models and methods may be adapted and used in other biodegradable materials, and can be considered fundamental tools in the design of regenerative medical devices where strain energy is an important requirement, such as, for example, ligaments, cartilage and stents

Effects of an irregular bedtime schedule on sleep quality, daytime sleepiness, and fatigue among university students in Taiwan

<p>Abstract</p> <p>Background</p> <p>An irregular bedtime schedule is a prevalent problem in young adults, and could be a factor detrimentally affecting sleep quality. The goal of the present study was to explore the association between an irregular bedtime schedule and sleep quality, daytime sleepiness, and fatigue among undergraduate students in Taiwan.</p> <p>Methods</p> <p>A total of 160 students underwent a semi-structured interview and completed a survey comprising 4 parts: Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), and a rating of irregular bedtime frequency. Participants were grouped into 3 groups in terms of irregular bedtime frequency: low, intermediate, or high according to their 2-week sleep log. To screen for psychological disorders or distress that may have affected responses on the sleep assessment measures, the Chinese health questionnaire-12 (CHQ-12) was also administered.</p> <p>Results</p> <p>We found an increase in bedtime schedule irregularity to be significantly associated with a decrease in average sleep time per day (Spearman r = -0.22, p = 0.05). Multivariate regression analysis revealed that irregular bedtime frequency and average sleep time per day were correlated with PSQI scores, but not with ESS or FSS scores. A significant positive correlation between irregular bedtime frequency and PSQI scores was evident in the intermediate (partial r = 0.18, p = 0.02) and high (partial r = 0.15, p = 0.05) frequency groups as compared to low frequency group.</p> <p>Conclusion</p> <p>The results of our study suggest a high prevalence of both an irregular bedtime schedule and insufficient sleep among university students in Taiwan. Students with an irregular bedtime schedule may experience poor sleep quality. We suggest further research that explores the mechanisms involved in an irregular bedtime schedule and the effectiveness of interventions for improving this condition.</p

Planet formation in Binaries

Spurred by the discovery of numerous exoplanets in multiple systems, binaries have become in recent years one of the main topics in planet formation research. Numerous studies have investigated to what extent the presence of a stellar companion can affect the planet formation process. Such studies have implications that can reach beyond the sole context of binaries, as they allow to test certain aspects of the planet formation scenario by submitting them to extreme environments. We review here the current understanding on this complex problem. We show in particular how each of the different stages of the planet-formation process is affected differently by binary perturbations. We focus especially on the intermediate stage of kilometre-sized planetesimal accretion, which has proven to be the most sensitive to binarity and for which the presence of some exoplanets observed in tight binaries is difficult to explain by in-situ formation following the "standard" planet-formation scenario. Some tentative solutions to this apparent paradox are presented. The last part of our review presents a thorough description of the problem of planet habitability, for which the binary environment creates a complex situation because of the presence of two irradation sources of varying distance.Comment: Review chapter to appear in "Planetary Exploration and Science: Recent Advances and Applications", eds. S. Jin, N. Haghighipour, W.-H. Ip, Springer (v2, numerous typos corrected

The Formation of the First Massive Black Holes

Supermassive black holes (SMBHs) are common in local galactic nuclei, and SMBHs as massive as several billion solar masses already exist at redshift z=6. These earliest SMBHs may grow by the combination of radiation-pressure-limited accretion and mergers of stellar-mass seed BHs, left behind by the first generation of metal-free stars, or may be formed by more rapid direct collapse of gas in rare special environments where dense gas can accumulate without first fragmenting into stars. This chapter offers a review of these two competing scenarios, as well as some more exotic alternative ideas. It also briefly discusses how the different models may be distinguished in the future by observations with JWST, (e)LISA and other instruments.Comment: 47 pages with 306 references; this review is a chapter in "The First Galaxies - Theoretical Predictions and Observational Clues", Springer Astrophysics and Space Science Library, Eds. T. Wiklind, V. Bromm & B. Mobasher, in pres