Hypoxia and muscle maintenance regulation: implications for chronic respiratory disease

PURPOSE OF REVIEW: Muscle wasting and impaired muscle oxidative metabolism are common extrapulmonary features of chronic respiratory failure (CRF) that significantly increase disease burden. This review aims to address the question whether hypoxia, an obvious consequence of this disease, actually plays a causal role in these muscle impairments. RECENT FINDINGS: In experimental models, a causal role for hypoxia in muscle atrophy and metabolic impairments has clearly been shown. Although the hypoxia-inducible factors and nuclear factor kappa B are putative mediators of these hypoxia-induced alterations, their true involvement remains to be proven. Molecular signatures of disrupted regulation of muscle mass and oxidative metabolism observed in these experimental models also have been shown in muscles of patients suffering from CRF, suggestive of but not conclusive for a causal role of hypoxia. Therapies, including but not restricted to those aimed at alleviating hypoxia, have been shown to partially but not completely restore muscle mass and oxidative capacity in CRF patients, which may imply an additive effect of nutritional modulation of substrate metabolism. SUMMARY: Although hypoxia clearly affects skeletal muscle maintenance, it remains to be confirmed whether and by which underlying molecular mechanisms hypoxia is causally involved in CRF-related muscle atrophy and impaired oxidative capacity

Mechanics of Granular Materials (MGM)

The constitutive behavior of uncemented granular materials such as strength, stiffness, and localization of deformations are to a large extend derived from interparticle friction transmitted between solid particles and particle groups. Interparticle forces are highly dependent on gravitational body forces. At very low effective confining pressures, the true nature of the Mohr envelope, which defines the Mohr-Coulomb failure criterion for soils, as well as the relative contribution of each of non-frictional components to soil's shear strength cannot be evaluated in terrestrial laboratories. Because of the impossibility of eliminating gravitational body forces on earth, the weight of soil grains develops interparticle compressive stresses which mask true soil constitutive behavior even in the smallest samples of models. Therefore the microgravity environment induced by near-earth orbits of spacecraft provides unique experimental opportunities for testing theories related to the mechanical behavior of terrestrial granular materials. Such materials may include cohesionless soils, industrial powders, crushed coal, etc. This paper will describe the microgravity experiment, 'Mechanics of Granular Materials (MGM)', scheduled to be flown on Space Shuttle-MIR missions. The paper will describe the experiment's hardware, instrumentation, specimen preparation procedures, testing procedures in flight, as well as a brief summary of the post-mission analysis. It is expected that the experimental results will significantly improve the understanding of the behavior of granular materials under very low effective stress levels

A New Swiss Federal Act on Gambling: From Missed Opportunities towards a Public Health Approach?

In January 2019, a new Swiss Federal Act on Gambling (Loi federal de jeux d'argent: LJAr) entered into force following a vote by the Swiss electorate. Intended to modernize and harmonize previous law and open the market for online casinos; the new regulations have highlighted the need for a comprehensive monitoring system. The present article outlines work undertaken by experts within the field to identify and elaborate the first steps towards developing such a monitoring system. This work includes the mapping of institutional actors and draft conceptualization of an impact model, including structural (i.e., prevention and intervention-based components), process (means), and outcomes (effect) indicators. Initial estimations of effective access to indicators and their perceived priority for data gathering are also described. Subsequent steps necessary for implementation of this public health approach for gambling are considered including grey areas for future action

MuSCA: A multi-scale source-sink carbon allocation model to explore carbon allocation in plants. An application to static apple tree structures

Background and aims: Carbon allocation in plants is usually represented at a topological scale, specific to each model. This makes the results obtained with different models, and the impact of their scales of representation, difficult to compare. In this study, we developed a multi-scale carbon allocation model (MuSCA) that allows the use of different, user-defined, topological scales of a plant, and assessment of the impact of each spatial scale on simulated results and computation time. Methods: Model multi-scale consistency and behaviour were tested on three realistic apple tree structures. Carbon allocation was computed at five scales, spanning from the metamer (the finest scale, used as a reference) up to first-order branches, and for different values of a sap friction coefficient. Fruit dry mass increments were compared across spatial scales and with field data. Key Results: The model was able to represent effects of competition for carbon assimilates on fruit growth. Intermediate friction parameter values provided results that best fitted field data. Fruit growth simulated at the metamer scale differed of ~1 % in respect to results obtained at growth unit scale and up to 60 % in respect to first order branch and fruiting unit scales. Generally, the coarser the spatial scale the more predicted fruit growth diverged from the reference. Coherence in fruit growth across scales was also differentially impacted, depending on the tree structure considered. Decreasing the topological resolution reduced computation time by up to four orders of magnitude. Conclusions: MuSCA revealed that the topological scale has a major influence on the simulation of carbon allocation. This suggests that the scale should be a factor that is carefully evaluated when using a carbon allocation model, or when comparing results produced by different models. Finally, with MuSCA, trade-off between computation time and prediction accuracy can be evaluated by changing topological scales

Supramolecular assemblies involving metal organic ring interactions: Heterometallic Cu(II)-Ln(III) two dimensional coordination polymers

Three isostructural two-dimensional coordination polymers of the general formula [Ln2(CuL)3(H2O)9]$5.5H2O, where Ln is La (1), Nd (2), and Gd (3), have been synthesized and isolated from aqueous solutions and their single-crystal structures determined by X-ray diffraction. The supramolecular interaction between the non-aromatic metallorings plays an important role in stabilizing the structure of these compounds. The thermal stability, reversible solvent uptake, electronic properties and magnetic studies of these compounds are also reported

Soil mechanical properties at the Apollo 14 site

The Apollo 14 lunar landing provided a greater amount of information on the mechanical properties of the lunar soil than previous missions because of the greater area around the landing site that was explored and because a simple penetrometer device, a special soil mechanics trench, and the modularized equipment transporter (Met) provided data of a type not previously available. The characteristics of the soil at shallow depths varied more than anticipated in both lateral and vertical directions. While blowing dust caused less visibility impairment during landing than on previous missions, analysis shows that eroded particles were distributed over a large area around the final touchdown point. Measurements on core-tube samples and the results of transporter track analyses indicate that the average density of the soil in the Fra Mauro region is in the range of 1.45 to 1.60 g/cm^3. The soil strength appears to be higher in the vicinity of the site of the Apollo 14 lunar surface experiments package, and trench data suggest that strength increases with depth. Lower-bound estimates of soil cohesion give values of 0.03 to 0.10 kN/m^2, which are lower than values of 0.35 to 0.70 kN/m^2 estimated for soils encountered in previous missions. The in situ modulus of elasticity, deduced from the measured seismic-wave velocity, is compatible with that to be expected for a terrestrial silty fine sand in the lunar gravitational field

Impaired exercise training-induced muscle fiber hypertrophy and Akt/mTOR pathway activation in hypoxemic patients with COPD

Exercise training (ExTr) is largely used to improve functional capacity of chronic obstructive pulmonary disease (COPD) patients. However, ExTr partially restores muscle function in COPD patients, suggesting that confounding factors may limit the efficiency of ExTr. In the present study, we hypothesized that skeletal muscle adaptations triggered by ExTr could be compromised in hypoxemic COPD patients. Vastus lateralis muscle biopsies were obtained from normoxemic (n = 15; resting arterial PO2 = 68.5 +/- 1.5 mm Hg) and hypoxemic (n = 8; resting arterial PO2 = 57.0 +/- 1.0 mm Hg) COPD patients before and after a 2 month-ExTr program. ExTr induced a significant increase in exercise capacity both in normoxemic and hypoxemic COPD patients. However, ExTr increased citrate synthase and lactate dehydrogenase enzyme activities only in skeletal muscle of normoxemic patients. Similarly, muscle fiber cross-sectional area and capillary-to-fiber ratio were only increased in normoxemic patients. Expression of atrogenes (MuRF1, MAFbx/Atrogin-1) and autophagy-related genes (Beclin, LC3, Bnip, Gabarapl) remained unchanged in both groups. The phosphorylation level of Akt (Ser473), GSK-3beta (Ser9) and p70S6k (Thr389), which was non-significantly increased in normoxemic patients in response to ExTr, was significantly decreased in hypoxemic patients. We further showed on C2C12 myotubes that hypoxia completely prevented IGF-1-induced phosphorylation of Akt, GSK-3beta and p70S6K. Together, our observations suggest a role for hypoxemia in the adaptive response of skeletal muscle of COPD patients to ExTr

Short-Term Long Chain Omega3 Diet Protects from Neuroinflammatory Processes and Memory Impairment in Aged Mice

Regular consumption of food enriched in omega3 polyunsaturated fatty acids (ω3 PUFAs) has been shown to reduce risk of cognitive decline in elderly, and possibly development of Alzheimer's disease. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are the most likely active components of ω3-rich PUFAs diets in the brain. We therefore hypothesized that exposing mice to a DHA and EPA enriched diet may reduce neuroinflammation and protect against memory impairment in aged mice. For this purpose, mice were exposed to a control diet throughout life and were further submitted to a diet enriched in EPA and DHA during 2 additional months. Cytokine expression together with a thorough analysis of astrocytes morphology assessed by a 3D reconstruction was measured in the hippocampus of young (3-month-old) and aged (22-month-old) mice. In addition, the effects of EPA and DHA on spatial memory and associated Fos activation in the hippocampus were assessed. We showed that a 2-month EPA/DHA treatment increased these long-chain ω3 PUFAs in the brain, prevented cytokines expression and astrocytes morphology changes in the hippocampus and restored spatial memory deficits and Fos-associated activation in the hippocampus of aged mice. Collectively, these data indicated that diet-induced accumulation of EPA and DHA in the brain protects against neuroinflammation and cognitive impairment linked to aging, further reinforcing the idea that increased EPA and DHA intake may provide protection to the brain of aged subjects

A Multi-Scale Model to explore Carbon Allocation in Plants

International audienceUnderstanding and simulating carbon allocation in plants is necessary to distribute carbohydrates among growing and competing organs and to predict plant growth and structure development in relation to climatic conditions. In this context several carbon allocation models have been developed but no clear consensus exists on (i) the most appropriate topological scale (organ, metamer, compartment...) to represent this process on complex plant structures, (ii) the importance of distances between organs in carbon transport, (iii) the priorities in carbon allocation among plant parts, that can depend on growth stages. Multi-scale tree graph (MTG) is a formalism allowing the representation of geometry and topology of a tree structure at different scales. In this study, several models were implemented to compute carbon allocation at user-defined spatial scales by using the MTG formalism. This allows multiple scales (e.g. metamer, growing unit, branch) to be combined during the computation of carbon allocation (e.g. allocation first within leafy shoots at metamer scale and then between growing units). The model describes carbon transport, taking into account the distances between sources and sinks, the strength of the sinks and the available carbohydrates, following the equations of the SIMWAL and QualiTree models. Simulations on simplified branching structures, represented at different scales, showed how the scales chosen to represent the system influence the results of predicted carbon allocation. This modelling approach will be first applied to apple tree to analyze the impact of the scale of representation (branch, growth unit, metamer, and inflorescence) on the predicted fruit growth variability which, in turn, will be compared with field observations. The present work is available through the OpenAlea platform and provides existing Functional Structural Plant Models with a new generic model to simulate carbon allocation in plants depending on user-defined biological hypotheses, such as the choice of the scale of representation or the effect of distance

Impaired Interleukin-1β and c-Fos Expression in the Hippocampus Is Associated with a Spatial Memory Deficit in P2X7 Receptor-Deficient Mice

Recent evidence suggests that interleukin-1β (IL-1β), which was originally identified as a proinflammatory cytokine, is also required in the brain for memory processes. We have previously shown that IL-1β synthesis in the hippocampus is dependent on P2X7 receptor (P2X7R), which is an ionotropic receptor of ATP. To substantiate the role of P2X7R in both brain IL-1β expression and memory processes, we examined the induction of IL-1β mRNA expression in the hippocampus of wild-type (WT) and homozygous P2X7 receptor knockout mice (P2X7R−/−) following a spatial memory task. The spatial recognition task induced both IL-1β mRNA expression and c-Fos protein activation in the hippocampus of WT but not of P2X7R−/− mice. Remarkably, P2X7R−/− mice displayed spatial memory impairment in a hippocampal-dependant task, while their performances in an object recognition task were unaltered. Taken together, our results show that P2X7R plays a critical role in spatial memory processes and the associated hippocampal IL-1β mRNA synthesis and c-Fos activation