Myostatin is a key mediator between energy metabolism and endurance capacity of skeletal muscle

Myostatin (Mstn) participates in the regulation of skeletal muscle size and has emerged as a regulator of muscle metabolism. Here, we hypothesized that lack of myostatin profoundly depresses oxidative phosphorylation-dependent muscle function. Toward this end, we explored Mstn/ mice as a model for the constitutive absence of myostatin and AAV-mediated overexpression of myostatin propeptide as a model of myostatin blockade in adult wild-type mice. We show that muscles from Mstn/ mice, although larger and stronger, fatigue extremely rapidly. Myostatin deficiency shifts muscle from aerobic toward anaerobic energy metabolism, as evidenced by decreased mitochondrial respiration, reduced expression of PPAR transcriptional regulators, increased enolase activity, and exercise-induced lactic acidosis. As a consequence, constitutively reduced myostatin signaling diminishes exercise capacity, while the hypermuscular state of Mstn/ mice increases oxygen consumption and the energy cost of running. We wondered whether these results are the mere consequence of the congenital fiber-type switch toward a glycolytic phenotype of constitutive Mstn/ mice. Hence, we overexpressed myostatin propeptide in adult mice, which did not affect fiber-type distribution, while nonetheless causing increased muscle fatigability, diminished exercise capacity, and decreased Pparb/d and Pgc1a expression. In conclusion, our results suggest that myostatin endows skeletal muscle with high oxidative capacity and low fatigability, thus regulating the delicate balance between muscle mass, muscle force, energy metabolism, and endurance capacity.

Designing Temperature-Responsive Biocompatible Copolymers and Hydrogels Based on 2-Hydroxyethyl(meth)acrylates

Free-radical copolymerization of 2-hydroxyethyl methacrylate with 2-hydroxyethyl acrylate can be successively utilized for the synthesis of water-soluble polymers and hydrogels with excellent physicochemical properties, thus showing promise for pharmaceutical and biomedical applications. In the work presented it has been demonstrated that water-soluble copolymers based on 2-hydroxyethyl methacrylate and 2-hydroxyethyl acrylate exhibit lower critical solution temperature in aqueous solutions, whereas the corresponding high molecular weight homopolymers do not have this unique property. The temperature-induced transitions observed upon heating the aqueous solutions of these copolymers proceed via liquid−liquid phase separation. The hydrogels were also synthesized by copolymerizing 2-hydroxyethyl methacrylate and 2-hydroxyethyl acrylate in the absence of a bifunctional cross-linker. The cross-linking of these copolymers during copolymerization is believed to be due to the presence of bifunctional admixtures or transesterification reactions. Transparency, swelling behavior, mechanical properties, and porosity of the hydrogels are dependent upon the monomer ratio in the copolymers. Hydrogel samples containing more 2-hydroxyethyl methacrylate are less transparent, have lower swelling capacity, higher elastic moduli, and pores of smaller size. The assessment of the biocompatibility of the copolymers using the slug mucosal irritation test revealed that they are also less irritant than poly(acrylic acid).

Health-related quality of life in Huntington's disease: which factors matter most?

The aim of this article was to determine which aspects of Huntington's disease (HD) are most important with regard to the health-related quality of life (HrQOL) of patients with this neurodegenerative disease. Seventy patients with HD participated in the study. Assessment comprised the Unified Huntington's Disease Rating Scale (UHDRS) motor, cognitive and functional capacity sections, and the Beck Depression inventory. Mental and physical HrQOL were assessed using summary scores of the SF-36. Multiple regression analyses showed that functional capacity and depressive mood were significantly associated with HrQOL, in that greater impairments in HrQOL were associated with higher levels of depressive mood and lower functional capacity. Motor symptoms and cognitive function were not found to be as closely linked with HrQOL. Therefore, it can be concluded that, depressive mood and greater functional incapacity are key factors in HrQOL for people with HD, and further longitudinal investigation will be useful to determine their utility as specific targets in intervention studies aimed at improving patient HrQOL, or whether other mediating variables. As these two factors had a similar association with the mental and physical summary scores of the SF-36, this generic HrQOL measure did not adequately capture and distinguish the true mental and physical health-related HrQOL in HD.

Dispersal capacity and diet breadth modify the response of wild bees to habitat loss

Habitat loss poses a major threat to biodiversity, and species-specific extinction risks are inextricably linked to life-history characteristics. This relationship is still poorly documented for many functionally important taxa, and at larger continental scales. With data from five replicated field studies from three countries, we examined how species richness of wild bees varies with habitat patch size. We hypothesized that the form of this relationship is affected by body size, degree of host plant specialization and sociality. Across all species, we found a positive species–area slope (z ¼ 0.19), and species traits modified this relationship. Large-bodied generalists had a lower z value than small generalists. Contrary to predictions, small specialists had similar or slightly lower z value compared with large specialists, and small generalists also tended to be more strongly affected by habitat loss as compared with small specialists. Social bees were negatively affected by habitat loss (z ¼ 0.11) irrespective of body size. We conclude that habitat loss leads to clear shifts in the species composition of wild bee communities.

Temperature-responsive properties and drug solubilization capacity of amphiphilic copolymers based on N-vinylpyrrolidone and vinyl propyl ether

A series of amphiphilic copolymers were synthesized by free-radical copolymerization of N-vinylpyrrolidone (NVP) with vinyl propyl ether (VPE), and the structure of the copolymers was characterized by elemental analysis and gel permeation chromatography. The reactivity of VPE in copolymerization was found to be significantly lower than the reactivity of NVP, which resulted in a decrease of copolymers’ yields and molecular weights with higher content of VPE in the feed mixture. An investigation of the behavior of the copolymers in aqueous solutions at different temperatures by dynamic light scattering revealed the presence of lower critical solution temperature, which depending on the content of VPE ranged within 23−38 °C. Aqueous solutions of these copolymers were studied by fluorescent spectroscopy with pyrene as a polarity probe to reveal the formation of hydrophobic domains. The copolymers were found to be useful for enhancing the solubility of riboflavin in water.

A comparison of two time-domain analysis procedures in the determination of VO2 kinetics by pseudorandom binary sequence exercise testing

The purpose of this study was to apply and compare two time-domain analysis procedures in the determination of oxygen uptake (VO2) kinetics in response to a pseudorandom binary sequence (PRBS) exercise test. PRBS exercise tests have typically been analysed in the frequency domain. However, the complex interpretation of frequency responses may have limited the application of this procedure in both sporting and clinical contexts, where a single time measurement would facilitate subject comparison. The relative potential of both a mean response time (MRT) and a peak cross-correlation time (PCCT) was investigated. This study was divided into two parts: a test-retest reliability study (part A), in which 10 healthy male subjects completed two identical PRBS exercise tests, and a comparison of the VO2 kinetics of 12 elite endurance runners (ER) and 12 elite sprinters (SR; part B). In part A, 95% limits of agreement were calculated for comparison between MRT and PCCT. The results of part A showed no significant difference between test and retest as assessed by MRT [mean (SD) 42.2 (4.2) s and 43.8 (6.9) s] or by PCCT [21.8 (3.7) s and 22.7 (4.5) s]. Measurement error (%) was lower for MRT in comparison with PCCT (16% and 25%, respectively). In part B of the study, the VO2 kinetics of ER were significantly faster than those of SR, as assessed by MRT [33.4 (3.4) s and 39.9 (7.1) s, respectively; P<0.01] and PCCT [20.9 (3.8) s and 24.8 (4.5) s; P < 0.05]. It is possible that either analysis procedure could provide a single test measurement Of VO2 kinetics; however, the greater reliability of the MRT data suggests that this method has more potential for development in the assessment Of VO2 kinetics by PRBS exercise testing.

Test performance indicators from a single soccer specific fitness test differentiate between highly trained and recreationally active soccer players

Aim. The aim of this study was to investigate whether a single soccer specific fitness test (SSFT) could differentiate between highly trained and recreationally active soccer players in selected test performance indicators. Methods. Subjects: 13 Academy Scholars (AS) from a professional soccer club and 10 Recreational Players (RP) agreed to participate in this study. Test 1-(V)over dotO(2) max was estimated from a progressive shuttle run test to exhaustion. Test 2-The SSFT was controlled by an automated procedure and alternated between walking, sprinting, jogging and cruise running speeds. Three activity blocks (1A, 2A and 3A) were separated by 3 min rest periods in which blood lactate samples were drawn. The 3 blocks of activity (Part A) were followed by 10 min of exercise at speeds alternating between jogging and cruise running (Part B). Results. Estimated (V)over dotO(2) max did not significantly differ between groups, although a trend for a higher aerobic capacity was evident in AS (p<0.09). Exercising heart rates did not differ between AS and RP, however, recovery heart rates taken from the 3 min rest periods were significantly lower in AS compared with RP following blocks 1A (124.65 b(.)min(-1) +/-7.73 and 133.98 b(.)min(-1) +/-6.63), (p<0.05) and 3A (129.91 b.min(-1) +/-10.21 and 138.85 b.min(-1) +/-8.70), (p<0.01). Blood lactate concentrations were significantly elevated in AS in comparison to RP following blocks 2A (6.91 mmol(.)l(-1) +/-2.67 and 4.74 mmol(.)l(-1) +/-1.28) and 3A (7.18 mmol(.)l(-1) +/-2.97 and 4.88 mmol(.)l(-1) +/-1.50), (p<0.05). AS sustained significantly faster average sprint times in block 3A compared with RP (3.18 sec +/-0.12 and 3.31 sec +/-0.12), (p<0.05). Conclusion. The results of this study show that highly trained soccer players are able to sustain, and more quickly recover from, high intensity intermittent exercise.

Differences in cell morphology, lipid and apo B secretory capacity in caco-2 cells following long term treatment with saturated and monounsaturated fatty acids

The suitability of the caco-2 cell line as a model for studying the long term impact of dietary fatty acids on intestinal lipid handling and chylomicron production was examined. Chronic supplementation of caco-2 cells with palmitic acid (PA) resulted in a lower triacylglycerol secretion than oleic acid (OA). This was coupled with a detrimental effect of PA, but not OA, on transepithelial electrical resistance (TER) measurements, suggesting a loss of structural integrity across the cell monolayer. Addition of OA reversed the adverse effects of PA and stearic acid on TER and increased the ability of cells to synthesise and accumulate lipid, but did not normalise the secretion of lipids by caco-2 cells. Increasing amounts of OA and decreasing amounts of PA in the incubation media markedly improved the ability of cells to synthesise apolipoprotein B and secrete lipids. Real time RT-PCR revealed a down regulation of genes involved in lipoprotein synthesis following PA than OA. Electron microscopy showed adverse effects of PA on cellular morphology consistent with immature enterocytes such as stunted microvilli and poor tight junction formation. In conclusion, previously reported differences in lipoprotein secretion by caco-2 cells supplemented with saturated fatty acids (SFA) and OA may partly reflect early cytotoxic effects of SFA on cellular integrity and function. (C) 2007 Elsevier B.V. All rights reserved.

Switching curve control of functional electrical stimulation assisted rowing exercise in paraplegia

An indoor rowing machine has been modified for functional electrical stimulation (FES) assisted rowing exercise in paraplegia. To perform the rowing manoeuvre successfully, however, the voluntarily controlled upper body movements must be co-ordinated with the movements of the electrically stimulated paralysed legs. To achieve such co-ordination, an automatic FES controller was developed that employs two levels of hierarchy. At the upper level, a finite state controller identifies the state or phase of the rowing cycle and activates the appropriate lower-level controller, in which electrical stimulation to the paralysed leg muscles is applied with reference to switching curves representing the desired seat velocity as a function of the seat position. In a pilot study, the hierarchical control of FES rowing was shown to be intuitive, reliable and easy to use. Compared with open-loop control of stimulation, all three variants of the closed-loop switching curve controllers used less muscle stimulation per rowing cycle (73% of the open-loop control on average). Further, the closed-loop controller that used switching curves derived from normal rowing kinematics used the lowest muscle stimulation (65% of the open-loop control) and was the most convenient to use for the client.

Institutional capacity and implementation issues in farmers' rights

Armed with the ‘equity’ and ‘conservation’ arguments that have a deep resonance with farming communities, developing countries are crafting a range of measures designed to protect farmers’ access to innovations, reward their contributions to the conservation and enhancement of plant genetic resources and provide incentives for sustained on-farm conservation. These measures range from the commericialization of farmers’ varieties to the conferment of a set of legally enforceable rights on farming communities – the exercise of which is expected to provide economic rewards to those responsible for on-farm conservation and innovation. The rights-based approach has been the cornerstone of legislative provision for implementing farmers’ rights in most developing countries. In drawing up these measures, developing countries do not appear to have systematically examined or provided for the substantial institutional capacity required for the effective implementation of farmers’ rights provisions. The lack of institutional capacity threatens to undermine any prospect of serious implementation of these provisions. More importantly, the expectation that significant incentives for on-farm conservation and innovation will flow from these ‘rights’ may be based on a flawed understanding of the economics of intellectual property rights. While farmers’ rights may provide only limited rewards for conservation, they may still have the effect of diluting the incentives for innovative institutional breeding programs – with the private sector increasingly relying on non-IPR instruments to profit from innovation. The focus on a rights-based approach may also draw attention away from alternative stewardship-based approaches to the realization of farmers’ rights objectives.

A case study to investigate the life cycle carbon emissions and carbon storage capacity of a cross laminated timber, multi-storey residential building

Forests are a store of carbon and an eco-system that continually removes carbon dioxide from the atmosphere. If they are sustainably managed, the carbon store can be maintained at a constant level, while the trees removed and converted to timber products can form an additional long term carbon store. The total carbon store in the forest and associated ‘wood chain’ therefore increases over time, given appropriate management. This increasing carbon store can be further enhanced with afforestation. The UK’s forest area has increased continually since the early 1900s, although the rate of increase has declined since its peak in the late 1980s, and it is a similar picture in the rest of Europe. The increased sustainable use of timber in construction is a key market incentive for afforestation, which can make a significant contribution to reducing carbon emissions. The case study presented in this paper demonstrates the carbon benefits of a Cross Laminated Timber (CLT) solution for a multi-storey residential building in comparison with a more conventional reinforced concrete solution. The embodied carbon of the building up to completion of construction is considered, together with the stored carbon during the life of the building and the impact of different end of life scenarios. The results of the study show that the total stored carbon in the CLT structural frame is 1215tCO2 (30tCO2 per housing unit). The choice of treatment at end of life has a significant effect on the whole life embodied carbon of the CLT frame, which ranges from -1017 tCO2e for re-use to +153tCO2e for incinerate without energy recovery. All end of life scenarios considered result in lower total CO2e emissions for the CLT frame building compared with the reinforced concrete frame solution.

Holocene alluvial environments at Barking, Lower Thames Valley (London, UK)

Deposit modelling based on archived borehole logs supplemented by a small number of dedicated boreholes is used to reconstruct the main boundary surfaces and the thickness of the main sediment units within the succession of Holocene alluvial deposits underlying the floodplain in the Barking Reach of the Lower Thames Valley. The basis of the modelling exercise is discussed and the models are used to assess the significance of floodplain relief in determining patterns of sedimentation. This evidence is combined with the results of biostratigraphical and geochronological investigations to reconstruct the environmental conditions associated with each successive stage of floodplain aggradation. The two main factors affecting the history and spatial pattern of Holocene sedimentation are shown to be the regional behaviour of relative sea level and the pattern of relief on the surface of the sub-alluvial, Late Devensian Shepperton Gravel. As is generally the case in the Lower Thames Valley, three main stratigraphic units are recognised, the Lower Alluvium, a peat bed broadly equivalent to the Tilbury III peat of Devoy (1979) and an Upper Alluvium. There is no evidence to suggest that the floodplain was substantially re-shaped by erosion during the Holocene. Instead, the relief inherited from the Shepperton Gravel surface was gradually buried either by the accumulation of peat or by deposition of fine-grained sediment from suspension in standing or slow-moving water. The palaeoenvironmental record from Barking confirms important details of the Holocene record observed elsewhere in the Lower Thames Valley, including the presence of Taxus in the valley-floor fen carr woodland between about 5000 and 4000 cal BP, and the subsequent growth of Ulmus on the peat surface.