The Impact of Step Reduction on Muscle Health in Aging: Protein and Exercise as Countermeasures

Declines in strength and muscle function with age—sarcopenia—contribute to a variety of negative outcomes including an increased risk of: falls, fractures, hospitalization, and reduced mobility in older persons. Population-based estimates of the loss of muscle after age 60 show a loss of ~1% per year while strength loss is more rapid at ~3% per year. These rates are not, however, linear as periodic bouts of reduced physical activity and muscle disuse transiently accelerate loss of muscle and declines in muscle strength and power. Episodic complete muscle disuse can be due to sickness-related bed rest or local muscle disuse as a result of limb immobilization/surgery. Alternatively, relative muscle disuse occurs during inactivity due to illness and the associated convalescence resulting in marked reductions in daily steps, often referred to as step reduction (SR). While it is a “milder” form of disuse, it can have a similar adverse impact on skeletal muscle health. The physiological consequences of even short-term inactivity, modeled by SR, show losses in muscle mass and strength, as well as impaired insulin sensitivity and an increase in systemic inflammation. Though seemingly benign in comparison to bed rest, periodic inactivity likely occurs, we posit, more frequently with advancing age due to illness, declining mental health and declining mobility. Given that recovery from inactivity in older adults is slow or possibly incomplete we hypothesize that accumulated periods of inactivity contribute to sarcopenia. Periodic activity, even in small quantities, and protein supplementation may serve as effective strategies to offset the loss of muscle mass with aging, specifically during periods of inactivity. The aim of this review is to examine the recent literature encompassing SR, as a model of inactivity, and to explore the capacity of nutrition and exercise interventions to mitigate adverse physiological changes as a result of SR

Covariation between oxygen and hydrogen stable isotopes declines along the path from xylem water to wood cellulose across an aridity gradient

Oxygen and hydrogen isotopes of cellulose in plant biology are commonly used to infer environmental conditions, often from time series measurements of tree rings. However, the covariation (or the lack thereof) between δ18O and δ2H in plant cellulose is still poorly understood. We compared plant water, and leaf and branch cellulose from dominant tree species across an aridity gradient in Northern Australia, to examine how δ18O and δ2H relate to each other and to mean annual precipitation (MAP). We identified a decline in covariation from xylem to leaf water, and onwards from leaf to branch wood cellulose. Covariation in leaf water isotopic enrichment (Δ) was partially preserved in leaf cellulose but not branch wood cellulose. Furthermore, whilst δ2H was well-correlated between leaf and branch, there was an offset in δ18O between organs that increased with decreasing MAP. Our findings strongly suggest that postphotosynthetic isotope exchange with water is more apparent for oxygen isotopes, whereas variable kinetic and nonequilibrium isotope effects add complexity to interpreting metabolic-induced δ2H patterns. Varying oxygen isotope exchange in wood and leaf cellulose must be accounted for when δ18O is used to reconstruct climatic scenarios. Conversely, comparing δ2H and δ18O patterns may reveal environmentally induced shifts in metabolism

EGRINs (Environmental Gene Regulatory Influence Networks) in Rice That Function in the Response to Water Deficit, High Temperature, and Agricultural Environments

Environmental gene regulatory influence networks (EGRINs) coordinate the timing and rate of gene expression in response to environmental signals. EGRINs encompass many layers of regulation, which culminate in changes in accumulated transcript levels. Here, we inferred EGRINs for the response of five tropical Asian rice (Oryza sativa) cultivars to high temperatures, water deficit, and agricultural field conditions by systematically integrating time-series transcriptome data, patterns of nucleosome-free chromatin, and the occurrence of known cis-regulatory elements. First, we identified 5447 putative target genes for 445 transcription factors (TFs) by connecting TFs with genes harboring known cis-regulatory motifs in nucleosome-free regions proximal to their transcriptional start sites. We then used network component analysis to estimate the regulatory activity for each TF based on the expression of its putative target genes. Finally, we inferred an EGRIN using the estimated transcription factor activity (TFA) as the regulator. The EGRINs include regulatory interactions between 4052 target genes regulated by 113 TFs. We resolved distinct regulatory roles for members of the heat shock factor family, including a putative regulatory connection between abiotic stress and the circadian clock. TFA estimation using network component analysis is an effective way of incorporating multiple genome-scale measurements into network inference

Potato Protein Isolate Stimulates Muscle Protein Synthesis at Rest and with Resistance Exercise in Young Women

Skeletal muscle myofibrillar protein synthesis (MPS) increases in response to protein feeding and to resistance exercise (RE), where each stimuli acts synergistically when combined. The efficacy of plant proteins such as potato protein (PP) isolate to stimulate MPS is unknown. We aimed to determine the effects of PP ingestion on daily MPS with and without RE in healthy women. In a single blind, parallel-group design, 24 young women (21 ± 3 years, n = 12/group) consumed a weight-maintaining baseline diet containing 0.8 g/kg/d of protein before being randomized to consume either 25 g of PP twice daily (1.6 g/kg/d total protein) or a control diet (CON) (0.8 g/kg/d total protein) for 2 wks. Unilateral RE (~30% of maximal strength to failure) was performed thrice weekly with the opposite limb serving as a non-exercised control (Rest). MPS was measured by deuterated water ingestion at baseline, following supplementation (Rest), and following supplementation + RE (Exercise). Ingestion of PP stimulated MPS by 0.14 ± 0.09 %/d at Rest, and by 0.32 ± 0.14 %/d in the Exercise limb. MPS was significantly elevated by 0.20 ± 0.11 %/d in the Exercise limb in CON (p = 0.008). Consuming PP to increase protein intake to levels twice the recommended dietary allowance for protein augmented rates of MPS. Performance of RE stimulated MPS regardless of protein intake. PP is a high-quality, plant-based protein supplement that augments MPS at rest and following RE in healthy young women

Mesocorticolimbic monoamine correlates of methamphetamine sensitization and motivation.

Methamphetamine (MA) is a highly addictive psychomotor stimulant, with life-time prevalence rates of abuse ranging from 5-10% world-wide. Yet, a paucity of research exists regarding MA addiction vulnerability/resiliency and neurobiological mediators of the transition to addiction that might occur upon repeated low-dose MA exposure, more characteristic of early drug use. As stimulant-elicited neuroplasticity within dopamine neurons innervating the nucleus accumbens (NAC) and prefrontal cortex (PFC) is theorized as central for addiction-related behavioral anomalies, we used a multi-disciplinary research approach in mice to examine the interactions between sub-toxic MA dosing, motivation for MA and mesocorticolimbic monoamines. Biochemical studies of C57BL/6J (B6) mice revealed short- (1 day), as well as longer-term (21 days), changes in extracellular dopamine, DAT and/or D2 receptors during withdrawal from 10, once daily, 2 mg/kg MA injections. Follow-up biochemical studies conducted in mice selectively bred for high vs. low MA drinking (respectively, MAHDR vs. MALDR mice), provided novel support for anomalies in mesocorticolimbic dopamine as a correlate of genetic vulnerability to high MA intake. Finally, neuropharmacological targeting of NAC dopamine in MA-treated B6 mice demonstrated a bi-directional regulation of MA-induced place-conditioning. These results extend extant literature for MA neurotoxicity by demonstrating that even subchronic exposure to relatively low MA doses are sufficient to elicit relatively long-lasting changes in mesocorticolimbic dopamine and that drug-induced or idiopathic anomalies in mesocorticolimbic dopamine may underpin vulnerability/resiliency to MA addiction

Corpus Callosum Morphology in Capuchin Monkeys Is Influenced by Sex and Handedness

Sex differences have been reported in both overall corpus callosum area and its regional subdivisions in humans. Some have suggested this reflects a unique adaptation in humans, as similar sex differences in corpus callosum morphology have not been reported in any other species of primate examined to date. Furthermore, an association between various measurements of corpus callosum morphology and handedness has been found in humans and chimpanzees. In the current study, we report measurements of corpus callosum cross-sectional area from midsagittal MR images collected in vivo from 14 adult capuchin monkeys, 9 of which were also characterized for hand preference on a coordinated bimanual task. Adult females were found to have a significantly larger corpus callosum: brain volume ratio, rostral body, posterior midbody, isthmus, and splenium than adult males. Left-handed individuals had a larger relative overall corpus callosum area than did right-handed individuals. Additionally, a significant sex and handedness interaction was found for anterior midbody, with right-handed males having a significantly smaller area than right-handed females. These results suggest that sex and handedness influences on corpus callosum morphology are not restricted to Homo sapiens

Forcing single-column models using high-resolution model simulations

To use single column models (SCMs) as a research tool for parametrisation development and process studies, the SCM must be supplied with realistic initial profiles, forcing fields and boundary conditions. We propose a new technique for deriving these required profiles, motivated by the increase in number and scale of high-resolution convection-permitting simulations. We suggest that these high-resolution simulations be coarse-grained to the required resolution of an SCM, and thereby be used as a proxy for the ‘true’ atmosphere. This paper describes the implementation of such a technique. We test the proposed methodology using high-resolution data from the UK Met Office’s Unified Model (MetUM), with a resolution of 4 km, covering a large tropical domain. This data is coarse grained and used to drive the European Centre for Medium-Range Weather Forecast’s (ECMWF) Integrated Forecasting 26 System (IFS) SCM. The proposed method is evaluated by deriving IFS SCM forcing profiles from a consistent T639 IFS simulation. The SCM simulations track the global model, indicating a consistency between the estimated forcing fields and the ‘true’ dynamical forcing in the global model. We demonstrate the benefits of selecting SCM forcing profiles from across a large-domain, namely robust statistics, and the ability to test the SCM over a range of boundary conditions. We also compare driving the SCM with the coarse-grained datase to driving it using the ECMWF operational analysis. We conclude by highlighting the importance of understanding biases in the high-resolution dataset, and suggest that our approach be used in combination with observationally derived forcing datasets

Fulminant hepatic failure in murine hepatitis virus strain 3 infection: tissue-specific expression of a novel fgl2 prothrombinase.

Activation of the immune coagulation system has been implicated in the pathogenesis of fulminant liver failure caused by murine hepatitis virus strain 3 (MHV-3). The recent discovery of the fgl2 gene, which encodes for MHV-3-induced prothrombinase (fgl2 prothrombinase), allows for fundamental studies to determine the molecular basis for fulminant liver failure. Transcription of the fgl2 gene and translation of the protein it encodes were examined in the liver and other organs of susceptible mice following MHV-3 infection. No constitutive expression of the fgl2 gene or the fgl2 prothrombinase was detected. Within 12 to 24 h of MHV-3 infection, however, fgl2 gene transcripts were detected in large amounts in the liver, spleen, and lungs, all of which are rich in reticuloendothelial cells, but were only focally present in small amounts in the kidney and brain. There was sequential detection of fgl2 prothrombinase in the liver, where it was localized specifically to the endothelium of intrahepatic veins and hepatic sinusoids; this was allowed by fibrin deposition, which resulted in confluent hepatocellular necrosis. These results provide further evidence for the role of the selective expression of this novel fgl2 prothrombinase in the pathogenesis of MHV-3-induced fulminant liver failure

Schools, families, and social reproduction

Neoliberal educational discourse across the Global North is marked by an increasing homogeneity, but this masks significant socio-spatial differences in the enactment of policy. The authors focus on four facets of roll-out neoliberalism in English education policy that have expanded the function of primary schools, and redrawn the boundary between state and family responsibilities. Specifically, these are increased state support for: (1) working parenthood through provision of wraparound childcare; (2) parent-child relationships through school-led provision of parenting classes; (3) parental involvement in children’s learning; and (4) child development through schools’ fostering of extracurricular activities. The politics of policies that both enhance state responsibility for, and influence in, matters that were previously within the purview of families are complex. The collective impact of these developments has been both to reform how the work of daily and generational social reproduction is done, and to reshape the social reproduction of a classed and gendered society