Effect of Short Term Exercise and High Fat Diet on Skeletal Muscle miR133a

Micro RNAs (miR) are small non-coding RNA that regulate gene expression at the post-transcriptional level. miR133a is abundant in cardiac and skeletal muscle. In skeletal muscle, miR133a is best known for its regulatory role in myogenesis and differentiation. Nie (2016) found that muscle miR133a expression increased after acute exercise and with 12w of treadmill exercise training in mice. Knockdown of miR133a in transgenic mice resulted in blunted skeletal muscle mitochondrial biogenesis and function in response to exercise training (Nie, 2016) suggesting a role for miR133a in regulating the normal skeletal muscle metabolic adaptive response to exercise. Among other miR, skeletal muscle miR133a is reported as downregulated in insulin-resistant muscle. Insulin resistance in mice fed a high-fat diet is detectable after 3 days on diet (Lee, 2011). In this study, voluntary, rather than forced, exercise was employed to test whether miR133a expression is regulated early in the adoption of increased daily physical activity

High-Precision Measurement of the 19Ne Half-Life and Implications for Right-Handed Weak Currents

We report a precise determination of the 19Ne half-life to be $T_{1/2} = 17.262 \pm 0.007$ s. This result disagrees with the most recent precision measurements and is important for placing bounds on predicted right-handed interactions that are absent in the current Standard Model. We are able to identify and disentangle two competing systematic effects that influence the accuracy of such measurements. Our findings prompt a reassessment of results from previous high-precision lifetime measurements that used similar equipment and methods.Comment: 5 pages and 5 figures. Paper accepted for publication in Phys. Rev. Let

Participatory budgeting, community engagement and impact on public services in Scotland

The institutional engagement and analysis needed to effectively integrate the requirements of equality legislation into participatory budgeting (PB) processes requires a transformational approach. Equality processes appear to exist in parallel with PB activity, rather than being operationalized as integral to the objectives and character of PB activity at local level. This paper proposes that PB and the Public Sector Equality Duty (PSED) in the Equality Act 2010 share a transformative intent and potential, but that this is undermined by siloed thinking on equalities and enduring discriminatory behaviour and practices. The paper concludes with propositions for aligning the conceptual links between equality and community empowerment and, thereby, participation in local financial decision-making in practice

Influenza nucleoprotein delivered with aluminium salts protects mice from an influenza virus that expresses an altered nucleoprotein sequence

Influenza virus poses a difficult challenge for protective immunity. This virus is adept at altering its surface proteins, the proteins that are the targets of neutralizing antibody. Consequently, each year a new vaccine must be developed to combat the current recirculating strains. A universal influenza vaccine that primes specific memory cells that recognise conserved parts of the virus could prove to be effective against both annual influenza variants and newly emergent potentially pandemic strains. Such a vaccine will have to contain a safe and effective adjuvant that can be used in individuals of all ages. We examine protection from viral challenge in mice vaccinated with the nucleoprotein from the PR8 strain of influenza A, a protein that is highly conserved across viral subtypes. Vaccination with nucleoprotein delivered with a universally used and safe adjuvant, composed of insoluble aluminium salts, provides protection against viruses that either express the same or an altered version of nucleoprotein. This protection correlated with the presence of nucleoprotein specific CD8 T cells in the lungs of infected animals at early time points after infection. In contrast, immunization with NP delivered with alum and the detoxified LPS adjuvant, monophosphoryl lipid A, provided some protection to the homologous viral strain but no protection against infection by influenza expressing a variant nucleoprotein. Together, these data point towards a vaccine solution for all influenza A subtypes

Pharmacological screening using an FXN-EGFP cellular genomic reporter assay for the therapy of Friedreich ataxia

Copyright @ 2013 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Friedreich ataxia (FRDA) is an autosomal recessive disorder characterized by neurodegeneration and cardiomyopathy. The presence of a GAA trinucleotide repeat expansion in the first intron of the FXN gene results in the inhibition of gene expression and an insufficiency of the mitochondrial protein frataxin. There is a correlation between expansion length, the amount of residual frataxin and the severity of disease. As the coding sequence is unaltered, pharmacological up-regulation of FXN expression may restore frataxin to therapeutic levels. To facilitate screening of compounds that modulate FXN expression in a physiologically relevant manner, we established a cellular genomic reporter assay consisting of a stable human cell line containing an FXN-EGFP fusion construct, in which the EGFP gene is fused in-frame with the entire normal human FXN gene present on a BAC clone. The cell line was used to establish a fluorometric cellular assay for use in high throughput screening (HTS) procedures. A small chemical library containing FDA-approved compounds and natural extracts was screened and analyzed. Compound hits identified by HTS were further evaluated by flow cytometry in the cellular genomic reporter assay. The effects on FXN mRNA and frataxin protein levels were measured in lymphoblast and fibroblast cell lines derived from individuals with FRDA and in a humanized GAA repeat expansion mouse model of FRDA. Compounds that were established to increase FXN gene expression and frataxin levels included several anti-cancer agents, the iron-chelator deferiprone and the phytoalexin resveratrol.Muscular Dystrophy Association (USA), the National Health and Medical Research Council (Australia), the Friedreich’s Ataxia Research Alliance (USA), the Brockhoff Foundation (Australia), the Friedreich Ataxia Research Association (Australasia), Seek A Miracle (USA) and the Victorian Government’s Operational Infrastructure Support Program

Corporate Social Responsibility and Sustainable Development Goal 9

With the spread of neoliberalism, corporate social responsibility (CSR) and private governance have become integral parts of corporate behavior. This entry discusses the aspects of Goal 9 (industry, innovation, and infrastructure) of the United Nations Sustainable Development Goals (SDGs) in relation to CSR. Goal 9 emphasizes sustainability, resilience, and equity of corporations, industries, and other social and economic actors in the processes of innovation and advancement of infrastructures. Although the concept of CSR, which represents positive social and environmental influences of corporations, is not explicitly mentioned in Goal 9, it is an important mechanism in accomplishing the objectives of the goal

Mass spectrometry imaging identifies palmitoylcarnitine as an immunological mediator during Salmonella Typhimurium infection

Salmonella Typhimurium causes a self-limiting gastroenteritis that may lead to systemic disease. Bacteria invade the small intestine, crossing the intestinal epithelium from where they are transported to the mesenteric lymph nodes (MLNs) within migrating immune cells. MLNs are an important site at which the innate and adaptive immune responses converge but their architecture and function is severely disrupted during S. Typhimurium infection. To further understand host-pathogen interactions at this site, we used mass spectrometry imaging (MSI) to analyse MLN tissue from a murine model of S. Typhimurium infection. A molecule, identified as palmitoylcarnitine (PalC), was of particular interest due to its high abundance at loci of S. Typhimurium infection and MLN disruption. High levels of PalC localised to sites within the MLNs where B and T cells were absent and where the perimeter of CD169+ sub capsular sinus macrophages was disrupted. MLN cells cultured ex vivo and treated with PalC had reduced CD4+CD25+ T cells and an increased number of B220+CD19+ B cells. The reduction in CD4+CD25+ T cells was likely due to apoptosis driven by increased caspase-3/7 activity. These data indicate that PalC significantly alters the host response in the MLNs, acting as a decisive factor in infection outcome

Climate-carbon cycle uncertainties and the Paris Agreement

The Paris Agreement aims to address the gap between existing climate policies and policies consistent with ‘holding the increase in global average temperature to well below 2C’. The feasibility of meeting the target has been questioned both in terms of the possible requirement for negative emissions, and ongoing debate on the sensitivity of the climate-carbon cycle system. Using a sequence of ensembles of a fully dynamic three-dimensional climate-carbon cycle model, forced by emissions from an integrated assessment model of regional-level climate policy, economy, and technological transformation, we show that a reasonable interpretation of the Paris Agreement is still technically achievable. Specifically, limiting peak (decadal) warming to less than 1.7°C, or end-century warming to less than 1.54°C, occurs in 50% of our simulations in a policy scenario without net negative emissions or excessive stringency in any policy domain. We evaluate two mitigation scenarios, with 200 GTC and 307 GTC post-2017 emissions, quantifying spatio-temporal variability of warming, precipitation, ocean acidification and marine productivity. Under rapid decarbonisation decadal variability dominates the mean response in critical regions, with significant implications for decision making, demanding impact methodologies that address non-linear spatio-temporal responses. Ignoring carbon-cycle feedback uncertainties (explaining 47% of peak warming uncertainty) becomes unreasonable under strong mitigation conditions.We acknowledge C-EERNG and Cambridge Econometrics for support, and funding from EPSRC (to J.-F.M., fellowship number EP/ K007254/1); the Newton Fund (to J.-F.M., P.S. and J.E.V., EPSRC grant number EP/N002504/1 and ESRC grant number ES/N013174/1), NERC (to N.R.E., P.H. and H.P., grant number NE/P015093/1), CONICYT (to P.S.), the Philomathia Foundation (to J.E.V.) and Horizon 2020 (to H.E.P. and J.-F.M., the Sim4Nexus project)