PL - 041 Effects of power resistance exercise and feeding on the expression of putative mechanosensing proteins in skeletal muscle of resistance-trained men

Objective Power resistance exercise involves high intensity (load and velocity) dynamic muscular contractions and is frequently performed by athletes to enhance performance via improved muscle function. To investigate the remodelling processes that contribute to improved muscle function, we investigated the expression of putative mechanosensing genes implicated in this process (Kojic et al., 2011): titin-linked Muscle Ankyrin Repeat Protein (MARPs) family CARP, Ankrd 2 and DARP, and the Z-disc associated muscle-LIM protein (MLP) in healthy, resistance-trained men (n = 7) following 90 min of rest (Rest) or power resistance exercise, with (Ex + Meal) or without (Ex only) feeding during recovery. Methods Percutaneous needle biopsy samples were obtained from the vastus lateralis of resistance-trained males using local anesthetic (2% Xylocaine), 3 h after performing each of the three experimental trials on separate days. Previously, we presented results from this study showing that the mRNA levels of CARP (~15-fold) and MLP (~2.5-fold) were upregulated in human skeletal muscle 3 h post power resistance exercise (Wette et al., 2012). Based on these results, we performed protein analyses on the same muscle samples to determine the protein levels of all MARPs and MLP in whole muscle homogenates after Rest, Ex only and Ex + Meal. To assess whether the exercise elicited a stress response in these resistance-trained individuals, the level of phosphorylated heat shock protein 27 at serine 15 (pHSP27-Ser15) was measured at Rest and 3 h after Ex only and Ex + Meal. The levels of pHSP27-Ser15 are typically upregulated 3 h after eccentric exercise in human skeletal muscle (Frankenberg et al., 2014). Results The 90 min exercise session consisted of 180 intermittent muscular contractions at high intensity (70-96% maximal strength). Compared to Rest, there were ~5.8- and 12.6-fold increases in pHSP27-Ser15 levels at 3 h post Ex only and Ex + Meal (both P = 0.049, one-way ANOVA) respectively. CARP protein levels were elevated ~2.7-fold after Ex only (P = 0.049, one-way ANOVA) and ~7.6-fold after Ex + Meal (P = 0.326), due to markedly higher levels (6-40-fold) in three of the seven participants. Pearson correlation analysis revealed a significant positive correlation between the levels of pHSP27-Ser-15 and CARP protein (r = 0.56, P = 0.008). Ankrd 2, DARP and MLP protein levels were unchanged (all P > 0.05) following Ex only and Ex + Meal. Conclusions These findings indicate that CARP is highly responsive to increased mechanical loading because the protein levels in skeletal muscle can be substantially increased as early as 3 h after stressful resistance exercise. This suggests a specialised role for CARP protein during the early phases of muscle remodelling that occur as a consequence of performing high intensity resistance exercise

SDSS Catalog of Stars in the Draco Dwarf Spheroidal Galaxy

The Sloan Digital Sky Survey (SDSS) has scanned the entire region containing the Draco dwarf spheroidal galaxy to 23rd magnitude in g*. We present a catalog of stars found in a 453 square arcminute, elliptical region centered on the Draco dwarf spheroidal galaxy. Objects in the catalog are matched with five previously published catalogs. The catalog contains SDSS photometry for 5634 individual objects, and also the photometry from matches to any of the other catalogs. A comparison of the photometry between catalogs allows us to identify 142 candidate variable objects. One hundred and twelve of the suspected variables have colors consistent with RR Lyrae variables.Comment: To appear in ApJS 14 pages, 6 figure

The Ghost of Sagittarius and Lumps in the Halo of the Milky Way

We identify new structures in the halo of the Milky Way Galaxy from positions, colors and magnitudes of five million stars detected in the Sloan Digital Sky Survey. Most of these stars are within 1.26 degrees of the celestial equator. We present color-magnitude diagrams (CMDs) for stars in two previously discovered, tidally disrupted structures. The CMDs and turnoff colors are consistent with those of the Sagittarius dwarf galaxy, as had been predicted. In one direction, we are even able to detect a clump of red stars, similar to that of the Sagittarius dwarf, from stars spread across 110 square degrees of sky. Focusing on stars with the colors of F turnoff objects, we identify at least five additional overdensities of stars. Four of these may be pieces of the same halo structure, which would cover a region of the sky at least 40 degrees in diameter, at a distance of 11 kpc from the Sun (18 kpc from the center of the Galaxy). The turnoff is significantly bluer than that of thick disk stars, and closer to the Galactic plane than a power-law spheroid. We suggest two models to explain this new structure. One possibility is that this new structure could be a new dwarf satellite of the Milky Way, hidden in the Galactic plane, and in the process of being tidally disrupted. The other possibility is that it could be part of a disk-like distribution of stars which is metal-poor, with a scale height of approximately 2 kpc and a scale length of approximately 10 kpc. The fifth overdensity, which is 20 kpc away, is some distance from the Sagittarius dwarf streamer orbit and is not associated with any known structure in the Galactic plane. It is likely that there are many smaller streams of stars in the Galactic halo.Comment: ApJ, in press; 26 figures including several in colo

Researching the mental health needs of hard-to-reach groups: managing multiple sources of evidence

Background: common mental health problems impose substantial challenges to patients, carers, and health care systems. A range of interventions have demonstrable efficacy in improving the lives of people experiencing such problems. However many people are disadvantaged, either because they are unable to access primary care, or because access does not lead to adequate help. New methods are needed to understand the problems of access and generate solutions. In this paper we describe our methodological approach to managing multiple and diverse sources of evidence, within a research programme to increase equity of access to high quality mental health services in primary care.Methods: we began with a scoping review to identify the range and extent of relevant published material, and establish key concepts related to access. We then devised a strategy to collect - in parallel - evidence from six separate sources: a systematic review of published quantitative data on access-related studies; a meta-synthesis of published qualitative data on patient perspectives; dialogues with local stakeholders; a review of grey literature from statutory and voluntary service providers; secondary analysis of patient transcripts from previous qualitative studies; and primary data from interviews with service users and carers.We synthesised the findings from these diverse sources, made judgements on key emerging issues in relation to needs and services, and proposed a range of potential interventions. These proposals were debated and refined using iterative electronic and focus group consultation procedures involving international experts, local stakeholders and service users.Conclusions: our methods break new ground by generating and synthesising multiple sources of evidence, connecting scientific understanding with the perspectives of users, in order to develop innovative ways to meet the mental health needs of under-served group

Drosophila evolution over space and time (DEST):A new population genomics resource

Drosophila melanogaster is a leading model in population genetics and genomics, and a growing number of whole-genome datasets from natural populations of this species have been published over the last years. A major challenge is the integration of disparate datasets, often generated using different sequencing technologies and bioinformatic pipelines, which hampers our ability to address questions about the evolution of this species. Here we address these issues by developing a bioinformatics pipeline that maps pooled sequencing (Pool-Seq) reads from D. melanogaster to a hologenome consisting of fly and symbiont genomes and estimates allele frequencies using either a heuristic (PoolSNP) or a probabilistic variant caller (SNAPE-pooled). We use this pipeline to generate the largest data repository of genomic data available for D. melanogaster to date, encompassing 271 previously published and unpublished population samples from over 100 locations in > 20 countries on four continents. Several of these locations have been sampled at different seasons across multiple years. This dataset, which we call Drosophila Evolution over Space and Time (DEST), is coupled with sampling and environmental meta-data. A web-based genome browser and web portal provide easy access to the SNP dataset. We further provide guidelines on how to use Pool-Seq data for model-based demographic inference. Our aim is to provide this scalable platform as a community resource which can be easily extended via future efforts for an even more extensive cosmopolitan dataset. Our resource will enable population geneticists to analyze spatio-temporal genetic patterns and evolutionary dynamics of D. melanogaster populations in unprecedented detail.DrosEU is funded by a Special Topic Networks (STN) grant from the European Society for Evolutionary Biology (ESEB). MK (M. Kapun) was supported by the Austrian Science Foundation (grant no. FWF P32275); JG by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (H2020-ERC-2014-CoG-647900) and by the Spanish Ministry of Science and Innovation (BFU-2011-24397); TF by the Swiss National Science Foundation (SNSF grants PP00P3_133641, PP00P3_165836, and 31003A_182262) and a Mercator Fellowship from the German Research Foundation (DFG), held as a EvoPAD Visiting Professor at the Institute for Evolution and Biodiversity, University of Münster; AOB by the National Institutes of Health (R35 GM119686); MK (M. Kankare) by Academy of Finland grant 322980; VL by Danish Natural Science Research Council (FNU) grant 4002-00113B; FS Deutsche Forschungsgemeinschaft (DFG) grant STA1154/4-1, Project 408908608; JP by the Deutsche Forschungsgemeinschaft Projects 274388701 and 347368302; AU by FPI fellowship (BES-2012-052999); ET Israel Science Foundation (ISF) grant 1737/17; MSV, MSR and MJ by a grant from the Ministry of Education, Science and Technological Development of the Republic of Serbia (451-03-68/2020-14/200178); AP, KE and MT by a grant from the Ministry of Education, Science and Technological Development of the Republic of Serbia (451-03-68/2020-14/200007); and TM NSERC grant RGPIN-2018-05551.Peer reviewe

Medial longitudinal arch development of school children : The College of Podiatry Annual Conference 2015: meeting abstracts

Background Foot structure is often classified into flat foot, neutral and high arch type based on the variability of the Medial Longitudinal Arch (MLA). To date, the literature provided contrasting evidence on the age when MLA development stabilises in children. The influence of footwear on MLA development is also unknown. Aim This study aims to (i) clarify whether the MLA is still changing in children from age 7 to 9 years old and (ii) explore the relationship between footwear usage and MLA development, using a longitudinal approach. Methods We evaluated the MLA of 111 healthy school children [age = 6.9 (0.3) years] using three parameters [arch index (AI), midfoot peak pressure (PP) and maximum force (MF: % of body weight)] extracted from dynamic foot loading measurements at baseline, 10-month and 22-month follow-up. Information on the type of footwear worn was collected using survey question. Linear mixed modelling was used to test for differences in the MLA over time. Results Insignificant changes in all MLA parameters were observed over time [AI: P = .15; PP: P = .84; MF: P = .91]. When gender was considered, the AI of boys decreased with age [P = .02]. Boys also displayed a flatter MLA than girls at age 6.9 years [AI: mean difference = 0.02 (0.01, 0.04); P = .02]. At baseline, subjects who wore close-toe shoes displayed the lowest MLA overall [AI/PP/MF: P < .05]. Subjects who used slippers when commencing footwear use experienced higher PP than those who wore sandals [mean difference = 31.60 (1.44, 61.75) kPa; post-hoc P = .04]. Discussion and conclusion Our findings suggested that the MLA of children remained stable from 7 to 9 years old, while gender and the type of footwear worn during childhood may influence MLA development. Clinicians may choose to commence therapy when a child presents with painful flexible flat foot at age 7 years, and may discourage younger children from wearing slippers when they commence using footwear

Multiple Signals Converge on a Differentiation MAPK Pathway

An important emerging question in the area of signal transduction is how information from different pathways becomes integrated into a highly coordinated response. In budding yeast, multiple pathways regulate filamentous growth, a complex differentiation response that occurs under specific environmental conditions. To identify new aspects of filamentous growth regulation, we used a novel screening approach (called secretion profiling) that measures release of the extracellular domain of Msb2p, the signaling mucin which functions at the head of the filamentous growth (FG) MAPK pathway. Secretion profiling of complementary genomic collections showed that many of the pathways that regulate filamentous growth (RAS, RIM101, OPI1, and RTG) were also required for FG pathway activation. This regulation sensitized the FG pathway to multiple stimuli and synchronized it to the global signaling network. Several of the regulators were required for MSB2 expression, which identifies the MSB2 promoter as a target “hub” where multiple signals converge. Accessibility to the MSB2 promoter was further regulated by the histone deacetylase (HDAC) Rpd3p(L), which positively regulated FG pathway activity and filamentous growth. Our findings provide the first glimpse of a global regulatory hierarchy among the pathways that control filamentous growth. Systems-level integration of signaling circuitry is likely to coordinate other regulatory networks that control complex behaviors