Effects of Three Modest Levels of Proximal Loading on Marathon Pace Running Economy

International Journal of Exercise Science 13(7): 1120-1131, 2020. This study examined the effect of modest increases in proximal body mass on running economy expressed as metabolic cost (MC). External loads of 1.6 (L), 2.4 (M), and 3.2 kg (H) were added to the anterior and posterior torso region of male (n = 18) and female (n = 18) runners using a double-layered compression garment with gel inserts. MC was evaluated using stoichiometry equations of data collected via indirect calorimetry. Data was collected during four, 5-min running bouts at marathon pace for the 3 load levels and an unloaded state (CON). When data from both sexes were combined, MC for CON (13.2 ± 2.7) was lower (p \u3c 0.05) versus L (13.5 ± 2.6), M (13.6 ± 2.6), and H (13.7 ± 2.6 kcal/min), but L did not differ from CON when data was analyzed for each sex. Male runners exhibited stepped increases in MC across loads and a weak-moderate relationship (r = 0.37; p \u3c 0.01) between percentage change in absolute MC and increased percent body mass. A prediction model for MC (∆% kcal/min = 0.98(∆% body mass) – 0.91; SEE = ± 2.5%) was developed. For female runners, L increased MC by ~3.5% above CON, but no differentiation was found among L, M, and H, limiting the development of a prediction equation for females. Modest increases in body mass can produce detectable and potentially important levels of running economy impairment, but the relationship between changes in body mass and RE are complex, particularly in regards to sex

Coordination of myeloid differentiation with reduced cell cycle progression by PU.1 Induction of microRNAs targeting cell cycle regulators and lipid anabolism

During macrophage development, myeloid progenitor cells undergo terminal differentiation coordinated with reduced cell cycle progression. Differentiation of macrophages from myeloid progenitors is accompanied by increased expression of the E26 transformation-specific transcription factor PU.1. Reduced PU.1 expression leads to increased proliferation and impaired differentiation of myeloid progenitor cells. It is not understood how PU.1 coordinates macrophage differentiation with reduced cell cycle progression. In this study, we utilized cultured PU.1- inducible myeloid cells to perform genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) analysis coupled with gene expression analysis to determine targets of PU.1 that may be involved in regulating cell cycle progression. We found that genes encoding cell cycle regulators and enzymes involved in lipid anabolism were directly and inducibly bound by PU.1 although their steady-state mRNA transcript levels were reduced. Inhibition of lipid anabolism was sufficient to reduce cell cycle progression in these cells. Induction of PU.1 reduced expression of E2f1, an important activator of genes involved in cell cycle and lipid anabolism, indirectly through microRNA 223. Next-generation sequencing identified microRNAs validated as targeting cell cycle and lipid anabolism for downregulation. These results suggest that PU.1 coordinates cell cycle progression with differentiation through induction of microRNAs targeting cell cycle regulators and lipid anabolism

AP-4 vesicles contribute to spatial control of autophagy via RUSC-dependent peripheral delivery of ATG9A.

Adaptor protein 4 (AP-4) is an ancient membrane trafficking complex, whose function has largely remained elusive. In humans, AP-4 deficiency causes a severe neurological disorder of unknown aetiology. We apply unbiased proteomic methods, including 'Dynamic Organellar Maps', to find proteins whose subcellular localisation depends on AP-4. We identify three transmembrane cargo proteins, ATG9A, SERINC1 and SERINC3, and two AP-4 accessory proteins, RUSC1 and RUSC2. We demonstrate that AP-4 deficiency causes missorting of ATG9A in diverse cell types, including patient-derived cells, as well as dysregulation of autophagy. RUSC2 facilitates the transport of AP-4-derived, ATG9A-positive vesicles from the trans-Golgi network to the cell periphery. These vesicles cluster in close association with autophagosomes, suggesting they are the "ATG9A reservoir" required for autophagosome biogenesis. Our study uncovers ATG9A trafficking as a ubiquitous function of the AP-4 pathway. Furthermore, it provides a potential molecular pathomechanism of AP-4 deficiency, through dysregulated spatial control of autophagy

Provision of non-invasive coronary and carotid vascular imaging results on changes in diet and physical activity in asymptomatic adults: A scoping review

Background: Although a healthy diet and physical activity have been shown to prevent or delay cardiovascular disease (CVD) hospitalizations and deaths, most adults do not meet current guidelines. Provision of coronary artery calcification (CAC) and carotid ultrasound (CUS) imaging results may motivate beneficial lifestyle changes. We scoped the existing literature for studies providing non-invasive vascular imaging results and reporting diet, physical activity, and/or anthropometric measures to identify knowledge gaps and opportunities for further research. Methods: A systematic search was performed across three electronic databases, in line with PRISMA ScR guidelines and Arksey and O\u27Malley\u27s scoping review framework. Results: Twenty studies (thirteen observational and seven randomized controlled trials) examining the impact of provision of CAC/CUS imaging results on diet and/or physical activity behaviors were included. Nearly half the studies did not clearly state whether participants received dietary and physical activity advice along with vascular imaging results, and these were secondary outcomes in most studies, with data assessment and reporting being inconsistent. Conclusion: Well-designed clinical trials with consistent and clear messaging based on detailed subjective and objective measures of diet and physical activity are needed to determine whether this approach may stimulate long-term dietary and physical activity change

COPI mediates recycling of an exocytic SNARE by recognition of a ubiquitin sorting signal

The COPI coat forms transport vesicles from the Golgi complex and plays a poorly defined role in endocytic trafficking. Here we show that COPI binds K63-linked polyubiquitin and this interaction is crucial for trafficking of a ubiquitinated yeast SNARE (Snc1). Snc1 is a v-SNARE that drives fusion of exocytic vesicles with the plasma membrane, and then recycles through the endocytic pathway to the Golgi for reuse in exocytosis. Removal of ubiquitin from Snc1, or deletion of a β’-COP subunit propeller domain that binds K63-linked polyubiquitin, disrupts Snc1 recycling causing aberrant accumulation in internal compartments. Moreover, replacement of the β’-COP propeller domain with unrelated ubiquitin-binding domains restores Snc1 recycling. These results indicate that ubiquitination, a modification well known to target membrane proteins to the lysosome or vacuole for degradation, can also function as recycling signal to sort a SNARE into COPI vesicles in a non-degradative pathway

Dietary nitrate and diet quality: An examination of changing dietary intakes within a representative sample of Australian women

Dietary nitrate is increasingly linked to a variety of beneficial health outcomes. Our purpose was to estimate dietary nitrate consumption and identify key dietary changes which have occurred over time within a representative sample of Australian women. Women from the 1946–1951 cohort of the Australian Longitudinal Study on Women’s Health with complete food frequency questionnaire data for both 2001 and 2013 were included for analysis. Dietary nitrate intakes were calculated using key published nitrate databases. Diet quality scores including the Australian Recommended Food Score, the Mediterranean Diet Score and the Nutrient Rich Foods Index were calculated along with food group serves as per the Australian Dietary Guidelines. Wilcoxon matched pairs tests were used to test for change in dietary intakes and Spearman’s correlations were used to examine associations. In our sample of 8161 Australian women, dietary nitrate intakes were on average 65–70 mg/day, and we detected a significant increase in dietary nitrate consumption over time (+6.57 mg/day). Vegetables were the primary source of dietary nitrate (81–83%), in particular lettuce (26%), spinach (14–20%), beetroot (10–11%), and celery (7–8%) contributed primarily to vegetable nitrate intakes. Further, increased dietary nitrate intakes were associated with improved diet quality scores (r = 0.3, p \u3c 0.0001). Although there is emerging evidence indicating that higher habitual dietary nitrate intakes are associated with reduced morbidity and mortality, future work in this area should consider how dietary nitrate within the context of overall diet quality can facilitate health to ensure consistent public health messages are conveyed

RNA:DNA hybrids are a novel molecular pattern sensed by TLR9.

The sensing of nucleic acids by receptors of the innate immune system is a key component of antimicrobial immunity. RNA:DNA hybrids, as essential intracellular replication intermediates generated during infection, could therefore represent a class of previously uncharacterised pathogen-associated molecular patterns sensed by pattern recognition receptors. Here we establish that RNA:DNA hybrids containing viral-derived sequences efficiently induce pro-inflammatory cytokine and antiviral type I interferon production in dendritic cells. We demonstrate that MyD88-dependent signalling is essential for this cytokine response and identify TLR9 as a specific sensor of RNA:DNA hybrids. Hybrids therefore represent a novel molecular pattern sensed by the innate immune system and so could play an important role in host response to viruses and the pathogenesis of autoimmune disease

Accretion of Planetary Material onto Host Stars

Accretion of planetary material onto host stars may occur throughout a star's life. Especially prone to accretion, extrasolar planets in short-period orbits, while relatively rare, constitute a significant fraction of the known population, and these planets are subject to dynamical and atmospheric influences that can drive significant mass loss. Theoretical models frame expectations regarding the rates and extent of this planetary accretion. For instance, tidal interactions between planets and stars may drive complete orbital decay during the main sequence. Many planets that survive their stars' main sequence lifetime will still be engulfed when the host stars become red giant stars. There is some observational evidence supporting these predictions, such as a dearth of close-in planets around fast stellar rotators, which is consistent with tidal spin-up and planet accretion. There remains no clear chemical evidence for pollution of the atmospheres of main sequence or red giant stars by planetary materials, but a wealth of evidence points to active accretion by white dwarfs. In this article, we review the current understanding of accretion of planetary material, from the pre- to the post-main sequence and beyond. The review begins with the astrophysical framework for that process and then considers accretion during various phases of a host star's life, during which the details of accretion vary, and the observational evidence for accretion during these phases.Comment: 18 pages, 5 figures (with some redacted), invited revie

Implementation, mechanisms of impact and key contextual factors involved in outcomes of the Modification of Diet, Exercise and Lifestyle (MODEL) randomised controlled trial in Australian adults: Protocol for a mixed-method process evaluation

Introduction The Modification of Diet, Exercise and Lifestyle (MODEL) study aims to examine the impact of providing visualisation and pictorial representation of advanced structural vascular disease (abdominal aortic calcification), on ‘healthful’ improvements to diet and lifestyle. This paper reports the protocol for the process evaluation for the MODEL study. Methods and analysis The overall aim of the process evaluation is to understand the processes that took place during participation in the MODEL study trial and which elements were effective or ineffective for influencing ‘healthful’ behavioural change, and possible ways of improvement to inform wider implementation strategies. A mixed-method approach will be employed with the use of structured questionnaires and semistructured in-depth interviews. All 200 participants enrolled in the trial will undertake the quantitative component of the study and maximum variation sampling will be used to select a subsample for the qualitative component. The sample size for the qualitative component will be determined based on analytical saturation. Interviews will be digitally recorded and transcribed verbatim. Qualitative data will be analysed thematically and reported according to the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines. Ethics and dissemination The MODEL study process evaluation has received approval from Edith Cowan University Human Research Ethics Committee (Project Number: 20513 HODGSON). Written informed consent will be obtained from all participants before they are included in the study. The study results will be shared with the individuals and institutions associated with this study as well as academic audiences through peer-reviewed publication and probable presentation at conferences

Taking the steps towards sustainable livestock: our multidisciplinary global farm platform journey

Implications The Global Farm Platform was conceived and established to explore multidisciplinary strategies for optimising the sustainability of ruminant livestock systems around the world. International sustainability issues are common, but the solutions are often region-specific; therefore, our farms, situated across all major agroclimatic zones, are a unique resource worldwide. Each farm is following ?steps to sustainable livestock? to improve their production system(s), thereby developing robust metrics to progress economic, environmental and social viability. The consortium works collaboratively to improve the sustainability of ruminants, which we argue are a vital component of global food systems, delivering both human and planetary health