New insights on Laminaria digitata ultrastructure through combined conventional chemical fixation and cryofixation

Acknowledgements The research leading to these results received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No .730984, ASSEMBLE Plus project, supporting access of CK and FCK to the Station Biologique de Roscoff. This work was conducted in conjunction with the European Marine Biological Resource Centre (EMBRC-ERIC), EMBRC-France. French state funds are managed by the ANR within the Investments of the Future program under reference ANR-10-INSB-02. Also, funding from the UK Natural Environment Research Council (NERC) through grants NE/D521522/1, NE/F012705/1, and Oceans 2025 (WP4.5) programs to FCK; the National Science Foundation (CHE-1664657) and the National Oceanic & Atmospheric Administration to CJC and FCK; and the MASTS pooling initiative (Marine Alliance for Science and Technology for Scotland, funded by the Scottish Funding Council and contributing institutions; grant reference HR09011) is gratefully acknowledged. Finally, we would like to acknowledge Susan Loiseaux-de Goër, Bernard Kloareg, Philippe Potin and Akira F. Peters for their hospitality and support to FCK and CK during their visit to RoscoffPeer reviewedPostprin

Changes in communication between muscle stem cells and their environment with aging

Aging is associated with both muscle weakness and a loss of muscle mass, contributing towards overall frailty in the elderly. Aging skeletal muscle is also characterised by a decreasing efficiency in repair and regeneration, together with a decline in the number of adult stem cells. Commensurate with this are general changes in whole body endocrine signalling, in local muscle secretory environment, as well as in intrinsic properties of the stem cells themselves. The present review discusses the various mechanisms that may be implicated in these age-associated changes, focusing on aspects of cell-cell communication and long-distance signalling factors, such as levels of circulating growth hormone, IL-6, IGF1, sex hormones, and inflammatory cytokines. Changes in the local environment are also discussed, implicating IL-6, IL-4, FGF-2, as well as other myokines, and processes that lead to thickening of the extra-cellular matrix. These factors, involved primarily in communication, can also modulate the intrinsic properties of muscle stem cells, including reduced DNA accessibility and repression of specific genes by methylation. Finally we discuss the decrease in the stem cell pool, particularly the failure of elderly myoblasts to re-quiesce after activation, and the consequences of all these changes on general muscle homeostasis

Optimized method for extraction of exosomes from human primary muscle cells

International audienceSkeletal muscle is increasingly considered an endocrine organ secreting myokines and extracellular vesicles (exosomes and microvesicles), which can affect physiological changes with an impact on different pathological conditions, including regenerative processes, aging, and myopathies. Primary human myoblasts are an essential tool to study the muscle vesicle secretome. Since their differentiation in conditioned media does not induce any signs of cell death or cell stress, artefactual effects from those processes are unlikely. However, adult human primary myoblasts senesce in long-term tissue culture, so a major technical challenge is posed by the need to avoid artefactual effects resulting from pre-senescent changes. Since these cells should be studied within a strictly controlled pre-senescent division count (30 times fewer differentiated myoblasts than what is required for the ultracentrifugation method. In addition, exosomes could still be integrated into recipient cells such as human myotubes or iPSC-derived motor neurons. Modified polymer-based precipitation combined with extra washing steps optimizes exosome yield from a lower number of differentiated myoblasts and less conditioned medium, avoiding senescence and allowing the execution of multiple experiments without exhausting the proliferative capacity of the myoblasts

Assessment of capacity for health policy and systems research and analysis in seven African universities: results from the CHEPSAA project

The importance of health policy and systems research and analysis (HPSR+A) is widely recognized. Universities are central to strengthening and sustaining the HPSR+A capacity as they teach the next generation of decision-makers and health professionals. However, little is known about the capacity of universities, specifically, to develop the field. In this article, we report results of capacity self- assessments by seven universities within five African countries, conducted through the Consortium for Health Policy and Systems Analysis in Africa (CHEPSAA). The capacity assessments focused on both capacity ‘assets’ and ‘needs’, and covered the wider context, as well as organizational and individual capacity levels. Six thematic areas of capacity were examined: leadership and governance, organizations’ resources, scope of HPSR+A teaching and research, communication, networking and getting research into policy and practice (GRIPP), demand for HPRS+A and resource environment. The self-assessments by each university used combinations of document reviews, semi-structured interviews and staff surveys, followed by comparative analysis. A framework approach, guided by the six thematic areas, was used to analyse data. We found that HPSR+A is an international priority, and an existing activity in Africa, though still neglected field with challenges including its reliance on unpredictable international funding. All universities have capacity assets, such as ongoing HPSR+A teaching and research. There are, however, varying levels of assets (such as differences in staff numbers, group sizes and amount of HPSR+A teaching and research), which, combined with different capacity needs at all three levels (such as individual training, improvement in systems for quality assurance and fostering demand for HPSR+A work), can shape a future agenda for HPSR+A capacity strengthening. Capacity assets and needs at different levels appear related. Possible integrated strategies for strengthening universities’ capacity include: refining HPSR+A vision, mainstreaming the subject into under- and post-graduate teaching, developing emerging leaders and aligning HPSR+A capacity strengthening within the wider organizational development.Web of Scienc

Manganese-Enhanced T₁ Mapping in the Myocardium of Normal and Infarcted Hearts

Background. Manganese-enhanced MRI (MEMRI) has the potential to identify viable myocardium and quantify calcium influx and handling. Two distinct manganese contrast media have been developed for clinical application, mangafodipir and EVP1001-1, employing different strategies to mitigate against adverse effects resulting from calcium-channel agonism. Mangafodipir delivers manganese ions as a chelate, and EVP1001-1 coadministers calcium gluconate. Using myocardial T1 mapping, we aimed to explore chelated and nonchelated manganese contrast agents, their mechanism of myocardial uptake, and their application to infarcted hearts. Methods. T1 mapping was performed in healthy adult male Sprague-Dawley rats using a 7T MRI scanner before and after nonchelated (EVP1001-1 or MnCl2 (22 μmol/kg)) or chelated (mangafodipir (22–44 μmol/kg)) manganese-based contrast media in the presence of calcium channel blockade (diltiazem (100–200 μmol/kg/min)) or sodium chloride (0.9%). A second cohort of rats underwent surgery to induce anterior myocardial infarction by permanent coronary artery ligation or sham surgery. Infarcted rats were imaged with standard gadolinium delayed enhancement MRI (DEMRI) with inversion recovery techniques (DEMRI inversion recovery) as well as DEMRI T1 mapping. A subsequent MEMRI scan was performed 48 h later using either nonchelated or chelated manganese and T1 mapping. Finally, animals were culled at 12 weeks, and infarct size was quantified histologically with Masson’s trichrome (MTC). Results. Both manganese agents induced concentration-dependent shortening of myocardial T1 values. This was greatest with nonchelated manganese, and could be inhibited by 30–43% with calcium-channel blockade. Manganese imaging successfully delineated the area of myocardial infarction. Indeed, irrespective of the manganese agent, there was good agreement between infarct size on MEMRI T1 mapping and histology (bias 1.4%, 95% CI −14.8 to 17.1 P&gt;0.05). In contrast, DEMRI inversion recovery overestimated infarct size (bias 11.4%, 95% CI −9.1 to 31.8 P=0.002), as did DEMRI T1 mapping (bias 8.2%, 95% CI −10.7 to 27.2 P=0.008). Increased manganese uptake was also observed in the remote myocardium, with remote myocardial ∆T1 inversely correlating with left ventricular ejection fraction after myocardial infarction (r=−0.61, P=0.022). Conclusions. MEMRI causes concentration and calcium channel-dependent myocardial T1 shortening. MEMRI with T1 mapping provides an accurate assessment of infarct size and can also identify changes in calcium handling in the remote myocardium. This technique has potential applications for the assessment of myocardial viability, remodelling, and regeneration.</jats:p

Street-scale dispersion modelling framework of road-traffic derived air pollution in Hanoi, Vietnam

Traffic is an important source of air pollution in Vietnamese cities. The spatio-temporal variation of air pollution derived from traffic is poorly understood. Application of dispersion modelling can help but is hindered by the local scarcity of suitable input data. This study fills the data gap, by establishing a framework employing open-access global data to model emission from traffic activities in Hanoi. The outlined methodology explicitly defines road sources, calculates their emission, and employs background pollution profiles from Copernicus Atmospheric Monitoring Service (CAMS) to produce street-scale distribution maps for CO, PM10 and PM2.5. Pollution hotspots are found near major traffic flows with the highest hourly average CO, PM10 and PM2.5 concentrations at 1206, 87.5 and 61.5 μgm−3, respectively. The relationship between concentrations and properties of the road network is assessed. Motorcycles are the main emitters of the traffic sector. Emission from Heavy Good Vehicles dominate during the night, with contribution percentages increase as it gets further away from the city core. Modelled concentrations are underestimated mainly due to low vehicular emission factor. Adjusting emission factors according to vehicle quality in Vietnam greatly improves agreement. The presence of non-traffic emission sources contributes to the model underestimation. Results for comparisons of daily averaged PM values are broadly in agreement between models and observations; however, diurnal patters are skewed. This results partly from the uncertainties linked with background pollution levels from CAMS, and partly from non-traffic sources which are not accounted for here. Further work is needed to assess the use of CAMS's concentrations in Vietnam. Meteorological input contributes to the temporal disagreement between the model and observations. The impact is most noticeable with CO concentrations during morning traffic rush hours. This study recommends approaches to improve input for future model iterations and encourage applications of dispersion modelling studies in similar economic settings