Multi-plane remote refocussing epifluorescence microscopy to image dynamic Ca2+ events

Rapid imaging of multiple focal planes without sample movement may be achieved through remote refocusing, where imaging is carried out in a plane conjugate to the sample plane. The technique is ideally suited to studying the endothelial and smooth muscle cell layers of blood vessels. These are intrinsically linked through rapid communication and must be separately imaged at a sufficiently high frame rate in order to understand this biologically crucial interaction. We have designed and implemented an epifluoresence-based remote refocussing imaging system that can image each layer at up to 20fps using different dyes and excitation light for each layer, without the requirement for optically sectioning microscopy. A novel triggering system is used to activate the appropriate laser and image acquisition at each plane of interest. Using this method, we are able to achieve axial plane separations down to 15 ????m, with a mean lateral stability of ≤ 0.32 ????m displacement using a 60x, 1.4NA imaging objective and a 60x, 0.7NA reimaging objective. The system allows us to image and quantify endothelial cell activity and smooth muscle cell activity at a high framerate with excellent lateral and good axial resolution without requiring complex beam scanning confocal microscopes, delivering a cost effective solution for imaging two planes rapidly. We have successfully imaged and analysed Ca2+ activity of the endothelial cell layer independently of the smooth muscle layer for several minutes

Pulsar-wind nebulae and magnetar outflows: observations at radio, X-ray, and gamma-ray wavelengths

We review observations of several classes of neutron-star-powered outflows: pulsar-wind nebulae (PWNe) inside shell supernova remnants (SNRs), PWNe interacting directly with interstellar medium (ISM), and magnetar-powered outflows. We describe radio, X-ray, and gamma-ray observations of PWNe, focusing first on integrated spectral-energy distributions (SEDs) and global spectral properties. High-resolution X-ray imaging of PWNe shows a bewildering array of morphologies, with jets, trails, and other structures. Several of the 23 so far identified magnetars show evidence for continuous or sporadic emission of material, sometimes associated with giant flares, and a few possible "magnetar-wind nebulae" have been recently identified.Comment: 61 pages, 44 figures (reduced in quality for size reasons). Published in Space Science Reviews, "Jets and Winds in Pulsar Wind Nebulae, Gamma-ray Bursts and Blazars: Physics of Extreme Energy Release

A Global Network of Science and Technology Advice in Foreign Ministries

This paper is a product of the International Dialogue on Science and Technology Advice in Foreign Ministries (Vienna Dialogue) in October 2016, involving more than twenty nations and several international organisations. The event was a key step to further develop the Foreign Minister Science and Technology Advisor Network (FMSTAN), growing from an initial group of five nations. The Vienna Dialogue was convened by the Fletcher School of Law and Diplomacy, Tufts University, and the International Institute for Applied Systems Analysis (IIASA) at the Vienna headquarters of IIASA, bringing together diplomats from foreign ministries to consider the value of evidence for informed decision-making by nations with regard to issues, impacts and resources within, across and beyond national boundaries. The evidence comes from the natural and social sciences with engineering and medicine as well as other areas of technology. By building common interests among nations, science is a tool of diplomacy, promoting cooperation and preventing conflict in our world. Science diplomacy was discussed as an international, interdisciplinary and inclusive process to help balance national interests and common interests in view of urgencies today and across generations in our globally-interconnected civilization

The risk of selenium deficiency in Malawi is large and varies over multiple spatial scales

Selenium (Se) is an essential human micronutrient. Deficiency of Se decreases the activity of selenoproteins and can compromise immune and thyroid function and cognitive development, and increase risks from non-communicable diseases. The prevalence of Se deficiency is unknown in many countries, especially in sub-Saharan Africa (SSA). Here we report that the risk of Se deficiency in Malawi is large among a nationally representative population of 2,761 people. For example, 62.5% and 29.6% of women of reproductive age (WRA, n = 802) had plasma Se concentrations below the thresholds for the optimal activity of the selenoproteins glutathione peroxidase 3 (GPx3; <86.9 ng mL−1) and iodothyronine deiodinase (IDI; <64.8 ng mL−1), respectively. This is the first nationally representative evidence of widespread Se deficiency in SSA. Geostatistical modelling shows that Se deficiency risks are influenced by soil type, and also by proximity to Lake Malawi where more fish is likely to be consumed. Selenium deficiency should be quantified more widely in existing national micronutrient surveillance programmes in SSA given the marginal additional cost this would incur

Identification of new susceptibility loci for osteoarthritis (arcOGEN):a genome-wide association study

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Osteoarthritis is the most common form of arthritis worldwide and is a major cause of pain and disability in elderly people. The health economic burden of osteoarthritis is increasing commensurate with obesity prevalence and longevity. Osteoarthritis has a strong genetic component but the success of previous genetic studies has been restricted due to insufficient sample sizes and phenotype heterogeneity. We undertook a large genome-wide association study (GWAS) in 7410 unrelated and retrospectively and prospectively selected patients with severe osteoarthritis in the arcOGEN study, 80% of whom had undergone total joint replacement, and 11,009 unrelated controls from the UK. We replicated the most promising signals in an independent set of up to 7473 cases and 42,938 controls, from studies in Iceland, Estonia, the Netherlands, and the UK. All patients and controls were of European descent. We identified five genome-wide significant loci (binomial test p≤5·0×10(-8)) for association with osteoarthritis and three loci just below this threshold. The strongest association was on chromosome 3 with rs6976 (odds ratio 1·12 [95% CI 1·08-1·16]; p=7·24×10(-11)), which is in perfect linkage disequilibrium with rs11177. This SNP encodes a missense polymorphism within the nucleostemin-encoding gene GNL3. Levels of nucleostemin were raised in chondrocytes from patients with osteoarthritis in functional studies. Other significant loci were on chromosome 9 close to ASTN2, chromosome 6 between FILIP1 and SENP6, chromosome 12 close to KLHDC5 and PTHLH, and in another region of chromosome 12 close to CHST11. One of the signals close to genome-wide significance was within the FTO gene, which is involved in regulation of bodyweight-a strong risk factor for osteoarthritis. All risk variants were common in frequency and exerted small effects. Our findings provide insight into the genetics of arthritis and identify new pathways that might be amenable to future therapeutic intervention.Arthritis Research UK 1803

Characteristics and sources of fluorescent aerosols in the central Arctic Ocean

The Arctic is sensitive to cloud radiative forcing. Due to the limited number of aerosols present throughout much of the year, cloud formation is susceptible to the presence of cloud condensation nuclei and ice nucleating particles (INPs). Primary biological aerosol particles (PBAP) contribute to INPs and can impact cloud phase, lifetime, and radiative properties. We present yearlong observations of hyperfluorescent aerosols (HFA), tracers for PBAP, conducted with a Wideband Integrated Bioaerosol Sensor, New Electronics Option during the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) expedition (October 2019–September 2020) in the central Arctic. We investigate the influence of potential anthropogenic and natural sources on the characteristics of the HFA and relate our measurements to INP observations during MOSAiC. Anthropogenic sources influenced HFA during the Arctic haze period. But surprisingly, we also found sporadic “bursts” of HFA with the characteristics of PBAP during this time, albeit with unclear origin. The characteristics of HFA between May and August 2020 and in October 2019 indicate a strong contribution of PBAP to HFA. Notably from May to August, PBAP coincided with the presence of INPs nucleating at elevated temperatures, that is, >−9°C, suggesting that HFA contributed to the “warm INP” concentration. The air mass residence time and area between May and August and in October were dominated by the open ocean and sea ice, pointing toward PBAP sources from within the Arctic Ocean. As the central Arctic changes drastically due to climate warming with expected implications on aerosol–cloud interactions, we recommend targeted observations of PBAP that reveal their nature (e.g., bacteria, diatoms, fungal spores) in the atmosphere and in relevant surface sources, such as the sea ice, snow on sea ice, melt ponds, leads, and open water, to gain further insights into the relevant source processes and how they might change in the future