MicroRNA profile of extracellular vesicles released by Müller glial cells

IntroductionAs with any other radial glia in the central nervous system, Müller glia derive from the same neuroepithelial precursors, perform similar functions, and exhibit neurogenic properties as radial glia in the brain. Müller glial cells retain progenitor-like characteristics in the adult human eye and can partially restore visual function upon intravitreal transplantation into animal models of glaucoma. Recently, it has been demonstrated that intracellular communication is possible via the secretion of nano-sized membrane-bound extracellular vesicles (EV), which contain bioactive molecules like microRNA (miRNA) and proteins that induce phenotypic changes when internalised by recipient cells.MethodsWe conducted high-throughput sequencing to profile the microRNA signature of EV populations secreted by Müller glia in culture and used bioinformatics tools to evaluate their potential role in the neuroprotective signalling attributed to these cells.ResultsSequencing of miRNA within Müller EV suggested enrichment with species associated with stem cells such as miR-21 and miR-16, as well as with miRNA previously found to play a role in diverse Müller cell functions in the retina: miR-9, miR-125b, and the let-7 family. A total of 51 miRNAs were found to be differentially enriched in EV compared to the whole cells from which EV originated. Bioinformatics analyses also indicated that preferential enrichment of species was demonstrated to regulate genes involved in cell proliferation and survival, including PTEN, the master inhibitor of the PI3K/AKT pathway.DiscussionThe results suggest that the release by Müller cells of miRNA-enriched EV abundant in species that regulate anti-apoptotic signalling networks is likely to represent a significant proportion of the neuroprotective effect observed after the transplantation of these cells into animal models of retinal ganglion cell (RGC) depletion. Future studies will seek to evaluate the modulation of putative genes as well as the activation of these pathways in in vitro and in vivo models following the internalisation of Müller-EV by target retinal neurons

The feasibility of community level interventions for pre-eclampsia in South Asia and sub-saharan Africa: A mixed-methods design

Background: Globally, pre-eclampsia and eclampsia are major contributors to maternal and perinatal mortality; of which the vast majority of deaths occur in less developed countries. In addition, a disproportionate number of morbidities and mortalities occur due to delayed access to health services. The Community Level Interventions for Pre-eclampsia (CLIP) Trial aims to task-shift to community health workers the identification and emergency management of pre-eclampsia and eclampsia to improve access and timely care. Literature revealed paucity of published feasibility assessments prior to initiating large-scale community-based interventions. Arguably, well-conducted feasibility studies can provide valuable information about the potential success of clinical trials prior to implementation. Failure to fully understand the study context risks the effective implementation of the intervention and limits the likelihood of post-trial scale-up. Therefore, it was imperative to conduct community-level feasibility assessments for a trial of this magnitude.Methods: A mixed methods design guided by normalization process theory was used for this study in Nigeria, Mozambique, Pakistan, and India to explore enabling and impeding factors for the CLIP Trial implementation. Qualitative data were collected through participant observation, document review, focus group discussion and in-depth interviews with diverse groups of community members, key informants at community level, healthcare providers, and policy makers. Quantitative data were collected through health facility assessments, self-administered community health worker surveys, and household demographic and health surveillance.Results: Refer to CLIP Trial feasibility publications in the current and/or forthcoming supplement.Conclusions: Feasibility assessments for community level interventions, particularly those involving task-shifting across diverse regions, require an appropriate theoretical framework and careful selection of research methods. The use of qualitative and quantitative methods increased the data richness to better understand the community contexts

Economic development, human development, and the pursuit of happiness, April 1, 2, and 3, 2004

This repository item contains a single issue of the Pardee Conference Series, a publication series that began publishing in 2006 by the Boston University Frederick S. Pardee Center for the Study of the Longer-Range Future. This was the Center's spring conference, which took place during April 1, 2, and 3, 2004.The conference asks the questions, how can we make sure that the benefits of economic growth flow into health, education, welfare, and other aspects of human development; and what is the relationship between human development and economic development? Speakers and participants discuss the role that culture, legal and political institutions, the UN Developmental Goals, the level of decision-making, and ethics, play in development

Nanostructure Engineering of Metal–Organic Derived Frameworks: Cobalt Phosphide Embedded in Carbon Nanotubes as an Efficient Orr Catalyst

Heteroatom doping is considered an efficient strategy when tuning the electronic and structural modulation of catalysts to achieve improved performance towards renewable energy applications. Herein, we synthesized a series of carbon-based hierarchical nanostructures through the controlled pyrolysis of Co-MOF (metal organic framework) precursors followed by in situ phosphidation. Two kinds of catalysts were prepared: metal nanoparticles embedded in carbon nanotubes, and metal nanoparticles dispersed on the carbon surface. The results proved that the metal nanoparticles embedded in carbon nanotubes exhibit enhanced ORR electrocatalytic performance, owed to the enriched catalytic sites and the mass transfer facilitating channels provided by the hierarchical porous structure of the carbon nanotubes. Furthermore, the phosphidation of the metal nanoparticles embedded in carbon nanotubes (P-Co-CNTs) increases the surface area and porosity, resulting in faster electron transfer, greater conductivity, and lower charge transfer resistance towards ORR pathways. The P-Co-CNT catalyst shows a half-wave potential of 0.887 V, a Tafel slope of 67 mV dec−1, and robust stability, which are comparatively better than the precious metal catalyst (Pt/C). Conclusively, this study delivers a novel path for designing multiple crystal phases with improved catalytic performance for energy devices. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Acknowledgments: S.S.A. Shah is grateful to the higher education commission (HEC) of Pakistan for IPFP funding at the Institute of Chemistry, The Islamia University of Bahawalpur, Pakistan. Furthermore, P. Tsiakaras, A. Brouzgou and C. Molochas thankfully acknowledge the co-financing by the European Union & Greek National funds through the Operational Program Competitiveness, Entrepreneurship, and Innovation, under the call RESEARCH–CREATE–INNOVATE (T1EDK-02442)

Tilted beam fabry-perot antenna with enhanced gain and broadband low backscattering

Communication with low radar signature platforms requires antennas with low backscatter, to uphold the low observability attribute of the platforms. In this work, we present the design for a Fabry–Perot (F-P) cavity antenna with low monostatic radar cross section (RCS) and enhanced gain. In addition, peak radiation is tilted inthe elevation plane. This is achieved by incorporating phase gradient metasurface (PGM) with absorptive frequency selective surface (FSS). The periodic surface of metallic square loops with lumped resistors forms the absorptive surface, placed on top of a partially reflecting surface (PRS) with an intervening air gap. The double-sided PRS consists of uniform metallic patches etched in a periodic fashion on its upper side. The bottom surface consists of variable-sized metallic patches, to realize phase gradient. The superstrate assembly is placed at about half free space wavelength above the patch antenna resonating at 6.6 GHz. The antenna’s ground plane and PRS together construct the F-P cavity. A peak gain of 11.5 dBi is achieved at 13◦ tilt of the elevation plane. Wideband RCS reduction is achieved, spanning 5.6–16 GHz, for x-and y-polarizations of normally incident plane wave. The average RCS reduction is 13 dB. Simulation results with experimental verifications are presented

Climate justice and the international regime: before, during and after Paris

With a focus on key themes and debates, this article aims to illustrate and assess how the interaction between justice and politics has shaped the international regime and defined the nature of the international agreement that was signed in COP21 Paris. The work demonstrates that despite the rise of neo-conservatism and self-interested power politics, questions of global distributive justice remain a central aspect of the international politics of climate change. However, while it is relatively easy to demonstrate that international climate politics is not beyond the reach of moral contestations, the assessment of exactly how much impact justice has on climate policies and the broader normative structures of the climate governance regime remains a very difficult task. As the world digests the Paris Agreement, it is vital that the current state of justice issues within the international climate change regime is comprehensively understood by scholars of climate justice and by academics and practitioners, not least because how these intractable issues of justice are dealt with (or not) will be a crucial factor in determining the effectiveness of the emerging climate regime

Familial hypercholesterolemia and elevated lipoprotein(a) : double heritable risk and new therapeutic opportunities

Vuorio A, Watts GF, Schneider WJ, Tsimikas S, Kovanen PT (Mehilainen Airport Health Centre, Vantaa; University of Helsinki, Helsinki, Finland; University of Western Australia, Perth, Australia; Royal Perth Hospital, Perth, Australia; Medical University of Vienna, Vienna, Austria; University of California San Diego, La Jolla, CA, USA; Wihuri Research Institute, Helsinki, Finland). Familial hypercholesterolemia and elevated lipoprotein(a): double heritable risk and new therapeutic opportunities (Review). J Intern Med 2020; 287: 2-18. There is compelling evidence that the elevated plasma lipoprotein(a) [Lp(a)] levels increase the risk of atherosclerotic cardiovascular disease (ASCVD) in the general population. Like low-density lipoprotein (LDL) particles, Lp(a) particles contain cholesterol and promote atherosclerosis. In addition, Lp(a) particles contain strongly proinflammatory oxidized phospholipids and a unique apoprotein, apo(a), which promotes the growth of an arterial thrombus. At least one in 250 individuals worldwide suffer from the heterozygous form of familial hypercholesterolemia (HeFH), a condition in which LDL-cholesterol (LDL-C) is significantly elevated since birth. FH-causing mutations in the LDL receptor gene demonstrate a clear gene-dosage effect on Lp(a) plasma concentrations and elevated Lp(a) levels are present in 30-50% of patients with HeFH. The cumulative burden of two genetically determined pro-atherogenic lipoproteins, LDL and Lp(a), is a potent driver of ASCVD in HeFH patients. Statins are the cornerstone of treatment of HeFH, but they do not lower the plasma concentrations of Lp(a). Emerging therapies effectively lower Lp(a) by as much as 90% using RNA-based approaches that target the transcriptional product of the LPA gene. We are now approaching the dawn of an era, in which permanent and significant lowering of the high cholesterol burden of HeFH patients can be achieved. If outcome trials of novel Lp(a)-lowering therapies prove to be safe and cost-effective, they will provide additional risk reduction needed to effectively treat HeFH and potentially lower the CVD risk in these high-risk patients even more than currently achieved with LDL-C lowering alone.Peer reviewe

Looking Good: Mediatisation and International NGOs

Many international NGOs value those parts of their work that are suited to media representation: campaigning, advocacy, projects that produce the right sort of images. In this article I make three points about this change. First, those parts of the NGO most reliant on media – such as the campaign desk – may be becoming more powerful. This can change the internal dynamics of NGOs. Second, the increasing use of media means that NGOs, like other organisations, hold themselves accountable in new ways. Third, NGOs may appear to look more and more like media organisations. These changes have received relatively little attention in the literature on NGOs, though they reflect a broader set of debates about the role of media in society. Using a case analysis of an international NGO, I suggest that the concept of mediatisation might be a useful way to understand some of the changes observed in the NGO sector