Lipoprotein-associated phospholipase A2 (Lp-PLA2) as a therapeutic target to prevent retinal vasopermeability during diabetes

Lipoprotein-associated phospholipase A2 (Lp-PLA2) hydrolyses oxidized low-density lipoproteins into proinflammatory products, which can have detrimental effects on vascular function. As a specific inhibitor of Lp-PLA2, darapladib has been shown to be protective against atherogenesis and vascular leakage in diabetic and hypercholesterolemic animal models. This study has investigated whether Lp-PLA2 and its major enzymatic product, lysophosphatidylcholine (LPC), are involved in blood-retinal barrier (BRB) damage during diabetic retinopathy. We assessed BRB protection in diabetic rats through use of species-specific analogs of darapladib. Systemic Lp-PLA2 inhibition using SB-435495 at 10 mg/kg (i.p.) effectively suppressed BRB breakdown in streptozotocin-diabetic Brown Norway rats. This inhibitory effect was comparable to intravitreal VEGF neutralization, and the protection against BRB dysfunction was additive when both targets were inhibited simultaneously. Mechanistic studies in primary brain and retinal microvascular endothelial cells, as well as occluded rat pial microvessels, showed that luminal but not abluminal LPC potently induced permeability, and that this required signaling by the VEGF receptor 2 (VEGFR2). Taken together, this study demonstrates that Lp-PLA2 inhibition can effectively prevent diabetes-mediated BRB dysfunction and that LPC impacts on the retinal vascular endothelium to induce vasopermeability via VEGFR2. Thus, Lp-PLA2 may be a useful therapeutic target for patients with diabetic macular edema (DME), perhaps in combination with currently administered anti-VEGF agents

Pleosporales

One hundred and five generic types of Pleosporales are described and illustrated. A brief introduction and detailed history with short notes on morphology, molecular phylogeny as well as a general conclusion of each genus are provided. For those genera where the type or a representative specimen is unavailable, a brief note is given. Altogether 174 genera of Pleosporales are treated. Phaeotrichaceae as well as Kriegeriella, Zeuctomorpha and Muroia are excluded from Pleosporales. Based on the multigene phylogenetic analysis, the suborder Massarineae is emended to accommodate five families, viz. Lentitheciaceae, Massarinaceae, Montagnulaceae, Morosphaeriaceae and Trematosphaeriaceae

The HST/ACS Coma Cluster Survey: I - Survey Objectives and Design

We describe the HST ACS Coma cluster Treasury survey, a deep two-passband imaging survey of one of the nearest rich clusters of galaxies, the Coma cluster (Abell 1656). The survey was designed to cover an area of 740 square arcmin in regions of different density of both galaxies and intergalactic medium within the cluster. The ACS failure of January 27th 2007 leaves the survey 28% complete, with 21 ACS pointings (230 square arcmin) complete, and partial data for a further 4 pointings (44 square arcmin). Predicted survey depth for 10 sigma detections for optimal photometry of point sources is g' = 27.6 in the F475W filter, and IC=26.8 mag in F814 (AB magnitudes). Initial simulations with artificially injected point sources show 90% recovered at magnitude limits of g' = 27.55 and IC = 26.65. For extended sources, the predicted 10 sigma limits for a 1 square arcsecond region are g' = 25.8 mag/sq. arcsec and IC = 25.0 mag/sq. arcsec. We highlight several motivating science goals of the survey, including study of the faint end of the cluster galaxy luminosity function, structural parameters of dwarf galaxies, stellar populations and their effect on colors and color gradients, evolution of morphological components in a dense environment, the nature of ultra compact dwarf galaxies, and globular cluster populations of cluster galaxies of a range of luminosities and types. This survey will also provide a local rich cluster benchmark for various well known global scaling relations and explore new relations pertaining to the nuclear properties of galaxies

The HST/ACS Coma Cluster Survey. II. Data Description and Source Catalogs

The Coma cluster was the target of a HST-ACS Treasury program designed for deep imaging in the F475W and F814W passbands. Although our survey was interrupted by the ACS instrument failure in 2007, the partially completed survey still covers ~50% of the core high-density region in Coma. Observations were performed for 25 fields that extend over a wide range of cluster-centric radii (~1.75 Mpc) with a total coverage area of 274 arcmin^2. The majority of the fields are located near the core region of Coma (19/25 pointings) with six additional fields in the south-west region of the cluster. In this paper we present reprocessed images and SExtractor source catalogs for our survey fields, including a detailed description of the methodology used for object detection and photometry, the subtraction of bright galaxies to measure faint underlying objects, and the use of simulations to assess the photometric accuracy and completeness of our catalogs. We also use simulations to perform aperture corrections for the SExtractor Kron magnitudes based only on the measured source flux and half-light radius. We have performed photometry for ~73,000 unique objects; one-half of our detections are brighter than the 10-sigma point-source detection limit at F814W=25.8 mag (AB). The slight majority of objects (60%) are unresolved or only marginally resolved by ACS. We estimate that Coma members are 5-10% of all source detections, which consist of a large population of unresolved objects (primarily GCs but also UCDs) and a wide variety of extended galaxies from a cD galaxy to dwarf LSB galaxies. The red sequence of Coma member galaxies has a constant slope and dispersion across 9 magnitudes (-21<M_F814W<-13). The initial data release for the HST-ACS Coma Treasury program was made available to the public in 2008 August. The images and catalogs described in this study relate to our second data release

Bringing Back a Healthy Buzz? Invertebrate Parasites and Reintroductions:A Case Study in Bumblebees

Reintroductions can play a key role in the conservation of endangered species. Parasites may impact reintroductions, both positively and negatively, but few case studies of how to manage parasites during reintroductions exist. Bumblebees are in decline at regional and global scales, and reintroductions can be used to re-establish extinct local populations. Here we report on how the risks associated with parasites are being managed in an ongoing reintroduction of the short-haired bumblebee, Bombus subterraneus, to the UK. Disease risk analysis was conducted and disease risk management plans constructed to design a capture-quarantine-release system that minimised the impacts on both the bumblebees and on their natural parasites. Given that bumblebee parasites are (i) generalists, (ii) geographically ubiquitous, and (iii) show evidence of local adaptation, the disease risk management plan was designed to limit the co-introduction of parasites from the source population in Sweden to the destination site in the UK. Results suggest that this process at best eliminated, or at least severely curtailed the co-introduction of parasites, and ongoing updates of the plan enabled minimization of impacts on natural host-parasite dynamics in the Swedish source population. This study suggests that methods designed for reintroductions of vertebrate species can be successfully applied to invertebrates. Future reintroductions of invertebrates where the parasite fauna is less well known should take advantage of next-generation barcoding and multiple survey years prior to the start of reintroductions, to develop comprehensive disease risk management plans

The concept of remembrance in Walter Benjamin

This thesis argues that the role played by the concept of remembrance (Eingedenken) in Walter Benjamin's 'theory of the knowledge of history' and in his engagement with Enlightenment universal history, is a crucial one. The implications of Benjamin's contention that history's 'original vocation' is 'remembrance' have hitherto gone largely unnoticed. The following thesis explores the meaning of the concept of remembrance and assesses the significance of this proposed link between history and memory, looking at both the mnemonic aspect of history and the historical facets of memory. It argues that by mobilising the simultaneously destructive and constructive capacities of remembrance, Benjamin sought to develop a critical historiography which would enable a radical encounter with a previously suppressed past. In so doing he takes up a stance (explicit and implicit) towards existing philosophical conceptions of history, in particular the idea of universal history found in German Idealism. Benjamin reveals an intention to retain the epistemological aspirations of universal history whilst ridding that approach of its apologetic moment. He criticises existing conceptions of history on the basis that each assumes homogeneous time to be the framework in which historical events occur. Insight into the distinctive temporality of remembrance proves to be the touchstone for this critique, and provides a paradigm for a very different conception of time. The thesis goes on to determine what is valid and what is problematic both in this concept of remembrance and in the theory of historical knowledge which it informs, by subjecting both to the most cogent criticisms which can be levelled at them. What emerges is not only the importance of this concept for an understanding of Benjamin's philosophy but the pertinence of this concept for any philosophical account of memory

Implications of squirrelpox virus for successful red squirrel translocations within mainland UK

Remnant red squirrel populations in the UK mainland are threatened by squirrelpox viral disease and the reservoir of the squirrelpox virus, the invasive grey squirrel, is expanding its range. Until this threat can be effectively mitigated, there is a high risk from disease outbreaks, following proposed conservation translocation of red squirrels

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

Computer-based technology and student engagement: a critical review of the literature

Computer-based technology has infiltrated many aspects of life and industry, yet there is little understanding of how it can be used to promote student engagement, a concept receiving strong attention in higher education due to its association with a number of positive academic outcomes. The purpose of this article is to present a critical review of the literature from the past 5 years related to how web-conferencing software, blogs, wikis, social networking sites (Facebook and Twitter), and digital games influence student engagement. We prefaced the findings with a substantive overview of student engagement definitions and indicators, which revealed three types of engagement (behavioral, emotional, and cognitive) that informed how we classified articles. Our findings suggest that digital games provide the most far-reaching influence across different types of student engagement, followed by web-conferencing and Facebook. Findings regarding wikis, blogs, and Twitter are less conclusive and significantly limited in number of studies conducted within the past 5 years. Overall, the findings provide preliminary support that computer-based technology influences student engagement, however, additional research is needed to confirm and build on these findings. We conclude the article by providing a list of recommendations for practice, with the intent of increasing understanding of how computer-based technology may be purposefully implemented to achieve the greatest gains in student engagement. © 2017, The Author(s)