Investigation of the role of endosomal Toll-like receptors in murine collagen-induced arthritis reveals a potential role for TLR7 in disease maintenance

INTRODUCTION Endosomal toll-like receptors (TLRs) have recently emerged as potential contributors to the inflammation observed in human and rodent models of rheumatoid arthritis (RA). This study aims to evaluate the role of endosomal TLRs and in particular TLR7 in the murine collagen induced arthritis (CIA) model. METHODS CIA was induced by injection of collagen in complete Freund's adjuvant. To investigate the effect of endosomal TLRs in the CIA model, mianserin was administered daily from the day of disease onset. The specific role of TLR7 was examined by inducing CIA in TLR7-deficient mice. Disease progression was assessed by measuring clinical score, paw swelling, serum anti-collagen antibodies histological parameters, cytokine production and the percentage of T regulatory (Treg) cells. RESULTS Therapeutic administration of mianserin to arthritic animals demonstrated a highly protective effect on paw swelling and joint destruction. TLR7-/- mice developed a mild arthritis, where the clinical score and paw swelling were significantly compromised in comparison to the control group. The amelioration of arthritis by mianserin and TLR7 deficiency both corresponded with a reduction in IL-17 responses, histological and clinical scores, and paw swelling. CONCLUSIONS These data highlight the potential role for endosomal TLRs in the maintenance of inflammation in RA and support the concept of a role for TLR7 in experimental arthritis models. This study also illustrates the potential benefit that may be afforded by therapeutically inhibiting the endosomal TLRs in RA

Where The Mill Stream Winds Its Way

https://digitalcommons.library.umaine.edu/mmb-vp/5367/thumbnail.jp

I\u27ll Take You Home Again, Pal O\u27 Mine : Waltz Song

https://digitalcommons.library.umaine.edu/mmb-vp/4937/thumbnail.jp

Ecological connectivity in marine protected areas in Swedish Baltic coastal waters - A coherence assessment

The Department of Aquatic Resources at the Swedish University of Agricultural Sciences (SLU Aqua) was commissioned by the Swedish Agency for Marine and Water Management to assess the ecological coherence of the marine protected area (MPA) network along the Swedish Baltic Sea coast, focusing on ecological connectivity and representativity, and species performing active migrations. The study also aimed to test the influence of anthropogenic pressures on connectivity and identify areas for expansion of the existing MPA network to maximise connectivity in the region. This report is the first to assess large-scale connectivity and ecological coherence of the MPA network in the Baltic Sea with a focus on coastal habitat-forming vegetation and fish species with active dispersal. Information on dispersal/migration distances was combined with species distribution models to produce connectivity maps. To align the coherence analyses with the conservation targets specified by responsible authorities, we included the nested targets for specific species ("preciserade bevarandevärden” in Swedish) listed within the Swedish framework for MPAs. Fish species like eel, salmon and trout, as well as birds and seals, which are also listed as nested targets, were not included in our analyses, since connectivity models of these long-distance migrants would be redundant as they do not affect the more small-scale connectivity patterns that are in focus in this study. Hotspot areas for connectivity were identified, and these were generally concentrated in a few, relatively small areas. These hotspot areas are, however, highly susceptible to coastal development and human activities, as they are often situated in bays, inlets and topographically complex archipelagos. Anthropogenic pressures, in this case physical disturbance, had a relatively large predicted impact on connectivity, particularly on certain species. The majority of these species are of freshwater origin and have shorter migration distances (e.g. crucian carp, roach, common rudd, common bream/silver bream, and common bleak) than marine species like cod, flounder and herring, which perform long-distance migrations between open sea and coastal areas as part of their life cycle. Also large predatory fish like pike, pike-perch and perch, as well as habitat-forming submerged aquatic vegetation (SAV), showed a pronounced decrease in connectivity when incorporating physical disturbance into the models. This may be explained by most human pressures being concentrated along the coastline, often in shallow sheltered bays and inlets where human development coincides with sensitive vegetated habitats and important breeding, spawning, nursery and feeding grounds for fish. Connectivity is reduced when habitats become fragmented or diminished and populations become smaller and more isolated. This may in turn have consequences on genetic diversity, viability of populations and ultimately ecosystem functioning. Representativity of habitats; i.e. amount of habitat protected, was below what is generally scientifically recommended and the new target of 30% protection by 2030 in the EU Biodiversity Strategy for all but three species (of 30 in total). Representativity was very poor regarding strict MPAs, an average of 2% across species. The target according to the EU Biodiversity Strategy is 10% strict protection. Similar results were found for connectivity where the amount connected habitat within MPAs was low. MPAs in the study area were sufficiently spaced (distance apart), but dominated by MPAs of small size. Priority areas with high connectivity (identified by the spatial prioritization software prioritizr) were insufficiently protected and the connectivity of the network could be greatly improved with targeted protection in just a few important locations. Areas that are well connected locally, but are isolated from other priority areas, are especially important to protect as they are critical to connectivity of the network. Regulations within the MPA network in Swedish Baltic Sea coastal waters are generally weak, particularly in the priority areas. Applying an ecosystem-based management approach and including stronger regulations of fisheries and of activities causing local physical disturbance in parts of the MPA network is encouraged in order to reach conservation goals. The results from this study can be used to improve planning and management of the Baltic Sea MPA network, marine spatial planning in the region and improving the green infrastructure, securing important ecosystem services for future generations

It\u27s Pronounced Zine

https://digitalcommons.chapman.edu/feminist_zines/1036/thumbnail.jp

Development of the Global Engineering Programming Model: A Participatory, Mixed-Methods Approach

Over the past few decades, higher education institutions have emphasized global education as a core aspect of their strategic goals, yet a gap exists in implementation at the school level, particularly in engineering. As engineering schools invest in internationalizing their programs, research is needed regarding key strategic areas and their relationship to sustained programming efforts. This study uses a participatory, integrative mixed-methods approach to develop an operational framework for global strategies, policies, and programs. A thematic, qualitative analysis of semi-structured interviews followed by a group concept mapping activity was conducted with directors of study abroad and vice provosts of global education from nine universities regarding their global programming strategies, intended outcomes, and organizational resources. The results of this research provide both implicit and explicit engineering school-wide global programming strategies, their sustainable development, and future program evaluation plans

Costs are not necessarily correlated with threats in conservation landscapes

The priority of an area for conservation is determined by three primary factors: its biodiversity value, the level of threat it is facing, and its cost. Although much attention has been paid to the spatial relationship between biodiversity value and threats, and between biodiversity value and costs, little is known about how costs and threats are spatially correlated. The orthodox assumption in conservation science is that costs and threats are positively correlated. Here, we adapt a classic economic theory of land use to explain how conservation scientists came to expect a positive correlation between costs and threats. We then use high‐resolution, ground‐truthed datasets of land sales and habitat clearance to show that this assumption is false in the state of Queensland, Australia. Our results provide an empirical counterargument to a widespread assumption in conservation science, and illustrate why spatial prioritization needs to include independent measures of costs and threats