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"White, David A"
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VEGF-A, PDGF-BB and HB-EGF engineered for promiscuous super affinity to the extracellular matrix improve wound healing in a model of type 1 diabetes
Chronic non-healing wounds, frequently caused by diabetes, lead to lower quality of life, infection, and amputation. These wounds have limited treatment options. We have previously engineered growth factors to bind to exposed extracellular matrix (ECM) in the wound environment using the heparin-binding domain of placental growth factor-2 (PlGF-2123–144), which binds promiscuously to ECM proteins. Here, in the type 1 diabetic (T1D) NOD mouse model, engineered growth factors (eGFs) improved both re-epithelialization and granulation tissue formation. eGFs were even more potent in combination, and the “triple therapy” of vascular endothelial growth factor-A (VEGF-PlGF-2123–144), platelet-derived growth factor-BB (PDGF-BB-PlGF-2123–144), and heparin-binding epidermal growth factor (HB-EGF-PlGF-2123–144) both improved wound healing and remained at the site of administration for significantly longer than wild-type growth factors. In addition, we also found that changes in the cellular milieu of a wound, including changing amounts of M1 macrophages, M2 macrophages and effector T cells, are most predictive of wound-healing success in the NOD mouse model. These results suggest that the triple therapy of VEGF-PlGF-2123–144, PDGF-BB-PlGF-2123–144, and HB-EGF-PlGF-2123–144 may be an effective therapy for chronic non-healing wounds in that occur as a complication of diabetes.
Journal Article
Climate change increases threat to plant diversity in tropical forests of Central America and southern Mexico
Global biodiversity is negatively affected by anthropogenic climate change. As species distributions shift due to increasing temperatures and precipitation fluctuations, many species face the risk of extinction. In this study, we explore the expected trend for plant species distributions in Central America and southern Mexico under two alternative Representative Concentration Pathways (RCPs) portraying moderate (RCP4.5) and severe (RCP8.5) increases in greenhouse gas emissions, combined with two species dispersal assumptions (limited and unlimited), for the 2061–2080 climate forecast. Using an ensemble approach employing three techniques to generate species distribution models, we classified 1924 plant species from the region’s (sub)tropical forests according to IUCN Red List categories. To infer the spatial and taxonomic distribution of species’ vulnerability under each scenario, we calculated the proportion of species in a threat category (Vulnerable, Endangered, Critically Endangered) at a pixel resolution of 30 arc seconds and by family. Our results show a high proportion (58–67%) of threatened species among the four experimental scenarios, with the highest proportion under RCP8.5 and limited dispersal. Threatened species were concentrated in montane areas and avoided lowland areas where conditions are likely to be increasingly inhospitable. Annual precipitation and diurnal temperature range were the main drivers of species’ relative vulnerability. Our approach identifies strategic montane areas and taxa of conservation concern that merit urgent inclusion in management plans to improve climatic resilience in the Mesoamerican biodiversity hotspot. Such information is necessary to develop policies that prioritize vulnerable elements and mitigate threats to biodiversity under climate change.
Journal Article
Body bones
This book contains facts about bone growth, the varieties of bones, and how bones work with other body systems. It includes photographs of people and animals which are overlaid with diagrams of skeletons.
BOOK
Twenty-Eight Years of Plant Community Development and Dynamics in the Balize Mississippi River Delta, Louisiana, USA
Deltaic landscapes go through cycles of birth, growth, decline, and death governed by intertwined geological, biological, and ecological processes. In this study, we tracked deltaic lobes in the Balize Mississippi River Delta, Louisiana, USA, over 28 years (1984–2012). Hydrologic and geomorphic patterns as well as sustained patterns of wetland plant richness, diversity, and biomass are described. Plant diversity and biomass were modeled by nMDS ordination. Taxa (53) were harvested and dried (116,706 g) from 965 (0.25 m2) plots and divided into three groups: I. four foundation species, corresponding to 78.9% of the total harvest; II. nine pioneer species, corresponding to 13.6% of the total harvest; and III. all other taxa, corresponding to 7.5% of the total harvest (eight miscellaneous grasses, eight miscellaneous sedges, and twenty-four miscellaneous herbs). Autogenic/allogenic processes (sedimentation, subsidence, plant colonization, and succession events) affected composition and biomass. Eleven important species were identified. Taxon richness increased on mudflats during primary succession (fifteen to twenty-five taxa per site), then declined to fewer than five taxa per site. The niche space theory explained patterns of community change, with a similar total biomass/yr (~500 g/m2/yr) at all study sites. Quantile regression analyses showed that the water quality and quantity of the Mississippi River influenced biomass, especially in springtime waters. Stochastic events (storms, herbivory, salt burn, and flood pulses) impacted biomass. Long-term studies like this are required in a future of climate unknowns.
Journal Article
Myth, Metaphysics and Dialectic in Plato's Statesman
Plato's dialogue The Statesman has often been found structurally puzzling by commentators because of its apparent diffuseness and disjointed transitions. In this book David White interprets the dialogue in ways which account for this problematic structure, and which also connect the primary themes of the dialogue with two subsequent dialogues The Philebus and The Laws. The central interpretive focus of the book is the extended myth, sometimes called the 'myth of the reversed cosmos'. As a result of this interpretative approach, White argues that The Statesman can be recognized (a) as both internally coherent and also profound in implication-the myth is crucial in both regards - and (b) as integrally related to the concerns of Plato's later dialogues.
eBook
Taos Society of Artists
\"\"A lavishly illustrated two-volume study of the Taos Society of Artists. Essays on the TSA and its founding plus scholarly biographical and art historical essays on twelve TSA artists with exemplary works of the artists studied\"-Provided by publisher\"-- Provided by publisher.
BOOK
Pro-Inflammatory Action of MIF in Acute Myocardial Infarction via Activation of Peripheral Blood Mononuclear Cells
Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, has been implicated in the pathogenesis of multiple inflammatory disorders. We determined changes in circulating MIF levels, explored the cellular source of MIF, and studied the role of MIF in mediating inflammatory responses following acute myocardial infarction (MI).
We recruited 15 patients with MI, 10 patients with stable angina and 10 healthy volunteers and measured temporal changes of MIF in plasma. Expression of MIF, matrix metalloproteinase-9 (MMP-9) and interleukin-6 (IL-6) in cultured peripheral blood mononuclear cells (PBMCs) and the media were measured by ELISA or real-time PCR. Compared to controls, plasma levels of MIF and IL-6 were significantly elevated at admission and 72 h post-MI. In contrast, expression of MIF, MMP-9 and IL-6 by PBMCs from MI patients was unchanged at admission, but significantly increased at 72 h. Addition of MIF activated cultured PBMCs by upregulating expression of inflammatory molecules and also synergistically enhanced stimulatory action of IL-1β which were inhibited by anti-MIF interventions. In a mouse MI model we observed similar changes in circulating MIF as seen in patients, with reciprocal significant increases in plasma MIF and reduction of MIF content in the infarct myocardium at 3 h after MI. MIF content in the infarct myocardium was restored at 72 h post-MI and was associated with robust macrophage infiltration. Further, anti-MIF intervention significantly reduced inflammatory cell infiltration and expression of monocyte chemoattractant protein-1 at 24 h and incidence of cardiac rupture in mice post-MI.
MI leads to a rapid release of MIF from the myocardium into circulation. Subsequently MIF facilitates PBMC production of pro-inflammatory mediators and myocardial inflammatory infiltration. Attenuation of these events, and post-MI cardiac rupture, by anti-MIF interventions suggests that MIF could be a potential therapeutic target following MI.
Journal Article