Age-related macular degeneration (AMD) is a major cause of loss of central vision in the elderly. The formation of drusen, an extracellular, amorphous deposit of material on Bruch's membrane in the ...macula of the retina, occurs early in the course of the disease. Although some of the molecular components of drusen are known, there is no understanding of the cell biology that leads to the formation of drusen. We have previously demonstrated increased mitochondrial DNA (mtDNA) damage and decreased DNA repair enzyme capabilities in the rodent RPE/choroid with age. In this study, we found that drusen in AMD donor eyes contain markers for autophagy and exosomes. Furthermore, these markers are also found in the region of Bruch's membrane in old mice. By in vitro modeling increased mtDNA damage induced by rotenone, an inhibitor of mitochondrial complex I, in the RPE, we found that the phagocytic activity was not altered but that there were: 1) increased autophagic markers, 2) decreased lysosomal activity, 3) increased exocytotic activity and 4) release of chemoattractants. Exosomes released by the stressed RPE are coated with complement and can bind complement factor H, mutations of which are associated with AMD. We speculate that increased autophagy and the release of intracellular proteins via exosomes by the aged RPE may contribute to the formation of drusen. Molecular and cellular changes in the old RPE may underlie susceptibility to genetic mutations that are found in AMD patients and may be associated with the pathogenesis of AMD in the elderly.
High-light leaves of the evergreen herb Galax urceolata exhibit a striking color change from green to red during winter months due to anthocyanin synthesis in outermost mesophyll cells. Here we ...investigate three possible functions of this color change. • To test the hypothesis that anthocyanins function as light attenuators, maximum photosystem II efficiency (Fv/Fm) of red and green leaves was measured during and after exposure to wavelengths either strongly or poorly absorbed by anthocyanin. To determine whether anthocyanins elevate radical-scavenging capacity, antioxidant activity of red and green leaves was assessed using the α,α-diphenyl-β-picrylhydrazyl assay. Nonstructural carbohydrate levels were analyzed to test the hypothesis that anthocyanins function as a carbon sink. • Declines in Fv/Fm under white and green light were significantly greater for green than red leaves, but were comparable under red light. Anthocyanin content positively correlated with antioxidant activity. Although levels of anthocyanins did not appear to be related to nonstructural carbohydrate concentration, high levels of sugars may be necessary for their photoinduction. • Results suggest that anthocyanins function as light attenuators and may also contribute to the antioxidant pool in winter leaves.
We present a global analysis of leptonic and semileptonic kaon decay data, including all recent results published by the BNL-E865, KLOE, KTeV, ISTRA+ and NA48 experiments. This analysis, in ...conjunction with precise lattice calculations of the hadronic matrix elements now available, leads to a very precise determination of |
V
us
| and allows us to perform several stringent tests of the Standard Model.
BackgroundCollaborations are often a cornerstone of global health research. Power dynamics can shape if and how local researchers are included in manuscripts. This article investigates how ...international collaborations affect the representation of local authors, overall and in first and last author positions, in African health research.MethodsWe extracted papers on ‘health’ in sub-Saharan Africa indexed in PubMed and published between 2014 and 2016. The author’s affiliation was used to classify the individual as from the country of the paper’s focus, from another African country, from Europe, from the USA/Canada or from another locale. Authors classified as from the USA/Canada were further subclassified if the author was from a top US university. In primary analyses, individuals with multiple affiliations were presumed to be from a high-income country if they contained any affiliation from a high-income country. In sensitivity analyses, these individuals were presumed to be from an African country if they contained any affiliation an African country. Differences in paper characteristics and representation of local coauthors are compared by collaborative type using χ² tests.ResultsOf the 7100 articles identified, 68.3% included collaborators from the USA, Canada, Europe and/or another African country. 54.0% of all 43 429 authors and 52.9% of 7100 first authors were from the country of the paper’s focus. Representation dropped if any collaborators were from USA, Canada or Europe with the lowest representation for collaborators from top US universities—for these papers, 41.3% of all authors and 23.0% of first authors were from country of paper’s focus. Local representation was highest with collaborators from another African country. 13.5% of all papers had no local coauthors.DiscussionIndividuals, institutions and funders from high-income countries should challenge persistent power differentials in global health research. South-South collaborations can help African researchers expand technical expertise while maintaining presence on the resulting research.
Both axon and myelin degeneration have significant impact on the long-term disability of patients with white matter disorder. However, the clinical manifestations of the neurological dysfunction ...caused by white matter disorders are not sufficient to determine the origin of neurological deficits. A noninvasive biological marker capable of detecting and differentiating axon and myelin degeneration would be a significant addition to currently available tools. Directional diffusivities derived from diffusion tensor imaging (DTI) have been previously proposed by this group as potential biological markers to detect and differentiate axon and myelin degeneration. To further test the hypothesis that axial (λ‖) and radial (λ⊥) diffusivities reflect axon and myelin pathologies, respectively, the optic nerve was examined serially using DTI in a mouse model of retinal ischemia. A significant decrease of λ‖, the putative DTI axonal marker, was observed 3 days after ischemia without concurrently detectable changes in λ⊥, the putative myelin marker. This result is consistent with histological findings of significant axonal degeneration with no detectable demyelination at 3 days after ischemia. The elevation of λ⊥ observed 5 days after ischemia is consistent with histological findings of myelin degeneration at this time. These results support the hypothesis that λ‖ and λ⊥ hold promise as specific markers of axonal and myelin injury, respectively, and, further, that the coexistence of axonal and myelin degeneration does not confound this utility.
Although the statement that age is the greatest risk factor for Age-related macular degeneration (AMD) is widely accepted, the cellular and molecular explanations for that clinical statement are not ...generally known. A major focus of AMD research is the retinal pigment epithelium (RPE)/choroid. The purpose of this study was to characterize the changes in the RPE/choroid with age that may provide a background for the development of AMD.
We compared the transcriptional profiles, key protein levels and histology of the RPE/choroid from young and old mice. Using three statistical methods, microarray data demonstrated marked changes in the old mouse. There were 315 genes differentially expressed with age; most of these genes were related to immune responses and inflammatory activity. Canonical pathways having significant numbers of upregulated genes in aged RPE/choroid included leukocyte extravasation, complement cascades, natural killer cell signaling and IL-10 signaling. By contrast, the adjacent neural retina showed completely different age-related changes. The levels of proteins that participate in leukocyte extravasation and complement pathways were consistently increased in the normal, aged RPE/choroid. Furthermore, there was increased gene expression and protein levels of leukocyte attracting signal, chemokine ligand 2 (Ccl2) in aged RPE/choroid. In old animals, there was marked extravasation and accumulation of leukocytes from the choroidal circulation onto Bruch's membrane and into the RPE.
These phenotypic changes indicate that the RPE/choroid in the normal, old mouse has become an immunologically active tissue. There are signals from the normal, aged RPE/choroid which recruit leukocytes from the circulation and activate the complement cascade. These age-related changes that occur in the RPE/choroid with age, to the extent that they occur in the human retina, may provide the background for an error in regulation of immunological activity to cause AMD to appear in an elderly individual.
Pollinating insects are vital to the survival of many primary producers in terrestrial ecosystems, as up to 80–85 % of the world’s flowering plants require pollinators for reproduction. Over the last ...few decades however, numerous pollinating insect populations have declined substantially. The causes of these declines are multifaceted and synergistic, and include pesticides, herbicides, monoculture, urbanization, disease, parasites, and climate change. Here, we present evidence for a generally understudied yet potentially significant source of pollinator mortality, collisions with vehicles. Negative impacts from roads have been observed for the majority of vertebrate groups but studies of the effects on invertebrates have remained largely absent from the scientific literature. We documented road mortality of pollinating insects along a 2 km stretch of highway in Ontario, Canada and used our findings to extrapolate expected levels of road mortality across a number of landscape scales. Our extrapolations demonstrate the potential for loss of hundreds of thousands (on our studied highway) to hundreds of billions (generalised across North America) of Lepidopterans, Hymenopterans and pollinating Dipterans each summer. Our projections of such high levels of annual road mortality highlight the need for research to assess whether the mortality levels observed are contributing to the substantial declines of pollinating insects occurring on a global scale, thus putting the ecological functioning of natural areas and agricultural productivity in jeopardy.
Age-related Macular Degeneration (AMD) is a major cause of central vision loss in the elderly and smoking is a primary risk factor associated with the prevalence and incidence of AMD. To better ...understand the cellular and molecular bases for the association between smoking and AMD, we determined the effects of Benzo(a)Pyrene (B(a)P), a toxic element in cigarette smoke, on cultured retinal pigment epithelia (RPE) and we examined the RPE/choroid from mice exposed to chronic cigarette smoke. We measured: mitochondrial DNA (mtDNA) damage, phagocytic activity, lysosomal enzymes, exosome markers and selected complement pathway components. In the presence of a non-cytotoxic dose of B(a)P, there was extensive mtDNA damage but no nuclear DNA damage. RPE phagocytic activity was not altered but there were increased lysosomal activity, exocytotic activity and complement pathway components. Retinas from mice exposed to cigarette smoke contained markers for mtDNA damage, exosomes and complement pathway components surrounding Bruch's membrane. Markers for these processes are found in drusen from AMD patients. Thus, smoking may cause damage to mtDNA and increased degradative processes in the RPE. These altered cell biological processes in the RPE may contribute to the formation of drusen in individuals who are cigarette smokers and underlie susceptibility to genetic mutations associated with AMD.
Age-related Macular Degeneration (AMD) is the leading cause of blindness among the elderly. While excellent treatment has emerged for neovascular disease, treatment for early AMD is lacking due to an ...incomplete understanding of the early molecular events. Cigarette smoking is the strongest epidemiologic risk factor, yet we do not understand how smoking contributes to AMD. Smoking related oxidative damage during the early phases of AMD may play an important role. This review explores how cigarette smoking and oxidative stress to the retinal pigmented epithelium (RPE) might contribute to AMD, and how the transcription factor Nrf2 can activate a cytoprotective response.
We discuss the predictions of the standard model for the scalar form factors of Kℓ3 decays. Our analysis is based on the results of chiral perturbation theory, large Nc estimates of low-energy ...couplings and dispersive methods. It includes a discussion of isospin-violating effects of strong and electromagnetic origin.
PDF
