131 research outputs found

    Oncostatin M Protects Rod and Cone Photoreceptors and Promotes Regeneration of Cone Outer Segment in a Rat Model of Retinal Degeneration

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    Retinitis pigmentosa (RP) is a group of photoreceptor degenerative disorders that lead to loss of vision. Typically, rod photoreceptors degenerate first, resulting in loss of night and peripheral vision. Secondary cone degeneration eventually affects central vision, leading to total blindness. Previous studies have shown that photoreceptors could be protected from degeneration by exogenous neurotrophic factors, including ciliary neurotrophic factor (CNTF), a member of the IL-6 family of cytokines. Using a transgenic rat model of retinal degeneration (the S334-ter rat), we investigated the effects of Oncostatin M (OSM), another member of the IL-6 family of cytokines, on photoreceptor protection. We found that exogenous OSM protects both rod and cone photoreceptors. In addition, OSM promotes regeneration of cone outer segments in early stages of cone degeneration. Further investigation showed that OSM treatment induces STAT3 phosphorylation in Müller cells but not in photoreceptors, suggesting that OSM not directly acts on photoreceptors and that the protective effects of OSM on photoreceptors are mediated by Müller cells. These findings support the therapeutic strategy using members of IL-6 family of cytokines for retinal degenerative disorders. They also provide evidence that activation of the STAT3 pathway in Müller cells promotes photoreceptor survival. Our work highlights the importance of Müller cell-photoreceptor interaction in the retina, which may serve as a model of glia-neuron interaction in general

    A Single Basis for Developmental Buffering of Drosophila Wing Shape

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    The nature of developmental buffering processes has been debated extensively, based on both theoretical reasoning and empirical studies. In particular, controversy has focused on the question of whether distinct processes are responsible for canalization, the buffering against environmental or genetic variation, and for developmental stability, the buffering against random variation intrinsic in developmental processes. Here, we address this question for the size and shape of Drosophila melanogaster wings in an experimental design with extensively replicated and fully controlled genotypes. The amounts of variation among individuals and of fluctuating asymmetry differ markedly among genotypes, demonstrating a clear genetic basis for size and shape variability. For wing shape, there is a high correlation between the amounts of variation among individuals and fluctuating asymmetry, which indicates a correspondence between the two types of buffering. Likewise, the multivariate patterns of shape variation among individuals and of fluctuating asymmetry show a close association. For wing size, however, the amounts of individual variation and fluctuating asymmetry are not correlated. There was a significant link between the amounts of variation between wing size and shape, more so for fluctuating asymmetry than for variation among individuals. Overall, these experiments indicate a considerable degree of shared control of individual variation and fluctuating asymmetry, although it appears to differ between traits

    Cheek Tooth Morphology and Ancient Mitochondrial DNA of Late Pleistocene Horses from the Western Interior of North America: Implications for the Taxonomy of North American Late Pleistocene Equus

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    Horses were a dominant component of North American Pleistocene land mammal communities and their remains are well represented in the fossil record. Despite the abundant material available for study, there is still considerable disagreement over the number of species of Equus that inhabited the different regions of the continent and on their taxonomic nomenclature. In this study, we investigated cheek tooth morphology and ancient mtDNA of late Pleistocene Equus specimens from the Western Interior of North America, with the objective of clarifying the species that lived in this region prior to the end-Pleistocene extinction. Based on the morphological and molecular data analyzed, a caballine (Equus ferus) and a non-caballine (E. conversidens) species were identified from different localities across most of the Western Interior. A second non-caballine species (E. cedralensis) was recognized from southern localities based exclusively on the morphological analyses of the cheek teeth. Notably the separation into caballine and non-caballine species was observed in the Bayesian phylogenetic analysis of ancient mtDNA as well as in the geometric morphometric analyses of the upper and lower premolars. Teeth morphologically identified as E. conversidens that yielded ancient mtDNA fall within the New World stilt-legged clade recognized in previous studies and this is the name we apply to this group. Geographic variation in morphology in the caballine species is indicated by statistically different occlusal enamel patterns in the specimens from Bluefish Caves, Yukon Territory, relative to the specimens from the other geographic regions. Whether this represents ecomorphological variation and/or a certain degree of geographic and genetic isolation of these Arctic populations requires further study

    Global mortality from dementia : Application of a new method and results from the Global Burden of Disease Study 2019

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    Introduction Dementia is currently one of the leading causes of mortality globally, and mortality due to dementia will likely increase in the future along with corresponding increases in population growth and population aging. However, large inconsistencies in coding practices in vital registration systems over time and between countries complicate the estimation of global dementia mortality. Methods We meta-analyzed the excess risk of death in those with dementia and multiplied these estimates by the proportion of dementia deaths occurring in those with severe, end-stage disease to calculate the total number of deaths that could be attributed to dementia. Results We estimated that there were 1.62 million (95% uncertainty interval [UI]: 0.41-4.21) deaths globally due to dementia in 2019. More dementia deaths occurred in women (1.06 million [0.27-2.71]) than men (0.56 million [0.14-1.51]), largely but not entirely due to the higher life expectancy in women (age-standardized female-to-male ratio 1.19 [1.10-1.26]). Due to population aging, there was a large increase in all-age mortality rates from dementia between 1990 and 2019 (100.1% [89.1-117.5]). In 2019, deaths due to dementia ranked seventh globally in all ages and fourth among individuals 70 and older compared to deaths from other diseases estimated in the Global Burden of Disease (GBD) study. Discussion Mortality due to dementia represents a substantial global burden, and is expected to continue to grow into the future as an older, aging population expands globally.Peer reviewe

    Global, regional, and national burden of neurological disorders during 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

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    Background Comparable data on the global and country-specific burden of neurological disorders and their trends are crucial for health-care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions. In this systematic analysis, we quantified the global disease burden due to neurological disorders in 2015 and its relationship with country development level. Methods We estimated global and country-specific prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) for various neurological disorders that in the GBD classification have been previously spread across multiple disease groupings. The more inclusive grouping of neurological disorders included stroke, meningitis, encephalitis, tetanus, Alzheimer's disease and other dementias, Parkinson's disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, medication overuse headache, brain and nervous system cancers, and a residual category of other neurological disorders. We also analysed results based on the Socio-demographic Index (SDI), a compound measure of income per capita, education, and fertility, to identify patterns associated with development and how countries fare against expected outcomes relative to their level of development. Findings Neurological disorders ranked as the leading cause group of DALYs in 2015 (250·7 [95% uncertainty interval (UI) 229·1 to 274·7] million, comprising 10·2% of global DALYs) and the second-leading cause group of deaths (9·4 [9·1 to 9·7] million], comprising 16·8% of global deaths). The most prevalent neurological disorders were tension-type headache (1505·9 [UI 1337·3 to 1681·6 million cases]), migraine (958·8 [872·1 to 1055·6] million), medication overuse headache (58·5 [50·8 to 67·4 million]), and Alzheimer's disease and other dementias (46·0 [40·2 to 52·7 million]). Between 1990 and 2015, the number of deaths from neurological disorders increased by 36·7%, and the number of DALYs by 7·4%. These increases occurred despite decreases in age-standardised rates of death and DALYs of 26·1% and 29·7%, respectively; stroke and communicable neurological disorders were responsible for most of these decreases. Communicable neurological disorders were the largest cause of DALYs in countries with low SDI. Stroke rates were highest at middle levels of SDI and lowest at the highest SDI. Most of the changes in DALY rates of neurological disorders with development were driven by changes in YLLs. Interpretation Neurological disorders are an important cause of disability and death worldwide. Globally, the burden of neurological disorders has increased substantially over the past 25 years because of expanding population numbers and ageing, despite substantial decreases in mortality rates from stroke and communicable neurological disorders. The number of patients who will need care by clinicians with expertise in neurological conditions will continue to grow in coming decades. Policy makers and health-care providers should be aware of these trends to provide adequate services

    A bodhisattva-spirit-oriented counselling framework: inspired by Vimalakīrti wisdom

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    Application and interpretation of multiple statistical tests to evaluate validity of dietary intake assessment methods

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    Retinal microvasculature and risk of spontaneous abortion in multiethnic Southeast Asian women

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    10.1016/j.fertnstert.2022.06.033Fertility and Sterility1184748-75
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