379 research outputs found

    Distinct roles of estrone and estradiol in endothelial colony-forming cells.

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    Our current understanding of the relationship between estrogen and human endothelial colony-forming cell (hECFC) function is based almost exclusively on studies investigating estradiol action at nuclear estrogen receptors. In the current study the hypothesis was tested that the less potent estrogen receptor agonist, estrone, affects hECFC proliferation, migration, secretion, and tube formation in a way that is unique from that of estradiol. The relationship between the estrogens, estradiol and estrone, is clinically important, particularly in postmenopausal women where estradiol levels wane and estrone becomes the predominant estrogen. Cultured hECFCs from peripheral blood mononuclear cell fractions were treated with concentrations of estradiol and estrone ranging from 1 nM to 1 μM separately and in combination. Following treatment, proliferation, migration, ability to attract other hECFCs (autocrine secretion), and ability to enhance endothelial cell tube formation (tubulogenesis) were tested. Functional assays revealed unique, concentration-dependent physiological effects of estrone and estradiol. Estradiol exposure resulted in increased hECFC proliferation, migration, secretion of chemoattractant, and enhancement of tube formation as expected. As with estradiol, hECFC secretion of chemoattractant increased significantly with each increase in estrone exposure. Estrone treatment produced a biphasic, concentration-dependent relationship with proliferation and tube formation and relatively no effect on hECFC migration at any concentration. The quantitative relationship between the effects of estrone and estradiol and each hECFC function was analyzed. The extent to which estrone was similar in effect to that of estradiol was dependent on both the concentrations of estradiol and estrone and the hECFC function measured. Interestingly, when the two estrogens were present, differing ratios resulted in unique functional responses. hECFCs that were treated with combinations of estrone and estradiol with high estrone to estradiol ratios showed decreased proliferative capacity. Conversely, hECFCs that were treated with combinations that were relatively high in estradiol, showed increased proliferative capacity. Cells that were treated with estrone and estradiol in equal concentrations showed an attenuated proliferative response that was decreased compared to the proliferation that either estrone or estradiol produced when they were present alone. This co-inhibitory relationship, which has not been previously reported, challenges the prevailing understanding of estrone as solely a weak agonist at estrogen receptors. This study provides evidence that estrone signaling is distinct from that of estradiol and that further investigation of estrone\u27s mechanism of action and the biological effect may provide important insight into understanding the dysfunction and decreased number of hECFCs, and the resulting cardiovascular disease risk observed clinically in menopausal women and women undergoing hormone replacement therapy

    Broader niches revealed by fossil data don’t reduce estimates of range loss and fragmentation of African montane trees

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    This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.The data supporting the results already exists and is freely available in the Global Biodiversity Information Facility (GBIF) and the African Pollen Database (APD).Aim: Many species’ climate tolerances are broader than those estimated from current native ranges. Indeed, some Afromontane trees’ niches are up to 50% larger after incorporating fossil data. This expansion could reduce estimates of species’ future range loss due to climate change but also implies strong non-climatic limitations on species’ current ranges. One such limitation is land use, which fossil data suggest influences Afromontane tree distribution, preventing these trees from occupying warmer conditions than they currently do. We aim to assess the degree to which the broader climatic tolerances revealed by fossil data buffers projected range loss from climate and land use for Afromontane trees. Location: Africa. Time period: Last 21,000 years. Major taxa studied: Afromontane trees. Methods: We used species distribution models informed by both current and fossil distributions to project future ranges under climate and land-use projections. Results: We found that projected range reductions are only slightly ameliorated by incorporating fossil distributions and these improvements diminish further under severe land use or climate change scenarios. Taxa that are less impacted by climate are more impacted by intense land use. Depending on the severity of climate and land use, the geographic extent of Afromontane tree species’ ranges will contract by 40-85% and the trees will completely be lost from large portions of Africa. We projected that the surviving species’ ranges will become increasingly fragmented. Main conclusions: Maintaining Afromontane ecosystems will require mitigation of both climate and land-use change and protecting areas to optimize connectivity. Our findings caution that species with climate tolerances broader than their current range might not necessarily fare better under strong changes in climate or land use

    Cutmarked bone of drought-tolerant extinct megafauna deposited with traces of fire, human foraging, and introduced animals in SW Madagascar

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    People could have hunted Madagascar’s megafauna to extinction, particularly when introduced taxa and drought exacerbated the effects of predation. However, such explanations are difficult to test due to the scarcity of individual sites with unambiguous traces of humans, introduced taxa, and endemic megaherbivores. We excavated three coastal ponds in arid SW Madagascar and present a unique combination of traces of human activity (modified pygmy hippo bone, processed estuarine shell and fish bone, and charcoal), along with bones of extinct megafauna (giant tortoises, pygmy hippos, and elephant birds), extirpated fauna (e.g., crocodiles), and introduced vertebrates (e.g., zebu cattle). The disappearance of megafauna from the study sites at ~ 1000 years ago followed a relatively arid interval and closely coincides with increasingly frequent traces of human foraging, fire, and pastoralism. Our analyses fail to document drought-associated extirpation or multiple millennia of megafauna hunting and suggest that a late combination of hunting, forest clearance, and pastoralism drove extirpations.Results - Subfossils and chronology. - Charcoal. Discussion Method

    Vegetation Controls on Weathering Intensity During the Last Deglacial Transition in Southeast Africa

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    Tropical climate is rapidly changing, but the effects of these changes on the geosphere are unknown, despite a likelihood of climatically-induced changes on weathering and erosion. The lack of long, continuous paleo-records prevents an examination of terrestrial responses to climate change with sufficient detail to answer questions about how systems behaved in the past and may alter in the future. We use high-resolution records of pollen, clay mineralogy, and particle size from a drill core from Lake Malawi, southeast Africa, to examine atmosphere-biosphere-geosphere interactions during the last deglaciation (~ 18-9 ka), a period of dramatic temperature and hydrologic changes. The results demonstrate that climatic controls on Lake Malawi vegetation are critically important to weathering processes and erosion patterns during the deglaciation. At 18 ka, afromontane forests dominated but were progressively replaced by tropical seasonal forest, as summer rainfall increased. Despite indication of decreased rainfall, drought-intolerant forest persisted through the Younger Dryas (YD) resulting from a shorter dry season. Following the YD, an intensified summer monsoon and increased rainfall seasonality were coeval with forest decline and expansion of drought-tolerant miombo woodland. Clay minerals closely track the vegetation record, with high ratios of kaolinite to smectite (K/S) indicating heavy leaching when forest predominates, despite variable rainfall. In the early Holocene, when rainfall and temperature increased (effective moisture remained low), open woodlands expansion resulted in decreased K/S, suggesting a reduction in chemical weathering intensity. Terrigenous sediment mass accumulation rates also increased, suggesting critical linkages among open vegetation and erosion during intervals of enhanced summer rainfall. This study shows a strong, direct influence of vegetation composition on weathering intensity in the tropics. As climate change will likely impact this interplay between the biosphere and geosphere, tropical landscape change could lead to deleterious effects on soil and water quality in regions with little infrastructure for mitigation

    Biological anthropology in the Indo-Pacific Region: New approaches to age-old questions

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    Biological anthropological research, the study of both modern and past humans, is a burgeoning field in the Indo-Pacific region. It is becoming increasingly apparent that the unique environments of the Indo-Pacific have resulted in an archaeological record that does not necessarily align with those in the northern hemisphere. New, regionally-specific archaeological models are being developed, and biological anthropological research has an important role to play in establishing past human experience within these models. In the Indo-Pacific, research using ancient and modern human tissues is adding insight into global processes of prehistoric settlement and migrations, subsistence change and human biosocial adaptation. This review synthesises current themes in biological anthropology in this region. It highlights the diverse methods and approaches used by biological anthropologists to address globally-relevant archaeological questions. In recent decades a collaborative approach between archaeologists, biological anthropologists and local communities has become the norm in the region. The many positive outcomes of this multi-disciplinary approach are highlighted here through the use of regionally-specific case studies. This review ultimately aims to stimulate further collaborations between archaeologists, biological anthropologists and the communities in the region, and demonstrate how the evidence from Indo-Pacific research may be relevant to global archaeological models

    Essential steps in primary care management of older people with Type 2 diabetes: an executive summary on behalf of the European geriatric medicine society (EuGMS) and the European diabetes working party for older people (EDWPOP) collaboration

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    We present an executive summary of a guideline for management of type 2 diabetes mellitus in primary care written by the European Geriatric Medicine Society, the European Diabetes Working Party for Older People with contributions from primary care practitioners and participation of a patient’s advocate. This consensus document relies where possible on evidence-based recommendations and expert opinions in the fields where evidences are lacking. The full text includes 4 parts: a general strategy based on comprehensive assessment to enhance quality and individualised care plan, treatments decision guidance, management of complications, and care in case of special conditions. Screening for frailty and cognitive impairment is recommended as well as a comprehensive assessment all health conditions are concerned, including end of life situations. The full text is available online at the following address: essential_steps_inprimary_care_in_older_people_with_diabetes_-_EuGMS-EDWPOP___3_.pdf
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