4,044 research outputs found

    Uncertainties in global aerosol simulations: Assessment using three meteorological data sets

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94950/1/jgrd13664.pd

    Fibromodulin Reduces Scar Formation in Adult Cutaneous Wounds by Eliciting a Fetal-Like Phenotype

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    Blocking transforming growth factor (TGF)β1 signal transduction has been a central strategy for scar reduction; however, this approach appears to be minimally effective. Here, we show that fibromodulin (FMOD), a 59-kD small leucine-rich proteoglycan critical for normal collagen fibrillogenesis, significantly reduces scar formation while simultaneously increasing scar strength in both adult rodent models and porcine wounds, which simulate human cutaneous scar repair. Mechanistically, FMOD uncouples pro-migration/contraction cellular signals from pro-fibrotic signaling by selectively enhancing SMAD3-mediated signal transduction, while reducing AP-1-mediated TGFβ1 auto-induction and fibrotic extracellular matrix accumulation. Consequently, FMOD accelerates TGFβ1-responsive adult fibroblast migration, myofibroblast conversion, and function. Furthermore, our findings strongly indicate that, by delicately orchestrating TGFβ1 activities rather than indiscriminately blocking TGFβ1, FMOD elicits fetal-like cellular and molecular phenotypes in adult dermal fibroblasts in vitro and adult cutaneous wounds in vivo, which is a unique response of living system undescribed previously. Taken together, this study illuminates the signal modulating activities of FMOD beyond its structural support functions, and highlights the potential for FMOD-based therapies to be used in cutaneous wound repair. © The Author(s) 2017

    Increased Energy Expenditure, Dietary Fat Wasting, and Resistance to Diet-Induced Obesity in Mice Lacking Renin

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    An overactive renin angiotensin system is associated with obesity and the metabolic syndrome. However, mechanisms behind it are unclear. Cleaving angiotensinogen to angiotensin I by renin is a rate-limiting step of angiotensin II production, but renin is suggested to have angiotensin-independent effects. We generated mice lacking renin (Ren1c) using embryonic stem cells from C57BL/6 mouse, a strain prone to diet-induced obesity. Ren1c-/- mice are lean, insulin sensitive, and resistant to diet-induced obesity without changes in food intake and physical activity. The lean phenotype is likely due to a higher metabolic rate, and gastrointestinal loss of dietary fat. Most of the metabolic changes in Ren1c-/- mice were reversed by angiotensin II administration. These results support a role for angiotensin II in the pathogenesis of diet-induced obesity and insulin resistance

    Tumor-derived exosomes: potential biomarker or therapeutic target in breast cancer?

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    Exosomes are released by normal and tumour cells, including those involved in breast cancer, and provide a means of intercellular communications. Exosomes with diameters ranging between 30-150 nm are involved in transferring biological information, via various lipids, proteins, different forms of RNAs, and DNA from one cell to another, and this can result in reprogramming of recipient cell functions. These vesicles are present in all body fluids, e.g., blood plasma/serum, semen, saliva, cerebrospinal fluid, breast milk, and urine. It has been recently reported that these particles are involved in the development and progression of different tumor types, including breast cancer. Furthermore, it has been suggested that exosomes have the potential to be used as drug transporters, or as biomarkers. This review highlights the potential roles of exosomes in normal and breast cancer cells and their potential applications as biomarkers with special focus on their potential applications in treatment of breast cancer

    How Much Will Safe Sanitation for all Cost? Evidence from Five Cities

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    Global sustainable development goals call for universal access to safely managed sanitation by 2030. Here, we demonstrate methods to estimate the financial requirements for meeting this commitment in urban settings of low-income countries. Our methods considered two financial requirements: (i) the subsidies needed to bridge the gap between the willingness-to-pay of low-income households and actual market prices of toilets and emptying services and (ii) the amounts needed to expand the municipal waste management infrastructure for unserved populations. We applied our methods in five cities– Kisumu, Malindi, Nakuru in Kenya; Kumasi in Ghana; and Rangpur in Bangladesh and compared three to five sanitation approaches in each city. We collected detailed cost data on the sanitation infrastructure, products, and services from 76 key informants across the five cities, and we surveyed a total of 2381 low-income households to estimate willingness-to-pay. We found that the total financial requirements for achieving universal sanitation in the next 10 years and their breakdown between household subsidies and municipal infrastructure varied greatly between sanitation approaches. Across our study cities, sewerage was the costliest approach (total financial requirements of 16–24 USD/person/year), followed by container-based sanitation (10–17 USD/person/year), onsite sanitation (2–14 USD/person/year), and mini-sewers connecting several toilets to communal septic tanks (3–5 USD/person/year). Further applications of our methods can guide sanitation planning in other cities
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