18 research outputs found

    Mycophenolate mofetil attenuates DOCA-salt hypertension: Effects on vascular tone

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    Inflammation is increasingly recognized as a driver of hypertension. Both genetic and pharmacological inhibition of B and T cells attenuates most forms of experimental hypertension. Accordingly, the immunosuppressive drug mycophenolate mofetil (MMF) reduces blood pressure in the deoxycorticosterone acetate (DOCA-) salt model. However, the mechanisms by which MMF prevent hypertension in the DOCA-salt model remain unclear. Recent studies indicate that immunosuppression can inhibit sodium transporter activity in the kidney, but its effect on vascular tone is not well characterized. Therefore, the aim of the present study was to analyze the vascular and renal tubular effects of MMF in the DOCA-salt model in rats (4 weeks without uninephrectomy). Co-treatment with MMF attenuated the rise in blood pressure from day 11 onward resulting in a significantly lower telemetric mean arterial pressure after 4 weeks of treatment (108 ± 7 vs. 130 ± 9 mmHg, P < 0.001 by two-way analysis of variance). MMF significantly reduced the number of CD3+ cells in kidney cortex and inner medulla, but not in outer medulla. In addition, MMF significantly reduced urinary interferon-γ excretion. Vascular tone was studied ex vivo using wire myographs. An angiotensin II type 2 (AT2) receptor antagonist blocked the effects of angiotensin II (Ang II) only in the vehicle group. Conversely, L-NAME significantly increased the Ang II response only in the MMF group. An endothelin A receptor blocker prevented vasoconstriction by endothelin-1 in the MMF but not in the vehicle group. MMF did not reduce the abundances of the kidney sodium transporters NHE3, NKCC2, NCC, or ENaC. Together, our ex vivo results suggest that DOCA-salt induces AT2 receptor-mediated vasoconstriction. MMF prevents this response and increases nitric oxide availability. These data provide insight in the antihypertensive mechanism of MMF and the role of inflammation in dysregulating vascular tone

    Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

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    Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk

    Photo curation practices on smartphones

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    With camera-enabled phones always at hand, people tend to build large photo collections on these devices, which in turn creates the need of curating such collections. This paper describes a study of curation activities performed on smartphones aiming to identify design opportunities for applications that will help users manage and organize their photo collections. Semi-structured interviews with young adults show that curation on smartphones does not happen without external triggers and is an activity that they postpone and avoid as much as possible. The most usual trigger for curation activities is running out of storage space. Rather than specialized applications participants are content with camera roll applications that are built into their phones. They do not like how photographs are mixed in the camera roll, but value the overview, chronological order and serendipity it allows in viewing. Furthermore, they appreciate automated backup of their photo collections

    NDVI derived from near-infrared-enabled digital cameras: Applicability across different plant functional types

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    Time series of vegetation indices (e.g. normalized difference vegetation index [NDVI]) and color indices (e.g. green chromatic coordinate [G CC ]) based on radiometric measurements are now available at different spatial and temporal scales ranging from weekly satellite observations to sub-hourly in situ measurements by means of near-surface remote sensing (e.g. spectral sensors or digital cameras). In situ measurements are essential for providing validation data for satellite-derived vegetation indices. In this study we used a recently developed method to calculate NDVI from near-infrared (NIR) enabled digital cameras (NDVI C ) at 17 sites (for a total of 74 year-sites) encompassing six plant functional types (PFT) from the PhenoCam network.The seasonality of NDVI C was comparable to both NDVI measured by ground spectral sensors and by the moderate resolution imaging spectroradiometer (MODIS). We calculated site- and PFT-specific scaling factors to correct NDVI C values and recommend the use of site-specific NDVI from MODIS in order to scale NDVI C . We also compared G CC extracted from red-green-blue images to NDVI C and found PFT-dependent systematic differences in their seasonalities. During senescence, NDVI C lags behind G CC in deciduous broad-leaf forests and grasslands, suggesting that G CC is more sensitive to changes in leaf color and NDVI C is more sensitive to changes in leaf area. In evergreen forests, NDVI C peaks later than G CC in spring, probably tracking the processes of shoot elongation and new needle formation. Both G CC and NDVI C can be used as validation tools for the MODIS Land Cover Dynamics Product (MCD12Q2) for deciduous broad-leaf spring phenology, whereas NDVI C is more comparable than G CC with autumn phenology derived from MODIS. For evergreen forests, we found a poor relationship between MCD12Q2 and camera-derived phenology, highlighting the need for more work to better characterize the seasonality of both canopy structure and leaf biochemistry in those ecosystems.Our results demonstrate that NDVI C is in excellent agreement with NDVI obtained from spectral measurements, and that NDVI C and G CC can complement each other in describing ecosystem phenology. Additionally, NDVI C allows the detection of structural changes in the canopy that cannot be detected by visible-wavelength imagery
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