33 research outputs found
Analysis of DNA methylation acquisition at the imprinted Dlk1 locus reveals asymmetry at CpG dyads
Bioavailability of Macro and Micronutrients Across Global Topsoils: Main Drivers and Global Change Impacts
Understanding the chemical composition of our planet\u27s crust was one of the biggest questions of the 20th century. More than 100 years later, we are still far from understanding the global patterns in the bioavailability and spatial coupling of elements in topsoils worldwide, despite their importance for the productivity and functioning of terrestrial ecosystems. Here, we measured the bioavailability and coupling of thirteen macro- and micronutrients and phytotoxic elements in topsoils (3–8 cm) from a range of terrestrial ecosystems across all continents (∼10,000 observations) and in response to global change manipulations (∼5,000 observations). For this, we incubated between 1 and 4 pairs of anionic and cationic exchange membranes per site for a mean period of 53 days. The most bioavailable elements (Ca, Mg, and K) were also amongst the most abundant in the crust. Patterns of bioavailability were biome-dependent and controlled by soil properties such as pH, organic matter content and texture, plant cover, and climate. However, global change simulations resulted in important alterations in the bioavailability of elements. Elements were highly coupled, and coupling was predictable by the atomic properties of elements, particularly mass, mass to charge ratio, and second ionization energy. Deviations from the predictable coupling-atomic mass relationship were attributed to global change and agriculture. Our work illustrates the tight links between the bioavailability and coupling of topsoil elements and environmental context, human activities, and atomic properties of elements, thus deeply enhancing our integrated understanding of the biogeochemical connections that underlie the productivity and functioning of terrestrial ecosystems in a changing world
Injury-induced pulmonary tuft cells are heterogenous, arise independent of key Type 2 cytokines, and are dispensable for dysplastic repair
While the lung bears significant regenerative capacity, severe viral pneumonia can chronically impair lung function by triggering dysplastic remodeling. The connection between these enduring changes and chronic disease remains poorly understood. We recently described the emergence of tuft cells within Krt5+ dysplastic regions after influenza injury. Using bulk and single-cell transcriptomics, we characterized and delineated multiple distinct tuft cell populations that arise following influenza clearance. Distinct from intestinal tuft cells which rely on Type 2 immune signals for their expansion, neither IL-25 nor IL-4ra signaling are required to drive tuft cell development in dysplastic/injured lungs. In addition, tuft cell expansion occurred independently of type I or type III interferon signaling. Furthermore, tuft cells were also observed upon bleomycin injury, suggesting that their development may be a general response to severe lung injury. While intestinal tuft cells promote growth and differentiation of surrounding epithelial cells, in the lungs of tuft cell deficient mice, Krt5+ dysplasia still occurs, goblet cell production is unchanged, and there remains no appreciable contribution of Krt5+ cells into more regionally appropriate alveolar Type 2 cells. Together, these findings highlight unexpected differences in signals necessary for murine lung tuft cell amplification and establish a framework for future elucidation of tuft cell functions in pulmonary health and disease
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Implementation research on community health workers’ provision of maternal and child health services in rural Liberia
Abstract Objective: To assess changes in the use of essential maternal and child health services in Konobo, Liberia, after implementation of an enhanced community health worker (CHW) programme. Methods: The Liberian Ministry of Health partnered with Last Mile Health, a nongovernmental organization, to implement a pilot CHW programme with enhanced recruitment, training, supervision and compensation. To assess changes in maternal and child health-care use, we conducted repeated cross-sectional cluster surveys before (2012) and after (2015) programme implementation. Findings: Between 2012 and 2015, 54 CHWs, seven peer supervisors and three clinical supervisors were trained to serve a population of 12 127 people in 44 communities. The regression-adjusted percentage of children receiving care from formal care providers increased by 60.1 (95% confidence interval, CI: 51.6 to 68.7) percentage points for diarrhoea, by 30.6 (95% CI: 20.5 to 40.7) for fever and by 51.2 (95% CI: 37.9 to 64.5) for acute respiratory infection. Facility-based delivery increased by 28.2 points (95% CI: 20.3 to 36.1). Facility-based delivery and formal sector care for acute respiratory infection and diarrhoea increased more in agricultural than gold-mining communities. Receipt of one-or-more antenatal care sessions at a health facility and postnatal care within 24 hours of delivery did not change significantly. Conclusion: We identified significant increases in uptake of child and maternal health-care services from formal providers during the pilot CHW programme in remote rural Liberia. Clinic-based services, such as postnatal care, and services in specific settings, such as mining areas, require additional interventions to achieve optimal outcomes
Complex Phosphatase Regulation of Ca2+-activated Cl− Currents in Pulmonary Arterial Smooth Muscle Cells*
The present study was undertaken to determine whether the two ubiquitously expressed Ca2+-independent phosphatases PP1 and PP2A regulate Ca2+-activated Cl− currents (ICl(Ca)) elicited by 500 nm [Ca2+]i in rabbit pulmonary artery (PA) myocytes dialyzed with or without 3 mm ATP. Reverse transcription-PCR experiments revealed the expression of PP1α, PP1β/δ, PP1γ, PP2Aα, PP2Aβ, PP2Bα (calcineurin (CaN) Aα), and PP2Bβ (CaN Aβ) but not PP2Bγ (CaN Aγ) in rabbit PA. Western blot and immunofluorescence experiments confirmed the presence of all three PP1 isoforms and PP2A. Intracellular dialysis with a peptide inhibitor of calcineurin (CaN-AIP); the non-selective PP1/PP2A inhibitors okadaic acid (0.5, 10, or 30 nm), calyculin A (10 nm), or cantharidin (100 nm); and the selective PP1 inhibitor NIPP-1 (100 pm) potently antagonized the recovery of ICl(Ca) in cells dialyzed with no ATP, whereas the PP2A-selective antagonist fostriecin (30 or 150 nm) was ineffective. The combined application of okadaic acid (10 nm) and CaN-autoinhibitory peptide (50 μm) did not potentiate the response of ICl(Ca) in 0 ATP produced by maximally inhibiting CaN or PP1/PP2A alone. Consistent with the non-additive effects of either classes of phosphatases, the PP1 inhibitor NIPP-1 (100 pm) antagonized the recovery of ICl(Ca) induced by exogenous CaN Aα (0.5 μm). These results demonstrate that ICl(Ca) in PA myocytes is regulated by CaN and PP1 and/or PP2A. Our data also suggest the existence of a functional link between these two classes of phosphatases
Implementation research on community health workers’ provision of maternal and child health services in rural Liberia
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Self-reported Patient Motivations for Seeking Cosmetic Procedures.
This multicenter observational study assesses the importance of self-reported factors that motivate patients to undergo minimally invasive cosmetic surgical procedures
Bioavailability of macro and micronutrients across global topsoils:Main drivers and global change impacts
Understanding the chemical composition of our planet's crust was one of the biggest questions of the 20th century. More than 100 years later, we are still far from understanding the global patterns in the bioavailability and spatial coupling of elements in topsoils worldwide, despite their importance for the productivity and functioning of terrestrial ecosystems. Here, we measured the bioavailability and coupling of thirteen macro‐ and micronutrients and phytotoxic elements in topsoils (3–8 cm) from a range of terrestrial ecosystems across all continents (∼10,000 observations) and in response to global change manipulations (∼5,000 observations). For this, we incubated between 1 and 4 pairs of anionic and cationic exchange membranes per site for a mean period of 53 days. The most bioavailable elements (Ca, Mg, and K) were also amongst the most abundant in the crust. Patterns of bioavailability were biome‐dependent and controlled by soil properties such as pH, organic matter content and texture, plant cover, and climate. However, global change simulations resulted in important alterations in the bioavailability of elements. Elements were highly coupled, and coupling was predictable by the atomic properties of elements, particularly mass, mass to charge ratio, and second ionization energy. Deviations from the predictable coupling‐atomic mass relationship were attributed to global change and agriculture. Our work illustrates the tight links between the bioavailability and coupling of topsoil elements and environmental context, human activities, and atomic properties of elements, thus deeply enhancing our integrated understanding of the biogeochemical connections that underlie the productivity and functioning of terrestrial ecosystems in a changing world