13 research outputs found

    Dual action antifungal small molecule modulates multidrug efflux and TOR signaling.

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    There is an urgent need for new strategies to treat invasive fungal infections, which are a leading cause of human mortality. Here, we establish two activities of the natural product beauvericin, which potentiates the activity of the most widely deployed class of antifungal against the leading human fungal pathogens, blocks the emergence of drug resistance, and renders antifungal-resistant pathogens responsive to treatment in mammalian infection models. Harnessing genome sequencing of beauvericin-resistant mutants, affinity purification of a biotinylated beauvericin analog, and biochemical and genetic assays reveals that beauvericin blocks multidrug efflux and inhibits the global regulator TORC1 kinase, thereby activating the protein kinase CK2 and inhibiting the molecular chaperone Hsp90. Substitutions in the multidrug transporter Pdr5 that enable beauvericin efflux impair antifungal efflux, thereby impeding resistance to the drug combination. Thus, dual targeting of multidrug efflux and TOR signaling provides a powerful, broadly effective therapeutic strategy for treating fungal infectious disease that evades resistance

    Global maps of soil temperature.

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    Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km <sup>2</sup> resolution for 0-5 and 5-15 cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km <sup>2</sup> pixels (summarized from 8519 unique temperature sensors) across all the world's major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (-0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications

    Assessment of climate extremes and its long term spatial variability over the Jharkhand state of India

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    This study examines the spatial climatic variability and climate extremes over the state of Jharkhand during 1984 to 2014. The climate extremes and the long-term fluctuation of climate parameters viz. maximum temperature, minimum temperature, rainfall, and solar radiation were assessed using least squares statistical method, for 71 locations in Jharkhand and interpolated spatially in Geographical Information System. The spatial analysis of the trend maps and climate index maps, demonstrates the regions with increasing number of summer days, increasing trend of maximum temperature and solar radiation, decreasing rainfall and thereby increased periods of consecutive dry days during monsoon season. The negative impact of climate extremes was observed as delay in transplanting/vegetative phase and reduced crop production, whereas an increase in the frequency of heat waves with 29 instances during 2004, 41 during 2005 and 100 during 2010 were observed. The findings of this study showed that average maximum temperature during 1984 to 2014 fluctuates with an increase of 1–1.5 °C to a decrease of 0.82–0.14 °C whereas the average minimum temperature fluctuates with a decrease of 0.79–0.39 °C to an increase of 0.59–0.41 °C. Rainfall fluctuates with a decrease of 26–270 mm to an increase of 19–440 mm. The highest average number of summer days is observed in Simdega with 340–348 days whereas the average consecutive dry days for the whole of Jharkhand has an increasing trend particularly in Palamu, Garhwa and Latehar districts, with 3.8–4.2 days of dryness during monsoon. Keywords: Summer days index, Consecutive dry days, Spatial climate variability, Trend analysi

    Reflechi twòp—Thinking Too Much: Description of a Cultural Syndrome in Haiti’s Central Plateau

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    Global maps of soil temperature

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    Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km2 resolution for 0–5 and 5–15 cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km2 pixels (summarized from 8519 unique temperature sensors) across all the world's major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (−0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological application

    Candidate genes for panic disorder: insight from human and mouse genetic studies

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