515 research outputs found

    Selective contribution of Tyk2 to cell activation by lipopolysaccharide

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    AbstractTyk2 deficient mice show a markedly reduced susceptibility to lipopolysaccharide (LPS) induced shock and a partial impairment of IL-12 and interferon (IFN) signals. To examine the underlying mechanisms, we analysed the activation of peritoneal macrophages (PMΦs) and spleen cells after LPS challenge. In PMΦs and spleen cells the contribution of Tyk2 to the induction of the T-cell co-stimulatory molecules CD86, CD40 and MHC II was small or insignificant. By contrast, induced expression of the early activation marker CD69 on PMΦs and splenic cell populations required type I interferons (IFN-I) and Tyk2. The data suggest a selective contribution of Tyk2 to the activation of inflammation-relevant cell types by LPS

    Predator-driven natural selection on risk-taking behavior in anole lizards

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    Biologists have long debated the role of behavior in evolution, yet understanding of its role as a driver of adaptation is hampered by the scarcity of experimental studies of natural selection on behavior in nature. After showing that individual Anolis sagrei lizards vary consistently in risk-taking behaviors, we experimentally established populations on eight small islands either with or without Leiocephalus carinatus, a major ground predator. We found that selection predictably favors different risk-taking behaviors under different treatments: Exploratory behavior is favored in the absence of predators, whereas avoidance of the ground is favored in their presence. On predator islands, selection on behavior is stronger than selection on morphology, whereas the opposite holds on islands without predators. Our field experiment demonstrates that selection can shape behavioral traits, paving the way toward adaptation to varying environmental contexts

    A time- and dose-dependent STAT1 expression system

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    BACKGROUND: The signal transducer and activator of transcription (STAT) family of transcription factors mediates a variety of cytokine dependent gene regulations. STAT1 has been mainly characterized by its role in interferon (IFN) type I and II signaling and STAT1 deficiency leads to high susceptibility to several pathogens. For fine-tuned analysis of STAT1 function we established a dimerizer-inducible system for STAT1 expression in vitro and in vivo. RESULTS: The functionality of the dimerizer-induced STAT1 system is demonstrated in vitro in mouse embryonic fibroblasts and embryonic stem cells. We show that this two-vector based system is highly inducible and does not show any STAT1 expression in the absence of the inducer. Reconstitution of STAT1 deficient cells with inducible STAT1 restores IFNγ-mediated gene induction, antiviral responses and STAT1 activation remains dependent on cytokine stimulation. STAT1 expression is induced rapidly upon addition of dimerizer and expression levels can be regulated in a dose-dependent manner. Furthermore we show that in transgenic mice STAT1 can be induced upon stimulation with the dimerizer, although only at low levels. CONCLUSION: These results prove that the dimerizer-induced system is a powerful tool for STAT1 analysis in vitro and provide evidence that the system is suitable for the use in transgenic mice. To our knowledge this is the first report for inducible STAT1 expression in a time- and dose-dependent manner

    Perspektiven auf eine Jugendberufsagentur: "mehr" als nur das Jobcenter?

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    Many-sorted logic in a learning theorem prover

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    Coupling 3D groundwater modeling with CFC-based age dating to classify local groundwater circulation in an unconfined crystalline aquifer

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    International audienceNitrogen pollution of freshwater and estuarine environments is one of the most urgent environmental crises. Shallow aquifers with predominantly local flow circulation are particularly vulnerable to agricultural contaminants. Water transit time and flow path are key controls on catchment nitrogen retention and removal capacity, but the relative importance of hydrogeological and topographical factors in determining these parameters is still uncertain. We used groundwater dating and numerical modeling techniques to assess transit time and flow path in an unconfined aquifer in Brittany, France. The 35.5 km2 study catchment has a crystalline basement underneath a ∼60 m thick weathered and fractured layer, and is separated into a distinct upland and lowland area by an 80 m-high butte. We used groundwater discharge and groundwater ages derived from chlorofluorocarbon (CFC) concentration to calibrate a free-surface flow model simulating groundwater flow circulation. We found that groundwater flow was highly local (mean travel distance = 350 m), substantially smaller than the typical distance between neighboring streams (∼1 km), while CFC-based ages were quite old (mean = 40 years). Sensitivity analysis revealed that groundwater travel distances were not sensitive to geological parameters (i.e. arrangement of geological layers and permeability profile) within the constraints of the CFC age data. However, circulation was sensitive to topography in the lowland area where the water table was near the land surface, and to recharge rate in the upland area where water input modulated the free surface of the aquifer. We quantified these differences with a local groundwater ratio (rGW-LOCAL), defined as the mean groundwater travel distance divided by the mean of the reference surface distances (the distance water would have to travel across the surface of the digital elevation model). Lowland, rGW-LOCAL was near 1, indicating primarily topographical controls. Upland, rGW-LOCAL was 1.6, meaning the groundwater recharge area is almost twice as large as the topographically-defined catchment for any given point. The ratio rGW-LOCAL is sensitive to recharge conditions as well as topography and it could be used to compare controls on groundwater circulation within or between catchments

    Representativeness of Eddy-Covariance flux footprints for areas surrounding AmeriFlux sites

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    Large datasets of greenhouse gas and energy surface-atmosphere fluxes measured with the eddy-covariance technique (e.g., FLUXNET2015, AmeriFlux BASE) are widely used to benchmark models and remote-sensing products. This study addresses one of the major challenges facing model-data integration: To what spatial extent do flux measurements taken at individual eddy-covariance sites reflect model- or satellite-based grid cells? We evaluate flux footprints—the temporally dynamic source areas that contribute to measured fluxes—and the representativeness of these footprints for target areas (e.g., within 250–3000 m radii around flux towers) that are often used in flux-data synthesis and modeling studies. We examine the land-cover composition and vegetation characteristics, represented here by the Enhanced Vegetation Index (EVI), in the flux footprints and target areas across 214 AmeriFlux sites, and evaluate potential biases as a consequence of the footprint-to-target-area mismatch. Monthly 80% footprint climatologies vary across sites and through time ranging four orders of magnitude from 103 to 107 m2 due to the measurement heights, underlying vegetation- and ground-surface characteristics, wind directions, and turbulent state of the atmosphere. Few eddy-covariance sites are located in a truly homogeneous landscape. Thus, the common model-data integration approaches that use a fixed-extent target area across sites introduce biases on the order of 4%–20% for EVI and 6%–20% for the dominant land cover percentage. These biases are site-specific functions of measurement heights, target area extents, and land-surface characteristics. We advocate that flux datasets need to be used with footprint awareness, especially in research and applications that benchmark against models and data products with explicit spatial information. We propose a simple representativeness index based on our evaluations that can be used as a guide to identify site-periods suitable for specific applications and to provide general guidance for data use
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