2,187 research outputs found

    SNAREs - engines for membrane fusion

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    TLR ligand-induced podosome disassembly in dendritic cells is ADAM17 dependent

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    Toll-like receptor (TLR) signaling induces a rapid reorganization of the actin cytoskeleton in cultured mouse dendritic cells (DC), leading to enhanced antigen endocytosis and a concomitant loss of filamentous actin–rich podosomes. We show that as podosomes are lost, TLR signaling induces prominent focal contacts and a transient reduction in DC migratory capacity in vitro. We further show that podosomes in mouse DC are foci of pronounced gelatinase activity, dependent on the enzyme membrane type I matrix metalloprotease (MT1-MMP), and that DC transiently lose the ability to degrade the extracellular matrix after TLR signaling. Surprisingly, MMP inhibitors block TLR signaling–induced podosome disassembly, although stimulated endocytosis is unaffected, which demonstrates that the two phenomena are not obligatorily coupled. Podosome disassembly caused by TLR signaling occurs normally in DC lacking MT1-MMP, and instead requires the tumor necrosis factor α–converting enzyme ADAM17 (a disintegrin and metalloprotease 17), which demonstrates a novel role for this “sheddase” in regulating an actin-based structure

    The Influence of Land Use and Climate Change on Forest Biomass and Composition in Massachusetts, USA

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    Land use and climate change have complex and interacting effects on naturally dynamic forest landscapes. To anticipate and adapt to these changes, it is necessary to understand their individual and aggregate impacts on forest growth and composition. We conducted a simulation experiment to evaluate regional forest change in Massachusetts, USA over the next 50 years (2010–2060). Our objective was to estimate, assuming a linear continuation of recent trends, the relative and interactive influence of continued growth and succession, climate change, forest conversion to developed uses, and timber harvest on live aboveground biomass (AGB) and tree species composition. We examined 20 years of land use records in relation to social and biophysical explanatory variables and used regression trees to create “probability-of-conversion” and “probability-of-harvest” zones. We incorporated this information into a spatially interactive forest landscape simulator to examine forest dynamics as they were affected by land use and climate change. We conducted simulations in a full-factorial design and found that continued forest growth and succession had the largest effect on AGB, increasing stores from 181.83 Tg to 309.56 Tg over 50 years. The increase varied from 49% to 112% depending on the ecoregion within the state. Compared to simulations with no climate or land use, forest conversion reduced gains in AGB by 23.18 Tg (or 18%) over 50 years. Timber harvests reduced gains in AGB by 5.23 Tg (4%). Climate change (temperature and precipitation) increased gains in AGB by 17.3 Tg (13.5%). Pinus strobus and Acer rubrum were ranked first and second, respectively, in terms of total AGB throughout all simulations. Climate change reinforced the dominance of those two species. Timber harvest reduced Quercus rubra from 10.8% to 9.4% of total AGB, but otherwise had little effect on composition. Forest conversion was generally indiscriminate in terms of species removal. Under the naïve assumption that future land use patterns will resemble the recent past, we conclude that continued forest growth and recovery will be the dominant mechanism driving forest dynamics over the next 50 years, and that while climate change may enhance growth rates, this will be more than offset by land use, primarily forest conversion to developed uses

    Reviewing two decades of energy system analysis with bibliometrics

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    Acknowledgements Dominik Franjo Dominkovi®c was funded by the CITIES project nr. DSF1305-00027B and Cool-Data project nr. 0177-00066B, both funded by the Danish Innovationsfonden. Fabian Scheller kindly acknowledges the financial support of the European Union’s research and innovation programme under the Marie Sklodowska-Curie grant agreement no. 713683 (COFUNDfellowsDTU). The authors also thank three anonymous reviewers for their helpful comments on an earlier version of this paper. The usual disclaimer applies.Peer reviewedPostprin

    Reviewing two decades of energy system analysis with bibliometrics

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    Acknowledgements Dominik Franjo Dominkovi®c was funded by the CITIES project nr. DSF1305-00027B and Cool-Data project nr. 0177-00066B, both funded by the Danish Innovationsfonden. Fabian Scheller kindly acknowledges the financial support of the European Union’s research and innovation programme under the Marie Sklodowska-Curie grant agreement no. 713683 (COFUNDfellowsDTU). The authors also thank three anonymous reviewers for their helpful comments on an earlier version of this paper. The usual disclaimer applies.Peer reviewedPostprin

    Hydrogels and Their Role in Biosensing Applications

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    Hydrogels play an important role in the field of biomedical research and diagnostic medicine. They are emerging as a powerful tool in the context of bioanalytical assays and biosensing. In this context, this review gives an overview of different hydrogels and the role they adopt in a range of applications. Not only are hydrogels beneficial for the immobilization and embedding of biomolecules, but they are also used as responsive material, as wearable devices, or as functional material. In particular, the scientific and technical progress during the last decade is discussed. The newest hydrogel types, their synthesis, and many applications are presented. Advantages and performance improvements are described, along with their limitations

    A neuroskeletal atlas: Spatial mapping and contextualization of axon subtypes innervating the long bones of C3H and B6 mice

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    Nerves in bone play well-established roles in pain and vasoregulation and have been associated with progression of skeletal disorders, including osteoporosis, fracture, arthritis, and tumor metastasis. However, isolation of the region-specific mechanisms underlying these relationships is limited by our lack of quantitative methods for neuroskeletal analysis and precise maps of skeletal innervation. To overcome these limitations, we developed an optimized workflow for imaging and quantitative analysis of axons in and around the bone, including validation of Baf53b-Cre in concert with R26R-tdTomato (Ai9) as a robust pan-neuronal reporter system for use in musculoskeletal tissues. In addition, we created comprehensive maps of sympathetic adrenergic and sensory peptidergic axons within and around the full length of the femur and tibia in two strains of mice (B6 and C3H). In the periosteum, these maps were related to the surrounding musculature, including entheses and myotendinous attachments to bone. Three distinct patterns of periosteal innervation (termed type I, II, III) were defined at sites that are important for bone pain, bone repair, and skeletal homeostasis. For the first time, our results establish a gradient of bone marrow axon density that increases from proximal to distal along the length of the tibia and define key regions of interest for neuroskeletal studies. Lastly, this information was related to major nerve branches and local maps of specialized mechanoreceptors. This detailed mapping and contextualization of the axonal subtypes innervating the skeleton is intended to serve as a guide during the design, implementation, and interpretation of future neuroskeletal studies and was compiled as a resource for the field as part of the NIH SPARC consortium. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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