41 research outputs found

    In vivo imaging of brown adipose tissue vasculature reactivity during adrenergic stimulation of non-shivering thermogenesis in mice

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    Brown adipose tissue (BAT) is a fat tissue specialized in heat production (non-shivering thermogenesis) and used by mammals to defend core body temperature when exposed to cold. Several studies have shown that during non-shivering thermogenesis the increase in BAT oxygen demand is met by a local and specific increase in tissue’s blood flow. While the vasculature of BAT has been extensively studied postmortem in rodents using histology, optical and CT imaging techniques, vasculature changes during stimulation of non-shivering thermogenesis have never been directly detected in vivo. Here, by using computed tomography (CT) angiography with gold nanoparticles we investigate, non-invasively, changes in BAT vasculature during adrenergic stimulation of non-shivering thermogenesis by norepinephrine, a vasoconstrictor known to mediate brown fat heat production, and by CL 316,243, a specific β3-adrenergic agonist also known to elicit BAT thermogenesis in rodents. We found that while CL 316,243 causes local vasodilation in BAT, with little impact on the rest of the vasculature throughout the body, norepinephrine leads to local vasodilation in addition to peripheral vasoconstriction. As a result, a significantly greater relative increase in BAT perfusion is observed following the injection of NE compared to CL. This study demonstrates the use of in vivo CT angiography as an effective tool in assessing vascular reactivity in BAT both qualitatively and quantitatively in preclinical studies

    An NLRP3 Mutation Causes Arthropathy and Osteoporosis in Humanized Mice

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    The NLRP3 inflammasome plays a critical role in host defense by facilitating caspase I activation and maturation of IL-1β and IL-18, whereas dysregulation of inflammasome activity results in autoinflammatory disease. Factors regulating human NLRP3 activity that contribute to the phenotypic heterogeneity of NLRP3-related diseases have largely been inferred from the study of Nlrp3 mutant mice. By generating a mouse line in which the NLRP3 locus is humanized by syntenic replacement, we show the functioning of the human NLRP3 proteins in vivo, demonstrating the ability of the human inflammasome to orchestrate immune reactions in response to innate stimuli. Humanized mice expressing disease-associated mutations develop normally but display acute sensitivity to endotoxin and develop progressive and debilitating arthritis characterized by granulocytic infiltrates, elevated cytokines, erosion of bones, and osteoporosis. This NLRP3-dependent arthritis model provides a platform for testing therapeutic reagents targeting the human inflammasome

    Tensor analysing powers for <sup>7</sup>Li induced transfer breakup reactions

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    The tensor analysing power T/sub 20/ has been measured for the /sup 120/Sn(/sup 7/Li, /sup 8/Be to 2 alpha )/sup 119/In and /sup 120/Sn(/sup 7/Li, /sup 6/Li* to alpha +d)/sup 121/Sn transfer breakup reactions at 70 MeV bombarding energy. Coupled channels and continuum discretized coupled channels calculations, incorporating a detector phase space correction, were found to give good agreement with the data
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