132 research outputs found

    Inferring metabolic mechanisms of interaction within a defined gut microbiota

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    The diversity and number of species present within microbial communities create the potential for a multitude of interspecies metabolic interactions. Here, we develop, apply, and experimentally test a framework for inferring metabolic mechanisms associated with interspecies interactions. We perform pairwise growth and metabolome profiling of co-cultures of strains from a model mouse microbiota. We then apply our framework to dissect emergent metabolic behaviors that occur in co-culture. Based on one of the inferences from this framework, we identify and interrogate an amino acid cross-feeding interaction and validate that the proposed interaction leads to a growth benefit in vitro. Our results reveal the type and extent of emergent metabolic behavior in microbial communities composed of gut microbes. We focus on growth-modulating interactions, but the framework can be applied to interspecies interactions that modulate any phenotype of interest within microbial communities

    FMR1 premutation and full mutation molecular mechanisms related to autism

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    Fragile X syndrome (FXS) is caused by an expanded CGG repeat (>200 repeats) in the 5′ un-translated portion of the fragile X mental retardation 1 gene (FMR1) leading to a deficiency or absence of the FMR1 protein (FMRP). FMRP is an RNA-binding protein that regulates the translation of a number of other genes that are important for synaptic development and plasticity. Furthermore, many of these genes, when mutated, have been linked to autism in the general population, which may explain the high comorbidity that exists between FXS and autism spectrum disorders (ASD). Additionally, premutation repeat expansions (55 to 200 CGG repeats) may also give rise to ASD through a different molecular mechanism that involves a direct toxic effect of FMR1 mRNA. It is believed that RNA toxicity underlies much of the premutation-related involvement, including developmental concerns like autism, as well as neurodegenerative issues with aging such as the fragile X-associated tremor ataxia syndrome (FXTAS). RNA toxicity can also lead to mitochondrial dysfunction, which is common in older premutation carriers both with and without FXTAS. Many of the problems with cellular dysregulation in both premutation and full mutation neurons also parallel the cellular abnormalities that have been documented in idiopathic autism. Research regarding dysregulation of neurotransmitter systems caused by the lack of FMRP in FXS, including metabotropic glutamate receptor 1/5 (mGluR1/5) pathway and GABA pathways, has led to new targeted treatments for FXS. Preliminary evidence suggests that these new targeted treatments will also be beneficial in non-fragile X forms of autism

    Correspondence between Roy H. McDuffie, Jr. and Zebulon Weaver, November 1933

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    Zebulon Weaver (1872-1948) was a lawyer and U.S. Representative from western North Carolina. He was a member of the North Carolina Park Commission and was involved in the land acquisition process that went towards establishment of the Great Smoky Mountain National Park and development of the Blue Ridge Parkway. This correspondence--a set of two letters--between Zebulon Weaver and Roy H. McDuffie, Jr. discusses the route for the construction of the scenic Park-to-Park Highway. Roy H. McDuffie, Jr. to Zebulon Weaver, November 19, 1933 In this letter McDuffie, manager of the Mountain Meadows Inn in Asheville requests Weaver that the Skyline route or the Park-to-Park Highway be constructed in a way so to intersect the scenic Elk Mountain Highway over Sunset Mountain into Asheville. According to McDuffie the Elk Mountain highway was very well travelled with people riding past the Inn. Zebulon Weaver to Roy H. McDuffie, Jr. , November 27, 1933 In this letter Weaver assures McDuffie that the highway would necessarily have to connect with the Elk Mountain scenic highway in order to be considered a scenic route
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