Charting the Microbiome Biodiversity of the Appalachian Highlands Region: A Novel Study

The rapid expansion of medical discoveries has been met with growing number of deaths from nosocomial multidrug-resistant bacteria. The dramatic rise of these antibiotic-resistant microorganisms has been placed on the World Health Organization’s watchlist as one of the biggest threats to the future of healthcare. There continues to be a shortage of effective antibiotics with the rise of these “superbugs”. With the growing number of deadly pathogens, the future of medicine relies on scientific findings of novel compounds to combat multidrug-resistant bacteria. The Appalachian Highlands Region holds the potential for discovering these new compounds. As the most biodiverse temperate forest region in North America, the Smoky Mountains contains a plethora of microorganisms that have become genetically diversified over millions of years. In order to compete with one another, many of these soil bacteria naturally produce their own antibiotics. With the wide variation of natural bacteria, Appalachia serves as a testing ground to harness the power of natural antibiotics and understand how these compounds can aide in clinic use. A gram of soil contains more than 10,000 different species of bacteria. The biodiversity of these microbes is still largely unknown, as almost 99% of these species cannot be cultured in a normal lab setting. Utilizing the 16S genomic region of microbes, this pilot project will lay the foundations of discovering Appalachia’s microbiome, which has, thus far, never been cataloged

Bicaudal is a conserved substrate for Drosophila and mammalian caspases and is essential for cell survival

Members of the caspase family of cysteine proteases coordinate cell death through restricted proteolysis of diverse protein substrates and play a conserved role in apoptosis from nematodes to man. However, while numerous substrates for the mammalian cell death-associated caspases have now been described, few caspase substrates have been identified in other organisms. Here, we have utilized a proteomics-based approach to identify proteins that are cleaved by caspases during apoptosis in Drosophila D-Mel2 cells, a subline of the Schneider S2 cell line. This approach identified multiple novel substrates for the fly caspases and revealed that bicaudal/betaNAC is a conserved substrate for Drosophila and mammalian caspases. RNAi-mediated silencing of bicaudal expression in Drosophila D-Mel2 cells resulted in a block to proliferation, followed by spontaneous apoptosis. Similarly, silencing of expression of the mammalian bicaudal homologue, betaNAC, in HeLa, HEK293T, MCF-7 and MRC5 cells also resulted in spontaneous apoptosis. These data suggest that bicaudal/betaNAC is essential for cell survival and is a conserved target of caspases from flies to man

Worldwide acceleration of mountain erosion under a cooling climate

Climate influences the erosion processes acting at the Earth’s surface. However, the effect of cooling during the Late Cenozoic era, including the onset of Pliocene–Pleistocene Northern Hemisphere glaciation (about two to three million years ago), on global erosion rates remains unclear1, 2, 3, 4. The uncertainty arises mainly from a lack of consensus on the use of the sedimentary record as a proxy for erosion3, 4 and the difficulty of isolating the respective contributions of tectonics and climate to erosion5, 6, 7. Here we compile 18,000 bedrock thermochronometric ages from around the world and use a formal inversion procedure8 to estimate temporal and spatial variations in erosion rates. This allows for the quantification of erosion for the source areas that ultimately produce the sediment record on a timescale of millions of years. We find that mountain erosion rates have increased since about six million years ago and most rapidly since two million years ago. The increase of erosion rates is observed at all latitudes, but is most pronounced in glaciated mountain ranges, indicating that glacial processes played an important part. Because mountains represent a considerable fraction of the global production of sediments9, our results imply an increase in sediment flux at a global scale that coincides closely with enhanced cooling during the Pliocene and Pleistocene epochs10, 11

Hypoxia: an alarm signal during intestinal inflammation

Intestinal epithelial cells that line the mucosal surface of the gastrointestinal tract are positioned between an anaerobic lumen and a highly metabolic lamina propria. As a result of this unique anatomy, intestinal epithelial cells function within a steep physiologic oxygen gradient relative to other cell types. Furthermore, during active inflammatory disease such as IBD, metabolic shifts towards hypoxia are severe. Studies in vitro and in vivo have shown that the activation of hypoxia-inducible factor (HIF) serves as an alarm signal to promote the resolution of inflammation in various mouse models of disease. Amelioration of disease occurs, at least in part, through transcriptional upregulation of nonclassic epithelial barrier genes. There is much interest in harnessing hypoxia-inducible pathways, including stabilizing HIF directly or via inhibition of prolyl hydroxylase enzymes, for therapy of IBD. In this Review, we discuss the signaling pathways involved in the regulation of hypoxia and discuss how hypoxia may serve as an endogenous alarm signal for the presence of mucosal inflammatory disease. We also discuss the pros and cons of targeting these pathways to treat patients with IBD.Deposited by bulk impor

Hypoxia: an alarm signal during intestinal inflammation

Intestinal epithelial cells that line the mucosal surface of the gastrointestinal tract are positioned between an anaerobic lumen and a highly metabolic lamina propria. As a result of this unique anatomy, intestinal epithelial cells function within a steep physiologic oxygen gradient relative to other cell types. Furthermore, during active inflammatory disease such as IBD, metabolic shifts towards hypoxia are severe. Studies in vitro and in vivo have shown that the activation of hypoxia-inducible factor (HIF) serves as an alarm signal to promote the resolution of inflammation in various mouse models of disease. Amelioration of disease occurs, at least in part, through transcriptional upregulation of nonclassic epithelial barrier genes. There is much interest in harnessing hypoxia-inducible pathways, including stabilizing HIF directly or via inhibition of prolyl hydroxylase enzymes, for therapy of IBD. In this Review, we discuss the signaling pathways involved in the regulation of hypoxia and discuss how hypoxia may serve as an endogenous alarm signal for the presence of mucosal inflammatory disease. We also discuss the pros and cons of targeting these pathways to treat patients with IBD.Deposited by bulk impor