181 research outputs found

    Tourmaline - A Prospecting Guide for Massive Base-Metal Sulfide Deposits in the Penobscot Bay Area, Maine

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    Tourmaline - A Prospecting Guide for Massive Base-Metal Sulfide Deposits in the Penobscot Bay Area, Maine by John F. Slack, U.S. Geological Survey Special Economic Studies Series No.8 Maine Geological Survey, Department of Conservation, Augusta, Maine (June, 1980). Contents: Abstract / Introduction / Geologic Setting / Massive Sulfide Deposits / Tourmaline Occurrences / Tourmaline: A Guide to Ore / Acknowledgements / References Citedhttps://digitalcommons.usm.maine.edu/me_collection/1124/thumbnail.jp

    Regional geochemical variations in a metamorphosed black shale: a reconnaissance study of the Silurian Smalls Falls Formation, Maine, USA

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    A reconnaissance geochemical study of 21 samples of sulphidic black phyllite and schist from the Silurian Smalls Falls Formation in Maine was undertaken in order to evaluate compositional changes during regional metamorphism. These samples represent variably metamorphosed black shale. Analyzed samples come from the chlorite zone in northern Maine and the biotite, garnet, and staurolite-andalusite zones in west-central Maine. Strata of the Smalls Falls Formation are distinctive in containing abundant pyrite and/or pyrrhotite (total S = 1.2–9.7 wt%), but only minor organic matter or graphite (TOC = 0.43–1.85 wt%); TOC/S ratios are uniformly low (average = 0.37 ± 0.22). Median enrichment factors were calculated for each element by normalizing the concentration to Ti in each sample to the Ti-normalized median composition of global black shale. In the chlorite zone, moderate to large decreases in enrichment factors (-23.1 to -49.8%) are evident for V, Cr, Cu, Ni, Zn, Pb, Sb, and U, attributed here to various factors during sedimentation plus variable element mobility during diagenesis. With increasing metamorphic grade (biotite through staurolite-andalusite zones), systematic small to extreme decreases (-14.5 to -99.0%) were found for Ba, Sb, Au, and U, together with less-systematic moderate to large decreases (-35.4 to -61.1%) for V and As. Molybdenum shows an extreme decrease (-94.7%) from the garnet to staurolite-andalusite zones. Excluding Ba, these results are interpreted to mainly reflect mobility of trace elements during pyrite recrystallization, and during the metamorphic transformations of organic matter to graphite and of pyrite to pyrrhotite. Moderate to large increases for Rb (+28.1 to +61.5%) and Th (+39.1 to +47.3%) from the biotite to staurolite-andalusite zones likely record the introduction of alkalis and mass loss, respectively, during metamorphism. Three samples from one site in the garnet zone differ in having anomalously high Fe/Al and low La/Yb ratios, attributed here to epigenetic formation of pyrite and related leaching of light rare earth elements during syn-metamorphic, channelized fluid flow.Geologic and geochemical data indicate that strata of the Smalls Falls Formation were deposited during an interval of anoxia on the northwestern flank of the Central Maine Basin, for which detrital sources included an evolved continental arc. Onset of anoxia coincided with deposition of the Mayflower Hill Formation of the Vassalboro Group, on the basin’s southeastern flank, related to emergence of the Brunswick subduction complex. We suggest that this emergence played a role in promoting both lateral and vertical circulation changes, nutrient loading, and deoxygenation through subsequent basin closure that culminated with Acadian deformation and metamorphism. Based on the relatively high contents of total sulphur present in our Smalls Falls samples, sediments in the Black Sea represent the only known plausible candidate among those in modern suboxic to euxinic basins

    A2: Smalls Falls Revisted: A Journey Through a Paleozoic Sedimentary Basin

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    Guidebook for field trips in Western Maine and Northern New Hampshire: New England Intercollegiate Geological Conference, p. 35-60

    Pharmacological characterization of the αvβ6 integrin binding and internalization kinetics of the foot-and-mouth disease virus derived peptide A20FMDV2

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    A20FMDV2 is a peptide derived from the foot-and-mouth disease virus with a high affinity and selectivity for the alphav beta-6 (αvβ6) arginyl-glycinyl-aspartic acid (RGD)-binding integrin. It has been shown to be an informative tool ligand in pre-clinical imaging studies for selective labelling of the αvβ6 integrin in a number of disease models. In a radioligand- binding assay using a radiolabelled form of the peptide ([3H]A20FMDV2), its high affinity (KD:0.22nmol/l) and selectivity (at least 85-fold) for αvβ6 over the other members of the RGD integrin family was confirmed. [3H]A20FMDV2 αvβ6 binding could be fully reversed only in the presence of EDTA, whereas a partial reversal was observed in the presence of excess concentrations of an RGD-mimetic small molecule (SC-68448) or unlabelled A20FMDV2. Using flow cytometry on bronchial epithelial cells, the ligand-induced internalization of αvβ6 by A20FMDV2 and LAP1 was shown to be fast (t1/2:1.5and 3.1 min, respectively), concentration-dependent (EC50:values 1.1 and 3.6nmol/l, respectively) and was followed by a moderately slow return of integrin to the surface. The results of the radioligand-binding studies suggest that the binding of A20FMDV2 to the RGD-binding site on αvβ6 is required to maintain its engagement with the hypothesised A20FMDV2 synergy site on the integrin. In addition, there is evidence from flow cytometric studies that the RGD-ligand engagement of αvβ6 post-internalization plays a role in delaying recycling of the integrin to the cell surface. This mechanism may act as a homeostatic control of membrane αvβ6 following RGD ligand engagement

    Translational pharmacology of an inhaled small molecule αvβ6 integrin inhibitor for idiopathic pulmonary fibrosis

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    The αvβ6 integrin plays a key role in the activation of transforming growth factor-β (TGFβ), a pro-fibrotic mediator that is pivotal to the development of idiopathic pulmonary fibrosis (IPF). We identified a selective small molecule αvβ6 RGD-mimetic, GSK3008348, and profiled it in a range of disease relevant pre-clinical systems. To understand the relationship between target engagement and inhibition of fibrosis, we measured pharmacodynamic and diseaserelated end points. Here we report, GSK3008348 binds to αvβ6 with high affinity in human IPF lung and reduces downstream pro-fibrotic TGFβ signaling to normal levels. In human lung epithelial cells, GSK3008348 induces rapid internalization and lysosomal degradation of the αvβ6 integrin. In the murine bleomycin-induced lung fibrosis model, GSK3008348 engages αvβ6, induces prolonged inhibition of TGFβ signaling and reduces lung collagen deposition and serum C3M, a marker of IPF disease progression. These studies highlight the potential of inhaled GSK3008348 as an anti-fibrotic therapy

    Evidence for early life in Earth’s oldest hydrothermal vent precipitates

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    Although it is not known when or where life on Earth began, some of the earliest habitable environments may have been submarine-hydrothermal vents. Here we describe putative fossilized microorganisms that are at least 3,770 million and possibly 4,280 million years old in ferruginous sedimentary rocks, interpreted as seafloor-hydrothermal vent-related precipitates, from the Nuvvuagittuq belt in Quebec, Canada. These structures occur as micrometre-scale haematite tubes and filaments with morphologies and mineral assemblages similar to those of filamentous microorganisms from modern hydrothermal vent precipitates and analogous microfossils in younger rocks. The Nuvvuagittuq rocks contain isotopically light carbon in carbonate and carbonaceous material, which occurs as graphitic inclusions in diagenetic carbonate rosettes, apatite blades intergrown among carbonate rosettes and magnetite–haematite granules, and is associated with carbonate in direct contact with the putative microfossils. Collectively, these observations are consistent with an oxidized biomass and provide evidence for biological activity in submarine-hydrothermal environments more than 3,770 million years ago

    Heparan Sulfate Proteoglycans Mediate Interstitial Flow Mechanotransduction Regulating MMP-13 Expression and Cell Motility via FAK-ERK in 3D Collagen

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    Interstitial flow directly affects cells that reside in tissues and regulates tissue physiology and pathology by modulating important cellular processes including proliferation, differentiation, and migration. However, the structures that cells utilize to sense interstitial flow in a 3-dimensional (3D) environment have not yet been elucidated. Previously, we have shown that interstitial flow upregulates matrix metalloproteinase (MMP) expression in rat vascular smooth muscle cells (SMCs) and fibroblasts/myofibroblasts via activation of an ERK1/2-c-Jun pathway, which in turn promotes cell migration in collagen. Herein, we focused on uncovering the flow-induced mechanotransduction mechanism in 3D.Cleavage of rat vascular SMC surface glycocalyx heparan sulfate (HS) chains from proteoglycan (PG) core proteins by heparinase or disruption of HS biosynthesis by silencing N-deacetylase/N-sulfotransferase 1 (NDST1) suppressed interstitial flow-induced ERK1/2 activation, interstitial collagenase (MMP-13) expression, and SMC motility in 3D collagen. Inhibition or knockdown of focal adhesion kinase (FAK) also attenuated or blocked flow-induced ERK1/2 activation, MMP-13 expression, and cell motility. Interstitial flow induced FAK phosphorylation at Tyr925, and this activation was blocked when heparan sulfate proteoglycans (HSPGs) were disrupted. These data suggest that HSPGs mediate interstitial flow-induced mechanotransduction through FAK-ERK. In addition, we show that integrins are crucial for mechanotransduction through HSPGs as they mediate cell spreading and maintain cytoskeletal rigidity.We propose a conceptual mechanotransduction model wherein cell surface glycocalyx HSPGs, in the presence of integrin-mediated cell-matrix adhesions and cytoskeleton organization, sense interstitial flow and activate the FAK-ERK signaling axis, leading to upregulation of MMP expression and cell motility in 3D. This is the first study to describe a flow-induced mechanotransduction mechanism via HSPG-mediated FAK activation in 3D. This study will be of interest in understanding the flow-related mechanobiology in vascular lesion formation, tissue morphogenesis, cancer cell metastasis, and stem cell differentiation in 3D, and also has implications in tissue engineering

    Pre-Bilaterian Origins of the Hox Cluster and the Hox Code: Evidence from the Sea Anemone, Nematostella vectensis

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    BACKGROUND: Hox genes were critical to many morphological innovations of bilaterian animals. However, early Hox evolution remains obscure. Phylogenetic, developmental, and genomic analyses on the cnidarian sea anemone Nematostella vectensis challenge recent claims that the Hox code is a bilaterian invention and that no “true” Hox genes exist in the phylum Cnidaria. METHODOLOGY/PRINCIPAL FINDINGS: Phylogenetic analyses of 18 Hox-related genes from Nematostella identify putative Hox1, Hox2, and Hox9+ genes. Statistical comparisons among competing hypotheses bolster these findings, including an explicit consideration of the gene losses implied by alternate topologies. In situ hybridization studies of 20 Hox-related genes reveal that multiple Hox genes are expressed in distinct regions along the primary body axis, supporting the existence of a pre-bilaterian Hox code. Additionally, several Hox genes are expressed in nested domains along the secondary body axis, suggesting a role in “dorsoventral” patterning. CONCLUSIONS/SIGNIFICANCE: A cluster of anterior and posterior Hox genes, as well as ParaHox cluster of genes evolved prior to the cnidarian-bilaterian split. There is evidence to suggest that these clusters were formed from a series of tandem gene duplication events and played a role in patterning both the primary and secondary body axes in a bilaterally symmetrical common ancestor. Cnidarians and bilaterians shared a common ancestor some 570 to 700 million years ago, and as such, are derived from a common body plan. Our work reveals several conserved genetic components that are found in both of these diverse lineages. This finding is consistent with the hypothesis that a set of developmental rules established in the common ancestor of cnidarians and bilaterians is still at work today
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