16 research outputs found

    Uif, a Large Transmembrane Protein with EGF-Like Repeats, Can Antagonize Notch Signaling in Drosophila

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    <div><h3>Background</h3><p>Notch signaling is a highly conserved pathway in multi-cellular organisms ranging from flies to humans. It controls a variety of developmental processes by stimulating the expression of its target genes in a highly specific manner both spatially and temporally. The diversity, specificity and sensitivity of the Notch signaling output are regulated at distinct levels, particularly at the level of ligand-receptor interactions.</p> <h3>Methodology/Principal Findings</h3><p>Here, we report that the <em>Drosophila</em> gene <em>uninflatable</em> (<em>uif</em>), which encodes a large transmembrane protein with eighteen EGF-like repeats in its extracellular domain, can antagonize the canonical Notch signaling pathway. Overexpression of Uif or ectopic expression of a neomorphic form of Uif, Uif*, causes Notch signaling defects in both the wing and the sensory organ precursors. Further experiments suggest that ectopic expression of Uif* inhibits Notch signaling <em>in cis</em> and acts at a step that is dependent on the extracellular domain of Notch. Our results suggest that Uif can alter the accessibility of the Notch extracellular domain to its ligands during Notch activation.</p> <h3>Conclusions/Significance</h3><p>Our study shows that Uif can modulate Notch activity, illustrating the importance of a delicate regulation of this signaling pathway for normal patterning.</p> </div

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    Rare earth elements in sedimentary phosphorite deposits: a global assessment

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    Each year an estimated 56,000 metric tons (t) of rare earth elements (REEs), including 23,000 t of heavy REEs (HREEs), are mined, beneficiated, and put into solution, but not recovered, by operations associated with the global phosphate fertilizer industry. Importantly, the REEs in sedimentary phosphorites are nearly 100% extractable, using technologies currently employed to meet global phosphate fertilizer needs. Our evaluation suggests that by-product REE production from these phosphate mines could meet global REE requirements. For example, the calculated REE flux accompanying phosphate production in the United States is approxi- mately 40% of the world’s total and, alone, could supply 65% of global HREEs needs. Moreover, recognition that the tonnages and HREE concentrations of some unmined phosphorite deposits dwarf the world’s richest REE deposits suggests that these deposits might constitute stand-alone REE deposits. The hypothesized genesis of these REE-rich occurrences strongly supports the long-debated suggestion that oceanic REE contents vary in a secular fashion and that associated high-grade REE abundances reflect oceanic redox state transitions during specific time periods. Here, we use this new process-based model, based on observed variations in global-secular REE abundances, to identify phosphorite horizons deposited during periods favorable for high- grade REE accumulation

    Impact of sedimentary-exhalative hydrothermal systems on marine chemistry and mass extinctions : applications for ore genesis research and mineral exploration

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    Times of metal-rich brine discharge into ancient ocean basins, associated with the formation of sedimentary-exhalative (sedex) Zn-Pb-Ba ore deposits, coincided with short-duration positive excursions ("spikes") in the global marine Sr isotope record. While these spikes are unexplained by conventional oceanic models, chronostratigraphic correlations, combined with mass balance evidence and oceanographic modeling, suggest that the flux of radiogenic Sr from sedex brines during ore formation is sufficient to explain these previously enigmatic Sr-87/Sr-86 spikes. We review existing Sr-87/Sr-86 data and present new data as verification of these global Sr-87/Sr-86 spikes and their correlations with the formation of giant sedex ore deposits. Major events include an 1 x 10(-4) (similar to 0.7078-similar to 0.7079) excursion contemporaneous with formation of the Rammelsberg deposit at -389 Ma; spikes on the order of 1 to 3 x 10(-4), coeval with formation of the Meggen deposit at similar to 381 Ma, several ore deposits in the Macmillan Pass district at similar to 379 to 375 Ma, and the Silvermines deposits at similar to 352 Ma; and two >6 x 10(-4) spikes coincident with formation of the giant Navan deposit at similar to 346 Ma and Red Dog deposits at similar to 337 Ma. Moreover, the timing of peak 8(87)Sr/Sr-86 spikes correlates with global delta C-13 and delta O-18 spikes,deposition of metal-rich black shales and ironstones, metal-induced malformation (teratology) of marine organisms, and mass extinctions. The relationships among these features were poorly understood, but our new model explains how the flux of key biolimiting nutrients and metals contained in sedex brines, demonstrably equivalent to or exceeding that of the total modern riverine flux to the ocean, spurred ocean eutrophication, which, ultimately, through a series of positive feedback mechanisms, may have triggered global chemical and biological events. If, as we hypothesize, sedex hydrothermal systems are recorded in the global marine isotopic, geologic, and biological records, our findings define a new approach to the study of and exploration for sedex deposits. We demonstrate that fluid inclusion solute chemistry and isotopic and stratigraphic studies of sedex deposits, coupled with chronostratigraphic correlation and high-resolution Sr-87/Sr-86 isotope chemostratigraphy, can be used to answer long-standing questions about geologic processes responsible for formation of these extraordinary deposits. This approach provides evidence for the age, duration, and fluxes of fluids and metals vented into the ocean by these giant hydrothermal systems. Accordingly, the marine Sr-87/Sr-86 curve constitutes a global exploration tool that could be applied to assess the mineral potential of sedimentary basins.To illustrate the potential of this tool to identify favorable stratigraphic ages and basins with potential for undiscovered giant sedex deposits, we highlight several spikes, on par with those characteristic of the Red Dog and Navan deposits, which have not been correlated with known metal deposits. Given these strong temporal correlations, mass balance estimates, and results of ocean chemistry modeling, our study suggests that further work is warranted to determine the extent to which periodic venting of hydrothermal basinal brines into the ocean has influenced the evolution of marine chemistry. Ultimately, these global signatures can be applied to the study of and exploration for sedex deposits
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