92 research outputs found

    Relations between Au / Sn-W mineralizations and late hercynian granite: Preliminary results from the Schistose Domain of Galicia-Trás-os-Montes Zone, Spain

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    International audienceAu and W-Sn mineralization of the Schistose Domain of Galicia-Trás-os-Montes are spatially related to late hercynian granites. The Bruès (Au) and the Mina Soriana W-(Sn) deposits are studied. Both show some similarities and are assumed to form in the same tectonic and metamorphic context, on top of the granites. The role of the granite as a source for mineralizing fluids and rheological control for vein emplacement is re-adressed and discussed

    Genome-wide association and meta-analysis in populations from Starr County, Texas, and Mexico City identify type 2 diabetes susceptibility loci and enrichment for expression quantitative trait loci in top signals

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    AIMS/HYPOTHESIS: We conducted genome-wide association studies (GWASs) and expression quantitative trait loci (eQTL) analyses to identify and characterise risk loci for type 2 diabetes in Mexican-Americans from Starr County, TX, USA. METHOD: Using 1.8 million directly interrogated and imputed genotypes in 837 unrelated type 2 diabetes cases and 436 normoglycaemic controls, we conducted Armitage trend tests. To improve power in this population with high disease rates, we also performed ordinal regression including an intermediate class with impaired fasting glucose and/or glucose tolerance. These analyses were followed by meta-analysis with a study of 967 type 2 diabetes cases and 343 normoglycaemic controls from Mexico City, Mexico. RESULT: The top signals (unadjusted p value <1×10(−5)) included 49 single nucleotide polymorphisms (SNPs) in eight gene regions (PER3, PARD3B, EPHA4, TOMM7, PTPRD, HNT [also known as RREB1], LOC729993 and IL34) and six intergenic regions. Among these was a missense polymorphism (rs10462020; Gly639Val) in the clock gene PER3, a system recently implicated in diabetes. We also report a second signal (minimum p value 1.52× 10(−6)) within PTPRD, independent of the previously implicated SNP, in a population of Han Chinese. Top meta-analysis signals included known regions HNF1A and KCNQ1. Annotation of top association signals in both studies revealed a marked excess of trans-acting eQTL in both adipose and muscle tissues. CONCLUSIONS/INTERPRETATION: In the largest study of type 2 diabetes in Mexican populations to date, we identified modest associations of novel and previously reported SNPs. In addition, in our top signals we report significant excess of SNPs that predict transcript levels in muscle and adipose tissues

    The Effect of a DNA Repair Gene on Cellular Invasiveness: Xrcc3 Over-Expression in Breast Cancer Cells

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    Over-expression of DNA repair genes has been associated with resistance to radiation and DNA-damage induced by chemotherapeutic agents such as cisplatin. More recently, based on the analysis of genome expression profiling, it was proposed that over-expression of DNA repair genes enhances the invasive behaviour of tumour cells. In this study we present experimental evidence utilizing functional assays to test this hypothesis. We assessed the effect of the DNA repair proteins known as X-ray complementing protein 3 (XRCC3) and RAD51, to the invasive behavior of the MCF-7 luminal epithelial-like and BT20 basal-like triple negative human breast cancer cell lines. We report that stable or transient over-expression of XRCC3 but not RAD51 increased invasiveness in both cell lines in vitro. Moreover, XRCC3 over-expressing MCF-7 cells also showed a higher tumorigenesis in vivo and this phenotype was associated with increased activity of the metalloproteinase MMP-9 and the expression of known modulators of cell-cell adhesion and metastasis such as CD44, ID-1, DDR1 and TFF1. Our results suggest that in addition to its' role in facilitating repair of DNA damage, XRCC3 affects invasiveness of breast cancer cell lines and the expression of genes associated with cell adhesion and invasion

    Parallel Evolution of a Type IV Secretion System in Radiating Lineages of the Host-Restricted Bacterial Pathogen Bartonella

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    Adaptive radiation is the rapid origination of multiple species from a single ancestor as the result of concurrent adaptation to disparate environments. This fundamental evolutionary process is considered to be responsible for the genesis of a great portion of the diversity of life. Bacteria have evolved enormous biological diversity by exploiting an exceptional range of environments, yet diversification of bacteria via adaptive radiation has been documented in a few cases only and the underlying molecular mechanisms are largely unknown. Here we show a compelling example of adaptive radiation in pathogenic bacteria and reveal their genetic basis. Our evolutionary genomic analyses of the α-proteobacterial genus Bartonella uncover two parallel adaptive radiations within these host-restricted mammalian pathogens. We identify a horizontally-acquired protein secretion system, which has evolved to target specific bacterial effector proteins into host cells as the evolutionary key innovation triggering these parallel adaptive radiations. We show that the functional versatility and adaptive potential of the VirB type IV secretion system (T4SS), and thereby translocated Bartonella effector proteins (Beps), evolved in parallel in the two lineages prior to their radiations. Independent chromosomal fixation of the virB operon and consecutive rounds of lineage-specific bep gene duplications followed by their functional diversification characterize these parallel evolutionary trajectories. Whereas most Beps maintained their ancestral domain constitution, strikingly, a novel type of effector protein emerged convergently in both lineages. This resulted in similar arrays of host cell-targeted effector proteins in the two lineages of Bartonella as the basis of their independent radiation. The parallel molecular evolution of the VirB/Bep system displays a striking example of a key innovation involved in independent adaptive processes and the emergence of bacterial pathogens. Furthermore, our study highlights the remarkable evolvability of T4SSs and their effector proteins, explaining their broad application in bacterial interactions with the environment

    Metallogeny of a Pan-African oceanic arc: VHMS and gold deposits in the Ariab-Arbaat belt, Haya terrane, Red Sea Hills (Sudan)

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    International audienceIn the Neoproterozoic Arabo-Nubian Shield, the mined gold in the Ariab district (Red Sea Hills, Sudan) is in gossans reconcentrating primary gold overprinted over volcanogenic massive sulphide (VHMS) deposits, formed in the context of a Tonian ensimatic arc of the Haiya terrane. All the primary gold occurrences of the Ariab belt, whatever their style (VHMS-, quartz lode- or shear-zone-hosted), appear to have been syn-to late-kinematic, i.e., formed in the context of the final Pan-African collision leading to the Arabian-Nubian Shield (D3 event). Gold concentration occurs as native gold or electrum deposited in late (syn- to post-metamorphic) tectonic features, usually in sets of (micro)cracks, mostly within earlier pyrite or arsenopyrite. It is associated with either galena or bismuth tellurides. Gold deposition occurred in relation to an intense fluid circulation of metamorphic CO2-H2O rich fluids, which underwent significant strong decompression from lithostatic to hydrostatic pressures. Decompression and temperature decrease and dilution are probably at the origin of gold deposition, although no clear evidence of unmixing of the volatile was observed. The late-D3 gold event in the Ariab belt has all the makings of an orogenic gold system, notably similar to the Late Carboniferous gold event in the West European Variscan belt. Thus, it is possible to propose that, at the end of the collision events, fluids released from the newly formed terrane root were channelled towards the upper crust through the major D3 shear zones (the Oko shear zone for the Ariab belt). The fluids outpouring from these major drains were then conveyed through fault plays and damaged zones, up to specific chemical traps within massive sulphide ore bodies or quartz veins systems. Thus, the Ariab gold district could be classified as a representative of the class of orogenic gold deposits
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