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

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

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

Amerind Ancestry, Socioeconomic Status and the Genetics of Type 2 Diabetes in a Colombian Population

The “thrifty genotype” hypothesis proposes that the high prevalence of type 2 diabetes (T2D) in Native Americans and admixed Latin Americans has a genetic basis and reflects an evolutionary adaptation to a past low calorie/high exercise lifestyle. However, identification of the gene variants underpinning this hypothesis remains elusive. Here we assessed the role of Native American ancestry, socioeconomic status (SES) and 21 candidate gene loci in susceptibility to T2D in a sample of 876 T2D cases and 399 controls from Antioquia (Colombia). Although mean Native American ancestry is significantly higher in T2D cases than in controls (32% v 29%), this difference is confounded by the correlation of ancestry with SES, which is a stronger predictor of disease status. Nominally significant association (P<0.05) was observed for markers in: TCF7L2, RBMS1, CDKAL1, ZNF239, KCNQ1 and TCF1 and a significant bias (P<0.05) towards OR>1 was observed for markers selected from previous T2D genome-wide association studies, consistent with a role for Old World variants in susceptibility to T2D in Latin Americans. No association was found to the only known Native American-specific gene variant previously associated with T2D in a Mexican sample (rs9282541 in ABCA1). An admixture mapping scan with 1,536 ancestry informative markers (AIMs) did not identify genome regions with significant deviation of ancestry in Antioquia. Exclusion analysis indicates that this scan rules out ∼95% of the genome as harboring loci with ancestry risk ratios >1.22 (at P < 0.05)

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

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

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

Phase separation and fluid mixing in subseafioor back arc hydrothermal systems: A microthermometric and oxygen isotope study of fluid inclusions in the barite-sulfide chimneys of the Lau basin

International audienceFluid inclusions in barite and sulfide in chimneys (both active and inactive) from three hydrothermal sites of the back arc Lau basin were studied with microthermometric and isotopic methods to determine the chemistry and evolution of hydrothermal aqueous fluids. Strontium isotope compositions of sulfides from the Lau basin reflect the presence of anhydrite and barite inclusions. The 87Sr/86Sr ratios of these two sulfate minerals vary from 0.7045 to 0.7078 and are interpreted as the result of mixing between various proportions of the hydrothermal end-member and pure seawater. The microthermometric study of fluid inclusions reveals that mixing with seawater involved different kinds of aqueous fluid end-members. A high-temperature Mg-depleted end-member of high salinity (>5.5 wt % eq NaC1) was found at the Vai Lili site. A uncommon low-temperature Mg-rich end-member was also identified at the Hine Hina site in association with barite deposition. At the Vai Lili site, very low salinity fluids were produced in addition to a very saline brine (>30 wt % NaC1) that was trapped inside anhydrite precipitated from an active vent at a temperature o[ 342øC. Oxygen isotope ratios of water inclusions range from 2%0 to 4.4%0 for chalcopyrite, barite, and sphalerite minerals. The 180 enrichment and the high salinities of many fluids from the Lau basin are accounted for by the specificity of the back arc setting. This non mid-ocean ridge setting is characterized by the shallow depth of the hydrothermal systems that allows frequent unmixing of high-temperature liquids. The abundance of silicic magmas also provided magmatic fluids (including brines) that mixed with seawater-derived aqueous fluids

Phase separation and fluid mixing in subseafioor back arc hydrothermal systems: A microthermometric and oxygen isotope study of fluid inclusions in the barite-sulfide chimneys of the Lau basin

International audienceFluid inclusions in barite and sulfide in chimneys (both active and inactive) from three hydrothermal sites of the back arc Lau basin were studied with microthermometric and isotopic methods to determine the chemistry and evolution of hydrothermal aqueous fluids. Strontium isotope compositions of sulfides from the Lau basin reflect the presence of anhydrite and barite inclusions. The 87Sr/86Sr ratios of these two sulfate minerals vary from 0.7045 to 0.7078 and are interpreted as the result of mixing between various proportions of the hydrothermal end-member and pure seawater. The microthermometric study of fluid inclusions reveals that mixing with seawater involved different kinds of aqueous fluid end-members. A high-temperature Mg-depleted end-member of high salinity (>5.5 wt % eq NaC1) was found at the Vai Lili site. A uncommon low-temperature Mg-rich end-member was also identified at the Hine Hina site in association with barite deposition. At the Vai Lili site, very low salinity fluids were produced in addition to a very saline brine (>30 wt % NaC1) that was trapped inside anhydrite precipitated from an active vent at a temperature o[ 342øC. Oxygen isotope ratios of water inclusions range from 2%0 to 4.4%0 for chalcopyrite, barite, and sphalerite minerals. The 180 enrichment and the high salinities of many fluids from the Lau basin are accounted for by the specificity of the back arc setting. This non mid-ocean ridge setting is characterized by the shallow depth of the hydrothermal systems that allows frequent unmixing of high-temperature liquids. The abundance of silicic magmas also provided magmatic fluids (including brines) that mixed with seawater-derived aqueous fluids

Phase separation and fluid mixing in subseafioor back arc hydrothermal systems: A microthermometric and oxygen isotope study of fluid inclusions in the barite-sulfide chimneys of the Lau basin

International audienceFluid inclusions in barite and sulfide in chimneys (both active and inactive) from three hydrothermal sites of the back arc Lau basin were studied with microthermometric and isotopic methods to determine the chemistry and evolution of hydrothermal aqueous fluids. Strontium isotope compositions of sulfides from the Lau basin reflect the presence of anhydrite and barite inclusions. The 87Sr/86Sr ratios of these two sulfate minerals vary from 0.7045 to 0.7078 and are interpreted as the result of mixing between various proportions of the hydrothermal end-member and pure seawater. The microthermometric study of fluid inclusions reveals that mixing with seawater involved different kinds of aqueous fluid end-members. A high-temperature Mg-depleted end-member of high salinity (>5.5 wt % eq NaC1) was found at the Vai Lili site. A uncommon low-temperature Mg-rich end-member was also identified at the Hine Hina site in association with barite deposition. At the Vai Lili site, very low salinity fluids were produced in addition to a very saline brine (>30 wt % NaC1) that was trapped inside anhydrite precipitated from an active vent at a temperature o[ 342øC. Oxygen isotope ratios of water inclusions range from 2%0 to 4.4%0 for chalcopyrite, barite, and sphalerite minerals. The 180 enrichment and the high salinities of many fluids from the Lau basin are accounted for by the specificity of the back arc setting. This non mid-ocean ridge setting is characterized by the shallow depth of the hydrothermal systems that allows frequent unmixing of high-temperature liquids. The abundance of silicic magmas also provided magmatic fluids (including brines) that mixed with seawater-derived aqueous fluids