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

Epitelizacija i kontrakcija rane nakon biopsije kože u kunića: matematički model zaraštavanja i remodelirajući indeksi

The objective of this study was to develop a standard operating procedure for the analysis of skin wound healing using histomorphometrical measurements and mathematical data analyses. The mathematical model is derived from observations of normal cutaneous healing in the rabbit. It is designed to allow a simple scoring of the major steps of healing and remodelling. Full-thickness punch biopsies were performed on the skin of the back of New Zealand-white rabbits and healing was analyzed by histopathological examination after 2, 5, 9 and 14 days, using different staining techniques. Histomorphological measurements were also made. The thickness of the epidermis and neo-epidermis were compared. Several indices relative to wound severity and contraction were computed in an attempt to defi ne a global healing index. A remodelling index was calculated based on a colorimetric analysis with Mallory Trichrome staining and hair migration. The changes in indeks values seemed to correlate with the histopathological analysis. No material flaws appeared when this model was applied to the natural healing process. This model was developed for scoring and accurate comparative evaluation of the effects of various treatments, biomaterials or pharmacological preparations on soft tissue healing and remodelling in rabbits. Although the healing of cutaneous wounds in rabbits differs from that in humans, this model may still be relevant for screening new wound healing preparations.Cilj ovog istraživanja je razvijanje osnovne metode za analizu zaraštavanja kože služeći se histomorfometrijskim mjerenjima i matematičkom analizom podataka. Matematički je model nastao promatranjem fi ziološkoga zarastanja kože u kunića. Model je razvijen za jednostavno mjerenje osnovnih faza zarastanja i remodeliranja rane. Potpuna biopsija kože provedena je na leđnoj koži novozelandskih bijelih kunića te je analiza zarastanja promatrana histopatološki nakon drugoga, petoga, devetoga i četrnaestoga dana rabeći različite metode bojenja. Također su izvršena histomorfološka mjerenja. Uspoređene su vrijednosti debljine fi ziološkoga i novonastaloga epidermisa. Nekoliko indeksa povezanih sa zarastanjem i kontrakcijom kože pribrajani su s pokušajem utvrđivanja potpunoga indeksa zaraštavanja. Kolometrijska analiza s Mallory trichrome bojenjem korištena je za izračun remodelirajućega indeksa i promatranja migracije dlačnoga folikula. Promjene u vrijednosti indeksa mogu se povezati s histopatološkom analizom. Prirodni proces zarastanja promatran je bez utjecaja čimbenika koji mogu doprinijeti ishodu samoga zarastanja. Taj je model razvijen kako bi se moglo promatrati i uspoređivati različita liječenja, biomaterijali i farmakološki pripravci za zarastanje i remodeliranje mekoga tkiva u kunića. Unatoč razlici u zarastanju kože kunića i čovjeka, ovaj model može biti koristan za promatranje novih pripravaka za zaraštavanje rana

Reposicionamiento de drogas efectos de la combinación de metformina y propanolol sobre modelos de cáncer colorrectal

El reposicionamiento de drogas en oncología se refiere al uso de fármacos originalmente formulados para otras indicaciones que mostraron potencial antitumoral. En este trabajo, se seleccionó un grupo de drogas en reposicionamiento que incluyen metformina (M, utilizada en el tratamiento de la diabetes), propranolol (P, indicado para tratar la hipertensión), cloroquina (CQ, se usa en el tratamiento o prevención de la malaria), DHEA (un precursor de hormonas sexuales), orlistat (empleado en el tratamiento de la obesidad), atorvastatina (utilizado para tratar niveles altos de colesterol) y dicloroacetato (un inhibidor de la piruvato deshidrogenasa cinasa). El potencial antitumoral de estos fármacos se evaluó in vitro en células de cáncer de colon humano HCT116 y HT29 a través de ensayos de viabilidad estándar, individualmente o de forma combinada. Todos los fármacos probados inhibieron significativamente la proliferación de células HCT116 y HT29 de una manera dependiente de la dosis. De las combinaciones probadas, M+P resultó la más atractiva en ambas líneas celulares, ya que mostró una fuerte inhibición del crecimiento incluso combinando dosis bajas de ambos fármacos (P <0,001). Adicionalmente, el tratamiento mostro efectos significativos tanto sobre la capacidad migratoria celular, aumentando el número de adhesiones focales en células tratadas, como en los niveles de apoptosis que también se vieron incrementados por el tratamiento. Los datos preliminares de un modelo in vivo con ratones BALB/c bajo un protocolo de carcinogénesis estándar de azoximetano (carcinógeno iniciador)/sulfato de dextrano (agente promotor) indicaron un beneficio potencial de la combinación M+P en la prevención del desarrollo de tumores de colon, sin síntomas asociados de toxicidad. A través de la tinción inmunohistoquímica para el antígeno Ki67 se detectó un menor número de células proliferativas en tumores tratados, lo que confirmó el efecto del tratamiento in vivo. En conjunto, nuestros resultados sugieren que la terapia con medicamentos reposicionados podría ser de interés para el tratamiento del cáncer de colon y, en particular, la combinación de M+P podría inhibir su desarrollo y potencialmente el desarrollo de metástasisFil: Anselmino L.E.. Universidad Nacional de RosarioFil: Baglioni M.V.. Universidad Nacional de RosarioFil: Rico M.J.. Universidad Nacional de RosarioFil: Rozados V.R.. Universidad Nacional de RosarioFil: Scharovsky O.G.. Universidad Nacional de RosarioFil: Fernández C.O.. Universidad Nacional de RosarioFil: Martínez-Marignac V.. Universidad Nacional de RosarioFil: Menacho-Márquez M.. Universidad Nacional de Rosari

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

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

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)

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