Association of single nucleotide polymorphisms in Pre-miR-27a, Pre-miR-196a2, Pre-miR-423, miR-608 and Pre-miR-618 with breast cancer susceptibility in a South American population

Indexación: Web of ScienceBackground MicroRNAs (miRNAs) are a novel class of endogenous, non-coding, single-stranded RNAs capable of regulating gene expression by suppressing translation or degrading mRNAs. Single nucleotide polymorphisms (SNP) can alter miRNA expression, resulting in diverse functional consequences. Previous studies have examined the association of miRNA SNPs with breast cancer (BC) susceptibility. The contribution of miRNA gene variants to BC susceptibility in South American women had been unexplored. Our study evaluated the association of the SNPs rs895819 in pre-miR27a, rs11614913 in pre-miR-196a2, rs6505162 in pre-miR-423, rs4919510 in miR-608, and rs2682818 in pre-mir-618 with familial BC and early-onset non-familial BC in non-carriers of BRCA1/2 mutations from a South American population. Results We evaluated the association of five SNPs with BC risk in 440 cases and 807 controls. Our data do not support an association of rs11614913:C > T and rs4919510:C > G with BC risk. The rs6505162:C > A was significantly associated with increased risk of familial BC in persons with a strong family history of BC (OR = 1.7 [95 % CI 1.0–2.0] p = 0.05). The rs2682818:C > A genotype C/A is associated with an increased BC risk in non-familial early-onset BC. For the rs895819:A > G polymorphism, the genotype G/G is significantly associated with reduced BC risk in families with a moderate history of BC (OR = 0.3 [95 % CI 0.1–0.8] p = 0.01). Conclusions The contribution of variant miRNA genes to BC in South American women had been unexplored. Our findings support the following conclusions: a) rs6505162:C > A in pre-miR-423 increases risk of familial BC in families with a strong history of BC; b) the C/A genotype at rs2682818:C > A (pre-miR-618) increases BC risk in non-familial early-onset BC; and c) the G/G genotype at rs895819:A > G (miR-27a) reduces BC risk in families with a moderate history of BC.http://bmcgenet.biomedcentral.com/articles/10.1186/s12863-016-0415-

Mitochondrial Dysfunction Increases Oxidative Stress and Decreases Chronological Life Span in Fission Yeast

Background: Oxidative stress is a probable cause of aging and associated diseases. Reactive oxygen species (ROS) originate mainly from endogenous sources, namely the mitochondria. Methodology/Principal Findings: We analyzed the effect of aerobic metabolism on oxidative damage in Schizosaccharomyces pombe by global mapping of those genes that are required for growth on both respiratory-proficient media and hydrogen-peroxide-containing fermentable media. Out of a collection of approximately 2700 haploid yeast deletion mutants, 51 were sensitive to both conditions and 19 of these were related to mitochondrial function. Twelve deletion mutants lacked components of the electron transport chain. The growth defects of these mutants can be alleviated by the addition of antioxidants, which points to intrinsic oxidative stress as the origin of the phenotypes observed. These respiration-deficient mutants display elevated steady-state levels of ROS, probably due to enhanced electron leakage from their defective transport chains, which compromises the viability of chronologically-aged cells. Conclusion/Significance: Individual mitochondrial dysfunctions have often been described as the cause of diseases or aging, and our global characterization emphasizes the primacy of oxidative stress in the etiology of such processes.This work was supported by Dirección General de Investigación of Spain Grant BFU2006-02610, and by the Spanish program Consolider-Ingenio 2010 Grant CSD 2007-0020 to E.H

The Southern Wide-field Gamma-ray Observatory reach for Primordial Black Hole evaporation

The Southern Wide-field Gamma-ray Observatory (SWGO) is a proposed ground-based gamma-ray detector that will be located in the Southern Hemisphere and is currently in its design phase. In this contribution, we will outline the prospects for Galactic science with this Observatory. Particular focus will be given to the detectability of extended sources, such as gamma-ray halos around pulsars; optimisation of the angular resolution to mitigate source confusion between known TeV sources; and studies of the energy resolution and sensitivity required to study the spectral features of PeVatrons at the highest energies. Such a facility will ideally complement contemporaneous observatories in studies of high energy astrophysical processes in our Galaxy

Simulating the performance of the Southern Wide-view Gamma-ray Observatory

The Southern Wide-view Gamma-ray Observatory (SWGO) will be a next-generation gamma-ray observatory using a large array of particle detectors at a high elevation site in South America. This project is currently in a three years R&D phase in which the design will be optimised for cost and performance. Therefore it is crucial to efficiently evaluate the impact of different design options on the scientific objectives of the observatory. In this contribution, we will introduce the strategy and the simulation framework in which this evaluation takes place

Study of water Cherenkov detector designs for the SWGO experiment

The Southern Wide-field Gamma-ray Observatory (SWGO) is a next-generation ground-based gamma-ray detector under development to reach a full sky coverage together with the current HAWC and LHAASO experiments in the northern hemisphere. It will complement the observation of transient and variable multi-wavelength and multi-messenger phenomena, offering moreover the possibility to access the Galactic Centre. One of the possible SWGO configurations consists of an array of water Cherenkov tanks, with a high fill-factor inner array and a low-density outer array, covering an overall area of one order of magnitude larger than HAWC. To reach a high detection efficiency and discrimination capability between gamma-ray and hadronic air showers, various tank designs were studied. Double-layer tanks with several sizes, shapes and number of photomultiplier tubes have been considered. Single-particle simulations have been performed to study the tank response, using muons, electrons, and gamma-rays with energies typical of extensive air showers particles, entering the tanks with zenith angles from 0 to 60 degrees. The tank response was evaluated considering the particle detection efficiency, the number of photoelectrons produced by the photomultiplier tubes, and the time resolution of the measurement of the first photon. The study allowed to compare the performance of tanks with circular and square base, to understand which design optimizes the performance of the array. The method used in the study and the results will be discussed in this paper

Galactic Science with the Southern Wide-field Gamma-ray Observatory

The Southern Wide-field Gamma-ray Observatory (SWGO) is a proposed ground-based gamma-ray detector that will be located in the Southern Hemisphere and is currently in its design phase. In this contribution, we will outline the prospects for Galactic science with this Observatory. Particular focus will be given to the detectability of extended sources, such as gamma-ray halos around pulsars; optimisation of the angular resolution to mitigate source confusion between known TeV sources; and studies of the energy resolution and sensitivity required to study the spectral features of PeVatrons at the highest energies. Such a facility will ideally complement contemporaneous observatories in studies of high energy astrophysical processes in our Galaxy

Benchmarking the Science for the Southern Wide-Field Gamma-ray Observatory (SWGO)

The Southern Wide-field Gamma-ray Observatory (SWGO) is the project to build a new extensive air shower particle detector for the observation of very-high-energy gamma-rays in South America. SWGO is currently planned for installation in the Southern Hemisphere, which grants it a unique science potential among ground-based gamma-ray detectors. It will complement the capabilities of CTA, working as a wide-field instrument for the monitoring of transient and variable phenomena, and will expand the sky coverage of Northern Hemisphere facilities like HAWC and LHAASO, thus granting access to the entire Galactic Plane and the Galactic Center. SWGO aims to achieve excellent sensitivity over a very large target energy range from about 100 GeV to the PeV, and improve on the performance of current sampling array instruments in all observational parameters, including energy and angular resolution, background rejection, and single-muon detection capabilities. The directives for the final observatory design will be given by a number of key science goals which are being defined over the course of the Project’s R&D phase. In this contribution we will present the core science topics and target performance goals that serve as benchmarks to guide SWGO’s design configuration

Double-layered Water Cherenkov Detector for SWGO

The Southern Wide-field Gamma-ray Observatory (SWGO) will use the well-established and cost-effective technique of detecting Cherenkov light produced in water-filled detection units for TeV gamma-ray astronomy. Leveraging detector material reflectivity together with an optimised aspect ratio is an option to improve the performance of an array of such detector units. The double-layered Water Cherenkov Detector units comprise chambers with single photosensors in each. A reflective upper compartment enhances sensitivity to impinging secondary particles. A shallow lower compartment enables muon tagging and consequently improves the gamma hadron separation power of the observatory. Here we present detailed studies on the double-layered unit design

Dynamics of the Multiplicity of Cellular Infection in a Plant Virus

Recombination, complementation and competition profoundly influence virus evolution and epidemiology. Since viruses are intracellular parasites, the basic parameter determining the potential for such interactions is the multiplicity of cellular infection (cellular MOI), i.e. the number of viral genome units that effectively infect a cell. The cellular MOI values that prevail in host organisms have rarely been investigated, and whether they remain constant or change widely during host invasion is totally unknown. Here, we fill this experimental gap by presenting the first detailed analysis of the dynamics of the cellular MOI during colonization of a host plant by a virus. Our results reveal ample variations between different leaf levels during the course of infection, with values starting close to 2 and increasing up to 13 before decreasing to initial levels in the latest infection stages. By revealing wide dynamic changes throughout a single infection, we here illustrate the existence of complex scenarios where the opportunity for recombination, complementation and competition among viral genomes changes greatly at different infection phases and at different locations within a multi-cellular host