An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

Towards a usage-based model of early code-switching:evidence from three language pairs

Abstract Usage-based studies trace children’s early language back to slot-and-frame patterns which dominate spontaneous language use. We apply the Traceback method to data from three bilingual children with English as one of their languages and Polish, German, or Finnish as the other to examine what these children’s code-switching has in common and how it differs in light of the genealogical distance between the languages used. Their bilingual constructions are derived from individual corpora of naturalistic interactions of each child respectively and traced back to monolingual language produced previously to establish whether they are unprocessed chunks or partially schematic units. Based on this, we propose a model of switching which helps us to distinguish between the qualitative aspects of bilingual use in these two types of combinations. Our results show that all three children filter out some mixing occurring in chunks before these give basis to longer units. Whatever bilingual combinations remain frozen in those units can be explained by phonological overlap of the children’s two languages, which is highest in the acquisition of English-German due to their genealogical proximity

Proyecto Ecomed: formación especializada en bioingeniería del suelo y fluvial en el entorno mediterráneo

Soil and water bioengineering involves the use of living plants or cut plant material, either alone or in combination with inert structures, to control soil erosion and the mass movement. Soil bioengineering is such a method that is being more and more adopted within the Mediterranean ecoregion. Bioengineering works have a clear dynamic and changing nature. At the beginning, the initial necessary rigidity is offered by the inert material utilized in the work, As time progresses, the evolving vegetation takes over the stabilizing roles. These particularities influence the design protocols and routines of this type of works. The difficulties engaged when using soil bioengineering in Mediterranean ecoregion requires a highly specialized knowledge triangle within the sector. The Ecomed Erasmus + project gives answer to this situation by including, as one of its main outputs, the development of a specialized modular training programme in soil and water bioengineering in the Mediterranean ecoregion.La bioingeniería del suelo y fluvial son un conjunto de técnicas basadas en la naturaleza (NBSs) cuyo objetivo es la mejora de la resiliencia de espacios con problemas de estabilidad y/o erosión. Estas técnicas están ganando fuerza dentro de las regiones mediterráneas. Las obras de bioingeniería tienen una naturaleza dinámica. Al principio, la necesaria rigidez inicial se desarrolla a través de los materiales inertes utilizados en la obra. Con el paso del tiempo, la vegetación desarrolla el efecto de refuerzo necesario y sustituye a los anteriores elementos en su función estabilizadora. Esta particularidad afecta a los protocolos y metodologías de cálculo de este tipo de obras. Los trabajos de seguimiento de la evolución de la intervención son esenciales para generar retroalimentaciones que permitan mejorar y calibrar los diseños de este tipo de obras. Las dificultades que afrontan este tipo de trabajos en un clima mediterráneo requieren un triángulo de conocimiento altamente especializado (nuevos procesos, métodos y servicios) dentro del sector. Teniendo en cuenta todo lo anterior, el Proyecto Europeo ECOMED (ERASMUS +) tiene, como uno de sus objetivos principales, generar para 2018 un programa de aprendizaje teórico-práctico específico y esencial para la especialización del sector de la bioingeniería mediterránea

DLC-treated aramid-fibre composites

This work aims to quantify the effect of a diamond-like carbon coating (DLC) treatment of aramid fibres and to reveal the conversion of a fibre-level performance leap on the macroscale mechanical behaviour. The DLC-based coating is applied directly to the reinforcement and laminates are infused with an epoxy matrix. After characterisation of the coated surfaces, the performance of the composite is analysed via interlaminar shear testing, fatigue testing and damage tolerance testing, microbond tests, and 3D finite element simulation using a cohesive zone model of the interface. The results show that the coating treatment improves the fatigue life and the S-N curve slope for the laminates, while the residual strength after impact damage and environmental conditioning (water immersion at 60 °C) remains high. The scaling factor to convert the performance on macroscale was determined to be 0.17–0.39 for the DLC-based fibre treatment.Peer reviewe