DNA resection in eukaryotes: deciding how to fix the break

DNA double-strand breaks are repaired by different mechanisms, including homologous recombination and nonhomologous end-joining. DNA-end resection, the first step in recombination, is a key step that contributes to the choice of DSB repair. Resection, an evolutionarily conserved process that generates single-stranded DNA, is linked to checkpoint activation and is critical for survival. Failure to regulate and execute this process results in defective recombination and can contribute to human disease. Here, I review recent findings on the mechanisms of resection in eukaryotes, from yeast to vertebrates, provide insights into the regulatory strategies that control it, and highlight the consequences of both its impairment and its deregulation

Improving mental and neurological health research in Latin America: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Research evidence is essential to inform policies, interventions and programs, and yet research activities in mental and neurological (MN) health have been largely neglected, particularly in low- and middle-income countries. Many challenges have been identified in the production and utilization of research evidence in Latin American countries, and more work is needed to overcome this disadvantageous situation. This study aims to address the situation by identifying initiatives that could improve MN health research activities and implementation of their results in the Latin American region.</p> <p>Methods</p> <p>Thirty-four MN health actors from 13 Latin American countries were interviewed as part of an initiative by the Global Forum for Health Research and the World Health Organization to explore the status of MN health research in low- and middle-income countries in Africa, Asia and Latin-America.</p> <p>Results</p> <p>A variety of recommendations to increase MN health research activities and implementation of their results emerged in the interviews. These included increasing skilled human resources in MN health interventions and research, fostering greater participation of stakeholders in the generation of research topics and projects, and engendering the interest of national and international institutions in important MN health issues and research methodologies. In the view of most participants, government agencies should strive to have research results inform the decision-making process in which they are involved. Thus these agencies would play a key role in facilitating and funding research. Participants also pointed to the importance of academic recognition and financial rewards in attracting professionals to primary and translational research in MN health. In addition, they suggested that institutions should create intramural resources to provide researchers with technical support in designing, carrying out and disseminating research, including resources to improve scientific writing skills.</p> <p>Conclusion</p> <p>Fulfillment of these recommendations would increase research production in MN health in Latin American countries. This, in turn, will raise the profile of these health problems, and consequently will underscore the need of continued high-quality and relevant research, thus fostering a virtuous cycle in the decision-making process to improve MN health care.</p

Incidence of traumatic brain injuries in head‐injured children with seizures

Objective: Incidence and short‐term outcomes of clinically important traumatic brain injury (ciTBI) in head‐injured children presenting to ED with post‐traumatic seizure (PTS) is not described in current literature. Methods: Planned secondary analysis of a prospective observational study undertaken in 10 Australasian Paediatric Research in Emergency Department International Collaborative (PREDICT) network EDs between 2011 and 2014 of head‐injured children 24 h (9 [2.7%] AR 2.5 [95% CI 0.8–4.2]) and neurosurgery (8 [2.4%] AR 2.0 [95% CI 0.4–3.7]), were higher than those without PTS. Children with PTS and GCS 15 or 14 had no neurosurgery, intubations or death, with two deaths in children with PTS and GCS ≤13. Conclusions: PTS was uncommon in head‐injured children presenting to the ED but associated with an increased risk of ciTBI in those with reduced GCS on arrival

All Effects of Psychophysical Variables on Color Attributes: A Classification System

This paper reports the research and structuring of a classification system for the effects of psychophysical variables on the color attributes. A basic role of color science is to psychophysically specify color appearance. An early stage is to specify the effects of the psychophysical variables (as singles, pairs, etc) on the color attributes (as singles, pairs, etc), for example to model color appearance. Current data on effects are often scarce or conflicting. Few effects are well understood, and the practice of naming effects after their discoverer(s) is inadequate and can be confusing. The number and types of possible effects have never been systematically analyzed and categorized. We propose a simple and rigorous system of classification including nomenclature. The total range of effects is computed from the possible combinations of three psychophysical variables (luminance, dominant wavelength, purity) and six color attributes (lightness, brightness, hue, chroma, colorfulness, saturation) in all modes of appearance. Omitting those effects that are normally impossible to perceive at any one time (such as four- or five-dimensional colors), the total number perceivable is 161 types of effects for all modes of appearance. The type of effect is named after the psychophysical stimulus (or stimuli) and the relevant color attribute(s), e.g., Luminance-on-hue effect (traditionally known as Bezold-Brucke effect). Each type of effect may include slightly different effects with infinite variations depending on experimental parameters.M. Melgosa was supported by the Ministry of Economy and Competitiveness of the Government of Spain, research project FIS2013-40661-P, with the European Research Development Fund

Emilin1 gene and essential hypertension: a two-stage association study in northern Han Chinese population

<p>Abstract</p> <p>Background</p> <p>Elastogenesis of elastic extracellular matrix (ECM) which was recognized as a major component of blood vessels has been believed for a long time to play only a passive role in the dynamic vascular changes of typical hypertension. Emilin1 gene participated in the transcription of ECM's formation and was recognized to modulate links TGF-β maturation to blood pressure homeostasis in animal study. Recently relevant advances urge further researches to investigate the role of Emilin1 gene in regulating TGF-β signals involved in elastogenesis and vascular cell defects of essential hypertension (EH).</p> <p>Methods</p> <p>We designed a two-stage case-control study and selected three single nucleotide polymorphisms (SNPs), rs3754734, rs2011616 and rs2304682 from the HapMap database, which covered Emilin1 gene. Totally 2,586 subjects were recruited from the International Collaborative Study of Cardiovascular Disease in Asia (InterASIA). In stage 1, all the three SNPs of the Emilin1 gene were genotyped and tested within a subsample including 503 cases and 490 controls, significant SNPs would enter into stage 2 including 814 cases with hypertension and 779 controls and analyze on the basis of testing total 2,586 subjects.</p> <p>Results</p> <p>In stage 1, single locus analyses showed that SNPs rs3754734 and rs2011616 had significant association with EH (P < 0.05). In stage 2, weak association for dominant model were observed by age stratification and odds ratio (ORs) of TG+GG vs. TT of rs3754734 were 0.768 (0.584-1.009), 0.985 (0.735-1.320) and 1.346 (1.003-1.806) in < 50, 50-59 and ≥ 60 years group and ORs of GA+AA vs. GG of rs2011616 were 0.745 (0.568-0.977), 1.013 (0.758-1.353) and 1.437 (1.072-1.926) in < 50, 50-59 and ≥ 60 years group respectively. Accordingly, significant interactions were detected between genotypes of rs3754734 and rs2011616 and age for EH, and ORs were 1.758 (1.180-2.620), P = 0.006 and 1.903 (1.281-2.825), P = 0.001, respectively. Results of haplotypes analysis showed that there weren't any haplotypes associated with EH directly, but the interaction of hap2 (GA) and age-group found to be significant after being adjusted for the covariates, OR was 1.220 (1.031-1.444), P value was 0.020.</p> <p>Conclusion</p> <p>Our findings don't support positive association of Emilin1 gene with EH, but the interaction of age and genotype variation of rs3754734 and rs2011616 might increase the risk to hypertension.</p