Double-strand break repair processes drive evolution of the mitochondrial genome in Arabidopsis

<p>Abstract</p> <p>Background</p> <p>The mitochondrial genome of higher plants is unusually dynamic, with recombination and nonhomologous end-joining (NHEJ) activities producing variability in size and organization. Plant mitochondrial DNA also generally displays much lower nucleotide substitution rates than mammalian or yeast systems. Arabidopsis displays these features and expedites characterization of the mitochondrial recombination surveillance gene <it>MSH1 </it>(MutS 1 homolog), lending itself to detailed study of <it>de novo </it>mitochondrial genome activity. In the present study, we investigated the underlying basis for unusual plant features as they contribute to rapid mitochondrial genome evolution.</p> <p>Results</p> <p>We obtained evidence of double-strand break (DSB) repair, including NHEJ, sequence deletions and mitochondrial asymmetric recombination activity in Arabidopsis wild-type and <it>msh1 </it>mutants on the basis of data generated by Illumina deep sequencing and confirmed by DNA gel blot analysis. On a larger scale, with mitochondrial comparisons across 72 Arabidopsis ecotypes, similar evidence of DSB repair activity differentiated ecotypes. Forty-seven repeat pairs were active in DNA exchange in the <it>msh1 </it>mutant. Recombination sites showed asymmetrical DNA exchange within lengths of 50- to 556-bp sharing sequence identity as low as 85%. <it>De novo </it>asymmetrical recombination involved heteroduplex formation, gene conversion and mismatch repair activities. Substoichiometric shifting by asymmetrical exchange created the appearance of rapid sequence gain and loss in association with particular repeat classes.</p> <p>Conclusions</p> <p>Extensive mitochondrial genomic variation within a single plant species derives largely from DSB activity and its repair. Observed gene conversion and mismatch repair activity contribute to the low nucleotide substitution rates seen in these genomes. On a phenotypic level, these patterns of rearrangement likely contribute to the reproductive versatility of higher plants.</p

The covariation of acoustic features of infant cries and autonomic state

The evolution of the autonomic nervous system provides an organizing principle to interpret the adaptive significance of physiological systems in promoting social behavior and responding to social challenges. This phylogenetic shift in neural regulation of the autonomic nervous system in mammals has produced a neuroanatomically integrated social engagement system, including neural mechanisms that regulate both cardiac vagal tone and muscles involved in vocalization. Mammalian vocalizations are part of a conspecific social communication system, with several mammalian species modulating acoustic features of vocalizations to signal affective state. Prosody, defined by variations in rhythm and pitch, is a feature of mammalian vocalizations that communicate emotion and affective state. While the covariation between physiological state and the acoustic frequencies of vocalizations is neurophysiologically based, few studies have investigated the covariation between vocal prosody and autonomic state. In response to this paucity of scientific evidence, the current study explored the utility of vocal prosody as a sensitive index of autonomic activity in human infants during the Still Face challenge. Overall, significant correlations were observed between several acoustic features of the infant vocalizations and autonomic state, demonstrating an association between shorter heart period and reductions in heart period and respiratory sinus arrhythmia following the challenge with the dampening of the modulation of acoustic features (fundamental frequency, variance, 50% bandwidth, and duration) that are perceived as prosody

Acoustic features of prairie vole (Microtus ochrogaster) ultrasonic vocalizations covary with heart rate

Vocalizations serve as a conspecific social communication system among mammals. Modulation of acoustic features embedded within vocalizations is used by several mammalian species to signal whether it is safe or dangerous to approach conspecific and heterospecific mammals. As described by the Polyvagal Theory, the phylogenetic shift in the evolution of mammals involved an adaptive neuroanatomical link between the neural circuits regulating heart rate and the muscles involved in modulating the acoustic features of vocalizations. However, few studies have investigated the covariation between heart rate and the acoustic features of vocalizations. In the current study, we document that specific features of vocalizations covary with heart rate in a highly social and vocal mammal, the prairie vole (Microtus ochrogaster). Findings with the prairie vole illustrate that higher pitch (i.e., fundamental frequency) and less variability in acoustic features of vocalizations (i.e., less vocal prosody) are associated with elevated heart rate. The study provides the first documentation that the acoustic features of prairie vole vocalizations may function as a surrogate index of heart rate

Equality, Equity, and Diversity: Educational Solutions in the Basque Country

Public education is one of the greatest achievements of European countries during the twentieth century. While schooling systems neither exclusively form citizens, nor are they sufficient to alleviate all inequalities, education plays an increasingly important strategic role in relieving social problems and promoting the civic and ethical upbringing of our children. Researchers and professors at the UPV/EHU have had the privilege to design and implement important educational projects in conjunction with government of Autonomous Community of the Basque Country, which has the authority over education in its territory. This book presents the timely (in most cases since 2000) observations, research, and programs that have resulted from this cooperation. Our stress—in both our theoretical and analytical dimensions—has been on the importance of diversity, the promotion of social and human values, and respect for basic human rights. In addition, we describe the cooperation that must be fostered—and the various needs met—between all educational "agents": academic researchers, administrators, teachers, parents, and the community at large to promote equality and fairness in our society.This book was published with generous financial support from the Basque Government.Introduction: Alfonso Unceta and Concepción Medrano ? Part 1 Education in the Basque Country ? 1. Education Provision in the Basque Country by Alfonso Unceta and Andrés Davila ? 2. Addressing Basque Diversity in the Classroom: Measures to Avoid Excluding At-Risk Youth by Begoña Martínez Domínguez ? 3. Improving Social Interaction: Experimentally Validated Proposals for Psycho-educational Intervention by Maite Garaigodobil and Jone Aliri ? 4. Socialization to Prevent Gender Violence in the Basque Country by Maria José Alonso Olea, Aitor Gómez González, and Nekane Beloki Arizti ? 5. Resolution and Transformation of At-School Conflicts by Ramón Alzate Sáez de Heredia, Lucía Gorbeña, and Cristina Merino ? Part 2 Socioeducational Context in the Basque Country ? 6. Learning Communities: A Basque Egalitarian Educational Project by Maite Arandia Loroño, Isabel Martínez Domínguez, and Iñaki Santa Cruz Ayo ? 7. Migrants en Route: Community Socioeducational Action by Miguel Arriaga Landeta and Begoña Abad Miguélez ? 8. Educating from the Family: A Proposal to Connect Homes and Institutions by Enrique Arranz Freijo, Fernando Olabarrieta Artetxe, Juan Luis Martín Ayala ? 9. The Development of Values and the Media by Concepción Medrano, Ana Aierbe, and Juan Ignacio Martínez de Morentin ? Index ? List of Contributor

Regional and large-scale patterns in Amazon forest structure and function are mediated by variations in soil physical and chemical properties

Forest structure and dynamics have been noted to vary across the Amazon Basin in an east-west gradient in a pattern which coincides with variations in soil fertility and geology. This has resulted in the hypothesis that soil fertility may play an important role in explaining Basin-wide variations in forest biomass, growth and stem turnover rates. To test this hypothesis and assess the importance of edaphic properties in affect forest structure and dynamics, soil and plant samples were collected in a total of 59 different forest plots across the Amazon Basin. Samples were analysed for exchangeable cations, C, N, pH with various Pfractions also determined. Physical properties were also examined and an index of soil physical quality developed. Overall, forest structure and dynamics were found to be strongly and quantitatively related to edaphic conditions. Tree turnover rates emerged to be mostly influenced by soil physical properties whereas forest growth rates were mainly related to a measure of available soil phosphorus, although also dependent on rainfall amount and distribution. On the other hand, large scale variations in forest biomass could not be explained by any of the edaphic properties measured, nor by variation in climate. A new hypothesis of self-maintaining forest dynamic feedback mechanisms initiated by edaphic conditions is proposed. It is further suggested that this is a major factor determining forest disturbance levels, species composition and forest productivity on a Basin wide scale

Non-productive angiogenesis disassembles Aß plaque-associated blood vessels

The human Alzheimer’s disease (AD) brain accumulates angiogenic markers but paradoxically, the cerebral microvasculature is reduced around Aß plaques. Here we demonstrate that angiogenesis is started near Aß plaques in both AD mouse models and human AD samples. However, endothelial cells express the molecular signature of non-productive angiogenesis (NPA) and accumulate, around Aß plaques, a tip cell marker and IB4 reactive vascular anomalies with reduced NOTCH activity. Notably, NPA induction by endothelial loss of presenilin, whose mutations cause familial AD and which activity has been shown to decrease with age, produced a similar vascular phenotype in the absence of Aß pathology. We also show that Aß plaque-associated NPA locally disassembles blood vessels, leaving behind vascular scars, and that microglial phagocytosis contributes to the local loss of endothelial cells. These results define the role of NPA and microglia in local blood vessel disassembly and highlight the vascular component of presenilin loss of function in AD

Genetic data: The new challenge of personalized medicine, insights for rheumatoid arthritis patients

Rapid advances in genotyping technology, analytical methods, and the establishment of large cohorts for population genetic studies have resulted in a large new body of information about the genetic basis of human rheumatoid arthritis (RA). Improved understanding of the root pathogenesis of the disease holds the promise of improved diagnostic and prognostic tools based upon this information. In this review, we summarize the nature of new genetic findings in human RA, including susceptibility loci and gene-gene and gene-environment interactions, as well as genetic loci associated with sub-groups of patients and those associated with response to therapy. Possible uses of these data are discussed, such as prediction of disease risk as well as personalized therapy and prediction of therapeutic response and risk of adverse events. While these applications are largely not refined to the point of clinical utility in RA, it seems likely that multi-parameter datasets including genetic, clinical, and biomarker data will be employed in the future care of RA patients

2 nd Brazilian Consensus on Chagas Disease, 2015

Abstract Chagas disease is a neglected chronic condition with a high burden of morbidity and mortality. It has considerable psychological, social, and economic impacts. The disease represents a significant public health issue in Brazil, with different regional patterns. This document presents the evidence that resulted in the Brazilian Consensus on Chagas Disease. The objective was to review and standardize strategies for diagnosis, treatment, prevention, and control of Chagas disease in the country, based on the available scientific evidence. The consensus is based on the articulation and strategic contribution of renowned Brazilian experts with knowledge and experience on various aspects of the disease. It is the result of a close collaboration between the Brazilian Society of Tropical Medicine and the Ministry of Health. It is hoped that this document will strengthen the development of integrated actions against Chagas disease in the country, focusing on epidemiology, management, comprehensive care (including families and communities), communication, information, education, and research

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P &lt;.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes