Context dependent substitution biases vary within the human genome

Background: Models of sequence evolution typically assume that different nucleotide positions evolve independently. This assumption is widely appreciated to be an over-simplification. The best known violations involve biases due to adjacent nucleotides. There have also been suggestions that biases exist at larger scales, however this possibility has not been systematically explored. Results: To address this we have developed a method which identifies over- and under-represented substitution patterns and assesses their overall impact on the evolution of genome composition. Our method is designed to account for biases at smaller pattern sizes, removing their effects. We used this method to investigate context bias in the human lineage after the divergence from chimpanzee. We examined bias effects in substitution patterns between 2 and 5 bp long and found significant effects at all sizes. This included some individual three and four base pair patterns with relatively large biases. We also found that bias effects vary across the genome, differing between transposons and non-transposons, between different classes of transposons, and also near and far from genes. Conclusions: We found that nucleotides beyond the immediately adjacent one are responsible for substantial context effects, and that these biases vary across the genome

Growth Endocrine Axis and Bovine Chromosome 5: Association of SNP Genotypes and Reproductive Phenotypes in an Angus, Brahman and Romosinuano Diallele

The growth endocrine axis influences reproduction. A QTL associated with enhanced ovulation exists on chromosome 5 in cattle and there are 6 genes underlying this region involved in the mechanisms of GH action. Resequencing exons, 5’ and 3’ untranslated regions and conserved non-coding regions of these genes in a multibreed resource population revealed 75 SNP usable for genotype to phenotype association studies. In the current study, phenotypes included age at first calving, calving interval, days to calving, and pregnancy rate. Data were collected from developing heifers (n = 650) of a diallele composed of Angus, Brahman, and Romosinuano breeds. A SNP in the promoter of the signal transducer and activator of transcription (STAT)2 gene, which is a second messenger of GH, had minor allele frequency \u3e 10% across the three breeds. This SNP did not deviate from Hardy- Weinberg equilibrium (X2 = 1.00, P \u3e 0.31), so deemed useful for genotype to phenotype association analyses. Since the remaining SNP appeared to predict breed, they were used to correct for population stratification using STRUCTURE, which revealed three distinctive ancestral clusters. No significant association was detected between the STAT2 genotype and reproductive traits in mixed effects analyses using genotype as a fixed term, sire as a random term, and coefficient of ancestry as a covariate; however, the interaction of SNP genotype and ancestral cluster was associated with the traits days to calving (P \u3c 0.05) and calving interval (P \u3c 0.10). Interaction plots revealed a higher estimated effect of heterozygous genotype in cluster 1 (inferred primarily from Brahman) and lower estimates in clusters 2 and 3 (inferred primarily from Bos taurus). The heterozygous genotype extended these trait levels ~100 d. A SNP in the promoter of the STAT2 gene was associated with fertility trait levels in admixed cows of the breeds Angus, Brahman, and Romosinuano. The effect appeared to be a non-additive genetic relationship as heterozygous genotype extended levels of traits indicative of postpartum rebreeding

The Pioneer Anomaly

Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit

Expression of a Serine Protease Gene prC Is Up-Regulated by Oxidative Stress in the Fungus Clonostachys rosea: Implications for Fungal Survival

BACKGROUND: Soil fungi face a variety of environmental stresses such as UV light, high temperature, and heavy metals. Adaptation of gene expression through transcriptional regulation is a key mechanism in fungal response to environmental stress. In Saccharomyces cerevisiae, the transcription factors Msn2/4 induce stress-mediated gene expression by binding to the stress response element. Previous studies have demonstrated that the expression of extracellular proteases is up-regulated in response to heat shock in fungi. However, the physiological significance of regulation of these extracellular proteases by heat shock remains unclear. The nematophagous fungus Clonostachys rosea can secret an extracellular serine protease PrC during the infection of nematodes. Since the promoter of prC has three copies of the stress response element, we investigated the effect of environmental stress on the expression of prC. METHODOLOGY/PRINCIPAL FINDINGS: Our results demonstrated that the expression of prC was up-regulated by oxidants (H(2)O(2) or menadione) and heat shock, most likely through the stress response element. After oxidant treatment or heat shock, the germination of conidia in the wild type strain was significantly higher than that in the prC mutant strain in the presence of nematode cuticle. Interestingly, the addition of nematode cuticle significantly attenuated the production of reactive oxygen species (ROS) induced by oxidants and heat shock in the wild type strain, but not in prC mutant strain. Moreover, low molecule weight (<3 kD) degradation products of nematode cuticle suppressed the inhibitory effect of conidial germination induced by oxidants and heat shock. CONCLUSIONS/SIGNIFICANCE: These results indicate that PrC plays a protective role in oxidative stress in C. rosea. PrC degrades the nematode cuticle to produce degradation products, which in turn offer a protective effect against oxidative stress by scavenging ROS. Our study reveals a novel strategy for fungi to adapt to environmental stress

Soil bacterial and fungal communities across a pH gradient in an arable soil

Soils collected across a long-term liming experiment (pH 4.0-8.3), in which variation in factors other than pH have been minimized, were used to investigate the direct influence of pH on the abundance and composition of the two major soil microbial taxa, fungi and bacteria. We hypothesized that bacterial communities would be more strongly influenced by pH than fungal communities. To determine the relative abundance of bacteria and fungi, we used quantitative PCR (qPCR), and to analyze the composition and diversity of the bacterial and fungal communities, we used a bar-coded pyrosequencing technique. Both the relative abundance and diversity of bacteria were positively related to pH, the latter nearly doubling between pH 4 and 8. In contrast, the relative abundance of fungi was unaffected by pH and fungal diversity was only weakly related with pH. The composition of the bacterial communities was closely defined by soil pH; there was as much variability in bacterial community composition across the 180-m distance of this liming experiment as across soils collected from a wide range of biomes in North and South America, emphasizing the dominance of pH in structuring bacterial communities. The apparent direct influence of pH on bacterial community composition is probably due to the narrow pH ranges for optimal growth of bacteria. Fungal community composition was less strongly affected by pH, which is consistent with pure culture studies, demonstrating that fungi generally exhibit wider pH ranges for optimal growth. The ISME Journal (2010) 4, 1340-1351; doi: 10.1038/ismej.2010.58; published online 6 May 2010&nbsp

La educación inclusiva frente a las desigualdades sociales: un estado de la cuestion y algunas reflexiones geograficas

Este artículo establece un estado de la cuestión e la educación inclusiva en el mundo y sugiere algunas reflexiones al respecto. El primer apartado recuerda las conexiones ineludibles entre las preocupaciones educativas por la educación inclusiva y las preocupaciones más generales por la desigualdad. El segundo consigna los criterios de búsqueda de las publicaciones académicas, y observa dos grandes temas en sus contenidos: sobre todo, el cambio interno de las escuelas atrae las miradas, pero en segundo plano también el entorno territorial despierta algunas inquietudes. El tercero anota los criterios de búsqueda de la documentación del Banco Mundial, la OCDE y la UNESCO. En este ámbito los simposios de la Oficina Internacional de la Educación de UNESCO revelan una interpretación dispar, aunque convergente, del concepto de educación inclusiva en las distintas regiones mundiales. Asimismo, todas las publicaciones oficiales muestran una atención prioritaria a las dinámicas internas de las escuelas, puesto que apenas algunas esbozan ciertas relaciones entre la educación inclusiva y las políticas públicas. El último apartado adelanta varios argumentos a favor de una mayor consideración de las escalas local y estatal de la educación inclusiva. Las principales razones para atender a la dimensión local provienen de la causalidad acumulativa de las privaciones sociales, de la necesidad de articular la acción de las escuelas y de la posibilidad de abrir un espacio significativo para la participación ciudadana. Asimismo, las principales razones para atender a la dimensión estatal surgen de las posibles sinergias entre la educación inclusiva y la expansión educativa (p. ej. ¿es correlativo el avance de la escolarización en los distintos ciclos escolares?) como también entre la educación inclusiva y la protección social (p. ej. ¿tienen una implicación pedagógica consistente las abundantes condiciones educativas de las transferencias sociales?

Mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia calcification

Familial idiopathic basal ganglia calcification (IBGC) or Fahr's disease is a rare neurodegenerative disorder characterized by calcium deposits in the basal ganglia and other brain regions, which is associated with neuropsychiatric and motor symptoms. Familial IBGC is genetically heterogeneous and typically transmitted in an autosomal dominant fashion. We performed a mutational analysis of SLC20A2, the first gene found to cause IBGC, to assess its genetic contribution to familial IBGC. We recruited 218 subjects from 29 IBGC-affected families of varied ancestry and collected medical history, neurological exam, and head CT scans to characterize each patient's disease status. We screened our patient cohort for mutations in SLC20A2. Twelve novel (nonsense, deletions, missense, and splice site) potentially pathogenic variants, one synonymous variant, and one previously reported mutation were identified in 13 families. Variants predicted to be deleterious cosegregated with disease in five families. Three families showed nonsegregation with clinical disease of such variants, but retrospective review of clinical and neuroimaging data strongly suggested previous misclassification. Overall, mutations in SLC20A2 account for as many as 41 % of our familial IBGC cases. Our screen in a large series expands the catalog of SLC20A2 mutations identified to date and demonstrates that mutations in SLC20A2 are a major cause of familial IBGC. Non-perfect segregation patterns of predicted deleterious variants highlight the challenges of phenotypic assessment in this condition with highly variable clinical presentation

A reflective perspective on the challenges facing research-led teaching in the performing and creative arts

This article provides a reflective perspective on the role that research-led teaching plays in the development of future arts workers in higher education. It explores the challenges faced by lecturers developing curricula in the performing and creative arts and argues that the increasing focus on employability can conflict with universities’ traditional aim of developing conceptual and critical thinkers. The article charges that the UK’s higher education sector is rapidly transforming itself into a two-tier system, which is serving to dichotomise vocational and academic learning even further. It concludes with a call for universities, students and employers to reject the false dichotomy between vocational and academic learning and perceive education in a more holistic, longitudinal sense, which might in turn develop more balanced graduates who excel in networked knowledge, conceptual and theoretical imagination and critical, lateral thinking