The Genomic Substrate for Adaptive Radiation: Copy Number Variation across 12 Tribes of African Cichlid Species

© 2019 Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution 2019. This work is written by US Government employees and is in the public domain in the US. The initial sequencing of five cichlid genomes revealed an accumulation of genetic variation, including extensive copy number variation in cichlid lineages particularly those that have undergone dramatic evolutionary radiation. Gene duplication has the potential to generate substantial molecular substrate for the origin of evolutionary novelty. We use array-based comparative heterologous genomic hybridization to identify copy number variation events (CNVEs) for 168 samples representing 53 cichlid species including the 5 species for which full genome sequence is available. We identify an average of 50-100 CNVEs per individual. For those species represented by multiple samples, we identify 150-200 total CNVEs suggesting a substantial amount of intraspecific variation. For these species, only ∼10% of the detected CNVEs are fixed. Hierarchical clustering of species according to CNVE data recapitulates phylogenetic relationships fairly well at both the tribe and radiation level. Although CNVEs are detected on all linkage groups, they tend to cluster in "hotspots" and are likely to contain and be flanked by transposable elements. Furthermore, we show that CNVEs impact functional categories of genes with potential roles in adaptive phenotypes that could reasonably promote divergence and speciation in the cichlid clade. These data contribute to a more complete understanding of the molecular basis for adaptive natural selection, speciation, and evolutionary radiation

A diet rich in fish oil and Leucine Ameliorates Hypercalcemia in tumour-induced cachectic mice

Background: Dietary supplementation with leucine and fish oil rich in omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) has previously been shown to reduce cachexia-related outcomes in C26 tumour-bearing mice. To further explore associated processes and mechanisms we investigated changes in plasma Ca2+ levels, the involvement of parathyroid hormone related protein (PTHrP), and its possible interactions with cyclooxygenase 2 (COX-2). Methods: CD2F1 mice were subcutaneously inoculated with C26 adenocarcinoma cells or sham treated and divided in: (1) controls, (2) tumour-bearing controls, and (3) tumour-bearing receiving experimental diets. After 20 days, body and organ masses and total plasma Ca2+ levels were determined. Furthermore, effects of DHA, EPA and leucine on production of PTHrP were studied in cultured C26 cells. Results: The combination of leucine and fish oil reduced tumour-associated hypercalcemia. Plasma Ca2+ levels negatively correlated with carcass mass and multiple organ masses. DHA was able to reduce PTHrP production by C26 cells in vitro. Results indicate that this effect occurred independently of COX-2 inhibition. Conclusion: Our results suggest that cancer-related hypercalcemia may be ameliorated by a nutritional intervention rich in leucine and fish oil. The effect of fish oil possibly relates to a DHA-induced reduction of PTHrP excretion by the tumour

Riemann-Hilbert problems from Donaldson-Thomas theory

We study a class of Riemann-Hilbert problems arising naturally in Donaldson-Thomas theory. In certain special cases we show that these problems have unique solutions which can be written explicitly as products of gamma functions. We briefly explain connections with Gromov-Witten theory and exact WKB analysis

A Logical Study of Distributed Transition Systems

AbstractWe extend labelled transition systems to distributed transition systems by labelling the transition relation with a finite set of actions, representing the fact that the actions occur as a concurrent step. We design an addition-based temporal logic in which one can explicity talk about steps. The logic is studied to establish a variety of positive and negative results in terms of axiomatizability and decidability. Our positive results show that the step notion is amenable to logical treatment via standard techniques. They also help us to obtain a logical characterization of two well known models for distributed systems: labelled elementary net systems and labelled prime event structures. Our negative results show that demanding deterministic structures when dealing with a "non-interleaved" notion of transitions is, from a logical standpoint, very expressive. They also show that another well known model of distributed systems called asynchronous transition systems exhibits a surprising amount of expressive power in a natural logical setting

A Genome‐Wide Association Study Meta‐Analysis of Alpha Angle Suggests Cam‐Type Morphology May Be a Specific Feature of Hip Osteoarthritis in Older Adults

Objective: To examine the genetic architecture of cam morphology using alpha angle (AA) as a proxy measure and conduct an AA genome‐wide association study (GWAS) followed by Mendelian randomization (MR) to evaluate its causal relationship with hip osteoarthritis (OA). Methods: Observational analyses examined associations between AA measurements derived from hip dual x‐ray absorptiometry (DXA) scans from the UK Biobank study and radiographic hip OA outcomes and subsequent total hip replacement. Following these analyses, an AA GWAS meta‐analysis was performed (N = 44,214) using AA measurements previously derived in the Rotterdam Study. Linkage disequilibrium score regression assessed the genetic correlation between AA and hip OA. Genetic associations considered significant (P < 5 × 10−8) were used as AA genetic instrument for 2‐sample MR analysis. Results: DXA‐derived AA showed expected associations between AA and radiographic hip OA (adjusted odds ratio [OR] 1.63 [95% confidence interval (95% CI) 1.58, 1.67]) and between AA and total hip replacement (adjusted hazard ratio 1.45 [95% CI 1.33, 1.59]) in the UK Biobank study cohort. The heritability of AA was 10%, and AA had a moderate genetic correlation with hip OA (rg = 0.26 [95% CI 0.10, 0.43]). Eight independent genetic signals were associated with AA. Two‐sample MR provided weak evidence of causal effects of AA on hip OA risk (inverse variance weighted OR 1.84 [95% CI 1.14, 2.96], P = 0.01). In contrast, genetic predisposition for hip OA had stronger evidence of a causal effect on increased AA (inverse variance weighted β = 0.09 [95% CI 0.04, 0.13], P = 4.58 × 10−5). Conclusion: Expected observational associations between AA and related clinical outcomes provided face validity for the DXA‐derived AA measurements. Evidence of bidirectional associations between AA and hip OA, particularly for risk of hip OA on AA, suggests that hip shape modeling secondary to a genetic predisposition to hip OA contributes to the well‐established relationship between hip OA and cam morphology in older adults

Avaliação da inserção do nutricionista na Rede Básica de Saúde dos municípios da Região Metropolitana de Campinas Evaluation of inserting a nutritionist in the Primary Health Network of the municipalities located in the Metropolitan Region of Campinas, São Paulo, Brazil

OBJETIVO: Este trabalho consistiu em uma pesquisa realizada na Rede Básica de Saúde dos municípios pertencentes à Região Metropolitana de Campinas, com o objetivo de descrever e avaliar ações desenvolvidas por nutricionistas. MÉTODOS: O método de pesquisa utilizado foi o quanti-qualitativo, com a realização de 12 entrevistas com nutricionistas da Rede Básica de Saúde de 8 municípios da Região Metropolitana de Campinas. O instrumento utilizado foi um questionário semi-estruturado com questões abertas e fechadas. Em seguida às entrevistas individuais, foi aplicada a técnica de grupo focal com 5 nutricionistas de diferentes municípios. RESULTADOS: As formas de contratação são variadas. Com relação às funções exercidas pelo profissional, destacam-se: prescrições e orientações dietéticas individuais, palestras para grupos, campanhas, participação em programas de suplementação, vigilância sanitária e visitas domiciliares. CONCLUSÃO: Conclui-se que menos da metade dos municípios conta com nutricionista na Rede Básica de Saúde: o número de nutricionistas é insuficiente, o nutricionista tende a acumular funções em diferentes setores e há predomínio das atividades assistenciais em detrimento de atividades de promoção à saúde.<br>OBJECTIVE: This work consisted of a research carried out in the Primary Health Network of the municipalities located in the metropolitan region of Campinas and the objective was to describe and evaluate actions developed by nutritionists. METHODS: The research method used was the quantitative and qualitative method twelve interviews were done with nutritionists from the Primary Health Network of 8 municipalities located in the metropolitan region of Campinas. The instrument used was a semi-structured questionnaire with open and closed questions. Following the individual interviews, the focal group technique was applied to 5 nutritionists from different municipalities. RESULTS: The professionals have varied work contracts. The following functions performed by the professionals stand out: individual prescriptions and dietary guidance, speeches for groups, campaigns, participation in supplementation programs, sanitary surveillance and home visits. CONCLUSION: We conclude that less than half of the municipalities have a nutritionist available at the Primary Health Network: the number of nutritionists is insufficient, the nutritionists tend to accumulate functions in different sectors and there is a prevalence of assistance activities in detriment of health promotion activities

The Genomic Substrate for Adaptive Radiation: Copy Number Variation across 12 Tribes of African Cichlid Species

International audienceThe initial sequencing of five cichlid genomes revealed an accumulation of genetic variation, including extensive copy number variation in cichlid lineages particularly those that have undergone dramatic evolutionary radiation. Gene duplication has the potential to generate substantial molecular substrate for the origin of evolutionary novelty. We use array-based comparative heterol-ogous genomic hybridization to identify copy number variation events (CNVEs) for 168 samples representing 53 cichlid species including the 5 species for which full genome sequence is available. We identify an average of 50-100 CNVEs per individual. For those species represented by multiple samples, we identify 150-200 total CNVEs suggesting a substantial amount of intraspecific variation. For these species, only $10% of the detected CNVEs are fixed. Hierarchical clustering of species according to CNVE data recapit-ulates phylogenetic relationships fairly well at both the tribe and radiation level. Although CNVEs are detected on all linkage groups, they tend to cluster in "hotspots" and are likely to contain and be flanked by transposable elements. Furthermore, we show that CNVEs impact functional categories of genes with potential roles in adaptive phenotypes that could reasonably promote divergence and speciation in the cichlid clade. These data contribute to a more complete understanding of the molecular basis for adaptive natural selection, speciation, and evolutionary radiation

Hypothalamic gene expression of appetite regulators in a cancer-cachectic mouse model [Dataset 1]

Appetite is frequently affected in cancer patients, leading to anorexia and consequently insufficient food intake. In this study, we report on hypothalamic gene expression profile of a cancer cachectic mouse model with increased food intake. In this model, mice bearing C26 colon adenocarcinoma have an increased food intake subsequently to the loss of body weight. We hypothesize that in this model, appetite regulating systems in the hypothalamus, which apparently fail in anorexia, are still able to adapt adequately to changes in energy balance. Therefore studying the changes that occur on appetite regulators in the hypothalamus might reveal targets for treatment of cancer-induced eating disorders. By applying transcriptomics, many appetite regulating systems in the hypothalamus could be taken into account, providing an overview of changes that occur in the hypothalamus during tumour growth. We show that hypothalamic expression of orexigenic neuropeptides NPY and AgRP was higher, whereas expression of anorexigenic genes CCK and POMC were lower in TB compared to controls. In addition, serotonin and dopamine signalling pathways were found to be significantly altered in TB mice. Serotonin levels in brain showed to be lower in TB mice compared to control mice, while dopamine levels did not change. Moreover, serotonin levels inversely correlated with food intake. Transcriptomic analysis of the hypothalamus of cachectic TB mice with an increased food intake showed changes in NPY, AgRP and serotonin signalling. Serotonin levels in the brain showed to correlate with changes in food intake. Targeting these systems seems a promising strategy to avoid the development of cancer-induced eating disorders