Quantifying metastatic inefficiency:rare genotypes versus rare dynamics

abstract: We introduce and solve a ‘null model’ of stochastic metastatic colonization. The model is described by a single parameter θ: the ratio of the rate of cell division to the rate of cell death for a disseminated tumour cell in a given secondary tissue environment. We are primarily interested in the case in which colonizing cells are poorly adapted for proliferation in the local tissue environment, so that cell death is more likely than cell division, i.e. θ 1), i.e. the statistics show a duality mapping (1 − θ) → (θ − 1). We conclude our analysis with a study of heterogeneity in the fitness of colonising cells, and describe a phase diagram delineating parameter regions in which metastatic colonization is dominated either by low or high fitness cells, showing that both are plausible given our current knowledge of physiological conditions in human cancer

A network-based approach for predicting key enzymes explaining metabolite abundance alterations in a disease phenotype

<p>Background The study of metabolism has attracted much attention during the last years due to its relevance in various diseases. The advance in metabolomics platforms allows us to detect an increasing number of metabolites in abnormal high/low concentration in a disease phenotype. Finding a mechanistic interpretation for these alterations is important to understand pathophysiological processes, however it is not an easy task. The availability of genome scale metabolic networks and Systems Biology techniques open new avenues to address this question.</p> <p>Results In this article we present a novel mathematical framework to find enzymes whose malfunction explains the accumulation/depletion of a given metabolite in a disease phenotype. Our approach is based on a recently introduced pathway concept termed Carbon Flux Paths (CFPs), which extends classical topological definition by including network stoichiometry. Using CFPs, we determine the Connectivity Curve of an altered metabolite, which allows us to quantify changes in its pathway structure when a certain enzyme is removed. The influence of enzyme removal is then ranked and used to explain the accumulation/depletion of such metabolite. For illustration, we center our study in the accumulation of two metabolites (L-Cystine and Homocysteine) found in high concentration in the brain of patients with mental disorders. Our results were discussed based on literature and found a good agreement with previously reported mechanisms. In addition, we hypothesize a novel role of several enzymes for the accumulation of these metabolites, which opens new strategies to understand the metabolic processes underlying these diseases.</p> <p>Conclusions With personalized medicine on the horizon, metabolomic platforms are providing us with a vast amount of experimental data for a number of complex diseases. Our approach provides a novel apparatus to rationally investigate and understand metabolite alterations under disease phenotypes. This work contributes to the development of Systems Medicine, whose objective is to answer clinical questions based on theoretical methods and high-throughput “omics” data.</p&gt

El portafolio como instrumento de evaluación docente: una experiencia en el sureste de México

En esta ponencia se examina la experiencia de un grupo de investigadores de la Universidad Autónoma de Yucatán que utilizaron el portafolio de enseñanza para la evaluación de necesidades de desarrollo de docentes de preparatoria en el estado. Los portafolios fueron muy útiles para obtener un panorama de la calidad del trabajo docente y necesidades de actualización de los profesores que no se hubiese podido obtenerse por medio de una encuesta. Asimismo, los resultados del estudio permitieron detectar áreas de mejora que posteriormente fueron utilizados para la operación de un programa de formación en todo el estado. El poder de los portafolios está en la calidad de la información que proporcionan sus elementos. Asimismo, la calidad de la evaluación depende de los productos que los profesores incluyan, que pueden ser o no ser elaborados por ellos mismos. Es importante tener presente que pueden existir otros elementos importantes para el mejoramiento de la calidad de la enseñanza de los profesores que sólo se obtienen por medio de observación directa en el aul

Family Relationships and Academic Performance via Belongingness among Cuban Medical Students: Examining Family Legacy and Sex as Moderators

Medical diplomacy is a foundational part of Cuban domestic and foreign policy (Feinsilver, 2010). Cuba has an abundance of doctors, encouraged by the country’s free medical education program (Hand et al., 2020), and has made a significant impact with its well-established healthcare system, provision of healthcare for all of its citizens, and healthcare support internationally. The current study aims to focus on processes underlying Cuban medical students’ academic performance, as they are a critical component of this successful system, and a population that has received limited empirical attention. Thus, the current study used path analyses to examine the relations between improved family relationships and academic performance mediated by belongingness and moderated by family legacy (i.e., having family members working in the medical field), and sex differences among Cuban medical students (N = 637) residing in Cuba (M age = 21.36, SD = 2.04). We found that improved family relationships significantly predicted increased belongingness to the field of medicine which, in turn, predicted increase perceptions of academic performance for Cuban medical students, this mediation only held for male and not female students. In other words, only male medical students with improved family relationships reported more feelings of belonging to the school of medicine and higher academic performance, this was not true for female students. Discussion on societal implications for sex differences will be addressed. Limitations, implications, and future direction will be further discussed

The transfer of IgA from mucus to plasma and the implications for diagnosis and control of nematode infections

Immunoglobulin A (IgA) activity has been associated with reduced growth and fecundity of Teladorsagia circumcincta. IgA is active at the site of infection in the abomasal mucus. However, while IgA activity in abomasal mucus is not easily measured in live animals without invasive methods, IgA activity can be readily detected in the plasma, making it a potentially valuable tool in diagnosis and control. We used a Bayesian statistical analysis to quantify the relationship between mucosal and plasma IgA in sheep deliberately infected with T. circumcincta. The transfer of IgA depends on mucosal IgA activity as well as its interaction with worm number and size; together these account for over 80% of the variation in plasma IgA activity. By quantifying the impact of mucosal IgA and worm number and size on plasma IgA, we provide a tool that can allow more meaningful interpretation of plasma IgA measurements and aid the development of efficient control programmes