A data mining approach for classifying DNA repair genes into ageing-related or non-ageing-related

<p>Abstract</p> <p>Background</p> <p>The ageing of the worldwide population means there is a growing need for research on the biology of ageing. DNA damage is likely a key contributor to the ageing process and elucidating the role of different DNA repair systems in ageing is of great interest. In this paper we propose a data mining approach, based on classification methods (decision trees and Naive Bayes), for analysing data about human DNA repair genes. The goal is to build classification models that allow us to discriminate between ageing-related and non-ageing-related DNA repair genes, in order to better understand their different properties.</p> <p>Results</p> <p>The main patterns discovered by the classification methods are as follows: (a) the number of protein-protein interactions was a predictor of DNA repair proteins being ageing-related; (b) the use of predictor attributes based on protein-protein interactions considerably increased predictive accuracy of attributes based on Gene Ontology (GO) annotations; (c) GO terms related to "response to stimulus" seem reasonably good predictors of ageing-relatedness for DNA repair genes; (d) interaction with the XRCC5 (Ku80) protein is a strong predictor of ageing-relatedness for DNA repair genes; and (e) DNA repair genes with a high expression in T lymphocytes are more likely to be ageing-related.</p> <p>Conclusions</p> <p>The above patterns are broadly integrated in an analysis discussing relations between Ku, the non-homologous end joining DNA repair pathway, ageing and lymphocyte development. These patterns and their analysis support non-homologous end joining double strand break repair as central to the ageing-relatedness of DNA repair genes. Our work also showcases the use of protein interaction partners to improve accuracy in data mining methods and our approach could be applied to other ageing-related pathways.</p

Economic factors influencing zoonotic disease dynamics: demand for poultry meat and seasonal transmission of avian influenza in Vietnam

While climate is often presented as a key factor influencing the seasonality of diseases, the importance of anthropogenic factors is less commonly evaluated. Using a combination of methods-wavelet analysis, economic analysis, statistical and disease transmission modelling-we aimed to explore the influence of climatic and economic factors on the seasonality of H5N1 Highly Pathogenic Avian Influenza in the domestic poultry population of Vietnam. We found that while climatic variables are associated with seasonal variation in the incidence of avian influenza outbreaks in the North of the country, this is not the case in the Centre and the South. In contrast, temporal patterns of H5N1 incidence are similar across these 3 regions: periods of high H5N1 incidence coincide with Lunar New Year festival, occurring in January-February, in the 3 climatic regions for 5 out of the 8 study years. Yet, daily poultry meat consumption drastically increases during Lunar New Year festival throughout the country. To meet this rise in demand, poultry production and trade are expected to peak around the festival period, promoting viral spread, which we demonstrated using a stochastic disease transmission model. This study illustrates the way in which economic factors may influence the dynamics of livestock pathogens

Increased Numbers of IL-7 Receptor Molecules on CD4+CD25−CD107a+ T-Cells in Patients with Autoimmune Diseases Affecting the Central Nervous System

BACKGROUND: High content immune profiling in peripheral blood may reflect immune aberrations associated with inflammation in multiple sclerosis (MS) and other autoimmune diseases affecting the central nervous system. METHODS AND FINDINGS: Peripheral blood mononuclear cells from 46 patients with multiple sclerosis (MS), 9 patients diagnosed with relapsing remitting MS (RRMS), 13 with secondary progressive multiple sclerosis (SPMS), 9 with other neurological diseases (OND) and well as 15 healthy donors (HD) were analyzed by 12 color flow cytometry (TCRalphabeta, TCRgammadelta, CD4, CD8alpha, CD8beta, CD45RA, CCR7, CD27, CD28, CD107a, CD127, CD14) in a cross-sectional study to identify variables significantly different between controls (HD) and patients (OND, RRMS, SPMS). We analyzed 187 individual immune cell subsets (percentages) and the density of the IL-7 receptor alpha chain (CD127) on 59 individual immune phenotypes using a monoclonal anti-IL-7R antibody (clone R34.34) coupled to a single APC molecule in combination with an APC-bead array. A non-parametric analysis of variance (Kruskal-Wallis test) was conducted in order to test for differences among the groups in each of the variables. To correct for the multiplicity problem, the FDR correction was applied on the p-values. We identified 19 variables for immune cell subsets (percentages) which allowed to segregate healthy individuals and individuals with CNS disorders. We did not observe differences in the relative percentage of IL-7R-positive immune cells in PBMCs. In contrast, we identified significant differences in IL-7 density, measured on a single cell level, in 2/59 variables: increased numbers of CD127 molecules on TCRalphabeta+CD4+CD25 (intermed) T-cells and on TCRalphabeta+CD4+CD25-CD107a+ T-cells (mean: 28376 Il-7R binding sites on cells from HD, 48515 in patients with RRMS, 38195 in patients with SPMS and 33692 IL-7 receptor binding sites on cells from patients with OND). CONCLUSION: These data show that immunophenotyping represents a powerful tool to differentiate healthy individuals from individuals suffering from neurological diseases and that the number of IL-7 receptor molecules on differentiated TCRalphabeta+CD4+CD25-CD107a+ T-cells, but not the percentage of IL-7R-positive cells, segregates healthy individuals from patients with neurological disorders

Disease-Aging Network Reveals Significant Roles of Aging Genes in Connecting Genetic Diseases

One of the challenging problems in biology and medicine is exploring the underlying mechanisms of genetic diseases. Recent studies suggest that the relationship between genetic diseases and the aging process is important in understanding the molecular mechanisms of complex diseases. Although some intricate associations have been investigated for a long time, the studies are still in their early stages. In this paper, we construct a human disease-aging network to study the relationship among aging genes and genetic disease genes. Specifically, we integrate human protein-protein interactions (PPIs), disease-gene associations, aging-gene associations, and physiological system–based genetic disease classification information in a single graph-theoretic framework and find that (1) human disease genes are much closer to aging genes than expected by chance; and (2) diseases can be categorized into two types according to their relationships with aging. Type I diseases have their genes significantly close to aging genes, while type II diseases do not. Furthermore, we examine the topological characters of the disease-aging network from a systems perspective. Theoretical results reveal that the genes of type I diseases are in a central position of a PPI network while type II are not; (3) more importantly, we define an asymmetric closeness based on the PPI network to describe relationships between diseases, and find that aging genes make a significant contribution to associations among diseases, especially among type I diseases. In conclusion, the network-based study provides not only evidence for the intricate relationship between the aging process and genetic diseases, but also biological implications for prying into the nature of human diseases

From Portugal to Europe. A micro-level Sociology of scientific migration in times of Eurozone crisis.

Academic international mobility and intra-European highly skilled migration are consolidated trends. Strongly stimulated by EU policies, the opportunities are highly dynamic, and circulation through different jobs and countries is a striking feature of the academic community. However, for a fragile economy and scientific system as the Portuguese ones, those trends are synonyms of brain drain, particularly in times of Eurozone crisis. In order to question the place of the economic crisis on scientists’ migration decision-making process, and considering that academic mobility is often associated with individual career perspectives and encouraged by European policies, five individual portraits are analysed

Gene duplication and phenotypic changes in the evolution of Mammalian metabolic networks

Metabolic networks attempt to describe the complete suite of biochemical reactions available to an organism. One notable feature of these networks in mammals is the large number of distinct proteins that catalyze the same reaction. While the existence of these isoenzymes has long been known, their evolutionary significance is still unclear. Using a phylogenetically-aware comparative genomics approach, we infer enzyme orthology networks for sixteen mammals as well as for their common ancestors. We find that the pattern of isoenzymes copy-number alterations (CNAs) in these networks is suggestive of natural selection acting on the retention of certain gene duplications. When further analyzing these data with a machine-learning approach, we found that that the pattern of CNAs is also predictive of several important phenotypic traits, including milk composition and geographic range. Integrating tools from network analyses, phylogenetics and comparative genomics both allows the prediction of phenotypes from genetic data and represents a means of unifying distinct biological disciplines

A genetic analysis of nitric oxide-mediated signaling during chronological aging in the yeast

In mammals, NO•, a signaling molecule is implicated in the regulation of vasodilation, neurotransmission and immune response. It is believed that NO• is a signaling molecule also in unicellular organism like yeast and may be involved in the regulation of apoptosis and sporulation. It has been reported that NO• is produced during chronological aging (CA) leading to an increase of the superoxide level, which in turn mediates apoptosis. Since this conclusion was based on indirect measurements of NO• by the Griess reaction, the role of NO• signaling during CA in the yeast remains uncertain. We investigated this issue more precisely using different genetic and biochemical methodologies. We used cells lacking the factors influencing nitrosative stress response like flavohemoglobin metabolizing NO•, S-nitrosoglutathione reductase metabolizing S-nitrosoglutathione and the transcription factor Fzf1p mediating NO• response. We measured the standard parameters describing CA and found an elevation in the superoxide level, percentage of death cells, the level of TUNEL positive cells and a decrease in proliferating potential. These observations showed no significant differences between wild type cells and the disruptants except for a small elevation of the superoxide level in the Δsfa1 mutant. The intracellular NO• level and flavohemoglobin expression decreased rather than increased during CA. Products of general nitrogen metabolism and protein tyrosine nitration were slightly decreased during CA, the magnitude of changes showing no differences between the wild type and the mutant yeast. Altogether, our data indicate that apoptosis during yeast CA is mediated by superoxide signaling rather than NO• signaling

Reference materials for phase equilibrium studies. 2. Solid-liquid equilibria (IUPAC Technical Report)

This article is the second of three projected IUPAC Technical Reports on reference materials for phase equilibrium studies. The goal of this project was to select reference systems with critically evaluated property values for the verification of instruments and techniques used in phase equilibrium studies of mixtures. This report proposes seven systems for solid–liquid equilibrium studies, covering the four most common categories of binary mixtures: aqueous systems with organic solutes, aqueous systems with inorganic solutes, non-aqueous systems, and systems with low solubility. For each system, the available literature sources, accepted data, smoothing equations, and estimated uncertainties are given

GiSAO.db: a database for ageing research

<p>Abstract</p> <p>Background</p> <p>Age-related gene expression patterns of <it>Homo sapiens </it>as well as of model organisms such as <it>Mus musculus</it>, <it>Saccharomyces cerevisiae</it>, <it>Caenorhabditis elegans </it>and <it>Drosophila melanogaster </it>are a basis for understanding the genetic mechanisms of ageing. For an effective analysis and interpretation of expression profiles it is necessary to store and manage huge amounts of data in an organized way, so that these data can be accessed and processed easily.</p> <p>Description</p> <p>GiSAO.db (Genes involved in senescence, apoptosis and oxidative stress database) is a web-based database system for storing and retrieving ageing-related experimental data. Expression data of genes and miRNAs, annotation data like gene identifiers and GO terms, orthologs data and data of follow-up experiments are stored in the database. A user-friendly web application provides access to the stored data. KEGG pathways were incorporated and links to external databases augment the information in GiSAO.db. Search functions facilitate retrieval of data which can also be exported for further processing.</p> <p>Conclusions</p> <p>We have developed a centralized database that is very well suited for the management of data for ageing research. The database can be accessed at <url>https://gisao.genome.tugraz.at</url> and all the stored data can be viewed with a guest account.</p

Socialização e percursos (e)migratórios em Portugal: uma análise a partir de retratos sociológicos

This article intends to study the link between socialization and highly qualify emigration, from a purposive sample of Portuguese citizens who were or had been emigrants in a European country, in the past six years. This sample is composed by highly qualified individuals or individuals who had an occupation corresponding to this qualification level. In this sense, the resulting twenty individual portraits allow the study of the socialization processes that facilitate the "brain drain". At an individual level, this research design enables the analysis of migratory social dispositions’ creation and mobilization, which are related to social and/or cultural mobility processes. One concludes that there are some cases of disposicional heterogeneity and disposicional rupture, but most portraits represent cases of dispositional coherence in favour of emigration. Qualified emigration seems to be a result of dispositions mutual reinforcing towards emigration, in addition to the will to pursue personal and professional projects that do not find fertile ground in Portuga