Structural and functional properties of genes involved in human cancer

Background: One of the main goals of cancer genetics is to identify the causative elements at the molecular level leading to cancer.Results: We have conducted an analysis of a set of genes known to be involved in cancer in order to unveil their unique features that can assist towards the identification of new candidate cancer genes. Conclusion: We have detected key patterns in this group of genes in terms of the molecular function or the biological process in which they are involved as well as sequence properties. Based on these features we have developed an accurate Bayesian classification model with which human genes have been scored for their likelihood of involvement in cancer.

Predicting cancer involvement of genes from heterogeneous data

Background: Systematic approaches for identifying proteins involved in different types of cancer are needed. Experimental techniques such as microarrays are being used to characterize cancer, but validating their results can be a laborious task. Computational approaches are used to prioritize between genes putatively involved in cancer, usually based on further analyzing experimental data. Results: We implemented a systematic method using the PIANA software that predicts cancer involvement of genes by integrating heterogeneous datasets. Specifically, we produced lists of genes likely to be involved in cancer by relying on: (i) protein-protein interactions; (ii) differential expression data; and (iii) structural and functional properties of cancer genes. The integrative approach that combines multiple sources of data obtained positive predictive values ranging from 23% (on a list of 811 genes) to 73% (on a list of 22 genes), outperforming the use of any of the data sources alone. We analyze a list of 20 cancer gene predictions, finding that most of them have been recently linked to cancer in literature. Conclusion: Our approach to identifying and prioritizing candidate cancer genes can be used to produce lists of genes likely to be involved in cancer. Our results suggest that differential expression studies yielding high numbers of candidate cancer genes can be filtered using protein interaction networks.

OSIRISv1.2: a named entity recognition system for sequence variants of genes in biomedical literature

Background: Single Nucleotide Polymorphisms, among other type of sequence variants, constitute key elements in genetic epidemiology and pharmacogenomics. While sequence data about genetic variation is found at databases such as dbSNP, clues about the functional and phenotypic consequences of the variations are generally found in biomedical literature. The identification of the relevant documents and the extraction of the information from them are hampered by the large size of literature databases and the lack of widely accepted standard notation for biomedical entities. Thus, automatic systems for the identification of citations of allelic variants of genes in biomedical texts are required. Results: Our group has previously reported the development of OSIRIS, a system aimed at the retrieval of literature about allelic variants of genes http://ibi.imim.es/osirisform.html. Here we describe the development of a new version of OSIRIS (OSIRISv1.2, http://ibi.imim.es/OSIRISv1.2.html webcite) which incorporates a new entity recognition module and is built on top of a local mirror of the MEDLINE collection and HgenetInfoDB: a database that collects data on human gene sequence variations. The new entity recognition module is based on a pattern-based search algorithm for the identification of variation terms in the texts and their mapping to dbSNP identifiers. The performance of OSIRISv1.2 was evaluated on a manually annotated corpus, resulting in 99% precision, 82% recall, and an F-score of 0.89. As an example, the application of the system for collecting literature citations for the allelic variants of genes related to the diseases intracranial aneurysm and breast cancer is presented. Conclusion: OSIRISv1.2 can be used to link literature references to dbSNP database entries with high accuracy, and therefore is suitable for collecting current knowledge on gene sequence variations and supporting the functional annotation of variation databases. The application of OSIRISv1.2 in combination with controlled vocabularies like MeSH provides a way to identify associations of biomedical interest, such as those that relate SNPs with diseases.

Is there a wage penalty for horizontal and vertical mismatch?

This paper studies how the horizontal and vertical mismatches in the labor market affect wage. We do so by taking into account that by choosing a job, wage and mismatches are simultaneously determined. The Seemingly Unrelated Equations model also allows us to control for any omitted variable that could cause biased estimators. We use REFLEX data for Spain. Results reveal that in most cases being horizontally matched has a wage premium and being over-educated does not affect wage. Results suggest that the modeling strategy successfully accounts for some omitted variable that affects simultaneously the probability of being horizontally matched and the wage. This could explain the existence of a wage penalty for over-educated workers when the omitted variable issue is not dealt with.

The Sociology of educational mismatch

This paper studies the theoretical relationships between core research lines of sociology such as intergenerational mobility, class structure, cultural capital and educational mismatches. By educational mismatch we mean two things. Firstly an individual can be horizontally mismatched whereby their field of study is inadequate for the job. Another direction of educational mismatch is the so called vertical mismatch where worker possesses more/less education than the job requires resulting in over-/under-education. While analyzing the educational mismatches I keep present the conclusions of Rational Action Theory on individuals’ rational choices in their educational careers. I arrive to conclusions where the influences between educational mismatches and social classes are bidirectional and one can establish fairly clear theoretical links between class of origins and likelihood of being educationally mismatched.

Unemployment vs. mismatch of talents: Reconsidering unemployment benefits

We develop an equilibrium search-matching model with risk-neutral agentsand two-sided ex-ante heterogeneity. Unemployment insurance has thestandard effect of reducing employment, but also helps workers to get a suitable job. The predictions of our simple modelare consistent with the contrasting performance of the labor market in Europeand US in terms of unemployment, productivity growth and wage inequality.To show this, we construct two fictitious economies with calibratedparameters which only differ by the degree of unemployment insurance andassume that they are hit by a common technological shock which enhancesthe importance of mismatch. This shock reduces the proportion of jobs whichworkers regards as acceptable in the economy with unemployment insurance(Europe). As a result, unemployment doubles in this economy.In the laissez-faire economy (US), unemployment remains constant,but wage inequality increases more and productivity grows less due to largermismatch. The model can be used to address a number of normative issues.

Estudio Farmacogenético en Pacientes con Cáncer de Pulmón No Microcítico Avanzado tratados con Quimioterapia basada en Platino

a partir de ADN genómico obtenido de las células nucleadas de sangre periférica de 103 pacientes con Cáncer de Pulmón No Microcítico (CPNM) avanzado tratados con quimioterapia basada en platino, hemos analizado la asociación entre supervivencia y cinco SNPs (Single Nucleotide Polymorphism) pertenecientes a dos grupos de genes: i) de la via metabólica del ácido fólico (Timidilato Sintetasa (TS), Metil-tetrahidrofolato Reductasa (MTHFR) y, ii) de la vía de reparación del ADN (Excision repair cross-complemeting group 1 (ERCC1) y Xeroderma pigmentosum group D (XPD).

Polymorphisms of pyrimidine pathway enzymes encoding genes and HLA-B*4001 carriage in stavudine-associated lipodystrophy in HIV-infected patients.

: To assess in a cohort of Caucasian patients exposed to stavudine (d4T) the association of polymorphisms in pyrimidine pathway enzymes and HLA-B*4001 carriage with HIV lipodystrophy syndrome (HALS). 336 patients, 187 with HALS and 149 without HALS, and 72 controls were recruited. HALS was associated with the presence of a low expression, thymidylate synthase (TS) genotype polymorphism. Methylene-tetrahydrofolate reductase (MTHFR) gene polymorphisms and HLA-B*4001 carriage were not associated with HALS or d4T-TP intracellular levels. In conclusion HALS is associated with combined low-expression TS and MTHFR associated with high activity polymorphisms but not with HLA-B*4001 carriage.

p38/MKP-1-regulated AKT coordinates macrophage transitions and resolution of inflammation during tissue repair

Repair of damaged tissue requires the coordinated action of inflammatory and tissue-specific cells to restore homeostasis, but the underlying regulatory mechanisms are poorly understood. In this paper, we report new roles for MKP-1 (mitogen-activated protein kinase [MAPK] phosphatase-1) in controlling macrophage phenotypic transitions necessary for appropriate muscle stem cell¿dependent tissue repair. By restricting p38 MAPK activation, MKP-1 allows the early pro- to antiinflammatory macrophage transition and the later progression into a macrophage exhaustion-like state characterized by cytokine silencing, thereby permitting resolution of inflammation as tissue fully recovers. p38 hyperactivation in macrophages lacking MKP-1 induced the expression of microRNA-21 (miR-21), which in turn reduced PTEN (phosphatase and tensin homologue) levels, thereby extending AKT activation. In the absence of MKP-1, p38-induced AKT activity anticipated the acquisition of the antiinflammatory gene program and final cytokine silencing in macrophages, resulting in impaired tissue healing. Such defects were reversed by temporally controlled p38 inhibition. Conversely, miR-21¿AKT interference altered homeostasis during tissue repair. This novel regulatory mechanism involving the appropriate balance of p38, MKP-1, miR-21, and AKT activities may have implications in chronic inflammatory degenerative diseases.

Eyes wide shut - unusual two stage repair of pectus excavatum and annuloaortic ectasia in a 37 year old marfan patient: Case report

We report about a 37 year old male patient with a pectus excavatum. The patient was in NYHA functional class III. After performed computed tomography the symptoms were thought to be related to the severity of chest deformation. A Ravitch-procedure had been accomplished in a district hospital in 2009. The crack of a metal bar led to a reevaluation 2010, in which surprisingly the presence of an annuloaortic ectasia (root 73 × 74 mm) in direct neighborhood of the formerly implanted metal-bars was diagnosed. Echocardiography revealed a severe aortic valve regurgitation, the left ventricle was massively dilated presenting a reduced ejection fraction of 45%. A marfan syndrome was suspected and the patient underwent a valve sparing aortic root replacement (David procedure) in our institution with an uneventful postoperative course. A review of the literature in combination with discussion of our case suggests the application of stronger recommendations towards preoperative cardiovascular assessment in patients with pectus excavatum.

Graduate labor mismatch in Central and Eastern Europe

[cat] Utilitzant l’enquesta REFLEX/HEGESCO, aquest article explora la probabilitat de desajustament entre educació i treball a l’Europa de l’Est i Central. Classifiquem els països en dos grups segons la transparència dels títols educatius al mercat de treball. Polònia, la República Txeca i Eslovènia formen el grup amb més transparència, i Hongria, Lituània i Estònia formen el grup amb més opacitat. Analitzem tres tipus de desajustaments: el vertical (infra‐, sobre‐educació), l’horitzontal (desajustament del camp d’estudi) i el desajust en habilitats. Focalitzem l’anàlisi en l’efecte dels camps d’estudi i les competències dels individus en el desajustament del mercat laboral en aquests països. Els resultats mostren importants diferències entre els dos grups de països estudiats.

Effective mass and dielectric constant mismatch effects in spherical multishell quantum dots

The role of effective mass and dielectric mismatches on chemical potentials and addition energies of many-electron multishell quantum dots (QDs) is explored within the framework of a recent extension of the spin density functional theory. It is shown that although the gross electronic density is located in the wells of these multishell QDs, taking position-dependent effective mass and dielectric constant into account can lead to the appearance of relevant differences in chemical potential and addition energies as compared to standard calculations in which the effective mass and the dielectric constant of the well is assumed for the whole multishell structure.

Conserved chromosomal clustering of genes governed by chromatin regulators in Drosophila

Background: The trithorax group (trxG) and Polycomb group (PcG) proteins are responsible for the maintenance of stable transcriptional patterns of many developmental regulators. They bind to specific regions of DNA and direct the post-translational modifications of histones, playing a role in the dynamics of chromatin structure.Results: We have performed genome-wide expression studies of trx and ash2 mutants in Drosophila melanogaster. Using computational analysis of our microarray data, we have identified 25 clusters of genes potentially regulated by TRX. Most of these clusters consist of genes that encode structural proteins involved in cuticle formation. This organization appears to be a distinctive feature of the regulatory networks of TRX and other chromatin regulators, since we have observed the same arrangement in clusters after experiments performed with ASH2, as well as in experiments performed by others with NURF, dMyc, and ASH1. We have also found many of these clusters to be significantly conserved in D. simulans, D. yakuba, D. pseudoobscura and partially in Anopheles gambiae.Conclusion: The analysis of genes governed by chromatin regulators has led to the identification of clusters of functionally related genes conserved in other insect species, suggesting this chromosomal organization is biologically important. Moreover, our results indicate that TRX and other chromatin regulators may act globally on chromatin domains that contain transcriptionally co-regulated genes.

Odorant Receptor (Or) genes: polymorphism and divergence in the D. melanogaster and D. pseudoobscura Lineages

Background: In insects, like in most invertebrates, olfaction is the principal sensory modality, which provides animals with essential information for survival and reproduction. Odorant receptors are involved in this response, mediating interactions between an individual and its environment, as well as between individuals of the same or different species. The adaptive importance of odorant receptors renders them good candidates for having their variation shaped by natural selection. Methodology/Principal Findings: We analyzed nucleotide variation in a subset of eight Or genes located on the 3L chromosomal arm of Drosophila melanogaster in a derived population of this species and also in a population of Drosophila pseudoobscura. Some heterogeneity in the silent polymorphism to divergence ratio was detected in the D. melanogaster/D. simulans comparison, with a single gene (Or67b) contributing ~37% to the test statistic. However, no other signals of a very recent selective event were detected at this gene. In contrast, at the speciation timescale, the MK test uncovered the footprint of positive selection driving the evolution of two of the encoded proteins in both D. melanogaster ¿OR65c and OR67a ¿and D. pseudoobscura ¿OR65b1 and OR67c. Conclusions: The powerful polymorphism/divergence approach provided evidence for adaptive evolution at a rather high proportion of the Or genes studied after relatively recent speciation events. It did not provide, however, clear evidence for very recent selective events in either D. melanogaster or D. pseudoobscura.