Genetic and genomic analysis modeling of germline c-MYC overexpression and cancer susceptibility

Background: Germline genetic variation is associated with the differential expression of many human genes. The phenotypic effects of this type of variation may be important when considering susceptibility to common genetic diseases. Three regions at 8q24 have recently been identified to independently confer risk of prostate cancer. Variation at 8q24 has also recently been associated with risk of breast and colorectal cancer. However, none of the risk variants map at or relatively close to known genes, with c-MYC mapping a few hundred kilobases distally. Results: This study identifies cis-regulators of germline c-MYC expression in immortalized lymphocytes of HapMap individuals. Quantitative analysis of c-MYC expression in normal prostate tissues suggests an association between overexpression and variants in Region 1 of prostate cancer risk. Somatic c-MYC overexpression correlates with prostate cancer progression and more aggressive tumor forms, which was also a pathological variable associated with Region 1. Expression profiling analysis and modeling of transcriptional regulatory networks predicts a functional association between MYC and the prostate tumor suppressor KLF6. Analysis of MYC/Myc-driven cell transformation and tumorigenesis substantiates a model in which MYC overexpression promotes transformation by down-regulating KLF6. In this model, a feedback loop through E-cadherin down-regulation causes further transactivation of c-MYC.Conclusion: This study proposes that variation at putative 8q24 cis-regulator(s) of transcription can significantly alter germline c-MYC expression levels and, thus, contribute to prostate cancer susceptibility by down-regulating the prostate tumor suppressor KLF6 gene.

Some reflections on Geobotany and Vegetation mapping

uivalent Spanish and Catalan terms.

Precession electron diffraction in the transmission electron Microscope: electron crystallography and orientational mapping

Precession electron diffraction (PED) is a hollow cone non-stationary illumination technique for electron diffraction pattern collection under quasikinematicalconditions (as in X-ray Diffraction), which enables “ab-initio” solving of crystalline structures of nanocrystals. The PED technique is recently used in TEMinstruments of voltages 100 to 300 kV to turn them into true electron iffractometers, thus enabling electron crystallography. The PED technique, when combined with fast electron diffraction acquisition and pattern matching software techniques, may also be used for the high magnification ultra-fast mapping of variable crystal orientations and phases, similarly to what is achieved with the Electron Backscatter Diffraction (EBSD) technique in Scanning ElectronMicroscopes (SEM) at lower magnifications and longer acquisition times.

Image-Based Coral Reef Classification and Thematic Mapping

This paper presents a novel image classification scheme for benthic coral reef images that can be applied to both single image and composite mosaic datasets. The proposed method can be configured to the characteristics (e.g., the size of the dataset, number of classes, resolution of the samples, color information availability, class types, etc.) of individual datasets. The proposed method uses completed local binary pattern (CLBP), grey level co-occurrence matrix (GLCM), Gabor filter response, and opponent angle and hue channel color histograms as feature descriptors. For classification, either k-nearest neighbor (KNN), neural network (NN), support vector machine (SVM) or probability density weighted mean distance (PDWMD) is used. The combination of features and classifiers that attains the best results is presented together with the guidelines for selection. The accuracy and efficiency of our proposed method are compared with other state-of-the-art techniques using three benthic and three texture datasets. The proposed method achieves the highest overall classification accuracy of any of the tested methods and has moderate execution time. Finally, the proposed classification scheme is applied to a large-scale image mosaic of the Red Sea to create a completely classified thematic map of the reef benthos

Conceptual Interpretation of LOM and its Mapping to Common Sense Ontologies

Peer-reviewed

The influence of genetic and environmental factors among MDMA users in cognitive performance

This study is aimed to clarify the association between MDMA cumulative use and cognitive dysfunction, and the potential role of candidate genetic polymorphisms in explaining individual differences in the cognitive effects of MDMA. Gene polymorphisms related to reduced serotonin function, poor competency of executive control and memory consolidation systems, and high enzymatic activity linked to bioactivation of MDMA to neurotoxic metabolites may contribute to explain variations in the cognitive impact of MDMA across regular users of this drug. Sixty ecstasy polydrug users, 110 cannabis users and 93 non-drug users were assessed using cognitive measures of Verbal Memory (California Verbal Learning Test, CVLT), Visual Memory (Rey-Osterrieth Complex Figure Test, ROCFT), Semantic Fluency, and Perceptual Attention (Symbol Digit Modalities Test, SDMT). Participants were also genotyped for polymorphisms within the 5HTT, 5HTR2A, COMT, CYP2D6, BDNF, and GRIN2B genes using polymerase chain reaction and TaqMan polymerase assays. Lifetime cumulative MDMA use was significantly associated with poorer performance on visuospatial memory and perceptual attention. Heavy MDMA users (>100 tablets lifetime use) interacted with candidate gene polymorphisms in explaining individual differences in cognitive performance between MDMA users and controls. MDMA users carrying COMT val/val and SERT s/s had poorer performance than paired controls on visuospatial attention and memory, and MDMA users with CYP2D6 ultra-rapid metabolizers performed worse than controls on semantic fluency. Both MDMA lifetime use and gene-related individual differences influence cognitive dysfunction in ecstasy users.

Combining genetic and demographic data for the conservation of a Mediterranean habitat-forming species

The integration of ecological and evolutionary data is highly valuable for conservation planning. However, it has been rarely used in the marine realm, where the adequate design of marine protected areas (MPAs) is urgently needed. Here, we examined the interacting processes underlying the patterns of genetic structure and demographic strucuture of a highly vulnerable Mediterranean habitat-forming species (i.e. Paramuricea clavata (Risso, 1826)), with particular emphasis on the processes of contemporary dispersal, genetic drift, and colonization of a new population. Isolation by distance and genetic discontinuities were found, and three genetic clusters were detected; each submitted to variations in the relative impact of drift and gene flow. No founder effect was found in the new population. The interplay of ecology and evolution revealed that drift is strongly impacting the smallest, most isolated populations, where partial mortality of individuals was highest. Moreover, the eco-evolutionary analyses entailed important conservation implications for P. clavata. Our study supports the inclusion of habitat-forming organisms in the design of MPAs and highlights the need to account for genetic drift in the development of MPAs. Moreover, it reinforces the importance of integrating genetic and demographic data in marine conservation.

Association study of lipoprotein(a) genetic markers, traditional risk factors, and coronary heart disease in HIV-1-infected patients.

Objectives: General population studies have shown associations between copy number variation (CNV) of the LPA gene Kringle-IV type-2 (KIV-2) coding region, single-nucleotide polymorphism (SNP) rs6415084 in LPA and coronary heart disease (CHD). Because risk factors for HIV-infected patients may differ from the general population, we aimed to assess whether these potential associations also occur in HIV-infected patients. Methods: A unicenter, retrospective, case-control (1:3) study. Eighteen HIV-patients with confirmed diagnosis of acute myocardial infarction (AMI) were adjusted for age, gender, and time since HIV diagnosis to 54 HIV-patients without CHD. After gDNA extraction from frozen blood, both CNV and SNP genotyping were performed using real-time quantitative PCR. All genetic and non-genetic variables for AMI were assessed in a logistic regression analysis. Results: Our results did not confirm any association in terms of lipoprotein(a) LPA structural genetic variants when comparing KIV-2 CNV (p = 0.67) and SNP genotypes (p = 0.44) between AMI cases and controls. However, traditional risk factors such as diabetes mellitus, hypertension, and CD4(+) T cell count showed association (p < 0.05) with CHD. Conclusion: Although significant associations of AMI with diabetes, hypertension and CD4(+) T cell count in HIV-patients were found, this study could not confirm the feasibility neither of KIV-2 CNV nor rs6415084 in LPA as genetic markers of CHD in HIV-infected patients.Highlights:● Individuals with HIV infection are at higher risk of coronary heart disease (CHD) than the non-infected population.● Our results showed no evidence of LPA structural genetic variants associated with CHD in HIV-1-infected patients.● Associations were found between diabetes mellitus, arterial hypertension, CD4(+) T cell count, and CHD.● The clinical usefulness of these biomarkers to predict CHD in HIV-1-infected population remains unproven.● Further studies are needed to assess the contribution of common genetic variations to CHD in HIV-infected individuals.

Genetic origin of the relationship between parental negativity and behavior problems from early childhood to adolescence: A longitudinal genetically sensitive study.

Little is known about how genetic and environmental factors contribute to the association between parental negativity and behavior problems from early childhood to adolescence. The current study fitted a cross-lagged model in a sample consisting of 4,075 twin pairs to explore (a) the role of genetic and environmental factors in the relationship between parental negativity and behavior problems from age 4 to age 12, (b) whether parent-driven and child-driven processes independently explain the association, and (c) whether there are sex differences in this relationship. Both phenotypes showed substantial genetic influence at both ages. The concurrent overlap between them was mainly accounted for by genetic factors. Causal pathways representing stability of the phenotypes and parent-driven and child-driven effects significantly and independently account for the association. Significant but slight differences were found between males and females for parent-driven effects. These results were highly similar when general cognitive ability was added as a covariate. In summary, the longitudinal association between parental negativity and behavior problems seems to be bidirectional and mainly accounted for by genetic factors. Furthermore, child-driven effects were mainly genetically mediated, and parent-driven effects were a function of both genetic and shared-environmental factors.

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.

Geological and Geomorphological Cartography at Scale 1: 10.000: a Tool of Management for Towns

Geological and geomorphological mapping at scale 1:10.000 besides from being an important source of scientific information it is also a necessary tool for municipal organs in order to make proper decisions when dealing with geo-environmental problems concerning integral territorial development. In this work, detailed information is given on the contents of such maps, their social and economical application, and a balance of the investment and gains that derives from them

Gene-disease network analysis reveals functional modules in mendelian, complex and environmental diseases

AbstractBACKGROUND: Scientists have been trying to understand the molecular mechanisms of diseases to design preventive and therapeutic strategies for a long time. For some diseases, it has become evident that it is not enough to obtain a catalogue of the disease-related genes but to uncover how disruptions of molecular networks in the cell give rise to disease phenotypes. Moreover, with the unprecedented wealth of information available, even obtaining such catalogue is extremely difficult.PRINCIPAL FINDINGS: We developed a comprehensive gene-disease association database by integrating associations from several sources that cover different biomedical aspects of diseases. In particular, we focus on the current knowledge of human genetic diseases including mendelian, complex and environmental diseases. To assess the concept of modularity of human diseases, we performed a systematic study of the emergent properties of human gene-disease networks by means of network topology and functional annotation analysis. The results indicate a highly shared genetic origin of human diseases and show that for most diseases, including mendelian, complex and environmental diseases, functional modules exist. Moreover, a core set of biological pathways is found to be associated with most human diseases. We obtained similar results when studying clusters of diseases, suggesting that related diseases might arise due to dysfunction of common biological processes in the cell.CONCLUSIONS: For the first time, we include mendelian, complex and environmental diseases in an integrated gene-disease association database and show that the concept of modularity applies for all of them. We furthermore provide a functional analysis of disease-related modules providing important new biological insights, which might not be discovered when considering each of the gene-disease association repositories independently. Hence, we present a suitable framework for the study of how genetic and environmental factors, such as drugs, contribute to diseases.AVAILABILITY: The gene-disease networks used in this study and part of the analysis are available at http://ibi.imim.es/DisGeNET/DisGeNETweb.html#Download

Lack of support for the association between facial shape and aggression: a reappraisal based on a worldwide population genetics perspective

Antisocial and criminal behaviors are multifactorial traits whose interpretation relies on multiple disciplines. Since these interpretations may have social, moral and legal implications, a constant review of the evidence is necessary before any scientific claim is considered as truth. A recent study proposed that men with wider faces relative to facial height (fWHR) are more likely to develop unethical behaviour mediated by a psychological sense of power. This research was based on reports suggesting that sexual dimorphism and selection would be responsible for a correlation between fWHR and aggression. Here we show that 4,960 individuals from 94 modern human populations belonging to a vast array of genetic and cultural contexts do not display significant amounts of fWHR sexual dimorphism. Further analyses using populations with associated ethnographical records as well as samples of male prisoners of the Mexico City Federal Penitentiary condemned by crimes of variable level of inter-personal aggression (homicide, robbery, and minor faults) did not show significant evidence, suggesting that populations/individuals with higher levels of bellicosity, aggressive behaviour, or power-mediated behaviour display greater fWHR. Finally, a regression analysis of fWHR on individual"s fitness showed no significant correlation between this facial trait and reproductive success. Overall, our results suggest that facial attributes are poor predictors of aggressive behaviour, or at least, that sexual selection was weak enough to leave a signal on patterns of between- and within-sex and population facial variation.

Aggressivity, violence, sociability and conflict resolution: What genes can tell us.

Conflicts are inherent to the human condition, as they are for all living beings. Disputes about resources or access to mating partners are among the most common causes of conflict. Conflict is herein defined as a struggle or contest between individuals or parties, and may involve a variety of aggressive behaviours. In humans, aggressiveness, violence and conflicts, including individual predisposal to conflict resolution, have traditionally been said to have deep cultural roots, but recent research in both neuroscience and genetics has shown the influence of genes on such complex behavioural traits. In this paper, recent data on the genetic aspects of these interrelated behaviours will be put together, including the effects of particular genes, the influence of stress and gender on gene regulation, and gene-environment interactions, all of which may influence biological predisposal to conflict resolution. Other genetically influenced behavioural aspects involved in conflicts and conflict resolution, such as sociability, will also be discussed. The importance of taking into account genetic and biological data to provide strategies for conflict resolution will be highlighted.

Promoter DNA Hypermethylation and Gene Repression in Undifferentiated Arabidopsis Cells

Maintaining and acquiring the pluripotent cell state in plants is critical to tissue regeneration and vegetative multiplication. Histone-based epigenetic mechanisms are important for regulating this undifferentiated state. Here we report the use of genetic and pharmacological experimental approaches to show that Arabidopsis cell suspensions and calluses specifically repress some genes as a result of promoter DNA hypermethylation. We found that promoters of the MAPK12, GSTU10 and BXL1 genes become hypermethylated in callus cells and that hypermethylation also affects the TTG1, GSTF5, SUVH8, fimbrin and CCD7 genes in cell suspensions. Promoter hypermethylation in undifferentiated cells was associated with histone hypoacetylation and primarily occurred at CpG sites. Accordingly, we found that the process specifically depends on MET1 and DRM2 methyltransferases, as demonstrated with DNA methyltransferase mutants. Our results suggest that promoter DNA methylation may be another important epigenetic mechanism for the establishment and/or maintenance of the undifferentiated state in plant cells.