VariScan Software

VariScan is a software package for the analysis of DNA sequence polymorphisms at the whole genome scale. Among other features, the software:(1) can conduct many population genetic analyses; (2) incorporates a multiresolution wavelet transform-based method that allows capturing relevant information from DNA polymorphism data; and (3) it facilitates the visualization of the results in the most commonly used genome browsers.

Concentrative nucleoside transporter 1 (hCNT1) promotes phenotypic changes relevant to tumor biology in a translocation independent manner

Nucleoside transporters (NTs) mediate the uptake of nucleosides and nucleobases across the plasma membrane, mostly for salvage purposes. The canonical NTs belong to two gene families, SLC29 and SLC28. The former encode equilibrative nucleoside transporter proteins (ENTs), which mediate the facilitative diffusion of natural nucleosides with broad selectivity, whereas the latter encode concentrative nucleoside transporters (CNTs), which are sodium-coupled and show high affinity for substrates with variable selectivity. These proteins are expressed in most cell types, exhibiting apparent functional redundancy. This might indicate that CNTs play specific roles in the physiology of the cell beyond nucleoside salvage. Here, we addressed this possibility using adenoviral vectors to restore tumor cell expression of hCNT1 or a polymorphic variant (hCNT1S546P) lacking nucleoside translocation ability. We found that hCNT1 restoration in pancreatic cancer cells significantly altered cell-cycle progression and phosphorylation status of key signal-transducing kinases, promoted poly-(ADP ribose) polymerase hyperactivation and cell death, and reduced tumor growth and cell migration. Importantly, the translocation-defective transporter triggered these same effects on cell physiology. These data predict a novel and totally unexpected biological role for the nucleoside transporter protein hCNT1 that appears to be independent of its role as mediator of nucleoside uptake by cells, thereby suggesting a transceptor function. Cell Death & Disease Anastasis Stephanou Receiving Editor Cell Death & Disease 19th Apr 2013 Dr Perez-Torras Av/ Diagonal 643. Edif. Prevosti, Pl -1 Barcelona 08028 Spain RE: Manuscript CDDIS-13-0136R, 'CDDIS-13-0136R' Dear Dr Perez-Torras, It is a pleasure to inform you that your manuscript has been evaluated at the editorial level and has now been officially accepted for publication in Cell Death & Disease, pending you meet the following editorial requirements: 1) the list of the abbreviations is missing please include Could you send us the revised text as word file via e-mail and we will proceed and transfer the paper onto our typesetters. Please download, print, sign, and return the Licence to Publish Form using the link below. This must be returned via FAX to ++ 39 06 7259 6977 before your manuscript can be published:

Aberrant features of the Messinian coral reefs, Spain

Se describen someramente los principales arrecifes del Messiniense en España, haciendo hincapié en el conjunto de 'anomalias' presentan los arrecifes del Neógeno inferior en comparación con las asociaciones arrecifales actuales. Se discute la importancia y significado de Porites sp. como coral claramente dominante, y a menudo exclusivo, en la construcción de edificios arrecifales.

The relative salience of facial features when differentiating faces based on an interference paradigm

Research on face recognition and social judgment usually addresses the manipulation of facial features (eyes, nose, mouth, etc.). Using a procedure based on a Stroop-like task, Montepare and Opeyo (J Nonverbal Behav 26(1):43-59, 2002) established a hierarchy of the relative salience of cues based on facial attributes when differentiating faces. Using the same perceptual interference task, we established a hierarchy of facial features. Twenty-three participants (13 men and 10 women) volunteered for the experiment to compare pairs of frontal faces. The participants had to judge if the eyes, nose, mouth and chin in the pair of images were the same or different. The factors manipulated were the target-distractive factor (4 face components 9 3 distractive factors), interference (absent vs. present) and correct answer (the same vs. different). The analysis of reaction times and errors showed that the eyes and mouth were processed before the chin and nose, thus highlighting the critical importance of the eyes and mouth, as shown by previous research.

Identification of Methylated Genes Associated with Aggressive Clinicopathological Features in Mantle Cell Lymphoma

Background: Mantle cell lymphoma (MCL) is genetically characterized by the t(11;14)(q13;q32) translocation and a high number of secondary chromosomal alterations. The contribution of DNA methylation to MCL lymphomagenesis is not well known. We sought to identify epigenetically silenced genes in these tumours that might have clinical relevance. Methodology/Principal Findings: To identify potential methylated genes in MCL we initially investigated seven MCL cell lines treated with epigenetic drugs and gene expression microarray profiling. The methylation status of selected candidate genes was validated by a quantitative assay and subsequently analyzed in a series of primary MCL (n=38). After pharmacological reversion we identified 252 potentially methylated genes. The methylation analysis of a subset of these genes (n=25) in the MCL cell lines and normal B lymphocytes confirmed that 80% of them were methylated in the cell lines but not in normal lymphocytes. The subsequent analysis in primary MCL identified five genes (SOX9,HOXA9,AHR,NR2F2 ,and ROBO1) frequently methylated in these tumours. The gene methylation events tended to occur in the same primary neoplasms and correlated with higher proliferation, increased number of chromosomal abnormalities, and shorter survival of the patients. Conclusions: We have identified a set of genes whose methylation degree and gene expression levels correlate with aggressive clinicopathological features of MCL. Our findings also suggest that a subset of MCL might show a CpG island methylator phenotype (CIMP) that may influence the behaviour of the tumours.

Defining ecologically relevant water quality targets for lakes in Europe

1. The implementation of the Water Framework Directive requires EU member states to establish and harmonize ecological status class boundaries for biological quality elements. In this paper, we describe an approach for defining ecological class boundaries that delineates shifts in lake ecosystem functioning and, therefore, provides ecologically meaningful targets for water policy in Europe. 2. We collected an extensive data set of 810 lake-years from nine Central European countries, and we used phytoplankton chlorophyll a, a metric widely used to measure the impact of eutrophication in lakes. Our approach establishes chlorophyll a target values in relation to three significant ecological effects of eutrophication: the decline of aquatic macrophytes, the dominance of potentially harmful cyanobacteria and the major functional switch from a clear water to a turbid state. 3. Ranges of threshold chlorophyll a concentrations are given for the two most common lake types in lowland Central Europe: for moderately deep lakes (mean depth 3–15 m), the greatest ecological shifts occur in the range 10–12 lg L 1 chlorophyll a, and for shallow lakes (<3 m mean depth), in the range 21–23 lg L 1 chlorophyll a. 4. Synthesis and applications. Our study provides class boundaries for determining the ecological status of lakes, which have robust ecological consequences for lake functioning and which, therefore, provide strong and objective targets for sustainable water management in Europe. The results have been endorsed by all participant member states and adopted in the European Commission legislation, marking the first attempt in international water policy to move from physico-chemical quality standards to harmonized ecologically based quality targets.

Use and perception of urban green spaces in Barcelona

Background: Although the mechanisms are not well understood yet, evidence exists of the benefits of urban green spaces for human health. As a consequence, one of the concerns of public health interventions must be to promote the use of urban green spaces within cities. Aims: This study aims to explore the citizens’ purposes of use of urban green spaces as well as the elements related to the characteristics of these places that condition their use. Methods: In-depth interviews were conducted with non-hospitalised people living in different areas of Barcelona, with different socioeconomic status and different residential distance to urban green spaces (n = 20). Thematic content analysis of the qualitative data was performed. Results: Physical pursuits and attention restoration were identified as prominent purposes of use of urban green spaces. The natural features of urban green spaces were identified as the most relevant determiners for the use of these places. Conclusions: To promote the use of urban green spaces, qualitative findings from this study suggest that purpose-built places should be provided. Moreover, natural features of urban green spaces must be particularly taken into account when designing and maintaining them.

CERKL Knockdown Causes Retinal Degeneration in Zebrafish

The human CERKL gene is responsible for common and severe forms of retinal dystrophies. Despite intense in vitro studies at the molecular and cellular level and in vivo analyses of the retina of murine knockout models, CERKL function remains unknown. In this study, we aimed to approach the developmental and functional features of cerkl in Danio rerio within an Evo-Devo framework. We show that gene expression increases from early developmental stages until the formation of the retina in the optic cup. Unlike the high mRNA-CERKL isoform multiplicity shown in mammals, the moderate transcriptional complexity in fish facilitates phenotypic studies derived from gene silencing. Moreover, of relevance to pathogenicity, teleost CERKL shares the two main human protein isoforms. Morpholino injection has been used to generate a cerkl knockdown zebrafish model. The morphant phenotype results in abnormal eye development with lamination defects, failure to develop photoreceptor outer segments, increased apoptosis of retinal cells and small eyes. Our data support that zebrafish Cerkl does not interfere with proliferation and neural differentiation during early developmental stages but is relevant for survival and protection of the retinal tissue. Overall, we propose that this zebrafish model is a powerful tool to unveil CERKL contribution to human retinal degeneration

Neotectonic features in the Catalan Coastal Ranges, Northeastern Spain

The Catalan Coastal Ranges constitute the northwestem emerged sector of the Catalan-Valencian domain of the Valencia trough. Since late Oligocene this domain of the Valencia trough was subjected to extension wich gradually attenuated during later periods. The Miocene tectonic evolution of the Catalan Coastal Ranges is relativelly well known while the Pliocene to-Quaternary stages have not been studied in detail. The recorded seismicity of the area is moderate and constant but not sufficiently intense to cliaracterize and locate recent tectonics. However, geological analysis provides further information. A morphotectonic and deformational analysis of the Catalan Coastal Ranges is presented in this paper.

Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes.

Background Chronic obstructive pulmonary disease (COPD) is increasingly considered a heterogeneous condition. It was hypothesised that COPD, as currently defined, includes different clinically relevant subtypes. Methods To identify and validate COPD subtypes, 342 subjects hospitalised for the first time because of a COPD exacerbation were recruited. Three months after discharge, when clinically stable, symptoms and quality of life, lung function, exercise capacity, nutritional status, biomarkers of systemic and bronchial inflammation, sputum microbiology, CT of the thorax and echocardiography were assessed. COPD groups were identified by partitioning cluster analysis and validated prospectively against cause-specific hospitalisations and all-cause mortality during a 4 year follow-up. Results Three COPD groups were identified: group 1 (n ¼ 126, 67 years) was characterised by severe airflow limitation (postbronchodilator forced expiratory volume in 1 s (FEV 1 ) 38% predicted) and worse performance in most of the respiratory domains of the disease; group 2 (n ¼ 125, 69 years) showed milder airflow limitation (FEV 1 63% predicted); and group 3 (n ¼ 91, 67 years) combined a similarly milder airflow limitation (FEV 1 58% predicted) with a high proportion of obesity, cardiovascular disorders, iabetes and systemic inflammation. During follow-up, group 1 had more frequent hospitalisations due to COPD (HR 3.28, p < 0.001) and higher all-cause mortality (HR 2.36, p ¼ 0.018) than the other two groups, whereas group 3 had more admissions due to cardiovascular disease (HR 2.87, p ¼ 0.014). Conclusions In patients with COPD recruited at their first hospitalisation, three different COPD subtypes were identified and prospectively validated:"severe respiratory COPD","moderate respiratory COPD", and"systemic COPD'

New features of the layer-by-layer deposition of microcrystalline silicon films revealed by spectroscopic ellipsometry and high resolution transmission electron microscopy

Spectroscopic ellipsometry and high resolution transmission electron microscopy have been used to characterize microcrystalline silicon films. We obtain an excellent agreement between the multilayer model used in the analysis of the optical data and the microscopy measurements. Moreover, thanks to the high resolution achieved in the microscopy measurements and to the improved optical models, two new features of the layer-by-layer deposition of microcrystalline silicon have been detected: i) the microcrystalline films present large crystals extending from the a-Si:H substrate to the film surface, despite the sequential process in the layer-by-layer deposition; and ii) a porous layer exists between the amorphous silicon substrate and the microcrystalline silicon film.

CBS: an open platform that integrates predictive methods and epigenetics information to characterize conserved regulatory features in multiple Drosophila genomes.

Background: Information about the composition of regulatory regions is of great value for designing experiments to functionally characterize gene expression. The multiplicity of available applications to predict transcription factor binding sites in a particular locus contrasts with the substantial computational expertise that is demanded to manipulate them, which may constitute a potential barrier for the experimental community. Results: CBS (Conserved regulatory Binding Sites, http://compfly.bio.ub.es/CBS) is a public platform of evolutionarily conserved binding sites and enhancers predicted in multiple Drosophila genomes that is furnished with published chromatin signatures associated to transcriptionally active regions and other experimental sources of information. The rapid access to this novel body of knowledge through a user-friendly web interface enables non-expert users to identify the binding sequences available for any particular gene, transcription factor, or genome region. Conclusions: The CBS platform is a powerful resource that provides tools for data mining individual sequences and groups of co-expressed genes with epigenomics information to conduct regulatory screenings in Drosophila.

Selecting the most relevant variables for anaerobic digestion imbalances : Two case studies

In this study, a wrapper approach was applied to objectively select the most important variables related to two different anaerobic digestion imbalances, acidogenic states and foaming. This feature selection method, implemented in artificial neural networks (ANN), was performed using input and output data from a fully instrumented pilot plant (1 m 3 upflow fixed bed digester). Results for acidogenic states showed that pH, volatile fatty acids, and inflow rate were the most relevant variables. Results for foaming showed that inflow rate and total organic carbon were among the relevant variables, both of which were related to the feed loading of the digester. Because there is not a complete agreement on the causes of foaming, these results highlight the role of digester feeding patterns in the development of foaming

Body Image in Eating Disorders: The Influence of Exposure to Virtual-Reality Environments.

The aim of this article was to study the effect of virtual-reality exposure to situations that are emotionally significant for patients with eating disorders (ED) on the stability of body-image distortion and body-image dissatisfaction. A total of 85 ED patients and 108 non-ED students were randomly exposed to four experimental virtual environments: a kitchen with low-calorie food, a kitchen with high-calorie food, a restaurant with low-calorie food, and a restaurant with high-calorie food. In the interval between the presentation of each situation, body-image distortion and body-image dissatisfaction were assessed. Several 2 x 2 x 2 repeated measures analyses of variance (high-calorie vs. low-calorie food x presence vs. absence of people x ED group vs. control group) showed that ED participants had significantly higher levels of body-image distortion and body dissatisfaction after eating high-calorie food than after eating low-calorie food, while control participants reported a similar body image in all situations. The results suggest that body-image distortion and body-image dissatisfaction show both trait and state features. On the one hand, ED patients show a general predisposition to overestimate their body size and to feel more dissatisfied with their body image than controls. On the other hand, these body-image disturbances fluctuate when participants are exposed to virtual situations that are emotionally relevant for them.

Influence of the claimant’s behavioural features on motor compensation outcomes

The decision to settle a motor insurance claim by either negotiation or trial is analysed. This decision may depend on how risk and confrontation adverse or pessimistic the claimant is. The extent to which these behavioural features of the claimant might influence the final compensation amount are examined. An empirical analysis, fitting a switching regression model to a Spanish database, is conducted in order to analyze whether the choice of the conflict resolution procedure is endogenous to the compensation outcomes. The results show that compensations awarded by courts are always higher, although 95% of cases are settled by negotiation. We show that this is because claimants are adverse to risk and confrontation, and are pessimistic about their chances at trial. By contrast, insurers are risk - confrontation neutral and more objective in relation to the expected trial compensation. During the negotiation insurers accept to pay the subjective compensation values of claimants, since these values are lower than their estimates of compensations at trial.