DisPhaseDB: An integrative database of diseases related variations in liquid-liquid phase separation proteins.

Motivation: Proteins involved in liquid-liquid phase separation (LLPS) and membraneless organelles (MLOs) are recognized to be decisive for many biological processes and also responsible for several diseases. The recent explosion of research in the area still lacks tools for the analysis and data integration among different repositories. Currently, there is not a comprehensive and dedicated database that collects all disease-related variations in combination with the protein location, biological role in the MLO, and all the metadata available for each protein and disease. Disease-related protein variants and additional features are dispersed and the user has to navigate many databases, with a different focus, formats, and often not user friendly. Results: We present DisPhaseDB, a database dedicated to disease-related variants of liquid-liquid phase separation proteins. It integrates 10 databases, contains 5,741 proteins, 1,660,059 variants, and 4,051 disease terms. It also offers intuitive navigation and an informative display. It constitutes a pivotal starting point for further analysis, encouraging the development of new computational tools.The database is freely available at http://disphasedb.leloir.org.ar.

Tejaas: reverse regression increases power for detecting trans-eQTLs.

Trans-acting expression quantitative trait loci (trans-eQTLs) account for ≥70% expression heritability and could therefore facilitate uncovering mechanisms underlying the origination of complex diseases. Identifying trans-eQTLs is challenging because of small effect sizes, tissue specificity, and a severe multiple-testing burden. Tejaas predicts trans-eQTLs by performing L2-regularized "reverse" multiple regression of each SNP on all genes, aggregating evidence from many small trans-effects while being unaffected by the strong expression correlations. Combined with a novel unsupervised k-nearest neighbor method to remove confounders, Tejaas predicts 18851 unique trans-eQTLs across 49 tissues from GTEx. They are enriched in open chromatin, enhancers, and other regulatory regions. Many overlap with disease-associated SNPs, pointing to tissue-specific transcriptional regulation mechanisms.

Peribulbar anesthesia for strabismus surgery in adult patients.

PURPOSE: To evaluate the efficacy and safety of peribulbar anesthesia during strabismus surgery. METHODS: Medical records of patients undergoing strabismus surgery and peribulbar anesthesia were reviewed. The overall efficacy of peribulbar anesthesia was evaluated as requirement of supplemental peribulbar anesthesia, impossibility to perform eye muscles surgery due to inadequate efficacy of the block and peribulbar block complications that occurred up to 6 weeks postoperatively. Presence of oculocardiac reflex (OCR) and presence of decreased visual acuity and afferent pupillary defect postoperatively were reported. RESULTS: A total of 510 patients comprised our study group. The total amount of peribulbar injections was 717. Four patients (0.7%) required supplemental injection in the superonasal quadrant. Five of 510 (0.9%) required an anesthesiologic intervention with intravenous atropine. Eighty patients of 510 (15.6%) complained about transitory complete ptosis and/or amaurosis postoperatively. No complications were observed up to 6 weeks postoperatively. CONCLUSION: Peribulbar anesthesia was an effective and safe option during strabismus surgery in adult patients.

PremPDI estimates and interprets the effects of missense mutations on protein-DNA interactions.

Protein-DNA interactions play important roles in regulations of many vital cellular processes, including transcription, translation, DNA replication and recombination. Sequence variants occurring in these DNA binding proteins that alter protein-DNA interactions may cause significant perturbations or complete abolishment of function, potentially leading to diseases. Developing a mechanistic understanding of impacts of variants on protein-DNA interactions becomes a persistent need. To address this need we introduce a new computational method PremPDI that predicts the effect of single missense mutation in the protein on the protein-DNA interaction and calculates the quantitative binding affinity change. The PremPDI method is based on molecular mechanics force fields and fast side-chain optimization algorithms with parameters optimized on experimental sets of 219 mutations from 49 protein-DNA complexes. PremPDI yields a very good agreement between predicted and experimental values with Pearson correlation coefficient of 0.71 and root-mean-square error of 0.86 kcal mol-1. The PremPDI server could map mutations on a structural protein-DNA complex, calculate the associated changes in binding affinity, determine the deleterious effect of a mutation, and produce a mutant structural model for download. PremPDI can be applied to many tasks, such as determination of potential damaging mutations in cancer and other diseases. PremPDI is available at http://lilab.jysw.suda.edu.cn/research/PremPDI/.

MISTIC2: comprehensive server to study coevolution in protein families.

Correlated mutations between residue pairs in evolutionarily related proteins arise from constraints needed to maintain a functional and stable protein. Identifying these inter-related positions narrows down the search for structurally or functionally important sites. MISTIC is a server designed to assist users to calculate covariation in protein families and provide them with an interactive tool to visualize the results. Here, we present MISTIC2, an update to the previous server, that allows to calculate four covariation methods (MIp, mfDCA, plmDCA and gaussianDCA). The results visualization framework has been reworked for improved performance, compatibility and user experience. It includes a circos representation of the information contained in the alignment, an interactive covariation network, a 3D structure viewer and a sequence logo. Others components provide additional information such as residue annotations, a roc curve for assessing contact prediction, data tables and different ways of filtering the data and exporting figures. Comparison of different methods is easily done and scores combination is also possible. A newly implemented web service allows users to access MISTIC2 programmatically using an API to calculate covariation and retrieve results. MISTIC2 is available at: https://mistic2.leloir.org.ar.

Exploring Protein-Protein Interactions as Drug Targets for Anti-cancer Therapy with In Silico Workflows.

We describe a computational protocol to aid the design of small molecule and peptide drugs that target protein-protein interactions, particularly for anti-cancer therapy. To achieve this goal, we explore multiple strategies, including finding binding hot spots, incorporating chemical similarity and bioactivity data, and sampling similar binding sites from homologous protein complexes. We demonstrate how to combine existing interdisciplinary resources with examples of semi-automated workflows. Finally, we discuss several major problems, including the occurrence of drug-resistant mutations, drug promiscuity, and the design of dual-effect inhibitors.

MutaBind estimates and interprets the effects of sequence variants on protein-protein interactions.

Proteins engage in highly selective interactions with their macromolecular partners. Sequence variants that alter protein binding affinity may cause significant perturbations or complete abolishment of function, potentially leading to diseases. There exists a persistent need to develop a mechanistic understanding of impacts of variants on proteins. To address this need we introduce a new computational method MutaBind to evaluate the effects of sequence variants and disease mutations on protein interactions and calculate the quantitative changes in binding affinity. The MutaBind method uses molecular mechanics force fields, statistical potentials and fast side-chain optimization algorithms. The MutaBind server maps mutations on a structural protein complex, calculates the associated changes in binding affinity, determines the deleterious effect of a mutation, estimates the confidence of this prediction and produces a mutant structural model for download. MutaBind can be applied to a large number of problems, including determination of potential driver mutations in cancer and other diseases, elucidation of the effects of sequence variants on protein fitness in evolution and protein design. MutaBind is available at http://www.ncbi.nlm.nih.gov/projects/mutabind/.

I-COMS: Interprotein-COrrelated Mutations Server.

Interprotein contact prediction using multiple sequence alignments (MSAs) is a useful approach to help detect protein-protein interfaces. Different computational methods have been developed in recent years as an approximation to solve this problem. However, as there are discrepancies in the results provided by them, there is still no consensus on which is the best performing methodology. To address this problem, I-COMS (interprotein COrrelated Mutations Server) is presented. I-COMS allows to estimate covariation between residues of different proteins by four different covariation methods. It provides a graphical and interactive output that helps compare results obtained using different methods. I-COMS automatically builds the required MSA for the calculation and produces a rich visualization of either intraprotein and/or interprotein covariating positions in a circos representation. Furthermore, comparison between any two methods is available as well as the overlap between any or all four methodologies. In addition, as a complementary source of information, a matrix visualization of the corresponding scores is made available and the density plot distribution of the inter, intra and inter+intra scores are calculated. Finally, all the results can be downloaded (including MSAs, scores and graphics) for comparison and visualization and/or for further analysis.

The emergence of sex differences in personality traits in early adolescence: A cross-sectional, cross-cultural study.

Although large international studies have found consistent patterns of sex differences in personality traits among adults (i.e., women scoring higher on most facets), less is known about cross-cultural sex differences in adolescent personality and the role of culture and age in shaping them. The present study examines the NEO Personality Inventory-3 (McCrae, Costa, & Martin, 2005) informant ratings of adolescents from 23 cultures (N = 4,850), and investigates culture and age as sources of variability in sex differences of adolescents' personality. The effect for Neuroticism (with females scoring higher than males) begins to take on its adult form around age 14. Girls score higher on Openness to Experience and Conscientiousness at all ages between 12 and 17 years. A more complex pattern emerges for Extraversion and Agreeableness, although by age 17, sex differences for these traits are highly similar to those observed in adulthood. Cross-sectional data suggest that (a) with advancing age, sex differences found in adolescents increasingly converge toward adult patterns with respect to both direction and magnitude; (b) girls display sex-typed personality traits at an earlier age than boys; and (c) the emergence of sex differences was similar across cultures. Practical implications of the present findings are discussed. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Kin-Driver: a database of driver mutations in protein kinases.

Somatic mutations in protein kinases (PKs) are frequent driver events in many human tumors, while germ-line mutations are associated with hereditary diseases. Here we present Kin-driver, the first database that compiles driver mutations in PKs with experimental evidence demonstrating their functional role. Kin-driver is a manual expert-curated database that pays special attention to activating mutations (AMs) and can serve as a validation set to develop new generation tools focused on the prediction of gain-of-function driver mutations. It also offers an easy and intuitive environment to facilitate the visualization and analysis of mutations in PKs. Because all mutations are mapped onto a multiple sequence alignment, analogue positions between kinases can be identified and tentative new mutations can be proposed for studying by transferring annotation. Finally, our database can also be of use to clinical and translational laboratories, helping them to identify uncommon AMs that can correlate with response to new antitumor drugs. The website was developed using PHP and JavaScript, which are supported by all major browsers; the database was built using MySQL server. Kin-driver is available at: http://kin-driver.leloir.org.ar/

Highlights from the 1st ISCB Latin American Student Council Symposium 2014. Introduction.

This report summarizes the scientific content and activities of the first edition of the Latin American Symposium organized by the Student Council of the International Society for Computational Biology (ISCB), held in conjunction with the Third Latin American conference from the International Society for Computational Biology (ISCB-LA 2014) in Belo Horizonte, Brazil, on October 27, 2014.

The Inaccuracy of National Character Stereotypes.

Consensual stereotypes of some groups are relatively accurate, whereas others are not. Previous work suggesting that national character stereotypes are inaccurate has been criticized on several grounds. In this article we (a) provide arguments for the validity of assessed national mean trait levels as criteria for evaluating stereotype accuracy; and (b) report new data on national character in 26 cultures from descriptions (N=3,323) of the typical male or female adolescent, adult, or old person in each. The average ratings were internally consistent and converged with independent stereotypes of the typical culture member, but were weakly related to objective assessments of personality. We argue that this conclusion is consistent with the broader literature on the inaccuracy of national character stereotypes.

MISTIC: Mutual information server to infer coevolution.

MISTIC (mutual information server to infer coevolution) is a web server for graphical representation of the information contained within a MSA (multiple sequence alignment) and a complete analysis tool for Mutual Information networks in protein families. The server outputs a graphical visualization of several information-related quantities using a circos representation. This provides an integrated view of the MSA in terms of (i) the mutual information (MI) between residue pairs, (ii) sequence conservation and (iii) the residue cumulative and proximity MI scores. Further, an interactive interface to explore and characterize the MI network is provided. Several tools are offered for selecting subsets of nodes from the network for visualization. Node coloring can be set to match different attributes, such as conservation, cumulative MI, proximity MI and secondary structure. Finally, a zip file containing all results can be downloaded. The server is available at http://mistic.leloir.org.ar. In summary, MISTIC allows for a comprehensive, compact, visually rich view of the information contained within an MSA in a manner unique to any other publicly available web server. In particular, the use of circos representation of MI networks and the visualization of the cumulative MI and proximity MI concepts is novel.

Stereotypes of age differences in personality traits: universal and accurate?

Age trajectories for personality traits are known to be similar across cultures. To address whether stereotypes of age groups reflect these age-related changes in personality, we asked participants in 26 countries (N = 3,323) to rate typical adolescents, adults, and old persons in their own country. Raters across nations tended to share similar beliefs about different age groups; adolescents were seen as impulsive, rebellious, undisciplined, preferring excitement and novelty, whereas old people were consistently considered lower on impulsivity, activity, antagonism, and Openness. These consensual age group stereotypes correlated strongly with published age differences on the five major dimensions of personality and most of 30 specific traits, using as criteria of accuracy both self-reports and observer ratings, different survey methodologies, and data from up to 50 nations. However, personal stereotypes were considerably less accurate, and consensual stereotypes tended to exaggerate differences across age groups.

Perceptions of aging across 26 cultures and their culture-level associates.

College students (N=3,435) in 26 cultures reported their perceptions of age-related changes in physical, cognitive, and socioemotional areas of functioning and rated societal views of aging within their culture. There was widespread cross-cultural consensus regarding the expected direction of aging trajectories with (a) perceived declines in societal views of aging, physical attractiveness, the ability to perform everyday tasks, and new learning; (b) perceived increases in wisdom, knowledge, and received respect; and (c) perceived stability in family authority and life satisfaction. Cross-cultural variations in aging perceptions were associated with culture-level indicators of population aging, education levels, values, and national character stereotypes. These associations were stronger for societal views on aging and perceptions of socioemotional changes than for perceptions of physical and cognitive changes. A consideration of culture-level variables also suggested that previously reported differences in aging perceptions between Asian and Western countries may be related to differences in population structure.

Gesture and metaphor comprehension: electrophysiological evidence of cross-modal coordination by audiovisual stimulation.

In recent years, studies have suggested that gestures influence comprehension of linguistic expressions, for example, eliciting an N400 component in response to a speech/gesture mismatch. In this paper, we investigate the role of gestural information in the understanding of metaphors. Event related potentials (ERPs) were recorded while participants viewed video clips of an actor uttering metaphorical expressions and producing bodily gestures that were congruent or incongruent with the metaphorical meaning of such expressions. This modality of stimuli presentation allows a more ecological approach to meaning integration. When ERPs were calculated using gesture stroke as time-lock event, gesture incongruity with metaphorical expression modulated the amplitude of the N400 and of the late positive complex (LPC). This suggests that gestural and speech information are combined online to make sense of the interlocutor's linguistic production in an early stage of metaphor comprehension. Our data favor the idea that meaning construction is globally integrative and highly context-sensitive.

Electrophysiological evidence of different interpretative strategies in irony comprehension.

We explore the hypothesis that induction of holistic or analytic strategies influences comprehension and processing of highly contextualized expressions of ordinary language, such as irony. Twenty undergraduate students were asked to categorize as coherent or incoherent a group of sentences. Each sentence completed a previous story, so that they could be ironical, literal or nonsensical endings. Participants were asked to evaluate whether each sentence was coherent or incoherent. Half of them were initially instructed to consider whether the sentences made sense (holistic condition); the other half were instructed to consider whether the sentences were congruent or incongruent (analytic condition). Behavioral responses and Event Related Potentials were registered during the experiment. Both behavioral and electrophysiological results allow clearly distinguishing between the holistic and the analytic strategies. The fact that the same set of stimuli elicits different ERP waveforms, depending on the strategy with which they are analyzed, suggests that different cognitive processes and different areas of the brain are operating in each case.

[Smoking habit in school age children, in Chile]. / Consumo de tabaco en población menor de 18 años: estudio de prevalencia en escolares de Chile.

BACKGROUND: In Chile, there is no information about the prevalence of smoking among basic and high school students. AIM: To study the prevalence of smoking among school age population. MATERAL AND METHODS: A cross sectional survey was conducted during 2001, assessing tobacco use and smoking habit in a representative sample of 15,119 randomly selected students. RESULTS: Sixty four percent of students had smoked at least once in their lifetime. Eighteen percent of students smoked daily and 15%, occasionally. The figures for women were higher (19 and 18% respectively). The mean age for the first contact with smoking was 12.3 years and, for starting the smoking habit, 13.2 years. Smokers increased the amount of cigarettes during weekends. Higher prevalence rates of smoking were observed in students from the Southern region of the country and of lower socioeconomic levels. From the 3rd grade on, there is an increased risk of having contact with tobacco and smoking for the first time and from 6th grade on, this risk becomes permanent. The adjusted Odds Ratio to be a smoker is significantly higher when the mother is a current or irregular smoker (OR 1.9 95 CI; 1.7-2.0). CONCLUSIONS: High smoking prevalence rates were detected in this survey, mainly in women. The risk for smoking starts early during school life. Therefore, health promotion programs must include elementary and high school students.

Consumo de tabaco en población menor de 18 años: estudio de prevalencia en escolares de Chile / Smoking habit in school age children, in Chile

Background: In Chile, there is no information about the prevalence of smoking among basic and high school students. Aim: To study the prevalence of smoking among school age population. Material and Methods: A cross sectional survey was conducted during 2001, assessing tobacco use and smoking habit in a representative sample of 15.119 randomly selected students. Results: Sixty four percent of students had smoked at least once in their lifetime. Eighteen percent of students smoked daily and 15 percent, occasionally. The figures for women were higher (19 and 18 percent respectively). The mean age for the first contact with smoking was 12.3 years and, for starting the smoking habit, 13.2 years. Smokers increased the amount of cigarettes during weekends. Higher prevalence rates of smoking were observed in students from the Southern region of the country and of lower socioeconomic levels. From the 3rd grade on, there is an increased risk of having contact with tobacco and smoking for the first time and from 6th grade on, this risk becomes permanent. The adjusted Odds Ratio to be a smoker is significantly higher when the mother is a current or irregular smoker (OR 1.9 95 CI; 1.7-2.0). Conclusions: High smoking prevalence rates were detected in this survey, mainly in women. The risk for smoking starts early during school life. Therefore, health promotion programs must include elementary and high school students.