A scale of functional divergence for yeast duplicated genes revealed from analysis of the protein-protein interaction network

BACKGROUND: Studying the evolution of the function of duplicated genes usually implies an estimation of the extent of functional conservation/divergence between duplicates from comparison of actual sequences. This only reveals the possible molecular function of genes without taking into account their cellular function(s). We took into consideration this latter dimension of gene function to approach the functional evolution of duplicated genes by analyzing the protein-protein interaction network in which their products are involved. For this, we derived a functional classification of the proteins using PRODISTIN, a bioinformatics method allowing comparison of protein function. Our work focused on the duplicated yeast genes, remnants of an ancient whole-genome duplication. RESULTS: Starting from 4,143 interactions, we analyzed 41 duplicated protein pairs with the PRODISTIN method. We showed that duplicated pairs behaved differently in the classification with respect to their interactors. The different observed behaviors allowed us to propose a functional scale of conservation/divergence for the duplicated genes, based on interaction data. By comparing our results to the functional information carried by GO annotations and sequence comparisons, we showed that the interaction network analysis reveals functional subtleties, which are not discernible by other means. Finally, we interpreted our results in terms of evolutionary scenarios. CONCLUSIONS: Our analysis might provide a new way to analyse the functional evolution of duplicated genes and constitutes the first attempt of protein function evolutionary comparisons based on protein-protein interactions

Subsolidus phase equilibria in the PbO-poor part of the TiO2-PbO-SiO2 system and its application in low-temperature thick-film dielectrics

Subsolidus equilibria in the PbO-poor part of the TiO2-PbO-SiO2 diagram were studied with the aim of investigating possible applications for low-temperature thick-film dielectrics. The tie lines are between PbTiO2 and PbSiO3, and between PbTiO3 and SiO2. The results show that the TiO2, when added to low-temperature softening point glasses, reacts with the PbO from the glass, so forming PbTiO3. These results were applied to a low-temperature firing dielectric, consisting of a lead-rich PbO-SiO2-B2O3 glass filled with a TiO2 powder. The conversion of TiO2 to the PbTiO3 crystalline phase was observed above firing temperatures of approximately 600 °C. The kinetics of the reaction depend on the particle size of the TiO

GOToolBox: functional analysis of gene datasets based on Gene Ontology

We have developed methods and tools based on the Gene Ontology (GO) resource allowing the identification of statistically over- or under-represented terms in a gene dataset; the clustering of functionally related genes within a set; and the retrieval of genes sharing annotations with a query gene. GO annotations can also be constrained to a slim hierarchy or a given level of the ontology. The source codes are available upon request, and distributed under the GPL license

Functional classification of proteins for the prediction of cellular function from a protein-protein interaction network

We here describe PRODISTIN, a new computational method allowing the functional clustering of proteins on the basis of protein-protein interaction data. This method, assessed biologically and statistically, enabled us to classify 11% of the Saccharomyces cerevisiae proteome into several groups, the majority of which contained proteins involved in the same biological process(es), and to predict a cellular function for many otherwise uncharacterized proteins

Postnatal Tshz3 Deletion Drives Altered Corticostriatal Function and Autism Spectrum Disorder–like Behavior

International audienceBACKGROUND: Heterozygous deletion of the TSHZ3 gene, encoding for the teashirt zinc-finger homeobox family member 3 (TSHZ3) transcription factor that is highly expressed in cortical projection neurons (CPNs), has been linked to an autism spectrum disorder (ASD) syndrome. Similarly, mice with Tshz3 haploinsufficiency show ASD-like behavior, paralleled by molecular changes in CPNs and corticostriatal synaptic dysfunctions. Here, we aimed at gaining more insight into "when" and "where" TSHZ3 is required for the proper development of the brain, and its deficiency crucial for developing this ASD syndrome. METHODS: We generated and characterized a novel mouse model of conditional Tshz3 deletion, obtained by crossing Tshz3 flox/flox with CaMKIIalpha-Cre mice, in which Tshz3 is deleted in CPNs from postnatal day 2 to 3 onward. We characterized these mice by a multilevel approach combining genetics, cell biology, electrophysiology, behavioral testing, and bioinformatics. RESULTS: These conditional Tshz3 knockout mice exhibit altered cortical expression of more than 1000 genes, w50% of which have their human orthologue involved in ASD, in particular genes encoding for glutamatergic syn-apse components. Consistently, we detected electrophysiological and synaptic changes in CPNs and impaired corticostriatal transmission and plasticity. Furthermore, these mice showed strong ASD-like behavioral deficits. CONCLUSIONS: Our study reveals a crucial postnatal role of TSHZ3 in the development and functioning of the corticostriatal circuitry and provides evidence that dysfunction in these circuits might be determinant for ASD pathogenesis. Our conditional Tshz3 knockout mouse constitutes a novel ASD model, opening the possibility for an early postnatal therapeutic window for the syndrome linked to TSHZ3 haploinsufficiency

TreeDyn: towards dynamic graphics and annotations for analyses of trees

BACKGROUND: Analyses of biomolecules for biodiversity, phylogeny or structure/function studies often use graphical tree representations. Many powerful tree editors are now available, but existing tree visualization tools make little use of meta-information related to the entities under study such as taxonomic descriptions or gene functions that can hardly be encoded within the tree itself (if using popular tree formats). Consequently, a tedious manual analysis and post-processing of the tree graphics are required if one needs to use external information for displaying or investigating trees. RESULTS: We have developed TreeDyn, a tool using annotations and dynamic graphical methods for editing and analyzing multiple trees. The main features of TreeDyn are 1) the management of multiple windows and multiple trees per window, 2) the export of graphics to several standard file formats with or without HTML encapsulation and a new format called TGF, which enables saving and restoring graphical analysis, 3) the projection of texts or symbols facing leaf labels or linked to nodes, through manual pasting or by using annotation files, 4) the highlight of graphical elements after querying leaf labels (or annotations) or by selection of graphical elements and information extraction, 5) the highlight of targeted trees according to a source tree browsed by the user, 6) powerful scripts for automating repetitive graphical tasks, 7) a command line interpreter enabling the use of TreeDyn through CGI scripts for online building of trees, 8) the inclusion of a library of packages dedicated to specific research fields involving trees. CONCLUSION: TreeDyn is a tree visualization and annotation tool which includes tools for tree manipulation and annotation and uses meta-information through dynamic graphical operators or scripting to help analyses and annotations of single trees or tree collections

Epidemiology and outcome predictors in 450 patients with hanging-induced cardiac arrest: a retrospective study

BackgroundCardiac arrest is the most life-threatening complication of attempted suicide by hanging. However, data are scarce on its characteristics and outcome predictors.MethodsThis retrospective observational multicentre study in 31 hospitals included consecutive adults admitted after cardiac arrest induced by suicidal hanging. Factors associated with in-hospital mortality were identified by multivariate logistic regression with multiple imputations for missing data and adjusted to the temporal trends over the study period.ResultsOf 450 patients (350 men, median age, 43 [34–52] years), 305 (68%) had a psychiatric history, and 31 (6.9%) attempted hanging while hospitalized. The median time from unhanging to cardiopulmonary resuscitation was 0 [0–5] min, and the median time to return of spontaneous circulation (ROSC) was 20 [10–30] min. Seventy-nine (18%) patients survived to hospital discharge. Three variables were independently associated with higher in-hospital mortality: time from collapse or unhanging to ROSC>20 min (odds ratio [OR], 4.71; 95% confidence intervals [95%CIs], 2.02–10.96; p = 0.0004); glycaemia >1.4 g/L at admission (OR, 6.38; 95%CI, 2.60–15.66; p < 0.0001); and lactate >3.5 mmol/L at admission (OR, 6.08; 95%CI, 1.71–21.06; p = 0.005). A Glasgow Coma Scale (GCS) score of >5 at admission was associated with lower in-hospital mortality (OR, 0.009; 95%CI, 0.02–0.37; p = 0.0009).ConclusionIn patients with hanging-induced cardiac arrest, time from collapse or unhanging to return of spontaneous circulation, glycaemia, arterial lactate, and coma depth at admission were independently associated with survival to hospital discharge. Knowledge of these risk factors may help guide treatment decisions in these patients at high risk of hospital mortality

Analyse bioinformatique de régions cis-régulatrices de Drosophila melanogaster

AIX-MARSEILLE2-BU Sci.Luminy (130552106) / SudocSudocFranceF

A knowledge base for D. melanogaster gene interactions involved in pattern formation

euzenat1997bInternational audienceThe understanding of pattern formation in Drosophila requires the handling of the many genetic and molecular interactions which occur between developmental genes. For that purpose, a knowledge base (KNIFE) has been developed in order to structure and manipulate the interaction data. KNIFE contains data about interactions published in the literature and gathered from various databases. These data are structured in an object knowledge representation system into various interrelated entities. KNIFE can be browsed through a WWW interface in order to select, classify and examine the objects and their references in other bases. It also provides specialised biological tools such as interaction network manipulation and diagnosis of missing interactions