Oscillations in the expression of a self-repressed gene induced by a slow transcriptional dynamics

We revisit the dynamics of a gene repressed by its own protein in the case where the transcription rate does not adapt instantaneously to protein concentration but is a dynamical variable. We derive analytical criteria for the appearance of sustained oscillations and find that they require degradation mechanisms much less nonlinear than for infinitely fast regulation. Deterministic predictions are also compared with stochastic simulations of this minimal genetic oscillator

Oscillations in the expression of a self-repressed gene induced by a slow transcriptional dynamics

We revisit the dynamics of a gene repressed by its own protein in the case where the transcription rate does not adapt instantaneously to protein concentration but is a dynamical variable. We derive analytical criteria for the appearance of sustained oscillations and find that they require degradation mechanisms much less nonlinear than for infinitely fast regulation. Deterministic predictions are also compared with stochastic simulations of this minimal genetic oscillator

Dissemination and geovisualization of territorial entities\u27 history

This paper describes an innovative solution for geovisualization of the demographic and administrative history of French municipalities named communes in French. This solution allows for the open dissemination of such data. The challenge is to provide a web interface for unskilled users in order to help them understand complex information about the demographic evolution of French territories. Our approach combines interactive thematic spatial and temporal views. We describe our architecture based on open-source technologies and the organization of this imperfect geo-historical information in our spatiotemporal database. Our second contribution concerns the concept of an acquaintance graph that has been used to obtain an efficient design with good performance in our geovisualization website

How Programmers Comment When They Think Nobody's Watching

Documentation is essential to software development. Experienced programmers know this well from having worked with poorly documented code. They wish to improve their documentation techniques and habits, but there is little consensus for them to follow. Somehow, the many different standards must be compared objectively. This desire motivates my work, which aims to better understand existing documentation practices. This work focuses exclusively on comments within the program code. Programming is a complex human activity, despite a widespread misconception among programmers that writing code is a mechanical process. This is especially true of comments, where programmers express themselves freely. My work fills a gap in research on software documentation by systematically investigating the comments in a unique database of code written by programmers under natural conditions. The true variety of programming behaviour is surprising. But this variety does not mean that the output of programmers is completely arbitrary; there are patterns in this data, which my research aims to understand. This work makes three contributions: A novel taxonomy of comments developed from the data, which to date is the most thorough description of commenting behaviour actually exhibited by programmers. Empirical hypotheses regarding large scale commenting behaviour, which were validated on separate test data. These hypotheses describe underlying regularities in programming which appear to transcend individual differences. The database of code I collected, which has unique opportunities for further research on software development, and is thus available for use by other researchers

Predominant expression of Alzheimer’s disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts

BIN1 is not expressed in human brain microglial cells. (A) Immunohistochemical staining of adjacent sections of normal human brain cortex with antibodies against BIN1 or Iba1 reveals that BIN1 immunoreactive cells that are morphologically distinct from microglia. The boxed region is shown at a higher magnification on the right. (B) Single and two-color immunostaining of the human brain using antibodies against BIN1 and CD45 reveals that perivenular CD45-positive cells of the hematopoietic lineage do not express BIN1. (TIFF 4392 kb

Comment évolue l’adaptation psychosociale des étudiants internationaux pendant leur cégep?

Comprend des références bibliographiques et webographiques"Le nombre d’étudiants internationaux (ÉI) est en constante augmentation dans les cégeps, notamment dans les régions dites « éloignées » des grands centres. Ces étudiantes et étudiants connaissent des processus accélérés d’adaptation (identitaire, socioculturel, etc.) qui peuvent être une source de stress importante. Nous avons donc réalisé une étude quantitative descriptive longitudinale par enquêtes (quatre temps de mesure) qui permettra de décrire l’évolution de leur adaptation émotionnelle, socioculturelle et scolaire, ainsi que de décrire les facteurs individuels et environnementaux qui sous-tendent une adaptation plus harmonieuse. Les résultats pourraient être utiles aux établissements afin de bonifier leurs stratégies pour soutenir le bienêtre et la motivation de leurs futurs ÉI." -- AQP

Exposure-Response Analyses of Asbestos and Lung Cancer Subtypes in a Pooled Analysis of Case-Control Studies

BackgroundEvidence is limited regarding risk and the shape of the exposure-response curve at low asbestos exposure levels. We estimated the exposure-response for occupational asbestos exposure and assessed the joint effect of asbestos exposure and smoking by sex and lung cancer subtype in general population studies.MethodsWe pooled 14 case-control studies conducted in 1985-2010 in Europe and Canada, including 17,705 lung cancer cases and 21,813 controls with detailed information on tobacco habits and lifetime occupations. We developed a quantitative job-exposure-matrix to estimate job-, time period-, and region-specific exposure levels. Fiber-years (ff/ml-years) were calculated for each subject by linking the matrix with individual occupational histories. We fit unconditional logistic regression models to estimate odds ratios (ORs), 95% confidence intervals (CIs), and trends.ResultsThe fully adjusted OR for ever-exposure to asbestos was 1.24 (95% CI, 1.18, 1.31) in men and 1.12 (95% CI, 0.95, 1.31) in women. In men, increasing lung cancer risk was observed with increasing exposure in all smoking categories and for all three major lung cancer subtypes. In women, lung cancer risk for all subtypes was increased in current smokers (ORs ~two-fold). The joint effect of asbestos exposure and smoking did not deviate from multiplicativity among men, and was more than additive among women.ConclusionsOur results in men showed an excess risk of lung cancer and its subtypes at low cumulative exposure levels, with a steeper exposure-response slope in this exposure range than at higher, previously studied levels. (See video abstract at, http://links.lww.com/EDE/B161.)

Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly.

International audienceThe genetic causes of malformations of cortical development (MCD) remain largely unknown. Here we report the discovery of multiple pathogenic missense mutations in TUBG1, DYNC1H1 and KIF2A, as well as a single germline mosaic mutation in KIF5C, in subjects with MCD. We found a frequent recurrence of mutations in DYNC1H1, implying that this gene is a major locus for unexplained MCD. We further show that the mutations in KIF5C, KIF2A and DYNC1H1 affect ATP hydrolysis, productive protein folding and microtubule binding, respectively. In addition, we show that suppression of mouse Tubg1 expression in vivo interferes with proper neuronal migration, whereas expression of altered γ-tubulin proteins in Saccharomyces cerevisiae disrupts normal microtubule behavior. Our data reinforce the importance of centrosomal and microtubule-related proteins in cortical development and strongly suggest that microtubule-dependent mitotic and postmitotic processes are major contributors to the pathogenesis of MCD

The role of RelA (p65) threonine 505 phosphorylation in the regulation of cell growth, survival, and migration

The NF-κB family of transcription factors is a well-established regulator of the immune and inflammatory responses and also plays a key role in other cellular processes, including cell death, proliferation, and migration. Conserved residues in the trans-activation domain of RelA, which can be posttranslationally modified, regulate divergent NF-κB functions in response to different cellular stimuli. Using rela(−/−) mouse embryonic fibroblasts reconstituted with RelA, we find that mutation of the threonine 505 (T505) phospho site to alanine has wide-ranging effects on NF-κB function. These include previously described effects on chemotherapeutic drug-induced apoptosis, as well as new roles for this modification in autophagy, cell proliferation, and migration. This last effect was associated with alterations in the actin cytoskeleton and expression of cellular migration–associated genes such as WAVE3 and α-actinin 4. We also define a new component of cisplatin-induced, RelA T505–dependent apoptosis, involving induction of NOXA gene expression, an effect explained at least in part through induction of the p53 homologue, p73. Therefore, in contrast to other RelA phosphorylation events, which positively regulate NF-κB function, we identified RelA T505 phosphorylation as a negative regulator of its ability to induce diverse cellular processes such as apoptosis, autophagy, proliferation, and migration

Enjeux et défis de l’adaptation, de l’intégration et de la réussite scolaire des étudiants internationaux dans les cégeps et les collèges francophones du Canada: Les cas du Nouveau-Brunswick, de l’Île-du-Prince-Édouard, de la Gaspésie et des Îles-de-la-Madeleine

Projet financé par le Réseau des cégeps et collèges francophones du Canada