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- Did Germinal Centers evolve under differential effects of diversity vs affinity?Publication . Faro, J.; Combadão, J.; Gordo, I.The classical view on the process of mutation and affinity maturation that occurs in GCs assumes that their major role is to generate high affinity levels of serum Abs, as well as a dominant pool of high affinity memory B cells, through a very efficient selection process. Here we present a model that considers different types of structures where a mutation selection process occurs, with the aim at discussing the evolution of Germinal Center reactions. Based on the results of this model, we suggest that in addition to affinity maturation, the diversity generated during the GC reaction may have also been important in the evolution towards the presently observed highly organized structure of GC in higher vertebrates.
- H3K4me3 - dependent epigenetic memory regulates transcriptional reactivation in the oocytePublication . Navarro-Costa, P.; Prudêncio, P.; J.D., Becker; R.G., MartinhoStudy question: How does the oocyte regulate its transcriptional activity in light of its prolonged meiotic arrest? Summary answer: A histone methylation-mediated epigenetic memory programed by the demethylase KDM5 is required for the correct temporal reactivation of the oocyte's transcriptional activity. What is known already: During oogenesis oocytes transit from stages of transcriptional activity to those of transcriptional quiescence, and such transitions are believed to be essential for proper gamete formation. Although the temporal regulation of these transitions has been well documented across diverse organisms, the molecular mechanisms underlying these processes remain largely unknown.
- Impact of changing cell-cell communication network in models of epithelial pattern formationPublication . Varela, Pedro L.; Monteiro, Pedro T.; Chaouiya, ClaudineWhen modelling multi-cellular systems, one has to account for cell-cell signalling in addition to the molecular networks driving cell behaviours. Here, we aim at exploring how the topology of the cell-cell communication network impacts the behaviour of the whole multicellular system. More precisely, we focus on epithelial pattern formation, on which our question can be rephrased in terms of cell sizes and shapes. Relying on a logical modelling framework, and using a simple lateral inhibition model over a population of epithelial cells, we assess the model behaviours considering a variety of communication networks. This study suggests that reasonable deviations from a fixed grid (with regular hexagonal shaped cells) do not change much the resulting patterns. We further explore the impact of cell shapes and show that characteristics such as network regularity and number of shared neighbours of contacting cells are relevant to qualify such deviations.
- Meeting report from the fourth meeting of the Computational Modeling in Biology Network (COMBINE)Publication . Waltemath, Dagmar; Bergmann, Frank T.; Chaouiya, Claudine; Czauderna, Tobias; Gleeson, Padraig; Goble, Carole; Golebiewski, Martin; Hucka, Michael; Juty, Nick; Krebs, Olga; Le Novère, Nicolas; Mi, Huaiyu; Moraru, Ion I.; Myers, Chris J.; Nickerson, David; Olivier, Brett G.; Rodriguez, Nicolas; Schreiber, Falk; Smith, Lucian; Zhang, Fengkai; Bonnet, EricThe Computational Modeling in Biology Network (COMBINE) is an initiative to coordinate the development of community standards and formats in computational systems biology and related fields. This report summarizes the topics and activities of the fourth edition of the annual COMBINE meeting, held in Paris during September 16-20 2013, and attended by a total of 96 people. This edition pioneered a first day devoted to modeling approaches in biology, which attracted a broad audience of scientists thanks to a panel of renowned speakers. During subsequent days, discussions were held on many subjects including the introduction of new features in the various COMBINE standards, new software tools that use the standards, and outreach efforts. Significant emphasis went into work on extensions of the SBML format, and also into community-building. This year’s edition once again demonstrated that the COMBINE community is thriving, and still manages to help coordinate activities between different standards in computational systems biology.
- Modelos de interacção genética de dois genes em fenótiposPublication . Sepúlveda, Nuno; Paulino, C.D.; Penha-Gonçalves, CarlosEm trabalhos anteriores foram propostos diversos modelos estatísticos para a penetrância de forma a inferir a interacção de dois genes dial´elicos na construção de fenótipos binários complexos: modelos de acção independente, modelos de inibição e modelos de número mínimo de alelos. Estes modelos baseiam-se numa decomposição da penetrância através da abordagem por penetrâncias alélicas, que permitiu a inclusão dos conceitos mendelianos de dominância e recessividade alélica na sua modelação. Pretende-se aqui dar a conhecer os avanços mais recentes na parte da modelação da interacção genética, apresentando uma nova decomposição da penetrância e uma nova formulação matemática da dominância e da recessividade. Aplicam-se ainda ferramentas bayesianas para o ajustamento dos modelos de interacção genética a dados experimentais com recurso ao método de amostragem de Gibbs. Toda a metodologia é exemplificada num conjunto de dados de um estudo da susceptibilidade da malária cerebral em ratinhos.