Essential role of the N-terminal region of TFII-I in viability and behavior

Background: GTF2I codes for a general intrinsic transcription factor and calcium channel regulator TFII-I, with high and ubiquitous expression, and a strong candidate for involvement in the morphological and neuro-developmental anomalies of the Williams-Beuren syndrome (WBS). WBS is a genetic disorder due to a recurring deletion of about 1,55-1,83 Mb containing 25-28 genes in chromosome band 7q11.23 including GTF2I. Completed homozygous loss of either the Gtf2i or Gtf2ird1 function in mice provided additional evidence for the involvement of both genes in the craniofacial and cognitive phenotype. Unfortunately nothing is now about the behavioral characterization of heterozygous mice. Methods: By gene targeting we have generated a mutant mice with a deletion of the first 140 amino-acids of TFII-I. mRNA and protein expression analysis were used to document the effect of the study deletion. We performed behavioral characterization of heterozygous mutant mice to document in vivo implications of TFII-I in the cognitive profile of WBS patients. Results: Homozygous and heterozygous mutant mice exhibit craniofacial alterations, most clearly represented in homozygous condition. Behavioral test demonstrate that heterozygous mutant mice exhibit some neurobehavioral alterations and hyperacusis or odynacusis that could be associated with specific features of WBS phenotype. Homozygous mutant mice present highly compromised embryonic viability and fertility. Regarding cellular model, we documented a retarded growth in heterozygous MEFs respect to homozygous or wild-type MEFs. Conclusion: Our data confirm that, although additive effects of haploinsufficiency at several genes may contribute to the full craniofacial or neurocognitive features of WBS, correct expression of GTF2I is one of the main players. In addition, these findings show that the deletion of the fist 140 amino-acids of TFII-I altered it correct function leading to a clear phenotype, at both levels, at the cellular model and at the in vivo model.

Avoiding transcription factor competition at promoter level increases the chances of obtaining oscillations

Background: The ultimate goal of synthetic biology is the conception and construction of genetic circuits that are reliable with respect to their designed function (e.g. oscillators, switches). This task remains still to be attained due to the inherent synergy of the biological building blocks and to an insufficient feedback between experiments and mathematical models. Nevertheless, the progress in these directions has been substantial. Results: It has been emphasized in the literature that the architecture of a genetic oscillator must include positive (activating) and negative (inhibiting) genetic interactions in order to yield robust oscillations. Our results point out that the oscillatory capacity is not only affected by the interaction polarity but by how it is implemented at promoter level. For a chosen oscillator architecture, we show by means of numerical simulations that the existence or lack of competition between activator and inhibitor at promoter level affects the probability of producing oscillations and also leaves characteristic fingerprints on the associated period/amplitude features. Conclusions: In comparison with non-competitive binding at promoters, competition drastically reduces the region of the parameters space characterized by oscillatory solutions. Moreover, while competition leads to pulse-like oscillations with long-tail distribution in period and amplitude for various parameters or noisy conditions, the non-competitive scenario shows a characteristic frequency and confined amplitude values. Our study also situates the competition mechanism in the context of existing genetic oscillators, with emphasis on the Atkinson oscillator.

Gènere i immigració en les narratives visuals de les noies dels països del sud d’Àsia escolaritzades a Catalunya

Aquesta recerca aborda la interpretació de les relacions entre escolarització, immigració i gènere de forma complexa mitjançant la construcció d’una recerca visual narrativa i d’històries de vida amb el grup de noies/dones immigrades procedent dels països del sud d’Àsia que viuen i han estat escolaritzades –totalment o parcialment– a Catalunya. La investigació dóna visibilitat a les trajectòries d’èxit escolar de les noies/dones immigrades al seu pas per l’escola secundària, tot narrant: les seves expectatives i desitjos, els moments i canvis, les identitats i relacions, així com els aprenentatges assolits i les perspectives de futur. La recerca s’ha portat a terme a partir d’observar, entrevistar i conversar amb diversos grups de noies immigrades (principalment de la regió del Panjab de l’Índia i el Pakistan) en 4 centres educatius i 1 entitat, de l’àmbit de Barcelona i la seva àrea metropolitana. La investigació reconstrueix la trajectòria de 20 noies immigrades com a protagonistes. El treball de camp etnogràfic i la construcció de les històries visuals de vida culmina amb l’edició d’un documental audiovisual. De forma resumida, l’anàlisi de les dades realitzada a partir del treball de camp etnogràfic, de les entrevistes en profunditat i les converses en els cinc contextos presentats, s’organitza d’acord amb els següents eixos temàtics: 1. Migracions, espacialització i mobilitat en un context transnacional i local; 2. La construcció de les subjectivitats i del gènere de les adolescents/adultes immigrades; 3. Processos d’escolarització i formació a Catalunya de les noies/dones immigrades; i 4. Visibilitat, visualitat i representació en la recerca.