Instruction of haematopoietic lineage choices, evolution of transcriptional landscapes and cancer stem cell hierarchies derived from an AML1-ETO mouse model.

The t(8;21) chromosomal translocation activates aberrant expression of the AML1-ETO (AE) fusion protein and is commonly associated with core binding factor acute myeloid leukaemia (CBF AML). Combining a conditional mouse model that closely resembles the slow evolution and the mosaic AE expression pattern of human t(8;21) CBF AML with global transcriptome sequencing, we find that disease progression was characterized by two principal pathogenic mechanisms. Initially, AE expression modified the lineage potential of haematopoietic stem cells (HSCs), resulting in the selective expansion of the myeloid compartment at the expense of normal erythro- and lymphopoiesis. This lineage skewing was followed by a second substantial rewiring of transcriptional networks occurring in the trajectory to manifest leukaemia. We also find that both HSC and lineage-restricted granulocyte macrophage progenitors (GMPs) acquired leukaemic stem cell (LSC) potential being capable of initiating and maintaining the disease. Finally, our data demonstrate that long-term expression of AE induces an indolent myeloproliferative disease (MPD)-like myeloid leukaemia phenotype with complete penetrance and that acute inactivation of AE function is a potential novel therapeutic option.

Entre el Gulag y el supermercado : en busca de Alexander Zinoviev

Aquest treball, que còpia en part el títol del llibre de Symons, intenta configurar-se també sobre un doble plànol expositiu. El priemr pla el primer objectiu-, es el més obvi: oferir un panorama del contingut de les principals obres d'un autor, Alexander Zinoviev, i tractar de contextualitzar-les (efectuant per allò incursions al pensament d'altres autors - a mode de breus razzies predatòries). Però el treball aspira a incloure una segona trama: l'intent d'observar una trajectòria intel·lectual determinada -en aquest cas, la de Zinoviev- de d'una certa distància i esbrinar si pot extreure's alguna lliçó no ja de les teories que l'autor va consignar per escrit, sinó de l'actitud existencial i intel·lectual amb la que un individu es va enfrontar als cataclismes produïts pels successius derrumbaments i encumbraments de les grans ideologies de la seva època.

De censuris Suarez ; De irregularitatibus / Collet. De simonia ; De oratione in communi [etc.] / Suarez. De oratione dominica / Natalis Alexander

Collection : Theologiae cursus completus ; 17

Space-time relatedness and Hamilton's rule for long-lasting behaviors in viscous populations.

Genes affect not only the behavior and fitness of their carriers but also that of other individuals. According to Hamilton's rule, whether a mutant gene will spread in the gene pool depends on the effects of its carrier on the fitness of all individuals in the population, each weighted by its relatedness to the carrier. However, social behaviors may affect not only recipients living in the generation of the actor but also individuals living in subsequent generations. In this note, I evaluate space-time relatedness coefficients for localized dispersal. These relatedness coefficients weight the selection pressures on long-lasting behaviors, which stem from a multigenerational gap between phenotypic expression by actors and the resulting environmental feedback on the fitness of recipients. Explicit values of space-time relatedness coefficients reveal that they can be surprisingly large for typical dispersal rates, even for hundreds of generations in the future.

[1-1-20], Angus [Alexander] capitaine de l'équipe d'Écosse [de rugby posant avant le match France-Écosse au Parc des princes] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 57442