LRF-mediated Dll4 repression in erythroblasts is necessary for hematopoietic stem cell maintenance.

Hematopoietic stem cells (HSCs) are the most primitive cells in the hematopoietic system and are under tight regulation for self-renewal and differentiation. Notch signals are essential for the emergence of definitive hematopoiesis in mouse embryos and are critical regulators of lymphoid lineage fate determination. However, it remains unclear how Notch regulates the balance between HSC self-renewal and differentiation in the adult bone marrow (BM). Here we report a novel mechanism that prevents HSCs from undergoing premature lymphoid differentiation in BM. Using a series of in vivo mouse models and functional HSC assays, we show that leukemia/lymphoma related factor (LRF) is necessary for HSC maintenance by functioning as an erythroid-specific repressor of Delta-like 4 (Dll4) expression. Lrf deletion in erythroblasts promoted up-regulation of Dll4 in erythroblasts, sensitizing HSCs to T-cell instructive signals in the BM. Our study reveals novel cross-talk between HSCs and erythroblasts, and sheds a new light on the regulatory mechanisms regulating the balance between HSC self-renewal and differentiation.

Os caminhos da lei de responsabilidade fiscal (lrf): instituições, idéias e incrementalismo

O tema fiscal incorporou-se à agenda política brasileira nos anos 90, tendo a redução do déficit público, a partir de então, se tornando issue premente para garantir a estabilidade econômica. O presente trabalho constitui um esforço tentativo de análise do ciclo de ajuste brasileiro desse período, com ênfase em um de seus pontos cruciais: a Lei da Responsabilidade Fiscal

Finanças públicas na nova ordem constitucional brasileira: uma análise comportamental dos municípios potiguares, nos anos antecedentes e posteriores à lei de responsabilidade fiscal LRF

The object of the present dissertation is to analyze the behavior of the public finances of the districts of the state of Rio Grande do Norte (RN), taking as reference a period fundamentally previous to the implementation of the Fiscal Responsibility Law LRF, comparatively to the first years, immediately after the advent of the mentioned institutional milestone. The central hypothesis of this study proposes that, from the institutions' viewpoint, the LRF sets securely consistent rules, in the orchestration of the behavior of the municipal revenues and expenses. These regulations, on the other hand, might be effective and reach the districts of the RN indiscriminately, apart from stabilizing tendencies and which are sustainable in the long run. In spite of this, the indicators calculated reveal that the districts researched show, during all the period under analysis, a diminished capacity of self-tax collection , and consequently, a high participation of the intergovernmental transfers in the composition of the current revenues. This behavior indicates that the goal of strengthening the municipal public finances, forecast in the LRF, tends to be only partially accomplished, due to the fiscal decentralism. The analysis and interpretation of the data are conducted from the literature of institutionalist orientation and in descriptive statistical tools applied to the municipal strata of the state of Rio Grande do Norte. Further on, it's used the econometrical method Pooled OLS, which demands the elimination of the municipal strata in order to allow the use of the model, in the attempt to strengthen and/or ratify the results of the research. Finally, the evidence reached in the dissertation show that the LRF brings better conditions to the potiguar municipal public finances, predominantly to the economically stronger districts; whereas the less dynamic municipal entities show rather divergent evidence, that is, their economies seem to be more oriented to a more pronounced state participation; therefore, it generates in the state of RN a certain antithesis in the results reached in the dissertation