CHD7 and Runx1 interaction provides a braking mechanism for hematopoietic differentiation.

Hematopoietic stem and progenitor cell (HSPC) formation and lineage differentiation involve gene expression programs orchestrated by transcription factors and epigenetic regulators. Genetic disruption of the chromatin remodeler chromodomain-helicase-DNA-binding protein 7 (CHD7) expanded phenotypic HSPCs, erythroid, and myeloid lineages in zebrafish and mouse embryos. CHD7 acts to suppress hematopoietic differentiation. Binding motifs for RUNX and other hematopoietic transcription factors are enriched at sites occupied by CHD7, and decreased RUNX1 occupancy correlated with loss of CHD7 localization. CHD7 physically interacts with RUNX1 and suppresses RUNX1-induced expansion of HSPCs during development through modulation of RUNX1 activity. Consequently, the RUNX1:CHD7 axis provides proper timing and function of HSPCs as they emerge during hematopoietic development or mature in adults, representing a distinct and evolutionarily conserved control mechanism to ensure accurate hematopoietic lineage differentiation.Bloodwise, CRUK, MRC, Wellcome Trust, NIH, Leukemia and Lymphoma Societ

"Proíbo a publicação e circulação..." - censura a livros na ditadura militar

Durante a ditadura militar brasileira (1964-1985), cerca de 140 livros de autores brasileiros foram oficialmente vetados pelo Estado. Este artigo apresenta parte dos resultados de um projeto que visou fazer o levantamento sistemático das obras censuradas e traçar um panorama da atuação censória do governo militar em relação a livros, destacadamente obras de autores brasileiros, com ênfase no período posterior a 1970. Além de fontes bibliográficas, utilizamos o arquivo de pareceres do Departamento de Censura de Diversões Públicas (DCDP), órgão do Ministério da Justiça, que a partir de 1970 passou a exercer a censura a livros e revistas. O presente artigo é uma versão modificada de trechos do livro Repressão e resistência: censura a livros na ditadura militar, publicado pela Edusp, com apoio da Fapesp, em 2011

Rescuing the attentional performance of rats with cholinergic losses by the M1 positive allosteric modulator TAK-071

AbstractLoss of basal forebrain cholinergic neurons contributes to the severity of the cognitive decline in age-related dementia and to impairments in gait and balance, and the resulting risks for falls, in patients with Parkinson’s disease (PD). Contrasting with the extensive evidence indicating an essential role of cholinergic activity in mediating cognitive, specifically attentional abilities, treatment with conventional acetylcholinesterase inhibitors (AChEIs) has not fulfilled the promise of efficacy of pro-cholinergic treatments. Here we investigated the potential usefulness of a muscarinic M1 positive allosteric modulator (PAM) in an animal model of cholinergic loss-induced impairments in attentional performance. Given evidence indicating that fast, transient cholinergic signaling mediates the detection of cues in attentional contexts, we hypothesized that an M1 PAM amplifies such transient signaling, thereby enhancing and rescuing attentional performance. Rats performed an operant sustained attention task (SAT), including in the presence of a distractor (dSAT) and during a post-distractor (post-dSAT) period assessing their capacity for recovering performance. Basal forebrain infusions of the cholino-specific immunotoxin 192 IgG-saporin impaired SAT performance, and greater cholinergic losses predicted lower post-dSAT performance recovery. Administration of TAK-071 (0.1, 0.3 mg/kg, p.o., administered over 6-day blocks) improved the performance of all rats during the post-dSAT period (main effect of dose). Drug-induced improvement of post-dSAT performance was relatively greater in lesioned rats, irrespective of sex, and also manifested in female control rats. TAK-071 primarily improved perceptual sensitivity (d’) in lesioned rats and facilitated the adoption of a more liberal response bias (B”D) in all female rats. Collectively, these findings suggest that TAK-071 may benefit the attentional performance of patients with partial cholinergic losses and specifically in situations that tax top-down, or goal-driven, attentional control.</jats:p