Qualitative assessments of anemia-related programs in Ghana reveal gaps and implementation challenges.

In spite of multiple program efforts in Ghana, progress in reducing the burden of anemia is slow. The objective was to conduct multilevel assessments of existing childhood (<5 years) anemia prevention and treatment programs according to UNICEF's conceptual framework of malnutrition, and to elucidate implementation gaps in Ghana. Purposive and snowball sampling strategies recruited 25 program personnel from 20 organizations to participate in audiorecorded interviews conducted through in-person, telephone, or email correspondence in August 2018. Interview guides constructed around UNICEF's conceptual framework of malnutrition identified context-specific immediate, underlying, and basic causes of anemia, and corresponding programs. Interviews were transcribed, coded, and analyzed using the Dedoose software version 8.1.8. Few programs addressed identified basic causes of anemia, such as inadequate human resources, housing/water/toilet facilities, and poverty/poor access to financial resources. Organizations implemented programs addressing ≥1 underlying cause. Five organizations provided food rations and/or supplements to address immediate causes. A key food-based gap identified was minimal education on fruit intake or antinutritive factors in foods; however, no interventions included vitamin C supplements. Food manufacturers mainly used cereals and grains in commercial food products. Multiple organizations worked in the same region on anemia with instances of an overlapping program focus. Food sources of vitamin C or supplements could be promoted in food-based interventions to increase the absorption of nonheme iron consumed.

Af9/Mllt3 interferes with Tbr1 expression through epigenetic modification of histone H3K79 during development of the cerebral cortex.

Mutations of leukemia-associated AF9/MLLT3 are implicated in neurodevelopmental diseases, such as epilepsy and ataxia, but little is known about how AF9 influences brain development and function. Analyses of mouse mutants revealed that during cortical development, AF9 is involved in the maintenance of TBR2-positive progenitors (intermediate precursor cells, IPCs) in the subventricular zone and prevents premature cell cycle exit of IPCs. Furthermore, in postmitotic neurons of the developing cortical plate, AF9 is implicated in the formation of the six-layered cerebral cortex by suppressing a TBR1-positive cell fate mainly in upper layer neurons. We show that the molecular mechanism of TBR1 suppression is based on the interaction of AF9 with DOT1L, a protein that mediates transcriptional control through methylation of histone H3 lysine 79 (H3K79). AF9 associates with the transcriptional start site of Tbr1, mediates H3K79 dimethylation of the Tbr1 gene, and interferes with the presence of RNA polymerase II at the Tbr1 transcriptional start site. AF9 expression favors cytoplasmic localization of TBR1 and its association with mitochondria. Increased expression of TBR1 in Af9 mutants is associated with increased levels of TBR1-regulated expression of NMDAR subunit Nr1. Thus, this study identified AF9 as a developmental active epigenetic modifier during the generation of cortical projection neurons.

Transforming growth factor beta promotes neuronal cell fate of mouse cortical and hippocampal progenitors in vitro and in vivo: identification of Nedd9 as an essential signaling component.

Transforming Growth Factor beta (Tgfbeta) and associated signaling effectors are expressed in the forebrain, but little is known about the role of this multifunctional cytokine during forebrain development. Using hippocampal and cortical primary cell cultures of developing mouse brains, this study identified Tgfbeta-regulated genes not only associated with cell cycle exit of progenitors but also with adoption of neuronal cell fate. Accordingly, we observed not only an antimitotic effect of Tgfbeta on progenitors but also an increased expression of neuronal markers in Tgfbeta treated cultures. This effect was dependent upon Smad4. Furthermore, in vivo loss-of-function analyses using Tgfbeta2(-/-)/Tgfbeta3(-/-) double mutant mice showed the opposite effect of increased cell proliferation and fewer neurons in the cerebral cortex and hippocampus. Gata2, Runx1, and Nedd9 were candidate genes regulated by Tgfbeta and known to be involved in developmental processes of neuronal progenitors. Using siRNA-mediated knockdown, we identified Nedd9 as an essential signaling component for the Tgfbeta-dependent increase in neuronal cell fate. Expression of this scaffolding protein, which is mainly described as a signaling molecule of the beta1-integrin pathway, was not only induced after Tgfbeta treatment but was also associated with morphological changes of the Nestin-positive progenitor pool observed upon exposure to Tgfbeta.