\ud Tanzania Health Insurance Regulatory Framework Review\ud

Make sure that current policy objectives – achieving universal coverage, social health protection, good governance and cost-containment – are reflected in the relevant legislative documents, and provide the requisite legal tools, reflecting the chosen policy options and the institutional consequences of those options. Consider reducing the fragmentation of the health financing legislation which reflects the current fragmentation in health financing and in governance and oversight of the health financing and insurance systems. Develop an explicit policy on competition in health financing to close the current gaps in legislation and to prevent the possibly negative side effects for Tanzania citizens of such competition in the event that the Government of Tanzania (GOT) opts for a competition-based model of health financing. The model ultimately chosen will have consequences not only for health financing practise, but also for the relevant legislation. Consider the establishment of an independent accreditation body for external assessment and gradual improvement of the quality of care of all health services providers, regardless of their sources of financing. Plug the identified gaps in single enactments which can be done without embarking on any big policy changes. The latter can be included in the development of a planned National Health Financing Strategy. During this development process, it will be possible to focus on specific areas of interest and make detailed recommendations. After national adoption of the strategy, new legislation will have to be drawn up.\ud \u

Interplay between diet, gut microbiota, epigenetic events, and colorectal cancer

Despite the success of colonoscopy screening, colorectal cancer (CRC) remains one of the most common and deadly cancers, and CRC incidence is rising in some countries where screening is not routine and populations have recently switched from traditional diets to western diets. Diet and energy balance influence CRC by multiple mechanisms. They modulate the composition and function of gut microbiota, which have a prodigious metabolic capacity and can produce oncometabolites or tumor-suppressive metabolites depending, in part, on which dietary factors and digestive components are present in the GI tract. Gut microbiota also have a profound effect on immune cells in the lamina propria, which influences inflammation and subsequently CRC. Nutrient availability, which is an outcome of diet and energy balance, determines the abundance of certain energy metabolites that are essential co-factors for epigenetic enzymes and therefore impinges upon epigenetic regulation of gene expression. Aberrant epigenetic marks accumulate during CRC, and epimutations that are selected for drive tumorigenesis by causing transcriptome profiles to diverge from the cell of origin. In some instances, the above mechanisms are intertwined as exemplified by dietary fiber being metabolized by colonic bacteria into butyrate, which is both a short-chain fatty acid (SCFA) and a histone deacetylase (HDAC) inhibitor that epigenetically upregulates tumor-suppressor genes in CRC cells and anti-inflammatory genes in immune cells

The microbiome and its potential as a cancer preventive intervention

It is becoming increasingly clear that microbiota which inhabit our body influence cancer predisposition and etiology. In addition to pathogens with oncogenic properties, our commensal and symbiotic microbiota have tumor-suppressive properties. Our diet and other environmental factors can modulate the abundance of certain members of microbial communities within our gastrointestinal tract and at other anatomical sites. Furthermore, some dietary factors are metabolized by commensal/symbiotic gut microbiota into bioactive food components believed to prevent cancer. For example, dietary fiber undergoes bacterial fermentation in the colon to yield butyrate, which is a short-chain fatty acid and histone deacetylase (HDAC) inhibitor that suppresses the viability and growth of colorectal cancer cell lines. A recent study utilizing gnotobiotic mouse models demonstrates that fiber can protect against colorectal tumorigenesis in a microbiota- and butyrate-dependent manner that involves the Warburg effect. This and other examples suggest that some of the inter-individual variation observed in epidemiology and intervention studies that have investigated associations between diet and cancer risk might be explained by differences in microbiota among the participants. Data from basic research studies also support the idea that probiotics and prebiotics could be plausible chemoprevention strategies that may be utilized to a greater extent in the future

Surface recombination velocity of phosphorus-diffused silicon solar cell emitters passivated with plasma enhanced chemical vapor deposited silicon nitride and thermal silicon oxide

The emitter saturation current density(JOe) and surface recombination velocity (Sp) of various high quality passivation schemes on phosphorus-diffused solar cell emitters have been determined and compared. The passivation schemes investigated were (i) stoichiometric plasma enhanced chemical vapor deposited(PECVD)silicon nitride (SiN), (ii) forming gas annealed thermally grown silicon oxide, and (iii) aluminum annealed (alnealed) thermal silicon oxide. Emitters with sheet resistances ranging from 30 to 430 and 50 to 380 Ω/□ were investigated for planar and random-pyramid textured silicon surfaces, which covers both industrial and laboratory emitters. The electronic surface passivation quality provided by PECVD SiN films was found to be good, with Sp values ranging from 1400 to 25 000 cm/s for planar emitters. Thin thermal silicon oxides were found to provide superior passivation to PECVD SiN, with the best passivation provided by an alnealed thin oxide (Sp values between 250 and 21 000 cm/s). The optimized PECVD SiN films are, nevertheless, sufficiently good for most silicon solar cell applications.This work was supported by funding from the Australian Research Council. One of the authors ~J.S.! gratefully acknowledges the support of a Feodor Lynen fellowship by the Alexander von Humboldt Foundation of Germany

A Brg1 mutation that uncouples ATPase activity from chromatin remodeling reveals an essential role for SWI/SNF-related complexes in -globin expression and erythroid development

The Brg1 catalytic subunit of SWI/SNF-related complexes has been implicated in many developmental and physiological processes, but null homozygotes die as blastocysts prior to implantation. To circumvent this early embryonic lethality, we performed an ENU mutagenesis screen and generated a Brg1 hypomorph mutation in the ATPase domain. The mutant Brg1 protein is stable, assembles into SWI/SNF-related complexes, and exhibits normal ATPase activity but is unable to establish DNase I hypersensitivity sites characteristic of open chromatin. Mutant embryos develop normally until midgestation but then exhibit a distinct block in the development of the erythroid lineage, leading to anemia and death. The mutant Brg1 protein is recruited to the β-globin locus, but chromatin remodeling and transcription are perturbed. Histone acetylation and DNA methylation are also affected. To our knowledge, Brg1 is the first chromatin-modifying factor shown to be required for β-globin regulation and erythropoiesis in vivo. Not only does this mutation establish a role for Brg1 during organogenesis, it also demonstrates that ATPase activity can be uncoupled from chromatin remodeling

Maternal BRG1 regulates zygotic genome activation in the mouse

Zygotic genome activation (ZGA) is a nuclear reprogramming event that transforms the genome from transcriptional quiescence at fertilization to robust transcriptional activity shortly thereafter. The ensuing gene expression profile in the cleavage-stage embryo establishes totipotency and is required for further development. Although little is known about the molecular basis of ZGA, oocyte-derived mRNAs and proteins that alter chromatin structure are likely crucial. To test this hypothesis, we generated a maternal-effect mutation of Brg1, which encodes a catalytic subunit of SWI/SNF-related complexes, utilizing Cre-loxP gene targeting. In conditional-mutant females, BRG1-depleted oocytes completed meiosis and were fertilized. However, embryos conceived from BRG1-depleted eggs exhibited a ZGA phenotype including two-cell arrest and reduced transcription for ∼30% of expressed genes. Genes involved in transcription, RNA processing, and cell cycle regulation were particularly affected. The early embryonic arrest is not a consequence of a defective oocyte because depleting maternal BRG1 after oocyte development is complete by RNA interference (RNAi) also resulted in two-cell arrest. To our knowledge, Brg1 is the first gene required for ZGA in mammals. Depletion of maternal BRG1 did not affect global levels of histone acetylation, whereas dimethyl-H3K4 levels were reduced. These data provide a framework for understanding the mechanism of ZGA

BRG1 directly regulates nucleosome structure and chromatin looping of the α globin locus to activate transcription

α globin expression must be regulated properly to prevent the occurrence of α-thalassemias, yet many questions remain unanswered regarding the mechanism of transcriptional activation. Identifying factors that regulate chromatin structure of the endogenous α globin locus in developing erythroblasts will provide important mechanistic insight. Here, we demonstrate that the BRG1 catalytic subunit of SWI/SNF-related complexes co-immunoprecipitates with GATA-1 and EKLF in murine fetal liver cells in vivo and is recruited to the far-upstream major-regulatory element (MRE) and α2 promoter. Furthermore, based on our analysis of Brg1null/ENU1 mutant mice, BRG1 regulates DNase I sensitivity, H3ac, and H3K4me2 but not CpG methylation at both sites. Most importantly, BRG1 is required for chromatin loop formation between the MRE and α2 promoter and for maximal RNA Polymerase II occupancy at the α2 promoter. Consequently, Brg1 mutants express α globin mRNA at only 5–10% of wild-type levels and die at mid-gestation. These data identify BRG1 as a chromatin-modifying factor required for nucleosome remodeling and transcriptional activation of the α globin locus. These data also demonstrate that chromatin looping between the MRE and α2 promoter is required as part of the transcriptional activation mechanism

Molecular Pathways: Gene-Environment Interactions Regulating Dietary Fiber Induction of Proliferation and Apoptosis via Butyrate for Cancer Prevention

Gene-environment interactions are so numerous and biologically complicated that it can be challenging to understand their role in cancer. However, dietary fiber and colorectal cancer prevention may represent a tractable model system. Fiber is fermented by colonic bacteria into short-chain fatty acids such as butyrate. One molecular pathway that has emerged involves butyrate having differential effects depending on its concentration and the metabolic state of the cell. Low-moderate concentrations, which are present near the base of colonic crypts, are readily metabolized in the mitochondria to stimulate cell proliferation via energetics. Higher concentrations, which are present near the lumen, exceed the metabolic capacity of the colonocyte. Unmetabolized butyrate enters the nucleus and functions as a histone deacetylase (HDAC) inhibitor that epigenetically regulates gene expression to inhibit cell proliferation and induce apoptosis as the colonocytes exfoliate into the lumen. Butyrate may therefore play a role in normal homeostasis by promoting turnover of the colonic epithelium. Because cancerous colonocytes undergo the Warburg effect, their preferred energy source is glucose instead of butyrate. Consequently, even moderate concentrations of butyrate accumulate in cancerous colonocytes and function as HDAC inhibitors to inhibit cell proliferation and induce apoptosis. These findings implicate a bacterial metabolite with metaboloepigenetic properties in tumor suppression