Recent studies indicate that neural cell development in the central nervous system (CNS) correlates with a reduction in acetylation of histone core proteins. Moreover, histone hypoacetylation is thought to be important to oligodendrocyte lineage development. The mechanisms mediating the reduction in acetylation during postnatal neural development remain to be defined. To begin to understand these mechanisms, we investigated the expression of histone deacetylase 11 (HDAC11), a newly identified HDAC, in mouse brain during postnatal development. We show that HDAC11 was widely expressed in the brain and that this expression gradually increased in a region-specific pattern between birth and 4 weeks of age. At the cellular level HDAC11 protein was predominately localized in the nuclei of mature oligodendrocytes but only minimally in astrocytes. Although dentate gyrus granule neurons abundantly expressed HDAC11, granule neuron precursors in the subgranule layer exhibited little HDAC11 immunoreactivity. Double-immunostaining of the corpus callosum and dentate gyrus demonstrated that HDAC11 and Ki67, a cell-proliferating marker, are rarely colocalized in same cells. Our data show that HDAC11 was expressed in the developing brain in a temporal and spatial pattern that correlates with the maturation of neural cells, including cells of the oligodendrocyte lineage. These findings support a role for HDAC11 in CNS histone deacetylation and the development of oligodendrocytes and neurons during postnatal development. KeywordsHDAC; deacetylation; oligodendrocytes; hippocampus Epigenetic modification of histone core proteins has been implicated in gene regulation and cellular development. Recent studies indicate that regulation of histone acetylation plays a pivotal role in the development of the central nervous system (CNS). Acetylation is a dynamic process that is regulated by two classes of enzymes: histone acetyltransferases (HATs) and histone deacetylases (HDACs). During postnatal development in rat corpus callosum and cortical neurons, acetylation of histones H3 and H4 gradually decreases with increasing age (Pina et al., 1988;Shen et al., 2005). Similarly, acetylation of H3 and H4 is reduced when cultured adult rat hippocampal neural precursor cells (NPCs) are induced to differentiate into mature oligodendrocytes and astrocytes by growth factors (Hsieh et al., 2004). Furthermore, global suppression of HDAC activity by inhibitors, such as vaproic acid and trichostatin A, blunts oligodendrocyte development and myelination in developing rats (Shen et al., 2005), in cultured rat adult hippocampi NPC (Hsieh et al., 2004), and in prenatal oligodendrocyte precursors (Liu et al., 2003 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptThe mechanisms by which acetylation of histone is regulated in the brain during postnatal development have not been elucidated. In a recent study of rat corpus callosum development, Shen et al. (2005) showed that the abundance of 2 HATs, p300 and CBP (cyclic AMP respons...
PACT is a stress-modulated, cellular activator of interferon (IFN)-induced double-stranded (ds) RNA-activated protein kinase (PKR) and is an important regulator of PKR-dependent signaling pathways. The research presented here is aimed at understanding the regulation of PACT expression in mammalian cells. PACT is expressed ubiquitously in different cell types at varying abundance. We have characterized the sequence elements in PACT promoter region that are required for its expression. Using deletion analysis of the promoter we have identified the minimal basal promoter of PACT to be within 101 nucleotides upstream of its transcription start site. Further mutational analyses within this region, followed by electrophoretic mobility shift analyses (EMSAs) and chromatin immunoprecipitation (ChiP) analysis have shown that Specificity protein 1 (Sp1) is the major transcription factor responsible for PACT promoter activity.
Treatment of drinking water at the point of use (POU) has demonstrated health benefits for people who have access only to microbially contaminated drinking water. In this work, the ceramic siphon POU water filter was evaluated for its ability to reduce indicator microorganisms in test waters. During batch challenge tests, the filter reduced Escherichia coli in filtered water by 7 log10 (99.999987%) and bacteriophage MS2 by 0.12 log10 (24.0%). Next, a novel continuous flow dosing system allowing sewage-amended feed water to constantly pass through the filters allowed for determination of changes in microbial reductions over time and total volume of water filtered. E. coli B, MS2 and fluorescent microspheres (as a surrogate for Cryptosporidium oocysts) were seeded into test water and dosed to filters at 10, 25 and 50% of the filter's volume lifespan. Microbial removal efficacy decreased as the volume of water filtered increased and test filters did not achieve their volume lifespan before physically failing. The ceramic siphon household water filter is effective in reducing E. coli and surrogates for Cryptosporidium in water, but filter modifications may be needed to achieve acceptable levels of virus removal and to reach the target 7,000 L volume lifespan of the filter.
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