65 research outputs found
A Case for Adult Two-Way Bilingual Immersion
No full textThe present study investigates 2-way bilingual immersion (TWBI) as a potentially viable pedagogical model for adult language learners. A review of the literature on TWBI at the K-6 level is provided, followed by an examination of key issues in adult second and foreign language education. Implications for potential adult TWBI programs are discussed along with recommendations for further investigation. Finally, the author presents an exploratory study of a nonformal, communitybased adult TWBI program in Los Angeles known as I HABLO U. The results of this study suggest that while adult TWBI shares many of the learner and administrative challenges documented in K-6 TWBI programs, adult learners in TWBI programs contend with a unique set of problems and also enjoy a number of advantages that K-6 learners may not experience. The author concludes that scholars must widen the focus of current research and evaluative efforts of TWBI to consider adult learners
Gaze as a Resource for CreatingCoherence across Speakers duringModerated Panel Discussions
No full textDysregulation of the histone demethylase KDM6B in alcohol dependence is associated with epigenetic regulation of inflammatory signaling pathways
No full textEpigenetic enzymes oversee long-term changes in gene expression by integrating genetic and environmental cues. While there are hundreds of enzymes that control histone and DNA modifications, their potential roles in substance abuse and alcohol dependence remain underexplored. A few recent studies have suggested that epigenetic processes could underlie transcriptomic and behavioral hallmarks of alcohol addiction. In the present study, we sought to identify epigenetic enzymes in the brain that are dysregulated during protracted abstinence as a consequence of chronic and intermittent alcohol exposure. Through quantitative mRNA expression analysis of over 100 epigenetic enzymes, we identified 11 that are significantly altered in alcohol-dependent rats compared with controls. Follow-up studies of one of these enzymes, the histone demethylase KDM6B, showed that this enzyme exhibits region-specific dysregulation in the prefrontal cortex and nucleus accumbens of alcohol-dependent rats. KDM6B was also upregulated in the human alcoholic brain. Upregulation of KDM6B protein in alcohol-dependent rats was accompanied by a decrease of trimethylation levels at histone H3, lysine 27 (H3K27me3), consistent with the known demethylase specificity of KDM6B. Subsequent epigenetic (chromatin immunoprecipitation [ChIP]–sequencing) analysis showed that alcohol-induced changes in H3K27me3 were significantly enriched at genes in the IL-6 signaling pathway, consistent with the well-characterized role of KDM6B in modulation of inflammatory responses. Knockdown of KDM6B in cultured microglial cells diminished IL-6 induction in response to an inflammatory stimulus. Our findings implicate a novel KDM6B-mediated epigenetic signaling pathway integrated with inflammatory signaling pathways that are known to underlie the development of alcohol addiction
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Absence of both MGME1 and POLG EXO abolishes mtDNA whereas absence of either creates unique mtDNA duplications
No full textBoth POLG and MGME1 are needed for mitochondrial DNA (mtDNA) maintenance in animal cells. POLG, the primary replicative polymerase of the mitochondria, has an exonuclease activity (3’→5’) that corrects for the misincorporation of bases. MGME1 serves as an exonuclease (5’→3’), producing ligatable DNA ends. Although both have a critical role in mtDNA replication and elimination of linear fragments, these mechanisms are still not fully understood. Using digital PCR to evaluate and compare mtDNA integrity, we show that Mgme1 knock out (Mgme1 KK) tissue mtDNA is more fragmented than POLG exonuclease deficient “Mutator” (Polg MM) or WT tissue. In addition, next generation sequencing of mutant hearts showed abundant duplications in/nearby the D-loop region and unique 100bp duplications evenly spaced throughout the genome only in Mgme1 KK hearts. However, despite these unique mtDNA features at steady-state, we observed a similar delay in the degradation of mtDNA after an induced double strand DNA break in both Mgme1 KK and Polg MM models. Lastly, we characterized double mutant (Polg MM/Mgme1 KK) cells and show that mtDNA cannot be maintained without at least one of these enzymatic activities. We propose a model for the generation of these genomic abnormalities which suggests a role for MGME1 outside of nascent mtDNA end ligation. Our results highlight the role of MGME1 in and outside of the D-loop region during replication, support the involvement of MGME1 in dsDNA degradation and demonstrate that POLG EXO and MGME1 can partially compensate for each other in maintaining mtDNA
Additional file 3: Table S3. of Epigenomic and metabolic responses of hypothalamic POMC neurons to gestational nicotine exposure in adult offspring
No full textExpression ranking of lncRNAs in POMC neurons. LncRNA genes referred to by Ensembl Gene ID (column A), gene name (column B), and gene type (column C) were ranked by average expression across all samples (column D). Only lncRNA genes expressed at levelsâ>â1 CPM were considered for analysis. CPM counts per million. (XLSX 98 kb
Additional file 2: Table S2. of Epigenomic and metabolic responses of hypothalamic POMC neurons to gestational nicotine exposure in adult offspring
No full textExpressed protein-coding genes in PANTHER pathways. Expressed protein-coding genes denoted by Ensembl Gene ID (column A), gene name and symbol (column B), Panther family/subfamily (column C), Panther protein class (column D), and average expression in CPM (column E) were assigned to PANTHER defined pathways, which are referred to by name and accession number. Only genes expressed at levelsâ>â1 CPM were considered for analysis. CPM counts per million. (XLSX 172 kb
Additional file 4: Table S4. of Epigenomic and metabolic responses of hypothalamic POMC neurons to gestational nicotine exposure in adult offspring
No full textCo-expressed lncRNAs and protein-coding genes in cis. Co-expression of lncRNAs (columns A and B) with their nearest (adjacent or overlapping) protein-coding gene (column D) was determined by the Pearson’s correlation coefficient r (column F). An r value > 0.602 or 1 CPM (columns K and L) were considered for analyses. LncRNA expression was in most cases less than that of the coding gene (column M). Coding genes function in various biological processes (column N). (XLSX 63 kb
Additional file 1: Table S1. of Epigenomic and metabolic responses of hypothalamic POMC neurons to gestational nicotine exposure in adult offspring
No full textGene list. Read-pairs were aligned by STAR to the mouse reference genome. STAR alignments were run through HTSeq for determination of read-pair counts by genes. Genes are denoted by their Ensembl gene ID, gene symbol, and gene type (columns AâC). EdgeR calculated average gene expression values across all offspring (column D) and fold-changes between nicotine-exposed and control offspring (FC (N/C), column E). EdgeR (column F), baySeq (column G), and DESeq (column H) determined differential gene expression. FDR false discovery rate-adjusted p value, CPM counts per million. (XLSX 2364 kb
Author Correction: Defective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis
No full textAuthor Correction to: "Defective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis
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