78 research outputs found

    Building Capacity in Nonprofit Organizations

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    Offers a capacity building model that is based on a review of civil society, sustainable development, and organizational management literature. Reviews effective capacity building programs sponsored or operated by foundations. Includes recommendations

    H2B ubiquitylation is part of chromatin architecture that marks exon-intron structure in budding yeast

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    <p>Abstract</p> <p>Background</p> <p>The packaging of DNA into chromatin regulates transcription from initiation through 3' end processing. One aspect of transcription in which chromatin plays a poorly understood role is the co-transcriptional splicing of pre-mRNA.</p> <p>Results</p> <p>Here we provide evidence that H2B monoubiquitylation (H2BK123ub1) marks introns in <it>Saccharomyces cerevisiae</it>. A genome-wide map of H2BK123ub1 in this organism reveals that this modification is enriched in coding regions and that its levels peak at the transcribed regions of two characteristic subgroups of genes. First, long genes are more likely to have higher levels of H2BK123ub1, correlating with the postulated role of this modification in preventing cryptic transcription initiation in ORFs. Second, genes that are highly transcribed also have high levels of H2BK123ub1, including the ribosomal protein genes, which comprise the majority of intron-containing genes in yeast. H2BK123ub1 is also a feature of introns in the yeast genome, and the disruption of this modification alters the intragenic distribution of H3 trimethylation on lysine 36 (H3K36me3), which functionally correlates with alternative RNA splicing in humans. In addition, the deletion of genes encoding the U2 snRNP subunits, Lea1 or Msl1, in combination with an <it>htb-K123R </it>mutation, leads to synthetic lethality.</p> <p>Conclusion</p> <p>These data suggest that H2BK123ub1 facilitates cross talk between chromatin and pre-mRNA splicing by modulating the distribution of intronic and exonic histone modifications.</p

    Redox cycling metals: Pedaling their roles in metabolism and their use in the development of novel therapeutics

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    Essential metals, such as iron and copper, play a critical role in a plethora of cellular processes including cell growth and proliferation. However, concomitantly, excess of these metal ions in the body can have deleterious effects due to their ability to generate cytotoxic reactive oxygen species (ROS). Thus, the human body has evolved a very well-orchestrated metabolic system that keeps tight control on the levels of these metal ions. Considering their very high proliferation rate, cancer cells require a high abundance of these metals compared to their normal counterparts. Interestingly, new anti-cancer agents that take advantage of the sensitivity of cancer cells to metal sequestration and their susceptibility to ROS have been developed. These ligands can avidly bind metal ions to form redox active metal complexes, which lead to generation of cytotoxic ROS. Furthermore, these agents also act as potent metastasis suppressors due to their ability to up-regulate the metastasis suppressor gene, N-myc downstream regulated gene 1. This review discusses the importance of iron and copper in the metabolism and progression of cancer, how they can be exploited to target tumors and the clinical translation of novel anti-cancer chemotherapeutics

    Climate-Mediated Changes to Linked Terrestrial and Marine Ecosystems across the Northeast Pacific Coastal Temperate Rainforest Margin

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    Coastal margins are important areas of materials flux that link terrestrial and marine ecosystems. Consequently, climate-mediated changes to coastal terrestrial ecosystems and hydrologic regimes have high potential to influence nearshore ocean chemistry and food web dynamics. Research from tightly coupled, high-flux coastal ecosystems can advance understanding of terrestrial–marine links and climate sensitivities more generally. In the present article, we use the northeast Pacific coastal temperate rainforest as a model system to evaluate such links. We focus on key above- and belowground production and hydrological transport processes that control the land-to-ocean flow of materials and their influence on nearshore marine ecosystems. We evaluate how these connections may be altered by global climate change and we identify knowledge gaps in our understanding of the source, transport, and fate of terrestrial materials along this coastal margin. Finally, we propose five priority research themes in this region that are relevant for understanding coastal ecosystem links more broadly.Ye

    Picture-Book Professors:Academia and Children's Literature

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    Use of the Massachusetts Youth Screening Instrument to assess mental health problems in young people within an Australian youth detention centre

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    To screen for mental health problems in an Australian adolescent forensic population, evaluate the Massachusetts Youth Screening Instrument Version 2 (MAYSI-2) in providing a preliminary assessment of those needs, and to explore the level of mental health problems in vulnerable populations within detention.Over a 6-month period, all young people admitted into detention were referred for screening by the MAYSI-2, a 7-scaled instrument developed to identify young people within the youth justice system at greatest risk for serious mental, emotional or behavioural disorders.High levels of mental health problems and trauma were reported, with 75.0% of males and 90.0% of females, and 81.2% of Indigenous and 75.0% of non-Indigenous youth screening above the clinical cut-off for at least one scale. Males screened highest on the Alcohol and Drug Use (58.9%), Angry-Irritable (28.2%) and Somatic Complaints (28.2%). Females screened highest on the Alcohol and Drug Use (67.5%), Somatic Complaints (45.0%), Depressed-Anxious (42.5%) and Suicide Ideation (30.0%) scales, with significantly higher rates than males on the Depressed-Anxious, Somatic Complaints and Suicide Ideation scales. No significant differences in screening rates were reported between Indigenous and non-Indigenous youth.This study confirmed the high rates of mental health problems in adolescents within youth detention. Appropriate use of screening tools improves our understanding and targets treatment of mental health problems in this cohort. We have reservations in recommending the MAYSI-2 as a valid screening tool for Indigenous young people in youth detention and recommend the development of a more appropriate screening tool

    The Standing of Ardetta Neoxena

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    Volume: 13Start Page: 11End Page: 1
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