10 research outputs found

    Nucleosome Binding by the Lysine Specific Demethylase 1 (LSD1) Enzyme Enables Histone H3 Demethylation

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    The essential human enzyme lysine specific demethylase 1 (LSD1) silences genes by demethylating mono- and dimethylated lysine 4 in histone H3 (H3K4me1/2). Studies of the minimal requirements for LSD1 activity are complicated by the heterogeneity of histone modification states in cells. We overcame this challenge by generating homogeneous mononucleosome substrates containing semisynthetic H3K4me2. Biophysical and biochemical assays with full-length LSD1 revealed its ability to bind and demethylate nucleosomes. Consistent with a requirement for nucleosome binding prior to demethylation, a competing nucleosome-binding peptide from the high-mobility group protein effectively inhibited LSD1 activity. Thus, our studies provide the first glimpse of nucleosome demethylation by LSD1 in the absence of other scaffolding proteins

    Strategic Identity: Bridging Self-Determination and Solidarity Among the Indigenous Peoples of Mindanao, the Philippines

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    This article introduces the concept of ‘strategic identity’ as a bridge between the indigenous peoples’ struggle for self-determination and their search for solidarity in the context of globalization, with a focus on the Lumads, or indigenous peoples in southern Philippines. The paper begins with an encounter with a global actor affecting a local community. We realize the impact of powerful, well-networked forces that challenge even the operation of the state. Without trivializing the threats associated with this model of globalization, we also insist that a realistic and hopeful approach may emerge if we acknowledge the many ‘selves’ in the indigenous peoples’ self-determination. At the heart of this proposal is a matrix that unpacks the complex ways that local, national, sectoral, and global actors can engage in conflict or solidarity with these strategic identity assertions. Solidarity work, then, becomes diversified and strategized in response to the evolving multiple indigenous identities that modernity paradoxically both endangers and engenders

    Angiotensin receptor neprilysin inhibition compared with enalapril on the risk of clinical progression in surviving patients with heart failure.

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