10 research outputs found

    Mutation of a single residue, β-glutamate-20, alters protein–lipid interactions of light harvesting complex II

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    It is well established that assembly of the peripheral antenna complex, LH2, is required for proper photosynthetic membrane biogenesis in the purple bacterium Rhodobacter sphaeroides. The underlying interactions are, as yet, not understood. Here we examined the relationship between the morphology of the photosynthetic membrane and the lipid–protein interactions at the LH2–lipid interface. The non-bilayer lipid, phosphatidylethanolamine, is shown to be highly enriched in the boundary lipid phase of LH2. Sequence alignments indicate a putative lipid binding site, which includes β-glutamate-20 and the adjacent carotenoid end group. Replacement of β-glutamate-20 with alanine results in significant reduction of phosphatidylethanolamine and concomitant raise in phosphatidylcholine in the boundary lipid phase of LH2 without altering the lipid composition of the bulk phase. The morphology of the LH2 housing membrane is, however, unaffected by the amino acid replacement. In contrast, simultaneous modification of glutamate-20 and exchange of the carotenoid sphaeroidenone with neurosporene results in significant enlargement of the vesicular membrane invaginations. These findings suggest that the LH2 complex, specifically β-glutamate-20 and the carotenoids' polar head group, contribute to the shaping of the photosynthetic membrane by specific interactions with surrounding lipid molecules

    Iron management in chronic kidney disease: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference

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    Before the introduction of erythropoiesis-stimulating agents (ESAs) in 1989, repeated transfusions given to patients with end-stage renal disease caused iron overload, and the need for supplemental iron was rare. However, with the widespread introduction of ESAs, it was recognized that supplemental iron was necessary to optimize hemoglobin response and allow reduction of the ESA dose for economic reasons and recent concerns about ESA safety. Iron supplementation was also found to be more efficacious via intravenous compared to oral administration, and the use of intravenous iron has escalated in recent years. The safety of various iron compounds has been of theoretical concern due to their potential to induce iron overload, oxidative stress, hypersensitivity reactions, and a permissive environment for infectious processes. Therefore, an expert group was convened to assess the benefits and risks of parenteral iron, and to provide strategies for its optimal use while mitigating the risk for acute reactions and other adverse effects

    Iron management in chronic kidney disease:Conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference

    Get PDF
    Before the introduction of erythropoiesis-stimulating agents (ESAs) in 1989, repeated transfusions given to patients with end-stage renal disease caused iron overload, and the need for supplemental iron was rare. However, with the widespread introduction of ESAs, it was recognized that supplemental iron was necessary to optimize hemoglobin response and allow reduction of the ESA dose for economic reasons and recent concerns about ESA safety. Iron supplementation was also found to be more efficacious via intravenous compared to oral administration, and the use of intravenous iron has escalated in recent years. The safety of various iron compounds has been of theoretical concern due to their potential to induce iron overload, oxidative stress, hypersensitivity reactions, and a permissive environment for infectious processes. Therefore, an expert group was convened to assess the benefits and risks of parenteral iron, and to provide strategies for its optimal use while mitigating the risk for acute reactions and other adverse effects

    Discovery and Development of Non-Dopaminergic Agents for the Treatment of Schizophrenia: Overview of the Preclinical and Early Clinical Studies

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    A DEMOGRAPHIC PARADOX: CAUSES AND CONSEQUENCES OF FEMALE GENITAL CUTTING IN NORTHEASTERN AFRICA

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    Iron management in chronic kidney disease: conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference

    No full text
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