421 research outputs found

    Familial mutants of α-synuclein with increased neurotoxicity have a destabilized conformation

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    A30P and A53T mutations of the presynaptic protein α-synuclein are associated with familial forms of Parkinson’s disease. NMR spectroscopy demonstrates that Parkinsonism-linked mutations greatly perturb specific tertiary interactions essential for the native state of α-synuclein. However, α-synuclein is not completely unfolded, but exhibits structural fluctuations on the time scale of secondary structure formation, and loses its native conformation gradually when protein stability decreases. The redistribution of the ensemble of α-synuclein conformers may underlie toxic gain-of-function by fostering self-association and altered binding affinity to ligands and receptors

    Structural characterization of copper(II) binding to α-Synuclein: Insights into the bioinorganic chemistry of Parkinson's disease

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    The aggregation of α -synuclein (AS) is characteristic of Parkinson’s disease and other neurodegenerative synucleinopathies. We demonstrate here that Cu(II) ions are effective in accelerating AS aggregation at physiologically relevant concentrations without altering the resultant fibrillar structures. By using numerous spectroscopic techniques (absorption, CD, EPR, and NMR), we have located the primary binding for Cu(II) to a specific site in the N terminus, involving His-50 as the anchoring residue and other nitrogen oxygen donor atoms in a square planar or distorted tetragonal geometry. The carboxylate-rich C terminus, originally thought to drive copper binding, is able to coordinate a second Cu(II) equivalent, albeit with a 300-fold reduced affinity. The NMR analysis of AS–Cu(II) complexes reveals the existence of conformational restrictions in the native state of the protein. The metallobiology of Cu(II) in Parkinson’s disease is discussed by a comparative analysis with other Cu(II)-binding proteins involved in neurodegenerative disorders

    Habitat use and abundance of goliath grouper Epinephelus itajara in Brazil: a participative survey

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    Developing survey strategies for threatened species is often limited by access to sufficient individuals to acquire information needed to design appropriate conservation measures. The goliath grouper (Epinephelus itajara) is a large reef fish, globally classified as critically endangered. In Brazil, fishing has been prohibited since 2002. Herein we investigated habitat use and abundance of E. itajara in Brazil drawn from a participative survey, which engaged volunteer divers in data-collection. A total of 188 reports were recorded between 2005 to 2011 throughout 13 Brazilian states. Our results revealed that habitat type influenced the relationship between total length and depth of occurrence of E. itajara. We observed a significant difference between habitats, artificial presented a nonlinear and natural an asymptotic relationship. This study underscores the importance of developing conservation measures addressing specific habitats and locations to enhance population recovery. Artificial structures (shipwrecks and manmade reefs) are critical habitats that must be considered as highly sensitive areas to E. itajara strategic conservation policies. We suggest the creation and implementation of marine protected areas, as key strategies for E. itajara conservation, especially for artificial habitats and aggregation sites124803810O desenvolvimento de estratégias de pesquisa para espécies ameaçadas é frequentemente limitado pelo acesso a indivíduos suficientes para adquirir informações necessárias para elaborar medidas de conservação adequadas. Dentre essas espécies, o mero (Epinephelus itajara) é um peixe recifal de grande tamanho, classificado globalmente como criticamente ameaçado. No Brasil, a pesca é proibida desde 2002. Investigou-se o uso de hábitat e abundância de E. itajara no Brasil através de uma pesquisa participativa, que engajou mergulhadores voluntários na coleta dos dados. Um total de 188 relatos foram registrados entre 2005 a 2011 em 13 estados brasileiros. Os resultados revelaram que o tipo de hábitat influenciou a relação entre o comprimento total e profundidade de ocorrência de E. itajara. Observou-se uma diferença significativa entre hábitats: hábitat artificial apresentou uma relação não linear e hábitat natural uma relação assintótica. Este estudo ressalta a importância do desenvolvimento de medidas de conservação abordando hábitats e locais específicos visando a recuperação populacional. Estruturas artificiais (naufrágios e recifes feitos pelo homem) são hábitats críticos que devem ser considerados como áreas relevantes para as estratégias políticas conservação de E. itajara. Sugere-se a criação e implementação de áreas marinhas protegidas como uma estratégia fundamental para a conservação de E. itajara, especialmente em hábitats artificiais e locais de agregaçãosem informaçã

    Batata 'cristal'.

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    Scattering length of the ground state Mg+Mg collision

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    We have constructed the X 1SIGMAg+ potential for the collision between two ground state Mg atoms and analyzed the effect of uncertainties in the shape of the potential on scattering properties at ultra-cold temperatures. This potential reproduces the experimental term values to 0.2 inverse cm and has a scattering length of +1.4(5) nm where the error is prodominantly due to the uncertainty in the dissociation energy and the C6 dispersion coefficient. A positive sign of the scattering length suggests that a Bose-Einstein condensate of ground state Mg atoms is stable.Comment: 15 pages, 3 figures, Submitted Phys. Rev.

    Nursing clinical competence in area medica

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    Introduzione Background • La nursing clinical competence • Il concetto di clinical competence in medicina interna • Declinare e classificare i livelli di competenza • Aree di assistenza nei contesti di area medica   • Il paziente cronico • Scompenso cardiaco • La broncopneumopatia cronica e ostruttiva • La cirrosi epatica • La pancreatite • Il diabete mellito • Il delirium • La depressione • Il paziente critico • L’ipertensione • La trombosi venosa profonda • L’ischemia cerebrale • La disfagia • Gli squilibri idroelettrolitici • Le polmoniti • I sanguinamenti gastro-intestinali • La sepsi • Il monitoraggio cardiaco • La ventilazione non-invasiva • L’ecografia operativa bedside • Somministrazione di terapia e chemioterapia • Le lesioni da pressione • Il dolore • Gli accessi vascolari • Il paziente fragile • La dimissione difficile • Il fine vita Obiettivo Metodi Risultati Conclusioni Bibliografi
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