25 research outputs found

    Brain tyrosinase overexpression implicates age-dependent neuromelanin production in Parkinson's disease pathogenesis

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    Brain tyrosinase; Neuromelanin production; Parkinson’sTirosinasa cerebral; Producció de neuromelanina; ParkinsonTirosinasa cerebral; Producción de neuromelanina; ParkinsonIn Parkinson's disease (PD) there is a selective degeneration of neuromelanin-containing neurons, especially substantia nigra dopaminergic neurons. In humans, neuromelanin accumulates with age, the latter being the main risk factor for PD. The contribution of neuromelanin to PD pathogenesis remains unknown because, unlike humans, common laboratory animals lack neuromelanin. Synthesis of peripheral melanins is mediated by tyrosinase, an enzyme also present at low levels in the brain. Here we report that overexpression of human tyrosinase in rat substantia nigra results in age-dependent production of human-like neuromelanin within nigral dopaminergic neurons, up to levels reached in elderly humans. In these animals, intracellular neuromelanin accumulation above a specific threshold is associated to an age-dependent PD phenotype, including hypokinesia, Lewy body-like formation and nigrostriatal neurodegeneration. Enhancing lysosomal proteostasis reduces intracellular neuromelanin and prevents neurodegeneration in tyrosinase-overexpressing animals. Our results suggest that intracellular neuromelanin levels may set the threshold for the initiation of PD

    Cognitive remediation interventions in schizoaffective disorder: A systematic review

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    Background: Patients with schizoaffective disorder (SAD) suffer from cognitive impairment, which negatively influences their functionality. Cognitive remediation (CR) interventions have been shown to be effective in patients with schizophrenia (SZ) and bipolar disorder (BD), but evidence in SAD is limited so far. The aim of this study is to systematically review the published data on CR interventions, either in neurocognition or social cognition, in patients with SAD. Methods: We conducted a comprehensive, computerized literature search using terms related to CR interventions in psychotic and affective disorders, and particularly in SAD. Pubmed, Embase, and Web of Knowledge databases were used up to February 28th, 2018 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search returned 2672 articles of which four were finally selected meeting the inclusion criteria. Results: Cognitive Enhancement Therapy, computerized Cognitive Remediation Therapy and Cognitive Training showed positive results in subsamples of patients with SAD regarding neurocognition and functioning in comparable terms to patients with schizophrenia as well as in a greater extent in quality of life. Benefits in social cognition were also described when Social Cognition Interaction Training was considered in patients with SAD. Conclusions: CR interventions seem to improve neurocognition and social cognition in patients with SAD as well as functioning and quality of life. However, further randomized controlled trials on CR interventions with an optimized design focusing on selected sample of patients with SAD are imperative

    Ocean acidification stress index for shellfish (OASIS): Linking Pacific oyster larval survival and exposure to variable carbonate chemistry regimes

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    Understanding larval bivalve responses to variable regimes of seawater carbonate chemistry requires realistic quantification of physiological stress. Based on a degree-day modeling approach, we developed a new metric, the ocean acidification stress index for shellfish (OASIS), for this purpose. OASIS integrates over the entire larval period the instantaneous stress associated with deviations from published sensitivity thresholds to aragonite saturation state (OAr) while experiencing variable carbonate chemistry. We measured survival to D-hinge and pre-settlement stage of four Pacific oyster ('Crassostrea gigas') cohorts with different histories of carbonate chemistry exposure at the Whiskey Creek Hatchery, Netarts Bay, OR, to test the utility of OASIS as a stress metric and document the effects of buffering seawater in mitigating acute and chronic exposure to ocean acidification. Each cohort was divided into four groups and reared under the following conditions: 1) stable, buffered seawater for the entire larval period; 2) stable, buffered seawater for the first 48 hours, then naturally variable, unbuffered seawater; 3) stable, unbuffered seawater for the first 48 hours, then buffered seawater; and 4) stable, unbuffered seawater for the first 48 hours, then naturally variable, unbuffered seawater. Patterns in Netarts Bay carbonate chemistry were dominated by seasonal upwelling at the time of the experimental work, resulting in naturally highly variable OAr for the larvae raised in the unbuffered treatments. Two of the four cohorts showed strongly positive responses to buffering in survival to 48 hours; three of the four, in survival to pre-settlement. OASIS accurately predicted survival for two of the three cohorts tested (the fourth excluded due to other environmental factors), suggesting that this new metric could be used to better understand larval bivalve survival in naturally variable environments. OASIS may also be useful to an array of diverse stakeholders with increasing access to highly resolved temporal measurements of carbonate chemistry

    Contrasting marine carbonate systems in two fjords in British Columbia, Canada: Seawater buffering capacity and the response to anthropogenic CO2 invasion.

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    The carbonate system in two contrasting fjords, Rivers Inlet and Bute Inlet, on the coast of British Columbia, Canada, was evaluated to characterize the mechanisms driving carbonate chemistry dynamics and assess the impact of anthropogenic carbon. Differences in the character of deep water exchange between these fjords were inferred from their degree of exposure to continental shelf water and their salinity relationships with total alkalinity and total dissolved inorganic carbon, which determined seawater buffering capacity. Seawater buffering capacity differed between fjords and resulted in distinct carbonate system characteristics with implications on calcium carbonate saturation states and sensitivity to increasing anthropogenic carbon inputs. Saturation states of both aragonite and calcite mineral phases of calcium carbonate were seasonally at or below saturation throughout the entire water column in Bute Inlet, while only aragonite was seasonally under-saturated in portions of the water column in Rivers Inlet. The mean annual saturation states of aragonite in Rivers Inlet and calcite in Bute Inlet deep water layers have declined to below saturation within the last several decades due to anthropogenic carbon accumulation, and similar declines to undersaturation are projected in their surface layers as anthropogenic carbon continues to accumulate. This study demonstrates that the degree of fjord water exposure to open shelf water influences the uptake and sensitivity to anthropogenic carbon through processes affecting seawater buffering capacity, and that reduced uptake but greater sensitivity occurs where distance to ocean source waters and freshwater dilution are greater

    Seawater carbonate chemistry and larval shell development and growth of marine bivalve

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    Ocean acidification results in co-varying inorganic carbon system variables. Of these, an explicit focus on pH and organismal acid–base regulation has failed to distinguish the mechanism of failure in highly sensitive bivalve larvae. With unique chemical manipulations of seawater we show definitively that larval shell development and growth are dependent on seawater saturation state, and not on carbon dioxide partial pressure or pH. Although other physiological processes are affected by pH, mineral saturation state thresholds will be crossed decades to centuries ahead of pH thresholds owing to nonlinear changes in the carbonate system variables as carbon dioxide is added. Our findings were repeatable for two species of bivalve larvae could resolve discrepancies in experimental results, are consistent with a previous model of ocean acidification impacts due to rapid calcification in bivalve larvae, and suggest a fundamental ocean acidification bottleneck at early life-history for some marine keystone species

    Slow shell building, a possible trait for resistance to the effects of acute ocean acidification

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    Increasing anthropogenic carbon dioxide is altering marine carbonate chemistry through a process called ocean acidification. Many calcium carbonate forming organisms are sensitive to changes in marine carbonate chemistry, especially mollusk bivalve larvae at the initial shell building stage. Rapid calcification, limited energy reserves, and more exposed calcification surfaces, are traits at this stage that increase vulnerability to ocean acidification through our previously argued kinetic-energetic hypothesis. These developmental traits are common to broadcast spawning bivalve species that are the focus of most ocean acidification studies to date. Some oyster species brood their young, which results in slower development of the embryos through the initial shell formation stage. We examined the responses of the brooding Olympia oyster, Ostrea lurida, during their initial shell building stage. We extracted fertilized eggs from, O. lurida, prior to shell development, then exposed developing embryos to a wide range of marine carbonate chemistry conditions. Surprisingly, O. lurida showed no acute negative response to any ocean acidification treatments. Compared to the broadcast spawning Pacific oyster, Crassostrea gigas, calcification rate and standardized endogenous energy lipid consumption rate were nearly 10 and 50 times slower, respectively. Our results suggest that slow shell building may lessen the energetic burden of acidification at this stage and provides additional support for our kinetic-energetic hypothesis. Furthermore, these results may represent an example of exaptation; fitness conveyed by a coopted trait that evolved for another purpose, a concept largely lacking in the current perspective of adaptation and global climate change

    Odontodisplasia regional: relato de caso clĂ­nico

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    Regional Odontodysplasia is a rare dental anomaly involving dental tissues of ectodermal (enamel) and mesodermal (dentin, pulp and cement) origin. The aim of this study was to report a case of regional odontodysplasia in a child. A nine-year-old male patient who the main complaint was the absence of some deciduous teeth and the non - eruption of permanent teeth in a specific area of the maxilla. The tooth 16, which had erupted, had hypoplastic and hypomineralized enamel, presenting a radiographic image lacking clearness, for that reason being known “ghost teeth”.  In this case report, clinical and radiographic aspects were presented and were highlighted the issues involved in the elaboration of a treatment plan. There are few available studies about regional odontodysplasia. The detailed anamnesis and the knowledge of the clinical and radiographic characteristics are essential for a correct diagnosis.A Odontodisplasia Regional Ă© uma anomalia dental rara, que envolve os tecidos dentários de origem ectodĂ©rmica (esmalte) e mesodĂ©rmica (dentina, polpa e cemento). O objetivo deste trabalho foi relatar um caso clĂ­nico de odontodisplasia regional em uma criança. Paciente de nove anos, sexo masculino, tendo como queixa principal a ausĂŞncia de alguns dentes decĂ­duos e a nĂŁo irrupção dos dentes permanentes em determinada regiĂŁo da maxila. O dente 16, que havia irrompido, apresentava-se clinicamente, com um esmalte hipoplásico e hipomineralizado e uma imagem radiográfica bastante tĂŞnue, por isso sendo conhecido como “dente fantasma”. Foram apresentados nesse relato, aspectos clĂ­nicos e radiográficos e destacadas as questões envolvidas na elaboração de um plano de tratamento. Há poucos estudos disponĂ­veis sobre a odontodisplasia regional. A anamnese detalhada e o conhecimento das caracterĂ­sticas clĂ­nicas e radiográficas sĂŁo imprescindĂ­veis para um correto diagnĂłstico. &nbsp
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