The presynaptic ribbon maintains vesicle populations at the hair cell afferent fiber synapse

The ribbon is the structural hallmark of cochlear inner hair cell (IHC) afferent synapses, yet its role in information transfer to spiral ganglion neurons (SGNs) remains unclear. We investigated the ribbon’s contribution to IHC synapse formation and function using KO mice lacking RIBEYE. Despite loss of the entire ribbon structure, synapses retained their spatiotemporal development and KO mice had a mild hearing deficit. IHCs of KO had fewer synaptic vesicles and reduced exocytosis in response to brief depolarization; a high stimulus level rescued exocytosis in KO. SGNs exhibited a lack of sustained excitatory postsynaptic currents (EPSCs). We observed larger postsynaptic glutamate receptor plaques, potentially compensating for the reduced EPSC rate in KO. Surprisingly, large-amplitude EPSCs were maintained in KO, while a small population of low-amplitude slower EPSCs was increased in number. The ribbon facilitates signal transduction at physiological stimulus levels by retaining a larger residency pool of synaptic vesicles.</jats:p

Lack of beta(2)-adrenoceptors aggravates heart failure-induced skeletal muscle myopathy in mice

Skeletal myopathy is a hallmark of heart failure (HF) and has been associated with a poor prognosis. HF and other chronic degenerative diseases share a common feature of a stressed system: sympathetic hyperactivity. Although beneficial acutely, chronic sympathetic hyperactivity is one of the main triggers of skeletal myopathy in HF. Considering that (2)-adrenoceptors mediate the activity of sympathetic nervous system in skeletal muscle, we presently evaluated the contribution of (2)-adrenoceptors for the morphofunctional alterations in skeletal muscle and also for exercise intolerance induced by HF. Male WT and (2)-adrenoceptor knockout mice on a FVB genetic background (2KO) were submitted to myocardial infarction (MI) or SHAM surgery. Ninety days after MI both WT and 2KO mice presented to cardiac dysfunction and remodelling accompanied by significantly increased norepinephrine and epinephrine plasma levels, exercise intolerance, changes towards more glycolytic fibres and vascular rarefaction in plantaris muscle. However, 2KO MI mice displayed more pronounced exercise intolerance and skeletal myopathy when compared to WT MI mice. Skeletal muscle atrophy of infarcted 2KO mice was paralleled by reduced levels of phosphorylated Akt at Ser 473 while increased levels of proteins related with the ubiquitin--proteasome system, and increased 26S proteasome activity. Taken together, our results suggest that lack of (2)-adrenoceptors worsen and/or anticipate the skeletal myopathy observed in HF.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ São Paulo, Escola Educ Fis & Esporte, BR-05508900 São Paulo, BrazilUniv São Paulo, Fac Med, Inst Heart, BR-05508900 São Paulo, BrazilUniv São Paulo, Sch Phys Educ & Sport, BR-14049 Ribeirao Preto, BrazilUniversidade Federal de São Paulo, Dept Med, Div Nephrol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, Div Nephrol, São Paulo, BrazilFAPESP: 2008/56483-1CNPq: 302201/2011-4FAPESP: 2010/50048-1Web of Scienc

Colaboración internacional y buenas prácticas en la gestión de enfermedades crónicas complejas a través de herramientas web 2.0: Observatorio de prácticas innovadoras en el manejo de enfermedades crónicas complejas OPIMEC

Ponencias de la Segunda Conferencia internacional sobre brecha digital e inclusión social, celebrada del 28 al 30 de octubre de 2009 en la Universidad Carlos III de MadridLas enfermedades crónicas (EC) constituyen un reto de salud mundial en el siglo XXI. La OMS las define como enfermedades de larga duración por lo general de progresión lenta y prevé que en 2020 serán responsables del 73% de las muertes y del 60% de la carga global de enfermedad (World Health Organization, 2002). Es primordial que la comunidad internacional de salud pública y de gestión sanitaria conozca y comparta información sobre los avances en las prácticas tecnológicas y organizativas más innovadoras en gestión de EC, con énfasis en las EC Complejas (ECC) asociadas a una mayor pérdida de autonomía y grado de dependencia y discapacidad. Con este propósito, a mediados de 2006, la Dirección General de Innovación Sanitaria, Sistemas y Tecnología de la Consejería de Salud de la Junta de Andalucía crea el «Observatorio de Prácticas Innovadoras para el Manejo de Enfermedades Crónicas Complejas» (OPIMEC) que impulsa la participación y generación de conocimiento en información sanitaria para profesionales y una Plataforma de Red en el ámbito de la gestión de ECC para el fomento de alianzas y colaboraciones desde Andalucía basadas en dar y recibir conocimiento abierto entre personas, equipos y organizaciones (Jadad AR, 1999, p. 761-764; Jadad AR, 2000, p.362-365). La Web del Observatorio de Prácticas Innovadoras en el Manejo de Enfermedades Crónicas Complejas (OPIMEC), http://www.opimec.org, va centrada en la creación de una plataforma basada en la Web 2.0. que permite el acceso y la edición colaborativa de contenidos para profesionales. El objetivo fundamental de esta plataforma es compartir y colaborar en la generación y difusión de conocimiento, todo ello facilitado con herramientas innovadoras de la Web 2.0. como son la publicación de contenidos, la votación, comentarios sobre los contenidos, la sindicación de contenidos y la creación de comunidades abiertas de trabajo colaborativo. El proyecto OPIMEC cuenta con una cadena de procesos de gestión de la información de los que podemos destacar su forma colaborativa de crear conocimiento por todas las personas usuarias de la plataforma, un equipo editorial encargado de asegurar la calidad de los contenidos y una evaluación por pares de las prácticas y organizaciones propuestas en la Web. Desde la edición, hasta la publicación y su distribución final el conocimiento es examinado metódicamente. Este proceso es automatizado a través de herramientas de software libre creadas para OPIMEC y asesorado por su Consejo Asesor Internacional. Así pues, la plataforma Web 2.0 que da soporte al observatorio OPIMEC está construida sobre tecnologías libres como: Framework Web Django (impulsado por Google Inc. entre otros), MySQL y GNU/Linux. La elección de esta combinación tecnológica se ha realizado tras un análisis exhaustivo sobre las tecnologías abiertas disponibles, en base a criterios de eficiencia, productividad y adaptabilidad a las necesidades actuales y futuras de OPIMEC. La Web OPIMEC tiene intención y vocación de convertirse en un destacado proyecto a nivel mundial con clara vertiente de cooperación internacional e innovación, mejorando la calidad de vida de la ciudadanía, aprovechando las herramientas que ofrece la difundida red global de Internet y promocionando la participación e iniciativa de los y las profesionales. Nuestra Web OPIMEC está estructurada en espacios que facilitan y propician la participación y consecución de los objetivos del proyecto, con el fin de que la asimilación de sus contenidos por parte de las personas usuarias sea eficiente y efectiva. Podemos encontrar en ella, herramientas existentes en las redes sociales así como algunas nuevas desarrolladas específicamente para OPIMEC, como son los “documentos colaborativos”, que facilitarán el trabajo, la conexión y la participación de profesionales desde cualquier parte del mundo, pudiendo así aprovechar los recursos al máximo, Se dispone por tanto de destacadas herramientas como una base de datos actualizada de eventos, noticias, recursos y documentos, directorios y mapas de organizaciones, prácticas y personas innovadoras, espacios de comunidad en las que los equipos de trabajo pueden desarrollarse, comunicarse y complementarse con otras personas usuarias, compartiendo buenas prácticas, innovación y contenidos novedosos en el manejo de enfermedades crónicas complejas. El aspecto importante de la plataforma es que las personas usuarias son de forma democrática, creadores, evaluadores y consumidores de los contenidos publicados, siendo así una herramienta de trabajo construida, ampliada, valorada y seguida por toda la comunidad de profesionales; facilitando la difusión del conocimiento construido por y para todos y todas los profesionales sanitarios, personal investigador, ciudadanos y ciudadanas en general en el manejo de enfermedades crónicas complejas. Un conocimiento ampliamente compartido es la clave para aumentar y mejorar el bienestar social y la calidad de vida

A pedagogic appraisal of the Priority Heuristic

We have explored how science and mathematics teachers made decisions when confronted with a dilemma in which a fictitious young woman, Deborah, may choose to have an operation that might address a painful spinal condition. We sought to explore the extent to which psychological heuristic models, in particular the Priority Heuristic, might successfully describe the decision-making process of these teachers and how an analysis of the role of personal and emotional factors in shaping the decision-making process might inform pedagogical design. A novel aspect of this study is that the setting in which the decision-making process is examined contrasts sharply with those used in psychological experiments. We found that to some extent, even in this contrasting setting, the Priority Heuristic could describe these teachers' decision-making. Further analysis of the transcripts yielded some insights into limitations on scope as well the richness and complexity in how personal factors were brought to bear. We see these limitations as design opportunities for educational intervention

Asexuality: Classification and characterization

This is a post-print version of the article. The official published version can be obtaineed at the link below.The term “asexual” has been defined in many different ways and asexuality has received very little research attention. In a small qualitative study (N = 4), individuals who self-identified as asexual were interviewed to help formulate hypotheses for a larger study. The second larger study was an online survey drawn from a convenience sample designed to better characterize asexuality and to test predictors of asexual identity. A convenience sample of 1,146 individuals (N = 41 self-identified asexual) completed online questionnaires assessing sexual history, sexual inhibition and excitation, sexual desire, and an open-response questionnaire concerning asexual identity. Asexuals reported significantly less desire for sex with a partner, lower sexual arousability, and lower sexual excitation but did not differ consistently from non-asexuals in their sexual inhibition scores or their desire to masturbate. Content analyses supported the idea that low sexual desire is the primary feature predicting asexual identity

Decision-making, cognitive distortions and alcohol use in adolescent problem and non-problem gamblers: an experimental study

In the psychological literature, many studies have investigated the neuropsychological and behavioral changes that occur developmentally during adolescence. These studies have consistently observed a deficit in the decision-making ability of children and adolescents. This deficit has been ascribed to incomplete brain development. The same deficit has also been observed in adult problem and pathological gamblers. However, to date, no study has examined decision-making in adolescents with and without gambling problems. Furthermore, no study has ever examined associations between problem gambling, decision-making, cognitive distortions and alcohol use in youth. To address these issues, 104 male adolescents participated in this study. They were equally divided in two groups, problem gamblers and non-problem gamblers, based on South Oaks Gambling Screen Revised for Adolescents scores. All participants performed the Iowa Gambling Task and completed the Gambling Related Cognitions Scale and the Alcohol Use Disorders Identification Test. Adolescent problem gamblers displayed impaired decision-making, reported high cognitive distortions, and had more problematic alcohol use compared to non-problem gamblers. Strong correlations between problem gambling, alcohol use, and cognitive distortions were observed. Decision-making correlated with interpretative bias. This study demonstrated that adolescent problem gamblers appear to have the same psychological profile as adult problem gamblers and that gambling involvement can negatively impact on decision-making ability that, in adolescence, is still developing. The correlations between interpretative bias and decision-making suggested that the beliefs in the ability to influence gambling outcomes may facilitate decision-making impairment

Logopenic and nonfluent variants of primary progressive aphasia are differentiated by acoustic measures of speech production

Differentiation of logopenic (lvPPA) and nonfluent/agrammatic (nfvPPA) variants of Primary Progressive Aphasia is important yet remains challenging since it hinges on expert based evaluation of speech and language production. In this study acoustic measures of speech in conjunction with voxel-based morphometry were used to determine the success of the measures as an adjunct to diagnosis and to explore the neural basis of apraxia of speech in nfvPPA. Forty-one patients (21 lvPPA, 20 nfvPPA) were recruited from a consecutive sample with suspected frontotemporal dementia. Patients were diagnosed using the current gold-standard of expert perceptual judgment, based on presence/absence of particular speech features during speaking tasks. Seventeen healthy age-matched adults served as controls. MRI scans were available for 11 control and 37 PPA cases; 23 of the PPA cases underwent amyloid ligand PET imaging. Measures, corresponding to perceptual features of apraxia of speech, were periods of silence during reading and relative vowel duration and intensity in polysyllable word repetition. Discriminant function analyses revealed that a measure of relative vowel duration differentiated nfvPPA cases from both control and lvPPA cases (r2 = 0.47) with 88% agreement with expert judgment of presence of apraxia of speech in nfvPPA cases. VBM analysis showed that relative vowel duration covaried with grey matter intensity in areas critical for speech motor planning and programming: precentral gyrus, supplementary motor area and inferior frontal gyrus bilaterally, only affected in the nfvPPA group. This bilateral involvement of frontal speech networks in nfvPPA potentially affects access to compensatory mechanisms involving right hemisphere homologues. Measures of silences during reading also discriminated the PPA and control groups, but did not increase predictive accuracy. Findings suggest that a measure of relative vowel duration from of a polysyllable word repetition task may be sufficient for detecting most cases of apraxia of speech and distinguishing between nfvPPA and lvPPA

Emotional intelligence buffers the effect of physiological arousal on dishonesty

We studied the emotional processes that allow people to balance two competing desires: benefitting from dishonesty and keeping a positive self-image. We recorded physiological arousal (skin conductance and heart rate) during a computer card game in which participants could cheat and fail to report a certain card when presented on the screen to avoid losing their money. We found that higher skin conductance corresponded to lower cheating rates. Importantly, emotional intelligence regulated this effect; participants with high emotional intelligence were less affected by their physiological reactions than those with low emotional intelligence. As a result, they were more likely to profit from dishonesty. However, no interaction emerged between heart rate and emotional intelligence. We suggest that the ability to manage and control emotions can allow people to overcome the tension between doing right or wrong and license them to bend the rules

Integrative Effect of Carvedilol and Aerobic Exercise Training Therapies on Improving Cardiac Contractility and Remodeling in Heart Failure Mice

The use of b-blockers is mandatory for counteracting heart failure (HF)-induced chronic sympathetic hyperactivity, cardiac dysfunction and remodeling. Importantly, aerobic exercise training, an efficient nonpharmacological therapy to HF, also counteracts sympathetic hyperactivity in HF and improves exercise tolerance and cardiac contractility; the latter associated with changes in cardiac Ca2+ handling. This study was undertaken to test whether combined b-blocker and aerobic exercise training would integrate the beneficial effects of isolated therapies on cardiac structure, contractility and cardiomyocyte Ca2+ handling in a genetic model of sympathetic hyperactivity-induced HF (alpha(2A)/alpha 2C(-)adrenergic receptor knockout mice, KO). We used a cohort of 5-7 mo male wild-type (WT) and congenic mice (KO) with C57Bl6/J genetic background randomly assigned into 5 groups: control (WT), saline-treated KO (KOS), exercise trained KO (KOT), carvedilol-treated KO (KOC) and, combined carvedilol-treated and exercise-trained KO (KOCT). Isolated and combined therapies reduced mortality compared with KOS mice. Both KOT and KOCT groups had increased exercise tolerance, while groups receiving carvedilol had increased left ventricular fractional shortening and reduced cardiac collagen volume fraction compared with KOS group. Cellular data confirmed that cardiomyocytes from KOS mice displayed abnormal Ca2+ handling. KOT group had increased intracellular peak of Ca2+ transient and reduced diastolic Ca2+ decay compared with KOS group, while KOC had increased Ca2+ decay compared with KOS group. Notably, combined therapies re-established cardiomyocyte Ca2+ transient paralleled by increased SERCA2 expression and SERCA2: PLN ratio toward WT levels. Aerobic exercise trained increased the phosphorylation of PLN at Ser16 and Thr17 residues in both KOT and KOCT groups, but carvedilol treatment reduced lipid peroxidation in KOC and KOCT groups compared with KOS group. the present findings provide evidence that the combination of carvedilol and aerobic exercise training therapies lead to a better integrative outcome than carvedilol or exercise training used in isolation.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Conselho Nacional de Pesquisa e DesenvolvimentoConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ São Paulo, Sch Phys Educ & Sport, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biosci, Santos, BrazilDept Circulat & Med Imaging, Trondheim, NorwayKG Jebsen Ctr Exercise Med, Trondheim, NorwayUniv Fed Minas Gerais, Dept Physiol & Biophys, Belo Horizonte, MG, BrazilUniv São Paulo, Heart Inst InCor, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biosci, Santos, BrazilFAPESP: FAPESP:2010/50048-1FAPESP: 06/56123-0CNPq: 302201/2011-4Web of Scienc

Thinking like a trader selectively reduces individuals' loss aversion

Research on emotion regulation has focused upon observers' ability to regulate their emotional reaction to stimuli such as affective pictures, but many other aspects of our affective experience are also potentially amenable to intentional cognitive regulation. In the domain of decision-making, recent work has demonstrated a role for emotions in choice, although such work has generally remained agnostic about the specific role of emotion. Combining psychologically-derived cognitive strategies, physiological measurements of arousal, and an economic model of behavior, this study examined changes in choices (specifically, loss aversion) and physiological correlates of behavior as the result of an intentional cognitive regulation strategy. Participants were on average more aroused per dollar to losses relative to gains, as measured with skin conductance response, and the difference in arousal to losses versus gains correlated with behavioral loss aversion across subjects. These results suggest a specific role for arousal responses in loss aversion. Most importantly, the intentional cognitive regulation strategy, which emphasized “perspective-taking,” uniquely reduced both behavioral loss aversion and arousal to losses relative to gains, largely by influencing arousal to losses. Our results confirm previous research demonstrating loss aversion while providing new evidence characterizing individual differences and arousal correlates and illustrating the effectiveness of intentional regulation strategies in reducing loss aversion both behaviorally and physiologically