Mutant huntingtin activates Nrf2-responsive genes and impairs dopamine synthesis in a PC12 model of Huntington's disease

<p>Abstract</p> <p>Background</p> <p>Huntington's disease is a progressive autosomal dominant neurodegenerative disorder that is caused by a CAG repeat expansion in the HD or Huntington's disease gene. Although micro array studies on patient and animal tissue provide valuable information, the primary effect of mutant huntingtin will inevitably be masked by secondary processes in advanced stages of the disease. Thus, cell models are instrumental to study early, direct effects of mutant huntingtin. mRNA changes were studied in an inducible PC12 model of Huntington's disease, before and after aggregates became visible, to identify groups of genes that could play a role in the early pathology of Huntington's disease.</p> <p>Results</p> <p>Before aggregation, up-regulation of gene expression predominated, while after aggregates became visible, down-regulation and up-regulation occurred to the same extent. After aggregates became visible there was a down-regulation of dopamine biosynthesis genes accompanied by down-regulation of dopamine levels in culture, indicating the utility of this model to identify functionally relevant pathways. Furthermore, genes of the anti-oxidant Nrf2-ARE pathway were up-regulated, possibly as a protective mechanism. In parallel, we discovered alterations in genes which may result in increased oxidative stress and damage.</p> <p>Conclusion</p> <p>Up-regulation of gene expression may be more important in HD pathology than previously appreciated. In addition, given the pathogenic impact of oxidative stress and neuroinflammation, the Nrf2-ARE signaling pathway constitutes a new attractive therapeutic target for HD.</p

Non-Standard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants

Binding the Smart City Human-Digital System with Communicative Processes

This chapter will explore the dynamics of power underpinning ethical issues within smart cities via a new paradigm derived from Systems Theory. The smart city is an expression of technology as a socio-technical system. The vision of the smart city contains a deep fusion of many different technical systems into a single integrated “ambient intelligence”. ETICA Project, 2010, p. 102). Citizens of the smart city will not experience a succession of different technologies, but a single intelligent and responsive environment through which they move. Analysis of such an environment requires a framework which transcends traditional ontologically-based models in order to accommodate this deep fusion. This chapter will outline a framework based on Latour’s Actor-Network Theory and Luhmann’s treatment of society as an autopoetic system. We shall use this framework to map the influence of relevant factors on ethical issues, irrespective of their composition or type. For example, under this treatment, both human praxis and technical design can be viewed as comparable tools of domination. This chapter will provide a framework for the analysis of relations between any elements of the smart city, ranging from top-level urban management processes down to individual device operations. While we will illustrate the use of this schema through examination of ethical issues arising from power dynamics within the smart city, it is intended that this example will demonstrate the wider utility of the model in general

Non-standard errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants

The working and limits of subliminal advertising

Contains fulltext : 129481.pdf (publisher's version ) (Open Access)Radboud Universiteit Nijmegen, 20 juni 2014Promotores : Wigboldus, D.H.J., Stroebe, W. Co-promotor : Karremans, J.C.T.M.159 p

Mimicking attractive opposite-sex others: The role of romantic relationship status

Based on the recent literature indicating that nonconscious behavioural mimicry is partly goal directed, three studies examined, and supported, the hypothesis that people who are involved in a romantic relationship nonconsciously mimic an attractive opposite-sex other to a lesser extent than people not involved in a relationship. Moreover, Studies 2 and 3 revealed that romantically involved persons tended to mimic an attractive alternative less to the extent that they were more close to their current partner. Finally, Study 3 provided preliminary support for a potential underlying mechanism, revealing that the effect of relationship status on level of mimicry displayed toward an opposite-sex other is mediated by perceived attractiveness of the opposite-sex other. The present findings suggest that behavioural mimicry serves an implicit self-regulatory function in relationship maintenance. Implications for both the literature on relationship maintenance and the literature on behavioral mimicry are discussed

Lowering the barriers to change: Can processing-related self-affirmations overcome resistance?

People often close themselves off to novel ideas without giving them adequate consideration. By doing so, they possibly miss out on important advantages these ideas may bring. One strategy that appears to effectively reduce such resistance involves self-affirming techniques, which aim to bolster one's self-concept by focusing on values of the self which are unrelated to the persuasion topic. The current study focuses on a new aspect that may be essential to increase its effectiveness, so-called “processing-related self-affirmations” which are related to how a person processes a message. We investigated the effect of processing-related self-affirmations on resistance to persuasion. Nonvegetarian participants were asked to apply a processing-related self-affirmation, an unrelated self-affirmation, or no self-affirmation before reading a scientific report about the merits of vegetarianism. Results showed participants were, depending on the weekly amount of meat consumed, more favorable toward the report after being affirmed on an unrelated value compared with participants who were not self-affirmed, but no similar effect was found for processing-related self-affirmations. We cautiously show that relatedness and compatibility with the persuasion domain may not be the only factors influencing this effect, and include relatedness of self-affirmations to the processing of the persuasive message as a possible new factor

Estudio de la atenuación de la escorrentía en techos verdes en altos de Cazucá, Soacha

Este trabajo evalúa la atenuación hídrica de un techo verde productivo mediante tres indicadores: lag-time (K), coeficiente de escorrentía (C) y porcentaje de retención volumétrica (Vp). Se utilizaron dos especies de plantas, una herbácea (Lactuca sativa) y una Crucífera (Raphanus sativus). Se registraron ocho eventos de lluvia en cuatro casas en el barrio La Isla en Soacha, Colombia (4° 34 22.3 , 74° 10 53.5 ) a 2701 msnm. . Se observaron retardos de la escorrentía hasta de 32 minutos, coeficiente equivalentes de escorrentía hasta de 0.078 y porcentajes de retención volumétrica máximos cercanos al 80 %. Se evaluaron los beneficios hidrológicos de implementar techos verdes comparando la infraestructura de drenaje requerida con y sin techos verdes y calculando sus respectivas probabilidades de inundación en el área de estudio (Barrio: La Isla, Soacha, Colombia). Los resultados obtenidos evidenciaron ahorros cercanos al 22 % y una reducción del 35 % de las probabilidades de inundación. Se simuló la respuesta del alcantarillado propuesto mediante la metodología Monte Carlo cuando en toda el área de drenaje se implementan techos verdes: el coeficiente de escorrentía se distribuyó aleatoriamente siguiendo una distribución Kernel correspondiente a los datos registrados en campo.The most common problem about rainfall in cities is the constant change of the hydrologic cycle (Araújo and González, 2010). This change is due to the construction of impervious areas, leading to the decrease of the percentages of infiltration and evaporation which modify times of concentration in an urban catchment: when a time of concentration decreases, the runoff flow has an important increment as result of land-use change and common sewers implementation. SUDS (Sustainable Urban Drainage Systems) were developed as a solution for the problems mentioned above (Butler and Davies, 2009, Niemczynowicz, 1999) as an alternative to manage rain water by mitigating flooding risks (Ballard and Kellagher, 2007a)