Rescuing over-activated microglia by acetominophen treatment restoers cognitive performance in the Dp(16) mouse model of Down Syndrome

Microglia are the resident immune cells of the brain and have been implicated in mechanisms essential for cognitive functions. Down syndrome (DS), the most frequent cause of genetic intellectual disability, is caused by the presence of a supernumerary chromosome 21, which contains genes essential for the function of the immune system. Here, we investigated the presence of microglial alterations and their implication for cognitive impairment in the Dp(16) mouse model of DS. In the hippocampus of Dp(16) mice and individuals with DS, we found microglial morphology indicative of an activated state. Accordingly, we found increased levels of pro-inflammatory cytokines and a phagocytosis marker in Dp(16) mice. In addition, Dp(16) mice showed decreased dendritic spine density and cognitive deficits. Remarkably, depletion of defective microglia by PLX3397 treatment or rescue of the microglia activated state by the commonly used anti-inflammatory drug acetaminophen fully rescued dendritic-spine density and cognitive deficits in Dp(16) mice. Our data suggest an involvement of microglia in the cognitive impairment of DS animals and identify a new therapeutic approach for the potential rescue of cognitive disabilities in individuals with DS

Avaliação da conectividade hidrossedimentológica em uma pequena bacia do planalto dos Campos Gerais no Rio Grande do Sul

A compreensão e previsão da dinâmica de sedimentos são um grande desafio. Muitos autores apontam a conectividade dos sedimentos como um dos estudos chave para compreensão da dependência da variabilidade espacial e temporal do processo de transferência de sedimentos e evolução da paisagem. A dinâmica de água e sedimento de uma bacia hidrográfica é controlada pelo (des)acoplamento encosta-canal, o qual é influenciado por vários fatores naturais e antropogênicos. Contudo, os estudos de conectividade hidrossedimentológica ainda são recentes, tendo inúmeros desafios a serem superados além de uma necessidade de explorar quais são os fenômenos e agentes governantes. Neste trabalho foram utilizado o monitoramento hidrossedimentológico e a aplicação de índices para caracterizar e avaliar aspectos da conectividade hidrossedimentológica em uma pequena bacia (0,89 km²), localizada no planalto dos Campos Gerais do Rio Grande do Sul. Os índices são uma combinação de variáveis conceitualmente conhecidas por controlar a organização espacial e a intensidade dos fluxos de sedimentos no sistema. A aplicação dessas ferramentas se demonstrou relevante na caracterização da conectividade estrutural e funcional da área de estudo. As ferramentas aplicadas foram: índice conectividade estrutural (IC), índice de conectividade hidrossedimentológico (IHC) aplicado em eventos observados e índice de conectividade de campo (FIC). A caracterização da conectividade estrutural destacou as depressões naturais do terreno e zonas de cobertura (blankets) como principais elementos de desconectividade da bacia. A conectividade funcional foi avaliada em 5 eventos de diferentes magnitudes, os resultados apresentaram uma correlação maior (0,7) da conectividade com o volume total do evento do que com a vazão máxima (0,3). Além disso, os eventos antecedentes se demonstraram determinantes à estimativa da conectividade funcional. A partir do índice de conectividade de campo (FIC) foi possível validar os índices teóricos na área de estudo, bem como evidenciar a importância de determinados limiares de acoplamento entre as inúmeros fontes de sedimento em um evento conhecido. O índice se demonstrou sensível ao tamanho da bacia, observando a área de estudo a conectividade diminuiu de acordo com o incremento da área de contribuição, mas considerando que a região é cabeceira das escarpas da serra geral em uma escala maior de análise (100 km²), esta tendência não é esperada. A temporalidade da conectividade ficou determinada pela capacidade de infiltração da bacia, onde o volume de chuva necessário para representar a conectividade potencial foi de 150mm.Understanding and predicting sediment dynamics are a major challenge. Many authors consider sediment connectivity as one of the key studies to understand the dependence of spatial and temporal variability of the sediment transfer processes and landscape evolution. Hydrological and sedimentological dynamics are controlled by hillslope-channel (de)coupling, whIHC is influenced by several natural and anthropogenic factors. However, studies on sediment connectivity are recent and present numerous challenges to be overcome. Furthermore, there is a need to explore and identify sediment connectivity governing processes and phenomena. In this study, hydrosedimentological monitoring and application of indexes were used to access aspects of hydrosedimentological connectivity in a small basin (0.89 km²), located in the Planalto dos Campos Gerais of Rio Grande do Sul. The indexes are a combination of variables conceptually known as controllers of the spatial organization and intensity of sediment flows in the system. The application of these tools proved to be relevant for the characterization of structural and functional connectivity of the study area. The tools applied were: structural connectivity index (CI); hydrosedimentological connectivity index (IHC). applied to observed events; field connectivity index (FIC). The characterization of structural connectivity highlighted natural sinks of the terrain and blankets zones as the main elements of disconnection in the watershed. The functional connectivity was evaluated for 5 distinct magnitude events, the results showed a higher correlation (0.7) between connectivity and the total volume of the event than the maximum discharge (0.3). The field connectivity index (FIC) validated the theoretical indexes in the study area and highlighted the importance of coupling thresholds between the numerous sediment sources in a known event. The indexes proved to be sensitive to spatial scale. In the study area connectivity decreased with the increment of contribution area, though this region is considered as a headwater region of Serra Geral escarpment in a large-scale analysis (100 km²), thus this trend was not expected. The temporality of connectivity was determined through watershed’s infiltration capacity, indicating that a rainfall of 150mm is required to represent potential connectivity

Discussing Identities through Game-Making: A Case Study

Identities should not be understood as a static, defining trait, but as a temporary articulation performed by diverse people. Based on data generated through the Playing Beowulf project, in which students produced their own games, I present a reflection on the meaning of a gamer identity and how diverse identities can be performed and articulated during game-making process. Understanding how these identities are orchestrated in a non-professional environment might help to clarify the relationship between them and the social and cultural position occupied by games, as well as to reflect on the validity and possible limits of a gamer identity

Power converters control for photovoltaic water pumping system

This work proposes solutions to challenges encountered in photovoltaic water pumping systems, such as the issue in the number of photovoltaic modules in low power systems, the maximum power point tracking and its implementation, as well as the pump control system. The maximum power point tracking is achieved via the addition of a step-up converter controlled by a proportional-integral controller. The system load is comprised by an induction motor, controlled by an open-loop scalar strategy. Simulations and real platform tests with solar radiance variation and variable number of photovoltaic modules were performed, validating the operation of the proposed solutions.Este trabalho propõe soluções para os desafios encontrados nos sistemas de bombagem fotovoltaica, como a questão do número de módulos fotovoltaicos em sistemas de baixa potência, o seguimento do ponto de potência máxima e sua implementação, bem como o sistema de controle da bomba. O seguimento do ponto de potência máximo é obtido através da adição de um conversor elevador, controlado por um controlador proporcional-integral. A carga do sistema é compreendida por um motor de indução, controlado por uma estratégia de controle escalar em malha aberta. Simulações e testes em uma plataforma real, com variação do nível de radiação solar e um número variável de módulos fotovoltaicos foram realizados, validando o funcionamento das soluções propostas

Platform, culture, identities: exploring young people's game-making

Digital games are an important component in the contemporary media landscape. They are cultural artefacts and, as such, are subjected to specific conventions. These conventions shape our imaginary about games, defining, for example, what a game is, who can play them and where. Different research has been developed to understand and challenge these conventions, and one of the strategies often adopted is fostering game-making among “gaming minorities”. By popularising games and their means of production, critical skills towards these objects could be developed, these conventions could be fought, and our perceptions of those artefacts could be transformed. Nevertheless, digital games, as obvious as it sounds, are also digital: they depend on technology to exist and are subjected to different technologies’ affordances and constraints. Technologies, however, are not neutral and objective, but are also cultural: they too are influenced by values and conventions. This means that, even if the means of production of digital games are distributed among more diverse groups, we should not ignore the role played by technology in this process of shaping our imaginary about games. Cultural and technical aspects of digital media are not, therefore, as conflicting as it might seem, finding themselves entangled in digital games. They are also equally influential in our understanding and our cultural uses of these artefacts; but how influential are they? How easy can one go against cultural and technical conventions when producing a game as a non-professional? Can anyone make any kind of game? In this research, I explore young people’s game-making practices in non-professional contexts to understand how repertoires, gaming conventions and platform affordances and constraints can be influential in this creative process. I organised two different game-making clubs for young people in London/UK (one at a community-led centre for Latin American migrants and other at a comprehensive primary school). The clubs consisted in a series of workshops offered in a weekly basis, totalling a minimum of 12 hours of instruction/production at each research site. The participants were aged between 11 and 18 and produced a total of 11 games across these two sites with MissionMaker, a software that facilitates the creation of 3D games by non-specialists through ready-made 3D assets, custom audio and image files, and a simplified drop-down-list-based scripting language. Three games and their production teams were selected as case studies and investigated through qualitative methods and under a descriptive-interpretive approach. Throughout the game-making clubs, short surveys, observations, unstructured and semi-structured interviews and a game archive (with week-by-week saves of participants’ games) were employed to generate data that was then analysed through a Multimodal Sociosemiotics framework to explore how cultural and technical conventions were appropriated by participants during this experience. Discourses, gaming conventions and MissionMaker’s affordances and constraints were appropriated in different ways by participants in the process of game production, culminating in the realisation of different discourses and the construction of diverse identities. These results are relevant since they restate the value of a more holistic approach – one that looks at both culture and technology – to critical videogame production within non-professional contexts. These results are also useful to the mapping of the influence of repertoires, conventions and platforms in non-professional game-making contexts, highlighting how these elements are influential but at the same time not prescriptive to the games produced, and how game development processes within these contexts are better understood as dialogical