Disruption of the Choroid Plexus Circadian Rhythm’s in Alzheimer’s Disease

Alzheimer´s disease (AD) is a neurodegenerative disorder, characterized by amyloid beta (Abeta) and tau protein deposition in the brain parenchyma and blood vessels. Abeta accumulation in areas of the brain controlling circadian rhythms can delay or shift activity rhythms. The circadian rhythm is coordinated by the master circadian pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus. The choroid plexus (CP), a recent characterized extra-SCN circadian oscillator, is also known to exhibit morphological changes in AD which are exacerbated by the presence of Abeta deposits in CP epithelial cells. Melatonin is a hormone secreted by the pineal gland and there’s some evidence that, in AD patients, the circulating levels of this hormone are diminished. Under normal circumstances, melatonin acts as a neuroprotector against AD, but how this protection occurs is still to be fully comprehended. It also acts as a Zeitgeber, synchronizing the rhythms of the circadian genes, regulating the body’s circadian clocks. In this study we addressed the question whether Abeta contributes to CP’s circadian clock disruption and if melatonin modulates circadian clock genes expression therein. Using an AD mouse model (APP/PS1), we investigated changes in the expression of CP clock genes at different time points, in female and male animals, aged 6 and 12 months old. In addition, in vitro studies using Z310 cell line treated with Abeta and melatonin were used to examine if melatonin modulated Bmal1 circadian expression. We demonstrated that only Bmal1 circadian expression is altered in AD mice model 12 months old. Contrarily, Cry2 and Per2 expression were not affected in the APP/PS1 model. In addition, we found that melatonin modulated several parameters in the circadian expression of Bmal1. These results indicate that Abeta deposition on the CP disrupted the rhythmic circadian expression of Bmal1 and that melatonin modulates CP clock gene circadian rhythms in the presence of Abeta.A doença de Alzheimer (AD) é uma doença neurodegenerativa caracterizada pela deposição do péptido beta-amilóide (Abeta) e proteína Tau no parênquima e vasos sanguíneos do cérebro. A acumulação destes, quando ocorre em áreas do cérebro responsáveis pelo controlo de ritmos circadianos, pode conduzir a alterações nos ritmos de atividade. O ritmo circadiano é coordenado por um marcador de atividade circadiana central que está localizado no núcleo supraquiasmático (SCN) do hipotálamo. No plexo coroide (CP), um oscilador extra-SCN recentemente caraterizado como tal, também se verificam alterações morfológicas na AD que são representadas pela acumulação de Abeta nas suas células epiteliais . A melatonina é uma hormona secretada pela glândula pineal, cujos níveis se encontram diminuídos na AD. Em condições normais, a melatonina tem uma função neuroprotetora na AD, e mesmo quando a doença já está instalada, esta ação continua presente, embora ainda se desconheça parcialmente os mecanismos responsáveis por esta neuroproteção. A melatonina funciona também como “Zeitgeber”, sincronizando os ritmos de expressão dos diferentes genes relógio, regulando desta forma os diversos relógios circadianos distribuídos pelo organismo. Neste estudo, foi utilizado um modelo de murganhos da AD (APP/PS1), de ambos os sexos e com idades de 6 e 12 meses, para determinar alterações na expressão dos genes relógio no CP, em diferentes momentos ao longo do tempo. Para os estudos in vitro foi utilizada a linha celular Z310 tratada com Abeta e melatonina de modo a avaliar se a melatonina tinha um efeito modulador na ritmicidade do Bmal1. Demonstramos que apenas o Bmal1 sofreu alterações na expressão circadiana e que esta ocorre em modelos APP/PS1 com 12 meses de idade. Contrariamente, a expressão do Per2 e Cry2 não é afetada no modelo APP/PS1. Também foi observado que a melatonina tem a capacidade de modular diversos parâmetros na ritmicidade do Bmal1. Estes resultados sugerem uma desregulação do ritmo circadiano da expressão do Bmal1 num modelo da AD, bem como um efeito modulador da melatonina na expressão dos genes relógio do C

Simplified guidelines for retrofitting scenarios in the european countries

A large part of the European building stock was built before implementing the recent energy and structural codes, resulting in buildings characterized by deficiencies in terms of comfort, energy savings and structural safety. The retrofitting and rehabilitation of the existing building stock need to be adequately performed, aiming to improve the seismic and energy performance simultaneously. The work summarized here is dedicated to defining priority scenarios for buildings’ retrofitting to improve the seismic safety and energy efficiency of the European Union (EU) building stock. First, the state of the EU building stock is analysed in terms of buildings’ age, types of structures, energy efficiency, energy consumption and energy poverty. Then, the EU climate demands are presented, namely the regions with higher temperature variations, i.e., heating or cooling degree days. The EU seismic risk is also presented and discussed in terms of average annual losses, average annual economic losses and average annual life losses. Based on these input parameters, nine seismic–climate regions in the EU are proposed using a simplified approach. Finally, retrofitting scenarios are proposed for two types of buildings (i.e., masonry and reinforced concrete) based on their seismic–climate region.publishe

Effect of the openings on the seismic response of an infilled reinforced concrete structure

The seismic behavior of the infill masonry infill walls has a significant impact on the global response of reinforced concrete frame structures. One factor influencing its behavior is the existence of openings in the walls, such as doors and windows, which are crucial for the infill seismic performance. Although the numerical simulation of the seismic behavior of RC buildings with infill walls has evolved significantly in recent years in terms of micro- and macro-modelling, most of the existing studies are only related to infill walls without openings. Based on this motivation, four main objectives were defined for this research work: (i) present a simplified modeling approach and its calibration to simulate the seismic behavior of infill walls with central openings such as windows; (ii) evaluate the impact of the openings on the global seismic response of an RC building; (iii) study the impact of the irregular distribution of the infill walls (vertical and in-plane) on the global seismic response of an RC building; and (iv) study the impact of the central openings ratio (i.e., relative percentage between opening and infill wall area) on the global seismic response of an RC building structure. A four-story infilled RC building was used as a case study to perform parametric analyses investigating the impact of the masonry infill walls’ irregular distribution (vertical and in-plan) and their openings ratio. The results are discussed in terms of natural frequencies and vibration modes, initial lateral stiffness, and maximum lateral resistance. This study found that the openings caused a reduction in the natural frequencies of about 20% compared with the full infill (without openings). The openings did not modify the vibration modes. In addition, the openings reduced the initial stiffness by about 20% compared with the model without openings. The maximum strength increased about 50% with the infill walls, but this was reduced by the openings by 20%.publishe

Flora Of The Cangas Of The Serra Dos Carajás, Pará, Brazil: Linderniaceae

This is a taxonomic study of the species of Linderniaceae from the cangas of the Serra dos Carajás, state of Pará, Brazil. Three species of Lindernia were recorded: L. brachyphylla, L. crustacea and L. diffusa, the first being restricted to South America and the two others with pantropical distribution. Here we present detailed descriptions, illustrations, photographs and notes on morphology, distribution and phenology of these species.6751399140

A review of the performance of infilled RC structures in recent earthquakes

The primary objective is to present the most representative types of damage observed in reinforced concrete (RC) structures due to earthquakes. Those damages are divided according to the ten most representative types. Examples and the main reasons that could trigger each failure mechanism are presented. The definition of these damage types is supported by post-earthquake damage reconnaissance missions in Sichuan (China) in 2008, L’Aquila (Italy) in 2009, Lorca (Spain) in 2011, Emilia-Romagna (Italy) in 2012, Gorkha (Nepal) in 2015, Muisne (Ecuador) in 2016 and Chiapas (Mexico) in 2017. An extensive discussion is presented concerning the infill walls’ seismic behaviour and their interaction with the RC structural elements. The presentation of the significant learnings and findings concerning the typical damage herein presented and discussed are compared with the common Southern European construction practice. The impact of the infill walls on the rehabilitation costs of damaged RC buildings is also studied. These costs are compared to those related to the structural damage and rehabilitation of the entire building structure to understand the impact of the infill walls. Finally, a case study is presented to study the effect of implementing simplified retrofitting strategies to prevent the soft-storey mechanism, one of the most common problems observed in past earthquake events.publishe

Influence of seismic loading on axial load variation in reinforced concrete columns

Experimental tests demonstrated the importance of the axial load variation in the seismic response of RC columns, namely, through the reduction in the strength capacity, reduced deformation capacity, and reduced energy dissipation capacity. Thus, this manuscript aims to study the axial load variability of RC columns, according to the plan and height disposition, and assess the relationship between the corresponding column flexure capacity and its influence on the global response of the structure. Hence, three RC structures were modeled using the software SeismoStruct and subjected to non-linear static pushover and dynamic analyses. According to the results, which are assessed in terms of capacity curves, axial load variation, and story/global shear capacity of each model, it can be concluded that the axial load variation is higher in the bottom storys and decreases with the story height of the structure. As observed, the corner columns reached a higher axial load variation than the façade and central columns

Simulação baseada em agente Ferramenta de diagnóstico para segurança de aeroporto: estudo de caso de um ataque com o agente biológico antraz no Aeroporto Internacional do Galeão

Diversos tipos de ameaças têm colocado em risco os aeroportos, sendo uma das ameaças mais preocupantes da sociedade atualmente é a ameaça biológica, pois é viável e crítica. As preocupações sobre doenças infecciosas e epidemias vieram à tona, o surto da gripe aviária que mostrou a fragilidade da segurança aeroportuária e fez crescer a importância do controle de acesso e das medidas de biossegurança nos aeroportos (BUZAN, 2012). O pânico generalizado, somado a um grande número de vítimas causa grande impacto sobre a mídia, além da grande concentração de pessoas no aeroporto, tornando factível deste tipo de ação. O artigo fará considerações sobre a modelagem baseada em agentes (MBA), nela definiremos o que são agentes, seu histórico, possibilidades e limitações, e ainda serão descritas as principais ferramentas utilizadas para MBA. Em seguida, discutirá quais são os problemas de segurança do aeroporto, em especial mostrará um caso bem sucedido mundialmente que é o sistema de segurança de aeroporto em Israel. Também serão descritas as novas tecnologias que são o estado da arte no setor. Por fim, explicará como utilizamos a MBA como ferramenta para segurança de aeroporto em um estudo de caso de um ataque com agente biológico Antraz no Aeroporto Internacional do Rio de Janeir

TRADE LIBERALIZATION, THE EXCHANGE RATE AND JOB AND WORKER FLOWS IN BRAZIL

Over the 1990's Brazil experienced a massive trade liberalization and wide variation in the real exchange rate. At the same time, employment growth was small and in manufacturing there was a significant reduction in total manufacturing. The main goal of this article is to idntify the effects of the exchange rate and trade liberalization on job and worker flows in Brazil. Using a novel sector exchange rate measure, our results suggest that a depreciation of the exchange rate affects net employment growth by increasing job creation and hires, with no effect on job reallocation. Tariffs have no effect on job or worker flows, while import penetration decrease job growth by increasing job destruction. The results suggest that the echange rate have a very important role on job and worker flows, even after controlling for openess and sector specificities.