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We characterized the world's second case with ascertained extreme resilience to autosomal dominant Alzheimer's disease (ADAD). Side-by-side comparisons of this male case and the previously reported female case with ADAD homozygote for the APOE3 Christchurch (APOECh) variant allowed us to discern common features. The male remained cognitively intact until 67 years of age despite carrying a PSEN1-E280A mutation. Like the APOECh carrier, he had extremely elevated amyloid plaque burden and limited entorhinal Tau tangle burden. He did not carry the APOECh variant but was heterozygous for a rare variant in RELN (H3447R, termed COLBOS after the Colombia-Boston biomarker research study), a ligand that like apolipoprotein E binds to the VLDLr and APOEr2 receptors. RELN-COLBOS is a gain-of-function variant showing stronger ability to activate its canonical protein target Dab1 and reduce human Tau phosphorylation in a knockin mouse. A genetic variant in a case protected from ADAD suggests a role for RELN signaling in resilience to dementia.

Air pollution is a growing threat to human health. Airborne pollution effects on respiratory, cardiovascular and skin health are well-established. The main mechanisms of air-pollution-induced health effects involve oxidative stress and inflammation. The present study evaluates the potential of a polyphenol-enriched food supplement ingredient comprising Lippia citriodora, Olea europaea, Rosmarinus officinalis, and Sophora japonica extracts in mitigating the adverse effects of environmental pollution on skin and cardiopulmonary systems. Both in vitro and ex vivo studies were used to assess the blend’s effects against pollution-induced damage. In these studies, the botanical blend was found to reduce lipid peroxidation, inflammation (by reducing IL-1α), and metabolic alterations (by regulating MT-1H, AhR, and Nrf2 expression) in human skin explants exposed to a mixture of pollutants. Similar results were also observed in keratinocytes exposed to urban dust. Moreover, the ingredient significantly reduced pollutant-induced ROS production in human endothelial cells and lung fibroblasts, while downregulating the expression of apoptotic genes (bcl-2 and bax) in lung fibroblasts. Additionally, the blend counteracted the effect of urban dust on the heart rate in zebrafish embryos. These results support the potential use of this supplement as an adjuvant method to reduce the impact of environmental pollution on the skin, lungs, and cardiovascular tissues.

Este estudo trata de um processo de formação de professores em Educação Ambiental, por meio da construção de audiovisuais socioambientais. As Tecnologias de Informação e Comunicação (TICs), foram usadas em uma experiência de educomunicação socioambiental com uso e produção de audiovisuais perpassada pela perspectiva da ecosofia, a qual propõe a criação de novos territórios existenciais a partir da interação entre o eu, o nós (socius) e o ambiente. Tem-se por objetivo deste estudo analisar produções audiovisuais socioambientais ecosóficas e suas potências para a efetivação da EA. A metodologia de pesquisa, caracteriza-se como qualitativa e bibliográfica, ancorada na pesquisa-ação com observação participante. Como procedimentos técnicos para a produção de dados, utilizaram-se diários de campo, gravações em áudio e transcrições de encontros realizados com professores, além de análises etnográficas dos dois audiovisuais produzidos durante a formação de quatro professoras de diferentes níveis e redes da Educação Básica. Os resultados demonstram que audiovisuais socioambientais constituem-se em uma estratégia para a reinvenção dos modos de fazer educação ambiental no espaço escolar e a ecosofia, enquanto pano de fundo, fornece diversas possibilidades para os diferentes fazeres da Educação Ambiental.

A patient with the PSEN1 E280A mutation and homozygous for APOE3 Christchurch (APOE3Ch) displayed extreme resistance to Alzheimer’s disease (AD) cognitive decline and tauopathy, despite having a high amyloid burden. To further investigate the differences in biological processes attributed to APOE3Ch, we generated induced pluripotent stem (iPS) cell-derived cerebral organoids from this resistant case and a non-protected control, using CRISPR/Cas9 gene editing to modulate APOE3Ch expression. In the APOE3Ch cerebral organoids, we observed a protective pattern from early tau phosphorylation. ScRNA sequencing revealed regulation of Cadherin and Wnt signaling pathways by APOE3Ch, with immunostaining indicating elevated β-catenin protein levels. Further in vitro reporter assays unexpectedly demonstrated that ApoE3Ch functions as a Wnt3a signaling enhancer. This work uncovered a neomorphic molecular mechanism of protection of ApoE3 Christchurch, which may serve as the foundation for the future development of protected case-inspired therapeutics targeting AD and tauopathies.

Abstract Thinking of urban gardens as an alternative for socio-environmental development in large cities leads to questioning which aspects of people’s lives are most significantly affected by activities in urban vegetable gardens in Teresina/Piauí. The objective of the article is to analyze how the social institutional, economic, and productive aspects are dynamized in the experiences of the gardeners inserted in the Community Gardens Project in Teresina. The research is exploratory and qualitative, based on a bibliographical, documental, and field study. 12 vegetable gardeners were interviewed in depth. Data treatment was based on textual analysis. As some of the results, it was evident that the gardens favor social ties and the expansion of income, as well as entrepreneurship, but even with the support of the city hall, there is a need for greater access to equipment and infrastructure elements, such as water and toilets, as well as training.

The impacts of climate change, excessive greenhouse gas emissions, and the current energy crisis have motivated the European Union to adopt mitigation and adaptation strategies. These strategies primarily focus on the building sector due to its crucial role in addressing these issues. Among the strategies, the implementation of resilient technologies for the building envelope, such as vertical greenery systems (VGSs) is gaining ground. The literature analysis shows that existing models are not sufficiently detailed in their description of the overall thermo-physical phenomena of VGSs. The aim of this work is to overcome the research gaps by selecting and improving two mathematical models for green façades and living walls. A dedicated calculation code to estimate the effect of VGSs on a building’s energy performance and indoor thermal comfort has been developed and implemented within the EnergyPlus calculation software (version 23.2). A BESTest Case from ASHRAE 140 was chosen to test the models and to assess benefits of VGSs. The results show that adopting green solutions for the building envelope can contribute to achieving the building’s energy efficiency goals and that the modelling of these technologies can be easily carried out within a dynamic energy simulation of the building.

Bacterial infections and the concurrent inflammation have been associated with increased long-term cardiovascular (CV) risk. In patients receiving peritoneal dialysis (PD), bacterial peritonitis is a common occurrence, and each episode further increases late CV mortality risk. However, the underlying mechanism(s) remains to be elucidated before safe and efficient anti-inflammatory interventions can be developed. Damage-Associated Molecular Patterns (DAMPs) have been shown to contribute to the acute inflammatory response to infections, but a potential role for DAMPs in mediating long-term vascular inflammation and CV risk following infection resolution in PD, has not been investigated. We found that bacterial peritonitis in mice that resolved within 24h led to CV disease-promoting systemic and vascular immune-mediated inflammatory responses that were maintained up to 28 days. These included higher blood proportions of inflammatory leukocytes displaying increased adhesion molecule expression, higher plasma cytokines levels, and increased aortic inflammatory and atherosclerosis-associated gene expression. These effects were also observed in infected nephropathic mice and amplified in mice routinely exposed to PD fluids. A peritonitis episode resulted in elevated plasma levels of the DAMP Calprotectin, both in PD patients and mice, here the increase was maintained up to 28 days. In vitro, the ability of culture supernatants from infected cells to promote key inflammatory and atherosclerosis-associated cellular responses, such as monocyte chemotaxis, and foam cell formation, was Calprotectin-dependent. In vivo, Calprotectin blockade robustly inhibited the short and long-term peripheral and vascular consequences of peritonitis, thereby demonstrating that targeting of the DAMP Calprotectin is a promising therapeutic strategy to reduce the long-lasting vascular inflammatory aftermath of an infection, notably PD-associated peritonitis, ultimately lowering CV risk.

Chronic Kidney Disease (CKD) is associated with markedly increased cardiovascular (CV) morbidity and mortality. Chronic inflammation, a hallmark of both CKD and CV diseases (CVD), is believed to drive this association. Pro-inflammatory endogenous TLR agonists, Damage-Associated Molecular Patterns (DAMPs), have been found elevated in CKD patients’ plasma and suggested to promote CVD, however, confirmation of their involvement, the underlying mechanism(s), the extent to which individual DAMPs contribute to vascular pathology in CKD and the evaluation of potential therapeutic strategies, have remained largely undescribed. A multi-TLR inhibitor, soluble TLR2, abrogated chronic vascular inflammatory responses and the increased aortic atherosclerosis-associated gene expression observed in nephropathic mice, without compromising infection clearance. Mechanistically, we confirmed elevation of 4 TLR DAMPs in CKD patients’ plasma, namely Hsp70, Hyaluronic acid, HMGB-1 and Calprotectin, which displayed different abilities to promote key cellular responses associated with vascular inflammation and progression of atherosclerosis in a TLR-dependent manner. These included loss of trans-endothelial resistance, enhanced monocyte migration, increased cytokine production, and foam cell formation by macrophages, the latter via cholesterol efflux inhibition. Calprotectin and Hsp70 most consistently affected these functions. Calprotectin was further elevated in CVD-diagnosed CKD patients and strongly correlated with the predictor of CV events CRP. In nephropathic mice, Calprotectin blockade robustly reduced vascular chronic inflammatory responses and pro-atherosclerotic gene expression in the blood and aorta. Taken together, these findings demonstrated the critical extent to which the DAMP-TLR pathway contributes to vascular inflammatory and atherogenic responses in CKD, revealed the mechanistic contribution of specific DAMPs and described two alternatives therapeutic approaches to reduce chronic vascular inflammation and lower CV pathology in CKD.

Abstract The transition to a low-carbon society will completely change the structure of energy systems from a standalone hierarchical centralised vision to cooperative and distributed Multi-Energy Systems. The analysis of these complex systems requires the collaboration of researchers from different disciplines in the energy, ICT, social, economic, and political sectors. Combining such disparate disciplines into a single tool for modeling and analyzing such a complex environment as a Multi-Energy System requires tremendous effort. Researchers have overcome this effort by using co-simulation techniques that give the possibility of integrating existing domain-specific simulators in a single environment. Co-simulation frameworks, such as Mosaik and HELICS, have been developed to ease such integration. In this context, an additional challenge is the different temporal and spatial scales that are involved in the real world and that must be addressed during co-simulation. In particular, the huge number of heterogeneous actors populating the system makes it difficult to represent the system as a whole. In this paper, we propose a comparison of the scalability performance of two major co-simulation frameworks (i.e. HELICS and Mosaik) and a particular implementation of a well-known multi-agent systems library (i.e. AIOMAS). After describing a generic co-simulation framework infrastructure and its related challenges in managing a distributed co-simulation environment, the three selected frameworks are introduced and compared with each other to highlight their principal structure. Then, the scalability problem of co-simulation frameworks is introduced presenting four benchmark configurations to test their ability to scale in terms of a number of running instances. To carry out this comparison, a simplified multi-model energy scenario was used as a common testing environment. This work helps to understand which of the three frameworks and four configurations to select depending on the scenario to analyse. Experimental results show that a Multi-processing configuration of HELICS reaches the best performance in terms of KPIs defined to assess the scalability among the co-simulation frameworks.

The various social, political, environmental, and economical mega-trends together with the rapid rise of digitalization are shaping cities worldwide including the way that citizens and products move within the urban environment. New mobility services are popping up which are showing the path toward more on-demand and personalized mobility patterns. The transformation of the urban mobility environment though constitutes a great challenge for policy-makers, as little is known about the impact of these trends on the city’s current mobility environment while the assessment of the future state of a mobility system can be considered a quite complex process taken its multi-parametric and multi-dimensional nature. This paper aims to simplify this process by presenting a coherent multi-actor consequence analysis framework as a tool for assessing future mobility scenarios which was developed in the framework of the H2020 SPROUT. This paper presents in detail the main components of this framework together with the list of key performance indicators used for assessing the performance in terms of sustainability of future mobility scenarios as well as indicative results from its use by the city of Padua.

Background: Plasmolipin (PLLP) is a membrane protein located in lipid rafts that participates in the formation of myelin. It is also implicated in many pathologies, such as neurological disorders, type 2 diabetes, and cancer metastasis. To better understand how PLLP interacts with raft components (gangliosides and cholesterol), we undertook a global study combining in silico simulations and physicochemical measurements of molecular interactions in various PLLP-ganglioside systems. Methods: In silico studies consisted of molecular dynamics simulations in reconstructed membrane environments. PLLP-ganglioside interaction measurements were performed by microtensiometry at the water-air interface on ganglioside monolayers. Results: We have elucidated the mode of interaction of PLLP with ganglioside GM1 and characterized this interaction at the molecular level. We showed that GM1 induces the structuring of the extracellular loops of PLLP and that this interaction propagates a conformational signal through the plasma membrane, involving a cholesterol molecule located between transmembrane domains. This conformational wave is finally transmitted to the intracellular domain of the protein, consistent with the role of PLLP in signal transduction. Conclusions: This study is a typical example of the epigenetic dimension of protein structure, a concept developed by our team to describe the chaperone effect of gangliosides on disordered protein motifs which associate with lipid rafts. From a physiological point of view, these data shed light on the role of gangliosides in myelin formation. From a pathological point of view, this study will help to design innovative therapeutic strategies focused on ganglioside-PLLP interactions in various PLLP-associated diseases.

[por] Tendo como desafio ampliar as relações da universidade com a comunidade, o curso de graduação em Jornalismo passou a incluir atividades que propõem o protagonismo dos alunos. Na disciplina Oficina de Jornalismo em Comunidades, do curso de Jornalismo da Universidade do Vale do Taquari (Univates), os estudantes foram convidados a realizar intervenções comunitárias junto a quatro grupos sociais, usando a linguagem audiovisual para abordar temas ambientais. O objetivo do estudo é analisar a potência das práticas de jornalismo comunitário para fazerem emergir gestos de criação. Problematiza-se como se dinamizaram as intervenções nos diferentes grupos sociais, como se caracterizam as abordagens dadas aos temas ambientais nos audiovisuais e que aproximações e distanciamentos observam-se em relação aos modos de fazer que emergiram. Trata-se de um estudo qualitativo, exploratório, descritivo e de cunho intervencionista. [en] With the challenge of expanding the university’s relations with the community, the undergraduate course in Journalism started to include activities that propose the students’ prota-gonism. In the course called Workshop on Journalism in Communities, part of the Journalism Program at the Universidade do Vale do Taquari (Univates), students were invited to carry out a communit y inter vention with four social groups, using audiovisual language to address environmental issues. The aim of the study is to analyze the power of community journalism practices of making gestures of creation emerge. Here we ask how the interventions in the different social groups were dynamized, how the approaches given to environmental themes are characterized in audiovisuals and what approximations and distances are observed in relation to the ways of doing that have emerged. It is a qualitative, explorator y, descriptive and inter ventionist study.

Uma escola pública, uma área verde, um grupo de alunos de 11 e 12 anos e um grupo de pesquisa que tinha como objetivo experienciar possibilidades de sensibilização ambiental baseadas em um método que explora atividades ao ar livre, visando à produção de uma subjetividade ambiental. Estes elementos foram geradores de encontros semanais que duraram três meses, optando-se por avaliar um processo de educação ambiental em continuidade, a fim de se estabelecer um vínculo com o grupo e observar com profundidade processos que os pesquisadores só investigavam em encontros esporádicos. A estratégia do grupo de pesquisa foi baseada no método do Aprendizado Sequencial de Joseph Cornell e na proposta ecosófica de Felix Guattari e suas três ecologias: subjetiva, social e ambiental. O objetivo foi investigar possibilidades de produção de subjetividade ambiental a partir da proposta ecosófica e de um método de educação ambiental ao ar livre. Como elemento conclusivo fundamental consideramos a evidência de que o contato coletivo com a natureza afeta as relações sociais, favorecendo a percepção do outro na sua singularidade. Ou seja, a natureza atua como facilitadora da abertura para o outro. A ecologia social e subjetiva ou mental, no caso em estudo, foram favorecidas pela ecologia do ambiente.

O presente artigo busca analisar como o uso das redes sociais contribui para o desenvolvimento da Quarta Onda Feminista no Brasil. Dados como o aumento do número de pesquisas em plataformas de busca online e a multiplicação de páginas de conteúdo feminista em redes sociais destacam o crescente debate sobre o assunto, e justificam a relevância do estudo. O artigo relata o desenvolvimento do movimento feminista, do seu surgimento até a atual insurreição, e a maneira como este se formou. Para isso, utiliza como metodologia estudos bibliográficos sobre feminismo e sobre o uso do espaço virtual por parte de movimentos sociais, bem como o estudo de caso do coletivo feminista brasileiro Não Me Kahlo. Também foi realizada a entrevista com uma das suas fundadoras e a análise quantitativa das publicações na página do coletivo na rede social Facebook, durante os meses de janeiro e junho de 2019. A partir desta metodologia, o estudo identifica a associação direta entre a atual insurreição feminista e o uso das redes sociais que são utilizadas como ferramentas de comunicação, organização epopularização do conteúdo feminista. A pesquisa também aponta os benefícios e as dificuldades que o uso das redes sociais acrescenta ao atual cenário da militância feminista.

Este artigo tem como objetivo descrever[A1] duas experiências de vivências com a natureza: um no município do Crato, estado do Ceará, Região Nordeste do Brasil, outro em Coimbra, na província da Beira Litoral, Região do Centro, Portugal. Os projetos têm suas singularidades, mas também convergências, o que possibilita a realização do estudo. Observaram-se as crianças participantes, registrando-se as ocorrências e analisando-se o que sucede em decorrência das atividades. As análises são compostas por três dimensões: ambientes, mediadores e métodos. Os dados empíricos apontam que, mesmo que de forma diferenciada, ambas as experiências favorecem o desenvolvimento infantil em seus diversos aspectos, conforme o foco dos métodos. Enquanto nas vivências com a natureza a interação com o contexto natural esteve focada em gerar experiências que exploravam os sentidos, no Limites Invisíveis buscava-se provocar experiências de aprendizagem. Em ambas as propostas o ambiente natural parece despertar nas crianças o que está latente, que não emerge, muitas vezes, por falta deste contato primordial com ambientes naturais.

Abstract The present study involves children diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) from public schools of the municipality of Crato - CE, northeastern region of Brazil. The overall objective was to analyze the profiles of six children, before and after interventions with nature, in order to identify potential changes in behavior resulting from experiencing direct contact with nature. The method used is exploratory and descriptive, and it is a multiple case study with an action-research character. The results showed changes in behavior with mitigated ADHD symptoms regarding cognitive and socio-affective aspects. Among other behavioral aspects, higher motivation for studying, better understanding and adaptation to rules, extended states of tranquility, higher receptivity to social contact, decreased aggressiveness, hyperactivity, impulsivity, and higher tolerance to oneself and others were noticeable.

Brewers' spent grains (BSG) are the main by-product of the brewery industry, accounting for more than 80 % of total produced by-products. Although this matrix is primarily composed of hemicellulose, cellulose, protein and lignin, the current end-of-life scenario for BSG is as livestock feed. In the present study, a valorisation approach for BSG that uses an edible fungus (Rhizopus oligosporus) in solid state fermentations (SSF) is proposed. First, a microbiological characterization is performed, to shed light on the indigenous microorganisms that are present in the BSG matrix. Then, an appropriate technology approach is used for the SSF that can be conducted both at laboratory and household levels. In the SSF experiments, different temperature (30-35 °C), mass of BSG substrate, inoculum ratio (10 and 15 % v/m) and drilling patters for the aeration of the systems are investigated. The fermentation products were characterized by preparing homogenized samples; it was registered an increase in protein content (5-64%), a slight acidification (?pH=0.1-1.2), a decrease of °Brix and the loss of organic matter (and water). The formation of the tempeh cakes was variable, and the differences are analyzed in terms of the operational parameters of each studied batch.

The brewers’ spent grain (BSG) is a rich biomass matrix containing several compounds of interest that require urgent and suitable valorisation strategies, due to its high production volume in the brewing industry. Among the most widespread approaches is the preparation of extracts, targeting particular compounds or soluble and/or insoluble fractions, after operating pre-treatment processes. In the present study, extraction experiments are carried out with fresh untreated BSG, under very gentle extraction conditions (room temperature and moderate agitation, in the 0-5 h interval), and using different solvents: deionized water, 0.1 M NaOH and 0.5 M NaOH in a 1:5 m/v solid-to-solvent ratio. The extraction dynamics were followed by monitoring the dry matter (DM) content obtained in the extracts after a centrifugation step. The protein content is estimated in each case by means of two different methods: direct measurements of absorbance at 280 nm (using bovine serum albumin, BSA, and commercial whey protein isolate as standards) as well as using the Bradford colorimetric method and BSA standard; the consistency of these measurements is contrasted against the DM values. The apparent extraction kinetics were studied, using a saturation model; the coefficients and their range of uncertainty were obtained. Extraction efficiencies in the range 14.24%-53.60% gDM ext/gDM BSG are achieved, which correspond to extraction yields of 38.88-150.09 gDM ext/kg fresh BSG. In addition, the energy footprint of the process is estimated at laboratory scale.

In this work, we address the beneficial role of noise in two different contexts, the human brain and financial markets. In particular, the similitude between the ability of financial markets to maintain in equilibrium asset prices is compared with the ability of the human nervous system to balance a stick on a fingertip. Numerical simulations of the human stick balancing phenomenon show that after the introduction of a small quantity of noise and a proper calibration of the main control parameters, intermittent changes in the angular velocity of the stick are able to reproduce the most basilar stylized facts involving price returns in financial markets. These results could also shed light on the relevance of the idea of the “planetary nervous system”, already introduced elsewhere, in the financial context.

Photobiomodulation (PBM) is rapidly gaining traction as a valuable tool in dermatology for treating many inflammatory skin conditions using low levels of visible light or near-infrared radiation. However, the physiological regulatory pathways responsible for the anti-inflammatory effect of PBM have not been well defined. Since previous studies showed that nuclear factor-erythroid 2 like 2 (Nrf2) is a master regulator of the skin inflammatory response, we have addressed its role in controlling inflammation by PBM. Primary human keratinocytes (KCs) stimulated with 2,4-dinitrochlorobenzene (DNCB) to mimic pro-inflammatory stress were illuminated with two wavelengths: 660 nm or 520 nm. Both lights significantly reduced the mRNA expression of the DNCB-triggered TNF-α, IL-6, and IL-8 cytokines in KCs, while they enhanced Nrf2 pathway activation. PBM-induced Nrf2 is a key regulator of the inflammatory response in KCs since its absence abolished the regulatory effect of light on cytokines production. Further investigations of the mechanisms contributing to the immunoregulatory effect of PBM in inflamed human skin explants showed that 660 nm light prevented Langerhans cells migration into the dermis, preserving their dendricity, and decreased pro-inflammatory cytokine production compared to the DNCB-treated group. This study is the first to report that the PBM-mediated anti-inflammatory response in KCs is Nrf2-dependent and further support the role of PBM in skin immunomodulation. Therefore, PBM should be considered a promising alternative or complementary therapeutic approach for treating skin-related inflammatory diseases.

The impacts of climate change, excessive greenhouse gas emissions, and the current energy crisis have motivated the European Union to adopt mitigation and adaptation strategies. These strategies primarily focus on the building sector due to its crucial role in addressing these issues. Among the strategies, the implementation of resilient technologies for the building envelope, such as vertical greenery systems (VGSs) is gaining ground. The literature analysis shows that existing models are not sufficiently detailed in their description of the overall thermo-physical phenomena of VGSs. The aim of this work is to overcome the research gaps by selecting and improving two mathematical models for green façades and living walls. A dedicated calculation code to estimate the effect of VGSs on a building's energy performance and indoor thermal comfort has been developed and implemented within the EnergyPlus calculation software (version 23.2). A BESTest Case from ASHRAE 140 was chosen to test the models and to assess benefits of VGSs. The results show that adopting green solutions for the building envelope can contribute to achieving the building's energy efficiency goals and that the modelling of these technologies can be easily carried out within a dynamic energy simulation of the building. [ABSTRACT FROM AUTHOR]