Alzheimer's disease and neuroinflammation: will new drugs in clinical trials pave the way to a multi-target therapy?

: Despite extensive research, no disease-modifying therapeutic option, able to prevent, cure or halt the progression of Alzheimer's disease [AD], is currently available. AD, a devastating neurodegenerative pathology leading to dementia and death, is characterized by two pathological hallmarks, the extracellular deposits of amyloid beta (Aβ) and the intraneuronal deposits of neurofibrillary tangles (NFTs) consisting of altered hyperphosphorylated tau protein. Both have been widely studied and pharmacologically targeted for many years, without significant therapeutic results. In 2022, positive data on two monoclonal antibodies targeting Aβ, donanemab and lecanemab, followed by the 2023 FDA accelerated approval of lecanemab and the publication of the final results of the phase III Clarity AD study, have strengthened the hypothesis of a causal role of Aβ in the pathogenesis of AD. However, the magnitude of the clinical effect elicited by the two drugs is limited, suggesting that additional pathological mechanisms may contribute to the disease. Cumulative studies have shown inflammation as one of the main contributors to the pathogenesis of AD, leading to the recognition of a specific role of neuroinflammation synergic with the Aβ and NFTs cascades. The present review provides an overview of the investigational drugs targeting neuroinflammation that are currently in clinical trials. Moreover, their mechanisms of action, their positioning in the pathological cascade of events that occur in the brain throughout AD disease and their potential benefit/limitation in the therapeutic strategy in AD are discussed and highlighted as well. In addition, the latest patent requests for inflammation-targeting therapeutics to be developed in AD will also be discussed

O cine ciências e o debate sobre a realidade

Anais do II Seminário Seminário Estadual PIBID do Paraná: tecendo saberes / organizado por Dulcyene Maria Ribeiro e Catarina Costa Fernandes — Foz do Iguaçu: Unioeste; Unila, 2014Na atualidade, diversos são os assuntos que estão presentes na realidade dos jovens, em especial dos jovens do campo. Neste sentido, em função de uma dinâmica cada vez maior e de uma complexidade crescente, diversos temas precisam ser trabalhados pela escola no sentido de dar respostas aos anseios trazidos pelos jovens. Deste modo, ao trabalhar com os jovens da Casa Familiar Rural de Dois Vizinhos, através do Cine Ciências, temas do cotidiano destes, apresentados de maneira que possibilite a reflexão critica sobre os assuntos, a escola contribui para que os educandos compreendam a realidade que os cerca. Assim, trabalharam- se assuntos relacionados aos agrotóxicos, drogas e tráfico human

Herpes simplex virus-type1 (HSV-1) impairs DNA repair in cortical neurons

Several findings suggest that Herpes simplex virus-1 (HSV-1) infection plays a role in the neurodegenerative processes that characterize Alzheimer's disease (AD), but the underlying mechanisms have yet to be fully elucidated. Here we show that HSV-1 productive infection in cortical neurons causes the accumulation of DNA lesions that include both single (SSBs) and double strand breaks (DSBs), which are reported to be implicated in the neuronal loss observed in neurodegenerative diseases. We demonstrate that HSV-1 downregulates the expression level of Ku80, one of the main components of non-homologous end joining (NHEJ), a major pathway for the repair of DSBs. We also provide data suggesting that HSV-1 drives Ku80 for proteasomal degradation and impairs NHEJ activity, leading to DSB accumulation. Since HSV-1 usually causes life-long recurrent infections, it is possible to speculate that cumulating damages, including those occurring on DNA, may contribute to virus induced neurotoxicity and neurodegeneration, further suggesting HSV-1 as a risk factor for neurodegenerative conditions

Role of thesauri in a scientific organisation

We aim to describe the mediation language between users and indexers in a document retrieval system for a big scientific community intimately related to European Union policies. We assume that this mediation is played by thesauri: sets of indexes apparently coordinating the possible searches by means of term-to-term relations like NT, RT and so on. While persons-to-terms relations are consequent to the use of thesauri for indexing and retrieval, person-to-person relations are embodied into a thesaurus via the implicit repre- sentation of the organisation it serves. In this way, thesauri constitute a network of mediation having historical, social and - because of the scien- tific community served - scientific and technological perspectives. These three perspectives are embedded in time, since changes in organisation change the person-to-person relations, change in retrieval and indexing needs change the person-to-term relations and changes in document type and science change term-to-term relations. In particular, we want to analyse the network originally proposed by the EURATOM thesaurus (1st ed.; European Atomic Energy Community. Information and Documentation Center, Brussels, 1964) and the network of relations - in the three perspectives above - it assumed. Subsequently, we compare the results of this analysis with a more recent thesaurus designed for a community very close to the one originating the EURATOM thesaurus. In doing this, we designed a system that aims the user to browse a path built through the relations. Its in- terface is based on different concepts: Focus+Context and Elastic Grid, which led to the creation of a flexible graphical structure characterised by hierarchically-arranged and scalable information visualisation

Ocorrência de incêndios florestais no Parque Nacional da Chapada dos Veadeiros, Goiás.

This work aimed at studying the fires in Parque Nacional da Chapada dos Veadeiros (PNCV) in Goiás, Brazil, from 1992 to 2003. The methodology included analysis of heat spots maps, reports and interviews with the fire crew members, besides interviews with the land owners who live close to the PNCV. The data showed the causes and the frequencies of fires annual burnt areas, seasons and origins of fire incident, and fire privation developed by the fire crew of PNCV. Furthermore, there was opinions by land owner related to the PNCV. Results showed that the fires in PNCV had annual frequency. The years 1995 and 2002 presented more fire occurrences. Most of the fires (88,2%) had criminal or unknown causes. The dry season caused more fire occurrences, mainly August, September and July.  The prevention activities were break fires construction and instruction folders related to fires release. The local land owners did not know how to deal with land management techniques without fire and asked for environmental education. Esta pesquisa objetivou a análise da ocorrência de incêndios florestais no Parque Nacional da Chapada dos Veadeiros (PNCV), GO, no período de 1992 a 2003. A metodologia utilizou mapas de focos de calor, dados dos relatórios de ocorrência de incêndios na Unidade de Conservação, entrevistas aos brigadistas e à comunidade do entorno. Com esses dados, foi possível analisar as causas e a freqüência de ocorrência de incêndios florestais, as áreas queimadas anualmente, os locais e épocas de incidência, o trabalho de prevenção e combate desenvolvido pelos brigadistas e a opinião da população em relação ao trabalho desenvolvido no Parque. Essas informações possibilitaram analisar as ocorrências de fogo no PNCV e alguns dados importantes sobre prevenção e combate aos incêndios. Os incêndios florestais no PNCV ocorreram praticamente em todos os anos, sendo que 1995 e 2002 foram os anos mais críticos. 88,2% dos incêndios florestais foram de origem criminosa, por negligência ou de causa desconhecida. A época em que mais ocorreram os incêndios foi a estação seca, sendo o pico o mês de agosto, seguido pelos meses de setembro e julho. As ações preventivas realizadas no PNCV são a construção de aceiros e a distribuição de cartazes educativos. A comunidade local salientou que falta estímulo à utilização de técnicas de substituição ao uso do fogo nas propriedades rurais e campanhas educativas de prevenção de incêndios florestais

Fires incident occurrence in Parque Nacional da Chapada dos Veadeiros, Goiás

Esta pesquisa objetivou a análise da ocorrência de incêndios florestais no Parque Nacional da Chapada dos Veadeiros (PNCV), GO, no período de 1992 a 2003. A metodologia utilizou mapas de focos de calor, dados dos relatórios de ocorrência de incêndios na Unidade de Conservação, entrevistas aos brigadistas e à comunidade do entorno. Com esses dados, foi possível analisar as causas e a freqüência de ocorrência de incêndios florestais, as áreas queimadas anualmente, os locais e épocas de incidência, o trabalho de prevenção e combate desenvolvido pelos brigadistas e a opinião da população em relação ao trabalho desenvolvido no Parque. Essas informações possibilitaram analisar as ocorrências de fogo no PNCV e alguns dados importantes sobre prevenção e combate aos incêndios. Os incêndios florestais no PNCV ocorreram praticamente em todos os anos, sendo que 1995 e 2002 foram os anos mais críticos. 88,2% dos incêndios florestais foram de origem criminosa, por negligência ou de causa desconhecida. A época em que mais ocorreram os incêndios foi a estação seca, sendo o pico o mês de agosto, seguido pelos meses de setembro e julho. As ações preventivas realizadas no PNCV são a construção de aceiros e a distribuição de cartazes educativos. A comunidade local salientou que falta estímulo à utilização de técnicas de substituição ao uso do fogo nas propriedades rurais e campanhas educativas de prevenção de incêndios florestais.This work aimed at studying the fires in Parque Nacional da Chapada dos Veadeiros (PNCV) in Goiás, Brazil, from 1992 to 2003. The methodology included analysis of heat spots maps, reports and interviews with the fire crew members, besides interviews with the land owners who live close to the PNCV. The data showed the causes and the frequencies of fires annual burnt areas, seasons and origins of fire incident, and fire privation developed by the fire crew of PNCV. Furthermore, there was opinions by land owner related to the PNCV. Results showed that the fires in PNCV had annual frequency. The years 1995 and 2002 presented more fire occurrences. Most of the fires (88,2%) had criminal or unknown causes. The dry season caused more fire occurrences, mainly August, September and July. The prevention activities were break fires construction and instruction folders related to fires release. The local land owners did not know how to deal with land management techniques without fire and asked for environmental education

CD85j (Leukocyte Ig-Like Receptor-1/Ig-Like Transcript 2) Inhibits Human Osteoclast-Associated Receptor-Mediated Activation of Human Dendritic Cells

Abstract Immature dendritic cells (DCs) derived from freshly isolated human monocytes were used to evaluate the effect of the inhibiting receptor CD85j (leukocyte Ig-like receptor-1/ILT2) on activation induced by cross-linking of the human osteoclast-associated receptor (hOSCAR). CD85j and hOSCAR were expressed consistently at the same density on monocytes and on monocyte-derived DCs (both immature and mature). Cross-linking of hOSCAR, which activates via the FcR-associated γ-chain, induced Ca2+ flux in DCs. Concomitant cross-linking of anti-CD85j mAb abolished this early activation event. Likewise, CD85j stimulation strongly reduced IL-8 and IL-12 production by hOSCAR-activated DCs. Inhibition of DCs via CD85j also impaired their ability to enhance Ag-specific T cell proliferation induced by hOSCAR. Finally, because hOSCAR prevents apoptosis of DCs in the absence of growth/survival factors, CD85j cross-linking was able to counteract completely this antiapoptotic effect and to reduce Bcl-2 expression enhanced by hOSCAR stimulation. Thus, CD85j is an inhibiting receptor that is functional in human DCs

Renal function and physical fitness after 12-mo supervised training in kidney transplant recipients

To evaluate the effect of a 12-mo supervised aerobic and resistance training, on renal function and exercise capacity compared to usual care recommendations

Acid functionalized carbons as catalyst for glycerol etherification with benzyl alcohol

In this paper, the catalytic behaviour of two different carbonaceous systems, commercial carbon (Cc) and synthetic carbon (Cs) functionalized with concentrated sulfuric acid (–SO₃H) and with reduced aryl diazonium salt (–PhSO₃H), was studied in the etherification of glycerol (Gly) with benzyl alcohol (BA). The catalytic activity and selectivity were studied varying the catalyst percentage (5, 10 and 15 wt%) and the initial reactant mass ratio. Taking into account the results obtained, the experimental conditions selected to continue with the catalytic studies were: temperature 393 K, Gly:BA molar ratio 3:1 and a catalyst loading of 10 wt%. Mono- and diethers were the main products. For the Cc-based catalysts, higher conversion (66%) and selectivity (90%) were obtained with the most acidic system, Cc–PhSO₃H. Changing the carbon functionalization method (–PhSO₃H for –SO₃H groups) produced a considerable increase in glycerol conversion (from 23 to 66%) and in selectivity to ME + DE (from 62 to 90%). On the other hand, for both Cs-based systems a great increase in performance was obtained, about 95% conversion after 360 min of reaction. Monoether was the major product of the reaction with a selectivity of 79% for Cs–SO₃H and 87% for Cs–PhSO₃H, which was maintained with reuse. Etherification of glycerol (Gly) with benzyl alcohol (BA) with two carbonaceous systems synthesized in the laboratory and functionalized with –SO₃H and –PhSO₃H.Facultad de Ciencias ExactasCentro de Investigación y Desarrollo en Ciencias Aplicada

FIRES INCIDENT OCCURRENCE IN PARQUE NACIONAL DA CHAPADA DOS VEADEIROS, GOI\uc1S

Esta pesquisa objetivou a an\ue1lise da ocorr\ueancia de inc\ueandios florestais no Parque Nacional da Chapada dos Veadeiros (PNCV), GO, no per\uedodo de 1992 a 2003. A metodologia utilizou mapas de focos de calor, dados dos relat\uf3rios de ocorr\ueancia de inc\ueandios na Unidade de Conserva\ue7\ue3o, entrevistas aos brigadistas e \ue0 comunidade do entorno. Com esses dados, foi poss\uedvel analisar as causas e a freq\ufc\ueancia de ocorr\ueancia de inc\ueandios florestais, as \ue1reas queimadas anualmente, os locais e \ue9pocas de incid\ueancia, o trabalho de preven\ue7\ue3o e combate desenvolvido pelos brigadistas e a opini\ue3o da popula\ue7\ue3o em rela\ue7\ue3o ao trabalho desenvolvido no Parque. Essas informa\ue7\uf5es possibilitaram analisar as ocorr\ueancias de fogo no PNCV e alguns dados importantes sobre preven\ue7\ue3o e combate aos inc\ueandios. Os inc\ueandios florestais no PNCV ocorreram praticamente em todos os anos, sendo que 1995 e 2002 foram os anos mais cr\uedticos. 88,2% dos inc\ueandios florestais foram de origem criminosa, por neglig\ueancia ou de causa desconhecida. A \ue9poca em que mais ocorreram os inc\ueandios foi a esta\ue7\ue3o seca, sendo o pico o m\ueas de agosto, seguido pelos meses de setembro e julho. As a\ue7\uf5es preventivas realizadas no PNCV s\ue3o a constru\ue7\ue3o de aceiros e a distribui\ue7\ue3o de cartazes educativos. A comunidade local salientou que falta est\uedmulo \ue0 utiliza\ue7\ue3o de t\ue9cnicas de substitui\ue7\ue3o ao uso do fogo nas propriedades rurais e campanhas educativas de preven\ue7\ue3o de inc\ueandios florestais.This work aimed at studying the fires in Parque Nacional da Chapada dos Veadeiros (PNCV) in Goi\ue1s, Brazil, from 1992 to 2003. The methodology included analysis of heat spots maps, reports and interviews with the fire crew members, besides interviews with the land owners who live close to the PNCV. The data showed the causes and the frequencies of fires annual burnt areas, seasons and origins of fire incident, and fire privation developed by the fire crew of PNCV. Furthermore, there was opinions by land owner related to the PNCV. Results showed that the fires in PNCV had annual frequency. The years 1995 and 2002 presented more fire occurrences. Most of the fires (88,2%) had criminal or unknown causes. The dry season caused more fire occurrences, mainly August, September and July. The prevention activities were break fires construction and instruction folders related to fires release. The local land owners did not know how to deal with land management techniques without fire and asked for environmental education