Lipocalin-2 regulates adult neurogenesis and contextual discriminative behaviours

In the adult mammalian brain, newborn granule cells are continuously integrated into hippocampal circuits, and the fine-tuning of this process is important for hippocampal function. Thus, the identification of factors that control adult neural stem cells (NSCs) maintenance, differentiation and integration is essential. Here we show that the deletion of the iron trafficking protein lipocalin-2 (LCN2) induces deficits in NSCs proliferation and commitment, with impact on the hippocampal-dependent contextual fear discriminative task. Mice deficient in LCN2 present an increase in the NSCs population, as a consequence of a G0/G1 cell cycle arrest induced by increased endogenous oxidative stress. Of notice, supplementation with the iron-chelating agent deferoxamine rescues NSCs oxidative stress, promotes cell cycle progression and improves contextual fear conditioning. LCN2 is, therefore, a novel key modulator of neurogenesis that, through iron, controls NSCs cell cycle progression and death, self-renewal, proliferation and differentiation and, ultimately, hippocampal function.AC Ferreira is a recipient of PhD fellowship and B Sampaio-Marques is a recipient of postdoctoral fellowship from the Foundation for Science and Technology (FCT, Portugal)/FEDER. F Marques is an assistant researcher IF/00231/2013 of the Foundation for Science and Technology (FCT, Portugal). This work was supported by Foundation for Science and Technology (FCT) and COMPETE through the project EXPL/NEU-OSD/2196/2013 (to F Marques) and by the Bial Foundation through Grant 217/12 (to JC Sousa). The work at ICVS/3B's has been developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER), and funded by FEDER funds through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038. The work at CICS-UBI has the support of FEDER funds through the POCI - COMPETE 2020 - Operational Programme Competitiveness and Internationalisation in Axis I - Strengthening research, technological development and innovation (Project POCI-01-0145-FEDER-007491) and National Funds by Foundation for Science and Technology (Project UID/Multi /00709/2013).info:eu-repo/semantics/publishedVersio

A Treatment with a Protease Inhibitor Recombinant from the Cattle Tick (Rhipicephalus Boophilus microplus) Ameliorates Emphysema in Mice

Aims: To determine whether a serine protease inhibitor treatment can prevent or minimize emphysema in mice.Methods: C57BL/6 mice were subjected to porcine pancreatic elastase (PPE) nasal instillation to induce emphysema and were treated with a serine protease inhibitor (rBmTI-A) before (Protocol 1) and after (Protocol 2) emphysema development. in both protocols, we evaluated lung function to evaluate the airway resistance (Raw), tissue damping (Gtis) and tissue elastance (Htis). the inflammatory profile was analyzed in the bronchoalveolar lavage (BALF) and through the use of morphometry; we measured the mean linear intercept (Lm) (to verify alveolar enlargement), the volume proportion of collagen and elastic fibers, and the numbers of macrophages and metalloprotease 12 (MMP-12) positive cells in the parenchyma. We showed that at both time points, even after the emphysema was established, the rBmTI-A treatment was sufficient to reverse the loss of elastic recoil measured by Htis, the alveolar enlargement and the increase in the total number of cells in the BALF, with a primary decrease in the number of macrophages. Although, the treatment did not control the increase in macrophages in the lung parenchyma, it was sufficient to decrease the number of positive cells for MMP-12 and reduce the volume of collagen fibers, which was increased in PPE groups. These findings attest to the importance of MMP-12 in PPE-induced emphysema and suggest that this metalloprotease could be an effective therapeutic target.Laboratorios de Investigacao Medica do Hospital das Clinicas da Faculdade de Medicina da USP (LIM/HC)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ São Paulo, Dept Med, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biol Sci, São Paulo, BrazilUNIFESP EPM, Dept Bioquim, São Paulo, BrazilUFABC, Ctr Ciencias Nat & Humanas, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biol Sci, São Paulo, BrazilUNIFESP EPM, Dept Bioquim, São Paulo, BrazilWeb of Scienc

ESTUDIOS MORFOLÓGICOS Y MORFOMÉTRICOS EN GANCHOS ROSTELLARES DEL PROTOESCOLICES DE ECHINOCOCCUS GRANULOSUS DEL PERÚ VISUALIZADA POR VARIAS TÉNICAS MICROSCÓPICAS

This study was undertaken to expand the current knowledge of the morphology and morphometry of rostellar hooks of protoscoleces from the metacestode E. granulosus. Protoscoleces were isolated from livers and lungs of naturally infected ovines and bovines obtained from abattoirs in Peruvian provinces (Arequipa, Cuzco, Puno, Huancavelica and Junin). Brightfield microscopy, confocal laser scanning microscopy, differential interference contrast and variable pressure scanning electron microscopy were used. Morphometry was made using computer image analysis. The application of these assay indicated that the large hooks frequently had thin guards and an irregular surface between the guard and handle. Data also showed that the small hooks presented rounded and stout guards. The blade did not show any relevant feature. No clear morphological distinction was observed between large and small hooks. Phenotypical polymorphism was evident in the shape and size of hooks. In conclusion, the current data show that large and small rostellar hooks have morphological polymorphism. Because the application of this knowledge for taxonomic study is limited, for this end morphometry techniques are required. Our study demonstrated the usefulness of combining conventional and new morphological tools to help to solve unresolved matters with regards to rostellar hooks features.Esta investigación fue realizada para incrementar el conocimiento actual de los datos morfológicos y morfométricos de los ganchos rostelares de la forma larvaria (metacestode) de Echinococcus granulosus. Los protoescoÛ lices fueron aislados de hígados y pulmones de ovinos y vacunos infectados naturalmente obtenidos de los mataderos en los departamentos del Perú (Arequipa, Cuzco, Puno, Huancavelica y Junín). Se utilizó la microscopia de campo claro, la microscopia confocal, la microscopia electrónica de barrido y contraste de interferencia diferencial. La morfometría se realizó mediante el análisis de imagen computacional. La aplicación de estos ensayos indican que los ganchos grandes con frecuencia presentaban finos protectores y de superficie irregular entre el protector y el mango. Los datos también indicaron que los ganchos pequeños presentaron proctectores redondeados y robustos. La hoja no mostroÛ ningún aspecto relevante. Se observoÛ que no existe distinción morfológica clara entre los ganchos grandes y pequeños. Fue evidente diferencias fenotípicas en la forma y el tamaño de los ganchos. En conclusión, la comparación de la morfología de los ganchos rostelares grandes y pequeños mostró ciertas diferencias. Nuestro estudio demostró la utilidad de la combinación de herramientas tradicionales y nuevas para los estudios morfológicos y ayudar a resolver las cuestiones pendientes con respecto a la morfología de los ganchos rostelares

In vivo biodistribution of carboxymethylchitosan/poly(amidoamine) dendrimer nanoparticles in rats

Carboxymethylchitosan/poly(amidoamine) dendrimer nanoparticles (CMCht/PAMAM) have recently been proposed for intracellular drug delivery purposes. These are constituted by a PAMAM dendrimer core grafted with chains of CMCht. Previous reports have shown that these nanoparticles disclosed an improved cytotoxic profile when compared to traditional dendrimers. Following on these results the present study aims to assess, for the first time, the short-term in vivo biodistribution of CMCht/PAMAM dendrimer nanoparticles upon intravenous injections in Wistar Han rats. The rats were injected in the tail vein with 1 and 10 µg/g, respectively, of fluorescein isothiocyanate (FITC) labeled CMCht/PAMAM dendrimer nanoparticles. Brain, liver, kidney and lung were collected at 24, 48 and 72 hours after injection and further stained with phalloidin-TRITC (red) and DAPI (blue) to trace the nanoparticles within the tissues. Liver, kidney and lung were also stained for haematoxylin and eosin in order to assess possible alterations in the morphology of these organs. CMCht/PAMAM dendrimer nanoparticles were observed within the vascular space and parenchyma of liver, kidney and lung, and in the choroid plexus, after 24, 48 and 72 hours upon intravenous injection of nanoparticles. No particles were observed in the brain parenchyma, nor any apparent deleterious histological changes, were observed within these organs. The present report revealed that CMCht/PAMAM dendrimer nanoparticles were stable in circulation for periods up to 72 hours, targeting the main organs/systems through internalization by the cells present in their parenchyma. These results provide positive indicators to their potential use in the future as intracellular drug delivery systems.Funds attributed by Fundação Calouste de Gulbenkian to A.J. Salgado under the scope of the The Gulbenkian Programme to Support Research in Life Sciences; Portuguese Foundation for Science and Technology (Science 2007 Program – A.J. Salgado, pre- and postdoctoral fellowships to J.M. Oliveira – SFRH/BPD/63175/2009, A.M. Frias – SFRH/BPD/45206/2008, F. Marques – SFRH/BPD/33379/2008, A.M. Falcão – SFRH/BD/44485/2008, S. Roque – SFRH/BD/24539/2005; S.R. Cerqueira – SFRH/BD/SFRH/BD/48406: 2008)

Proinflammatory and anti-inflammatory cytokines in the CSF of patients with Alzheimer's disease and their correlation with cognitive decline

Cumulative data suggest that neuroinflammation plays a prominent role in Alzheimer's disease (AD) pathogenesis. The purpose of this work was to assess if patients with AD present a specific cerebrospinal fluid (CSF) cytokine profile and if it correlates to disease progression. We determined the levels of 27 cytokines in CSF of patients with AD and compared them with patients with frontotemporal dementia and nondemented controls. In addition, we correlated the cytokine levels with cognitive status and disease progression after 12 months. Patients with AD had higher levels of proinflammatory and anti-inflammatory cytokines (eotaxin, interleukin [IL]-1ra, IL-4, IL-7, IL-8, IL-9, IL-10, IL-15, granulocyte colony-stimulating factor, monocyte chemotactic protein 1, platelet-derived growth factor, tumor necrosis factor alfa) compared to nondemented controls. There was a negative correlation between the disease progression and the levels of several cytokines (IL-1β, IL-4, IL-6, IL-9, IL-17A, basic fibroblast growth factor, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interferon gamma, macrophage inflammatory proteins-1β). To the best of our knowledge, this is the first study reporting a "protective" role of the upregulation of specific intrathecal cytokine levels in AD. This finding supports that a fine "rebalancing" of the immune system represents a new target in AD therapeutic approach.The work at ICVS/3B's has been developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Program (NORTE, 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) and funded by FEDER funds through the Competitiveness Factors Operational Program (COMPETE) and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038. The work at Centro Hospitalar do Porto (CHP) work was funded by "Bolsa para Investigacao" of Departamento de Ensino Formacao e Investigacao (DEFI) do CHP. S.P. das Neves is a recipient of a PhD fellowship with the reference PD/BD/114120/2015, from POCH through FCT National Funds

HISTOPATOLOGÍA DEL HÍGADO CAUSADA POR LA INFECCIÓN POR ECHINOCOCCUS GRANULOSUS EN SUS SCROFA PROCEDENTE DE BRASIL

Museum specimens represent a valuable resource for helminthological research. We examined formalin-fixed livers preserved for periods in excess of 50 years from naturally infected pigs in archival material from the Helminthological Collection of the Oswaldo Cruz Institute (CHIOC), Oswaldo Cruz Foundation (FIOCRUZ). Microscopic examination revealed evidence of parasites in unilocular cystic structures containing a bladder worm vesicle lined with a thin laminated membrane. The inner germinal layer contained parasite debris and a proteinaceous hydatid-like fluid. The hepatic parenchyma showed a dense inflammatory infiltrate near the cyst, thick-walled arterial vessels, and occasionally necrosis. The adjacent hepatic parenchyma showed inter- and intra-lobular thin fibrosis, inflammatory cell infiltration and occasionally necrosis. Other histo-pathological sections showed a thick laminated wall cystic structure with brood capsules in the germinal layer containing small round projections with central internal vesicles on the inner surface, suggesting the presence of protoscolices. Given that Echinococcus multilocularis does not occur in Brazil, our histological findings were identified as Echinococcus granulosus in origin. In conclusion, the protocol presented in this study highlights the possibility of achieving remarkably high quality histological results in archival formalin-fixed and paraffin-embedded tissues retrieved from museum specimens that have been preserved for many years.Los especímenes de museo representan un recurso valioso para la investigación helmintológica. Hemos examinado los hígados fijados en formalina conservados por períodos de más de 50 años a partir de cerdos infectados naturalmente en el material de archivo de la Colección Helmintológica del Instituto Oswaldo Cruz (CHIOC), Fundación Oswaldo Cruz (FIOCRUZ). El examen microscópico reveló evidencia de parásitos en estructuras quísticas uniloculares que contienen una vesícula de la membrana del parásito recubierto con una lámina delgada. La capa interna germinal contiene los restos del parásito y un líquido proteíco como hidatídico. El parénquima hepático mostró un denso infiltrado inflamatorio cerca del quiste, los vasos arteriales de paredes gruesas y necrosis de vez en cuando. El parénquima hepático adyacente mostró fibrosis delgada inter e intralobular, la infiltración de células inflamatorias y necrosis de vez en cuando. Otros cortes histológicos mostraron una estructura de pared gruesa laminada quística con cápsulas de cría en la capa germinal que contienen proyecciones pequeñas y redondas con el centro de las vesículas internas en la superficie interna, lo que sugiere la presencia de protoescólices. Teniendo en cuenta que Echinococcus multilocularis no ocurre en Brasil, nuestros hallazgos histológicos fueron identificados como Echinococcus granulosus de origen. En conclusión, el protocolo que se presenta en este estudio pone de relieve la posibilidad de lograr resultados histológicos de muy alta calidad en archivos fijados en formalina y parafina de tejidos embebidos recuperados de especímenes de museo que se han conservado durante muchos años

GQ-16, a TZD-derived partial PPARγ agonist, induces the expression of thermogenesis- related genes in brown fat and visceral white fat and decreases visceral adiposity in obese and hyperglycemic mice

Background Beige adipocytes comprise a unique thermogenic cell type in the white adipose tissue (WAT) of rodents and humans, and play a critical role in energy homeostasis. In this scenario, recruitment of beige cells has been an important focus of interest for the development of novel therapeutic strategies to treat obesity. PPARγ activation by full agonists (thiazolidinediones, TZDs) drives the appearance of beige cells, a process so-called browning of WAT. However, this does not translate into increased energy expenditure, and TZDs are associated with weight gain. Partial PPARγ agonists, on the other hand, do not induce weight gain, but have not been shown to drive WAT browning. The present study was designed to investigate the effects of GQ-16 on BAT and on browning of WAT in obese mice. Methods Male Swiss mice with obesity and hyperglycemia induced by high fat diet were treated with vehicle, rosiglitazone (4 mg/kg/d) or the TZD-derived partial PPARγ agonist GQ-16 (40 mg/ kg/d) for 14 days. Fasting blood glucose, aspartate aminotransferase, alanine aminotransferase and lipid profile were measured. WAT and brown adipose tissue (BAT) depots were excised for determination of adiposity, relative expression of Ucp-1, Cidea, Prdm16, Cd40 and Tmem26 by RT-qPCR, histological analysis, and UCP-1 protein expression analysis by immunohistochemistry. Liver samples were also removed for histological analysis and determination of hepatic triglyceride content. Results GQ-16 treatment reduced high fat diet-induced weight gain in mice despite increasing energy intake. This was accompanied by reduced epididymal fat mass, reduced liver triglyceride content, morphological signs of increased BAT activity, increased expression of thermogenesis- related genes in interscapular BAT and epididymal WAT, and increased UCP-1 protein expression in interscapular BAT and in epididymal and inguinal WAT. Conclusion This study suggests for the first time that a partial PPARγ agonist may increase BAT activity and induce the expression of thermogenesis-related genes in visceral WAT. General Significance These findings suggest that PPARγ activity might be modulated by partial agonists to induce WAT browning and treat obesity

Recursos locais para aplicações multifuncionais de captação de energia com base em tetraedrite

CIES2020 - XVII Congresso Ibérico e XIII Congresso Ibero-americano de Energia SolarRESUMO: Este trabalho descreve as principais linhas de investigação que estão em curso no âmbito do projeto LocalEnergy (http://localenergy.lneg.pt). LocalEnergy é um projeto multidisciplinar de Investigação, Desenvolvimento e Inovação (I&D&I), envolvendo atividades no domínio da ciência dos materiais, da geologia e das energias renováveis. Essas atividades estão orientadas para a indústria e assentam numa abordagem disruptiva visando o desenvolvimento de materiais termoelétricos, através da utilização de materiais à base de tetraedrites naturais e sintéticas, e o desenvolvimento de novos absorsores para células solares de filmes finos, usando materiais à base de tetraedrites sintéticas. Considerando que Portugal é um dos países europeus com maior nível de irradiação de energia solar e que a tetraedrite é um recurso mineral local, presente na Zona Sul Portuguesa da Faixa Piritosa Ibérica, o projeto LocalEnergy representa uma oportunidade para o desenvolvimento de sistemas energéticos sustentáveis baseados na maximização e exploração de dois importantes recursos endógenos (energia solar e recursos minerais).ABSTRACT: This work describes the main lines of investigation that are underway within LocalEnergy project (http://localenergy.lneg.pt). LocalEnergy is a multidisciplinary Research, Development and Innovation project, involving activities in the field of materials science, geology and renewable energies. These activities are oriented towards the industry and are based on a disruptive approach aimed at the development of thermoelectric materials, through the use of materials based on natural and synthetic tetrahedrites, and the development of new absorbers for thin film solar cells, using materials based on synthetic tetrahedrites. Considering that Portugal is one of the European countries with the highest level of irradiation of solar energy and that tetrahedrite is a local mineral resource, present in the Portuguese zone of the Iberian Pyrite Belt, LocalEnergy project represents an opportunity for the development of sustainable energy systems based on the maximization and exploration of two important endogenous resources (solar energy and mineral resources).info:eu-repo/semantics/publishedVersio