The cholesterol 24-hydroxylase activates autophagy and decreases mutant huntingtin build-up in a neuroblastoma culture model of Huntington’s disease

Objective Compromised brain cholesterol turnover and altered regulation of brain cholesterol metabolism have been allied with some neurodegenerative diseases, including Huntington’s disease (HD). Following our previous studies in HD, in this study we aim to investigate in vitro in a neuroblastoma cellular model of HD, the effect of CYP46A1 overexpression, an essential enzyme in cholesterol metabolism, on huntingtin aggregation and levels. Results We found that CYP46A1 reduces the quantity and size of mutant huntingtin aggregates in cells, as well as the levels of mutant huntingtin protein. Additionally, our results suggest that the observed beneficial effects of CYP46A1 in HD cells are linked to the activation of autophagy. Taken together, our results further demonstrate that CYP46A1 is a pertinent target to counteract HD progression.This work was supported by Brainvectis and E.rare: E-Rare Joint Transnational Call for Proposals 2017 “Transnational Research Projects for Innovative Therapeutic Approaches for Rare Diseases”. CN laboratory is supported by the French Muscular Dystrophy Association (AFM-Téléthon), the Ataxia UK, and the Fundação para a Ciência e Tecnologia (project ALG-01-0145-FEDER-29480 “SeGrPolyQ”). AM is supported by a Ph.D. fellowship from FCT (SFRH/BD/133192/2017)info:eu-repo/semantics/publishedVersio

Steel slag and recycled concrete aggregates: replacing quarries to supply sustainable materials for the asphalt paving industry

Various researchers are developing efforts to integrate waste and by-products as alternative materials in road construction and maintenance, reducing environmental impacts and promoting a circular economy. Among the alternative materials that several authors have studied regarding their use as partial or total substitutes for natural aggregates in the asphalt paving industry, the steel slag aggregate (SSA) and recycled concrete aggregate (RCA) from construction demolition waste (CDW) stand out. This paper reviews and discusses the characteristics and performance of these materials when used as aggregates in asphalt mixtures. Based on the various studies analyzed, it was possible to conclude that incorporating SSA or RCA in asphalt mixtures for road pavements has functional, mechanical, and environmental advantages. However, it is essential to consider some possible drawbacks of these aggregates that are discussed in this paper, to define the acceptable uses of SSA and RCA as sustainable feedstocks for road paving works.This research was funded by the "Environment, Climate Change and Low Carbon Economy Programme-Environment Programme" (EEA financial mechanism 2014-2021) through the Funding Mechanism Commission established by Iceland, Liechtenstein, Norway, and Portugal, under the scope of project CirMat-CIRcular aggregates for sustainable road and building MATerials. This study was also supported by Fundacao para a Ciencia e a Tecnologia through the Ph.D. grants number 2021.06428.BD and 2021.08004.BD

Avaliação da atividade enzimática de fungos isolados do Bioma Amazônico / Evaluation of the enzymatic activity of fungi isolated from the Amazonian Biome

A geração de energia renovável é uma das maneiras de solucionar o acúmulo deresíduos agroindustriais. A estratégia de sucesso para produzir enzimas celulolíticas inclui seleção de microrganismos e melhorias nas condições do processo fermentativo. Este trabalho descreve aanálise das atividades enzimáticas de celulases usando diferentes fontes de substratos a partir de fungos degradantes de biomassa da floresta Amazônica. As fermentações foram realizadas em agitadores a 150 rpm, 30 °C durante 240 h. Foram determinadas três atividades enzimáticas: CMCase, FPase e ?-glicosidase. O substrato comercial AVICEL® apresentou as maiores atividades enzimáticas, principalmente após 96 horas de fermentação, tanto para a cepa 511 quanto 519

Mechanical and environmental performance of asphalt concrete with high amounts of recycled concrete aggregates (RCA) for use in surface courses of pavements

Using aggregates from alternative sources has been considerably encouraged in recent decades. Reducing the consumption of natural aggregates from quarries (which have a substantial economic, visual, and environmental impact) is increasingly a concern. These needs have led to the broader use of more sustainable aggregates, increasing the incorporation percentages and extending their use to more demanding pavement layers (e.g., surface). In order to prove the efficiency of recycled concrete aggregates (RCAs) under such conditions, the “CirMat” project was developed. Among other works and tests, an asphalt concrete (AC) incorporating 52.3% RCA was characterized mechanically and environmentally. Empirical properties were evaluated, including the Marshall test (S = 20.2 kN; F = 2.9 mm) and resistance to permanent deformation (WTS = 0.10 mm/103 cycles), as well as a life cycle assessment (LCA), which confirmed that nine indicators were improved (from 1% to 93%). The test samples were taken from mixtures produced in the laboratory and at a plant (after which they were applied on a construction site). Comparing the results with those obtained in a reference AC (with natural aggregates), it was possible to conclude that the performance of the AC with RCAs was very similar. Therefore, the use of these aggregates, at high rates, does not represent additional risks for asphalt mixtures and has lower environmental impacts in most categories.This research was funded by the “Environment, Climate Change and Low Carbon Economy Programme—Environment Programme” (EEA financial mechanism 2014–2021) through the Funding Mechanism Commission established by Iceland, Liechtenstein, Norway, and Portugal, under the scope of project “CirMat—CIRcular aggregates for sustainable road and building MATerials” (Project 16 Call#2). This study was also supported by Fundação para a Ciência e a Tecnologia through the PhD grants number 2021.06428.BD and 2021.08004.BD. This work was also partly financed by FCT/MCTES through national funds (PIDDAC) under the R&D Unit Institute for Sustainability and Innovation in Structural Engineering (ISISE), under reference UIDB/04029/2020, and under the Associate Laboratory Advanced Production and Intelligent Systems ARISE under reference LA/P/0112/2020

Strong relationships between soil and vegetation in reference ecosystems of a riparian atlantic rainforest in the upper Doce River watershed, southeastern Brazil

Habitat loss and fragmentation have been impacting ecosystem services essential for human survival. The Brazilian Atlantic rainforest, a biodiversity hotspot, has suffered from historical deforestation and, more recently, from an environmental disaster caused by the Fundão dam collapse that released ore tailings drastically affecting a large territory in the Doce River watershed. This work aims to assess the relationships between soil properties and vegetation in a reference ecosystem to provide guidelines for restoration projects in areas affected by the dam collapse. We conducted phytosociological (vegetation characteristic) and soil quality studies in three distinct natural sites and studied different vegetation strata to better understand plant species composition in reference sites along the impacted Doce River and their potential role in community structuring and functioning. We recorded 140 species, 78 in the tree stratum, and 90 in the sapling stratum. Furthermore, our results highlight the influence of soil on floristic composition in the Atlantic rainforest. Smallscale edaphic variation influenced species composition in both sapling and tree strata. We also identified species of the same genus with strong association with the extremes of the edaphic gradient. Therefore, we highlight that studies in various regions along the Doce River watershed are of utmost importance to evaluate the association between species and soils. The particularities of the species are crucial to the effectiveness of restoration processes since this plant-soil correlation should not be extrapolated even within the same genus. This knowledge is of strategic relevance to provide scientificbased guidance for restoring these environments, aiming at the recovery of biodiversity and ecosystem services.Fil: Ramos, Letícia. Universidade Federal de Minas Gerais; BrasilFil: Negreiros, Daniel. Universidade Federal de Minas Gerais; BrasilFil: Ferreira, Bárbara S. Silva. Universidade Federal de Minas Gerais; BrasilFil: Figueiredo, João Carlos Gomes. Universidade Estadual de Montes Claros; BrasilFil: Paiva, Dario C.. Florida International University; Estados UnidosFil: Oki, Yumi. Universidade Federal de Minas Gerais; BrasilFil: De Souza Justino, Wénita. Universidade Federal de Minas Gerais; BrasilFil: Dos Santos, Rubens Manoel. Universidade Federal de Lavras; BrasilFil: Aguilar, Ramiro. Universidade Federal de Minas Gerais; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Nunes, Yule Roberta Ferreira. Universidade Estadual de Montes Claros; BrasilFil: Fernandes, G Wilson. Universidade Federal de Minas Gerais; Brasi

Systemic Correlates of Angiographic Coronary Artery Disease

Coronary angiography allows a direct evaluation of coronary anatomy. The aim of the present investigation was to search for correlations between the magnitude of coronary artery disease, as assessed by angiography, and a number of systemic parameters. A group of 116 patients (80 male, 36 female) with coronary heart disease diagnosed by angiography, aged 62.0±10.5 years, was the subject of an observational study. Correlation and linear regression analysis using coronary artery disease burden (CADB - sum of the percentage of the luminal stenosis encountered in all the lesions of the coronary arterial trees) as dependent variable, and age, sex, plasma calcium, phosphorus, magnesium, glucose, HDL cholesterol, LDL cholesterol, triglycerides, uric acid, estimated glomerular filtration rate and body mass index as independent variables, were carried out. Significant correlation values versus CADB were seen with age (r 0.19, p 0.04), uric acid (r 0.18, p 0.048) and fasting plasma glucose (r 0.33, p<0.001). Linear regression analysis, yielding a global significance level of 0.002, showed a significant value for glucose (p 0.018) and for sex (0.008). In conclusion, among several systemic parameters studied, plasma glucose was found to be correlated to coronary artery atherosclerosis lesions

Mapping Molecular Recognition of β1,3-1,4-Glucans by a Surface Glycan-Binding Protein from the Human Gut Symbiont Bacteroides ovatus

This work was supported by Fundação para a Ciência e a Tecnologia (FCT-MCTES), Portugal, through project grant PTDC/BIA-MIB/31730/2017 (to A.S.P.), fellowships PD/BD/105727/2014 (to V.G.C.) and SFRH/BD/143494/2019 (to F.T.), and program contract DL-57/2016 (to B.A.P. and C.N.) and by Wellcome Trust Biomedical Resource grants number WT108430/Z/15/Z and WT218304/Z/19/Z, a March of Dimes (Arlington, VA, USA) Prematurity Research Center grant (number 22-FY18-821) for the funding to the Carbohydrate Microarray Facility, Associate Laboratory projects LAQV-REQUIMTE (UIDB/50006/2020) and CICECO-Aveiro Institute of Materials (UIDB/50011/2020 & UIDP/50011/2020), and by the Applied Molecular Biosciences Unit (UCIBIO), which is financed by Portuguese national funds from FCT-MCTES (UIDP/04378/2020 and UIDB/04378/2020).A multigene polysaccharide utilization locus (PUL) encoding enzymes and surface carbohydrate (glycan)-binding proteins (SGBPs) was recently identified in prominent members of Bacteroidetes in the human gut and characterized in Bacteroides ovatus. This PUL-encoded system specifically targets mixed-linkage β1,3-1,4-glucans, a group of diet-derived carbohydrates that promote a healthy microbiota and have potential as prebiotics. The BoSGBPMLG-A protein encoded by the BACOVA_2743 gene is a SusD-like protein that plays a key role in the PUL's specificity and functionality. Here, we perform a detailed analysis of the molecular determinants underlying carbohydrate binding by BoSGBPMLG-A, combining carbohydrate microarray technology with quantitative affinity studies and a high-resolution X-ray crystallography structure of the complex of BoSGBPMLG-A with a β1,3-1,4-nonasaccharide. We demonstrate its unique binding specificity toward β1,3-1,4-gluco-oligosaccharides, with increasing binding affinities up to the octasaccharide and dependency on the number and position of β1,3 linkages. The interaction is defined by a 41-Å-long extended binding site that accommodates the oligosaccharide in a mode distinct from that of previously described bacterial β1,3-1,4-glucan-binding proteins. In addition to the shape complementarity mediated by CH-π interactions, a complex hydrogen bonding network complemented by a high number of key ordered water molecules establishes additional specific interactions with the oligosaccharide. These support the twisted conformation of the β-glucan backbone imposed by the β1,3 linkages and explain the dependency on the oligosaccharide chain length. We propose that the specificity of the PUL conferred by BoSGBPMLG-A to import long β1,3-1,4-glucan oligosaccharides to the bacterial periplasm allows Bacteroidetes to outcompete bacteria that lack this PUL for utilization of β1,3-1,4-glucans. IMPORTANCE With the knowledge of bacterial gene systems encoding proteins that target dietary carbohydrates as a source of nutrients and their importance for human health, major efforts are being made to understand carbohydrate recognition by various commensal bacteria. Here, we describe an integrative strategy that combines carbohydrate microarray technology with structural studies to further elucidate the molecular determinants of carbohydrate recognition by BoSGBPMLG-A, a key protein expressed at the surface of Bacteroides ovatus for utilization of mixed-linkage β1,3-1,4-glucans. We have mapped at high resolution interactions that occur at the binding site of BoSGBPMLG-A and provide evidence for the role of key water-mediated interactions for fine specificity and affinity. Understanding at the molecular level how commensal bacteria, such as prominent members of Bacteroidetes, can differentially utilize dietary carbohydrates with potential prebiotic activities will shed light on possible ways to modulate the microbiome to promote human health.publishersversionpublishe

Production of thermostable β-glucosidase and CMCase by Penicillium sp. LMI01 isolated from the Amazon region

Background: Cellulolytic enzymes of microbial origin have great industrial importance because of their wide application in various industrial sectors. Fungi are considered the most efficient producers of these enzymes. Bioprospecting survey to identify fungal sources of biomass-hydrolyzing enzymes from a high-diversity environment is an important approach to discover interesting strains for bioprocess uses. In this study, we evaluated the production of endoglucanase (CMCase) and β-glucosidase, enzymes from the lignocellulolytic complex, produced by a native fungus. Penicillium sp. LMI01 was isolated from decaying plant material in the Amazon region, and its performance was compared with that of the standard isolate Trichoderma reesei QM9414 under submerged fermentation conditions. Results: The effectiveness of LMI01 was similar to that of QM9414 in volumetric enzyme activity (U/mL); however, the specific enzyme activity (U/mg) of the former was higher, corresponding to 24.170 U/mg of CMCase and 1.345 U/mg of β-glucosidase. The enzymes produced by LMI01 had the following physicochemical properties: CMCase activity was optimal at pH 4.2 and the β-glucosidase activity was optimal at pH 6.0. Both CMCase and β-glucosidase had an optimum temperature at 60°C and were thermostable between 50 and 60°C. The electrophoretic profile of the proteins secreted by LMI01 indicated that this isolate produced at least two enzymes with CMCase activity, with approximate molecular masses of 50 and 35 kDa, and β-glucosidases with molecular masses between 70 and 100 kDa. Conclusions: The effectiveness and characteristics of these enzymes indicate that LMI01 can be an alternative for the hydrolysis of lignocellulosic materials and should be tested in commercial formulations

Production of thermostable \u3b2-glucosidase and CMCase by Penicillium sp. LMI01 isolated from the Amazon region

Background: Cellulolytic enzymes of microbial origin have great industrial importance because of their wide application in various industrial sectors. Fungi are considered the most efficient producers of these enzymes. Bioprospecting survey to identify fungal sources of biomass-hydrolyzing enzymes from a high-diversity environment is an important approach to discover interesting strains for bioprocess uses. In this study, we evaluated the production of endoglucanase (CMCase) and \u3b2-glucosidase, enzymes from the lignocellulolytic complex, produced by a native fungus. Penicillium sp. LMI01 was isolated from decaying plant material in the Amazon region, and its performance was compared with that of the standard isolate Trichoderma reesei QM9414 under submerged fermentation conditions. Results: The effectiveness of LMI01was similar to that of QM9414 in volumetric enzymeactivity (U/mL); however, the specific enzyme activity (U/mg) of the former was higher, corresponding to 24.170 U/mg of CMCase and 1.345 U/mg of \u3b2-glucosidase. The enzymes produced by LMI01 had the following physicochemical properties: CMCase activity was optimal at pH 4.2 and the \u3b2-glucosidase activity was optimal at pH 6.0. Both CMCase and \u3b2-glucosidase had an optimum temperature at 60\ub0C and were thermostable between 50 and 60\ub0C. The electrophoretic profile of the proteins secreted by LMI01 indicated that this isolate produced at least two enzymes with CMCase activity, with approximate molecular masses of 50 and 35 kDa, and \u3b2-glucosidases with molecular masses between 70 and 100 kDa. Conclusions: The effectiveness and characteristics of these enzymes indicate that LMI01 can be an alternative for the hydrolysis of lignocellulosic materials and should be tested in commercial formulations

PHYTOPLANKTON BIOMASS INCREASES IN A SILT-IMPACTED AREA IN AN AMAZONIAN FLOOD-PLAIN LAKE OVER 15 YEARS

Funding Information: We thank Mineração Rio do Norte S.A. and Limnologia/UFRJ for fieldwork support, Dr. Janet W. Reid (JWR Associates) for language revision, and Leonardo Preza Rodrigues for map charting. VLMH, JCN, FAE, RLB, and FR are partially supported by the National Council for Scientific and Technological Development (CNPq), Brazil, RLB, and FAE by FAPERJ, Brazil, and CGR financially supported by Sakari Alhopuro Foundation, Finland. Publisher Copyright: © 2022, Universidade Federal do Rio de Janeiro. All rights reserved.Tailings from bauxite mining in Porto Trombetas (Pará state, Central Amazonia, Brazil) was discharged (1979–1989) into Batata Lake affecting about 30% of its area. The lake belongs to a clear-water flood-plain system along the Trombetas River, a tributary of the Amazon River. Siltation is the main perceived factor impacting aquatic and flooded communities. Besides natural regeneration, a program to restore a section of igapó forest in the impacted area (IA) has been conducted since 1991. Decreased light is the main factor reducing total phytoplankton biomass (PhyBM) in IA. We hypothesized that PhyBM in IA increases over time because of the improvement of the underwater light conditions due to the natural regeneration and restoration. We sampled quarterly PhyBM and limnological variables (depth, transparency, temperature, pH, conductivity, dissolved oxygen, turbidity, suspended solids, total Kjeldahl nitrogen, and total phosphorus), over 15 years (2005–2019) at eight sampling sites in the two areas (N = 349). We also obtained daily climatic and hydrologic data. PhyBM was higher in NIA than in IA. The temporal trend in the annual mean of PhyBM increased significantly over time only in the IA, approximating the NIA values, confirming our general hypothesis. The increase of PhyBM in the IA was negatively related to the residual light attenuation caused by non-phytoplankton turbidity and to total phosphorus, and positively to air temperature and site depth (p < 0.05; Marginal r2 = 0.18; Conditional r2 = 0.29). Instead, in NIA, PhyBM was explained only by the increase in air temperature (p < 0.05; Marginal r2 = 0.15; Conditional r2 = 0.34). We concluded that the PhyBM in the IA positively responds to the synergy between increasing light availability, air temperature, and site depth, and decreasing total phosphorus concentrations, regardless of hydrologic phase.Peer reviewe