Abundância de três espécies de aranhas (Araneae) em ecossistemas nativos e manejados no Rio Grande do Sul, Brasil

We assessed the abundance patterns of three theridiid species: Hetschkia gracilis (Keyserling 1886); Phycosoma altum (Keyserling 1886); and Thwaitesia affinis O.P.-Cambridge, 1882 in four habitats: Araucaria Forest (native forest) and plantations of A. angustifolia, Pinus spp., and Eucalyptus spp. in Floresta Nacional de São Francisco de Paula Reserve, southern Brazil. The plantation stands in the study system are managed by the selective cutting of adult trees, allowing longer rotation intervals. We collected spiders in 2003 and 2004 by beating the vegetation inside three replicates of each forest type. We performed a permanova to test whether there were differences on species abundances between habitats. We tested the influence of the stand sizes, distance between stands, and vegetation cover composition on each spider species abundance. Stands with higher vegetation cover of bushes and vines presented higher abundances of Hetschkia gracilis and Thwaitesia affinis. Phycosoma altum abundance did not respond to any explanatory variables. Results highlighted the importance of alternative management of plantation stands to enhance and maintain the understory vegetation diversity, which in turn support the spider populations.Key words: Araucaria Forest, Habitat structure, Pinus plantation, Eucalyptus plantation, Forest management.Os padrões de abundância de três espécies de Theridiidae - Hetschkia gracilis, Phycosoma altum e Thwaitesia affinis foram analisados em quatro habitats florestais: Floresta com Araucária, plantação de Araucária, plantação de Pinus e plantação de Eucalyptus na Floresta Nacional de São Francisco de Paula, sul do Brasil. O manejo florestal aplicado na área de estudo consiste no corte seletivo e no longo período de rotação. As coletas foram realizadas com guarda-chuva entomológico entre 2003 e 2004 em três repetições de cada tipo florestal. Diferenças nas abundâncias entre os habitats foram avaliadas através de permanova. Para testar a influência do tamanho dos talhões, da distância entre eles e da composição da cobertura vegetal sobre as abundâncias das três espécies, utilizou-se regressão múltipla. As abundâncias de Hetschkia gracilis e de Thwaitesia affinis estiveram diretamente correlacionadas com a presença de lianas e arbustos, enquanto a de Phycosoma altum não respondeu a nenhuma variável explicativa. Os resultados realçam a importância do manejo alternativo realizado nesta Floresta Nacional para o incremento e a manutenção da diversidade da vegetação do sub-bosque, o que proporciona estrutura para sustentar as populações de aranhas.Palavras-chave: Floresta com Araucária, Estrutura de habitat, Plantação de Pinus, Plantação de Eucalyptus, Manejo florestal

Dieta do mão-pelada (Procyon cancrivorus, Procyonidae, Carnivora) no Parque Estadual de Itapuã, sul do Brasil

The raccoon (Procyon cancrivorus, F. Cuvier, 1798) is the only procyonid that occurs in Itapuã State Park. This conservation area has 5,566.5 ha and it is located in Porto Alegre metropolitan area. The purpose of this study was to do qualitative and quantitative analyses of the alimentary items consumed by the raccoons in the park, as well as investigate the seasonality influence upon the diet of these animals. Every month in 2002 fecal samples on fixed transects were collected, adding up two hundred and three samples. Forty-one alimentary items were found (53% fruits and 47% of animal origin items). The Arecaceae botanic family was the most eaten food, denoting the Syagrus romanzoffiana (Cham.) Glassman like the key resource of the raccoon diet, and the Butia capitata (Mart.) Becc. like an important seasonal alimentary resource. Other fruits like Ficus sp., Vitex megapotamica (Spreng.) Mold., Psidium sp., and Eugenia uruguayensis Cambess. were registered as additional items, sustaining the opportunist behavior of this species. Orthoptera, Blattaria, and Coleoptera were the most eaten invertebrate animals in the four seasons. The high relative frequencies of birds, rodents, and other mammals on the raccoon’s taxodiet during the winter and spring denote its needs for a more improved diet of proteins in this time, due probably to low temperatures and to the birth of the cubs. The difference in the diet composition was proved using the randomization test (?=0.05) to all the seasons, except between the winter and the spring. This result indicates that the diet of Procyon cancrivorus in PEI reflects the seasonal changes. Key words: fecal analysis, feeding items, Procyon, southern Brazil.O mão-pelada (Procyon cancrivorus, F. Cuvier, 1798) é o único procionídeo que ocorre no Parque Estadual de Itapuã (PEI), com uma área de 5.566,5 ha, na região metropolitana de Porto Alegre. O objetivo deste estudo foi o de analisar, por estação do ano, qualiquantitativamente, a dieta desta espécie no interior do Parque. Mensalmente, durante o ano de 2002, foi coletado um total de 203 amostras fecais em transecções pré-estabelecidas. Foram identificados 41 itens alimentares (53% frutas e 47% itens de origem animal). A família botânica Arecaceae foi a mais frequente, Syagrus romanzoffiana (Cham.) Glassman foi considerado recurso-chave e Butia capitata (Mart.) Becc foi um importante recurso alimentar sazonal. Outros frutos, tais como Ficus sp., Vitex megapotamica (Spreng.) Mold., Psidium sp. e Eugenia uruguayensis Cambess., foram itens adicionais, indicando comportamento oportunista da espécie. Dentre os animais, insetos das ordens Orthoptera, Blattaria e Coleoptera foram os mais consumidos nas quatro estações do ano. As maiores frequências de aves, roedores e outros mamíferos durante os meses de inverno e de primavera demonstraram a necessidade de uma ingestão mais proteica nesse período do ano, relacionada, provavelmente, às baixas temperaturas e aos cuidados dos filhotes. Por meio de análise de variância com aleatorização (?=0.05), houve diferença significativa na dieta entre as estações do ano, exceto entre os meses de inverno e primavera, refletindo um comportamento alimentar generalista e oportunista da espécie. Palavras-chave: análise fecal, itens alimentares, Procyon, sul do Brasil

Drug-induced trafficking of p-glycoprotein in human brain capillary endothelial cells as demonstrated by exposure to mitomycin C.

P-glycoprotein (Pgp; ABCB1/MDR1) is a major efflux transporter at the blood-brain barrier (BBB), restricting the penetration of various compounds. In other tissues, trafficking of Pgp from subcellular stores to the cell surface has been demonstrated and may constitute a rapid way of the cell to respond to toxic compounds by functional membrane insertion of the transporter. It is not known whether drug-induced Pgp trafficking also occurs in brain capillary endothelial cells that form the BBB. In this study, trafficking of Pgp was investigated in human brain capillary endothelial cells (hCMEC/D3) that were stably transfected with a doxycycline-inducible MDR1-EGFP fusion plasmid. In the presence of doxycycline, these cells exhibited a 15-fold increase in Pgp-EGFP fusion protein expression, which was associated with an increased efflux of the Pgp substrate rhodamine 123 (Rho123). The chemotherapeutic agent mitomycin C (MMC) was used to study drug-induced trafficking of Pgp. Confocal fluorescence microscopy of single hCMEC/D3-MDR1-EGFP cells revealed that Pgp redistribution from intracellular pools to the cell surface occurred within 2 h of MMC exposure. Pgp-EGFP exhibited a punctuate pattern at the cell surface compatible with concentrated regions of the fusion protein in membrane microdomains, i.e., lipid rafts, which was confirmed by Western blot analysis of biotinylated cell surface proteins in Lubrol-resistant membranes. MMC exposure also increased the functionality of Pgp as assessed in three functional assays with Pgp substrates (Rho123, eFluxx-ID Gold, calcein-AM). However, this increase occurred with some delay after the increased Pgp expression and coincided with the release of Pgp from the Lubrol-resistant membrane complexes. Disrupting rafts by depleting the membrane of cholesterol increased the functionality of Pgp. Our data present the first direct evidence of drug-induced Pgp trafficking at the human BBB and indicate that Pgp has to be released from lipid rafts to gain its full functionality

Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts

Peer reviewe

A large-scale genome-wide association study meta-analysis of cannabis use disorder

Summary Background Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50–70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. Methods To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. Findings We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07–1·15, p=1·84 × 10−9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86–0·93, p=6·46 × 10−9). Cannabis use disorder and cannabis use were genetically correlated (rg 0·50, p=1·50 × 10−21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. Interpretation These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder. Funding National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain & Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences.Peer reviewe

Shared genetic risk between eating disorder- and substance-use-related phenotypes:Evidence from genome-wide association studies

First published: 16 February 202

Leveraging genome-wide data to investigate differences between opioid use vs. opioid dependence in 41,176 individuals from the Psychiatric Genomics Consortium

To provide insights into the biology of opioid dependence (OD) and opioid use (i.e., exposure, OE), we completed a genome-wide analysis comparing 4503 OD cases, 4173 opioid-exposed controls, and 32,500 opioid-unexposed controls, including participants of European and African descent (EUR and AFR, respectively). Among the variants identified, rs9291211 was associated with OE (exposed vs. unexposed controls; EUR z = -5.39, p = 7.2 × 10-8). This variant regulates the transcriptomic profiles of SLC30A9 and BEND4 in multiple brain tissues and was previously associated with depression, alcohol consumption, and neuroticism. A phenome-wide scan of rs9291211 in the UK Biobank (N > 360,000) found association of this variant with propensity to use dietary supplements (p = 1.68 × 10-8). With respect to the same OE phenotype in the gene-based analysis, we identified SDCCAG8 (EUR + AFR z = 4.69, p = 10-6), which was previously associated with educational attainment, risk-taking behaviors, and schizophrenia. In addition, rs201123820 showed a genome-wide significant difference between OD cases and unexposed controls (AFR z = 5.55, p = 2.9 × 10-8) and a significant association with musculoskeletal disorders in the UK Biobank (p = 4.88 × 10-7). A polygenic risk score (PRS) based on a GWAS of risk-tolerance (n = 466,571) was positively associated with OD (OD vs. unexposed controls, p = 8.1 × 10-5; OD cases vs. exposed controls, p = 0.054) and OE (exposed vs. unexposed controls, p = 3.6 × 10-5). A PRS based on a GWAS of neuroticism (n = 390,278) was positively associated with OD (OD vs. unexposed controls, p = 3.2 × 10-5; OD vs. exposed controls, p = 0.002) but not with OE (p = 0.67). Our analyses highlight the difference between dependence and exposure and the importance of considering the definition of controls in studies of addiction

A large-scale genome-wide association study meta-analysis of cannabis use disorder

Background: Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50-70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. Methods: To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. Findings: We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07-1·15, p=1·84 × 10-9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86-0·93, p=6·46 × 10-9). Cannabis use disorder and cannabis use were genetically correlated (rg 0·50, p=1·50 × 10-21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. Interpretation: These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder