Genome-wide identification, phylogeny, and gene duplication of the epigenetic regulators in Fagaceae

Epigenetic regulators are proteins involved in controlling gene expression. Informationabout the epigenetic regulators within the Fagaceae, a relevant family of trees andshrubs of the northern hemisphere ecosystems, is scarce. With the intent to character-ize these proteins in Fagaceae, we searched for orthologs of DNA methyltransferases(DNMTs) and demethylases (DDMEs) and Histone modifiers involved in acetylation(HATs), deacetylation (HDACs), methylation (HMTs), and demethylation (HDMTs) inFagus,Quercus,andCastaneagenera. Blast searches were performed in the availablegenomes, and freely available RNA-seq data were used to de novo assemble transcrip-tomes. We identified homologs of seven DNMTs, three DDMEs, six HATs, 11 HDACs,32 HMTs, and 21 HDMTs proteins. Protein analysis showed that most of them havethe putative characteristic domains found in these protein families, which suggeststheir conserved function. Additionally, to elucidate the evolutionary history of thesegenes within Fagaceae, paralogs were identified, and phylogenetic analyses were per-formed with DNA and histone modifiers. We detected duplication events in all speciesanalyzed with higher frequency inQuercusandCastaneaand discuss the evidence oftransposable elements adjacent to paralogs and their involvement in gene duplication.The knowledge gathered from this work is a steppingstone to upcoming studies con-cerning epigenetic regulation in this economically important family of Fagaceaeinfo:eu-repo/semantics/publishedVersio

Response of non-motor symptoms to levodopa in late-stage Parkinson's disease: results of a levodopa challenge test

Article under a CC-BY-NC-ND license - https://creativecommons.org/licenses/by-nc-nd/4.0/"BACKGROUND: Non-motor symptoms (NMS) are extremely common among late-stage Parkinson's disease (LSPD) patients. Levodopa (L-dopa) responsiveness seems to decrease with disease progression but its effect on NMS in LSPD still needs to be investigated. OBJECTIVE: To assess the response of blood pressure (BP), pain, fatigue and anxiety to L-dopa in LSPD patients. METHODS: 20 LSPD patients, defined as Schwab and England ADL Scale 3 (MED ON) and 22 PD patients treated with subthalamic deep brain stimulation (advanced PD group) underwent an L-dopa challenge. BP and orthostatic hypotension (OH) assessment, a visual analogue scale (VAS) for pain and fatigue and the Strait Trait Anxiety (STAI) were evaluated before and after the L-dopa challenge. RESULTS: Systolic BP dropped significantly after L-dopa intake (p < 0.05) in LSPD patients, while there was no change in pain, fatigue or anxiety. L-dopa significantly improved (p < 0.05) pain and anxiety in the advanced PD group, whereas it had no effect on BP or fatigue. L-dopa-related adverse effects (AEs), namely OH and sleepiness, were more common among LSPD patients. 40% and 65% of LSPD patients were not able to fill out the VAS and the STAI, respectively, while measurement of orthostatic BP was not possible in four LSPD patients. CONCLUSIONS: This exploratory study concludes that some non-motor variables in LSPD do not benefit from the acute action of L-dopa while it can still induce disabling AEs. There is a need for assessment tools of NMS adapted to these disabled LSPD patients."info:eu-repo/semantics/publishedVersio

Geocronologia e geologia isotópica dos terrenos pré-cambrianos da porção sul-oriental do Estado de São Paulo

In the southeastern region of São Paulo State four major tectonic domains were defined. The Embu Domain, north of the Cubatão Shear Zone (CSZ), is composed of metasedimentary rocks, and peraluminous granites (ca. 600 Ma), whose intrusion was controlled by E-NE shear zones, and which have model Nd Tdm age around 2.0 Ga. Gneiss-migmatite rocks (612 Ma) and related granites (580 Ma) predominate in the Mongaguá Domain, which is limited by the Cubatão and Itariri shear zones. These rocks have different model Nd Tdm ages between 1.7 and 2.2 Ga. The Registro Domain, between Cubatão - Itariri Shear System (CISS) and the Serrinha Shear Zone (SSZ), is formed by metasediments and granitic rocks with migmatitic features, and represents a paleoproterozoic domain (1.9 - 2.2 Ga) intensely affected in Neoproterozoic times (750 - 580 Ma). Rocks of the Iguape Domain, limited to the north by the SSZ, include granites (ca. 600 Ma) and low grade metasediments. It is probable that all these tectonic blocks were juxtaposed during a short time interval at the end of Neoproterozoic. The joining of the Registro to the Embu Domain occurred at about 596 Ma along an E-W shear zone. The 598 Ma peraluminous granites of the Embu Domain may register the arrival of the Mongaguá Domain against the newly formed Registro-Embu Domain. The welding of the Iguape and Registro domains probably occurred at 575 Ma, as suggested by the U-Pb (monazite) age of the protomylonitic granites of the SSZ.Na porção sul do Cinturão Ribeira, especificamente região sul-oriental do Estado de São Paulo, quatro domínios tectônicos distintos foram definidos, delimitados por importantes zonas de cisalhamento neoproterozóicas. O Domínio Embu, situado a norte da Zona de Cisalhamento Cubatão (ZCC), compreende metassedimentos parcialmente fundidos e granitos peraluminosos intrusivos, que são balizados por zonas de cisalhamento ENE e apresentam idades U-Pb em torno de 600 Ma, e idade Tdm de 2,0 Ga. Rochas gnáissico-migmatíticas (612 Ma) e graníticas associadas (580 Ma) predominam no Domínio Mongaguá, limitadas a NW pela ZCC, e a sul pela Zona de Cisalhamento Itariri (ZCI), com idades Tdm variadas, entre 1,7 e 2,2 Ga. O Domínio Registro é limitado a norte pelo Sistema de Cisalhamento Cubatão Itariri (SCCI) e a sul pela Zona de Cisalhamento Serrinha (ZCS), composto por rochas metassedimentares de alto grau e rochas graníticas com feições migmatíticas. Representa um terreno paleoproterozóico (1,9 - 2,2 Ga) fortemente afetado durante o Neoproterozóico (750 - 580 Ma). O Domínio Iguape é limitado a norte pela ZCS e compreende rochas graníticas, com cerca de 600 Ma, intrudidas em metassedimentos de baixo grau. Granitos semelhantes aos da Suíte intrusiva Serra do Mar ocorrem nos Domínios Registro e Iguape, com idades em torno de 580 Ma. Possivelmente, a justaposição destes domínios tectônicos ocorreu em épocas neoproterozóicas próximas: 1) a justaposição do Domínio Registro ao Embu, através de zona de cisalhamento EW, teve como época máxima 596 Ma; 2) granitos intrusivos no Domínio Embu, com cerca de 598 Ma, controlados pelo SCCI podem estar associados à justaposição do Domínio Mongaguá, aos Domínios Registro e Embu; 3) a época mais provável da colagem Domínio Iguape / Registro de 575 Ma é sugerida através de datações U-Pb (monazita) em protomilonito granítico da ZCS

Migração de orógenos e superposição de orogêneses: um esboço da colagem brasiliana no Sul do Cráton do São Francisco, SE - Brasil

O Orógeno Tocantins Meridional representa a pilha colisional de nappes entre três ambientes tectônicos principais (de WSW para ENE): domínio de arco magmático desenvolvido na margem continental ativa da Placa Paranapanema (Nappe Socorro-Guaxupé), domínio continental subductado (Terreno Andrelândia) e domínios com afinidades de margem passiva e/ou relacionados à Placa Sanfranciscana (Sistema de Nappes Carrancas e Nappe Lima Duarte). O magmatismo relacionado ao período de subducção remonta a 670 Ma, com auge metamórfico (geoterma relaxada na margem ativa e perturbada no terreno subductado) há 625 Ma. A atividade de arco na margem ativa foi contemporânea à sedimentação tipo-flysch no Terreno Andrelândia. Os processos metamórficos e deformacionais da etapa orogênica controlada por colisão frontal migraram para ENE de ca. 620 a 580 Ma. A duração dos processos foi"instantânea" na nappe interna ocidental (ca. 7 Ma, com plutonismo pós-orogênico há 612 Ma) e perdurou por ca. de 20 Ma na nappe oriental de alta pressão. O terreno subductado registrou rápida velocidade de exumação (ca. 2,2 mm/ano). Atividades magmáticas superimpostas, controladas por regimes extensionais (Cinturão Itu) acompanharam a exumação do orógeno e precederam a instalação de bacias sucessoras continental-marinhas há 570 Ma. O Orógeno Araçuaí, relacionado à convergência entre a margem passiva oriental Sanfranciscana e o Terreno Juiz de Fora (microplaca em ambiente de margem ativa) registrou o auge metamórfico colisional no domínio interno há 563 Ma. A migração das nappes Araçuaí contra o domínio cratônico, com o pico térmico metamórfico há 530 Ma, reflete a superposição de eventos colisionais múltiplos no Sistema Orogênico Mantiqueira. O embasamento da borda cratônica foi regenerado no Cambriano e engajado ductilmente no orógeno. Cavalga o domínio de foreland, no Quadrilátero Ferrífero, caracterizado por sistema thin-skinned de cavalgamento segmentado por domos do embasamento e calhas sinformais das supra-crustais. A colisão oblíqua entre o Sistema Orogênico Mantiqueira e o protocontinente consolidado pelo Orógeno Tocantins Meridional foi responsável pelo metamorfismo facies xisto-verde baixo das bacias sucessoras e migrou para norte, de 555 a 500 Ma. A colagem orogênica brasiliana, no sul do Cráton do São Francisco, representou a interação entre etapas orogênicas curtas em um longo processo de convergência, consumo de placas e migração de orógenos até o limite Cambro-Ordoviciano. O último evento metamórfico pré-colagem no embasamento cratônico ocorreu entre 2,03 - 2,06 Ga provavelmente sob regime extensional.The Meridional Tocantins Orogen represents a collision nappe pile involving three different tectonic environments. A magmatic arc domain developed in the Paranapanema continental active margin (Socorro-Guaxupé Nappe); a subducted continental domain (Andrelândia Terrane); and a passive margin domain and/or related to the Sanfranciscana plate (Carrancas and Lima Duarte Nappe systems). The magmatic activity related to the subduction started at 670 Ma and its metamorphism took place around 625Ma (active margin geothermal pattern modified in the subducted domain). The magmatic arc was active during flysch-type sedimentation in the Andrelândia terrane. Deformation and metamorphism related to the collisional process migrated from E to NE between 620 and 580 Ma. In the western internal nappe the tectonic process was very short-lived, less than 7 Ma, with some 612 Ma post-tectonic plutonism. On the other hand, in the eastern nappe the same process lasted ca. 20 Ma. Exhumation in the subducted terrane was very fast (ca. 2,2 mm/year). Superposed magmatic activities controlled by extensional regimes (Itu Granite Belt) followed orogen exhumation and preceded installation of continental-marine successor basins at 570 Ma. The Araçuaí Orogen produced by convergence between the eastern passive margin of the Sanfranciscana plate and the Juiz de Fora Terrane (a microplate in an active margin environment) exhibits a metamorphic peak in the internal domain at around 560 Ma. The migration of the Araçuaí nappes towards the cratonic domain (thermal metamorphic event ca. 530 Ma) reflects the superposition of the Mantiqueira Orogenic System. In the Cambrian the basement of the cratonic border was regenerated and included in the Araçuaí orogen which involved the foreland in a thin-skinned thrust system well documented in the Quadrilátero Ferrífero. Oblique collision between the Mantiqueira Orogenic system and the proto-continent formed during the Meridional Tocantins orogeny was responsible for greenschist metamorphism at about 550 Ma in the successor basins. After this, the collisional process migrated northwards until 500 Ma. In the southern part of the São Francisco Craton the Brasiliano orogenic collage represents the interaction of several short orogenic steps in a long, convergent tectonic process involving plate consumption with eastward polarity and westward orogenic migration that lasted until the Cambro-Ordovician limit. The latest documented pre-collage metamorphism observed in the cratonic basement occurred between 2.03 and 2.06 Ga, probably under extensional conditions

Serum soluble-Fas is a predictor of red blood cell transfusion in critically ill patients

OBJECTIVE: To investigate the relation between the need for red blood cell transfusion and serum levels of soluble-Fas, erythropoietin and inflammatory cytokines in critically ill patients with and without acute kidney injury. METHODS: We studied critically ill patients with acute kidney injury (n=30) and without acute kidney injury (n=13), end-stage renal disease patients on hemodialysis (n=25) and healthy subjects (n=21). Serum levels of soluble-Fas, erythropoietin, interleukin 6, interleukin 10, iron status, hemoglobin and hematocrit concentration were analyzed in all groups. The association between these variables in critically ill patients was investigated. RESULTS: Critically ill patients (acute kidney injury and non-acute kidney injury patients) had higher serum levels of erythropoietin than the other groups. Hemoglobin concentration was lower in the acute kidney injury patients than in other groups. Serum soluble-Fas levels were higher in acute kidney injury and end-stage renal disease patients. Critically ill patients requiring red blood cell transfusions had higher serum levels of soluble-Fas (5,906±2,047 and 1,920±1,060; p<0.001), interleukin 6 (518±537 and 255+502; p=0.02) and interleukin 10 (35.8±30.7 and 18.5±10.9; p=0.02), better iron status and higher mortality rates in the first 28 days in intensive care unit. Serum soluble-Fas levels were independently associated with the number of red blood cell units transfused (p=0.02). Serum soluble-Fas behaved as an independent predictor of the need for red blood cell transfusion in critically ill patients (p=0.01). CONCLUSIONS: Serum soluble-Fas level is an independent predictor of the need for red blood cell transfusion in critically ill patients with or without acute kidney injury. Further studies are warranted to reconfirm this finding.OBJETIVO: Investigar a relação entre a transfusão de hemácias e os níveis séricos de Fas solúvel, eritropoietina e citocinas inflamatórias em pacientes gravemente enfermos, com e sem insuficiência renal aguda. MÉTODOS: Os seguintes grupos foram estudados: pacientes gravemente enfermos com insuficiência renal aguda (n=30) e sem insuficiência renal aguda (n=13), pacientes portadores de doença renal crônica terminal em hemodiálise (n=25) e indivíduos saudáveis (n=21). Os níveis séricos de Fas solúvel, eritropoietina, interleucina 6, interleucina 10 e ferro, além da concentração de hemoglobina e de hematócrito, foram analisados em todos os grupos. A associação entre tais variáveis foram estudadas nos pacientes gravemente enfermos. RESULTADOS: Os níveis séricos de eritropoietina mostraram-se mais elevados nos pacientes gravemente enfermos do que nos dos demais grupos. Concentrações mais baixas de hemoglobina foram documentadas nos pacientes com insuficiência renal aguda em relação aos demais. Níveis séricos mais elevados de Fas solúvel foram observados nos pacientes com insuficiência renal aguda e doença renal crônica terminal. Pacientes gravemente enfermos transfundidos apresentaram níveis séricos mais elevados de Fas solúvel (5.906±2.047 e 1.920±1.060; p<0,001), interleucina 6 (518±537 e 255±502; p=0,02), interleucina 10 (35,8±30,7 e 18,5±10,9; p=0,02) e ferro, além de maior mortalidade em 28 dias. Os níveis séricos de Fas solúvel mostraram-se independentemente associados ao número de transfusões (p=0,02). O nível sérico de Fas solúvel foi um preditor independente da necessidade de transfusão de hemácias em pacientes gravemente enfermos (p=0,01). CONCLUSÃO: O nível sérico de Fas solúvel é um preditor independente da necessidade de transfusão de hemácias em pacientes gravemente enfermos, com ou sem insuficiência renal aguda. Mais estudos clínicos e laboratoriais são necessários para confirmar tal resultado.Universidade Federal de São Paulo (UNIFESP)Hospital Israelita Albert EinsteinUNIFESPSciEL

Comparative study of GC-MS characterization, antioxidant activity and hyaluronidase inhibition of different species of Lavandula and Thymus essential oils

The chemical compositions of essential oils of Lavandula angustifolia, Lavandula latifolia, Lavandula hybrida cultivar Grosso and cultivar Super, Thymus zygis with high proportions of thymol and linalool and Thymus hyemalis, from Murcia country (Spain), were studied in relative (%), absolute (mM) and chiral concentrations by GC/MS. Hyaluronidase inhibition and antioxidant activities of the essential oils were evaluated using ABTS(center dot+), DPPH center dot, ORAC, chelating power, hydroxyl radical, nitric oxide, TBARS and reducing power assays. Linalool and linalyl acetate were the most abundant components in the Lavandula genus whereas thymol, linalool and 1,8-cineole were the most abundant molecules in the respective Thymus species. Chiral determination of the main components showed (+)-enantiomers like terpinen-4-ol, beta-pinene, borneol and a-terpineol and (-)-enantiomers like linalool, linalyl acetate and camphene in Lavandula sp. In the case of Thymus sp. (+)-enantiomers like a-pinene, limonene, terpinen-4-ol and a-terpineol and (-)-enantiomers like borneol were found. Essential oils containing thymol were found especially powerful in all assays but chelating power, ORAC and hydroxyl radical scavenging assays. The capacity for inhibiting hyaluronidase showed that T. zygis with a high proportion of thymol was the most effective inhibitor. Essential oils containing thymol and linalool/linalyl acetate have a potential use as antioxidant agents. Thymol shows strong inhibition of hyaluronidase. Copyright (C) 2015 John Wiley & Sons, Ltd

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

The germline mutational landscape of BRCA1 and BRCA2 in Brazil

The detection of germline mutations in BRCA1 and BRCA2 is essential to the formulation of clinical management strategies, and in Brazil, there is limited access to these services, mainly due to the costs/availability of genetic testing. Aiming at the identification of recurrent mutations that could be included in a low-cost mutation panel, used as a first screening approach, we compiled the testing reports of 649 probands with pathogenic/likely pathogenic variants referred to 28 public and private health care centers distributed across 11 Brazilian States. Overall, 126 and 103 distinct mutations were identified in BRCA1 and BRCA2, respectively. Twenty-six novel variants were reported from both genes, and BRCA2 showed higher mutational heterogeneity. Some recurrent mutations were reported exclusively in certain geographic regions, suggesting a founder effect. Our findings confirm that there is significant molecular heterogeneity in these genes among Brazilian carriers, while also suggesting that this heterogeneity precludes the use of screening protocols that include recurrent mutation testing only. This is the first study to show that profiles of recurrent mutations may be unique to different Brazilian regions. These data should be explored in larger regional cohorts to determine if screening with a panel of recurrent mutations would be effective.This work was supported in part by grants from Barretos Cancer Hospital (FINEP - CT-INFRA, 02/2010), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, 2013/24633-2 and 2103/23277-8), Fundação de Apoio à Pesquisa do Rio Grande do Norte (FAPERN), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), Ministério da Saúde, the Breast Cancer Research Foundation (Avon grant #02-2013-044) and National Institute of Health/National Cancer Institute (grant #RC4 CA153828-01) for the Clinical Cancer Genomics Community Research Network. Support in part was provided by grants from Fundo de Incentivo a Pesquisa e Eventos (FIPE) from Hospital de Clínicas de Porto Alegre, by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, BioComputacional 3381/2013, Rede de Pesquisa em Genômica Populacional Humana), Secretaria da Saúde do Estado da Bahia (SESAB), Laboratório de Imunologia e Biologia Molecular (UFBA), INCT pra Controle do Câncer and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). RMR and PAP are recipients of CNPq Productivity Grants, and Bárbara Alemar received a grant from the same agencyinfo:eu-repo/semantics/publishedVersio