TRACTOR_DB: a database of regulatory networks in gamma-proteobacterial genomes

Experimental data on the Escherichia coli transcriptional regulatory system has been used in the past years to predict new regulatory elements (promoters, transcription factors (TFs), TFs' binding sites and operons) within its genome. As more genomes of gamma-proteobacteria are being sequenced, the prediction of these elements in a growing number of organisms has become more feasible, as a step towards the study of how different bacteria respond to environmental changes at the level of transcriptional regulation. In this work, we present TRACTOR_DB (TRAnscription FaCTORs' predicted binding sites in prokaryotic genomes), a relational database that contains computational predictions of new members of 74 regulons in 17 gamma-proteobacterial genomes. For these predictions we used a comparative genomics approach regarding which several proof-of-principle articles for large regulons have been published. TRACTOR_DB may be currently accessed at http://www.bioinfo.cu/Tractor_DB, http://www.tractor.lncc.br/ or at http://www.cifn.unam.mx/Computational_Genomics/tractorDB. Contact Email id is [email protected]

Collaborative process design for waste management: co-constructing strategies with stakeholders

Funding Information: Thanks are due to all UrbanWINS project partners. Also, the authors acknowledge FCT - Foundation for Science and Technology (Portugal) through the strategic project UIDB/04292/2020 granted to MARE - Marine and Environmental Sciences Centre. And to NOVA School of Science and Technology - NOVA University Lisbon, to several other team members Ana Gomes, Pedro Santos and Mario Ramos Waste@nova team members that collaborate in several activities of the project, as well as to Prof. Joaquim Pina and Prof. Ana Silveira. The UrbanWINS project presented in this paper was funded by the European Union's Horizon 2020 research and innovation program under grant agreement no.690047.Waste management is currently facing multiple challenges worldwide. The population growth in urban areas and related environmental concerns have increased the need to promote urban sustainability, namely where urban waste is a challenge. Thus, research on efficient waste management to reduce resources overload and to develop more sustainable production and consumption is key. Having this in mind, modern society is now seeking for an active voice and to be part of the decision-making processes that directly affect citizens. Citizens need to play an active role on decision-making to co-construct action guidelines, aiming a higher implementation success for an effective and inclusive management of urban waste. In this sense, UrbanWINS project was developed to promote co-construction and implementation of pilot actions involving citizens. In this paper the authors described the framework developed, and reflect critically on the results achieved.publishersversionepub_ahead_of_prin

A Lexically Scoped Distributed π\pi-Calculus

We define the syntax, the operational semantics, and a type system for lsd-pi, an asynchronous and distributed $\pi$-calculus with local communication and process migration. The calculus follows a simple model of distribution for mobile calculi, with a lexical scoping mechanism that provides both for remote communication and for process migration, making explicit migration primitives superfluou

Insights into the in vitro antitumor mechanism of action of a new pyranoxanthone

Naturally occurring xanthones have been docu mented as having antitumor properties, with some of them presently undergoing clinical trials. In an attempt to improve the biological activities of dihydroxyxanthones, prenylation and other mole cular modifications were performed. All the com pounds reduced viable cell number in a leukemia cell line K-562, with the fused xanthone 3, 4-dihydro-12-hydroxy-2,2-dimethyl-2H,6H-pyrano[3, 2-b]xanthen-6-one (5) being the most potent. The pyranoxanthone 5 was particularly effective in additional leukemia cell lines (HL-60 and BV-173). Furthermore, the pyranoxanthone 5 decreased cel lular proliferation and induced an S-phase cell cycle arrest. In vitro, the pyranoxanthone 5 increased the percentage of apoptotic cells which was confirmed by an appropriate response at the protein level (e.g., PARP cleavage). Using a com puter screening strategy based on the structure of several anti- and pro-apoptotic proteins, it was verified that the pyranoxanthone 5 may block the binding of anti-apoptotic Bcl-xL to pro-apoptotic Bad and Bim. The structure-based screening revealed the pyranoxanthone 5 as a new scaffold that may guide the design of small molecules with better affinity profile for Bcl-xL.info:eu-repo/semantics/publishedVersio

Intraclonal Genome Stability of the Metallo-beta-lactamase SPM-1-producing Pseudomonas aeruginosa ST277, an Endemic Clone Disseminated in Brazilian Hospitals

Carbapenems represent the mainstay therapy for the treatment of serious P aeruginosa infections. However, the emergence of carbapenem resistance has jeopardized the clinical use of this important class of compounds. The production of SPM-1 metallo-beta-lactamase has been the most common mechanism of carbapenem resistance identified in P. aeruginosa isolated from Brazilian medical centers. Interestingly, a single SPM-1-producing P. aeruginosa clone belonging to the ST277 has been widely spread within the Brazilian territory. In the current study, we performed a next-generation sequencing of six SPM-1-producing P. aeruginosa ST277 isolates. The core genome contains 5899 coding genes relative to the reference strain P. aeruginosa PAO1. A total of 26 genomic islands were detected in these isolates. We identified remarkable elements inside these genomic islands, such as copies of the bla(spM-1) gene conferring resistance to carbapenems and a type I-C CRISPR-Cas system, which is involved in protection of the chromosome against foreign DNA. In addition, we identified single nucleotide polymorphisms causing amino acid changes in antimicrobial resistance and virulence-related genes. Together,these factors could contribute to the marked resistance and persistence of the SPM-1-producing P aeruginosa ST277 clone. A comparison of the SPM-1-producing P. aeruginosa ST277 genomes showed that their core genome has a high level nucleotide similarity and synteny conservation. The variability observed was mainly due to acquisition of genomic islands carrying several antibiotic resistance genes.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Lab Nacl Comp Cient, Lab Bioinformat, Petropolis, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Internal Med, Lab Alerta,Div Infect Dis, Sao Paulo, BrazilLaboratório Alerta, Division of Infectious Diseases, Department of Internal Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, BrazilCNPq: 305535/2014-5CNPq: 302768/2011-4CNPq: 312864/2015-9FAPERJ: E-26/202.903/2016Web of Scienc

Testagem anti-HIV em mulheres grávidas no Brasil: taxas e preditores

OBJETIVO: Estimar las tasas de oferta y realización de la prueba anti-HIV y sus predictivos entre mujeres que recibieron atención prenatal. MÉTODOS: Se realizó un estudio transversal, de base poblacional, con 2.234 puérperas en 12 ciudades de Brasil. Las muestras probabilísticas fueron seleccionadas independientemente por ciudad, entre puérperas que asistieron a por lo menos una visita prenatal. Se colectaron datos sociodemográficos, informaciones sobre cuidado prenatal y acceso a intervenciones de prevención del HIV durante el embarazo, con la utilización de una encuesta. Se realizaron análisis bivariadas y multivariadas para verificar los efectos independientes de las co-variables en la oferta y realización de la prueba anti-HIV. Los datos fueron colectados en el período de noviembre de 1999 a abril de 2000. RESULTADOS: La realización de la prueba anti-HIV durante el embarazo fue realizada por el 77,5% de las encuestadas. La oferta de la prueba fue positivamente asociada con: el conocimiento previo sobre la prevención de la transmisión materno-infantil del HIV; mayor número de visitas prenatal; mayor nivel de escolaridad y presencia de color blanco de piel. La tasa de aceptación de la prueba anti-HIV fue de 92,5%. CONCLUSIONES: Los resultados indican que La diseminación de la información sobre prevención de la transmisión materno-infantil del HIV puede contribuir para aumentar la cobertura de la evaluación anti-HIV durante el embarazo. Las mujeres no-blancas con menores niveles de educación deben ser priorizadas. La estrategias para aumentar la participación de poblaciones vulnerables al cuidado prenatal y la sensibilización de trabajadores de la salud son de gran importancia.OBJETIVO: Estimar as taxas de oferta e realização do teste anti-HIV e seus preditores entre mulheres que receberam atendimento pré-natal. MÉTODOS: Foi conduzido estudo transversal, de base populacional, com 2.234 puérperas em 12 cidades do Brasil. Amostras probabilísticas foram selecionadas independentemente por cidade, entre puérperas que compareceram a pelo menos uma visita pré-natal. Foram coletados dados sociodemográficos, informações sobre cuidado pré-natal e acesso a intervenções de prevenção do HIV durante a gravidez corrente, com a utilização de um questionário. Foram realizadas análises bivariadas e multivariadas para verificar os efeitos independentes das covariáveis na oferta e realização do teste anti-HIV. Os dados foram coletados no período de novembro de 1999 a abril de 2000. RESULTADOS: A realização do teste na gravidez foi relatada por 77,5% das entrevistadas. A oferta do teste anti-HIV foi positivamente associada a: conhecimento prévio sobre a prevenção da transmissão materno-infantil do HIV; maior número de visitas pré-natal; maior nível de escolaridade e ter cor da pele branca. A taxa de aceitação do teste anti-HIV foi de 92,5%. CONCLUSÕES: Os resultados indicam que a disseminação da informação sobre prevenção da transmissão materno-infantil do HIV pode contribuir para aumentar a cobertura da testagem anti-HIV durante a gravidez. Mulheres não-brancas com menores níveis educacionais devem ser priorizadas. Estratégias para aumentar a participação de populações vulneráveis ao cuidado pré-natal e a sensibilização de trabalhadores de saúde são de grande importância.OBJECTIVE: To assess rates of offering and uptake of HIV testing and their predictors among women who attended prenatal care. METHODS: A population-based cross-sectional study was conducted among postpartum women (N=2,234) who attended at least one prenatal care visit in 12 cities. Independent and probabilistic samples were selected in the cities studied. Sociodemographic data, information about prenatal care and access to HIV prevention interventions during the current pregnancy were collected. Bivariate and multivariate analyses were carried out to assess independent effects of the covariates on offering and uptake of HIV testing. Data collection took place between November 1999 and April 2000. RESULTS: Overall, 77.5% of the women reported undergoing HIV testing during the current pregnancy. Offering of HIV testing was positively associated with: previous knowledge about prevention of mother-to-child transmission of HIV; higher number of prenatal care visits; higher level of education and being white. HIV testing acceptance rate was 92.5%. CONCLUSIONS: The study results indicate that dissemination of information about prevention of mother-to-child transmission among women may contribute to increasing HIV testing coverage during pregnancy. Non-white women with lower level of education should be prioritized. Strategies to increase attendance of vulnerable women to prenatal care and to raise awareness among health care workers are of utmost importance

Flower extracts of Filipendula ulmaria (L.) Maxim inhibit cell growth of human tumour cell lines

According to the World Health Organization, cancer is the leading cause of death worldwide and its mortality is expected to rise in the next few years. Despite all efforts, the current therapeutic arsenal is not sufficient to reduce these numbers. Therefore, it is imperative to identify new sources of anticancer drugs. Filipendula ulmaria (L.) Maxim is part of the ethnobothanical patrimony of the Iberian Peninsula. For centuries, it has been used as a medicinal species due to its rich antioxidant content, which includes flavonoids and ascorbic acid [l]. Nonetheless, little is known about its antiproliferative activity in cancer cells. Thus, the aims of this project were to: i) investigate if different flower extracts of F. ulmaria have cell growth inhibitory activity in human tumour cell lines and ii) study the mechanism of action of one of the most potent extracts. Four flower extracts obtained by different extraction methods (decoction, infusion, methanol and methanol:water 80:20, v!v) were screened for tumour cell growth inhibitory activity in three human tumour cell lines: NCI-H460 (non-small cell lung cancer), A375-C5 (melanoma) and MCF-7 (breast adenocarcinoma). One of the most potent extracts (obtained by decoction) was further studied in the NCI-H460 cell line (one of the most sensitive), by investigating its effect on viable cell number, programmed cell death, cellular proliferation and cell cycle profile. Results showed that all extracts have growth inhibitory activity in the studied cell lines, in particular the extract obtained by decoction (GI50 of 70.0 ± 8.6, 96.0 ± 12.4 and 63.3 ± 7.6 flg/mL in the NCI-H460, MCF-7 and A373-C5 cells, respectively). Further studies in the NCI-H460 cell line showed that this extract reduced viable cell number. Moreover, treatment with this extract resulted in a strong reduction of cellular proliferation, with a slight increase in the percentage of cells in the G l phase of the cell cycle. No significant alterations in programmed cell death were observed, although results showed a statistically significant increase in the cellular levels of p53 and p2l. Future work will confirm if this extract is non-toxic to human non-tumour cells

Exploratory Analysis of the Copy Number Alterations in Glioblastoma Multiforme

The Cancer Genome Atlas project (TCGA) has initiated the analysis of multiple samples of a variety of tumor types, starting with glioblastoma multiforme. The analytical methods encompass genomic and transcriptomic information, as well as demographic and clinical data about the sample donors. The data create the opportunity for a systematic screening of the components of the molecular machinery for features that may be associated with tumor formation. The wealth of existing mechanistic information about cancer cell biology provides a natural reference for the exploratory exercise.Glioblastoma multiforme DNA copy number data was generated by The Cancer Genome Atlas project for 167 patients using 227 aCGH experiments, and was analyzed to build a catalog of aberrant regions. Genome screening was performed using an information theory approach in order to quantify aberration as a deviation from a centrality without the bias of untested assumptions about its parametric nature. A novel Cancer Genome Browser software application was developed and is made public to provide a user-friendly graphical interface in which the reported results can be reproduced. The application source code and stand alone executable are available at (http://code.google.com/p/cancergenome) and (http://bioinformaticstation.org), respectively.The most important known copy number alterations for glioblastoma were correctly recovered using entropy as a measure of aberration. Additional alterations were identified in different pathways, such as cell proliferation, cell junctions and neural development. Moreover, novel candidates for oncogenes and tumor suppressors were also detected. A detailed map of aberrant regions is provided