CMRegNet-An interspecies reference database for corynebacterial and mycobacterial regulatory networks

BACKGROUND: Organisms utilize a multitude of mechanisms for responding to changing environmental conditions, maintaining their functional homeostasis and to overcome stress situations. One of the most important mechanisms is transcriptional gene regulation. In-depth study of the transcriptional gene regulatory network can lead to various practical applications, creating a greater understanding of how organisms control their cellular behavior. DESCRIPTION: In this work, we present a new database, CMRegNet for the gene regulatory networks of Corynebacterium glutamicum ATCC 13032 and Mycobacterium tuberculosis H37Rv. We furthermore transferred the known networks of these model organisms to 18 other non-model but phylogenetically close species (target organisms) of the CMNR group. In comparison to other network transfers, for the first time we utilized two model organisms resulting into a more diverse and complete network of the target organisms. CONCLUSION: CMRegNet provides easy access to a total of 3,103 known regulations in C. glutamicum ATCC 13032 and M. tuberculosis H37Rv and to 38,940 evolutionary conserved interactions for 18 non-model species of the CMNR group. This makes CMRegNet to date the most comprehensive database of regulatory interactions of CMNR bacteria. The content of CMRegNet is publicly available online via a web interface found at http://lgcm.icb.ufmg.br/cmregnet

DISMIRA: Prioritization of disease candidates in miRNA-disease associations based on maximum weighted matching inference model and motif-based analysis

Background MicroRNAs (miRNAs) have increasingly been found to regulate diseases at a significant level. The interaction of miRNA and diseases is a complex web of multilevel interactions, given the fact that a miRNA regulates upto 50 or more diseases and miRNAs/diseases work in clusters. The clear patterns of miRNA regulations in a disease are still elusive. Methods In this work, we approach the miRNA-disease interactions from a network scientific perspective and devise two approaches - maximum weighted matching model (a graph theoretical algorithm which provides the result by solving an optimization equation of selecting the most prominent set of diseases) and motif-based analyses (which investigates the motifs of the miRNA-disease network and selects the most prominent set of diseases based on their maximum number of participation in motifs, thereby revealing the miRNA-disease interaction dynamics) to determine and prioritize the set of diseases which are most certainly impacted upon the activation of a group of queried miRNAs, in a miRNA-disease network. Results and Conclusion Our tool, DISMIRA implements the above mentioned approaches and presents an interactive visualization which helps the user in exploring the networking dynamics of miRNAs and diseases by analyzing their neighbors, paths and topological features. A set of miRNAs can be used in this analysis to get the associated diseases for the input group of miRs with ranks and also further analysis can be done to find key miRs or diseases, shortest paths etc

Factor structure of the Positive and Negative Syndrome Scale (PANSS) in Brazil: convergent validation of the Brazilian version

Objectives: The Positive and Negative Syndrome Scale (PANSS) was developed to assess the symptoms of schizophrenia dimensionally. Although it is widely used in clinical trials in Brazil, it is not fully validated. The aim of this study is to assess the factor structure of the Brazilian PANSS and generate validation data for its current version. Methods: A total of 292 patients diagnosed with schizophrenia were enrolled. Results: Principal component analysis suggested a forced five-factor final model that accounted for 58.44% of the total variance, composed of negative, disorganization/cognition, excitement, positive, and depression/anxiety. Conclusion: The Brazilian PANSS has a similar factor structure and internal consistency compared to its other country versions.Universidade Federal de São Paulo (UNIFESP) Department of Psychiatry Interdisciplinary Laboratory in Clinical Neuroscience (LiNC)UNIFESP Schizophrenia Program (PROESQ)Faculdade de Ciências Médicas da Santa Casa de São Paulo Center for Integrated Mental HealthUniversidade Federal de São Paulo (UNIFESP) Department of PsychiatryUNIFESP Genetics Division, Department of Morphology and GeneticsUNIFESP, Department of Psychiatry Interdisciplinary Laboratory in Clinical Neuroscience (LiNC)UNIFESP, Schizophrenia Program (PROESQ)UNIFESP, Department of PsychiatryUNIFESP, Genetics Division, Department of Morphology and GeneticsSciEL

Comparative analysis of two complete Corynebacterium ulcerans genomes and detection of candidate virulence factors

Trost E, Al-Dilaimi A, Papavasiliou P, et al. Comparative analysis of two complete Corynebacterium ulcerans genomes and detection of candidate virulence factors. BMC Genomics. 2011;12(1): 383.ABSTRACT: Corynebacterium ulcerans has been detected as a commensal in domestic and wild animals that may serve as reservoirs for zoonotic infections. During the last decade, the frequency and severity of human infections associated with C. ulcerans appear to be increasing in various countries. As the knowledge of genes contributing to the virulence of this bacterium was very limited, the complete genome sequences of two C. ulcerans strains detected in the metropolitan area of Rio de Janeiro were determined and characterized by comparative genomics: C. ulcerans 809 was initially isolated from an elderly woman with fatal pulmonary infection and C. ulcerans BR-AD22 was recovered from a nasal sample of an asymptomatic dog. The circular chromosome of C. ulcerans 809 has a total size of 2,502,095 bp and encodes 2,182 predicted proteins, whereas the genome of C. ulcerans BR-AD22 is 104,279 bp larger and comprises 2,338 protein-coding regions. The minor difference in size of the two genomes is mainly caused by additional prophage-like elements in the C. ulcerans BR-AD22 chromosome. Both genomes show a highly similar order of orthologous coding regions; and both strains share a common set of 2,076 genes, demonstrating their very close relationship. A screening for prominent virulence factors revealed the presence of phospholipase D (Pld), neuraminidase H (NanH), endoglycosidase E (EndoE), and subunits of adhesive pili of the SpaDEF type that are encoded in both C. ulcerans genomes. The rbp gene coding for a putative ribosome-binding protein with striking structural similarity to Shiga-like toxins was additionally detected in the genome of the human isolate C. ulcerans 809. The molecular data deduced from the complete genome sequences provides considerable knowledge of virulence factors in C. ulcerans that is increasingly recognized as an emerging pathogen. This bacterium is apparently equipped with a broad and varying set of virulence factors, including a novel type of a ribosome-binding protein. Whether the respective protein contributes to the severity of human infections (and a fatal outcome) remains to be elucidated by genetic experiments with defined bacterial mutants and host model systems

Evidence for Reductive Genome Evolution and Lateral Acquisition of Virulence Functions in Two Corynebacterium pseudotuberculosis Strains

Ruiz JC, D'Afonseca V, Silva A, et al. Evidence for Reductive Genome Evolution and Lateral Acquisition of Virulence Functions in Two Corynebacterium pseudotuberculosis Strains. PLoS ONE. 2011;6(4): e18551.Background: Corynebacterium pseudotuberculosis, a Gram-positive, facultative intracellular pathogen, is the etiologic agent of the disease known as caseous lymphadenitis (CL). CL mainly affects small ruminants, such as goats and sheep; it also causes infections in humans, though rarely. This species is distributed worldwide, but it has the most serious economic impact in Oceania, Africa and South America. Although C. pseudotuberculosis causes major health and productivity problems for livestock, little is known about the molecular basis of its pathogenicity. Methodology and Findings: We characterized two C. pseudotuberculosis genomes (Cp1002, isolated from goats; and CpC231, isolated from sheep). Analysis of the predicted genomes showed high similarity in genomic architecture, gene content and genetic order. When C. pseudotuberculosis was compared with other Corynebacterium species, it became evident that this pathogenic species has lost numerous genes, resulting in one of the smallest genomes in the genus. Other differences that could be part of the adaptation to pathogenicity include a lower GC content, of about 52%, and a reduced gene repertoire. The C. pseudotuberculosis genome also includes seven putative pathogenicity islands, which contain several classical virulence factors, including genes for fimbrial subunits, adhesion factors, iron uptake and secreted toxins. Additionally, all of the virulence factors in the islands have characteristics that indicate horizontal transfer. Conclusions: These particular genome characteristics of C. pseudotuberculosis, as well as its acquired virulence factors in pathogenicity islands, provide evidence of its lifestyle and of the pathogenicity pathways used by this pathogen in the infection process. All genomes cited in this study are available in the NCBI Genbank database (http://www.ncbi.nlm.nih.gov/genbank/) under accession numbers CP001809 and CP001829

Marcadores imunológicos na exposição mercurial na Região Amazônica

Immune dysfunctions can appear by combination between genetic susceptibility and environmental factors. There are evidences, in humans exposed to total mercury (Hgt), of alterations in immune response, by Hgt induced autoantibodies. This work investigated the occurrence of Hgt-induced autoimmunity (HgtIA) among human being exposed to Hgt in the Tapajós region (Barreiras, Brasília Legal, São Luís do Tapajós), as well as in the riverines from Tocantins region (Panacauera) without exposition to Hgt. The of hair and blood samples were collected from 236 individuals during June of 2004 to December of 2006, in which the total mercury in hair was determined by atomic absorption spectrophotometer, and in the serum, autoantibodies were analyzed by indirect immunofluorescence microscopy, using human epithelial cells (HEp-2) as substrate. The highest Hgtotal levels was found in São Luís do Tapajós (11.24 ± 2.23 μg/g), following for Brasília Legal (10.00 ± 0.99) and Barreiras (8.64 ± 1.13), and the lowest were found in Panacauera (2.98 ± 0.20). When considering the variable sex, association with the levels of Hgtotal in hair was observed only in Brasília Legal. Regarding mercury exposure, the autoantibodies in serum was more frequent in riverine of the Tapajós (79.65%) than in the control group (31.25%). Most of the autoantibodies patterns identified by immunofluorescence were: mixed (50.96%), nuclear (31.21%), nucleolar (14.65%) and mitotic apparatus/cytoplasmatic (3.18%). The mixed and nuclear autoantibodies patterns were observed in exposed communities (p10μg/g) with age group above 50 years (p>0.01). Finally, additional studies are indispensable to confirm the specificity of these autoantibodies associated with the mercurial exposure, as well as to elucidate the mechanisms immunotoxicologicals of action of the mercury on the human immune system.CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorDisfunções imunes podem surgir pela combinação entre susceptibilidade genética e fatores ambientais. Existem evidências, em humanos expostos ao mercúrio (Hg), de alterações da resposta imunológica por auto-anticorpos induzidos por Hg. Este trabalho investigou a ocorrência de auto-imunidade induzida por Hgtotal entre indivíduos ribeirinhos da região do Tapajós (Brasília Legal, São Luiz do Tapajós e Barreiras), expostos ao Hgtotal, e da comunidade ribeirinha da região do Tocantins (Panacauera) não exposta ao Hgtotal. No período de junho de 2004 a dezembro de 2006 foram coletadas 236 pares de amostras de cabelo e sangue, nas quais a concentração de Hgtotal no cabelo foi determinada por espectrofotometria de absorção atômica, e no soro, os auto-anticorpos foram analisados por microscopia de imunofluorescência (IF) usando substrato de células epiteliais humanas (Hep-2). Os mais altos níveis de Hgtotal no cabelo foram os de São Luiz do Tapajós (11,24 ± 2,23 μg/g), seguido por Brasília Legal (10,00 ± 0,99) e Barreiras (8,64 ± 1,13), e os mais baixos foram os de Panacauera (2,98 ± 0,20). Em relação à variável sexo, foi observada associação somente em Brasília Legal, com níveis de Hgtotal mais altos no cabelo dos homens. Cerca de 79,65% ribeirinhos do Tapajós e 31,25% da região do Tocantins apresentaram no soro autoanticorpos induzidos por Hg. Os padrões de auto-anticorpos identificados por IF foram: misto (50,96%), nuclear (31,21%), nucleolar (14,65%) e aparelho mitótico/citoplasmático (3,18%), observando-se maior prevalência dos padrões misto e nuclear nas comunidades expostas (p0,01). Finalmente, estudos adicionais são indispensáveis para confirmar a especificidade destes auto-anticorpos induzidos pela exposição mercurial, bem como elucidar os mecanismos imunotoxicológicos da ação do mercúrio sobre o sistema imune humano