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1.  The kynurenine pathway is involved in bacterial meningitis 
Bacterial meningitis (BM) is characterized by an intense host inflammatory reaction, which contributes to the development of brain damage and neuronal sequelae. Activation of the kynurenine (KYN) pathway (KP) has been reported in various neurological diseases as a consequence of inflammation. Previously, the KP was shown to be activated in animal models of BM, and the association of the SNP AADAT + 401C/T (kynurenine aminotransferase II - KAT II) with the host immune response to BM has been described. The aim of this study was to investigate the involvement of the KP during BM in humans by assessing the concentrations of KYN metabolites in the cerebrospinal fluid (CSF) of BM patients and their relationship with the inflammatory response compared to aseptic meningitis (AM) and non-meningitis (NM) groups.
The concentrations of tryptophan (TRP), KYN, kynurenic acid (KYNA) and anthranilic acid (AA) were assessed by HPLC from CSF samples of patients hospitalized in the Giselda Trigueiro Hospital in Natal (Rio Grande do Norte, Brazil). The KYN/TRP ratio was used as an index of indoleamine 2,3-dioxygenase (IDO) activity, and cytokines were measured using a multiplex cytokine assay. The KYNA level was also analyzed in relation to AADAT + 401C/T genotypes.
In CSF from patients with BM, elevated levels of KYN, KYNA, AA, IDO activity and cytokines were observed. The cytokines INF-γ and IL-1Ra showed a positive correlation with IDO activity, and TNF-α and IL-10 were positively correlated with KYN and KYNA, respectively. Furthermore, the highest levels of KYNA were associated with the AADAT + 401 C/T variant allele.
This study suggests a downward modulatory effect of the KP on CSF inflammation during BM.
PMCID: PMC4189685  PMID: 25274277
Bacterial meningitis; Kynurenine; IDO activity; CSF; Cytokines; AADAT + 401C/T
2.  Taxonomic and functional profiles of soil samples from Atlantic forest and Caatinga biomes in northeastern Brazil 
MicrobiologyOpen  2014;3(3):299-315.
Although microorganisms play crucial roles in ecosystems, metagenomic analyses of soil samples are quite scarce, especially in the Southern Hemisphere. In this work, the microbial diversity of soil samples from an Atlantic Forest and Caatinga was analyzed using a metagenomic approach. Proteobacteria and Actinobacteria were the dominant phyla in both samples. Among which, a significant proportion of stress-resistant bacteria associated to organic matter degradation was found. Sequences related to metabolism of amino acids, nitrogen, and DNA and stress resistance were more frequent in Caatinga soil, while the forest sample showed the highest occurrence of hits annotated in phosphorous metabolism, defense mechanisms, and aromatic compound degradation subsystems. The principal component analysis (PCA) showed that our samples are close to the desert metagenomes in relation to taxonomy, but are more similar to rhizosphere microbiota in relation to the functional profiles. The data indicate that soil characteristics affect the taxonomic and functional distribution; these characteristics include low nutrient content, high drainage (both are sandy soils), vegetation, and exposure to stress. In both samples, a rapid turnover of organic matter with low greenhouse gas emission was suggested by the functional profiles obtained, reinforcing the importance of preserving natural areas.
PMCID: PMC4082704  PMID: 24706600
Atlantic forest; bioinformatic; caatinga; comparative metagenomics; pyrosequencing.
3.  Cerebrospinal-fluid cytokine and chemokine profile in patients with pneumococcal and meningococcal meningitis 
BMC Infectious Diseases  2013;13:326.
Bacterial meningitis is characterized by an intense inflammatory reaction contributing to neuronal damage. The aim of this study was to obtain a comparative analysis of cytokines and chemokines in patients with pneumococcal (PM) and meningococcal meningitis (MM) considering that a clear difference between the immune response induced by these pathogens remains unclear.
The cyto/chemokines, IL-1β, IL-2, IL-6, TNF-α, IFN-γ, IL-10, IL-1Ra, CXCL8/IL-8, CCL2/MCP-1, CLL3/MIP-1α, CCL4/MIP-1γ and G-CSF, were measured in cerebrospinal fluid (CSF) samples from patients with PM and MM. Additionally, a literature review about the expression of cytokines in CSF samples of patients with MB was made.
Concerning cytokines levels, only IFN-γ was significantly higher in patients with Streptococcus pneumoniae compared to those with Neisseria meningitidis, regardless of the time when the lumbar puncture (LP) was made. Furthermore, when samples were compared considering the timing of the LP, higher levels of TNF-α (P <0.05) were observed in MM patients whose LP was made within 48 h from the initial symptoms of disease. We also observed that the index of release of cyto/chemokines per cell was significantly higher in PM. From the literature review, it was observed that TNF-α, IL-1β and IL-6 are the best studied cytokines, while reports describing the concentration of the cytokine IL-2, IL-1Ra, G-CSF and CCL4/MIP-1β in CSF samples of patients with bacterial meningitis were not found.
The data obtained in this study and the previously published data show a similar profile of cytokine expression during PM and MM. Nevertheless, the high levels of IFN-γ and the ability to release high levels of cytokines with a low number of cells are important factors to be considered in the pathogenesis of PM and thereby should be further investigated. Moreover, differences in the early response induced by the pathogens were observed. However, the differences observed are not sufficient to trigger changes in the current therapy of corticosteroids adopted in both the PM and MM.
PMCID: PMC3717124  PMID: 23865742
Pneumococcal meningitis; Meningococcal meningitis; Cytokines; Chemokines; Interferon gamma; Cerebrospinal fluid
4.  Profiling the resting venom gland of the scorpion Tityus stigmurus through a transcriptomic survey 
BMC Genomics  2012;13:362.
The scorpion Tityus stigmurus is widely distributed in Northeastern Brazil and known to cause severe human envenoming, inducing pain, hyposthesia, edema, erythema, paresthesia, headaches and vomiting. The present study uses a transcriptomic approach to characterize the gene expression profile from the non-stimulated venom gland of Tityus stigmurus scorpion.
A cDNA library was constructed and 540 clones were sequenced and grouped into 153 clusters, with one or more ESTs (expressed sequence tags). Forty-one percent of ESTs belong to recognized toxin-coding sequences, with transcripts encoding antimicrobial toxins (AMP-like) being the most abundant, followed by alfa KTx- like, beta KTx-like, beta NaTx-like and alfa NaTx-like. Our analysis indicated that 34% of the transcripts encode “other possible venom molecules”, which correspond to anionic peptides, hypothetical secreted peptides, metalloproteinases, cystein-rich peptides and lectins. Fifteen percent of ESTs are similar to cellular transcripts. Sequences without good matches corresponded to 11%.
This investigation provides the first global view of gene expression of the venom gland from Tityus stigmurus under resting conditions. This approach enables characterization of a large number of venom gland component molecules, which belong either to known or non yet described types of venom peptides and proteins from the Buthidae family.
PMCID: PMC3444934  PMID: 22853446
5.  Swine and Poultry Pathogens: the Complete Genome Sequences of Two Strains of Mycoplasma hyopneumoniae and a Strain of Mycoplasma synoviae†  
Vasconcelos, Ana Tereza R. | Ferreira, Henrique B. | Bizarro, Cristiano V. | Bonatto, Sandro L. | Carvalho, Marcos O. | Pinto, Paulo M. | Almeida, Darcy F. | Almeida, Luiz G. P. | Almeida, Rosana | Alves-Filho, Leonardo | Assunção, Enedina N. | Azevedo, Vasco A. C. | Bogo, Maurício R. | Brigido, Marcelo M. | Brocchi, Marcelo | Burity, Helio A. | Camargo, Anamaria A. | Camargo, Sandro S. | Carepo, Marta S. | Carraro, Dirce M. | de Mattos Cascardo, Júlio C. | Castro, Luiza A. | Cavalcanti, Gisele | Chemale, Gustavo | Collevatti, Rosane G. | Cunha, Cristina W. | Dallagiovanna, Bruno | Dambrós, Bibiana P. | Dellagostin, Odir A. | Falcão, Clarissa | Fantinatti-Garboggini, Fabiana | Felipe, Maria S. S. | Fiorentin, Laurimar | Franco, Gloria R. | Freitas, Nara S. A. | Frías, Diego | Grangeiro, Thalles B. | Grisard, Edmundo C. | Guimarães, Claudia T. | Hungria, Mariangela | Jardim, Sílvia N. | Krieger, Marco A. | Laurino, Jomar P. | Lima, Lucymara F. A. | Lopes, Maryellen I. | Loreto, Élgion L. S. | Madeira, Humberto M. F. | Manfio, Gilson P. | Maranhão, Andrea Q. | Martinkovics, Christyanne T. | Medeiros, Sílvia R. B. | Moreira, Miguel A. M. | Neiva, Márcia | Ramalho-Neto, Cicero E. | Nicolás, Marisa F. | Oliveira, Sergio C. | Paixão, Roger F. C. | Pedrosa, Fábio O. | Pena, Sérgio D. J. | Pereira, Maristela | Pereira-Ferrari, Lilian | Piffer, Itamar | Pinto, Luciano S. | Potrich, Deise P. | Salim, Anna C. M. | Santos, Fabrício R. | Schmitt, Renata | Schneider, Maria P. C. | Schrank, Augusto | Schrank, Irene S. | Schuck, Adriana F. | Seuanez, Hector N. | Silva, Denise W. | Silva, Rosane | Silva, Sérgio C. | Soares, Célia M. A. | Souza, Kelly R. L. | Souza, Rangel C. | Staats, Charley C. | Steffens, Maria B. R. | Teixeira, Santuza M. R. | Urmenyi, Turan P. | Vainstein, Marilene H. | Zuccherato, Luciana W. | Simpson, Andrew J. G. | Zaha, Arnaldo
Journal of Bacteriology  2005;187(16):5568-5577.
This work reports the results of analyses of three complete mycoplasma genomes, a pathogenic (7448) and a nonpathogenic (J) strain of the swine pathogen Mycoplasma hyopneumoniae and a strain of the avian pathogen Mycoplasma synoviae; the genome sizes of the three strains were 920,079 bp, 897,405 bp, and 799,476 bp, respectively. These genomes were compared with other sequenced mycoplasma genomes reported in the literature to examine several aspects of mycoplasma evolution. Strain-specific regions, including integrative and conjugal elements, and genome rearrangements and alterations in adhesin sequences were observed in the M. hyopneumoniae strains, and all of these were potentially related to pathogenicity. Genomic comparisons revealed that reduction in genome size implied loss of redundant metabolic pathways, with maintenance of alternative routes in different species. Horizontal gene transfer was consistently observed between M. synoviae and Mycoplasma gallisepticum. Our analyses indicated a likely transfer event of hemagglutinin-coding DNA sequences from M. gallisepticum to M. synoviae.
PMCID: PMC1196056  PMID: 16077101

Results 1-5 (5)