An arginine deprivation response pathway is induced in Leishmania during macrophage invasion

Amino acid sensing is an intracellular function that supports nutrient homeostasis, largely through controlled release of amino acids from lysosomal pools. The intracellular pathogen Leishmania resides and proliferates within human macrophage phagolysosomes. Here we describe a new pathway in Leishmania that specifically senses the extracellular levels of arginine, an amino acid that is essential for the parasite. During infection, the macrophage arginine pool is depleted due to its use to produce metabolites (NO and polyamines) that constitute part of the host defense response and its suppression, respectively. We found that parasites respond to this shortage of arginine by up-regulating expression and activity of the Leishmania arginine transporter (LdAAP3), as well as several other transporters. Our analysis indicates the parasite monitors arginine levels in the environment rather than the intracellular pools. Phosphoproteomics and genetic analysis indicates that the arginine-deprivation response is mediated through a mitogen-activated protein kinase-2-dependent signaling cascade

Microflora fúngica de sementes de milho em ambientes de armazenamento

Durante o armazenamento, vários fungos podem permanecer associados às sementes de milho, causando deterioração ou se mantendo viáveis, infectando posteriormente a plântula. Objetivou-se neste trabalho verificar a sobrevivência de fungos associados às sementes de milho durante 12 meses de armazenamento, em câmara fria (14ºC; 40% UR) e em ambiente não controlado. Observaram-se com maior freqüência os fungos de campo Alternaria alternata, Bipolaris maydis, Cephalosporium acremonium, Cladosporium herbarum, Fusarium moniliforme e Rhizoctonia solani, além de Rhizopus spp. e Trichoderma spp., cuja sobrevivência decresceu ao longo do armazenamento, de modo muito mais acentuado em condição de ambiente não controlado, em comparação à câmara fria. Aspergillus e Penicillium tiveram suas incidências aumentadas ao longo do período, principalmente em ambiente não controlado. Nessa condição, a sobrevivência de Fusarium moniliforme foi reduzida gradativamente até o final dos doze meses; comparativamente, em câmara fria, a viabilidade do fungo foi menos afetada. Bipolaris maydis manteve-se viável na maioria dos lotes, durante todo o armazenamento em câmara fria; em ambiente não controlado, o fungo sobreviveu durante quatro a dez meses, dependendo do lote avaliado. O armazenamento em ambiente não controlado, embora tenha provocado a redução do inóculo de F. moniliforme e outros fungos importantes, poderia acelerar o processo de deterioração das sementes. Em câmara fria, por outro lado, a viabilidade dos fungos é favorecida, comprometendo a qualidade sanitária das sementes.During storage, several kinds of fungi can remain associated to corn seeds, either causing their deterioration or simply remaining viable to infect germinating seedlings. The objective of this work was to evaluate the survival of fungi in corn seeds stored for twelve months in a cold chamber (14°C and 40% RH) or stored under uncontrolled conditions. A larger frequency of Alternaria alternata, Bipolaris maydis, Cephalosporium acremonium, Cladosporium herbarum, Fusarium moniliforme, Rhizoctonia solani, Rhizopus spp. and Trichoderma spp. occurred in the cold condition. The survival decreased with the storage period mainly under uncontrolled atmosphere as compared to the cold environment. The incidence of Aspergillus and Penicillium increased with the storage, mainly under the uncontrolled ambient. Fusarium moniliforme, on the other hand, decreased sharply under ambiental conditions at the end of the period. In the cold chamber, the F. moniliforme viability was less affected. Bipolaris maydis remained viable in most of the seed lots during the entire storage period in the cold chamber. Under uncontrolled conditions, this fungus survived for four to twelve months, depending on the lot studied. The seed storage under uncontrolled ambient may reduce the inoculum of F. moniliforme and other important fungi for the maize crop, but this condition may accelerate seed deterioration. In the cold condition, otherwise, the ambient is favorable to preserve the physiological quality of the seeds, but the maintenance of fungi viability may reduce their sanitary quality

A radiação ionizante como forma de tratamento nas mulheres com cancer de colo de útero em Araguaína-TO, nos anos de 2000 a 2015 / Ionizing radiation as a treatment for women with cervical cancer in Araguaína-TO, from 2000 to 2015

Introdução: O câncer está se apresentando como um grave problema de saúde pública em todo o mundo como sociedades globais, especialmente em países subdesenvolvidos. (10,3% do total), excluídos por causas indeterminadas. Este é o segundo câncer mais comum entre as mulheres em todo o mundo. Radioterapia, que é uma das formas de tratamento dos estágios da IA2. Nos EUA IB2-IIA-IIB-IIIA-IIIB e IVA, o tratamento com radiação é quimioterapia concomitante. O tratamento concomitante com quimioterapia aumenta a probabilidade de sobrevivência de 40% para 52% no final do primeiro ano de tratamento.Metodologia: Estudo descritivo, retrospectivo, quantitativo-interpretativo, com análise de dados para o período de 2000 a 2015, do Registro Hospitalar de Atenção à Saúde (SIS-RHC), vinculado ao Hospital Regional de Araguaína. Os dados foram tabulados em planilhas para análise das variáveis analisadas.Resultados: Foram analisadas 2.664 mulheres com câncer de colo de útero no Hospital Regional de Araguaína. O consumo de 37,8% das mulheres sem diagnóstico e sem tratamento é de 45,0%, com diagnóstico e sem tratamento. A radioterapia apresentou 53,6% do total de tratamentos.Conclusões: A radioterapia é considerada um dos principais diagnósticos tardios, assim como a radioterapia é considerada a principal forma de tratamento. 

A bacterial glycan core linked to surface (S)-layer proteins modulates host immunity through Th17 suppression

Tannerella forsythia is a pathogen implicated in periodontitis, an inflammatory disease of the tooth-supporting tissues often leading to tooth loss. This key periodontal pathogen is decorated with a unique glycan core O-glycosidically linked to the bacterium's proteinaceous surface (S)-layer lattice and other glycoproteins. Herein, we show that the terminal motif of this glycan core acts to modulate dendritic cell effector functions to suppress T-helper (Th)17 responses. In contrast to the wild-type bacterial strain, infection with a mutant strain lacking the complete S-layer glycan core induced robust Th17 and reduced periodontal bone loss in mice. Our findings demonstrate that surface glycosylation of this pathogen may act to ensure its persistence in the host likely through suppression of Th17 responses. In addition, our data suggest that the bacterium then induces the Toll-like receptor 2–Th2 inflammatory axis that has previously been shown to cause bone destruction. Our study provides a biological basis for pathogenesis and opens opportunities in exploiting bacterial glycans as therapeutic targets against periodontitis and a range of other infectious diseases

Porphyromonas gingivalis–dendritic cell interactions: consequences for coronary artery disease

An estimated 80 million US adults have one or more types of cardiovascular diseases. Atherosclerosis is the single most important contributor to cardiovascular diseases; however, only 50% of atherosclerosis patients have currently identified risk factors. Chronic periodontitis, a common inflammatory disease, is linked to an increased cardiovascular risk. Dendritic cells (DCs) are potent antigen presenting cells that infiltrate arterial walls and may destabilize atherosclerotic plaques in cardiovascular disease. While the source of these DCs in atherosclerotic plaques is presently unclear, we propose that dermal DCs from peripheral inflamed sites such as CP tissues are a potential source. This review will examine the role of the opportunistic oral pathogen Porphyromonas gingivalis in invading DCs and stimulating their mobilization and misdirection through the bloodstream. Based on our published observations, combined with some new data, as well as a focused review of the literature we will propose a model for how P. gingivalis may exploit DCs to gain access to systemic circulation and contribute to coronary artery disease. Our published evidence supports a significant role for P. gingivalis in subverting normal DC function, promoting a semimature, highly migratory, and immunosuppressive DC phenotype that contributes to the inflammatory development of atherosclerosis and, eventually, plaque rupture

Comparative analysis between radioactive seed localization and wire-guided for non-palpable breast cancer surgery

The conservative surgery for impalpable breast cancer requires an intraoperative localization method that guides the identification and correct excision of the lesion. The aim of this study is to comparatively analyze two intraoperative breast localization technologies, wire guided localization (WGL) and radioactive seed localization (RSL), regarding their surgical efficacy through the outcomes of surgical margins, intraoperative re-excision, reoperation and recurrence. To this end, a systematic search was realized in databases for clinical trials that match with the study eligibility criteria. The selected studies were evaluated for their methodological quality; the data were then collected and quantitatively synthesized. The results comprised thirty-eight studies that match the eligibility criteria. The main outcomes reported demonstrating that the RSL is at least equivalent to the WGL in efficiency rates. These results confirm the method applicability for impalpable breast lesions surgery in an effective way, in addition to presenting organizational optimization of radiology and surgery services by allowing the surgery to be performed up to two months after seed implantation

Por Secretion System-Dependent Secretion and Glycosylation of Porphyromonas gingivalis Hemin-Binding Protein 35

The anaerobic Gram-negative bacterium Porphyromonas gingivalis is a major pathogen in severe forms of periodontal disease and refractory periapical perodontitis. We have recently found that P. gingivalis has a novel secretion system named the Por secretion system (PorSS), which is responsible for secretion of major extracellular proteinases, Arg-gingipains (Rgps) and Lys-gingipain. These proteinases contain conserved C-terminal domains (CTDs) in their C-termini. Hemin-binding protein 35 (HBP35), which is one of the outer membrane proteins of P. gingivalis and contributes to its haem utilization, also contains a CTD, suggesting that HBP35 is translocated to the cell surface via the PorSS. In this study, immunoblot analysis of P. gingivalis mutants deficient in the PorSS or in the biosynthesis of anionic polysaccharide-lipopolysaccharide (A-LPS) revealed that HBP35 is translocated to the cell surface via the PorSS and is glycosylated with A-LPS. From deletion analysis with a GFP-CTD[HBP35] green fluorescent protein fusion, the C-terminal 22 amino acid residues of CTD[HBP35] were found to be required for cell surface translocation and glycosylation. The GFP-CTD fusion study also revealed that the CTDs of CPG70, peptidylarginine deiminase, P27 and RgpB play roles in PorSS-dependent translocation and glycosylation. However, CTD-region peptides were not found in samples of glycosylated HBP35 protein by peptide map fingerprinting analysis, and antibodies against CTD-regions peptides did not react with glycosylated HBP35 protein. These results suggest both that the CTD region functions as a recognition signal for the PorSS and that glycosylation of CTD proteins occurs after removal of the CTD region. Rabbits were used for making antisera against bacterial proteins in this study

Involvement of the Wbp pathway in the biosynthesis of Porphyromonas gingivalis lipopolysaccharide with anionic polysaccharide

The periodontal pathogen Porphyromonas gingivalis has two different lipopolysaccharide (LPS) molecules, O-LPS and A-LPS. We have recently shown that P. gingivalis strain HG66 lacks A-LPS. Here, we found that introduction of a wild-type wbpB gene into strain HG66 restored formation of A-LPS. Sequencing of the wbpB gene from strain HG66 revealed the presence of a nonsense mutation in the gene. The wbpB gene product is a member of the Wbp pathway, which plays a role in the synthesis of UDP-ManNAc(3NAc)A in Pseudomonas aeruginosa; UDP-ManNAc(3NAc)A is sequentially synthesized by the WbpA, WbpB, WbpE, WbpD and WbpI proteins. We then determined the effect of the PGN-0002 gene, a wbpD homolog, on the biosynthesis of A-LPS. A PGN-0002-deficient mutant demonstrated an A-LPS biosynthesis deficiency. Taken together with previous studies, the present results suggest that the final product synthesized by the Wbp pathway is one of the sugar substrates necessary for the biosynthesis of A-LPS