Cell wall changes during maturation of conidia in Pseudallescheria boydii

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Cell wall modifications during conidial maturation of the human pathogenic fungus Pseudallescheria boydii

This is the final version of the article. Available from the publisher via the DOI in this record.Progress in extending the life expectancy of cystic fibrosis (CF) patients remains jeopardized by the increasing incidence of fungal respiratory infections. Pseudallescheria boydii (P. boydii), an emerging pathogen of humans, is a filamentous fungus frequently isolated from the respiratory secretions of CF patients. It is commonly believed that infection by this fungus occurs through inhalation of airborne conidia, but the mechanisms allowing the adherence of Pseudallescheria to the host epithelial cells and its escape from the host immune defenses remain largely unknown. Given that the cell wall orchestrates all these processes, we were interested in studying its dynamic changes in conidia as function of the age of cultures. We found that the surface hydrophobicity and electronegative charge of conidia increased with the age of culture. Melanin that can influence the cell surface properties, was extracted from conidia and estimated using UV-visible spectrophotometry. Cells were also directly examined and compared using electron paramagnetic resonance (EPR) that determines the production of free radicals. Consistent with the increased amount of melanin, the EPR signal intensity decreased suggesting polymerization of melanin. These results were confirmed by flow cytometry after studying the effect of melanin polymerization on the surface accessibility of mannose-containing glycoconjugates to fluorescent concanavalin A. In the absence of melanin, conidia showed a marked increase in fluorescence intensity as the age of culture increased. Using atomic force microscopy, we were unable to find rodlet-forming hydrophobins, molecules that can also affect conidial surface properties. In conclusion, the changes in surface properties and biochemical composition of the conidial wall with the age of culture highlight the process of conidial maturation. Mannose-containing glycoconjugates that are involved in immune recognition, are progressively masked by polymerization of melanin, an antioxidant that is commonly thought to allow fungal escape from the host immune defenses.The study was funded by “Région Pays de la Loire” in the frame of “Myco-AFM” research program). BED was supported by the Dutch Virgo Consortium (FES0908, NGI 050-060-452) and CAPES/BRASIL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Maternal and neonatal characteristics and early neonatal mortality in Greater Metropolitan São Paulo, Brazil

O objetivo foi descrever as características do recém-nascido, da mãe e da mortalidade neonatal precoce, segundo local de parto, na Região Metropolitana de São Paulo, Brasil. Utilizou-se coorte de nascidos vivos vinculados aos respectivos óbitos neonatais precoces, por técnica determinística. Identificou-se o parto domiciliar a partir da Declaração de Nascido Vivo e os ocorridos em estabelecimentos a partir da vinculação com o Cadastro Nacional de Estabelecimentos de Saúde. Foram estudados 154.676 nascidos vivos, dos quais 0,3% dos nascimentos ocorreram acidentalmente em domicílio, 98,7% em hospitais e menos de 1% em outro serviço de saúde. A mortalidade foi menor no Centro de Parto Normal e nas Unidades Mistas de Saúde, condizente com o perfil de baixo risco obstétrico. As taxas mais elevadas ocorreram nos prontos-socorros (54,4 óbitos por mil nascidos vivos) e domicílios (26,7), representando um risco de morte, respectivamente, 9,6 e 4,7 vezes maior que nos hospitais (5,6). Apesar da alta predominância do parto hospitalar, há um segmento de partos acidentais tanto em domicílios como em prontos-socorros que merece atenção, por registrar elevadas taxas de mortalidade neonatal precoce.The objective was to describe maternal and neonatal characteristics and early neonatal mortality rate according to place of delivery in Greater Metropolitan São Paulo, Brazil. The study linked the databases on live births and early neonatal deaths with the national hospital registry. Place of delivery was identified through certificates of live birth. There were a total of 154,676 live births: 98.7% in-hospital; 0.3% home deliveries, and 1% in other health services. Deliveries in birthing centers and small hospital units were associated with low obstetric risk and a low proportion of preterm and low birth weight infants, and as a result these services showed the lowest early neonatal mortality rate. Compared to hospital maternity ward deliveries, the early neonatal mortality rate was 4.7 times higher for home deliveries and 9.6 higher for emergency room deliveries. There is a high rate of hospital delivery care in São Paulo, but there is still a small portion of accidental home births and deliveries occurring in inappropriate health services, probably as a result of obstetric emergencies and difficulties in accessing hospital services.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Genome-wide association studies of Shigella spp. and Enteroinvasive Escherichia coli isolates demonstrate an absence of genetic markers for prediction of disease severity

BACKGROUND: We investigated the association of symptoms and disease severity of shigellosis patients with genetic determinants of infecting Shigella and entero-invasive Escherichia coli (EIEC), because determinants that predict disease outcome per individual patient could be used to prioritize control measures. For this purpose, genome wide association studies (GWAS) were performed using presence or absence of single genes, combinations of genes, and k-mers. All genetic variants were derived from draft genome sequences of isolates from a multicenter cross-sectional study conducted in the Netherlands during 2016 and 2017. Clinical data of patients consisting of binary/dichotomous representation of symptoms and their calculated severity scores were also available from this study. To verify the suitability of the methods used, the genetic differences between the genera Shigella and Escherichia were used as control. RESULTS: The isolates obtained were representative of the population structure encountered in other Western European countries. No association was found between single genes or combinations of genes and separate symptoms or disease severity scores. Our benchmark characteristic, genus, resulted in eight associated genes and > 3,000,000 k-mers, indicating adequate performance of the algorithms used. CONCLUSIONS: To conclude, using several microbial GWAS methods, genetic variants in Shigella spp. and EIEC that can predict specific symptoms or a more severe course of disease were not identified, suggesting that disease severity of shigellosis is dependent on other factors than the genetic variation of the infecting bacteria. Specific genes or gene fragments of isolates from patients are unsuitable to predict outcomes and cannot be used for development, prioritization and optimization of guidelines for control measures of shigellosis or infections with EIEC

Условия формирования и проблемы функционирования крупных диверсифицированных производственно-корпоративных структур в Украине

У статті розглянуто умови формування та функціонування, а також історія розвитку великих диверсифікованих виробничо-корпоративних структур в Україні. Пропонуються підходи оцінки результативності процесу диверсифікації з використанням різних методик. Визначено, що в даний час оцінка результативності процесу диверсифікації можлива лише непрямими математичними методами.В статье рассмотрены условия формирования и функционирования, а также история развития крупных диверсифицированных производственно-корпоративных структур в Украине. Предлагаются подходы оценки результативности процесса диверсификации с использованием разных методик. Определено, что в настоящее время оценка результативности процесса диверсификации возможна лишь косвенными математическими методами.In the article address the formation and functioning of the conditions, as well as story development of large industrial and corporate structures, becoming diversification in Ukraine. Proposes approaches assessing impact of the process of diversification, using of different methods. Proved that the current performance assessment process of diversification can only be indirect mathematical methods