TLR2 Is a Negative Regulator of Th17 Cells and Tissue Pathology in a Pulmonary Model of Fungal Infection

To study the role of TLR2 in a experimental model of chronic pulmonary infection, TLR2-deficient and wild-type mice were intratracheally infected with Paracoccidioides brasiliensis, a primary fungal pathogen. Compared with control, TLR2(-/-) mice developed a less severe pulmonary infection and decreased NO synthesis. Equivalent results were detected with in vitro-infected macrophages. Unexpectedly, despite the differences in fungal loads both mouse strains showed equivalent survival times and severe pulmonary inflammatory reactions. Studies on lung-infiltrating leukocytes of TLR2(-/-) mice demonstrated an increased presence of polymorphonuclear neutrophils that control fungal loads but were associated with diminished numbers of activated CD4(+) and CD8(+) T lymphocytes. TLR2 deficiency leads to minor differences in the levels of pulmonary type 1 and type 2 cytokines, but results in increased production of KC, a CXC chemokine involved in neutrophils chemotaxis, as well as TGF-beta, IL-6, IL-23, and IL-17 skewing T cell immunity to a Th17 pattern. In addition, the preferential Th17 immunity of TLR2(-/-) mice was associated with impaired expansion of regulatory CD4(+)CD25(+)FoxP3(+) T cells. This is the first study to show that TLR2 activation controls innate and adaptive immunity to P. brasiliensis infection. TLR2 deficiency results in increased Th17 immunity associated with diminished expansion of regulatory T cells and increased lung pathology due to unrestrained inflammatory reactions. The Journal of Immunology, 2009, 183: 1279-1290.

Influence of macro- and micronutrient fertilization on fungal contamination and fumonisin production in corn grains

The aim of this study was to investigate the effects of nutrients (nitrogen, zinc and boron) on fungal growth and fumonisins production in corn samples obtained at the beginning of grain formation and at harvest. Three nitrogen doses were applied to the corn plants through soil in combination with three zinc doses and two boron doses during sowing. Mycological analysis of grains, using Dichloran Rose-Bengal Chloramphenicol Agar, collected at the beginning of formation demonstrated a fungal population predominantly of yeasts. Analysis of freshly harvested corn revealed a higher frequency of Penicillium spp. (72%) and F verticillioides (27%). High Performance Liquid Chromatography analysis revealed that 100% of grains were contaminated with fumonisins B, at levels ranging from 0.3 to 24.3 mg/kg and 93% contaminated with fumonisin B(2) at levels ranging from 0.05 to 5.42 mg/kg. Nitrogen (50 kg/ha) in combination with boron (0.5 kg/ha) resulted in an increased fumonisin B2 production. (c) 2007 Elsevier Ltd. All rights reserved.

Evaluation of Fungal Burden and Aflatoxin Presence in Packed Medicinal Plants Treated by Gamma Radiation

This study was developed to evaluate the fungal burden, toxigenic molds, and mycotoxin contamination and to verify the effects of gamma radiation in four kinds of medicinal plants stored before and after 30 days of irradiation treatment. Eighty samples of medicinal plants (Peumus boldus, Camellia sinensis, Maytenus ilicifolia. and Cassia angustifolia) purchased from drugstores, wholesale, and open-air markets in Sao Paulo city, Brazil, were analyzed. The samples were treated using a (60)Co gamma ray source (Gammacell) with doses of 5 and 10 kGy. Nonirradiated samples were used as controls of fungal isolates. For enumeration of fungi on medicinal plants, serial dilutions of the samples were plated in duplicate onto dichloran 18% glycerol agar. The control samples revealed a high burden of molds, including toxigenic fungi. The process of gamma radiation was effective in reducing the number of CFU per gram in all irradiated samples of medicinal plants after 30 days of storage, using a dose of 10 kGy and maintaining samples in a protective package. No aflatoxins were detected. Gamma radiation treatment can be used as an effective method for preventing fungal deterioration of medicinal plants subject to long-term storage.

A Survey of Fungal Contamination on Books in Public Libraries with Mechanical and Natural Ventilation

Libraries are very propitious environments for the growth of fungi. The great concentration of organic material available for these microorganisms, and often with the lack of adequate ventilation or climate control, would favour this situation. This study was conducted in 2003 to determine the predominant genera of fungi in public libraries by a survey of fungi contaminating the upper surface of books, with and without air conditioning in the city of Sao Paulo, Brazil, in the winter and summer, during the respective periods with high and low levels of airborne fungi in that city. Six libraries were chosen, located on the campus of the University of Sao Paulo, three of them with air conditioning and the other three with natural ventilation. In these six libraries, 31 genera of fungi were identified in total. The genera and frequency of contaminant fungi recovered differed significantly between the libraries with and without air conditioning and in the samples collected in the summer as opposed to the winter. Cladosporium was the most frequent in the libraries with and without air conditioning, and in the winter. Aspergillus was isolated more often in the summer.

Biochemical characterization of potential virulence markers in the human fungal pathogen Pseudallescheria boydii

The ubiquitous Pseudallescheria boydii (anamorph Scedosporium apiospermum) is a saprophytic filamentous fungus recognized as a potent etiologic agent of a wide variety of infections in immunocompromised as well as in immunocompetent patients. Very little is known about the virulence factors expressed by this fungal pathogen. The present review provides an overview of recent discoveries related to the identification and biochemical characterization of potential virulence attributes produced by P. boydii, with special emphasis on surface and released molecules. These structures include polysaccharides (glucans), glycopeptides (peptidorhamnomannans), glycolipids (glucosylceramides) and hydrolytic enzymes (proteases, phosphatases and superoxide dismutase), which have been implicated in some fundamental cellular processes in P. boydii including growth, differentiation and interaction with host molecules. Elucidation of the structure of cell surface components as well as the secreted molecules, especially those that function as virulence determinants, is of great relevance to understand the pathogenic mechanisms of P. boydii.

The opportunistic fungal pathogen Scedosporium prolificans: Carbohydrate epitopes of its glycoproteins

Isolated from the mycelium, of Scedosporium prolificans were complex glycoproteins (RMP-Sp), with three structurally related components (HPSEC). RMP-Sp contained 35% protein and 62% carbohydrate with Rha, Ara, Man, Gal, Glc, and GlcNH(2) in a 18:1:24:8:6:5 molar ratio. Methylation analysis showed mainly nonreducing end- of Galp (13%), nonreducing end- (9%),2-O-(13%), and 3-O-subst. Rhap (7%), nonreducing end-(11%), 2-O-(10%), 3-O-(14%), and 2,6-di-O-subst. Manp units (13%). Mild reductive P-elimination of RMP-Sp gave alpha-L-Rhap-(1-->2)-alpha-L-Rhap-(1-->3)-alpha-L-Rhap-(1-->3)-alpha-D-Manp-(1-->2)-D-Man-ol, with Man-ol substituted at O-6 with beta-D-Galp units, a related pentasaccharide lacking beta-D-Galp units, and beta-D-Galp-(1-->6)-[alpha-D-Manp-(1-->2)]-D-Man-ol in a 16:3:1 w/w ratio. Traces of Man-ol and Rha-ol were detected. ESI-MS showed HexHex-o1 and HCX(3-6)Hex-ol components. Three rhamnosyl units were peeled off successively from the penta- and hexasaccharide by ESI-MS-MS. The carbohydrate epitopes of RMP-Sp differ from those of the glycoprotein of Pseudallescheria boydii, a related opportunistic pathogen. (C) 2007 Elsevier B.V. All rights reserved.

Metallopeptidase inhibitors arrest vital biological processes in the fungal pathogen Scedosporium apiospermum

P>Scedosporium apiospermum is an emerging agent of opportunistic mycoses in humans. Previously, we showed that mycelia of S. apiospermum secreted metallopeptidases which were directly linked to the destruction of key host proteins. In this study, we analysed the effect of metallopeptidase inhibitors on S. apiospermum development. As germination of inhaled conidia is a crucial event in the infectious process of S. apiospermum, we studied the morphological transformation induced by the incubation of conidia in Sabouraud-dextrose medium at 37 degrees C. After 6 h, some conidia presented a small projection resembling a germ-tube. A significant increase, around sixfold, in the germ-tube length was found after 12 h, and hyphae were exclusively observed after 24 h. Three distinct metallopeptidase inhibitors were able to arrest the transformation of conidia into hyphae in different ways; for instance, 1,10-phenanthroline (PHEN) completely blocked this process at 10 mu mol l-1, while ethylenediamine tetraacetic acid (EDTA) and ethylene glycol-bis (beta-aminoethyl ether; EGTA) only partially inhibited the differentiation at up to 10 mmol l-1. EGTA did not promote any significant reduction in the conidial growth, while PHEN and EDTA, both at 10 mmol l-1, inhibited the proliferation around 100% and 65%, respectively. The secretion of polypeptides into the extracellular environment and the metallopeptidase activity secreted by mycelia were completely inhibited by PHEN. These findings suggest that metallo-type enzymes could be potential targets for future therapeutic interventions against S. apiospermum.

INVASIVE AQUATIC INVASION: THE SPREAD OF VARIABLE LEAF MILFOIL IN MAINE

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Invasive Aquatic Invasion: The Spread of Variable Leaf Milfoil in Maine

Variable leaf milfoil, Myriophyllum heterophyllum, has been present in Maine since 1970. We created an analysis area including seventeen infestation sites and all bodies of water within a forty mile buffer. We also eliminated all water locations with a size less than 7,101 km2, the size of the smallest infestation site, Shagg Pond. Within those specifications we randomly selected seventeen un-infested bodies of water and used them as our uncontaminated sample. We looked for relationships between presence and number of boat launches, and proximity to a populated area. Using the Mann-Whitney test, we compared the sample size of non-infested lakes to the infested lakes. We found there was no significant difference in all three variables on the infestation of variable leaf milfoil.

Risco soberano Brasil : uma explicação do spread e dos outliers

Este trabalho tem como objetivo propor um exame sistemático do chamado prêmio do risco soberano dos títulos emitidos pelo governo brasileiro que permita a categorização dos fatores que possam ser entendidos como geradores do conceito de risco soberano.

A influência da lei de falência no spread bancário

Este trabalho tem como objetivo estudar, dentro da agenda de reformas microeconômicas, quais as influências que uma lei, especialmente a lei de falências, pode gerar na economia. Uma vez que o Brasil havia atravessado diversas reformas macroeconômicas nos anos 90, mas que a-inda não eram visíveis enquanto mudanças na igualdade social do país, estabeleceu-se o que foi chamado de “agenda perdida”. Dentro dessa agenda, de reformas microeconômicas, estava a in-trodução de uma nova lei de falências, que permitisse aos credores terem acesso ao seu capital emprestado no caso de insolvência ou recuperação de uma empresa. Tentamos aqui avaliar se es-sa nova lei foi ou não capaz de causar mudanças no spread bancário brasileiro, dada uma possí-vel redução no risco.

Mercado secundário de títulos públicos: microestrutura, liquidez e spread de compra e venda para o mercado de LTNs no Brasil

Este trabalho está dividido em dois ensaios. O primeiro ensaio examina aspectos da liquidez do mercado secundário de títulos públicos no Brasil no período 2003 a 2006 e os determinantes do spread de compra e venda no mercado secundário de LTN - Letra do Tesouro Nacional no período 2005 a 2006. Os spreads foram calculados com base em dados diários de alta freqüência, para períodos de 30 minutos e de um dia. Em linhas gerais, a liquidez é um determinante importante no cálculo do spread. Especificamente os spreads diminuem quando os volumes ofertados aumentam. No caso dos prazos de vencimento, os spreads aumentam quando os prazos se ampliam. LTNs com prazos de vencimentos até 30 dias apresentaram spreads de 1 centavo de reais (1.89 bp) enquanto que LTNs com prazos acima de dois anos apresentaram spreads médios em torno de 54 centavos de reais (3.84 bp) para intervalos de 30 minutos e 81 centavos de reais (5.72 bp) para intervalos de um dia. Os testes econométricos foram realizados com base em um modelo apresentado por Chakravarty e Sarkar (1999) e aplicado ao mercado americano de bonds no período de 1995 e 1997. Os testes foram feitos utilizando-se a técnica do Método dos Momentos Generalizados (GMM). Os resultados confirmam o spread de compra e venda como medida importante no acompanhamento da liquidez. O segundo ensaio compara aspectos da liquidez e da microestrutura do mercado de títulos públicos em alguns paises como Brasil, Chile, México, Coréia, Singapura, Polônia e Estados Unidos. A análise utiliza algumas dimensões da microestrutura como a liquidez do mercado secundário (spread de compra e venda, giro do estoque de títulos e vencimentos mais negociados), os custos de eficiência, a estrutura e transparência do mercado primário e secundário e, por último, a segurança do mercado. O objetivo é comparar as características e o funcionamento dos mercados secundários desses paises e, confrontar com a realidade do mercado brasileiro face ao desenvolvimento da microestrutura. Apesar da falta de alongamento dos prazos dos títulos públicos, o mercado secundário no Brasil apresenta aspectos da microestrutura semelhantes aos paises em consideração o que sugere a existência de outros fatores fora a microestrutura que limitam o aumento dos prazos. Os resultados do primeiro ensaio ajudam nas comparações dos demais paises. Como resultado, encontramos que embora a liquidez do mercado secundário de títulos públicos no Brasil concentra-se em papéis de prazo menor, este fato provavelmente não se deve a questões de microestrutura do mercado.

Fatores que influenciam o spread das debêntures no Brasil

Este trabalho verificou quais são os fatores que influenciam o spread e o rating das emissões de debêntures no Brasil. A principal contribuição em relação aos trabalhos publicados anteriormente está relacionada com a assimetria de informações. Testamos se esta variável, presente em maior escala nos setores não regulados da economia, explicam o spread e o rating das debêntures. A base de dados utilizada consiste de emissões realizadas entre 2003 e 2008 por empresas dos setores de energia, construção civil, telecomunicações, siderurgia e metalurgia, concessões rodoviárias e petróleo e gás. As debêntures são indexadas à Taxa DI, ao IGP-M ou ao IPCA. Os resultados encontrados indicam que a assimetria de informações é importante na determinação do rating das emissões. O rating também é mais alto para empresas maiores e/ou que atuam em setores regulados da economia e para emissões com maior duration. Encontramos relação positiva em média entre risco-país e spread. Os parâmetros estimados indicam também que, em média, quanto maior o rating menor é o spread pago, havendo evidências de não linearidade nesta relação.

A precificação do spread de liquidez no mercado secundário de debêntures

O objetivo desse trabalho é analisar e precificar o prêmio de liquidez exigido pelos investidores nas negociações de debêntures do mercado secundário brasileiro, com base no yield to maturity diário desses papéis. Os testes econométricos foram realizados com base no modelo apresentado por Houweling, Mentink e Vorst (2005) e aplicado ao mercado de eurobonds nos períodos de 1999 a 2001. Foi implementado um modelo de 5 variáveis para controlar, através de betas e características, os outros tipos de risco determinantes do spread das debêntures que não a liquidez. O conhecido modelo de títulos de renda fixa de dois fatores Fama-French (1993) foi utilizado para controlar os riscos de crédito e de taxas de juros, foram incorporados efeitos marginais, através das características individuais (rating e duration) das debêntures e uma adaptação para as particularidades do mercado brasileiro foi realizada, com a inclusão de um fator baseado na taxa PréxDI da duration dos portfólios. Para esse estudo, foram consideradas 4 proxies de liquidez largamente utilizadas na literatura: Volume de Emissão, Idade da Emissão, Número de Transações no dia e Spread de Compra e Venda, sendo o modelo estimado uma vez para cada proxy analisada. Para realizar os testes de regressão e precificar o prêmio de liquidez no mercado secundário de debêntures do Brasil, todas as variáveis do modelo foram calculadas para cada uma das amostras de dados. Posteriormente, para cada proxy de liquidez foram construídos diariamente portfólios mutuamente excludentes, com as debêntures segregadas em portfólios de acordo com a proxy de liquidez em questão, conforme a metodologia proposta por Brennan e Subrahmanyam (1996). A base de dados, que somou 16.083 amostras, se fundamentou nas cotações de mercado fornecidas diariamente pelo Sistema Nacional de Debêntures no período de Maio de 2004 a Novembro de 2006. A hipótese nula de que não existe prêmio de liquidez embutido nos spreads das debêntures negociadas no mercado secundário brasileiro é rejeitada para todas as proxies analisadas. De acordo com a proxy de liquidez utilizada, o prêmio de liquidez no mercado secundário de debêntures varia de 8 a 30 basis points.