227 research outputs found

    IL-1R and inflammasomes mediate early pulmonary protective mechanisms in respiratory brucella abortus infection

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    Brucella spp. infection is frequently acquired through contaminated aerosols. The role of interleukin-1 beta (IL-1β) in the early pulmonary response to respiratory Brucella infection is unknown. As shown here, IL-1β levels in lung homogenates and bronchoalveolar lavage fluid (BALF) of mice intratracheally inoculated with B. abortus were increased at 3 and 7 days p.i. At 7 days p.i., pulmonary CFU numbers were higher in IL-1 receptor (IL-1R) knockout (KO) mice than in wild type (WT) mice. At different times p.i. CFU in lungs and BALF were higher in mice lacking some inflammasome components (caspase-1, AIM2, NLRP3) than in WT mice. At 2 days p.i. pulmonary levels of IL-1b and CXCL1 (neutrophils chemoattractant) were lower in caspase-1/11 KO mice. At day 3 p.i., neutrophils counts in BALF were lower in caspase-1/11 KO mice than in WT mice. During in vitro infections, IL-1β secretion was lower in alveolar macrophages from caspase-1/11, NLRP3 or AIM2 KO mice than in WT controls. Similarly, IL-1β production by B. abortus-infected alveolar epithelial cells was reduced by pretreatment with a specific caspase-1 inhibitor. This study shows that IL-1R, probably through IL-1β action, and the NLRP3 and AIM2 inflammasomes are involved in pulmonary innate immune protective mechanisms against respiratory B. abortus infection.Fil: Hielpos, María Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Fernandez, Andrea Giselle. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Falivene, Juliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Alonso Paiva, Iván Mathias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Muñoz González, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Ferrero, Mariana Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Campos, Priscila C.. Universidade Federal de Minas Gerais; BrasilFil: Vieira, Angelica T.. Universidade Federal de Minas Gerais; BrasilFil: Oliveira, Sergio Costa. Universidade Federal de Minas Gerais; BrasilFil: Baldi, Pablo Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentin

    Desequilíbrios genômicos na cardiopatia congênita sindrômica

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    To identify pathogenic genomic imbalances in patients presenting congenital heart disease (CHD) with extra cardiac anomalies and exclusion of 22q11.2 deletion syndrome (22q11.2 DS). Methods: 78 patients negative for the 22q11.2 deletion, previously screened by fluorescence in situ hybridization (FISH) and/or multiplex ligation probe amplification (MLPA) were tested by chromosomal microarray analysis (CMA). Results: Clinically significant copy number variations (CNVs ≥300. kb) were identified in 10% (8/78) of cases. In addition, potentially relevant CNVs were detected in two cases (993. kb duplication in 15q21.1 and 706. kb duplication in 2p22.3). Genes inside the CNV regions found in this study, such as IRX4, BMPR1A, SORBS2, ID2, ROCK2, E2F6, GATA4, SOX7, SEMAD6D, FBN1, and LTPB1 are known to participate in cardiac development and could be candidate genes for CHD. Conclusion: These data showed that patients presenting CHD with extra cardiac anomalies and exclusion of 22q11.2 DS should be investigated by CMA. The present study emphasizes the possible role of CNVs in CHD. © 2017 Sociedade Brasileira de Pediatria.To identify pathogenic genomic imbalances in patients presenting congenital heart disease (CHD) with extra cardiac anomalies and exclusion of 22q11.2 deletion syndrome (22q11.2 DS). Methods: 78 patients negative for the 22q11.2 deletion, previously screen935497507FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO2008/10596-0, 2008/50421-4, 2009/08756-1, 2011/23794-7149600/2010-0, 471422/2011-8; 471422/2011-8; 2011/23794-7Identificar desequilíbrios genômicos patogênicos em pacientes que apresentam cardiopatias congênitas (CC) e anomalias extracardíacas e exclusão da síndrome de deleção 22q11.2 (SD22q11.2). Foram avaliados por microarray cromossômico (CMA) 78 pacientes neg

    First isolation of human Leptospira strains, Azores, Portugal.

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    OBJECTIVES The aim of this study was the first identification of Leptospira isolates from Azorean inpatients. METHODS Whole blood samples from 68 inpatients attending the São Miguel Hospital between 2006 and 2008, with a clinical and epidemiological suspicion of leptospirosis, were inoculated in a transport medium broth at the patient's bedside and further processed using a serial dilution technique prior to culture. At admission, 62 (91%) patients were also analyzed for the presence of leptospiral DNA by a nested PCR and 40 (59%) for specific agglutinins by microscopic agglutination test (MAT). The isolates obtained were first assigned at the serogroup level by both MAT reactivity with hyperimmune rabbit antisera and a PCR-based assay with the single primer iRep1. The species identification was performed by DNA sequencing. The use of monoclonal antibodies allowed intraspecific discrimination at the serovar level. RESULTS Of the 10 (14.7%) human Leptospira isolates, seven were identified as Leptospira interrogans serovar Copenhageni and three as Leptospira borgpetersenii serovar Arborea, which is in agreement with previous data from the Azorean rodent population. CONCLUSIONS This study represents a great step towards the definitive identification of the pathogenic leptospires in Azorean patients and confirms the bacteriological human-rodent connection for the first time.publishersversionpublishe

    The BINGO project: V. Further steps in component separation and bispectrum analysis

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    Context. Observing the neutral hydrogen distribution across the Universe via redshifted 21 cm line intensity mapping constitutes a powerful probe for cosmology. However, the redshifted 21 cm signal is obscured by the foreground emission from our Galaxy and other extragalactic foregrounds. This paper addresses the capabilities of the BINGO survey to separate such signals. Aims. We show that the BINGO instrumental, optical, and simulations setup is suitable for component separation, and that we have the appropriate tools to understand and control foreground residuals. Specifically, this paper looks in detail at the different residuals left over by foreground components, shows that a noise-corrected spectrum is unbiased, and shows that we understand the remaining systematic residuals by analyzing nonzero contributions to the three-point function. Methods. We use the generalized needlet internal linear combination, which we apply to sky simulations of the BINGO experiment for each redshift bin of the survey. We use binned estimates of the bispectrum of the maps to assess foreground residuals left over after component separation in the final map. Results. We present our recovery of the redshifted 21 cm signal from sky simulations of the BINGO experiment, including foreground components. We test the recovery of the 21 cm signal through the angular power spectrum at different redshifts, as well as the recovery of its non-Gaussian distribution through a bispectrum analysis. We find that non-Gaussianities from the original foreground maps can be removed down to, at least, the noise limit of the BINGO survey with such techniques. Conclusions. Our component separation methodology allows us to subtract the foreground contamination in the BINGO channels down to levels below the cosmological signal and the noise, and to reconstruct the 21 cm power spectrum for different redshift bins without significant loss at multipoles 20≲ l ≲ 500. Our bispectrum analysis yields strong tests of the level of the residual foreground contamination in the recovered 21 cm signal, thereby allowing us to both optimize and validate our component separation analysis

    IL-1R and Inflammasomes Mediate Early Pulmonary Protective Mechanisms in Respiratory Brucella Abortus Infection

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    Brucella spp. infection is frequently acquired through contaminated aerosols. The role of interleukin-1 beta (IL-1β) in the early pulmonary response to respiratory Brucella infection is unknown. As shown here, IL-1β levels in lung homogenates and bronchoalveolar lavage fluid (BALF) of mice intratracheally inoculated with B. abortus were increased at 3 and 7 days p.i. At 7 days p.i., pulmonary CFU numbers were higher in IL-1 receptor (IL-1R) knockout (KO) mice than in wild type (WT) mice. At different times p.i. CFU in lungs and BALF were higher in mice lacking some inflammasome components (caspase-1, AIM2, NLRP3) than in WT mice. At 2 days p.i. pulmonary levels of IL-1β and CXCL1 (neutrophils chemoattractant) were lower in caspase-1/11 KO mice. At day 3 p.i., neutrophils counts in BALF were lower in caspase-1/11 KO mice than in WT mice. During in vitro infections, IL-1β secretion was lower in alveolar macrophages from caspase-1/11, NLRP3 or AIM2 KO mice than in WT controls. Similarly, IL-1β production by B. abortus-infected alveolar epithelial cells was reduced by pretreatment with a specific caspase-1 inhibitor. This study shows that IL-1R, probably through IL-1β action, and the NLRP3 and AIM2 inflammasomes are involved in pulmonary innate immune protective mechanisms against respiratory B. abortus infection

    Regional and large-scale patterns in Amazon forest structure and function are mediated by variations in soil physical and chemical properties

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    Forest structure and dynamics have been noted to vary across the Amazon Basin in an east-west gradient in a pattern which coincides with variations in soil fertility and geology. This has resulted in the hypothesis that soil fertility may play an important role in explaining Basin-wide variations in forest biomass, growth and stem turnover rates. To test this hypothesis and assess the importance of edaphic properties in affect forest structure and dynamics, soil and plant samples were collected in a total of 59 different forest plots across the Amazon Basin. Samples were analysed for exchangeable cations, C, N, pH with various Pfractions also determined. Physical properties were also examined and an index of soil physical quality developed. Overall, forest structure and dynamics were found to be strongly and quantitatively related to edaphic conditions. Tree turnover rates emerged to be mostly influenced by soil physical properties whereas forest growth rates were mainly related to a measure of available soil phosphorus, although also dependent on rainfall amount and distribution. On the other hand, large scale variations in forest biomass could not be explained by any of the edaphic properties measured, nor by variation in climate. A new hypothesis of self-maintaining forest dynamic feedback mechanisms initiated by edaphic conditions is proposed. It is further suggested that this is a major factor determining forest disturbance levels, species composition and forest productivity on a Basin wide scale
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