Schistosoma mansoni venom allergen-like proteins:Phylogenetic relationships, stage-specific transcription and tissue localization as predictors of immunological cross-reactivity

O artigo encontra-se disponível para download no site do Editor.Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2019-07-15T18:23:01Z No. of bitstreams: 1 Farias, L.P. Schistosoma mansoni venom...2019.pdf: 1118803 bytes, checksum: 1ddd953840abbbd5d56675c8d6c4fa6e (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2019-07-15T18:39:31Z (GMT) No. of bitstreams: 1 Farias, L.P. Schistosoma mansoni venom...2019.pdf: 1118803 bytes, checksum: 1ddd953840abbbd5d56675c8d6c4fa6e (MD5)Made available in DSpace on 2019-07-15T18:39:31Z (GMT). No. of bitstreams: 1 Farias, L.P. Schistosoma mansoni venom...2019.pdf: 1118803 bytes, checksum: 1ddd953840abbbd5d56675c8d6c4fa6e (MD5) Previous issue date: 2019Welcome Trust (UK) (WT084273/Z/07/Z) to KFH, Fundação Butantan, Fundação de Amparo à Pesquisa do Estado de São Paulo (Brazil) to LPF and LLC (2012/23124-4), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) to LCCL and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001, and by fellowships from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Brazil) to LPF (2008/57946-5) and HKF (2007/07685-8) and from CNPq to MIK (160861/2017-9). We thank Dra. Eliana Nakano and Ms. Patricia A. Miyasato for supplying the parasite stages and to Alexsander Seixas de Souza for confocal microscopy (FAPESP 00/11624-5) imaging support, all from Instituto Butantan, Brazil.Instituto Butantan. Centro de Biotecnologia. São Paulo, SP, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.Aberystwyth University. Institute of Biological. Environmental and Rural Sciences. Aberystwyth, UK.Aberystwyth University. Institute of Biological. Environmental and Rural Sciences. Aberystwyth, UK.Instituto Butantan. Centro de Biotecnologia. São Paulo, SP, Brasil.Aberystwyth University. Institute of Biological. Environmental and Rural Sciences. Aberystwyth, UK.Aberystwyth University. Institute of Biological. Environmental and Rural Sciences. Aberystwyth, UK.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.Instituto Butantan. Centro de Biotecnologia. São Paulo, SP, Brasil / Universidade de São Paulo. Pós-Graduação Interunidades em Biotecnologia. São Paulo, SP, Brasil.Leiden University Medical Centre. Center for Proteomics and Metabolomics. RC Leiden, The Netherlands.Leiden University Medical Centre. Department of Parasitology. RC Leiden, The Netherlands.Instituto Butantan. Centro de Biotecnologia. São Paulo, SP, Brasil.Aberystwyth University. Institute of Biological. Environmental and Rural Sciences. Aberystwyth, UK.Schistosoma mansoni venom allergen-like proteins (SmVALs) are part of a diverse protein superfamily partitioned into two groups (group 1 and group 2). Phylogenetic analyses of group 1 SmVALs revealed that members could be segregated into subclades (A-D); these subclades share similar gene expression patterns across the parasite lifecycle and immunological cross-reactivity. Furthermore, whole-mount in situ hybridization demonstrated that the phylogenetically, transcriptionally and immunologically-related SmVAL4, 10, 18 and 19 (subclade C) were all localized to the pre-acetabular glands of immature cercariae. Our results suggest that SmVAL group 1 phylogenetic relationships, stage-specific transcriptional profiles and tissue localization are predictive of immunological cross-reactivity

Magnetically aligned dust and SiO maser polarisation in the envelope of the red supergiant VY Canis Majoris

International audienceWe use Atacama Large Millimeter/submillimeter Array Band 5 science verification observations of the red supergiant VY CMa to study the polarization of SiO thermal/masers lines and dust continuum at ~1.7 mm wavelength. We analyse both linear and circular polarization and derive the magnetic field strength and structure, assuming the polarization of the lines originates from the Zeeman effect, and that of the dust originates from aligned dust grains. We also discuss other effects that could give rise to the observed polarization. We detect, for the first time, significant polarization (~3%) of the circumstellar dust emission at millimeter wavelengths. The polarization is uniform with an electric vector position angle of $\sim8^\circ$. Varying levels of linear polarization are detected for the J=4-3 28SiO v=0, 1, 2, and 29SiO v=0, 1 lines, with the strongest polarization fraction of ~30% found for the 29SiO v=1 maser. The linear polarization vectors rotate with velocity, consistent with earlier observations. We also find significant (up to ~1%) circular polarization in several lines, consistent with previous measurements. We conclude that the detection is robust against calibration and regular instrumental errors, although we cannot yet fully rule out non-standard instrumental effects. Emission from magnetically aligned grains is the most likely origin of the observed continuum polarization. This implies that the dust is embedded in a magnetic field >13 mG. The maser line polarization traces the magnetic field structure. The magnetic field in the gas and dust is consistent with an approximately toroidal field configuration, but only higher angular resolution observations will be able to reveal more detailed field structure. If the circular polarization is due to Zeeman splitting, it indicates a magnetic field strength of ~1-3 Gauss, consistent with previous maser observations

In situ Immune Signatures and Microbial Load at the Nasopharyngeal Interface in Children With Acute Respiratory Infection

Acute respiratory infection (ARI) is the most frequent cause for hospitalization in infants and young children. Using multiplexed nCounter technology to digitally quantify 600 human mRNAs in parallel with 14 virus- and 5 bacterium-specific RNAs, we characterized viral and bacterial presence in nasopharyngeal aspirates (NPA) of 58 children with ARI and determined the corresponding in situ immune profiles. NPA contained different groups of organisms and these were classified into bacterial (n = 27), viral (n = 5), codetection [containing both viral and bacterial transcripts (n = 21), or indeterminate intermediate where microbial load is below threshold (n = 5)]. We then identified differentially expressed immune transcripts (DEITs) comparing NPAs from symptomatic children vs. healthy controls, and comparing children presenting NPAs with detectable microbial load vs. indeterminate. We observed a strong innate immune response in NPAs, due to the presence of evolutionarily conserved type I Interferon (IFN)-stimulated genes (ISG), which was correlated with total bacterial and/or viral load. In comparison with indeterminate NPAs, adaptive immunity transcripts discriminated among viral, bacterial, and codetected microbial profiles. In viral NPAs, B cell transcripts were significantly enriched among DEITs, while only type III IFN was correlated with viral load. In bacterial NPAs, myeloid cells and coinhibitory transcripts were enriched and significantly correlated with bacterial load. In conclusion, digital nCounter transcriptomics provide a microbial and immunological in situ “snapshot” of the nasopharyngeal interface in children with ARI. This enabled discrimination among viral, bacterial, codetection, and indeterminate transcripts in the samples using non-invasive sampling

Essential oil of Thymus vulgaris: preparation of pharmaceutical mouthwash formulation and in vitro evaluation of the bacterial plaque-inhibiting properties

O objetivo deste estudo foi avaliar in vitro o efeito do óleo essencial de Thymus vulgaris (tomilho) puro ou incorporado em uma formulação farmacêutica de uso oral (enxaguatório bucal), frente ao Streptococcus mutans (ATCC 25175), determinando-se sua concentração inibitoria minima (CIM) e o efeito na formação da placa bacteriana. A CIM obtida para o óleo essencial de tomilho foi de 100 μg/mL (1 %). Procedeu-se o desenvolvimento de enxaguatório bucal com efeito antiplaca contendo o óleo essencial comercial de tomilho. As análises da formação da placa bacteriana (ensaios microbiológicos, análise macroscópica de aderência e análises por MEV) confirmaram a eficácia destas novas formulações de enxaguatórios, sem álcool, contendo óleo essencial de T. vulgaris como agentes antiplaca bacteriana com possível emprego na odontologia preventiva. A caracterização química do óleo essencial bioativo foi realizada por CG-MS, verificando-se a presença de carvacrol, p-cimeno e α-pineno como constituintes majoritáriosThe aim of this study was to evaluate the in vitro effect of the essential oil of Thymus vulgaris (thyme) pure or incorporate in a alcohol-free pharmaceutical mouthwash formulation, against Streptococcus mutans (ATCC 25175), being determined the Minimal Inhibitory Concentration (MIC) and the effect in the bacterial plate formation. The MIC value obtained for the essential oil was 100 μg/mL (1 %). The mouthwash pharmaceutical formulation containing commercial essential oil of T. vulgaris was preparated. Microbiological and macroscopic analysis as well as analyses for MEV confirmed the effectiveness of this new alcohol-free mouthwash formulation containing essential oil of T. vulgaris as agent with plaqueinhibiting properties and possible application in the preventive dentistry. The chemical characterization of the bioactive essential oil was accomplished by CG-MS, being verified the presence of carvacrol, p-cimene and α- pinene as major constituents.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Glycogen Synthase Kinase (GSK) 3β phosphorylates and protects nuclear myosin 1c from proteasome-mediated degradation to activate rDNA transcription in early G1 cells

Nuclear myosin 1c (NM1) mediates RNA polymerase I (pol I) transcription activation and cell cycle progression by facilitating PCAF-mediated H3K9 acetylation, but the molecular mechanism by which NM1 is regulated remains unclear. Here, we report that at early G1 the glycogen synthase kinase (GSK) 3β phosphorylates and stabilizes NM1, allowing for NM1 association with the chromatin. Genomic analysis by ChIP-Seq showed that this mechanism occurs on the rDNA as active GSK3β selectively occupies the gene. ChIP assays and transmission electron microscopy in GSK3β-/- mouse embryonic fibroblasts indicated that at G1 rRNA synthesis is suppressed due to decreased H3K9 acetylation leading to a chromatin state incompatible with transcription. We found that GSK3β directly phosphorylates the endogenous NM1 on a single serine residue (Ser-1020) located within the NM1 C-terminus. In G1 this phosphorylation event stabilizes NM1 and prevents NM1 polyubiquitination by the E3 ligase UBR5 and proteasome-mediated degradation. We conclude that GSK3β-mediated phosphorylation of NM1 is required for pol I transcription activation

(Sub)stellar companions shape the winds of evolved stars

Binary interactions dominate the evolution of massive stars, but their role is less clear for low- and intermediate-mass stars. The evolution of a spherical wind from an asymptotic giant branch (AGB) star into a nonspherical planetary nebula (PN) could be due to binary interactions. We observed a sample of AGB stars with the Atacama Large Millimeter/submillimeter Array (ALMA) and found that their winds exhibit distinct nonspherical geometries with morphological similarities to planetary nebulae (PNe). We infer that the same physics shapes both AGB winds and PNe; additionally, the morphology and AGB mass-loss rate are correlated. These characteristics can be explained by binary interaction. We propose an evolutionary scenario for AGB morphologies that is consistent with observed phenomena in AGB stars and PNe

ATOMIUM: ALMA tracing the origins of molecules in dust forming oxygen rich M-type stars: Motivation, sample, calibration, and initial results

This overview paper presents atomium, a Large Programme in Cycle 6 with the Atacama Large Millimeter/submillimeter Array (ALMA). The goal of atomium is to understand the dynamics and the gas phase and dust formation chemistry in the winds of evolved asymptotic giant branch (AGB) and red supergiant (RSG) stars. A more general aim is to identify chemical processes applicable to other astrophysical environments. Seventeen oxygen-rich AGB and RSG stars spanning a range in (circum)stellar parameters and evolutionary phases were observed in a homogeneous observing strategy allowing for an unambiguous comparison. Data were obtained between 213.83 and 269.71 GHz at high (0.025-0.050), medium (0.13-0.24), and low (~1) angular resolution. The sensitivity per ~1.3 km s-1 channel was 1.5-5 mJy beam-1, and the line-free channels were used to image the millimetre wave continuum. Our primary molecules for studying the gas dynamics and dust formation are CO, SiO, AlO, AlOH, TiO, TiO2, and HCN; secondary molecules include SO, SO2, SiS, CS, H2O, and NaCl. The scientific motivation, survey design, sample properties, data reduction, and an overview of the data products are described. In addition, we highlight one scientific result - the wind kinematics of the atomium sources. Our analysis suggests that the atomium sources often have a slow wind acceleration, and a fraction of the gas reaches a velocity which can be up to a factor of two times larger than previously reported terminal velocities assuming isotropic expansion. Moreover, the wind kinematic profiles establish that the radial velocity described by the momentum equation for a spherical wind structure cannot capture the complexity of the velocity field. In fifteen sources, some molecular transitions other than 12CO v = 0 J = 2 - 1 reach a higher outflow velocity, with a spatial emission zone that is often greater than 30 stellar radii, but much less than the extent of CO. We propose that a binary interaction with a (sub)stellar companion may (partly) explain the non-monotonic behaviour of the projected velocity field. The atomium data hence provide a crucial benchmark for the wind dynamics of evolved stars in single and binary star models

The VLT/SPHERE view of the ATOMIUM cool evolved star sample. I. Overview:Sample characterization through polarization analysis

Aims. Through the ATOMIUM project, based on an ALMA large program, we aim to present a consistent view of a sample of 17 nearby cool evolved stars (Aymptotic Giant Branch and red supergiant stars). Methods. Here we present VLT/SPHERE-ZIMPOL polarimetric maps obtained in the visible of 14 out of the 17 ATOMIUM sources. They were obtained contemporaneously with the ALMA high spatial resolution data. To help interpret the polarized signal, we produced synthetic maps of light scattering by dust, through 3D radiative transfer simulations with the RADMC3D code. Results. The degree of linear polarization (DoLP) observed by ZIMPOL spreads across several optical filters. We infer that it primarily probes dust located just outside of the point spread function, and in or near the plane of the sky, with a total optical depth close to unity in the line of sight, representing only a fraction of the total circumstellar dust. The maximum DoLP ranges from 0.03-0.38 depending on the source, fractions that can be reproduced by our 3D pilot models for grains composed of common dust species. The spatial structure of the DoLP shows a diverse set of shapes. Only for three sources do we note a correlation between the ALMA CO and SiO lines, which trace the gas density, and the DoLP, which traces the dust. Conclusion. The clumpiness of the DoLP and the lack of a consistent correlation between the gas and the dust location show that, in the inner circumstellar environment (CSE), dust formation occurs at very specific sites. This has potential consequences for the derived mass-loss rates and dust-to-gas ratio in the inner region of the CSE. Except for $\pi^1$~Gru and perhaps GY Aql, we do not detect interactions between the circumstellar wind and the hypothesized companions that shape the wind at larger scales. This suggests that the orbits of any other companions are tilted out of the plane of the sky.Comment: Accepted for publication in Astronomy & Astrophysics. 22 pages, 15 figures, 5 table

The VLT/SPHERE view of the ATOMIUM cool evolved star sample. I. Overview: Sample characterization through polarization analysis

Aims. Through the ATOMIUM project, based on an ALMA large program, we aim to present a consistent view of a sample of 17 nearby cool evolved stars (Aymptotic Giant Branch and red supergiant stars). Methods. Here we present VLT/SPHERE-ZIMPOL polarimetric maps obtained in the visible of 14 out of the 17 ATOMIUM sources. They were obtained contemporaneously with the ALMA high spatial resolution data. To help interpret the polarized signal, we produced synthetic maps of light scattering by dust, through 3D radiative transfer simulations with the RADMC3D code. Results. The degree of linear polarization (DoLP) observed by ZIMPOL spreads across several optical filters. We infer that it primarily probes dust located just outside of the point spread function, and in or near the plane of the sky, with a total optical depth close to unity in the line of sight, representing only a fraction of the total circumstellar dust. The maximum DoLP ranges from 0.03-0.38 depending on the source, fractions that can be reproduced by our 3D pilot models for grains composed of common dust species. The spatial structure of the DoLP shows a diverse set of shapes. Only for three sources do we note a correlation between the ALMA CO and SiO lines, which trace the gas density, and the DoLP, which traces the dust. Conclusion. The clumpiness of the DoLP and the lack of a consistent correlation between the gas and the dust location show that, in the inner circumstellar environment (CSE), dust formation occurs at very specific sites. This has potential consequences for the derived mass-loss rates and dust-to-gas ratio in the inner region of the CSE. Except for $\pi^1$~Gru and perhaps GY Aql, we do not detect interactions between the circumstellar wind and the hypothesized companions that shape the wind at larger scales. This suggests that the orbits of any other companions are tilted out of the plane of the sky.Comment: Accepted for publication in Astronomy & Astrophysics. 22 pages, 15 figures, 5 table

(Sub)stellar companions shape the winds of evolved stars

Binary interactions dominate the evolution of massive stars, but their role is less clear for low- and intermediate-mass stars. The evolution of a spherical wind from an asymptotic giant branch (AGB) star into a nonspherical planetary nebula (PN) could be due to binary interactions. We observed a sample of AGB stars with the Atacama Large Millimeter/submillimeter Array (ALMA) and found that their winds exhibit distinct nonspherical geometries with morphological similarities to planetary nebulae (PNe). We infer that the same physics shapes both AGB winds and PNe; additionally, the morphology and AGB mass-loss rate are correlated. These characteristics can be explained by binary interaction. We propose an evolutionary scenario for AGB morphologies that is consistent with observed phenomena in AGB stars and PNe