20 research outputs found
The SARAO MeerKAT 1.3 GHz Galactic Plane Survey
We present the SARAO MeerKAT Galactic Plane Survey (SMGPS), a 1.3 GHz continuum survey of almost half of the Galactic Plane (251○ ≤l ≤ 358○ and 2○ ≤l ≤ 61○ at |b| ≤ 1
5). SMGPS is the largest, most sensitive and highest angular resolution 1 GHz survey of the Plane yet carried out, with an angular resolution of 8″ and a broadband RMS sensitivity of ∼10–20 μJy beam−1. Here we describe the first publicly available data release from SMGPS which comprises data cubes of frequency-resolved images over 908–1656 MHz, power law fits to the images, and broadband zeroth moment integrated intensity images. A thorough assessment of the data quality and guidance for future usage of the data products are given. Finally, we discuss the tremendous potential of SMGPS by showcasing highlights of the Galactic and extragalactic science that it permits. These highlights include the discovery of a new population of non-thermal radio filaments; identification of new candidate supernova remnants, pulsar wind nebulae and planetary nebulae; improved radio/mid-IR classification of rare Luminous Blue Variables and discovery of associated extended radio nebulae; new radio stars identified by Bayesian cross-matching techniques; the realisation that many of the largest radio-quiet WISE H II region candidates are not true H II regions; and a large sample of previously undiscovered background H I galaxies in the Zone of Avoidance
Human-impacted areas of France are environmental reservoirs of the Pseudallescheria boydii/Scedosporium apiospermum species complex.
International audience: Species of the Pseudallescheria boydii/Scedosporium apiospermum complex (PSC) are emerging fungal pathogens able to chronically colonize the airways of patients with cystic fibrosis (CF). As P. boydii was found more frequently colonizing the lungs of CF patients in France than in other European countries in a previous report, the present study was conducted in order to clarify distribution of PSC species in France and to characterize their natural habitat. The highest densities of PSC isolates were found in human-impacted areas, i.e. agricultural areas, fluids obtained from wastewater treatment plants, playgrounds and industrial areas. PSC was not detected from soil samples collected in forests. Most PSC culture-positive soil samples exhibited a pH range of 6-8. Scedosporium dehoogii, the most abundant species, was detected in all human-impacted area types except vineyards, whereas Scedosporium aurantiacum was mostly found in agricultural areas. Pseudallescheria boydii and S. apiospermum were predominantly isolated from seashores and playgrounds respectively. Pseudallescheria minutispora was found only once from a playground. This study highlights potential sources of contamination of the patients, especially in the CF context
Rasamsonia species isolated from cystis fibrosis patients: MALDI-TOF/MS identification and antifungal susceptibility by EUCAST method
International audienceA wide variety of filamentous fungi are able to colonize respiratory tract of patients with cystic fibrosis (CF). Recently, fungi of the genus Rasamsonia (formely Geosmithia) have been described as a new emergent group of fungi pathogen in CF patients. The genus Rasamsonia comprises nine species including Rasamsonia argillacea (sensu lato) which is a complex of species (R. argillacea sensu stricto, R. piperina , R. eburnea, and R. aegroticola). Only species belonging to species complex R. argillacea have been yet isolated from patients with chronic granulomatous disease and CF. Accurate identification at the species level of the members of the Rasamsonia complex on the basis of morphology criteria is challenging, and frequent misidentification with a Penicillium emersonii have been reported.Matrix-assisted laser desorption ionization (MALDI)-time of flight (TOF)/mass spectrometry (MS) is a powerful tool to rapidly identify moulds at the species level. We investigated the potential of this technology to discriminate Rasamsonia species. Nine reference strains were used to build a reference database library. Profiles from 3-, 5- and 7-day-old cultures of each reference strain were analysed to identify species-specific discriminating profiles. The database was tested for accuracy using a set of 74 clinical isolates collected from 29 CF-patients in 4 French hospitals (Rouen, Giens, Angers and Paris). For each isolate, the species identification obtained using MALDI-TOF/MS was compared to this obtained by Diversilab method. Our results showed a high reliability of the MALDI-TOF analysis.Antifungal susceptibility testing was also performed for 20 isolates (identified as R. argillacea, R. aegroticola or R. piperina) from 13 patients using the microdilution broth reference method of the Antifungal Susceptibility Testing Subcommittee of EUCAST. All isolates tested showed a high MIC of > 8 mg/L to voriconazole, and the majority also showed high MICs to itraconazole (MIC > 8 mg/L), except for R. piperina strains (MIC 0.5 - 1 mg/L). The susceptibility to amphotericin B was variable (MIC: 0.5 - > 8 mg/L), with no specific distinction according to Rasamsonia species. Finally, all isolates exhibited low MICs to micafungin (0.0312 - 0.125 mg/L).Altogether, our results show that MALDI-TOF/MS is a powerful tool for rapid identification of Rasamsonia species that cannot be currently identified by morphological examination in the clinical setting, and confirm that the members of R. argillacea complex, colonizing respiratory tract in CF patients, have a very low susceptibility to available antifungal agents.</p
Case Report: Profound newborn leukopenia related to a novel RAC2 variant
We report the case of a 1-week-old male born full-term, who had two inconclusive severe combined immunodeficiency (SCID) newborn screens and developed scalp cellulitis and Escherichia coli bacteremia. He did not pass early confirmatory hearing screens. Initial blood counts and lymphocyte flow cytometry revealed profound neutropenia and lymphopenia with a T-/B-/NK- phenotype. Red blood cell adenosine deaminase 1 activity was within normal limits. A presumptive diagnosis of reticular dysgenesis was considered. Granulocyte colony-stimulating factor was started, but there was no improvement in neutrophil counts. Subsequent lymphocyte flow cytometry at around 4 weeks of age demonstrated an increase in T-, B- and NK-cell numbers, eliminating suspicion for SCID and raising concern for congenital neutropenia and bone marrow failure syndromes. Genetic testing revealed a novel variant in RAC2 [c.181C>A (p.Gln61Lys)] (Q61K). RAC2, a Ras-related GTPase, is the dominant RAC protein expressed in hematopoietic cells and is involved with various downstream immune-mediated responses. Pathogenic RAC2 variants show significant phenotypic heterogeneity (spanning from neutrophil defects to combined immunodeficiency) across dominant, constitutively activating, dominant activating, dominant negative, and autosomal recessive subtypes. Given the identification of a novel variant, functional testing was pursued to evaluate aberrant pathways described in other RAC2 pathogenic variants. In comparison to wild-type RAC2, the Q61K variant supported elevated superoxide production under both basal and PMA-stimulated conditions, increased PAK1 binding, and enhanced plasma membrane ruffling, consistent with other dominant, constitutively active mutations. This case highlights the diagnostic challenge associated with genetic variants identified via next-generation sequencing panels and the importance of functional assays to confirm variant pathogenicity
Antibody-Mediated Inhibition of Cathepsin S Blocks Colorectal Tumor Invasion and Angiogenesis
Cognitive function and health literacy are independently associated with heart failure knowledge
Translocation of proteins homologous to human neutrophil p47phox and p67phox to the cell membrane in activated hemocytes of Galleria mellonella
Immunogenetics associated with severe coccidioidomycosis
Disseminated coccidioidomycosis (DCM) is caused by Coccidioides, pathogenic fungi endemic to the southwestern United States and Mexico. Illness occurs in approximately 30% of those infected, less than 1% of whom develop disseminated disease. To address why some individuals allow dissemination, we enrolled patients with DCM and performed whole-exome sequencing. In an exploratory set of 67 patients with DCM, 2 had haploinsufficient STAT3 mutations, and defects in β-glucan sensing and response were seen in 34 of 67 cases. Damaging CLEC7A and PLCG2 variants were associated with impaired production of β-glucan-stimulated TNF-α from PBMCs compared with healthy controls. Using ancestry-matched controls, damaging CLEC7A and PLCG2 variants were overrepresented in DCM, including CLEC7A Y238* and PLCG2 R268W. A validation cohort of 111 patients with DCM confirmed the PLCG2 R268W, CLEC7A I223S, and CLEC7A Y238* variants. Stimulation with a DECTIN-1 agonist induced DUOX1/DUOXA1-derived hydrogen peroxide [H2O2] in transfected cells. Heterozygous DUOX1 or DUOXA1 variants that impaired H2O2 production were overrepresented in discovery and validation cohorts. Patients with DCM have impaired β-glucan sensing or response affecting TNF-α and H2O2 production. Impaired Coccidioides recognition and decreased cellular response are associated with disseminated coccidioidomycosis