Effect of U(VI) aqueous speciation on the binding of uranium by the cell surface of Rhodotorula mucilaginosa, a natural yeast isolate from bentonites

This study presents the effect of aqueous uranium speciation (U-hydroxides and U-hydroxo-carbonates) on the interaction of this radionuclide with the cells of the yeast Rhodotorula mucigilanosa BII-R8. This strain was isolated from Spanish bentonites considered as reference materials for the engineered barrier components of the future deep geological repository of radioactive waste. X-ray absorption and infrared spectroscopy showed that the aqueous uranium speciation has no effect on the uranium binding process by this yeast strain. The cells bind mobile uranium species (U-hydroxides and U-hydroxo-carbonates) from solution via a time-dependent process initiated by the adsorption of uranium species to carboxyl groups. This leads to the subsequent involvement of organic phosphate groups forming uranium complexes with a local coordination similar to that of the uranyl mineral phase meta-autunite. Scanning transmission electron microscopy with high angle annular dark field analysis showed uranium accumulations at the cell surface associated with phosphorus containing ligands. Moreover, the effect of uranium mobile species on the cell viability and metabolic activity was examined by means of flow cytometry techniques, revealing that the cell metabolism is more affected by higher concentrations of uranium than the cell viability. The results obtained in this work provide new insights on the interaction of uranium with bentonite natural yeast from genus Rhodotorula under deep geological repository relevant conditions

Tobramycin-induced secretion of <i>P. aeruginosa</i> 5′ tRNA-fMet halves suppresses lung inflammation via AGO2 gene silencing

AbstractAlthough inhaled tobramycin increases lung function in people with cystic fibrosis (pwCF), the density of P. aeruginosa in the lungs is only modestly reduced by tobramycin; hence, the mechanism whereby tobramycin improves lung function is unclear. Here, we demonstrate that tobramycin increases the abundance of two 5′ tRNA-fMet halves in outer membrane vesicles (OMVs) secreted by P. aeruginosa and that the 5′ tRNA-fMet halves reduce IL-8 secretion by CF bronchial epithelial cells (CF-HBECs). In mouse lung, the 5′ tRNA-fMet halves attenuate KC secretion and neutrophil recruitment. We also report that the 5′ tRNA-fMet halves suppress pro-inflammatory network gene expression by an Argonaut 2 (AGO2)-mediated gene silencing mechanism, thereby reducing IL-8 secretion in CF-HBECs. Moreover, tobramycin reduces the IL-8 concentration and neutrophil content in bronchoalveolar lavage fluid of pwCF. Thus, we conclude that tobramycin improves lung function in part by reducing chronic inflammation and neutrophil-mediated lung damage in pwCF.</jats:p

Variability in Antifungal Use for Pediatric Acute Myeloid Leukemia At Children's Hospitals Across the United States

Abstract Abstract 4278 Background Pediatric acute myeloid leukemia (AML) survival rates have improved primarily because of treatment protocol advancement via cooperative-group clinical trials. Contrary to the consistency in chemotherapy protocols, there is often a lack of consensus for supportive care therapies leading to significant variation in practice. Invasive fungal infections are a major cause of treatment-related morbidity and mortality in pediatric AML. However, the lack of pediatric-specific guidelines for antifungal therapy has the potential to result in either under- or over-utilization of antifungal agents across institutions. We aimed to explore the variability in antifungal use across hospitals caring for children that were treated for de novo AML with a homogeneous induction regimen. Methods The Pediatric Health Information System (PHIS) administrative database was used to establish a cohort of children treated for de novo AML between 1999 and 2010 at one of 43 freestanding children's hospitals across the United States. Only institutions with 15 or more AML patients during the study period were considered in the final analysis. Patients were included if they were assigned an ICD-9 discharge diagnosis code for myeloid or unspecified leukemia and if their daily pharmaceutical billing data supported the receipt of an ADE induction regimen (cytarabine, daunorubicin, and etoposide with or without gemtuzumab ozogamicin). The induction period was defined as the start of the first to the initiation of the third course of chemotherapy. Each institution's inpatient induction period antifungal use, including azoles, echinocandins and amphotericin products, was reported as days of antifungal use per 1000 induction hospital days. A negative binomial regression analysis was performed to adjust rates of antifungal use by demographic variables (age, gender and race) and frequency of severe illness days. Severe illness days were defined by the need for intensive care resources such as intubation, mechanical ventilation or vasopressors. The all-cause induction case fatality rate for each institution was also determined. Results We identified 931 ADE-treated AML patients from 38 children's hospitals with an overall induction case fatality rate of 3.8%. Variation in antifungal use was defined for 28 institutions caring for 815 patients. (Figure 1) Antifungal use exposure days varied widely across institutions ranging from 384 per 1000 hospital days to 958 per 1000 hospital days (median: 836 per 1000 hospital days). Azoles were most commonly used (591 per 1000 hospital days) followed by amphotericin products (120 per 1000 hospital days) and echinocandins (60 per 1000 hospital days). After adjusting for demographic characteristics and the frequency of severe hospital days, variation in antifungal use persisted across institutions, ranging from 393 per 1000 hospital days to 946 per 1000 hospital days. (Figure 2) Induction case fatality rates also varied by institution but did not correlate with antifungal use (Spearman's rho=0.28, p=0.15) (Figure 2). Conclusions Wide variability in inpatient antifungal use for children with AML exists across pediatric institutions in the United States, but this variability does not appear to correlate with induction case fatality rates. Additional studies are necessary to define the ideal approach to optimizing antifungal therapy for children with AML. Disclosures: No relevant conflicts of interest to declare. </jats:sec

Activity patterns at the Arctic Circle: nocturnal eagle owls and interspecific interactions during continuous midsummer daylight

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