Enhanced direct oxidation of diclofenac (DCF) at a carbon paste electrode (CPE) modified with cellulose and its biodegradability by Scedosporium dehoogii

A novel carbon paste electrode modified with cellulose fibers and dedicated to diclofenac electroanalysis was prepared, optimized, and used for the determination of the kinetic parameters of DCF biodegradation by a filamentous fungus. The electrochemical response of the modified CPE was compared to that of the unmodified. This study conducted by cyclic voltammetry and linear sweep voltammetry allowed the optimization of the cellulose fibers modified CPE in terms of absence/presence of cellulose fibers, accumulation time (250 s), and initial potential (- 0.4 V/Ag/AgCl). Interestingly, in these conditions, the limit of detection observed through linear sweet voltammetry was found to be as low as 0.020 µmol L-1. This electrode was then used to follow the degradation of DCF. Our results demonstrated that among species belonging to the Scedosporium genus, S. dehoogii displayed the best assets in our process in terms of growth temperature and ability to metabolize DCF. More precisely, DCF biodegradation using S. dehoogii in the process revealed a kinetic of order of 1, a kinetic constant k of 0.012 day-1 and a half time of 57.8 days for an initial concentration of DCF of 1.65 ± 0.05 mg L-1 and at a temperature of 25°C. This study constitutes a solid proof of concept for future developments of fungal wastewater treatments for bioremediation of DCF which is refractory to standard bacterial-based bioprocesses

Promising pre-clinical validation of targeted radionuclide therapy using a [131I] labelled iodoquinoxaline derivative for an effective melanoma treatment

Targeted internal radionuclide therapy (TRT) would be an effective alternative to current therapies for dissemi- nated melanoma treatment. At our institution, a class of iodobenzamides has been developed as potent melanoma- seeking agents. This review described the preclinical vali- dations of a quinoxaline derivative molecule (ICF01012) as tracer for TRT application. It was selected for its high, specific and long-lasting uptake in tumour with rapid clear- ance from non-target organs providing suitable dosimetry parameters for TRT. Extended in vivo study of metabolic profiles confirmed durable tumoural concentration of the unchanged molecule form. Moreover melanin specificity of ICF01012 was determined by binding assay with syn- thetic melanin and in vivo by SIMS imaging. Then, we showed in vivo that [131I] ICF01012 treatment drastically inhibited growth of B16F0, B16Bl6 and M4Beu tumours whereas [131I] NaI or unlabelled ICF01012 treatment was without significant effect. Histological analysis showed that residual tumour cells exhibit a significant loss of aggres- siveness after treatment. This anti-tumoural effect was associated with a lengthening of the treated-mice survival time and an inhibition of lung dissemination for B16Bl6 model. Results presented here support the concept of TRT using a [131I] labelled iodoquinoxaline derivative for an effective melanoma treatment.<br /

Spin-photon interface and spin-controlled photon switching in a nanobeam waveguide

Access to the electron spin is at the heart of many protocols for integrated and distributed quantum-information processing [1-4]. For instance, interfacing the spin-state of an electron and a photon can be utilized to perform quantum gates between photons [2,5] or to entangle remote spin states [6-9]. Ultimately, a quantum network of entangled spins constitutes a new paradigm in quantum optics [1]. Towards this goal, an integrated spin-photon interface would be a major leap forward. Here we demonstrate an efficient and optically programmable interface between the spin of an electron in a quantum dot and photons in a nanophotonic waveguide. The spin can be deterministically prepared with a fidelity of 96\%. Subsequently the system is used to implement a "single-spin photonic switch", where the spin state of the electron directs the flow of photons through the waveguide. The spin-photon interface may enable on-chip photon-photon gates [2], single-photon transistors [10], and efficient photonic cluster state generation [11]

The injury epidemiology of cyclists based on a road trauma registry

<p>Abstract</p> <p>Background</p> <p>Bicycle use has increased in some of France's major cities, mainly as a means of transport. Bicycle crashes need to be studied, preferably by type of cycling. Here we conduct a descriptive analysis.</p> <p>Method</p> <p>A road trauma registry has been in use in France since 1996, in a large county around Lyon (the Rhône, population 1.6 million). It covers outpatients, inpatients and fatalities. All injuries are coded using the Abbreviated Injury Scale (AIS). Proxies were used to identify three types of cycling: learning = children (0-10 years old); sports cycling = teenagers and adults injured outside towns; cycling as means of transport = teenagers and adults injured in towns. The study is based on 13,684 cyclist casualties (1996-2008).</p> <p>Results</p> <p>The percentage of cyclists injured in a collision with a motor vehicle was 8% among children, 17% among teenagers and adults injured outside towns, and 31% among those injured in towns. The percentage of serious casualties (MAIS 3+) was 4.5% among children, 10.9% among adults injured outside towns and 7.2% among those injured in towns. Collisions with motor-vehicles lead to more internal injuries than bicycle-only crashes.</p> <p>Conclusion</p> <p>The description indicates that cyclist type is associated with different crash and injury patterns. In particular, cyclists injured in towns (where cycling is increasing) are generally less severely injured than those injured outside towns for both types of crash (bicycle-only crashes and collisions with a motor vehicle). This is probably due to lower speeds in towns, for both cyclists and motor vehicles.</p

Draft Genome Sequence of the Pathogenic Fungus Scedosporium apiospermum

This is the final version of the article. Available from the publisher via the DOI in this record.The first genome of one species of the Scedosporium apiospermum complex, responsible for localized to severe disseminated infections according to the immune status of the host, will contribute to a better understanding of the pathogenicity of these fungi and also to the discovery of the mechanisms underlying their low susceptibility to current antifungals.This work was supported by a grant (RF20120600725) from the association Vaincre la Mucoviscidose (France), which is gratefully acknowledged

Ultrastructural pathology of primary ciliary dyskinesia: report about 125 cases in Germany

<p>Abstract</p> <p>Background</p> <p>Primary ciliary dyskinesia (PCD) is a rare genetically induced disorder of cilia inducing mainly respiratory diseases. Transmission electron microscopy (TEM) analysis of ciliary ultrastructure is classically used for diagnosis. We report our experience of TEM investigations in a large series of patients.</p> <p>Methods</p> <p>TEM analysis performed of 742 biopsies from patients with suspected PCD was reviewed retrospectively. Ultrastructural defects were analysized further in 125 cases with changes typical for PCD.</p> <p>Results</p> <p>In 18.1% of patients diagnosis of PCD was made because of morphological alterations, in 68.2% secondary changes were seen. In 13.7% material was not feasible for analysis. Mostly defects of dynein arms were detected in PCD (96.8%). In particular defects of the inner arms (51.2%) and combined dynein defects (37.6%) were found. Total loss of dynein arms was dominant. Only in 3.2% deficiencies of central structures were found alone. Associated situs inversus or dextracardia was reported clinically in 21.4%.</p> <p>Conclusions</p> <p>TEM analysis is possible in most patients and a useful tool for diagnosis of PCD. Functional and genetic analysis should be done additionally. Registers should be installed to collect all available informations and push further research.</p

Propofol Directly Increases Tau Phosphorylation

In Alzheimer's disease (AD) and other tauopathies, the microtubule-associated protein tau can undergo aberrant hyperphosphorylation potentially leading to the development of neurofibrillary pathology. Anesthetics have been previously shown to induce tau hyperphosphorylation through a mechanism involving hypothermia-induced inhibition of protein phosphatase 2A (PP2A) activity. However, the effects of propofol, a common clinically used intravenous anesthetic, on tau phosphorylation under normothermic conditions are unknown. We investigated the effects of a general anesthetic dose of propofol on levels of phosphorylated tau in the mouse hippocampus and cortex under normothermic conditions. Thirty min following the administration of propofol 250 mg/kg i.p., significant increases in tau phosphorylation were observed at the AT8, CP13, and PHF-1 phosphoepitopes in the hippocampus, as well as at AT8, PHF-1, MC6, pS262, and pS422 epitopes in the cortex. However, we did not detect somatodendritic relocalization of tau. In both brain regions, tau hyperphosphorylation persisted at the AT8 epitope 2 h following propofol, although the sedative effects of the drug were no longer evident at this time point. By 6 h following propofol, levels of phosphorylated tau at AT8 returned to control levels. An initial decrease in the activity and expression of PP2A were observed, suggesting that PP2A inhibition is at least partly responsible for the hyperphosphorylation of tau at multiple sites following 30 min of propofol exposure. We also examined tau phosphorylation in SH-SY5Y cells transfected to overexpress human tau. A 1 h exposure to a clinically relevant concentration of propofol in vitro was also associated with tau hyperphosphorylation. These findings suggest that propofol increases tau phosphorylation both in vivo and in vitro under normothermic conditions, and further studies are warranted to determine the impact of this anesthetic on the acceleration of neurofibrillary pathology

Topological data analysis reveals genotype-phenotype relationships in primary ciliary dyskinesia

Background: Primary ciliary dyskinesia (PCD) is a heterogeneous inherited disorder caused by mutations in approximately 50 cilia-related genes. PCD genotype-phenotype relationships have mostly arisen from small case series because existing statistical approaches to investigate relationships have been unsuitable for rare diseases. / Methods: We applied a topological data analysis (TDA) approach to investigate genotype-phenotype relationships in PCD. Data from separate training and validation cohorts included 396 genetically defined individuals carrying pathogenic variants in PCD genes. To develop the TDA models, twelve clinical and diagnostic variables were included. TDA-driven hypotheses were subsequently tested using traditional statistics. / Results: Disease severity at diagnosis measured by FEV1 z-score was (i) significantly worse in individuals with CCDC39 mutations compared to other gene mutations and (ii) better in those with DNAH11 mutations; the latter also reported less neonatal respiratory distress. Patients without neonatal respiratory distress had better preserved FEV1 at diagnosis. Individuals with DNAH5 mutations were phenotypically diverse. Cilia ultrastructure and beat pattern defects correlated closely to specific causative gene groups, confirming these tests can be used to support a genetic diagnosis. / Conclusions: This large scale multi-national study presents PCD as a syndrome with overlapping symptoms and variation in phenotype, according to genotype. TDA modelling confirmed genotype-phenotype relationships reported by smaller studies (e.g. FEV1 worse with CCDC39 mutations), and identified new relationships, including FEV1 preservation with DNAH11 mutations and diversity of severity with DNAH5 mutations

Novel insights into host-fungal pathogen interactions derived from live-cell imaging

Acknowledgments The authors acknowledge funding from the Wellcome Trust (080088, 086827, 075470 and 099215) including a Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377 and FP7-2007–2013 grant agreement HEALTH-F2-2010-260338–ALLFUN to NARG.Peer reviewedPublisher PD

Antifungal Activity of Resveratrol Derivatives against Candida Species

trans-Resveratrol (1a) is a phytoalexin produced by plants in response to infections by pathogens. Its potential activity against clinically relevant opportunistic fungal pathogens has previously been poorly investigated. Evaluated herein are the candidacidal activities of oligomers (2a, 3–5) of 1a purified from Vitis vinifera grape canes and several analogues (1b–1j) of 1a obtained through semisynthesis using methylation and acetylation. Moreover, trans-ε-viniferin (2a), a dimer of 1a, was also subjected to methylation (2b) and acetylation (2c) under nonselective conditions. Neither the natural oligomers of 1a (2a, 3–5) nor the derivatives of 2a were active against Candida albicans SC5314. However, the dimethoxy resveratrol derivatives 1d and 1e exhibited antifungal activity against C. albicans with minimum inhibitory concentration (MIC) values of 29–37 μg/mL and against 11 other Candida species. Compound 1e inhibited the yeast-to-hyphae morphogenetic transition of C. albicans at 14 μg/mL