Although hydrogen peroxide (HO) has been highly used in nuclear chemistry for more than 75 years, the preparation and literature description of tetravalent actinide peroxides remain surprisingly scarce. A new insight is given in this topic through the synthesis and thorough structural characterization of a new peroxo compound of Pu(IV).
View Article and Find Full Text PDFThe UNC-51-like kinase-1 (ULK1) is one of the central upstream regulators of the autophagy pathway, represents a key target for the development of molecular probes to abrogate autophagy and explore potential therapeutic avenues. Here we report the discovery, structure-activity and structure-property relationships of selective, potent, and cell-active ULK1/2 inhibitors based on a 7-azaindole scaffold. Using structure-based drug design, we have developed a series of analogs with excellent binding affinity and biochemical activity against ULK1/2 (ICÂ <Â 25Â nM).
View Article and Find Full Text PDFIn this article, the speciation and behavior of anthropogenic metallic uranium deposited on natural soil are approached by combining EXAFS (extended X-ray absorption fine structure) and TRLFS (time-resolved laser-induced fluorescence spectroscopy). First, uranium (uranyl) speciation was determined along the vertical profile of the soil and bedrock by linear combination fitting of the EXAFS spectra. It shows that uranium migration is strongly limited by the sorption reaction onto soil and rock constituents, mainly mineral carbonates and organic matter.
View Article and Find Full Text PDFThe industrial hemp plant Cannabis sativa is a source of vegetable fiber for both textiles and biocomposite applications. After harvesting, the plant stems are laid out on the ground and colonized by microorganisms (bacteria and fungi) naturally present in the soil and on the stems. By producing hydrolytic enzymes that degrade the plant wall polymers, the natural cement that binds the fiber bundles together is removed, thus facilitating their dissociation (retting process) which is required for producing high-performant fibers.
View Article and Find Full Text PDFSpecific inhibition of a single kinase isoform is a challenging task due to the highly conserved nature of ATP-binding sites. Casein kinase 1 (CK1) δ and ε share 97% sequence identity in their catalytic domains. From a comparison of the X-ray crystal structures of CK1δ and CK1ε, we developed a potent and highly CK1ε-isoform-selective inhibitor (SR-4133).
View Article and Find Full Text PDFLittle is known about localized osteoarticular Scedosporiosis (LOS). Most data come from case reports and small case series. Here we present an ancillary study of the nationwide French Scedosporiosis Observational Study (SOS), describing 15 consecutive cases of LOS diagnosed between January 2005 and March 2017.
View Article and Find Full Text PDFThere are several analytical procedures available for the monitoring of volatile organic compounds (VOCs) in the air, which differ mainly on sampling procedures. The Coriolis micro air sampler is a tool normally designed for biological air sampling. In this paper, the Coriolis micro bio collector is used to evaluate its ability to sample organic contaminants sampling and detecting them when combined GC-MS.
View Article and Find Full Text PDFBackground: Leptomeningeal disease (LMD) occurs as a late complication of several human cancers and has no rationally designed treatment options. A major barrier to developing effective therapies for LMD is the lack of cell-based or preclinical models that recapitulate human disease. Here, we describe the development of in vitro and in vivo cultures of patient-derived cerebrospinal fluid circulating tumor cells (PD-CSF-CTCs) from patients with melanoma as a preclinical model to identify exploitable vulnerabilities in melanoma LMD.
View Article and Find Full Text PDFThe main goal of this preliminary study was to quantify airborne particles and characterize the dominant cultivable bacterial species as well as some Gram-positive species, and their antibiotic resistance pattern, from environmental samples taken inside and outside of a dairy milking parlour. Sampling was performed over 2 days, in different seasons. The small viable particulate matter < 10 μm (bioaerosols) and cultivable bacteria reached their highest concentrations in the milking parlour.
View Article and Find Full Text PDFDabrafenib plus trametinib combination is approved in Europe for V600E-mutant metastatic non-small-cell lung cancer (NSCLC). The objective of this study was to assess efficacy and safety of this combination in a real-world setting. This retrospective multicentric study included 40 patients with advanced NSCLC harboring V600E mutation and receiving dabrafenib plus trametinib.
View Article and Find Full Text PDFAlthough gemcitabine is the cornerstone of care for pancreatic ductal adenocarcinoma (PDA), patients lack durable responses and relapse is inevitable. While the underlying mechanisms leading to gemcitabine resistance are likely to be multifactorial, there is a strong association between activating gemcitabine metabolism pathways and clinical outcome. This study evaluated casein kinase 1 delta (CK1δ) as a potential therapeutic target for PDA and bladder cancer, in which CK1δ is frequently overexpressed.
View Article and Find Full Text PDFEstrogenic compounds are contaminants that may be active at low concentrations and are a major concern for environmental quality. They interact with organisms via Estrogen Receptors (ER). Some detection methods which have been developed use the ability of ER to interact with short consensus DNA sequences known as Estrogen Response Elements (ERE).
View Article and Find Full Text PDFA multiphase study was proposed to examine microbial communities linked to the nitrogen cycle in the first stage of four full-scale French vertical flow treatment systems. To this end, denaturing gradient gel electrophoresis (DGGE) was performed for structural assessment and quantitative PCR (qPCR) to enumerate the abundance of ammonia-oxidizing (AOB). 16S rRNA sequencing was used to assess the taxonomic profile followed by putative assessment of functional genes.
View Article and Find Full Text PDFrisk assessment is nowadays based on the presence and concentration of either . Many species of can cause Legionnaires' disease, indeed about half of the known species have been associated with infection. The aim of this work was to develop a method to assess the composition of the species community in an environmental sample in order to have a better understanding of the contamination of the ecosystem by pathogenic strains.
View Article and Find Full Text PDFEpigenetic regulation enables tumors to respond to changing environments during tumor progression and metastases and facilitates treatment resistance. Targeting chromatin modifiers or catalytic effectors of transcription is an emerging anti-cancer strategy. The cyclin-dependent kinases (CDKs) 12 and 13 phosphorylate the C-terminal domain of RNA polymerase II, regulating transcription and co-transcriptional processes.
View Article and Find Full Text PDFAs people spend more and more time inside, the quality of indoor air becomes crucial matter. This study explores the germicidal potential of two dark-operating germicidal composite materials designed to be applied for the indoor air disinfection under flow conditions. The first material, MnO2/AlPO4/γ-Al2O3 beads, is a donor-acceptor interactive composite capable of creating hydroxyl radicals HO∙.
View Article and Find Full Text PDFgranulovirus, in particular CpGV-M isolate, is used as a biological control against the codling moth (CM), . As a result of intensive control over the years, codling moth populations have developed resistance against this isolate. This resistance is now called type I resistance.
View Article and Find Full Text PDFBackground: Mutation of human receptor tyrosine kinase epidermal growth factor receptor-2 (HER2) is a rare event, found in approximately 1% non-small cell lung cancers (NSCLC). The objective was to investigate the clinical characteristics and management of HER2-mutated NSCLCs in a real-life setting.
Methods: This multicenter study described NSCLCs harboring HER2 mutations diagnosed between January 2012 and December 2014, according their clinical characteristics, management, and outcomes: response rate (RR), progression-free survival (PFS), and overall survival (OS).
Background: Mutations in are rare oncogene mutations, found in 2% of non-small-cell lung cancers (nsclcs). Little information is available about the management of patients with mutated nsclc, except for those included in clinical trials. We undertook the present study to assess the clinical characteristics, management, and outcomes of those patients in a real-life setting.
View Article and Find Full Text PDFInt J Environ Res Public Health
March 2018
New emerging issues appears regarding the possible aerosolization of micro-organisms from biofilters to the ambient air. Traditional bioaerosol sampling and cultural methods used in literature offer relative efficiencies. In this study, a new method revolving around a particle counter capable of detecting total and viable particles in real time was used.
View Article and Find Full Text PDFBioorg Med Chem Lett
February 2018
The development of a new series of apoptosis signal-regulating kinase 1 (ASK1) inhibitors is described. Starting from purine, pyrimidine and quinazoline scaffolds identified by high throughput screening, we used tools of structure-based drug design to develop a series of potent kinase inhibitors, including 2-arylquinazoline derivatives 12 and 23, with submicromolar inhibitory activities against ASK1. Kinetic analysis demonstrated that the 2-arylquinazoline scaffold ASK1 inhibitors described herein are ATP competitive.
View Article and Find Full Text PDFEur J Clin Microbiol Infect Dis
September 2017
During prosthetic joint infection (PJI), optimal surgical management with exchange of the device is sometimes impossible, especially in the elderly population. Thus, prolonged suppressive antibiotic therapy (PSAT) is the only option to prevent acute sepsis, but little is known about this strategy. We aimed to describe the characteristics, outcome and tolerance of PSAT in elderly patients with PJI.
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