Occupational exposure to aerosols in two French airports: multi-year lung function changes.

As differential exposure to airport-generated aerosols may affect employee lung function, the main objective of this study was to longitudinally evaluate spirometry measures among Air France employees. In addition, an exploratory exposure assessment to airport aerosol was performed in a small cohort of workers using personal monitoring devices. Change in lung function over a ~6.

Quantification of Intracellular DNA-Protein Cross-Links with N7-Methyl-2'-Deoxyguanosine and Their Contribution to Cytotoxicity.

The major product of DNA-methylating agents, N7-methyl-2'-deoxyguanosine (MdG), is a persistent lesion , but it is not believed to have a large direct physiological impact. However, MdG reacts with histone proteins to form reversible DNA-protein cross-links (DPC), a family of DNA lesions that can significantly threaten cell survival. In this paper, we developed a tandem mass spectrometry method for quantifying the amounts of MdG and DPC in nuclear DNA by taking advantage of their chemical lability and the concurrent release of N7-methylguanine.

Hybrid CdSe/ZnS Quantum Dot-Gold Nanoparticle Composites Assembled by Click Chemistry: Toward Affordable and Efficient Redox Photocatalysts Working with Visible Light.

A new modular, easy-to-synthesize photocatalyst was prepared by assembling colloidal CdSe/ZnS quantum dots (QD) and gold nanoparticles (AuNP) via their ligands thanks to copper-catalyzed azide to alkyne cycloaddition (CuAAC) click chemistry. The resulting composite (QD-AuNP) photocatalyst was tested with a benchmark photoredox system previously reported by our group, for which QD alone acted as a photocatalyst but with a modest quantum yield (QY = 0.06%) and turnover number (TON = 350 in 3 h) due to poor charge separation.

Perinatal foodborne titanium dioxide exposure-mediated dysbiosis predisposes mice to develop colitis through life.

Background: Perinatal exposure to titanium dioxide (TiO), as a foodborne particle, may influence the intestinal barrier function and the susceptibility to develop inflammatory bowel disease (IBD) later in life. Here, we investigate the impact of perinatal foodborne TiO exposure on the intestinal mucosal function and the susceptibility to develop IBD-associated colitis. Pregnant and lactating mother mice were exposed to TiO until pups weaning and the gut microbiota and intestinal barrier function of their offspring was assessed at day 30 post-birth (weaning) and at adult age (50 days).

The thiolation of uridine 34 in tRNA, which controls protein translation, depends on a [4Fe-4S] cluster in the archaeum Methanococcus maripaludis.

Thiolation of uridine 34 in the anticodon loop of several tRNAs is conserved in the three domains of life and guarantees fidelity of protein translation. U34-tRNA thiolation is catalyzed by a complex of two proteins in the eukaryotic cytosol (named Ctu1/Ctu2 in humans), but by a single NcsA enzyme in archaea. We report here spectroscopic and biochemical experiments showing that NcsA from Methanococcus maripaludis (MmNcsA) is a dimer that binds a [4Fe-4S] cluster, which is required for catalysis.

Structural and functional insights into the activation of the dual incision activity of UvrC, a key player in bacterial NER.

Bacterial nucleotide excision repair (NER), mediated by the UvrA, UvrB and UvrC proteins is a multistep, ATP-dependent process, that is responsible for the removal of a very wide range of chemically and structurally diverse DNA lesions. DNA damage removal is performed by UvrC, an enzyme possessing a dual endonuclease activity, capable of incising the DNA on either side of the damaged site to release a short single-stranded DNA fragment containing the lesion. Using biochemical and biophysical approaches, we have probed the oligomeric state, UvrB- and DNA-binding abilities and incision activities of wild-type and mutant constructs of UvrC from the radiation resistant bacterium, Deinococcus radiodurans.

A noncanonical response to replication stress protects genome stability through ROS production, in an adaptive manner.

Cells are inevitably challenged by low-level/endogenous stresses that do not arrest DNA replication. Here, in human primary cells, we discovered and characterized a noncanonical cellular response that is specific to nonblocking replication stress. Although this response generates reactive oxygen species (ROS), it induces a program that prevents the accumulation of premutagenic 8-oxoguanine in an adaptive way.

Fine Tuning of Quantum Dots Photocatalysts for the Synthesis of Tropane Alkaloid Skeletons.

Several types of Quantum Dots (QDs) (CdS, CdSe and InP, as well as core-shell QDs such as type I InP-ZnS, quasi type-II CdSe-CdS and inverted type-I CdS-CdSe) were considered for generating α-aminoalkyl free radicals. The feasibility of the oxidation of the N-aryl amines and the generation of the desired radical was evidenced experimentally by quenching of the photoluminescence of the QDs and by testing a vinylation reaction using an alkenylsulfone radical trap. The QDs were tested in a radical [3+3]-annulation reaction giving access to tropane skeletons and that requires the completion of two consecutive catalytic cycles.

A subclass of archaeal U8-tRNA sulfurases requires a [4Fe-4S] cluster for catalysis.

Sulfuration of uridine 8, in bacterial and archaeal tRNAs, is catalyzed by enzymes formerly known as ThiI, but renamed here TtuI. Two different classes of TtuI proteins, which possess a PP-loop-containing pyrophosphatase domain that includes a conserved cysteine important for catalysis, have been identified. The first class, as exemplified by the prototypic Escherichia coli enzyme, possesses an additional C-terminal rhodanese domain harboring a second cysteine, which serves to form a catalytic persulfide.

In vitro reconstitution of an efficient nucleotide excision repair system using mesophilic enzymes from Deinococcus radiodurans.

Nucleotide excision repair (NER) is a universal and versatile DNA repair pathway, capable of removing a very wide range of lesions, including UV-induced pyrimidine dimers and bulky adducts. In bacteria, NER involves the sequential action of the UvrA, UvrB and UvrC proteins to release a short 12- or 13-nucleotide DNA fragment containing the damaged site. Although bacterial NER has been the focus of numerous studies over the past 40 years, a number of key questions remain unanswered regarding the mechanisms underlying DNA damage recognition by UvrA, the handoff to UvrB and the site-specific incision by UvrC.

Reactivity of Singlet Oxygen with DNA, an Update.

The reactivity of singlet oxygen with DNA constituents and in particular with the guanine base has been studied during more than four decades but the exact mechanisms by which such a reactive oxygen species reacts with DNA is still a matter of debate. In this review article, a summary of the data that were obtained from several laboratories and using complementary experimental and theoretical approaches are presented. Reaction mechanisms of O with guanine and its oxidation product 8-oxo7,8-dihydroguanine are presented both at the nucleoside level and when the base is inserted into DNA since significant differences have been observed.

Iron-sulfur biology invades tRNA modification: the case of U34 sulfuration.

Sulfuration of uridine 34 in the anticodon of tRNAs is conserved in the three domains of life, guaranteeing fidelity of protein translation. In eubacteria, it is catalyzed by MnmA-type enzymes, which were previously concluded not to depend on an iron-sulfur [Fe-S] cluster. However, we report here spectroscopic and iron/sulfur analysis, as well as in vitro catalytic assays and site-directed mutagenesis studies unambiguously showing that MnmA from Escherichia coli can bind a [4Fe-4S] cluster, which is essential for sulfuration of U34-tRNA.

Dose-dependent genomic DNA hypermethylation and mitochondrial DNA damage in Japanese tree frogs sampled in the Fukushima Daiichi area.

The long-term consequences of the nuclear disaster at the Fukushima Daiichi Nuclear Power Plant (FDNPP) that occurred on March 2011, have been scarcely studied on wildlife. We sampled Japanese tree frogs (Dryophytes japonicus), in a 50 -km area around the FDNPP to test for an increase of DNA damages and variation of DNA methylation level. The ambient dose rate ranged between 0.

Impairment of Base Excision Repair in Dermal Fibroblasts Isolated From Nevoid Basal Cell Carcinoma Patients.

The nevoid basal cell carcinoma syndrome (NBCCS), also called Gorlin syndrome is an autosomal dominant disorder whose incidence is estimated at about 1 per 55,600-256,000 individuals. It is characterized by several developmental abnormalities and an increased predisposition to the development of basal cell carcinomas (BCCs). Cutaneous fibroblasts from Gorlin patients have been shown to exhibit an increased sensitivity to ionizing radiations.

Chromatin recruitment of OGG1 requires cohesin and mediator and is essential for efficient 8-oxoG removal.

One of the most abundant DNA lesions induced by oxidative stress is the highly mutagenic 8-oxoguanine (8-oxoG), which is specifically recognized by 8-oxoguanine DNA glycosylase 1 (OGG1) to initiate its repair. How DNA glycosylases find small non-helix-distorting DNA lesions amongst millions of bases packaged in the chromatin-based architecture of the genome remains an open question. Here, we used a high-throughput siRNA screening to identify factors involved in the recognition of 8-oxoG by OGG1.

A "Population Dynamics" Perspective on the Delayed Life-History Effects of Environmental Contaminations: An Illustration with a Preliminary Study of Cadmium Transgenerational Effects over Three Generations in the Crustacean .

We explore the delayed consequences of parental exposure to environmentally relevant cadmium concentrations on the life-history traits throughout generations of the freshwater crustacean . We report the preliminary results obtained during a challenging one-year laboratory experiment in this environmental species and propose the use of population modeling to interpret the changes in offspring life-history traits regarding their potential demographic impacts. The main outcome of this first long-term transgenerational assay is that the exposure of spawners during a single gametogenesis cycle (3 weeks) could result in severe cascading effects on the life-history traits along three unexposed offspring generations (one year).

Solid-phase synthesis of branched oligonucleotides containing a biologically relevant dCyd341 interstrand crosslink DNA lesion.

Branched oligonucleotides containing a biologically relevant DNA lesion, dCyd341, which involves an interstrand crosslink between a cytosine base on one strand and a ribose moiety on the opposite strand, were prepared in a single automated solid-phase synthesis. For this, we first prepared the phosphoramidite analogue of dCyd341 bearing an orthogonal levulinyl protecting group. Then, following the synthesis of the first DNA strand containing dCyd341, the levulinic group was removed and the synthesis was then continued from the free base hydroxyl group at the branching point, using traditional phosphoramidites.

Probing interaction of a trilysine peptide with DNA underlying formation of guanine-lysine cross-links: insights from molecular dynamics.

DNA-protein cross-links constitute bulky DNA lesions that interfere with the cellular machinery. Amongst these stable covalently tethered adducts, the efficient nucleophilic addition of the free amino group of lysines onto the guanine radical cation has been evidenced. In vitro addition of a trilysine peptide onto a guanine radical cation generated in a TGT oligonucleotide is so efficient that competitive addition of a water molecule, giving rise to 8-oxo-7,8-dihydroguanine, is not observed.

Targeting G-Rich DNA Structures with Photoreactive Bis-Cyclometallated Iridium(III) Complexes.

The synthesis and characterisation of three novel iridium(III) bis-cyclometallated complexes is reported. Their photophysics have been fully characterised by classical methods and revealed charge-transfer (CT) and ligand-centred (LC) transitions. Their ability to selectively interact with G-quadruplex telomeric DNA over duplex DNA has been studied by circular dichroism (CD), bio-layer interferometry (BLI) and surface plasmon resonance (SPR) analyses.

The three Endonuclease III variants of Deinococcus radiodurans possess distinct and complementary DNA repair activities.

Endonuclease III (EndoIII) is a bifunctional DNA glycosylase that removes oxidized pyrimidines from DNA. The genome of Deinococcus radiodurans encodes for an unusually high number of DNA glycosylases, including three EndoIII enzymes (drEndoIII1-3). Here, we compare the properties of these enzymes to those of their well-studied homologues from E.

Natural variability and modulation by environmental stressors of global genomic cytosine methylation levels in a freshwater crustacean, Gammarus fossarum.

To improve the assessment of aquatic organism responses to environmental stressors, there is an interest in studying epigenetic marks in addition to other validated biomarkers. Indeed, the epigenetic marks may be influenced by the surrounding environment. Non-model invertebrates such as gammarids are sentinel organisms representative of the diversity of natural stream communities.

Pancreatic β-cell tRNA hypomethylation and fragmentation link TRMT10A deficiency with diabetes.

Transfer RNAs (tRNAs) are non-coding RNA molecules essential for protein synthesis. Post-transcriptionally they are heavily modified to improve their function, folding and stability. Intronic polymorphisms in CDKAL1, a tRNA methylthiotransferase, are associated with increased type 2 diabetes risk.