Comparative study of diesel and biodiesel exhausts on lung oxidative stress and genotoxicity in rats.

The contribution of diesel exhaust to atmospheric pollution is a major concern for public health, especially in terms of occurrence of lung cancers. The present study aimed at addressing the toxic effects of a repeated exposure to these emissions in an animal study performed under strictly controlled conditions. Rats were repeatedly exposed to the exhaust of diesel engine.

Medicinal chemistry of antischistosomal drugs: Praziquantel and oxamniquine.

Neglected tropical diseases (NTDs) are a group of diseases that, besides prevailing in poverty conditions, contribute to the maintenance of social inequality, being a strong barrier to a country development. Schistosomiasis, a NTD, is a tropical and subtropical disease caused by the trematode Schistosoma mansoni (Africa, Middle East, Caribbean, Brazil, Venezuela, Suriname), japonicum (China, Indonesia, the Philippines), mekongi (several districts of Cambodia and the Lao People's Democratic Republic), intercalatum and guianensis (areas of tropical rainforests in Central Africa) and hematobium (Middle East Africa, Corsica, France) whose adult forms inhabit the mesenteric vessels of the host, while the intermediate forms are found in the aquatic gastropod snails of the genus Biomphalaria. Currently, praziquantel (PZQ) is the first line drug chosen for the treatment of schistosomiasis according to the World Health Organization (WHO) Model List of Essential Medicines, 2015.

An evolutionary perspective on leaf economics: phylogenetics of leaf mass per area in vascular plants.

In plant leaves, resource use follows a trade-off between rapid resource capture and conservative storage. This "worldwide leaf economics spectrum" consists of a suite of intercorrelated leaf traits, among which leaf mass per area, LMA, is one of the most fundamental as it indicates the cost of leaf construction and light-interception borne by plants. We conducted a broad-scale analysis of the evolutionary history of LMA across a large dataset of 5401 vascular plant species.

'Clickable' 2,5-diketopiperazines as scaffolds for ligation of biomolecules: their use in Aβ inhibitor assembly.

The synthesis of 1,3,6-trisubstituted-2,5-diketopiperazine scaffolds bearing up to three 'clickable' sites for further oxime bond or alkyne-azide cycloaddition ligations is described. The orthogonally Boc/Alloc protected DKP precursors prepared from L-lysine residues and an aminohexyl arm are efficiently prepared on a gram scale by sequentially using Fukuyama-Mitsunobu alkylation, dipeptide coupling and diketopiperazine ring formation as key steps. These scaffolds, with their glyoxylyl, aminooxy, alkynyl or azido functions, are "ready-to-use" platforms for biomolecular assembly.

[Cellular and molecular effects of the antidepressant hyperforin on brain cells: Review of the literature].

Introduction: Hypericum perforatum is, with Ginkgo biloba, one of the most frequently prescribed medicinal plants in the world. Its popular name, St. John's wort (SJW), is due to the fact that its flowers, yellow, are gathered around the feast of St.

Intracellular shunting of O2(-) contributes to charge compensation and preservation of neutrophil respiratory burst in the absence of voltage-gated proton channel activity.

Proton efflux via voltage-gated proton channels (Hv1) is considered to mediate the charge compensation necessary to preserve NADPH oxidase activity during the respiratory burst. Using the Hv1 inhibitor Zn(2+), we found that the PMA-induced respiratory burst of human neutrophils is inhibited when assessed as extracellular production of O2(-) and H2O2, in accordance with literature studies, but, surprisingly, unaffected when measured as oxygen consumption or total (extracellular plus intracellular) H2O2 production. Furthermore, we show that inhibiting Hv1 with Zn(2+) results in an increased production of intracellular ROS.

4-Demethylwyosine synthase from Pyrococcus abyssi is a radical-S-adenosyl-L-methionine enzyme with an additional [4Fe-4S](+2) cluster that interacts with the pyruvate co-substrate.

Wybutosine and its derivatives are found in position 37 of tRNA encoding Phe in eukaryotes and archaea. They are believed to play a key role in the decoding function of the ribosome. The second step in the biosynthesis of wybutosine is catalyzed by TYW1 protein, which is a member of the well established class of metalloenzymes called "Radical-SAM.

Icatibant , the bradykinin B2 receptor antagonist with target to the interconnected kinin systems.

Introduction: HOE-140/ Icatibant is a selective, competitive antagonist to bradykinin (BK) against its binding to the kinin B2 receptor. Substitution of five non-proteogeneic amino acid analogues makes icatibant resistant to degradation by metalloproteases of kinin catabolism. Icatibant has clinical applications in inflammatory and vascular leakage conditions caused by an acute (non-controlled) production of kinins and their accumulation at the endothelium B2 receptor.

Inhibition of p-aminobenzoate and folate syntheses in plants and apicomplexan parasites by natural product rubreserine.

Glutamine amidotransferase/aminodeoxychorismate synthase (GAT-ADCS) is a bifunctional enzyme involved in the synthesis of p-aminobenzoate, a central component part of folate cofactors. GAT-ADCS is found in eukaryotic organisms autonomous for folate biosynthesis, such as plants or parasites of the phylum Apicomplexa. Based on an automated screening to search for new inhibitors of folate biosynthesis, we found that rubreserine was able to inhibit the glutamine amidotransferase activity of the plant GAT-ADCS with an apparent IC(50) of about 8 μM.

Asymmetric synthesis of cyclobutanones: synthesis of cyclobut-G.

A simple, efficient, and stereoselective approach has been developed for obtaining chiral cis- and trans-disubstituted cyclobutanones from readily available alkyl- and functionalized alkyl-substituted enol ethers. The usefulness of these cyclobutanones is illustrated by an enantioselective synthesis of cyclobut-G (Lobucavir).

Yeast ADP/ATP carrier isoform 2: conformational dynamics and role of the RRRMMM signature sequence methionines.

The mitochondrial ADP/ATP carrier, or Ancp, is a member of the mitochondrial carrier family responsible for exchanging ADP and ATP across the mitochondrial inner membrane. ADP/ATP transport involves Ancp switching between two conformational states. These can be analyzed using specific inhibitors, carboxyatractyloside (CATR) and bongkrekic acid (BA).

Snapshots of enzymatic Baeyer-Villiger catalysis: oxygen activation and intermediate stabilization.

Baeyer-Villiger monooxygenases catalyze the oxidation of carbonylic substrates to ester or lactone products using NADPH as electron donor and molecular oxygen as oxidative reactant. Using protein engineering, kinetics, microspectrophotometry, crystallography, and intermediate analogs, we have captured several snapshots along the catalytic cycle which highlight key features in enzyme catalysis. After acting as electron donor, the enzyme-bound NADP(H) forms an H-bond with the flavin cofactor.

An expeditious access to 5-pyrimidinol derivatives from cyclic methylglyoxal diadducts, formation of argpyrimidines under physiological conditions and discovery of new CFTR inhibitors.

In the study of previously reported modulators of CFTR chloride channels that are cyclic methylglyoxal (MG) diadducts (CMGD) to aromatic α-aminoazaheterocycles, we optimized a new expeditious one pot route for preparing in water novel aromatic polycyclic azaheterocycles and described 5-pyrimidinols antioxidants through the formation of 2-oxoaldehyde diadducts to aromatic α-aminoazaheterocycles, amidines, guanidines and thiourea. In regard to the importance as biomarkers of diabetic complications of the 5-pyrimidinols "argpyrimidines" formed in proteins from MG and arginine residues, we demonstrated that argpyrimidines are slowly formed under physiological conditions from CMGD to arginine derivatives according to the synthesis route described. Among the 5-pyrimidinol derivatives prepared, two polycyclic derivatives appeared to inhibit strongly the activity of CFTR channels in wt-CHO cells.

Enhancement of plant and bacterial lectin binding affinities by three-dimensional organized cluster glycosides constructed on helical poly(phenylacetylene) backbones.

A series of poly(phenylacetylene)s bearing diverse saccharide pendants--N-acetyl-D-glucosamine, D-lactose, and N-acetyl-D-neuraminic acid--were synthesized by rhodium-mediated polymerizations of the corresponding acetyl-protected glycosylated phenylacetylenes followed by deprotection. The circular dichroism spectra of these glycosylated poly(phenylacetylene)s each displayed split-type Cotton effects in the long absorption region of the conjugated polymer backbone (260-500 nm), thus indicating predominantly one-handed helical conformations in their backbones. The binding affinities of these glycosylated poly(phenylacetylene)s, and those of previously reported phenylacetylenes bearing D-galactose, towards plant and bacterial lectins were investigated by hemagglutination inhibition assay and isothermal titration calorimetry (ITC).

Conformational dynamics of the bovine mitochondrial ADP/ATP carrier isoform 1 revealed by hydrogen/deuterium exchange coupled to mass spectrometry.

The mitochondrial adenine nucleotide carrier (Ancp) catalyzes the transport of ADP and ATP across the mitochondrial inner membrane, thus playing an essential role in cellular energy metabolism. During the transport mechanism the carrier switches between two different conformations that can be blocked by two toxins: carboxyatractyloside (CATR) and bongkrekic acid. Therefore, our understanding of the nucleotide transport mechanism can be improved by analyzing structural differences of the individual inhibited states.

Iodination of verapamil for a stronger induction of death, through GSH efflux, of cancer cells overexpressing MRP1.

The multidrug resistance protein 1 (MRP1), involved in multidrug resistance (MDR) of cancer cells, was found to be modulated by verapamil, through stimulation of GSH transport, leading to apoptosis of MRP1-overexpressing cells. In this study, various iodinated derivatives of verapamil were synthesized, including iodination on the B ring, known to be involved in verapamil cardiotoxicity, and assayed for the stimulation of GSH efflux by MRP1. The iodination, for nearly all compounds, led to a higher stimulation of GSH efflux.

Structural basis of the affinity for oligomannosides and analogs displayed by BC2L-A, a Burkholderia cenocepacia soluble lectin.

The opportunistic pathogen Burkholderia cenocepacia contains three soluble carbohydrate-binding proteins, related to the fucose-binding lectin PA-IIL from Pseudomonas aeruginosa. All contain a PA-IIL-like domain and two of them have an additional N-terminal domain that displays no sequence similarities with known proteins. Printed arrays screening performed on the shortest one, B.

Enantioseparation by MEKC using a ligand exchange-based chiral pseudostationary phase.

In this paper, a new ligand-exchange -MEKC mode, based on the design of a unique lipohilic species (4'-octadecylneamine derivative), which served both as micelle-forming surfactant (by its hydrophobic part) and central ion-complexing ligand (by its hydrophilic part) is described. The CMC of the used lipophilic neamine derivative was first determined by surface tension measurements. Subsequent NMR experiments were performed in order to investigate the Cu(II) binding properties of the neamine micellar phase.

Noncompetitive fluorescence polarization aptamer-based assay for small molecule detection.

In this paper, a new fluorescence polarization (FP) assay strategy is described reporting the first demonstration of a noncompetitive FP technique dedicated to the small molecule sensing. This approach was based on the unique induced-fit binding mechanism of nucleic acid aptamers which was exploited to convert the small target binding event into a detectable fluorescence anisotropy signal. An anti-L-tyrosinamide DNA aptamer, labeled by a single fluorescent dye at its extremity, was employed as a model functional nucleic acid probe.

New generation sequencers as a tool for genotyping of highly polymorphic multilocus MHC system.

Accurate genotyping of complex systems, such as the major histocompatibility complex (MHC) often requires simultaneous analysis of multiple co-amplifying loci. Here we explore the utility of the massively parallel 454 sequencing method as a universal tool for genotyping complex MHC systems in nonmodel vertebrates. The power of this approach stems from the use of tagged polymerase chain reaction (PCR) primers to identify individual amplicons which can be simultaneously sequenced to the arbitrarily chosen coverage.

Assessment of selective real-time PCR for quantitation of lamivudine and adefovir hepatitis B virus-resistant strains and comparison with direct sequencing and line probe assays.

A selective real-time PCR (sPCR) assay has been developed to detect the rtM204V/I and rtN236T mutations of hepatitis B virus (HBV) associated with resistance to lamivudine and adefovir. Using mixtures of mutant and wild-type plasmids, this sPCR was able to detect 0.1% of mutated strain in a total plasmid population of 10(5) copies and was more sensitive in detecting resistant strains than the line probe INNO-LiPA-DR-v2 assay and a direct sequencing assay.

Chiral ligand-exchange chromatography of amino acids using porous graphitic carbon coated with a dinaphthyl derivative of neamine.

In this paper, we describe the preparation and the evaluation of a porous graphitic carbon (PGC) column coated with a new dinaphthyl derivative of neamine for chiral ligand-exchange (LE) chromatography. It was shown that the graphitic surface/dinaphthyl anchor system efficiently (1.15 micromol/m(2)) and stably (three months of intensive use) adsorbs the neamine template onto the chromatographic support.

A genome-wide and metabolic analysis determined the adaptive response of Arabidopsis cells to folate depletion induced by methotrexate.

Control of folate homeostasis is essential to sustain the demand for one-carbon (C1) units that are necessary for major biological functions, including nucleotide synthesis and methylation reactions. In this study, we analyzed the genome-wide and metabolic adaptive response of Arabidopsis (Arabidopsis thaliana) cells to folate depletion induced by the antifolate methotrexate. Drug treatment induced a response typical to xenobiotic stress and important changes in folate content and composition.

High-cell-density regulation of the Pseudomonas aeruginosa type III secretion system: implications for tryptophan catabolites.

The Pseudomonas aeruginosa type III secretion system (T3SS) is known to be a very important virulence factor in acute human infections, but it is less important in maintaining chronic infections in which T3SS genes are downregulated. In vitro, the activation of T3SS expression involves a positive activating loop that acts on the transcriptional regulator ExsA. We have observed that in vivo T3SS expression is cell density-dependent in a manner that does not need known quorum-sensing (QS) signals.