Clinically relevant cell culture model of inflammatory bowel diseases for identification of new therapeutic approaches.

Inflammatory Bowel Diseases (IDB) are chronic disorders characterized by gut inflammation, mucosal damage, increased epithelial permeability and altered mucus layer. No accurate in vitro model exists to simulate these characteristics. In this context, drug development for IBD or intestinal inflammation requires in vivo evaluations to verify treatments efficacy.

Modulation of bitter taste receptors by yeast extracts.

Yeast extracts (YEs) are used in foods because of their flavour properties and ability to reduce bitterness. The adenosine 5'-monophosphate (AMP) found in YEs is known to decrease the bitterness of some compounds. This study aimed to investigate the ability of YEs to inhibit bitter taste receptors (TAS2Rs) using in vitro cell-based assays.

Active nanoparticle targeting of MUC5AC ameliorates therapeutic outcome in experimental colitis.

Inflammatory bowel diseases (IBDs), which include Crohn's disease (CD) and ulcerative colitis (UC), are chronic inflammatory diseases of the gastrointestinal tract and are characterized by chronic recurrent ulceration of the bowels. Colon-targeted drug delivery systems (DDS) have received significant attention for their potential to treat IBD by improving the inflamed tissue selectivity. Herein, antiMUC5AC-decorated drug loaded nanoparticles (NP) are suggested for active epithelial targeting and selective adhesion to the inflamed tissue in experimental colitis.

Polymer Retention Determination in Porous Media for Polymer Flooding in Unconsolidated Reservoir.

Polymer flooding is a well-established technique aimed at improved recovery factors from oilfields. Among the important parameters affecting the feasibility of a large deployment, polymer retention is one of the most critical since it directly impacts the oil bank delay and therefore the final economics of the project. This paper describes the work performed for the East-Messoyakhskoe oilfield located in Northern Siberia (Russia).

Homogeneous time-resolved G protein-coupled receptor-ligand binding assay based on fluorescence cross-correlation spectroscopy.

G protein-coupled receptors (GPCRs) mediate many important physiological functions and are considered as one of the most successful therapeutic target classes for a wide spectrum of diseases. Drug discovery projects generally benefit from a broad range of experimental approaches for screening compound libraries and for the characterization of binding modes of drug candidates. Owing to the difficulties in solubilizing and purifying GPCRs, assay formats have been so far mainly limited to cell-based functional assays and radioligand binding assays.

Rapid kill of malaria parasites by artemisinin and semi-synthetic endoperoxides involves ROS-dependent depolarization of the membrane potential.

Objectives: Artemisinin and artemisinin semi-synthetic derivatives (collectively known as endoperoxides) are first-line antimalarials for the treatment of uncomplicated and severe malaria. Endoperoxides display very fast killing rates and are generally recalcitrant to parasite resistance development. These key pharmacodynamic features are a result of a complex mechanism of action, the details of which lack consensus.

Targeting the mitochondrial electron transport chain of Plasmodium falciparum: new strategies towards the development of improved antimalarials for the elimination era.

Despite intense efforts, there has not been a truly new antimalarial, possessing a novel mechanism of action, registered for over 10 years. By virtue of a novel mode of action, it is hoped that the global challenge of multidrug-resistant parasites can be overcome, as well as developing drugs that possess prophylaxis and/or transmission-blocking properties, towards an elimination agenda. Many target-based and whole-cell screening drug development programs have been undertaken in recent years and here an overview of specific projects that have focused on targeting the parasite's mitochondrial electron transport chain is presented.

Generation of quinolone antimalarials targeting the Plasmodium falciparum mitochondrial respiratory chain for the treatment and prophylaxis of malaria.

There is an urgent need for new antimalarial drugs with novel mechanisms of action to deliver effective control and eradication programs. Parasite resistance to all existing antimalarial classes, including the artemisinins, has been reported during their clinical use. A failure to generate new antimalarials with novel mechanisms of action that circumvent the current resistance challenges will contribute to a resurgence in the disease which would represent a global health emergency.

HDQ, a potent inhibitor of Plasmodium falciparum proliferation, binds to the quinone reduction site of the cytochrome bc1 complex.

The mitochondrial bc(1) complex is a multisubunit enzyme that catalyzes the transfer of electrons from ubiquinol to cytochrome c coupled to the vectorial translocation of protons across the inner mitochondrial membrane. The complex contains two distinct quinone-binding sites, the quinol oxidation site of the bc(1) complex (Q(o)) and the quinone reduction site (Q(i)), located on opposite sides of the membrane within cytochrome b. Inhibitors of the Q(o) site such as atovaquone, active against the bc(1) complex of Plasmodium falciparum, have been developed and formulated as antimalarial drugs.

Cytochrome b mutation Y268S conferring atovaquone resistance phenotype in malaria parasite results in reduced parasite bc1 catalytic turnover and protein expression.

Atovaquone is an anti-malarial drug used in combination with proguanil (e.g. Malarone(TM)) for the curative and prophylactic treatment of malaria.

Genome dedoubling by DCJ and reversal.

Background: Segmental duplications in genomes have been studied for many years. Recently, several studies have highlighted a biological phenomenon called breakpoint-duplication that apparently associates a significant proportion of segmental duplications in Mammals, and the Drosophila species group, to breakpoints in rearrangement events.

Results: In this paper, we introduce and study a combinatorial problem, inspired from the breakpoint-duplication phenomenon, called the Genome Dedoubling Problem.

Efficient nickel-mediated intramolecular amination of aryl chlorides.

The use of an in situ generated Ni(0) catalyst associated with 2,2'-bipyridine or N,N'-bis(2,6-diisopropylphenyl)dihydroimidazol-2-ylidene (SIPr) as a ligand and NaO-t-Bu as the base for the intramolecular coupling of aryl chlorides with amines is described. The procedure has been applied to the formation of five-, six-, and seven-membered rings. [reaction: see text]