Activity of Riminophenazines against Mycobacterium tuberculosis: A Review of Studies that Might be Contenders for Use as Antituberculosis Agents

Tuberculosis is one of the leading cause of death in the world, mainly due to the increasing number of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) strains. Factors such as the HIV pandemic contribute further. Also, the ineffectiveness of the chemotherapy in current use increases the mortality rate. Therefore, new and repurposed antituberculosis drugs are urgently needed for the treatment of MDR-TB, and riminophenazines are among those drugs that are being reinvestigated for their potential in the treatment of TB. This review delivers a brief historical account of riminophenazines, their general synthesis, mechanisms of action, and their physicochemical properties. The discussion is limited to those studies that investigated the activity of these compounds as antituberculosis agents. Given their unique properties, this review will be of great significance in giving direction towards the design and development of new riminophenazine analogues.     

Key factors that influence the UX of a dual-player game for the cognitive stimulation and motor rehabilitation of older adults

Universal Access in the Information Society - In this work, the results of usability and user experience (UX) evaluation of a serious video game for the cognitive stimulation and motor...     

MQDM: An Iterative Fuzzy Method for Group Decision Making in Structured Social Networks

Modern human societies have evolved into an almost entirely connected world, giving place to a remarkable increase in social interactions. In this new context and because of the globalization of all human activities, the collective participation in decision‐making processes takes an increasingly prominent role. In this paper, a method for group decision making from a set of imprecise opinions called “moviQuest Decision Making” (MQDM), is presented. This method allows to integrate the opinions of heterogeneous groups of agents in a structured social network along a sequence of voting rounds for collective decision making.     

A comparison of approaches for finding minimum identifying codes on graphs

In order to formulate mathematical conjectures likely to be true, a number of base cases must be determined. However, many combinatorial problems are NP-hard and the computational complexity makes this research approach difficult using a standard brute force approach on a typical computer. One sample problem explored is that of finding a minimum identifying code. To work around the computational issues, a variety of methods are explored and consist of a parallel computing approach using MATLAB, an adiabatic quantum optimization approach using a D-Wave quantum annealing processor, and lastly using satisfiability modulo theory (SMT) and corresponding SMT solvers. Each of these methods requires the problem to be formulated in a unique manner. In this paper, we address the challenges of computing solutions to this NP-hard problem with respect to each of these methods.     

Starch‐poly(acrylamide‐co‐2‐acrylamido‐2‐methylpropanesulfonic acid) graft copolymers prepared by reactive extrusion

Graft copolymers of starch with acrylamide and 2‐acrylamido‐2‐methylpropanesulfonic acid (AMPS) were prepared by reactive extrusion in a twin‐screw extruder. The weight ratio of total monomer to starch was fixed at 1 : 3, while the molar fraction of AMPS in the monomer feed ranged from 0 to 0.119. Monomer to polymer conversions were 85% or greater, with grafting efficiencies of 68% (highest AMPS content) to 85% (no AMPS). Absorbency in distilled water at pH 7 increased linearly with the mole fraction AMPS in the grafted polymer, while absorbencies in 0.9% NaCl were independent of AMPS content. When swollen in water/ethanol mixtures, swelling decreased gradually with increasing ethanol volume fraction, followed by a large decrease over a narrow ethanol concentration. This behavior is similar to that observed for AMPS‐acrylamide gels. The swelling properties suggest these graft copolymers may have applications as responsive materials. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42405.     

Increased HDL Size and Enhanced Apo A-I Catabolic Rates Are Associated With Doxorubicin-Induced Proteinuria in New Zealand White Rabbits

The catabolism and structure of high‐density lipoproteins (HDL) may be the determining factor of their atheroprotective properties. To better understand the role of the kidney in HDL catabolism, here we characterized HDL subclasses and the catabolic rates of apo A‐I in a rabbit model of proteinuria. Proteinuria was induced by intravenous administration of doxorubicin in New Zealand white rabbits (n = 10). HDL size and HDL subclass lipids were assessed by electrophoresis of the isolated lipoproteins. The catabolic rate of HDL‐apo A‐I was evaluated by exogenous radiolabelling with iodine‐131. Doxorubicin induced significant proteinuria after 4 weeks (4.47 ± 0.55 vs. 0.30 ± 0.02 g/L of protein in urine, P < 0.001) associated with increased uremia, creatininemia, and cardiotoxicity. Large HDL2b augmented significantly during proteinuria, whereas small HDL3b and HDL3c decreased compared to basal conditions. HDL2b, HDL2a, and HDL3a subclasses were enriched with triacylglycerols in proteinuric animals as determined by the triacylglycerol‐to‐phospholipid ratio; the cholesterol content in HDL subclasses remained unchanged. The fractional catabolic rate (FCR) of [¹³¹I]‐apo A‐I in the proteinuric rabbits was faster (FCR = 0.036 h^?1) compared to control rabbits group (FCR = 0.026 h^?1, P < 0.05). Apo E increased and apo A‐I decreased in HDL, whereas PON‐1 activity increased in proteinuric rabbits. Proteinuria was associated with an increased number of large HDL2b particles and a decreased number of small HDL3b and 3c. Proteinuria was also connected to an alteration in HDL subclass lipids, apolipoprotein content of HDL, high paraoxonase‐1 activity, and a rise in the fractional catabolic rate of the [¹³¹I]‐apo A‐I.     

Inhibition of Hydroperoxy-, Keto- and Hydroxy-FAME by Alpha- and Delta-Tocopherol at Rancimat Conditions

The effects of α‐ and δ‐tocopherol on inhibition of hydroperoxides, keto and hydroxy compounds under Rancimat conditions, i.e. 100 °C and air bubbling, were studied in samples of fatty acid methyl esters (FAME) obtained from high linoleic (HL) and high oleic (HO) sunflower oils. Primary hydroperoxides from methyl linoleate and methyl oleate and secondary keto and hydroxy compounds derived from methyl linoleate hydroperoxides were analyzed by HPLC–UV‐ELS. Different tocopherol concentrations, namely, 10, 50, 100, 500 and 1000 mg/kg, were tested. Irrespective of the lipid substrate and the initial concentration of tocopherol, results showed that the content of hydroperoxides accumulated during the induction period was remarkably higher in the samples containing δ‐tocopherol. The relative concentrations of oleate hydroperoxides in the HO samples were also higher in the presence of δ‐tocopherol. α‐Tocopherol was more effective in inhibiting hydroperoxides at low levels, with 100 mg/kg as optimal concentration, while δ‐tocopherol displayed optimal protection at 1000 mg/kg. Under the oxidation conditions applied, neither α‐ nor δ‐tocopherol showed a protective effect on hydroperoxide decomposition at any level assayed. Formation of keto‐ and hydroxy‐dienes was more related to the concentration of their hydroperoxide precursors. Furthermore, both tocopherols gave rise to increased concentrations of ketodienes at 500 and 1000 mg/kg compared to the controls. Such an effect was more pronounced for α‐tocopherol and in the HL samples.     

Capture‐Tag‐Release: A Strategy for Small Molecule Labeling of Native Enzymes

A strategy for labeling native enzymes in a manner that preserves their activity is reported: capture–tag–release (CTR). Key to this approach is the small molecule CTR probe that contains an enzyme inhibitor, benzophenone crosslinker, and aryl phosphine ester. After UV‐derived capture of the enzyme, addition of an azide‐containing tag triggers a Staudinger ligation that labels the enzyme. A further consequence of the Staudinger ligation is fragmentation of the CTR probe, thus releasing the inhibitor and restoring enzymatic activity. As a proof‐of‐principle, the CTR strategy was applied to the hydrolase β‐galactosidase. The enzyme was efficiently labeled with biotin, and the kinetic data for the biotinylated enzyme were comparable to those for unlabeled β‐galactosidase. The CTR probe exhibits excellent targeting specificity, as it selectively labeled β‐galactosidase in a complex protein mixture.     

Orthogonal Peptide-Templated Labeling Elucidates Lateral ETAR/ETBR Proximity and Reveals Altered Downstream Signaling

Fine-tuning of G protein-coupled receptor (GPCR) signaling is important to maintain cellular homeostasis. Recent studies demonstrated that lateral GPCR interactions in the cell membrane can impact signaling profiles. Here, we report on a one-step labeling method of multiple membrane-embedded GPCRs. Based on short peptide tags, complementary probes transfer the cargo (e. g. a fluorescent dye) by an acyl transfer reaction with high spatial and temporal resolution within 5 min. We applied this approach to four receptors of the cardiovascular system: the endothelin receptor A and B (ET_AR and ET_BR), angiotensin II receptor type 1, and apelin. Wild type-like G protein activation after N-terminal modification was demonstrated for all receptor species. Using FRET-competent dyes, a constitutive proximity between hetero-receptors was limited to ET_AR/ET_BR. Further, we demonstrate, that ET_AR expression regulates the signaling of co-expressed ET_BR. Our orthogonal peptide-templated labeling of different GPCRs provides novel insight into the regulation of GPCR signaling.