Plasmodium telomeric sequences: structure, stability and quadruplex targeting by small compounds

The increasing resistance of Plasmodium falciparum to the most commonly used antimalarial drugs makes it necessary to identify new therapeutic targets. The telomeres of the parasite could constitute an attractive target. They are composed of repetitions of a degenerate motif ((5')GGGTTYA(3'), where Y is T or C), different from the human one ((5')GGGTTA(3')). In this report we investigate the possibility of targeting Plasmodium telomeres with G-quadruplex ligands. Through solution hybridisation assays we provide evidence of the existence of a telomeric 3' G-overhang in P. falciparum genomic DNA. Through UV spectroscopy studies we demonstrate that stable G-quadruplex structures are formed at physiological temperature by sequences composed of the degenerate Plasmodium telomeric motif. Through a FRET melting assay we show stabilisation of Plasmodium telomeric G-quadruplexes by a variety of ligands. Many of the tested ligands display strong quadruplex versus duplex selectivity, but show little discrimination between human and Plasmodium telomeric quadruplexes.     

Biological Functions and Metabolism of Oleoylethanolamide

The present review is focused on the metabolism and the emerging roles of oleoylethanolamide (OEA) with emphasis on its effects on food intake control and lipid metabolism. The biological mechanism of action, including a non-genomic effect mediated through peroxisome proliferator-activated receptor alpha (PPAR-alpha) and transient receptor potential vanilloid type 1 (TRPV1) receptor, is discussed. The research related to fatty acid ethanolamides has been focused until recently on anandamide and its interaction with cannabinoid receptor subtype 1. The roles of other N-acyl ethanolamine fatty acid derivatives have been neglected until it was demonstrated that OEA can modulate food intake control through interaction with PPAR-alpha. Further investigations demonstrated that OEA modulates lipid and glucose metabolism, and recent study confirmed that OEA is an antagonist of TRVP1. It has been demonstrated that OEA has beneficial effects on health by inducing food intake control, lipid beta-oxidation, body weight loss and analgesic effects. The investigation of the mechanism of action revealed that OEA activates PPAR-alpha and stimulates the vagal nerve through the capsaicin receptor TRPV1. Pre-clinical studies showed that OEA remains active when administered orally.     

Do European Corn Borer Females Detect and Avoid Laying Eggs in the Presence of 20-Hydroxyecdysone?

European corn borer larvae detect and avoid feeding in the presence of phytoecdysteroids (PEs) such as 20-hydroxyecdysone (20E). Therefore, we hypothesized that females would have taste receptors similar to larvae and avoid laying eggs in the presence of 20E. We found female-specific taste sensilla on the tarsi that respond to 20E at concentrations as low as 10⁻⁶ M, a threshold comparable to that of larvae. However, in choice tests, females laid a similar number of eggs on 20E-treated and on nontreated artificial substrates (filter paper, glass, and nylon), although they spent significantly more time in behavioral sequences related to substrate assessment when 20E was present. In contrast, when given a choice between maize plants (eight leaves) sprayed with 20E or only the solvent, females laid 70% fewer eggs on the treated than on control plants. These observations suggest that other chemical cues of plant origin must be present at the same time as 20E for females to modify their oviposition behavior.     

Hydrosoluble Benzo[e]pyridoindolones as Potent Inhibitors of Aurora Kinases

Aurora kinases play an essential role in mitotic progression and are potentially druggable targets in cancer therapy. We identified benzo[e]pyridoindoles (BePI) as powerful aurora kinase inhibitors. Their efficiency was demonstrated both in enzymatic inhibition studies and in cell culture assays. New BePI molecules were synthesized, and a structure–activity relationship study was conducted with the aim of improving the activity and solubility of the lead compound. Tetracyclic BePI derivatives are characterized by a particular curved shape, and the presence of an oxo group on the pyridine ring was found to be required for aurora kinase B inhibition. New hydrosoluble benzo[e]pyridoindolones were subsequently designed, and their efficacy was tested by a combination of cell‐cycle analysis and time‐lapse experiments in live cells. The most active BePI derivative, 13 b , inhibited the cell cycle, drove cells to polyploidy, and eventually induced apoptosis. It exhibited high antiproliferative activity in HeLa cells with an IC₅₀ value of 63 nM . Relative to compounds tested in clinical trials, this antiproliferative potency places 13 b among the top 10 aurora kinase inhibitors. Our results justify further in vivo evaluation in preclinical animal models of cancer.     

Design of highly tough poly(l‐lactide)‐based ternary blends for automotive applications

Technical renewable poly(l ‐lactide) (PLA)‐based blends represent an elegant way to achieve attractive properties for engineering applications. Recently, the miscibility between PLA and poly(methyl methacrylate) (PMMA) gave rise to new formulations with enhanced thermo‐mechanical properties but their high brittleness still remains a challenge to be overcome. This work here focuses on rubber‐toughened PLA/PMMA formulations for injection‐molding processes upon the addition of a commercially available ethylene‐acrylate impact modifier (BS). The miscibility between PLA and PMMA is not altered by the presence of BS but the incorporation of BS (17% by weight) into a PLA/PMMA matrix could enhance both ductility and toughness of PLA/PMMA blends for PMMA content up to 50 wt %. An optimum range of particle sizes (d_n ～0.5 µm) of the dispersed domains for high impact toughness is identified. These bio‐based ternary blends appear as promising alternatives to petro‐sourced blends such as ABS‐based blends in engineering injection‐molding parts. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43402.     

Rheological behavior of nanofibrillated cellulose/acrylic polymer nanocomposites: Effect of melt extrusion

Nanocomposite films based on nanofibrillated cellulose (NFC) and acrylic latex were prepared by film casting and their melt rheology was investigated under dynamic conditions in both the linear and the nonlinear regimes. The addition of cellulose nanofiller increased the storage modulus G′ and the dynamic viscosities η* of the nanocomposites monotonically, with NFC contents up to 6wt%. In addition, a transition from liquid‐like to solid‐like viscoelastic behavior was observed up to 1wt% of the added NFC with a terminal plateau in the low‐frequency range. This was explained in terms of the formation of an interconnected network involving the filler. After melt extrusion, a considerable change in the rheological properties was observed, with a major downward shift in the magnitude of G′ vs. the frequencies along with an upward shift to higher strain in the linear viscoelastic range. Such a transition was attributed to the irreversible break‐down and disruption of the NFC network. POLYM. COMPOS., 2011. © 2011 Society of Plastics Engineers     

Küstenschutzmaßnahmen in Togo — Stabilisierung erosionsgefährdeter Strandabschnitte und Schutz des Containerterminals Lomé durch den Neubau einer Buhne

Die Küste Togos am Golf von Guinea in Westafrika verfügt über keinen natürlichen Schutz, z. B. durch vorgelagerte Inseln oder felsige Uferabschnitte. Der gesamte rd. 65 km lange Küstenstreifen besteht aus Sand und ist daher dem Wellenangriff des Atlantiks und der überwiegend vorhandenen West‐Ost‐Strömung ausgesetzt. Da die Uferbereiche traditionell dicht bewohnt sind, stellen Landverluste durch Erosion ein großes Problem für die Bevölkerung und die Infrastruktur dar. Die Erosionsproblematik wird daher von der togoischen Regierung sehr intensiv verfolgt. Von den rd. 6 bis 7 Millionen Togoern leben rd. 2,5 Millionen im Großraum Lomé direkt an der Küste. Durch den Bau zusätzlicher und die Rehabilitierung vorhandener Buhnen sollen langfristig der Küs tenabschnitt Togos stabilisiert und die Schutzziele erreicht werden. Die technische Umsetzung der von der INROS LACKNER AG geplanten und zu überwachenden Küstenschutzmaßnahmen wird detailliert beschrieben. Coastal protection measures in Togo — stabilization of erosionthreatened sections of the beach and protection of the container terminal Lomé by means of a sea groyne. The coast of Togo at the Gulf of Guinea, situated in West Africa is not sheltered by natural protection, such as offshore islands or rocky shorelines. The approximately 65 km long Atlantic Ocean coastline does mainly consist of sand, which is prone to erosion due to wave attacks and the prevailing west‐east current. With a traditionally dense populated coast, the land losses caused by erosion constitute a main issue for the Togolese as well as for the infrastructure in general. The problems caused by erosion are therefore vigorously pursued by the Togolese Government. Greater Lomé, located at the coast, accommodates 2,5 Million of the 6 to 7 Million Togolese people. The construction of additional and maintaining of existing groins would stabilize Togo’s coastline. The article describes the technical implementation of coastal protection measures designed and supervised by INROS LACKNER AG.