Gradualistic characean lineages in the Upper Cretaceous–Palaeocene of southern Europe

Two charophyte lineages from the Upper Cretaceous–Palaeocene of southern Europe are described here, constituting a useful biostratigraphic tool for correlating non-marine stratigraphic sequences. The Peckichara pectinata lineage, ranging from the middle Campanian to the middle–upper Maastrichtian, consists of four successive gyrogonite morphotypes that displayed progressively more complex gyrogonite ornamentation and increasingly smaller gyrogonites with time. The Peckichara sertulata lineage, ranging from the middle Campanian to the Danian, consists of three morphotypes that followed a more common evolutionary trend, developing progressively larger gyrogonites without any changes in ornamentation. Intermediate forms between the successive morphotypes suggest that they corresponded to anagenetic varieties of the same evolutionary species rather than to separate species. The different trends observed appear to be palaeoenvironmentally controlled. The grades of the P. pectinata lineage first occurred in permanent lakes that later shifted to fluvial influenced floodplain ponds, this shift accounting for the reduction in gyrogonite size. By contrast, the P. sertulata lineage mainly occurred in permanent lakes, where stable palaeoenvironmental conditions enabled a steady rise in gyrogonite size to increase the space available for the zygote.     

Pheromone-mediated communication disruption in Guatemalan potato moth, Tecia solanivora

Chemical analysis of pheromone gland extracts followed by behavioural studies in the wind tunnel and by field trapping tests show that the sex pheromone of the Guatemalan potato moth, Tecia (Scrobipalpopsis) solanivora Povolny (Lepidoptera: Gelechiidae), is a blend of (E)‐3‐dodecenyl acetate, (Z)‐3‐dodecenyl acetate, and dodecyl acetate. A 100 : 1 : 20 blend of these compounds, formulated at 1000 µg on rubber septa, captured more males than the main compound alone. This lure was species‐specific and did not capture the potato tubermoth, Phthorimaea operculella. A potato field was treated with a blend of these three compounds at a rate of 28 g ha^?1. Male T. solanivora attraction to synthetic pheromone traps was almost completely suppressed for 2 months, demonstrating the potential use of pheromones for control of this economically important insect pest of potato in Central and Southern America.     

The degradation of two fluoroquinolone based antimicrobials by SilA,an alkaline laccase from <Emphasis Type="Italic">Streptomyces ipomoeae</Emphasis>

The presence of fluoroquinolone based antimicrobials in natural waters represents a significant emerging environmental problem. In this study the suitability of a novel alkaline bacterial laccase, SilA, from Streptomyces ipomoeae to degrade two key antimicrobials, Ciprofloxacin and Norfloxacin under alkaline conditions in the presence of natural mediators was assessed. Results showed that only the selected SilA-acetosyringone system was able to degrade more than 90 % of both fluoroquinolones. HPLC analysis of the degradation products obtained after enzyme treatment confirmed the disappearance of the antimicrobials and the mediator after 24 h. The time course of the degradation showed that during the first 4 h a 75 % of degradation of fluoroquinolones was detected while the mediator remained stable. A concomitant appearance of new chromatographic peaks derived from the fluoroquinolones and/or the mediator was detected. Moreover, toxicity assays demonstrated that the SilA-acetosyringone system was able to reduce the toxicity of Ciprofloxacin and Norfloxacin by 90 and 70 %, respectively. In conclusion, these findings support the suitability of a low cost and environmentally friendly strategy based on the SilA-acetosyringone system for a primary treatment of contaminated alkaline wastewaters with this type of emerging pollutants.     

Anti-enterovirus activity and structure-activity relationship of a series of 2,6-dihalophenyl-substituted 1H,3H-thiazolo[3,4-a]benzimidazoles

Despite the fact that enteroviruses are implicated in a variety of human diseases, there is no approved therapy for the treatment of enteroviral infections. Here, a series of 2,6-dihalophenyl-substituted 1H,3H-thiazolo[3,4-a]benzimidazoles with anti-enterovirus activity is reported. The compounds elicit potent activity against coxsackievirus A9, echovirus 9 and 11 and all six strains of coxsackievirus B. A structure-activity relationship analysis revealed that the presence of substituents at position 6 of the tricyclic system positively influences the antiviral activity, whereas substitutions at position 7 are less favorable. In particular a 6-trifluoromethyl substitution leads to a substantial improvement of the antiviral activity as compared to the unsubstituted structure. Furthermore, an additional introduction of a 2-Cl, 6-F substitution on the phenyl at C-1 results in a further increase of the antiviral activity. Hence, 1-(2-chloro-6-fluorophenyl)-6-trifluoromethyl-1H,3H-thiazolo[3,4-a]benzimidazole results in a dose-dependent inhibition of viral replication with a 50% effective concentration (EC50) of 0.41 microg/ml without any detectable cytotoxicity at the highest concentration (100 microg/ml) tested.     

Stimulated production of diosgenin in Dioscorea galeottiana cell suspension cultures by abiotic and biotic factors

Dioscorea deltoidea cell suspension cultures were established in modified Murashige and Skoog medium. The diosgenin production increased from 0.10 g^–1 to 3.98 g^–1 dry cell weight when cells were cultivated in the light and in a growth medium limited in phosphate and sucrose. The addition of 1.3 g of autoclaved fungal mycelium of Alternaria tenuis per litre of cell culture growing in the dark induced the production of 0.04 mg diosgenin g^–1 dry cell weight. In both cases, the production of diosgenin was preceded by a transient induction of isopentenyl diphosphate isomerase activity.     

Determination of new 2,3-benzodiazepines in rat plasma using high-performance liquid chromatography with ultraviolet detection

A method for the analysis of [1-(4-aminophenyl)-3,5-dihydro-7,8-dimethoxy-4H-2,3-benzodiazepin-4-one] (CFM-2) and its analogues CFM-3, CFM-4 and CFM-5 in rat plasma was developed. The 2,3-benzodiazepines (2,3-BZs) were extracted by liquid–liquid extraction and analyzed using high-performance liquid chromatography (HPLC) with ultraviolet detection (UV) at 240 nm. The method exhibited a large linear range from 0.05 to 2 μg/ml with an intra-assay accuracy for all studied compounds ranging from 92 to 105.5%; whereas the intra-assay precision ranged from 0.59 to 8.16% in rat plasma. The inter-assay accuracy of CFM-2, CFM-4 and their 3-methyl derivatives, CFM-3 and CFM-5 ranged from 92.2 to 107% and the inter-assay precision ranged from 2.17 to 11.9% in rat plasma. The lower limit of detection was 5.5 ng/ml for CFM-2, 6.5 ng/ml for CFM-3, 7 ng/ml for CFM-4 and 8.5 ng/ml for CFM-5 in rat plasma. The pharmacokinetic study demonstrated that 2,3-BZs achieved a peak plasma concentration between 45 and 75 min after drug administration. Moreover, we observed that plasma chromatograms of rats treated with CFM-3, CFM-4 and CFM-5, respectively, showed a peak consistent with CFM-2. Our study suggests that CFM-4, CFM-5 and CFM-3 are prodrugs of CFM-2, in which they are biotransformed in vivo via different metabolic pathways. In particular, CFM-2 has been proven to possess anticonvulsant activity in various models of seizures, acting as α-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) receptor antagonist.     

Development of 5-hydroxypyrazole derivatives as reversible inhibitors of lysine specific demethylase 1

A series of reversible inhibitors of lysine specific demethylase 1 (LSD1) with a 5-hydroxypyrazole scaffold have been developed from compound 7, which was identified from the patent literature. Surface plasmon resonance (SPR) and biochemical analysis showed it to be a reversible LSD1 inhibitor with an IC₅₀ value of 0.23 µM. Optimisation of this compound by rational design afforded compounds with K_d values of <10 nM. In human THP-1 cells, these compounds were found to upregulate the expression of the surrogate cellular biomarker CD86. Compound 11p was found to have moderate oral bioavailability in mice suggesting its potential for use as an in vivo tool compound.