SAR and biological evaluation of SEN12333/WAY-317538: Novel alpha 7 nicotinic acetylcholine receptor agonist

Alpha 7 nicotinic acetylcholine receptor (α₇ nAChR) agonists are promising therapeutic candidates for the treatment of cognitive impairment associated with a variety of disorders including Alzheimer’s disease and schizophrenia. Alpha 7 nAChRs are expressed in brain regions associated with cognitive function, regulate cholinergic neurotransmission and have been shown to be down regulated in both schizophrenia and Alzheimer’s disease. Herein we report a novel, potent small molecule agonist of the alpha 7 nAChR, SEN12333/WAY-317538. This compound is a selective agonist of the α₇ nAChR with excellent in vitro and in vivo profiles, excellent brain penetration and oral bioavailability, and demonstrates in vivo efficacy in multiple behavioural cognition models. The SAR and biological evaluation of this series of compounds are discussed.     

Phytoplankton assemblage structure and dynamics as indicator [-2pt] of the recent trophic and biological evolution of the western basin of Lake Como (N. Italy)

We studied the phytoplankton assemblage of the western basin of Lake Como (Northern Italy) during 1997. The phytoplankton assemblage was composed of 65 taxa, belonging to six taxonomic groups. Chlorophyta were represented by the highest number of taxa (28) followed by Bacillariophyceae (17), Cyanoprokaryota (9), Dinophyceae (6), Chrysophyceae (3) and Cryptophyta (2). The total assemblage density and biomass ranged from 902 ind ml^–1 and 134.5 mm³ m^–3 in February to 58 766 ind ml^–1 and 9360 mm³ m^–3 in October. The density and biomass variation at three stations showed a common pattern, with higher values in the southern part of the basin where TP concentrations were always greater. The phytoplankton succession was analysed by cluster analysis (average linkage clustering) and non-metric multidimensional scaling (NMDS) ordination, both applied to a dissimilarity matrix obtained from a calculation of the Bray–Curtis index. In general, the seasonal succession followed a simple pattern, with a clear spring phase. These results are discussed considering the trophic evolution of the lake and its recent colonization by Dreissena polymorpha.     

Assessing lake typologies and indicator fish species for Italian natural lakes using past fish richness and assemblages

In order to establish a fish-based typology of Italian lakes and identify possible reference and indicator fish species for each lake type, we analysed historical data on fish assemblages of all Italian natural lakes >0.5 km² from the period prior to the major decline in water quality in the 1950s. General linear regression models showed the ecoregion and lake altitude being the best predictors of fish species richness. The number of species was significantly higher in the Alpine than in the Mediterranean ecoregion. Among Alpine lakes, the number of fish species increased significantly with lake volume whilst decreased with altitude. In the Mediterranean lakes, none of the selected parameters was significant. Cluster analysis of fish assemblages (presence/absence) divided the lakes of the Alpine and Mediterranean ecoregions into four and two types, respectively. Pike (Esox lucius), rudd (Scardinius erythrophthalmus) and tench (Tinca tinca) were the main indicator species for the small and mostly shallow lakes in both the Alpine (Type 1) and Mediterranean (Type 6) ecoregions, minnow (Phoxinus phoxinus) for the alpine high altitude lakes (Type 2) and landlocked shad (Alosa fallax lacustris), European whitefish (Coregonus lavaretus) and burbot (Lota lota) for the large and very deep alpine lakes (Type 4). The European whitefish was the only indicator species for the deep Mediterranean lakes (Type 5). These species and associated fish assemblages may be useful indicators in future assessments of the ecological status of Italian lakes according to the European Directives (2000/60/EC and 2008/105/EC).     

Spatial and temporal trends of target organic and inorganic micropollutants in Lake Maggiore and Lake Lugano (Italian-Swiss water bodies): contamination in sediments and biota

DDx, PCBs, PBDEs, Hg, and As contamination in sediments and aquatic organisms of different trophic levels (zooplankton, mussel, fish) were analyzed in Lake Maggiore and Lake Lugano, two large deep perialpine lakes. In the period 2001–2015, we analyzed the spatial and temporal trends of the considered pollutants to detect potential contamination sources and to compare concentrations with Sediment Quality Guidelines (SQGs) or existing Quality Standards (QSs). DDx and Hg contamination deriving from past industrial activities in the Pallanza Basin still exceeded SQGs in sediments and QSs in fish, with potential risks for the ecosystem. Banned in Europe in 1985, PCBs showed low residual values, while recent PBDE peaks resulted in the exceedance of the QSs for biota in both lakes, probably due to current industrial activities. Arsenic mainly derives from geochemical origin. The analysis of the biomagnification of toxicants in a pelagic food chain in Lake Maggiore (zooplankton–fish) according to a stable isotope approach is also presented, according to both the Trophic Magnification Factor and the Trophic Level-adjusted BioMagnification Factor: the importance of seasonality and a Hg > DDx ≈ PBDEs biomagnification capacity were observed. Low PCB bioaccumulation was detected in biota, probably because equilibrium was not reached yet in young fish.