A series of N-monoalkylsubstituted 1,2,3,4-tetrahydro-9-aminoacridines have been prepared after modelling simulation of the AChE-inhibitor complex. Molecular modelling has predicted a number of hydrophobic residues to be involved in the catalytic mechanism of this interaction between the binding sites of AChE and this series of aminoacridines. In these compounds the acridine moiety becomes sandwiched between the rings of PHE330 and TRP84. In particular, the alkyl chain shows the important role of aromatic groups as binding sites. Their in vitro inhibitory properties (enzyme from Electrophorus electricus) confirm the aromatic groups as a general and significant characteristic of the mechanism of AChE inhibition.
A well known characteristic of the oxidative metabolism of Antarctic fishes is their preferential utilization of the lipid metabolic pathway. Since oxidative metabolism may lead to a significant production of oxygen-derived free radicals, which may have several harmful effects on biological structures, it seemed worthwhile to investigate the presence, in various tissues from different Antarctic fishes, of those ions and molecules which are known to be at the basis of the antioxidant defense mechanisms. Hence, the Coenzyme Q and trace elements (selenium, copper, and zinc) content of tissues from several Antarctic fishes was determined and compared with that of non-Antarctic species. Unlike temperate fishes, in which the Coenzyme Q is Q 10 , all the Antarctic species examined displayed the homolog Q 9 form. This particular finding was related to the difference in the crystallisation temperature existing between Coenzyme Q 10 and Coenzyme Q 9 . Taken together, the results indicate a higher level of antioxidant defenses for Antarctic species, with respect to temperate fishes. This may be considered a stimulating basis for further studies on the adaptation mechanisms centered on the oxidative metabolism of organisms living in extreme environments.
In this study the authors attempt to correlate kinetic constants for carbamylation of AChE, by a series of carbamate inhibitors, with the conformational positioning of Trp84 in transition state complexes of the same carbamates with Torpedo AChE, as obtained by computerized molecular modelling. They present evidence for changes in the distance of the carbamates from the center of the indole ring which can be correlated with the bimolecular rate constants for inhibition. As a result the greater the distance from Trp84, the smaller the bimolecular inhibition constant value, ki (= k2/Ka), becomes. In conclusion, the value of the bimolecular rate constant for selected AChE inhibitors (structural changes that have been hypothesised or natural alkaloids of unknown activity) which possess similar size and rigidity, can be obtained. Under these conditions energy minimization alone seems to be sufficient even to accurately predict protein-substrate interactions that actually occur. Modelling studies also suggest that conformational re-orientation of Trp84 in the transition state could produce an overall movement of the Cys67-Cys94 loop.
The eighth edition of the Italian Conference on Computational Linguistics (CLiC-it 2021) was held at Università degli Studi di Milano-Bicocca from 26th to 28th January 2022.After the edition of 2020, which was held in fully virtual mode due to the health emergency related to Covid-19, CLiC-it 2021 represented the first moment for the Italian research community of Computational Linguistics to meet in person after more than one year of full/partial lockdown. Although the conference was held in dual mode, we strongly suggested the participants to attend it coming to Milan. Indeed, we received a strong feedback on this aspect from the community, which was eager to meet in person and enjoy both the scientific and social events together with the colleagues. In total, 99 participants registered to the conference benefiting from the early registration fee, 91 out of which expressed their intention to attend the event in person, which we consider as a very positive indication of enthusiasm from the community, given the uncertain situation due to the evolution of the pandemic in Italy.In total, we received 68 proposals, organized in the following specific tracks: Information Extraction,
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