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Alzheimer’s disease (AD) belongs to the most common forms of dementia that causes a progressive loss of brain cells and leads to memory impairment and decline of other thinking skills. There is yet no effective treatment for AD; hence, the search for new drugs that could improve memory and other cognitive functions is one of the hot research topics worldwide. Scientific efforts are also directed toward combating behavioral and psychological symptoms of dementia, which are an integral part of the disease. Several studies have indicated that glycogen synthase kinase 3 beta (GSK3β) plays a crucial role in the pathogenesis of AD. Moreover, GSK3β inhibition provided beneficial effects on memory improvement in multiple animal models of AD. The present review aimed to update the most recent reports on the discovery of novel multifunctional ligands with GSK3β inhibitory activity as potential drugs for the symptomatic and disease-modifying therapy of AD. Compounds with GSK3β inhibitory activity seem to be an effective pharmacological approach for treating the causes and symptoms of AD as they reduced neuroinflammation and pathological hallmarks in animal models of AD and provided relief from cognitive and neuropsychiatric symptoms. These compounds have the potential to be used as drugs for the treatment of AD, but their precise pharmacological, pharmacokinetic, toxicological and clinical profiles need to be defined.

A set of 31 diversified 5-HT7receptor antagonists was automatically docked to a conformational ensemble of rhodopsin-based 5-HT7R models (flexible docking). It was found that ergolines, aporphines, and tricyclic psychotropic agents were always docked in a pocket formed by TMHs 4-6, and besides the main ionic bond with Asp3.32, they had specific interactions with Phe6.52, Phe6.51, Trp6.48, and Ser5.42. The arylpiperidine, arylpiperazine, or -carboline fragment of the complex ligands occupied the same pocket, whereas the terminal amide/imide part of those compounds reached the second cavity formed by TMHs 7-3 and interacted with Phe3.28, Arg7.36, and Tyr7.43. A similar orientation of selective antagonists of the group of arylsulfonamidoalkylamines was observed, that is, the sulfonamide part was located in the second pocket. Coherent docking results allowed the generation of two receptor-based pharmacophores:? first containing features necessary for high 5-HT7R affinity and the other defining selectivity for this receptor subtype. The latter model indicated the importance of specific interactions with the residues of the TMHs 7-3 pocket (especially nonconserved Arg7.36) for selectivity over other monoamine GPCRs.

A total of six high-resolution FT-IR spectra for trans-glyoxal-d2, trans-glyoxal-d1and trans-glyoxal-13C2were recorded with a resolution ranging from 0.003 to 0.004 cm−1. By means of a simultaneous ground state combination difference analysis for each of these isotopologues using the Watson Hamiltonian in A-reduction and Ir-representation the ground state rotational constants are obtained. An empiricalequilibrium structure is determined for trans-glyoxal using these experimental ground state rotational constants and vibration–rotation interaction constants calculated at the CCSDTcc-pVTZ level of theory. The least-squares fit yields the following structural parameters for trans-glyoxal: reC–C  1.5145338 Å, reC–H  1.1007126 Å, reCO  1.2045027 Å, αeCCH  115.25124°, and αeHCO  123.47219° in excellent agreement with theoretical predictions at the CCSDTcc-pVQZ level of theory.

A method and tools recently applied in animation are presented, and the associated problems connected with combining the real and the virtual world are described. Approaches include creating computer graphics libraries of realistic 3-D objects and describing their animation in 3-D space. The presented method simplifies the process of virtual-object generation and provides the shape and movement of the monitored object. Optical structured-light methods supported by photogrammetry are proposed for gathering the information about a shape, deformations of shape, and shifts of 3-D objects. The authors apply the spatiotemporal approach, in which the spatial analysis of fringe pattern delivers information about the shape of the object, while the temporal analysis of the intensity variation l(t)at a given pixel provides information about shape variations and out-of-plane displacement. The function I(t)is analyzed by the Fourier-transform method. Rigid-body motion of the object is determined by a photogrammetry-based marker tracking method. The methodology of measurement is presented, together with experimental results. © 2002 Society of Photo-Optical Instrumentation Engineers.

The results of the first Critical Assessment of Fully Automated Structure Prediction (CAFASP‐1) are presented. The objective was to evaluate the success rates of fully automatic web servers for fold recognition which are available to the community. This study was based on the targets used in the third meeting on the Critical Assessment of Techniques for Protein Structure Prediction (CASP‐3). However, unlike CASP‐3, the study was not a blind trial, as it was held after the structures of the targets were known. The aim was to assess the performance of methods without the user intervention that several groups used in their CASP‐3 submissions. Although it is clear that “human plus machine” predictions are superior to automated ones, this CAFASP‐1 experiment is extremely valuable for users of our methods; it provides an indication of the performance of the methods alone, and not of the “human plus machine” performance assessed in CASP. This information may aid users in choosing which programs they wish to use and in evaluating the reliability of the programs when applied to their specific prediction targets. In addition, evaluation of fully automated methods is particularly important to assess their applicability at genomic scales. For each target, groups submitted the top‐ranking folds generated from their servers. In CAFASP‐1 we concentrated on fold‐recognition web servers only and evaluated only recognition of the correct fold, and not, as in CASP‐3, alignment accuracy. Although some performance differences appeared within each of the four target categories used here, overall, no single server has proved markedly superior to the others. The results showed that current fully automated fold recognition servers can often identify remote similarities when pairwise sequence search methods fail. Nevertheless, in only a few cases outside the family‐level targets has the score of the top‐ranking fold been significant enough to allow for a confident fully automated prediction.Because the goals, rules, and procedures of CAFASP‐1 were different from those used at CASP‐3, the results reported here are not comparable with those reported in CASP‐3. Nevertheless, it is clear that current automated fold recognition methods can not yet compete with “human‐expert plus machine” predictions. Finally, CAFASP‐1 has been useful in identifying the requirements for a future blind trial of automated served‐based protein structure prediction. Proteins Suppl 1999;3:209–217. © 1999 Wiley‐Liss, Inc.