Співвідношення категорій природного та позитивного права: сучасні погляди та концепції

В статье проведен анализ позитивных и негативных сторон естественно-правового и позитивного правопонимания и осуществлен поиск идеальной системы, объединяющий положительные моменты обеих концепций.In the article the analysis of positive and negative sides of absolute law and positive rights understanding is conducted and the search of the ideal system, uniting the positive moments of both conceptions, is carried out

Coupling proteomics and metabolomics for the unsupervised identification of protein-metabolite interactions in Chaetomium thermophilum

Protein-metabolite interactions play an important role in the cell's metabolism and many methods have been developed to screen them in vitro. However, few methods can be applied at a large scale and not alter biological state. Here we describe a proteometabolomic approach, using chromatography to generate cell fractions which are then analyzed with mass spectrometry for both protein and metabolite identification. Integrating the proteomic and metabolomic analyses makes it possible to identify protein-bound metabolites. Applying the concept to the thermophilic fungus Chaetomium thermophilum, we predict 461 likely protein-metabolite interactions, most of them novel. As a proof of principle, we experimentally validate a predicted interaction between the ribosome and isopentenyl adenine

Haloadaptation: Insights from comparative modeling studies of halophilic archaeal DHFRs

Proteins of halophilic archaea function in high-salt concentrations that inactivate or precipitate homologous proteins from non-halophilic species. Haloadaptation and the mechanism behind the phenomenon are not yet fully understood. In order to obtain useful information, homology modeling studies of dihydrofolate reductases (DHFRs) from halophilic archaea were performed that led to the construction of structural models. These models were subjected to energy minimization, structural evaluation and analysis. Complementary approaches concerning calculations of the amino acid composition and visual inspection of the surfaces and cores of the models, as well as calculations of electrostatic surface potentials, in comparison to non-halophilic DHFRs were also performed. The results provide evidence that sheds some light on the phenomenon of haloadaptation: DHFRs from halophilic archaea may maintain their fold, in high-salt concentrations, by sharing highly negatively charged surfaces and weak hydrophobic cores. © 2007 Elsevier B.V. All rights reserved

BRCA1-BRCT mutations alter the subcellular localization of BRCA1 in vitro

Background/Aim: Numerous missense mutations have been determined in the BRCT domain of the BRCA1 gene, affecting localization and interaction of BRCA1 with other proteins. Materials and Methods: We examined whether the M1775K and V1809F mutations in the BRCT domain affect BRCA1 cellular localization. Cells were transfected with pEGFP-C3-BRCA1 and detected by fluorescence microscopy. Results: Following induction of DNA damage, cytoplasmic mislocalization was observed for both M1775K and V1809F mutants compared to EGFP-BRCA1wt and the less common variant M1652I. These results indicate that M1775K and V1809F mutations may change the function of the protein by affecting BRCA1 localization. Conclusion: There is a correlation between subcellular localization of BRCA1 and diminished DNA repair observed in breast cancer cells, which may be explained by structural variations and altered binding properties of phosphopeptides. © 2021 International Institute of Anticancer Research. All rights reserved

Solvated protein-protein docking using Kyte-Doolittle-based water preferences

HADDOCK is one of the few docking programs that can explicitly account for water molecules in the docking process. Its solvated docking protocol starts from hydrated molecules and a fraction of the resulting interfacial waters is subsequently removed in a biased Monte Carlo procedure based on water-mediated contact probabilities. The latter were derived from an analysis of water contact frequencies from high-resolution crystal structures. Here, we introduce a simple water mediated amino acid - amino acid contact probability scale derived from the Kyte-Doolittle hydrophobicity scale and assess its performance on the largest high-resolution dataset developed to date for solvated docking. Both scales yield high-quality docking results. The novel and simple hydrophobicity scale, which should reflect better the physico-chemical principles underlying contact propensities, leads to a performance improvement of around 10% in ranking, cluster quality and water recovery at the interface compared to the statistics-based original solvated docking protocol