Long range molecular dynamics study of regulation of eukaryotic glucosamine-6-phosphate synthase activity by UDP-GlcNAc

Glucosamine-6-phosphate (GlcN-6-P) synthase catalyses the first and practically irreversible step in hexosamine metabolism. The final product of this pathway, uridine 5’ diphospho N-acetyl-D-glucosamine (UDP-GlcNAc), is an essential substrate for assembly of bacterial and fungal cell walls. Moreover, the enzyme is involved in phenomenon of hexosamine induced insulin resistance in type II diabetes, which makes it a potential target for antifungal, antibacterial and antidiabetic therapy. The crystal structure of the isomerase domain of GlcN-6-P synthase from human pathogenic fungus Candida albicans, in complex with UDP-GlcNAc has been solved recently but it has not revealed the molecular mechanism of inhibition taking place under UDP-GlcNAc influence, the unique feature of the eukaryotic enzyme. UDP-GlcNAc is a physiological inhibitor of GlcN-6-P synthase, binding about 1 nm away from the active site of the enzyme. In the present work, comparative molecular dynamics simulations of the free and UDP-GlcNAc-bounded structures of GlcN-6-P synthase have been performed. The aim was to complete static X-ray structural data and detect possible changes in the dynamics of the two structures. Results of the simulation studies demonstrated higher mobility of the free structure when compared to the liganded one. Several amino acid residues were identified, flexibility of which is strongly affected upon UDP-GlcNAc binding. Importantly, the most fixed residues are those related to the inhibitor binding process and to the catalytic reaction. The obtained results constitute an important step toward understanding of mechanism of GlcN-6-P synthase inhibition by UDP-GlcNAc molecule

Kontekstowy, jednosektorowy, nieregularny model rozmyty oparty na 4 punktach wiedzy

W artykule przedstawiona została metoda konstruowania nieregularnego modelu rozmytego opartego na czterech punktach wiedzy eksperckiej. Nieregularne modele rozmyte różnią się znacznie od modeli regularnych, które oparte są na regularnym, prostokątnym podziale przestrzeni wejść. Posiadają one wiele zalet, m.in. pozwalają na znaczne zmniejszenie liczby reguł przy zachowaniu dokładności modelu rozmytego, czyli umożliwiają konstruowanie oszczędnych modeli rozmytych. Dzięki temu istnieje możliwość skutecznego pokonywania zjawiska "przekleństwa wymiarowości". Nieregularne modelowanie rozmyte nie jest chyba możliwe bez nowego układu współrzędnych. Układ taki nazwany został kontekstowym, nierównoległym układem współrzędnych, który jest uogólnieniem powszechnie stosowanego układu kartezjańskiego. Dla lepszego zrozumienia zagadnienia w artykule, w kilku krokach, przedstawiono sposób zastosowania kontekstowego układu współrzędnych w nieregularnym modelowaniu rozmytym. Metodę zilustrowano przykładem.The paper presents a method how to construct a non-regular fuzzy model based on 4 points of expert knowledge. Non-regular fuzzy models considerably differ from regular ones, which are based on the regular, rectangular partition of the input space. They allow for considerable decreasing the rule number and thus for constructing sparse models and for overcoming the phenomenon called "curse of dimensionality". Non-regular fuzzy modeling is rather not possible without a new coordinate system, which was called contextual, non-parallel coordinate system that also is described in the paper. The non-regular modeling method was illustrated by an example

Great potential of ultrasound elastography for the assessment of the masseter muscle in patients with temporomandibular disorders. A systematic review

Objective: To summarize the available evidence on the use of elastography in the assessment of the masseter muscle in healthy individuals and patients with masseter muscle disorders.Methods: Systematic literature review has been performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.Results: 16 of 142 studies identified were analyzed. Elastography was used in seven studies. Heterogeneity was observed in terms of study protocols, devices, patients, units of measure, and results. Elasticity values showed a correlation between the left and right masseter muscle side in healthy people, but not in patients with temporomandibular disorders (TMDs). Elasticity values increased in TMD and were correlated with the severity of TMD symptoms. Phantom studies proved the high reliability of elastography.Conclusion: Elastography is a promising tool for the assessment of the masseter muscle elasticity, but the evidence is insufficient. Studies on larger groups are needed to determine the accuracy of elastography to characterize masticatory muscle disorders.Radiolog