PHYSICOCHEMICAL CHARACTERIZATION OF RIBAVIRIN WITH SPECTROSCOPY AND MOLECULAR MODELING

This work was supported by Mendeleev University of Chemical Technology of Russia. Project Number K-003-2018

Amyloid Oligomer Conformation in a Group of Natively Folded Proteins

Recent in vitro and in vivo studies suggest that destabilized proteins with defective folding induce aggregation and toxicity in protein-misfolding diseases. One such unstable protein state is called amyloid oligomer, a precursor of fully aggregated forms of amyloid. Detection of various amyloid oligomers with A11, an anti-amyloid oligomer conformation-specific antibody, revealed that the amyloid oligomer represents a generic conformation and suggested that toxic β-aggregation processes possess a common mechanism. By using A11 antibody as a probe in combination with mass spectrometric analysis, we identified GroEL in bacterial lysates as a protein that may potentially have an amyloid oligomer conformation. Surprisingly, A11 reacted not only with purified GroEL but also with several purified heat shock proteins, including human Hsp27, 40, 70, 90; yeast Hsp104; and bovine Hsc70. The native folds of A11-reactive proteins in purified samples were characterized by their anti-β-aggregation activity in terms of both functionality and in contrast to the β-aggregation promoting activity of misfolded pathogenic amyloid oligomers. The conformation-dependent binding of A11 with natively folded Hsp27 was supported by the concurrent loss of A11 reactivity and anti-β-aggregation activity of heat-treated Hsp27 samples. Moreover, we observed consistent anti-β-aggregation activity not only by chaperones containing an amyloid oligomer conformation but also by several A11-immunoreactive non-chaperone proteins. From these results, we suggest that the amyloid oligomer conformation is present in a group of natively folded proteins. The inhibitory effects of A11 antibody on both GroEL/ES-assisted luciferase refolding and Hsp70-mediated decelerated nucleation of Aβ aggregation suggested that the A11-binding sites on these chaperones might be functionally important. Finally, we employed a computational approach to uncover possible A11-binding sites on these targets. Since the β-sheet edge was a common structural motif having the most similar physicochemical properties in the A11-reactive proteins we analyzed, we propose that the β-sheet edge in some natively folded amyloid oligomers is designed positively to prevent β aggregation

ТРАНСПЛАНТИРОВАННОЕ СЕРДЦЕ. ПРАВОЖЕЛУДОЧКОВАЯ НЕДОСТАТОЧНОСТЬ, ОТТОРЖЕНИЕ ИЛИ МИОКАРДИТ?

The differentiation of the cases of the right ventricular failure in transplanted heart should be complex and challenging. The 28-year old man with dilated cardiomyopathy underwent orthotopic heart transplantation. After transplantation developed right ventricular failure. The biopsy (n = 5) didn’t reveal any signs of myocardial rejection. There were noted some signs of inflammation in lateral right ventricular wall only by gated SPECT. The right ventricular failure increased and 6 months later there was successfully performed the heart retransplantation on the patient. The virusological study revealed the Epstein–Barr virus in myocardium. The explanted heart research excluded limphoproliferative disease by immunogystochemical tests. The final diagnosis is myocarditis. Дифференцирование причин правожелудочковой недостаточности пересаженного сердца должно быть комплексным. Мужчина 28 лет с дилатационной кардиомиопатией был подвергнут ортотопической трансплантации сердца. После трансплантации развилась прогрессирующая правожелудочковая недо- статочность. Биопсия (в количестве 5) не выявила признаков отторжения миокарда. Только при gated SPECT были отмечены признаки воспаления в боковой стенке ПЖ. Правожелудочковая недостаточность нарастала, и спустя 6 месяцев больному успешно была выполнена ретрансплантация сердца. Вирусоло- гическое исследование выявило наличие вируса Эпштейна–Барр в миокарде. Иммуногистохимические исследования эксплантированного сердца исключили лимфопролиферативное заболевание. Заключи- тельный диагноз – миокардит.

Micromechanical Properties of Injection-Molded Starch–Wood Particle Composites

The micromechanical properties of injection molded starch–wood particle composites were investigated as a function of particle content and humidity conditions. The composite materials were characterized by scanning electron microscopy and X-ray diffraction methods. The microhardness of the composites was shown to increase notably with the concentration of the wood particles. In addition,creep behavior under the indenter and temperature dependence were evaluated in terms of the independent contribution of the starch matrix and the wood microparticles to the hardness value. The influence of drying time on the density and weight uptake of the injection-molded composites was highlighted. The results revealed the role of the mechanism of water evaporation, showing that the dependence of water uptake and temperature was greater for the starch–wood composites than for the pure starch sample. Experiments performed during the drying process at 70°C indicated that the wood in the starch composites did not prevent water loss from the samples.Peer reviewe

Inorganic thin-film sensor membranes with PLD-prepared chalcogenide glasses: challenges and implementation

Chalcogenide glasses offer an excellent "challenge" for their use and implementation in sensor arrays due to their good sensor-specific advantages in comparison to their crystalline counterparts. This paper will give an introduction on the preparation of chalcogenide glasses in the thin-film state. First, single microsensors have been prepared with the methods of semiconductor technology. In a next step, three microsensors are implemented onto one single silicon substrate to an "one chip" sensor array. Different ion-selective chalcogenide glass membranes (PbSAgIAs2S3, CdSAgIAs2S3, CuAgAsSeTe and TlAgAsIS) were prepared by means of the pulsed laser deposition (PLD) process. The different sensor membranes and structures have been physically characterized by means of Rutherford backscattering spectrometry, scanning electron microscopy and video microscopy. The electrochemical behavior has been investigated by potentiometric measurements