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The work presents results of the in vitro and in silico study of formation of amyloid-like structures under harsh denaturing conditions by non-specific OmpF porin of Yersinia pseudotuberculosis (YpOmpF), a membrane protein with β-barrel conformation. It has been shown that in order to obtain amyloid-like porin aggregates, preliminary destabilization of its structure in a buffer solution with acidic pH at elevated temperature followed by long-term incubation at room temperature is necessary. After heating at 95°C in a solution with pH 4.5, significant conformational rearrangements are observed in the porin molecule at the level of tertiary and secondary structure of the protein, which are accompanied by the increase in the content of total β-structure and sharp decrease in the value of characteristic viscosity of the protein solution. Subsequent long-term exposure of the resulting unstable intermediate YpOmpF at room temperature leads to formation of porin aggregates of various shapes and sizes that bind thioflavin T, a specific fluorescent dye for the detection of amyloid-like protein structures. Compared to the initial protein, early intermediates of the amyloidogenic porin pathway, oligomers, have been shown to have increased toxicity to the Neuro-2aCCL-131™ mouse neuroblastoma cells. The results of computer modeling and analysis of the changes in intrinsic fluorescence during protein aggregation suggest that during formation of amyloid-like aggregates, changes in the structure of YpOmpF affect not only the areas with an internally disordered structure corresponding to the external loops of the porin, but also main framework of the molecule, which has a rigid spatial structure inherent to β-barrel. [ABSTRACT FROM AUTHOR]

Information about potential earthquake sources is a key issue for seismic hazard assessment. This study presents the application of a phenomenological approach based on pattern recognition to determine the possible locations of strong earthquakes in the Bulgarian region. The technique assumes the origin of strong earthquakes in morphostructural nodes formed around the intersections of morphostructural lineaments identified by morphostructural zoning. For the territory of the Bulgaria and neighbouring regions, 178 nodes were defined in this work. The CORA-3 pattern recognition algorithm identified 59 seismogenic nodes analysing a set of geophysical and geological node's characteristics. The identified seismogenic nodes are capable to generate earthquakes with magnitude equal to or greater than 6 and are located at the boundaries between the largest tectonic domains: Rila, Pirin, and Rhodope orogens; the Serbian-Macedonian massif; and in the Stara Planina belt. The set of characteristic features of seismogenic nodes indicates that the vicinity of potential nodes is characterized by a high contrast of neotectonic movements of the Earth's crust and the presence of deep heterogeneities in the Earth's crust. About 40% of the recognized nodes are not associated with any earthquakes, while the rest of the recognized seismogenic nodes are characterized by an area with a radius of 25 km where earthquakes are known to occur. Part of these "non active" seismogenic nodes are close to the historical events with magnitudes higher than 5.5 since the magnitude and location of historical events have large uncertainties. Another part of the seismogenic nodes may slightly change the location due to the uncertainties in morphostructural zonation. Other nodes may indicate unknown historical seismicity or paleoearthquakes. Defined M6+ seismogenic nodes can fill the potential gaps in the recorded seismicity on the territory of Bulgaria, thus to improve the seismic hazard assessment of the studied region. [ABSTRACT FROM AUTHOR]

The relevance of this study is due to the specifics of the subculture global context, supplemented by a semantic paradigm determined by the linguistic and cultural traditions and the social and cultural background of the Russian language community. The study aims to identify the perception of proper names in rap texts, their axiological understanding as cultural dominants that make up the individual cognitive base. Based on the conducted research, the proper name property to act as metaphorical intertextual signs of conceptualization and categorization of the real world, inherent for rap discourse, has been established. [ABSTRACT FROM AUTHOR]

The rheological, mechanical, and electrical properties and structure of rods and wires made of aluminum alloy concentration of 1% REM (0.6% Ce and 0.4% La) are investigated and presented. The rods were produced by combined rolling-extrusion (CRE) from two different types of billets: casting into a mold 14×14 mm and into electromagnetic mold (EMM) Ø12.5 mm. A database of the DEFORM 3D complex was created for computer modeling of the CRE process. The tensile strength of rods Ø9 and 5 mm obtained using CRE method is 120–140 MPa and elongation to failure is 15–26% for billets from EMM. For billets 14×14 mm, the ultimate tensile strength is 112–125 MPa, which is comparatively lower than that of rods made from round billets (elongation to failure is 26–34%). The plastic properties of the final wire Ø2 mm from a round billet after EMM are higher than wire Ø2 mm from a billet obtained by casting into a mold 14×14 mm. Rods after CRE from both types of billets are characterized by fairly high ductility. To obtain Ø2-mm wire from rods, no intermediate annealing was required. The values of electrical resistance are taken from 0.02271 to 0.0301 Ω‧mm2/m for rods from 12.5-mm billets and from 0.02776 to 0.03413 Ω‧mm2/m for rods from billets 14×14 mm. The electrical resistance values for wire Ø2 mm from billets 14×14 mm are higher than for wire obtained from rods after EMM. Microstructure shows that the final wire after CRE from billet in EMM has a more extensive structure than after CRE from billets with dimensions of 14×14 mm. [ABSTRACT FROM AUTHOR]

It was found that a single-dose immunization of mice with Yersiniapseudotuberculosis porins OmpF and OmpC causes development of pathological changes in the deep layers of cerebral cortex characterized by dystrophic changes in the cells against the background of the increasing titer of specific antibodies. At the same time, the increased level of caspase-3 expression is observed in the neurons, which indicates induction of proapoptotic signaling pathways. The obtained results indicate potential ability of nonspecific pore-forming proteins of the outer membrane of Gram-negative bacteria to initiate development of degenerative changes in brain cells. [ABSTRACT FROM AUTHOR]

• The new mono- and bis(aminomethylenediphosphonic) acids are synthesized in the presence of Me 3 SiOTf as a catalyst. • The catalytic schema of the resulting compounds syntheses include the formation of highly reactive iminium salts. • The target substances are structural analogues of well-known drugs and may be considered as promising polydentate ligands, antibacterial and antiviral compounds. The new mono- and bis(aminomethylenediphosphonic) acids are synthesized for the first time via unique reaction of tris(trimethylsilyl) phosphite and various N -formyl amino alkanols or bis(N -formyl amino) alkanes at the presence of effective catalyst – trimethylsilyl triflate under mild conditions. The further treatment of initially formed trimethylsilyl intermediates with the methanol excess resulted in the crystalline mono- and bis(aminomethylenediphosphonic) acids in high yields. The catalytic scheme of target substances formation is proposed and discussed in detail. The structures of target acids were confirmed by the 1H, 13C, 31P NMR spectra and high resolution mass spectra (HRMS). The resulting compounds are of great interest as perspective bioactive substances with versatile properties and effective polydentate ligands. [Display omitted] [ABSTRACT FROM AUTHOR]

• Study assesses HIV DRM among individuals experiencing ART failure in Russia. • 61.5% of study patients had HIV DRM detected. • 38.5% of patients had no DRM point at the insufficient ART adherence. • Observed DRM profiles differ between adults and children. • Region, gender, VL level and CD4 cell count had associations with DRM. Increasing HIV drug resistance is an important public health concern. The current study aimed to assess HIV drug resistance among people who live with HIV (PLWH) experiencing virological failure. Blood samples and epidemiological characteristics were collected in four Siberian regions from PLWH experiencing ART failure. Partial pol gene sequences were obtained for the study individuals. Drug resistance mutations (DRMs) were predicted using the Stanford HIVdb Program. The association of HIV DRM with epidemiological characteristics was estimated using logistic regression analysis. Further analysis was performed for children (0–14 y old) and adults (≥15 y old) separately. In total, 815 (89.4%) patients were included in the final dataset. Overall, 501 (61.5%) patients had DRM detected. NRTI DRM was more common in children, while NRTI+NNRTI DRM was more frequent in adults (P < 0.001). Krasnoyarsk region, male sex and high viral load were positively associated with the presence of DRM in adults, while higher CD4 cell count and PI/INSTI-based ART had a negative association. No association between epidemiological characteristics and DRM was identified in children. The remaining 38.5% of patients with virological failure had no DRM detected; those patients were likely to have insufficient ART adherence. Most (55.5%) patients had HIV CRF63_02A6, followed by sub-subtype A6 (39.2%). This study revealed poor ART adherence as a main factor driving ART failure among PLWH in the Siberian region. DRM was detected in over 60% of PLWH experiencing ART failure. The current results highlight an urgent need for the introduction of special programs focusing on ART adherence improvement. [Display omitted] [ABSTRACT FROM AUTHOR]

The recombinant OmpF porin of Yersinia pseudotuberculosis as a model of transmembrane protein of the β-barrel structural family was used to study low growth temperature effect on the structure of the produced inclusion bodies (IBs). This porin showed a very low expression level in E. coli at a growth temperature below optimal 37 °C. The introduction of a N-terminal hexahistidine tag into the mature porin molecule significantly increased the biosynthesis of the protein at low cultivation temperatures. The recombinant His-tagged porin (rOmpF-His) was expressed in E. coli at 30 and 18 °C as inclusion bodies (IB-30 and IB-18). The properties and structural organization of IBs, as well as the structure of rOmpF-His solubilized from the IBs with urea and SDS, were studied using turbidimetry, electron microscopy, dynamic light scattering, optical spectroscopy, and amyloid-specific dyes. IB-18, in comparison with IB-30, has a higher solubility in denaturants, suggesting a difference between IBs in the conformation of the associated polypeptide chains. The spectroscopic analysis revealed that rOmpF-His IBs have a high content of secondary structure with a tertiary-structure elements, including a native-like conformation, the proportion of which in IB-18 is higher than in IB-30. Solubilization of the porin from IBs is accompanied by a modification of its secondary structure. The studied IBs also contain amyloid-like structures. The results obtained in this study expand our knowledge of the structural organization of IBs formed by proteins of different structural classes and also have a contribution into the new approaches development of producing functionally active recombinant membrane proteins. [Display omitted] • Yersinia pseudotuberculosis OmpF porin forms the inclusion bodies (IBs) when expressed in E. coli. • N-terminal hexahistidine tag is required for efficient expression of the recombinant porin at low cultivation temperatures. • Porin species in native-like conformation are present in IBs and their content increases with decreasing growth temperature. • CD spectroscopy in combination with stepwise IB solubilization provides valid information on the porin secondary structure. [ABSTRACT FROM AUTHOR]

This work aims to obtain new transformations and auto-Bäcklund transformations for generalized Liouville equations with exponential nonlinearity having a factor depending on the first derivatives. This paper discusses the construction of Bäcklund transformations for nonlinear partial second-order derivatives of the soliton type with logarithmic nonlinearity and hyperbolic linear parts. The construction of transformations is based on the method proposed by Clairin for second-order equations of the Monge–Ampere type. For the equations studied in the article, using the Bäcklund transformations, new equations are found, which make it possible to find solutions to the original nonlinear equations and reveal the internal connections between various integrable equations. [ABSTRACT FROM AUTHOR]

• The new methylenediphosphonates with non-proteinogenic amino acid and aminosulfonic acid moieties are synthesized in the presence of Me 3 SiOTf as a catalyst. • The catalytic schema of the resulting compounds syntheses include the formation of highly reactive iminium salts. • The target substances are structural analogues of well-known drugs and may be considered as promising polydentate ligands, antibacterial and antiviral compounds. The new non-proteinogenic amino acids with methylenebisphosphonic acids moieties are synthesized for the first time via unique reaction of tris(trimethylsilyl) phosphite and various N -formyl amino acids at the presence of effective catalyst – trimethylsilyl triflate under mild conditions. The further treatment of initially formed trimethylsilyl intermediates with the methanol excess resulted in the water-soluble non-proteinogenic amino acids with methylenebisphosphonic acids moieties in high yields. The catalytic scheme of target substances formation is proposed and discussed in detail. The structures of target functionalized amino acids and their precursors were confirmed by the 1H, 13C, 31P NMR spectra and high resolution mass spectra. The resulted compounds are of great interest as promising antiviral substances and effective ligands. [Display omitted] [ABSTRACT FROM AUTHOR]