A tendency to dimerize in the presence of lipids was found for the protegrin. The dimer formation by the protegrin-1 (PG-1) is the first step for further oligomeric membrane pore formation. Generally there are two distinct model of PG-1 dimerization in either a parallel or antiparallel β-sheet. But despite the wealth of data available today, protegrin dimer structure and pore formation is still not completely understood. In order to investigate a more detailed dimerization process of PG-1 and if it will be the same for another type of protegrins, in this work we used a high-resolution NMR spectroscopy for structure determination of protegrin-3 (RGGGL-CYCRR-RFCVC-VGR) in the presence of perdeuterated DPC micelles and demonstrate that PG-3 forms an antiparallel NCCN dimer with a possible association of these dimers. This structural study complements previously published solution, solid state and computational studies of PG-1 in various environments and validate the potential of mean force simulations of PG-1 dimers and association of dimers to form octameric or decameric β-barrels.

Middle cerebral artery flow pulsatility and basilar artery velocity are higher in patients with right-sided migraine compared with left-sided migraineurs, during the headache-free period. Although these parameters were similar to controls, the differences found during the headache-free period in migraineurs may indicate vascular involvement predisposing to the unilateral headache recurrence.

Protegrin pore formation is believed to occur in a stepwise fashion that begins with a nonspecific peptide interaction with the negatively charged bacterial cell walls via hydrophobic and positively charged amphipathic surfaces. There are five known nature protegrins (PG1-PG5), and early studies of PG-1 (PDB ID:1PG1) shown that it could form antiparallel dimer in membrane mimicking environment which could be a first step for further oligomeric membrane pore formation. Later, we solved PG-2 (PDB ID:2MUH) and PG-3 (PDB ID:2MZ6) structures in the same environment and for PG-3 observed a strong d NOE effects between residues R18 and F12, V14, and V16. These "inconsistent" with monomer structure NOEs appears due to formation of an additional antiparallel β-sheet between two monomers. It was also suggested that there is a possible association of protegrins dimers to form octameric or decameric β-barrels in an oligomer state. In order to investigate a more detailed oligomerization process of protegrins, in the present article we report the monomer (PDB ID: 2NC7) and octamer pore structures of the protegrin-5 (PG-5) in the presence of DPC micelles studied by solution NMR spectroscopy. In contrast to PG-1, PG-2, and PG-3 studies, for PG-5 we observed not only dimer NOEs but also several additional NOEs between side chains, which allows us to calculate an octamer pore structure of PG-5 that was in good agreement with previous AFM and PMF data.

PG-1 adopts a dimeric structure in dodecylphosphocholine (DPC) micelles, and a channel is formed by the association of several dimers but the molecular mechanisms of the membrane damage by non-α-helical peptides are still unknown. The formation of the PG-1 dimer is important for pore formation in the lipid bilayer, since the dimer can be regarded as the primary unit for assembly into the ordered aggregates. It was supposed that only 12 residues (RGGRL-CYCRR-RFCVC-V) are needed to endow protegrin molecules with strong antibacterial activity and that at least four additional residues are needed to add potent antifungal properties. Thus, the 16-residue protegrin (PG-2) represents the minimal structure needed for broad-spectrum antimicrobial activity encompassing bacteria and fungi. As the peptide conformation and peptide-to-membrane binding properties are very sensitive to single amino acid substitutions, the solution structure of PG-2 in solution and in a membrane mimicking environment are crucial. In order to find evidence if the oligomerization state of PG-1 in a lipid environment will be the same or not for another protegrins, we investigate in the present work the PG-2 NMR solution structure in the presence of perdeuterated DPC micelles. The NMR study reported in the present work indicates that PG-2 form a well-defined structure (PDB: 2MUH) composed of a two-stranded antiparallel β-sheet when it binds to DPC micelles.

<p class="0abstract">The development of digital technologies necessitates the formation of digital literacy and entrepreneurship skills in the modern "digital generation". The study has as the objective to identify the aspects of consumer demand for educational services in the process of testing the conceptual model of mobile learning adapted to the modern business environment in the context of digital transformations of the socio-economic life. The concept of an educational course based on the Sakai mobile learning platform with a focus on the formation of digital literacy in the business segment has been proposed in the study. The educational and applied course "Entrepreneurship in the Digital Mode" was tested within the educational programs of the State University of Management (Lyubertsy, Russia) and Herzen State Pedagogical University of Russia (St. Petersburg, Russia). The experiment made it possible to identify key aspects of consumer demand for distance education based on the characteristics of the participants' perception of the advantages and effectiveness of mobile learning. Most participants confirmed their professional achievements and the fact of the implementation of personal educational goals. Mobile learning was described as an easy, comfortable, interesting, innovative and modern method of learning compared to traditional classroom lessons. In the process of mobile learning, students demonstrated an increase in personal responsibility and self-organization while practical classes and the synergy of the educational content with real business cases greatly contributed to their involvement and productivity. Until now, research has not dealt with real measurable in terms of real income from specific activities, the results of the application of mobile learning. The contribution of this study to the area under study is to establish pedagogical demands that can be satisfied with mobile learning.</p>