Чинники підвищення конкурентоспроможності вищої освіти в концепції сталого розвитку держави

The article is devoted to the selection and research of factors for increasing the competitiveness of higher education within the framework of the concept of sustainable development of the state. The theoretical and methodological basis of this research is the fundamental provisions of management, social sciences, economic theory, as well as a wide range of general scientific and special research methods, including the system method, the method of analysis and synthesis, the method of induction and deduction, the graphic method, and others. It has been proven that one of the essential problems of the higher education system in the context of ensuring sustainable development at the stage of its transformation is increasing competitiveness. The study of this definition made it possible to reflect the view on its understanding and revealed the dependence of this category on many factors, such as: political, socio-economic, socio-cultural, demographic, normative-legal and innovative-technological, which act in a complex manner, exerting a systemic influence.Стаття присвячена виокремленню та дослідженню факторів підвищення конкурентоспроможності вищої освіти в рамках концепції сталого розвитку держави. Теоретико-методологічною основою даного дослідження є фундаментальні положення менеджменту, суспільних наук, економічної теорії, а також широкий спектр загальнонаукових і спеціальних методів дослідження, зокрема системний метод, метод аналізу та синтезу, метод індукція і дедукція, графічний метод та ін. Доведено, що однією з суттєвих проблем системи вищої освіти в контексті забезпечення сталого розвитку на етапі її трансформації є підвищення конкурентоспроможності. Дослідження даного визначення дозволило відобразити погляд на його розуміння та виявило залежність даної категорії від багатьох факторів, таких як: політичні, соціально-економічні, соціокультурні, демографічні, нормативно-правові та інноваційно-технологічні, які діють комплексно, надаючи системний вплив

Conformational landscapes of DNA polymerase I and mutator derivatives establish fidelity checkpoints for nucleotide insertion

The fidelity of DNA polymerases depends on conformational changes that promote the rejection of incorrect nucleotides before phosphoryl transfer. Here, we combine single-molecule FRET with the use of DNA polymerase I and various fidelity mutants to highlight mechanisms by which active-site side chains influence the conformational transitions and free-energy landscape that underlie fidelity decisions in DNA synthesis. Ternary complexes of high fidelity derivatives with complementary dNTPs adopt mainly a fully closed conformation, whereas a conformation with a FRET value between those of open and closed is sparsely populated. This intermediate-FRET state, which we attribute to a partially closed conformation, is also predominant in ternary complexes with incorrect nucleotides and, strikingly, in most ternary complexes of low-fidelity derivatives for both correct and incorrect nucleotides. The mutator phenotype of the low-fidelity derivatives correlates well with reduced affinity for complementary dNTPs and highlights the partially closed conformation as a primary checkpoint for nucleotide selection

Antimicrobial Nanoplexes meet Model Bacterial Membranes: the key role of Cardiolipin

Antimicrobial resistance to traditional antibiotics is a crucial challenge of medical research. Oligonucleotide therapeutics, such as antisense or Transcription Factor Decoys (TFDs), have the potential to circumvent current resistance mechanisms by acting on novel targets. However, their full translation into clinical application requires efficient delivery strategies and fundamental comprehension of their interaction with target bacterial cells. To address these points, we employed a novel cationic bolaamphiphile that binds TFDs with high affinity to form self-assembled complexes (nanoplexes). Confocal microscopy revealed that nanoplexes efficiently transfect bacterial cells, consistently with biological efficacy on animal models. To understand the factors affecting the delivery process, liposomes with varying compositions, taken as model synthetic bilayers, were challenged with nanoplexes and investigated with Scattering and Fluorescence techniques. Thanks to the combination of results on bacteria and synthetic membrane models we demonstrate for the first time that the prokaryotic-enriched anionic lipid Cardiolipin (CL) plays a key-role in the TFDs delivery to bacteria. Moreover, we can hypothesize an overall TFD delivery mechanism, where bacterial membrane reorganization with permeability increase and release of the TFD from the nanoplexes are the main factors. These results will be of great benefit to boost the development of oligonucleotides-based antimicrobials of superior efficacy

siRNA-Like Double-Stranded RNAs Are Specifically Protected Against Degradation in Human Cell Extract

RNA interference (RNAi) is a set of intracellular pathways in eukaryotes that controls both exogenous and endogenous gene expression. The power of RNAi to knock down (silence) any gene of interest by the introduction of synthetic small-interfering (si)RNAs has afforded powerful insight into biological function through reverse genetic approaches and has borne a new field of gene therapeutics. A number of questions are outstanding concerning the potency of siRNAs, necessitating an understanding of how short double-stranded RNAs are processed by the cell. Recent work suggests unmodified siRNAs are protected in the intracellular environment, although the mechanism of protection still remains unclear. We have developed a set of doubly-fluorophore labeled RNAs (more precisely, RNA/DNA chimeras) to probe in real-time the stability of siRNAs and related molecules by fluorescence resonance energy transfer (FRET). We find that these RNA probes are substrates for relevant cellular degradative processes, including the RNase H1 mediated degradation of an DNA/RNA hybrid and Dicer-mediated cleavage of a 24-nucleotide (per strand) double-stranded RNA. In addition, we find that 21- and 24-nucleotide double-stranded RNAs are relatively protected in human cytosolic cell extract, but less so in blood serum, whereas an 18-nucleotide double-stranded RNA is less protected in both fluids. These results suggest that RNAi effector RNAs are specifically protected in the cellular environment and may provide an explanation for recent results showing that unmodified siRNAs in cells persist intact for extended periods of time