Endogenous antimicrobial peptides (AMPs) are evolutionary ancient molecular factors of innate immunity that play a key role in host defense. Among the most active and stable under physiological ...conditions AMPs are the peptides of animal origin that adopt a β-hairpin conformation stabilized by disulfide bridges. In this study, a novel BRICHOS-domain related AMP from the marine polychaeta
, named capitellacin, was produced as the recombinant analogue and investigated. The mature capitellacin exhibits high homology with the known β-hairpin AMP family-tachyplesins and polyphemusins from the horseshoe crabs. The β-hairpin structure of the recombinant capitellacin was proved by CD and NMR spectroscopy. In aqueous solution the peptide exists as monomeric right-handed twisted β-hairpin and its structure does not reveal significant amphipathicity. Moreover, the peptide retains this conformation in membrane environment and incorporates into lipid bilayer. Capitellacin exhibits a strong antimicrobial activity in vitro against a wide panel of bacteria including extensively drug-resistant strains. In contrast to other known β-hairpin AMPs, this peptide acts apparently via non-lytic mechanism at concentrations inhibiting bacterial growth. The molecular mechanism of the peptide antimicrobial action does not seem to be related to the inhibition of bacterial translation therefore other molecular targets may be assumed. The reduced cytotoxicity against human cells and high antibacterial cell selectivity as compared to tachyplesin-1 make it an attractive candidate compound for an anti-infective drug design.
The article’s relevance lies in need for empirical testing of theoretical concepts in the new economic conditions caused by the corona crisis. The purpose of the paper is to identify the ...manifestations of macroeconomic instability in the period before and after the pandemic and to demonstrate the effectiveness of the use of fiscal instruments of regulatory competition to achieve the goals of the stabilization policy of the governments of countries with developed economies. The research is based on the categories of theoretical and empirical levels of knowledge. The use of the method of analysis, abstraction and synthesis, induction and deduction, as well as the system-structural method, the method of idealization, made it possible to identify new forms of manifestation of the phenomenon of fiscal regulatory competition and establish its place in the implementation of the stabilization and incentive programs of the government. It was found that the stimulation of economic activity and the increase in net exports using the instruments of fiscal neo-protectionism occurs due to a simultaneous increase in employment and a decrease in the cost of domestically produced goods, accompanied by the rise in relative consumer prices for imported goods. Using economic analysis and mathematical modelling methods confirmed the hypothesis about the stimulating effect of fiscal policy. Based on the regression analysis of the mechanism of the fiscal channel of the stabilization policy of developed countries, which influenced the dynamics of the conjuncture in the period from 2018 to 2022, a conclusion was drawn regarding the strength of its impulse. It has been found that the fiscal channel less clearly transmits the impulse from the growth of expenditures (financed by loans) to the real sector. It is assumed that in the process of signal transmission, it scatters. It has been established that in the short term, in a recession, the fiscal impulse also does not cause a jump in inflation. In the context of inflationary growth in the United States, Japan, and Germany, there is a turn towards tightening monetary policy, which limits the use of financial instruments to counter the recession and therefore increases the demand for the benefit of fiscal tools to counter the recession
The article explores the methodological principles of the national security strategy development and the ways of their improvement in order to more effectively respond to modern challenges, threats ...and changes in the security environment. Author proves the necessity of further development of the theoretical foundations of national security taking into account the concept of national resilience. The role of the national security strategy in the system of medium and long-term planning in the field of national security is determined. The evolution of the Strategy of National Security of Ukraine since the adoption of its first edition is researched. Recommendations on preparation of a new edition of the National Security Strategy of Ukraine in accordance with the requirements of the Law of Ukraine "On National Security of Ukraine" are developed. The principles of ensuring national resilience are determined. The most important of them are comprehensive approach, collaboration, awareness, continuity, preparedness, and communications. The introduction of these principles allows to modernize the system of ensuring national security in order to adapt it to the rapid changes of the modern security environment and the impact of threats of the hybrid type. Author proves that there is no reason to talk about replacing the system of ensuring national security with the system of ensuring national resilience. As well there is no need for the parallel operation of the both systems. It is more rational to ensure national security on the principles of national resilience, since it can cause a synergistic effect in the form of new qualitiesof the national security system. At the same time, it allows to improve the effectiveness of counteracting modern threats and challenges, as well as rational use of limited state resourcessignificantly. It is proved that the key principles of building national resilience should be reflected in the new strategic documents of the state, first of all, in the National Security Strategy of Ukraine.
In recent years, there has been an increasing tendency to create drugs based on certain commensal bacteria of the human microbiota and their ingredients, primarily focusing on live biotherapeutics ...(LBPs) and postbiotics. The creation of such drugs, termed pharmacobiotics, necessitates an understanding of their mechanisms of action and the identification of pharmacologically active ingredients that determine their target properties. Typically, these are complexes of biologically active substances synthesized by specific strains, promoted as LBPs or postbiotics (including vesicles): proteins, enzymes, low molecular weight metabolites, small RNAs, etc. This study employs omics technologies, including genomics, proteomics, and metabolomics, to explore the potential of Limosilactobacillus fermentum U-21 for innovative LBP and postbiotic formulations targeting neuroinflammatory processes. Proteomic techniques identified and quantified proteins expressed by L. fermentum U-21, highlighting their functional attributes and potential applications. Key identified proteins include ATP-dependent Clp protease (ClpL), chaperone protein DnaK, protein GrpE, thioredoxin reductase, LysM peptidoglycan-binding domain-containing protein, and NlpC/P60 domain-containing protein, which have roles in disaggregase, antioxidant, and immunomodulatory activities. Metabolomic analysis provided insights into small-molecule metabolites produced during fermentation, revealing compounds with anti-neuroinflammatory activity. Significant metabolites produced by L. fermentum U-21 include GABA (γ-aminobutyric acid), niacin, aucubin, and scyllo-inositol. GABA was found to stabilize neuronal activity, potentially counteracting neurodegenerative processes. Niacin, essential for optimal nervous system function, was detected in vesicles and culture fluid, and it modulates cytokine production, maintaining immune homeostasis. Aucubin, an iridoid glycoside usually secreted by plants, was identified as having antioxidant properties, addressing issues of bioavailability for therapeutic use. Scyllo-inositol, identified in vesicles, acts as a chemical chaperone, reducing abnormal protein clumps linked to neurodegenerative diseases. These findings demonstrate the capability of L. fermentum U-21 to produce bioactive substances that could be harnessed in the development of pharmacobiotics for neurodegenerative diseases, contributing to their immunomodulatory, anti-neuroinflammatory, and neuromodulatory activities. Data of the HPLC-MS/MS analysis are available via ProteomeXchange with identifier PXD050857.
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Most studies of the current crisis in the EU electricity sector offer a simplified approach to the interpretation of its dynamics and causes. In this article, the approach is expanded, i.e., first, ...the crisis in the European electricity sector is considered taking into account the long-term trends of its development. Second, the main trends in the performance of individual electricity sectors and in the context of EU member countries are analyzed in detail. This approach allowed us to draw the following fundamental conclusions: the crisis in the EU electricity sector began in 2021 and was caused by the mistakes of regulators who excessively urged the construction of generating capacities in “green” energy and decommissioning of capacities that traditionally provided basic loading in the system; the crisis of 2022 was provoked by the unreliability of nuclear generation due to the obsolescence of reactors, as well as the failure of hydropower due to long-term climate change. The exogenous shock generated by the geopolitical crisis in and around Ukraine became an important factor in the outbreak of a protracted crisis in the European electricity sector. The European Commission and some major European countries proposed to accelerate the construction of generating capacities in solar and wind energy to overcome the crisis, while shifting the costs of the energy transition, the price of which has noticeably increased, to end consumers of electricity. There is a representative group of countries in the EU whose national climate strategies are based, among other things, on promoting nuclear energy, which requires the development of the capacity market; in general, energy prices in the EU soared and further development of “green” energy will by all means push electricity prices up.
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The article analyzes the energy transformation trends in the three largest economic centers that set the dynamics of the global energy transition. It is concluded that the structure and speed of ...the energy transition are determined by the specific conditions of development and the individual characteristics of countries and integration associations. The United States has set a course for the accelerated development of “green energy,” which has taken a central place in industrial policy. Particular attention is paid to the development of natural solutions for the purposes of decarbonization. In Europe, the energy crisis that began in the second half of 2021 is far from over. The European Commission and industry regulators believe that the fundamental cause of the crisis lies in the insufficient speed of the energy transition and are trying to force it through the advancing development of wind and solar generation and mechanisms such as greenhouse gas emissions trading and cross-border carbon regulation. Faced with the problem of maintaining sufficiently high economic growth rates, China, on the one hand, continues to rely on coal energy, on the other hand, it is rapidly building generating capacities on new renewable energy sources. The PRC is also experimenting with climate policy mechanisms such as carbon trading and natural solutions. The modern energy transition is developing in the expectation that large-scale and diverse state support will allow, by the end of this decade, to create effective market solutions in key technologies that support the transition. The United States and China are taking a more pragmatic course and relying more on market solutions. In Europe, ideological attitudes have a strong influence on the energy transition.
The purpose of the study is to characterize the phenomena of "digital inequality" and "digital divide" from the standpoint of global challenges of socio-economic development and international trade ...in the context of techno-globalism. It is argued that technoglobalism is both a kind of constructor of a new economic reality, in which technology is entrusted with the function of a generator of economic development and growth, and the result of increased asymmetries of international division in the context of the transnationalization of the world economy: on the one hand, governments of countries and corporations in the conditions of innovative rivalry all they compete more actively for the opportunity to develop new market niches, taking a course towards the technological complication of products that are in the arsenal of their specialization, not avoiding the use of market distortion and protectionism tools, despite the development of new forms of public-private partnership; on the other hand, although the geopolitical struggle, often centered around the issue of digital patents, standards and production, significantly weakens multilateral decision-making and collective action in the field of innovation, the growth of international scientific and technological cooperation, the intensification of the exchange of patents and licenses, the diffusion of knowledge through channels of exchange of scientific personnel, testify to the inevitability of a global technological dialogue. The analysis made it possible to establish that the digital divide is most clearly manifested, firstly, in the use of digital technologies (due to the availability of basic infrastructure, accessibility, etc.), secondly, in the benefits received from digital technologies, and, thirdly, in the level of digital skills. The parameters by which the digital divide is defined include mainly the state of development of a country compared to other countries (capacity gap, participation gap, performance gap), the state of development of urban and rural areas and their populations, indicators of individual income, level of education, age structures (access gap, literacy gap, use gap) within a country and compared between countries. Because this digital divide exists in all digital technologies, it has the potential to widen. The digital transformation of the economy is accompanied by an increase in demand for automation of production processes, resulting in an unlimited pool of robotic workforce in a sector prone to automation, distorting the international labor market. This "reserve army of robots" is gradually displacing the workforce from the automation-prone sector to the automationresistant sector, in a process that can be called "digital crowding out" and accompanied by rising unemployment and lower wage costs, indicating a worsening social economic inequality. Although income inequality in most developed countries has been increasing even before the spread of global dominance of technology companies, it can be assumed that the further spread of ICT will increase the sources of income of market participants who use digital technologies. Outlined is a manifestation of the network effect in markets where the value of the product increases with each additional unit sold/produced, then the early advantage allows for increased value for each subsequent user, creating a Matthew effect. Keywords: socio-economic development, global inequality, technological development, innovative development, technoglobalism, digital economy, digital divide, digital inequality, digital business models, digital trade, international trade, world economy, labor market, unemployment, pandemic.
The change of the global climate is most pronounced in
the Arctic, where the air temperature increases 2 to 3 times faster
than the global average. This process is associated with an increase in the
...concentration of greenhouse gases in the atmosphere. There are publications
predicting the sharp increase in methane emissions into the atmosphere due
to permafrost thawing. Therefore, it is important to study how the air
composition in the Arctic changes in the changing climate. In the Russian
sector of the Arctic, the air composition was measured only in the surface
atmospheric layer at the coastal stations or earlier at the drifting
stations. Vertical distributions of gas constituents of the atmosphere and
aerosol were determined only in a few small regions. That is why the
integrated experiment was carried out to measure the composition of the
troposphere in the entire Russian sector of the Arctic from on board the
Optik Tu-134 aircraft laboratory in the period of 4 to 17 September of 2020.
The aircraft laboratory was equipped with contact and remote measurement
facilities. The contact facilities were capable of measuring the
concentrations of CO2, CH4, O3, CO, NOx, and SO2,
as well as the disperse composition of particles in the size range from 3 nm
to 32 µm, black carbon, and organic and inorganic components of
atmospheric aerosol. The remote facilities were operated to measure the
water transparency in the upper layer of the ocean, the chlorophyll content
in water, and spectral characteristics of the underlying surface. The
measured data have shown that the ocean continues absorbing CO2. This
process is most intense over the Barents and Kara seas. The recorded methane
concentration was increased over all the Arctic seas, reaching 2090 ppb in
the near-water layer over the Kara Sea. The contents of other gas components
and black carbon were close to the background level. In bioaerosol, bacteria predominated among the identified microorganisms. In
most samples, they were represented by coccal forms, less often
spore-forming and non-spore-bearing rod-shaped bacteria. No dependence of
the representation of various bacterial genera on the height and the
sampling site was revealed. The most turbid during the experiment was the
upper layer of the Chukchi and Bering seas. The Barents Sea turned out to be
the most transparent. The differences in extinction varied by more than a factor of 1.5. In all measurements, except for the Barents Sea, the tendency of an
increase in chlorophyll fluorescence in more transparent waters was
observed.
Capitellacin is the β-hairpin membrane-active cationic antimicrobial peptide from the marine polychaeta
. Capitellacin exhibits antibacterial activity, including against drug-resistant strains. To ...gain insight into the mechanism of capitellacin action, we investigated the structure of the peptide in the membrane-mimicking environment of dodecylphosphocholine (DPC) micelles using high-resolution NMR spectroscopy. In DPC solution, two structural forms of capitellacin were observed: a monomeric β-hairpin was in equilibrium with a dimer formed by the antiparallel association of the
-terminal β-strands and stabilized by intermonomer hydrogen bonds and Van der Waals interactions. The thermodynamics of the enthalpy-driven dimerization process was studied by varying the temperature and molar ratios of the peptide to detergent. Cooling the peptide/detergent system promoted capitellacin dimerization. Paramagnetic relaxation enhancement induced by lipid-soluble 12-doxylstearate showed that monomeric and dimeric capitellacin interacted with the surface of the micelle and did not penetrate into the micelle interior, which is consistent with the "carpet" mode of membrane activity. An analysis of the known structures of β-hairpin AMP dimers showed that their dimerization in a membrane-like environment occurs through the association of polar or weakly hydrophobic surfaces. A comparative analysis of the physicochemical properties of β-hairpin AMPs revealed that dimer stability and hemolytic activity are positively correlated with surface hydrophobicity. An additional positive correlation was observed between hemolytic activity and AMP charge. The data obtained allowed for the provision of a more accurate description of the mechanism of the oligomerization of β-structural peptides in biological membranes.
The relevance of the study lies in the consideration of transmission channels through which the influence of monetary policy carried out by the governments and central banks of the United States, ...Japan and Germany was realized. The purpose of the article is to consider the phenomenon of the monetary trap as a special case of an unforeseen macroeconomic reaction to the stabilization anti-crisis policy pursued by the state, which is designed to stimulate economic activity and contribute to the growth of aggregate output. The article identified the potential of economic theory (with an emphasis on the New Macroeconomic Consensus) to illuminate the current practice of state stabilization policy, taking into account new historical challenges, as well as modeling the impact of monetary instruments of stabilization policy on the potential for economic recovery of the United States, Japan and Germany. To achieve the goal of the study, scientific and special research methods were used, namely: methods of analysis, abstraction and synthesis, induction and deduction, as well as a system-structural method; hypothetical-deductive method; idealization method; methods of economic and mathematical modeling. An analysis of the consequences of the state policy to counteract the downturn in the economic situation as a result of the COVID-19 pandemic made it possible to periodize it and establish that the stabilization measures at the first stage were mainly of a fiscal nature, while at the second stage they were focused on monetary containment of the volatility of commodity prices. A regression express analysis of the relationship between monetary incentives and changes in GDP and inflation in the United States, Japan, and Germany made it possible to establish that the influence of monetary impulses on price stability manifests itself over a longer period of time and depends on the influence of many factors, including price fluctuations, changes in nominal wages, exchange rate dynamics and expectations of economic agents.
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