Active Complex Research Articles

Improving the governance of a regional research network: from needs’ assessment to policy making

Abstract Clinical research is a pivotal element for the Emilia-Romagna (Italy) healthcare system. Since 2009, several regional legislative acts established that clinical research was one of healthcare workers’ institutional activity as well as healthcare assistance and recommended each public Hospitals and Local Health Trusts (LHTs) to set up a research infrastructure (RI) to support clinical researchers. The goal of this intervention was both to assess the regional RI organization and to design a policy fostering the development of a RIs’ regional network. Our work, that took place in one year, consists of three-steps conducting: (I) a survey on all 15 RIs to assess their organizational model; (II) an interview to the key informants of each RIs to assess their strengths and weaknesses; (III) a three-round Delphi survey to evaluate the stratification of the activities in terms of complexity. The survey showed a high level of heterogeneity among RIs in terms of organizational structure, activities, human and instrumental resources and strengths and weaknesses. For example technological, economic, and human resources were considered opportunities, although difficulty at hiring data managers emerged as a potential threat. The Delphi panel assigned 3 levels of complexity (low, medium, high) to each activity carried out by RIs: 14 (47%) were considered low (mandatory for all RIs); 11 (37%) were considered medium (needed in RIs with medium volume/complexity of research activities) and, lastly, only 1 (3%) was considered high (needed in RIs with high complexity of research activities); for 4 (13%) activities no consensus was reached. The survey showed high level of heterogeneity and fragmentation among regional RIs in terms of organization, activities, resources and support offered to researchers. It also identified which level of complexity each RI should have and proposed possible solutions fostering a regional network of RIs to improve research activities in our Region. Key messages • Research is a key element of any innovative healthcare system. Public research needs a strong coordination. • This work enabled policymakers to draft a policy based on evidence coming from stakeholders.

Synthesis, characterization, molecular docking and molecular dynamics simulations of novel 2,5-disubstituted-1,3,4-thiadiazole derivatives as potential cholinesterase/monoamine oxidase dual inhibitors for Alzheimer’s disease

Designing multi-targeted drugs (MTD) for Alzheimer’s disease (AD) is now one of the priorities for medicinal chemists, as the disease has a complicated not fully understood pathological nature and the approved mono-targeted drugs only alleviate the symptoms. In this study, the synthesis, spectral analyses and in vitro inhibition activity against cholinesterase (ChE) and monoamine oxidase (MAO) enzymes of a novel series of N-[5-(adamantan-1-yl)-1,3,4-thiadiazol-2-yl]-2-(4-un/substituted) cyclic secondary amino-acetamide/propanamide derivatives were done. Generally, derivatives were more selective against acetylcholinesterase (AChE) and h-MAO-B than butyrylcholinesterase (BChE) and h-MAO-A, respectively. Derivatives 4a, 4b, 3a, 3d and 3b ordered from the most potent to the least displayed significant inhibition against AChE. Also, derivatives 4a, 4b and 3a still maintained their significant inhibition against h-MAO-B in the same potency order, making them dual inhibitors and MTD candidates for AD. Binding interactions with several crucial amino acid residues for activity and selectivity as well as the stability of the most active derivatives-enzyme complex were confirmed utilizing molecular docking and molecular dynamic simulation studies. Communicated by Ramaswamy H. Sarma

ОСОБЛИВОСТІ ПРОЕКТУВАННЯ ГОТЕЛІВ

The hotel industry plays an important role in the modern world of business and tourism. The growing number of international trips, the development of business communications and the increase in demand for comfortable accommodation create prospects for the opening of business hotels. The design of a business hotel is critical to its success and competitiveness in the market. Designing a hotel is a multifaceted task. This is a whole complex of activities: building architecture, interior design and landscaping. All together, it creates a finished image that corresponds to the general idea of the hotel. Designing a hotel requires taking into account many factors: location, capacity, type and class, priority area of activity. The building and territory must strictly comply with sanitary, technical, environmental and other regional norms and rules. When designing city hotels, it is necessary to take into account that the plot should be close to the central part of the city, but preferably not on a noisy street. A great convenience is the proximity of the train station, shopping and cultural institutions. It is very important that there is a park, garden or hotel square nearby. A successful business hotel should have a strategic location, efficient design, high-quality infrastructure and improved services. Demand for hotel buildings increases when cities become attractive to tourists and attract large numbers of visitors. The main design task is to competently place and connect different functional areas in order to, on the one hand, avoid technological problems during the operation of the hotel, and on the other hand, to create a cozy and attractive interior space, as well as beautiful facades , which are remembered. The hotel is a place for short-term stay of guests of the city. It is important that the hotel has the ability to provide various services, such as recreation, holding conferences, organizing business meetings, holding various public events, exhibitions, festivals, press conferences, as well as opportunities for sports and providing communication via telephone and electronic devices. The hotel is the most significant component of the tourism industry and affects the volume of domestic and foreign tourism in the country. The hotel building should attract attention and be remembered. When planning a hotel, it is important to develop a unique concept with an attractive interior and exterior layout. In order to obtain a competitive advantage in the hotel industry, it is necessary to constantly adapt to the changing needs and expectations of customers, to improve the quality of hotel design and construction in accordance with the requirements of the city or country.

Ciudadanía digital: definición y construcción de un índice nacional basado en actividades

Digital activity impacts multiple aspects of contemporary society, including the economy, government, and education. Furthermore, taking into account the complexity of online activities and the development of the digital society, Digital Citizenship should be considered a scale that encompasses various levels of digital participation and skills. Therefore, it is necessary to have adequate methods to evaluate and optimally monitor this dimension based on people's online activity. The article focuses on the definition and construction of a Digital Activity Index (InAD) in Peru with the objective of identifying patterns in access (incidence) and use (intensity) of the Internet that represent opportunities to improve the digital profile in Peru. The study uses the Alkire-Foster methodology to create the InAD Peru based on data from the National Household Survey (ENAHO) from 2015 to 2023. The results of the InAD Peru show a constant increase in digital activity. However, this is mainly explained by greater connectivity and it is highlighted that not all digital activities are carried out in the same proportion. Results are also providedby region, allowing you to identify areas with specific needs. In conclusion, it is relevant to measure and understand digital citizenship in Peru through a more complete approach such as with the InAD. It is hoped that InAD can help promote a stronger digital profile in Peruvian society and potentially serve as a model for other countries.

OXPHOS Organization and Activity in Mitochondria of Plants with Different Life Strategies.

The study of the supramolecular organization of the mitochondrial oxidative phosphorylation system (OXPHOS) in various eukaryotes has led to the accumulation of a considerable amount of data on the composition, stoichiometry, and architecture of its constituent superstructures. However, the link between the features of system arrangement and the biological characteristics of the studied organisms has been poorly explored. Here, we report a comparative investigation into supramolecular and functional OXPHOS organization in the mitochondria of etiolated shoots of winter wheat (Triticum aestivum L.), maize (Zea mays L.), and pea (Pisum sativum L.). Investigations based on BN-PAGE, in-gel activity assays, and densitometric analysis revealed both similarities and specific OXPHOS features apparently related to the life strategies of each species. Frost-resistant winter wheat was distinguished by highly stable basic I1III2IVa/b respirasomes and V2 dimers, highly active complex I, and labile complex IV, which were probably essential for effective OXPHOS adaptation during hypothermia. Maize, a C4 plant, had the highly stable dimers IV2 and V2, less active complex I, and active alternative NAD(P)H dehydrogenases. The latter fact could contribute to successful chloroplast-mitochondrial cooperation, which is essential for highly efficient photosynthesis in this species. The pea OXPHOS contained detergent-resistant high-molecular respirasomes I1-2III2IVn, highly active complexes IV and V, and stable succinate dehydrogenase, suggesting an active energy metabolism in organelles of this plant. The results and conclusions are in good agreement with the literature data on the respiratory activity of mitochondria from these species and are summarized in a proposed scheme of organization of OXPHOS fragments.

The power of multivariate approach in identifying EEG correlates of interlimb coupling.

Interlimb coupling refers to the interaction between movements of one limb and movements of other limbs. Understanding mechanisms underlying this effect is important to real life because it reflects the level of interdependence between the limbs that plays a role in daily activities including tool use, cooking, or playing musical instruments. Interlimb coupling involves multiple brain regions working together, including coordination of neural activity in sensory and motor regions across the two hemispheres. Traditional neuroscience research took a univariate approach to identify neural features that correspond to behavioural coupling measures. Yet, this approach reduces the complexity of the neural activity during interlimb tasks to one value. In this brief research report, we argue that identifying neural correlates of interlimb coupling would benefit from a multivariate approach in which full patterns from multiple sources are used to predict behavioural coupling. We demonstrate the feasibility of this approach in an exploratory EEG study where participants (n = 10) completed 240 trials of a well-established drawing paradigm that involves interlimb coupling. Using artificial neural network (ANN), we show that multivariate representation of the EEG signal significantly captures the interlimb coupling during bimanual drawing whereas univariate analyses failed to identify such correlates. Our findings demonstrate that analysing distributed patterns of multiple EEG channels is more sensitive than single-value techniques in uncovering subtle differences between multiple neural signals. Using such techniques can improve identification of neural correlates of complex motor behaviours.

Reconstitution of Human CCR4-NOT Complex from Purified Proteins and an Assay of Its Deadenylation Activity.

We describe protocols to produce and reconstitute an active human CCR4-NOT complex. Individual recombinant subunits are expressed in E. coli or baculovirus-infected insect cells, purified using column chromatography, and reconstituted into a stable complex containing all eight core subunits. In addition, we describe the biochemical assay of deadenylation using the reconstituted complex.

RNase III participates in control of quorum sensing, pigmentation and oxidative stress resistance in Rhodobacter sphaeroides.

RNase III is a dsRNA-specific endoribonuclease, highly conserved in bacteria and eukarya. In this study, we analysed the effects of inactivation of RNase III on the transcriptome and the phenotype of the facultative phototrophic α-proteobacterium Rhodobacter sphaeroides. RNA-seq revealed an unexpectedly high amount of genes with increased expression located directly downstream to the rRNA operons. Chromosomal insertion of additional transcription terminators restored wild type-like expression of the downstream genes, indicating that RNase III may modulate the rRNA transcription termination in R. sphaeroides. Furthermore, we identified RNase III as a major regulator of quorum-sensing autoinducer synthesis in R. sphaeroides. It negatively controls the expression of the autoinducer synthase CerI by reducing cerI mRNA stability. In addition, RNase III inactivation caused altered resistance against oxidative stress and impaired formation of photosynthetically active pigment-protein complexes. We also observed an increase in the CcsR small RNAs that were previously shown to promote resistance to oxidative stress. Taken together, our data present interesting insights into RNase III-mediated regulation and expand the knowledge on the function of this important enzyme in bacteria.

Comprehensive rehabilitation of preschool children with attention deficit hyperactivity disorder

Introduction. High incidence and great social significance of attention deficit hyperactivity disorder (ADHD) in preschool children determines the search and development of new options for their rehabilitation.Aim. To analyse the patient outcomes of the most up-to-date treatment and rehabilitation complex (biofeedback, sensory integration, psychological and speech, physiotherapeutic effects) and the possibility of its widespread practical application for the rehabilitation of preschool children with ADHD.Materials and methods. A total of 63 children (33 boys and 30 girls) aged 5–8 years were included in the prospective study. Patients were divided into two groups: Group I – 34 children aged 5 years – 5 years 11 months, 29 days with ADHD, and Group II – 29 children aged 6 years – 6 years 11 months, 29 days with ADHD. The follow-up period for each patient was 15 months. The children were examined by a neurologist, rehabilitation therapist, neuropsychologist, and speech pathologist with an assessment of active attention measures using the B. Bourdon scale for children of Group I and the Toulouse-Pieron scale (adapted by L.A. Yasyukova) for children of Group 2. Parents were surveyed and questioned using special questionnaires. Results. Before initiation of treatment, all children were diagnosed with active attention disorders of isolated (26.5 and 23.8%) and mixed (73.5 and 62.5%) nature in Groups I and II, respectively. After the rehabilitation activities complex was provided, a significant decrease in not only isolated, but also mixed attention disorders in children with ADHD was detected in both groups. Evaluation of electroencephalograms after the rehabilitation activities complex showed a decrease of theta power and an increase of low beta frequency power in 18.7% of children of Group I and in 16.2% of children of Group II, which indicated an improvement in neurodynamic functions and sufficient cognitive potential in that cohort of children.Conclusion. Early start and prolonged use of the proposed rehabilitation complex will enhance learning ability and prevent school and social maladjustment of children with ADHD.

IdeS, a secreted proteinase of Streptococcus pyogenes, is bound to a nuclease at the bacterial surface where it inactivates opsonizing IgG antibodies

The important bacterial pathogen Streptococcus pyogenes secretes IdeS (immunoglobulin G-degrading enzyme of S.pyogenes), a proteinase that cleaves human immunoglobulin G (IgG) antibodies in the hinge region resulting in Fc (fragment crystallizable) and F(ab')2 (fragment antigen-binding) fragments and protects the bacteria against phagocytic killing. Experiments with radiolabeled IdeS and flow cytometry demonstrated that IdeS binds to the surface of S.pyogenes, and the interaction was most prominent in conditions resembling those in the pharynx (acidic pH and low salt), the habitat for S.pyogenes. SpnA (S. pyogenes nuclease A) is a cell wall-anchored DNase. A dose-dependent interaction between purified SpnA and IdeS was demonstrated in slot binding and surface plasmon resonance spectroscopy experiments. Gel filtration showed that IdeS forms proteolytically active complexes with SpnA in solution, and super-resolution fluorescence microscopy revealed the presence of SpnA-IdeS complexes at the surface of S.pyogenes. Finally, specific IgG antibodies binding to S.pyogenes surface antigens were efficiently cleaved by surface-associated IdeS. IdeS is secreted by all S.pyogenes isolates and cleaves IgG antibodies with a unique degree of specificity and efficiency. These properties and the finding here that the proteinase is present and fully active at the bacterial surface in complex with SpnA implicate an important role for IdeS in S.pyogenes biology and pathogenesis.

Anti-Proliferation and DNA Cleavage Activities of Copper(II) Complexes of N3O Tripodal Polyamine Ligands

Four ligands based on the 2-tert-butyl-4-X-6-{Bis[(6-methoxy-pyridin-2-ylmethyl)-amino]-methyl}-phenol unit are synthesized: X = CHO (HLCHO), putrescine-pyrene (HLpyr), putrescine (HLamine), and 2-tert-butyl-4-putrescine-6-{Bis[(6-methoxy-pyridin-2-ylmethyl)-amino]-methyl}-phenol (H2Lbis). Complexes 1, 2, 3, and 4 are formed upon chelation to copper(II). The crystal structure of complex 1 shows a square pyramidal copper center with a very weakly bound methoxypridine moiety in the apical position. The pKa of the phenol moiety is determined spectrophotometrically at 2.82–4.39. All the complexes show a metal-centered reduction in their CV at Epc,red = −0.45 to −0.5 V vs. SCE. The copper complexes are efficient nucleases towards the ϕX174 DNA plasmid in the presence of ascorbate. The corresponding IC50 value reaches 7 μM for 2, with a nuclease activity that follows the trend: 2 > 3 > 1. Strand scission is promoted by the hydroxyl radical. The cytotoxicity is evaluated on bladder cancer cell lines sensitive (RT112) or resistant to cisplatin (RT112 CP). The IC50 of the most active complexes (2 and 4) is 1.2 and 1.0 μM, respectively, for the RT112 CP line, which is much lower than cisplatin (23.8 μM).

Phase separation underlies signaling activation of oncogenic NTRK fusions

NTRK (neurotrophic tyrosine receptor kinase) gene fusions that encode chimeric proteins exhibiting constitutive activity of tropomyosin receptor kinases (TRK), are oncogenic drivers in multiple cancer types. However, the underlying mechanisms in oncogenesis that involve various N-terminal fusion partners of NTRK fusions remain elusive. Here, we show that NTRK fusion proteins form liquid-like condensates driven by their N-terminal fusion partners. The kinase reactions are accelerated in these condensates where the complexes for downstream signaling activation are also concentrated. Our work demonstrates that the phase separation driven by NTRK fusions is not only critical for TRK activation, but the condensates formed through phase separation serve as organizational hubs for oncogenic signaling.

Functionalized Calixarenes as Promising Antibacterial Drugs to Face Antimicrobial Resistance.

Since the discovery of polyphenolic resins 150 years ago, the study of polymeric compounds named calix[n]arene has continued to progress, and those skilled in the art perfectly know now how to modulate this phenolic ring. Consequently, calix[n]arenes are now used in a large range of applications and notably in therapeutic fields. In particular, the calix[4]arene exhibits multiple possibilities for regioselective polyfunctionalization on both of its rims and offers researchers the possibility of precisely tuning the geometry of their structures. Thus, in the crucial research of new antibacterial active ingredients, the design of calixarenes finds its place perfectly. This review provides an overview of the work carried out in this aim towards the development of intrinsically active prodrogues or metallic calixarene complexes. Out of all the work of the community, there are some excellent activities emerging that could potentially place these original structures in a very good position for the development of new active ingredients.

Possible molecular exploration of herbal pair Haizao-Kunbu in the treatment of Graves' disease by network pharmacology, molecular docking, and molecular dynamic analysis.

To promote the development and therapeutic application of new medications, it is crucial to conduct a thorough investigation into the mechanism by which the traditional Chinese herb pair of Haizao-Kunbu (HK) treats Graves' disease (GD). Chemical ingredients of HK, putative target genes, and GD-associated genes were retrieved from online public databases. Using Cytoscape 3.9.1, a compound-gene target network was established to explore the association between prosperous ingredients and targets. STRING, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway analyses visualized core targets and disease pathways. Additionally, we conducted a refined analysis of the binding interactions between active ingredients and their respective targets. To visualize these findings, we employed precise molecular docking techniques. Furthermore, we carried out molecular dynamics simulations to gain insights into the formation of more tightly bound complexes. We found that there were nine key active ingredients in HK, which mainly acted on 21 targets. These targets primarily regulated several biological processes such as cell population proliferation, protein phosphorylation, and regulation of kinase activity, and acted on PI3K-AKT and MAPK pathways to treat GD. Analysis of the molecular interaction simulation under computer technology revealed that the key targets exhibited strong binding activity to active ingredients, and Fucosterol-AKT1 and Isofucosterol-AKT1 complexes were highly stable in humans. This study demonstrates that HK exerts therapeutic effects on GD in a multi-component, multi-target, and multi-pathway manner by regulating cell proliferation, differentiation, inflammation, and immunomodulatory-related targets. This study provides a theoretical foundation for further investigation into GD.

Illuminating miRNA Inhibition: Visualizing the Interaction between Anti-miRNA Oligonucleotide and Target miRNA Using FRET.

Anti-miRNA oligonucleotides (anti-miRs) effectively and specifically inhibit the function of individual miRNAs and have the potential to serve as a novel class of nucleic acid therapeutic. However, the details of the mechanisms of anti-miRs in cells have not yet been clarified sufficiently. In particular, the localization of the complexes of anti-miRs and target miRNA in cells remains unclear. We previously developed anti-miRs composed of serinol nucleic acid (SNA) that very effectively inhibited miRNA-mediated silencing activity. Here we describe an imaging system based on the fluorescence resonance energy transfer (FRET) designed by miRNAs labeled with fluorophore-quencher pairs and an SNA-based anti-miR labeled with an acceptor dye. We discovered that the anti-miR hybridizes with the miRNA in the miRNA-induced silencing complex (miRISC), which is the active complex formed by miRNA and Ago2 in cells within P-bodies. Based on FRET ratio analysis, we hypothesize that the complex formed by the anti-miR and the miRNA in P-bodies is dynamic, with anti-miR complexing the miRISC, followed by miRNA release and degradation. Our findings provide valuable insights into the mechanism of action of anti-miRs and enable further studies of miRNA-targeted therapeutics.

The rs2228145 Variant of the Interleukin-6 Receptor (IL-6R) Gene Impacts on In Vitro Cellular Responses to SARS-CoV-2 VOC B1.1.7 Recombinant Spike Protein

Given the variability in inflammatory responses to SARS-CoV-2 infection observed within human populations, we aimed to develop an in vitro model system (based on monocyte-macrophages, a key relevant cell type) that could yield insights regarding the impact of rs2228145, a clinically relevant polymorphism within the coding region of a key inflammatory gene in the body’s response to SARS-CoV-2 infection: the interleukin-6 receptor (IL-6R) gene. Three monocyte-macrophage cell-lines (U937, THP-1, MM6) were shown to exhibit AA, AC and CC rs2228145 genotypes, respectively, and to exhibit an MM6 > THP-1 > U937 pattern regarding basal levels of soluble IL-6R (sIL-6R) release. Similar MM6 > THP-1 > U937 patterns were seen regarding the extents to which (i) circulating levels of the IL-6/sIL-6R ‘active complex’ increased and (ii) phosphorylation of the downstream transcription-factor STAT3 occurred, following treatment with SARS-CoV-2 spike protein (SP). Moreover, a blocking antibody for the ACE-2 entry receptor for SARS-CoV-2 suppressed effects (i) and (ii), suggesting that interaction between SP and ACE-2 is the initial event that triggers IL-6/IL-6R signalling in our system. Production of IL-8 occurred to greater extents in A549 lung epithelial cells treated with tissue-culture supernatants from SP-treated MM6 cultures than SP-treated THP-1 or U937 cultures. Our data indicate that the rs2228145 genotype significantly impacts upon SP-associated IL-6/sIL-6R signalling in vitro, suggesting that it may influence in vivo risk of developing severe COVID-19 and/or long-COVID symptoms following infection by SARS-CoV-2. Thus, the rs2228145 genotype may have potential as a biomarker that differentiates between patients at risk of developing severe and/or prolonged symptoms following infection by SARS-CoV-2 and those who are at less risk.

Study on the Multimodal Anticancer Mechanism of Ru(II)/Ir(III) Complexes Bearing a Poly(ADP-ribose) Polymerase 1 Inhibitor.

A series of novel ruthenium(II) and iridium(III) complexes (Ru1-Ru3 and Ir1-Ir3) with different ancillary ligands and a PARP-1-inhibitory chelating ligand 2-(2,3-dibromo-4,5-dimethoxybenzylidene)hydrazine-1-carbothioamide (L1) were designed and prepared. The target complexes were structurally characterized by NMR and ESI-MS techniques. Among them, the crystal and molecular structures of Ir1 and Ir2 were also determined by X-ray crystallography. These complexes retained the PARP-1 enzyme inhibitory effect of L1 and showed potent antiproliferative activity on the tested cancer cell lines. The ruthenium(II) complexes Ru1-Ru3 were found to be more cytotoxic than the iridium(III) complexes Ir1-Ir3. Further investigations revealed that the most active complex Ru3 induced apoptosis in MCF-7 cells by multiple modes, inclusive of inducing DNA damage, suppressing DNA damage repair, disturbing cell cycle distribution, decreasing the mitochondrial membrane potential, and increasing the intracellular reactive oxygen species levels.

Coupled catalytic states and the role of metal coordination in Cas9.

Controlling the activity of the CRISPR-Cas9 system is essential to its safe adoption for clinical and research applications. Although the conformational dynamics of Cas9 are known to control its enzymatic activity, details of how Cas9 influences the catalytic processes at both nuclease domains remain elusive. Here we report five cryo-electron microscopy structures of the active Acidothermus cellulolyticus Cas9 complex along the reaction path at 2.2-2.9 Å resolution. We observed that a large movement in one nuclease domain, triggered by the cognate DNA, results in noticeable changes in the active site of the other domain that is required for metal coordination and catalysis. Furthermore, the conformations synchronize the reaction intermediates, enabling coupled cutting of the two DNA strands. Consistent with the roles of conformations in organizing the active sites, adjustments to the metal-coordination residues lead to altered metal specificity of A. cellulolyticus Cas9 and commonly used Streptococcus pyogenes Cas9 in cells.

Interaction-motif-based classification of self-organizing metabolic cycles

Particles that are catalytically-active and chemotactic can interact through the concentration fields upon which they act, which in turn may lead to wide-scale spatial self-organization. When these active particles interact through several fields, these interactions gain an additional structure, which can result in new forms of collective behavior. Here, we study a mixture of active species which catalyze the conversion of a substrate chemical into a product chemical, and chemotax in concentration gradients of both substrate and product. Such species develop non-reciprocal, specific interactions that we coarse-grain into attractive and repulsive, which can lead to a potentially complex interaction network. We consider the particular case of a metabolic cycle of three species, each of which interacts with itself and both other species in the cycle. We find that the stability of a cycle of species that only chemotax in gradients of their substrate is piloted by a set of two parameter-free conditions, which we use to classify the low number of corresponding interaction networks. In the more general case of substrate- and product-chemotactic species, we can derive a set of two high-dimensional stability conditions, which can be used to classify the stability of all the possible interaction networks based on the self- and pair-interaction motifs they contain. The classification scheme that we introduce can help guide future studies on the dynamics of complex interaction networks and explorations of the corresponding large parameter spaces in such metabolically active complex systems.

Avatar legal protection as an atypical copyright object

The legal protection of an avatar as an atypical copyright object has been investigated. The originality and objective form of an avatar have been established and characterised, which will allow correlating an avatar with atypical copyright objects, and the atypicality of an avatar as an object of copyright has been emphasised.
 It has been determined that the phenomenon of an avatar as a legal category is that it is a complex category which has a different legal regime. It has been noted that it is most appropriate to relate an avatar to an object of rights, in particular, in the field of personal non-property rights and intellectual property rights. Creating objects with the help of a neural network, in particular, an avatar in the form of a computer copy of a person, is a complex work of different people. At the same time, this work has signs of intellectual, scientific and creative activity. Due to the complexity of such activity, it may fall under different legal regimes of intellectual property rights, in particular copyright and patent law. An avatar as a game character can be considered as an object of copyright. If an avatar is created using digital tools offered by the developers of a computer game, the copyright belongs to the respective developers.
 It has been proved that an avatar is an intangible benefit that can include such virtual objects as: a game character tied to a specific user; a social network profile of a person; a computer copy of a person with unique identification features, originality and objective form. It has the following characteristics: the presence of a digital objective form that makes it possible to perceive the avatar in the digital environment, originality, uniqueness, and the availability of legal access to use the avatar. The legal protection of an avatar within the framework of copyright may be carried out under two legal regimes: copyright protection; and the institute of rights of a special kind (sui generis). It would be appropriate to supplement the Law of Ukraine “On Copyright and Related Rights” with a definition of an avatar and rights to it.