This study delves into the intricate dynamics of tourism-induced water pollution through a systematic literature review, aiming to unravel complexities using a system dynamics (SD) modeling approach coupled with the PRISMA analysis methodology. Employing a comprehensive PRISMA analysis of 68 pertinent articles, the study establishes a metamodel for comprehending plastic pollution in water ecosystems resulting from tourism. The methodology emphasizes economic and environmental dimensions, causal conditions, and interventions, with a specific focus on the role of Information and Communication Technology (ICT). The results highlight integrated strategies as crucial in mitigating tourism-induced water pollution. These strategies advocate for the incorporation of environmental conservation and sustainable management practices. The study underlines the pivotal role of environmental education, awareness, and investments in protection as effective interventions. The findings offer valuable insights for policymakers and stakeholders in the tourism industry, emphasizing the necessity for proactive planning and management. The study advocates for knowledge-based decision-making to optimize tourism's environmental impacts and underscores the significance of quick and flexible responses to environmental challenges.

• Klíčová slova
• Microplastics, Plastics, System dynamics models, Tourism, Water pollution,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Alzheimer's disease is one of the most common mental illnesses. It is posited that more than 25% of the population is affected by some mental disease during their lifetime. Treatment of each patient draws resources from the economy concerned. Therefore, it is important to quantify the potential economic impact. METHODS: Agent-based, system dynamics and numerical approaches to dynamic modeling of the population of the European Union and its patients with Alzheimer's disease are presented in this article. Simulations, their characteristics, and the results from different modeling tools are compared. RESULTS: The results of these approaches are compared with EU population growth predictions from the statistical office of the EU by Eurostat. The methodology of a creation of the models is described and all three modeling approaches are compared. The suitability of each modeling approach for the population modeling is discussed. CONCLUSION: In this case study, all three approaches gave us the results corresponding with the EU population prediction. Moreover, we were able to predict the number of patients with AD and, based on the modeling method, we were also able to monitor different characteristics of the population.

• Klíčová slova
• Alzheimer’s disease, agent-based model, numerical model, population modeling, population prediction, system dynamics.,
• MeSH
• Alzheimerova nemoc diagnóza   epidemiologie   MeSH
• biologické modely MeSH
• lidé MeSH
• systémová analýza * MeSH
• teoretické modely * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

INTRODUCTION: Alzheimer's disease (AD) is a slowly progressing neurodegenerative brain disease with irreversible brain effects; it is the most common cause of dementia. With increasing age, the probability of suffering from AD increases. In this research, population growth of the European Union (EU) until the year 2080 and the number of patients with AD are modeled. AIM: The aim of this research is to predict the spread of AD in the EU population until year 2080 using a computer simulation. METHODS: For the simulation of the EU population and the occurrence of AD in this population, a system dynamics modeling approach has been used. System dynamics is a useful and effective method for the investigation of complex social systems. Over the past decades, its applicability has been demonstrated in a wide variety of applications. In this research, this method has been used to investigate the growth of the EU population and predict the number of patients with AD. The model has been calibrated on the population prediction data created by Eurostat. RESULTS: Based on data from Eurostat, the EU population until year 2080 has been modeled. In 2013, the population of the EU was 508 million and the number of patients with AD was 7.5 million. Based on the prediction, in 2040, the population of the EU will be 524 million and the number of patients with AD will be 13.1 million. By the year 2080, the EU population will be 520 million and the number of patients with AD will be 13.7 million. CONCLUSION: System dynamics modeling approach has been used for the prediction of the number of patients with AD in the EU population till the year 2080. These results can be used to determine the economic burden of the treatment of these patients. With different input data, the simulation can be used also for the different regions as well as for different noncontagious disease predictions.

• Klíčová slova
• Alzheimer’s disease, population modeling, prediction model, system dynamics,
• Publikační typ
• časopisecké články MeSH

Understanding the interplay of different traits in a co-infection system with multiple strains has many applications in ecology and epidemiology. Because of high dimensionality and complex feedback between traits manifested in infection and co-infection, the study of such systems remains a challenge. In the case where strains are similar (quasi-neutrality assumption), we can model trait variation as perturbations in parameters, which simplifies analysis. Here, we apply singular perturbation theory to many strain parameters simultaneously and advance analytically to obtain their explicit collective dynamics. We consider and study such a quasi-neutral model of susceptible-infected-susceptible (SIS) dynamics among N strains, which vary in 5 fitness dimensions: transmissibility, clearance rate of single- and co-infection, transmission probability from mixed coinfection, and co-colonization vulnerability factors encompassing cooperation and competition. This quasi-neutral system is analyzed with a singular perturbation method through an appropriate slow-fast decomposition. The fast dynamics correspond to the embedded neutral system, while the slow dynamics are governed by an N-dimensional replicator equation, describing the time evolution of strain frequencies. The coefficients of this replicator system are pairwise invasion fitnesses between strains, which, in our model, are an explicit weighted sum of pairwise asymmetries along all trait dimensions. Remarkably these weights depend only on the parameters of the neutral system. Such model reduction highlights the centrality of the neutral system for dynamics at the edge of neutrality and exposes critical features for the maintenance of diversity.

• Klíčová slova
• Co-infection, Frequency dynamics, High-dimensional polymorphism, Quasi-neutrality, Replicator equation, SIS multi-strain dynamics, Singular perturbation, Slow–fast dynamics, Tychonov’s theorem,
• MeSH
• ekologie MeSH
• fenotyp MeSH
• koinfekce * MeSH
• lidé MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The serine/threonine protein phosphatase type 5 (PP5) is a promising target for designing new antitumor drugs. This enzyme is a member of the PPP phosphatases gene family, which catalyzes a dephosphorylation reaction: a regulatory process in the signal transduction pathway that controls various biological processes. The aim of this work is to study and compare the inhibition of PP5 by ten cantharidin-like inhibitors in order to bring about contributions relevant to the better comprehension of their inhibitory activity. In this theoretical investigation, we used molecular dynamics techniques to understand the role of key interactions that occur in the protein active site; QM calculations were employed to study the interaction mode of these inhibitors in the enzyme. In addition, atoms in molecules (AIM) calculations were carried out to characterize the chemical bonds among the atoms involved and investigate the orbital interactions with their respective energy values. The obtained results suggest that the Arg275, Asn303, His304, His352, Arg400, His427, Glu428, Val429, Tyr451, and Phe446 residues favorably contribute to the interactions between inhibitors and PP5. However, the Asp271 and Asp244 amino acid residues do not favor such interactions for some inhibitors. Through the QM calculations, we can suggest that the reactional energy of the coordination mechanism of these inhibitors in the PP5 active site is quite important and is responsible for the inhibitory activity. The AIM technique employed in this work was essential to get a better comprehension of the transition states acquired from the mechanism simulation. This work offers insights of how cantharidin-like inhibitors interact with human PP5, potentially allowing the design of more specific and even less cytotoxic drugs for cancer treatments. Graphical Abstract Interactions of cantharidin-like inhibitors with human protein phosphatase-5 in a Mg2+ system.

• Klíčová slova
• AIM, Cantharidin-like inhibitors, Molecular dynamics, QM/MM, Serine/threonine phosphatase 5,
• MeSH
• hořčík chemie   MeSH
• inhibitory enzymů farmakologie   MeSH
• jaderné proteiny antagonisté a inhibitory   chemie   MeSH
• kantharidin analogy a deriváty   chemie   farmakologie   MeSH
• katalytická doména MeSH
• kationty dvojmocné chemie   MeSH
• lidé MeSH
• proteinfosfatasy antagonisté a inhibitory   chemie   MeSH
• racionální návrh léčiv MeSH
• simulace molekulární dynamiky * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hořčík MeSH
• inhibitory enzymů MeSH
• jaderné proteiny MeSH
• kantharidin MeSH
• kationty dvojmocné MeSH
• protein phosphatase 5 MeSH Prohlížeč
• proteinfosfatasy MeSH

The flexibility, active site volume, solvation, and access path dynamics of six metabolically active mammalian cytochromes P450 (human 2A6, 2C9, 2D6, 2E1, 3A4 and rabbit 2B4) are extensively studied using molecular dynamics (MD) simulations. On average, the enzymes' overall structures equilibrate on a 50+ ns timescale. The very open CYP2B4 structure closes slowly over the course of the simulation. The volumes of the active sites fluctuate by more than 50% during the MD runs; these fluctuations are mainly due to movements of the main chains, with only a handful of amino acid residues in CYP2B4, CYP2D6, CYP2A6 and CYP2C9 showing significant independent side chain movement. The volume of the active site of CYP2E1 fluctuates heavily, ranging from 220 to 1310 A(3), due to the opening and closing of gates to two adjacent cavities. CYP2E1 has the least hydrated active site of the studied CYPs; this is consistent with its preference for non-polar substrates. The CYP2A6 and CYP2E1 active sites are deeply buried, with access paths that are narrower than the radius of a water molecule. However, waters are still able to access these active sites due to local adaptations of the channel to accommodate their passage. This finding may imply that the access paths of the CYPs never fully open prior to contact with the substrate; instead, the substrate may induce adaptive conformational changes during its passage to the active site. This may also explain why some substrate recognition sites are localized along individual enzymes' access paths.

• MeSH
• katalytická doména * MeSH
• králíci MeSH
• lidé MeSH
• simulace molekulární dynamiky MeSH
• systém (enzymů) cytochromů P-450 chemie   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• systém (enzymů) cytochromů P-450 MeSH

Tumor regrowth and heterogeneity are important clinical parameters during radiotherapy, and the probability of treatment benefit critically depends on the tumor progression pattern in the interval between the fractional irradiation treatments. We propose an analytic, easy-to-use method to take into account clonal subpopulations with different specific growth rates and radiation resistances. The different strain regrowth effects, as described by Gompertz law, require a dose-boost to reproduce the survival probability of the corresponding homogeneous system and for uniform irradiation. However, the estimate of the survival fraction for a tumor with a hypoxic subpopulation is more reliable when there is a slow specific regrowth rate and when the dependence on the oxygen enhancement ratio of radiotherapy is consistently taken into account. The approach is discussed for non-linear two-population dynamics for breast cancer and can be easily generalized to a larger number of components and different tumor phenotypes.

• Klíčová slova
• dose-boost, radiotherapy, tumor instability,
• Publikační typ
• časopisecké články MeSH

Identifying general patterns and trends underlying the impacts and dynamics of biological invasions has proven elusive for scientists. Recently, the impact curve was proposed as a means to predict temporal impacts of invasive alien species, characterised by a sigmoidal growth pattern with an initial exponential increase, followed by a subsequent rate of decline and approaching a saturation level in the long-term where impact is maximised. While the impact curve has been empirically demonstrated with monitoring data of a single invasive alien species (the New Zealand mud snail, Potamopyrgus antipodarum), broadscale applicability remains to be tested for other taxa. Here, we examined whether the impact curve can adequately describe the invasion dynamics of 13 other aquatic species (within Amphipoda, Bivalvia, Gastropoda, Hirudinea, Isopoda, Mysida, and Platyhelminthes) at the European level, employing multi-decadal time series of macroinvertebrate cumulative abundances from regular benthic monitoring efforts. For all except one tested species (the killer shrimp, Dikerogammarus villosus), the sigmoidal impact curve was strongly supported (R2 > 0.95) on a sufficiently long time-scale. For D. villosus, the impact had not yet reached saturation, likely reflecting the ongoing European invasion. The impact curve facilitated estimation of introduction years and lag phases, as well as parameterisation of growth rates and carrying capacities, providing strong support for the boom-bust dynamics typically observed in several invader populations. These findings suggest that impact can grow rapidly before saturating at a high level, with timely monitoring often lacking for the detection of invasive alien species post-introduction. We further confirm the applicability of the impact curve to determine trends in invasion stages, population dynamics, and impacts of pertinent invaders, ultimately helping inform the timing of management interventions. We hence call for improved monitoring and reporting of invasive alien species over broad spatio-temporal scales to permit further testing of large-scale impact consistencies across various habitat types.

• Klíčová slova
• Biological invasion, Impact prediction, Invasion curve, Population dynamics, Rivers, Time series,
• MeSH
• Amphipoda * MeSH
• ekosystém MeSH
• plži * MeSH
• populační dynamika MeSH
• zavlečené druhy MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Human stimulator of interferon genes (hSTING) is a signaling adaptor protein that triggers innate immune system by response to cytosolic DNA and second messenger cyclic dinucleotides (CDNs). Natural CDNs contain purine nucleobase with different phosphodiester linkage types (3'-3', 2'-2' or mixed 2'-3'-linkages) and exhibit different binding affinity towards hSTING, ranging from micromolar to nanomolar. High-affinity CDNs are considered as suitable candidates for treatment of chronic hepatitis B and cancer. We have used molecular dynamics simulations to investigate dynamical aspects of binding of natural CDNs (specifically, 2'-2'-cGAMP, 2'-3'-cGAMP, 3'-3'-cGAMP, 3'-3'-c-di-AMP, and 3'-3'-c-di-GMP) with hSTINGwt protein. Our results revealed that CDN/hSTINGwt interactions are controlled by the balance between fluctuations (conformational changes) in the CDN ligand and the protein dynamics. Binding of different CDNs induces different degrees of conformational/dynamics changes in hSTINGwt ligand binding cavity, especially in α1-helices, the so-called lid region and α2-tails. The ligand residence time in hSTINGwt protein pocket depends on different contribution of R232 and R238 residues interacting with oxygen atoms of phosphodiester groups in ligand, water distribution around interacting charged centers (in protein residues and ligand) and structural stability of closed conformation state of hSTINGwt protein. These findings may perhaps guide design of new compounds modulating hSTING activity.Communicated by Ramaswamy H. Sarma.

• Klíčová slova
• Human stimulator of interferon genes STING, Molecular Dynamics, cyclic dinucleotides CDNs,
• MeSH
• dinukleosidfosfáty * chemie   MeSH
• DNA MeSH
• lidé MeSH
• ligandy MeSH
• oligonukleotidy MeSH
• simulace molekulární dynamiky * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• dinukleosidfosfáty * MeSH
• DNA MeSH
• ligandy MeSH
• oligonukleotidy MeSH

The objective of this paper is the study of the dynamical properties analysis of an original specification of the classical Cournot heterogeneous model with optimal response; specifically, a new approach that considers ordinal utility instead of cardinal monetary amounts is proposed where the classical decision of quantity is disentangled from the decision on imitation. The analysis is performed by means of bifurcation diagrams, the 0-1 test for chaos, power spectral density, histograms, and trajectory analysis. For this purpose, a new perturbation parameter ε of the initial condition is introduced, and together with the intensity of choice parameter β determining the share of responders vs imitators, the system is researched. Depending on ε and β, extreme reach dynamics, and coexisting attractors, periodic and chaotic trajectories are investigated through massive simulations. Those dynamics represent alternation between stability, cycles and chaos in the market. As the dynamics are completely endogenous, it means that swings in economy are intrinsic to the system and that they may persist unless controlled.

• MeSH
• nelineární dynamika * MeSH
• Publikační typ
• časopisecké články MeSH