Progressive Structural Changes Research Articles

Changes in the Cyto- and Fibroarchitectonics of the Cerebellar Cortex in Rats Subjected to Extreme Physical Activity.

Physical overexertion surpassing the functional capacity of the nervous system causes the hyperactivation of the neural structures of the cerebellum. In turn, it causes the depletion of intracellular resources and progressive structural changes in cerebellar cells and fibers. These degenerative changes may lead to cerebellar dysfunction, including the worsening of coordination, balance, and motor functions. In order to maintain the health and functioning of the cerebellum and the nervous system in general, one needs to avoid physical overexertion and have enough time to recover. Three major types of Purkinje cells were identified in control group animals. After the forced swimming test, animals had significant morphological changes in pyriform cells, granule cells, internuncial neurons, and neuroglial cells. In particular, the extreme degeneration of granule cells was manifested via their fusion into conglomerates. These changes demonstrate that neurodegeneration in the cerebellum takes place in response to physical overexertion.

Functional MRI for the Assessment of Brain Connectivity in Neurodegenerative Diseases: An Observational Study in Mexico City

Introduction: Neurodegenerative diseases are characterized by progressive brain dysfunction and structural changes. Functional MRI (fMRI), a non-invasive imaging technique, offers the potential to assess brain connectivity and identify early biomarkers of these diseases. Methods: This observational study included patients with Alzheimer's disease (AD), Parkinson's disease (PD), and healthy controls in Mexico City. Resting-state fMRI data was acquired, and brain connectivity was analyzed using independent component analysis (ICA) and seed-based correlation analysis (SCA). Results: fMRI revealed altered brain connectivity patterns in AD and PD compared to healthy controls. In AD, decreased connectivity was observed within the default mode network (DMN), while PD patients showed reduced connectivity in the motor network. Conclusion: fMRI provides valuable insights into brain connectivity changes in neurodegenerative diseases. These findings contribute to the development of early diagnostic tools and potential therapeutic targets for AD and PD.

Inhibition of Calcineurin with FK506 Reduces Tau Levels and Attenuates Synaptic Impairment Driven by Tau Oligomers in the Hippocampus of Male Mouse Models.

Alzheimer's disease (AD) is the most common age-associated neurodegenerative disorder, characterized by progressive cognitive decline, memory impairment, and structural brain changes, primarily involving Aβ plaques and neurofibrillary tangles of hyperphosphorylated tau protein. Recent research highlights the significance of smaller Aβ and Tau oligomeric aggregates (AβO and TauO, respectively) in synaptic dysfunction and disease progression. Calcineurin (CaN), a key calcium/calmodulin-dependent player in regulating synaptic function in the central nervous system (CNS) is implicated in mediating detrimental effects of AβO on synapses and memory function in AD. This study aims to investigate the specific impact of CaN on both exogenous and endogenous TauO through the acute and chronic inhibition of CaN. We previously demonstrated the protective effect against AD of the immunosuppressant CaN inhibitor, FK506, but its influence on TauO remains unclear. In this study, we explored the short-term effects of acute CaN inhibition on TauO phosphorylation and TauO-induced memory deficits and synaptic dysfunction. Mice received FK506 post-TauO intracerebroventricular injection and TauO levels and phosphorylation were assessed, examining their impact on CaN and GSK-3β. The study investigated FK506 preventive/reversal effects on TauO-induced clustering of CaN and GSK-3β. Memory and synaptic function in TauO-injected mice were evaluated with/without FK506. Chronic FK506 treatment in 3xTgAD mice explored its influence on CaN, Aβ, and Tau levels. This study underscores the significant influence of CaN inhibition on TauO and associated AD pathology, suggesting therapeutic potential in targeting CaN for addressing various aspects of AD onset and progression. These findings provide valuable insights for potential interventions in AD, emphasizing the need for further exploration of CaN-targeted strategies.

Salt induced slowdown of kinetics and dynamics during thermal gelation of egg-yolk.

We investigated the effect of the NaCl concentration (0.3-2M) on the structure and dynamics of hen egg yolk at room temperature and during thermal gelation at temperatures in the range of 66-90 °C utilizing low-dose x-ray photon correlation spectroscopy in ultra-small angle x-ray scattering geometry. With an increase in the salt concentration, we observe progressive structural and dynamic changes at room temperature, indicating the disruption of yolk components such as yolk-granules and yolk-plasma proteins. Temperature- and salt-dependent structural and dynamic investigations suggest a delay in the gel formation and aggregation of yolk low-density lipoproteins with increasing ionic strength. However, the time-temperature superposition relationship observed in all samples suggests an identical mechanism underlying protein aggregation-gelation with a temperature-dependent reaction rate. The sol-gel transition time extracted from kinetic and dynamic information follows Arrhenius's behavior, and the activation energy (460kJ/mol) is found to be independent of the salt concentration.

Aproximación práctica para la caracterización de la miocardiopatía auricular en pacientes con fibrilación auricular

Atrial fibrillation (AF) causes progressive structural and electrical changes in the atria that can be summarized within the general concept of atrial remodeling. In parallel, other clinical characteristics and comorbidities may also affect atrial tissue properties and make the atria susceptible to AF initiation and its long-term persistence. Overall, pathological atrial changes lead to atrial cardiomyopathy with important implications for rhythm control. Although there is general agreement on the role of the atrial substrate for successful rhythm control in AF, the current classification oversimplifies clinical management. The classification uses temporal criteria and does not establish a well-defined strategy to characterize the individual-specific degree of atrial cardiomyopathy. Better characterization of atrial cardiomyopathy may improve the decision-making process on the most appropriate therapeutic option. We review current scientific evidence and propose a practical characterization of the atrial substrate based on 3 evaluation steps starting with a clinical evaluation (step 1), then assess outpatient complementary data (step 2), and finally include information from advanced diagnostic tools (step 3). The information from each of the steps or a combination thereof can be used to classify AF patients in 4 stages of atrial cardiomyopathy, which we also use to estimate the success on effective rhythm control.

Practical approach for atrial cardiomyopathy characterization in patients with atrial fibrillation

Atrial fibrillation (AF) causes progressive structural and electrical changes in the atria that can be summarized within the general concept of atrial remodeling. In parallel, other clinical characteristics and comorbidities may also affect atrial tissue properties and make the atria susceptible to AF initiation and its long-term persistence. Overall, pathological atrial changes lead to atrial cardiomyopathy with important implications for rhythm control. Although there is general agreement on the role of the atrial substrate for successful rhythm control in AF, the current classification oversimplifies clinical management. The classification uses temporal criteria and does not establish a well-defined strategy to characterize the individual-specific degree of atrial cardiomyopathy. Better characterization of atrial cardiomyopathy may improve the decision-making process on the most appropriate therapeutic option. We review current scientific evidence and propose a practical characterization of the atrial substrate based on 3 evaluation steps starting with a clinical evaluation (step 1), then assess outpatient complementary data (step 2), and finally include information from advanced diagnostic tools (step 3). The information from each of the steps or a combination thereof can be used to classify AF patients in 4 stages of atrial cardiomyopathy, which we also use to estimate the success on effective rhythm control.

Synthesis of Bis(cyclic carbonates) from Epoxy Resin under Microwave Irradiation: The Structural Analysis and Evaluation of Thermal Properties.

This article describes the use of microwave irradiation in the synthesis of bis(cyclo carbonate) compounds (BCCs) in bulk (without solvent) from carbon dioxide capture using an epoxidized compound-a commercial epoxy resin-and compares this process to the conventional method. CO2 cycloaddition to epoxides is an ecological and efficient method for the formation of bis(cyclic carbonates). Moreover, the introduction of gas into the reaction mixture was carried out at atmospheric pressure with a controlled flow rate, which is advantageous from an economic point of view. Progressive structural changes and the presence of characteristic chemical groups were monitored using attenuated total reflectance infrared spectroscopy with Fourier transform. The obtained crude products were purified to obtain three fractions, which were subjected to detailed structural analysis using FT-IR and 13CNMR. The formation of the main product with two cyclic carbonates was confirmed. The presence of monomers, dimers and trimers in individual fractions as well as their thermal stability were determined, and the molecular masses in individual fractions were determined using gel permeation chromatography (GPC).

THE METABOLIC ROLE OF IL-4 AND IL-10 IN INTERVERTEBRAL DISC DEGENERATION

Intervertebral disc (IVD) degeneration is a pathological process often associated with chronic back pain and considered a leading cause of disability worldwide1. During degeneration, progressive structural and biochemical changes occur, leading to blood vessel and nerve ingrowth and promoting discogenic pain2. In the last decades, several cytokines have been applied to IVD cells in vitro to investigate the degenerative cascade. Particularly, IL-10 and IL-4 have been predicted as important anabolic factors in the IVD according to a regulatory network model based in silico approach3. Thus, we aim to investigate the potential presence and anabolic effect of IL-10 and IL-4 in human NP cells (in vitro) and explants (ex vivo) under hypoxia (5% O2) after a catabolic induction.Primary human NP cells were expanded, encapsulated in 1.2% alginate beads (4 × 106 cells/ml) and cultured for two weeks in 3D for phenotype recovery while human NP explants were cultured for five days. Afterwards, both alginate and explant cultures were i) cultured for two days and subsequently treated with 10 ng/ml IL-10 or IL-4 (single treatments) or ii) stimulated with 0.1 ng/ml IL-1β for two days and subsequently treated with 10 ng/ml IL-10 or IL-4 (combined treatments).The presence of IL-4 receptor, IL-4 and IL-10 was confirmed in human intact NP tissue (Fig 1). Additionally, IL-4 single and combined treatments induced a significant increase of proinflammatory protein secretion in vitro (Fig. 2A-C) and ex vivo (Fig. 2D and E). In contrast, no significant differences were observed in the secretome between IL-10 single and combined treatments compared to control group.Overall, IL-4 containing treatments promote human NP cell and explant catabolism in contrast to previously reported IL-4 anti-inflammatory performance4. Thus, a possible pleiotropic effect of IL-4 could occur depending on the IVD culture and environmental condition.Acknowledgements: This project was supported by the Marie Skłodowska Curie International Training Network “disc4all” under the grant agreement #955735.For any figures and tables, please contact the authors directly.

The prevalence of dilated cardiomyopathy in the Weimaraner dog breed

Dilated cardiomyopathy (DCM) is a well-recognised cause of cardiac morbidity and death in humans and dogs. It causes progressive structural changes in the myocardium, which leads to congestive heart failure or sudden death. Dilated cardiomyopathy is the second most common acquired cardiac disease and the most common cardiomyopathy in dogs. The highest prevalence is found in large and giant breeds of dogs; the most frequently affected dogs are Doberman Pinschers. Other breeds such as the Great Dane, Boxer, Irish Wolfhound or Cocker Spaniel also have a high prevalence of DCM. No study has yet been reported in regard to the prevalence of DCM in the Weimaraner and its genetic causes. In the study, a total of 232 Weimaraner dogs were enrolled. Out of this total number, 223 dogs were short-haired Weimaraners and 9 dogs were long-haired Weimaraners. The most frequently diagnosed disease was DCM but other diseases were identified. In our study, the prevalence of DCM in Weimaraners was 9.8%.

Progressive brain structural abnormality in cerebral small vessel disease assessed with MR imaging by using causal network analysis

AimsCerebral small vessel disease (CSVD) is a complex condition characterized by a combination of microcirculation disorders and neurodegenerative processes, CSVD is associated with structural abnormalities in multiple brain regions. However, the progressive pattern of structural changes remains unknown. MethodsIn order to detail the progressive structural changes in CSVD patients according to the degree of cognitive impairment, we recruited 121 CSVD patients and 104 healthy controls (HCs). Voxel-based morphometry was employed to measure the gray matter volume (GMV) of each participant. According to the VICCCS-2 diagnostic criteria, patients were initially divided into three stage groups, then we investigated the GMV changes in each stage and their causal relationships using causal structure covariance network (CaSCN) analysis. ResultsOverall, patients with CSVD presented stage-specific GMV alterations compared with HCs. With the worsening of cognitive impairment, the decrease in gray matter volume starts from the right hippocampus and gradually spreads to the cortical-subcortical brain regions. Importantly, the right hippocampus in CSVD patients plays a driving role in the directional network and forms both positive and negative causal effect networks with cortical-subcortical brain regions. ConclusionsThis study reveals the significance of the right hippocampus as an early pathological area in CSVD patients and its causal impact on brain GMV changes with disease progression, shedding light on structural brain damage hierarchy and compensatory mechanisms.

Progressive mechanical and structural changes in anterior cerebral arteries with Alzheimer’s disease

Alzheimer's disease (AD) is a neurodegenerative disease and the main cause for dementia. The irreversible neurodegeneration leads to a gradual loss of brain function characterized predominantly by memory loss. Cerebrovascular changes are common neuropathologic findings in aged subjects with dementia. Cerebrovascular integrity is critical for proper metabolism and perfusion of the brain, as cerebrovascular remodeling may render the brain more susceptible to pulse pressure and may be associated with poorer cognitive performance and greater risk of cerebrovascular events. The objective of this study is to provide understanding of cerebrovascular remodeling with AD progression. Anterior cerebral arteries (ACAs) from a total of 19 brain donor participants from controls and pathologically diagnosed AD groups (early—Braak stages I-II; intermediate—Braak stages III-IV; and advanced—Braak stages V-VI) were included in this study. Mechanical testing, histology, advanced optical imaging, and mass spectrometry were performed to study the progressive structural and functional changes of ACAs with AD progression. Biaxial extension-inflation tests showed that ACAs became progressively less compliant, and the longitudinal stress in the intermediate and advanced AD groups was significantly higher than that from the control group. With pathological AD development, the inner and outer diameters of the ACAs remained almost unchanged; however, histology study revealed progressive smooth muscle cell atrophy and loss of elastic fibers which led to compromised structural integrity of the arterial wall. Multiphoton imaging demonstrated elastin degradation at the media-adventitia interface, which led to the formation of an empty band of 21.0 ± 15.4 μm and 32.8 ± 9.24 μm in width for the intermediate and advanced AD groups, respectively. Furthermore, quantitative birefringence microscopy showed disorganized adventitial collagen with AD development. Mass spectrometry analysis provided further evidence of altered collagen content and other extracellular matrix (ECM) molecule and smooth muscle cell changes that were consistent with the mechanical and structural alterations. Collectively, our study provides understanding of the mechanical and structural cerebrovascular deterioration in cerebral arteries with AD, which may be related to neurodegenration and pathology in the brain.

Multimodal magnetic resonance imaging after experimental moderate and severe traumatic brain injury: A longitudinal correlative assessment of structural and cerebral blood flow changes.

Traumatic brain injury (TBI) is a worldwide problem that results in death or disability for millions of people every year. Progressive neurological complications and long-term impairment can significantly disrupt quality of life. We demonstrated the feasibility of multiple magnetic resonance imaging (MRI) modalities to investigate and predict aberrant changes and progressive atrophy of gray and white matter tissue at several acute and chronic time points after moderate and severe parasagittal fluid percussion TBI. T2-weighted imaging, diffusion tensor imaging (DTI), and perfusion weighted imaging (PWI) were performed. Adult Sprague-Dawley rats were imaged sequentially on days 3, 14, and 1, 4, 6, 8, and 12 months following surgery. TBI caused dynamic white and gray matter alterations with significant differences in DTI values and injury-induced alterations in cerebral blood flow (CBF) as measured by PWI. Regional abnormalities after TBI were observed in T2-weighted images that showed hyperintense cortical lesions and significant cerebral atrophy in these hyperintense areas 1 year after TBI. Temporal DTI values indicated significant injury-induced changes in anisotropy in major white matter tracts, the corpus callosum and external capsule, and in gray matter, the hippocampus and cortex, at both early and chronic time points. These alterations were primarily injury-severity dependent with severe TBI exhibiting a greater degree of change relative to uninjured controls. PWI evaluating CBF revealed sustained global reductions in the cortex and in the hippocampus at most time points in an injury-independent manner. We next sought to investigate prognostic correlations across MRI metrics, timepoints, and cerebral pathology, and found that diffusion abnormalities and reductions in CBF significantly correlated with specific vulnerable structures at multiple time points, as well as with the degree of cerebral atrophy observed 1 year after TBI. This study further supports using DTI and PWI as a means of prognostic imaging for progressive structural changes after TBI and emphasizes the progressive nature of TBI damage.

Exploratory Longitudinal Study of Ocular Structural and Visual Functional Changes in Subjects at High Genetic Risk of Developing Alzheimer's Disease.

This study aimed to analyze the evolution of visual changes in cognitively healthy individuals at risk for Alzheimer's disease (AD). Participants with a first-degree family history of AD (FH+) and carrying the Ε4+ allele for the ApoE gene (ApoE ε4+) underwent retinal thickness analysis using optical coherence tomography (OCT) and visual function assessments, including visual acuity (VA), contrast sensitivity (CS), color perception, perception digital tests, and visual field analysis. Structural analysis divided participants into FH+ ApoE ε4+ and FH- ApoE ε4- groups, while functional analysis further categorized them by age (40-60 years and over 60 years). Over the 27-month follow-up, the FH+ ApoE ε4+ group exhibited thickness changes in all inner retinal layers. Comparing this group to the FH- ApoE ε4- group at 27 months revealed progressing changes in the inner nuclear layer. In the FH+ ApoE ε4+ 40-60 years group, no progression of visual function changes was observed, but an increase in VA and CS was maintained at 3 and 12 cycles per degree, respectively, compared to the group without AD risk at 27 months. In conclusion, cognitively healthy individuals at risk for AD demonstrated progressive retinal structural changes over the 27-month follow-up, while functional changes remained stable.

Kinetics of combustion of lignocellulosic biomass: recent research and critical issues

Predicting biomass combustion at temperatures of practical interest requires kinetic expression robust and reliable over a large temperature range.The present work examines experimental works on combustion kinetics of lignocellulosic biomass published since 2015 and reports the experimental methods used and the kinetic parameters obtained therein. The most common experimental strategy, used in 39 referenced works, was non-isothermal thermogravimetric analysis, yet the kinetic parameters obtained varied by order of magnitude.The large variability of the kinetic parameters found in literature cannot be only explained by the feedstock heterogeneity or the different data analysis methods. One possible and apparently neglected source of error lies in the fact lignocellulosic biomasses are complex materials, constituted by different components, thus thermogravimetric curves are the resultant of multiple and partly overlapping stages of mass loss. Kinetic analysis in this case easily generates errors. Another criticality that the work wants to emphasize is the fact that biomass pyrolyses, burns and even thermally anneals throughout a TGA experiment. These progressive structural changes are a further problem for application of conventional kinetic analysis methods.Altogether, it can be concluded that it is difficult to obtain from conventional TGA analysis reliable kinetic expressions of biomass combustion to be used for boilers modelling. For complex materials like biomass, it is recommended to adopt expert-case sensitive approaches. As an example, the case of walnut shells combustion is presented. For this material, four components with different combustion reactivity have been identified and simplified single rate kinetics are proposed according to the temperature interval of interest.

DEVELOPMENT OF INNOVATIVE ECOSYSTEM OF UKRAINE AT THE NATIONAL LEVEL

The article explores the theoretical and methodological aspects of the main idea of the formation of an innovation ecosystem at the national level, which consists in close cooperation and unification of the efforts of the participants in the innovation process on mutually beneficial terms of partnership, resources and competencies in building up the country’s innovative potential. It has been established that the innovation ecosystem at the national level is a synergistic partnership and collaboration of science, education and business as an institutionally coordinated mechanism of relationships from the generation and transfer of knowledge to the commercialization of innovations, that is, the entire innovation cycle of neo-industrial development of the national economy of Ukraine, its restoration in the European integration space. It is substantiated that the innovation ecosystem as a type of ecosystems in the economy allows cooperating efforts to create and promote innovations on the market. The concept of an innovation ecosystem gives a much better idea of the nature of innovation processes taking place in modern realities than the traditional systems approach. The main problems and obstacles to the development and implementation of the innovation ecosystem of Ukraine at the national level are outlined. Speaking about the fact that it is higher scientific institutions (universities) of education that should become generators of progressive structural changes in the economy and take the main place in the innovation ecosystem, the article considers the progressive experience of new types of universities. That is why it is proposed to single out the main instruments of these changes: 1) identification of target markets and segments; 2) building a system of client-centric key performance indicators; 3) optimization of the structure and partnership activities of scientific and higher educational institutions.

Post-ovulatory aging is associated with altered patterns for small ubiquitin-like modifier (SUMO) proteins and SUMO-specific proteases.

Mammalian oocytes are ovulated arrested at metaphase of the second meiotic division. If they are not fertilized within a short period, the oocyte undergoes several progressive morphological, structural, and molecular changes during a process called oocyte aging. Herein, we focused on those functional events associated with proper cytoskeleton organization and those that correlate with spindle displacement and chromosome misalignment or scatter. Post-translational modifications by Small Ubiquitin-like Modifier (SUMO) proteins are involved in spindle organization and here we demonstrate that the SUMO pathway is involved in spindle morphology changes and chromosome movements during oocyte aging. SUMO-2/3 as well as the SUMO-specific proteases SENP-2 localization are affected by postovulatory aging in vitro. Consistent with these findings, UBC9 decreases during oocyte aging while differential ubiquitination patterns also correlate with in vitro oocyte aging. These results are consistent with postovulatory aging-related alterations in the posttranslational modifications of the spindle apparatus by SUMO and its SENP proteases. These findings are suggestive that such age-related changes in SUMOylation and the deSUMOylation of key target proteins in the spindle apparatus and kinetochore may be involved with spindle and chromosome alignment defects during mammalian oocyte postovulatory aging. Such findings may have implications for ART-related human oocyte aging in vitro regarding the activities of the SUMO pathway and fertilization success.

Effect of fat on non-linear rheological behavior of processed cheese spreads using coupled amplitude-frequency sweeps, Fourier Transform-Chebyshev polynomials method, sequence of physical processes, and quantitative network analysis

The nonlinear rheological behavior of high and low-fat cheese spreads was investigated at strains between 0 and 1000% using 4 different methods. The first method consisted of frequency sweeps at selected strains where the strain sweep was stopped, and a frequency sweep was conducted immediately in the linear viscoelastic region. Secondly, the strain sweep was analyzed with the FTC method in the non-linear region. The third method used SPP to create Cole-Cole plots to quantify elastic and viscous transient moduli throughout the oscillation cycle. Lastly, quantitative network analysis was done on SEM images relating non-linear rheological properties to progressive structural changes in the casein network. The coupled amplitude-frequency sweep method along with SEM and network analysis help elucidate the relationship between the non-linear rheological behavior and microstructure. High-fat samples showed a denser network in SEM images. G’ and G” were higher at small strain amplitudes (<10%) but high-fat samples decayed faster at higher strains (10–1000%). Both formulations recorded shear-thinning and strain-stiffening behavior in the nonlinear region.

Antipsychotics and structural brain changes: could treatment adherence explain the discrepant findings?

Progressive structural brain changes are well documented in schizophrenia and have been linked to both illness progression and the extent of antipsychotic treatment exposure. Literature reporting longitudinal changes in brain structure in individuals with schizophrenia is selectively reviewed to assess the roles of illness, antipsychotic treatment, adherence and other factors in the genesis of these changes. This narrative review considers literature investigating longitudinal changes in brain structure in individuals with schizophrenia. The review focusses on structural changes in the cortex, basal ganglia and white matter. It also examines effects of medication non-adherence and relapse on the clinical course of the illness and on structural brain changes. Studies investigating structural magnetic resonance imaging changes in patients treated with long-acting injectable antipsychotics are reviewed. Temporal changes in brain structure in schizophrenia can be divided into those that are associated with antipsychotic treatment and those that are not. Changes associated with treatment include increases in basal ganglia and white matter volumes. Relapse episodes may be a critical factor in illness progression and brain volume reductions. Medication adherence may be an important factor that could explain the findings that brain volume reductions are associated with poor treatment response, higher intensity of antipsychotic treatment exposure and more time spent in relapse. Improved adherence via long-acting injectable antipsychotics and adherence focussed psychosocial interventions could maximize protective effects of antipsychotics against illness progression.

Innovation ecosystem as factor of providing progressive structural changes in the economy

The article reveals issues of building the innovative ecosystem institutions problem in context of the growing role of research Universities in ensuring innovative structural changes in the economy of Ukraine. International comparisons of the actual state of effectiveness and development potential of Ukraine’s innovation ecosystem have shown that it lags behind almost all indicators of the European Innovation Scoreboard. It is a confirmed necessity to form in Ukraine a state innovation policy based on criteria of the European Innovation Scoreboard with the goal of improving all its indicators, which comprehensively reflect the state of the national innovation ecosystem.It has been focused on the formation of the central link of the innovation ecosystem – the entrepreneurial innovation University as a progressive structural change’s generator in the economy. The justified urgency of increasing the state support for the priority development of research, design and development, and educational institutions that are part of national and regional innovation ecosystems. It is necessary to radically increase the volume and change structure of the state funding of institutions in the field of research and development, as well as innovation activity, reducing the share of the state funding of individual projects and individual grants, which should be financed mainly by business structures.It is shown that the main practical problem in determining the place and role of research Universities and other scientific and educational institutions in the structural innovation transformation of the economy of Ukraine is insufficient attention to formation and implementation of the practical function of basic innovations as the main factor of economic growth. It is suggested under formation of the Ukrainian state innovation policy, a separate priority area related to the creation of higher education institutions (Universities) of new generation as innovative entrepreneurial Universities should be identified, while it is important to develop Universities and scientific centres that demonstrate the presence of cumulative human capital, despite their temporary state of crisis.&#x0D; JEL classіfіcatіon: I23, I25, L52, O38, P52

A Potential Role of Cholinergic Dysfunction on Impaired Colon Motility in Experimental Intestinal Chagas Disease.

Background/AimsChagasic megacolon is caused by Trypanosoma cruzi, which promotes in several cases, irreversible segmental colonic dilation. This alteration is the major anatomic-clinical disorder, characterized by the enteric nervous system and muscle wall structural damage. Herein, we investigate how T. cruzi-induced progressive colonic structural changes modulate the colonic contractile pattern activity.MethodsWe developed a murine model of T. cruzi-infection that reproduced long-term modifications of the enlarged colon. We evaluated colonic and total intestinal transit time in animals. The patterns of motor response at several time intervals between the acute and chronic phases were evaluated using the organ bath assays. Enteric motor neurons were stimulated by electric field stimulation. The responses were analyzed in the presence of the nicotinic and muscarinic acetylcholine receptor antagonists. Western blot was performed to evaluate the expression of nicotinic and muscarinic receptors. The neurotransmitter expression was analyzed by real-time polymerase chain reaction.ResultsIn the chronic phase of infection, there was decreased intestinal motility associated with decreased amplitude and rhythmicity of intestinal contractility. Pharmacological tests suggested a defective response mediated by acetylcholine receptors. The contractile response induced by acetylcholine was decreased by atropine in the acute phase while the lack of its action in the chronic phase was associated with tissue damage, and decreased expression of choline acetyltransferase, nicotinic subunits of acetylcholine receptors, and neurotransmitters.ConclusionsT. cruzi-induced damage of smooth muscles was accompanied by motility disorders such as decreased intestinal peristalsis and cholinergic system response impairment. This study allows integration of the natural history of Chagasic megacolon motility disorders and opens new perspectives for the design of effective therapeutic.