IT for Innovative Educational Environments: Exploring, Authoring and Programming

The paper presents a novel approach based on using a single educational environment to achieve various methods for supporting educational activities – exploring prebuilt learning modules, using authoring tools to create educational modules and programming activities. This approach builds a solid foundation for subject-neutral and multidisciplinary applications and utilized modern IT techniques like virtual reality, interactivity and explorativity

A Parsimonious Generalised Height-Diameter Model for Scots Pine Plantations in Bulgaria: a Pragmatic Approach

Considering the state-of-the-art of forest inventory in Bulgaria, our investigation pursued development of a parsimonious generalised height-diameter model for the Scots pine plantations in the country. A number of 2-, 3- and 4-predictor candidate models were examined and compared based on their goodness-of-fit statistics. Data records obtained in variable-sized sample plots, established throughout the distribution range of the plantations and covering the variety of sites, densities and growth stages were used to fit the models. Two hundred twenty-four plot-level measurements and 3056 tree height-diameter pairs were utilised for parameterization. An independent data set of tree-level measurements and two sets of dominant height-diameter pairs, estimated for differently defined top height tree collectives, were used for model validation. Statistical analyses were carried out using packages nlstools, moments, equivalence, car, nlme, stats and the results were illustrated with ggplot2 and graphics packages of R software environment. A modified form of Gaffrey’s model was selected, which estimates the height of a tree through the breast-height tree diameter, mean stand height and diameter, and accounts for the tree social status. It was fitted by generalised non-linear least squares method, with residual variance weighted by a product of tree diameter and mean stand height exponential functions. An adjusted coefficient of determination of 0.917 and residual standard error of 0.794 m indicated the high predictive potential of the derived model. Validation tests showed that the estimated regression line is very well fitted to the independent data and is appropriate to forecast dominant stand heights. The range of errors, relative to the predicted dominant height values, was narrow, ±25-30%, with low magnitude of the average of their absolute values (4-5%). The equivalence tests rejected the null hypothesis of dissimilarity regarding model bias (observations-predictions line intercept) for all validation data sets, for a region of equivalence as narrow as ±5%. The 3-predictor generalised height-diameter model developed in our study needs information readily available from the inventories and therefore can be broadly used. Its application in dominant stand height prediction is recommended

Biodesulphurized subbituminous coal by different fungi and bacteria studied by reductive pyrolysis. Part 1: Initial coal

One of the perspective methods for clean solid fuels production is biodesulphurization. In order to increase the effect of this approach it is necessary to apply the advantages of more informative analytical techniques. Atmospheric pressure temperature programming reduction (AP-TPR) coupled with different detection systems gave us ground to attain more satisfactory explanation of the effects of biodesulphurization on the treated solid products. Subbituminous high sulphur coal from ‘‘Pirin” basin (Bulgaria) was selected as a high sulphur containing sample. Different types of microorganisms were chosen and maximal desulphurization of 26% was registered. Biodesulphurization treatments were performed with three types of fungi: ‘‘Trametes Versicolor” – ATCC No. 200801, ‘‘Phanerochaeta Chrysosporium” – ME446, Pleurotus Sajor-Caju and one Mixed Culture of bacteria – ATCC No. 39327. A high degree of inorganic sulphur removal (79%) with Mixed Culture of bacteria and consecutive reduction by 13% for organic sulphur (Sorg) decrease with ‘‘Phanerochaeta Chrysosporium” and ‘‘Trametes Versicolor” were achieved. To follow the Sorg changes a set of different detection systems i.e. AP-TPR coupled ‘‘on-line” with mass spectrometry (AP-TPR/MS), on-line with potentiometry (AP-TPR/pot) and by the ‘‘off-line” AP-TPR/GC/MS analysis was used. The need of applying different atmospheres in pyrolysis experiments was proved and their effects were discussed. In order to reach more precise total sulphur balance, oxygen bomb combustion followed by ion chromatography was used

Mesenchymal Stem Cells in a Transgenic Mouse Model of Multiple System Atrophy: Immunomodulation and Neuroprotection

Mesenchymal stem cells (MSC) are currently strong candidates for cell-based therapies. They are well known for their differentiation potential and immunoregulatory properties and have been proven to be potentially effective in the treatment of a large variety of diseases, including neurodegenerative disorders. Currently there is no treatment that provides consistent long-term benefits for patients with multiple system atrophy (MSA), a fatal late onset α-synucleinopathy. Principally neuroprotective or regenerative strategies, including cell-based therapies, represent a powerful approach for treating MSA. In this study we investigated the efficacy of intravenously applied MSCs in terms of behavioural improvement, neuroprotection and modulation of neuroinflammation in the (PLP)-αsynuclein (αSYN) MSA model.MSCs were intravenously applied in aged (PLP)-αSYN transgenic mice. Behavioural analyses, defining fine motor coordination and balance capabilities as well as stride length analysis, were performed to measure behavioural outcome. Neuroprotection was assessed by quantifying TH neurons in the substantia nigra pars compacta (SNc). MSC treatment on neuroinflammation was analysed by cytokine measurements (IL-1α, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17, GM-CSF, INFγ, MCP-1, TGF-β1, TNF-α) in brain lysates together with immunohistochemistry for T-cells and microglia. Four weeks post MSC treatment we observed neuroprotection in the SNc, as well as downregulation of cytokines involved in neuroinflammation. However, there was no behavioural improvement after MSC application.To our knowledge this is the first experimental approach of MSC treatment in a transgenic MSA mouse model. Our data suggest that intravenously infused MSCs have a potent effect on immunomodulation and neuroprotection. Our data warrant further studies to elucidate the efficacy of systemically administered MSCs in transgenic MSA models

Increased anxiety-like behavior following circuit-specific catecholamine denervation in mice

Parkinson's disease (PD) presents with a constellation of non-motor symptoms, notably increased anxiety, which are currently poorly treated and underrepresented in animal models of the disease. Human post-mortem studies report loss of catecholaminergic neurons in the pre-symptomatic phases of PD when anxiety symptoms emerge, and a large literature from rodent and human studies indicate that catecholamines are important mediators of anxiety via their modulatory effects on limbic regions such as the amygdala. On the basis of these observations, we hypothesized that anxiety in PD could result from an early loss of catecholaminergic inputs to the amygdala and/or other limbic structures. To interrogate this hypothesis, we bilaterally injected the neurotoxin 6-OHDA in the mouse basolateral amygdala (BL). This produced a restricted pattern of catecholaminergic (tyrosine-hydroxylase-labeled) denervation in the BL, intercalated cell masses and ventral hippocampus, but not the central amygdala or prefrontal cortex. We found that this circuit-specific lesion did not compromise performance on multiple measures of motor function (home cage, accelerating rotarod, beam balance, pole climbing), but did increase anxiety-like behavior in the elevated plus-maze and light-dark exploration tests. Fear behavior in the pavlovian cued conditioning and passive avoidance assays was, by contrast, unaffected; possibly due to preservation of catecholamine innervation of the central amygdala from the periaqueductal gray. These data provide some of the first evidence implicating loss of catecholaminergic neurotransmission in midbrain-amygdala circuits to increased anxiety-like behavior. Our findings offer an initial step towards identifying the neural substrates for pre-motor anxiety symptoms in PD

Systemic proteasome inhibition triggers neurodegeneration in a transgenic mouse model expressing human α-synuclein under oligodendrocyte promoter: implications for multiple system atrophy

Multiple system atrophy (MSA) is a progressive late onset neurodegenerative α-synucleinopathy with unclear pathogenesis. Recent genetic and pathological studies support a central role of α-synuclein (αSYN) in MSA pathogenesis. Oligodendroglial cytoplasmic inclusions of fibrillar αSYN and dysfunction of the ubiquitin–proteasome system are suggestive of proteolytic stress in this disorder. To address the possible pathogenic role of oligodendroglial αSYN accumulation and proteolytic failure in MSA we applied systemic proteasome inhibition (PSI) in transgenic mice with oligodendroglial human αSYN expression and determined the presence of MSA-like neurodegeneration in this model as compared to wild-type mice. PSI induced open field motor disability in transgenic αSYN mice but not in wild-type mice. The motor phenotype corresponded to progressive and selective neuronal loss in the striatonigral and olivopontocerebellar systems of PSI-treated transgenic αSYN mice. In contrast no neurodegeneration was detected in PSI-treated wild-type controls. PSI treatment of transgenic αSYN mice was associated with significant ultrastructural alterations including accumulation of fibrillar human αSYN in the cytoplasm of oligodendroglia, which resulted in myelin disruption and demyelination characterized by increased g-ratio. The oligodendroglial and myelin pathology was accompanied by axonal degeneration evidenced by signs of mitochondrial stress and dysfunctional axonal transport in the affected neurites. In summary, we provide new evidence supporting a primary role of proteolytic failure and suggesting a neurodegenerative pathomechanism related to disturbed oligodendroglial/myelin trophic support in the pathogenesis of MSA

Changes in the transcriptome of the prefrontal cortex of OXYS rats as the signs of Alzheimer’s disease development

Alzheimer’s disease (AD) is the most prevalent neuro­degenerative disease. It produces atrophic changes in the brain, which cause dementia. The incidence of AD is increasing with increasing life expectancy and gradual aging of the population in developed countries. There are no effective prophylactic inter­ventions because of insufficient understanding of the AD pathogenesis and the absence of adequate experimental models. Recently, we showed that senescence-accelerated OXYS rats represent a promis­ing model of AD; in these rats, accelerated aging of the brain is accompanied by the typical signs of AD: degenerative alterations and death of neurons, a de­crease in synaptic density, mitochondrial dysfunction, hyperphosphorylation of the tau protein, an increased level of amyloid β (Aβ1–42), and the formation of amyloid plaques. To elucidate how these signs develop, we used a nextgeneration RNA sequencing technique (RNA-Seq) to study the prefron­tal-cortex transcriptome of OXYS rats during the manifestation of AD signs (at an age of 5 months) and during their active progres­sion (at an age of 18 months), using age-matched Wistar rats (parental strain) as controls. At the age of 5 months, there were significant differences between OXYS and Wistar rats (p < 0.01) in the mRNA expression of more than 900 genes (> 2000 genes at the age of 18 months) in the prefrontal cortex. Most of these genes were related to neuronal plasticity, protein phosphorylation, Са2+ homeostasis, hypoxia, immune processes, and apoptosis. Between the ages of 5 and 18 months, there were changes in the expression of 499 genes in Wistar rats and changes in the expres­sion of 5500 genes in OXYS rats. Only 333 genes were common between these sets. This finding points to differences in the mechanisms and rates of age-related changes in the brain between normal aging and the period of development of AD-specific neuro­degene­rative processes

Ameliorative effects of the flavonoid fustin in a rat model of trinitrobenzensulfonic acid-induced colitis

Trinitrobenzene sulfonic acid (TNBS)-induced colitis is a widely used animal model that mimics the signs and symptoms of inflammatory bowel disease. Fustin is a flavonoid found in Cotinus coggygria. The aim of the present study was to investigate the effect of fustin isolated from Cotinus coggygria heartwood in a rat model of TNBS-induced colitis. In this experiment, 30 male Wistar rats were used, allocated to three groups: Control, TNBS and TNBS+F10. Colitis was induced by rectal application of TNBS. After the induction of colitis, fustin at a dose of 10 mg/kg was administered orally to TNBS+F10 group in the course of 8 days. Severity of colitis, oxidative stress and inflammation were assessed by macroscopic, histopathological, immunohistochemical and biochemical analyses. Rats from TNBS group demonstrated severe colonic damage. Fustin treatment ameliorated most of the macroscopic and some of the histopathological indices of colonic damage, and restored the activity of the endogenous antioxidant superoxide dismutase in tissue homogenate but did not affect the signs of inflammation measured by the activity of alkaline phosphatase in serum and tissue homogenate, as well as the expression of NF-kB in the colon. In conclusion, the ameliorative effects of fustin in the experimental TNBS-induced colitis might be the result of its antioxidant properties.International Conference: Kliment's Days 2023 - 60 years Faculty of Biology 09/11/2023 - 11/11/2023 Sofia, Bulgari

Influence of Antioxidant SkQ1 on Accumulation of Mitochondrial DNA Deletions in the Hippocampus of Senescence-Accelerated OXYS Rats

Human and animal aging is associated with gradual decline of cognitive functions (especially learning ability and memory) and increased risk of development of neurodegenerative diseases 596 Abbreviations: bp, base pairs; mtDNA, mitochondrial DNA; ∆mtDNA, deletion in mitochondrial DNA; ∆mtDNA 4834 , 4834-bp mitochondrial DNA deletion; ROS, reactive oxygen species; SkQ1, antioxidant 10-(6′-plastoquinonyl)decyltriphenylphosphonium. * To whom correspondence should be addressed. Abstract-Reduction of efficiency of oxidative phosphorylation associated with aging and the development of neurodegenerative diseases including Alzheimer's disease is thought to be linked to the accumulation of deletions in mitochondrial DNA (∆mtDNA), which are seen as a marker of oxidative damage. Recently, we have shown that mitochondria-targeted antioxidant SkQ1 (10-(6′-plastoquinonyl)decyltriphenylphosphonium) can slow the development of signs of Alzheimer's disease in senescence-accelerated OXYS rats. The purpose of this study was to explore the relationship between the development of neurodegenerative changes in the brain of OXYS rats and changes in the amount of mtDNA and the 4834-bp mitochondrial DNA deletion (∆mtDNA 4834 ) as well as the effect of SkQ1. We studied the relative amount of mtDNA and ∆mtDNA 4834 in the hippocampus of OXYS and Wistar (control) rats at ages of 1, 2, 6, 10, and 20 days and 3, 6, and 24 months. During the period crucial for manifestation of the signs of accelerated aging of OXYS rats (from 1.5 to 3 months of age), we evaluated the effects of administration of SkQ1 (250 nmol/kg) and vitamin E (670 mmol/kg, reference treatment) on the amount of mtDNA and ∆mtDNA 4834 and on the formation of the behavioral feature of accelerated senescence in OXYS rats -passive type of behavior in the open field test. In OXYS rats, the level of ∆mtDNA 4834 in the hippocampus is increased compared to the Wistar rats, especially at the stage of completion of brain development in the postnatal period. This level remains elevated not only at the stages preceding the manifestation of the signs of accelerated brain aging and the development of pathological changes linked to Alzheimer's disease, but also during their progression. However, at age of 24 months, there were no detectable differences between the two strains. SkQ1 treatment reduced the level of ∆mtDNA 4834 in the hippocampus of Wistar and OXYS rats and slowed the formation of passive behavior in OXYS rats. These results support the possible use of SkQ1 for prophylaxis of brain aging. Influence of Antioxidant SkQ1 o