Supplementary data for article: Mehmeti, E.; Stanković, D. M.; Chaiyo, S.; Zavasnik, J.; Žagar, K.; Kalcher, K. Wiring of Glucose Oxidase with Graphene Nanoribbons: An Electrochemical Third Generation Glucose Biosensor. Microchimica Acta 2017, 184 (4), 1127–1134. https://doi.org/10.1007/s00604-017-2115-5

Supplementary material for: [https://doi.org/10.1007/s00604-017-2115-5]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2438

A preliminary study of the miRNA restitution effect on CNV-induced miRNA downregulation in CAKUT

Background The majority of CAKUT-associated CNVs overlap at least one miRNA gene, thus affecting the cellular levels of the corresponding miRNA. We aimed to investigate the potency of restitution of CNV-affected miRNA levels to remediate the dysregulated expression of target genes involved in kidney physiology and development in vitro. Methods Heterozygous MIR484 knockout HEK293 and homozygous MIR185 knockout HEK293 cell lines were used as models depicting the deletion of the frequently affected miRNA genes by CAKUT-associated CNVs. After treatment with the corresponding miRNA mimics, the levels of the target genes have been compared to the non-targeting control treatment. For both investigated miRNAs, MDM2 and PKD1 were evaluated as common targets, while additional 3 genes were investigated as targets of each individual miRNA (NOTCH3, FIS1 and APAF1 as hsa-miR-484 targets and RHOA, ATF6 and CDC42 as hsa-miR-185-5p targets). Results Restitution of the corresponding miRNA levels in both knockout cell lines has induced a change in the mRNA levels of certain candidate target genes, thus confirming the potential to alleviate the CNV effect on miRNA expression. Intriguingly, HEK293 WT treatment with investigated miRNA mimics has triggered a more pronounced effect, thus suggesting the importance of miRNA interplay in different genomic contexts. Conclusions Dysregulation of multiple mRNA targets mediated by CNV-affected miRNAs could represent the underlying mechanism behind the unresolved CAKUT occurrence and phenotypic variability observed in CAKUT patients. Characterizing miRNAs located in CNVs and their potential to become molecular targets could eventually help in understanding and improving the management of CAKUT

An approach for the automated synthesis of technical processes

This paper considers the implications of introducing the computational method for technical process synthesis founded on the Theory of Technical Systems as an addition to the current Computational Design Synthesis (CDS) methods and tools. A computational method containing formal model of technical process based on labelled multidigraph and formal model of technical process synthesis that is based on labelled multidigraph graph-grammar transformations will be presented. The result of applying transformation to the multigraph is generation of variants showing how technical process could be accomplished

Supplementary data for the article: Samphao, A.; Kunpatee, K.; Prayoonpokarach, S.; Wittayakun, J.; Švorc, L.; Stankovic, D. M.; Zagar, K.; Ceh, M.; Kalcher, K. An Ethanol Biosensor Based on Simple Immobilization of Alcohol Dehydrogenase on Fe3O4"Au Nanoparticles. Electroanalysis 2015, 27 (12), 2829–2837. https://doi.org/10.1002/elan.201500315

Supporting information for: [ https://doi.org/10.1002/elan.201500315]Related to published version:[http://cherry.chem.bg.ac.rs/handle/123456789/2034

Odnosi silvijevog kanala sa okolnim delovima mozga i lobanje mereni anatomski i magnetnom rezonancom

Introducton/Objective: Insufficiency of relevant anatomic data and great neurological and neurosurgical significance were the reasons for this study with scientific and practical implications. The purpose was to determine, at the transverse in situ section of the head, the position and relations of the sylvian aqueduct of the mesencephalon by measuring its distances from particular brain and calvaria structures. Also, the aim was to determine the same distances according to axial sections by using MRI. Methods: The material consisted of twenty autopsy human heads. The section of the head was made at the level of the tentorial hiatus and the midbrain. After that, we measured the distances between the cerebral aqueduct and a) posterior border of the optic chiasm, b) upper border of the dorsum sellae, c) terminal bifurcation of the basilar artery, d) beginning of the straight sinus, e) internal occipital protuberance, f ) tentorial edge (lateral from the aqueduct), and g) internal surface of the calvaria (lateral to the aqueduct). We determined the same distances by the MRI system. The measurements were made in 37 subjects. Results: The numerical data obtained by this study will be of benefit to neurosurgeons in choosing a surgical approach to the contents of the incisural space, and to neurologists for the exact localization of the lesion and interpretation of certain signs and symptoms. Conclusion: The results of a detailed examination of the sylvian aqueduct position and relations have shown that the use of MRI is the morphometric method of choice, because it is more precise for all the parameters monitored than in situ measurements.Uvod/Cilj: Nedostatak odgovarajućih anatomskih podataka i veliki neurološki i neurohirurški značaj su bili razlozi za pokretanje ove studije sa naučnim i praktičnim značajem. Cilj rada je bio da se, na poprečnom preseku glave, odrede položaj i odnosi Silvijevog kanala srednjeg mozga merenjem razdaljina do određenih struktura mozga i lobanje. Takođe, cilj je i da se odrede iste razdaljine korišćenjem poprečnih preseka magnetne rezonance (MR) glave. Metode rada: Materijal su činili preseci 20 glava dobijeni tokom rutinske obdukcije. Preseci glave i mozga su pravljeni u nivou zjapa šatora malog mozga i srednjeg mozga. Merili smo rastojanja između Silvijevog kanala i a) zadnje ivice optičke raskrsnice, b) gornje ivice leđnog dela hipofizne jame, v) završne račve bazilarne arterije, g) početka pravog sinusa, d) unutrašnje potiljačne kvrge, đ) ivice tentorijuma (upolje od kanala srednjeg mozga) i e) unutrašnje površine krova lobanje (upolje od kanala srednjeg mozga). Merili smo iste razdaljine korišćenjem MR. Merenje je obavljeno na 37 osoba. Rezultati: Numerički podaci dobijeni ovom studijom biće od koristi neurohirurzima u pronalaženju hirurškog pristupa sadržaju prostora između slobodnih ivica tentorijuma, kao i neurolozima za preciznu lokalizaciju lezija i interpretaciju nekih znakova i simptoma. Zaključak: Rezultati detaljnog proučavanja položaja i odnosa Silvijevog kanala pokazali su da je korišćenje MR morfometrijska metoda izbora jer je mnogo preciznije za sve posmatrane parametre od merenja tokom obdukcije

miRNA-free rare pathogenic CNVs could drive toward variable CAKUT phenotypes

Introduction: Genetic studies of congenital anomalies of the kidney and urinary tract (CAKUT) have demonstrated variable penetrability and expressivity of the associated genetic defects. Previously, it was shown that deletions of 17q12 and 22q11.2 regions were specific for kidney anomalies (KA) while 16p11.2 and 1q21.1 loci showed extensive pleiotropy in CAKUT phenotypes. CNVs affecting miRNA gene dosage have been described to have functional influence on gene expression. We aimed to conduct comprehensive in silico analysis using publicly available databases to analyze miRNA content of CAKUT-associated CNVs in quoted chromosomal loci with regard to pleiotropy. Methods: Extensive literature review was conducted to collect data about pathogenic rCNVs associated with CAKUT. UCSC genome browser tool was employed for mapping miRNAs onto collected rCNV regions. Results: Analysis of CNVs in CAKUT included four studies counting more than 2500 patients. In further analysis we included 191 patients harboring pathogenic CNVs. Surprisingly, CAKUT pleiotropic regions (16p11.2, 1q21.2) did not contain any miRNA. 22q11.2 showed the densest miRNAs content (n = 21). Conclusions: Absence of miRNAs may potentially pronounce the pleiotropy of the CAKUT genetic defects, thus leading to the variety of phenotypes. Contrary, abundancy of miRNAs in 22q11.2 might be associated with reproducible phenotype, such as KA, producing the functional effect when deleted. This assumption agrees with recent results of miRNA expression variability in 22q11.2 deletion syndrome.54th European Society of Human Genetics (ESHG) Conference; August 28-31, 2021; Virtual ConferenceAbstracts from the 54th European Society of Human Genetics (ESHG) Conference: e-Poster

Supplementary data for article: Mehmeti, E.; Stanković, D. M.; Chaiyo, S.; Zavasnik, J.; Žagar, K.; Kalcher, K. Wiring of Glucose Oxidase with Graphene Nanoribbons: An Electrochemical Third Generation Glucose Biosensor. Microchimica Acta 2017, 184 (4), 1127–1134. https://doi.org/10.1007/s00604-017-2115-5

Supplementary material for: [https://doi.org/10.1007/s00604-017-2115-5]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2438

The Role of Macrophage Inhibitory Factor in TAA-Induced Liver Fibrosis in Mice: Modulatory Effects of Betaine

Macrophage inhibitory factor (MIF) is a multipotent cytokine, involved in the inflammatory response to infections or injuries. This study investigates the role of MIF in liver fibrosis and the modulating effect of betaine on MIF in thioacetamide (TAA)-induced liver fibrosis. The wild-type and knockout MIF−/− C57BL/6 mice were divided into the following groups: control; Bet group, which received betaine; MIF−/−; MIF−/−+Bet; TAA group, which received TAA; TAA+Bet; MIF−/−+TAA; and MIF−/−+TAA+Bet group. After eight weeks of treatment, liver tissue was collected for further analysis. The results revealed that TAA-treated MIF-deficient mice had elevated levels of hepatic TGF-β1 and PDGF-BB, as well as MMP-2, MMP-9, and TIMP-1 compared to TAA-treated wild-type mice. However, the administration of betaine to TAA-treated MIF-deficient mice reduced hepatic TGF-β1 and PDGF-BB levels and also the relative activities of MMP-2, MMP-9 and TIMP-1, albeit less effectively than in TAA-treated mice without MIF deficiency. Furthermore, the antifibrogenic effect of MIF was demonstrated by an increase in MMP2/TIMP1 and MMP9/TIMP1 ratios. The changes in the hepatic levels of fibrogenic factors were confirmed by a histological examination of liver tissue. Overall, the dual nature of MIF highlights its involvement in the progression of liver fibrosis. Its prooxidant and proinflammatory effects may exacerbate tissue damage and inflammation initially, but its antifibrogenic activity suggests a potential protective role against fibrosis development. The study showed that betaine modulates the antifibrogenic effects of MIF in TAA-induced liver fibrosis, by decreasing TGF-β1, PDGF-BB, MMP-2, MMP-9, TIMP-1, and the deposition of ECM (Coll1 and Coll3) in the liver

Identification of micro RNA from common copy number variants as risk factors for CAKUT

Introduction: Congenital anomalies of the kidney and urinary tracts(CAKUT) are a diverse spectrum of defects with complex etiology and not fully explained genetic background. miRNA-containing copy number variants (CNVs) are described as genetic risk factor for the disease development. We aimed to identify miRNAs with the maximum regulatory coverage of previously reported differentially expressed genes in CAKUT tissue compared to controls and bioinformatically characterize a set of these miRNAs which are located in common CNVs. Methods: Differentially expressed genes were identified from ureter tissue transcriptome open data GSE83946 from 15 CAKUT patients and 7 healthy controls, generated in house previously. miRPathDB v2.0 was used for identification of miRNAs with maximum coverage of DEGs(miRNAs which complimentarily regulate all DEGs). Mapping of maximum coverage miRNAs onto common CNVs (frequency >0.2) was performed using UCSC genome browser and gnomAD database. miRNA mapping common CNVs were further bioinformatically analyzed using miRPathDB v2.0. Results: In a maximum coverage set of 50 miRNAs interacting with DEGs in CAKUT, we have identified 3 miRNA geneslocated in the common CNVs(hsa-miR-663b, hsa-miR-3180-3p and hsa-miR-1302). Using Reactome database we identified all three miRNAsto be significantly enriched in the pathway Neuronal System: -log(p-value)>2.326 for hsa-miR-1302; -log(p-value)>1.556 for hsa-miR-3180-3p; and -log(pvalue)>1.703 for hsa-miR-663b. Conclusion: CAKUT is characterized with variable penetrability and expressivity and often followed with other comorbiditiessuch as neurodevelopmental disorders. miRNAsinvolved in DEG networks and prone to CNV effects could present modulating factors of the disease phenotype. Further studies should provide additional evidence about hsa-miR-1302, hsa-miR-3180-3p and hsa-miR-663b involvements in CAKUT etiologyThe Second Congress of Molecular Biologists of Serbia; October 6-8, Belgrade, 2023