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The library has always been a constitutive element of the urbanscape, defined by its space, architecture, function, and the attribute of “being public.” The library and the open public space it is a part of, create a unit in the urbanscape, adding a whole new layer to the open public spaces network. As a node and a connector in the urban fabric, this unit become a part of the urban infrastructure and a powerful tool in urbanscape transformation.

Azo dyes are known as structurally diverse class of organic compounds bearing one or more azo groups (–N=N–) as a bridge between organic residues of which at least one is an aromatic moiety. This group of synthetic dyes is obtained easily by the reaction of diazo coupling with high yield. The importance of azo dyes is reflected in the fact that they account for 60 % of the total number of the dye structures known to be manufactured and used in the coloration of textiles, leather, plastics and cosmetics. Aside from their traditional usage, azo dyes are known for their therapeutic properties and wide range of applications in biomedicine and pharmaceutical industry. Hereby, the present study aims to investigate the relationship between the chemical structure and pharmacological activity of four azo pyridone dyes taking into account the tautomeric form of dyes. The relationship was determined empirically using appropriate software packages as well as in vitro using the 2, 2’-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) method. The results of in silico prediction suggested that all investigated compounds possess good oral bioavailability, while the results of the ABTS assay indicate poor to excellent antioxidant activity depending on the substituent in the phenyl ring. Considering the broad applications of arylazo pyridone dyes, as well as the fact that their relative importance may increase in the future, results obtained in this study serve as a basis for further investigations., Azo boje predstavljaju strukturno najraznovrsniju klasu organskih jedinjenja koja sadrže jednu ili više azo grupa (–N=N–) koje premošćavaju dva organska motiva od kojih je bar jedan aromatičan. Ova grupa sintetskih boja dobija se jednostavnom sintezom koja uključuje reakciju diazo-kuplovanja u visokom prinosu. Da su azo boje od neprocenjivog značaja u različitim granama industrije gde se primenjuju za nijansiranje tekstila, kože, plastike i kozmetičkih proizvoda, govori i činjenica da su zastupljene sa preko 60%. Pored tradicionalne primene, azo boje su poznate i po sve većoj upotrebu u biomedicini i farmaceutskoj industriji. Na osnovu navedeneg, cilj ovog rada je da se detaljnije ispita veza između hemijske strukture četiri azo piridonske boje i njihove farmakološke aktivnosti uzimajući u obzir tautomerni oblik boje. Ova veza određena je empirijski korišćenjem odgovarajućih softverskih paketa kao i in vitro određivanjem njihove antioksidativne aktivnosti primenom ABTS metode. Rezultati in silico predikcije pokazuju da sva ispitivana jedinjenja poseduju dobru oralnu bioraspoloživost i nisku do odličnu antioksidativnu aktivnost u zavisnosti od spupsptituenta u fenilnom jezgru. Uzimajući u obzir širok spektar primene arilazo piridonskih boja kao i činjenicu da će njihov značaj konstantno rasti, rezultati ostvareni u ovom radu predstavljaju interesantnu osnovu za buduća istraživanja.

Genome-wide association studies (GWAS) have provided strong evidence that early- and late-onset MG have different genetic backgrounds. Recent in silico analysis based on GWAS results revealed rs231735 and rs231770 variants within CTLA-4 locus as possible MG causative genetic factors. We aimed to explore the association of rs231735 and rs231770 with MG in a representative cohort of Serbian patients. We conducted an age-, sex-, and ethnicity-matched case–control study. Using TaqMan allele discrimination assays, the frequency of rs231735 and rs231770 genetic variants was examined in 447 AChR-MG patients and 447 matched controls. There was no significant association of rs231735 and rs231770 with the entire MG cohort (P > 0.05). Nevertheless, when stratifying patients into early-onset (n = 183) and late-onset MG (n = 264), we found early-onset patients had a significantly lower frequency of the rs231735 allele T compared to controls (OR = 0.734, 95% CI = 0.575–0.938, p10e6 permutation < 0.05), and rs231735 genotype TT and rs231770 genotype TT had a protective effect on early-onset MG (OR = 0.548, 95% CI = 0.339–0.888, and OR = 0.563, 95% CI = 0.314–1.011, p10e6 permutation < 0.05). Consequently, we found that individuals with the rs231735-rs231770 haplotype GC had a higher risk for developing early-onset MG (OR = 1.360, P = 0.027, p10e6 permutation < 0.05). Our results suggest that CTLA-4 rs231735 and rs231770 may be risk factors only for patients with early-onset MG in Serbian population.

Edukativna uloga geografskih ekskurzija u zaštićenim područjima sastoji se u formiranju vrednosnih stavova i ekološkog ponašanja učenika kroz upoznavanje sa pojmovima iz ekologije i neposredne životne sredine koji obogaćuju njihov rečnik. Geografske ekskurzije imaju posebne didaktičko-metodičke specifičnosti jer omogućavaju učenicima direktan kontakt sa prirodom u kojoj samostalno mogu da uoče ekološke probleme i razviju svest o životnoj sredini. To podrazumeva sticanje funkcionalnih znanja, razvijanje veština i navika, kao i formiranje stavova o ekološkim osobenostima i zakonima u životnoj sredini. Glavni cilj geografskih ekskurzija sastoji se u formiranju odnosa svakog učenika prema sredini koja ga okružuje. Kako bi se razvila ekološka svest kod učenika, potrebno je adekvatno planirati i istaći vrednost geografskih ekskurzija u zaštićenim područjima. Svaki odlazak u prirodu najčešće je za učenike doživljaj, ali doživljaj u kome će učenici učiti kako da prepoznaju vrstu ptice, imenuju cveće, lekovito bilje, drveće, uoče zagađenje, sagledaju posledice, predlože moguća rešenja i navedu konkretne akcije koje bi dovele do očuvanja i unapređivanja životne sredine.

Periodontitis (PD) is a degenerative, bacteria-induced chronic disease of periodontium causing bone resorption and teeth loss. It includes a strong reaction of immune cells through the secretion of proinflammatory factors such as Interleukin-17 (IL-17). PD treatment may consider systemic oral antibiotics application, including doxycycline (Dox), exhibiting antibacterial and anti-inflammatory properties along with supportive activity in wound healing, thus affecting alveolar bone metabolism. In the present study, we aimed to determine whether Dox can affect the regenerative potential of periodontal ligament mesenchymal stem cells (PDLSCs) modulated by IL-17 in terms of cell migration, osteogenic potential, bioenergetics and expression of extracellular matrix metalloproteinase 2 (MMP-2). Our findings indicate that Dox reduces the stimulatory effect of IL-17 on migration and MMP-2 expression in PDLSCs. Furthermore, Dox stimulates osteogenic differentiation of PDLSCs, annulling the inhibitory effect of IL-17 on PDLSCs osteogenesis. In addition, analyses of mitochondrial respiration reveal that Dox decreases oxygen consumption rate in PDLSCs exposed to IL-17, suggesting that changes in metabolic performance can be involved in Dox-mediated effects on PDLSCs. The pro-regenerative properties of Dox in inflammatory microenvironment candidates Dox in terms of regenerative therapy of PD-affected periodontium are observed.

Parodontopatija je hronično progresivno inflamatorno oboljenje tkiva parodoncijuma uzrokovano bakterijama zubnog plaka. Destrukcija parodoncijuma je posledica prekomerne aktivacije inflamatornog odgovora domaćina na bakterijsku infekciju i posledične produkcije citokina uključujući Interleukin-17 (IL-17). Lečenje parodontopatije podrazumeva i sistemsku primenu oralnih antibiotika poput doksociklina. Ovaj antibiotik iz klase tetraciklina ispoljava kako antibakterijska, tako i antiinflamatorna svojstva, a poznato je da utiče i na reparaciju tkiva i metabolizam alveolarnih kostiju. Cilj ove studije je bio da utvrdimo da li doksociklin utiče na regenerativni potencijal mezenhimskih matičnih ćelija periodoncijuma (PDL-MMĆ) tretiranih sa IL-17. Naši rezultati su pokazali da doksociklin značajno smanjuje stimulativni efekat IL-17 na migraciju i ekspresiju matriksne metaloproteinaze 2 u PDL-MMĆ. Pored toga, doksociklin stimuliše osteogenu diferencijaciju PDL-MMĆ poništavajući inhibitorni efekat IL-17 na osteogenezu ovih ćelija. Analize ćelijske respiracije su otkrile da doksociklin smanjuje stopu potrošnje kiseonika i mitohondrijalnu biogenezu u IL-17-tretiranim PDL-MMĆ. Pokazana pro-regenerativna svojstva doksociklina u inflamatornom okruženju ukazuju na potencijal njegove primene u razvoju novih pristupa za terapiju parodontopatije.

Periodontal disease is a chronic infection of periodontal tissue characterized by extracellular matrix (ECM) degradation due to increased expression of plasminogen activators and matrix metalloproteinases (MMPs) and various proinflammatory cytokines, including interleukin (IL)-17. Successful regeneration of damaged periodontal tissues depends on the proper functionality of periodontal ligament mesenchymal stem cells (PDLMSCs), especially the production of extracellular matrix proteases. We investigated the influence of IL-17 on ECM remodeling through modulation of urokinasetype plasminogen activator (uPA) and MMP2/MMP9 expression in human PDLMSCs at mRNA, protein and activity levels using by RT-PCR, Western blotting and zymography, respectively. Investigation of the involvement of MAPKs in these processes in PDLMSCs was determined by Western blotting, as well as by utilizing specific p38 and MEK1/2 inhibitors. Our results show that IL-17 activates MAPK signaling in PDLMSCs. Moreover, IL-17 had no effect on MMP9 expression, but it stimulated uPA and MMP2 gene and protein expression in PDLMSCs through the activation of the ERK1/2 MAPK signaling pathway. The obtained data suggest that IL-17 contributes to ECM degradation in the periodontal ligament by stimulating uPA and MMP2 expression and activity in PDLMSCs. This information is important for understanding periodontal disease development and defining future directions of its treatment.

A convenient and efficient approach toward the synthesis of six 3-(4-substituted benzyl)-6,7-benzo-1,3-diazaspiro[4.5]decane-2,4-diones (1‒6) by Bucherer-Bergs reaction and further alkylation at position 3 of the hydantoin ring is reported. Further, their chemical structure was confirmed by melting points, elemental analysis, FT-IR, NMR and UV–Vis spectroscopic methods. To gain an insight into interactions which the investigated spirohydantoins establish with their environment, their absorption spectra were recorded in selected solvents of different polarity and the solvent effects on the UV-Vis absorption band positions, intensity and shape, were discussed. Substiuent effects on the solvatochromism of compounds 1−6 were analyzed using the Hammett's equation. Considering the broad applications of hydantoin derivatives, as well as the fact that their relative importance may increase in the future, results obtained in this study serve as a basis for further investigations.

Here we have included the conformational gating by Glu242 into a framework of the proposed His291 pumping model [4]. DFT/electrostatic calculations are employed to obtain energetics of the proton and electron transfer reaction steps during the O→E transition [2, 3, 5–7]. In addition, transition state theory estimates activation energies and kinetic barriers from the rate constant of transitions. The energy profile of the reaction mechanism is studied by exploring how the redox state of the metal centers, dielectric solvation effects, and membrane potential gradient affect the energy levels and possible leakage of the protein pump through the Glu242 gating site. Particular emphasis is made on side reactions that may short-circuit the pump, resulting in a loss of proton pumping, and how this may be avoided in natural biological systems [2, 3]. CcO employs several control mechanisms and gating situations to ensure the proton translocation unidirectionality and prevent proton leak in the opposite direction

With computer simulations that assess pKas of critical residues, explore electron and proton pathways, and evaluate the energetics of PT and ET processes, we can provide a more in-depth understanding of the molecular mechanism and catalytic cycle of CcO. Combining the DFT electronic structure and energy calculations with reaction and protein field contributions allows self-consistent solvation energy calculations to be iteratively performed. Moreover, valuable insights into mechanistic details and energetics of proton pumping and coupled ET/PT reactions are gained at the atomic level.

The present study describes representative examples of supramolecular arrangement of 5-phenylhydantoins achieved through various N–H⋯O hydrogen-bonding patterns. Four derivatives, 5-ethyl-5-(4-methylphenyl)hydantoin (1) and three 5-methyl-5-(3- or 4-substituted phenyl)hydantoins (2–4), were synthesized by the Bucherer–Bergs reaction and their crystal structures were determined by the single crystal X-ray diffraction method. A racemate, racemic hydrate and conglomerate as outcomes of crystallization from racemic solutions were found here. The crystal structures were firstly subjected to Hirshfeld surfaces analysis. The development of hydrogen bonding driven two-dimensional assemblies such as tapes, ribbons and sheets was further analysed using DFT calculations in terms of contribution of dimeric motifs as building blocks, which are associated with the presence of intermolecular interactions. To explore qualitative correlations between intermolecular interactions determining the crystal structures of the investigated compounds and those underlying their biological activity, we performed a docking study on the neuronal voltage gated sodium channels, matrix metalloproteinase 12 and aldose reductase. The supramolecular profiles of the investigated compounds are also maintained in biological systems and as such are responsible for differences in their biological activities.

The catalytic degradation of hazardous organic contaminants in industrial wastewater is a promising technology. Reactions of tartrazine, the synthetic yellow azo dye, with Oxone® in the presence of catalyst in strong acidic condition (pH 2), were detected by using UV–Vis spectroscopy. In order to extend the applicability profile of Co-supported Al-pillared montmorillonite catalyst an investigation of Oxone® induced reactions were performed in extreme acidic environment. The products of the reactions were identified by liquid chromatography–mass spectrometry (LC-MS). Along with the catalytic decomposition of tartrazine induced by radical attack (confirmed as unique reaction path under neutral and alkaline conditions), the formation of tartrazine derivatives by reaction of nucleophilic addition was also detected. The presence of derivatives under acidic conditions slowed down the hydrolysis of tartrazine diazo bond in comparison to the reactions in neutral environment. Nevertheless, the reaction in acidic conditions (pH 2) is faster than the one conducted in alkaline conditions (pH 11). Theoretical calculations were used to complete and clarify the mechanisms of tartrazine derivatization and degradation, as well as to predict the UV–Vis spectra of compounds which could serve as predictors of certain reaction phases. ECOSAR program, used to estimate toxicological profile of compounds to aquatic animals, indicated an increase in the harmfulness of the compounds identified by LC-MS as degradation products from the reaction conducted for 240min. It could be concluded that an intensification of the process parameters (higher concentration of Oxone®, higher catalyst loading, increased reaction time, etc.) is needed in order to obtain only biodegradable products.

Geographic territory is the condition and framework of tourist development, the origin and destination of tourist movements. Natural resources, their attractiveness, quality and environmental preservation represent an extremely important potential for the development of tourism. The uniqueness and specificity of the natural resources of the Danube region in Serbia is an important part of the heritage, and its attractiveness is a significant component in the tourist offer of Serbia. The natural and throughout history strategic importance of the Danube has also influenced the rich and diverse cultural and historical heritage. Functionally connected natural and cultural values of historical importance represent an important tourist attraction and a prerequisite for the further development of this area. The tourist area of the Danube region in Serbia includes protected areas and individual localities of national and international importance, unique natural beauty and cultural values: Special Nature Reserve "Gornje Podunavlje", National Park "Đerdap", Bačka, Petrovaradinska, Beogradska, Smederevska, Ramska, Golubačka and Fetislam fortress, Lepenski Vir, Viminacium and numerous other specific landscape entities and localities. The geographical and historical connection of protected natural and cultural assets predetermines the use of this area for various types of tourism. This creates opportunities and activates the conditions for the development of complementary activities and affects the protection and improvement of the environment of the entire area. The planned development of tourism is defined through numerous sustainable development strategies both at the national and international levels. The Danube region is characterized by a unity of diversity that should be promoted as a spatially connected whole. The combined diverse natural and cultural-historical wealth of the Danube region in Serbia, as part of the European natural and cultural heritage, represents a grea

Current research data reveal microenvironment as a significant modifier of physical functions, pathologic changes, as well as the therapeutic effects of stem cells. When comparing regeneration potential of various stem cell types used for cytotherapy and tissue engineering, mesenchymal stem cells (MSCs) are currently the most attractive cell source for bone and tooth regeneration due to their differentiation and immunomodulatory potential and lack of ethical issues associated with their use. The microenvironment of donors and recipients selected in cytotherapy plays a crucial role in regenerative potential of transplanted MSCs, indicating interactions of cells with their microenvironment indispensable in MSC-mediated bone and dental regeneration. Since a variety of MSC populations have been procured from different parts of the tooth and tooth-supporting tissues, MSCs of dental origin and their achievements in capacity to reconstitute various dental tissues have gained attention of many research groups over the years. This review discusses recent advances in comparative analyses of dental MSC regeneration potential with regards to their tissue origin and specific microenvironmental conditions, giving additional insight into the current clinical application of these cells.

Periodontal disease is a chronic infection of periodontal tissue characterized by extracellular matrix (ECM) degradation due to increased expression of plasminogen activators and matrix metalloproteinases (MMPs) and various proinflammatory cytokines, including interleukin (IL)-17. Successful regeneration of damaged periodontal tissues depends on the proper functionality of periodontal ligament mesenchymal stem cells (PDLMSCs), especially the production of extracellular matrix proteases. We investigated the influence of IL-17 on ECM remodeling through modulation of urokinasetype plasminogen activator (uPA) and MMP2/MMP9 expression in human PDLMSCs at mRNA, protein and activity levels using by RT-PCR, Western blotting and zymography, respectively. Investigation of the involvement of MAPKs in these processes in PDLMSCs was determined by Western blotting, as well as by utilizing specific p38 and MEK1/2 inhibitors. Our results show that IL-17 activates MAPK signaling in PDLMSCs. Moreover, IL-17 had no effect on MMP9 expression, but it stimulated uPA and MMP2 gene and protein expression in PDLMSCs through the activation of the ERK1/2 MAPK signaling pathway. The obtained data suggest that IL-17 contributes to ECM degradation in the periodontal ligament by stimulating uPA and MMP2 expression and activity in PDLMSCs. This information is important for understanding periodontal disease development and defining future directions of its treatment.

Current research data reveal microenvironment as a significant modifier of physical functions, pathologic changes, as well as the therapeutic effects of stem cells. When comparing regeneration potential of various stem cell types used for cytotherapy and tissue engineering, mesenchymal stem cells (MSCs) are currently the most attractive cell source for bone and tooth regeneration due to their differentiation and immunomodulatory potential and lack of ethical issues associated with their use. The microenvironment of donors and recipients selected in cytotherapy plays a crucial role in regenerative potential of transplanted MSCs, indicating interactions of cells with their microenvironment indispensable in MSC-mediated bone and dental regeneration. Since a variety of MSC populations have been procured from different parts of the tooth and tooth-supporting tissues, MSCs of dental origin and their achievements in capacity to reconstitute various dental tissues have gained attention of many research groups over the years. This review discusses recent advances in comparative analyses of dental MSC regeneration potential with regards to their tissue origin and specific microenvironmental conditions, giving additional insight into the current clinical application of these cells.

Two spirohydantoin derivatives, 3-(4-chlorobenzoyl)-1,3-diazaspiro[4.5]decane-2,4-dione (1) and 3-(4-bromobenzoyl)-1,3-diazaspiro[4.5]decane-2,4-dione (2), were synthesized and analyzed by single crystal X-ray diffraction, DFT and QTAIM calculations. Simple substitution of the benzoyl unit gave rise to different crystal structures. In 1, a parallel stack along the b-axis with alternating perpendicular separation is formed, while in 2 the R46(32) nets are joined together to form stacks which enclose linear channels. Hierarchical development of these crystal structures was analyzed through dimeric motifs associated with the presence of intermolecular interactions. By including the previously reported structurally-related spirohydantoin derivatives, we created a set of structures which enabled us to evaluate substituent effects on their conformational preferences, i.e., widening of the dihedral angle between the hydantoin and substituted benzoyl unit when going from F to Br. A conformational search revealed that the value of the torsion angle N3-C11-C12-C13 can be regarded as a compromise between the extended conjugation between the carbonyl and phenyl group and intramolecular C-H⋯O interaction between these two groups. This intramolecular effect is more pronounced on the torsion angle C2-N3-C11-C12, which defines the relative orientation between the hydantoin ring and the carbonyl bridge. The present work may provide a basis for design of new cyclohexane-5-spirohydantoins with potential for pharmaceutical applications both at the molecular and supramolecular level.

Derivat cikloheksan-5-spirohidantoina (Slika 1) je sintetisan, određena je njegova kristalna struktura i urađena kvantno-hemijska analiza. Kristalno pakovanje grade mreže supramolekulskih R6 4 (32) prstenova postavljenih međusobno paralelno, pri čemu se formiraju linearni kanali. Određene su vrednosti energije intermolekulskih interakcija za različite dimerne motive dobijene iz kristalne strukture. Uzimajući u razmatranje prethodno strukturno okarakterisane srodne spirohidantoine [1], dobijena je serija jedinjenja koja je omogućila procenu uticaja supstituenata na njihovu molekulsku i kristalnu strukturu., A spirohydantoin derivative (Figure 1) was synthesized and its crystal structure was determined by single crystal X-ray diffraction and analysed by DFT calculations. The crystal packing is made of supramolecular nets of R6 4 (32) rings linked together to form stacks that enclose linear channels. The intermolecular interaction energies are quantified for various dimeric motifs. By including the previously reported structurally-related spirohydantoins [1], we created a set of compounds that enabled us to evaluate substituent effects on both molecular and crystal structures.

Educational tourism is a selective form of thematic tourism and implies a trend of acquiring new knowledge, transferring knowledge to others, as well as improving skills outside the classroom. It implies a tourist activity in which education is the primary or secondary motive for staying at the destination. The main goal of the travel is focused on activities that include visits to other countries to learn about different cultures. These include student exchange programs and study trips, work, and skills development in different and new environments, such as numerous international internships. There is a difference between travels where education is not the main motive; however, during the holiday guests are educated about certain aspects of the tourist offer (e.g. cultural attractions) and travels where education is the main motive for travel and stay at the destination.