891. Hazard characterization of Alternaria toxins to identify data gaps and improve risk assessment for human healthHenriqueta Louro, Ariane Vettorazzi, Adela López de Cerain, Bojana Žegura, Matjaž Novak, 2024, pregledni znanstveni članek Povzetek: Fungi of the genus Alternaria are ubiquitous plant pathogens and saprophytes which are able to grow under varying temperature and moisture conditions as well as on a large range of substrates. A spectrum of structurally diverse secondary metabolites with toxic potential has been identified, but occurrence and relative proportion of the different metabolites in complex mixtures depend on strain, substrate, and growth conditions. This review compiles the available knowledge on hazard identification and characterization of Alternaria toxins. Alternariol (AOH), its monomethylether AME and the perylene quinones altertoxin I (ATX-I), ATX-II, ATX-III, alterperylenol (ALP), and stemphyltoxin III (STTX-III) showed in vitro genotoxic and mutagenic properties. Of all identified Alternaria toxins, the epoxide-bearing analogs ATX-II, ATX-III, and STTX-III show the highest cytotoxic, genotoxic, and mutagenic potential in vitro. Under hormone-sensitive conditions, AOH and AME act as moderate xenoestrogens, but in silico modeling predicts further Alternaria toxins as potential estrogenic factors. Recent studies indicate also an immunosuppressive role of AOH and ATX-II; however, no data are available for the majority of Alternaria toxins. Overall, hazard characterization of Alternaria toxins focused, so far, primarily on the commercially available dibenzo-α-pyrones AOH and AME and tenuazonic acid (TeA). Limited data sets are available for altersetin (ALS), altenuene (ALT), and tentoxin (TEN). The occurrence and toxicological relevance of perylene quinone-based Alternaria toxins still remain to be fully elucidated. We identified data gaps on hazard identification and characterization crucial to improve risk assessment of Alternaria mycotoxins for consumers and occupationally exposed workers. Ključne besede: mycotoxin, exposure routes, genotoxicity, endocrine disruption, immunosuppression, biotransformation, toxicokinetics, tenuazonic acid, alternariol, altenuene, tentoxin, altertoxin Objavljeno v DiRROS: 07.08.2024; Ogledov: 327; Prenosov: 262 Celotno besedilo (3,22 MB) Gradivo ima več datotek! Več... |
892. Groundwater is a hidden global keystone ecosystemMattia Saccò, Stefano Mammola, Florian Altermatt, Roman Alther, Rossano Bolpagni, Anton Brancelj, David Brankovits, Cene Fišer, Vasilis Gerovasileiou, Špela Di Batista Borko, Maja Zagmajster, 2024, pregledni znanstveni članek Povzetek: Groundwater is a vital ecosystem of the global water cycle, hosting unique biodiversity and providing essential services to societies. Despite being the largest unfrozen freshwater resource, in a period of depletion by extraction and pollution, groundwater environments have been repeatedly overlooked in global biodiversity conservation agendas. Disregarding the importance of groundwater as an ecosystem ignores its critical role in preserving surface biomes. To foster timely global conservation of groundwater, we propose elevating the concept of keystone species into the realm of ecosystems, claiming groundwater as a keystone ecosystem that influences the integrity of many dependent ecosystems. Our global analysis shows that over half of land surface areas (52.6%) has a medium-to-high interaction with groundwater, reaching up to 74.9% when deserts and high mountains are excluded. We postulate that the intrinsic transboundary features of groundwater are critical for shifting perspectives towards more holistic approaches in aquatic ecology and beyond. Furthermore, we propose eight key themes to develop a science-policy integrated groundwater conservation agenda. Given ecosystems above and below the ground intersect at many levels, considering groundwater as an essential component of planetary health is pivotal to reduce biodiversity loss and buffer against climate change. Ključne besede: groundwater, keystone ecosystem, surface-subterranean connectivity Objavljeno v DiRROS: 07.08.2024; Ogledov: 357; Prenosov: 294 Celotno besedilo (8,83 MB) Gradivo ima več datotek! Več... |
893. Synthesis, purification, and cell-toxicity of a choline betainateLucija Jurko, Gregor Hostnik, Tobias Alexander Steindorfer, Alja Štern, Perica Bošković, Matej Bračič, Bojana Žegura, Rupert Kargl, 2024, izvirni znanstveni članek Povzetek: In this work, choline chloride and betaine hydrochloride were condensed into a - to our knowledge - unreported choline betainate (N,N,N-trimethyl-2-oxo-2-(2-(trimethylammonio)ethoxy)ethanaminium chloride) using 1,1′-carbonyldiimidazole (CDI) activation of betaine hydrochloride in dimethylsulfoxide. The product and reaction intermediates were isolated, purified by preparative HPLC and analyzed in detail by infrared and nuclear magnetic resonance spectroscopy. The final product has a high cytotoxicity for L929 mouse fibroblasts, and low antibacterial activity against P. Aeruginosa and S. Aureus at concentrations of up to 20 mg/ml. It could potentially further be investigated for similar uses as suxamethonium chloride, a muscle relaxant drug. Ključne besede: choline chloride, betaine hydrochloride, carbonyldiimidazole, HPLC, antimicrobial, cytotoxicity Objavljeno v DiRROS: 07.08.2024; Ogledov: 369; Prenosov: 368 Celotno besedilo (3,60 MB) Gradivo ima več datotek! Več... |
894. In-depth comparison of adeno-associated virus containing fractions after CsCl ultracentrifugation gradient separationMojca Janc, Kaja Zevnik, Ana Dolinar, Tjaša Jakomin, Maja Štalekar, Katarina Bačnik, Denis Kutnjak, Magda Tušek-Žnidarič, Lorena Zentilin, Dmitri G. Fedorov, David Dobnik, 2024, izvirni znanstveni članek Povzetek: Recombinant adeno-associated viruses (rAAVs) play a pivotal role in the treatment of genetic diseases. However, current production and purification processes yield AAV-based preparations that often contain unwanted empty, partially filled or damaged viral particles and impurities, including residual host cell DNA and proteins, plasmid DNA, and viral aggregates. To precisely understand the composition of AAV preparations, we systematically compared four different single-stranded AAV (ssAAV) and self-complementary (scAAV) fractions extracted from the CsCl ultracentrifugation gradient using established methods (transduction efficiency, analytical ultracentrifugation (AUC), quantitative and digital droplet PCR (qPCR and ddPCR), transmission electron microscopy (TEM) and enzyme-linked immunosorbent assay (ELISA)) alongside newer techniques (multiplex ddPCR, multi-angle light-scattering coupled to size-exclusion chromatography (SEC-MALS), multi-angle dynamic light scattering (MADLS), and high-throughput sequencing (HTS)). Suboptimal particle separation within the fractions resulted in unexpectedly similar infectivity levels. No single technique could simultaneously provide comprehensive insights in the presence of both bioactive particles and contaminants. Notably, multiplex ddPCR revealed distinct vector genome fragmentation patterns, differing between ssAAV and scAAV. This highlights the urgent need for innovative analytical and production approaches to optimize AAV vector production and enhance therapeutic outcomes. Ključne besede: recombinant adeno-associated viruses (rAAVs), CsCl ultracentrifugation gradient, analytical methods, digital droplet PCR (ddPCR), transmission electron microscopy (TEM), analytical ultracentrifugation (AUC), size-exclusion chromatography coupled with multi-angle light scattering (SEC-MALS), Illumina sequencing, virology Objavljeno v DiRROS: 07.08.2024; Ogledov: 408; Prenosov: 338 Celotno besedilo (8,47 MB) Gradivo ima več datotek! Več... |
895. Oxytetracycline hyper-production through targeted genome reduction of Streptomyces rimosusAlen Pšeničnik, Lucija Slemc, Martina Avbelj, Miha Tome, Martin Šala, Paul R. Herron, Maksym Shmatkov, Marko Petek, Špela Baebler, Peter Mrak, Daslav Hranueli, Antonio Starcevic, Iain S. Hunter, Hrvoje Petković, 2024, izvirni znanstveni članek Povzetek: Most biosynthetic gene clusters (BGC) encoding the synthesis of important microbial secondary metabolites, such as antibiotics, are either silent or poorly expressed; therefore, to ensure a strong pipeline of novel antibiotics, there is a need to develop rapid and efficient strain development approaches. This study uses comparative genome analysis to instruct rational strain improvement, using Streptomyces rimosus, the producer of the important antibiotic oxytetracycline (OTC) as a model system. Sequencing of the genomes of two industrial strains M4018 and R6-500, developed independently from a common ancestor, identified large DNA rearrangements located at the chromosome end. We evaluated the effect of these genome deletions on the parental S. rimosus Type Strain (ATCC 10970) genome where introduction of a 145 kb deletion close to the OTC BGC in the Type Strain resulted in massive OTC overproduction, achieving titers that were equivalent to M4018 and R6-500. Transcriptome data supported the hypothesis that the reason for such an increase in OTC biosynthesis was due to enhanced transcription of the OTC BGC and not due to enhanced substrate supply. We also observed changes in the expression of other cryptic BGCs; some metabolites, undetectable in ATCC 10970, were now produced at high titers. This study demonstrated for the first time that the main force behind BGC overexpression is genome rearrangement. This new approach demonstrates great potential to activate cryptic gene clusters of yet unexplored natural products of medical and industrial value.
Ključne besede: genome reduction, antibiotic biosynthesis, oxytetracycline, cryptic metabolites Objavljeno v DiRROS: 07.08.2024; Ogledov: 342; Prenosov: 273 Celotno besedilo (5,08 MB) Gradivo ima več datotek! Več... |
896. Hepatic alterations in a BTBR T + Itpr3tf/J mouse model of autism and improvement using melatonin via mitigation oxidative stress, inflammation and ferroptosisRita Rezzani, Marzia Gianò, Daniela Pinto, Fabio Rinaldi, Cornelis J. F. van Noorden, Gaia Favero, 2024, izvirni znanstveni članek Povzetek: Autism spectrum disorder (ASD) is a complicated neurodevelopmental disorder, and its etiology is not well understood. It is known that genetic and nongenetic factors determine alterations in several organs, such as the liver, in individuals with this disorder. The aims of the present study were to analyze morphological and biological alterations in the liver of an autistic mouse model, BTBR T + Itpr3tf/J (BTBR) mice, and to identify therapeutic strategies for alleviating hepatic impairments using melatonin administration. We studied hepatic cytoarchitecture, oxidative stress, inflammation and ferroptosis in BTBR mice and used C57BL6/J mice as healthy control subjects. The mice were divided into four groups and then treated and not treated with melatonin, respectively. BTBR mice showed (a) a retarded development of livers and (b) iron accumulation and elevated oxidative stress and inflammation. We demonstrated that the expression of ferroptosis markers, the transcription factor nuclear factor erythroid-related factor 2 (NFR2), was upregulated, and the Kelch-like ECH-associated protein 1 (KEAP1) was downregulated in BTBR mice. Then, we evaluated the effects of melatonin on the hepatic alterations of BTBR mice; melatonin has a positive effect on liver cytoarchitecture and metabolic functions.
Ključne besede: autism spectrum disorder, liver, oxidative stress, inflammation, ferroptosis Objavljeno v DiRROS: 07.08.2024; Ogledov: 346; Prenosov: 270 Celotno besedilo (12,47 MB) Gradivo ima več datotek! Več... |
897. Retrospective survey of Dickeya fangzhongdai using a novel validated real-time PCR assayŠpela Alič, Katarina Bačnik, Tanja Dreo, 2024, izvirni znanstveni članek Povzetek: Dickeya fangzhongdai, an aggressive plant pathogen, causes symptoms on a variety of crops and ornamental plants including bleeding canker of Asian pear trees. Historical findings stress the need for a specific detection tool for D. fangzhongdai to prevent overlooking the pathogen or assigning it to general Dickeya spp. Therefore, a qualitative real-time PCR for specific detection of D. fangzhongdai has been developed and validated. The developed assay shows selectivity of 100%, diagnostic sensitivity of 76% and limit of detection with 95% confidence interval in plant matrices ranging from 311 to 2,275 cells/mL of plant extracts. The assay was successfully used in a retrospective survey of selected host plants of relevance to Europe and environmental niches relevant to D. fangzhongdai. Samples of potato tubers and plants, plants from the Malinae subtribe (apple, pear, quince, and Asian pear tree) and fresh surface water from Slovenia were analyzed. D. fangzhongdai was not detected in any plant samples, however, 12% of surface water samples were found to be positive. Ključne besede: molecular testing, diagnostics, plant pathogen, real-time PCR, Dickeya, survey, water Objavljeno v DiRROS: 07.08.2024; Ogledov: 345; Prenosov: 238 Celotno besedilo (1,94 MB) Gradivo ima več datotek! Več... |
898. The Superblock model : a review of an innovative urban model for sustainability, liveability, health and well-beingMark J. Nieuwenhuijsen, Audrey De Nazelle, Marta Cirach Pradas, Carolyn Daher, Angel M. Dzhambov, Cynthia Echave, Stefan Gössling, Tamara Iungman, Haneen Khreis, Nicolina Kirby, Jernej Tiran, 2024, izvirni znanstveni članek Povzetek: Introduction
Current urban and transport planning practices have significant negative health, environmental, social and economic impacts in most cities. New urban development models and policies are needed to reduce these negative impacts. The Superblock model is one such innovative urban model that can significantly reduce these negative impacts through reshaping public spaces into more diverse uses such as increase in green space, infrastructure supporting social contacts and physical activity, and through prioritization of active mobility and public transport, thereby reducing air pollution, noise and urban heat island effects. This paper reviews key aspects of the Superblock model, its implementation and initial evaluations in Barcelona and the potential international uptake of the model in Europe and globally, focusing on environmental, climate, lifestyle, liveability and health aspects.
Methods
We used a narrative meta-review approach and PubMed and Google scholar databases were searched using specific terms.
Results
The implementation of the Super block model in Barcelona is slow, but with initial improvement in, for example, environmental, lifestyle, liveability and health indicators, although not so consistently. When applied on a large scale, the implementation of the Superblock model is not only likely to result in better environmental conditions, health and wellbeing, but can also contribute to the fight against the climate crisis. There is a need for further expansion of the program and further evaluation of its impacts and answers to related concerns, such as environmental equity and gentrification, traffic and related environmental exposure displacement. The implementation of the Superblock model gained a growing international reputation and variations of it are being planned or implemented in cities worldwide. Initial modelling exercises showed that it could be implemented in large parts of many cities.
Conclusion
The Superblock model is an innovative urban model that addresses environmental, climate, liveability and health concerns in cities. Adapted versions of the Barcelona Superblock model are being implemented in cities around Europe and further implementation, monitoring and evaluation are encouraged. The Superblock model can be considered an important public health intervention that will reduce mortality and morbidity and generate cost savings for health and other sectors. Ključne besede: urban geography, transport, public health, pollution, sustainable development, Barcelona (Spain) Objavljeno v DiRROS: 07.08.2024; Ogledov: 413; Prenosov: 307 Celotno besedilo (4,38 MB) Gradivo ima več datotek! Več... |
899. Identification of triazolopyrimidinyl scaffold SARS-CoV-2 papain-like protease (PLpro) inhibitorSebastjan Kralj, Marko Jukič, Miha Bahun, Luka Kranjc, Anja Kolarič, Milan Hodošček, Nataša Poklar Ulrih, Urban Bren, 2024, izvirni znanstveni članek Povzetek: The global impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its companion disease, COVID-19, has reminded us of the importance of basic coronaviral research. In this study, a comprehensive approach using molecular docking, in vitro assays, and molecular dynamics simulations was applied to identify potential inhibitors for SARS-CoV-2 papain-like protease (PLpro), a key and underexplored viral enzyme target. A focused protease inhibitor library was initially created and molecular docking was performed using CmDock software (v0.2.0), resulting in the selection of hit compounds for in vitro testing on the isolated enzyme. Among them, compound 372 exhibited promising inhibitory properties against PLpro, with an IC50 value of 82 ± 34 μM. The compound also displayed a new triazolopyrimidinyl scaffold not yet represented within protease inhibitors. Molecular dynamics simulations demonstrated the favorable binding properties of compound 372. Structural analysis highlighted its key interactions with PLpro, and we stress its potential for further optimization. Moreover, besides compound 372 as a candidate for PLpro inhibitor development, this study elaborates on the PLpro binding site dynamics and provides a valuable contribution for further efforts in pan-coronaviral PLpro inhibitor development.
Ključne besede: drug design, protease inhibitor, SARS-CoV-2, papain-like protease, PLpro, antiviral design, in silico drug design, CADD, virtual screening, HTVS, structure-based design Objavljeno v DiRROS: 07.08.2024; Ogledov: 362; Prenosov: 271 Celotno besedilo (6,86 MB) Gradivo ima več datotek! Več... |
900. On the occurrence of early life stage of the king of herrings, Regalectus glesne (Actinopterygii: Lampriformes: Regalectidae), in the Adriatic SeaBranko Dragičević, Armin Pallaoro, Robert Grgičević, Lovrenc Lipej, Jakov Dulčić, 2011, drugi znanstveni članki Povzetek: The occurrence of an early life stage of the king of herrings, Regalecus glesne Ascanius, 1772, is reported for the first time from the Adriatic waters. A single larva (SL = 103.4 mm) was found alive in the waters of open Adriatic near a remote Island PalagruĹľa. Findings of early life stages of this species are very rare in the Mediterranean and have previously been reported only from the waters of the Strait of Sicily and Elba Island.
Ključne besede: fishes, ichthyology, Adriatic sea, Regalectidae, Regalectus glesne, oar fish, Adriatic Sea, larva, diversity, early life stage, record, king of herrings, Central Adriatic Objavljeno v DiRROS: 07.08.2024; Ogledov: 314; Prenosov: 282 Celotno besedilo (1,87 MB) Gradivo ima več datotek! Več... |