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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: 398; Prenosov: 335
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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: 345; Prenosov: 269
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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: 410; Prenosov: 305
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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: 309; Prenosov: 279
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Povzetek: The authors report on the record of the moray eel (Muraena helena) in Slovenian coastal waters (Gulf of Trieste, northern Adriatic). The specimen was caught by a diver with a speargun in June 2011. The moray eel measured 1,127 mm in total length and weighed 4,120 g. The estimated age of the moray eel was about 12 years. This is the first recorded case of the occurrence of moray eel in Slovenian waters.
Ključne besede: moray eel, Murenae helena, zoogeography, Gulf of Trieste
Objavljeno v DiRROS: 07.08.2024; Ogledov: 355; Prenosov: 159
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