171. Energy metabolism in IDH1 wild-type and IDH1-mutated glioblastoma stem cells : a novel target for therapy?Cornelis J. F. van Noorden, Vashendriya V. V. Hira, Amber J. van Dijck, Metka Novak, Barbara Breznik, Remco J. Molenaar, 2021, pregledni znanstveni članek Povzetek: Cancer is a redox disease. Low levels of reactive oxygen species (ROS) are beneficial for cells and have anti-cancer effects. ROS are produced in the mitochondria during ATP production by oxidative phosphorylation (OXPHOS). In the present review, we describe ATP production in primary brain tumors, glioblastoma, in relation to ROS production. Differentiated glioblastoma cells mainly use glycolysis for ATP production (aerobic glycolysis) without ROS production, whereas glioblastoma stem cells (GSCs) in hypoxic periarteriolar niches use OXPHOS for ATP and ROS production, which is modest because of the hypoxia and quiescence of GSCs. In a significant proportion of glioblastoma, isocitrate dehydrogenase 1 (IDH1) is mutated, causing metabolic rewiring, and all cancer cells use OXPHOS for ATP and ROS production. Systemic therapeutic inhibition of glycolysis is not an option as clinical trials have shown ineffectiveness or unwanted side effects. We argue that systemic therapeutic inhibition of OXPHOS is not an option either because the anti-cancer effects of ROS production in healthy cells is inhibited as well. Therefore, we advocate to remove GSCs out of their hypoxic niches by the inhibition of their binding to niches to enable their differentiation and thus increase their sensitivity to radiotherapy and/or chemotherapy. Ključne besede: glioblastoma stem cells, IDH1-mutation, energy metabolism Objavljeno v DiRROS: 05.08.2024; Ogledov: 172; Prenosov: 175
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172. From plastics to microplastics and organismsOliver Bajt, 2021, pregledni znanstveni članek Povzetek: The amount of plastic waste and microplastics released into marine environments has increased rapidly in recent decades. The durability of plastic materials results in major problems following their release into the environment. This study provides an overview of recent findings on issues related to plastic degradation, the accumulation of microplastics in mussels and fishes, and the toxicological effects associated with the ingestion of microplastics. These findings confirm the serious problem of slowly degrading plastics (which rarely degrade fully) in natural marine environments. Microplastics have become widespread pollutants and have been detected in mussels and fish around the world. Microplastic particles, whether virgin or with adsorbed pollutants on their surfaces, pose a health problem after being ingested by marine organisms. This paper ends by highlighting the need for certain improvements in studies of these phenomena. Objavljeno v DiRROS: 05.08.2024; Ogledov: 166; Prenosov: 112
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173. Stem cells of aquatic invertebrates as an advanced tool for assessing ecotoxicological impactsAmalia Rosner, Jean Armengaud, Loriano Ballarin, Stéphanie Barnay-Verdier, Francesca Cima, Ana Varela Coelho, Isabelle Domart-Coulon, Damjana Drobne, Anne-Marie Geneviere, Anita Jemec Kokalj, Ewa Kotlarska, Andreja Ramšak, 2021, pregledni znanstveni članek Povzetek: Environmental stressors are assessed through methods that quantify their impacts on a wide range of metrics including species density, growth rates, reproduction, behaviour and physiology, as on host-pathogen interactions and immunocompetence. Environmental stress may induce additional sublethal effects, like mutations and epigenetic signatures affecting offspring via germline mediated transgenerational inheritance, shaping phenotypic plasticity, increasing disease susceptibility, tissue pathologies, changes in social behaviour and biological invasions.
The growing diversity of pollutants released into aquatic environments requires the development of a reliable, standardised and 3R (replacement, reduction and refinement of animals in research) compliant in vitro toolbox. The tools have to be in line with REACH regulation 1907/2006/EC, aiming to improve strategies for potential ecotoxicological risks assessment and monitoring of chemicals threatening human health and aquatic environments.
Aquatic invertebrates' adult stem cells (ASCs) are numerous and can be pluripotent, as illustrated by high regeneration ability documented in many of these taxa. This is of further importance as in many aquatic invertebrate taxa, ASCs are able to differentiate into germ cells. Here we propose that ASCs from key aquatic invertebrates may be harnessed for applicable and standardised new tests in ecotoxicology. As part of this approach, a battery of modern techniques and endpoints are proposed to be tested for their ability to correctly identify environmental stresses posed by emerging contaminants in aquatic environments.
Consequently, we briefly describe the current status of the available toxicity testing and biota-based monitoring strategies in aquatic environmental ecotoxicology and highlight some of the associated open issues such as replicability, consistency and reliability in the outcomes, for understanding and assessing the impacts of various chemicals on organisms and on the entire aquatic environment. Following this, we describe the benefits of aquatic invertebrate ASC-based tools for better addressing ecotoxicological questions, along with the current obstacles and possible overhaul approaches. Objavljeno v DiRROS: 05.08.2024; Ogledov: 177; Prenosov: 180
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174. Angiogenesis in gynecological cancers and the options for anti-angiogenesis therapyBahar Yetkin-Arik, Arnoud W. Kastelein, Ingeborg Klaassen, Charlotte H. J. R. Jansen, Yani P. Latul, Miloš Vittori, Aydan Biri, Korhan Kahraman, Arjan W. Griffioen, Frederic Amant, Christianne A. R. Lok, Reinier O. Schlingemann, Cornelis J. F. van Noorden, 2021, pregledni znanstveni članek Povzetek: Angiogenesis is required in cancer, including gynecological cancers, for the growth of primary tumors and secondary metastases. Development of anti-angiogenesis therapy in gynecological cancers and improvement of its efficacy have been a major focus of fundamental and clinical research. However, survival benefits of current anti-angiogenic agents, such as bevacizumab, in patients with gynecological cancer, are modest. Therefore, a better understanding of angiogenesis and the tumor microenvironment in gynecological cancers is urgently needed to develop more effective anti-angiogenic therapies, either or not in combination with other therapeutic approaches. We describe the molecular aspects of (tumor) blood vessel formation and the tumor microenvironment and provide an extensive clinical overview of current anti-angiogenic therapies for gynecological cancers. We discuss the different phenotypes of angiogenic endothelial cells as potential therapeutic targets, strategies aimed at intervention in their metabolism, and approaches targeting their (inflammatory) tumor microenvironment. Ključne besede: angiogenesis, anti-angiogenic therapy, endothelial cells, endothelial cell metabolism, gynecological cancer, non-tip cells, tip cells, tumor microenvironment, vascular disrupting agents Objavljeno v DiRROS: 05.08.2024; Ogledov: 148; Prenosov: 136
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175. Guidelines for the reliable use of high throughput sequencing technologies to detect plant pathogens and pestsSébastien Massart, Ian Adams, Maher Al Rwahnih, Steve Baeyen, Guillaume J. Bilodeau, Arnaud G. Blouin, Neil Boonham, Thierry Candresse, Anne Chandellier, Kris De Jonghe, Denis Kutnjak, Nataša Mehle, 2022, pregledni znanstveni članek Povzetek: High-throughput sequencing (HTS) technologies have the potential to become one of the most significant advances in molecular diagnostics. Their use by researchers to detect and characterize plant pathogens and pests has been growing steadily for more than a decade and they are now envisioned as a routine diagnostic test to be deployed by plant pest diagnostics laboratories. Nevertheless, HTS technologies and downstream bioinformatics analysis of the generated datasets represent a complex process including many steps whose reliability must be ensured. The aim of the present guidelines is to provide recommendations for researchers and diagnosticians aiming to reliably use HTS technologies to detect plant pathogens and pests. These guidelines are generic and do not depend on the sequencing technology or platform. They cover all the adoption processes of HTS technologies from test selection to test validation as well as their routine implementation. A special emphasis is given to key elements to be considered: undertaking a risk analysis, designing sample panels for validation, using proper controls, evaluating performance criteria, confirming and interpreting results. These guidelines cover any HTS test used for the detection and identification of any plant pest (viroid, virus, bacteria, phytoplasma, fungi and fungus-like protists, nematodes, arthropods, plants) from any type of matrix. Overall, their adoption by diagnosticians and researchers should greatly improve the reliability of pathogens and pest diagnostics and foster the use of HTS technologies in plant health. Objavljeno v DiRROS: 05.08.2024; Ogledov: 146; Prenosov: 160
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176. Organelles and phytohormones : a network of interactions in plant stress responsesAndras Bittner, Agata Cieśla, Kristina Gruden, Tjaša Lukan, Sakil Mahmud, Markus Teige, Ute Vothknecht, Bernhard Wurzinger, 2022, pregledni znanstveni članek Povzetek: Phytohormones are major signaling components that contribute to nearly all aspects of plant life. They constitute an interconnected communication network to fine-tune growth and development in response to the ever-changing environment. To this end, they have to coordinate with other signaling components, such as reactive oxygen species and calcium signals. On the one hand, the two endosymbiotic organelles, plastids and mitochondria, control various aspects of phytohormone signaling and harbor important steps of hormone precursor biosynthesis. On the other hand, phytohormones have feedback actions on organellar functions. In addition, organelles and phytohormones often act in parallel in a coordinated matter to regulate cellular functions. Therefore, linking organelle functions with increasing knowledge of phytohormone biosynthesis, perception, and signaling will reveal new aspects of plant stress tolerance. In this review, we highlight recent work on organelle–phytohormone interactions focusing on the major stress-related hormones abscisic acid, jasmonates, salicylic acid, and ethylene. Ključne besede: abscisic acid (ABA), chloroplast, ethylene, mitochondria, jasmonates, plant organelles, phytohormones, salicylic acid (SA), plastids, stress signaling, retrograde signaling Objavljeno v DiRROS: 05.08.2024; Ogledov: 155; Prenosov: 162
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177. TGA transcription factors : structural characteristics as basis for functional variabilityŠpela Tomaž, Kristina Gruden, Anna Coll Rius, 2022, pregledni znanstveni članek Povzetek: TGA transcription factors are essential regulators of various cellular processes, their activity connected to different hormonal pathways, interacting proteins and regulatory elements. Belonging to the basic region leucine zipper (bZIP) family, TGAs operate by binding to their target DNA sequence as dimers through a conserved bZIP domain. Despite sharing the core DNA-binding sequence, the TGA paralogues exert somewhat different DNA-binding preferences. Sequence variability of their N- and C-terminal protein parts indicates their importance in defining TGA functional specificity through interactions with diverse proteins, affecting their DNA-binding properties. In this review, we provide a short and concise summary on plant TGA transcription factors from a structural point of view, including the relation of their structural characteristics to their functional roles in transcription regulation. Ključne besede: DOG1 domain, functional variability, intrinsically disordered regions, plant transcription regulation, post-translational modifications, structural characteristics, TGA transcription factors Objavljeno v DiRROS: 05.08.2024; Ogledov: 156; Prenosov: 182
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178. Data mining of Saccharomyces cerevisiae mutants engineered for increased tolerance towards inhibitors in lignocellulosic hydrolysatesElena Cámara, Lisbeth Olsson, Jan Zrimec, Aleksej Zelezniak, Cecilia Geijer, Yvonne Nygård, 2022, pregledni znanstveni članek Povzetek: The use of renewable plant biomass, lignocellulose, to produce biofuels and biochemicals using microbial cell factories plays a fundamental role in the future bioeconomy. The development of cell factories capable of efficiently fermenting complex biomass streams will improve the cost-effectiveness of microbial conversion processes. At present, inhibitory compounds found in hydrolysates of lignocellulosic biomass substantially influence the performance of a cell factory and the economic feasibility of lignocellulosic biofuels and chemicals.
Here, we present and statistically analyze data on Saccharomyces cerevisiae mutants engineered for altered tolerance towards the most common inhibitors found in lignocellulosic hydrolysates: acetic acid, formic acid, furans, and phenolic compounds. We collected data from 7971 experiments including single overexpression or deletion of 3955 unique genes. The mutants included in the analysis had been shown to display increased or decreased tolerance to individual inhibitors or combinations of inhibitors found in lignocellulosic hydrolysates. Moreover, the data included mutants grown on synthetic hydrolysates, in which inhibitors were added at concentrations that mimicked those of lignocellulosic hydrolysates. Genetic engineering aimed at improving inhibitor or hydrolysate tolerance was shown to alter the specific growth rate or length of the lag phase, cell viability, and vitality, block fermentation, and decrease product yield. Different aspects of strain engineering aimed at improving hydrolysate tolerance, such as choice of strain and experimental set-up are discussed and put in relation to their biological relevance. While successful genetic engineering is often strain and condition dependent, we highlight the conserved role of regulators, transporters, and detoxifying enzymes in inhibitor tolerance. The compiled meta-analysis can guide future engineering attempts and aid the development of more efficient cell factories for the conversion of lignocellulosic biomass. Objavljeno v DiRROS: 05.08.2024; Ogledov: 150; Prenosov: 197
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179. Bioactive peptides from venoms against glioma progressionBernarda Majc, Metka Novak, Tamara Lah Turnšek, Igor Križaj, 2022, pregledni znanstveni članek Povzetek: Venoms are complex mixtures of different molecules and ions. Among them, bioactive peptides have been found to affect cancer hallmarks, such as cell proliferation, cell invasion, cell migration, and can also modulate the immune response of normal and cancer-bearing organisms. In this article, we review the mechanisms of action on these cancer cell features, focusing on bioactive peptides being developed as potential therapeutics for one of the most aggressive and deadly brain tumors, glioblastoma (GB). Novel therapeutic approaches applying bioactive peptides may contribute to multiple targeting of GB and particularly of GB stem cells. Bioactive peptides selectively target cancer cells without harming normal cells. Various molecular targets related to the effects of bioactive peptides on GB have been proposed, including ion channels, integrins, membrane phospholipids and even immunomodulatory treatment of GB. In addition to therapy, some bioactive peptides, such as disintegrins, can also be used for diagnostics or are used as labels for cytotoxic drugs to specifically target cancer cells. Given the limitations described in the last section, successful application in cancer therapy is rather low, as only 3.4% of such peptides have been included in clinical trials and have passed successfully phases I to III. Combined approaches of added bioactive peptides to standard cancer therapies need to be explored using advanced GB in vitro models such as organoids. On the other hand, new methods are also being developed to improve translation from research to practice and provide new hope for GB patients and their families. Objavljeno v DiRROS: 05.08.2024; Ogledov: 160; Prenosov: 122
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180. Coastal high-frequency radars in the Mediterranean : Applications in support of science priorities and societal needsEmma Reyes, Eva Aguiar, Michele Bendoni, Maristella Berta, Carlo Brandini, Alejandro Cáceres-Euse, Fulvio Capodici, Vanessa Cardin, Daniela Cianelli, Giuseppe Ciraolo, Matjaž Ličer, 2022, pregledni znanstveni članek Povzetek: The Mediterranean Sea is a prominent climate-change hot spot, with many socioeconomically vital coastal areas being the most vulnerable targets for maritime safety, diverse met-ocean hazards and marine pollution. Providing an unprecedented spatial and temporal resolution at wide coastal areas, high-frequency radars (HFRs) have been steadily gaining recognition as an effective land-based remote sensing technology for continuous monitoring of the surface circulation, increasingly waves and occasionally winds. HFR measurements have boosted the thorough scientific knowledge of coastal processes, also fostering a broad range of applications, which has promoted their integration in coastal ocean observing systems worldwide, with more than half of the European sites located in the Mediterranean coastal areas. In this work, we present a review of existing HFR data multidisciplinary science-based applications in the Mediterranean Sea, primarily focused on meeting end-user and science-driven requirements, addressing regional challenges in three main topics: (i) maritime safety, (ii) extreme hazards and (iii) environmental transport process. Additionally, the HFR observing and monitoring regional capabilities in the Mediterranean coastal areas required to underpin the underlying science and the further development of applications are also analyzed. The outcome of this assessment has allowed us to provide a set of recommendations for future improvement prospects to maximize the contribution to extending science-based HFR products into societally relevant downstream services to support blue growth in the Mediterranean coastal areas, helping to meet the UN's Decade of Ocean Science for Sustainable Development and the EU's Green Deal goals. Ključne besede: coastal monitoring, Mediterranean Sea, multi-platform observing systems, oceanography Objavljeno v DiRROS: 05.08.2024; Ogledov: 181; Prenosov: 142
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