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Abstract: Abstract The chemokine CCL5/RANTES is a versatile inflammatory mediator, which interacts with the receptor CCR5, promoting cancer cell interactions within the tumor microenvironment. Glioblastoma is a highly invasive tumor, in which CCL5 expression correlates with shorter patient survival. Using immunohistochemistry, we identified CCL5 and CCR5 in a series of glioblastoma samples and cells, including glioblastoma stem cells. CCL5 and CCR5 gene expression were significantly higher in a cohort of 38 glioblastoma samples, compared to low-grade glioma and non-cancerous tissues. The in vitro invasion of patients-derived primary glioblastoma cells and glioblastoma stem cells was dependent on CCL5-induced CCR5 signaling and is strongly inhibited by the small molecule CCR5 antagonist maraviroc. Invasion of these cells, which was enhanced when co-cultured with mesenchymal stem cells (MSCs), was inhibited by maraviroc, suggesting that MSCs release CCR5 ligands. In support of this model, we detected CCL5 and CCR5 in MSC monocultures and glioblastoma-associated MSC in tissue sections. We also found CCR5 expressing macrophages were in close proximity to glioblastoma cells. In conclusion, autocrine and paracrine cross-talk in glioblastoma and, in particular, glioblastoma stem cells with its stromal microenvironment, involves CCR5 and CCL5, contributing to glioblastoma invasion, suggesting the CCL5/CCR5 axis as a potential therapeutic target that can be targeted with repositioned drug maraviroc.
Keywords: CCL5, CCR5, chemokines, glioblastoma, invasion, maraviroc, mesenchymal stem cells
Published in DiRROS: 22.07.2024; Views: 14; Downloads: 5
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Abstract: Marine organisms produce a vast diversity of metabolites with biological activities useful for humans, e.g., cytotoxic, antioxidant, anti-microbial, insecticidal, herbicidal, anticancer, pro-osteogenic and pro-regenerative, analgesic, anti-inflammatory, anti-coagulant, cholesterol-lowering, nutritional, photoprotective, horticultural or other beneficial properties. These metabolites could help satisfy the increasing demand for alternative sources of nutraceuticals, pharmaceuticals, cosmeceuticals, food, feed, and novel bio-based products. In addition, marine biomass itself can serve as the source material for the production of various bulk commodities (e.g., biofuels, bioplastics, biomaterials). The sustainable exploitation of marine bio-resources and the development of biomolecules and polymers are also known as the growing field of marine biotechnology. Up to now, over 35,000 natural products have been characterized from marine organisms, but many more are yet to be uncovered, as the vast diversity of biota in the marine systems remains largely unexplored. Since marine biotechnology is still in its infancy, there is a need to create effective, operational, inclusive, sustainable, transnational and transdisciplinary networks with a serious and ambitious commitment for knowledge transfer, training provision, dissemination of best practices and identification of the emerging technological trends through science communication activities. A collaborative (net)work is today compelling to provide innovative solutions and products that can be commercialized to contribute to the circular bioeconomy. This perspective article highlights the importance of establishing such collaborative frameworks using the example of Ocean4Biotech, an Action within the European Cooperation in Science and Technology (COST) that connects all and any stakeholders with an interest in marine biotechnology in Europe and beyond.
Keywords: marine biotechnology, marine natural products, blue growth, marine biodiversity and chemodiversity, responsible research and innovation, stakeholder engagement, science communication, sustainability
Published in DiRROS: 22.07.2024; Views: 12; Downloads: 8
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Abstract: Ocean acidification (OA) is a global problem with profoundly negative environmental, social and economic consequences. From a governance perspective, there is a need to ensure a coordinated effort to directly address it. This study reviews 90 legislative documents from 17 countries from the European Economic Area (EEA) and the UK that primarily border the sea. The primary finding from this study is that the European national policies and legislation addressing OA is at best uncoordinated. Although OA is acknowledged at the higher levels of governance, its status as an environmental challenge is greatly diluted at the European Union Member State level. As a notable exception within the EEA, Norway seems to have a proactive approach towards legislative frameworks and research aimed towards further understanding OA. On the other hand, there was a complete lack of, or inadequate reporting in the Marine Strategy Framework Directive by the majority of the EU Member States, with the exception of Italy and the Netherlands. We argue that the problems associated with OA and the solutions needed to address it are unique and cannot be bundled together with traditional climate change responses and measures. Therefore, European OA-related policy and legislation must reflect this and tailor their actions to mitigate OA to safeguard marine ecosystems and societies. A stronger and more coordinated approach is needed to build environmental, economic and social resilience of the observed and anticipated changes to the coastal marine systems.
Published in DiRROS: 22.07.2024; Views: 12; Downloads: 5
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Abstract: Aim A wholistic biogeographical reconstruction should combine a phylogeny with specifics of organismal biology, plate tectonics and consequent probabilities of historic dispersal events. Here, we demonstrate this approach by reconstructing the geographical origin and sequence of intercontinental colonization of the golden orbweaving spiders, a global clade. We test two alternative hypotheses about their ancestral range. Due to the highest contemporary species diversity in Africa, the ‘Out of Africa’ hypothesis predicts the Afrotropics as their most likely ancestral area. The alternative, ‘Out of West Burma’ hypothesis aims to explain a Burmese amber fossil as stem nephilid. Because the West Burma block probably detached from Australia, then rafted towards Laurasia, either on its own or with India, this hypothesis predicts either Australasia or Indomalaya (or both) as the ancestral area. Location Worldwide. Taxon Golden orbweaving spiders, family Nephilidae. Methods We construct an expanded phylogeny of nephilid spiders and apply RASP (Reconstruct Ancestral State in Phylogenies) to infer their global biogeographical history. We fit the data to six integrated biogeographical models: DEC, DIVALIKE, BAYAREALIKE and their +j variants. We fine-tune the analysis by evaluating varying probabilities of dispersal between geographical areas throughout the clade's evolutionary history. We use the physical distance between the areas as a proxy for dispersal probabilities, thus accounting for plate tectonics. Results The best supported model reconstructs both Australasia and Indomalaya as ancestral area. In several parts of the phylogeny, these areas persist for the estimated 130-million-year evolutionary history. However, numerous intercontinental shifts in nephilid biogeographical history are also inferred. Since nephilid origins are clearly Gondwanan, our study supports the interpretations that Burmese amber contains Gondwanan biota. Main conclusions These results are consistent with the Out of West Burma hypothesis but reject the Out of Africa hypothesis. That certain clades persist in their ancestral ranges while others may shift continents aligns well with the known nephilid biology. Our methodological approach that assesses organismal specific dispersal probabilities through concrete distances measured though time slices of the Earth's history can be applied to biogeographical reconstruction of any lineage.
Keywords: spiders, golden orbweavers, Nephilidae, reconstruction of lineage, biogeography
Published in DiRROS: 22.07.2024; Views: 17; Downloads: 6
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Abstract: A method to reconstruct missing data in sea surface temperature data using a neural network is presented. Satellite observations working in the optical and infrared bands are affected by clouds, which obscure part of the ocean underneath. In this paper, a neural network with the structure of a convolutional auto-encoder is developed to reconstruct the missing data based on the available cloud-free pixels in satellite images. Contrary to standard image reconstruction with neural networks, this application requires a method to handle missing data (or data with variable accuracy) in the training phase. The present work shows a consistent approach which uses the satellite data and its expected error variance as input and provides the reconstructed field along with its expected error variance as output. The neural network is trained by maximizing the likelihood of the observed value. The approach, called DINCAE (Data INterpolating Convolutional Auto-Encoder), is applied to a 25-year time series of Advanced Very High Resolution Radiometer (AVHRR) sea surface temperature data and compared to DINEOF (Data INterpolating Empirical Orthogonal Functions), a commonly used method to reconstruct missing data based on an EOF (empirical orthogonal function) decomposition. The reconstruction error of both approaches is computed using cross-validation and in situ observations from the World Ocean Database. DINCAE results have lower error while showing higher variability than the DINEOF reconstruction.
Published in DiRROS: 19.07.2024; Views: 54; Downloads: 14
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