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  • 1
    Online Resource
    Online Resource
    High levels of floridoside at high salinity link osmoadaptation with bleaching susceptibility in the cnidarian-algal endosymbiosis
    The Company of Biologists ; 2019
    In:  Biology Open Vol. 8, No. 12 ( 2019-12-15)
    Details
    In: Biology Open, The Company of Biologists, Vol. 8, No. 12 ( 2019-12-15)
    Abstract: Coral reefs are in global decline mainly due to increasing sea surface temperatures triggering coral bleaching. Recently, high salinity has been linked to increased thermotolerance and decreased bleaching in the sea anemone coral model Aiptasia. However, the underlying processes remain elusive. Using two Aiptasia host­–endosymbiont pairings, we induced bleaching at different salinities and show reduced reactive oxygen species (ROS) release at high salinities, suggesting a role of osmoadaptation in increased thermotolerance. A subsequent screening of osmolytes revealed that this effect was only observed in algal endosymbionts that produce 2-O-glycerol-α-D-galactopyranoside (floridoside), an osmolyte capable of scavenging ROS. This result argues for a mechanistic link between osmoadaptation and thermotolerance, mediated by ROS-scavenging osmolytes (e.g., floridoside). This sheds new light on the putative mechanisms underlying the remarkable thermotolerance of corals from water bodies with high salinity such as the Red Sea or Persian/Arabian Gulf and holds implications for coral thermotolerance under climate change. This article has an associated First Person interview with the first author of the paper.
    Type of Medium: Online Resource
    ISSN: 2046-6390
    URL: Article
    DOI: 10.1242/bio.045591
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2019
    detail.hit.zdb_id: 2632264-X
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  • 2
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    Online Resource
    Salt and Sugars May Help Overheating Corals
    Frontiers Media SA ; 2022
    In:  Frontiers for Young Minds Vol. 10 ( 2022-11-3)
    Details
    In: Frontiers for Young Minds, Frontiers Media SA, Vol. 10 ( 2022-11-3)
    Abstract: You may have heard that coral reefs are overheating and are vanishing from our planet. Although this is certainly the case, the news is not all grim and gloomy! Every so often, surprising experiments show us that there is still hope for corals and much more to learn from them. Working along the Red Sea coast, we were surprised to find that corals living in very salty water seemed to be stronger during overheating periods. Moreover, we also found a link between the saltiness of water and the ability of anemones (the close cousins of corals) to deal with heat. In this article, we will explore this relationship by zooming into anemone cells to measure molecules invisible to the naked eye—all with the aim of figuring out how salt can make anemones and corals stronger in the face of increasing temperatures.
    Type of Medium: Online Resource
    ISSN: 2296-6846
    URL: Article
    DOI: 10.3389/frym.2022.708922
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2742758-4
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  • 3
    Online Resource
    Online Resource
    High salinity conveys thermotolerance in the coral model Aiptasia
    The Company of Biologists ; 2017
    In:  Biology Open
    Details
    In: Biology Open, The Company of Biologists
    Abstract: The endosymbiosis between dinoflagellate algae of the genus Symbiodinium and stony corals provides the foundation of coral reef ecosystems. Coral bleaching, the expulsion of endosymbionts from the coral host tissue as a consequence of heat or light stress, poses a threat to reef ecosystem functioning on a global scale. Hence, a better understanding of the factors contributing to heat stress susceptibility and tolerance is needed. In this regard, some of the most thermotolerant corals also live in particularly saline habitats, but possible effects of high salinity on thermotolerance in corals are anecdotal. Here we test the hypothesis that high salinity may lead to increased thermotolerance. We conducted a heat stress experiment at low, intermediate, and high salinities using a set of host-endosymbiont combinations of the coral model Aiptasia. As expected, all host-endosymbiont combinations showed reduced photosynthetic efficiency and endosymbiont loss during heat stress, but the severity of bleaching was significantly reduced with increasing salinities for one of the host-endosymbiont combinations. Our results show that higher salinities can convey increased thermotolerance in Aiptasia, although this effect seems to be dependent on the particular host strain and/or associated symbiont type. This finding may help explain the extraordinarily high thermotolerance of corals in high salinity environments such as the Red Sea and the Persian/Arabian Gulf and provides novel insight regarding factors that contribute to thermotolerance. Since our results are based on a salinity effect in symbiotic sea anemones, it remains to be determined whether this salinity effect can also be observed in stony corals.
    Type of Medium: Online Resource
    ISSN: 2046-6390
    URL: Article
    DOI: 10.1242/bio.028878
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2017
    detail.hit.zdb_id: 2632264-X
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  • 4
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    Online Resource
    Table_1.xlsx
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-2-19)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-2-19)
    Abstract: The liver is the central hub for processing and maintaining homeostatic levels of dietary nutrients especially essential amino acids such as tryptophan (Trp). Trp is required not only to sustain protein synthesis but also as a precursor for the production of NAD, neurotransmitters and immunosuppressive metabolites. In light of these roles of Trp and its metabolic products, maintaining homeostatic levels of Trp is essential for health and well-being. The liver regulates global Trp supply by the immunosuppressive enzyme tryptophan-2,3-dioxygenase (TDO2), which degrades Trp down the kynurenine pathway (KP). In the current study, we show that isolated primary hepatocytes when exposed to hypoxic environments, extensively rewire their Trp metabolism by reducing constitutive Tdo2 expression and differentially regulating other Trp pathway enzymes and transporters. Mathematical modelling of Trp metabolism in liver cells under hypoxia predicted decreased flux through the KP while metabolic flux through the tryptamine branch significantly increased. In line, the model also revealed an increased accumulation of tryptamines under hypoxia, at the expense of kynurenines. Metabolic measurements in hypoxic hepatocytes confirmed the predicted reduction in KP metabolites as well as accumulation of tryptamine. Tdo2 expression in cultured primary hepatocytes was reduced upon hypoxia inducible factor (HIF) stabilisation by dimethyloxalylglycine (DMOG), demonstrating that HIFs are involved in the hypoxic downregulation of hepatic Tdo2 . DMOG abrogated hepatic luciferase signals in Tdo2 reporter mice, indicating that HIF stability also recapitulates hypoxic rewiring of Trp metabolism in vivo . Also in WT mice HIF stabilization drove homeostatic Trp metabolism away from the KP towards enhanced tryptamine production, leading to enhanced levels of tryptamine in liver, serum and brain. As tryptamines are the most potent hallucinogens known, the observed upregulation of tryptamine in response to hypoxic exposure of hepatocytes may be involved in the generation of hallucinations occurring at high altitude. KP metabolites are known to activate the aryl hydrocarbon receptor (AHR). The AHR-activating properties of tryptamines may explain why immunosuppressive AHR activity is maintained under hypoxia despite downregulation of the KP. In summary our results identify hypoxia as an important factor controlling Trp metabolism in the liver with possible implications for immunosuppressive AHR activation and mental disturbances.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2021.590532
    DOI: 10.3389/fimmu.2021.590532.s001
    DOI: 10.3389/fimmu.2021.590532.s002
    DOI: 10.3389/fimmu.2021.590532.s003
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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  • 5
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    Online Resource
    Tryptophan metabolism drives dynamic immunosuppressive myeloid states in IDH-mutant gliomas
    Springer Science and Business Media LLC ; 2021
    In:  Nature Cancer Vol. 2, No. 7 ( 2021-05-24), p. 723-740
    Details
    In: Nature Cancer, Springer Science and Business Media LLC, Vol. 2, No. 7 ( 2021-05-24), p. 723-740
    Abstract: The dynamics and phenotypes of intratumoral myeloid cells during tumor progression are poorly understood. Here we define myeloid cellular states in gliomas by longitudinal single-cell profiling and demonstrate their strict control by the tumor genotype: in isocitrate dehydrogenase (IDH)-mutant tumors, differentiation of infiltrating myeloid cells is blocked, resulting in an immature phenotype. In late-stage gliomas, monocyte-derived macrophages drive tolerogenic alignment of the microenvironment, thus preventing T cell response. We define the IDH-dependent tumor education of infiltrating macrophages to be causally related to a complex re-orchestration of tryptophan metabolism, resulting in activation of the aryl hydrocarbon receptor. We further show that the altered metabolism of IDH-mutant gliomas maintains this axis in bystander cells and that pharmacological inhibition of tryptophan metabolism can reverse immunosuppression. In conclusion, we provide evidence of a glioma genotype-dependent intratumoral network of resident and recruited myeloid cells and identify tryptophan metabolism as a target for immunotherapy of IDH-mutant tumors.
    Type of Medium: Online Resource
    ISSN: 2662-1347
    URL: Article
    DOI: 10.1038/s43018-021-00201-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 3005299-3
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  • 6
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    Online Resource
    Heat stress destabilizes symbiotic nutrient cycling in corals
    Proceedings of the National Academy of Sciences ; 2021
    In:  Proceedings of the National Academy of Sciences Vol. 118, No. 5 ( 2021-02-02)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 118, No. 5 ( 2021-02-02)
    Abstract: Recurrent mass bleaching events are pushing coral reefs worldwide to the brink of ecological collapse. While the symptoms and consequences of this breakdown of the coral–algal symbiosis have been extensively characterized, our understanding of the underlying causes remains incomplete. Here, we investigated the nutrient fluxes and the physiological as well as molecular responses of the widespread coral Stylophora pistillata to heat stress prior to the onset of bleaching to identify processes involved in the breakdown of the coral–algal symbiosis. We show that altered nutrient cycling during heat stress is a primary driver of the functional breakdown of the symbiosis. Heat stress increased the metabolic energy demand of the coral host, which was compensated by the catabolic degradation of amino acids. The resulting shift from net uptake to release of ammonium by the coral holobiont subsequently promoted the growth of algal symbionts and retention of photosynthates. Together, these processes form a feedback loop that will gradually lead to the decoupling of carbon translocation from the symbiont to the host. Energy limitation and altered symbiotic nutrient cycling are thus key factors in the early heat stress response, directly contributing to the breakdown of the coral–algal symbiosis. Interpreting the stability of the coral holobiont in light of its metabolic interactions provides a missing link in our understanding of the environmental drivers of bleaching and may ultimately help uncover fundamental processes underpinning the functioning of endosymbioses in general.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2022653118
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2021
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 7
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    Online Resource
    A Salty Coral Secret: How High Salinity Helps Corals To Be Stronger
    Frontiers Media SA ; 2019
    In:  Frontiers for Young Minds Vol. 7 ( 2019-3-7)
    Details
    In: Frontiers for Young Minds, Frontiers Media SA, Vol. 7 ( 2019-3-7)
    Type of Medium: Online Resource
    ISSN: 2296-6846
    URL: Article
    DOI: 10.3389/frym.2019.00038
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
    detail.hit.zdb_id: 2742758-4
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  • 8
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    Online Resource
    Table1.XLSX
    Frontiers Media SA ; 2022
    In:  Frontiers in Chemistry Vol. 10 ( 2022-4-25)
    Details
    In: Frontiers in Chemistry, Frontiers Media SA, Vol. 10 ( 2022-4-25)
    Abstract: Metabolic profiling harbors the potential to better understand various disease entities such as cancer, diabetes, Alzheimer’s, Parkinson’s disease or COVID-19. To better understand such diseases and their intricate metabolic pathways in human studies, model animals are regularly used. There, standardized rearing conditions and uniform sampling strategies are prerequisites towards a successful metabolomic study that can be achieved through model organisms. Although metabolomic approaches have been employed on model organisms before, no systematic assessment of different conditions to optimize metabolite extraction across several organisms and sample types has been conducted. We address this issue using a highly standardized metabolic profiling assay analyzing 630 metabolites across three commonly used model organisms (Drosophila, mouse, and zebrafish) to find an optimal extraction protocol for various matrices. Focusing on parameters such as metabolite coverage, concentration and variance between replicates we compared seven extraction protocols. We found that the application of a combination of 75% ethanol and methyl tertiary-butyl ether (MTBE), while not producing the broadest coverage and highest concentrations, was the most reproducible extraction protocol. We were able to determine up to 530 metabolites in mouse kidney samples, 509 in mouse liver, 422 in zebrafish and 388 in Drosophila and discovered a core overlap of 261 metabolites in these four matrices. To enable other scientists to search for the most suitable extraction protocol in their experimental context and interact with this comprehensive data, we have integrated our data set in the open-source shiny app “MetaboExtract”. Hereby, scientists can search for metabolites or compound classes of interest, compare them across the different tested extraction protocols and sample types as well as find reference concentration values.
    Type of Medium: Online Resource
    ISSN: 2296-2646
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fchem.2022.869732
    DOI: 10.3389/fchem.2022.869732.s001
    DOI: 10.3389/fchem.2022.869732.s002
    DOI: 10.3389/fchem.2022.869732.s003
    DOI: 10.3389/fchem.2022.869732.s004
    DOI: 10.3389/fchem.2022.869732.s005
    DOI: 10.3389/fchem.2022.869732.s006
    DOI: 10.3389/fchem.2022.869732.s007
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2711776-5
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  • 9
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    Online Resource
    Heat stress reduces the contribution of diazotrophs to coral holobiont nitrogen cycling
    Springer Science and Business Media LLC ; 2022
    In:  The ISME Journal Vol. 16, No. 4 ( 2022-04), p. 1110-1118
    Details
    In: The ISME Journal, Springer Science and Business Media LLC, Vol. 16, No. 4 ( 2022-04), p. 1110-1118
    Abstract: Efficient nutrient cycling in the coral-algal symbiosis requires constant but limited nitrogen availability. Coral-associated diazotrophs, i.e., prokaryotes capable of fixing dinitrogen, may thus support productivity in a stable coral-algal symbiosis but could contribute to its breakdown when overstimulated. However, the effects of environmental conditions on diazotroph communities and their interaction with other members of the coral holobiont remain poorly understood. Here we assessed the effects of heat stress on diazotroph diversity and their contribution to holobiont nutrient cycling in the reef-building coral Stylophora pistillata from the central Red Sea. In a stable symbiotic state, we found that nitrogen fixation by coral-associated diazotrophs constitutes a source of nitrogen to the algal symbionts. Heat stress caused an increase in nitrogen fixation concomitant with a change in diazotroph communities. Yet, this additional fixed nitrogen was not assimilated by the coral tissue or the algal symbionts. We conclude that although diazotrophs may support coral holobiont functioning under low nitrogen availability, altered nutrient cycling during heat stress abates the dependence of the coral host and its algal symbionts on diazotroph-derived nitrogen. Consequently, the role of nitrogen fixation in the coral holobiont is strongly dependent on its nutritional status and varies dynamically with environmental conditions.
    Type of Medium: Online Resource
    ISSN: 1751-7362 , 1751-7370
    URL: Article
    DOI: 10.1038/s41396-021-01158-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2299378-2
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  • 10
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    Online Resource
    A single-sample workflow for joint metabolomic and proteomic analysis of clinical specimens
    Springer Science and Business Media LLC ; 2024
    In:  Clinical Proteomics Vol. 21, No. 1 ( 2024-12)
    Details
    In: Clinical Proteomics, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2024-12)
    Abstract: Understanding the interplay of the proteome and the metabolome helps to understand cellular regulation and response. To enable robust inferences from such multi-omics analyses, we introduced and evaluated a workflow for combined proteome and metabolome analysis starting from a single sample. Specifically, we integrated established and individually optimized protocols for metabolomic and proteomic profiling (EtOH/MTBE and autoSP3, respectively) into a unified workflow (termed MTBE-SP3), and took advantage of the fact that the protein residue of the metabolomic sample can be used as a direct input for proteome analysis. We particularly evaluated the performance of proteome analysis in MTBE-SP3, and demonstrated equivalence of proteome profiles irrespective of prior metabolite extraction. In addition, MTBE-SP3 combines the advantages of EtOH/MTBE and autoSP3 for semi-automated metabolite extraction and fully automated proteome sample preparation, respectively, thus advancing standardization and scalability for large-scale studies. We showed that MTBE-SP3 can be applied to various biological matrices (FFPE tissue, fresh-frozen tissue, plasma, serum and cells) to enable implementation in a variety of clinical settings. To demonstrate applicability, we applied MTBE-SP3 and autoSP3 to a lung adenocarcinoma cohort showing consistent proteomic alterations between tumour and non-tumour adjacent tissue independent of the method used. Integration with metabolomic data obtained from the same samples revealed mitochondrial dysfunction in tumour tissue through deregulation of OGDH, SDH family enzymes and PKM. In summary, MTBE-SP3 enables the facile and reliable parallel measurement of proteins and metabolites obtained from the same sample, benefiting from reduced sample variation and input amount. This workflow is particularly applicable for studies with limited sample availability and offers the potential to enhance the integration of metabolomic and proteomic datasets. Graphical Abstract
    Type of Medium: Online Resource
    ISSN: 1542-6416 , 1559-0275
    URL: Article
    DOI: 10.1186/s12014-024-09501-9
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2024
    detail.hit.zdb_id: 2163624-2
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