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  • 1
    Online Resource
    Online Resource
    The Company of Biologists ; 2023
    In:  Journal of Experimental Biology Vol. 226, No. 8 ( 2023-04-15)
    In: Journal of Experimental Biology, The Company of Biologists, Vol. 226, No. 8 ( 2023-04-15)
    Abstract: Lipids make up more than half of the human brain's dry weight, yet the composition and function of the brain lipidome is not well characterized. Lipids not only provide the structural basis of cell membranes, but also take part in a wide variety of biochemical processes. In neurodegenerative diseases, lipids can facilitate neuroprotection and serve as diagnostic biomarkers. The study of organisms adapted to extreme environments may prove particularly valuable in understanding mechanisms that protect against stressful conditions and prevent neurodegeneration. The brain of the hooded seal (Cystophora cristata) exhibits a remarkable tolerance to low tissue oxygen levels (hypoxia). While neurons of most terrestrial mammals suffer irreversible damage after only short periods of hypoxia, in vitro experiments show that neurons of the hooded seal display prolonged functional integrity even in severe hypoxia. How the brain lipidome contributes to the hypoxia tolerance of marine mammals has been poorly studied. We performed an untargeted lipidomics analysis, which revealed that lipid species are significantly modulated in marine mammals compared with non-diving mammals. Increased levels of sphingomyelin species may have important implications for efficient signal transduction in the seal brain. Substrate assays also revealed elevated normoxic tissue levels of glucose and lactate, which suggests an enhanced glycolytic capacity. Additionally, concentrations of the neurotransmitters glutamate and glutamine were decreased, which may indicate reduced excitatory synaptic signaling in marine mammals. Analysis of hypoxia-exposed brain tissue suggests that these represent constitutive mechanisms rather than an induced response towards hypoxic conditions.
    Type of Medium: Online Resource
    ISSN: 0022-0949 , 1477-9145
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2023
    detail.hit.zdb_id: 1482461-9
    SSG: 12
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  • 2
    In: Neuroscience, Elsevier BV, Vol. 451 ( 2020-12), p. 226-239
    Type of Medium: Online Resource
    ISSN: 0306-4522
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 1498423-4
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2017
    In:  Climate Dynamics Vol. 48, No. 9-10 ( 2017-5), p. 2837-2858
    In: Climate Dynamics, Springer Science and Business Media LLC, Vol. 48, No. 9-10 ( 2017-5), p. 2837-2858
    Type of Medium: Online Resource
    ISSN: 0930-7575 , 1432-0894
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 382992-3
    detail.hit.zdb_id: 1471747-5
    SSG: 16,13
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  • 4
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Physiology Vol. 13 ( 2022-12-16)
    In: Frontiers in Physiology, Frontiers Media SA, Vol. 13 ( 2022-12-16)
    Abstract: While foraging, marine mammals undertake repetitive diving bouts. When the animal surfaces, reperfusion makes oxygen readily available for the electron transport chain, which leads to increased production of reactive oxygen species and risk of oxidative damage. In blood and several tissues, such as heart, lung, muscle and kidney, marine mammals generally exhibit an elevated antioxidant defence. However, the brain, whose functional integrity is critical to survival, has received little attention. We previously observed an enhanced expression of several antioxidant genes in cortical neurons of hooded seals ( Cystophora cristata ). Here, we studied antioxidant gene expression and enzymatic activity in the visual cortex, cerebellum and hippocampus of harp seals ( Pagophilus groenlandicus ) and hooded seals. Moreover, we tested several genes for positive selection. We found that antioxidants in the first line of defence, such as superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione (GSH) were constitutively enhanced in the seal brain compared to mice ( Mus musculus ), whereas the glutaredoxin and thioredoxin systems were not. Possibly, the activity of the latter systems is stress-induced rather than constitutively elevated. Further, some, but not all members, of the glutathione-s-transferase (GST) family appear more highly expressed. We found no signatures of positive selection, indicating that sequence and function of the studied antioxidants are conserved in pinnipeds.
    Type of Medium: Online Resource
    ISSN: 1664-042X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2564217-0
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  • 5
    In: Ecology and Evolution, Wiley, Vol. 1, No. 4 ( 2011-12), p. 451-458
    Type of Medium: Online Resource
    ISSN: 2045-7758
    Language: English
    Publisher: Wiley
    Publication Date: 2011
    detail.hit.zdb_id: 2635675-2
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  • 6
    Online Resource
    Online Resource
    The Royal Society ; 2017
    In:  Proceedings of the Royal Society B: Biological Sciences Vol. 284, No. 1859 ( 2017-07-26), p. 20170853-
    In: Proceedings of the Royal Society B: Biological Sciences, The Royal Society, Vol. 284, No. 1859 ( 2017-07-26), p. 20170853-
    Abstract: In a range of taxa, the relatedness between mates influences both pre- and post-mating processes of sexual selection. However, relatively little is known about the genetic loci facilitating such a bias, with the exception of the major histocompatibility complex. Here, we performed tightly controlled replicated in vitro fertilization trials to explore the impact of relatedness on two possible mechanisms of cryptic female choice (CFC) in Chinook salmon ( Oncorhynchus tshawytscha ). We tested (i) whether relatedness of mates, assessed using 682 single nucleotide polymorphisms (SNPs) on 29 SNP-linkage groups (LGs), biases a male's sperm velocity in ovarian fluid (a parameter previously shown to predict male fertilization success), and (ii) whether relatedness of mates governs fertilization success via other mechanisms, probably via sperm–egg interactions. We found that relatedness on three LGs explained the variation in sperm velocity, and relatedness on two LGs explained fertilization success, which might indicate the presence of genes important in sperm–ovarian fluid and sperm–egg interactions in these genomic regions. Mapping of the SNPs on these LGs to the rainbow trout genome revealed two genes that affect fertility in humans and represent candidate genes for further studies. Our results thereby provide a novel contribution to the understanding of the mechanism of CFC.
    Type of Medium: Online Resource
    ISSN: 0962-8452 , 1471-2954
    Language: English
    Publisher: The Royal Society
    Publication Date: 2017
    detail.hit.zdb_id: 1460975-7
    SSG: 12
    SSG: 25
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  • 7
    In: Nature Ecology & Evolution, Springer Science and Business Media LLC, Vol. 4, No. 6 ( 2020-03-30), p. 841-852
    Abstract: Sturgeons seem to be frozen in time. The archaic characteristics of this ancient fish lineage place it in a key phylogenetic position at the base of the ~30,000 modern teleost fish species. Moreover, sturgeons are notoriously polyploid, providing unique opportunities to investigate the evolution of polyploid genomes. We assembled a high-quality chromosome-level reference genome for the sterlet, Acipenser ruthenus . Our analysis revealed a very low protein evolution rate that is at least as slow as in other deep branches of the vertebrate tree, such as that of the coelacanth. We uncovered a whole-genome duplication that occurred in the Jurassic, early in the evolution of the entire sturgeon lineage. Following this polyploidization, the rediploidization of the genome included the loss of whole chromosomes in a segmental deduplication process. While known adaptive processes helped conserve a high degree of structural and functional tetraploidy over more than 180 million years, the reduction of redundancy of the polyploid genome seems to have been remarkably random.
    Type of Medium: Online Resource
    ISSN: 2397-334X
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2879715-2
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  • 8
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Molecular Neuroscience Vol. 15 ( 2022-5-9)
    In: Frontiers in Molecular Neuroscience, Frontiers Media SA, Vol. 15 ( 2022-5-9)
    Abstract: The mammalian brain is characterized by high energy expenditure and small energy reserves, making it dependent on continuous vascular oxygen and nutritional supply. The brain is therefore extremely vulnerable to hypoxia. While neurons of most terrestrial mammals suffer from irreversible damage after only short periods of hypoxia, neurons of the deep-diving hooded seal ( Cystophora cristata ) show a remarkable hypoxia-tolerance. To identify the molecular mechanisms underlying the intrinsic hypoxia-tolerance, we excised neurons from the visual cortices of hooded seals and mice ( Mus musculus ) by laser capture microdissection. A comparison of the neuronal transcriptomes suggests that, compared to mice, hooded seal neurons are endowed with an enhanced aerobic metabolic capacity, a reduced synaptic transmission and an elevated antioxidant defense. Publicly available whole-tissue brain transcriptomes of the bowhead whale ( Balaena mysticetus ), long-finned pilot whale ( Globicephala melas ), minke whale ( Balaenoptera acutorostrata ) and killer whale ( Orcinus orca ), supplemented with 2 newly sequenced long-finned pilot whales, suggest that, compared to cattle ( Bos taurus ), the cetacean brain also displays elevated aerobic capacity and reduced synaptic transmission. We conclude that the brain energy balance of diving mammals is preserved during diving, due to reduced synaptic transmission that limits energy expenditure, while the elevated aerobic capacity allows efficient use of oxygen to restore energy balance during surfacing between dives.
    Type of Medium: Online Resource
    ISSN: 1662-5099
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2452967-9
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  • 9
    Online Resource
    Online Resource
    American Society of Hematology ; 2005
    In:  Blood Vol. 106, No. 11 ( 2005-11-16), p. 1372-1372
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 1372-1372
    Abstract: The tyrosine kinase inhibitor imatinib mesylate (STI571) is a potent therapeutic agent for treatment of chronic myeloid leukemia (CML) due to its specific inhibition of bcr-abl kinase. However, patients with CML always relapse after withdrawal of imatinib therapy. With CML being the paradigm for a stem cell disease, we sought to investigate the influence of imatinib on the most primitive stem cell compartment. Imatinib has recently been reported to be a high affinity substrate for the ABC-transporters ABCG2/BCRP (breast cancer resistance protein) and MDR1 (P-Glycoprotein). Given the high expression of these ABC-transporters in Hematopoietic Stem Cells (HSC), we examined the influence of imatinib on ABCG2- and MDR1-activity in human and murine HSC by using Hoechst- and Rhodamine-efflux assays. MDR1-mediated Rhodamine-efflux was only mildly influenced by Imatinib. However, addition of imatinib at therapeutic dosages completely abrogated the SP phenotype of total bone marrow after Hoechst 33342 staining. This effect was even more pronounced in cells of the HSC-phenotype, i.e., lineage-negative/AC133+ or c-kit+/Sca-1+/lin− (KSL) of human and murine marrow, respectively. In order to determine the effect of imatinib on stem cells in vivo, we isolated SP cells from 13 CML patients at various stages of disease using FACS. We employed quantitative RT-PCR-analysis for bcr-abl and demonstrated that the majority of CML patients had bcr-abl-negative SP cells, while peripheral blood mononuclear cells were mostly bcr-abl-positive. However, two patients in complete cytogenetic and molecular-genetic remission proved to be bcr-abl-positive within the SP cell population. This supports the notion that continuous imatinib-therapy may not eradicate the malignant stem cell pool and the leukemic clone may be able to expand even during permanent imatinib-therapy. Furthermore, these data imply that the detoxifying function of ABC transporters on stem cells may be altered under imatinib treatment. Using HEK-293 cells transfected with ABCG2, we demonstrate that imatinib reverses mitoxantrone-resistance - potentially due to high affinity substrate inhibition. In summary, our data suggest the novel resistance mechanism of imatinib being actively extruded from primitive leukemic stem cells, and that addition of chemotherapeutic agents to imatinib therapy may facilitate the eradication of bcr-abl-positive stem cells in chronic myeloid leukemia.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 10
    In: BMC Neuroscience, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2022-10-15)
    Abstract: The hooded seal ( Cystophora cristata ) exhibits impressive diving skills and can tolerate extended durations of asphyxia, hypoxia and oxidative stress, without suffering from irreversible neuronal damage. Thus, when exposed to hypoxia in vitro, neurons of fresh cortical and hippocampal tissue from hooded seals maintained their membrane potential 4–5 times longer than neurons of mice. We aimed to identify the molecular mechanisms underlying the intrinsic neuronal hypoxia tolerance. Previous comparative transcriptomics of the visual cortex have revealed that S100B and clusterin (apolipoprotein J), two stress proteins that are involved in neurological disorders characterized by hypoxic conditions, have a remarkably high expression in hooded seals compared to ferrets. When overexpressed in murine neuronal cells (HN33), S100B and clusterin had neuroprotective effects when cells were exposed to hypoxia. However, their specific roles in hypoxia have remained largely unknown. Methods In order to shed light on potential molecular pathways or interaction partners, we exposed HN33 cells transfected with either S100B, soluble clusterin (sCLU) or nuclear clusterin (nCLU) to normoxia, hypoxia and oxidative stress for 24 h. We then determined cell viability and compared the transcriptomes of transfected cells to control cells. Potential pathways and upstream regulators were identified via Gene Ontology (GO) and Ingenuity Pathway Analysis (IPA). Results HN33 cells transfected with sCLU and S100B demonstrated improved glycolytic capacity and reduced aerobic respiration at normoxic conditions. Additionally, sCLU appeared to enhance pathways for cellular homeostasis to counteract stress-induced aggregation of proteins. S100B-transfected cells sustained lowered energy-intensive synaptic signaling. In response to hypoxia, hypoxia-inducible factor (HIF) pathways were considerably elevated in nCLU- and sCLU-transfected cells. In a previous study, S100B and sCLU decreased the amount of reactive oxygen species and lipid peroxidation in HN33 cells in response to oxidative stress, but in the present study, these functional effects were not mirrored in gene expression changes. Conclusions sCLU and S100B overexpression increased neuronal survival by decreasing aerobic metabolism and synaptic signaling in advance to hypoxia and oxidative stress conditions, possibly to reduce energy expenditure and the build-up of deleterious reactive oxygen species (ROS). Thus, a high expression of CLU isoforms and S100B is likely beneficial during hypoxic conditions.
    Type of Medium: Online Resource
    ISSN: 1471-2202
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2041344-0
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