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  • 1
    Online Resource
    Online Resource
    Video_1.wmv
    Frontiers Media SA ; 2023
    In:  Frontiers in Marine Science Vol. 10 ( 2023-6-22)
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    In: Frontiers in Marine Science, Frontiers Media SA, Vol. 10 ( 2023-6-22)
    Abstract: Subterranean estuaries are connective zones between inland aquifers and the open sea where terrestrial freshwater and circulating seawater mix and undergo major biogeochemical changes. They are biogeochemical reactors that modify groundwater chemistry prior to discharge into the sea. We propose that subterranean estuaries of high-energy beaches are particularly dynamic environments, where the effect of the dynamic boundary conditions propagates tens of meters into the subsurface, leading to strong spatio-temporal variability of geochemical conditions. We hypothesize that they form a unique habitat with an adapted microbial community unlike other typically more stable subsurface environments. So far, however, studies concerning subterranean estuaries of high-energy beaches have been rare and therefore their functioning, and their importance for coastal ecosystems, as well as for carbon, nutrient and trace element cycling, is little understood. We are addressing this knowledge gap within the interdisciplinary research project DynaDeep by studying the combined effect of surface (hydro- and morphodynamics) on subsurface processes (groundwater flow and transport, biogeochemical reactions, microbiology). A unique subterranean estuary observatory was established on the northern beach of the island of Spiekeroog facing the North Sea, serving as an exemplary high-energy research site and model system. It consists of fixed and permanent infrastructure such as a pole with measuring devices, multi-level groundwater wells and an electrode chain. This forms the base for autonomous measurements, regular repeated sampling, interdisciplinary field campaigns and experimental work, all of which are integrated via mathematical modelling to understand and quantify the functioning of the biogeochemical reactor. First results show that the DynaDeep observatory is collecting the intended spatially and temporally resolved morphological, sedimentological and biogeochemical data. Samples and data are further processed ex-situ and combined with experiments and modelling. Ultimately, DynaDeep aims at elucidating the global relevance of these common but overlooked environments.
    Type of Medium: Online Resource
    ISSN: 2296-7745
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fmars.2023.1189281
    DOI: 10.3389/fmars.2023.1189281.s001
    DOI: 10.3389/fmars.2023.1189281.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2757748-X
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  • 2
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    Online Resource
    Table_1.docx
    Frontiers Media SA ; 2023
    In:  Frontiers in Neurology Vol. 13 ( 2023-1-9)
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    In: Frontiers in Neurology, Frontiers Media SA, Vol. 13 ( 2023-1-9)
    Abstract: Mechanical thrombectomy (MT) is highly effective in large vessel occlusion (LVO) stroke. In north-east Germany, many rural hospitals do not have continuous neurological expertise onsite and secondary transport to MT capable comprehensive stroke centers (CSC) is necessary. In metropolitan areas, small hospitals often have neurology departments, but cannot perform MT. Thus, interhospital transport to CSCs is also required. Here, we compare time-to-care metrics and outcomes in patients receiving MT after interhospital transfer from primary stroke centers (PCSs) to CSCs in rural vs. metropolitan areas. Methods Patients from ten rural telestroke centers (RTCs) and nine CSCs participated in this study under the quality assurance registry for thrombectomies of the Acute Neurological care in North-east Germany with TeleMedicine (ANNOTeM) telestroke network. For the metropolitan area, we included patients admitted to 13 hospitals without thrombectomy capabilities (metropolitan primary stroke centers, MPSCs) and transferred to two CSCs. We compared groups regarding baseline variables, time-to-care metrics, clinical, and technical outcomes. Results Between October 2018 and June 2022, 50 patients were transferred from RTCs within the ANNOTeM network and 42 from MPSCs within the Berlin metropolitan area. RTC patients were older (77 vs. 72 yrs, p = 0.05) and had more severe strokes (NIHSS 17 vs. 10 pts., p & lt; 0.01). In patients with intravenous thrombolysis (IVT; 34.0 and 40.5%, respectively), time from arrival at the primary stroke center to start of IVT was longer in RTCs (65 vs. 37 min, p & lt; 0.01). However, RTC patients significantly quicker underwent groin puncture at CSCs (door-to-groin time: 42 vs. 60 min, p & lt; 0.01). Despite longer transport distances from RTCs to CSCs (55 vs. 22 km, p & lt; 0.001), there was no significant difference of times between arrival at the PSC and groin puncture (210 vs. 208 min, p = 0.96). In adjusted analyses, there was no significant difference in clinical and technical outcomes. Conclusion Despite considerable differences in the setting of stroke treatment in rural and metropolitan areas, overall time-to-care metrics were similar. Targets of process improvement should be door-to-needle times in RTCs, transfer organization, and door-to-groin times in CSCs wherever such process times are above best-practice models.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    URL: Article
    URL: Article
    DOI: 10.3389/fneur.2022.1046564
    DOI: 10.3389/fneur.2022.1046564.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2564214-5
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  • 3
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    Online Resource
    Data_Sheet_1.doc
    Frontiers Media SA ; 2022
    In:  Frontiers in Aging Neuroscience Vol. 14 ( 2022-12-1)
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    In: Frontiers in Aging Neuroscience, Frontiers Media SA, Vol. 14 ( 2022-12-1)
    Abstract: Multiple sclerosis (MS) is a chronic inflammatory and degenerative disease of central nervous system (CNS). Aging is the most significant risk factor for the progression of MS. Dietary modulation (such as ketogenic diet) and caloric restriction, can increase ketone bodies, especially β-hydroxybutyrate (BHB). Increased BHB has been reported to prevent or improve age-related disease. The present studies were performed to understand the therapeutic effect and potential mechanisms of exogenous BHB in cuprizone (CPZ)-induced demyelinating model. In this study, a continuous 35 days CPZ mouse model with or without BHB was established. The changes of behavior function, pathological hallmarks of CPZ, and intracellular signal pathways in mice were detected by Open feld test, Morris water maze, RT-PCR, immuno-histochemistry, and western blot. The results showed that BHB treatment improved behavioral performance, prevented myelin loss, decreased the activation of astrocyte as well as microglia, and up-regulated the neurotrophin brain-derived neurotrophic factor in both the corpus callosum and hippocampus. Meanwhile, BHB treatment increased the number of MCT1 + cells and APC + oligodendrocytes. Furthermore, the treatment decreased the expression of HDAC3, PARP1, AIF and TRPA1 which is related to oligodendrocyte (OL) apoptosis in the corpus callosum, accompanied by increased expression of TrkB. This leads to an increased density of doublecortin (DCX) + neuronal precursor cells and mature NeuN + neuronal cells in the hippocampus. As a result, BHB treatment effectively promotes the generation of PDGF-Ra + (oligodendrocyte precursor cells, OPCs), Sox2 + cells and GFAP + (astrocytes), and decreased the production of GFAP + TRAP1 + cells, and Oligo2 + TRAP1 + cells in the corpus callosum of mouse brain. Thus, our results demonstrate that BHB treatment efficiently supports OPC differentiation and decreases the OLs apoptosis in CPZ-intoxicated mice, partly by down-regulating the expression of TRPA1 and PARP, which is associated with the inhibition of the p38-MAPK/JNK/JUN pathway and the activation of ERK1/2, PI3K/AKT/mTOR signaling, supporting BHB treatment adjunctive nutritional therapy for the treatment of chronic demyelinating diseases, such as multiple sclerosis (MS).
    Type of Medium: Online Resource
    ISSN: 1663-4365
    URL: Article
    URL: Article
    DOI: 10.3389/fnagi.2022.1075161
    DOI: 10.3389/fnagi.2022.1075161.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2558898-9
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  • 4
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    Online Resource
    Evidence for Quantum Chemical Effects in Receptor-Ligand Binding Between Integrin and Collagen Fragments — A Computational Investigation With an Impact on Tissue Repair, Neurooncolgy and Glycobiology
    Frontiers Media SA ; 2021
    In:  Frontiers in Molecular Biosciences Vol. 8 ( 2021-11-16)
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    In: Frontiers in Molecular Biosciences, Frontiers Media SA, Vol. 8 ( 2021-11-16)
    Abstract: The collagen-integrin interactions are mediated by the doubly charged Mg 2+ cation. In nature this cation seems to have the optimal binding strength to stabilize this complex. It is essential that the binding is not too weak so that the complex becomes unstable, however, it is also of importance that the ligand-receptor binding is still labile enough so that the ligand can separate from the receptor in a suited environment. In the case of crystal growing for experimentally useful integrin-collagen fragment complexes it turned out that Co 2+ cations are ideal mediators to form stable complexes for such experiments. Although, one can argue that Co 2+ is in this context an artificial cation, however, it is now of special interest to test the impact of this cation in cell-culture experiments focusing on integrin-ligand interactions. In order to examine, in particular, the role cobalt ions we have studied a Co 2+ based model system using quantum chemical calculations. Thereby, we have shown that hybrid and long-range corrected functional, which are approximations provide already a sufficient level of accuracy. It is of interest to study a potential impact of cations on the binding of collagen-fragments including collagens from various species because different integrins have numerous biological functions (e.g. Integrin – NCAM (Neural cell adhesion molecule) interactions) and are triggered by intact and degraded collagen fragments. Since integrin–carbohydrate interactions play a key role when bio-medical problems such as tumor cell adhesion and virus-host cell infections have to be addressed on a sub-molecular level it is essential to understand the interactions with heavy-metal ions also at the sub-atomic level. Our findings open new routes, especially, in the fields of tissue repair and neuro-oncology for example for cell-culture experiments with different ions. Since Co 2+ ions seem to bind stronger to integrin than Mg 2+ ions it should be feasible to exchange these cations in suited tumor tissues although different cations are present in other metalloproteins which are active in such tissues. Various staining methods can be applied to document the interactions of integrins with carbohydrate chains and other target structures. Thereby, it is possible to study a potential impact of these interactions on biological functions. It was therefore necessary to figure out first which histological–glycobiological experimental settings of tumor cells are suited for our purpose. Since the interactions of several metalloproteins (integrin, ADAM12) with polysialic acid and the HNK-1 epitope play a crucial role in tumor tissues selected staining methods are proper tools to obtain essential information about the impact of the metal ions under study.
    Type of Medium: Online Resource
    ISSN: 2296-889X
    URL: Article
    DOI: 10.3389/fmolb.2021.756701
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2814330-9
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  • 5
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    Immunomonitoring of Stage IV Relapsed Neuroblastoma Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplantation and Subsequent GD2 (ch14.18/CHO) Antibody Treatment
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-7-22)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-7-22)
    Abstract: Haploidentical stem cell transplantation (haplo SCT) in Stage IV neuroblastoma relapsed patients has been proven efficacious, while immunotherapy utilizing the anti-GD2 antibody dinutuximab beta has become a standard treatment for neuroblastoma. The combinatorial therapy of haplo SCT and dinutuximab may potentiate the efficacy of the immunotherapy. To gain further understanding of the synergistic effects, functional immunomonitoring was assessed during the clinical trial CH14.18 1021 Antibody and IL2 After haplo SCT in Children with Relapsed Neuroblastoma (NCT02258815). Rapid immune reconstitution of the lymphoid compartment was confirmed, with clinically relevant dinutuximab serum levels found in all patients over the course of treatment. Only one patient developed human anti-chimeric antibodies (HACAs). In-patient monitoring revealed highly functional NK cell posttransplant capable of antibody-dependent cellular cytotoxicity (ADCC). Degranulation of NK cell subsets revealed a significant response increased by dinutuximab. This was irrespective of the KIR receptor–ligand constellation within the NK subsets, defined by the major KIR receptors CD158a, CD158b, and CD158e. Moreover, complement-dependent cytotoxicity (CDC) was shown to be an extremely potent effector-cell independent mechanism of tumor cell lysis, with a clear positive correlation to GD2 expression on the cancer cells as well as to the dinutuximab concentrations. The ex vivo testing of patient-derived effector cells and the sera collected during dinutuximab therapy demonstrated both high functionality of the newly established lymphoid immune compartment and provided confidence that the antibody dosing regimen was sufficient over the duration of the dinutuximab therapy (up to nine cycles in a 9-month period). During the course of the dinutuximab therapy, proinflammatory cytokines and markers (sIL2R, TNFa, IL6, and C reactive protein) were significantly elevated indicating a strong anti-GD2 immune response. No impact of FcGR polymorphism on event-free and overall survival was found. Collectively, this study has shown that in-patient functional immunomonitoring is feasible and valuable in contributing to the understanding of anti-cancer combinatorial treatments such as haplo SCT and antibody immunotherapy.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    DOI: 10.3389/fimmu.2021.690467
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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