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  • Frontiers Media SA  (133)
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  • Frontiers Media SA  (133)
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  • 1
    Online-Ressource
    Online-Ressource
    Frontiers Media SA ; 2023
    In:  Frontiers in Molecular Neuroscience Vol. 16 ( 2023-2-22)
    In: Frontiers in Molecular Neuroscience, Frontiers Media SA, Vol. 16 ( 2023-2-22)
    Kurzfassung: Astrocytes play an important role in the pathogenesis of Alzheimer’s disease (AD). It is widely involved in energy metabolism in the brain by providing nutritional and metabolic support to neurons; however, the alteration in the metabolism of astrocytes in AD remains unknown. Through integrative analysis of single-nucleus sequencing datasets, we revealed metabolic changes in various cell types in the prefrontal cortex of patients with AD. We found the depletion of some important metabolites (acetyl-coenzyme A, aspartate, pyruvate, 2-oxoglutarate, glutamine, and others), as well as the inhibition of some metabolic fluxes (glycolysis and tricarbocylic acid cycle, glutamate metabolism) in astrocytes of AD. The abnormality of glutamate metabolism in astrocytes is unique and important. Downregulation of GLUL ( GS ) and GLUD1 ( GDH ) may be the cause of glutamate alterations in astrocytes in AD. These results provide a basis for understanding the characteristic changes in astrocytes in AD and provide ideas for the study of AD pathogenesis.
    Materialart: Online-Ressource
    ISSN: 1662-5099
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2023
    ZDB Id: 2452967-9
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    In: Frontiers in Physiology, Frontiers Media SA, Vol. 10 ( 2019-10-18)
    Kurzfassung: Aquaporin-2 (AQP2) is a molecular water channel protein responsible for water reabsorption by the kidney collecting ducts. Many water balance disorders are associated with defects in AQP2 gene expression regulated by the peptide hormone vasopressin. Here, we studied roles of Elf3 (E26 transformation-specific (Ets)-related transcription factor 3) in AQP2 gene expression in the collecting duct cells (mpkCCD). Vasopressin increased AQP2 mRNA and protein levels without affecting AQP2 mRNA degradation, indicative of transcriptional regulation. Elf3 knockdown and overexpression, respectively, reduced and increased AQP2 gene expression under basal and vasopressin-stimulated conditions. However, the vasopressin-to-basal ratios of AQP2 gene expression levels remained constant, indicating that Elf3 does not directly mediate vasopressin response but modulates the level of AQP2 gene expression inducible by vasopressin. The Elf3-modulated AQP2 gene expression was associated with AQP2 promoter activity, in line with Elf3’s ability to bind an Ets element in the AQP2 promoter. Mutation in the Ets element reduced both basal and vasopressin-stimulated AQP2 promoter activity, again without affecting vasopressin-to-basal ratios of the AQP2 promoter activity. Lithium chloride reduced both Elf3 and AQP2 mRNA in the mpkCCD cells as well as in mouse kidney inner medulla. We conclude that Elf3 modulates AQP2 promoter activity thereby gauging vasopressin-inducible AQP2 gene expression levels. Our data provide a potential explanation to lithium-induced nephrogenic diabetes insipidus where lithium reduces Elf3 and hence AQP2 abundance.
    Materialart: Online-Ressource
    ISSN: 1664-042X
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2019
    ZDB Id: 2564217-0
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    Online-Ressource
    Online-Ressource
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-10-4)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-10-4)
    Kurzfassung: Bacterial infections cause huge losses in aquaculture and a wide range of health issues in humans. A vaccine is the most economical, efficient, and environment-friendly agent for protecting hosts against bacterial infections. This study aimed to identify broad, cross-protective antigens from the extracellular secretory proteome of the marine bacterium Vibrio alginolyticus . Of the 69 predicted extracellular secretory proteins in its genome, 16 were randomly selected for gene cloning to construct DNA vaccines, which were used to immunize zebrafish (Danio rerio). The innate immune response genes were also investigated. Among the 16 DNA vaccines, 3 (AT730_21605, AT730_22220, and AT730_22910) were protective against V. alginolyticus infection with 47–66.7% increased survival compared to the control, while other vaccines had lower or no protective effects. Furthermore, AT730_22220, AT730_22910, and AT730_21605 also exhibited cross-immune protective effects against Pseudomonas fluorescens and/or Aeromonas hydrophila infection. Mechanisms for cross-protective ability was explored based on conserved epitopes, innate immune responses, and antibody neutralizing ability. These results indicate that AT730_21605, AT730_22220, and AT730_22910 are potential polyvalent vaccine candidates against bacterial infections. Additionally, our results suggest that the extracellular secretory proteome is an antigen pool that can be used for the identification of cross-protective immunogens.
    Materialart: Online-Ressource
    ISSN: 1664-3224
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2021
    ZDB Id: 2606827-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    Online-Ressource
    Online-Ressource
    Frontiers Media SA ; 2021
    In:  Frontiers in Pharmacology Vol. 12 ( 2021-11-25)
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-11-25)
    Kurzfassung: Aims: Long-term salt diet induces the oxidative stress in the paraventricular nucleus (PVN) and increases the blood pressure. Extracellular superoxide dismutase (Ec-SOD) is a unique antioxidant enzyme that exists in extracellular space and plays an essential role in scavenging excessive reactive oxygen species (ROS). However, the underlying mechanism of Ec-SOD in the PVN remains unclear. Methods: Sprague–Dawley rats (150–200 g) were fed either a high salt diet (8% NaCl, HS) or normal salt diet (0.9% NaCl, NS) for 6 weeks. Each group of rats was administered with bilateral PVN microinjection of AAV-Ec-SOD (Ec-SOD overexpression) or AAV-Ctrl for the next 6 weeks. Results: High salt intake not only increased mean arterial blood pressure (MAP) and the plasma noradrenaline (NE) but also elevated the NAD(P)H oxidase activity, the NAD(P)H oxidase components (NOX2 and NOX4) expression, and ROS production in the PVN. Meanwhile, the NOD-like receptor protein 3 (NLRP3)–dependent inflammatory proteins (ASC, pro-cas-1, IL-β, CXCR, CCL2) expression and the tyrosine hydroxylase (TH) expression in the PVN with high salt diet were higher, but the GSH level, Ec-SOD activity, GAD67 expression, and GABA level were lower than the NS group. Bilateral PVN microinjection of AAV-Ec-SOD decreased MAP and the plasma NE, reduced NAD(P)H oxidase activity, the NOX2 and NOX4 expression, and ROS production, attenuated NLRP3-dependent inflammatory expression and TH, but increased GSH level, Ec-SOD activity, GAD67 expression, and GABA level in the PVN compared with the high salt group. Conclusion: Excessive salt intake not only activates oxidative stress but also induces the NLRP3-depensent inflammation and breaks the balance between inhibitory and excitability neurotransmitters in the PVN. Ec-SOD, as an essential anti-oxidative enzyme, eliminates the ROS in the PVN and decreases the blood pressure, probably through inhibiting the NLRP3-dependent inflammation and improving the excitatory neurotransmitter release in the PVN in the salt-induced hypertension.
    Materialart: Online-Ressource
    ISSN: 1663-9812
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2021
    ZDB Id: 2587355-6
    SSG: 15,3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    Online-Ressource
    Online-Ressource
    Frontiers Media SA ; 2022
    In:  Frontiers in Physiology Vol. 13 ( 2022-5-24)
    In: Frontiers in Physiology, Frontiers Media SA, Vol. 13 ( 2022-5-24)
    Kurzfassung: Water permeability of the kidney collecting ducts is regulated in part by the amount of the molecular water channel protein aquaporin-2 (AQP2), whose expression, in turn, is regulated by the pituitary peptide hormone vasopressin. We previously showed that stable glucocorticoid receptor knockdown diminished the vasopressin-induced Aqp2 gene expression in the collecting duct cell model mpkCCD. Here, we investigated the pathways regulated by the glucocorticoid receptor by comparing transcriptomes of the mpkCCD cells with or without stable glucocorticoid receptor knockdown. Glucocorticoid receptor knockdown downregulated 5,394 transcripts associated with 55 KEGG pathways including “vasopressin-regulated water reabsorption,” indicative of positive regulatory roles of these pathways in the vasopressin-induced Aqp2 gene expression. Quantitative RT-PCR confirmed the downregulation of the vasopressin V2 receptor transcript upon glucocorticoid receptor knockdown. Glucocorticoid receptor knockdown upregulated 3,785 transcripts associated with 42 KEGG pathways including the “TNF signaling pathway” and “TGFβ signaling pathway,” suggesting the negative regulatory roles of these pathways in the vasopressin-induced Aqp2 gene expression. Quantitative RT-PCR confirmed the upregulation of TNF and TGFβ receptor transcripts upon glucocorticoid receptor knockdown. TNF or TGFβ inhibitor alone, in the absence of vasopressin, did not induce Aqp2 gene transcription. However, TNF or TGFβ blunted the vasopressin-induced Aqp2 gene expression. In particular, TGFβ reduced vasopressin-induced increases in Akt phosphorylation without inducing epithelial-to-mesenchymal transition or interfering with vasopressin-induced apical AQP2 trafficking. In summary, our RNA-seq transcriptomic comparison revealed positive and negative regulatory pathways maintained by the glucocorticoid receptor for the vasopressin-induced Aqp2 gene expression.
    Materialart: Online-Ressource
    ISSN: 1664-042X
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2022
    ZDB Id: 2564217-0
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    Online-Ressource
    Online-Ressource
    Frontiers Media SA ; 2021
    In:  Frontiers in Physiology Vol. 12 ( 2021-12-2)
    In: Frontiers in Physiology, Frontiers Media SA, Vol. 12 ( 2021-12-2)
    Kurzfassung: Water permeability of the kidney collecting ducts is regulated by the peptide hormone vasopressin. Between minutes and hours (short-term), vasopressin induces trafficking of the water channel protein aquaporin-2 to the apical plasma membrane of the collecting duct principal cells to increase water permeability. Between hours and days (long-term), vasopressin induces aquaporin-2 gene expression. Here, we investigated the mechanisms that bridge the short-term and long-term vasopressin-mediated aquaporin-2 regulation by α-actinin 4, an F-actin crosslinking protein and a transcription co-activator of the glucocorticoid receptor. Vasopressin induced F-actin depolymerization and α-actinin 4 nuclear translocation in the mpkCCD collecting duct cell model. Co-immunoprecipitation followed by immunoblotting showed increased interaction between α-actinin 4 and glucocorticoid receptor in response to vasopressin. ChIP-PCR showed results consistent with α-actinin 4 and glucocorticoid receptor binding to the aquaporin-2 promoter. α-actinin 4 knockdown reduced vasopressin-induced increases in aquaporin-2 mRNA and protein expression. α-actinin 4 knockdown did not affect vasopressin-induced glucocorticoid receptor nuclear translocation, suggesting independent mechanisms of vasopressin-induced nuclear translocation of α-actinin 4 and glucocorticoid receptor. Glucocorticoid receptor knockdown profoundly reduced vasopressin-induced increases in aquaporin-2 mRNA and protein expression. In the absence of glucocorticoid analog dexamethasone, vasopressin-induced increases in glucocorticoid receptor nuclear translocation and aquaporin-2 mRNA were greatly reduced. α-actinin 4 knockdown further reduced vasopressin-induced increase in aquaporin-2 mRNA in the absence of dexamethasone. We conclude that glucocorticoid receptor plays a major role in vasopressin-induced aquaporin-2 gene expression that can be enhanced by α-actinin 4. In the absence of vasopressin, α-actinin 4 crosslinks F-actin underneath the apical plasma membrane, impeding aquaporin-2 membrane insertion. Vasopressin-induced F-actin depolymerization in one hand facilitates aquaporin-2 apical membrane insertion and in the other hand frees α-actinin 4 to enter the nucleus where it binds glucocorticoid receptor to enhance aquaporin-2 gene expression.
    Materialart: Online-Ressource
    ISSN: 1664-042X
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2021
    ZDB Id: 2564217-0
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    In: Frontiers in Psychology, Frontiers Media SA, Vol. 13 ( 2022-10-13)
    Kurzfassung: Acupuncture therapy has been used for cognitive impairment-related diseases, however, there are still few studies on the overall trend of acupuncture therapy on cognitive impairment based on bibliometric analysis. The purpose of this study was to explore the research trend of the impact of acupuncture on cognitive impairment in the past 15 years, analyze the research trends and hotspots, and provide new ideas and theoretical basis for future research directions. Methods From the Web of Science Core Collection (WoSCC), the relevant literature on the treatment of cognitive impairment with acupuncture from 2007 to 2022 was retrieved. Then, based on the CiteSpace and VOSviewer software of the Java platform, the cooperation between countries and institutions in this field, the co-citation of journals and documents, and the cooperation between authors and authors, etc. were analyzed. In addition, the co-occurrence and burst analysis of keywords are also carried out, and a visual knowledge map is drawn. Results As of August 08, 2022, a total of 394 records related to the treatment of cognitive impairment with acupuncture were identified. The analysis results show: The number and rate of annual publications have steadily increased, with some fluctuations from year to year. The countries that contribute the most to this field are China and the USA. Among them, Beijing University of Chinese Medicine and Capital Medical University are tied for first place in terms of the number of published papers. Tao Jing is the most prolific author and the number one cited author. Conclusions The number of publications on acupuncture for cognitive impairment is expected to increase rapidly in future research, suggesting a bright future for the field. Future research hotspots will focus on pain, injury, protocol, diagnosis, guidelines, etc. It is also necessary to strengthen cross-regional and cross-country cooperation among various academic groups.
    Materialart: Online-Ressource
    ISSN: 1664-1078
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2022
    ZDB Id: 2563826-9
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-5-2)
    Kurzfassung: An effective COVID-19 vaccine against broad SARS-CoV-2 variants is still an unmet need. In the study, the vesicular stomatitis virus (VSV)-based vector was used to express the SARS-CoV-2 Spike protein to identify better vaccine designs. The replication-competent of the recombinant VSV-spike virus with C-terminal 19 amino acid truncation (SΔ19 Rep) was generated. A single dose of SΔ19 Rep intranasal vaccination is sufficient to induce protective immunity against SARS-CoV-2 infection in hamsters. All the clones isolated from the SΔ19 Rep virus contained R682G mutation located at the Furin cleavage site. An additional S813Y mutation close to the TMPRSS2 cleavage site was identified in some clones. The enzymatic processing of S protein was blocked by these mutations. The vaccination of the R682G-S813Y virus produced a high antibody response against S protein and a robust S protein-specific CD8 + T cell response. The vaccinated animals were protected from the lethal SARS-CoV-2 (delta variant) challenge. The S antigen with resistance to enzymatic processes by Furin and TMPRSS2 will provide better immunogenicity for vaccine design.
    Materialart: Online-Ressource
    ISSN: 1664-3224
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2022
    ZDB Id: 2606827-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    Online-Ressource
    Online-Ressource
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-11-16)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-11-16)
    Kurzfassung: Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or & lt;5 patients per year, p = 0.12) or age (≥60 or & lt;60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count ( & gt;10 × 10 9 /L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future.
    Materialart: Online-Ressource
    ISSN: 2234-943X
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2021
    ZDB Id: 2649216-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    In: Frontiers in Pediatrics, Frontiers Media SA, Vol. 6 ( 2019-1-8)
    Materialart: Online-Ressource
    ISSN: 2296-2360
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2019
    ZDB Id: 2711999-3
    Standort Signatur Einschränkungen Verfügbarkeit
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