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  • 1
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 13 ( 2022-9-2)
    Abstract: Type I interferons (IFNs) are potent inhibitors of viral replication. Here, we reformatted the natural murine and human type I interferon-α/β receptors IFNAR1 and IFNAR2 into fully synthetic biological switches. The transmembrane and intracellular domains of natural IFNAR1 and IFNAR2 were conserved, whereas the extracellular domains were exchanged by nanobodies directed against the fluorescent proteins Green fluorescent protein (GFP) and mCherry. Using this approach, multimeric single-binding GFP-mCherry ligands induced synthetic IFNAR1/IFNAR2 receptor complexes and initiated STAT1/2 mediated signal transduction via Jak1 and Tyk2. Homodimeric GFP and mCherry ligands showed that IFNAR2 but not IFNAR1 homodimers were sufficient to induce STAT1/2 signaling. Transcriptome analysis revealed that synthetic murine type I IFN signaling was highly comparable to IFNα4 signaling. Moreover, replication of vesicular stomatitis virus (VSV) in a cell culture-based viral infection model using MC57 cells was significantly inhibited after stimulation with synthetic ligands. Using intracellular deletion variants and point mutations, Y510 and Y335 in murine IFNAR2 were verified as unique phosphorylation sites for STAT1/2 activation, whereas the other tyrosine residues in IFNAR1 and IFNAR2 were not involved in STAT1/2 phosphorylation. Comparative analysis of synthetic human IFNARs supports this finding. In summary, our data showed that synthetic type I IFN signal transduction is originating from IFNAR2 rather than IFNAR1.
    Type of Medium: Online Resource
    ISSN: 1664-302X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587354-4
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  • 2
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Neuroscience Vol. 16 ( 2022-10-27)
    In: Frontiers in Neuroscience, Frontiers Media SA, Vol. 16 ( 2022-10-27)
    Abstract: Prospective randomized controlled trials on hormonal contraceptive (HC) effects on the brain are rare due to a number of methodological challenges. Thus, much of the evidence on HC effects on the brain comes from cross-sectional studies comparing HC-users to non-users. In interpreting these findings, it is of importance to be aware of potential confounds associated with women’s contraceptive choices. Previous studies have discussed age, education, social status, sexual orientation, relationship status, and tolerability of HC. Given the current trend toward a reduction in HC use and increased skepticism toward HC it seems relevant to also identify variables associated with women’s attitudes toward HC and whether they may represent confounds for neuroscientific studies. In the present study, we investigated whether women’s personality characteristics were associated with their choice to use or not use HC in the present, past and future and the type of HC chosen. 1,391 females aged 18–45 years participated in an online survey including the HEXACO-60 personality questionnaire, as well as two different measures of gender role, and provided information about their current and previous contraceptive status, as well as experiences with and attitudes toward contraceptive use. We compared (i) current, previous and never-users of HC, (ii) prospective users of HC to women who opposed future HC use, and (iii) current users of IUDs to current users of oral contraceptives. Results revealed that associations between personality and the decision to use or not use HC were negligible, while differences in personality were observed corresponding to contraceptive type. Current users of IUDs showed higher agreeableness and extraversion compared to current users of oral contraceptives. The results suggest that personality is more strongly associated to the choice of contraceptive type rather than the choice between hormonal and non-hormonal options.
    Type of Medium: Online Resource
    ISSN: 1662-453X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2411902-7
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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2019
    In:  Frontiers in Environmental Science Vol. 7 ( 2019-10-22)
    In: Frontiers in Environmental Science, Frontiers Media SA, Vol. 7 ( 2019-10-22)
    Type of Medium: Online Resource
    ISSN: 2296-665X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
    detail.hit.zdb_id: 2741535-1
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  • 4
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 13 ( 2022-7-28)
    Abstract: Repetitive neuromuscular magnetic stimulation (rNMS) of the trapezius muscles showed beneficial effects in preventing episodic migraine. However, clinical characteristics that predict a favorable response to rNMS are unknown. The objective of this analysis is to identify such predictors. Methods Thirty participants with a diagnosis of episodic migraine (mean age: 24.8 ± 4.0 years, 29 females), who were prospectively enrolled in two non-sham-controlled studies evaluating the effects of rNMS were analyzed. In these studies, the interventional stimulation of the bilateral trapezius muscles was applied in six sessions and distributed over two consecutive weeks. Baseline and follow-up assessments included the continuous documentation of a headache calendar over 30 days before and after the stimulation period, the Migraine Disability Assessment Score (MIDAS) questionnaire (before stimulation and 90 days after stimulation), and measurements of pain pressure thresholds (PPTs) above the trapezius muscles by algometry (before and after each stimulation session). Participants were classified as responders based on a ≥25% reduction in the variable of interest (headache frequency, headache intensity, days with analgesic intake, MIDAS score, left-sided PPTs, right-sided PPTs). Post-hoc univariate and multivariate binary logistic regression analyses were performed. Results Lower headache frequency ( P = 0.016) and intensity at baseline ( P = 0.015) and a migraine diagnosis without a concurrent tension-type headache component ( P = 0.011) were significantly related to a ≥25% reduction in headache frequency. Higher headache frequency ( P = 0.052) and intensity at baseline ( P = 0.014) were significantly associated with a ≥25% reduction in monthly days with analgesic intake. Lower right-sided PPTs at baseline were significantly related to a ≥25% increase in right-sided PPTs ( P = 0.015) and left-sided PPTs ( P =0.030). Performance of rNMS with higher stimulation intensities was significantly associated with a ≥25% reduction in headache intensity ( P = 0.046). Conclusions Clinical headache characteristics at baseline, the level of muscular hyperalgesia, and stimulation intensity may inform about how well an individual patient responds to rNMS. These factors may allow an early identification of patients that would most likely benefit from rNMS.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2564214-5
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  • 5
    In: Frontiers in Bioengineering and Biotechnology, Frontiers Media SA, Vol. 8 ( 2020-12-16)
    Abstract: Mesenchymal stem/stromal cells (MSCs) exert beneficial effects during wound healing, and cell-seeded scaffolds are a promising method of application. Here, we compared the suitability of a clinically used collagen/elastin scaffold (Matriderm) with an electrospun Poly(ε-caprolactone)/poly(l-lactide) (PCL/PLA) scaffold as carriers for human amnion-derived MSCs (hAMSCs). We created an epidermal-like PCL/PLA scaffold and evaluated its microstructural, mechanical, and functional properties. Sequential spinning of different PCL/PLA concentrations resulted in a wide-meshed layer designed for cell-seeding and a dense-meshed layer for apical protection. The Matriderm and PCL/PLA scaffolds then were seeded with hAMSCs, with or without Matrigel coating. The quantity and quality of the adherent cells were evaluated in vitro . The results showed that hAMSCs adhered to and infiltrated both scaffold types but on day 3, more cells were observed on PCL/PLA than on Matriderm. Apoptosis and proliferation rates were similar for all carriers except the coated Matriderm, where apoptotic cells were significantly enhanced. On day 8, the number of cells decreased on all carrier types except the coated Matriderm, which had consistently low cell numbers. Uncoated Matriderm had the highest percentage of proliferative cells and lowest apoptosis rate of all carrier types. Each carrier also was topically applied to skin wound sites in a mouse model and analyzed in vivo over 14 days via optical imaging and histological methods, which showed detectable hAMSCs on all carrier types on day 8. On day 14, all wounds exhibited newly formed epidermis, and all carriers were well-integrated into the underlying dermis and showing signs of degradation. However, only wounds treated with uncoated PCL/PLA maintained a round appearance with minimal contraction. Overall, the results support a 3-day in vitro culture of scaffolds with hAMSCs before wound application. The PCL/PLA scaffold showed higher cell adherence than Matriderm, and the effect of the Matrigel coating was negligible, as all carrier types maintained sufficient numbers of transplanted cells in the wound area. The anti-contractive effects of the PCL/PLA scaffold offer potential new therapeutic approaches to wound care.
    Type of Medium: Online Resource
    ISSN: 2296-4185
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2719493-0
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