Hochschule Bonn-Rhein-Sieg

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    7939 research outputs found

    Cell-free electrophysiology of human VDACs incorporated into nanodiscs: An improved method

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    Voltage-dependent anion-selective channel (VDAC) is one of the main proteins of the outer mitochondrial membrane of all eukaryotes, where it forms aqueous, voltage-sensitive, and ion-selective channels. Its electrophysiological properties have been thoroughly analyzed with the planar lipid bilayer technique. To date, however, available results are based on isolations of VDACs from tissue or from recombinant VDACs produced in bacterial systems. It is well known that the cytosolic overexpression of highly hydrophobic membrane proteins often results in the formation of inclusion bodies containing insoluble aggregates. Purification of properly folded proteins and restoration of their full biological activity requires several procedures that considerably lengthen experimental times. To overcome these restraints, we propose a one-step reaction that combines in vitro cell-free protein expression with nanodisc technology to obtain human VDAC isoforms directly integrated in a native-like lipid bilayer. Reconstitution assays into artificial membranes confirm the reliability of this new methodological approach and provide results comparable to those of VDACs prepared with traditional protein isolation and reconstitution protocols. The use of membrane-mimicking nanodisc systems represents a breakthrough in VDAC electrophysiology and may be adopted to further structural studies

    Blue-light treatment reduces spontaneous and evoked pain in a human experimental pain model

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    Introduction: Chronic pain is a frequent severe disease and often associated with anxiety, depression, insomnia, disability, and reduced quality of life. This maladaptive condition is further characterized by sensory loss, hyperalgesia, and allodynia. Blue light has been hypothesized to modulate sensory neurons and thereby influence nociception. Objectives: Here, we compared the effects of blue light vs red light and thermal control on pain sensation in a human experimental pain model. Methods: Pain, hyperalgesia, and allodynia were induced in 30 healthy volunteers through high-density transcutaneous electrical stimulation. Subsequently, blue light, red light, or thermal control treatment was applied in a cross-over design. The nonvisual effects of the respective light treatments were examined using a well-established quantitative sensory testing protocol. Somatosensory parameters as well as pain intensity and quality were scored. Results: Blue light substantially reduced spontaneous pain as assessed by numeric rating scale pain scoring. Similarly, pain quality was significantly altered as assessed by the German counterpart of the McGill Pain Questionnaire. Furthermore, blue light showed antihyperalgesic, antiallodynic, and antihypesthesic effects in contrast to red light or thermal control treatment. Conclusion: Blue-light phototherapy ameliorates pain intensity and quality in a human experimental pain model and reveals antihyperalgesic, antiallodynic, and antihypesthesic effects. Therefore, blue-light phototherapy may be a novel approach to treat pain in multiple conditions

    Solarstrahlung - Gemeinsame Herausforderungen für die Atmosphärenwissenschaften und den Energiesektor

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    In den Atmosphärenwissenschaften spielt die Strahlungsbilanz der Erde eine wichtige Rolle für unser Verständnis des Klimasystems. Hier liefern ausgereifte Satellitenprodukte dekadische Klimazeitreihen mit einer so hohen Genauigkeit, dass z.B. Änderungen im Zusammenhang mit dem Klimawandel detektiert werden können. Dies gilt insbesondere auch für die solaren Strahlungsflüsse an der Erdoberfläche. Beim Vergleich dieser Satellitenprodukte mit instantanen Beobachtungen der Strahlung am Erdboden sind jedoch oft erhebliche Abweichungen feststellbar, die hauptsächlich durch kleinskalige Variabilität in der räumlichen Struktur von Wolken und ihrer Strahlungswirkung verursacht werden. Hier ist auch zu bedenken, dass Bodenbeobachtungen fast einer Punktmessung entsprechen, während Satellitenpixel eine Fläche in der Größenordnung von Quadratkilometern abtasten

    Homozygous variant p. Arg90His in NCF1 is associated with early-onset Interferonopathy: a case report

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    BACKGROUND Biallelic loss-of-function variants in NCF1 lead to reactive oxygen species deficiency and chronic granulomatous disease (CGD). Heterozygosity for the p.Arg90His variant in NCF1 has been associated with susceptibility to systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome in adult patients. This study demonstrates the association of the homozygous p.Arg90His variant with interferonopathy with features of autoinflammation and autoimmunity in a pediatric patient. CASE PRESENTATION A 5-year old female of Indian ancestry with early-onset recurrent fever and headache, and persistently elevated antinuclear, anti-Ro, and anti-La antibodies was found to carry the homozygous p.Arg90His variant in NCF1 through exome sequencing. Her unaffected parents and three other siblings were carriers for the mutant allele. Because the presence of two NCF1 pseudogenes, this variant was confirmed by independent genotyping methods. Her intracellular neutrophil oxidative burst and NCF1 expression levels were normal, and no clinical features of CGD were apparent. Gene expression analysis in peripheral blood detected an interferon gene expression signature, which was further supported by cytokine analyses of supernatants of cultured patient's cells. These findings suggested that her inflammatory disease is at least in part mediated by type I interferons. While her fever episodes responded well to systemic steroids, treatment with the JAK inhibitor tofacitinib resulted in decreased serum ferritin levels and reduced frequency of fevers. CONCLUSION Homozygosity for p.Arg90His in NCF1 should be considered contributory in young patients with an atypical systemic inflammatory antecedent phenotype that may evolve into autoimmunity later in life. The complex genomic organization of NCF1 poses a difficulty for high-throughput genotyping techniques and variants in this gene should be carefully evaluated when using the next generation and Sanger sequencing technologies. The p.Arg90His variant is found at a variable allele frequency in different populations, and is higher in people of South East Asian ancestry. In complex genetic diseases such as SLE, other rare and common susceptibility alleles might be necessary for the full disease expressivity

    Unfallversicherung: Sonderrechtsnachfolge / Meldung Berufskrankheit

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