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Ole J Hamming Ewa Terczyńska‐Dyla Gabrielle Vieyres Ronald Dijkman Sanne E Jørgensen Hashaam Akhtar Piotr Siupka Thomas Pietschmann Volker Thiel Rune Hartmann 《The EMBO journal》2013,32(23):3055-3065
The IFNL4 gene is a recently discovered type III interferon, which in a significant fraction of the human population harbours a frameshift mutation abolishing the IFNλ4 ORF. The expression of IFNλ4 is correlated with both poor spontaneous clearance of hepatitis C virus (HCV) and poor response to treatment with type I interferon. Here, we show that the IFNL4 gene encodes an active type III interferon, named IFNλ4, which signals through the IFNλR1 and IL‐10R2 receptor chains. Recombinant IFNλ4 is antiviral against both HCV and coronaviruses at levels comparable to IFNλ3. However, the secretion of IFNλ4 is impaired compared to that of IFNλ3, and this impairment is not due to a weak signal peptide, which was previously believed. We found that IFNλ4 gets N‐linked glycosylated and that this glycosylation is required for secretion. Nevertheless, this glycosylation is not required for activity. Together, these findings result in the paradox that IFNλ4 is strongly antiviral but a disadvantage during HCV infection. 相似文献
93.
Constanze Hartmann Fabienne Mayenzet Jean-Paul Larcinese Olivier P. Haefliger Andrea Buettner Christian Starkenmann 《Steroids》2013,78(2):156-160
A method was developed for the quantification of 5-α-androst-16-en-3-one in human breast milk based on application of a stable isotope dilution assay using 5α-androst-16-en-3-one-6, 6-d2. The procedure includes extraction of the human milk by hexane with subsequent clean-up of the obtained extract by gel permeation and silica gel column chromatography. The extracted samples were analyzed by gas chromatography–mass spectrometry. Using this method 5-α-androst-16-en-3-one could be identified and for the first time quantified in a concentration range of 26–155 ng/kg in human milk. 相似文献
94.
Nicole Sommer Tina Junne Kai-Uwe Kalies Martin Spiess Enno Hartmann 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2013,1833(12):3104-3111
Membrane protein insertion and topogenesis generally occur at the Sec61 translocon in the endoplasmic reticulum membrane. During this process, membrane spanning segments may adopt two distinct orientations with either their N- or C-terminus translocated into the ER lumen. While different topogenic determinants in membrane proteins, such as flanking charges, polypeptide folding, and hydrophobicity, have been identified, it is not well understood how the translocon and/or associated components decode them. Here we present evidence that the translocon-associated protein (TRAP) complex is involved in membrane protein topogenesis in vivo. Small interfering RNA (siRNA)-mediated silencing of the TRAP complex in HeLa cells enhanced the topology effect of mutating the flanking charges of a signal-anchor, but not of increasing signal hydrophobicity. The results suggest a role of the TRAP complex in moderating the ‘positive-inside’ rule. 相似文献
95.
Camila Arantes Hartmann Vilma Regina Martins Flavia Regina Souza Lima 《FEBS letters》2013,587(2):238-244
Prion protein (PrPC) has neuroprotective functions and herein we demonstrate that astrocytes from PrPC-over-expressing mice are more resistant to induced cell death than wild-type astrocytes. The Stress-Inducible-Protein 1 (STI1), a PrPC ligand, prevents cell death in both wild-type and PrPC-over-expressing astrocytes through the activation of protein-kinase-A. Cultured embryonic astrocytes and brain extracts from PrPC-over-expressing mice show higher glial fibrillary acidic protein expression and reduced vimentin and nestin levels when compared to wild-type astrocytes, suggesting faster astrocyte maturation in the former mice. Our data indicate that PrPC levels modulate astrocyte development, and that PrPC–STI1 interaction contributes to protect against astrocyte death. 相似文献
96.
Although selective or whole body cooling combined with optimal intensive care improves outcomes following neonatal encephalopathy in high-income countries, the safety and efficacy of cooling in low-and middle-income countries is not known.
Objective
We performed a systematic review and meta-analysis of all published randomised or quasi-randomised controlled trials of cooling therapy for neonatal encephalopathy in low-and middle-income countries.Results
Seven trials, comprising a total of 567 infants were included in the meta-analysis. Most study infants had mild (15%) or moderate encephalopathy (48%) and did not receive invasive ventilation (88%). Cooling devices included water-circulating cooling caps, frozen gel packs, ice, water bottles, and phase-changing material. No statistically significant reduction in neonatal mortality was seen with cooling (risk ratio: 0.74, 95% confidence intervals: 0.44 to 1.25). Data on other neonatal morbidities and long-term neurological outcomes were insufficient.Conclusion
Cooling therapy was not associated with a statistically significant reduction in neonatal mortality in low-and middle-income countries although the confidence intervals were wide and not incompatible with results seen in high-income countries. The apparent lack of treatment effect may be due to the heterogeneity and poor quality of the included studies, inefficiency of the low technology cooling devices, lack of optimal neonatal intensive care, sedation and ventilatory support, overuse of oxygen, or may be due to the intrinsic difference in the population, for example higher rates of perinatal infection, obstructed labor, intrauterine growth retardation and maternal malnutrition. Evaluation of the safety and efficacy of cooling in adequately powered randomised controlled trials is required before cooling is offered in routine clinical practice in low-and middle-income countries. 相似文献97.
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