A heterozygous gain-of-function mutation in STING can cause familial chilblain lupus. These findings expand the genetic spectrum of type I IFN-dependent disorders and suggest that JAK inhibition may be of therapeutic value.
Immune recognition of cytosolic DNA represents a central antiviral defence mechanism. Within the host, short single-stranded DNA (ssDNA) continuously arises during the repair of DNA damage induced by endogenous and environmental genotoxic stress. Here we show that short ssDNA traverses the nuclear membrane, but is drawn into the nucleus by binding to the DNA replication and repair factors RPA and Rad51. Knockdown of RPA and Rad51 enhances cytosolic leakage of ssDNA resulting in cGAS-dependent type I IFN activation. Mutations in the exonuclease TREX1 cause type I IFN-dependent autoinflammation and autoimmunity. We demonstrate that TREX1 is anchored within the outer nuclear membrane to ensure immediate degradation of ssDNA leaking into the cytosol. In TREX1-deficient fibroblasts, accumulating ssDNA causes exhaustion of RPA and Rad51 resulting in replication stress and activation of p53 and type I IFN. Thus, the ssDNA-binding capacity of RPA and Rad51 constitutes a cell intrinsic mechanism to protect the cytosol from self DNA.
X-ray phase-contrast imaging is a promising method for medical imaging and non-destructive testing. Information about the attenuation, small-angle scattering and phase-shifting properties of an object can be gained simultaneously in three image modalities using a Talbot-Lau interferometer. This is a highly sensitive approach for retrieving this information. Nevertheless, until now, Talbot-Lau interferometry has been a time-consuming process due to image acquisition by phase-stepping procedures. Thus, methods to accelerate the image acquisition process in Talbot-Lau interferometry would be desirable. This is especially important for medical applications to avoid motion artifacts. In this work, the Talbot-Lau interferometry is combined with the moiré imaging approach. Firstly, the reconstruction algorithm of moiré imaging is improved compared to the standard reconstruction methods in moiré imaging that have been published until now. Thus, blurring artifacts resulting from the reconstruction in the frequency domain can be reduced. Secondly, the improved reconstruction algorithm allows for reducing artifacts in the reconstructed images resulting from inhomogeneities of the moiré pattern in large fields of view. Hence, the feasibility of differential phase-contrast imaging with regard to the integration into workflows in medical imaging and non-destructive testing is improved considerably. New fields of applications can be gained due to the accelerated imaging process-for example, live imaging in medical applications.
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