12 research outputs found
Defective removal of ribonucleotides from DNA promotes systemic autoimmunity
Genome integrity is continuously challenged by the DNA damage that arises during normal cell metabolism. Biallelic mutations in the genes encoding the genome surveillance enzyme ribonuclease H2 (RNase H2) cause Aicardi-Goutières syndrome (AGS), a pediatric disorder that shares features with the autoimmune disease systemic lupus erythematosus (SLE). Here we determined that heterozygous parents of AGS patients exhibit an intermediate autoimmune phenotype and demonstrated a genetic association between rare RNASEH2 sequence variants and SLE. Evaluation of patient cells revealed that SLE- and AGS-associated mutations impair RNase H2 function and result in accumulation of ribonucleotides in genomic DNA. The ensuing chronic low level of DNA damage triggered a DNA damage response characterized by constitutive p53 phosphorylation and senescence. Patient fibroblasts exhibited constitutive upregulation of IFN-stimulated genes and an enhanced type I IFN response to the immunostimulatory nucleic acid polyinosinic:polycytidylic acid and UV light irradiation, linking RNase H2 deficiency to potentiation of innate immune signaling. Moreover, UV-induced cyclobutane pyrimidine dimer formation was markedly enhanced in ribonucleotide-containing DNA, providing a mechanism for photosensitivity in RNase H2-associated SLE. Collectively, our findings implicate RNase H2 in the pathogenesis of SLE and suggest a role of DNA damage-associated pathways in the initiation of autoimmunity
COMMENTS CONCERNING PARAMETERS OF THE SHORT-RANGE ORDER EVOLUTION DETERMINED FROM THE DATA ON KINETICS OF A HEAT-CAPACITY RELAXATION FOR Lu–H ALLOY
Isolated Complete Rupture of the Biceps Femoris Insertion: A Surgical Repair Technique Manuscript
Isolated rupture of the distal biceps femoris insertion is rare. Current literature offers limited case reports and outcome measures after surgical management. We describe a knotless suture anchor fixation technique for this tear pattern. At surgery, the retracted biceps tendon and insertion site is debrided to healthy tissue, FiberTape suture (Arthrex) is passed in a Kracków fashion through the tendon, and the 2 ends of the suture are brought down to a SwiveLock anchor (Arthrex) at the anatomic insertion. FiberWire sutures (Arthrex) from the anchor are brought over the remnant stump, completing the repair
Magnetic Particle Imaging meets Computed Tomography: first simultaneous imaging
Magnetic Particle Imaging (MPI) is a promising new tomographic modality for fast as well as three-dimensional visualization of magnetic material. For anatomical or structural information an additional imaging modality such as computed tomography (CT) is required. In this paper, the first hybrid MPI-CT scanner for multimodal imaging providing simultaneous data acquisition is presented