A RING-type ubiquitin ligase family member required to repress follicular helper T cells and autoimmunity

Despite the sequencing of the human and mouse genomes, few genetic mechanisms for protecting against autoimmune disease are currently known. Here we systematically screen the mouse genome for autoimmune regulators to isolate a mouse strain, sanroque, with severe autoimmune disease resulting from a single recessive defect in a previously unknown mechanism for repressing antibody responses to self. The sanroque mutation acts within mature T cells to cause formation of excessive numbers of follicular helper T cells and germinal centres. The mutation disrupts a repressor of ICOS, an essential co-stimulatory receptor for follicular T cells, and results in excessive production of the cytokine interleukin-21. sanroque mice fail to repress diabetes-causing T cells, and develop high titres of autoantibodies and a pattern of pathology consistent with lupus. The causative mutation is in a gene of previously unknown function, roquin (Rc3h1), which encodes a highly conserved member of the RING-type ubiquitin ligase protein family. The Roquin protein is distinguished by the presence of a CCCH zinc-finger found in RNA-binding proteins, and localization to cytosolic RNA granules implicated in regulating messenger RNA translation and stability.     

Atomic inner-shell X-ray laser at 1.46 nanometres pumped by an X-ray free-electron laser

Since the invention of the laser more than 50 years ago, scientists have striven to achieve amplification on atomic transitions of increasingly shorter wavelength. The introduction of X-ray free-electron lasers makes it possible to pump new atomic X-ray lasers with ultrashort pulse duration, extreme spectral brightness and full temporal coherence. Here we describe the implementation of an X-ray laser in the kiloelectronvolt energy regime, based on atomic population inversion and driven by rapid K-shell photo-ionization using pulses from an X-ray free-electron laser. We established a population inversion of the Kα transition in singly ionized neon at 1.46 nanometres (corresponding to a photon energy of 849 electronvolts) in an elongated plasma column created by irradiation of a gas medium. We observed strong amplified spontaneous emission from the end of the excited plasma. This resulted in femtosecond-duration, high-intensity X-ray pulses of much shorter wavelength and greater brilliance than achieved with previous atomic X-ray lasers. Moreover, this scheme provides greatly increased wavelength stability, monochromaticity and improved temporal coherence by comparison with present-day X-ray free-electron lasers. The atomic X-ray lasers realized here may be useful for high-resolution spectroscopy and nonlinear X-ray studies.     

Dependence of Z-DNA antibody binding to polytene chromosomes on acid fixation and DNA torsional strain

There is considerable interest in the existence and significance of alternative conformations of DNA to the right-handed B-form described originally by Watson and Crick. The indirect immunofluorescence observations of Nordheim et al., Arndt-Jovin et al. and Lemeunier et al. that antibodies against left-handed Z-DNA bind to polytene chromosomes have thus assumed considerable importance. However, there is a paradox: some workers observe Z-DNA in interbands and others in bands. We report here that binding of Z-DNA antibodies to Drosophila polytene chromosomes prepared without acid fixation is at background level, and that following acid fixation the same antibody treatment leads to intense fluorescence. Depending on the extent of exposure to 45% acetic acid, fluorescence can occur primarily in interbands or in bands. Furthermore, antibody binding is dependent on elastic torsional strain in the DNA molecules.