Evaluation of Adjunctive Mycophenolate for Large Vessel Giant Cell Arteritis

Funding: We are grateful to Versus Arthritis (grant 22088) and PMR/GCA Scotland for supporting our workPeer reviewedPublisher PD

Diversity of Pol IV Function Is Defined by Mutations at the Maize rmr7 Locus

Mutations affecting the heritable maintenance of epigenetic states in maize identify multiple small RNA biogenesis factors including NRPD1, the largest subunit of the presumed maize Pol IV holoenzyme. Here we show that mutations defining the required to maintain repression7 locus identify a second RNA polymerase subunit related to Arabidopsis NRPD2a, the sole second largest subunit shared between Arabidopsis Pol IV and Pol V. A phylogenetic analysis shows that, in contrast to representative eudicots, grasses have retained duplicate loci capable of producing functional NRPD2-like proteins, which is indicative of increased RNA polymerase diversity in grasses relative to eudicots. Together with comparisons of rmr7 mutant plant phenotypes and their effects on the maintenance of epigenetic states with parallel analyses of NRPD1 defects, our results imply that maize utilizes multiple functional NRPD2-like proteins. Despite the observation that RMR7/NRPD2, like NRPD1, is required for the accumulation of most siRNAs, our data indicate that different Pol IV isoforms play distinct roles in the maintenance of meiotically-heritable epigenetic information in the grasses

The sex locus is tightly linked to factors conferring sex-specific lethal effects in the mosquito Aedes aegypti

In many taxa, sex chromosomes are heteromorphic and largely non-recombining. Evolutionary models predict that spread of recombination suppression on the Y chromosome is fueled by the accumulation of sexually antagonistic alleles in close linkage to the sex determination region. However, empirical evidence for the existence of sexually antagonistic alleles is scarce. In the mosquito Aedes aegypti, the sex-determining chromosomes are homomorphic. The region of suppressed recombination, which surrounds the male-specific sex-determining gene, remains very small, despite ancient origin of the sex chromosomes in the Aedes lineage. We conducted a genetic analysis of the A. aegypti chromosome region tightly linked to the sex locus. We used a strain with an enhanced green fluorescent protein (EGFP)-tagged transgene inserted near the male-determining gene to monitor crossing-over events close to the boundary of the sex-determining region (SDR), and to trace the inheritance pattern of the transgene in relation to sex. In a series of crossing experiments involving individuals with a recombinant sex chromosome we found developmental abnormalities leading to 1:2 sex biases, caused by lethality of half of the male or female progeny. Our results suggest that various factors causing sex-specific lethal effects are clustered within the neighborhood of the SDR, which in the affected sex are likely lost or gained through recombination, leading to death. These may include genes that are recessive lethal, vital for development and/or sexually antagonistic. The sex chromosome fragment in question represents a fascinating test case for the analysis of processes that shape stable boundaries of a non-recombining region

Searching for low-mass dark matter via the Migdal effect in COSINE-100

We report on the search for weakly interacting massive particle (WIMP) dark matter candidates in the galactic halo that interact with sodium and iodine nuclei in the COSINE-100 experiment and produce energetic electrons that accompany recoil nuclei via the the Migdal effect. The WIMP mass sensitivity of previous COSINE-100 searches that relied on the detection of ionization signals produced by target nuclei recoiling from elastic WIMP-nucleus scattering was restricted to WIMP masses above ∼5 GeV/c2 by the detectors' 1 keVee energy-electron-equivalent threshold. The search reported here looks for recoil signals enhanced by the Migdal electrons that are ejected during the scattering process. This is particularly effective for the detection of low-mass WIMP scattering from the crystals' sodium nuclei in which a relatively larger fraction of the WIMP's energy is transferred to the nucleus recoil energy and the excitation of its orbital electrons. In this analysis, the low-mass WIMP search window of the COSINE-100 experiment is extended to WIMP mass down to 200 MeV/c2. The low-mass WIMP sensitivity will be further improved by lowering the analysis threshold based on a multivariable analysis technique. We consider the influence of these improvements and recent developments in detector performance to re-evaluate sensitivities for the future COSINE-200 experiment. With a 0.2 keVee analysis threshold and high light-yield NaI(Tl) detectors (22 photoelectrons/keVee), the COSINE-200 experiment can explore low-mass WIMPs down to 20 MeV/c2 and probe previously unexplored regions of parameter space

Searching for low-mass dark matter via Migdal effect in COSINE-100 [preprint]

We report on the search for weakly interacting massive particle (WIMP) dark matter candidates in the galactic halo that interact with sodium and iodine nuclei in the COSINE-100 experiment and produce energetic electrons that accompany recoil nuclei via the the Migdal effect. The WIMP mass sensitivity of previous COSINE-100 searches that relied on the detection of ionization signals produced by target nuclei recoiling from elastic WIMP-nucleus scattering was restricted to WIMP masses above $\sim$5 GeV/$c^2$ by the detectors' 1 keVee energy-electron-equivalent threshold. The search reported here looks for recoil signals enhanced by the Migdal electrons that are ejected during the scattering process. This is particularly effective for the detection of low-mass WIMP scattering from the crystals' sodium nuclei in which a relatively larger fraction of the WIMP's energy is transferred to the nucleus recoil energy and the excitation of its orbital electrons. In this analysis, the low-mass WIMP search window of the COSINE-100 experiment is extended to WIMP mass down to 200 MeV/c. The low-mass WIMP sensitivity will be further improved by lowering the analysis threshold based on a multivariable analysis technique. We consider the influence of these improvements and recent developments in detector performance to re-evaluate sensitivities for the future COSINE-200 experiment. With a 0.2 keVee analysis threshold and high light-yield NaI(Tl) detectors (22photoelectrons/keVee), the COSINE-200 experiment can explore low-mass WIMPs down to 20 MeV/c2 and probe previously unexplored regions of parameter space