The vast bacteriophage population harbors an immense reservoir of genetic information. Almost 2000 phage genomes have been sequenced from phages infecting hosts in the phylum Actinobacteria, and analysis of these genomes reveals substantial diversity, pervasive mosaicism, and novel mechanisms for phage replication and lysogeny. Here, we describe the isolation and genomic characterization of 46 phages from environmental samples at various geographic locations in the U.S. infecting a single Arthrobacter sp. strain. These phages include representatives of all three virion morphologies, and Jasmine is the first sequenced podovirus of an actinobacterial host. The phages also span considerable sequence diversity, and can be grouped into 10 clusters according to their nucleotide diversity, and two singletons each with no close relatives. However, the clusters/singletons appear to be genomically well separated from each other, and relatively few genes are shared between clusters. Genome size varies from among the smallest of siphoviral phages (15,319 bp) to over 70 kbp, and G+C contents range from 45–68%, compared to 63.4% for the host genome. Although temperate phages are common among other actinobacterial hosts, these Arthrobacter phages are primarily lytic, and only the singleton Galaxy is likely temperate.
Quaking RNA binding protein (QKI) is essential for oligodendrocyte development as myelination requires myelin basic protein mRNA regulation and localization by the cytoplasmic isoforms (e.g., QKI-6). QKI-6 is also highly expressed in astrocytes, which were recently demonstrated to have regulated mRNA localization. Here, we define the targets of QKI in the mouse brain via CLIPseq and we show that QKI-6 binds 3′UTRs of a subset of astrocytic mRNAs. Binding is also enriched near stop codons, mediated partially by QKI-binding motifs (QBMs), yet spreads to adjacent sequences. Using a viral approach for mosaic, astrocyte-specific gene mutation with simultaneous translating RNA sequencing (CRISPR-TRAPseq), we profile ribosome associated mRNA from QKI-null astrocytes in the mouse brain. This demonstrates a role for QKI in stabilizing CLIP-defined direct targets in astrocytes in vivo and further shows that QKI mutation disrupts the transcriptional changes for a discrete subset of genes associated with astrocyte maturation.
Dapsone is a commonly used second line drug for prophylaxis of pneumocystis jirovecii pneumonia (PJP) in immunocompromised patients. Oxidant hemolysis, caused by dapsone’s metabolite hydroxylamine, is a common side effect, and screening for glucose-6-phosphate dehydrogenase (G6PD) deficiency is recommended before the drug is started in order to prevent potential hemolytic reactions. We report a case of dapsone induced hemolytic anemia in a patient with ANCA associated glomerulonephritis and normal G6PD level. Her anemia improved after cessation of therapy with dapsone. We review the literature of dapsone induced hemolysis in patients who have normal G6PD level and discuss potential pathways leading to hemolytic anemia and its implications for clinical practice.
This study demonstrates that PR3 ANCA+ patients may be more likely to experience relapse post-transplant. Further investigation of the predictors of vasculitis relapse among AAV patients who are ANCA+ at the time of RTx needs to be pursued.
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