Catalysis-dependent stabilization of Bre1 fine-tunes histone H2B ubiquitylation to regulate gene transcription

Monoubiquitylation of histone H2B on Lys123 (H2BK123ub1) plays a multifaceted role in diverse DNA-templated processes, yet the mechanistic details by which this modification is regulated are not fully elucidated. Here we show in yeast that H2BK123ub1 is regulated in part through the protein stability of the E3 ubiquitin ligase Bre1. We found that Bre1 stability is controlled by the Rtf1 subunit of the polymerase-associated factor (PAF) complex and through the ability of Bre1 to catalyze H2BK123ub1. Using a domain in Rtf1 that stabilizes Bre1, we show that inappropriate Bre1 levels lead to defects in gene regulation. Collectively, these data uncover a novel quality control mechanism used by the cell to maintain proper Bre1 and H2BK123ub1 levels, thereby ensuring proper control of gene expression.     

Brief Report: Trends in U.S. National Autism Awareness from 2004 to 2014: The Impact of National Autism Awareness Month

We sought to evaluate the potential for using historical web search data on autism spectrum disorders (ASD)-related topics as an indicator of ASD awareness. Analysis of Google Trend data suggested that National Autism Awareness Month and televised reports concerning autism are an effective method of promoting online search interest in autism.     

Gene Deletions in Mycobacterium bovis BCG Stimulate Increased CD8+ T Cell Responses

Mycobacteria, the etiological agents of tuberculosis and leprosy, have coevolved with mammals for millions of years and have numerous ways of suppressing their host''s immune response. It has been suggested that mycobacteria may contain genes that reduce the host''s ability to elicit CD8⁺ T cell responses. We screened 3,290 mutant Mycobacterium bovis bacillus Calmette Guerin (BCG) strains to identify genes that decrease major histocompatibility complex (MHC) class I presentation of mycobacterium-encoded epitope peptides. Through our analysis, we identified 16 mutant BCG strains that generated increased transgene product-specific CD8⁺ T cell responses. The genes disrupted in these mutant strains had disparate predicted functions. Reconstruction of strains via targeted deletion of genes identified in the screen recapitulated the enhanced immunogenicity phenotype of the original mutant strains. When we introduced the simian immunodeficiency virus (SIV) gag gene into several of these novel BCG strains, we observed enhanced SIV Gag-specific CD8⁺ T cell responses in vivo. This study demonstrates that mycobacteria carry numerous genes that act to dampen CD8⁺ T cell responses and suggests that genetic modification of these genes may generate a novel group of recombinant BCG strains capable of serving as more effective and immunogenic vaccine vectors.     

Bioaerosol exposure to personnel in a clinical environment absent patients

Nosocomial infections pose a significant and escalating threat to both patients and healthcare workers (HCWs). By their nature, hospitals induce antibiotic resistance in virulent and commensal strains, leading to increasingly severe hospital-acquired infections. This study measured environmental exposure experienced by domestic staff cleaning vacated patient rooms of a community hospital to bacteria in ambient bioaerosols. While they cleaned the room, participants wore an N95 filtering facepiece respirator (FFR), from which coupons were cut and bacteria were extracted, cultured and enumerated. Extrapolation to the full area of the respirator yielded measured exposures of 0.2–1.4 × 10⁴ colony-forming units/hour, of which ～97% collected on the front layer of the N95, suggesting a possible role for minimal respiratory protection in nonpatient environments. Random resistance testing of 1.6% of the isolates showed that ～70% of both Gram-positive and Gram-negative organisms exhibited resistance to oxacillin and ～9% of the Gram-positives displayed resistance to vancomycin. These data provide an estimate for mask bioaerosol loading that can be used in risk modeling and to refine strategies for reuse of FFRs during critical shortages.