Evolutionary specialization of recoding: frameshifting in the expression of S. cerevisiae antizyme mRNA is via an atypical antizyme shift site but is still +1

Journal ArticleAn autoregulatory translational shift to the +1 frame is required for the expression of ornithine decarboxylase antizyme from fungi to mammals. In most eukaryotes, including all vertebrates and a majority of the studied fungi/yeast, the site on antizyme mRNA where the shift occurs is UCC-UGA. The mechanism of the frameshift on this sequence likely involves nearly universal aspects of the eukaryotic translational machinery. Nevertheless, a mammalian antizyme frameshift cassette yields predominantly -2 frameshift in Saccharomyces cerevisiae, instead of the +1 in mammals. The recently identified endogenous S. cerevisiae antizyme mRNA has an atypical shift site: UGC-GCG-UGA. It is shown here that endogenous S. cerevisiae antizyme frameshifting is +1 rather than -2. We discuss how antizyme frameshifting in budding yeasts exploits peculiarities of their tRNA balance, and relate this to prior studies on Ty frameshifting

Neurophysiology

Contains reports on one research project.National Science FoundationOffner Electronics, IncorporatedTeagle FoundationBell Telephone Laboratories, Incorporate

Neurophysiology

Contains reports on three research projects.Bell Telephone Laboratories, IncorporatedTeagle FoundationNational Science FoundationOffner Electronics, Incorporate

Neurophysiology

Contains reports on four research projects.Bell Telephone Laboratories, IncorporatedThe Teagle Foundation, IncorporatedNational Science Foundatio

Glassy transition in a disordered model for the RNA secondary structure

We numerically study a disordered model for the RNA secondary structure and we find that it undergoes a phase transition, with a breaking of the replica symmetry in the low temperature region (like in spin glasses). Our results are based on the exact evaluation of the partition function.Comment: 4 pages, 3 figure

A mutate-and-map protocol for inferring base pairs in structured RNA

Chemical mapping is a widespread technique for structural analysis of nucleic acids in which a molecule's reactivity to different probes is quantified at single-nucleotide resolution and used to constrain structural modeling. This experimental framework has been extensively revisited in the past decade with new strategies for high-throughput read-outs, chemical modification, and rapid data analysis. Recently, we have coupled the technique to high-throughput mutagenesis. Point mutations of a base-paired nucleotide can lead to exposure of not only that nucleotide but also its interaction partner. Carrying out the mutation and mapping for the entire system gives an experimental approximation of the molecules contact map. Here, we give our in-house protocol for this mutate-and-map strategy, based on 96-well capillary electrophoresis, and we provide practical tips on interpreting the data to infer nucleic acid structure.Comment: 22 pages, 5 figure

Neurophysiology

Contains a report on a research project

Automated real-time collection of pathogen-specific diagnostic data: Syndromic infectious disease epidemiology

© Lindsay Meyers, Christine C Ginocchio, Aimie N Faucett, Frederick S Nolte, Per H Gesteland, Amy Leber, Diane Janowiak,. Background: Health care and public health professionals rely on accurate, real-time monitoring of infectious diseases for outbreak preparedness and response. Early detection of outbreaks is improved by systems that are comprehensive and specific with respect to the pathogen but are rapid in reporting the data. It has proven difficult to implement these requirements on a large scale while maintaining patient privacy. Objective: The aim of this study was to demonstrate the automated export, aggregation, and analysis of infectious disease diagnostic test results from clinical laboratories across the United States in a manner that protects patient confidentiality. We hypothesized that such a system could aid in monitoring the seasonal occurrence of respiratory pathogens and may have advantages with regard to scope and ease of reporting compared with existing surveillance systems. Methods: We describe a system, BioFire Syndromic Trends, for rapid disease reporting that is syndrome-based but pathogen-specific. Deidentified patient test results from the BioFire FilmArray multiplex molecular diagnostic system are sent directly to a cloud database. Summaries of these data are displayed in near real time on the Syndromic Trends public website. We studied this dataset for the prevalence, seasonality, and coinfections of the 20 respiratory pathogens detected in over 362,000 patient samples acquired as a standard-of-care testing over the last 4 years from 20 clinical laboratories in the United States. Results: The majority of pathogens show influenza-like seasonality, rhinovirus has fall and spring peaks, and adenovirus and the bacterial pathogens show constant detection over the year. The dataset can also be considered in an ecological framework; the viruses and bacteria detected by this test are parasites of a host (the human patient). Interestingly, the rate of pathogen codetections, on average 7.94% (28,741/362,101), matches predictions based on the relative abundance of organisms present. Conclusions: Syndromic Trends preserves patient privacy by removing or obfuscating patient identifiers while still collecting much useful information about the bacterial and viral pathogens that they harbor. Test results are uploaded to the database within a few hours of completion compared with delays of up to 10 days for other diagnostic-based reporting systems. This work shows that the barriers to establishing epidemiology systems are no longer scientific and technical but rather administrative, involving questions of patient privacy and data ownership. We have demonstrated here that these barriers can be overcome. This first look at the resulting data stream suggests that Syndromic Trends will be able to provide high-resolution analysis of circulating respiratory pathogens and may aid in the detection of new outbreaks

Neurophysiology

Contains research objectives and reports on four research projects.Bell Telephone Laboratories, IncorporatedNational Institutes of HealthNational Science FoundationTeagle Foundation, Incorporate

Neurophysiology

Contains research objectives and reports on three research projects.National Aeronautics and Space Administration (Grant NsG-496)U.S. Air Force (Aeronautical Systems Division) under Contract AF33 (616)-7783The Teagle Foundation, Inc.National Institutes of Health (Grant MH-04737-03)National Institutes of Health (Grant NB-04897-01)National Science Foundation (Grant G-16526)Bell Telephone Laboratories, Inc