A mutant allele of essential, general translation initiation factor DED1 selectively inhibits translation of a viral mRNA

Positive-strand RNA virus genomes are substrates for translation, RNA replication, and encapsidation. To identify host factors involved in these functions, we used the ability of brome mosaic virus (BMV) RNA to replicate in yeast. We report herein identification of a mutation in the essential yeast gene DED1 that inhibited BMV RNA replication but not yeast growth. DED1 encodes a DEAD (Asp-Glu-Ala-Asp)-box RNA helicase required for translation initiation of all yeast mRNAs. Inhibition of BMV RNA replication by the mutant DED1 allele (ded1–18) resulted from inhibited expression of viral polymerase-like protein 2a, encoded by BMV RNA2. Inhibition of RNA2 translation was selective, with no effect on general cellular translation or translation of BMV RNA1-encoded replication factor 1a, and was independent of p20, a cellular antagonist of DED1 function in translation. Inhibition of RNA2 translation in ded1–18 yeast required the RNA2 5′ noncoding region (NCR), which also conferred a ded1–18-specific reduction in expression on a reporter gene mRNA. Comparison of the similar RNA1 and RNA2 5′ NCRs identified a 31-nucleotide RNA2-specific region that was required for the ded1–18-specific RNA2 translation block and attenuated RNA2 translation in wild-type yeast. Further comparisons and RNA structure predictions suggest a modular arrangement of replication and translation signals in RNA1 and RNA2 5′ NCRs that appears conserved among bromoviruses. The 5′ attenuator and DED1 dependence of RNA2 suggest that, despite its divided genome, BMV regulates polymerase translation relative to other replication factors, just as many single-component RNA viruses use translational read-through and frameshift mechanisms to down-regulate polymerase. The results show that a DEAD-box helicase can selectively activate translation of a specific mRNA and may provide a paradigm for translational regulation by other members of the ubiquitous DEAD-box RNA helicase family.

Comparison of potency of inhaled beclomethasone and budesonide in New Zealand: retrospective study of computerised general practice records

Objective To determine whether inhaled budesonide and beclomethasone are equipotent in the treatment of asthma in primary care.

From trial data to practical knowledge: qualitative study of how general practitioners have accessed and used evidence about statin drugs in their management of hypercholesterolaemia

Objectives To explore how general practitioners have accessed and evaluated evidence from trials on the use of statin lipid lowering drugs and incorporated this evidence into their practice. To draw out the practical implications of this study for strategies to integrate clinical evidence into general medical practice.

Power of attorney for Joseph Chip, 1804 December 21

Handwritten draft of a power of attorney, in Croswell's hand, authorizing John Jones to act for mariner Joseph Chip.

[Grants of the General Court for 1737 and 1750 to President Holyoke], undated

One folio-sized leaf containing a handwritten list of grants received by President Holyoke from the Massachusetts General Court between 1737 and 1750, presumably copied from a record book cited as "M.S. No. II," pages 26-56.

Members of the General Court, 1798-1799

Notebook with paper cover containing a handwritten list of the members of the Massachusetts General Court arranged by county and town. Pearson identified characteristics of the politicians including whether they were chosen by the people or Legislature, were for or against the College, were for or against the Virginia Resolutions, and whether they were "a good Federalist."

Power of Attorney, [?] Wellington for Thomas Durant, Sept. 22, 1787

Signed by Thomas Durant and witnessed by Ebenezer Bradish. It is possible that Shapleigh used this document as a guide when drafting his own power of attorney documents.

Power of Attorney, Samuel Shapleigh for Thomas Adams, Jan. 12, 1791

Signed by Thomas Adams and witnessed by Abraham Biglow and Daniel Clarke Sanders.

Power of Attorney, Samuel Shapleigh for James Otis Prentiss, Aug. 18, 1791

Document also contains what appears to be a bill for medical services rendered by Prentiss, a doctor, to William Boman.

[Power of attorney between Stephen Sewall and Thomas Wigglesworth], 1794 August 21

This one-page printed form appoints Thomas Wigglesworth as the "true and lawful Attorney" for Stephen Sewall. The form is notarized by Samuel Barrett and witnessed by Barrett and his daughter Peggy Barrett.

Power of Attorney, Samuel Shapleigh for Thomas Thompson, May 18, 1791

Signed by Thomas Thompson and witnessed by Thaddeus Mason Harris and Otis(?) Clarke.

Report of the Michigan Academy of Science.

1907