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K Richards

Publications and source records attributed to K Richards.

At least 91 records · Page 5Linked to original sources

Nucleotide sequence at the 5' extremity of tobacco-mosaic-virus RNA. 1. The noncoding region (nucleotides 1-68).

The sequence of the 5' noncoding region of tobacco mosaic virus RNA has been determined. The noncoding region is 68 nucleotides long and is unusual in that it contains no internal guanosine residues. The long T1 oligonucleotide containing the guanosine-free tract was isolated from a T1 ribonuclease digest of tobacco mosaic virus RNA and sequenced by labelling techniques in vitro using polynucleotide kinase. The guanosine-free tract is terminated by the first potential initiation codon in the RNA molecule and several lines of evidence suggest that this AUG triplet is operational in initiating viral protein synthesis (see following paper). The 5'-noncoding region cannot base-pair extensively with the 3'-terminal sequence of 18-S ribosomal RNA from rabbit reticulocytes.

Base Sequence↗

Nucleotide sequence at the 5' extremity of tobacco-mosaic-virus RNA. 2. The coding region (nucleotides 69-236).

In the preceding paper it was shown that the first A-U-G codon in tobacco mosaic virus RNA is separated from the 5' terminus by a sequence of 68 nucleotides devoid of internal guanosine residues. In this paper we present the sequence of 165 residues immediately following the first potential initiation codon. The characterized sequence contains four nonsense codons but none are in phase with the prospective initiation codon. Several lines of evidence, including direct characterization of the portion of the RNA molecule which binds to and is protected by the ribosome in the course of initiation, all support the idea that the A-U-G at position 69-71 is a functional initiation signal for viral protein synthesis.

Base Sequence↗

Nucleotide sequence (n=159) of the amino-acid-accepting 3'-OH extremity of turnip-yellow-mosaic-virus RNA and the last portion of its coat-protein cistron.

The experiments described in this paper and the following one establish the sequence of the 3'-OH terminal 159 nucleotides of turnip yellow mosaic virus RNA. Uniformly 32P-labeled turnip yellow mosaic virus RNA was partially digested with T1 ribonuclease and the fragments were fractionated by polyacrylamide gel electrophoresis. Fragments originating from the 3'-OH end of the RNA molecule were identified by testing for the 3'-terminal oligonucleotide, C-COH, after total U2 ribonuclease hydrolysis. Once identified, the 3'-OH terminal fragments were sequenced by the methods of Sanger et al. The first 51 nucleotides of the longest of the sequenced fragments (158 nucleotides) extends into the 3'-terminal part of the coat protein cistron. The coat protein cistron is followed by a stretch of 108 untranslated nucleotides whose function, though still unknown, is probably linked to the tRNA-like properties which have been attributed to the 3'-OH extremity of this viral RNA. Two possible secondary structures are proposed for the sequence and the implications of the findings with regard to the tRNA-like properties of the extremity are discussed.

Base Sequence↗

Mechanism and prevention of fixed high vascular resistance in autografted and allografted lungs.

The fixed vascular resistance observed in tranisplanted Ilunlgs and attriblted to denervation can be avoided by angioplastic wideniing of the pulmonary artery anastotosis. With distenisible arterial anrastomoses, aultografted an, d allografted Ilunzgs vasodilate niormzally with inicreased flow and cani sutstaini dogs whose contralateral pulmonary artery is ligated imumediately after lutng transplanitation.

Animals↗

Compendium of gene expression profiles comprising a baseline model of the human liver drug metabolism transcriptome.

Oligonucleotide microarrays were used to study the variability of pharmacokinetics and drug metabolism (PKDM)-related gene expression in 75 normal human livers. The objective was to define and use absorption, distribution, metabolism and excretion (ADME) gene expression variability to discern co-regulated genes and potential surrogate biomarkers of inducible gene expression. RNA was prepared from donor tissue and hybridized on Agilent microarrays against an RNA mass balanced pool from all donors. Clustering of PKDM gene sets revealed donors with distinct patterns of gene expression that grouped genes known to be regulated by the nuclear receptor, pregnane X-receptor (PXR). Fold range metrics and frequency distributions from the heterogeneous human population were used to define the variability of individual PKDM genes in the 75 human livers and were placed in context by comparing expression data with basal ADME gene expression variability in an inbred and diet/environment controlled population of 27 Rhesus livers. The most variable genes in the hepatic transcriptome were mainly related to drug metabolism, intermediary metabolism, inflammation and cell cycle control. Unique patterns of expression across 75 individuals of inducible ADME gene expression allowed their expression to be correlated with the expression of many other genes. Correlated genes for AhR, CAR and PXR responsive genes (CYP1A2, CYP2B6 and CYP3A4) were identified that may be co-regulated and, therefore, provide clues to the identity of surrogate gene or protein markers for CYP induction. In conclusion, microarrays were used to define the variable expression of hepatic ADME genes in a diverse human population, the expression variability of ADME genes was compared with the expression variability in an inbred population of Rhesus monkeys, and genes were defined that may be co-regulated with important inducible CYP genes.

Animals↗