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A R McKenzie

Publications and source records attributed to A R McKenzie.

12 recordsLinked to original sources
PubMed1993

The influence of the base-paired flanking region on structure and function of the ferritin mRNA iron regulatory element.

Ferritin and transferrin receptors are co-ordinately regulated by the same RNA-protein interaction: the conserved iron regulatory element (IRE) in mRNA and the IRE-binding protein (IRE-BP/IRP/FRP/P-90). The 28 nucleotide IRE in ferritin mRNA is a single copy, with base-paired flanking regions (FL), located near the 5' cap. In the transferrin receptor mRNA, the IRE is located in the 3' untranslated region, as five variable copies and lacking predicted base-paired flanking regions; an alternate predicted structure without IREs has similar stability. When iron is scarce, ferritin mRNA does not form polyribosomes whereas the transferrin receptor mRNA is translated; when iron is abundant, ferritin mRNA forms polyribosomes and the transferrin receptor mRNA is degraded. To investigate structures which contribute to differences in the regulation of the two mRNAs, the effect of mutation of the ferritin FL was studied. Changes in structure (changes in reactivity with RNase V1 and RNase S1. Fe-bleomycin) and changes in function (translation in rabbit reticulocyte extracts) were compared for mutant and wild-type FL sequences in ferritin mRNA. The disruption of a triplet of base-pairs in the FL had diminished regulation; a second mutation to restore the triplet base-pairs conferred wild-type translational regulation. Conformation of the mutant RNA-IRE-BP complex was also different. We show that the triplet of base-pairs is conserved; the triplet is also the location of IRE-BP-dependent conformational changes in the FL structure previously observed. Increasing FL base-pairs had no effect on function. Structural changes associated with altered function included bleomycin sites in the IRE, suggesting an alternate conformation of the hairpin, and different base-stacking (V1 sensitivity) in the FL. The function of the FL, which is altered by mutation of phylogenetically conserved triplet base-pairs, may be enhancement of formation of a particular IRE stem-loop-protein interaction.

Animals↗
PubMed1991

Ferritin mRNA: interactions of iron regulatory element with translational regulator protein P-90 and the effect on base-paired flanking regions.

The ferritin iron regulatory element (IRE), a conserved sequence of 28 nucleotides in a hairpin loop, is a conserved mRNA-specific translational regulatory element; flanking the IRE are regions of varying sequence, which form 9-17 base pairs close to the 5' cap. P-90 is a ferritin mRNA-specific translation regulatory protein purified from animal liver and reticulocytes. To study the P-90-RNA interaction, protein nucleases (RNase S1 and T1) and chemical nucleases FeEDTA and/or 1,10-phenanthroline-Cu were used as probes of an oligonucleotide (n = 55), containing the IRE and flanking regions (FL), and natural ferritin mRNA. Footprints and "toeprints" showed that P-90 binding was confined to the stem and loop of the IRE itself. However, P-90 altered the structure of the flanking region by increasing base stacking or helicity (RNase V1 sensitivity). Comparison of the reactivity of the IRE and flanking regions in natural mRNA and the 55-mer showed that long-range interactions included protecting bulges, single-stranded, and stacked regions from protein nucleases as well as stabilizing the P-90-RNA interaction. Structural integration of the IRE with the base-paired flanking regions was indicated by common features of reactivity (periodic hypersensitivity to FeEDTA) and changes in the FL region caused by P-90. The increased secondary structure of the IRE flanking regions caused by P-90 binding to the IRE provides a likely mechanism for blocking initiation of ferritin mRNA translation, since the combined structure (IRE + FL) is so close (8-17 nucleotides) to the cap.

Animals↗
PubMed1990

Binaural hearing aids for high-frequency hearing loss.

A recent study has examined the differences between certain monaural and binaural frequency responses as used in hearing aids for persons with high-frequency (often noise induced) hearing loss, in terms of both speech discrimination score and subjective rating methods. Slight variations in speech discrimination score resulted from changing the frequency response of a monaurally fitted aid while subjective preferences favoured an aid with adaptive low-frequency gain regulation for more severe high-frequency losses. A much more pronounced improvement, was however found for a binaural fitting of the preferred aid, resulting in increased discrimination score and subjective ratings of sound quality, speech clarity and overall impression. A binaural fitting of a subjectively preferred monaural hearing aid produced speech discrimination scores which were at least as good as, if not better than, those obtained from the optimum monoaural fitting. These findings are thought to have important implications for the fitting of hearing aids.

Hearing Aids↗
PubMed1987

Self-noise problems in hearing aids.

A study has been carried out to determine the extent to which the self-noise of a hearing aid constitutes a problem for aid users. A survey of hearing aid users was carried out followed by a laboratory study. None of the 75 hearing aid users seen during the survey complained of being troubled by self-noise and none of the subjects investigated at the Institute of Sound and Vibration Research was able to hear any self-noise at normal aid settings when listened for in a sound proofed room. Tests confirmed that aid noise becomes audible only when the noise level in any 1/3 octave band rises above the threshold for a pure tone at the centre of that band, and typical equivalent input noise levels indicate that audible self-noise is caused by gain being applied over a frequency band where the aid user has negligible or no hearing loss, as is likely in the case of persons with 'ski-slope' hearing loss. It is suggested that anyone else complaining of problems with self-noise is probably mistaking external background noise for self-noise of the aid.

Adult↗
PubMed1986

Differences in the lymphoproliferative response of cattle and sheep to bovine leucosis virus infection.

Lymphoblastic leukaemia, preceded by a significantly increasing percentage of prolymphocytes in peripheral blood smears for from 12 to 68 weeks before death was a feature of sheep which developed lymphosarcoma following inoculation with the Australian strain of bovine leucosis virus (BLV). Lymphocytosis and/or the appearance of immature cells were a reliable predictor of tumour formation in sheep, but not in cattle. There was a terminal lymphoblastic leukaemia in only 43 of 84 cattle with lymphosarcoma. Differences in the morphological appearance and glycogen content of the leukaemic lymphoblasts of sheep and cattle were observed. In spite of these differences the high frequency of lymphocytosis and lymphosarcoma in experimentally infected sheep suggests that they could be a useful model for studying the pathological and immunological responses to BLV infection.

Animals↗