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Articles by K Smith
Total Records ( 6 ) for K Smith
  A. A Pohl , C. W Sugnet , T. A Clark , K Smith , P. A Fujita and M. S. Cline

Summary: Most genes in human, mouse and rat produce more than one transcript isoform. The Affymetrix Exon Array is a tool for studying the many processes that regulate RNA production, with separate probesets measuring RNA levels at known and putative exons. For insights on how exons levels vary between normal tissues, we constructed the Affy Exon Tissues track from tissue data published by Affymetrix. This track reports exon probeset intensities as log ratios relative to median values across the dataset and renders them as colored heat maps, to yield quick visual identification of exons with intensities that vary between normal tissues.

  R. C Laxton , Y Hu , J Duchene , F Zhang , Z Zhang , K. Y Leung , Q Xiao , R. S Scotland , C. P Hodgkinson , K Smith , J Willeit , C Lopez Otin , I. A Simpson , S Kiechl , A Ahluwalia , Q Xu and S. Ye

Rationale: Atherosclerotic lesions express matrix metalloproteinase (MMP)8, which possesses proteolytic activity on matrix proteins particularly fibrillar collagens and on nonmatrix proteins such as angiotensin (Ang) I.

Objective: We studied whether MMP8 plays a role in atherogenesis.

Methods and Results: In atherosclerosis-prone apolipoprotein E–deficient mice, inactivating MMP8 resulted in a substantial reduction in atherosclerotic lesion formation. Immunohistochemical examinations showed that atherosclerotic lesions in MMP8-deficient mice had significantly fewer macrophages but increased collagen content. In line with results of in vitro assays showing that Ang I cleavage by MMP8 generated Ang II, MMP8 knockout mice had lower Ang II levels and lower blood pressure. In addition, we found that products of Ang I cleavage by MMP8 increased vascular cell adhesion molecule (VCAM)-1 expression and that MMP8-deficient mice had reduced VCAM-1 expression in atherosclerotic lesions. Intravital microscopy analysis showed that leukocyte rolling and adhesion on vascular endothelium was reduced in MMP8 knockout mice. Furthermore, we detected an association between MMP8 gene variation and extent of coronary atherosclerosis in patients with coronary artery disease. A relationship among MMP8 gene variation, plasma VCAM-1 level, and atherosclerosis progression was also observed in a population-based, prospective study.

Conclusions: These results indicate that MMP8 is an important player in atherosclerosis.

  V Kumar , P Atherton , K Smith and M. J. Rennie

Skeletal muscle demonstrates extraordinary mutability in its responses to exercise of different modes, intensity, and duration, which must involve alterations of muscle protein turnover, both acutely and chronically. Here, we bring together information on the alterations in the rates of synthesis and degradation of human muscle protein by different types of exercise and the influences of nutrition, age, and sexual dimorphism. Where possible, we summarize the likely changes in activity of signaling proteins associated with control of protein turnover. Exercise of both the resistance and nonresistance types appears to depress muscle protein synthesis (MPS), whereas muscle protein breakdown (MPB) probably remains unchanged during exercise. However, both MPS and MPB are elevated after exercise in the fasted state, when net muscle protein balance remains negative. Positive net balance is achieved only when amino acid availability is increased, thereby raising MPS markedly. However, postexercise-increased amino acid availability is less important for inhibiting MPB than insulin, the secretion of which is stimulated most by glucose availability, without itself stimulating MPS. Exercise training appears to increase basal muscle protein turnover, with differential responses of the myofibrillar and mitochondrial protein fractions to acute exercise in the trained state. Aging reduces the responses of myofibrillar protein and anabolic signaling to resistance exercise. There appear to be few, if any, differences in the response of young women and young men to acute exercise, although there are indications that, in older women, the responses may be blunted more than in older men.

  S. A Wood , M. J Prentice , K Smith and D. P. Hamilton

The relationship between heterocyte frequency, water temperature, nutrient concentrations and densities of Anabaena planktonica was examined in monomictic, eutrophic Lower Karori Reservoir (max. depth 21 m, area 0.034 km2), Wellington, New Zealand. Anabaena planktonica formed blooms and strongly dominated the phytoplankton assemblage during summer. The development of blooms of A. planktonica was associated with the set-up of stratification and increases in surface water temperature, with the peak of the bloom almost synchronous with maximum water temperature. The annual peak in heterocyte frequency preceded the bloom and occurred during a period of intensifying stratification. At this time, there were sustained low concentrations of dissolved inorganic nitrogen (DIN: nitrate-N + ammonium-N) and the lowest ratios of DIN to soluble reactive phosphorus (SRP), though ratios of total nitrogen to total phosphorus (TN:TP) were more variable. The apparent increase in nitrogen fixation capacity, based on increased heterocyte frequency, appears to be an important prerequisite to bloom formation for A. planktonica in the Lower Karori Reservoir. Monitoring heterocyte frequency may be a useful predictor for the occurrence of blooms of heterocytous cyanobacteria in eutrophic lakes due to the asynchronous nature of development of nitrogen limitation, heterocytes and vegetative cells.

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