Gene Expression Changes Associated with the Airway Wall Response to Injury

Understanding the way in which the airway heals in response to injury is fundamental to dissecting the mechanisms underlying airway disease pathology. As only limited data is available in relation to the in vivo characterisation of the molecular features of repair in the airway we sought to characterise the dynamic changes in gene expression that are associated with the early response to physical injury in the airway wall.We profiled gene expression changes in the airway wall using a large animal model of physical injury comprising bronchial brush biopsy in anaesthetised sheep. The experimental design featured sequential studies in the same animals over the course of a week and yielded data relating to the response at 6 hours, and 1, 3 and 7 days after injury. Notable features of the transcriptional response included the early and sustained preponderance of down-regulated genes associated with angiogenesis and immune cell activation, selection and differentiation. Later features of the response included the up-regulation of cell cycle genes at d1 and d3, and the latter pronounced up-regulation of extracellular matrix-related genes at d3 and d7.It is possible to follow the airway wall response to physical injury in the same animal over the course of time. Transcriptional changes featured coordinate expression of functionally related genes in a reproducible manner both within and between animals. This characterisation will provide a foundation against which to assess the perturbations that accompany airway disease pathologies of comparative relevance

Association of selected SNP with carcass and taste panel assessed meat quality traits in a commercial population of Aberdeen Angus-sired beef cattle

Abstract Background The purpose of this study was to evaluate the effects of eight single nucleotide polymorphisms (SNP), previously associated with meat and milk quality traits in cattle, in a population of 443 commercial Aberdeen Angus-cross beef cattle. The eight SNP, which were located within five genes: μ-calpain (CAPN1), calpastatin (CAST), leptin (LEP), growth hormone receptor (GHR) and acylCoA:diacylglycerol acyltransferase 1 (DGAT1), are included in various commercial tests for tenderness, fatness, carcass composition and milk yield/quality. Methods A total of 27 traits were examined, 19 relating to carcass quality, such as carcass weight and fatness, one mechanical measure of tenderness, and the remaining seven were sensory traits, such as flavour and tenderness, assessed by a taste panel. Results An SNP in the CAPN1 gene, CAPN316, was significantly associated with tenderness measured by both the tenderometer and the taste panel as well as the weight of the hindquarter, where animals inheriting the CC genotype had more tender meat and heavier hindquarters. An SNP in the leptin gene, UASMS2, significantly affected overall liking, where animals with the TT genotype were assigned higher scores by the panellists. The SNP in the GHR gene was significantly associated with odour, where animals inheriting the AA genotype produced steaks with an intense odour when compared with the other genotypes. Finally, the SNP in the DGAT1 gene was associated with sirloin weight after maturation and fat depth surrounding the sirloin, with animals inheriting the AA genotype having heavier sirloins and more fat. Conclusion The results of this study confirm some previously documented associations. Furthermore, novel associations have been identified which, following validation in other populations, could be incorporated into breeding programmes to improve meat quality.</p

Node and edge graph used to visualise co-ordinately expressed genes from the 1145 unique genes that were significantly differentially regulated (with greater than twofold change in expression) at least once during the course of the injury response.

<p>Separate clusters of co-ordinately expressed genes identified on the basis of application of the Markov clustering algorithm are differentially coloured. Functional annotation of the genes present in the four largest clusters shown (Clusters 001–004) indicated that there was a significant enrichment for biological process terms within each cluster. The mean fold-change of gene expression during the time-course of the injury response is also shown for each cluster.</p

The results of DAVID functional annotation clustering applied to the genes sharing a coordinate pattern of expression as identified using BioLayout Express 3D.

<p>In this instance the functional annotation is applied to the genes of cluster 002, and the results indicate that the gene lists are enriched for terms relating to the biological processes of extracellular matrix organisation, collagen fibril organisation, collagen metabolism, and skeletal system development. See the legend for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058930#pone-0058930-t002" target="_blank">table 2</a> for a description of the column headings.</p

STRING-9.0 analysis (<i>Homo sapiens</i> at: (http://string-db.org/); parameters: default setting) of proteins coded by genes significantly up-regulated more than two-fold at 6 h after physical injury to the airway wall that were enriched for terms relating to the biological processes of response to wounding, and inflammatory and defence responses.

<p>The figure summarizes the network of predicted associations for this group of proteins. The network nodes are proteins. The edges which represent the predicted functional associations are drawn in coloured lines. These lines represent the existence of the types of evidence used in predicting the associations. A green line indicates the presence of neighbourhood evidence, a blue line – co-ocurrence evidence, a purple line – experimental evidence, a light blue line – database evidence and a black line – co-expression evidence.</p

The results of DAVID functional annotation clustering applied to the genes sharing a coordinate pattern of expression as identified using BioLayout Express 3D.

<p>In this instance the functional annotation is applied to the genes of cluster 004, and the results indicate that the gene lists are enriched for terms relating to the biological processes of ribosome and ribonucleoprotein biogenesis. See the legend for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058930#pone-0058930-t002" target="_blank">table 2</a> for a description of the column headings.</p