Measuring the combinatorial expression of solute transporters and metalloproteinases transcripts in colorectal cancer

Published: 19 August 2009Background: It was hypothesised that colorectal cancer (CRC) could be diagnosed in biopsies by measuring the combined expression of a small set of well known genes. Genes were chosen based on their role in either the breakdown of the extracellular matrix or with changes in cellular metabolism both of which are associated with CRC progression. Findings: Gene expression data derived from quantitative real-time PCR for the solute transporter carriers (SLCs) and the invasion-mediating matrix metalloproteinases (MMPs) were examined using a Linear Descriminant Analysis (LDA). The combination of MMP-7 and SLC5A8 was found to be the most predictive of CRC. Conclusion: A combinatorial analysis technique is an effective method for both furthering our understanding on the molecular basis of some aspects of CRC, as well as for leveraging well defined cancer-related gene sets to identify cancer. In this instance, the combination of MMP-7 and SLC5A8 were optimal for identifying CRC.Caroline A. Kerr, Robert Dunne, Barney M. Hines, Michelle Zucker, Leah Cosgrove, Andrew Ruszkiewicz, Trevor Lockett and Richard Hea

Mineral nutrition in penaeid shrimp

This review summarises the current knowledge of mineral nutrition for penaeid shrimp. It investigates how the aquatic environment and the lifecycle of shrimp affect requirements and the role that minerals play in shrimp health. Methods of supplying minerals via either water or to feed, and novel ways of supplementing minerals within feed, are discussed. The requirements for individual minerals are summarised with recommendations for minimum levels of dietary inclusion for semi-intensive and intensive commercial shrimp culture presented where data permits. Estimates of dietary requirement remain broad for most minerals for the main shrimp production species (Penaeus vannamei, Penaeus monodon and Penaeus japonicus), with some essential minerals remaining unstudied (Table 2 in Section 5.10). Mineral nutrition will become more important as intensification and diversification of production systems provide new challenges to shrimp aquaculture.</p

In vitro anti-thrombotic activity of extracts from blacklip abalone (Haliotis rubra) processing waste

Waste generated from the processing of marine organisms for food represents an underutilized resource that has the potential to provide bioactive molecules with pharmaceutical applications. Some of these molecules have known anti-thrombotic and anti-coagulant activities and are being investigated as alternatives to common anti-thrombotic drugs, like heparin and warfarin that have serious side effects. In the current study, extracts prepared from blacklip abalone (Haliotis rubra) processing waste, using food grade enzymes papain and bromelain, were found to contain sulphated polysaccharide with anti-thrombotic activity. Extracts were found to be enriched with sulphated polysaccharides and assessed for anti-thrombotic activity in vitro through heparin cofactor-II (HCII)-mediated inhibition of thrombin. More than 60% thrombin inhibition was observed in response to 100 &mu;g/mL sulphated polysaccharides. Anti-thrombotic potential was further assessed as anti-coagulant activity in plasma and blood, using prothrombin time (PT), activated partial thromboplastin time (aPTT), and thromboelastography (TEG). All abalone extracts had significant activity compared with saline control. Anion exchange chromatography was used to separate extracts into fractions with enhanced anti-thrombotic activity, improving HCII-mediated thrombin inhibition, PT and aPTT almost 2-fold. Overall this study identifies an alternative source of anti-thrombotic molecules that can be easily processed offering alternatives to current anti-thrombotic agents like heparin

Insecticidal activities of histone deacetylase inhibitors against a dipteran parasite of sheep, Lucilia cuprina

Histone deacetylase inhibitors (HDACi) are being investigated for the control of various human parasites. Here we investigate their potential as insecticides for the control of a major ectoparasite of sheep, the Australian sheep blowfly, Lucilia cuprina. We assessed the ability of HDACi from various chemical classes to inhibit the development of blowfly larvae in vitro, and to inhibit HDAC activity in nuclear protein extracts prepared from blowfly eggs. The HDACi prodrug romidepsin, a cyclic depsipeptide that forms a thiolate, was the most potent inhibitor of larval growth, with equivalent or greater potency than three commercial blowfly insecticides. Other HDACi with potent activity were hydroxamic acids (trichostatin, CUDC 907, AR-42), a thioester (KD5170), a disulphide (Psammaplin A), and a cyclic tetrapeptide bearing a ketone (apicidin). On the other hand, no insecticidal activity was observed for certain other hydroxamic acids, fatty acids, and the sesquiterpene lactone parthenolide. The structural diversity of the 31 hydroxamic acids examined here revealed some structural requirements for insecticidal activity; for example, among compounds with flexible linear zinc binding extensions, greater potency was observed in the presence of branched capping groups that likely make multiple interactions with the blowfly HDAC enzymes. The insecticidal activity correlated with inhibition of HDAC activity in blowfly nuclear protein extracts, indicating that the toxicity was most likely due to inhibition of HDAC enzymes in the blowfly larvae. The inhibitor potencies against blowfly larvae are different from inhibition of human HDACs, suggesting some selectivity for human over blowfly HDACs, and a potential for developing compounds with the inverse selectivity. In summary, these novel findings support blowfly HDAC enzymes as new targets for blowfly control, and point to development of HDAC inhibitors as a promising new class of insecticides. (C) 2017 The Authors. Published by Elsevier Ltd on behalf of Australian Society for Parasitology

Genomic homeostasis is dysregulated in favour of apoptosis in the colonic epithelium of the azoxymethane treated rat

Background The acute response to genotoxic carcinogens in rats is an important model for researching cancer initiation events. In this report we define the normal rat colonic epithelium by describing transcriptional events along the anterior-posterior axis and then investigate the acute effects of azoxymethane (AOM) on gene expression, with a particular emphasis on pathways associated with the maintenance of genomic integrity in the proximal and distal compartments using whole genome expression microarrays. Results There are large transcriptional changes that occur in epithelial gene expression along the anterior-posterior axis of the normal healthy rat colon. AOM administration superimposes substantial changes on these basal gene expression patterns in both the distal and proximal rat colonic epithelium. In particular, the pathways associated with cell cycle and DNA damage and repair processes appear to be disrupted in favour of apoptosis. Conclusions The healthy rats\u27 colon exhibits extensive gene expression changes between its proximal and distal ends. The most common changes are associated with metabolism, but more subtle expression changes in genes involved in genomic homeostasis are also evident. These latter changes presumably protect and maintain a healthy colonic epithelium against incidental dietary and environmental insults. AOM induces substantial changes in gene expression, resulting in an early switch in the cell cycle process, involving p53 signalling, towards cell cycle arrest leading to the more effective process of apoptosis to counteract this genotoxic insult

The marine microbial biomass, Novacq™, a useful feed additive for postlarvae and juvenile Litopenaeus vannamei

Although Litopenaeus vannamei is the most produced and researched shrimp species worldwide, there are no published studies evaluating the use of the microbial biomass, Novacq™, in L. vannamei feeds. This study investigated the effects of supplementing Novacq™ at 100 g kg in practical and commercial feeds in postlarvae 12 (PL 12) and juvenile white leg shrimp. Three experiments were carried out. In Experiment 1, PL12 were fed for 21 days with a Control, Novacq™ or Commercial feed. The Novacq feed was equal in PL12 performance to the Commercial diet and superior to the Control (final individual weight = 0.169, 0.167 and 0.087 g; percentage weight gain = 8014, 7956 and 4091% for Novacq™, Commercial and Control feeds, respectively). No statistical differences in survival, coefficient of variation and daily feed offered were observed across dietary treatments. In Experiments 2 and 3 the performance of juvenile shrimp fed practical and Commercial feeds supplemented with Novacq™ for 42 days, respectively. In Experiment 2, Novacq™ feed outperformed the Control feed by improving survival (89 vs. 51%), final individual weight (7.4 vs. 3.5 g), weight gain (7.1 vs. 3.2 g), and percentage weight gain (1997 vs. 898%). In Experiment 3 supplementing Novacq™ into the Commercial feed improved performance (final individual weight = 6.4 vs. 5.5 g, weight gain = 6.0 vs. 5.1 g, and percentage weight gain = 1712 vs 1443%) and reduced the coefficient of variation (19 vs 53%). Shrimp fed feeds containing Novacq™ also displayed numerically reduced daily feed offered and estimated feed conversion ratio values in comparison to the other dietary treatments. Whole-body composition was similar across dietary treatments. In summary, supplementation of Novacq™ in practical and Commercial feeds improved growth and efficiency of PL12 and juvenile shrimp suggesting its validity as a useful feed additive in the nutrition of white leg shrimp

Corporate strategy formulation and taxation: evidence from UK Firms

This paper considers the relationship between corporate strategy formulation and taxation. Drawing on prior literature we briefly review the important influence that international taxation has on an array of corporate strategy decisions. We then consider issues in strategy formulation and taxation planning in order to develop an understanding of when and how taxation factors impinge on strategic decision-making. We draw out the apparent paradox between the nature of strategic decision-making and financial decision-making and look for areas of reconciliation. In order to shed light on some of these issues we present findings from the qualitative analysis of a set of personal interviews undertaken with senior tax practitioners in seven UK-based multinational enterprises and then consider quantitative responses from the tax practitioners working in 145 UK firms

Measuring the combinatorial expression of solute transporters and metalloproteinases transcripts in colorectal cancer

Conclusion: A combinatorial analysis technique is an effective method for both furthering our understanding on the molecular basis of some aspects of CRC, as well as for leveraging well defined cancer-related gene sets to identify cancer. In this instance, the combination of MMP-7 and SLC5A8 were optimal for identifying CRC.