Investigating How Genetic Merit and Country of Origin Impact the Profitability of Grass-Based Sheep Production Systems.

The objective of this study was to simulate and assess the profitability of sheep production systems that varied in maternal genetic merit (high or low) and country of origin (New Zealand (NZ) or Ireland), using the Teagasc Lamb Production Model (TLPM). A production system study performed at Teagasc Athenry, Co. Galway, Ireland, from 2016 to 2019, inclusive, provided key animal performance input parameters, which were compared across three scenarios: high maternal genetic merit NZ (NZ), high maternal genetic merit Irish (High Irish) and low maternal genetic merit Irish (Low Irish). Prior to the beginning of the study ewes and rams were imported from New Zealand to Ireland in order to compare animals within the same management system. Ewes were selected based on the respective national maternal genetic indexes; i.e., either the New Zealand Maternal Worth (NZ group) or the €uro-star Replacement index (Irish groups). The TLPM was designed to simulate the impact of changes in physical and technical outputs (such as number of lambs, drafting rates and replacement rates) on a range of economic parameters including variable costs, fixed costs, gross margin and net profit. Results showed that total farm costs (variable and fixed) were similar across the three scenarios, driven by the similar number of ewes in each scenario. The number of lambs produced and the cost of production per lamb was 14.05 lambs per hectare for the NZ scenario at a cost of EUR 82.35 per lamb, 11.40 lambs per hectare for the High Irish scenario at a cost of EUR 101.42 per lamb and 11.00 lambs per hectare for the Low Irish scenario at a cost of EUR 105.72 per lamb. The net profit of the three scenarios was EUR 514, EUR 299, and EUR 258 per hectare, for the NZ, High Irish and Low Irish scenarios, respectively. Overall, the NZ scenario had a lower cost of production in comparison to either Irish group, while the High Irish scenario had a 14% greater net profit than the Low Irish scenario, equating to an additional EUR 41 per hectare net profit. Output from this simulation model reiterates the importance, for overall farm profitability, of maximising the number of lambs weaned per hectare, particularly through maximising income and diluting the total farm costs. To conclude, the use of high-maternal-genetic-merit animals, regardless of their country of origin impacts farm profitability.

Validation of maternal and terminal sheep breeding objectives using Irish field data.

Genetic evaluations provide producers with a tool to aid in breeding decisions and highlight the increase in performance achievable at the farm level through genetic gain. Despite this, large-scale validation of sheep breeding objectives using field data is lacking in the scientific literature. The objective of the present study was to evaluate the phenotypic differences for a range of economically important traits for animals divergent in genetic merit for the Irish national maternal and terminal sheep breeding objectives. A dataset of 17,356 crossbred ewes and 54,322 progeny differing in their maternal and terminal breeding index recorded in 139 commercial flocks was available. The association of the maternal index of the ewe or terminal index of the ram and a range of phenotypic performance traits, including lambing, lamb performance, ewe performance, and health traits, were undertaken. Ewes excelling on the maternal index had higher litter sizes and produced progeny with greater perinatal lamb survival, heavier live weights from birth to postweaning and reduced days to slaughter (P < 0.05). Ewe maternal index had no quantifiable impact on lambing ease, carcass conformation, or fat, the health status of the ewe or lamb, ewe barren rate, or ewe live weight. Lambs born to rams of superior terminal index produced heavier lambs from preweaning onwards, with a reduced day to slaughter (P < 0.05). Lambing traits, lamb health, and carcass characteristics of the progeny did not differ between sires stratified as low or high on the terminal index (P > 0.05). Results from this study highlight that selecting either ewes or rams of superior maternal or terminal attributes will result in an improvement on pertinent performance traits of the national sheep flock, resulting in greater flock productivity and profitability.

Description, evaluation, and validation of the Teagasc Pig Production Model1.

The Teagasc Pig Production Model (TPPM), a stochastic simulation model of a farrow-to-finish pig farm, was developed to investigate effects of changes in production systems on farm profitability. The model simulates, on a weekly basis, the annual production of a farm. Biological [e.g., herd size, number of litters/sow/year, and mortality rates (%)], physical (e.g., infrastructure), and technical (e.g., feeding practices) variables and their associated costs are included as components of the model. These inputs are used to calculate physical (e.g., feed usage and number of pigs slaughtered) and financial (e.g., annual cash flow, profit and loss account, and balance sheet) outputs. The model was validated using the Delphi method and by comparing the TPPM outputs to data recorded on 20 Irish pig farms through the Teagasc e-Profit monitor system and with complete receipts for the year 2016. Results showed that the TPPM closely simulates physical and financial performance of pig farms indicating that the TPPM can be used with confidence to study pig production systems under Irish conditions. Model applicability was demonstrated by investigating the impact of 2 changes in technical performance: 1) building of extra accommodation to increase body weight (BW) at sale by 15 kg (EXTRA ROOM) and 2) a change in feeding practices by providing finisher feed from 28 kg of BW (EARLY FINISHER) compared with over 38 kg of BW. In both scenarios, the same biological parameters were used. Mortality rates, feed ingredients costs, and price per kg of meat produced were included as stochastic variables with the input distributions derived based on historical data simulated using Monte Carlo sampling using the Microsoft Excel add-in @Risk. Annual mean net profit was €198,101 (90% confidence interval [CI]: €119,606-€275,539) for the TPPM base farm, €337,078 (90% CI: €246,320-€426,809) for the EXTRA ROOM, and €225,598 (90% CI: €146,685-€303,590) for the EARLY FINISHER. EXTRA ROOM was associated with higher costs and required higher income to cover the additional costs. The 90% CI of the EARLY FINISHER was similar to the TPPM base farm while the EXTRA ROOM scenario resulted in a wider confidence interval, suggesting that a change in feeding practices could be a better option for farmers looking to improve profit with minimum investment. Thus, the TPPM could be used to facilitate decision making in farrow-to-finish pig farms.

Tumor necrosis factor alpha blockade restores growth hormone signaling in murine colitis.

BACKGROUND & AIMS: Cytokines including tumor necrosis factor alpha (TNFalpha) may create a state of growth hormone (GH) resistance in Crohn's disease. Anabolic effects of GH are mediated via phosphorylation of the signal transducer and activator of transcription (STAT)5b transcription factor. Although GH resistance in other settings has been linked to a defect in janus kinase-STAT signaling, the molecular basis for GH resistance in colitis was not known. We hypothesized that the GH-induced phosphorylation of STAT5b would be impaired in colitis, and that TNFalpha blockade would restore GH signaling. METHODS: Growth, body composition, and molecular regulators of GH signaling were determined in interleukin-10 null mice with chronic colitis and wild-type controls, +/- treatment with an anti-TNFalpha antibody. RESULTS: Interleukin-10 null mice exhibited significant alterations in growth, body composition, and feed efficiency. Liver insulin-like growth factor 1 expression was reduced in colitic mice. This was associated with down-regulation of GH receptor (GHR) expression and impaired GH-dependent STAT5b activation. Down-regulation of GHR expression was associated with reduced nuclear abundance and DNA binding of the GHR gene-promoter transactivator, Sp3. TNFalpha down-regulated GHR abundance and prevented GH-induced tyrosine phosphorylation of STAT5 in rat hepatocytes in culture. TNFalpha neutralization up-regulated liver GHR abundance and restored GH activation of STAT5 and serum insulin-like growth factor 1 levels in colitic mice; this preceded improvements in weight gain and disease activity. CONCLUSIONS: GH resistance in experimental colitis is caused by down-regulation of GHR expression, thereby reducing GH-dependent STAT5 activation. TNFalpha blockade restores liver GH signaling and improves anabolic metabolism in this setting.

Tumor necrosis factor alpha-dependent up-regulation of Lrh-1 and Mrp3(Abcc3) reduces liver injury in obstructive cholestasis.

Mrp3(Abcc3) is markedly induced following bile duct ligation (BDL) in the rat and in some human cholestatic liver diseases and is believed to ameliorate liver injury in this setting. Recently, the orphan nuclear receptor fetoprotein transcription factor/cholesterol-7alpha-hydroxylase promoter factor (CPF/FTF/Lrh-1) has been shown to activate Mrp3 expression. However, whether inflammatory cytokines or elevated bile acid levels increased Lrh-1/Mrp3 expression in obstructive cholestasis was not known. We hypothesized that induction of Mrp3 would be associated with Lrh-1 up-regulation and would require intact cytokine signaling. Male tumor necrosis factor (Tnf) receptor I (Tnfr-/-) mice and C57BLJ wild type (WT) controls were subjected to sham surgery or bile duct ligation. HepG2 cells were treated with bile acids or cytokines. Immunoblot assay and real time reverse transcriptase-PCR were used to determine expression of MRP3/Mrp3, CPF/Lrh-1, Mrp2, and Bsep. CPF/Lrh-1 DNA binding to the MRP3/Mrp3 promoter was assessed using electrophoretic mobility shift assay, and promoter activity was determined by luciferase assay. Total bile acids and lactate dehydrogenase were measured using colorimetric assays, and cytokine abundance was determined by enzyme-linked immunosorbent assay. Lrh-1 and Mrp3 were significantly induced after BDL in WT but not Tnfr-/- mice. This was associated with more severe hepatocellular necrosis in Tnfr-/- mice. Lrh-1 binding to the Mrp3 promoter increased after BDL in WT but not in Tnfr-/- mice. Tnfalpha treatment of HepG2 cells also up-regulated CPF and MRP3, increased CPF binding to the MRP3 promoter, and up-regulated MRP3 promoter activity. These results indicate that induction of Mrp3 after BDL is due to Tnfalpha-dependent up-regulation of Lrh-1. They provide strong evidence that induction of Mrp3 plays a significant role in hepatocyte protection during obstructive cholestasis.

Organ-specific alterations in RAR alpha:RXR alpha abundance regulate rat Mrp2 (Abcc2) expression in obstructive cholestasis.

BACKGROUND & AIMS: Obstructive cholestasis is associated with adaptive changes in expression of hepatocyte transport proteins. These include a significant reduction in hepatic expression of Mrp2 (Abcc2), the principal canalicular multispecific organic anion transporter. Renal Mrp2 expression is preserved under these conditions. We have recently reported that the rat Mrp2 promoter is activated by RAR alpha:RXR alpha, and that interleukin 1 beta (IL-1 beta) repressed promoter activity via this element. We hypothesized that cytokines, which are up-regulated in obstructive cholestasis, would reduce nuclear RAR alpha:RXR alpha levels, and that this would be associated with suppression of hepatic Mrp2 expression. METHODS: Male Sprague-Dawley rats were subjected to bile duct ligation (BDL) or sham surgery, and liver and kidney RNA and protein were isolated. Primary rat hepatocytes were treated with bile acids, retinoids, or cytokines, and RNA and protein were isolated. Mrp2 and RAR alpha:RXR alpha protein abundance and activity were assessed by using electrophoretic mobility shift assays (EMSA) and immunoblots. IL-1 beta abundance was determined by enzyme-linked immunosorbent assay. RAR alpha, RXR alpha, and Mrp2 RNA levels were determined by using ribonuclease protection assays (RPA). RESULTS: Mrp2 down-regulation and IL-1 beta up-regulation were observed in liver after BDL. This was temporally associated with down-regulation of liver RAR alpha:RXR alpha nuclear protein levels and binding to the Mrp2 promoter cis element. Renal RAR alpha:RXR alpha and Mrp2 expression were preserved under these conditions. IL-1 beta treatment of primary hepatocytes reduced Mrp2 and RXR alpha expression. CONCLUSIONS: Organ-specific regulation of Mrp2 expression in obstructive cholestasis is associated with cytokine-dependent alterations in RAR alpha:RXR alpha nuclear receptors. Preservation of renal Mrp2 expression may permit urinary excretion of toxic organic anions and xenobiotics under conditions in which biliary excretion is impaired.

Mechanisms of hepatic transport of drugs: implications for cholestatic drug reactions.

Hepatocellular and canalicular transport proteins are major determinants of the hepatic uptake and biliary excretion of xenobiotics and their metabolites. Recent advances in molecular cloning have resulted in the characterization of many of these transport systems. These advances have enabled the identification of a number of drugs that are substrates for the transporters, and it has facilitated studies of mechanisms of drug-induced cholestasis. This review summarizes the normal function of hepatobiliary transporters and their alteration by drugs or other foreign compounds. Although most of these investigations have been performed in animal models of drug-induced cholestasis, the application to human forms of drug-induced cholestasis is also discussed when possible. One important finding is that genetic polymorphisms can result in changes in drug transporter expression and function that could increase susceptibility to cholestatic drug reactions.