From research to farm : ex ante evaluation of strategic deworming in pig finishing

This paper upgrades generic and partial information from parasitological research for farm-specific decision support, using two methods from managerial sciences: partial budgeting and frontier analysis. The analysis focuses on strategic deworming in pig finishing and assesses both effects on economic performance and nutrient efficiency. The application of partial budgeting and frontier analysis is based on a production-theoretical system analysis which is necessary to integrate parasitological research results to assess aggregate economic and environmental impacts. Results show that both statistically significant and insignificant parasitological research results have to be taken into account. Partial budgeting and frontier analysis appear to be complementary methods: partial budgeting yields more discriminatory and communicative results, while frontier methods provide additional diagnostics through exploring optimization possibilities and economic-environmental trade-offs. Strategic deworming results in a win-win effect on economic and environmental performances. Gross margin increases with 3 to 12 € per average present finisher per year, depending on the cyclic pig price conditions. The impact on the nutrient balance ranges from +0.2 to –0.5 kg nitrogen per average present finisher per year. The observed efficiency improvements are mainly technical and further economic and environmental optimizations can be achieved through input re-allocation. A user-friendly spreadsheet is provided to translate the generic experimental information to farm-specific conditions

Birth weight threshold for identifying piglets at-risk for preweaning mortality

Citation: Feldpausch, J. A., Jourquin, J., Bergstrom, J. R., Bokenkroger, C. D., Nelssen, J. L., Ritter, M. J., . . . Gonzalez, J. M. (2016). Birth weight threshold for identifying piglets at-risk for preweaning mortality. Journal of Animal Science, 94, 34-34. doi:10.2527/msasas2016-074The association of piglet birth weight (BtW) with early-life mortality risk is strongly supported by research of numerous studies reporting decreased preweaning piglet mortality as individual piglet BtW increases. The purpose of the present analysis was to identify a BtW threshold associated with reduced odds of preweaning survival. Observations from 2 studies with a total of 4068 piglets originating from 394 litters on 4 different commercial farms (3 European, 1 U.S.) were compiled for meta-analysis. Overall preweaning mortality rate across all farms was 12.2%. Data used in the analysis was weight of piglets within 24 h of birth and their corresponding survival outcome (dead or live) by weaning at 3 to 4 wk of age. A mixed effects logistic regression model was fit to estimate the probability of preweaning mortality based on BtW. A random effect of study was included to account for overall differences in mortality between the 2 studies. A piecewise linear predictor was selected to best represent the drastic decrease in preweaning mortality found as BtW increased in the range of 0.5 to 1.0 kg and the less extreme change in preweaning mortality observed for changes in weight above 1.0 kg. The model change point was determined by comparing model fit for BtW ranging from 0.5 kg to 2.0 kg based on maximizing the likelihood. A linear predictor equation was also generated to estimate the associated preweaning mortality probability associated with every 50 g of piglet BtW. Results indicated a 1.11 kg BtW change point in the log odds of piglet preweaning mortality, thus, implicating that every incremental change in BtW below 1.11 kg has a greater impact on mortality risk than incremental changes in BtW above 1.11 kg. Among the farms in this analysis, 14.9% of all piglets had BtW < 1.11 kg. These findings imply that interventions targeted at increasing the BtW of piglets having BtW less than 1.11 kg have tremendous potential to improve piglet preweaning survivability. A large percentage of the neonatal pig population falls below this weight threshold, and postnatal management strategies to decrease neonatal mortality should be directed toward these at-risk piglets

Linking Changes in Epithelial Morphogenesis to Cancer Mutations Using Computational Modeling

Most tumors arise from epithelial tissues, such as mammary glands and lobules, and their initiation is associated with the disruption of a finely defined epithelial architecture. Progression from intraductal to invasive tumors is related to genetic mutations that occur at a subcellular level but manifest themselves as functional and morphological changes at the cellular and tissue scales, respectively. Elevated proliferation and loss of epithelial polarization are the two most noticeable changes in cell phenotypes during this process. As a result, many three-dimensional cultures of tumorigenic clones show highly aberrant morphologies when compared to regular epithelial monolayers enclosing the hollow lumen (acini). In order to shed light on phenotypic changes associated with tumor cells, we applied the bio-mechanical IBCell model of normal epithelial morphogenesis quantitatively matched to data acquired from the non-tumorigenic human mammary cell line, MCF10A. We then used a high-throughput simulation study to reveal how modifications in model parameters influence changes in the simulated architecture. Three parameters have been considered in our study, which define cell sensitivity to proliferative, apoptotic and cell-ECM adhesive cues. By mapping experimental morphologies of four MCF10A-derived cell lines carrying different oncogenic mutations onto the model parameter space, we identified changes in cellular processes potentially underlying structural modifications of these mutants. As a case study, we focused on MCF10A cells expressing an oncogenic mutant HER2-YVMA to quantitatively assess changes in cell doubling time, cell apoptotic rate, and cell sensitivity to ECM accumulation when compared to the parental non-tumorigenic cell line. By mapping in vitro mutant morphologies onto in silico ones we have generated a means of linking the morphological and molecular scales via computational modeling. Thus, IBCell in combination with 3D acini cultures can form a computational/experimental platform for suggesting the relationship between the histopathology of neoplastic lesions and their underlying molecular defects

Tissue inhibitor of metalloproteinases-1 protects human neurons from staurosporine and HIV-1-induced apoptosis: mechanisms and relevance to HIV-1-associated dementia

HIV-1-associated dementia (HAD)-relevant proinflammatory cytokines robustly induce astrocyte tissue inhibitor of metalloproteinases-1 (TIMP-1). As TIMP-1 displays pleotropic functions, we hypothesized that TIMP-1 expression may serve as a neuroprotective response of astrocytes. Previously, we reported that chronically activated astrocytes fail to maintain elevated TIMP-1 expression, and TIMP-1 levels are lower in the brain of HAD patients; a phenomenon that may contribute to central nervous system pathogenesis. Further, the role of TIMP-1 as a neurotrophic factor is incompletely understood. In this study, we report that staurosporine (STS) and HIV-1ADA virus, both led to induction of apoptosis in cultured primary human neurons. Interestingly, cotreatment with TIMP-1 protects neurons from apoptosis and reverses neuronal morphological changes induced by these toxins. Further, the anti-apoptotic effect was not observed with TIMP-2 or -3, but was retained in a mutant of the N-terminal TIMP-1 protein with threonine-2 mutated to glycine (T2G) that is deficient in matrix metalloproteinase (MMP)-1, -2 and -3 inhibitory activity. Therefore, the mechanism is specific to TIMP-1 and partially independent of MMP-inhibition. Additionally, TIMP-1 modulates the Bcl-2 family of proteins and inhibits opening of mitochondrial permeability transition pores induced by HIV-1 or STS. Together, these findings describe a novel function, mechanism and direct role of TIMP-1 in neuroprotection, suggesting its therapeutic potential in HAD and possibly in other neurodegenerative diseases

Sub region-specific modulation of synchronous neuronal burst firing after a kainic acid insult in organotypic hippocampal cultures

<p>Abstract</p> <p>Background</p> <p>Excitotoxicity occurs in a number of pathogenic states including stroke and epilepsy. The adaptations of neuronal circuits in response to such insults may be expected to play an underlying role in pathogenesis. Synchronous neuronal firing can be induced in isolated hippocampal slices and involves all regions of this structure, thereby providing a measure of circuit activity. The effect of an excitotoxic insult (kainic acid, KA) on Mg²⁺-free-induced synchronized neuronal firing was tested in organotypic hippocampal culture by measuring extracellular field activity in CA1 and CA3.</p> <p>Results</p> <p>Within 24 hrs of the insult regional specific changes in neuronal firing patterns were evident as: (i) a dramatic <it>reduction </it>in the ability of CA3 to generate firing; and (ii) a contrasting <it>increase </it>in the frequency and duration of synchronized neuronal firing events in CA1. Two distinct processes underlie the increased propensity of CA1 to generate synchronized burst firing; a lack of ability of the CA3 region to 'pace' CA1 resulting in an increased frequency of synchronized events; and a change in the 'intrinsic' properties limited to the CA1 region, which is responsible for increased event duration. Neuronal quantification using NeuN immunoflurescent staining and stereological confocal microscopy revealed no significant cell loss in hippocampal sub regions, suggesting that changes in the properties of neurons within this region were responsible for the KA-mediated excitability changes.</p> <p>Conclusion</p> <p>These results provide novel insight into adaptation of hippocampal circuits following excitotoxic injury. KA-mediated disruption of the interplay between CA3 and CA1 clearly increases the propensity to synchronized firing in CA1.</p

Resuscitation of Newborn Piglets. Short-Term Influence of FiO2 on Matrix Metalloproteinases, Caspase-3 and BDNF

Perinatal hypoxia-ischemia is a major cause of mortality and cerebral morbidity, and using oxygen during newborn resuscitation may further harm the brain. The aim was to examine how supplementary oxygen used for newborn resuscitation would influence early brain tissue injury, cell death and repair processes and the regulation of genes related to apoptosis, neurodegeneration and neuroprotection.Anesthetized newborn piglets were subjected to global hypoxia and then randomly assigned to resuscitation with 21%, 40% or 100% O(2) for 30 min and followed for 9 h. An additional group received 100% O(2) for 30 min without preceding hypoxia. The left hemisphere was used for histopathology and immunohistochemistry and the right hemisphere was used for in situ zymography in the corpus striatum; gene expression and the activity of various relevant biofactors were measured in the frontal cortex. There was an increase in the net matrix metalloproteinase gelatinolytic activity in the corpus striatum from piglets resuscitated with 100% oxygen vs. 21%. Hematoxylin-eosin (HE) staining revealed no significant changes. Nine hours after oxygen-assisted resuscitation, caspase-3 expression and activity was increased by 30-40% in the 100% O(2) group (n = 9/10) vs. the 21% O(2) group (n = 10; p<0.04), whereas brain-derived neurotrophic factor (BDNF) activity was decreased by 65% p<0.03.The use of 100% oxygen for resuscitation resulted in increased potentially harmful proteolytic activities and attenuated BDNF activity when compared with 21%. Although there were no significant changes in short term cell loss, hyperoxia seems to cause an early imbalance between neuroprotective and neurotoxic mechanisms that might compromise the final pathological outcome