Towards the quantitative characterisation of piglets' robustness to weaning: a modelling approach.

Weaning is a critical transition phase in swine production in which piglets must cope with different stressors that may affect their health. During this period, the prophylactic use of antibiotics is still frequent to limit piglet morbidity, which raises both economic and public health concerns such as the appearance of antimicrobial-resistant microbes. With the interest of developing tools for assisting health and management decisions around weaning, it is key to provide robustness indexes that inform on the animals' capacity to endure the challenges associated with weaning. This work aimed at developing a modelling approach for facilitating the quantification of piglet resilience to weaning. A total of 325 Large White pigs weaned at 28 days of age were monitored and further housed and fed conventionally during the post-weaning period without antibiotic administration. Body weight and diarrhoea scores were recorded before and after weaning, and blood was sampled at weaning and 1 week later for collecting haematological data. A dynamic model was constructed based on the Gompertz-Makeham law to describe live weight trajectories during the first 75 days after weaning, following the rationale that the animal response is partitioned in two time windows (a perturbation and a recovery window). Model calibration was performed for each animal. Our results show that the transition time between the two time windows, as well as the weight trajectories are characteristic for each individual. The model captured the weight dynamics of animals at different degrees of perturbation, with an average coefficient of determination of 0.99, and a concordance correlation coefficient of 0.99. The utility of the model is that it provides biologically meaningful parameters that inform on the amplitude and length of perturbation, and the rate of animal recovery. Our rationale is that the dynamics of weight inform on the capability of the animal to cope with the weaning disturbance. Indeed, there were significant correlations between model parameters and individual diarrhoea scores and haematological traits. Overall, the parameters of our model can be useful for constructing weaning robustness indexes by using exclusively the growth curves. We foresee that this modelling approach will provide a step forward in the quantitative characterisation of robustness.

Review: divergent selection for residual feed intake in the growing pig.

This review summarizes the results from the INRA (Institut National de la Recherche Agronomique) divergent selection experiment on residual feed intake (RFI) in growing Large White pigs during nine generations of selection. It discusses the remaining challenges and perspectives for the improvement of feed efficiency in growing pigs. The impacts on growing pigs raised under standard conditions and in alternative situations such as heat stress, inflammatory challenges or lactation have been studied. After nine generations of selection, the divergent selection for RFI led to highly significant (P<0.001) line differences for RFI (-165 g/day in the low RFI (LRFI) line compared with high RFI line) and daily feed intake (-270 g/day). Low responses were observed on growth rate (-12.8 g/day, P<0.05) and body composition (+0.9 mm backfat thickness, P=0.57; -2.64% lean meat content, P<0.001) with a marked response on feed conversion ratio (-0.32 kg feed/kg gain, P<0.001). Reduced ultimate pH and increased lightness of the meat (P<0.001) were observed in LRFI pigs with minor impact on the sensory quality of the meat. These changes in meat quality were associated with changes of the muscular energy metabolism. Reduced maintenance energy requirements (-10% after five generations of selection) and activity (-21% of time standing after six generations of selection) of LRFI pigs greatly contributed to the gain in energy efficiency. However, the impact of selection for RFI on the protein metabolism of the pig remains unclear. Digestibility of energy and nutrients was not affected by selection, neither for pigs fed conventional diets nor for pigs fed high-fibre diets. A significant improvement of digestive efficiency could likely be achieved by selecting pigs on fibre diets. No convincing genetic or blood biomarker has been identified for explaining the differences in RFI, suggesting that pigs have various ways to achieve an efficient use of feed. No deleterious impact of the selection on the sow reproduction performance was observed. The resource allocation theory states that low RFI may reduce the ability to cope with stressors, via the reduction of a buffer compartment dedicated to responses to stress. None of the experiments focussed on the response of pigs to stress or challenges could confirm this theory. Understanding the relationships between RFI and responses to stress and energy demanding processes, as such immunity and lactation, remains a major challenge for a better understanding of the underlying biological mechanisms of the trait and to reconcile the experimental results with the resource allocation theory.

FGF1 C-terminal domain and phosphorylation regulate intracrine FGF1 signaling for its neurotrophic and anti-apoptotic activities.

Fibroblast growth factor 1 (FGF1) is a prototypic member of the FGFs family overexpressed in various tumors. Contrarily to most FGFs, FGF1 lacks a secretion peptide signal and acts mainly in an intracellular and nuclear manner. Intracellular FGF1 induces cell proliferation, differentiation and survival. We previously showed that intracellular FGF1 induces neuronal differentiation and inhibits both p53- and serum-free-medium-induced apoptosis in PC12 cells. FGF1 nuclear localization is required for these intracellular activities, suggesting that FGF1 regulates p53-dependent apoptosis and neuronal differentiation by new nuclear pathways. To better characterize intracellular FGF1 pathways, we studied the effect of three mutations localized in the C-terminal domain of FGF1 (i.e., FGF1(K132E), FGF1(S130A) and FGF1(S130D)) on FGF1 neurotrophic and anti-apoptotic activities in PC12 cells. The change of the serine 130 to alanine precludes FGF1 phosphorylation, while its mutation to aspartic acid mimics phosphorylation. These FGF1 mutants kept both a nuclear and cytosolic localization in PC12 cells. Our study highlights for the first time the role of FGF1 phosphorylation and the implication of FGF1 C-terminal domain on its intracellular activities. Indeed, we show that the K132E mutation inhibits both the neurotrophic and anti-apoptotic activities of FGF1, suggesting a regulatory activity for FGF1 C terminus. Furthermore, we observed that both FGF1(S130A) and FGF1(S130D) mutant forms induced PC12 cells neuronal differentiation. Therefore, FGF1 phosphorylation does not regulate FGF1-induced differentiation of PC12 cells. Then, we showed that only FGF1(S130A) protects PC12 cells against p53-dependent apoptosis, thus phosphorylation appears to inhibit FGF1 anti-apoptotic activity in PC12 cells. Altogether, our results show that phosphorylation does not regulate FGF1 neurotrophic activity but inhibits its anti-apoptotic activity after p53-dependent apoptosis induction, giving new insight into the poorly described FGF1 intracrine/nuclear pathway. The study of nuclear pathways could be crucial to identify key regulators involved in neuronal differentiation, tumor progression and resistances to radio- and chemo-therapy.