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Kasper, C.

Publications and source records attributed to Kasper, C..

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A large-effect locus on chromosome 4 underlies circadian feeding rhythmicity in pigs

Circadian feeding rhythmicity reflects the distribution of feed intake across the daily 24-hour cycle. Regular feeding-fasting cycles play an important role in regulating metabolism and maintaining health, but endogenous and environmental factors can disrupt the normal circadian pattern of feed intake. Here, we quantified hourly feed intake in 3,470 Swiss Landrace and 15,181 Swiss Large White pigs using 40.5 million records from automated feeding systems. We used the proportion of days exhibiting a significant feeding rhythm after wavelet analysis to investigate variation in circadian feeding organization. Circadian feeding rhythmicity was influenced by sex and age, with higher rhythmicity observed in females and older animals. Variance components analysis revealed a strong additive genetic contribution and a high heritability (0.53-0.57). Pigs with higher circadian feeding rhythmicity had reduced nocturnal intake, improved feed conversion ratio, and lower day-to-day variability in feed intake, suggesting improved feed efficiency and resilience. Genome-wide association testing of 15.7 and 23.1 million imputed sequence variants identified a QTL on chromosome 4 explaining 5.3% and 2.9% of the phenotypic variance of circadian feeding rhythmicity in Swiss Landrace and Swiss Large White pigs, respectively. The QTL overlaps OPRK1 and NPBWR1, two genes implicated in the regulation of feeding behavior, reward and energy homeostasis. Collectively, our findings establish circadian feeding behavior as a heritable trait in pigs and provide a basis to further investigate the genetic regulation of feeding rhythms in mammals and explore its use in animal breeding programs to improve feed efficiency and resilience.

genetics↗

Nitrogen use efficiency in pigs is associated with transcriptomic signatures related to amino acid metabolism, immune activity, and nutrient partitioning

Dietary protein restriction challenges the allocation of amino acids to growth and other physiological functions and therefore requires coordinated metabolic adaptation. Domestic pigs provide an informative system in which to study such responses, because nitrogen retention directly affects lean growth and can be quantified accurately under controlled feeding and housing conditions. Under reduced-protein diets, pigs differ in how effectively they retain nitrogen, and this variation has a genetic basis, making them well suited to investigate the molecular regulation of nitrogen use efficiency (NUE). Here, we characterise differential gene expression and enriched pathways in liver and skeletal muscle of more than 80 pigs with two divergent NUE phenotypes (high and low) maintained under the same protein-reduced, ad libitum dietary conditions. The two NUE phenotypes were clearly distinct at the transcriptomic level, with 177 differentially expressed genes in the liver and 133 in the muscle. In the liver, differential expression and enrichment analyses indicate reduced amino acid catabolism, lower inflammatory and detoxification activity, and a metabolic state that favours lipid processing and insulin-related regulation over the use of amino acids as energy sources. In skeletal muscle, they point to reduced lipid uptake, lower reliance on amino acid oxidation, and a greater emphasis on protein synthesis, translational regulation, mitochondrial energy metabolism, and growth-related processes. These gene-level patterns were supported and extended by pathway and gene-set enrichment analyses. Together, the results suggest that high and low-NUE pigs differ through coordinated, tissue-specific molecular adaptations. Overall, variation in NUE appears to reflect coordinated, tissue-specific differences in how nutrients are allocated between energy use, storage, and lean tissue growth.

genomics↗

Integrating three genetic dimensions relating to piglet birth weight: direct and maternal effects on the mean and genetic control of residual variance

Uniformity of production traits is desired for different traits in livestock species, including the uniformity of within-litter birth weights in piglets. Birth weight (BW) in pigs is associated with increased vitality and survival until weaning. However, as uniformity of BW increases, the importance of initial weight decreases as competition between piglets decreases. The aim of this study was to estimate the direct and maternal genetic components of BW, jointly with the maternal genetic component of the residual variance for within-litter BW, and their genetic correlations. We used two distinct datasets of Swiss Large White pigs: 1) the experimental farm dataset and 2) the commercial farms dataset, comprising 43,135 and 23,313 records of individual piglet birth weight, respectively. For statistical analysis, the heteroscedastic (or canalising selection) model was used. This model assumes that both the mean BW and the residual variance are affected by systematic and random effects, with the residual variance being heterogeneous and partially under genetic control. Despite the best fitting model was the most complex one including both genetic effects for the mean trait, the results indicated that direct genetic effects, or correlations with such effects, are negligible. The genetic environmental variance for BW ranged between 0.071 and 0.131 for experimental farm and 0.037 to 0.094. The genetic correlation between the mean BW and its variability was always positive and ranged between 0.149 and 0.307 for the experimental farm and between 0.220 and 0.589 for the commercial farms. It is thus sufficient to model BW and its variability by including only the maternal genetic effect for both traits. In addition, even though moderate genetic correlations exist between the mean and the variance of BW, focusing selection on BW uniformity within litters would be preferable to creating a selection index for both traits simultaneously. ImplicationsMonitoring within-litter birth weight variability is important for efficient piglet production and welfare. Our findings suggest that maternal genetic effects are sufficient to model birth weight and its variability as genetic components of environmental variance. For both traits, direct genetic variance and its correlations with other components are negligible. However, since there are moderate genetic correlations between the mean and variance of birth weight, it is preferable to focus solely on selecting for within-litter birth weight uniformity rather than combining both traits in the selection index. This approach simplifies breeding strategies while maintaining the goal of improving piglets welfare. HighlightsO_LIData on individual piglet birth weight were collected on Swiss farms over 18 years C_LIO_LIHeteroscedastic animal models integrated three dimensions of genetic components C_LIO_LIThe direct genetic effect and its correlations are minimal and irrelevant for selection C_LIO_LIMaternal genetic effects are crucial for birth weight and its variability C_LIO_LISelection for uniformity is preferable to selection for both traits simultaneously C_LI

genetics↗

Genome-wide association study and regional heritability mapping of protein efficiency and performance traits in Swiss Large White pigs

BackgroundThe improvement of protein efficiency (PE) is a key factor for a sustainable pig production as nitrogen excretion contributes substantially to environmental pollution. Protein efficiency has been shown to be clearly heritable and genetically correlated with some performance traits, such as feed conversion ratio (FCR) and average daily feed intake (ADFI). This study aimed to identify genomic regions associated with these traits through genome-wide association studies (GWAS) and regional heritability mapping (RHM) using whole-genome sequence variants from low-pass sequencing of more than 1,000 Swiss Large White pigs. ResultsThe genomic-based heritability estimates using [~]15 million variants were moderate to high, ranging from 0.33 to 0.47. Using GWAS, no significant variants were found at the genome-wide thresholds for PE and FCR, but 45 variants were identified for ADFI on chromosome 1and one for ADG on chromosome 14. No region was found to be significantly associated with PE and FCR using RHM. We identified five suggestive regions on chromosome 1 for ADFI and one on chromosome 14 for ADG. Combining both analyses, we were able to highlight putative candidate genes for PE, which included PHYKPL, COL23A1, PPFIBP2, GVIN1, SYT9, RBMXL2, ZNF215 and olfactory receptor genes. ConclusionsCombining GWAS and RHM allowed us to suggest genomic regions that potentially influence PE and production traits. The apparent difficulty in detecting significant regions for these traits probably reflects the relatively small sample size, differences in genetic architecture across experimental conditions, and the possibility that polymorphisms explaining large parts of the trait variation may not segregate in the population. Nevertheless, we identified plausible functional candidate genes in the highlighted regions, including those involved in nutrient sensing, the urea cycle, and metabolic pathways, in particular IGF1-insulin), and have previously been reported in association with nitrogen metabolism in cattle, muscle and adipose tissue metabolism and feed intake in pigs. We also highlighted a range of noncoding RNAs, and their targets and gene regulation in general in this context should be investigated in the future.

genomics↗

Protein efficiency and pig welfare: no trade-offs for mitigating nitrogen pollution

Pig manure contributes significantly to environmental pollution through nitrogen compounds. Reducing protein in feed can help, but it may lead to damaging behaviors if pigs nutritional needs are not met. Breeding pigs for higher protein efficiency (PE) is a long-term solution to reduce nitrogen pollution, but concerns about pig welfare remain. We studied 95 pigs involved in a project on the genetic basis of PE on a 20% protein restricted diet to investigate the phenotypic connection between PE and welfare. These pigs represented natural PE variations in the population. At around 100 days, before their PE was known, we observed their behaviors. Only three pigs engaged in tail biting and manipulation of vulnerable regions, but this was not associated with PE. There was no clear link between PE and manipulating pen mates less vulnerable regions. Such behaviors are normal but can cause stress and injury if carried out excessively due to boredom or stress. Overall, pigs with higher PE showed no major behavioral abnormalities in this study. Considering the lack of genetic knowledge, the risk of increased harmful behaviors when selecting for higher PE appears low when inferred from this purely phenotypic association.

animal behavior and cognition↗

Genetic analysis of protein efficiency and its association with performance and meat quality traits under a protein-restricted diet

BackgroundAn essential component in the development of a sustainable pig production is the reduction of nitrogen excretion in fattening pigs. Pig feeds typically contain high levels of dietary crude protein, and due to incomplete conversion to muscle tissue, excess nitrogen is excreted, resulting in environmental problems such as nitrate pollution and greenhouse gas emissions. Therefore, improving protein efficiency (PE), i.e., the proportion of dietary protein that remains in the carcass, is desirable. This study aimed to estimate the heritability (h2) of PE and its genetic correlations with phosphorus efficiency, three performance, seven meat quality and two carcass quality traits when pigs were fed a 20% protein-restricted diet, using a total of 1,071 Swiss Large White pigs. To determine PE, the intake of feed with known nutrient content was accurately recorded for each pig and the nitrogen and phosphorus content of the carcass was determined using dual-energy X-ray absorptiometry. ResultsWe found an average PE of 0.39 {+/-} 0.04 and a heritability of 0.60 {+/-} 0.08. PE showed a high genetic correlation with phosphorus efficiency (0.68 {+/-} 0.08), moderate genetic correlations with feed conversion ratio (-0.53 {+/-} 0.13) and average daily feed intake (-0.42 {+/-} 0.13), and very little to no genetic correlation with average daily gain (-0.06 {+/-} 0.16). While PE has favourable genetic correlations with the performance traits and some meat quality traits, there is a potentially unfavourable relationship of PE with meat colour (redness [rg = -0.26 {+/-} 0.17]; yellowness [rg = -0.30 {+/-} 0.18]) and intra-muscular fat (IMF; rg = -0.39 {+/-} 0.15). Feed conversion ratio (FCR) also showed unfavourable genetic correlations with meat lightness, redness yellowness, IMF and cooking loss. ConclusionsPE is heritable and can be considered in breeding to reduce the environmental impact of pig production. We found no strong negative influence on meat quality traits (except for meat color and IMF), and there is the potential for indirectly selecting for improved phosphorus efficiency. Selecting nutrient efficiencies might be a more suitable strategy to reduce nitrogen pollution from manure than focusing on FCR because the latter also shows genetic antagonism with some meat quality traits in our population.

genetics↗

Fatty sweet symphony: Decoding distinct ganglioside patterns of native and differentiated mesenchymal stem cells by a novel glycolipidomics profiling strategy

Gangliosides are an indispensable glycolipid class concentrated on cell surfaces with a critical role in stem cell differentiation. Nonetheless, owing to the lack of suitable methods for scalable analysis covering the full scope of ganglioside molecular diversity, their mechanistic properties in signaling and differentiation remain undiscovered to a large extent. This work introduces a sensitive and comprehensive ganglioside assay based on liquid chromatography, high-resolution mass spectrometry, and multistage fragmentation. Complemented by an open-source data evaluation workflow, we provide automated in-depth lipid species-level and molecular species-level annotation based on decision rule sets for all major ganglioside classes. Compared to conventional state-of-the-art methods, the presented ganglioside assay offers (1) increased sensitivity, (2) superior structural elucidation, and (3) the possibility to detect novel ganglioside species. A major reason for the highly improved sensitivity is the optimized spectral readout based on the unique capability of two parallelizable mass analyzers for multistage fragmentation. In addition to the significant technological advance, we identified 263 ganglioside species including cell-state-specific markers and previously unreported gangliosides in native and differentiated human mesenchymal stem cells. A general increase of the ganglioside numbers upon differentiation was observed as well as cell-state-specific clustering based on the ganglioside species patterns. By proving the predictive power of gangliosides as ubiquitous cell state-specific markers, we demonstrated the high throughput universal capability of our novel analytical strategy, which comes with new insights on the biological role of gangliosides in stem cell differentiation. Our analytical workflow will pave the way for new ganglioside- and glycolipid-based clusters of differentiation markers to determine stem cell phenotypes.

biochemistry↗

Machine learning algorithms can predict tail biting outbreaks in pigs using feeding behaviour records

Tail biting is a damaging behaviour that impacts the welfare and health of pigs. Early detection of precursor sig outbreaks, using feeding behaviour data recorded by an electronic feeder. Prediction capacities of seven machine learning algorithms (Generalized Linear Model with Stepwise Feature Selection, random forest, Support Vector Machines with Radial Basis Function Kernel, Bayesian Generalized Linear Model, Neural network, K-nearest neighbour, and Partial Least Squares Discriminant Analysis) were evaluated from daily feeding data collected from 65 pens originating from two herds of grower-finisher pigs (25-100kg), in which 27 tail biting events occurred. Data were divided into training and testing data in two different ways, either by randomly splitting data into 75% (training set) and 25% (testing set), or by randomly selecting pens to constitute the testing set. In the first data splitting, the model is regularly updated with previous data from the pen, whereas in the second data splitting, the model tries to predict for a pen that it has never seen before. The K-nearest neighbour algorithm was able to predict 78% of the upcoming events with an accuracy of 96%, when predicting events in pens for which it had previous data. The detection of events for unknown pens was less sensitive, and the neural network model was able to detect 14% of the upcoming events with an accuracy of 63%. Our results indicate that machine learning models can be considered for implementation into automatic feeder systems for real-time prediction of tail biting events.

animal behavior and cognition↗

Short communication: Applicability of feeding behaviour traits as high-throughput phenotyping methods for identifying protein-efficient pigs

The improvement of efficiency traits, such as protein efficiency (PE), digestible energy efficiency (EnE) and lipid gain (LipG), are relevant given their associations with environmental pollution, cost of productions, and the quality of meat. However, these traits are difficult traits to measure and usually require slaughtering of pigs. Efficiency traits are complex, and several factors, such as genetic predisposition, feed composition, but also individual feeding behaviour may contribute to efficiency. The objective of this study was therefore to evaluate the potential of using feeding behaviour traits to predict efficiency traits under dietary protein restriction. A total of 587 Swiss Large White pigs, consisting of 312 females and 275 castrated males, had ad libitum access to feed and water, and were fed a protein-reduced diet (80% of recommended digestible protein and essential amino acids) from 22.5 {+/-} 1.6 to 106.6 {+/-} 4.6 kg BW. Individual feed intake was monitored and carcass composition (lean and fat mass) at slaughter was determined by dual-energy X-ray absorptiometry (DXA). The PE and EnE were calculated as the ratio of protein or energy in the carcass (estimated by DXA) to the total protein or energy consumed. Feeding behaviour traits monitored were daily feed intake (DFI; g/day), feed intake per meal (FIM; g/meal), number of daily meals (NDM; meals/day), duration of meal (DUM; min/meal), feeding rate (FR; g/min), and feeder occupation (FO; min/day). A partial least square (PLS) regression was used to predict PE, EnE and LipG from feeding behaviour traits, while including farrowing series (for PE only), age at slaughter and body weight at slaughter. Accuracy of PLS regression was assessed based on RMSE and R2 for calibration and validation sets, and on concordance correlation coefficient (CCC), which were estimated over 100 replicates of calibration and validation sets. Models with a number of latent variables of 5, 2 and 3 were identified as optimal for PE, EnE, and LipG, which explained 34.64%, 55.42% and 82.68% of the total variation in PE, EnE, and LipG, respectively. Significant CCC were found between predicted and observed values for PE (0.50), EnE (0.70), and LipG (0.90). In conclusion, individual feeding behaviour traits can better predict EnE and LipG than for PE under dietary protein restriction when fed ad libitum. ImplicationsThis study suggests that five feeding behaviour traits, which are automatically recorded via feeder stations in large numbers with little effort, together with body weight and age, may be used to predict protein efficiency, energy efficiency and lipid gain in Swiss Large White pigs receiving a protein reduced diet with considerable accuracy. This will allow for easy collection of large amounts of data on these traits for precision feeding and genetic selection strategies, especially when additional traits are added in the future to further improve accuracy.

physiology↗

Accuracy of predicting chemical body composition of growing pigs using dual-energy X-ray absorptiometry

AO_SCPLOWBSTRACTC_SCPLOWStudies in animal science assessing nutrient and energy efficiency or determining nutrient requirements necessitate gathering exact measurements of body composition or body nutrient contents. Wet chemical analysis methods or standardized dissection are commonly applied, but both are destructive. Harnessing human medical imaging techniques for animal science can enable repeated measurements of individuals over time and reduce the number of individuals required for research. Among imaging techniques, dual-energy X-ray absorptiometry (DXA) is particularly promising. However, the measurements obtained with DXA do not perfectly match dissections or chemical analyses, requiring the adjustment of the DXA via calibration equations. Several calibration regressions have been published, but comparative studies are pending. Thus, it is currently not clear whether existing regression equations can be directly used to convert DXA measurements into chemical values or whether each individual DXA device will require its own calibration. Our study builds prediction equations that relate body composition to the content of single nutrients in growing entire male pigs (body weight range 20-100 kg) as determined by both DXA and chemical analyses, with R2 ranging between 0.89 for ash and 0.99 for water and crude protein. Moreover, we show that the chemical composition of the empty body can be satisfactorily determined by DXA scans of carcasses, with the prediction error rCV ranging between 4.3% for crude protein and 12.6% for ash. Finally, we compare existing prediction equations for pigs of a similar range of body weights with the equations derived from our DXA measurements and evaluate their fit with our chemical analyses data. We found that existing equations for absolute contents that were built using the same DXA beam technology predicted our data more precisely than equations based on different technologies and percentages of fat and lean mass. This indicates that the creation of generic regression equations that yield reliable estimates of body composition in pigs of different growth stages, sexes and genetic breeds could be achievable in the near future. DXA may be a promising tool for high-throughput phenotyping for genetic studies, because it efficiently measures body composition in a large number and wide array of animals.

physiology↗

From 3D to 3D: isolation of mesenchymal stem/stromal cells into a three-dimensional human platelet lysate matrix

Mesenchymal stem/stromal cells (MSCs) are considered an important candidate in cell therapy and tissue engineering approaches. The culture of stem cells in a 3D environment is known to better resemble the in vivo situation and to promote therapeutically relevant effects in isolated cells. Therefore, the aim of this study was to develop an approach for the isolation of MSCs from adipose tissue into a 3D environment. Furthermore, the use of cryoprotective medium for cryopreservation of whole adipose tissue was evaluated. For the isolation of MSCs, a novel human platelet lysate-based hydrogel was used as matrix and the migration, yield, viability and metabolic activity of cells from the 3D matrix were compared to cells from 2D explant culture. Also, the surface marker profile and differentiation capacity of MSCs from the 3D matrix were evaluated and compared to MSCs from isolation by enzymatic treatment. We found that cryopreservation of whole adipose tissue is feasible, and therefore adipose tissue can be stored and is available for MSC isolation on demand. Also, we demonstrate the isolation of MSCs into the 3D matrix and that cells from this condition display a similar phenotype and differentiation capacity like MSCs derived by traditional isolation procedure. The presented approach allows, for the first time, to isolate MSCs directly into a soft 3D hydrogel environment, avoiding any contact to a 2D plastic culture surface.\n\nSignificance StatementIn this paper we present a new method for the isolation of mesenchymal stem cells. Usually, these cells grow on two-dimensional plastic surfaces which is far away from their physiologic environment. Our new method allows for the first time the direct outgrowth of cells from primary tissue into a three-dimensional environment, avoiding any contact to a two-dimensional plastic surface. In future, this will allow an entirely three-dimensional in vitro cultivation of stem cells. Using 3D isolated cells will probably also increase the physiologic relevance of in vitro models.

cell biology↗