Transcriptional signature of a hypersensitive glucocorticoid receptor variant in the neuroendocrine system suggests enhanced vulnerability to brain disorders.

The natural substitution Ala610Val in the porcine glucocorticoid receptor (GR) leads to a profound compensatory downregulation of the hypothalamic-pituitary-adrenal (HPA) axis in early ontogeny. In this study, we leveraged this unique animal model to explore mechanisms of HPA axis regulation and consequences of its genetically-based persistent hypoactivity. To this end, we examined transcriptional signature of GR in the hypothalamus, hippocampus, amygdala and adrenal gland in resting conditions (i.

Transcriptional responses to diets without mineral phosphorus supplementation in the jejunum of two high-yielding laying hen strains.

Phosphorus (P) is an essential mineral for all forms of life including laying hens, playing a crucial role in growth and efficient egg production. Recent studies suggest that current P recommendations might exceed the physiological demand, leading to unnecessarily high P excretions. This study on Lohmann Brown (LB) and Lohmann Selected Leghorn (LSL) laying hens (n=80; 10 replicates per strain, production period, and dietary group) investigates transcriptional changes in the jejunum, a critical intestinal segment for mineral absorption, in response to a diet either without (P-) or with (P+) a mineral supplement from monocalcium phosphate, administered over a 4-week period during the transition (15-19 weeks) or onset of laying (20-24 weeks).

Dynamics of DNA methylation during osteogenic differentiation of porcine synovial membrane mesenchymal stem cells from two metabolically distinct breeds.

Mesenchymal stem cells (MSCs), with the ability to differentiate into osteoblasts, adipocytes, or chondrocytes, show evidence that the donor cell's metabolic type influences the osteogenic process. Limited knowledge exists on DNA methylation changes during osteogenic differentiation and the impact of diverse donor genetic backgrounds on MSC differentiation. In this study, synovial membrane mesenchymal stem cells (SMSCs) from two pig breeds (Angeln Saddleback, AS; German Landrace, DL) with distinct metabolic phenotypes were isolated, and the methylation pattern of SMSCs during osteogenic induction was investigated.

Exposure to artificial ultraviolet-B light mediates alterations on the hepatic transcriptome and vitamin D metabolism in pigs.

In the currently prevailing pig husbandry systems, the vitamin D status is almost exclusively dependent on dietary supply. Additional endogenous vitamin D production after exposure to ultraviolet-B (UVB) light might allow the animals to utilize minerals in a more efficient manner, as well as enable the production of functional vitamin D-enriched meat for human consumption. In this study, growing pigs (n = 16) were subjected to a control group or to a daily narrowband UVB exposure of 1 standard erythema dose (SED) for a period of 9 weeks until slaughter at a body weight of 105 kg.

Liver transcriptome profiles of dairy cows with different serum metabotypes.

In a previously established animal model, 38 multiparous Holstein cows were assigned to 2 groups fed different diets to achieve either a normal (NBCS) or high (HBCS) body condition score (BCS) and backfat thickness (BFT) until dry-off at -49 d before calving (NBCS: BCS <3.5 [3.02 ± 0.

Metabolic Pathway Modeling in Muscle of Male Marathon Mice (DUhTP) and Controls (DUC)-A Possible Role of Lactate Dehydrogenase in Metabolic Flexibility.

In contracting muscles, carbohydrates and fatty acids serve as energy substrates; the predominant utilization depends on the workload. Here, we investigated the contribution of non-mitochondrial and mitochondrial metabolic pathways in response to repeated training in a polygenic, paternally selected marathon mouse model (DUhTP), characterized by exceptional running performance and an unselected control (DUC), with both lines descended from the same genetic background. Both lines underwent three weeks of high-speed treadmill training or were sedentary.

RNA-Seq-based discovery of genetic variants and allele-specific expression of two layer lines and broiler chicken.

Recent advances in the selective breeding of broilers and layers have made poultry production one of the fastest-growing industries. In this study, a transcriptome variant calling approach from RNA-seq data was used to determine population diversity between broilers and layers. In total, 200 individuals were analyzed from three different chicken populations (Lohmann Brown (LB),  = 90), Lohmann Selected Leghorn (LSL,  = 89), and Broiler (BR,  = 21).

Microbial signature inferred from genomic breeding selection on milk urea concentration and its relation to proxies of nitrogen-utilization efficiency in Holsteins.

Increasing the nitrogen-utilization efficiency (NUE) of dairy cows by breeding selection would offer advantages from nutritional, environmental, and economic perspectives. Because data collection of NUE phenotypes is not feasible in large cow cohorts, the cow individual milk urea concentration (MU) has been suggested as an indicator trait. Considering the symbiotic interplay between dairy cows and their rumen microbiome, individual MU was thought to be influenced by host genetics and by the rumen microbiome, the latter in turn being partly attributed to host genetics.

An atlas of regulatory elements in chicken: A resource for chicken genetics and genomics.

A comprehensive characterization of regulatory elements in the chicken genome across tissues will have substantial impacts on both fundamental and applied research. Here, we systematically identified and characterized regulatory elements in the chicken genome by integrating 377 genome-wide sequencing datasets from 23 adult tissues. In total, we annotated 1.

The dynamics of molecular, immune and physiological features of the host and the gut microbiome, and their interactions before and after onset of laying in two hen strains.

Aggregation of data, including deep sequencing of mRNA and miRNA data in jejunum mucosa, abundance of immune cells, metabolites, or hormones in blood, composition of microbiota in digesta and duodenal mucosa, and production traits collected along the lifespan, provides a comprehensive picture of lifelong adaptation processes. Here, respective data from two laying hen strains (Lohmann Brown-Classic (LB) and Lohmann LSL-Classic (LSL) collected at 10, 16, 24, 30, and 60 wk of age were analyzed. Data integration revealed strain- and stage-specific biosignatures, including elements indicative of molecular pathways discriminating the strains.

Regulation of Porcine Oviduct Epithelium Functions via Progesterone and Estradiol Is Influenced by Cortisol.

Preimplantation maternal stress, characterized by elevated glucocorticoids (GCs), has been linked to reproductive failures caused by impaired oviduct functionality, which is known to be predominantly regulated by the sex steroids, progesterone (P4) and (17)estradiol (E2). Although steroid receptors share analogous structures and binding preferences, the interaction between GCs and E2/P4 in the oviduct has attracted little attention. Using an air-liquid interface culture model, porcine oviduct epithelial cells were stimulated with single (cortisol, E2, P4) or hormone mixtures (cortisol/E2, cortisol/P4) for 12 hours and 72 hours.

SNP discovery and association study for growth, fatness and meat quality traits in Iberian crossbred pigs.

Iberian pigs and its crosses are produced to obtain high-quality meat products. The objective of this work was to evaluate a wide panel of DNA markers, selected by biological and functional criteria, for association with traits related to muscle growth, fatness, meat quality and metabolism. We used 18 crossbred Iberian pigs with divergent postnatal growth patterns for whole genome sequencing and SNP discovery, with over 13 million variants being detected.

Ruminal background of predisposed milk urea (MU) concentration in Holsteins.

Efforts to reduce nitrogen (N) emissions are currently based on the optimization of dietary- N supply at average herd N requirements. The implementation of the considerable individual differences and predispositions in N- use efficiency and N- excretion in breeding programs is hampered by the difficulty of data collection. Cow individual milk urea (MU) concentration has been proposed as an easy-to-measure surrogate trait, but recent studies questioned its predictive power.

DNA methylation landscapes from pig's limbic structures underline regulatory mechanisms relevant for brain plasticity.

Epigenetic dynamics are essential for reconciling stress-induced responses in neuro-endocrine routes between the limbic brain and adrenal gland. CpG methylation associates with the initiation and end of regulatory mechanisms underlying responses critical for survival, and learning. Using Reduced Representation Bisulfite Sequencing, we identified methylation changes of functional relevance for mediating tissue-specific responses in the hippocampus, amygdala, hypothalamus, and adrenal gland in pigs.

Inhibition of KRAS, MEK and PI3K Demonstrate Synergistic Anti-Tumor Effects in Pancreatic Ductal Adenocarcinoma Cell Lines.

Kirsten rat sarcoma virus () mutations are widespread in pancreatic ductal adenocarcinoma (PDAC) and contribute significantly to tumor initiation, progression, tumor relapse/resistance, and prognosis of patients. Although inhibitors against mutations have been developed, this therapeutic approach is not routinely used in PDAC patients. We investigated the anti-tumor efficacy of two KRAS inhibitors BI-3406 (KRAS::SOS1 inhibitor) and sotorasib (KRAS G12C inhibitor) alone or in combination with MEK1/2 inhibitor trametinib and/or PI3K inhibitor buparlisib in seven PDAC cell lines.

Prenatal transcript levels and metabolomics analyses reveal metabolic changes associated with intrauterine growth restriction and sex.

The metabolic changes associated with intrauterine growth restriction (IUGR) particularly affect the liver, which is a central metabolic organ and contributes significantly to the provision of energy and specific nutrients and metabolites. Therefore, our aim was to decipher and elucidate the molecular pathways of developmental processes mediated by miRNAs and mRNAs, as well as the metabolome in fetal liver tissue in IUGR compared to appropriate for gestational age groups (AGA). Discordant siblings representing the extremes in fetal weight at day 63 post conception (dpc) were selected from F2 fetuses of a cross of German Landrace and Pietrain.

MicroRNA profiling of subcutaneous adipose tissue in periparturient dairy cows at high or moderate body condition.

A growing body of evidence shows that microRNA (miRNA), play important roles in regulating adipose tissue (AT) physiology and function. The objective was to characterize the AT miRNA profile in over-conditioned (HBCS, n = 19) versus moderate-conditioned (MBCS, n = 19) periparturient dairy cows. Tail-head subcutaneous AT biopsied on d -49 and 21 relative to parturition were used for miRNA sequencing.

Epigenetic Regulation of Phenotypic Sexual Plasticity Inducing Skewed Sex Ratio in Zebrafish.

The plasticity of sexual phenotype in response to environmental conditions results in biased sex ratios, and their variation has an effect on population dynamics. Epigenetic modifications can modulate sex ratio variation in species, where sex is determined by genetic and environmental factors. However, the role of epigenetic mechanisms underlying skewed sex ratios is far from being clear and is still an object of debate in evolutionary developmental biology.

Genetic regulation and variation of expression of miRNA and mRNA transcripts in fetal muscle tissue in the context of sex, dam and variable fetal weight.

Background: Impaired skeletal muscle growth in utero can result in reduced birth weight and pathogenesis of intrauterine growth restriction. Fetal and placental growth is influenced by many factors including genetic, epigenetic and environmental factors. In fact, the sex and genotype of the fetus itself, as well as the mother providing it with a suitable environment, influence the growth of the fetus.

Multi-Omics Reveals Different Strategies in the Immune and Metabolic Systems of High-Yielding Strains of Laying Hens.

Lohmann Brown (LB) and Lohmann Selected Leghorn (LSL) are two commercially important laying hen strains due to their high egg production and excellent commercial suitability. The present study integrated multiple data sets along the genotype-phenotype map to better understand how the genetic background of the two strains influences their molecular pathways. In total, 71 individuals were analyzed (LB, = 36; LSL, = 35).

Maternal Conjugated Linoleic Acid Supply in Combination With or Without Essential Fatty Acids During Late Pregnancy and Early Lactation: Investigations on Physico-Chemical Characteristics of the Jejunal Content and Jejunal Microbiota in Neonatal Calves.

Conjugated linoleic acids (CLAs) modulate the fatty acid composition in dairy cow milk, which represents the most important nutrient source of neonatal calves. In turn, dietary fatty acids are known to influence the gut microbiota. The current preliminary study investigated effects of a maternal fatty acid supplementation (MFAS) during transition period with coconut oil (CON, control), CLA (Lutalin®), or CLA + EFA (Lutalin® + essential fatty acids-linseed oil; safflower oil) on physico-chemical characteristics of jejunal content and microbiota of 5-day-old calves.

Central Suppression of the GH/IGF Axis and Abrogation of Exercise-Related mTORC1/2 Activation in the Muscle of Phenotype-Selected Male Marathon Mice (DUhTP).

The somatotropic axis is required for a number of biological processes, including growth, metabolism, and aging. Due to its central effects on growth and metabolism and with respect to its positive effects on muscle mass, regulation of the GH/IGF-system during endurance exercise is of particular interest. In order to study the control of gene expression and adaptation related to physical performance, we used a non-inbred mouse model, phenotype-selected for high running performance (DUhTP).

Ablation of Red Stable Transfected Claudin Expressing Canine Prostate Adenocarcinoma and Transitional Cell Carcinoma Cell Lines by C-CPE Gold-Nanoparticle-Mediated Laser Intervention.

Claudin (CLDN) proteins are commonly expressed in cancers and targeted in novel therapeutic approaches. The C-terminal of enterotoxin (C-CPE) efficiently binds several claudins. In this study, recombinant C-CPE conjugated to gold nanoparticles (AuNPs) has been used for prostate adenocarcinoma (PAC) and transitional cell carcinoma (TCC) cell killing in vitro using gold-nanoparticle-mediated laser perforation (GNOME-LP).

Insights into molecular pathways and fatty acid membrane composition during the temperature stress response in the murine C2C12 cell model.

Daily and seasonal temperature fluctuations are inevitable due to climate change, which highlights the importance of studying the detrimental effects of temperature fluctuations on the health, productivity, and product quality of farm animals. Muscle membrane composition and the molecular signals are vital for muscle cell differentiation and muscle growth, but their response to temperature stress is not well characterized. Temperature changes can lead to modification of membrane components of the cell, which may affect its surroundings and intracellular signaling pathways.