In this study, we evaluated the effects of a probiotic supplement in distiller’s dried grains with solubles (DDGS) feeds on the hepatic transcriptome of Berkshire finisher pigs. At high levels, DDGS has been shown to reduce nutrient utilization, cause inflammation, and result increased adipose tissue which reduces carcass quality. Over a 35-day period that spanned August and September of 2024, twenty-four, 4-month old Berkshire pigs weighing 64.8±4.8 kg were randomly assigned to four diets: “15% DDGS” (Control), “15% DDGS + Probiotic” (Treatment 1), “15% DDGS + Xylanase (Treatment 2), and 15% DDGS + Probiotic/Xylanase (Treatment 3). This study focuses on the comparison of the hepatic transcriptomes of pigs fed the “15% DDGS + Probiotic” (Treatment 1) diet and pigs fed the “15% DDGS” (Control) diet. The probiotic supplement (Lactobacillus) was added to the DDGS feed at a concentration of 1kg/ton. Livers from these animals were harvested for RNA isolation, cDNA library construction, and RNA-sequencing using the NovaSeq X Plus platform from Illumina. The reads were mapped back to reference genome, Sscrofa11.1 and counted to assess differential expression (DE) (P ≤ 0.05, Log2 Fold Change ≥ 1.0) using DESeq2 package in the R Version 4.6.0. The Benjamini-Hochberg method was used to control for false positives. When comparing Treatment 1 to the Control, there were 585 differentially expressed genes, 304 up-regulated and 281 down-regulated. GO analysis was used to characterize the functions of the differentially expressed genes. The overrepresented functions among these differentially expressed genes were associated with cell surface, inflammation, apoptosis inhibition (PI3K signaling), transmembrane signaling (protein tyrosine kinase activity), intracellular signaling, ERK1/2 cascade, regulation of ERK1/2 cascade, and positive regulation of ERK1/2 cascade. The ERK1/2 signaling cascade activation may be associated with reducing lipid accumulation through fatty acid oxidation and the export of triglycerides, while the hepatic cell surface and transmembrane differentially expressed genes my play a role in lipid transport. We conclude that the addition of the probiotic supplement to the high-carbohydrate, DDGS diet results in increased uptake of glucose molecules by these Berkshire finishers. Due to previous studies noting hyperglycemic pigs employing alternative metabolic pathways to convert glucose to lipids which are subject to oxidation and peroxidation, we also conclude that probiotic supplementation in this study resulted in lipid accumulation that led to inflammation and tissue damage in the liver as a result of the ERK1/2 cascade.
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It is demonstrated that linker-free PROTACs can outperform traditional designs, marking a paradigm shift in PROTAC development for targeted protein degradation.
Pinal, a 16-billion-parameter foundation model that produces protein candidates from natural-language functional descriptions, supports natural language as a high-level interface for candidate generation in protein design, enabling programmable exploration with reduced reliance on manually specified structural or seque...
A new machine-learning framework aims to improve the success rate of computational protein design while moving away from results that reproduce sequences found in nature.