Inflammatory response in dairy cows caused by heat stress and biological mechanisms for maintaining homeostasis.

Climate change increases global temperatures, which is lethal to both livestock and humans. Heat stress is known as one of the various livestock stresses, and dairy cows react sensitively to high-temperature stress. We aimed to better understand the effects of heat stress on the health of dairy cows and observing biological changes. Individual cows were divided into normal (21-22 °C, 50-60% humidity) and high temperature (31-32 °C, 80-95% humidity), respectively, for 7-days. We performed metabolomic and transcriptome analyses of the blood and gut microbiomes of feces. In the high-temperature group, nine metabolites including linoleic acid and fructose were downregulated, and 154 upregulated and 72 downregulated DEGs (Differentially Expressed Genes) were identified, and eighteen microbes including Intestinimonas and Pseudoflavonifractor in genus level were significantly different from normal group. Linoleic acid and fructose have confirmed that associated with various stresses, and functional analysis of DEG and microorganisms showing significant differences confirmed that high-temperature stress is related to the inflammatory response, immune system, cellular energy mechanism, and microbial butyrate production. These biological changes were likely to withstand high-temperature stress. Immune and inflammatory responses are known to be induced by heat stress, which has been identified to maintain homeostasis through modulation at metabolome, transcriptome and microbiome levels. In these findings, heat stress condition can trigger alteration of immune system and cellular energy metabolism, which is shown as reduced metabolites, pathway enrichment and differential microbes. As results of this study did not include direct phenotypic data, we believe that additional validation is required in the future. In conclusion, high-temperature stress contributed to the reduction of metabolites, changes in gene expression patterns and composition of gut microbiota, which are thought to support dairy cows in withstanding high-temperature stress via modulating immune-related genes, and cellular energy metabolism to maintain homeostasis.

Impact of nsSNPs in human AIM2 and IFI16 gene: a comprehensive in silico analysis.

AIM2 and IFI16 are the most studied members of AIM2-like receptors (ALRs) in humans and share a common N-Terminal PYD domain and C-terminal HIN domain. The HIN domain binds to dsDNA in response to the invasion of bacterial and viral DNA, and the PYD domain directs apoptosis-associated speck-like protein via protein-protein interactions. Hence, activation of AIM2 and IFI16 is crucial for protection against pathogenic assaults, and any genetic variation in these inflammasomes can dysregulate the human immune system. In this study, different computational tools were used to identify the most deleterious and disease-causing non-synonymous single nucleotide polymorphisms (nsSNPs) in AIM2 and IFI16 proteins. Molecular dynamic simulation was performed for the top damaging nsSNPs to study single amino acid substitution-induced structural alterations in AIM2 and IFI16. The observed results suggest that the variants G13V, C304R, G266R, and G266D for AIM2, and G13E and C356F are deleterious and affect structural integrity. We hope that the suggested deleterious nsSNPs and structural dynamics of AIM2 and IFI16 variants will guide future research to better understand the function of these variants with large-scale studies and may assist in fresher therapeutics focusing on these polymorphisms.Communicated by Ramaswamy H. Sarma.

Genome-wide association study using a single-step approach for teat number in Duroc, Landrace and Yorkshire pigs in Korea.

We investigated the genetic basis of teat number in sows, which is an important factor in their reproductive performance. We collected genotyping data from 20 353 pigs of three breeds (Duroc, Landrace and Yorkshire) using the Porcine SNP60K Bead Chip, and analyzed phenotypic data from 240 603 pigs. The heritability values of total teat number were 0.33 ± 0.02, 0.51 ± 0.01 and 0.50 ± 0.01 in Duroc, Landrace and Yorkshire pigs, respectively. A genome-wide association study was used to identify significant chromosomal regions associated with teat number in SSC7 and SSC9 in Duroc pig, SSC3, SSC7 and SSC18 in Landrace pig, and SSC7, SSC8 and SSC10 in Yorkshire pig. Among the markers, MARC0038565, located between the vertnin (VRTN) and synapse differentiation-inducing 1-like (SYNDIG1L) genes, showed the strongest association in the Duroc pig and was significant in all breeds. In Landrace and Yorkshire pigs, the most significant markers were located within the apoptosis resistant E3 ubiquitin protein ligase 1 (AREL1) and latent transforming growth factor beta-binding protein 2 (LTBP2) genes in SSC7, respectively. VRTN is a candidate gene regulating the teat number. Most markers were located in SSC7, indicating their significance in determining teat number and their potential as valuable genomic selection targets for improving this trait. Extensive linkage disequilibrium blocks were identified in SSC7, supporting their use in genomic selection strategies. Our study provides valuable insights into the genetic architecture of teat numbers in pigs, and helps identify candidate genes and genomic regions that may contribute to this economically important trait.

Deciphering the intrinsic dynamics of unphosphorylated IRAK4 kinase bound to type I and type II inhibitors.

Interleukin-1 receptor-associated kinase 4 (IRAK4) is a vital protein involved in Toll-like and interleukin-1 receptor signal transduction. Several studies have reported regarding the crystal structure, dynamic properties, and interactions with inhibitors of the phosphorylated form of IRAK4. However, no dynamic properties of inhibitor-bound unphosphorylated IRAK4 have been previously studied. Herein, we report the intrinsic dynamics of unphosphorylated IRAK4 (uIRAK4) bound to type I and type II inhibitors. The corresponding apo and inhibitor-bound forms of uIRAK4 were subjected to three independent simulations of 500 ns (total 1.5 µs) each, and their trajectories were analyzed. The results indicated that all three systems were relatively stable, except for the type II inhibitor-bound form of uIRAK4, which exhibited less compact folding and higher solvent surface area. The intra-hydrogen bonds corroborated the structural deformation of the type-II inhibitor-bound complex, which could be attributed to the long molecular structure of the type-II inhibitor. Moreover, the type II inhibitor bound to uIRAK4 showed higher binding free energy with uIRAK4 than the type I inhibitor. The free energy landscape analysis showed a reorientation of Phe330 side chain from the DFG motif at different metastable states for all the systems. The intra-residual distance between residues Lys213, Glu233, Tyr262, and Phe330 suggests a functional interplay when the inhibitors are bound to uIRAK4, thereby hinting at their crucial role in the inhibition mechanism. Ultimately, the intrinsic dynamics study observed between type I/II inhibitor-bound forms of uIRAK4 may assist in better understanding the enzyme and designing therapeutic compounds.

Genome-wide association studies on collagen contents trait for meat quality in Hanwoo.

Beef consumers valued meat quality traits such as texture, tenderness, juiciness, flavor, and meat color that determining consumers' purchasing decision. Most research on meat quality has focused on marbling, a key characteristic related to meat eating quality. However, other important traits such as meat texture, tenderness, and color have not much studied in cattle. Among these traits, meat tenderness and texture of cattle are among the most important factors affecting quality evaluation of consumers. Collagen is the main component of connective tissues.It greatly affects meat tenderness. The objective of this study was to determine significant variants and candidate genes associated with collagen contents trait (total collagen) through genome-wide association studies (GWAS). Phenotypic and genomic data from 135 Hanwoo were used. The BLUPF90 family program and GRAMMAR method for GWAS were applied in this study. A total of 73 potential single nucleotide polymorphisms (SNPs) showed significant associations with collagen content. They were located in or near 108 candidate genes. TMEM135 and ME3 genes were identified to have the most significant SNPs associated with collagen contents trait. Data indicated that these genes were related to collagen. Biological processes and pathways for the prediction of biological functions of candidate genes were confirmed. We found that candidate genes were involved in positive regulation of CREB transcription factor activity and actin cytoskeleton related to tenderness and texture of beef. Three genes (CRTC3, MYO1C and MYLK4) belonging to these biological functions were related to tenderness. These results provide a basis for improving genomic characteristics of Hanwoo for the production of tender beef. Furthermore, they could be used they could be used as an index to select desired traits for consumers.

Oropharyngeal, proximal colonic, and vaginal microbiomes of healthy Korean native black pig gilts.

BACKGROUND: Exploring the microbiome in multiple body sites of a livestock species informs approaches to promote its health and performance through efficient and sustainable modulation of these microbial ecosystems. Here, we employed 16S rRNA gene sequencing to describe the microbiome in the oropharyngeal cavity, proximal colon, and vaginal tract of Jeju Black pigs (JBP), which are native to the Korean peninsula. RESULTS: We sampled nine 7-month-old JBP gilts raised under controlled conditions. The most abundant phyla that we found within the oropharyngeal microbiota were Proteobacteria, Bacteroidetes, Fusobacteria and Firmicutes, collectively providing core features from twenty-five of their genera. We also found a proximal colonic microbial core composed of features from twenty of the genera of the two predominant phyla, Firmicutes, and Bacteroidetes. Remarkably, within the JBP vaginal microbiota, Bacteroidetes dominated at phylum level, contrary to previous reports regarding other pig breeds. Features of the JBP core vaginal microbiota, came from seventeen genera of the major phyla Bacteroidetes, Firmicutes, Proteobacteria, and Fusobacteria. Although these communities were distinct, we found some commonalities amongst them. Features from the genera Streptococcus, Prevotella, Bacillus and an unclassified genus of the family Ruminococcaceae were ubiquitous across the three body sites. Comparing oropharyngeal and proximal colonic communities, we found additional shared features from the genus Anaerorhabdus. Between oropharyngeal and vaginal ecosystems, we found other shared features from the genus Campylobacter, as well as unclassified genera from the families Fusobacteriaceae and Flavobacteriaceae. Proximal colonic and vaginal microbiota also shared features from the genera Clostridium, Lactobacillus, and an unclassified genus of Clostridiales. CONCLUSIONS: Our results delineate unique and ubiquitous features within and across the oropharyngeal, proximal colonic and vaginal microbial communities in this Korean native breed of pigs. These findings provide a reference for future microbiome-focused studies and suggest a potential for modulating these communities, utilizing ubiquitous features, to enhance health and performance of the JBP.

Bacillus-supplemented diet improves growth performance in Jeju native pigs by modulating myogenesis and adipogenesis.

Probiotics are used in pigs as nutritional supplements to improve health and induce the development of muscle and adipose tissue for enhancing growth performance and harvesting quality meat. In this study, we investigated the effects of Bacillus-based probiotic supplementation on the physiological and biochemical changes in Jeju native pigs (JNPs), including growth performance, backfat layers, blood parameters, serum IgG levels, myogenic and adipogenic markers, and expression of inflammatory markers. Average daily gain and feed efficiency were higher in the Bacillus diet group than in the basal diet group, while backfat thickness was lower in the Bacillus diet group than in the basal diet group. Blood biochemical parameters and hematological profiles were not altered significantly by Bacillus-based probiotic supplementation. Serum IgG concentration increased in the Bacillus diet group compared to the basal diet group. The Bacillus diet group showed increased adipogenic and myogenic markers expression in the longissimus dorsi muscle and adipose tissues. Overall, the data suggest that the Bacillus-based probiotics-supplemented diet regulates myogenesis and adipogenesis in JNPs and improves growth performance. We postulate that this may be due to the changes in the gut microbiota of pigs due to probiotic supplementation.

Structure-based virtual screening and molecular dynamics studies to explore potential natural inhibitors against 3C protease of foot-and-mouth disease virus.

Foot-and-mouth disease (FMD) is a highly infectious animal disease caused by foot-and-mouth disease virus (FMDV) and primarily infects cloven-hoofed animals such as cattle, sheep, goats, and pigs. It has become a significant health concern in global livestock industries because of diverse serotypes, high mutation rates, and contagious nature. There is no specific antiviral treatment available for FMD. Hence, based on the importance of 3C protease in FMDV viral replication and pathogenesis, we have employed a structure-based virtual screening method by targeting 3C protease with a natural compounds dataset (n = 69,040) from the InterBioScreen database. Virtual screening results identified five potential compounds, STOCK1N-62634, STOCK1N-96109, STOCK1N-94672, STOCK1N-89819, and STOCK1N-80570, with a binding affinity of -9.576 kcal/mol, -8.1 kcal/mol, -7.744 kcal/mol, -7.647 kcal/mol, and - 7.778 kcal/mol, respectively. The compounds were further validated through physiochemical properties and density functional theory (DFT). Subsequently, the comparative 300-ns MD simulation of all five complexes exhibited overall structural stability from various MD analyses such as root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent accessible surface area (SASA), H-bonds, principal component analysis (PCA), and free energy landscape (FEL). Furthermore, MM-PBSA calculation suggests that all five compounds, particularly STOCK1N-62634, STOCK1N-96109, and STOCK1N-94672, can be considered as potential inhibitors because of their strong binding affinity toward 3C protease. Thus, we hope that these identified compounds can be studied extensively to develop natural therapeutics for the better management of FMD.

High-quality metagenome-assembled genomes from proximal colonic microbiomes of synbiotic-treated korean native black pigs reveal changes in functional capacity.

Synbiotics are feed supplements with the potential to promote health and productivity in pigs partly, through modulation of the intestinal microbiome. Our study used shotgun sequencing and 16S rRNA gene sequencing techniques to characterize the effect of a synbiotic containing three Lactobacillus species and a fructo-oligosaccharide on the proximal colonic microbiome of 4- to 7-month-old Korean native black gilts. With shotgun sequencing we constructed unique metagenome-assembled genomes of gut microbiota in Native Black Pig for the first time, which we then used for downstream analysis. Results showed that synbiotic treatment did not alter microbial diversity and evenness within the proximal colons, but altered composition of some members of the Lactobacillaceae, Enterococcaceae and Streptococcaceae families. Functional analysis of the shotgun sequence data revealed 8 clusters of orthologous groups (COGs) that were differentially represented in the proximal colonic microbiomes of synbiotic-treated Jeju black pigs relative to controls. In conclusion, our results show that administering this synbiotic causes changes in the functional capacity of the proximal colonic microbiome of the Korean native black pig. This study improves our understanding of the potential impact of synbiotics on the colonic microbiome of Korean native black pigs.

Transcriptome-wide analysis reveals gluten-induced suppression of small intestine development in young chickens.

Wheat gluten is an increasingly common ingredient in poultry diets but its impact on the small intestine in chicken is not fully understood. This study aimed to identify effects of high-gluten diets on chicken small intestines and the variation of their associated transcriptional responses by age. A total of 120 broilers (Ross Strain) were used to perform two animal experiments consisting of two gluten inclusion levels (0% or 25%) by bird's age (1 week or 4 weeks). Transcriptomics and histochemical techniques were employed to study the effect of gluten on their duodenal mucosa using randomly selected 12 broilers (3 chicks per group). A reduction in feed intake and body weight gain was found in the broilers fed a high-gluten containing diet at both ages. Histochemical photomicrographs showed a reduced villus height to crypt depth ratio in the duodenum of gluten-fed broilers at 1 week. We found mainly a significant effect on the gene expression of duodenal mucosa in gluten-fed broilers at 1 week (289 differentially expressed genes [DEGs]). Pathway analyses revealed that the significant DEGs were mainly involved in ribosome, oxidative phosphorylation, and peroxisome proliferator-activated receptor (PPAR) signaling pathways. These pathways are involved in ribosome protein biogenesis, oxidative phosphorylation and fatty acid metabolism, respectively. Our results suggest a pattern of differential gene expression in these pathways that can be linked to chronic inflammation, suppression of cell proliferation, cell cycle arrest and apoptosis. And via such a mode of action, high-gluten inclusion levels in poultry diets could lead to the observed retardation of villi development in the duodenal mucosa of young broiler chicken.

Long-term artificial selection of Hanwoo (Korean) cattle left genetic signatures for the breeding traits and has altered the genomic structure.

Indigenous Korean breeds such as Hanwoo (Korean) cattle have adapted to their local environment during the past 5000 years. In the 1980s, the National Genetic Improvement Program was established to develop a modern economic breed for beef production in Korea through artificial selection. This process is thought to have altered the genomic structure of breeding traits over time. The detection of genetic variants under selection could help to elucidate the genetic mechanism of artificial selection in modern cattle breeds. Indigenous Hanwoo cattle have adapted in response to local natural and artificial selection during a 40-year breeding program. We analyzed genomic changes in the selection signatures of an unselected population (USP; n = 362) and a selected population (KPN; n = 667) of Hanwoo cattle. Genomic changes due to long-term artificial selection were identified using a genome-wide integrated haplotype score (iHS) and a genome-wide association study (GWAS). Signatures of recent selection were detected as positive (piHS > 6) or negative (piHS < -6) iHS scores spanning more than 46 related genes in KPN cattle, but none in USP cattle. A region adjacent to the PLAG1 gene was found to be under strong selection for carcass weight. The GWAS results also showed a selection signature on BTA14, but none on BTA13. Pathway and quantitative trait locus analysis results identified candidate genes related to energy metabolism, feed efficiency, and reproductive traits in Hanwoo cattle. Strong selection significantly altered Hanwoo cattle genome structural properties such as linkage disequilibrium (LD) and haplotypes through causal mutation for target traits. Haplotype changes of genome structure which are changes of ancestral allele to derived alleles due to selection were clearly identified on BTA13 and BTA14; however, the structure of the LD block was not clearly observed except BTA14. Thus, selection based on EBVs would be working very well in Hanwoo cattle breeding program appears to have been highly successful.

PKC-ß modulates Ca2+ mobilization through Stim1 phosphorylation.

BACKGROUND: Calcium ions play a pivotal role in cell proliferation, differentiation, and migration. Under basal conditions, the calcium level is tightly regulated; however, cellular activation by growth factors increase the ion level through calcium pumps in the plasma membrane and endoplasmic reticulum for calcium signaling. Orai1 is a major calcium channel in the cell membrane of non-excitable cells, and its activity depends on the stromal interaction molecule 1 (Stim1). Several groups reported that the store-operated calcium entry (SOCE) can be modulated through phosphorylation of Stim1 by protein kinases such as extracellular signal-regulated kinase (ERK), protein kinase A (PKA), and p21-activated kinase (PAK). PKC is a protein kinase that is activated by calcium and diacylglycerol (DAG), but it remains unclear what role activated PKC plays in controlling the intracellular calcium pool. OBJECTIVES: Here, we investigated whether PKC-ß controls intracellular calcium dynamics through Stim1. METHODS: Several biochemical methods such as immune-precipitation, site directed mutagenesis, in vitro kinase assay were employed to investigate PKC interaction with and phosphorylation of Stim1. Intracellular calcium mobilization, via Stim1 mediated SOCE channel, were studied using in the presence of PKC activator or inhibitor under a confocal microscope. RESULTS: Our data demonstrate that PKC interacts with and phosphorylates Stim1 in vitro. phosphorylation of Stim1 at its C-terminal end appears to be important in the regulation of SOCE activity in HEK293 and HeLa cells. Additionally, transient intracellular calcium mobilization assays demonstrate that the SOCE activity was inhibited by PKC activators or activated by PKC inhibitors. CONCLUSION: In sum, our data suggest a repressive role of PKC in regulating calcium entry through SOCE.

Elucidating breed-specific variants of native pigs in Korea: insights into pig breeds' genomic characteristics.

Although conserving native pig breeds is important in Korea, research on the genomic aspects to identify breed-specific variations in native pig breeds is uncommon. Single nucleotide polymorphisms (SNPs) can be a powerful source for identifying breed-specific variants. We used whole genome sequencing data, including Jeju Native Pig (JNP), Korean Native Pig (KNP), Korean Wild Boar (KWB), and other western commercial pig breeds to determine native pig breed-specific SNPs. Furthermore, the goal was not only to determine the genomic specificity of native pig breeds but also to identify SNPs that carry breed-specific information (breed-informative SNPs) that can be related to breed characteristics. The representative characteristics of native pigs are their unique meat quality and disease resistance. We surveyed the gene ontology (GO) of native pigs with breed-specific SNPs. Examining the genes associated with GO may contribute to revealing the reasons for the unique characteristics of native pig breeds. The enriched GOs terms were neuron projection development, cell surface receptor signaling pathway, ion homeostasis in JNP, cell adhesion and wound healing in KNP, and DNA repair and reproduction in KWB. We expect that this study of breed-specific SNPs will enable us to gain a deeper understanding of native pigs in Korea.

High-throughput sequencing-based metagenomic and transcriptomic analysis of intestine in piglets infected with salmonella.

Salmonella enterica serovar Typhimurium isolate HJL777 is a virulent bacterial strain in pigs. The high rate of salmonella infection are at high risk of non-typhoidal salmonella gastroenteritis development. Salmonellosis is most common in young pigs. We investigated changes in gut microbiota and biological function in piglets infected with salmonella via analysis of rectal fecal metagenome and intestinal transcriptome using 16S rRNA and RNA sequencing. We identified a decrease in Bacteroides and increase in harmful bacteria such as Spirochaetes and Proteobacteria by microbial community analysis. We predicted that reduction of Bacteroides by salmonella infection causes proliferation of salmonella and harmful bacteria that can cause an intestinal inflammatory response. Functional profiling of microbial communities in piglets with salmonella infection showed increasing lipid metabolism associated with proliferation of harmful bacteria and inflammatory responses. Transcriptome analysis identified 31 differentially expressed genes. Using gene ontology and Innate Immune Database analysis, we identified that BGN, DCN, ZFPM2 and BPI genes were involved in extracellular and immune mechanisms, specifically salmonella adhesion to host cells and inflammatory responses during infection. We confirmed alterations in gut microbiota and biological function during salmonella infection in piglets. Our findings will help prevent disease and improve productivity in the swine industry.

Complete genome sequencing and comparative genomic analysis of Lactobacillus acidophilus C5 as a potential canine probiotics.

Lactobacillus acidophilus is a gram-positive, microaerophilic, and acidophilic bacterial species. L. acidophilus strains in the gastrointestinal tracts of humans and other animals have been profiled, but strains found in the canine gut have not been studied yet. Our study helps in understanding the genetic features of the L. acidophilus C5 strain found in the canine gut, determining its adaptive features evolved to survive in the canine gut environment, and in elucidating its probiotic functions. To examine the canine L. acidophilus C5 genome, we isolated the C5 strain from a Korean dog and sequenced it using PacBio SMRT sequencing technology. A comparative genomic approach was used to assess genetic relationships between C5 and six other strains and study the distinguishing features related to different hosts. We found that most genes in the C5 strain were related to carbohydrate transport and metabolism. The pan-genome of seven L. acidophilus strains contained 2,254 gene families, and the core genome contained 1,726 gene families. The phylogenetic tree of the core genes in the canine L. acidophilus C5 strain was very close to that of two strains (DSM20079 and NCFM) from humans. We identified 30 evolutionarily accelerated genes in the L. acidophilus C5 strain in the ratio of non-synonymous to synonymous substitutions (dN/dS) analysis. Five of these thirty genes were associated with carbohydrate transport and metabolism. This study provides insights into genetic features and adaptations of the L. acidophilus C5 strain to survive the canine intestinal environment. It also suggests that the evolution of the L. acidophilus genome is closely related to the host's evolutionary adaptation process.

Antitumorigenic effect of insect-derived peptide poecilocorisin-1 in human skin cancer cells through regulation of Sp1 transcription factor.

Malignant melanoma is highly resistant to conventional treatments and is one of the most aggressive types of skin cancers. Conventional cancer treatments are limited due to drug resistance, tumor selectivity, and solubility. Therefore, new treatments with fewer side effects and excellent effects should be developed. In previous studies, we have analyzed antimicrobial peptides (AMPs), which showed antibacterial and anti-inflammatory effects in insects, and some AMPs also exhibited anticancer efficacy. Anticancer peptides (ACPs) are known to have fewer side effects and high anticancer efficacy. In this study, the insect-derived peptide poecilocorisin-1 (PCC-1) did not induce toxicity in the human epithelial cell line HaCaT, but its potential as an anticancer agent was confirmed through specific effects of antiproliferation, apoptosis, and cell cycle arrest in two melanoma cell lines, SK-MEL-28 and G361. Additionally, we discovered a novel anticancer mechanism of insect-derived peptides in melanoma through the regulation of transcription factor Sp1 protein, which is overexpressed in cancer, apoptosis, and cell cycle-related proteins. Taken together, this study aims to clarify the anticancer efficacy and safety of insect-derived peptides and to present their potential as future therapeutic agents.

GPS Coordinates for Modelling Correlated Herd Effects in Genomic Prediction Models Applied to Hanwoo Beef Cattle.

It is widely known that the environment influences phenotypic expression and that its effects must be accounted for in genetic evaluation programs. The most used method to account for environmental effects is to add herd and contemporary group to the model. Although generally informative, the herd effect treats different farms as independent units. However, if two farms are located physically close to each other, they potentially share correlated environmental factors. We introduce a method to model herd effects that uses the physical distances between farms based on the Global Positioning System (GPS) coordinates as a proxy for the correlation matrix of these effects that aims to account for similarities and differences between farms due to environmental factors. A population of Hanwoo Korean cattle was used to evaluate the impact of modelling herd effects as correlated, in comparison to assuming the farms as completely independent units, on the variance components and genomic prediction. The main result was an increase in the reliabilities of the predicted genomic breeding values compared to reliabilities obtained with traditional models (across four traits evaluated, reliabilities of prediction presented increases that ranged from 0.05 ± 0.01 to 0.33 ± 0.03), suggesting that these models may overestimate heritabilities. Although little to no significant gain was obtained in phenotypic prediction, the increased reliability of the predicted genomic breeding values is of practical relevance for genetic evaluation programs.

Multi-Probiotic Lactobacillus Supplementation Improves Liver Function and Reduces Cholesterol Levels in Jeju Native Pigs.

We evaluated the dietary effects of multiple probiotics in Jeju native pigs, using basal diet and multi-probiotic Lactobacillus (basal diet with 1% multi-probiotics) treatments (n = 9 each) for 3 months. We analyzed growth performance, feed efficiency, backfat thickness, blood parameters, hematological profiles, adipokines, and immune-related cytokines in pig tissues. Average daily gain, feed intake, feed efficiency, backfat thickness, and body weight were not significantly different between both groups. In Lactobacillus group, total protein (p < 0.08) and bilirubin (p < 0.03) concentrations increased; blood urea nitrogen (p < 0.08), alkaline phosphatase (p < 0.08), and gamma-glutamyltransferase (p < 0.08) activities decreased. Lactobacillus group showed decreased adiponectin (p < 0.05), chemerin (p < 0.05), and visfatin expression in adipose tissues, and increased TLR4 (p < 0.05), MYD88 (p < 0.05), TNF-α (p < 0.001), and IFN-γ (p < 0.001) expression in the liver. Additionally, NOD1 (p < 0.05), NOD2 (p < 0.01), and MYD88 (p < 0.05) mRNA levels in proximal colon tissue upregulated significantly. Colon, longissimus dorsi muscle, fat tissue, and liver histological analyses revealed no significant differences between the groups. Conclusively, Lactobacillus supplementation improved liver function and reduced cholesterol levels. Its application may treat metabolic liver disorders, especially cholesterol-related disorders.

Computational Insights into the Structural Dynamics of MDA5 Variants Associated with Aicardi-Goutières Syndrome and Singleton-Merten Syndrome.

Melanoma differentiation-associated protein 5 (MDA5) is a crucial RIG-I-like receptor RNA helicase enzyme encoded by IFIH1 in humans. Single nucleotide polymorphisms in the IFIH1 results in fatal genetic disorders such as Aicardi-Goutières syndrome and Singleton-Merten syndrome, and in increased risk of type I diabetes in humans. In this study, we chose four different amino acid substitutions of the MDA5 protein responsible for genetic disorders: MDA5L372F, MDA5A452T, MDA5R779H, and MDA5R822Q and analyzed their structural and functional relationships using molecular dynamic simulations. Our results suggest that the mutated complexes are relatively more stable than the wild-type MDA5. The radius of gyration, interaction energies, and intra-hydrogen bond analysis indicated the stability of mutated complexes over the wild type, especially MDA5L372F and MDA5R822Q. The dominant motions exhibited by the wild-type and mutant complexes varied significantly. Moreover, the betweenness centrality of the wild-type and mutant complexes showed shared residues for intra-signal propagation. The observed results indicate that the mutations lead to a gain of function, as reported in previous studies, due to increased interaction energies and stability between RNA and MDA5 in mutated complexes. These findings are expected to deepen our understanding of MDA5 variants and may assist in the development of relevant therapeutics against the disorders.

Erratum to: Comparisons of Chemical Composition, Flavor and Bioactive Substances between Korean and Imported Velvet Antler Extracts.

[This corrects the article DOI: 10.5851/kosfa.2021.e4.].