Abstract
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.
Cattle pastoralism plays a central role in human livelihood in Africa. However, the genetic history of its success remains unknown. Here, through whole-genome sequence analysis of 172 indigenous ...African cattle from 16 breeds representative of the main cattle groups, we identify a major taurine × indicine cattle admixture event dated to circa 750-1,050 yr ago, which has shaped the genome of today's cattle in the Horn of Africa. We identify 16 loci linked to African environmental adaptations across crossbred animals showing an excess of taurine or indicine ancestry. These include immune-, heat-tolerance- and reproduction-related genes. Moreover, we identify one highly divergent locus in African taurine cattle, which is putatively linked to trypanotolerance and present in crossbred cattle living in trypanosomosis-infested areas. Our findings indicate that a combination of past taurine and recent indicine admixture-derived genetic resources is at the root of the present success of African pastoralism.
Febrifugine, the bioactive constituent of one of the 50 fundamental herbs of traditional Chinese medicine, has been characterized for its therapeutic activity, though its molecular target has ...remained unknown. Febrifugine derivatives have been used to treat malaria, cancer, fibrosis and inflammatory disease. We recently demonstrated that halofuginone (HF), a widely studied derivative of febrifugine, inhibits the development of T(H)17-driven autoimmunity in a mouse model of multiple sclerosis by activating the amino acid response (AAR) pathway. Here we show that HF binds glutamyl-prolyl-tRNA synthetase (EPRS), inhibiting prolyl-tRNA synthetase activity; this inhibition is reversed by the addition of exogenous proline or EPRS. We further show that inhibition of EPRS underlies the broad bioactivities of this family of natural product derivatives. This work both explains the molecular mechanism of a promising family of therapeutics and highlights the AAR pathway as an important drug target for promoting inflammatory resolution.
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.
The history of African indigenous cattle and their adaptation to environmental and human selection pressure is at the root of their remarkable diversity. Characterization of this diversity is an ...essential step towards understanding the genomic basis of productivity and adaptation to survival under African farming systems.
We analyze patterns of African cattle genetic variation by sequencing 48 genomes from five indigenous populations and comparing them to the genomes of 53 commercial taurine breeds. We find the highest genetic diversity among African zebu and sanga cattle. Our search for genomic regions under selection reveals signatures of selection for environmental adaptive traits. In particular, we identify signatures of selection including genes and/or pathways controlling anemia and feeding behavior in the trypanotolerant N'Dama, coat color and horn development in Ankole, and heat tolerance and tick resistance across African cattle especially in zebu breeds.
Our findings unravel at the genome-wide level, the unique adaptive diversity of African cattle while emphasizing the opportunities for sustainable improvement of livestock productivity on the continent.
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
The importance of probiotics in swine production is widely acknowledged as crucial. However, gaps still remain in the exact roles played by probiotics in modulation of gut microbiota and immune ...response. This study determined the roles of probiotic Lactobacillus plantarum strain JDFM LP11in gut microbiota modulation and immune response in weaned piglets. L. plantarum JDFM LP11 increased the population of lactic acid bacteria in feces and enhanced the development of villi in the small intestine. Metagenome analysis showed that microbial diversity and richness (Simpson, Shannon, ACE, Chao1) and the relative abundance of the Firmicutes were higher in weaned piglets fed probiotics. Five bacterial families were different in the relative abundance, especially; Prevotellaceae occupied the largest part of microbial community showed the most difference between two groups. Transcriptome analysis identified 25 differentially expressed genes using RNA-sequencing data of the ileum. Further gene ontology and immune DB analysis determined 8 genes associated with innate defense response and cytokine production. BPI, RSAD2, SLPI, LUM, OLFM4, DMBT1 and C6 genes were down-regulated by probiotic supplementation except PLA2G2A. PICRUSt analysis predicting functional profiling of microbial communities indicated branched amino acid biosynthesis and butyrate metabolism promoting gut development and health were increased by probiotics. Altogether, our data suggest that L. plantarum JDFM LP11 increases the diversity and richness in the microbial community, and attenuates the ileal immune gene expression towards gut inflammation, promoting intestinal development in weaned piglets.
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.
Probiotics in livestock feed supplements are considered a replacement for antibiotics that enhance gastrointestinal immunity. Although bacterial cell wall components have been proposed to be ...associated with probiotic function, little evidence demonstrates that they are responsible for probiotic functions in livestock. The present study demonstrated that lipoteichoic acid (LTA) of
(Lp.LTA) confers anti-inflammatory responses in porcine intestinal epithelial cell line, IPEC-J2. A synthetic analog of viral double-stranded RNA, poly I:C, dose-dependently induced IL-8 production at the mRNA and protein levels in IPEC-J2 cells. Lp.LTA, but not lipoprotein or peptidoglycan from
, exclusively suppressed poly I:C-induced IL-8 production. Compared with LTAs from other probiotic
strains including
,
, and
GG, Lp.LTA had higher potential to suppress poly I:C-induced IL-8 production. Dealanylated or deacylated Lp.LTA did not suppress poly I:C-induced IL-8 production, suggesting that D-alanine and lipid moieties in the Lp.LTA structure were responsible for the inhibition. Furthermore, Lp.LTA attenuated the phosphorylation of ERK and p38 kinase as well as the activation of NF-κB, resulting in decreased IL-8 production. Taken together, these results suggest that Lp.LTA acts as an effector molecule to inhibit viral pathogen-induced inflammatory responses in porcine intestinal epithelial cells.
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 (
= 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.
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