Pre- and post-transcriptional modifications of gene expression are emerging as foci of disease studies, with some studies revealing the importance of non-coding transcripts, like long non-coding RNAs (lncRNAs) and microRNAs (miRNAs). We hypothesize that transcription factors (TFs), lncRNAs and miRNAs modulate immune response in bovine mastitis and could potentially serve as disease biomarkers and/or drug targets. With computational analyses, we identified candidate genes potentially regulated by miRNAs and lncRNAs base pair complementation and thermodynamic stability of binding regions. Remarkably, we found six miRNAs, two being bta-miR-223 and bta-miR-24-3p, to bind to several targets. LncRNAs NONBTAT027932.1 and XR_003029725.1, were identified to target several genes. Functional and pathway analyses revealed lipopolysaccharide-mediated signaling pathway, regulation of chemokine (C-X-C motif) ligand 2 production and regulation of IL-23 production among others. The overarching interactome deserves further in vitro/in vivo explication for specific molecular regulatory mechanisms during bovine mastitis immune response and could lay the foundation for development of disease markers and therapeutic intervention.

Journal of Animal Science and Technology (JAST) is a peer-reviewed, open access journal publishing original research, review articles and notes in all fields of animal science. Topics covered by the journal include: genetics and breeding, physiology, nutrition of monogastric animals, nutrition of ruminants, animal products (milk, meat, eggs and their by-products) and their processing, grasslands and roughages, livestock environment, animal biotechnology, animal behavior and welfare.

Background and Aim: Global Health is threatened by the rapid emergence of multidrug-resistant bacteria. Antibiotic resistomes rapidly evolve, yet conserved motifs elucidated in our study have the potential for future drug targets for precision medicine. This study aimed to identify conserved genetic sequences and their evolutionary pathways among vancomycin-resistant Enterococcus species such as Enterococcus faecium and Enterococcus faecalis. Materials and Methods: We retrieved a total of 26 complete amino acid and nucleotide sequences of resistance determinant genes against vancomycin (vanA and vanB), streptomycin (aac-aah), and penicillin (pbp5) from the publicly available genetic sequence database, GenBank. The sequences were comprised of bacteria classified under the genera of Enterococcus, Staphylococcus, Amycolatopsis, Ruminococcus, and Clostridium. Sequences were aligned with Clustal Omega Multiple Sequence Alignment program and Percent Identity Matrices were derived. Phylogenetic analyses to elucidate evolutionary relationships between sequences were conducted with the neighbor-end joining method through the Molecular Evolutionary Genetics Analysis (MEGAX) software, developed by the Institute of Molecular Evolutionary Genetics at Pennsylvania State University. Subsequent network analyses of the resistance gene, vanB, within E. faecium were derived from ScanProsite and InterPro. Results: We observed the highest nucleotide sequence similarity of vanA regions within strains of E. faecium (100%) and E. faecalis (100%). Between Enterococcus genera, we continued to observe high sequence conservation for vanA and vanB, up to 99.9% similarity. Phylogenetic tree analyses suggest rapid acquisition of these determinants between strains within vanA and vanB, particularly between strains of Enterococcus genera, which may be indicative of horizontal gene transfer. Within E. faecium, Adenosine 5'-Triphosphate (ATP)-Grasp and D-ala-D-ala ligase (Ddl) were found as conserved domains of vanA and vanB. We additionally found that there is notable sequence conservation, up to 66.67%, between resistomes against vancomycin and streptomycin among E. faecium. Conclusion: Resistance genes against vancomycin have highly conserved sequences between strains of Enterococcus bacteria. These conserved sequences within vanA and vanB encode for ATP-Grasp and Ddl motifs, which have functional properties for maintaining cell wall integrity. High sequence conservation is also observed among resistance genes against penicillin and streptomycin, which can inform future drug targets for broader spectrum therapies.

Renal cell carcinoma (RCC), a prevalent form of renal malignancy, is distinguished by its proclivity for robust tumor proliferation and metastatic dissemination. Long non-coding RNAs (lncRNAs) have emerged as pivotal modulators of gene expression, exerting substantial influence over diverse biological processes, encompassing the intricate landscape of cancer development. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), an exemplar among lncRNAs, has been discovered to assume functional responsibilities within the context of RCC. The conspicuous expression of MALAT-1 in RCC cells has been closely linked to the advancement of tumors and an unfavorable prognosis. Experimental evidence has demonstrated the pronounced ability of MALAT-1 to stimulate RCC cell proliferation, migration, and invasion, thereby underscoring its active participation in facilitating the metastatic cascade. Furthermore, MALAT-1 has been implicated in orchestrating angiogenesis, an indispensable process for tumor expansion and metastatic dissemination, through its regulatory influence on pro-angiogenic factor expression. MALAT-1 has also been linked to the evasion of immune surveillance in RCC, as it can regulate the expression of immune checkpoint molecules and modulate the tumor microenvironment. Hence, the potential utility of MALAT-1 as a diagnostic and prognostic biomarker in RCC emerges, warranting further investigation and validation of its clinical significance. This comprehensive review provides an overview of the diverse functional roles exhibited by MALAT-1 in RCC.

We investigated whole blood and hepatic mRNA expressions of immune genes and rumen microbiome of crossbred beef steers with divergent residual feed intake phenotype to identify relevant biological processes underpinning feed efficiency in beef cattle. Low-RFI beef steers (n = 20; RFI = − 1.83 kg/d) and high-RFI beef steers (n = 20; RFI = + 2.12 kg/d) were identified from a group of 108 growing crossbred beef steers (average BW = 282 ± 30.4 kg) fed a high-forage total mixed ration after a 70-d performance testing period. At the end of the 70-d testing period, liver biopsies and blood samples were collected for total RNA extraction and cDNA synthesis. Rumen fluid samples were also collected for analysis of the rumen microbial community. The mRNA expression of 84 genes related to innate and adaptive immunity was analyzed using pathway-focused PCR-based arrays. Differentially expressed genes were determined usingP-value ≤ 0.05 and fold change (FC) ≥ 1.5 (in whole blood) or ≥ 2.0 (in the liver). Gene ontology analysis of the differentially expressed genes revealed that pathways related to pattern recognition receptor activity, positive regulation of phagocytosis, positive regulation of vitamin metabolic process, vascular endothelial growth factor production, positive regulation of epithelial tube formation and T-helper cell differentiation were significantly enriched (FDR < 0.05) in low-RFI steers. In the rumen, the relative abundance ofPeH15, Arthrobacter, Moryella, Weissella, and Muribaculaceaewas enriched in low-RFI steers, whileMethanobrevibacter, Bacteroidales_BS11_gut_group, Bacteroides and Clostridium_sensu_stricto_1were reduced. In conclusion, our study found that low-RFI beef steers exhibit increased mRNA expression of genes related to immune cell functions in whole blood and liver tissues, specifically those involved in pathogen recognition and phagocytosis regulation. Additionally, these low-RFI steers showed differences in the relative abundance of some microbial taxa which may partially account for their improved feed efficiency compared to high-RFI steers.

The cluster differentiation gene (CD14) is a family of monocyte differentiating genes that works in conjunction with lipopolysaccharide binding protein, forming a complex with TLR4 or LY96 to mediate innate immune response to pathogens. In this paper, we used different computational methods to elucidate the evolution of CD14 gene coding region in 14 mammalian species. Our analyses identified leucine-rich repeats as the only significant domain across the CD14 protein of the 14 species, presenting with frequencies ranging from one to four. Importantly, we found signal peptides located at mutational hotspots demonstrating that this gene is conserved across these species. Out of the 10 selected variants analyzed in this study, only six were predicted to possess significant deleterious effect. Our predicted protein interactome showed a significant varying protein–protein interaction with CD14 protein across the species. This may be important for drug target and therapeutic manipulation for the treatment of many diseases. We conclude that these results contribute to our understanding of the CD14 molecular evolution, which underlays varying species response to complex disease traits.