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Endometritis is an inflammatory disease that negatively influences fertility and is common in milk-producing cows. An in vitro model for bovine endometrial inflammation was used to identify enrichment of cis-acting regulatory elements in differentially methylated regions (DMRs) in the genome of in vitro-cultured primary bovine endometrial epithelial cells (bEECs) before and after treatment with lipopolysaccharide (LPS) from E. coli, a key player in the development of endometritis. The enriched regulatory elements contain binding sites for transcription factors with established roles in inflammation and hypoxia including NFKB and Hif-1α. We further showed co-localization of certain enriched cis-acting regulatory motifs including ARNT, Hif-1α, and NRF1. Our results show an intriguing interplay between increased mRNA levels in LPS-treated bEECs of the mRNAs encoding the key transcription factors such as AHR, EGR2, and STAT1, whose binding sites were enriched in the DMRs. Our results demonstrate an extraordinary cis-regulatory complexity in these DMRs having binding sites for both inflammatory and hypoxia-dependent transcription factors. Obtained data using this in vitro model for bacterial-induced endometrial inflammation have provided valuable information regarding key transcription factors relevant for clinical endometritis in both cattle and humans. [ABSTRACT FROM AUTHOR]

Cashmere goats possess two types of hair follicles, with the secondary hair follicles producing valuable cashmere fiber used for textiles. The growth of cashmere exhibits a seasonal pattern arising from photoperiod change. Transcription factors play crucial roles during this process. The transcription factor, cold-shock domain, containing C2 (Csdc2) plays a crucial role in modulating cell proliferation and differentiation. Our preceding research indicated that the expression of Csdc2 changes periodically during anagen to telogen. However, the mechanisms of Csdc2 in regulating SHF growth remain unclear. Here, we found that the knockdown of Csdc2 inhibits the proliferation of dermal papilla cells. ChIP-Seq analysis showed that Csdc2 had a unique DNA binding motif in SHFs. Through conjoint analysis of ChIP-Seq and RNA-Seq, we revealed a total of 25 candidate target genes of Csdc2. Notably, we discovered a putative Csdc2 binding site within roundabout guidance receptor 2 (Robo2) on chromosome 1 of the goat genome. Furthermore, qRT-PCR and dual-luciferase reporter assay confirmed Csdc2's positive regulatory influence on Robo2. These findings expand the research field of hair follicle transcriptional regulatory networks, offering insights into molecular breeding strategies to enhance cashmere production in goats. [ABSTRACT FROM AUTHOR]

In this study, our primary aim was to explore the genomic landscape of Barka cattle, a breed recognized for high milk production in a semi-arid environment, by focusing on genes with known roles in milk production traits. We employed genome-wide analysis and three selective sweep detection methods (ZFST, θπ ratio, and ZHp) to identify candidate genes associated with milk production and composition traits. Notably, ACAA1, P4HTM, and SLC4A4 were consistently identified by all methods. Functional annotation highlighted their roles in crucial biological processes such as fatty acid metabolism, mammary gland development, and milk protein synthesis. These findings contribute to understanding the genetic basis of milk production in Barka cattle, presenting opportunities for enhancing dairy cattle production in tropical climates. Further validation through genome-wide association studies and transcriptomic analyses is essential to fully exploit these candidate genes for selective breeding and genetic improvement in tropical dairy cattle. [ABSTRACT FROM AUTHOR]

The evolutionary conserved Notch signaling pathway functions as a mediator of direct cell–cell communication between neighboring cells during development. Notch plays a crucial role in various fundamental biological processes in a wide range of tissues. Accordingly, the aberrant signaling of this pathway underlies multiple genetic pathologies such as developmental syndromes, congenital disorders, neurodegenerative diseases, and cancer. Over the last two decades, significant data have shown that the Notch signaling pathway displays a significant function in the mature brains of vertebrates and invertebrates beyond neuronal development and specification during embryonic development. Neuronal connection, synaptic plasticity, learning, and memory appear to be regulated by this pathway. Specific mutations in human Notch family proteins have been linked to several neurodegenerative diseases including Alzheimer's disease, CADASIL, and ischemic injury. Neurodegenerative diseases are incurable disorders of the central nervous system that cause the progressive degeneration and/or death of brain nerve cells, affecting both mental function and movement (ataxia). There is currently a lot of study being conducted to better understand the molecular mechanisms by which Notch plays an essential role in the mature brain. In this study, an in silico analysis of polymorphisms and mutations in human Notch family members that lead to neurodegenerative diseases was performed in order to investigate the correlations among Notch family proteins and neurodegenerative diseases. Particular emphasis was placed on the study of mutations in the Notch3 protein and the structure analysis of the mutant Notch3 protein that leads to the manifestation of the CADASIL syndrome in order to spot possible conserved mutations and interpret the effect of these mutations in the Notch3 protein structure. Conserved mutations of cysteine residues may be candidate pharmacological targets for the potential therapy of CADASIL syndrome. [ABSTRACT FROM AUTHOR]

Simple Summary: Abigar cattle, native to southwestern Ethiopia's hot and humid environment, are recognized for their adaptability and vital contribution to local livelihoods and the livestock value chain. Investigating their genetic basis for adaptive traits is crucial for sustainable use. However, there is a paucity of studies on genomic diversity, population structure, and selection signatures of Abigar cattle. This study introduces the first whole-genome sequencing of Abigar cattle, revealing genes linked to heat tolerance, immune response, and stress resilience in tropical conditions. These findings offer essential genomic insights for future Abigar cattle breeding. Over time, indigenous cattle breeds have developed disease resistance, heat tolerance, and adaptability to harsh environments. Deciphering the genetic mechanisms underlying adaptive traits is crucial for their improvement and sustainable utilization. For the first time, we performed whole-genome sequencing to unveil the genomic diversity, population structure, and selection signatures of Abigar cattle living in a tropical environment. The population structure analysis revealed that Abigar cattle exhibit high nucleotide diversity and heterozygosity, with low runs of homozygosity and linkage disequilibrium, suggesting a genetic landscape less constrained by inbreeding and enriched by diversity. Using nucleotide diversity (Pi) and population differentiation (FST) selection scan methods, we identified 83 shared genes that are likely associated with tropical adaption. The functional annotation analysis revealed that some of these genes are potentially linked to heat tolerance (HOXC13, DNAJC18, and RXFP2), immune response (IRAK3, MZB1, and STING1), and oxidative stress response (SLC23A1). Given the wider spreading impacts of climate change on cattle production, understanding the genetic mechanisms of adaptation of local breeds becomes crucial to better respond to climate and environmental changes. In this context, our finding establishes a foundation for further research into the mechanisms underpinning cattle adaptation to tropical environments. [ABSTRACT FROM AUTHOR]

Lipopolysaccharide (LPS) is a component of the outer membrane of Gram-negative bacteria involved in the pathogenic processes leading to mastitis and metritis in animals such as dairy cattle. LPS causes cell proliferation associated with endometrium inflammation. Former in vitro studies have demonstrated that LPS induces an intense stimulation of the proliferation of a pure population of bovine endometrial epithelial cells. In a follow-up transcriptomic study based on RNA-sequencing data obtained after 24 h exposure of primary bovine endometrial epithelial cells to 0, 2, and 8 μg/mL LPS, 752 and 727 differentially expressed genes (DEGs) were detected between the controls and LPS-treated samples that encode proteins known to be associated with either proliferation or apoptosis, respectively. The present bioinformatic analysis was performed to decipher the gene networks involved to obtain a deeper understanding of the mechanisms underlying the proliferative and apoptosis processes. Our findings have revealed 116 putative transcription factors (TFs) and the most significant number of interactions between these TFs and DEGs belong to NFKβ1, TP53, STAT1, and HIF1A. Moreover, our results provide novel insights into the early signaling and metabolic pathways in bovine endometrial epithelial cells associated with the innate immune response and cell proliferation to Escherichia coli-LPS infection. The results further indicated that LPS challenge elicited a strong transcriptomic response, leading to potent activation of pro-inflammatory pathways that are associated with a marked endometrial cancer, Toll-like receptor, NFKβ, AKT, apoptosis, and MAPK signaling pathways. This effect may provide a mechanistic explanation for the relationship between LPS and cell proliferation. [ABSTRACT FROM AUTHOR]

Anaerobic digestion (AD) has long been critical technology for green energy, but the majority of the microorganisms involved are unknown and are currently not cultivable, which makes abundance tracking difficult. Developments in nanopore long-read sequencing make it a promising approach for monitoring microbial communities via metagenomic sequencing. For reliable monitoring of AD via long reads, we established a robust protocol for obtaining less fragmented, high-quality DNA, while preserving bacteria and archaea composition, for a broad range of different biogas reactors. Samples from 20 different biogas/wastewater reactors were investigated, and a median of 20.5 Gb sequencing data per nanopore flow cell was retrieved for each reactor using the developed DNA isolation protocol. The nanopore sequencing data were compared against Illumina sequencing data while using different taxonomic indices for read classifications. The Genome Taxonomy Database (GTDB) index allowed sufficient characterisation of the abundance of bacteria and archaea in biogas reactors with a dramatic improvement (1.8- to 13-fold increase) in taxonomic classification compared to the RefSeq index. Both technologies performed similarly in taxonomic read classification with a slight advantage for Illumina in regard to the total proportion of classified reads. However, nanopore sequencing data revealed a higher genus richness after classification. Metagenomic read classification via nanopore provides a promising approach to monitor the abundance of taxa present in a microbial AD community as an alternative to 16S ribosomal RNA studies or Illumina Sequencing. [ABSTRACT FROM AUTHOR]

Syntrophic acetate oxidation operates close to the thermodynamic equilibrium and very little is known about the participating organisms and their metabolism. Clostridium ultunense is one of the most abundant syntrophic acetate-oxidising bacteria (SAOB) that are found in engineered biogas processes operating with high ammonia concentrations. It has been proven to oxidise acetate in cooperation with hydrogenotrophic methanogens. There is evidence that the Wood-Ljungdahl (WL) pathway plays an important role in acetate oxidation. In this study, we analysed the physiological and metabolic capacities of C. ultunense strain Esp and strain BST on genome scale and conducted a comparative study of all the known characterised SAOB, namely Syntrophaceticus schinkii, Thermacetogenium phaeum, Tepidanaerobacter acetatoxydans, and Pseudothermotoga lettingae. The results clearly indicated physiological robustness to be beneficial for anaerobic digestion environments and revealed unexpected metabolic diversity with respect to acetate oxidation and energy conservation systems. Unlike S. schinkii and Th. phaeum, C. ultunense clearly does not employ the oxidative WL pathway for acetate oxidation, as its genome (and that of P. lettingae) lack important key genes. In both of those species, a proton motive force is likely formed by chemical protons involving putative electron-bifurcating [Fe-Fe] hydrogenases rather than proton pumps. No genes encoding a respiratory Ech (energy-converting hydrogenase), as involved in energy conservation in Th. phaeum and S. schinkii, were identified in C. ultunense and P. lettingae. Moreover, two respiratory complexes sharing similarities to the proton-translocating ferredoxin:NAD+ oxidoreductase (Rnf) and the Na+ pumping NADH:quinone hydrogenase (NQR) were predicted. These might form a respiratory chain that is involved in the reduction of electron acceptors rather than protons. However, involvement of these complexes in acetate oxidation in C. ultunense and P. lettingae needs further study. This genome-based comparison provides a solid platform for future meta-proteomics and meta-transcriptomics studies and for metabolic engineering, control, and monitoring of SAOB. [ABSTRACT FROM AUTHOR]