Systemic identification of functionally conserved lncRNA metabolic regulators in human and mouse livers.

Background & Aims: Unlike protein-coding genes, the majority of human long non-coding RNAs (lncRNAs) lack conservation based on their sequences, posing a challenge for investigating their role in a pathophysiological context for clinical translation. This study explores the hypothesis that non-conserved lncRNAs in human and mouse livers may share similar metabolic functions, giving rise to functionally conserved lncRNA metabolic regulators (fcLMRs).

Methods: We developed a sequence-independent strategy to select putative fcLMRs, and performed extensive analysis to determine the functional similarities of putative human and mouse LMR pairs (h/mLMRs).

An Integrative Transcriptome Subtraction Strategy to Identify Human lncRNAs That Specifically Play a Role in Activation of Human Hepatic Stellate Cells.

Fibrotic liver features excessive deposition of extracellular matrix (ECM), primarily produced from "activated" hepatic stellate cells (HSCs). While targeting human HSCs (hHSCs) in fibrosis therapeutics shows promise, the overall understanding of hHSC activation remains limited, in part because it is very challenging to define the role of human long non-coding RNAs (lncRNAs) in hHSC activation. To address this challenge, we identified another cell type that acts via a diverse gene network to promote fibrogenesis.

Comprehensive gene profiling of the metabolic landscape of humanized livers in mice.

Background & Aims: The human liver transcriptome is complex and highly dynamic, e.g. one gene may produce multiple distinct transcripts, each with distinct posttranscriptional modifications.

FcRn is not the receptor mediating the transfer of serum IgG to colostrum in pigs.

In contrast to humans or rabbits, in which maternal IgG is transmitted to offspring prenatally via the placenta or the yolk sac, large domestic animals such as pigs, cows and sheep transmit IgG exclusively through colostrum feeding after delivery. The extremely high IgG content in colostrum is absorbed by newborns via the small intestine. Although it is widely accepted that the neonatal Fc receptor, FcRn, is the receptor mediating IgG transfer across both the placenta and small intestine, it remains unclear whether FcRn also mediates serum IgG transfer across the mammary barrier to colostrum/milk, especially in large domestic animals.

Identification of Accessible Hepatic Gene Signatures for Interindividual Variations in Nutrigenomic Response to Dietary Supplementation of Omega-3 Fatty Acids.

Dietary supplementation is a widely adapted strategy to maintain nutritional balance for improving health and preventing chronic diseases. Conflicting results in studies of similar design, however, suggest that there is substantial heterogenicity in individuals' responses to nutrients, and personalized nutrition is required to achieve the maximum benefit of dietary supplementation. In recent years, nutrigenomics studies have been increasingly utilized to characterize the detailed genomic response to a specific nutrient, but it remains a daunting task to define the signatures responsible for interindividual variations to dietary supplements for tissues with limited accessibility.

Long noncoding RNAs-a new dimension in the molecular architecture of the bile acid/FXR pathway.

Bile acids, regarded as the body's detergent for digesting lipids, also function as critical signaling molecules that regulate cholesterol and triglyceride levels in the body. Bile acids are the natural ligands of the nuclear receptor, FXR, which controls an intricate network of cellular pathways to maintain metabolic homeostasis. In recent years, growing evidence supports that many cellular actions of the bile acid/FXR pathway are mediated by long non-coding RNAs (lncRNAs), and lncRNAs are in turn powerful regulators of bile acid levels and FXR activities.

In Vivo Functional Analysis of Nonconserved Human lncRNAs Using a Humanized Mouse Model.

LncRNAs (long noncoding RNAs) are transcripts that are at least 200 nucleotides long and lack any predicted coding potential. Whereas significant progress has been made in deciphering the function of mouse lncRNAs, critical gaps remain in understanding how human lncRNAs exercise their function in a physiological context. As most human lncRNAs are currently considered nonconserved and often do not have homologs in mouse, the technical bottleneck is the lack of a suitable model to study the physiological function.

Comparative Transcriptomics Analyses in Livers of Mice, Humans, and Humanized Mice Define Human-Specific Gene Networks.

Mouse is the most widely used animal model in biomedical research, but it remains unknown what causes the large number of differentially regulated genes between human and mouse livers identified in recent years. In this report, we aim to determine whether these divergent gene regulations are primarily caused by environmental factors or some of them are the result of cell-autonomous differences in gene regulation in human and mouse liver cells. The latter scenario would suggest that many human genes are subject to human-specific regulation and can only be adequately studied in a human or humanized system.

Identification of human long noncoding RNAs associated with nonalcoholic fatty liver disease and metabolic homeostasis.

A growing number of long noncoding RNAs (lncRNAs) have emerged as vital metabolic regulators. However, most human lncRNAs are nonconserved and highly tissue specific, vastly limiting our ability to identify human lncRNA metabolic regulators (hLMRs). In this study, we established a pipeline to identify putative hLMRs that are metabolically sensitive, disease relevant, and population applicable.

In vivo functional analysis of non-conserved human lncRNAs associated with cardiometabolic traits.

Unlike protein-coding genes, the majority of human long non-coding RNAs (lncRNAs) are considered non-conserved. Although lncRNAs have been shown to function in diverse pathophysiological processes in mice, it remains largely unknown whether human lncRNAs have such in vivo functions. Here, we describe an integrated pipeline to define the in vivo function of non-conserved human lncRNAs.

Corrigendum: Genetic Removal of the CH1 Exon Enables the Production of Heavy Chain-Only IgG in Mice.

[This corrects the article DOI: 10.3389/fimmu.2018.

Genetic Removal of the CH1 Exon Enables the Production of Heavy Chain-Only IgG in Mice.

Nano-antibodies possess great potential in many applications. However, they are naturally derived from heavy chain-only antibodies (HcAbs), which lack light chains and the CH1 domain, and are only found in camelids and sharks. In this study, we investigated whether the precise genetic removal of the CH1 exon of the γ1 gene enabled the production of a functional heavy chain-only IgG1 in mice.

Analysis of TCRβ and TCRγ genes in Chinese alligator provides insights into the evolution of TCR genes in jawed vertebrates.

All jawed vertebrates have four T cell receptor (TCR) chains that are expressed by thymus-derived lymphocytes and play a major role in animal immune defence. However, few studies have investigated the TCR chains of crocodilians compared with those of birds and mammals, despite their key evolutionary position linking amphibians, reptiles, birds and mammals. Here, employing an Alligator sinensis genomic bacterial artificial chromosome (BAC) library and available genome data, we characterized the genomic organization, evolution and expression of TRB and TRG loci in Alligator sinensis.

Truncation of the Murine Neonatal Fc Receptor Cytoplasmic Tail Does Not Alter IgG Metabolism or Transport In Vivo.

The neonatal Fc receptor (FcRn) is involved in IgG metabolism and transport in placental mammals. However, whether FcRn is responsible for IgG transfer from maternal serum to colostrum/milk is controversial. Interestingly, large domestic animals, such as cows, pigs, sheep, and horses, in which passive IgG transfer is exclusively completed via colostrum/milk, all express an FcRn α-chain that is shorter in the cytoplasmic tail (CYT) than its counterparts in humans and rodents.

A comprehensive analysis of the germline and expressed TCR repertoire in White Peking duck.

Recently, many immune-related genes have been extensively studied in ducks, but relatively little is known about their TCR genes. Here, we determined the germline and expressed repertoire of TCR genes in White Peking duck. The genomic organization of the duck TCRα/δ, TCRγ and unconventional TCRδ2 loci are highly conserved with their counterparts in mammals or chickens.

The interactions between nerve growth factor and gonadotrophins in bovine oviduct.

Nerve growth factor promotes the survival and differentiation of nervous cells and is thought to play an important role in the development of reproductive tissues. The aims of this work were to detect the presence of NGF and its receptor NTRK1 in bovine oviduct samples, and to investigate the regulatory interactions between NGF/NTRK1 and gonadotrophins in bovine oviduct epithelial cells. Both transcripts and proteins of NGF and NTRK1 were detected by RT-PCR and Western blotting, and the corresponding proteins were specifically immunolocalized in oviduct epithelial cells.

Interaction between neurotrophin 4 and gonadotrophin in bovine oviducts.

The expression and localization of neurotrophin 4 (NT4) and its receptor, tyrosine kinase B (TRKB), in the bovine oviduct, and their interaction with gonadotrophins in bovine oviduct epithelial cells (BOECs), were examined. Transcripts for NT4 and TRKB were detected by reverse transcription polymerase chain reaction (RT-PCR) in bovine oviducts in the follicular and luteal phases, and their proteins were immunolocalized in BOECs. Based on real time PCR, NT4 mRNA did not differ significantly between the two phases of the cycle, although TRKB mRNA expression was higher (P < 0.

Molecular cloning, polymorphism and tissue distribution of the MHC class IIB gene in the Chinese goose (Anser cygnoides).

1. The goose major histocompatibility complex (MHC) class IIB cDNA (Ancy-MHCII) was cloned by homology cloning and rapid amplification of cDNA ends by polymerase chain reaction (RACE-PCR), and the genomic structure and tissue expression were investigated. 2.

Construction and characterization of a recombinant canine adenovirus expressing GP5 and M proteins of porcine reproductive and respiratory syndrome virus.

The causative agent of porcine reproductive and respiratory syndrome (PRRS) is PRRS virus (PRRSV), which belongs to the family Arteriviridae. GP5/M protein complex of PRRSV binds to sialoadhesion expressed on the cells to infect the cells. In this study, we developed a canine adenovirus type 2 (CAV-2) recombinant, termed rCAV2-GP5/M, expressing GP5 and M proteins.