Myostatin, a member of the transforming growth factor-β (TGF-β) superfamily, has been shown to be a negative regulator of myogenesis. Here we show that myostatin functions by controlling the proliferation of muscle precursor cells. When C2C12 myoblasts were incubated with myostatin, proliferation of myoblasts decreased with increasing levels of myostatin. Fluorescence-activated cell sorting analysis revealed that myostatin prevented the progression of myoblasts from the G1- to S-phase of the cell cycle. Western analysis indicated that myostatin specifically up-regulated p21Waf1, Cip1, a cyclin-dependent kinase inhibitor, and decreased the levels and activity of Cdk2 protein in myoblasts. Furthermore, we also observed that in myoblasts treated with myostatin protein, Rb was predominately present in the hypophosphorylated form. These results suggests that, in response to myostatin signaling, there is an increase in p21 expression and a decrease in Cdk2 protein and activity thus resulting in an accumulation of hypophosphorylated Rb protein. This, in turn, leads to the arrest of myoblasts in G1-phase of cell cycle. Thus, we propose that the generalized muscular hyperplasia phenotype observed in animals that lack functional myostatin could be as a result of deregulated myoblast proliferation.

Myostatin, a negative regulator of muscle growth, functions by inhibiting myoblast proliferation.

MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.

MicroRNAs: Target Recognition and Regulatory Functions

The overuse of veterinary antibiotics in animal production and the subsequent land applications of manures contribute to the elevated antibiotic resistance in the soil environment. To minimize the risk of antibiotic resistance, it is important to understand the fate of antibiotics and the spread of antibiotic resistance genes (ARGs) from animal production systems to soil. In this paper, we review recent studies on veterinary antibiotic use, the concentrations of antibiotics and the abundance and diversity of AGRs in animal manures and in soil that receives manures or manure composts. The mechanisms of ARG dissemination in the environment are also discussed. Although we focus on China where around 3 billion tons of animal manures are produced and more than 84 000 tons of antibiotics are consumed annually in animal production industries, the problem is worldwide. Approximately 58% of the veterinary antibiotics consumed are excreted into the environment, more than half of which end up in the soil. The abundance of ARGs in manures can reach up to 10−1 of the 16S rRNA genes. Applications of manures or manure composts can enrich soil ARGs in at least three ways: (i) by the direct introduction of manure-derived ARGs, (ii) by elevating the intrinsic soil ARGs and (iii) by imposing a selection of ARGs with the antibiotics in the manures. We also discuss the need for more stringent regulations on the use of veterinary antibiotics and future research directions on the mechanisms of antibiotic resistance and resistance management.

Antibiotics and antibiotic resistance from animal manures to soil: a review

Colistin (Polymyxin E) is one of the few cationic antimicrobial peptides commercialized in both human and veterinary medicine. For several years now, colistin has been considered the last line of defense against infections caused by multidrug-resistant (MDR) Gram-negative such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Colistin has been extensively used orally since the 1960s in food animals and particularly in swine for the control of Enterobacteriaceae infections. However, with the recent discovery of plasmid-mediated colistin resistance encoded by the mcr-1 gene and the higher prevalence of samples harboring this gene in animal isolates compared to other origins, livestock has been singled out as the principal reservoir for colistin resistance amplification and spread. Co-localization of the mcr-1 gene and Extended-Spectrum- β-lactamase (ESBL) genes on a unique plasmid has been also identified in many isolates from animal origin. The use of colistin in pigs as a growth promoter and for prophylaxis purposes should be banned, and the implantation of sustainable measures in pig farms for microbial infection prevention should be actively encouraged and financed. The scientific research should be encouraged in swine medicine to generate data helping to reduce the exacerbation of colistin resistance in pigs and in manure. The establishment of guidelines ensuring a judicious therapeutic use of colistin in pigs, in countries where this drug is approved, is of crucial importance. The implementation of a microbiological withdrawal period that could reduce the potential contamination of consumers with colistin resistant bacteria of porcine origin should be encouraged. Moreover, the management of colistin resistance at the human-pig-environment interface requires the urgent use of the One Health approach for effective control and prevention. This approach needs the collaborative effort of multiple disciplines and close cooperation between physicians, veterinarians, and other scientific health and environmental professionals. This review is an update on the chemistry of colistin, its applications and antibacterial mechanism of action, and on Enterobacteriaceae resistance to colistin in pigs. We also detail and discuss the One Health approach and propose guidelines for colistin resistance management.

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Colistin in Pig Production: Chemistry, Mechanism of Antibacterial Action, Microbial Resistance Emergence, and One Health Perspectives.

Non-coding RNAs (ncRNAs) are regulators of intracellular and intercellular signaling in breast cancer. ncRNAs modulate intracellular signaling to control diverse cellular processes, including levels and activity of estrogen receptor α (ERα), proliferation, invasion, migration, apoptosis, and stemness. In addition, ncRNAs can be packaged into exosomes to provide intercellular communication by the transmission of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) to cells locally or systemically. This review provides an overview of the biogenesis and roles of ncRNAs: small nucleolar RNA (snRNA), circular RNAs (circRNAs), PIWI-interacting RNAs (piRNAs), miRNAs, and lncRNAs in breast cancer. Since more is known about the miRNAs and lncRNAs that are expressed in breast tumors, their established targets as oncogenic drivers and tumor suppressors will be reviewed. The focus is on miRNAs and lncRNAs identified in breast tumors, since a number of ncRNAs identified in breast cancer cells are not dysregulated in breast tumors. The identity and putative function of selected lncRNAs increased: nuclear paraspeckle assembly transcript 1 (NEAT1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), steroid receptor RNA activator 1 (SRA1), colon cancer associated transcript 2 (CCAT2), colorectal neoplasia differentially expressed (CRNDE), myocardial infarction associated transcript (MIAT), and long intergenic non-protein coding RNA, Regulator of Reprogramming (LINC-ROR); and decreased levels of maternally-expressed 3 (MEG3) in breast tumors have been observed as well. miRNAs and lncRNAs are considered targets of therapeutic intervention in breast cancer, but further work is needed to bring the promise of regulating their activities to clinical use.

Non-Coding RNAs in Breast Cancer: Intracellular and Intercellular Communication.

Long noncoding RNAs (lncRNAs) have been reported to play diverse roles in biologic and pathologic processes, including myogenesis. We found that lncRNA AK017368 is highly expressed in skeletal muscle cells. Functional analyses showed that overexpression of AK017368 promoted proliferation and restrained differentiation of myoblasts; whereas inhibition of AK017368 had completely opposite effects in vitro In mice, knockdown of AK017368 promoted muscle hypertrophy in vivo RNA molecules of AK017368 acted mechanistically as competing endogenous RNAs to target micro-RNA (miR)-30c, which was supported by the results of bioinformatics analyses and dual-luciferase reporter assays. It has been shown that lncRNA AK017368 competes with trinucleotide repeat containing-6A (Tnrc6a) for miR-30c. Tnrc6a was previously reported to promote proliferation and inhibit differentiation of myoblast cells, whereas miR-30c targets the 3'-UTR of Tnrc6a mRNA to weaken its function. Taken together, lncRNA AK017368 promotes proliferation and inhibits differentiation of myoblast cells by attenuating function of miR-30c.-Liang, T., Zhou, B., Shi, L., Wang, H., Chu, Q., Xu, F., Li, Y., Chen, R., Shen, C., Schinckel, A. P. lncRNA AK017368 promotes proliferation and suppresses differentiation of myoblasts in skeletal muscle development by attenuating the function of miR-30c.

lncRNA AK017368 promotes proliferation and suppresses differentiation of myoblasts in skeletal muscle development by attenuating the function of miR-30c.

MicroRNA-128 targets myostatin at coding domain sequence to regulate myoblasts in skeletal muscle development.

Stocking density affects welfare indicators of growing pigs of different group sizes after regrouping

Estrus expression by gilts and sows is hereditable and important for heat detection. To better understand the molecular biological mechanisms of estrus expression in gilts, the mRNA expression profiles of follicular tissue from Large White gilts in diestrus (LD, n = 3) and estrus (LE, n = 3), and Chinese indigenous Mi gilts in diestrus (MD, n = 2) and estrus (ME, n = 3) were investigated using RNA sequencing. We detected 122,804-335,295 SNPs, 6,140-14,947 InDel and 12 types of AS events (39.57% TSS, 34.90% TTS) in 11 samples. A total of 2,838 differentially expressed genes (DEGs) were found in LD vs MD, LE vs ME, LE vs LD, or ME vs MD comparisons. Two DEGs (ACP5 and PIGS) were observed in all comparisons. Two new genes (ENSSSCG00000028235 and ENSSSCG00000021903) were exclusively expressed in Mi and Large White gilts, respectively. Bioinformatics analyses indicate that these DEGs are involved in single-organism process, catalytic activity, cell adhesion and enriched in ECM-receptor interaction, olfactory transduction, ovarian steroidogenesis, steroid biosynthesis and CAMs signaling pathways. These results of RNA-Seq have provided important information for screening the key functional genes or molecular markers of estrus expression in gilts.

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Genome-wide differential mRNA expression profiles in follicles of two breeds and at two stages of estrus cycle of gilts

Micro-696 (miR-696) has been previously known as an exercise related miRNA, which has a profound role in fatty acid oxidation and mitochondrial biogenesis of skeletal muscle. However, its role in skeletal myoblast proliferation and differentiation is still unclear. In this study, we found that miR-696 expressed highly in skeletal muscle and reduced during C2C12 myoblasts differentiation. MiR-696 overexpression repressed C2C12 myoblast proliferation and myofiber formation, while knockdown of endogenous miR-696 expression showed opposite results. During myogenesis, we observed an inversed expression pattern between miR-696 and CNTFRα in vitro, and demonstrated that miR-696 could specifically target CNTFRα and repress the expression of CNTFRα. Additionally, we further found that knockdown of CNTFRα suppressed the proliferation and differentiation of C2C12 cells. Taking all things together, we propose a novel insight that miR-696 down-regulates C2C12 cell myogenesis by inhibiting CNTFRα expression.

/pdf/mir-696-regulates-c2c12-cell-proliferation-and-2318qtn4sd.pdf

Tingting Liang

Papers

lncRNA AK017368 promotes proliferation and suppresses differentiation of myoblasts in skeletal muscle development by attenuating the function of miR-30c.

MicroRNA-128 targets myostatin at coding domain sequence to regulate myoblasts in skeletal muscle development.

Stocking density affects welfare indicators of growing pigs of different group sizes after regrouping

Genome-wide differential mRNA expression profiles in follicles of two breeds and at two stages of estrus cycle of gilts

MiR-696 Regulates C2C12 Cell Proliferation and Differentiation by Targeting CNTFRα.