Meeting report on the 2019 international symposium of molecular design breeding in animals (Yangling,China) with the consensus on genome-editing agricultural animals and their regulation

Transgenic Research -     

Anti-IL-23 exerted protective effects on cerebral ischemia–reperfusion injury through JAK2/STAT3 signaling pathway

Molecular Biology Reports - Ischemia–reperfusion frequently occurs in ischemic cerebral vascular disease, during which the inflammatory signaling plays essential roles. The aim of this study...     

Unlocking the Recovery Potential: JMJD3 Inhibition-Mediated SAPK/JNK Signaling Inactivation Supports Endogenous Oligodendrocyte-Lineage Commitment Post Mammalian Spinal Cord Injury

Spinal cord injury (SCI) induced catastrophic neurological disability is often incurable at present. The injury triggered immediately oligodendrocytes loss and overwhelming demyelination are regarded as an insurmountable barrier to SCI recovery. To date, effective strategy to promote the endogenous oligodendrocytes replacement post SCI remains elusive. Epigenetic modifications are emerging as critical molecular switches of gene expression in CNS. However, the epigenetic mechanisms underlying oligodendrogenesis post SCI yet to be discovered. In this study, we report that H3K27me3 demethylase JMJD3 exists as a pivotal epigenetic regulator which manipulates the endogenous oligodendrogenesis post SCI. We found that JMJD3 inhibition promotes the oligodendrocyte linage commitment of neural stem/progenitor cells (NPCs) in vitro and in vivo. Moreover, we demonstrated that JMJD3 inhibition mediated SAPK/JNK signaling inactivation is functionally necessary for endogenous oligodendrocyte-lineage commitment post SCI. Our results also suggested that JMJD3 is downstream of SAPK/JNK pathway, and capable of translates SCI induced SAPK/JNK signaling into epigenetic codes readable by spinal cord endogenous NPCs. Taken together, our findings provide novel evidence of JMJD3 mediated oligodendrocyte-lineage commitment orchestration post SCI, which would be a potential epigenetic approach to induce the mature mammalian endogenous recovery.

     

A whole-genome association approach for large-scale interspecies traits

Science China Life Sciences -     

Circadian misalignment promotes vascular smooth muscle cell apoptosis via defective autophagy

Journal of Molecular Histology - Defective autophagy in vascular smooth muscle cells (VSMCs) in response to oxidative stress can lead to cellular apoptosis and plaque instability. Previous studies...     

The Fat Mass and Obesity-Associated (FTO) Gene is Associated with Intramuscular Fat Content and Growth Rate in the Pig

The association of the FTO gene with obesity has been implicated in various human populations. The FTO gene is also most likely involved in the regulation of energy balance and feed intake. Here, the FTO gene was studied as a candidate gene for fatness and growth rate traits in pigs. The amino acid sequence of the FTO gene showed high conservation among human, pig, and other important domestic animals. Twelve variants including ten SNPs and two indels were detected, and then five SNPs within different genomic regions were genotyped in the ISU Berkshire × Yorkshire pig resource family. The linkage disequilibrium analyses revealed that most of these FTO variants were not in strong LD with each other. The SNPs c.46–139A > T within intron 1 and a synonymous mutation c.594C > G (Ala198Ala) within exon 3 had significant (P < 0.01) associations with average daily gain on test and total lipid percentage in muscle, respectively. Five major haplotypes were identified and the subsequent association analyses suggested that haplotype 2 (-CTTGG-) was the most favorable for increased growth rate, while haplotype 1 (-CTACG-) was unfavorably associated with intramuscular fatness traits.     

Neurotoxicity of Perfluorooctane Sulfonate to Hippocampal Cells in Adult Mice

Perfluorooctane sulfonate (PFOS) is a ubiquitous pollutant and found in the environment and in biota. The neurotoxicity of PFOS has received much concern among its various toxic effects when given during developing period of brain. However, little is known about the neurotoxic effects and potential mechanisms of PFOS in the mature brain. Our study demonstrated the neurotoxicity and the potential mechanisms of PFOS in the hippocampus of adult mice for the first time. The impairments of spatial learning and memory were observed by water maze studies after exposure to PFOS for three months. Significant apoptosis was found in hippocampal cells after PFOS exposure, accompanied with a increase of glutamate in the hippocampus and decreases of dopamine (DA) and 3,4-dihydrophenylacetic acid (DOPAC) in Caudate Putamen in the 10.75 mg/kg PFOS group. By two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE) analysis, seven related proteins in the hippocampus that responded to PFOS exposure were identified, among which, Mib1 protein (an E3 ubiquitin-protein ligase), Herc5 (hect domain and RLD 5 isoform 2) and Tyro3 (TYRO3 protein tyrosine kinase 3) were found down-regulated, while Sdha (Succinate dehydrogenase flavoprotein subunit), Gzma (Isoform HF1 of Granzyme A precursor), Plau (Urokinase-type plasminogen activator precursor) and Lig4 (DNA ligase 4) were found up-regulated in the 10.75 mg/kg PFOS-treated group compare with control group. Furthermore, we also found that (i) increased expression of caspase-3 protein and decreased expression of Bcl-2, Bcl-XL and survivin proteins, (ii) the increased glutamate release in the hippocampus. All these might contribute to the dysfunction of hippocampus which finally account for the impairments of spatial learning and memory in adult mice.     

PAI-1 -675 4G/5G Polymorphism in Association with Diabetes and Diabetic Complications Susceptibility: a Meta-Analysis Study

A meta-analysis was performed to assess the association between the PAI-1 -675 4G/5G polymorphism and susceptibility to diabetes mellitus (DM), diabetic nephropathy (DN), diabetic retinopathy (DR) and diabetic coronary artery disease (CAD). A literature-based search was conducted to identify all relevant studies. The fixed or random effect pooled measure was calculated mainly at the allele level to determine heterogeneity bias among studies. Further stratified analyses and sensitivity analyses were also performed. Publication bias was examined by the modified Begg’s and Egger’s test. Twenty published articles with twenty-seven outcomes were included in the meta-analysis: 6 studies with a total of 1,333 cases and 3,011 controls were analyzed for the PAI-1 -675 4G/5G polymorphism with diabetes risk, 7 studies with 1,060 cases and 1,139 controls for DN risk, 10 studies with 1,327 cases and 1,557 controls for DR and 4 studies with 610 cases and 1,042 controls for diabetic CAD risk respectively. Using allelic comparison (4G vs. 5G), the PAI-1 -675 4G/5G polymorphism was observed to have no significant association with diabetes (REM OR 1.07, 95% CI 0.96, 1.20), DN (REM OR 1.10, 95% CI 0.98, 1.25), DR (REM OR 1.09, 95% CI 0.97, 1.22) or diabetic CAD risk (REM OR 1.07, 95% CI 0.81, 1.42), and similar results were obtained in the dominant, recessive and co-dominant models. Our meta-analyses suggest that the PAI-1 -675 4G/5G polymorphism might not be a risk factor for DM, DN, DR or diabetic CAD risk in the populations investigated. This conclusion warrants confirmation by further studies.