DNA Methylation Fluctuation Induced by Virus Infection Differs between MD-resistant and -susceptible Chickens

Marek’s disease (MD) is a lymphoproliferative disease induced by Marek’s disease virus (MDV) infection. To augment vaccination measures in MD control, host genetic resistant to MD becomes obviously more and more important. To elucidate the mechanism of MD-resistance, most of researches were focused on the genetic differences between resistant and susceptible chickens. However, epigenetic features between MD resistant and susceptible chickens are poorly characterized. Using bisulfite pyrosequencing method, we found some candidate genes have higher promoter methylation in the MD-susceptible (L72) chickens than in the MD-resistant (L63) chickens. The hypermethylated genes, involved in cellular component organization, responding to stimulus, cell adhesion, and immune system process, may play important role in susceptibility to disease by deregulation of these genes. MDV infection induced the expression changes of all three methyltransferases genes (DNMT1, DNMT3a, and DNMT3b) in both lines of chickens. The DNMT1 was up-regulated in L72, whereas the DNMT3b was down-regulated in L63 at 21 dpi. Interestingly, a dynamic change of promoter methylation was observed during MDV life cycle. Some genes, including HDAC9, GH, STAT1, CIITA, FABP3, LATS2, and H2Ac, showed differential methylation behaviors between the two lines of chickens. In summary, the findings from this study suggested that DNA methylation heterogeneity and MDV infection induced methylation alterations differences existed between the two lines of chickens. Therefore, it is suggested that epigenetic mechanisms may be involved in modulating the resistance and/or susceptibility to MD in chickens

Gene Expression Analysis Reveals Novel Gene Signatures Between Young and Old Adults in Human Prefrontal Cortex

Human neurons function over an entire lifetime, yet the molecular mechanisms which perform their functions and protecting against neurodegenerative disease during aging are still elusive. Here, we conducted a systematic study on the human brain aging by using the weighted gene correlation network analysis (WGCNA) method to identify meaningful modules or representative biomarkers for human brain aging. Significantly, 19 distinct gene modules were detected based on the dataset GSE53890; among them, six modules related to the feature of brain aging were highly preserved in diverse independent datasets. Interestingly, network feature analysis confirmed that the blue modules demonstrated a remarkably correlation with human brain aging progress. Besides, the top hub genes including PPP3CB, CAMSAP1, ACTR3B, and GNG3 were identified and characterized by high connectivity, module membership, or gene significance in the blue module. Furthermore, these genes were validated in mice of different ages. Mechanically, the potential regulators of blue module were investigated. These findings highlight an important role of the blue module and its affiliated genes in the control of normal brain aging, which may lead to potential therapeutic interventions for brain aging by targeting the hub genes

Histone modifications induced by MDV infection at early cytolytic and latency phases

Marek’s disease (MD) is a highly contagious, lymphomatous disease of chickens induced by a herpesvirus, Marek’s disease virus (MDV) that is the cause of major annual losses to the poultry industry. MD pathogenesis involves multiple stages including an early cytolytic phase and latency, and transitions between these stages are governed by several host and environmental factors. The success of vaccination strategies has led to the increased virulence of MDV and selective breeding of naturally resistant chickens is seen as a viable alternative. While multiple gene expression studies have been performed in resistant and susceptible populations, little is known about the epigenetic effects of infection. In this study, we investigated temporal chromatin signatures induced by MDV by analyzing early cytolytic and latent phases of infection in the bursa of Fabricius of MD-resistant and –susceptible birds. Major global variations in chromatin marks were observed at different stages of MD in the two lines. Differential H3K27me3 marks were associated with immune-related pathways, such as MAP kinase signaling, focal adhesion and neuroactive ligand receptor interaction, and suggested varying degrees of silencing in response to infection. Immune-related microRNAs, e.g. gga-miR-155 and gga-miR-10b, bore chromatin signatures, which suggested their contribution to MD-susceptibility. Finally, several members of the focal adhesion pathway, e.g. THBS4 and ITGA1, showed marked concordance between gene expression and chromatin marks indicating putative epigenetic regulation in response to MDV infection. Our comprehensive analysis of chromatin signatures, therefore, revealed further clues about the epigenetic effects of MDV infection although further studies are necessary to elucidate the functional implications of the observed variations in histone modifications.https://doi.org/10.1186/s12864-015-1492-

Temporal transcriptome changes induced by MDV in marek's disease-resistant and -susceptible inbred chickens

<p>Abstract</p> <p>Background</p> <p>Marek's disease (MD) is a lymphoproliferative disease in chickens caused by Marek's disease virus (MDV) and characterized by T cell lymphoma and infiltration of lymphoid cells into various organs such as liver, spleen, peripheral nerves and muscle. Resistance to MD and disease risk have long been thought to be influenced both by genetic and environmental factors, the combination of which contributes to the observed outcome in an individual. We hypothesize that after MDV infection, genes related to MD-resistance or -susceptibility may exhibit different trends in transcriptional activity in chicken lines having a varying degree of resistance to MD.</p> <p>Results</p> <p>In order to study the mechanisms of resistance and susceptibility to MD, we performed genome-wide temporal expression analysis in spleen tissues from MD-resistant line 6₃, susceptible line 7₂and recombinant congenic strain M (RCS-M) that has a phenotype intermediate between lines 6₃and 7₂after MDV infection. Three time points of the MDV life cycle in chicken were selected for study: 5 days post infection (dpi), 10dpi and 21dpi, representing the early cytolytic, latent and late cytolytic stages, respectively. We observed similar gene expression profiles at the three time points in line 6₃and RCS-M chickens that are both different from line 7₂. Pathway analysis using Ingenuity Pathway Analysis (IPA) showed that MDV can broadly influence the chickens irrespective of whether they are resistant or susceptible to MD. However, some pathways like cardiac arrhythmia and cardiovascular disease were found to be affected only in line 7₂; while some networks related to cell-mediated immune response and antigen presentation were enriched only in line 6₃and RCS-M. We identified 78 and 30 candidate genes associated with MD resistance, at 10 and 21dpi respectively, by considering genes having the same trend of expression change after MDV infection in lines 6₃and RCS-M. On the other hand, by considering genes with the same trend of expression change after MDV infection in lines 7₂and RCS-M, we identified 78 and 43 genes at 10 and 21dpi, respectively, which may be associated with MD-susceptibility.</p> <p>Conclusions</p> <p>By testing temporal transcriptome changes using three representative chicken lines with different resistance to MD, we identified 108 candidate genes for MD-resistance and 121 candidate genes for MD-susceptibility over the three time points. Genes included in our resistance or susceptibility genes lists that are also involved in more than 5 biofunctions, such as <it>CD8α</it>, <it>IL8</it>, <it>USP18</it>, and <it>CTLA4</it>, are considered to be important genes involved in MD-resistance or -susceptibility. We were also able to identify several biofunctions related with immune response that we believe play an important role in MD-resistance.</p

Histone methylation analysis and pathway predictions in chickens after MDV infection.

Marek's disease (MD) is a lymphoproliferative disease in chicken induced by Marek's disease virus (MDV). Although studies have focused on the genetic differences between the resistant and susceptible chicken, less is known about the role of epigenetic factors in MD. In this study, genome-wide histone modifications in the non-MHC-associated resistant and susceptible chicken lines were examined. We found that tri-methylation at histone H3 Lys4 (H3K4me3) enrichment is positively correlated with the expression of protein coding genes as well as microRNA (miRNA) genes, whereas tri-methylation at histone H3 Lys27 (H3K27me3) exhibits a negative correlation. By identifying line-specific histone modifications in MDV infection, we found unique H3K4me3 islands in the resistant chicken activated genes, which are related to immune response and cell adhesion. Interestingly, we also found some miRNAs from unique H3K27me3 patterns in the susceptible chickens that targeted genes involved in 5-hydroxytryptamine (5-HT)-receptor and adrenergic receptor pathways. In conclusion, dynamic line-specific histone modifications in response to MDV infection suggested that intrinsic epigenetic mechanisms may play a role in MD-resistance and -susceptibility

The Role of Acupuncture Improving Cognitive Deficits due to Alzheimer’s Disease or Vascular Diseases through Regulating Neuroplasticity

Dementia affects millions of elderly worldwide causing remarkable costs to society, but effective treatment is still lacking. Acupuncture is one of the complementary therapies that has been applied to cognitive deficits such as Alzheimer’s disease (AD) and vascular cognitive impairment (VCI), while the underlying mechanisms of its therapeutic efficiency remain elusive. Neuroplasticity is defined as the ability of the nervous system to adapt to internal and external environmental changes, which may support some data to clarify mechanisms how acupuncture improves cognitive impairments. This review summarizes the up-to-date and comprehensive information on the effectiveness of acupuncture treatment on neurogenesis and gliogenesis, synaptic plasticity, related regulatory factors, and signaling pathways, as well as brain network connectivity, to lay ground for fully elucidating the potential mechanism of acupuncture on the regulation of neuroplasticity and promoting its clinical application as a complementary therapy for AD and VCI