There is evidence for hypercortisolemia playing a role in the generation of psychiatric symptoms and for epigenetic variation within hypothalamic-pituitary-adrenal (HPA) axis genes mediating behavioral changes. We tested the hypothesis that expression changes would be induced in Fkbp5 and other HPA axis genes by chronic exposure to corticosterone and that these changes would occur through the epigenetic mechanism of loss or gain of DNA methylation (DNAm). We administered corticosterone (CORT) to C57BL/6J mice via their drinking water for 4 wk and tested for behavioral and physiological changes and changes in gene expression levels using RNA extracted from hippocampus, hypothalamus, and blood for the following HPA genes: Fkbp5, Nr3c1, Hsp90, Crh, and Crhr1. The CORT mice exhibited anxiety-like behavior in the elevated plus maze test. Chronic exposure to CORT also caused a significant decrease in the hippocampal and blood mRNA levels of Nr3c1 and a decrease in Hsp90 in blood and caused an increase in Fkbp5 for all tissues. Differences were seen in Fkbp5 methylation in hippocampus and hypothalamus. To isolate a single-cell type, we followed up with an HT-22 mouse hippocampal neuronal cell line exposed to CORT. After 7 d, we observed a 2.4-fold increase in Fkbp5 expression and a decrease in DNAm. In the CORT-treated mice, we also observed changes in blood DNAm in Fkbp5. Our results suggest DNAm plays a role in mediating effects of glucocorticoid exposure on Fkbp5 function, with potential consequences for behavior.

Sweet osmanthus (Osmanthus fragrans) is a very popular ornamental tree species throughout Southeast Asia and USA particularly for its extremely fragrant aroma. We constructed a chromosome-level reference genome of O. fragrans to assist in studies of the evolution, genetic diversity, and molecular mechanism of aroma development. A total of over 118 Gb of polished reads was produced from HiSeq (45.1 Gb) and PacBio Sequel (73.35 Gb), giving 100× depth coverage for long reads. The combination of Illumina-short reads, PacBio-long reads, and Hi-C data produced the final chromosome quality genome of O. fragrans with a genome size of 727 Mb and a heterozygosity of 1.45 %. The genome was annotated using de novo and homology comparison and further refined with transcriptome data. The genome of O. fragrans was predicted to have 45,542 genes, of which 95.68 % were functionally annotated. Genome annotation found 49.35 % as the repetitive sequences, with long terminal repeats (LTR) being the richest (28.94 %). Genome evolution analysis indicated the evidence of whole-genome duplication 15 million years ago, which contributed to the current content of 45,242 genes. Metabolic analysis revealed that linalool, a monoterpene is the main aroma compound. Based on the genome and transcriptome, we further demonstrated the direct connection between terpene synthases (TPSs) and the rich aromatic molecules in O. fragrans. We identified three new flower-specific TPS genes, of which the expression coincided with the production of linalool. Our results suggest that the high number of TPS genes and the flower tissue- and stage-specific TPS genes expressions might drive the strong unique aroma production of O. fragrans.

A polymorphism in the mu-opioid receptor (MOR) (A118G) has been shown to increase b-endorphin binding affinity, theoretically placing greater inhibitory tone on hypothalamic corticotropin-releasing hormone (CRH) neurons. We hypothesized that the minor allele (G) would predict cortisol responses to both pharmacological (naloxone) and psychological (stress) activation of the hypothalamicpituitary-adrenal (HPA) axis. Healthy subjects (mean age 25.2 years, SD 9.2 years) completed a naloxone challenge (n ¼ 74) and/or the modified Trier Social Stress Test (TSST) (n ¼ 86). For the naloxone challenge, two baseline blood samples were obtained. Then, five increasing doses of i.v. naloxone were administered at 30-min intervals and 12 additional blood samples were collected at 15-min intervals. The TSST consisted of 5-min of public speaking and 5-min of mental arithmetic exercises. Three baseline and five post-TSST blood samples were drawn. Both the naloxone and TSST groups had significant adrenocorticotropin (ACTH) and cortisol responses to their respective challenges (Po0.001). There were no differences in baseline ACTH, baseline cortisol, or ACTH response by genotype in either the naloxone or the TSST group. Among subjects expressing a G allele, there was a higher cortisol response to naloxone (P ¼ 0.046), but a lower cortisol response to the TSST (P ¼ 0.044). In conclusion, the minor allele (G) was associated with a robust cortisol response to naloxone blockade, but a blunted response to psychosocial stress. We speculate that increased opioid avidity of the minor allele receptor contributes to the differential response to naloxone vs stress.

Since May 2015, severe outbreaks of hepatitis-hydropericardium syndrome (HHS) associated with infections of fowl aviadenovirus (FAdV) have emerged in broiler chickens in several Chinese provinces. To identify the genotype and gain a better understanding of the genetic properties of the FAdV strains responsible for the recent HHS outbreaks in China, the complete genome sequences of five isolates from outbreaks of HHS in broiler chickens in five provinces were determined. The results demonstrated that a novel fowl aviadenovirus 4 (FAdV-4) genotype was epidemic in China. To investigate the molecular characteristics of these Chinese FAdV-4 isolates, their genome contents were compared with those of reported pathogenic and non-pathogenic FAdV-4 strains. The comparative analysis revealed that the novel Chinese FAdV-4 isolates contain various genomic deletions and multiple distinct amino-acid mutations in their major structural genes. Two additional putative genetic virulence markers in the fiber 2 gene were identified. These findings confirmed some of the genetic differences between the pathogenic and non-pathogenic FAdV-4 isolates. The data presented in this report will enhance the current understanding of the molecular epidemiology and genetic diversity of FAdV-4 isolates in China and will provide additional insight into the critical factors that determine the pathogenicity of FAdV-4 strains. Finally, the emergence of this novel and highly pathogenic FAdV-4 genotype emphasizes that preventive measures against FAdV-4 infections on poultry farms should be implemented in China.