Project description:The gut microbiota is the largest and most complex microecosystem in animals. It is influenced by the host's dietary habits and living environment, and its composition and diversity play irreplaceable roles in animal nutrient metabolism, immunity, and adaptation to the environment. Although the gut microbiota of red deer has been studied, the composition and function of the gut microbiota in Gansu red deer (Cervus elaphus kansuensis), an endemic subspecies of red deer in China, has not been reported. In this study, the composition and diversity of the gut microbiome and fecal metabolomics of C. elaphus kansuensis were identified and compared for the first time by using 16S rDNA sequencing, metagenomic sequencing, and LC-MS/MS. There were significant differences in gut microbiota structure and diversity between wild and farmed C. elaphus kansuensis. The 16S rDNA sequencing results showed that the genus UCRD-005 was dominant in both captive red deer (CRD) and wild red deer (WRD). Metagenomic sequencing showed similar results to those of 16S rDNA sequencing for gut microbiota in CRD and WRD at the phylum and genus levels. 16S rDNA and metagenomics sequencing data suggested that Bacteroides and Bacillus might serve as marker genera for CRD and WRD, respectively. Fecal metabolomics results showed that 520 metabolites with significant differences were detected between CRD and WRD and most differential metabolites were involved in lipid metabolism. The results suggested that large differences in gut microbiota composition and fecal metabolites between CRD and WRD, indicating that different dietary habits and living environments over time have led to the development of stable gut microbiome characteristics for CRD and WRD to meet their respective survival and reproduction needs. KEY POINTS: • Environment and food affected the gut microbiota and fecal metabolites in red deer • Genera Bacteroides and Bacillus may play important roles in CRD and WRD, respectively • Flavonoids and ascorbic acid in fecal metabolites may influence health of red deer.
Project description:Circadian rhythm disturbances have long been associated with the development of psychiatric disorders, including mood and substance use disorders. Adolescence is a particularly vulnerable time for the onset of psychiatric disorders and for circadian rhythm and sleep disruptions. Preclinical studies have found that circadian rhythm disruption (CRD) impacts the brain and behavior, but this research is largely focused on adult disruptions. Here, we sought to determine the long-term behavioral and neurobiological effects of CRD during early adolescence by exposing mice to 12 h shifts in the light/dark cycle. We hypothesized that adolescent CRD would have a greater effect on psychiatric-related behaviors, relative to adult disruption. To identify possible mechanisms, we also measured gene expression in brain regions relevant to circadian rhythms, mood and reward. We found that disruption during early adolescence, but not adulthood, persistently increased exploratory drive (risk-taking behavior) and cocaine preference when tested later in life. Interestingly, we found sex differences when intravenous cocaine self-administration was tested. While female mice with a history of adolescent CRD had a greater propensity to self-administer cocaine, as well as increased motivation and cue-induced reinstatement, male adolescent CRD mice had reduced motivation and extinction responding. Overall, adolescent CRD in mice caused persistent increases in risky behavior, cocaine reward and cocaine self-administration, which suggests that CRD during adolescence may predispose individuals towards substance use disorders. Importantly, we found that many transcripts were affected by adolescent CRD and these were largely distinct across sex and brain region. Future research is required to elucidate how adolescent CRD affects behaviors relevant to mood- and substance use-related disorders across the 24-hour day, as well as to identify intervention strategies to alleviate disruption during adolescence and novel therapeutic approaches once symptoms have begun.
Project description:Methylation profiling in colorectal cancer : adjacent normal tissue vs colon tumor tissue indirect comparison experiment : CRD(common reference DNA) vs tumor-adjacent normal, CRD vs Colon tumor
Project description:Frequent shift work causes disruption of the circadian rhythm and might on the long-term result in increased health risk. Current biomarkers evaluating the presence of circadian rhythm disturbance (CRD) require 24-hr (around the clock) measurements, which is not practical for use in large-scale (human) studies. The aim of the present study was to identify universal biomarkers for CRD independent of time of day using a transcriptomics approach. Female FVB mice were exposed to six shifts in a clockwise (CW) and counterclockwise (CCW) CRD protocol and sacrificed at baseline and after 1 shift, 6 shifts, 5 days recovery and 14 days recovery, respectively. At six time-points during the day, livers were collected for mRNA microarray analysis. Bioinformatics analysis identified a set of universal markers for CRD. These biomarkers might be useful to measure CRD and can be used later on for monitoring the effectiveness of intervention strategies aiming to prevent or minimize chronic adverse health effects.
Project description:To characterize any differences in the effects of Circadian rhythm disorders (CRD) on mice of various ages, we selected young (8-week-old), and aged (18-month-old) mice and created a model of CRD by modifying the light/dark cycle under which they were housed.
Project description:CDCA7, encoding a protein with a C-terminal cysteine-rich domain (CRD), is mutated in immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome, a disease related to hypomethylation of peri/centromeric satellite DNA. Previous work suggests that the CDCA7 CRD is implicated in DNA binding, which plays a key role in directing the DNA methylation mechinery to peri/centromeric regions. To identify potential genomic targets of CDCA7, we performed ChIP-Seq using CDCA7 knockout (KO) mouse embryonic stem cells (mESCs) stably expressing HA-tagged wild-type (WT) or ICF mutant (R285H) mCDCA7.
Project description:Transducin is a heterotrimeric G protein that is a component of the phototransduction cascade in rod and cone photoreceptor cells of the retina. Gnat1, a rod-specific transducin α-subunit, regulates light/dark adaptation by changing its subcellular localization depending on light. Our previous study revealed that Gnat1 translocation in rod photoreceptor cells under light/dark conditions requires E3 ligase Klhl18-mediated ubiquitination and degradation of Unc119, a Gnat1-binding protein. A mutation in the human UNC119 gene is associated with cone-rod dystrophy (CRD); however, the underlying pathological mechanism remains unclear. In this study, we generated and analyzed Unc119-deficient (Unc119−/−) mice. We found that Unc119-deficienct mouse retina exhibited progressive photoreceptor degeneration, resembling CRD in humans. We also found that Unc119 interacts with Gnat2 in cone photoreceptor cells and that Unc119 is essential for the translocation of Gnat2 to the outer segment in cone photoreceptor cells. RNA-seq and subsequent bioinformatics analysis revealed the predicted activation of the JAK-STAT and NF-κB pathways in the Unc119−/− retina. Treatment of Unc119−/− mice with curcumin, an inhibitor of the JAK-STAT and NF-κB pathways, suppressed inflammation and cone photoreceptor cell degradation in Unc119−/− retinas. Furthermore, a human CRD associated-UNC119 mutant protein inhibited the interaction between UNC119 and GNAT1 or GNAT2. Taken together, the current study suggests that UNC119 dysfunction leads to CRD by affecting the JAK-STAT and NF-κB pathways, and may advance our understanding of the pathological mechanisms of CRD.