Project description:Psychedelics are a broad class of drugs defined by their ability to induce an altered state of consciousness. These drugs have been used for millennia in both spiritual and medicinal contexts, and a number of recent clinical successes have spurred a renewed interest in developing psychedelic therapies. Nevertheless, a unifying mechanism that can account for these shared phenomenological and therapeutic properties remains unknown. Here we demonstrate in mice that the ability to reopen the social reward learning critical period is a shared property across psychedelics. Interestingly, the time course of critical period reopening is proportional to the duration of acute subjective effects reported in humans. Furthermore, the ability to reinstate social reward learning in adulthood is paralleled by metaplastic restoration of oxytocin mediated long-term depression (OT-LTD) in the Nucleus Accumbens (NAc). Finally, identification of differentially expressed genes in the ‘open state’ versus ‘closed state’, provides evidence that reorganization of the extracellular matrix (ECM) is a common downstream mechanism underlying psychedelic mediated critical period reopening. Together these results have significant implications for the implementation of psychedelics in clinical practice, as well as the design of novel compounds for the treatment of neuropsychiatric disease.
Project description:To investigate the differential dynamic plasma miRNA profiles during the peri-implantation period in patients with different reproductive outcomes following embryo transfer. 10 negative pregnancy (NP) patients, 10 biochemical pregnancy loss (BPL) patients, and 10 clinical pregnancy (CP) patients were enrolled for miRNA-seq in this study. Peripheral blood samples were collected at three time-points (ET0, ET11, and ET14) from BPL patients and CP patients, and samples were collected at two time-points (ET0 and ET11) from NP patients. Small RNA libraries were constructed using peripheral plasma RNA. miRNA-seq was used to investigate the differential dynamic peripheral miRNA changes between the three groups during the peri-implantation period.
Project description:Conceptus implantation to the uterine endometrium is required for pregnancy establishment, during which non-invasive trophoblasts attach and adhere to the uterine endometrium or invasive trophoblasts invade into the uterine stroma, followed by placental formation in most mammalian species. During peri-implantation period, conceptuses must communicate with the uterine endometrium if they are to survive and proceed to attachment to the uterine epithelium. Despite numerous studies performed on the bovine species, molecular mechanisms associated with their attachment processes, particularly the initial attachment to the endometrial epithelium, have not been well characterized.
Project description:In this study, we performed a comprehensive evaluation of proteomic profile in the pituitary gland of Huoyan geese during laying period compared to pre-laying period and using iTRAQ based approach. 684 proteins which including 418 up-regulated and 266 down-regulated were identified. Subsequently, GO enrichment and KEGG pathway analyses of those proteins were conducted.
Project description:In the developing brain, heightened plasticity during the critical period enables the proper formation of neural circuits. Here we identify the “navigator” neurons, a group of perinatally born olfactory sensory neurons, as playing an essential role in establishing the olfactory map during the critical period. The navigator axons project circuitously in the olfactory bulb and traverse multiple glomeruli before terminating in perspective glomeruli. These neurons undergo a phase of exuberant axon growth and exhibit a shortened lifespan. Single cell transcriptome analyses reveal distinct molecular signatures for the navigators. Extending their lifespan prolongs the period of exuberant growth and perturbs axon convergence. Conversely, genetic ablation experiment indicates that, despite postnatal neurogenesis, only the navigators are endowed with the ability to establish a convergent map. The presence and the proper removal of the navigator neurons are both required to establish tight axon convergence into the glomeruli.
Project description:The metabolome is a central determinant of human phenotypes and includes the plethora of small molecules produced by host and microbiome, or taken up from exogenous sources. However, studies of the metabolome have so far focused predominantly on urban, industrialized populations. Through an untargeted metabolomic analysis of 90 fecal samples from human individuals from Africa and the Americas—the birthplace and the last continental expansion of our species, respectively—we characterized a shared human fecal metabolome. The majority of detected metabolite features were ubiquitous across populations, despite any geographic, dietary, or behavioral differences. Such shared metabolite features included hyocholic acid and cholesterol. However, any characterization of the shared human fecal metabolome is insufficient without exploring the influence of industrialization. Here, we show chemical differences along an industrialization gradient, where the degree of industrialization correlates with metabolomic changes. We identified differential metabolite features like amino acid-conjugated bile acids and urobilin as major metabolic correlates of these behavioral shifts. Additionally, co-analyses with over 5,000 publicly available human fecal samples and co-occurrence probability analyses with the gut microbiome highlight connections between the human fecal metabolome and gut microbiome. Our results indicate that industrialization significantly influences the human fecal metabolome, but diverse human lifestyles and behavior still maintain a shared human fecal metabolome. This study represents the first characterization of the shared human fecal metabolome through untargeted analyses of populations along an industrialization gradient.