BACKGROUND AND AIM Cholestasis comprises a spectrum of liver diseases characterized by accumulation of bile acids. Bile acids and activation of the bile acid receptor FXR can inhibit autophagy, a cellular self-digestion process necessary for cell homeostasis and regeneration. In mice autophagy appears to be impaired in cholestasis and induction of autophagy may reduce liver injury. METHODS Here we explored autophagy in human cholestasis in vivo and investigated the underlying molecular mechanisms in vitro. RESULTS In cholestatic patients and individuals treated with the FXR ligand obeticholic acid (OCA) autophagy processing appeared to be impaired. In vitro, chenodeoxycholic acid and OCA inhibited autophagy at the level of autophagosome-to-lysosome fusion in an FXR dependent manner. FXR ChIP-seq and ChIP-qPCR in a human cholestatic liver sample combined with luciferase promoter studies revealed that Rubicon, which inhibits autophago-lysosomal maturation, is a direct FXR target and is induced in cholestasis and by FXR agonistic bile acids. Genetic inhibition of Rubicon reversed bile acid induced autophagic flux impairment. In contrast to OCA, ursodeoxycholic acid (UDCA), which is a non-FXR-agonistic bile acid, induced autophago-lysosome formation FXR independently and enhanced autophagic flux along with reduction of Rubicon. CONCLUSION Autophagy processing is impaired in models of human cholestatic conditions in an FXR dependent manner, in part by induction of Rubicon. UDCA is a potent inducer of hepatic autophagy. Manipulating autophagy and Rubicon may represent a novel treatment concept for cholestatic liver diseases. The role of gonadotropins during early ovarian development in fish remains little understood. Concentrations of gonadotropins were therefore experimentally elevated in vivo by administration of recombinant follicle-stimulating hormone (rec-Fsh) or human chorionic gonadotropin (hCG) and the effects on ovarian morphology, sex steroid levels and mRNA levels of genes expressed in pituitary and ovary examined. Hormones were injected thrice at weekly intervals in different doses (20, 100 or 500 µg/kg BW for rec-Fsh and 20, 100 or 500 IU/kg BW for hCG). All treatments, especially at the highest doses of either rec-Fsh or hCG, induced ovarian development, reflected in increased oocyte size and lipid uptake. Both gonadotropins up-regulated follicle-stimulating hormone receptor (fshr) mRNA levels and plasma levels of estradiol-17β (E2). Exogenous gonadotropins largely decreased the expression of follicle-stimulating hormone β-subunit (fshb) and had little effect on those of luteinizing hormone β-subunit (lhb) in the pituitary. It is proposed that the effects of hCG on ovarian development in previtellogenic eels could be indirect as a significant increase in plasma levels of 11-ketotestosterone (11-KT) was found in eels treated with hCG. Using rec-Fsh and hCG has potential for inducing puberty in eels in captivity, and indeed, in teleost fish at large. Epidermal growth factor (EGF) has important physiological functions that are mediated by the epidermal growth factor receptor (EGFR); however, to date, the changes in cellular behaviours and signalling properties of EGF/EGFR with aging remain unclear in the pig tissue models. Hence, the present study used porcine hepatocytes as a model to explore this issue. The study revealed the following results 1) EGF could activate the intra-cellular signalling pathways in a time- and dose-dependent manner both in the young- and aged-pig hepatocytes, EGF induced tyrosine phosphorylation of EGFR, signal transducers and activators of transcription 3 (STAT3), protein kinase B (AKT) and extra-cellular signal-regulated kinase 1/2 (ERK1/2). Nevertheless, the EGF's signalling ability in the aged-pig hepatocytes was significantly reduced compared with that of the young-pig hepatocytes; 2) although EGF/EGFR can still be internalised into cells in a time-dependent manner with aging, the endocytic pathway differs between the young- and aged-pig hepatocytes. Furthermore, the results of the present study indicated that caveolin may play a pivotal role in the endocytosis of EGF/EGFR in the aged-pig hepatocytes, which is different from that of EGF/EGFR's endocytosis in young-pig hepatocytes; 3) It is well-known that EGFR carried out its biological effects via two signalling pathways, cytoplasmic pathway (traditional) and nuclear pathway; however, we found that the nuclear localisation of EGFR was significantly reduced in the aged-pig hepatocytes, which indicated that EGFR may lose its nuclear pathway with aging. Collectively, the present study lays the foundation for further study regarding the biological functional changes occurring in EGF/EGFR with aging. The present study investigates hemispheric asymmetry of the ERPs and low-frequency oscillatory responses evoked in both hemispheres of the brain by the sound stimuli with delayed onset of motion. https://www.selleckchem.com/products/nivolumab.html EEG was recorded for three patterns of sound motion produced by changes in interaural time differences. Event-related spectral perturbation (ERSP) and inter-trial phase coherence (ITC) were computed from the time-frequency decomposition of EEG signals. The participants either read books of their choice (passive listening) or indicated the sound trajectories perceived using a graphic tablet (active listening). Our goal was to find out whether the lateralization of the motion-onset response (MOR) and oscillatory responses to sound motion were more consistent with the right-hemispheric dominance, contralateral or neglect model of interhemispheric asymmetry. Apparent dominance of the right hemisphere was found only in the ERSP responses. Stronger contralaterality of the left hemisphere corresponding to the "neglect model" of asymmetry was shown by the MOR components and by the phase coherence of the delta-alpha oscillations. Velocity and attention did not change consistently the interhemispheric asymmetry of both the MOR and the oscillatory responses. Our findings demonstrate how the lateralization pattern shown by the MOR potential was interrelated with that of the motion-related single-trial measures.