157 research outputs found

    Interactions between sleep, stress, and metabolism: From physiological to pathological conditions

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    AbstractPoor sleep quality due to sleep disorders and sleep loss is highly prevalent in the modern society. Underlying mechanisms show that stress is involved in the relationship between sleep and metabolism through hypothalamic–pituitary–adrenal (HPA) axis activation. Sleep deprivation and sleep disorders are associated with maladaptive changes in the HPA axis, leading to neuroendocrine dysregulation. Excess of glucocorticoids increase glucose and insulin and decrease adiponectin levels. Thus, this review provides overall view of the relationship between sleep, stress, and metabolism from basic physiology to pathological conditions, highlighting effective treatments for metabolic disturbances

    Primary Human Hepatocytes Repopulate Livers of Mice After In Vitro Culturing and Lentiviral-Mediated Gene Transfer

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    Cell-based therapies represent a promising alternative to orthotopic liver transplantation. However, therapeutic effects are limited by low cell engraftment rates. We recently introduced a technique creating human hepatocyte spheroids for potential therapeutic application. The aim of this study was to evaluate whether these spheroids are suitable for engraftment in diseased liver tissues. Intrasplenic spheroid transplantation into immunodeficient uPA/SCID/beige mice was performed. Hepatocyte transduction ability prior to transplantation was tested by lentiviral labeling using red-green-blue (RGB) marking. Eight weeks after transplantation, animals were sacrificed and livers were analyzed by immunohistochemistry and immunofluorescence. To investigate human hepatocyte-specific gene expression profiles in mice, quantitative real-time-PCR was applied. Human albumin and alpha-1-antitrypsin concentrations in mouse serum were quantified to assess the levels of human chimerism. Precultured human hepatocytes reestablished their physiological liver tissue architecture and function upon transplantation in mice. Positive immunohistochemical labeling of the proliferating cell nuclear antigen revealed that human hepatocytes retained their in vivo proliferation capacity. Expression profiles of human genes analyzed in chimeric mouse livers resembled levels determined in native human tissue. Extensive vascularization of human cell clusters was detected by demonstration of von Willebrand factor activity. To model gene therapy approaches, lentiviral transduction was performed ex vivo and fluorescent microscopic imaging revealed maintenance of RGB marking in vivo. Altogether, this is the first report demonstrating that cultured and retroviral transduced human hepatocyte spheroids are able to engraft and maintain their regenerative potential in vivo

    A deep learning approach to identify local structures in atomic-resolution transmission electron microscopy images

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    Recording atomic-resolution transmission electron microscopy (TEM) images is becoming increasingly routine. A new bottleneck is then analyzing this information, which often involves time-consuming manual structural identification. We have developed a deep learning-based algorithm for recognition of the local structure in TEM images, which is stable to microscope parameters and noise. The neural network is trained entirely from simulation but is capable of making reliable predictions on experimental images. We apply the method to single sheets of defected graphene, and to metallic nanoparticles on an oxide support.Comment: v2: Typo in author list correcte

    High-Resolution Electron Microscopy of Semiconductor Heterostructures and Nanostructures

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    This chapter briefly describes the fundamentals of high-resolution electron microscopy techniques. In particular, the Peak Pairs approach for strain mapping with atomic column resolution, and a quantitative procedure to extract atomic column compositional information from Z-contrast high-resolution images are presented. It also reviews the structural, compositional, and strain results obtained by conventional and advanced transmission electron microscopy methods on a number of III–V semiconductor nanostructures and heterostructures

    Sleep and immune function

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    Sleep and the circadian system exert a strong regulatory influence on immune functions. Investigations of the normal sleep–wake cycle showed that immune parameters like numbers of undifferentiated naïve T cells and the production of pro-inflammatory cytokines exhibit peaks during early nocturnal sleep whereas circulating numbers of immune cells with immediate effector functions, like cytotoxic natural killer cells, as well as anti-inflammatory cytokine activity peak during daytime wakefulness. Although it is difficult to entirely dissect the influence of sleep from that of the circadian rhythm, comparisons of the effects of nocturnal sleep with those of 24-h periods of wakefulness suggest that sleep facilitates the extravasation of T cells and their possible redistribution to lymph nodes. Moreover, such studies revealed a selectively enhancing influence of sleep on cytokines promoting the interaction between antigen presenting cells and T helper cells, like interleukin-12. Sleep on the night after experimental vaccinations against hepatitis A produced a strong and persistent increase in the number of antigen-specific Th cells and antibody titres. Together these findings indicate a specific role of sleep in the formation of immunological memory. This role appears to be associated in particular with the stage of slow wave sleep and the accompanying pro-inflammatory endocrine milieu that is hallmarked by high growth hormone and prolactin levels and low cortisol and catecholamine concentrations

    Towards project management 2030: Why is change needed?

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