In this video collection, authors of findings published in The Journal of Clinical Investigation present personally guided tours of their results. The JCI accepts video submissions from authors of recently accepted manuscripts. Instructions can be found on the Author's Take Guidelines page.
Immune-mediated rejection of donor tissues is one of the largest challenges in transplant biology. While routine biopsy to monitor transplanted organs can be informative, this procedure is invasive and carries several risks. In this episode, Prashanth Vallabhajosyula and colleagues evaluated changes in transplant-derived exosomes in murine models and human transplant recipients. Their work indicates that changes in donor-derived exosomes can be used to noninvasively monitor transplant rejection.
Obesity, diabetes, and other metabolic diseases have known underlying genetic causes; however, environmental factors also play an important role in the onset and development of metabolic dysfunction. In this episode, Mitchell Lazar and Raymond Soccio discuss their study, which compared high fat-diet-induced effects on gene expression and the epigenome in mice genetically prone to diet-induced obesity and in animals that are resistant to diet-induced metabolic disease. They find that the thermogenic gene Ucp1 is repressed in the obesity-prone mice, but that either cold-exposure or treatment with the insulin-sensitizing drug rosiglitazone restores Ucp1 expression to levels similar to that in obesity-resistant strains. The results of this study demonstrate that genetic defects in metabolism can be rescued by environmentally-driven epigenomic modifications.
PET allows noninvasive visualization of several physiological, neurochemical, and pharmacological processes within patients. Application of PET in the brain has been limited due to a lack of radiotracers that label specific neurons or regions. In this episode, Jacob Hooker, Mark Alberts, and Genevieve C. Van de Bittner describe the discovery and characterization of [11C]GV1-57 (Neuroflux), which specifically labels mature olfactory sensory neurons in the olfactory epithelium. This radiotracer has potential as a powerful tool for monitoring olfactory neurogenesis under both normal and disease states.
The hormone kisspeptin is essential for reproductive function, an effect that is mediated by its actions in the hypothalamus. Recent studies suggest that kisspeptin and its receptor are also expressed in other regions of the brain; however, little is known about the effects of this hormone in the brain in regions outside of the hypothalamus. In this episode, Waljit Dhillo and colleagues evaluate limbic system-specific effects of kisspeptin administration in healthy male volunteers. The data from this study indicate that kisspeptin action in the limbic system mediates sexual and emotional brain processing.
Retinitis pigmentosa (RP) is a heterogeneous genetic disorder that is characterized by a progressive loss of photoreceptors that results in deterioration of vision. While gene therapy has shown promise for some forms of RP, over 60 genes have been implicated in this disorder; therefore, non-gene-targeted therapies are of great interest. In this episode, Stephen Tsang and colleagues discuss their study, which shows that upregulation of glycolytic flux, via targeted downregulation of sirtuin 6, in rod photoreceptors improves photoreceptor survival and preserves vision in a mouse model of RP. As this strategy is not gene-specific, it may be beneficial for a range of neurodegenerative disorders.