Selective mitochondrial antioxidant MitoTEMPO reduces renal dysfunction and systemic inflammation in experimental sepsis in rats

BACKGROUND: Excess mitochondrial reactive oxygen species (mROS) in sepsis is associated with organ failure, in part by generating inflammation through the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome. We determined the impact of a mitochondrial-targeted antioxidant (MitoTEMPO) on mitochondrial dysfunction in renal proximal tubular epithelial cells, peritoneal immune cell function ex vivo, and organ dysfunction in a rat model of sepsis. METHODS: The effects of MitoTEMPO were assessed ex vivo using adenosine triphosphate and lipopolysaccharide-stimulated rat peritoneal immune cells and fresh rat kidney slices exposed to serum from septic rats. We assessed mROS production and phagocytotic capacity (flow cytometry), mitochondrial functionality (multiphoton imaging, respirometry), and NLRP3 inflammasome activation in cell culture. The effect of MitoTEMPO on organ dysfunction was evaluated in a rat model of faecal peritonitis. RESULTS: MitoTEMPO decreased septic serum-induced mROS (P0.05). In vivo, compared with untreated septic animals, MitoTEMPO reduced systemic IL-1β (P=0.01), reduced renal oxidative stress as determined by urine isoprostane levels (P=0.04), and ameliorated renal dysfunction (reduced serum urea (P<0.001) and creatinine (P=0.05). CONCLUSIONS: Reduction of mROS by a mitochondria-targeted antioxidant reduced IL-1β, and protected mitochondrial, cellular, and organ functionality after septic insults

The Spectrum of Angiographic Findings in Transitional Cell Carcinoma of the Kidney

The spectrum of angiographic finding in 20 patients with transitional cell carcinomas of the kidney is described. In 15 of 20 patients (75%), prospective diagnosis of transitional cell carcinomas were made because of a combination of the angiographic findings; tumour vessels, tumour stain, prominent pelviureteric arteries and arterial encasement. In 4 patients with negative angiograms the lesions were relatively small in size and were situated within the renal parenchyma, primarily involving the calyces. The use of pharmacoangiographic agents such as epine-phrine and priscoline improved the angiographic visualization of transitional cell carcinomas of the kidney. For the past several years angiography has had a central role in the evaluation of patients with hematuria and renal masses 1 . 5,6,7,8. Although the use of diagnostic ultrasound and renal puncture have eliminated angiography from the diagnosis of renal cysts, most renal masses which are solid or which have equivocal findings at ultrasound still undergo angiography. At the same time, the decreasing use of retrograde urography has resulted in more frequent angiography in patients with unilateral nonfunctioning kidneys. Transitional cell carcinomas of the renal pelvis are an important cause of both hematuria and non-functioning kidneys. We have therefore reviewed our material to reassess the angiographic abnormalities caused by the transitional cell carcinomas and the overall accuracy of the angiography in the diagnosis of these lesions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73228/1/j.1440-1673.1977.tb03191.x.pd

Single-cell analysis of long non-coding RNAs in the developing human neocortex

Single cell transcriptomics of lncRNA expression in K562 cell cultures. A Distributions of median lncRNA expression to median mRNA expression ratios (lncRNA:mRNA) in populations, in silico merged single cells, and single cells from K562 cultures. B Proportion of K562 cells that expressed each lncRNA (blue) and mRNA (red), separated by maximum expression in single cells. C Same as in (B) but grouped by maximum expression quantile. D Distributions of non-zero lncRNA (blue) and mRNA (red) expression in 46 single K562 cells. Green squares, housekeeping genes; black triangles, ERCC Spike-In Controls. (PDF 454 kb

Effect of root age on the biomechanics of seminal and nodal roots of barley (<i>Hordeum vulgare L.</i>) in contrasting soil environments

Acknowledgments The James Hutton Institute receives funding from the Scottish Government. The authors would also like to thank Jim McNicol from Biomathematics and Statistics Scotland for his advice on statistical analysis.Peer reviewedPostprin

Human iPSC-Derived Cerebral Organoids Model Cellular Features of Lissencephaly and Reveal Prolonged Mitosis of Outer Radial Glia

Classical lissencephaly is a genetic neurological disorder associated with mental retardation and intractable epilepsy, and Miller-Dieker syndrome (MDS) is the most severe form of the disease. In this study, to investigate the effects of MDS on human progenitor subtypes that control neuronal output and influence brain topology, we analyzed cerebral organoids derived from control and MDS-induced pluripotent stem cells (iPSCs) using time-lapse imaging, immunostaining, and single-cell RNA sequencing. We saw a cell migration defect that was rescued when we corrected the MDS causative chromosomal deletion and severe apoptosis of the founder neuroepithelial stem cells, accompanied by increased horizontal cell divisions. We also identified a mitotic defect in outer radial glia, a progenitor subtype that&nbsp;is largely absent from lissencephalic rodents but critical for human neocortical expansion. Our study,&nbsp;therefore, deepens our understanding of MDS cellular pathogenesis and highlights the broad utility of cerebral organoids for modeling human neurodevelopmental disorders