25 research outputs found

    Profilin 1 is essential for retention and metabolism of mouse hematopoietic stem cells in bone marrow

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    How stem cells interact with the microenvironment to regulate their cell fates and metabolism is largely unknown. Here we demonstrated that the deletion of the cytoskeleton-modulating protein profilin 1 (pfn1) in hematopoietic stem cell (HSCs) led to bone marrow failure, loss of quiescence, and mobilization and apoptosis of HSCs in vivo. A switch from glycolysis to mitochondrial respiration with increased reactive oxygen species (ROS) level was also observed in HSCs on pfn1 deletion. Importantly, treatment of pfn1-deficient mice with the antioxidant N-acetyl-l-cysteine reversed the ROS level and loss of quiescence of HSCs, suggesting that the metabolism is mechanistically linked to the cell cycle quiescence of stem cells. The actin-binding and proline-binding activities of pfn1 are required for its function in HSCs. Our study provided evidence that pfn1 at least partially acts through the axis of pfn1/Gα13/EGR1 to regulate stem cell retention and metabolism in the bone marrow

    Correlation between serum lactate levels and outcome in pediatric patients undergoing congenital heart surgery

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    WOS: 000439420000006Background: This study aimed to investigate the correlation between perioperative arterial lactate levels and morbidity and mortality in children undergoing cardiac surgery. Methods: A total of 236 patients who underwent open heart surgery due to congenital heart disease (121 males, 115 females; mean age 56.4 month (median: 42 month): range, 1 day to 204 month) between June 2014 and May 2016 were retrospectively analyzed. The arterial blood gas analysis results at baseline (after insertion of arterial cannula), during the cooling and warming-up phases in cardiopulmonary bypass, during the sternal closure, and at 0, 6, 12, and 24 hours in the postoperative intensive care unit stay were recorded. The patients were divided into two groups according to their lactate levels: Group 1 (lactate level = 4.5 mmol/L, n=53). Correlation between the lactate groups and demographic data, intraoperative and postoperative variables, postoperative complications, and mortality were investigated. Results: Sixty-nine patients (29.2%) had cyanotic heart disease. A total of 53 patients (22.5%) had lactate levels of >= 4.5 mmol/L. At least one complication occurred in 41% of the patients. Development of at least one complication (p=0.027) and mortality rate (p= 4.5 mmol/L. Seventeen patients (7.2%) died in the postoperative period, and 15 of them had lactate levels of >= 4.5 mmol/L at least once within the first 24 hours. In terms of mortality, lactate levels of >= 4.5 mmol/L at any time, prolonged mechanical ventilation (>48 hours), and undergoing complex surgery (high the Risk-adjusted Classification for Congenital Heart Surgery-1 score, category 4-6) were the independent risk factors for mortality. Conclusion: Blood arterial lactate level of >= 4.5 mmol/L was found to be a risk factor for postoperative morbidity and mortality in pediatric patients undergoing congenital heart surgery

    Aligned carbon nanotubes as polarization-sensitive, molecular near-field detectors

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    Near-field scanning optical microscopes are widely used in imaging of subwavelength features in various material systems and nanostructures. For a variety of applications, polarization-sensitive near-field probes can provide valuable information on the nature and symmetry of the imaged nanoparticles and emitters. Conventional near-field optical microscopy lacks in-plane polarization sensitivity. Here, we use aligned single-wall carbon nanotubes as polarization-sensitive molecular scale probes to image the transverse near-field components of an optical Hertzian dipole antenna. Because of the Raman “antenna effect” in carbon nanotubes, only the near-field components along the nanotube axis are detected. These findings demonstrate that aligned carbon nanotubes can be used as polarization-sensitive near-field detectors

    Intraflagellar transport drives flagellar surface motility

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    The assembly and maintenance of all cilia and flagella require intraflagellar transport (IFT) along the axoneme. IFT has been implicated in sensory and motile ciliary functions, but the mechanisms of this relationship remain unclear. Here, we used Chlamydomonas flagellar surface motility (FSM) as a model to test whether IFT provides force for gliding of cells across solid surfaces. We show that IFT trains are coupled to flagellar membrane glycoproteins (FMGs) in a Ca(2+)-dependent manner. IFT trains transiently pause through surface adhesion of their FMG cargos, and dynein-1b motors pull the cell towards the distal tip of the axoneme. Each train is transported by at least four motors, with only one type of motor active at a time. Our results demonstrate the mechanism of Chlamydomonas gliding motility and suggest that IFT plays a major role in adhesion-induced ciliary signaling pathways. DOI:http://dx.doi.org/10.7554/eLife.00744.001

    Intraflagellar transport drives flagellar surface motility.

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    The assembly and maintenance of all cilia and flagella require intraflagellar transport (IFT) along the axoneme. IFT has been implicated in sensory and motile ciliary functions, but the mechanisms of this relationship remain unclear. Here, we used Chlamydomonas flagellar surface motility (FSM) as a model to test whether IFT provides force for gliding of cells across solid surfaces. We show that IFT trains are coupled to flagellar membrane glycoproteins (FMGs) in a Ca(2+)-dependent manner. IFT trains transiently pause through surface adhesion of their FMG cargos, and dynein-1b motors pull the cell towards the distal tip of the axoneme. Each train is transported by at least four motors, with only one type of motor active at a time. Our results demonstrate the mechanism of Chlamydomonas gliding motility and suggest that IFT plays a major role in adhesion-induced ciliary signaling pathways. DOI:http://dx.doi.org/10.7554/eLife.00744.001

    Is Serum Caveolin-1 a Useful Biomarker for Progression in Patients with Colorectal Cancer?

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    Background: Colorectal cancer (CRC) is the third most common cause of cancer diagnosed in males and the second in females. Survival is strongly related to stage at diagnosis. There is an urgent need to find a noninvasive biomarker that can be commonly applied for screening diagnosis, early detection of recurrence, and monitoring of metastatic CRC. Protein caveolin-1 (CAV-1) has been known to be expressed abnormally in colon cancer and appears to contribute to aberrant signaling and protein trafficking. There are controversial results regarding the role of CAV-1 in cancer. We hypothesized that levels of CAV-1 in serum of patients with CRC might be important to estimate the progression of the disease. Therefore, the purpose of this study is to investigate whether serum CAV-1 might be used as a factor determining progression of CRC
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