KIN-4/MAST kinase promotes PTEN-mediated longevity of Caenorhabditis elegans via binding through a PDZ domain

PDZ domain-containing proteins (PDZ proteins) act as scaffolds for protein-protein interactions and are crucial for a variety of signal transduction processes. However, the role of PDZ proteins in organismal lifespan and aging remains poorly understood. Here, we demonstrate that KIN-4, a PDZ domain-containing microtubule-associated serine-threonine (MAST) protein kinase, is a key longevity factor acting through binding PTEN phosphatase in Caenorhabditis elegans. Through a targeted genetic screen for PDZ proteins, we find that kin-4 is required for the long lifespan of daf-2/insulin/IGF-1 receptor mutants. We then show that neurons are crucial tissues for the longevity-promoting role of kin-4. We find that the PDZ domain of KIN-4 binds PTEN, a key factor for the longevity of daf-2 mutants. Moreover, the interaction between KIN-4 and PTEN is essential for the extended lifespan of daf-2 mutants. As many aspects of lifespan regulation in C. elegans are evolutionarily conserved, MAST family kinases may regulate aging and/or age-related diseases in mammals through their interaction with PTEN.11Ysciescopu

Production of Transgenic Cloned Miniature Pigs with Membrane-bound Human Fas Ligand (FasL) by Somatic Cell Nuclear Transfer

Cell-mediated xenograft rejection, including NK cells and CD8+ CTL, is a major obstacle in successful pig-to-human xenotransplantation. Human CD8+ CTL and NK cells display high cytotoxicity for pig cells, mediated at least in part by the Fas/FasL pathway. To prevent cell-mediated xenocytotoxicity, a membrane-bound form of human FasL (mFasL) was generated as an inhibitor for CTL and NK cell cytotoxicity that could not be cleaved by metalloproteinase to produce putative soluble FasL. We produced two healthy transgenic pigs harboring the mFasL gene via somatic cell nuclear transfer (SCNT). In a cytotoxicity assay using transgenic clonal cell lines and transgenic pig ear cells, the rate of CD8+ CTL-mediated cytotoxicity was significantly reduced in transgenic pig's ear cells compared with that in normal minipig fetal fibroblasts. Our data indicate that grafts of transgenic pigs expressing membrane-bound human FasL control the cellular immune response to xenografts, creating a window of opportunity to facilitate xenograft survival

A Pulmonary Paragonimiasis Case Mimicking Metastatic Pulmonary Tumor

Pulmonary paragonimiasis is a relatively rare cause of lung disease revealing a wide variety of radiologic findings, such as air-space consolidation, nodules, and cysts. We describe here a case of pulmonary paragonimiasis in a 27-year-old woman who presented with a 2-month history of cough and sputum. Based on chest computed tomography (CT) scans and fluorodeoxyglucose positron emission tomography (FDG-PET) findings, the patient was suspected to have a metastatic lung tumor. However, she was diagnosed as having Paragonimus westermani infection by an immunoserological examination using ELISA. Follow-up chest X-ray and CT scans after chemotherapy with praziquantel showed an obvious improvement. There have been several reported cases of pulmonary paragonimiasis mimicking lung tumors on FDG-PET. However, all of them were suspected as primary lung tumors. To our knowledge, this patient represents the first case of paragonimiasis mimicking metastatic lung disease on FDG-PET CT imaging

Development of a 2-Channel Embedded Infrared Fiber-Optic Temperature Sensor Using Silver Halide Optical Fibers

A 2-channel embedded infrared fiber-optic temperature sensor was fabricated using two identical silver halide optical fibers for accurate thermometry without complicated calibration processes. In this study, we measured the output voltages of signal and reference probes according to temperature variation over a temperature range from 25 to 225 °C. To decide the temperature of the water, the difference between the amounts of infrared radiation emitted from the two temperature sensing probes was measured. The response time and the reproducibility of the fiber-optic temperature sensor were also obtained. Thermometry with the proposed sensor is immune to changes if parameters such as offset voltage, ambient temperature, and emissivity of any warm object. In particular, the temperature sensing probe with silver halide optical fibers can withstand a high temperature/pressure and water-chemistry environment. It is expected that the proposed sensor can be further developed to accurately monitor temperature in harsh environments

Atomic Scale Study on Growth and Heteroepitaxy of ZnO Monolayer on Graphene

Atomically thin semiconducting oxide on graphene carries a unique combination of wide band gap, high charge carrier mobility, and optical transparency, which can be widely applied for optoelectronics. However, study on the epitaxial formation and properties of oxide monolayer on graphene remains unexplored due to hydrophobic graphene surface and limits of conventional bulk deposition technique. Here, we report atomic scale study of heteroepitaxial growth and relationship of a single-atom-thick ZnO layer on graphene using atomic layer deposition. We demonstrate atom-by-atom growth of zinc and oxygen at the preferential zigzag edge of a ZnO monolayer on graphene through in situ observation. We experimentally determine that the thinnest ZnO monolayer has a wide band gap (up to 4.0 eV), due to quantum confinement and graphene-like structure, and high optical transparency. This study can lead to a new class of atomically thin two-dimensional heterostructures of semiconducting oxides formed by highly controlled epitaxial growth.ope

Developmental endothelial locus-1 as a potential biomarker for the incidence of acute exacerbation in patients with chronic obstructive pulmonary disease

Background Despite the high disease burden of chronic obstructive pulmonary disease (COPD) and risk of acute COPD exacerbation, few COPD biomarkers are available. As developmental endothelial locus-1 (DEL-1) has been proposed to possess beneficial effects, including anti-inflammatory effects, we hypothesized that DEL-1 could be a blood biomarker for COPD. Objective To elucidate the role of plasma DEL-1 as a biomarker of COPD in terms of pathogenesis and for predicting acute exacerbation. Methods Cigarette smoke extract (CSE) or saline was intratracheally administered to wild-type (WT) and DEL-1 knockout (KO) C57BL/6 mice. Subsequently, lung sections were obtained to quantify the degree of emphysema using the mean linear intercept (MLI). Additionally, plasma DEL-1 levels were compared between COPD and non-COPD participants recruited in ongoing prospective cohorts. Using negative binomial regression analysis, the association between the plasma DEL-1 level and subsequent acute exacerbation risk was evaluated in patients with COPD. Results In the in vivo study, DEL-1 KO induced emphysema (KO saline vs. WT saline; P = 0.003) and augmented CSE-induced emphysema (KO CSE vs. WT CSE; P < 0.001) in 29 mice. Among 537 participants, patients with COPD presented plasma log (DEL-1) levels lower than non-COPD participants (P = 0.04), especially non-COPD never smokers (P = 0.019). During 1.2 ± 0.3 years, patients with COPD in the lowest quartile of Log(DEL-1) demonstrated an increased risk of subsequent acute exacerbation, compared with those in the highest quartile of Log(DEL-1) (adjusted incidence rate ratio, 3.64; 95% confidence interval, 1.03–12.9). Conclusion Low DEL-1 levels are associated with COPD development and increased risk of subsequent COPD acute exacerbation. DEL-1 can be a useful biomarker in patients with COPD.This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2019R1C1C1007918). This research was also supported by funds (2016ER670100, 2016ER670101, 2016ER670102 and 2018ER670100, 2018ER670101, 2018ER670102) from Research of Korea Centers for Disease Control and Prevention