An Innovative Method to Identify Autoantigens Expressed on the Endothelial Cell Surface: Serological Identification System for Autoantigens Using a Retroviral Vector and Flow Cytometry (SARF)

Autoantibodies against integral membrane proteins are usually pathogenic. Although anti-endothelial cell antibodies (AECAs) are considered to be critical, especially for vascular lesions in collagen diseases, most molecules identified as autoantigens for AECAs are localized within the cell and not expressed on the cell surface. For identification of autoantigens, proteomics and expression library analyses have been performed for many years with some success. To specifically target cell-surface molecules in identification of autoantigens, we constructed a serological identification system for autoantigens using a retroviral vector and flow cytometry (SARF). Here, we present an overview of recent research in AECAs and their target molecules and discuss the principle and the application of SARF. Using SARF, we successfully identified three different membrane proteins: fibronectin leucine-rich transmembrane protein 2 (FLRT2) from patients with systemic lupus erythematosus (SLE), intercellular adhesion molecule 1 (ICAM-1) from a patient with rheumatoid arthritis, and Pk (Gb3/CD77) from an SLE patient with hemolytic anemia, as targets for AECAs. SARF is useful for specific identification of autoantigens expressed on the cell surface, and identification of such interactions of the cell-surface autoantigens and pathogenic autoantibodies may enable the development of more specific intervention strategies in autoimmune diseases

Cortical electrical activity changes in healthy aging using EEG-eLORETA analysis

Brain aging causes loss of synaptic spines, neuronal apoptosis, and a reduction in neurotransmitter levels. These aging phenomena disturb cortical electrical activity and its synchronization with connected regions. Previous electroencephalography (EEG) studies reported an age-related decrease in electrical activity in the alpha frequency band at occipital, parietal, and temporal areas as well as a decrease in occipital delta activity. However, there is an ongoing debate about whether there is an increase or decrease of the activity in other frequency bands with aging due to inconsistent study findings. In this study, we aimed to detect age-related changes of cortical electrical activities in all five frequency bands (delta, theta, alpha, beta, and gamma) in a large sample of healthy subjects for the first time. Using eLORETA (exact low-resolution brain electromagnetic tomography) analysis, we applied an eLORETA source estimation method to resting-state EEG data in 147 healthy subjects (median age 55, IQR 26.5–67.0) to obtain cortical electrical activity and assessed age-related changes in this activity using correlation analysis with multiple comparison correction. The combination of the eLORETA source estimation method and correlation analysis implemented in eLORETA software detected age-related changes in specific cortical regions for each frequency band: (1) delta and theta cortical electrical activities decreased at the occipital area with age, (2) alpha cortical electrical activity decreased at the occipitoparietotemporal areas with age, (3) beta cortical electrical activity increased at the insula, sensorimotor area, supplementary motor area, premotor area, and right temporal areas with age (most significant correlation at the right insula), (4) gamma cortical electrical activity increased at the frontoparietal and left temporal areas with age. These findings extend previous EEG study findings and provide valuable information related to mechanisms of healthy aging. Overall, our findings revealed that even healthy aging greatly affects cortical electrical activities in a region-specific way

Factors Influencing Breast Density in Japanese Women Aged 40-49 in Breast Cancer Screening Mammography

A relatively large number of women in their 40s with high-density breasts, in which it can be difficult to detect lesions, are encountered in mammography cancer screenings in Japan. Here, we retrospectively investigated factors related to breast density. Two hundred women (40-49 years old) were examined at the screening center in our hospital. Multivariate analysis showed that factors such as small abdominal circumference, high HDL cholesterol, and no history of childbirth were related to high breast density in women in their 40s undergoing mammography. Other non-mammographic screening methods should be considered in women with abdominal circumferences ＜76cm, HDL-C >53mg/dl, and no history of childbirth, as there is a strong possibility of these women having high-density breasts that can make lesion detection difficult

Dissolved methane distribution in surface seawater and its controlling factors in mid- and high-latitudes in the Southern Ocean

第6回極域科学シンポジウム分野横断セッション：[IB1] 海氷域における生物地球化学的研究11月17日（火）　統計数理研究所 セミナー室1（D305

Cyclophosphamide Promotes Arrested Development of the Dental Root in Mice

Cyclophosphamide (CPA) is a commonly used chemotherapeutic agent to treat cancer. Among its many side effects is the well-known consequence on tooth development when administered at early ages. This study elucidated the effects of CPA on development of the mandibular molar in mice. Mice received a single intraperitoneal injection of CPA at different doses and development times. CPA treatment led to weight loss and alopecia but had no effect on disturbances in tooth eruption or crown shape. However, at higher doses, there was arrested root development and early apical foramen closure histologically related to the formation of the cervical loop structure in the apical portion of the root. In cell culture experiments, the Hertwig\u27s epithelial root sheath cell line (HERS01a) was cultured with or without CPA. At high doses of CPA, HERS01a cells showed decreases in E-cadherin expression, while N-cadherin expression was upregulated, indicating that this cadherin switch may promote an epithelial-to-mesenchymal transition (EMT)-like phenomenon. These findings suggest that administration of high doses of CPA can lead to arrested root development of the molars and an EMT-like phenomenon.福岡歯科大学2019年

The formation of the ocean’s anthropogenic carbon reservoir

The shallow overturning circulation of the oceans transports heat from the tropics to the mid-latitudes. This overturning also influences the uptake and storage of anthropogenic carbon (Cant). We demonstrate this by quantifying the relative importance of ocean thermodynamics, circulation and biogeochemistry in a global biochemistry and circulation model. Almost 2/3 of the Cant ocean uptake enters via gas exchange in waters that are lighter than the base of the ventilated thermocline. However, almost 2/3 of the excess Cant is stored below the thermocline. Our analysis shows that subtropical waters are a dominant component in the formation of subpolar waters and that these water masses essentially form a common Cant reservoir. This new method developed and presented here is intrinsically Lagrangian, as it by construction only considers the velocity or transport of waters across isopycnals. More generally, our approach provides an integral framework for linking ocean thermodynamics with biogeochemistry

Relationship between postprandial glucose level and carotid artery stiffness in patients without diabetes or cardiovascular disease

BACKGROUND: The aim of this study was to evaluate the relationship between postprandial glucose level and atherosclerosis in patients without diabetes and cardiovascular disease by determining carotid ultrasonographic variables and serum levels of 1,5-anhydroglucitol (1,5-AG). METHODS: The subjects were 72 patients without diabetes and cardiovascular disease being treated for hypertension or dyslipidemia. The clinical characteristics of all subjects, including the serum level of 1,5-AG, which appears to be well suited for monitoring postprandial hyperglycemia, were evaluated after an overnight fast. The average intima-media thickness (IMT) and the average pulsatility index (PI) of the right and left common carotid arteries were determined with high-resolution ultrasonography and used as ultrasonographic variables. The subjects were divided into a Lower 1,5-AG group (n = 36) and a Higher 1,5-AG group (n = 36). We evaluated the relationship between clinical characteristics and ultrasonographic variables of the carotid artery in both groups. RESULTS: The average PI in the Lower 1,5-AG group was significantly higher than that in the Higher 1,5-AG group, but the average IMT did not differ between the groups. Linear regression analysis, with the ultrasonographic variables as the dependent variables, with 1,5-AG as the independent variable, and adjusted for other clinical characteristics, showed significant correlation between 1,5-AG and the PI but not between 1,5-AG and IMT. CONCLUSION: Our results suggest that postprandial hyperglycemia increases carotid artery stiffness, but not morphological change, in patients without diabetes or cardiovascular disease