Modeling SARS-CoV-2 infection and its individual differences with ACE2-expressing human iPS cells

ACE発現ヒトiPS細胞を用いたSARS-CoV-2感染の個人差再現と原因究明. 京都大学プレスリリース. 2021-04-19.Stem cells show gender differences in COVID-19 risk. 京都大学プレスリリース. 2021-04-19.Genetic differences are a primary reason for differences in the susceptibility and severity of COVID-19. As induced pluripotent stem (iPS) cells maintain the genetic information of the donor, they can be used to model individual differences in SARS-CoV-2 infection in vitro. We found that human iPS cells expressing the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) (ACE2-iPS cells) can be infected w SARS-CoV-2. In infected ACE2-iPS cells, the expression of SARS-CoV-2 nucleocapsid protein, budding of viral particles, and production of progeny virus, double membrane spherules, and double-membrane vesicles were confirmed. We performed SARS-CoV-2 infection experiments on ACE2-iPS/ embryonic stem (ES) cells from eight individuals. Male iPS/ES cells were more capable of producing the virus compared with female iPS/ES cells. These findings suggest that ACE2-iPS cells can not only reproduce individual differences in SARS-CoV-2 infection in vitro but also are a useful resource to clarify the causes of individual differences in COVID-19 due to genetic differences

Inhibition of cell movement and proliferation by cell–cell contact-induced interaction of Necl-5 with nectin-3

Immunoglobulin-like Necl-5/Tage4/poliovirus receptor (PVR)/CD155, originally identified as the PVR, has been shown to be up-regulated in cancer cells and to enhance growth factor–induced cell movement and proliferation. In addition, Necl-5 heterophilically trans-interacts with nectin-3, a cell–cell adhesion molecule known to form adherens junctions in cooperation with cadherin. We show here that Necl-5 was down-regulated from cell surface upon cell–cell contacts in NIH3T3 cells. This down-regulation of Necl-5 was initiated by its interaction with nectin-3 and was mainly mediated by clathrin-dependent endocytosis. Then, the down-regulation of Necl-5 induced in this way reduced movement and proliferation of NIH3T3 cells. These results indicate that the down-regulation of Necl-5 induced by its interaction with nectin-3 upon cell–cell contacts may be at least one mechanism underlying contact inhibition of cell movement and proliferation

A reduced brain and liver FDG uptake

Purpose : To investigate whether or not the physiological brain and liver FDG uptake are decreased in patients with highly accelerated glycolysis lesions. Methods : We retrospectively analyzed 51 patients with malignant lymphoma. We compared the FDG uptake in the brain and liver of the patients with that in a control group. In 24 patients with a complete response (CR) or partial response (PR) to treatment, we compared the brain and liver uptake before and after treatment. Results : The maximum standardized uptake value (SUVmax) and total glycolytic volume (TGV) of the brain as well as the SUVmax and mean standardized uptake value (SUVmean) of the liver in malignant lymphoma patients were 13.1 ± 2.3, 7386.3 ± 1918.4, 3.2 ± 0.5, and 2.3 ± 0.4, respectively ; in the control group, these values were 14.9 ± 2.4, 8566.2 ± 1659.5, 3.4 ± 0.4, and 2.5 ± 0.3, respectively. The SUVmax and TGV of the brain and the SUVmean of the liver in malignant lymphoma patients were significantly lower than the control group. The SUVmax and TGV of the brain after treatment were significantly higher than before treatment. Both the SUVmax and SUVmean of liver after treatment were higher than before treatment, but not significant. Conclusion : A decreased physiological brain and liver FDG uptake is caused by highly accelerated lesion glycolysis

Blue Sky Focusing : Experiential Articulations and Anxiety Reducing Effects

青空フォーカシング（BSF）とは、“青空の瞑想”を含む広い意味でのマインドフルネスと、フォーカシングという心理療法を組み合わせたものである。近年、マインドフルネスは心理臨床領域で注目を集めており、うつ症状や不安を改善する効果があることが明らかになっている。また、フォーカシングの一部であるクリアリング・ア・スペースにも、不安低減効果があることが報告されている。そこで、BSFにも不安を低減させる効果があるのではないかと考え、本論の研究1では、青空フォーカシングの不安低減効果を検討した。BSFを短期間体験したことがある19名の参加者の状態不安を、新版STAIを用いて、BSFの前後に測定して比較した。実際にはフォーカサーとリスナーのペアでBSFを行い、そのあとで役割交代をするため、データは2セッションから収集された。結果は参加者がフォーカサーであった場合（t（10）＝ 3.203, p<.01; t（9）＝4.906, p<.01）とリスナーであった場合 （t（10）＝ 4.232, p<.01; t（9）＝ 2.818, p<.05）のいずれの場合にも有意な状態不安の低下が見られた。研究IIではBSFの実際の体験を明らかにするために、体験記述を参加者が記入した「振り返りシート」を元に検討した。フォーカサーとリスナーの双方がフォーカサーの体験やフェルトセンスを歓迎し、思いやりをもって関わることが重要であることが考察された。Blue Sky Focusing (BSF) was developed from Focusing, a form of psychotherapy, and "Blue Sky Meditation", a mindfulness based meditation in a broad sense of the term. Recently mindfulness has attracted much attention in the field of psychotherapy since it was demonstrated to improve depression and anxiety. Anxiety reducing effects of Clearing A Space, one of the steps of Focusing: Short Form, have also been reported. Thus, it can be speculated that BSF would also have anxiety reducing effects. Study 1 in this paper compared state anxiety, using the STAI, before and after BSF in 19 participants who had some experience with BSF. Subjects were paired as focusers and listeners and switched roles in the second session. A comparison of pre-post state anxiety from these 2 sessions showed significant anxiety reduction when participants engaged in either role, as focusers (t(10) = 3.203, p < .01; t(9) = 4.906, p < .01) or as listeners (t(10) = 4.232, p < .01; t(9) = 2.818, p < .05). In Study 2, an experiential articulation of the actual experience of BSF was examined from a worksheet that participants had filled out. The authors concluded that in the practice of BSF, it is important that both focuser and listener welcome the focuser\u27s experience and attend to felt senses with compassion

Methodological Features and Background of "Blue Sky Focusing"

本論では、池見によって考案された青空フォーカシングを紹介した。はじめに、池見が「青空の瞑想」に出会い、フォーカシングと組み合わせながら実践を行い、青空フォーカシングが現在の形になった経緯を紹介した。次に青空フォーカシングの具体的な方法をマインドフルネス、雲のイメージ、空になる、慈悲というステップに分け提示した。青空フォーカシングは実際にセッションを実施するPart1と振り返って観てみるPart2という二つのPartから成り立っている。青空フォーカシングにもPart1での“前反省的” （pre-reflexive）な体験とPart2での“反省的”（reflexive）に振り返って観るという相互作用のなかで、新たな意味が生成されるという池見の心理療法実践の特徴がみられる。青空フォーカシングにはフォーカシングの過程の他に複数の要素が含まれている。そこで、その方法論的特色を検討するために、その背景にある理論について、マインドフルネス、青空の瞑想（体の微細な感覚を見る瞑想、慈悲の瞑想、呼吸瞑想）、クリアリング・ア・スペース、雲という指定イメージのメタファー機能という4点から論考した。最後に、青空フォーカシングの自然なあり方と、近年、注目されているマインドフルネスとの関連について検討した。This paper introduces "Blue Sky Focusing", which was developed by A. Ikemi. First, we introduced the background of Blue Sky Focusing: Ikemi\u27s initial encounter with "Blue Sky Meditation" and how he has currently developed Blue Sky Focusing by combining meditation and focusing. Concrete methods of Blue Sky Focusing are then indicated by dividing it into four steps as follows: mindfulness, symbolizing the body-sense as a cloud, becoming the sky, and compassion. Blue Sky Focusing consists of Part 1: practicing Blue Sky Focusing and Part 2: reflecting on the practice. Characteristics of Ikemi\u27s psychotherapy practice, where new meanings are created through interactions of pre-reflexive experience in Part 1 and the reflexive process in Part 2, are apparent in Blue Sky Focusing. Some elements other than the process of focusing are also involved in Blue Sky Focusing. To examine these methodological elements, theories of their background are discussed from four viewpoints: mindfulness, Blue Sky Meditation, Clearing A Space, and the function of the cloud metaphor. Finally, we discussed the significance of Blue Sky Focusing in relation to mindfulness, a topic that has rapidly gathered attention in recent year

Difference in Temperament and Character Inventory scores between depressed patients with bipolar II and unipolar major depressive disorders

Background: Although some core personality variables are known to be characteristic of unipolar or bipolar depression, few studies have compared the personality profile between these two disorders. Methods: Temperament and Character Inventory (TCI) was employed to assess the personality of 36 depressed patients with bipolar II disorder (BPII), 90 patients with unipolar major depressive disorder (UP), and 306 healthy controls. The TCI was administered during the depressive episode in BPII and UP patients so that the results can be applied in a clinical setting. Results: Significantly higher scores in harm avoidance (p<0.0001) and lower scores in self-directedness (p<0.0001) and cooperativeness (p<0.05) were observed in both BPII and UP patients compared to controls. Lower novelty seeking in UP patients compared to BPII patients and controls was observed in females (p<0.0001, p<0.01. respectively). A significant difference in self-transcendence score was observed between BPII and UP patients in females (p<0.0005), with higher scores in BPII (p = 0.009) and lower scores in UP (p = 0.046) patients compared to controls. A logistic regression model predicted BPII in depressed females based on novelty seeking and self-transcendence scores with a sensitivity of 89% and a specificity of 73%, but did not accurately predict BPII in males. Limitations: Patients in our study were limited to those receiving outpatient treatments, and bipolar patients were limited to those with BPII. Conclusions: Novelty seeking and self-transcendence scores of TCI might be useful in the differentiation of UP and BPII in female patients.ArticleJOURNAL OF AFFECTIVE DISORDERS. 132(3):319-324 (2011)journal articl

Prediction of Japanese children at risk for complications of childhood obesity : gender differences for intervention approaches

Childhood obesity is one of the most serious public health problems in Japan, especially in Tokushima compared with other prefectures. This study was designed to clarify the life habits which predispose to development of obesity and can be modified through an appropriate intervention program to combat childhood obesity and its lifestyle-related diseases. A total of 216 school children from Itano Town, a municipality of Tokushima Prefecture, Japan, who are attending the fourth grade (9-10 years) of elementary schools, participated in the study from 2004 to 2007. The study included child’s life habits questionnaire, investigating physical activity by recording the daily steps using a pedometer, anthropometric measurements, hematological examination and hemodynamometry in a cross-sectional survey during a two-month period from June to July every year. We conclude that there are considerable gender-related differences for developing obesity and other lifestyle-related diseases ; and all intervention strategies against obesity must consider such gender differences. For example, restriction of television watching hours must be intervened for controlling obesity in boys, however for girls, promotion of exercise practice or making more steps per day with adequate sleeping periods should be intervened as the proper approaches for preventing and controlling obesity and other lifestyle-related diseases