Early Spectroscopy of the 2010 Outburst of U Scorpii

We present early spectroscopy of the recurrent nova U~Sco during the outburst in 2010. We successfully obtained time-series spectra at $t_{\rm d}=$0.37--0.44~d, where $t_{\rm d}$ denotes the time from the discovery of the present outburst. This is the first time-resolved spectroscopy on the first night of U Sco outbursts. At $t_{\rm d}\sim 0.4$~d the H$\alpha$ line consists of a blue-shifted ($-5000$ km s$^{-1}$) narrow absorption component and a wide emission component having triple peaks, a blue ($\sim -3000$ km s$^{-1}$), a central ($\sim 0$ km s$^{-1}$) and a red ($\sim +3000$ km s$^{-1}$) ones. The blue and red peaks developed more rapidly than the central one during the first night. This rapid variation would be caused by the growth of aspherical wind produced during the earliest stage of the outburst. At $t_{\rm d}=1.4$~d the H$\alpha$ line has a nearly flat-topped profile with weak blue and red peaks at $\sim \pm 3000$ km s$^{-1}$. This profile can be attributed to a nearly spherical shell, while the asphericity growing on the first night still remains. The wind asphericity is less significant after $t_{\rm d}=9$ d.Comment: 5 pages, 3 figures, Accepted for publication of PASJ Letter

Human induced pluripotent stem cells generated from a patient with idiopathic basal ganglia calcification

Idiopathic basal ganglia calcification (IBGC) is a rare neurodegenerative disease, characterized by abnormal calcium deposits in basal ganglia of the brain. The affected individuals exhibit movement disorders, and progressive deterioration of cognitive and psychiatric ability. The genetic cause of the disease is mutation in one of several different genes, SLC20A2, PDGFB, PDGFRB, XPR1 or MYORG, which inheritably or sporadically occurs. Here we generated an induced pluripotent stem cell (iPSC) line from an IBGC patient, which is likely be a powerful tool for revealing the pathomechanisms and exploring potential therapeutic candidates of IBGC

Simple derivation of skeletal muscle from human pluripotent stem cells using temperature‐sensitive Sendai virus vector

温度感受性センダイウイルスベクターを用いて ヒトES細胞／iPS細胞から骨格筋細胞を簡便に作製する技術開発 --神経筋疾患病態モデル構築と創薬研究への利用--. 京都大学プレスリリース. 2021-09-13.Human pluripotent stem cells have the potential to differentiate into various cell types including skeletal muscles (SkM), and they are applied to regenerative medicine or in vitro modelling for intractable diseases. A simple differentiation method is required for SkM cells to accelerate neuromuscular disease studies. Here, we established a simple method to convert human pluripotent stem cells into SkM cells by using temperature-sensitive Sendai virus (SeV) vector encoding myoblast determination protein 1 (SeV-Myod1), a myogenic master transcription factor. SeV-Myod1 treatment converted human embryonic stem cells (ESCs) into SkM cells, which expressed SkM markers including myosin heavy chain (MHC). We then removed the SeV vector by temporal treatment at a high temperature of 38℃, which also accelerated mesodermal differentiation, and found that SkM cells exhibited fibre-like morphology. Finally, after removal of the residual human ESCs by pluripotent stem cell-targeting delivery of cytotoxic compound, we generated SkM cells with 80% MHC positivity and responsiveness to electrical stimulation. This simple method for myogenic differentiation was applicable to human-induced pluripotent stem cells and will be beneficial for investigations of disease mechanisms and drug discovery in the future

Prospective association of soft drink consumption with depressive symptoms.

OBJECTIVE: Consumption of soft drinks has become a serious public health issue worldwide. However, prospective evidence is limited regarding the relationship between soft drink consumption and depression, especially in Asia. The aim of this study was to investigate the prospective association between soft drink consumption and the development of depressive symptoms. METHODS: We evaluated an occupational cohort of 935 adults in Japan (2012-2016), who were free from depressive symptoms at baseline and attended a 3-y follow-up assessment. Soft drink consumption was assessed using a self-administered diet history questionnaire. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression scale. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from multivariate logistic regression analysis controlling for sociodemographic, lifestyle, dietary, and occupational covariates. RESULTS: Over the 3-y study period, 16.9% (158 cases) of the study participants reported depressive symptoms. Higher soft drink consumption was associated with higher odds of depressive symptoms. The multivariable-adjusted OR was 1.91 (95% CI, 1.11-3.29; Ptrend = 0.015) when comparing soft drink consumption of ≥4 cups/wk with consumption of <1 cup/wk. CONCLUSION: The present results suggested that greater consumption of soft drinks would increase the likelihood of exhibiting depressive symptoms.This study was supported by JSPS KAKENHI Grant Numbers 25293146, 25702006, Practical Research Project for Life-Style related Diseases including Cardiovascular Diseases and Diabetes Mellitus (15ek0210021h0002) from the Japan Agency for Medical Research and Development, and the Industrial Health Foundation. F.I. was funded by the Medical Research Council Epidemiology Unit, United Kingdom (MC_UU_12015/5)

Establishment of induced pluripotent stem cells from schizophrenia discordant fraternal twins

Schizophrenia (SCZ) is one of the major psychiatric disorders. The genetic factor is certainly influential in the onset of the disease but is not decisive. There is no identified molecular/cellular marker of the disease, and the pathomechanism is still unknown. In this study, we generated human induced pluripotent stem cells (iPSCs) derived from SCZ-discordant fraternal twins, and they could contribute to elucidation of the pathomechanism of SCZ

iPSC screening for drug repurposing identifies anti‐RNA virus agents modulating host cell susceptibility

RNAウイルスの感染を阻害する既存薬の同定 --複数の異なるRNAウイルスに対して宿主細胞の感受性を下げることにより感染を抑制する薬剤--. 京都大学プレスリリース. 2021-04-07.iPS cells in drug screenings for COVID-19. 京都大学プレスリリース. 2021-04-07.Human pathogenic RNA viruses are threats to public health because they are prone to escaping the human immune system through mutations of genomic RNA, thereby causing local outbreaks and global pandemics of emerging or re‐emerging viral diseases. While specific therapeutics and vaccines are being developed, a broad‐spectrum therapeutic agent for RNA viruses would be beneficial for targeting newly emerging and mutated RNA viruses. In this study, we conducted a screen of repurposed drugs using Sendai virus (an RNA virus of the family Paramyxoviridae), with human‐induced pluripotent stem cells (iPSCs) to explore existing drugs that may present anti‐RNA viral activity. Selected hit compounds were evaluated for their efficacy against two important human pathogens: Ebola virus (EBOV) using Huh7 cells and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) using Vero E6 cells. Selective estrogen receptor modulators (SERMs), including raloxifene, exhibited antiviral activities against EBOV and SARS‐CoV‐2. Pioglitazone, a PPARγ agonist, also exhibited antiviral activities against SARS‐CoV‐2, and both raloxifene and pioglitazone presented a synergistic antiviral effect. Finally, we demonstrated that SERMs blocked entry steps of SARS‐CoV‐2 into host cells. These findings suggest that the identified FDA‐approved drugs can modulate host cell susceptibility against RNA viruses

Prediction Model of Amyotrophic Lateral Sclerosis by Deep Learning with Patient Induced Pluripotent Stem Cells

Deep LearningとALS iPS細胞を用いた疾患予測テクノロジー --人工知能のALS検知・診断への応用--. 京都大学プレスリリース. 2021-02-24.Deep learning amyotrophic lateral sclerosis by taking pictures. 京都大学プレスリリース. 2021-02-24.In amyotrophic lateral sclerosis (ALS), early diagnosis is essential for both current and potential treatments. To find a supportive approach for the diagnosis, we constructed an artificial intelligence‐based prediction model of ALS using induced pluripotent stem cells (iPSCs). Images of spinal motor neurons derived from healthy control subject and ALS patient iPSCs were analyzed by a convolutional neural network, and the algorithm achieved an area under the curve of 0.97 for classifying healthy control and ALS. This prediction model by deep learning algorithm with iPSC technology could support the diagnosis and may provide proactive treatment of ALS through future prospective research. ANN NEUROL 202

Deep Learning and ALS

In amyotrophic lateral sclerosis (ALS), early diagnosis is essential for both current and potential treatments. To find a supportive approach for the diagnosis, we constructed an artificial intelligence-based prediction model of ALS using induced pluripotent stem cells (iPSCs). Images of spinal motor neurons derived from healthy control subject and ALS patient iPSCs were analyzed by a convolutional neural network, and the algorithm achieved an area under the curve of 0.97 for classifying healthy control and ALS. This prediction model by deep learning algorithm with iPSC technology could support the diagnosis and may provide proactive treatment of ALS through future prospective research

Cellular analysis of SOD1 protein-aggregation propensity and toxicity: a case of ALS with slow progression harboring homozygous SOD1-D92G mutation

Mutations within Superoxide dismutase 1 (SOD1) cause amyotrophic lateral sclerosis (ALS), accounting for approximately 20% of familial cases. The pathological feature is a loss of motor neurons with enhanced formation of intracellular misfolded SOD1. Homozygous SOD1-D90A in familial ALS has been reported to show slow disease progression. Here, we reported a rare case of a slowly progressive ALS patient harboring a novel SOD1 homozygous mutation D92G (homD92G). The neuronal cell line overexpressing SOD1-D92G showed a lower ratio of the insoluble/soluble fraction of SOD1 with fine aggregates of the misfolded SOD1 and lower cellular toxicity than those overexpressing SOD1-G93A, a mutation that generally causes rapid disease progression. Next, we analyzed spinal motor neurons derived from induced pluripotent stem cells (iPSC) of a healthy control subject and ALS patients carrying SOD1-homD92G or heterozygous SOD1-L144FVX mutation. Lower levels of misfolded SOD1 and cell loss were observed in the motor neurons differentiated from patient-derived iPSCs carrying SOD1-homD92G than in those carrying SOD1-L144FVX. Taken together, SOD1-homD92G has a lower propensity to aggregate and induce cellular toxicity than SOD1-G93A or SOD1-L144FVX, and these cellular phenotypes could be associated with the clinical course of slowly progressive ALS