Altered functional organization within the insular cortex in adult males with high-functioning autism spectrum disorder: evidence from connectivity-based parcellation

Determination of the optimal number of clusters based on VI and MI in intracalcarine cortex. The intracalcarine cortex was selected as a control region. The VI and MI values are shown for every clustering solution for k values ranging from 2 to 10. Arrows indicate either local minima of VI or local maxima of MI. Dashed lines denote the optimal number of solutions as determined using both VI and MI. The error bars denote standard errors of the mean for 100 repetitions of the split-half procedure (see the “Estimation of the optimal number of clusters” section). “n.s.” indicates no statistically significant difference between points. (PDF 334 kb

Atypical gaze patterns in children and adults with autism spectrum disorders dissociated from developmental changes in gaze behaviour

Eye tracking has been used to investigate gaze behaviours in individuals with autism spectrum disorder (ASD). However, traditional analysis has yet to find behavioural characteristics shared by both children and adults with ASD. To distinguish core ASD gaze behaviours from those that change with development, we examined temporo-spatial gaze patterns in children and adults with and without ASD while they viewed video clips. We summarized the gaze patterns of 104 participants using multidimensional scaling so that participants with similar gaze patterns would cluster together in a two-dimensional plane. Control participants clustered in the centre, reflecting a standard gaze behaviour, whereas participants with ASD were distributed around the periphery. Moreover, children and adults were separated on the plane, thereby showing a clear effect of development on gaze behaviours. Post hoc frame-by-frame analyses revealed the following findings: (i) both ASD groups shifted their gaze away from a speaker earlier than the control groups; (ii) both ASD groups showed a particular preference for letters; and (iii) typical infants preferred to watch the mouth rather than the eyes during speech, a preference that reversed with development. These results highlight the importance of taking the effect of development into account when addressing gaze behaviours characteristic of ASD

The right temporoparietal junction during a cooperation dilemma: An rTMS study

Cooperation enhances interpersonal communication and nurtures society. However, efforts to socially cooperate may often evoke conflict. Individuals may selfishly pursue a greater reward or success by exploiting the efforts of other individuals or taking unnecessary risk to oneself. Such a cooperation dilemma is highly prevalent in real life; thus, it has been studied in various disciplines. Although published functional magnetic resonance imaging studies have shown the involvement of the right temporoparietal junction (TPJ) in resolving a dilemma through cooperation, a causal relationship between the two has rarely been explored. Hence, we investigated this issue by combining repetitive transcranial magnetic stimulation with a priority game task (modified snowdrift game). In this game task, participants and opponent players jointly faced a problem whereby their collaboration was anticipated to defuse the situation. This conflicted with a choice in the participant's self-interest that was more rewarding but risky. We further included conditions with and without explicit social cues using figures describing elderly/pregnant passengers in the game opponent's car, and measured participants' prosocial traits to examine any cue-induced effect as well as the personality-cooperation relationship, respectively. The cooperation ratio was not statistically different in both the no-cue and with-cue conditions between the sham stimulation and inhibitory continuous theta burst stimulation (cTBS). However, after cTBS, in the no-cue condition, the strength of the association between cooperation ratio and empathy traits decreased significantly. These results add to our knowledge about the right TPJ's role in social cognition, which may be extraordinarily complex. This topic is deserving of further examination

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

iPSC-Based Compound Screening and In Vitro Trials Identify a Synergistic Anti-amyloid β Combination for Alzheimer’s Disease

In the process of drug development, in vitro studies do not always adequately predict human-specific drug responsiveness in clinical trials. Here, we applied the advantage of human iPSC-derived neurons, which offer human-specific drug responsiveness, to screen and evaluate therapeutic candidates for Alzheimer’s disease (AD). Using AD patient neurons with nearly 100% purity from iPSCs, we established a robust and reproducible assay for amyloid β peptide (Aβ), a pathogenic molecule in AD, and screened a pharmaceutical compound library. We acquired 27 Aβ-lowering screen hits, prioritized hits by chemical structure-based clustering, and selected 6 leading compounds. Next, to maximize the anti-Aβ effect, we selected a synergistic combination of bromocriptine, cromolyn, and topiramate as an anti-Aβ cocktail. Finally, using neurons from familial and sporadic AD patients, we found that the cocktail showed a significant and potent anti-Aβ effect on patient cells. This human iPSC-based platform promises to be useful for AD drug development

Co-processing of Saturated and Unsaturated Triglycerides in Catalytic Cracking Process for Hydrocarbon Fuel Production

With the aim of the efficient use of plant oils as alternative fuels, the deoxygenation of saturated and unsaturated triglycerides in a catalytic cracking process was investigated using a fluid catalytic cracking catalyst with enhanced hydrogen-transfer activity. The decomposition and deoxygenation of sun flower oil (unsaturated triglycerides) proceeded rapidly and produced a large amount of aromatic hydrocarbons, which are unsuitable for fuel applications. In contrast, the rate of deoxygenation of coconut oil (saturated triglycerides) was slow and some oxygen-containing species were observed as products. During the co-processing of saturated and unsaturated triglycerides, the deoxygenation of saturated triglycerides was accelerated and complete deoxygenation was achieved. The acceleration of the deoxygenation reaction was attributed to the rapid formation of hydrogen donors, such as olefins and naphthenes, from the decomposition of unsaturated triglycerides. The olefins and naphthenes released hydrogen species by cyclization and aromatization reactions. These hydrogen species then reacted with saturated triglycerides and their derivatives (fatty acids and aldehydes) in hydrogen-transfer reactions, accelerating the hydrodeoxygenation of saturated triglycerides. The hydrodeoxygenation of saturated triglycerides produced paraffins and olefins rather than aromatics. The increase in the amount of paraffins and olefins produced by the accelerated deoxygenation of saturated triglycerides was larger than the amount of aromatic hydrocarbons derived from unsaturated triglycerides. Thus, co-processing of saturated and unsaturated triglycerides was confirmed to be effective for simultaneously achieving both the acceleration of saturated triglyceride deoxygenation and the suppression of aromatic hydrocarbon formation.ArticleJOURNAL OF CHEMICAL ENGINEERING OF JAPAN.51(9):778-785(2018)journal articl

Hydrocarbon Fuel Production from Lignocellulosic Biomass by Solvolysis and Catalytic Cracking

Utilization of lignocellulosic biomass for alternative fuels requires efficient and low-cost processes for deoxygenation and conversion to hydrocarbons. We propose a 2-step biomass conversion process consisting of solvolysis pretreatment and co-processing with heavy petroleum oil in catalytic cracking. High liquefied yield (> 90 C%) was achieved by solvolysis in guaiacol and water with acetic acid catalysts. Bio-oil was mainly converted to gaseous hydrocarbons and coke by co-processing with model heavy oil (n-eicosane). Deoxygenation pathway to H2O formation was accelerated by enhancing hydrogen-transfer activity even without supplying hydrogen. Hydrogen-transfer deoxygenation proceeded preferentially to olefin hydrogenation. Consequently, enhancing hydrogen-transfer activity in the co-processing of bio-oil and heavy petroleum oil was effective for efficient deoxygenation without lowering octane rating.ArticleJOURNAL OF THE JAPAN PETROLEUM INSTITUTE.61(5):302-310(2018)journal articl