Long-term effectiveness and cost-effectiveness of guided internet-based cognitive behavioral therapy for obsessive-compulsive disorder: 24-month follow-up.

This study investigated the long-term effectiveness and cost-effectiveness of guided internet-based cognitive behavioral therapy (ICBT) for obsessive-compulsive disorder (OCD). Twenty-five patients with OCD who had undergone guided ICBT in a randomized controlled trial or a single-arm trial were followed up for 6, 12, and 24 months. Missing data were imputed using the mice package in R, and a one-way analysis of variance with repeated measures was performed. The total Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score significantly decreased from baseline to all endpoints (p < 0.001). OCD remission (the total Y-BOCS score < 14) rates significantly increased from post-treatment (48 %) at the 12 months (80 %) and 24 months (76 %) follow-up (χ2 (1) = 7.11-11.08, p < 0.01) post guided ICBT. Regression analysis predicted the maintenance of remission at 12 and 24 months following post-treatment remission (z = 2.20, p = 0.03). An incremental cost-effectiveness ratio was calculated to assess the cost-effectiveness of guided ICBT. The incremental cost-effectiveness ratio was JPY 999,495, below the JPY 5 million threshold for willingness to pay in Japan. Our findings demonstrate the long-term effectiveness and cost-effectiveness of guided ICBT for OCD. Guided ICBT can mitigate the severity of OCD even after treatment.

Feasibility of Guided Internet-Based Cognitive Behavioral Therapy for Panic Disorder and Social Anxiety Disorder in Japan: Pilot Single-Arm Trial.

BACKGROUND: Cognitive behavioral therapy (CBT) is effective in treating anxiety disorders. Accessibility to CBT has been limited in Japan due to the shortage of therapists. While an open-source e-learning system can be used to create a simple internet-based cognitive behavioral therapy (ICBT) program, the safety and outpatient acceptance of this treatment approach have not been explored in Japan. OBJECTIVE: The aim of this study was to investigate whether outpatients with anxiety disorders could accept and successfully complete the ICBT program with guidance by CBT therapists when implementing therapeutic modules and CBT tasks. Due to being in the initial phase of a novel treatment in Japan, this study was intended for verification with a small sample size. METHODS: In total, 6 adults, including 4 male participants and 2 female participants, were enrolled in a single-arm trial. The intervention involved guided ICBT comprising 12 sessions, including CBT text, comprehension confirmation tests, and explanatory videos about cognitive behavioral models, accessible through a website. The therapist guided the participants in accessing the ICBT program and answering their questions using a chat tool. The primary outcome was anxiety severity assessed using the State-Trait Anxiety Inventory-Trait. Secondary outcomes included the Panic Disorder Severity Scale, Liebowitz Social Anxiety Scale (LSAS), Beck Anxiety Inventory (BAI), Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Working Alliance Inventory-Short Form (WAI-SF). Statistical analyses were performed using paired 2-tailed t tests to assess the changes in clinical symptoms. The total WAI-SF score at the final session was used to evaluate the therapeutic alliance. For statistical analyses, mean changes for total State-Trait Anxiety Inventory-Trait, BAI, Panic Disorder Severity Scale, LSAS, Patient Health Questionnaire-9, and Generalized Anxiety Disorder-7 scores were analyzed using the paired 2-tailed t test. The 2-sided significance level for hypothesis testing was set at 5%, and 2-sided 95% CIs were calculated. RESULTS: Most participants diligently engaged with the ICBT program. No adverse events were reported. The mean total scores for the primary outcome decreased by 11.0 (SD 9.6) points (95% CI -22.2 to 0.20; Hedges g=0.95), but it was not statistically significant. The mean total scores for the secondary outcomes that assess clinical symptoms decreased, with a significant reduction observed in the BAI of 15.7 (SD 12.1) points (95% CI -28.4 to -3.0; P=.03; Hedges g=1.24). The mean total scores for PDSS and LSAS decreased significantly, by 12.0 (SD 4.24) points (95% CI -50.1 to 26.1; P=.16; Hedges g=1.79) and 32.4 (SD 11.1) points (95% CI -59.7 to -4.3; P=.04; Hedges g=1.38), respectively. Of the participants, 67% (n=4) showed treatment response, and 50% (n=3) achieved remission after the intervention. The therapeutic alliance, measured using the WAI-SF, was moderate. CONCLUSIONS: Guided ICBT may be feasible for the treatment of outpatients with panic disorder and social anxiety disorder in Japan. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry UMIN0000038118; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000043439.

Difference in target dose distributions between Acuros XB and collapsed cone convolution/superposition and the impact of the tumor locations in clinical cases of stereotactic ablative body radiotherapy for lung cancer.

Objectives: The objective of the study is to analyze the difference in target dose distributions between Acuros XB (AXB) and collapsed cone convolution (CCC)/superposition and the impact of the tumor locations in clinical cases of stereotactic ablative body radiotherapy (SABR) for lung cancer. Materials and Methods: Ninety-six patients underwent SABR for lung cancers Kyushu University Hospital from 2014 to 2017. We recalculated clinical plans originally calculated by AXB using CCC with the identical monitor units (MUs) and beam arrangements. We calculated the following dosimetric parameters: maximum dose (Dmax), minimum dose (Dmin), homogeneity index (HI), conformity index (CI), and D95 of the planning target volume (PTV). We investigated the difference between the results of two calculations and examined the impact of tumor location. Moreover, we determined the target central dose using a thorax phantom and assessed the calculation accuracy of the two algorithms for each fraction. Results: CCC significantly overestimated the dose to PTV, compared to AXB (P < 0.05). The mean differences of Dmax, Dmin, and D95 were 1.17, 1.95, and 1.85 Gy, respectively. The mean differences of HI and CI were 0.02 and - 0.06. Dmin, HI, and D95 had significant correlations with the tumor location, and the difference was greater when the PTV was included the chest wall (P < 0.05). The discrepancy between the calculated and irradiated dose was 2.48% for CCC, whereas it was 0.14% for AXB. Conclusions: We demonstrated that CCC significantly overestimated the dose to PTV relative to AXB in clinical cases of lung SABR.

Guided Internet-Based Cognitive Behavioral Therapy for Women With Bulimia Nervosa: Protocol for a Multicenter Randomized Controlled Trial.

BACKGROUND: Individual face-to-face cognitive behavioral therapy is known to be effective for bulimia nervosa (BN). Since foods vary considerably between regions and cultures in which patients live, cultural adaptation of the treatment program is particularly important in cognitive behavioral therapy for BN. Recently, an internet-based cognitive behavioral therapy (ICBT) program was developed for Japanese women with BN, adapted to the Japanese food culture. However, no previous randomized controlled trial has examined the effectiveness of ICBT. OBJECTIVE: This paper presents a research protocol for strategies to examine the effects of guided ICBT. METHODS: This study is designed as a multicenter, prospective, assessor-blinded randomized controlled trial. The treatment groups will be divided into treatment as usual (TAU) alone as the control group and ICBT combined with TAU as the intervention group. The primary outcome is the total of binge eating and purging behaviors assessed before and after treatment by an independent assessor. Secondary outcomes will include measures of eating disorder severity, depression, anxiety, quality of life, treatment satisfaction, and working alliances. Treatment satisfaction and working alliances will be measured post assessment only. Other measures will be assessed at baseline, post intervention, and follow-up, and the outcomes will be analyzed on an intention-to-treat basis. RESULTS: This study will be conducted at 7 different medical institutions in Japan from August 2022 to October 2026. Recruitment of participants began on August 19, 2022, and recruitment is scheduled to continue until July 2024. The first participants were registered on September 8, 2022. CONCLUSIONS: This is the first multicenter randomized controlled trial in Japan comparing the effectiveness of ICBT and TAU in patients with BN. TRIAL REGISTRATION: University Hospital Medical Information Network UMIN000048732; https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000055522. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49828.

Dismantling cognitive-behavioural therapy components for attention-deficit hyperactivity disorder in adolescents and adults: protocol for a network meta-analysis.

INTRODUCTION: Cognitive-behavioural therapy (CBT) consists of multiple treatment techniques for each treatment model and is tailored to the patient's characteristics. Randomised controlled trials (RCTs) have reported that CBT is effective for attention-deficit/hyperactivity disorder (ADHD); however, which CBT components are effective is unknown. In order to provide the best treatment technique, it is important to know which therapeutic component or combination thereof is more effective and what the specific effect size is. METHODS AND ANALYSIS: We will perform component network meta-analysis (cNMA). The search will include studies published from database inception up to 31 March 2022, in English. The electronic databases of MEDLINE (via PubMed), EMBASE, PsycINFO, ClinicalTrials.gov and Cochrane Library will be searched. We will systematically identify all RCTs in the treatment of ADHD between the ages of 10 and 60 years, comparing interventions composed of various CBT components with controlled interventions. We will perform pairwise and network meta-analysis with random effects to estimate summary ORs and standardised mean differences. We will assess the risk of bias in selected studies using the Cochrane risk of bias tool. ETHICS AND DISSEMINATION: Since we will review published papers, ethical approval is not required. The results from this cNMA will provide a panorama of the CBT-based ADHD studies. The results of this study will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022323898.

Relative Biological Effectiveness Values of Spot-scanning Proton Beam Therapy at Shonan Kamakura General Hospital.

BACKGROUND/AIM: This study aimed to confirm the relative biological effectiveness (RBE) values of the proton beam therapy (PBT) system installed in Shonan Kamakura General Hospital. MATERIALS AND METHODS: Clonogenic cell-survival assays were performed with a human salivary gland (HSG) cell line, a human tongue squamous-cell carcinoma cell line (SAS), and a human osteosarcoma cell line (MG-63). Cells were irradiated with proton beams and X-rays with different doses (1.8, 3.6, 5.5, and 7.3 Gy for proton beams, and 2, 4, 6, and 8 Gy for X-rays). Proton beam irradiation used spot-scanning methods and three different depths (at the proximal, center, and distal sides of the spread-out Bragg peak). RBE values were obtained from a comparison of the dose that resulted in a surviving fraction of 10% (D10). RESULTS: D10 of proton beams at the proximal, center, and distal sides and X-rays in HSG were 4.71, 4.71, 4.51, and 5.25 Gy, respectively; those in SAS were 5.08, 5.04, 5.01, and 5.59 Gy, respectively; and those in MG-63 were 5.36, 5.42, 5.12, and 6.06 Gy, respectively. The RBE10 values at the proximal, center, and distal sides in HSG were 1.11, 1.11, and 1.16 respectively; those in SAS were 1.10, 1.11, and 1.12, respectively; and those in MG-63 were 1.13, 1.12, and 1.18, respectively. CONCLUSION: RBE10 values of 1.10-1.18 were confirmed by in vitro experiments using the PBT system. These results are considered acceptable for clinical use in terms of therapeutic efficacy and safety.

Impact of cognitive reserve on bipolar disorder: a systematic review.

Background: Cognitive reserve (CR) is a complex concept that includes premorbid IQ, years of education, and exposure to neuropsychological stimuli through work and leisure. Previous studies have suggested that CR has a positive impact on several aspects of bipolar disorder. Synthesizing the evidence to date is an important work in providing directions for future studies. The objectives of this systematic review to summary impact of CR on onsetting, relapsing bipolar episodes, buffering cognitive dysfunctions, and maintaining quality of life (QOL) in bipolar disorder. Methods: Two researchers independently reviewed selected paper from three database as PubMed, PsychINFO, and Web of Science. The search keywords were "bipolar disorder" and "cognitive reserve." The selected studies were classified as the levels of evidence according to the criteria of the Oxford Center for Evidence- Based Medicine. The results of the selected studies were summarized according to the objectives. Results: Thrity six studies were included in this review. People with high CR may have fewer bipolar episodes and alleviate cognitive impairments and dysfunction. CR may keep the functional level in patients with bipolar disorder. Conclusion: The results of this systematic review suggest that CR may be involved in preventing relapse of bipolar episodes and may alleviate cognitive dysfunction. However, effect on prevention of onset-risk and relapse of bipolar episodes need further investigation in prospective studies. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021270293, the protocol was registered with PROSERO (CRD42021270293).

Impact of the Coronavirus Disease 2019 Pandemic on the Clinical Features of Pediatric Respiratory Syncytial Virus Infection in Japan.

Background: Mitigation measures implemented during the coronavirus disease 2019 (COVID-19) pandemic remarkably reduced the incidence of infectious diseases among children. However, a re-emergence of respiratory syncytial virus (RSV) infection was observed in 2021 in Japan. We compared the clinical characteristics of hospitalized patients with RSV infection before and during COVID-19. Methods: We retrospectively enrolled children aged <6 years who were hospitalized with RSV infection in 18 hospitals and compared their clinical characteristics before (January 2019 to April 2020, 1675 patients) and during COVID-19 (September 2020 to December 2021, 1297 patients). Results: The mean age of patients with RSV infection was significantly higher during COVID-19 than before (17.4 vs 13.7 months, P < .001). Compared with before COVID-19, a 2.6-fold increase in RSV cases in the 2-5 years age group was observed from sentinel surveillance during COVID-19, whereas a 1.2-fold increase was noted in the same age group among hospitalized patients. On average for all patients, consolidation shadows obtained on radiography were less frequently observed (26.1 vs 29.6%, P = .04), and reduced respiratory assistance (42.2% vs 48.7%, P < .001) and hospitalization stay (5.7 vs 6.0 days, P < .001) was required in patients with RSV infection during COVID-19. Conclusions: Coronavirus disease 2019 and social activity restriction caused epidemiological changes in pediatric RSV infections, and a majority of patients with RSV infection aged ≥2 years did not develop severe symptoms requiring hospitalization. The RSV symptoms during the COVID-19 outbreak were equivalent to or milder than in the previous seasons.

The Lack of Alterations in Metabolites in the Medial Prefrontal Cortex and Amygdala, but Their Associations with Autistic Traits, Empathy, and Personality Traits in Adults with Autism Spectrum Disorder: A Preliminary Study.

Proton magnetic resonance spectroscopy (1H-MRS) has shown inconsistent alterations in brain metabolites of adults with autism spectrum disorder (ASD). We investigated brain metabolites in the medial prefrontal cortex and amygdala of 24 drug-naive adults with ASD and no intellectual disability and 24 non-ASD control subjects, using 3 T 1H-MRS. Adults with ASD showed no significant differences from control in glutamate, glutamate plus glutamine, N-acetylaspartate, glycerophosphorylcholine plus phosphorylcholine, creatine plus phosphocreatine, or myo-inositol in either region. However, ASD subjects did show significant correlations of localized brain metabolites with autistic traits, empathy deficits, and personality traits using the Autism-Spectrum Quotient, Questionnaire of Cognitive and Affective Empathy, Interpersonal Reactivity Index, and NEO Personality Inventory-Revised. These findings should be taken as preliminary or exploratory.

Development of a culturally adaptable internet-based cognitive behavioral therapy for Japanese women with bulimia nervosa.

Background: The process of cultural adaptation of internet-based cognitive behavioral therapy (ICBT) programs for bulimia nervosa (BN) have rarely been reported despite the potential influence of cultural adaptation of psychosocial interventions on therapeutic response. Aim: This study aimed to illustrate development process of an ICBT program for Japanese women with bulimia nervosa (BN). Methods: A mixed methods approach was used to assess cultural adaptation of the prototype of an original ICBT program by using the Cultural Relevance Questionnaire (CRQ). Five women with BN and seven clinicians were interviewed using the CRQ. Results: Quantitative analyses were conducted to assess cultural adaptation of the prototype of the program and participants rated cultural adaptation as high. A qualitative analysis of the mixed method supported the culturally sensitive changes implemented. Conclusions: The results of this study show that a series of processes can make ICBT programs more culturally adapted.

Impact of post-COVID conditions on mental health: a cross-sectional study in Japan and Sweden.

BACKGROUND: Due to the coronavirus disease 2019 (COVID-19) pandemic, people have undermined their mental health. It has been reported that post-COVID conditions at a certain rate. However, information on the mental health of people with post-COVID conditions is limited. Thus, this study investigated the relationship between post-COVID conditions and mental health. METHODS: Design of the present study was an International and collaborative cross-sectional study in Japan and Sweden from March 18 to June 15, 2021. The analyzed data included 763 adults who participated in online surveys in Japan and Sweden and submitted complete data. In addition to demographic data including terms related to COVID-19, psychiatric symptoms such as depression, anxiety, and post-traumatic stress were measured by using the fear of COVID-19 scale (FCV-19S), Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder-7 item (GAD-7), and Impact of Event Scale-Revised (IES-R). RESULTS: Of the 135 COVID-19 survivors among the 763 total participants, 37.0% (n = 50/135) had COVID-19-related sequelae. First, the results of the Bonferroni-corrected Mann Whitney U test showed that the group infected SARS-CoV-2 with post-COVID conditions scored significantly higher than those without one and the non-infected group on all clinical symptom scales (P ≤ .05). Next, there was a significant difference that incidence rates of clinical-significant psychiatric symptoms among each group from the results of the Chi-squared test (P ≤ .001). Finally, the results of the multivariate logistic model revealed that the risk of having more severe clinical symptoms were 2.44-3.48 times higher among participants with post-COVID conditions. CONCLUSION: The results showed that approximately half had some physical symptoms after COVID-19 and that post-COVID conditions may lead to the onset of mental disorders. TRIAL REGISTRATION: The ethics committee of Chiba University approved this cross-sectional study (approval number: 4129). However, as no medical intervention was conducted, a clinical trial registration was not necessary.

Guided internet-based cognitive behavioral therapy for obsessive-compulsive disorder: A multicenter randomized controlled trial in Japan.

Few studies have compared the effectiveness of internet-based cognitive behavior therapy (ICBT) for obsessive-compulsive disorder (OCD) with treatment as usual (TAU). We investigated the effectiveness of guided ICBT for patients with OCD. This prospective, randomized, controlled, assessor-blinded, multicenter clinical trial was conducted at three facilities in Japan from January 2020 to March 2021. Thirty-one patients with OCD as the primary diagnosis participated in the trial and were randomly assigned to either the intervention group or the control group. The primary outcome was the Yale-Brown obsessive-compulsive scale score; the assessors were blinded. Results of the analysis of covariance among the groups were significantly different between the groups (p < 0.01, effect size Cohen's d = 1.05), indicating the superiority of guided ICBT. The results suggest that guided ICBT is more effective than TAU for treating OCD. RCT REGISTRATION: UMIN Clinical Trials Registry (UMIN000039375).

Feasibility of guided internet-based cognitive behavioral therapy for patients with anorexia nervosa.

Objective: The objective of the present study was to investigate the feasibility of guided internet cognitive behavioral therapy (ICBT) for anorexia nervosa. Methods: We conducted a prospective single-arm study between January 2020 and March 2021. The intervention was built using videos, web programs, and chat tools. The intervention program was largely based on metacognitive training. Participants performed the self-help program once a week for 12 consecutive weeks. The primary outcome was the global Eating Disorder Examination Questionnaire (EDE-Q) score. Secondary outcomes included clinical symptoms of eating disorders, metacognitive function, body mass index, depression, and generalized anxiety. The main statistical analysis examined whether the EDE-Q score and other outcomes at the end of the intervention differed from the baseline. Results: Fourteen participants underwent the trial treatment, and 13 completed the intervention. There was a significant reduction in the global EDE-Q score from 3.48 (SD = 1.4) to 2.54 (SD = 1.5, p = 0.02, Cohen's d = 0.75) from baseline to post-intervention. Some EDE-Q subscales and body checking questionnaire scale demonstrated statistically significant improvements, with moderate to large effect sizes. Although there was no significant improvement in body mass index, metacognitive function, or depressive symptoms, there was a significant improvement in the severity of generalized anxiety (M = -4.0, p = 0.01, Cohen's d = 0.95). No adverse events were observed. Discussion: Our findings suggest that guided ICBT for anorexia nervosa is well accepted by female patients and practical as a telemedicine approach that improves symptoms. In the future, tightly controlled randomized controlled trials should be conducted for efficacy verification.

Associations among autistic traits, cognitive and affective empathy, and personality traits in adults with autism spectrum disorder and no intellectual disability.

Reported empathy deficits in autism spectrum disorder (ASD) could be attributable to other ASD-related features. We evaluated 28 ASD adults with no intellectual disability and 24 age-matched non-ASD control subjects using the Autism-Spectrum Quotient (AQ), Questionnaire of Cognitive and Affective Empathy (QCAE), Interpersonal Reactivity Index (IRI), and NEO Personality Inventory-Revised (NEO). Compared to the controls, ASD participants showed lower scores for perspective taking, online simulation, cognitive empathy, and peripheral responsivity on the QCAE, and lower scores for perspective taking and empathic concern on the IRI. Within the ASD group, the AQ scores showed significant relationships with perspective taking, online simulation and cognitive empathy on the QCAE, and perspective taking on the IRI. The ASD group also showed higher scores for neuroticism and lower scores for extraversion on the NEO compared to the controls. However, there were no relationships between AQ scores and NEO factors within the ASD group. Multiple regression analysis with stepwise linear regression demonstrated that perspective taking score on the QCAE and extraversion score on the NEO were good predictor variables to autistic traits on the AQ. These findings help us to understand empathy and personality traits in ASD adults with no intellectual disability.

Effectiveness of Videoconference-Delivered Cognitive Behavioral Therapy for Adults With Psychiatric Disorders: Systematic and Meta-Analytic Review.

BACKGROUND: Cognitive behavioral therapy (CBT) is the gold standard of psychotherapy for psychiatric disorders. However, the format of delivering CBT in person limits access to the intervention. The advancements in information and communication technology, especially the internet, present an opportunity for cognitive behavioral therapists to service patients or clients in remote areas through videoconferencing. Although many randomized controlled trials of videoconference-delivered cognitive behavioral therapy (VCBT) have already been conducted, the overall estimated effect size of VCBT for psychiatric disorders has not been examined by systematic reviews and meta-analyses. OBJECTIVE: This study attempts to evaluate the effectiveness of VCBT for psychiatric disorders through a systematic and meta-analytic review. METHODS: A systematic review and meta-analysis of studies in which VCBT was directly compared to control groups (such as treatment as usual, attention control, wait-list control, and other minimal supports) was carried out. To identify previous studies that meet our study objective, 2 independent reviewers undertook a systematic search through seven databases: MEDLINE (via PubMed), Web of Science, Science Direct, PsycINFO, CINAHL, LILACS, and SciELO. Other databases (ClinicalTrials.gov and Cochrane Central Resister of Controlled Trials) were also checked. All studies included in the review were assessed using the quality criteria of the Cochrane Collaboration. Statistical analysis was performed by using Cochrane Review Manager (RevMan, version 5.4.0). Standardized mean difference was used in major meta-analyses where a P value of .05 or less was the threshold for statistical significance. A heterogeneity test and the chi-square test were performed to assess the presence and extent of statistical heterogeneity with significance set at P<.10. Funnel plots were visually inspected to assess the risk of bias. Subgroup analyses were conducted for each disorder to estimate intervention effects. RESULTS: The systematic search resulted in 16 studies (total N=1745) that met the criteria for this study and were included in the review. There were 10 studies on depressive symptoms, 3 on chronic pain, 1 on generalized anxiety disorder, 1 on obsessive-compulsive disorder, and 1 on hypochondriasis. The quality and risk of bias was also assessed. Results showed a pooled effect size (Hedge g) post treatment of -0.49 (95% CI -0.68 to -0.29), indicating that VCBT is effective for clients with psychiatric disorders. Study quality did not affect outcomes. CONCLUSIONS: While the overall results indicate the effectiveness of VCBT, there are still only a limited number of studies on specific psychiatric and somatic conditions. Therefore, more randomized controlled trials are needed to establish the effectiveness of VCBT for different disorders. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) CRD42021224832; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=224832.

Histone chaperone-mediated co-expression assembly of tetrasomes and nucleosomes.

The nucleosome, a basic unit of chromatin found in all eukaryotes, is thought to be assembled through the orchestrated activity of several histone chaperones and chromatin assembly factors in a stepwise manner, proceeding from tetrasome assembly, to H2A/H2B deposition, and finally to formation of the mature nucleosome. In this study, we demonstrate chaperone-mediated assembly of both tetrasomes and nucleosomes on the well-defined Widom 601 positioning sequence using a co-expression/reconstitution wheat germ cell-free system. The purified tetrasomes and nucleosomes were positioned around the center of a given sequence. The heights and diameters were measured by atomic force microscopy. Together with the reported unmodified native histones produced by the wheat germ cell-free platform, our method is expected to be useful for downstream applications in the field of chromatin research.

Imagining How Lines Were Drawn: The Appreciation of Calligraphy and the Facilitative Factor Based on the Viewer's Rating and Heart Rate.

For this study, we examined how recognizing the writing process of calligraphy influences the cognitive and affective processes related to appreciating it, with the aim of contributing to both graphonomics and the psychology of aesthetics. To this end, we conducted two Web-based experiments in which some participants were instructed to view calligraphy by tracing it with their eyes (the tracing method), while others were told to feel free to think and imagine whatever they wanted. Study 1 (N = 103) revealed that the tracing method elicits stronger admiration, inspiration, and empathy in viewers. Study 2 (N = 87) showed that the tracing method decreases the average heart rate of those who do not frequently engage in calligraphy appreciation as they gaze at calligraphy for a minute-and-a-half (during the second half of the stimulus duration); this suggests that the tracing method could keep viewers from becoming bored while looking at calligraphy. In sum, the tracing method has positive effects on viewing calligraphy. From a broader perspective, the results imply that how in detail viewers recognize the process of creating an artwork will be a key determinant of art appreciation. In addition, our findings demonstrate how we can measure cardiac activities using the emerging technology of the photoplethysmogram (PPG).

Mannose- and Mannobiose-Specific Responses of the Insect-Associated Cellulolytic Bacterium Streptomyces sp. Strain SirexAA-E.

The cellulolytic insect symbiont bacterium Streptomyces sp. strain SirexAA-E secretes a suite of carbohydrate-active enzymes (CAZymes), which are involved in the degradation of various polysaccharides in the plant cell wall, in response to the available carbon sources. Here, we examined a poorly understood response of this bacterium to mannan, one of the major plant cell wall components. SirexAA-E grew well on mannose, carboxymethyl cellulose (CMC), and locust bean gum (LBG) as sole carbon sources in the culture medium. The secreted proteins from each culture supernatant were tested for their polysaccharide-degrading ability, and the composition of secreted CAZymes in each sample was determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results indicated that mannose, LBG, and CMC induced the secretion of mannan and cellulose-degrading enzymes. Interestingly, two α-1,2-mannosidases were abundantly secreted during growth on mannose and LBG. Using genomic analysis, we found a unique 12-bp palindromic sequence motif at 4 locations in the SirexAA-E genome, two of which were found upstream of the above-mentioned α-1,2-mannosidase genes, along with a newly identified mannose and mannobiose-responsive transcriptional regulator, SsManR. Furthermore, the previously reported cellobiose-responsive repressor, SsCebR, was determined to also use mannobiose as an effector ligand. To test whether mannobiose induces the sets of genes under the control of the two regulators, SirexAA-E was grown on mannobiose, and the secretome composition was analyzed. As hypothesized, the composition of the mannobiose secretome combined sets of CAZymes found in both LBG and CMC secretomes, and thus they are likely under the regulation of both SsManR and SsCebR. IMPORTANCEStreptomyces sp. SirexAA-E, a microbial symbiont of biomass-harvesting insects, secretes a suite of polysaccharide-degrading enzymes dependent on the available carbon sources. However, the response of this bacterium to mannan has not been documented. In this study, we investigated the response of this bacterium to mannose, mannobiose, and galactomannan (LBG). By combining biochemical, proteomic, and genomic approaches, we discovered a novel mannose and mannobiose responsive transcriptional regulator, SsManR, which selectively regulates three α-1,2-mannosidase-coding genes. We also demonstrated that the previously described cellobiose responsive regulator, SsCebR, could use mannobiose as an effector ligand. Overall, our findings suggest that the Streptomyces sp. SirexAA-E responds to mannose and mannooligosaccharides through two different transcriptional repressors that regulate the secretion of the plant cell wall-degrading enzymes to extract carbon sources in the host environment.