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Abstract Purpose This study examines the preliminary reliability and validity of the PedsQL™ Family Impact Module (PedsQL™ FIM) in parents of children with congenital muscular dystrophy (CMD). Methods The participants in this study were 28 parents of children with CMD and 39 parents of unaffected children. Both groups of parents completed the PedsQL™ FIM and a demographic information form. Cronbach’s alpha was used to examine the internal consistency reliability, and the known-groups method was used to assess construct validity. Three distinct models were used to estimate the mean score differences of the PedsQL™ FIM between the two groups: an unadjusted model, a multivariate regression model, and propensity score matching with inverse probability of treatment weighting. Results Cronbach’s alpha coefficients for all scales exceeded 0.70, supporting evidence for the internal consistency reliability of the PedsQL™ FIM. The construct validity of the PedsQL™ FIM demonstrated that the mean differences between the CMD and unaffected groups were significantly different (p

Theory: The successful implementation of computational thinking into primary schools requires that primary school teachers feel safe and confident in teaching this topic to young learners. However, many student teachers face low expectancy of success and heightened anxiety towards computational thinking. Self-worth theory suggests that this may lead to a self-worth threat and in consequence to engagement in self-protective behaviours, hampering the successful acquisition of skills needed to implement computational thinking into their future classrooms. Aims: This study aims to investigate potential self-worth threats as amplifiers of student teachers’ resistance to engage in computational thinking. Method: 323 student teachers participated in the study. Participants filled out a questionnaire on expectancy of success and anxiety towards computational thinking, and rated how likely they were to engage in self-protective behaviours, i.e., self-handicapping, avoiding novelty, and academic cheating, when learning about computational thinking at the start of the semester. Results: Students showed heightened levels of anxiety and low levels of expectancy towards computational thinking. Further, they reported that they would be likely to engage in self-protective behaviours. A structural equation model showed that anxiety towards computational thinking was positively related to self-protective behaviours. Moreover, expectancy had a negative indirect effect via anxiety towards computational thinking on self-protective behaviours. Discussion: Student teachers might experience self-worth threats when learning about computational thinking and engage in self-protective behaviours that might hamper their success. Our findings caution the impact of possible self-worth threats on teaching methods, thus influencing children's learning in the 21st century.

# Background Ecological momentary assessment (EMA) as a real-time data collection method can provide insight into the daily experiences of family caregivers. # Purpose This systematic review aimed to synthesize studies involving EMA completed by family caregivers of adults with chronic conditions. # Methods A systematic search was conducted within six databases for articles published from the inception of the database through September 2023. We extracted the characteristics of the included studies and data on EMA-specific methods to determine the quality of the included studies. # Results A total of 12 studies involving EMA completed by family caregivers of adults with chronic conditions were identified, with almost all studies focused on caregivers of persons with Alzheimer's or dementia-related conditions. The average compliance rate across the included studies was 75%, below the recommended rate. In addition, most of the included studies did not collect the family caregivers' daily activities and care contexts in their responses (i.e., affect, stress, well-being, care demand, and fatigue) to the EMA prompts. # Discussion This review showed that using EMA to collect information on family caregivers of adults with chronic health conditions appeared feasible and acceptable. However, the methodology or design of using EMA to collect caregiver information in this population is still preliminary. The limited number of existing studies that have used EMA to capture the daily experiences of family caregivers does not provide key information that could improve understanding of caregivers' emotional experiences and well-being in real-life situations. We identified gaps in the literature that warrant additional EMA studies for this population.

Abstract Process data are becoming more and more popular in education research. In the field of computer-based assessments of collaborative problem solving (ColPS), process data have been used to identify students’ test-taking strategies while working on the assessment, and such data can be used to complement data collected on accuracy and overall performance. Such information can be used to understand, for example, whether students are able to use a range of styles and strategies to solve different problems, given evidence that such cognitive flexibility may be important in labor markets and societies. In addition, process information might help researchers better identify the determinants of poor performance and interventions that can help students succeed. However, this line of research, particularly research that uses these data to profile students, is still in its infancy and has mostly been centered on small- to medium-scale collaboration settings between people (i.e., the human-to-human approach). There are only a few studies involving large-scale assessments of ColPS between a respondent and computer agents (i.e., the human-to-agent approach), where problem spaces are more standardized and fewer biases and confounds exist. In this study, we investigated students’ ColPS behavioral patterns using latent profile analyses (LPA) based on two types of process data (i.e., response times and the number of actions) collected from the Program for International Student Assessment (PISA) 2015 ColPS assessment, a large-scale international assessment of the human-to-agent approach. Analyses were conducted on test-takers who: (a) were administered the assessment in English and (b) were assigned the Xandar unit at the beginning of the test. The total sample size was N = 2,520. Analyses revealed two profiles (i.e., Profile 1 [95%] vs. Profile 2 [5%]) showing different behavioral characteristics across the four parts of the assessment unit. Significant differences were also found in overall performance between the profiles.

Ptecticus tenebrifer (Walker, 1849), which is endemic in East Asia, plays a critical role in natural processing of organic waste. In this study, we found that the complete mitochondrial genome of P. tenebrifer is 15681 bp in length obtained from the MGIseq system (MGI) with 150 bp paired-end reads. As with typical animal mitochondrial genomes, it contains 13 protein coding genes, 22 tRNA genes, and 2 rRNA genes. The phylogenetic analysis was performed using the maximum likelihood method with a bootstrap value of 500 and the Tamura-Nei model and reveals the close relationship with P. aurifer.

This research was conducted to determine the biodiversity of higher fungi at the supersite of Mt. Jeombong from July to October 2017 during the second long-term ecology research by the National Institute of Ecology under the management of the Ministry of Environment of Korea. Forty-three families, 74 genera, and 130 species of higher fungi were found within the permanent square area of Mt. Jeombong and a 10 m radius of the ecological flux tower. Russulaceae (54 species, 21.9%), Amanitaceae (17 species, 6.9%), and Boletaceae (17 species, 6.9%) were the top three species taxa found in mycorrhizal mushrooms. Mycenaceae (nine species, 8.5%), Polyporaceae (11 species, 4.5%), and Strophariaceae (11 species, 4.5%) were the top three species taxa found in saprophytic mushrooms. These results were analyzed and compared with those of previous fungal mushroom studies.

Abstract Background Dental care in cancer patients tends to be less prioritized. However, limited research has focused on major dental treatment events in cancer patients after the diagnosis. This study aimed to examine dental treatment delays in cancer patients compared to the general population using a national claims database in South Korea. Method The Korea National Health Insurance Service-National Sample Cohort version 2.0, collected from 2002 to 2015, was analyzed. Treatment events were considered for stomatitis, tooth loss, dental caries/pulp disease, and gingivitis/periodontal disease. For each considered event, time-dependent hazard ratios and associated 95% confidence intervals were calculated by applying a subdistribution hazard model with time-varying covariates. Mortality was treated as a competing event. Subgroup analyses were conducted by type of cancer. Results The time-dependent subdistribution hazard ratios (SHRs) of stomatitis treatment were greater than 1 in cancer patients in all time intervals, 2.04 within 30 days after cancer diagnosis, and gradually decreased to 1.15 after 5 years. The SHR for tooth loss was less than 0.70 within 3 months after cancer diagnosis and increased to 1 after 5 years. The trends in SHRs of treatment events for other dental diseases were similar to those observed for tooth loss. Subgroup analyses by cancer type suggested that probability of all dental treatment event occurrence was higher in head and neck cancer patients, particularly in the early phase after cancer diagnosis. Conclusion Apart from treatments that are associated with cancer therapy, dental treatments in cancer patients are generally delayed and cancer patients tend to refrain from dental treatments. Consideration should be given to seeking more active and effective means for oral health promotion in cancer patients.

Abstract Huntington’s disease (HD) is a severe inherited neurological disorder caused by a CAG repeat expansion in the huntingtin gene (HTT), leading to the accumulation of mutant huntingtin with polyglutamine repeats. Despite its severity, there is no cure for this debilitating disease. HTT lowering strategies, including antisense oligonucleotides (ASO) showed promising results very recently. Attempts to develop stem cell-based therapeutics have shown efficacy in preclinical HD models. Using an HD patient’s autologous cells, which have genetic defects, may hamper therapeutic efficacy due to mutant HTT. Pretreating these cells to reduce mutant HTT expression and transcription may improve the transplanted cells’ therapeutic efficacy. To investigate this, we targeted the SUPT4H1 gene that selectively supports the transcription of long trinucleotide repeats. Transplanting SUPT4H1-edited HD-induced pluripotent stem cell-derived neural precursor cells (iPSC-NPCs) into the YAC128 HD transgenic mouse model improved motor function compared to unedited HD iPSC-NPCs. Immunohistochemical analysis revealed reduced mutant HTT expression without compensating wild-type HTT expression. Further, SUPT4H1 editing increased neuronal and decreased reactive astrocyte differentiation in HD iPSC-NPCs compared to the unedited HD iPSC-NPCs. This suggests that ex vivo editing of SUPT4H1 can reduce mutant HTT expression and provide a therapeutic gene editing strategy for autologous stem cell transplantation in HD.

Objective. This study examined the preliminary reliability and validity of the PedsQL™ Family Impact Module (PedsQL FIM) in families of children with Barth syndrome (BTHS). Method. A total of 72 parents with children or youth between the ages of 5 and 19 participated in this study. Thirty-three parents of children with BTHS and 39 parents of unaffected children completed the PedsQL FIM and a demographic information form. Internal consistency reliability and item-total correlations were calculated to test the reliability of the PedsQL FIM. Construct validity was examined using the known-groups method. We estimated the mean score differences of the PedsQL FIM between the two groups using three different models, including unadjusted, multivariate regression, and propensity score matching with inverse probability of treatment weighting (PS-IPTW) models. Results. The Cronbach’s alpha coefficients were greater than 0.70 for all scales of the PedsQL FIM, except for the communication scale. The item-total correlations were significant for all scales with moderate to high correlations (p

BackgroundAcceptance and commitment therapy (ACT) is an empirically supported transdiagnostic approach that involves mindfulness processes and behavior change processes for valued living. ObjectiveThis systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to assess the efficacy of internet-based ACT (iACT) for depressive symptoms, anxiety, stress, psychological distress, and quality of life (QoL). MethodsPubMed, CINAHL, PsycINFO, and SCOPUS databases were searched to identify relevant RCTs published up to June 5, 2021. The included RCTs were assessed using the Cochrane Collaboration risk-of-bias tool. The use of either a random effects model or fixed effects model was determined using I2 statistic values for heterogeneity. Subgroup analyses were conducted according to the type of control group, the use of therapist guidance, delivery modes, and the use of targeted participants, when applicable. ResultsA total of 39 RCTs met the inclusion criteria. Meta-analyses found small effects of iACT on depressive symptoms, anxiety, stress, psychological distress, and QoL at the immediate posttest and follow-up. There was no significant effect of iACT on stress at follow-up. Subgroup analyses showed small to medium effects of iACT on all the outcomes at the immediate posttest and follow-up compared with the passive control groups. In contrast, subgroup analyses that compared iACT with active control groups found no differences between groups on stress, psychological distress, and QoL at the immediate posttest or on depressive symptoms, anxiety, and stress at follow-up. In addition, subgroup analyses conducted according to the use of therapist guidance, delivery modes, and the use of targeted participants found no statistically significant subgroup differences among studies in all the outcomes, except for the subgroup difference among studies according to the use of targeted participants for depressive symptoms at the immediate posttest (ie, a statistically significant, larger effect of iACT when studies targeted people with depressive symptoms). The overall risk of bias across the studies was unclear. ConclusionsThe findings of this study contribute to the body of evidence regarding the effects of iACT on depressive symptoms, anxiety, stress, psychological distress, and QoL and may be applicable in any population, as ACT is a transdiagnostic approach. Few studies have compared iACT with active control conditions, especially for stress and psychological distress at the immediate posttest and follow-up. In addition, the active control conditions varied among the included studies. Further high-quality studies are needed to better understand whether iACT is comparable or superior to other evidence-based interventions, such as cognitive behavioral therapy, in decreasing depressive symptoms, anxiety, stress, and psychological distress and improving QoL.

This study was conducted to find the biodiversity of higher fungi at the supersite of Mt. Jeombong from July to October 2016 during the Second Long Term Ecology Research project. A total of 31 families, 52 genera, and 120 species of higher fungi were found within the permanent 1 ha qaudrat and in a 10 m radius of the ecological flux tower. From a taxonomical and ecological perspcetive, Russulaceae (22 species, 18.0%), Boletaceae (17 species, 13.9%), and Amanitaceae (10 species, 8.2%) were the top 3 taxa with the most species found in mycorrhizal mushrooms. Marasmiaceae (10 species, 9.8%), Mycenaceae (8 species, 6.6%), and Polyporaceae (6 species, 4.9%) were also the top 3 taxa with the most species found in saprophytic mushrooms.

BackgroundAcceptance and commitment therapy (ACT) is based on a psychological flexibility model that encompasses 6 processes: acceptance, cognitive defusion, self-as-context, being present, values, and committed action. ObjectiveThis systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to examine the effects of internet-based ACT (iACT) on process measures. MethodsA comprehensive search was conducted using 4 databases. The quality of the included RCTs was assessed using the Cochrane Collaboration Risk of Bias Tool. A random-effects or fixed-effects model was used. Subgroup analyses for each outcome were conducted according to the type of control group, use of therapist guidance, delivery modes, and use of targeted participants, when applicable. ResultsA total of 34 RCTs met the inclusion criteria. This meta-analysis found that iACT had a medium effect on psychological flexibility and small effects on mindfulness, valued living, and cognitive defusion at the immediate posttest. In addition, iACT had a small effect on psychological flexibility at follow-up. The overall risk of bias across studies was unclear. ConclusionsRelatively few studies have compared the effects of iACT with active control groups and measured the effects on mindfulness, valued living, and cognitive defusion. These findings support the processes of change in iACT, which mental health practitioners can use to support the use of iACT.

Open access to information is now a universal phenomenon thanks to rapid technological developments across the globe. This open and universal access to information is a key value of democratic societies because, in principle, it supports well-informed decision-making on individual, local, and global matters. In practice, however, without appropriate readiness for navigation in a dynamic information landscape, such access to information can become a threat to public health, safety, and economy, as the COVID-19 pandemic has shown. In the past, this readiness was often conceptualized in terms of adequate literacy levels, but the contemporarily observed highest-ever literacy levels have not immunized our societies against the risks of misinformation. Therefore, in this Perspective, we argue that democratization of access to information endows citizens with new responsibilities, and second, these responsibilities demand readiness that cannot be reduced to mere literacy levels. In fact, this readiness builds on individual adequate literacy skills, but also requires rational thinking and awareness of own information processing. We gather evidence from developmental, educational, and cognitive psychology to show how these aspects of readiness could be improved through education interventions, and how they may be related to healthy work-home balance and self-efficacy. All these components of education are critical to responsible global citizenship and will determine the future direction of our societies.

Background: It is well-documented that active coping strategies can lead to better positive adjustment and psycho-social outcomes among individuals with disabilities and illnesses. However, little information exists related to exploring how coping is related to health benefits such as personal growth and life satisfaction in an international context. Thus, this study examined how the use of coping strategies is associated with personal growth and life satisfaction among individuals with physical disabilities in non-Western settings. Methods: In this cross-sectional study, we employed a nonprobability methodology, purposivesampling, to recruit 351 participants who adults over the age of 18 living with a physicaldisability and currently enrolled in the Korean Disability Association. A hierarchical linearregression analysis was conducted to determine which types of coping strategies predictedpersonal growth and life satisfaction, while controlling for the effects of the demographicvariables (i.e., gender and age). Results: With regard to personal growth, problem-solving coping strategy (β = 0.663, P < 0.001,95% CI [0.51, 0.70]) was the strongest predictor, followed by avoidance coping strategy(β = -0.263, P < 0.001, 95% CI [-0.37, -0.20]). As for life satisfaction, problem-solving copingstrategy (β = 0.268, P < 0.001, 95% CI [0.18, 0.70]) was the strongest predictor, followed bysocial support seeking coping strategy (β = 0.264, P < 0.001, 95% CI [-0.19, 0.10]). Conclusion: Our study suggests that problem-focused and social support coping strategies playimportant roles in improving the personal growth and life satisfaction among Korean individualswith physical disabilities. This study provides implications for health professionals seeking waysto facilitate the personal growth and enhance the life satisfaction of individuals with physicaldisabilities.

Background: People with cancer often report high levels of negative psychological symptoms and poor perception of health due to cancer treatment and activity limitations. Prior studies have suggested that participation in leisure time physical activity (LTPA) can reduce negative psychological symptoms and improve health perception. However, a few studies have examined the contribution of LTPA to health benefits among people with cancer. Thus, we aimed to examine how a different level of LTPA engagement contributed to mental health and health perceptions among people with cancer. Methods: Using the 2017 Health Information National Trends Survey (HINTS) data, cross sectional data of 504 respondents diagnosed with any types of 22 cancers listed in the survey questionnaire were analyzed. A multivariate analysis of variance (MANOVA) was used to test for mean differences in mental health and health perception among the three different LTPA groups(i.e., inactive, moderately active, and vigorously active groups). Results: Results indicated that people with cancer who reported higher levels of LTPA scored higher on mental health and health perception than those with lower levels of LTPA (Pillai’s trace= 0.060, F (4,944) = 15.06, P < 0.001). Conclusion: This finding suggests that individuals with cancer gained more health benefits through high engagement in LTPA. Moreover, we suggested that LTPA can be used as an important therapeutic intervention to promote health quality and wellbeing among people with cancer. Implications for practical suggestions are further discussed.

Nephrogenesis ceases after postnatal day 2 in the mouse or after the 36th week of gestation in humans, but how this is regulated is unclear. Here, the authors identify a role for the RNA-binding protein Lin28 and suppression of let-7 microRNA in regulating the duration of nephrogenesis.

Research suggests that different levels of intensity of leisure walking can affect the mental health of older adults. Unfortunately, insufficient evidence exists as to the recommended intensity levels of leisure walking for their health benefits. The purpose of this study was to investigate how leisure walking intensity levels are associated with the mental health and health perceptions of older adults. Using a purposive sampling method, the data of 4,737 adults over the age of 65 were drawn from the 2017 California Health and Interview Survey. The results of analysis of these data showed that older adults who engaged in moderate and vigorous leisure walking reported higher health perceptions than those involved in light leisure walking. In addition, older adults who participated in moderate leisure walking reported higher mental health than those who engaged in light leisure walking. This study suggests that moderate and/or vigorous leisure walking can increase the mental health and health perceptions of older adults.

Objective. Autism spectrum disorder is a neurodevelopmental disorder that affects communication, social skills, and behavior and can present in early childhood. The present study is aimed at investigating the effects of family-centered early intervention on the quality of social interaction and social interaction skills in infants with suspected autism spectrum disorder using a single-subject design. Method. As a single-subject design study, evaluations were conducted at baseline phase A, intervention phase B, baseline phase A′, and follow-up phase. The family-centered early intervention program was implemented during the intervention phase. Family-centered early intervention programs included home environmental modification, play video recording and training, task and feedback, related information training, and question and answer. The Modified Checklist for Autism in Toddlers, Revised, with Follow-Up and Evaluation of Social Interaction was used for evaluation. Result. Three participants completed the study. After applying the family-centered early intervention program, the quality of social interaction and social interaction skills of all participants improved. In addition, the risk of autism spectrum disorder in all participants was reduced. Conclusion. Family-centered early intervention was confirmed to have a positive effect on the improvement of social interaction skills in infants with suspected autism spectrum disorder.

In this current research, mesoporous nano-hydroxyapatite (HAp) and F-doped hydroxyapatite (FHAp) were effectively obtained through a citric acid-enabled microwave hydrothermal approach. Citric acid was used as a chelating and modifying agent for tuning the structure and porosity of the HAp structure. This is the first report to use citric acid as a modifier for producing mesoporous nano HAp and F-doped FHAp. The obtained samples were characterized by different analyses. The XRD data revealed that F is incorporated well into the HAp crystal structure. The crystallinity of HAp samples was improved and the unit cell volume was lowered with fluorine incorporation. Transmission electron microscopy (TEM) images of the obtained samples revealed that a nano rod-like shape was obtained. The mesoporous structures of the produced HAp samples were confirmed by Brunauer–Emmett–Teller (BET) analysis. In vivo studies performed using zebrafish and C. elegans prove the non-toxic behavior of the synthesized F doped HAp samples. The obtained samples are also analyzed for antimicrobial activity using Gram-negative and Gram-positive bacteria, which are majorly involved in implant failure. The F doped samples revealed excellent bactericidal activity. Hence, this study confirms that the non-toxic and excellent antibacterial mesoporous F doped HAp can be a useful candidate for biocidal implant application.

Objective The purpose of this study is to introduce a standardised assessment tool by verifying the reliability of the translated Korean version of the Feeding Abilities Assessment (K-FAA), which was developed to suit Korean culture. Methods The research subjects were 65 patients with dementia living in nursing homes. The K-FAA was completed by verifying the suitability of translation and reverse translation. The validity of the K-FAA was established through content validity, while its reliability was analysed based on internal consistency reliability for the items, test–retest reliability and inter-rater reliability. Results The content validity index determined, based on the assessment of professors, occupational therapists, and nurses, was more than .70. Cronbach’s α was more than .929, showing good internal consistency. A test–retest reliability of .884 was derived using Pearson’s correlation coefficient (p

Rationale: Current knowledge in experiences and potential benefits of group-based activity programmes on people with dementia and their caregivers is inconsistent, depending on the quality of interventions. Lacking standardisation in the programme’s content and structure, therefore, requires research in a structured group-based activity programme with more details. Objectives This study explored perspectives of spouses of people with dementia and older volunteers about Stepping Stones , involving a theme-based activity group and a support group. Methodology: Interpretative phenomenological analysis was used to analyse individual interview data with 12 people. Results Findings suggest that (1) Stepping Stones promotes participation of people with dementia in a happy, comfortable and accepting environment; (2) Stepping Stones fulfils a deep need of family caregivers; (3) Stepping Stones is well organised with a purpose and expertise and (4) The partnership between the community and the university makes the programme unique. Conclusion Programmes like Stepping Stones can be beneficial by promoting participation of people with dementia and fulfilling a need of caregivers. These findings contribute to evidence of group-based activity programmes, in which activities were well planned by a faculty and students in occupational therapy.

There is a dearth of information pertaining to ethnicity and serious leisure among immigrants. The purpose of our study was to explore the health benefits of serious engagement in sports among Korean immigrants who are part of club activities. Using semi-structured in-depth interviews, we identified three themes associated with the benefits of serious leisure: (a) coping with acculturative stress, (b) creating ethnic strength, and (c) personal benefits. Participants gain personal and social benefits by pursuing leisure activities in a serious manner within their ethnic in-group.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Research indicates that participation in culturally meaningful activity is beneficial for immigrants’ health and well-being, yet older Korean immigrants struggle with accepting new cultural perspectives, which can negatively affect their health and well-being. Using in-depth interviews, this study was designed to capture the value of culturally meaningful activities for health among older Korean immigrants. Three themes were identified: (a) improved psychological well-being, (b) enhanced positive emotions and feelings, and (c) social connections developed with others. The findings suggest that by engaging in various culturally meaningful activities, older Korean immigrants gain a sense of social, cultural, and psychological significance in life. This study also provided evidence that older Korean immigrants maintain and develop their cultural identity through culturally meaningful activities.

The existing literature suggests that serious engagement in leisure activities leads to happiness, life satisfaction, and successful aging among older adults. This qualitative study was used to examine the benefits of serious involvement in leisure activities among older Korean adults who were members of a sports club. Using an analytic data analysis, we identified three main themes associated with the benefits of serious engagement in leisure activities: 1) the experience of psychological benefits, 2) the creation of social support, and 3) the enhancement of physical health. These themes indicate that, through serious involvement in certain physical activities, participants gain various health benefits, which may contribute to successful aging.

The splicing regulator Polypyrimidine Tract Binding Protein (PTBP1) has four RNA binding domains that each binds a short pyrimidine element, allowing recognition of diverse pyrimidine-rich sequences. This variation makes it difficult to evaluate PTBP1 binding to particular sites based on sequence alone and thus to identify target RNAs. Conversely, transcriptome-wide binding assays such as CLIP identify many in vivo targets, but do not provide a quantitative assessment of binding and are informative only for the cells where the analysis is performed. A general method of predicting PTBP1 binding and possible targets in any cell type is needed. We developed computational models that predict the binding and splicing targets of PTBP1. A Hidden Markov Model (HMM), trained on CLIP-seq data, was used to score probable PTBP1 binding sites. Scores from this model are highly correlated (ρ = -0.9) with experimentally determined dissociation constants. Notably, we find that the protein is not strictly pyrimidine specific, as interspersed Guanosine residues are well tolerated within PTBP1 binding sites. This model identifies many previously unrecognized PTBP1 binding sites, and can score PTBP1 binding across the transcriptome in the absence of CLIP data. Using this model to examine the placement of PTBP1 binding sites in controlling splicing, we trained a multinomial logistic model on sets of PTBP1 regulated and unregulated exons. Applying this model to rank exons across the mouse transcriptome identifies known PTBP1 targets and many new exons that were confirmed as PTBP1-repressed by RT-PCR and RNA-seq after PTBP1 depletion. We find that PTBP1 dependent exons are diverse in structure and do not all fit previous descriptions of the placement of PTBP1 binding sites. Our study uncovers new features of RNA recognition and splicing regulation by PTBP1. This approach can be applied to other multi-RRM domain proteins to assess binding site degeneracy and multifactorial splicing regulation.

We show that the splicing regulator PTBP2 controls a genetic program essential for neuronal maturation. Depletion of PTBP2 in developing mouse cortex leads to degeneration of these tissues over the first three postnatal weeks, a time when the normal cortex expands and develops mature circuits. Cultured Ptbp2−/− neurons exhibit the same initial viability as wild type, with proper neurite outgrowth and marker expression. However, these mutant cells subsequently fail to mature and die after a week in culture. Transcriptome-wide analyses identify many exons that share a pattern of mis-regulation in the mutant brains, where isoforms normally found in adults are precociously expressed in the developing embryo. These transcripts encode proteins affecting neurite growth, pre- and post-synaptic assembly, and synaptic transmission. Our results define a new genetic regulatory program, where PTBP2 acts to temporarily repress expression of adult protein isoforms until the final maturation of the neuron.