1. Abouzed M, Salama B, Gabr A, Elag KA, Soliman M, Elsaadouni N, Elzahab NA. Impact of smart technology use on sleep quality in individuals with autism spectrum disorder: a mixed-methods investigation. Front Psychiatry;2024;15:1411993.

BACKGROUND: Sleep disturbances are common among individuals with autism spectrum disorder (ASD) and can have a negative impact on their daily functioning and core symptoms. As the use of smart technologies continues to rise, it is crucial to understand how these devices affect the sleep quality of individuals with ASD. AIM: The objective of this study was to examine the relationship between the use of smart technology and sleep quality in individuals with ASD. METHODS: A mixed-methods approach was employed, combining both quantitative and qualitative data collection techniques. A sample of 83 individuals with ASD, aged between 8 and 25 years, assessed their sleep quality using the Pittsburgh Sleep Quality Index. Additionally, information regarding patterns of smart technology use and relevant covariates was collected. Correlation and regression analyses were conducted to analyze the data. Furthermore, semi-structured interviews were conducted with a subset of participants and their caregivers. RESULTS: Significant positive correlations were found between poorer sleep quality scores and total screen time (r = 0.42, p < 0.001), pre-bedtime technology use (r = 0.51, p < 0.001), gaming (r = 0.32, p = 0.003), and social media use (r = 0.29, p = 0.008). Pre-bedtime technology use was a significant predictor of poorer sleep quality (β = 0.32, p = 0.006), even after controlling for age, gender, and ASD severity. CONCLUSION: The findings of this study emphasize the significant associations between the use of smart technology, particularly before bedtime, and poorer sleep quality in individuals with ASD. These results underscore the importance of developing evidence-based interventions and guidelines to promote healthy sleep habits and mitigate the negative effects of technology exposure in this population.

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2. Braddock B, Turner K, Kumarason K, Bock L, Stumpe K, Wallace M, Heithaus J, Goretzke S, Portnoy S. Improving Access to Autism Evaluation: A Coordinated Developmental-Behavioral Pediatrics and Pediatric Neurology Diagnostic Pathway. Mo Med;2024 (May-Jun);121(3):225-230.

A shortage of board-certified developmental-behavioral pediatricians generates a bottleneck for children and families who seek autism diagnostic services. Wait time for autism evaluation commonly exceeds a year. To improve access, clinicians developed a coordinated Developmental-Behavioral Pediatrics and Pediatric Neurology autism diagnostic pathway. For a subset of children referred to neurology clinic, pediatric neurologists completed the medical part of an autism evaluation and Knights of Columbus Developmental Center psychologists or speech-language pathologists completed developmental assessments. Forty-four autism diagnostic evaluations completed through this coordinated pathway over the course of six months had shortened wait time [mean=50.89 days; range 3 to 184 days; median= 48.50 day]. Parents reported satisfaction with the autism evaluation and resources navigation process. Sustainability and scalability efforts are discussed.

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3. Burnett LE, Koppensteiner P, Symonova O, Masson T, Vega-Zuniga T, Contreras X, Rülicke T, Shigemoto R, Novarino G, Joesch M. Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice. PLoS Biol;2024 (Jun 10);22(6):e3002668.

Despite the diverse genetic origins of autism spectrum disorders (ASDs), affected individuals share strikingly similar and correlated behavioural traits that include perceptual and sensory processing challenges. Notably, the severity of these sensory symptoms is often predictive of the expression of other autistic traits. However, the origin of these perceptual deficits remains largely elusive. Here, we show a recurrent impairment in visual threat perception that is similarly impaired in 3 independent mouse models of ASD with different molecular aetiologies. Interestingly, this deficit is associated with reduced avoidance of threatening environments-a nonperceptual trait. Focusing on a common cause of ASDs, the Setd5 gene mutation, we define the molecular mechanism. We show that the perceptual impairment is caused by a potassium channel (Kv1)-mediated hypoexcitability in a subcortical node essential for the initiation of escape responses, the dorsal periaqueductal grey (dPAG). Targeted pharmacological Kv1 blockade rescued both perceptual and place avoidance deficits, causally linking seemingly unrelated trait deficits to the dPAG. Furthermore, we show that different molecular mechanisms converge on similar behavioural phenotypes by demonstrating that the autism models Cul3 and Ptchd1, despite having similar behavioural phenotypes, differ in their functional and molecular alteration. Our findings reveal a link between rapid perception controlled by subcortical pathways and appropriate learned interactions with the environment and define a nondevelopmental source of such deficits in ASD.

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4. Demirpençe Seçinti D, Diş D, Albayrak ZS, Şen E. Depression and parental distress among caregivers of autistic children: a serial mediator analysis in caregivers of autistic children. BMC Psychol;2024 (Jun 10);12(1):339.

BACKGROUND: This study aimed to investigate the relationship between the severity of autism, emotional and behavioral problems of autistic children, internalized stigma, depressive symptoms, and primary caregiver parental stress. Specifically, we explored the mediating role of internal stigmatization and total difficulties of individuals with autism on parenting stress and depressive symptoms of the primary caregiver. METHOD: Mothers of 93 children with autism were included in the study. The mothers were given the Beck Depression Inventory (BDI), The Internalized Stigma of Mental Illness Scale (ISMI), the Autism Behavior Checklist, the Parenting Stress Index-Short Form, Strength, and Difficulties Questionnaire -Parent Form (SDQ-P). RESULTS: As a result of our study, the emotional and behavioral problems of the child and the internalized stigmatization felt by the parent played a mediator role in the relationship between the child’s autism severity and the parent’s stress and depressive symptoms. CONCLUSIONS: Our findings highlight that internalized stigmatization and behavioral characteristics of individuals with autism are among the most critical problems for their primary caregivers. These results have important implications for the development of interventions aimed at reducing the internalized stigma experienced by primary caregivers of individuals with autism and for improving their mental health outcomes.

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5. Hazan S, Haroon J, Jordan S, Walker SJ. Correction to: Improvements in Gut Microbiome Composition and Clinical Symptoms Following Familial Fecal Microbiota Transplantation in a Nineteen-Year-Old Adolescent With Severe Autism. J Med Cases;2024 (Jun);15(6):115.

[This corrects the article DOI: 10.14740/jmc4209.].

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6. Huang CH, Wong LC, Chu YJ, Hsu CJ, Wang HP, Tsai WC, Lee WT. The sleep problems in individuals with Rett syndrome and their caregivers. Autism;2024 (Jun 9):13623613241254620.

Sleep problems are common and impactful among individuals with Rett syndrome (RTT) and their caregivers. We examined the sleep patterns of 29 RTT patients and their primary caregivers using various assessment tools. The study found that a majority of the patients experienced sleep disturbances, with younger patients showing more sleep difficulties. Caregivers also reported poor sleep quality. The findings emphasize the need to address sleep problems in RTT management, as improving sleep quality can positively impact the well-being of individuals with RTT and their caregivers.

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7. Lee K, Jung Y, Vyas Y, Mills Z, McNamara L, Montgomery JM. Differential effectiveness of dietary zinc supplementation with autism-related behaviours in Shank2 knockout mice. Philos Trans R Soc Lond B Biol Sci;2024 (Jul 29);379(1906):20230230.

The family of SHANK proteins have been shown to be critical in regulating glutamatergic synaptic structure, function and plasticity. SHANK variants are also prevalent in autism spectrum disorders (ASDs), where glutamatergic synaptopathology has been shown to occur in multiple ASD mouse models. Our previous work has shown that dietary zinc in Shank3(-/-) and Tbr1(+/-) ASD mouse models can reverse or prevent ASD behavioural and synaptic deficits. Here, we have examined whether dietary zinc can influence behavioural and synaptic function in Shank2(-/-) mice. Our data show that dietary zinc supplementation can reverse hyperactivity and social preference behaviour in Shank2(-/-) mice, but it does not alter deficits in working memory. Consistent with this, at the synaptic level, deficits in NMDA/AMPA receptor-mediated transmission are also not rescued by dietary zinc. In contrast to other ASD models examined, we observed that SHANK3 protein was highly expressed at the synapses of Shank2(-/-) mice and that dietary zinc returned these to wild-type levels. Overall, our data show that dietary zinc has differential effectiveness in altering ASD behaviours and synaptic function across ASD mouse models even within the Shank family. This article is part of a discussion meeting issue ‘Long-term potentiation: 50 years on’.

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8. Low LL, Chua KY, Ching BH. Effectiveness of social skills group among children with mild autism spectrum disorder. Clin Exp Pediatr;2024 (May 31)

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9. McCluskey KE, Stovell KM, Law K, Kostyanovskaya E, Schmidt J, Exner CRT, Dea J, Brimble E, State MW, Willsey AJ, Willsey HR. Autism gene variants disrupt enteric neuron migration and cause gastrointestinal dysmotility. bioRxiv;2024 (May 29)

The comorbidity of autism spectrum disorders and severe gastrointestinal symptoms is well-established, yet the molecular underpinnings remain unknown. The identification of high-confidence large-effect autism risk genes offers the opportunity to identify convergent, underlying biology by studying these genes in the context of the gastrointestinal system. Here we show that the expression of these genes is enriched in human prenatal gut neurons as well as their migratory progenitors, suggesting that the development and/or function of these neurons may be disrupted by autism-associated pathogenic variants, leading to gastrointestinal dysfunction. Here we document the prevalence of gastrointestinal issues in patients with large-effect variants in sixteen of these genes, highlighting dysmotility, consistent with potential enteric neuron dysfunction. Using the high-throughput diploid frog Xenopus tropicalis , we individually target five of these genes ( SYNGAP1, CHD8, SCN2A, CHD2 , and DYRK1A ) and observe disrupted enteric neuronal progenitor migration for each. More extensive analysis of DYRK1A reveals that perturbation causes gut dysmotility in vivo , which can be ameliorated by treatment with a selective serotonin reuptake inhibitor (escitalopram) or a serotonin receptor 6 agonist, identified by in vivo drug screening. This work suggests that atypical development of enteric neurons contributes to the gastrointestinal distress commonly seen in individuals with autism and that increasing serotonin signaling may be a productive therapeutic avenue.

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10. Narimani S, Ayati A, Tayebi A, Jalai A, Amirsardari Z, Sahebjam M, Zoroufian A. Three-dimensional transesophageal echocardiography measurements of ASD sizing parameters in comparison to balloon sizing method in percutaneous ASD closure. Echocardiography;2024 (Jun);41(6):e15822.

BACKGROUND: Balloon sizing (BS) has been used for device size selection in percutaneous atrial septal defect (ASD) closure. Due to its limitations, alternative imaging techniques like three-dimensional transesophageal echocardiography (3D-TEE) are valuable for guiding ASD device size selection during ASD closure procedures. The purpose of this study was to compare ASD sizing using measurements obtained from 3D-TEE to those utilizing the standard balloon sizing method. METHODS: We identified 53 patients with single secundum type ASD without PFO who underwent percutaneous closure at the Tehran Heart Center between 2019 and 2022. Balloon sizing was performed in all patients with the stop-flow technique, and the choice of device size was determined based on the sizing derived from BS. 3D-TEE imaging was performed before the intervention, and the ASD shape and quality of ASD rims were assessed. RESULTS: Among the 53 patients who underwent single ASD device closure, multiple 3D TEE measurements significantly correlated with balloon sizing results. This included defect area, perimeter, and diameter obtained from 3D-TEE images multi-planar reconstruction. ASD perimeter detected by 3D TEE had the best correlation with BS results. When divided by the shape of ASD, there was no significant difference between our 3D-images data and BS in round or oval-shaped ASDs. CONCLUSION: The 3D-TEE study is reliable for assessing ASD configurational characteristics in percutaneous device closure candidates. 3D-TEE has the potential to accurately determine the appropriate device size and reduce complications, costs, and procedural duration. Further research is needed to validate these findings and establish the role of 3D-TEE measurements in guiding the best treatment decisions for ASD closure.

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11. Pui Ying LP, Hoi Wan FE, Tung Megan CY, Ming LC, McGrath CP, Kar Yung YC. Psychological behavioral therapies to improve autistic children’s behaviors during dental visits: A systematic review and meta-analysis. Autism;2024 (Jun 10):13623613241255302.

This research review looked at how well different psychological behavioral therapies help improve the behavior of autistic children during dental visits. The researchers studied 18 different studies and found that, on average, about 56% of autistic children were able to cooperate with a dental exam using an oral mirror during their first visit. The number increased to about 64% during their second visit. However, using visual pedagogies or teaching aids did not seem to make a big difference in how many children could accept the dental exams. The results for other psychological behavioral techniques were also inconsistent, including Treatment and Education of Autistic and related Communication-handicapped CHildren, Picture Exchange Communication System, Applied Behavior Analysis, video modeling, and distractions. Many of the studies were small and did not include a comparison group. They also did not consider factors like how severe the autism was, other conditions the children had, or their previous dental experiences. Because of these limitations, the evidence supporting the use of psychological behavioral techniques to improve dental visits for autistic children is limited and uncertain. More research with larger studies and proper control groups is needed to better understand this topic.

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12. Qin L, Wang H, Ning W, Cui M, Wang Q. New advances in the diagnosis and treatment of autism spectrum disorders. Eur J Med Res;2024 (Jun 10);29(1):322.

Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders that affect individuals’ social interactions, communication skills, and behavioral patterns, with significant individual differences and complex etiology. This article reviews the definition and characteristics of ASD, epidemiological profile, early research and diagnostic history, etiological studies, advances in diagnostic methods, therapeutic approaches and intervention strategies, social and educational integration, and future research directions. The highly heritable nature of ASD, the role of environmental factors, genetic-environmental interactions, and the need for individualized, integrated, and technology-driven treatment strategies are emphasized. Also discussed is the interaction of social policy with ASD research and the outlook for future research and treatment, including the promise of precision medicine and emerging biotechnology applications. The paper points out that despite the remarkable progress that has been made, there are still many challenges to the comprehensive understanding and effective treatment of ASD, and interdisciplinary and cross-cultural research and global collaboration are needed to further deepen the understanding of ASD and improve the quality of life of patients.

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13. Rivera MD, Aponte SN, Rivera F, Arciniegas NJ, Carlo S. MED13 Gene Mutation Related to Autism Spectrum Disorder: A Case Report. Cureus;2024 (May);16(5):e59904.

This case report highlights an association between the MED13 gene and autism spectrum disorder (ASD). ASD is a neurodevelopmental disorder characterized by impaired social interactions, communication difficulties, and repetitive behaviors. The MED13 gene encodes a subunit of the Mediator complex, which plays a key role in gene expression regulation and transcriptional processes. In this case report, we present a case of a child diagnosed with ASD who underwent whole exome sequencing (WES) and revealed an uncertain heterozygous variant in the MED13 gene. The patient exhibited typical features of ASD, including the following: social and communication deficits, restricted interests, repetitive behaviors, and characteristic dysmorphic facial features. The identification of this MED13 gene variant provides further evidence of its potential involvement in ASD pathogenesis. This case adds to the growing body of evidence linking MED13 gene mutations to ASD susceptibility. Understanding the genetic basis of ASD through case reports can aid in early diagnosis, personalized treatment strategies, and genetic counseling for affected individuals and their families. Further research is warranted to explain the precise mechanisms underlying MED13 gene involvement in ASD.

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14. Serrada-Tejeda S, May-Benson TA, Bundy A, Santos-Del-Riego SE, Rodríguez-Pérez MP, Pérez-de-Heredia-Torres M. Ideational Praxis, Play, and Playfulness: A Cross-Sectional Study of Autistic Children. Am J Occup Ther;2024 (Jul 1);78(4)

IMPORTANCE: Assessment of praxis skills is an essential aspect of understanding autistic children’s development of play and playfulness. OBJECTIVE: To assess the relationship and influence of ideational praxis skills on play skills and playfulness among autistic children. DESIGN: A cross-sectional study. SETTINGS: Homes, schools, and early care centers across Spain. PARTICIPANTS: Children ages 4 yr 6 mo to 6 yr 11 mo (45 typically developing [TP] and 45 with autism spectrum disorder [ASD]). OUTCOMES AND MEASURES: Student’s t tests were used to compare means between the two groups. Pearson’s correlation and multiple linear regression were used to determine possible effects of ideational skills on play and playfulness. RESULTS: Scores for the TP group were significantly higher than those of the ASD group on all play dimensions-space management, t(88) = 4.58; material management, t(88) = 5.86; pretense-symbolism, t(88) = 8.12; and participation, t(88) = 7.31-and on the Test of Playfulness (ToP), t(88) = 10.18, and Test of Ideational Praxis (TIP), t(88) = 4.38 (all ps < .001). Multiple linear regression revealed a statistically significant effect of TIP dimensions-space management, F(3, 41) = 4.83, p < .042; material management, F(3.41) = 8.49. p < .001; pretense-symbolism, F(3, 41) = 5.66. p < .002; and participation, F(3.41) = 7.81. p < .001-and on the ToP, F(3, 41) = 5.96. p < .002. CONCLUSIONS AND RELEVANCE: Ideational praxis skills combined with diagnostic information significantly predicted play skills and playfulness, highlighting the influence of ideation on play. Plain-Language Summary: This article provides data supporting the influence of ideational praxis skills on the play skills and playfulness of autistic children. Understanding how ideational praxis skills affect the ability to recognize and act on object affordances might promote greater possibilities for play interactions among autistic children.

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15. Sung CYW, Li M, Jonjic S, Sanchez V, Britt WJ. Cytomegalovirus infection lengthens the cell cycle of granule cell precursors during postnatal cerebellar development. JCI Insight;2024 (Jun 10);9(11)

Human cytomegalovirus (HCMV) infection in infants infected in utero can lead to a variety of neurodevelopmental disorders. However, mechanisms underlying altered neurodevelopment in infected infants remain poorly understood. We have previously described a murine model of congenital HCMV infection in which murine CMV (MCMV) spreads hematogenously and establishes a focal infection in all regions of the brain of newborn mice, including the cerebellum. Infection resulted in disruption of cerebellar cortical development characterized by reduced cerebellar size and foliation. This disruption was associated with altered cell cycle progression of the granule cell precursors (GCPs), which are the progenitors that give rise to granule cells (GCs), the most abundant neurons in the cerebellum. In the current study, we have demonstrated that MCMV infection leads to prolonged GCP cell cycle, premature exit from the cell cycle, and reduced numbers of GCs resulting in cerebellar hypoplasia. Treatment with TNF-α neutralizing antibody partially normalized the cell cycle alterations of GCPs and altered cerebellar morphogenesis induced by MCMV infection. Collectively, our results argue that virus-induced inflammation altered the cell cycle of GCPs resulting in a reduced numbers of GCs and cerebellar cortical hypoplasia, thus providing a potential mechanism for altered neurodevelopment in fetuses infected with HCMV.

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16. Thacker JS, Bettio L, Liang S, Shkolnikov I, Collingridge GL, Christie BR. Adiponectin rescues synaptic plasticity in the dentate gyrus of a mouse model of Fragile X Syndrome. Philos Trans R Soc Lond B Biol Sci;2024 (Jul 29);379(1906):20230221.

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and is the leading known single-gene cause of autism spectrum disorder. Patients with FXS display varied behavioural deficits that include mild to severe cognitive impairments in addition to mood disorders. Currently, there is no cure for this condition; however, there is an emerging focus on therapies that inhibit mechanistic target of rapamycin (mTOR)-dependent protein synthesis owing to the clinical effectiveness of metformin for alleviating some behavioural symptoms in FXS. Adiponectin (APN) is a neurohormone that is released by adipocytes and provides an alternative means to inhibit mTOR activation in the brain. In these studies, we show that Fmr1 knockout mice, like patients with FXS, show reduced levels of circulating APN and that both long-term potentiation (LTP) and long-term depression (LTD) in the dentate gyrus (DG) are impaired. Brief (20 min) incubation of hippocampal slices in APN (50 nM) was able to rescue both LTP and LTD in the DG and increased both the surface expression and phosphorylation of GluA1 receptors. These results provide evidence for reduced APN levels in FXS playing a role in decreasing bidirectional synaptic plasticity and show that therapies which enhance APN levels may have therapeutic potential for this and related conditions.This article is part of a discussion meeting issue ‘Long-term potentiation: 50 years on’.

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17. Thibaudeau A, Schmitt K, François L, Chatrousse L, Hoffmann D, Cousin L, Weiss A, Vuidel A, Jacob CB, Sommer P, Benchoua A, Wilbertz JH. Pharmacological modulation of developmental and synaptic phenotypes in human SHANK3 deficient stem cell-derived neuronal models. Transl Psychiatry;2024 (Jun 10);14(1):249.

Phelan-McDermid syndrome (PMDS) arises from mutations in the terminal region of chromosome 22q13, impacting the SHANK3 gene. The resulting deficiency of the postsynaptic density scaffolding protein SHANK3 is associated with autism spectrum disorder (ASD). We examined 12 different PMDS patient and CRISPR-engineered stem cell-derived neuronal models and controls and found that reduced expression of SHANK3 leads to neuronal hyperdifferentiation, increased synapse formation, and decreased neuronal activity. We performed automated imaging-based screening of 7,120 target-annotated small molecules and identified three compounds that rescued SHANK3-dependent neuronal hyperdifferentiation. One compound, Benproperine, rescued the decreased colocalization of Actin Related Protein 2/3 Complex Subunit 2 (ARPC2) with ß-actin and rescued increased synapse formation in SHANK3 deficient neurons when administered early during differentiation. Neuronal activity was only mildly affected, highlighting Benproperine’s effects as a neurodevelopmental modulator. This study demonstrates that small molecular compounds that reverse developmental phenotypes can be identified in human neuronal PMDS models.

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18. Tseng YJ, Krans A, Malik I, Deng X, Yildirim E, Ovunc S, Tank EMH, Jansen-West K, Kaufhold R, Gomez NB, Sher R, Petrucelli L, Barmada SJ, Todd PK. Ribosomal quality control factors inhibit repeat-associated non-AUG translation from GC-rich repeats. Nucleic Acids Res;2024 (Jun 10);52(10):5928-5949.

A GGGGCC (G4C2) hexanucleotide repeat expansion in C9ORF72 causes amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD), while a CGG trinucleotide repeat expansion in FMR1 leads to the neurodegenerative disorder Fragile X-associated tremor/ataxia syndrome (FXTAS). These GC-rich repeats form RNA secondary structures that support repeat-associated non-AUG (RAN) translation of toxic proteins that contribute to disease pathogenesis. Here we assessed whether these same repeats might trigger stalling and interfere with translational elongation. We find that depletion of ribosome-associated quality control (RQC) factors NEMF, LTN1 and ANKZF1 markedly boost RAN translation product accumulation from both G4C2 and CGG repeats while overexpression of these factors reduces RAN production in both reporter assays and C9ALS/FTD patient iPSC-derived neurons. We also detected partially made products from both G4C2 and CGG repeats whose abundance increased with RQC factor depletion. Repeat RNA sequence, rather than amino acid content, is central to the impact of RQC factor depletion on RAN translation-suggesting a role for RNA secondary structure in these processes. Together, these findings suggest that ribosomal stalling and RQC pathway activation during RAN translation inhibits the generation of toxic RAN products. We propose augmenting RQC activity as a therapeutic strategy in GC-rich repeat expansion disorders.

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19. Volianskis R, Lundbye CJ, Petroff GN, Jane DE, Georgiou J, Collingridge GL. Cage effects on synaptic plasticity and its modulation in a mouse model of fragile X syndrome. Philos Trans R Soc Lond B Biol Sci;2024 (Jul 29);379(1906):20230484.

Fragile X syndrome (FXS) is characterized by impairments in executive function including different types of learning and memory. Long-term potentiation (LTP), thought to underlie the formation of memories, has been studied in the Fmr1 mouse model of FXS. However, there have been many discrepancies in the literature with inconsistent use of littermate and non-littermate Fmr1 knockout (KO) and wild-type (WT) control mice. Here, the influence of the breeding strategy (cage effect) on short-term potentiation (STP), LTP, contextual fear conditioning (CFC), expression of N-methyl-d-aspartate receptor (NMDAR) subunits and the modulation of NMDARs, were examined. The largest deficits in STP, LTP and CFC were found in KO mice compared with non-littermate WT. However, the expression of NMDAR subunits was unchanged in this comparison. Rather, NMDAR subunit (GluN1, 2A, 2B) expression was sensitive to the cage effect, with decreased expression in both WT and KO littermates compared with non-littermates. Interestingly, an NMDAR-positive allosteric modulator, UBP714, was only effective in potentiating the induction of LTP in non-littermate KO mice and not the littermate KO mice. These results suggest that commonly studied phenotypes in Fmr1 KOs are sensitive to the cage effect and therefore the breeding strategy may contribute to discrepancies in the literature.This article is part of a discussion meeting issue ‘Long-term potentiation: 50 years on’.

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20. Wang L, Qin Y, Yang S, Jin D, Zhu Y, Li X, Li W, Wang Y, Jin C. Posterior default mode network is associated with the social performance in male children with autism spectrum disorder: A dynamic causal modeling analysis based on triple-network model. Hum Brain Mapp;2024 (Jun 1);45(8):e26750.

The triple-network model has been widely applied in neuropsychiatric disorders including autism spectrum disorder (ASD). However, the mechanism of causal regulations within the triple-network and their relations with symptoms of ASD remains unclear. 81 male ASD and 80 well matched typically developing control (TDC) were included in this study, recruited from Autism Brain Image Data Exchange-I datasets. Spatial reference-based independent component analysis was used to identify the anterior and posterior part of default-mode network (aDMN and pDMN), salience network (SN), and bilateral executive-control network (ECN) from resting-state functional magnetic resonance imaging data. Spectral dynamic causal model and parametric empirical Bayes with Bayesian model reduction/average were adopted to explore the effective connectivity (EC) within triple-network and the relationship between EC and autism diagnostic observation schedule (ADOS) scores. After adjusting for age and site effect, ASD and TDC groups both showed inhibition patterns. Compared with TDC, ASD group showed weaker self-inhibition in aDMN and pDMN, stronger inhibition in pDMN→aDMN, weaker inhibition in aDMN→LECN, pDMN→SN, LECN→SN, and LECN→RECN. Furthermore, negative relationships between ADOS scores and pDMN self-inhibition strength, as well as with the EC of pDMN→aDMN were observed in ASD group. The present study reveals imbalanced effective connections within triple-networks in ASD children. More attentions should be focused at the pDMN, which modulates the core symptoms of ASD and may serve as an important region for ASD diagnosis and the target region for ASD treatments.

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21. Zhou R, Sun C, Sun M, Ruan Y, Li W, Gao X. Altered intra- and inter-network connectivity in autism spectrum disorder. Aging (Albany NY);2024 (Jun 10);16(11):10004-10015.

OBJECTIVE: A neurodevelopmental illness termed as the autism spectrum disorder (ASD) is described by social interaction impairments. Previous studies employing resting-state functional imaging (rs-fMRI) identified both hyperconnectivity and hypoconnectivity patterns in ASD people. However, specific patterns of connectivity within and between networks linked to ASD remain largely unexplored. METHODS: We utilized a meticulously selected subset of high-quality data, comprising 45 individuals diagnosed with ASD and 47 HCs, obtained from the ABIDE dataset. The pre-processed rs-fMRI time series signals were partitioned into ninety regions of interest. We focused on eight intrinsic connectivity networks and further performed intra- and inter-network analysis. Finally, support vector machine was used to discriminate ASD from HC. RESULTS: Through different sparsities, ASD exhibited significantly decreased intra-network connectivity within default mode network and dorsal attention network, increased connectivity between limbic network and subcortical network, and decreased connectivity between default mode network and limbic network. Using the classifier trained on altered intra- and inter-network connectivity, multivariate pattern analyses classified the ASD from HC with 71.74% accuracy, 70.21% specificity and 75.56% sensitivity in 10% sparsity of functional connectivity. CONCLUSIONS: ASD showed characteristic reorganization of the brain networks and this provided new insight into the underlying process of the functional connectome dysfunction in ASD.

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