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BACKGROUND: Behavioral symptom trajectories are informative of the development of young children at increased likelihood for autism spectrum disorder (ASD). METHODS: Developmental trajectories of early signs were examined in a cohort of siblings of children diagnosed with ASD (n = 502) from 6 to 18 months using the Autism Observation Scale for Infants (AOSI), and from 18 months to 5-7 years using the Autism Diagnostic Observation Schedule (ADOS). Diagnostic outcomes for ASD at age 3 confirmed diagnosis for 137 children. We further analyzed the conditional probability of a switch from a trajectory measured with the AOSI to a trajectory measured with the ADOS as well as predictors from age 6 months. RESULTS: We derived three early trajectories of behavioral signs ("Low," "Intermediate," and "Increasing") from 6 to 18 months using the AOSI. We then derived three similar, distinct trajectories for the evolution of symptom severity between 18 and 60-84 months of age (Low, Intermediate, Increasing) using the ADOS. Globally, the Low trajectory included children showing fewer ASD signs or symptoms and the Increasing trajectory included children showing more severe symptoms. We also found that most children in the Low AOSI trajectory stayed in the corresponding ADOS trajectory, whereas children in an Increasing AOSI trajectory tended to transition to an Intermediate or Increasing ADOS trajectory. Developmental measures taken at 6 months (early signs of ASD, Fine Motor, and Visual Reception skills) were predictive of trajectory membership. CONCLUSIONS: Results confirm substantial heterogeneity in the early emergence of ASD signs in children at increased likelihood for ASD. Moreover, we showed that the way those early behavioral signs emerge in infants is predictive of later symptomatology. Results yield clear clinical implications, supporting the need to repeatedly assess infants at increased likelihood for ASD as this can be highly indicative of their later development and behavior.
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Trastorno del Espectro Autista , Trastorno Autístico , Humanos , Niño , Lactante , Preescolar , Trastorno del Espectro Autista/diagnóstico , HermanosRESUMEN
BACKGROUND: Although early autism spectrum disorder (ASD) detection strategies tend to focus on differences at a point in time, behavioral symptom trajectories may also be informative. METHODS: Developmental trajectories of early signs of ASD were examined in younger siblings of children diagnosed with ASD (n = 499) and infants with no family history of ASD (n = 177). Participants were assessed using the Autism Observation Scale for Infants (AOSI) from 6 to 18 months. Diagnostic outcomes were determined at age 3 years blind to previous assessments. RESULTS: Semiparametric group-based modeling using AOSI scores identified three distinct trajectories: Group 1 ('Low', n = 435, 64.3%) was characterized by a low level and stable evolution of ASD signs, group 2 ('Intermediate', n = 180, 26.6%) had intermediate and stable levels, and group 3 ('Inclining', n = 61, 9.3%) had higher and progressively elevated levels of ASD signs. Among younger siblings, ASD rates at age 3 varied by trajectory of early signs and were highest in the Inclining group, membership in which was highly specific (94.5%) but poorly sensitive (28.5%) to ASD. Children with ASD assigned to the inclining trajectory had more severe symptoms at age 3, but developmental and adaptive functioning did not differ by trajectory membership. CONCLUSIONS: These prospective data emphasize variable early-onset patterns and the importance of a multipronged approach to early surveillance and screening for ASD.
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Trastorno del Espectro Autista , Trastorno Autístico , Trastorno del Espectro Autista/epidemiología , Niño , Preescolar , Estudios de Cohortes , Humanos , Lactante , Estudios Prospectivos , HermanosRESUMEN
Background: In preschoolers with autism spectrum disorder (ASD) symptom, severity has a negative impact on the development of adaptive functioning, with critical consequences on the quality of life of those children. Developmental features such as reduced social interest or the presence of behavioral problems can further impede daily life learning experiences. Objectives: The first aim of this study is to confirm the negative impact of high symptom severity on adaptive functioning trajectories in preschoolers with ASD. The second objective intends to explore whether reduced social interest and severe behavioral problems negatively affect developmental trajectories of adaptive functioning in young children with ASD. Methods: In total, 68 children with ASD and 48 age and gender-matched children with typical development (TD) between 1.6 and 6 years were included in our study, and longitudinal data on adaptive functioning were collected (mean length of the longitudinal data collection was 1.4 years ± 0.6). Baseline measures of symptom severity, social interest, and behavioral problems were also obtained. Results: We confirmed that children with ASD show parallel developmental trajectories but a significantly lower performance of adaptive functioning compared with children with TD. Furthermore, analyses within ASD children demonstrated that those with higher symptom severity, reduced social interest, and higher scores of behavioral problems exhibited especially lower or faster declining trajectories of adaptive functioning. Conclusions: These findings bolster the idea that social interest and behavioral problems are crucial for the early adaptive functioning development of children with autism. The current study has clinical implications in pointing out early intervention targets in children with ASD.
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Adaptación Psicológica/fisiología , Trastorno del Espectro Autista/fisiopatología , Trastorno del Espectro Autista/psicología , Conducta Infantil/psicología , Niño , Preescolar , Femenino , Humanos , Lactante , Estudios Longitudinales , Masculino , Problema de Conducta/psicología , Calidad de Vida/psicología , Índice de Severidad de la Enfermedad , Conducta SocialRESUMEN
LAY ABSTRACT: Language development can greatly vary among autistic children. Children who struggle with language acquisition often face many challenges and experience lower quality of life. However, little is known about the early language trajectories of autistic preschoolers and their moderators. Autistic language can be stratified into three profiles. Language unimpaired experience little to no language difficulties; language impaired show significant difficulties in language; minimally verbal never develop functional language. In this study, we used a longitudinal sample of preschoolers with autism and with typical development (aged 1.5-5.7 years). We replicated the three language profiles through a data-driven approach. We also found that different factors modulated the language outcome within each group. For instance, non-verbal cognition at age 2.4 moderated the participants' attribution to each language profile. Moreover, early intervention moderated verbal outcome in the language impaired profile. In conclusion, we provided a detailed description of how autistic preschoolers acquire language, and what factors might influence their trajectories. Our findings could inspire more personalized intervention for early autistic language difficulties.
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Children with autism spectrum disorder (ASD) often face challenges in early social communication skills, prompting the need for a detailed exploration of specific behaviors and their impact on cognitive and adaptive functioning. This study aims to address this gap by examining the developmental trajectories of early social communication skills in preschoolers with ASD aged 18-60 months, comparing them to age-matched typically developing (TD) children. Utilizing the early social communication scales (ESCS), the research employs a longitudinal design to capture changes over time. We apply a principal component analysis (PCA) to ESCS variables to identify underlying components, and cluster analysis to identify subgroups based on preverbal communication profiles. The results reveal consistent differences in early social communication skills between ASD and TD children, with ASD children exhibiting reduced skills. PCA identifies two components, distinguishing objects-directed behaviors and social interaction-directed behaviors. Cluster analysis identifies three subgroups of autistic children, each displaying specific communication profiles associated with distinct cognitive and adaptive functioning trajectories. In conclusion, this study provides a nuanced understanding of early social communication development in ASD, emphasizing the importance of low-level behaviors. The identification of subgroups and their unique trajectories contributes to a more comprehensive understanding of ASD heterogeneity. These findings underscore the significance of early diagnosis, focusing on specific behaviors predicting cognitive and adaptive functioning outcomes. The study encourages further research to explore the sequential development of these skills, offering valuable insights for interventions and support strategies.
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RYR1 is the most commonly mutated gene associated with congenital myopathies, a group of early-onset neuromuscular conditions of variable severity. The functional effects of a number of dominant RYR1 mutations have been established; however, for recessive mutations, these effects may depend on multiple factors, such as the formation of a hypomorphic allele, or on whether they are homozygous or compound heterozygous. Here, we functionally characterize a new transgenic mouse model knocked-in for mutations identified in a severely affected child born preterm and presenting limited limb movement. The child carried the homozygous c.14928C>G RYR1 mutation, resulting in the p.F4976L substitution. In vivo and ex vivo assays revealed that homozygous mice fatigued sooner and their muscles generated significantly less force compared with their WT or heterozygous littermates. Electron microscopy, biochemical, and physiological analyses showed that muscles from RyR1 p.F4976L homozygous mice have the following properties: (1) contain fewer calcium release units and show areas of myofibrillar degeneration, (2) contain less RyR1 protein, (3) fibers show smaller electrically evoked calcium transients, and (4) their SR has smaller calcium stores. In addition, single-channel recordings indicate that RyR1 p.F4976L exhibits higher Po in the presence of 100 µM [Ca2+]. Our mouse model partly recapitulates the clinical picture of the homozygous human patient and provides significant insight into the functional impact of this mutation. These results will help understand the pathology of patients with similar RYR1 mutations.
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Calcio , Enfermedades Musculares , Animales , Niño , Humanos , Ratones , Modelos Animales de Enfermedad , Homeostasis , Ratones Transgénicos , Músculos , Canal Liberador de Calcio Receptor de Rianodina/genéticaRESUMEN
Atypical deployment of social gaze is present early on in toddlers with autism spectrum disorders (ASDs). Yet, studies characterizing the developmental dynamic behind it are scarce. Here, we used a data-driven method to delineate the developmental change in visual exploration of social interaction over childhood years in autism. Longitudinal eye-tracking data were acquired as children with ASD and their typically developing (TD) peers freely explored a short cartoon movie. We found divergent moment-to-moment gaze patterns in children with ASD compared to their TD peers. This divergence was particularly evident in sequences that displayed social interactions between characters and even more so in children with lower developmental and functional levels. The basic visual properties of the animated scene did not account for the enhanced divergence. Over childhood years, these differences dramatically increased to become more idiosyncratic. These findings suggest that social attention should be targeted early in clinical treatments.
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Trastorno del Espectro Autista , Trastorno Autístico , Humanos , Niño , Interacción Social , Atención , Fijación OcularRESUMEN
BACKGROUND: Imitation skills play a crucial role in social cognitive development from early childhood. Many studies have shown a deficit in imitation skills in children with autism spectrum disorders (ASD). Little is known about the development of imitation behaviors in children with ASD. This study aims to measure the trajectories of early imitation skills in preschoolers with ASD and how these skills impact other areas of early development. METHODS: For this purpose, we assessed imitation, language, and cognition skills in 177 children with ASD and 43 typically developing children (TD) aged 2 to 5 years old, 126 of which were followed longitudinally, yielding a total of 396 time points. RESULTS: Our results confirmed the presence of an early imitation deficit in toddlers with ASD compared to TD children. The study of the trajectories showed that these difficulties were marked at the age of 2 years and gradually decreased until the age of 5 years old. Imitation skills were strongly linked with cognitive and language skills and level of symptoms in our ASD group at baseline. Moreover, the imitation skills at baseline were predictive of the language gains a year later in our ASD group. Using a data-driven clustering method, we delineated different developmental trajectories of imitation skills within the ASD group. CONCLUSIONS: The clinical implications of the findings are discussed, particularly the impact of an early imitation deficit on other areas of competence of the young child.
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Trastorno del Espectro Autista , Trastorno del Espectro Autista/psicología , Preescolar , Humanos , Conducta Imitativa , LenguajeRESUMEN
Altered social orienting (SO) was proposed as the primary source of socio-communicative difficulties in autism spectrum disorder (ASD). Eye-tracking studies generally confirm a decreased SO in ASD population. However, SO has been scarcely investigated using minimally social stimuli such as cartoons. The extent to which SO might be decreased when watching cartoons is therefore unknown. Yet, it could allow for malleable and child-friendly paradigms that could be sensitive to early atypical visual preference. In this study, 90 preschoolers with ASD (age = 3.19 ± 0 .88) and 20 TD (age = 2.95 ± 1.26) watched two eye-tracking preference tasks. One Realistic task, displaying children dancing versus geometric shapes moving repetitively and a Cartoon task, displaying social and non-social cartoon stimuli with similar movements. We measured SO percentage along with refined visual exploration parameters and compared those of ASD children to TDs. In addition, we investigated their relations with behavioral measures such as symptom severity, developmental and adaptive levels. We evidenced a decreased SO percentage in ASD compared to TD children when watching the Realistic task but not the Cartoon task. We did not identify any other between groups differences. However, we identified several correlations between eye-tracking measures and developmental as well as adaptive measures within the Cartoon task. Together, our results support a preferential orientation of children with autism towards repetitively moving shapes but no decreased SO when measured with minimally social stimuli. Nonetheless, when investigating finer visual exploration parameters, even socially simple stimuli elicited atypical gaze patterns related to early developmental delay.
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Trastorno del Espectro Autista , Preescolar , Humanos , LactanteRESUMEN
Evidence-based, early intervention significantly improves developmental outcome in young children with autism. Nonetheless, there is high interindividual heterogeneity in developmental trajectories during the therapy. It is established that starting intervention as early as possible results in better developmental outcomes. But except for younger age at start, there is no clear consensus about behavioral characteristics that could provide a reliable individual prediction of a child's developmental outcome after receiving an early intervention. In this study, we analyze developmental trajectories of preschoolers with autism who received 2 years of intervention using the Early Start Denver Model (ESDM) approach in Geneva, Switzerland in an individual setting (n = 55, aged 28.7 ± 5.1 months with a range of 15-42). Our aim was to identify early predictors of response to intervention. We applied a cluster analysis to distinguish between 3 groups based on their cognitive level at intake, and rates of cognitive change over the course of intervention. The first group of children only had a mild cognitive delay at intake and nearly no cognitive delay by the end of intervention (Higher Cognitive at baseline: HC). The children in the two other groups all presented with severe cognitive delay at baseline. However, they had two very different patterns of response to intervention. The majority significantly improved developmental scores over the course of intervention (Optimal Responders: OptR) whereas a minority of children showed only modest improvement (Minimal Responders: MinR). Further analyses showed that children who ended up having an optimal 2-year intervention outcome (OptR) were characterized by higher adaptive functioning at baseline combined with rapid developmental improvement during the first 6 months of intervention. Inversely, less significant progress by the sixth month of intervention was associated with a less optimal response to treatment (MinR).
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To date there are no therapies for patients with congenital myopathies, muscle disorders causing poor quality of life of affected individuals. In approximately 30% of the cases, patients with congenital myopathies carry either dominant or recessive mutations in the ryanodine receptor 1 (RYR1) gene; recessive RYR1 mutations are accompanied by reduction of RyR1 expression and content in skeletal muscles and are associated with fiber hypotrophy and muscle weakness. Importantly, muscles of patients with recessive RYR1 mutations exhibit increased content of class II histone deacetylases and of DNA genomic methylation. We recently created a mouse model knocked-in for the p.Q1970fsX16+ p.A4329D RyR1 mutations, which are isogenic to those carried by a severely affected child suffering from a recessive form of RyR1-related multi-mini core disease. The phenotype of the RyR1 mutant mice recapitulates many aspects of the clinical picture of patients carrying recessive RYR1 mutations. We treated the compound heterozygous mice with a combination of two drugs targeting DNA methylases and class II histone deacetylases. Here, we show that treatment of the mutant mice with drugs targeting epigenetic enzymes improves muscle strength, RyR1 protein content, and muscle ultrastructure. This study provides proof of concept for the pharmacological treatment of patients with congenital myopathies linked to recessive RYR1 mutations.
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Enfermedades Musculares , Miotonía Congénita , Animales , ADN/metabolismo , Modelos Animales de Enfermedad , Histona Desacetilasas/genética , Histona Desacetilasas/metabolismo , Humanos , Metiltransferasas/metabolismo , Ratones , Fuerza Muscular/genética , Músculo Esquelético/metabolismo , Mutación , Miotonía Congénita/tratamiento farmacológico , Miotonía Congénita/genética , Calidad de Vida , Canal Liberador de Calcio Receptor de Rianodina/genética , Canal Liberador de Calcio Receptor de Rianodina/metabolismoRESUMEN
Delays in motor development are not considered a core feature of autism spectrum disorder (ASD). Yet, recent studies of infant siblings of children with ASD suggest that early delays in motor skills may be associated with later delays in developmental areas considered to be core features of an ASD diagnosis. While these studies demonstrate the longitudinal association between core features and motor delays observed at single time points, there is considerable interest in studying the trajectories of motor development over the first 3 years of life. To accomplish this, we investigated early trajectories of motor development in a cohort of 499 infant siblings of children with ASD and 176 children with no family history of ASD. Data for the current study were drawn from the prospective, multi-site, Canadian Infant Sibling Study. We evaluated trajectories of fine and gross motor development over the first 3 years using group-based trajectory modeling. Our results show that membership for both fine and gross motor trajectory groups was related to expressive language skills, receptive language skills, ASD symptom severity scores, and diagnostic classification at age 3. These results provide evidence that the trajectory of a child's early motor development may have important prognostic implications in ASD.
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Trastorno del Espectro Autista , Trastorno del Espectro Autista/complicaciones , Trastorno del Espectro Autista/diagnóstico , Canadá , Niño , Preescolar , Humanos , Lactante , Destreza Motora , Estudios Prospectivos , HermanosRESUMEN
Congenital myopathies are a group of early onset muscle diseases of variable severity often with characteristic muscle biopsy findings and involvement of specific muscle types. The clinical diagnosis of patients typically relies on histopathological findings and is confirmed by genetic analysis. The most commonly mutated genes encode proteins involved in skeletal muscle excitation-contraction coupling, calcium regulation, sarcomeric proteins and thin-thick filament interaction. However, mutations in genes encoding proteins involved in other physiological functions (for example mutations in SELENON and MTM1, which encode for ubiquitously expressed proteins of low tissue specificity) have also been identified. This intriguing observation indicates that the presence of a genetic mutation impacts the expression of other genes whose product is important for skeletal muscle function. The aim of the present investigation was to verify if there are common changes in transcript and microRNA expression in muscles from patients with genetically heterogeneous congenital myopathies, focusing on genes encoding proteins involved in excitation-contraction coupling and calcium homeostasis, sarcomeric proteins, transcription factors and epigenetic enzymes. Our results identify RYR1, ATPB2B and miRNA-22 as common transcripts whose expression is decreased in muscles from congenital myopathy patients. The resulting protein deficiency may contribute to the muscle weakness observed in these patients. This study also provides information regarding potential biomarkers for monitoring disease progression and response to pharmacological treatments in patients with congenital myopathies.
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The beneficial effect of early intervention is well described for children with autism spectrum disorder (ASD). Response to early intervention is, however, highly heterogeneous in affected children, and there is currently only scarce information about predictors of response to intervention. Based on the hypothesis that impaired social orienting hinders the subsequent development of social communication and interactions in children with ASD, we sought to examine whether the level of social orienting modulates treatment outcome in young children with ASD. We used eye-tracking technology to measure social orienting in a group of 111 preschoolers, comprising 95 young children with ASD and 16 children with typical development, as they watched a 29 s video of a woman engaging in child-directed speech. In line with previous studies, we report that attention to face is robustly correlated with autistic symptoms and cognitive and adaptive skills at baseline. We further leverage longitudinal data in a subgroup of 81 children with ASD and show that the level of social orienting at baseline is a significant predictor of developmental gains and treatment outcome. These results pave the way for identifying subgroups of children who show a better response to early and intensive intervention, a first step toward precision medicine for children with autism.
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Autism spectrum disorders (ASD) are associated with disruption of large-scale brain network. Recently, we found that directed functional connectivity alterations of social brain networks are a core component of atypical brain development at early developmental stages in ASD. Here, we investigated the spatio-temporal dynamics of whole-brain neuronal networks at a subsecond scale in 113 toddlers and preschoolers (66 with ASD) using an EEG microstate approach. We first determined the predominant microstates using established clustering methods. We identified five predominant microstate (labeled as microstate classes A-E) with significant differences in the temporal dynamics of microstate class B between the groups in terms of increased appearance and prolonged duration. Using Markov chains, we found differences in the dynamic syntax between several maps in toddlers and preschoolers with ASD compared to their TD peers. Finally, exploratory analysis of brain-behavioral relationships within the ASD group suggested that the temporal dynamics of some maps were related to conditions comorbid to ASD during early developmental stages.
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Trastorno del Espectro Autista/fisiopatología , Mapeo Encefálico , Encéfalo/fisiopatología , Vías Nerviosas/fisiopatología , Preescolar , Femenino , Humanos , Lactante , MasculinoRESUMEN
Diminished orienting to social stimuli, and particularly to faces, is a core feature of autism spectrum disorders (ASDs). Impaired face processing has been linked to atypical attention processes that trigger a cascade of pathological development contributing to impaired social communication. The aim of the present study is to explore the processing of emotional and neutral faces using an eye-tracking paradigm (the emotional faces task) with a group of 24 children with ASD aged 6 and under and a group of 22 age-matched typically developing (TD) children. We also measure habituation to faces in both groups based on the presentation of repeated facial expressions. Specifically, the task consists of 32 pairs of faces, a neutral face and an emotional face from the same identity, shown side by side on the screen. We observe differential exploration of emotional faces in preschoolers with ASD compared with TD. Participants with ASD make fewer fixations to emotional faces than their TD peers, and the duration of their first fixation on emotional faces is equivalent to their first fixation on neutral faces. These results suggest that emotional faces may be less interesting for children with ASD. We also observe a habituation process to neutral faces in both children with ASD and TD, who looked less at neutral faces during the last quarter of the task compared with the first quarter. By contrast, TD children show increased interest in emotional faces throughout the task, looking slightly more at emotional faces during the last quarter of the task than during the first quarter. Children with ASD demonstrate neither habituation nor increased interest in the changing emotional expressions over the course of the task, looking at the stimuli for equivalent time throughout the task. A lack of increased interest in emotional faces may suggest a lack of sensitivity to changes in expression in young children with ASD.
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This study aims to identify predictors of treatment outcome in young children with ASD within a European context, where service provision of intervention remains sporadic. We investigated whether a child's age at baseline, intensity of the intervention provided, type of intervention, child's level of social orienting and cognitive skills at baseline predicted changes in autistic symptoms and cognitive development after 1 year of intervention, in a sample of 60 children with ASD. Our results strongly support early and intensive intervention. We also observed that lower cognitive skills at baseline were related to greater cognitive gains. Finally, we show that a child's interest in social stimuli may contribute to intervention outcome.
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Trastorno del Espectro Autista/diagnóstico , Trastorno del Espectro Autista/terapia , Intervención Médica Temprana/métodos , Habilidades Sociales , Trastorno del Espectro Autista/epidemiología , Preescolar , Cognición/fisiología , Humanos , Lactante , Masculino , Valor Predictivo de las Pruebas , Suiza/epidemiología , Resultado del TratamientoRESUMEN
Cells of the facultative photosynthetic bacterium Rhodobacter capsulatus exploit the simultaneous presence in the cultural medium of the toxic oxyanion tellurite (TeO32-) and the redox mediator lawsone (2-hydroxy-1,4-naphthoquinone) by reducing tellurite to metal Te0 nanoprecipitates (TeNPs) outside the cells. Here we have studied the mechanism by which lawsone interacts with metabolically active cells and analysed both structure and composition of the TeNPs collected from the growth medium of phototrophycally grown R. capsulatus. High Resolution Transmission Electron Microscopy (HR-TEM) images and Energy-Dispersive X-ray (EDX) microanalysis of TeNPs showed a central core of polycrystalline tellurium interspersed in an organic matrix with a predominant protein-based composition. The main proteins from Te0 nanostructures were identified by Liquid Chromatography tandem-Mass Spectrometry and were all correlated with the cell outer membrane composition. The interaction of reduced lawsone with tellurite and with the bacterial cells was probed by Cyclic Voltammetry and Scanning ElectroChemical Microscopy (SECM). We concluded that lawsone is required for the reduction of tellurite to metal Te0 in a reaction mechanism dependent on reducing equivalents deriving from the cell photosynthetic metabolism. SECM experiments demonstrate that lawsone, by diffusing inside the bacterial cells, is effectively available at the membrane site of the photosynthetic electron transport chain.
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Nanopartículas/metabolismo , Naftoquinonas/metabolismo , Rhodobacter capsulatus/metabolismo , Telurio/metabolismo , Cristalización , Nanopartículas/ultraestructura , Oxidación-Reducción , Rhodobacter capsulatus/citología , Telurio/análisisRESUMEN
Sensory processing issues have been frequently reported in individuals with Autism Spectrum Disorders (ASD), but their relationship with social and overall adaptive functioning has not been extensively characterized to date. Here, we investigate how sensory processing atypicalities relate with deficits in social skills, impaired social cognition, and general adaptive functioning in a group of preschoolers with ASD. Sixty-four children with ASD aged 3 to 6 were included in this study, along with 36 age-matched typically-developing (TD) peers. Parent-reported measures of sensory processing, social difficulties and overall adaptive functioning were collected for all children. We also obtained precise measures of social attention deployment using a custom-design eye-tracking task depicting naturalistic social scenes. Within the group of children with ASD, higher intensities of sensory issues were associated with more prominent social difficulties and lower adaptive functioning. We also found that children with ASD who had more sensory issues showed visual exploration patterns of social scenes that strongly deviated from the one seen in the TD group. The association of sensory processing atypicalities with "higher-order" functional domains such as social and adaptive functioning in children with ASD stresses the importance of further research on sensory symptoms in autism.
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Autism spectrum disorder (ASD) represents a group of neurodevelopmental disabilities that can be difficult to identify before the age of 2 or 3 years, the age when the full range of behavioral symptoms has emerged in most cases. Initiation of joint attention is an important developmental function in which impairments are already observable before the second birthday and can predict children's ASD symptomatology. In the first part of this review, we summarize results pertaining to retrospective studies of initiation of joint attention in children with ASD and prospective studies of infants at high risk for ASD during the first 2 years, when this behavior is becoming more complex in terms of frequency, quality, and variety. We will also discuss the implications of impairments in dyadic engagement, a precursor of joint attention behavior, for the early development of joint attention. Finally, the early development of initiation of joint attention has been related to specific visual attention mechanisms such as social orienting and visual disengagement. In the second part of this review, we provide an overview of the relationship between those visual attention mechanisms and subsequent social-communication impairments. Clinical and research implications of these findings for both early detection and early intervention will be discussed.