RESUMEN
Kif16A, a member of the kinesin-3 family of motor proteins, has been shown to play crucial roles in inducing mitotic arrest, apoptosis, and mitotic cell death. However, its roles during oocyte meiotic maturation have not been fully defined. In this study, we report that Kif16A exhibits unique accumulation on the spindle apparatus and colocalizes with microtubule fibers during mouse oocyte meiotic maturation. Targeted depletion of Kif16A using gene-targeting siRNA disrupts the progression of the meiotic cell cycle. Furthermore, Kif16A depletion leads to aberrant spindle assembly and chromosome misalignment in oocytes. Our findings also indicate that Kif16A depletion reduces tubulin acetylation levels and compromises microtubule resistance to depolymerizing drugs, suggesting its crucial role in microtubule stability maintenance. Notably, we find that the depletion of Kif16A results in a notably elevated incidence of defective kinetochore-microtubule attachments and the absence of BubR1 localization at kinetochores, suggesting a critical role for Kif16A in the activation of the spindle assembly checkpoint (SAC) activity. Additionally, we observe that Kif16A is indispensable for proper actin filament distribution, thereby impacting spindle migration. In summary, our findings demonstrate that Kif16A plays a pivotal role in regulating microtubule and actin dynamics crucial for ensuring both spindle assembly and migration during mouse oocyte meiotic maturation.
Asunto(s)
Cinesinas , Meiosis , Microtúbulos , Oocitos , Huso Acromático , Animales , Cinesinas/metabolismo , Cinesinas/genética , Meiosis/fisiología , Oocitos/metabolismo , Microtúbulos/metabolismo , Ratones , Huso Acromático/metabolismo , Femenino , Actinas/metabolismo , Cinetocoros/metabolismoRESUMEN
OBJECTIVES: To investigate the differences in visual perception between children with autism spectrum disorder (ASD) and typically developing (TD) children when watching different intention videos, and to explore the feasibility of machine learning algorithms in objectively distinguishing between ASD children and TD children. METHODS: A total of 58 children with ASD and 50 TD children were enrolled and were asked to watch the videos containing joint intention and non-joint intention, and the gaze duration and frequency in different areas of interest were used as original indicators to construct classifier-based models. The models were evaluated in terms of the indicators such as accuracy, sensitivity, and specificity. RESULTS: When using eight common classifiers, including support vector machine, linear discriminant analysis, decision tree, random forest, and K-nearest neighbors (with K values of 1, 3, 5, and 7), based on the original feature indicators, the highest classification accuracy achieved was 81.90%. A feature reconstruction approach with a decision tree classifier was used to further improve the accuracy of classification, and then the model showed the accuracy of 91.43%, the specificity of 89.80%, and the sensitivity of 92.86%, with an area under the receiver operating characteristic curve of 0.909 (P<0.001). CONCLUSIONS: The machine learning model based on eye-tracking data can accurately distinguish ASD children from TD children, which provides a scientific basis for developing rapid and objective ASD screening tools.
Asunto(s)
Trastorno del Espectro Autista , Niño , Humanos , Trastorno del Espectro Autista/diagnóstico , Tecnología de Seguimiento Ocular , Intención , Algoritmos , Aprendizaje AutomáticoRESUMEN
BACKGROUND: Altered automatic attention cueing has been reported in autistic children. Yet less is known about how autistic children would respond when the social cue that directs attention occurs in an implied social interaction. METHODS: By using eye-tracking, the current study examined orienting responses to a socially-relevant target or a nonsocial target cued by a goal-directed social gesture in autistic children. Saccadic reaction time and pupillary responses were employed to measure gaze behavior and physiological arousal of autistic children. RESULTS: Both groups of children showed reflexive orienting to the target regardless of its sociality, whereas typically developing (TD) children exhibited faster gaze shift than autistic children when the target was a social stimulus. An increased pupil dilation was observed in autistic children in response to stimuli relative to TD children. Further, autistic children showed larger baseline pupil response. CONCLUSIONS: Autistic children show attenuated sensitivity to social targets and atypical pupil responses, which may be due to the dysfunction of locus coeruleus (LC) - norepinephrine (NE) system.
RESUMEN
Accumulating evidence suggests that individuals with autism spectrum disorder (ASD) show impairments in using contextual priors to predict others' actions and make intention inference. Yet less is known about whether and how children with ASD acquire contextual priors during action observation and how contextual priors relate to their action prediction and intention inference. To form proper contextual priors, individuals need to observe the social scenes in a reliable manner and focus on socially relevant information. By employing a data-driven scan path method and areas of interest (AOI)-based analysis, the current study investigated how contextual priors would relate to action prediction and intention understanding in 4-to-9-year-old children with ASD (N = 56) and typically developing (TD) children (N = 50) during free viewing of dynamic social scenes with different intentions. Results showed that children with ASD exhibited higher intra-subject variability when scanning social scenes and reduced attention to socially relevant areas. Moreover, children with high-level action prediction and intention understanding showed lower intra-subject variability and increased attention to socially relevant areas. These findings suggest that altered fixation patterns might restrain children with ASD from acquiring proper contextual priors, which has cascading downstream effects on their action prediction and intention understanding.
RESUMEN
Gaze abnormalities are well documented in infants at elevated risk for autism spectrum disorder (ASD). However, variations in experimental design and stimuli across studies have led to mixed results. The current meta-analysis aimed to identify which type of eye tracking task and stimulus are most effective at differentiating high-risk infants (siblings of children with ASD) who later meet diagnosis criteria from low-risk infants without familial autism. We synthesized 35 studies that used eye tracking to investigate gaze behavior in infants at high genetic risk for autism before 2 years of age. We found that stimulus features, regions of interest (ROIs) and study quality moderated effect sizes across studies. Overall, dynamic stimuli and socially-relevant regions in the social stimuli (i.e. the target and activity of characters' shared focus) reliably detected high-risk infants who later develop ASD. Attention disengagement task and stimuli depicting interactions between human and nonhuman characters could identify high-risk infants who later develop ASD and those who have autism-related symptoms but do not meet the diagnostic criteria as well. These findings provide sensitive and reliable early markers of ASD, which is helpful to develop objective and quantitative early autism screening and intervention tools.