Biology subjects

Shi, Z.

Publications and source records attributed to Shi, Z..

At least 127 records · Page 7Linked to original sources

bioRxiv2023

Single-cell sequencing for the molecular identity involved in zinc therapy for spinal cord injury

Spinal cord injury (SCI) is a severe traumatic neurological condition often caused by car accidents, violent impacts, or unintentional falls and can have devastating consequences for the patient. SCI include primary and secondary injuries. Followed by primary injury, and secondary injuries including inflammatory responses and oxidative stress, which exacerbate the disease process of SCI. Therefore, the treatment of SCI, especially the suppression of secondary injuries, is a major focus of attention in the field of neuroscience. In previous studies, we have demonstrated that zinc therapy can exert neuroprotective effects in mice after acute SCI, including reducing the inflammatory response in the central nervous system, decreasing the neuronal apoptosis and downregulating oxidative stress at the region of injury. However, little is known about how zinc therapy systematically alleviates SCI. Here, we have systematically analysed and mapped the single-cell atlas of the spinal cord in mice with SCI treated by zinc therapy, which provides a systematic analysis of the transcriptome of individual cells in the spinal cord. Among the results, we found that zinc therapy-induced alterations in the IL-17 inflammatory pathway and produced immune heterogeneity in microglia which are the inherent immune cells in the central nervous system. By cell subpopulations clustering analysis, we defined seven microglia subpopulations in zinc-therapy spinal cord tissue and identified the presence of novel VEGFA+ microglia. This finding presents that the microglia subpopulations affected by zinc therapy may have the potential to promote angiogenesis, which is a potential mechanism for the treatment of SCI. In conclusion, this study maps/reveals the transcriptomic of zinc therapy for the treatment of acute SCI with unprecedented resolution and provides a molecular basis for the clinical application.

genomics↗

bioRxiv2023

MASH Native: A Unified Solution for Native Top-Down Proteomics Data Processing

Native top-down proteomics (nTDP) integrates native mass spectrometry (nMS) with top-down proteomics (TDP) to provide comprehensive analysis of protein complexes together with proteoform identification and characterization. Despite significant advances in nMS and TDP software developments, a unified and user-friendly software package for analysis of nTDP data remains lacking. Herein, we have developed MASH Native to provide a unified solution for nTDP to process complex datasets with database searching capabilities in a user-friendly interface. MASH Native supports various data formats and incorporates multiple options for deconvolution, database searching, and spectral summing to provide a one-stop shop for characterizing both native protein complexes and proteoforms. The MASH Native app, video tutorials, written tutorials and additional documentation are freely available for download at https://labs.wisc.edu/gelab/MASH_Explorer/MASHNativeSoftware.php. All data files shown in user tutorials are included with the MASH Native software in the download .zip file.

bioinformatics↗

bioRxiv2022

Nanofluidic Device for Manipulation and Modification of DNA by Proteins

Single-molecule techniques provide important details supplementing the framework obtained from traditional bulk experiments. Many cellular processes such as DNA replication, DNA repair, and telomere maintenance involve interaction among multiple proteins, their co-factors, and DNA. To investigate such interactions and to differentiate the function of each component necessitate a technique that allows the combinatorial exposure of DNA to multiple proteins and co-factors as well as manipulation of the DNA configuration. We present a nanofluidic device with the capability of active combinatorial exchange of up to three buffers in real-time and dynamic manipulation of DNA under physiologically relevant conditions. We demonstrate its utility in monitoring compaction of DNA by telomeric proteins, DNA modification by an endonuclease, and DNA loop extrusion by cohesin.

biophysics↗

bioRxiv2022

Cdkn2a regulates beige fat maintenance through BECN1-mediated autophagy

A potential therapeutic target to curb the obesity and diabetes epidemic is thermogenic beige adipocytes. However, beige adipocytes quickly transition into white adipocytes upon removing stimuli. Here, we define the critical role of Cdkn2a as a molecular pedal for the beige-to-white transition. Beige adipocytes lacking Cdkn2a exhibit prolonged lifespan, and mice are more resistant to diet-induced obesity, along with enhanced energy expenditure and improved glucose tolerance. Mechanistic studies demonstrate that Cdkn2a promotes the expression and activity of BECN1 by directly binding to its mRNA and its negative regulator BCL2L1, activating autophagy and accelerating the beige-to-white transition. Notably, reactivating autophagy by pharmacological or genetic methods abolishes beige adipocyte maintenance induced by Cdkn2a-ablation. Furthermore, hyperactive BECN1 alone significantly accelerates the beige-to-white transition. Collectively, these findings show that Cdkn2a-mediated autophagy serves as a brake system for beige adipocyte maintenance and is a highly promising target for anti-obesity and anti-diabetes therapy. HighlightsO_LICdkn2a ablation promotes beige fat maintenance and ameliorates diet-induced obesity C_LIO_LILoss of Cdkn2a retains beige adipocytes by inhibiting BECN1-mediated autophagy C_LIO_LICdkn2a modulates BECN1 by binding to its mRNA and its inhibitor BCL2L1, respectively C_LIO_LIHyperactive BECN1 is sufficient to accelerate the beige-to-white transition C_LI

cell biology↗

bioRxiv2022

An e-cigarette aerosol generation, animal exposure and toxicants quantification system to characterize in vivo nicotine kinetics in arterial and venous blood

The increasing e-cigarette use worldwide presents an urgent need to characterize their nicotine delivery property, brain stimulation and potential long-term health effects. We constructed an end-to-end system enabling combustible-cigarette (c-cigarette) and e-cigarette aerosol generation, animal exposure, and effect assessment. The system consists of (1) a 10-channel aerosol generator resembling human smoking/vaping scenarios, (2) nose-only and whole-body exposure chambers suitable for long- or short-duration studies, (3) a lab protocol for animal exposure and collecting arterial and venous blood <1 minute after the exposure, and (4) chromatograph and mass spectrometry to quantify nicotine concentrations in aerosol and biospecimens. We applied the system in a proof-of-principle study characterizing in vivo nicotine delivery after e-cigarette aerosol inhalation. Groups of Sprague-Dawley rats were exposed to e-cigarette aerosols for 1, 2 and 4 minutes, respectively. Arterial and venous blood samples were collected immediately after the exposure. We also directly compared nose-only and whole-body exposure approaches. After nose-only e-cigarette aerosol exposure, the nicotine concentration in arterial blood was substantially higher (11.32 ng/mL in average) than in veins. Similar arterio-venous concentration difference was observed in whole-body exposure experiments. In summary, we described a complete system ideal for e- and c-cigarette in vivo nicotine kinetics and long-term health research. Our findings highlight arterial blood as the suitable bio-specimen for e-cigarette nicotine delivery studies. HighlightO_LIWe constructed a combustible- and e-cigarette aerosol generation - exposure - effect assessment system resembling real world human smoking/vaping scenarios. C_LIO_LIProof-of-principle study characterized in vivo nicotine delivery from e-cigarette aerosol to arterial and venous blood at high temporal resolution. C_LIO_LIAfter exposure, the nicotine concentration was substantially higher (11.32 ng/mL) in arterial blood than in veins. C_LIO_LIOur results suggest arterial blood as the suitable bio-specimen to study nicotine delivery and brain stimulation. C_LI

pharmacology and toxicology↗

bioRxiv2022

Splicing-dependent transcriptional activation

Transcription and splicing are intrinsically coupled. Transcription dynamics regulate splicing, and splicing feeds back to transcription initiation to jointly determine gene expression profiles. A recently described phenomenon called exon-mediated activation of transcription starts (EMATS) shows that splicing of internal exons can regulate transcription initiation and activate cryptic promoters. Here, we present the first complete catalog of human EMATS genes that have a weak alternative promoter located upstream and proximate to an efficiently spliced internal skipped exon. We found that EMATS genes are associated with Mendelian genetic diseases --specifically intellectual development disorders, cardiomyopathy, and immunodeficiency-- and provide a list of EMATS genes with pathological variants. EMATS was originally described as a natural mechanism used during evolution to fine-tune gene expression through punctual genomic mutations that affect splicing. Here, we show that EMATS can be used to manipulate gene expression with therapeutic purposes. We constructed stable cell lines expressing a splicing reporter based on the alternative splicing of exon 7 of SMN2 gene under the regulation of different promoters. Using a small molecule (Risdiplam) and an antisense oligonucleotide (ASO) modeled after Spinraza, we promoted the inclusion of SMN2 exon 7 which triggered an increase in gene expression up to 40-folds by activating transcription initiation. We observed the strongest effects in reporters under the regulation of weak human promoters, where the highest drug doses dramatically increased exon inclusion. Overall, our findings present evidence to develop the first therapeutic strategy to use EMATS to activate gene expression using small molecules and ASOs that affect splicing.

molecular biology↗

bioRxiv2022

CTCF and R-loops are boundaries of cohesin-mediated DNA looping

Cohesin and CCCTC-binding factor (CTCF) are key regulatory proteins of three-dimensional (3D) genome organization. Cohesin extrudes DNA loops that are anchored by CTCF in a polar orientation. Here, we present direct evidence that CTCF binding polarity controls cohesin-mediated DNA looping. Using single-molecule imaging of CTCF-cohesin collisions, we demonstrate that a critical N-terminal motif of CTCF blocks cohesin translocation and DNA looping. The cryo-electron microscopy structure of the intact cohesin-CTCF complex reveals that this CTCF motif ahead of zinc-fingers can only reach its binding site on the STAG1 cohesin subunit when the N-terminus of CTCF faces cohesin. Remarkably, a C-terminally oriented CTCF accelerates DNA compaction by cohesin. DNA-bound Cas9 and Cas12a ribonucleoproteins are also polar cohesin barriers, indicating that stalling is intrinsic to cohesin itself, and other proteins can substitute for CTCF in fruit flies and other eukaryotes. Finally, we show that RNA-DNA hybrids (R-loops) block cohesin-mediated DNA compaction in vitro and are enriched with cohesin subunits in vivo, likely forming TAD boundaries. Our results provide direct evidence that CTCF orientation and R-loops shape the 3D genome by directly regulating cohesin.

molecular biology↗

bioRxiv2022

SPEX: A modular end-to-end analytics tool for spatially resolved omics of tissues

Recent advancements in transcriptomics and proteomics have opened the possibility for spatially resolved molecular characterization of tissue architecture with the promise of enabling a deeper understanding of tissue biology in either homeostasis or disease. The wealth of data generated by these technologies has recently driven the development of a wide range of computational methods. These methods have the requirement of advanced coding fluency to be applied and integrated across the full spatial omics analysis process thus presenting a hurdle for widespread adoption by the biology research community. To address this, we introduce SPEX (Spatial Expression Explorer), a web-based analysis platform that employs modular analysis pipeline design, accessible through a user-friendly interface. SPEXs infrastructure allows for streamlined access to open source image data management systems,analysis modules, and fully integrated data visualization solutions. Analysis modules include essential steps covering image processing, single-cell and spatial analysis. We demonstrate SPEXs ability to facilitate the discovery of biological insights in spatially resolved omics datasets from healthy tissue to tumor samples.

bioinformatics↗

bioRxiv2022

Sirt3 enhanced Bufalin sensitivity of colorectal cancer cells through P53-dependent pathway of apoptosis Sirt3 enhanced Bufalin sensitivity of colorectal cancer cells through P53-dependent pathway of apoptosis

Sirt3, one of class III histone deacetylase, is mainly localized in mitochondria and plays a significant role in the control of the metabolic activity, senescence and death [1]. Recently, Sirt3 emerged as a novel member of anticancer. However, the role of Sirt3 in colorectal cancer (CRC) has never been explained exactly. In this study, we found that sirt3 is down-regulated after Bufalin treatment. We also found that AC-P53 is up-regulated which induces Bax translocation to mitochondrion and open the mitochondrial permeability transition (mPTP) pores result in the release of cytochrome C lead to the activation of caspase-dependent apoptosis pathway. Collectively, our data suggests that Sirt3 may play an important role in CRC development and progression and may be a promising therapeutic target for CRC.

cancer biology↗

bioRxiv2022

Asymmetric learning of dynamic spatial regularities in visual search: facilitation of anticipated target locations, no suppression of predictable distractor locations

Static statistical regularities in the placement of targets and salient distractors within the search display can be learned and used to optimize attentional guidance. Whether statistical learning also extends to dynamic regularities governing the placement of targets and distractors on successive trials has been less investigated. Here, we applied the same dynamic cross-trial regularity (one-step shift of the critical item in clock-/counterclockwise direction) either to the target or a distractor, and additionally varied whether the distractor was defined in a different (color) or the same dimension (shape) as the target. We found robust learning of the predicted target location: processing of the target at this (vs. a random) location was facilitated. But we found no evidence of proactive suppression of the predictable distractor location. Facilitation of the anticipated target location was associated with explicit awareness of the dynamic regularity, whereas participants showed no awareness of the distractor regularity. We propose that this asymmetry arises because, owing to the targets central role in the task set, its location is explicitly encoded in working memory, enabling the learning of dynamic regularities. In contrast, the distractor is not explicitly encoded; so, statistical learning of distractor locations is limited to static regularities. Public significance statementCan we learn the cross-trial dynamic regularity of a target or a task-irrelevant salient distractor (e.g., one-step shift of the critical item in clock-/counterclockwise direction) to boost search performance? The present study found robust learning of the predicted target location, but no evidence of proactive suppression of the predictable distractor location. Facilitation of the anticipated target location was associated with explicit awareness of the dynamic regularity. This asymmetry highlights the important role of the target-centered task set in the learning of dynamic regularities.

neuroscience↗

bioRxiv2022

Membrane curvature governs the distribution of Piezo1 in cellulo

Piezo1 is a bona fide mechanosensitive ion channel ubiquitously expressed in mammalian cells. The distribution of Piezo1 within a cell is essential for various biological processes including cytokinesis, cell migration, and wound healing. However, the underlying principles that guide the subcellular distribution of Piezo1 remain largely unexplored. Here, we demonstrate that membrane curvature serves as a key regulator of the spatial distribution of Piezo1 in the plasma membrane of living cells. Piezo1 depletes from highly curved membrane protrusions such as filopodia and enriches to nanoscale membrane invaginations. Quantification of the curvaturedependent sorting of Piezo1 directly reveals the in situ nano-geometry of the Piezo1-membrane complex. Piezo1 density on filopodia increases upon activation, independent of Ca2+, suggesting flattening of the channel upon opening. Consequently, the expression of Piezo1 inhibits filopodia formation, an effect that diminishes with channel activation.

biophysics↗

bioRxiv2022

Decreasing photosystem antenna size: a double-edged sword for canopy photo-synthetic efficiency

Optimization of antenna size of photosynthetic systems is one strategy to increase plant canopy photosynthesis and crop yield potential. The relationship between antenna size and photosynthesis rate has been extensively studied recently. However, conflicting results have been obtained. Here we show that the extent of decrease in antenna size is a major factor determining the consequences of decreasing antenna on photosynthesis and growth-related parameters. Specifically, we constructed transgenic rice lines with artificial microRNA (amiRNA) targeting to Chlorophyll Synthesis (YGL1) to generate transgene heterozygous and homozygous lines with different leaf chlorophyll contents and antenna sizes. We found that canopy photosynthesis (Ac), biomass and grain yield of the heterozygote were not significantly different from those of WT while the Ac, biomass and grain yield of the homozygote were lower than those of WT. Further, when the maximal quantum yield of photosystem II (Fv/Fm) was larger than 0.8, decreasing antenna size by reducing chlorophyll biosynthesis did not affect leaf photosynthesis; but when Fv/Fm was lower than 0.8, there is a positive relationship between antenna size and leaf photosynthesis. There is large variation in both leaf chlorophyll content and antenna size in elite rice cultivars, suggesting that there is a large scope to decrease leaf chlorophyll content to increase nitrogen use efficiency as long as the quantum yield of PSII is not compromised.

systems biology↗

bioRxiv2022

Learning to suppress likely distractor locations in visual search is driven by the local distractor frequency

Salient but task-irrelevant distractors interfere less with visual search when they appear in a display region where distractors have appeared more frequently in the past ( distractor-location probability cueing). This effect could reflect the (re-)distribution of a global, limited attentional inhibition resource. Accordingly, changing the frequency of distractor appearance in one display region should also affect the magnitude of interference generated by distractors in a different region. Alternatively, distractor-location learning may reflect a local response (e.g., habituation) to distractors occurring at a particular location. In this case, the local distractor frequency in one display region should not affect distractor interference in a different region. To decide between these alternatives, we conducted three experiments in which participants searched for an orientation-defined target while ignoring a more salient orientation distractor that occurred more often in one vs. another display region. Experiment 1 varied the ratio of distractors appearing in the frequent vs. rare regions (60/40-90/10), with a fixed global distractor frequency. The results revealed the cueing effect to increase with increasing probability ratio. In Experiments 2 and 3, one ( test) region was assigned the same local distractor frequency as in one of the conditions of Experiment 1, but a different frequency in the other region - dissociating local from global distractor frequency. Together, the three experiments showed that distractor interference in the test region was not significantly influenced by the frequency in the other region, consistent with purely local learning. We discuss the implications for theories of statistical distractor-location learning. Public Significance StatementWe are frequently distracted by salient visual stimuli which are irrelevant to the task at hand. Previous studies have shown that knowledge of the location(s) where a distractor is most likely to occur helps the observer to mitigate distraction. In this study we compared different theories of how the frequency and spatial distribution of distractor occurrence in different locations could influence the ability to avoid distraction. The results favored a local learning account: the ability to avoid distraction by distractors occuring in a particular spatial region is primarily influenced by how often distractors have occurred in that region.

neuroscience↗

bioRxiv2022

VMHdm/cSF-1 Neuronal Circuits Regulate Skeletal Muscle PGC1-α via the Sympathoadrenal Drive

ObjectiveTo adapt to metabolically challenging environments, the central nervous system (CNS) orchestrates metabolism of peripheral organs including skeletal muscle. The organ-communication between the CNS and skeletal muscle has been investigated, yet our understanding of the neuronal pathway from the CNS to skeletal muscle is still limited. Neurons in the dorsomedial and central parts of the ventromedial hypothalamic nucleus (VMHdm/c) expressing steroidogenic factor-1 (VMHdm/cSF-1 neurons) are key for metabolic adaptations to exercise, including increased basal metabolic rate and skeletal muscle mass in mice. However, the mechanisms by which VMHdm/cSF-1 neurons regulate skeletal muscle function remain unclear. Here, we show that VMHdm/cSF-1 neurons increase the sympathoadrenal activity and regulate skeletal muscle peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1) in mice via multiple downstream nodes. MethodsOptogenetics was used to specifically manipulate VMHdm/cSF-1 neurons combined with genetically-engineered mice and surgical manipulation of the sympathoadrenal activity. ResultsOptogenetic activation of VMHdm/cSF-1 neurons dramatically elevates mRNA levels of skeletal muscle Pgc-1, which regulates a spectrum of skeletal muscle function including protein synthesis and metabolism. Mechanistically, the sympathoadrenal drive coupled with {beta}2 adrenergic receptor ({beta}2AdR) is essential for VMHdm/cSF-1 neurons-mediated increases in skeletal muscle PGC1-. Specifically, both adrenalectomy and {beta}2AdR knockout block augmented skeletal muscle PGC1- by VMHdm/cSF-1 neuronal activation. Optogenetic functional mapping reveals that downstream nodes of VMHdm/cSF-1 neurons are functionally redundant to increase circulating epinephrine and skeletal muscle PGC1-. ConclusionsCollectively, we propose that VMHdm/cSF-1 neurons-skeletal muscle pathway, VMHdm/cSF-1 neurons[->]multiple downstream nodes[->]the adrenal gland[->]skeletal muscle {beta}2AdR, underlies augmented skeletal muscle function for metabolic adaptations.

neuroscience↗

bioRxiv2022

Pore-forming protein βγ-CAT promptly responses to fasting with capacity to deliver macromolecular nutrients

During animal fasting, the nutrient supply and metabolism switch from carbohydrates to a new reliance on the catabolism of energy-dense lipid stores. Assembled under tight regulation, {beta}{gamma}-CAT is a pore-forming protein and trefoil factor complex identified in toad Bombina maxima. Here, we determined that this protein complex is a constitutive component in toad blood, that actively responds to the animal fasting. The protein complex was able to promote cellular albumin and albumin-bound fatty acid uptake in a variety of epithelial and endothelial cells, and the effects were attenuated by a macropinocytosis inhibitor. Endothelial cell-derived exosomes containing largely enriched albumin and fatty acids, called nutrisomes, were released in the presence of {beta}{gamma}-CAT. These specific nutrient vesicles were readily taken by starved muscle cells to support their survival. The results uncovered that pore-forming protein {beta}{gamma}-CAT is a fasting responsive element able to drive cell vesicular import and export of macromolecular nutrients.

cell biology↗

bioRxiv2022

Duration reproduction under memory pressure: Modeling the roles of visual memory load in duration encoding and reproduction

Duration estimates are often biased by the sampled statistical context, yielding the classical central-tendency effect, i.e., short durations are over- and long duration underestimated. Most studies of the central-tendency bias have primarily focused on the integration of the sensory measure and the prior information, without considering any cognitive limits. Here, we investigated the impact of cognitive (visual working-memory) load on duration estimation in the duration encoding and reproduction stages. In four experiments, observers had to perform a dual, attention-sharing task: reproducing a given duration (primary) and memorizing a variable set of color patches (secondary). We found an increase in memory load (i.e., set size) during the duration-encoding stage to increase the central-tendency bias, while shortening the reproduced duration in general; in contrast, increasing the load during the reproduction stage prolonged the reproduced duration, without influencing the central tendency. By integrating an attentional-sharing account into a hierarchical Bayesian model, we were able to predict both the general over- and underestimation and the central-tendency effects observed in all four experiments. The model suggests that memory pressure during the encoding stage increases the sensory noise, which elevates the central-tendency effect. In contrast, memory pressure during the reproduction stage only influences the monitoring of elapsed time, leading to a general duration over-reproduction without impacting the central tendency.

neuroscience↗

bioRxiv2022

Multiphasic hepatitis B virus kinetic patterns in humanized chimeric mice can be explained via stochastic agent-based modeling of intracellular virion production cycles

Serum hepatitis B virus (HBV) kinetics in urokinase-type plasminogen activator/severe combined immunodeficient (uPA-SCID) mice reconstituted with humanized livers from inoculation to steady state is highly dynamic despite the absence of an adaptive immune response. We developed a stochastic agent-based model that includes virion production cycles in individual infected human hepatocytes. The model was calibrated using a genetic algorithm approach with the serum HBV kinetics observed in mice inoculated with 108 HBV genome equivalents and fit the data well when the following viral production parameters were assumed: (1) An eclipse phase lasting 5-50 hours and (2) a post-eclipse phase production rate that is based on increasing production cycles initially starting with a long production cycle of 1 virion per 20 hours that gradually reaches 1 virion per hour after approximately 3-4 days before virion production increases dramatically to reach to a steady state production rate of 4 virions per hour per cell. The model was then validated by showing it could accurately simulate the viral kinetics observed with lower HBV inoculation doses (104-107 genome equivalents) in which similar, but delayed patterns were observed. Together, modeling suggests that it is the cyclic nature of the virus lifecycle combined with an initial slow but increasing rate of HBV production from each cell that plays a role in generating the observed multiphasic HBV kinetic patterns in humanized mice.

systems biology↗

bioRxiv2022

Predictive coding in ASD: inflexible weighting of prediction errors when switching from stable to volatile environments

The nature of predictive-processing differences between individuals with autism spectrum disorder (ASD) and typically developing (TD) individuals is widely debated. Some studies suggest impairments in predictive processing in ASD, while others report intact processes, albeit with atypical learning dynamics. Here, we assessed duration reproduction tasks in high- and low-volatility settings to examine the updating dynamics of prior beliefs and sensory estimates. Employing a two-state Bayesian model, we differentiated how individuals with ASD and TD controls update their priors and perceptual estimates, and how these updates affect long-term prediction and behavior. Our findings indicate that individuals with ASD use prior knowledge and sensory input similarly to TD controls in perceptual estimates. However, they place a greater weight on sensory inputs specifically for iteratively updating their priors. This distinct approach to prior updating led to slower adaptation across trials; individuals with ASD relied less on their priors in perceptual estimates during the first half of sessions but achieved comparable integration weights as TD controls by the end of the session. By differentiating these aspects, our study highlights the importance of considering inter-trial updating dynamics to reconcile diverse findings of predictive processing in ASD. In consequence to the current findings, we suggest the distinct iterative updating account of predictive processing in ASD. Significance StatementResearch on predictive processing in Autism Spectrum Disorder (ASD) remains controversial. The current study employed a two-state Bayesian model in varied volatility settings to explore inter-trial updating dynamics in ASD compared to typically developing (TD) peers. We found that individuals with ASD, while utilizing prior knowledge similarly to TD controls, place a disproportionate emphasis on sensory inputs when updating their priors. This unique pattern of slower adaptation during iterative updating leads to significant behavioral differences in the first half of trials between the two groups, but comparable levels by the end of the session. These findings not only highlight the importance of considering different timescales and dynamic updating processes in ASD, but also suggest that the predictive processing framework in ASD involves unique prior updating mechanisms that is likely associated with increased sensory reliance.

neuroscience↗