Biology subjects

Chua, R.

Publications and source records attributed to Chua, R..

13 recordsLinked to original sources

bioRxiv2026

Perceptual versus motor awareness of explicit contributions to visuomotor adaptation

In the current experiment, we compared reported perceptual awareness of the visuomotor rotation to motor awareness of changes in reaches established using the process dissociation procedure and drawing task following visuomotor adaptation to a large (50 degrees; R50 group) or a small (30 degrees; R30 group) cursor rotation. Results revealed that perceptual and motor awareness did not differ in magnitude for the R50 group and were significantly correlated. In contrast, while the R30 group perceptually reported being aware of the visuomotor rotation, motor awareness was significantly less and responses were not significantly correlated across tasks. Overall, results suggest that perceptual and motor tasks assess different processes underlying visuomotor adaptation to a small cursor rotation, such that perceptual awareness of the visuomotor rotation is not reflected in reaching performance on tasks assessing motor awareness.

neuroscience↗

bioRxiv2026

Dissociating the behavioral and computational features of implicit motor learning and explicit perturbation detection

The human sensorimotor system is remarkably effective at automatically parsing total movement error into its constituent parts, the error component due to a perturbation, or externally-generated error (EGE), versus the error component due to motor noise, or internally-generated error (IGE). Participants robustly, and implicitly, adapt to minuscule (2{degrees}) EGEs in the form of randomized visuomotor rotations while ignoring identically-sized errors caused by IGE. This error parsing, and its associated perceptual processes, directly contrasts previous work showing that humans must observe rotations that are > 1.5x the standard deviations of their motor variability, or [≥] 4{degrees}, before explicitly reporting their presence. While the combined results suggest a dissociation between perception for action--which allows for precise and automatic error parsing--and perception for conscious detection, this must be inferred across studies using different methodologies. Here, we combined a within-subjects study design and computational modeling to shed light on the principles underlying implicit adaptation to a perturbation and explicit perturbation detection. Neuro-typical adults participated in two experiments consisting of pseudo-randomized rotations during reaches to a single target, with one session requiring explicit reports after each reach of whether a perturbation was detected. Participants demonstrated a clear dissociation between implicit responses to a perturbation and explicit detection, with robust adaptation to 1{degrees} EGEs, but an inability to reliably report the presence of an EGE until it reached [~] 4{degrees}. For the adaptation task, a model that assumes the participant compares proprioceptive and visual cues to detect a perturbation and corrects for a proportion of this error best fit the data. For signal-detection, a Bayesian causal-inference model in which sensory cues are optimally integrated with a prior on their cause best fit those data. These results indicate that implicit adaptation is dissociated from explicit perturbation detection and the sensorimotor system applies distinct computational strategies to these behaviors.

neuroscience↗

bioRxiv2026

Two orthogonal MAP3K-driven pathways of NLRP1 inflammasome activation revealed by poisonous beetles.

Environmental toxins that cause irritant dermatitis remain poorly understood as activators of innate immune pathways. Here, we identify rove beetle (Paederus) and blister beetle (Meloidae) toxins as previously unrecognized triggers of the human NLRP1 inflammasome in keratinocytes. Rove beetles, likely through the ribosome inhibitor pederin, activate NLRP1 via translational stalling and the ZAK-dependent ribotoxic stress response. In contrast, the phosphatase inhibitor cantharidin from blister beetles induces NLRP1 through TAK1-driven hyperphosphorylation of its linker region, independent of ZAK. In their hyperactivated states, ZAK and TAK1 share overlapping phosphosites on the NLRP1 disordered linker, including a common essential TZ motif. In addition, we show that TAK1 and ZAK are jointly responsible for NLRP1 linker phosphorylation and activation caused by dsRNA and CHIKV infection. These findings reveal medically relevant insect toxins as activators of NLRP1, and uncover parallel MAP3 kinase pathways as converging upstream activating signals for the human NLRP1 inflammasome. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=172 HEIGHT=200 SRC="FIGDIR/small/701189v1_ufig1.gif" ALT="Figure 1000"> View larger version (50K): org.highwire.dtl.DTLVardef@ee34b9org.highwire.dtl.DTLVardef@c79ec9org.highwire.dtl.DTLVardef@189c373org.highwire.dtl.DTLVardef@17ec853_HPS_FORMAT_FIGEXP M_FIG C_FIG KEY POINTSTwo dermatitis-causing beetle species induce NLRP1-driven pyroptosis of human keratinocytes Rove beetles, likely via pederin, activate NLRP1 via ribosome inhibition and ZAK[a]-driven RSR Cantharidin from blister beetles activates human via TAK1-, instead of ZAK[a]-driven hyperphosphorylation of the NLRP1 linker region Shared phosphosites by TAK1 and ZAK[a] on NLRP1 contribute to dsRNA-driven NLRP1 activation

immunology↗

bioRxiv2026

A TAK1-Driven NLRP1 Inflammasome Pathway Revealed by Phosphatase-Targeting Environmental Toxins

Human NLRP1 is highly sensitive to phosphorylation-dependent activation, indicating a need for tight phosphatase control to prevent excessive inflammasome activity. In this study, we identified the phosphatases PP1 and PP2A as negative regulators of the NLRP1 inflammasome in human keratinocytes. Accordingly, exposure to the environmental toxins Dinophysistoxin, Okadaic acid, and Cantharidin, which inhibit PP1 and PP2A, triggered NLRP1 inflammasome activation. Notably, this toxin-induced activation process relied on hyperactivation of the MAP3 kinase TAK1. Mechanistically, both TAK1 and its downstream effectors p38 kinases phosphorylated and activated the NLRP1 inflammasome. Further studies underscored that TAK1 also contributed to the NLRP1 inflammasome activation during double-stranded RNA stimulation and viral infection. Finally, human native skins exposed to environmental toxins underlined the role of the PP1/PP2A-regulated TAK1/p38 axis in the development of skin dermatitis. Thus, these findings reveal a novel pathway of phosphorylation-driven NLRP1 activation and expand our understanding of its regulation in epithelial immunity. One Sentence SummaryPP1/PP2A phosphatases restrict TAK1-driven NLRP1 inflammasome response. O_FIG O_LINKSMALLFIG WIDTH=146 HEIGHT=200 SRC="FIGDIR/small/701233v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@128de37org.highwire.dtl.DTLVardef@151fbdorg.highwire.dtl.DTLVardef@d6b98aorg.highwire.dtl.DTLVardef@12f419d_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO Schematic representation of the phosphorylation-driven hNLRP1 inflammasome response upon exposure to environmental toxins and to dsRNA/viral infection. C_FIG

immunology↗

bioRxiv2025

Increased attentive use leads to more idiosyncratic functional connections

Experience is thought to modify neural connections to adapt the network to be more optimal for the environment. Given the brains complexity, multiple network changes could each move the system toward optimality. Standard methods ignore this multiplicity and examine each connection independently; these studies have often shown considerable inter-individual variability and modest effects (1). Here, we take a different strategy, determining how a whole-brain connection pattern differs from the typical pattern, that is, how idiosyncratic the pattern is. We examined how the idiosyncrasy of whole brain connection patterns varies with frequency of the use of that part of cortex for attention-demanding tasks, focusing on central versus peripheral vision in healthy individuals (where individuals use central vision more frequently for attention-demanding tasks). We found that the whole-brain pattern of functional connections to the cortical representations of central vision is idiosyncratic, whereas patterns of connections to representations of peripheral vision were very similar person-to-person. In a second set of analyses, we examined the brains of people with central vision loss who use a portion of peripheral vision (called the preferred retinal locus) more frequently for attention-demanding tasks in their daily lives. The cortical representation of the preferred retinal locus exhibits more idiosyncratic connections, compared to a control brain region, or compared to the same brain region in matched control participants with healthy vision. These results are consistent with the hypothesis that increased attentive use of a brain area results in idiosyncratic patterns of whole brain connections. Significance StatementWe found that increased attentive use of a brain region results in more idiosyncratic patterns of connections of that region to the rest of the brain. Our findings support the view that V1 retains the capacity for plasticity well beyond the critical period and that these adaptations are idiosyncratic to the individuals experiences. This approach suggests that tailoring personalized rehabilitation plans for individuals with retinal diseases may be more effective than a one size fits all approach. More generally, it offers a promising framework for investigating brain plasticity in both typical and clinical populations, especially in the context of sensory loss and compensatory adaptation.

neuroscience↗

bioRxiv2025

Clarifying the priming requirement and activator specificity for the NLRP3 inflammasome in human keratinocytes in vitro

While NLRP3 has been extensively studied in myeloid cells, its existence and regulation in epithelial cells, including keratinocytes, are unclear. In fact, whether human keratinocytes express a functional NLRP3 inflammasome at all remains a matter of debate in the inflammasome field. Here, we provide additional evidence that NLRP3 is repressed in human keratinocytes cultured under non-inflammatory conditions but can be sharply induced by interferon-{gamma} (IFN{gamma})--but not lipopolysaccharide (LPS). In this IFN{gamma}-primed state, not all established NLRP3 activators are specific to NLRP3. We report that nigericin-driven keratinocyte pyroptosis occurs via both NLRP1 and NLRP3, whereas Staphylococcus aureus -hemolysin (Hla) exclusively and nonredundantly activates NLRP3, even though both require K+ efflux. Furthermore, in the presence of T cells, certain virulent S. aureus strains can cause NLRP3-dependent pyroptotic death in keratinocytes in vitro through the cooperative actions of superantigens (SAgs) and Hla. In summary, our findings establish the strict inducibility and functional relevance of the NLRP3 inflammasome in non-myeloid, epithelial cells in vitro. These results resolve conflicting reports and position keratinocytes as a context-specific, non-hematopoietic cellular model for studying NLRP3 activation in host-microbe interactions at barrier tissues. KEY FINDINGSO_LIAdditional evidence that NLRP3 is absent in resting, nonstimulated human keratinocytes in vitro C_LIO_LIIFN{gamma}, but not LPS, is a potent priming signal for NLRP3 in human keratinocytes in vitro C_LIO_LIIn IFN{gamma}-primed keratinocytes, S. aureus -hemolysin (Hla) selectively activates NLRP3, whereas nigericin activates both NLRP1 and NLRP3 in vitro C_LIO_LISAg and Hla kill keratinocytes via NLRP3-driven pyroptosis in the presence of T cells in vitro C_LI GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=156 SRC="FIGDIR/small/669639v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@4996f4org.highwire.dtl.DTLVardef@155a2a9org.highwire.dtl.DTLVardef@12a21a0org.highwire.dtl.DTLVardef@105bc15_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2025

Dual agonist and antagonist muscle vibration produces a bias in end point with no change in variability

Muscle spindles provide critical proprioceptive feedback about muscle length to the central nervous system (CNS). Single muscle tendon vibration can stimulate muscle spindles, causing participants to misjudge limb position, while dual muscle tendon vibration is thought to produce a noisy proprioceptive system. It is currently unclear exactly how the CNS uses kinesthetic feedback from the agonist and antagonist muscles during target-directed reaches. The purpose of the current project was to investigate the effects of agonist, antagonist, and dual agonist/antagonist during target-directed reaching. Using an elbow extension task, we found that antagonist muscle vibration produced an undershooting effect relative to the no-vibration control, while agonist muscle vibration produced an overshooting effect relative to the no-vibration control. Neither of the single muscle vibrations produced any change in the variable error of the movements. While it was originally hypothesized that dual agonist/antagonist vibration would increase participants variable error with no change in bias, the opposite was found. Participants undershot relative to the no-vibration control with no change in variable error. Overall, the results from this study suggest that dual vibration does not necessarily create a noisy proprioceptive system but can produce a bias in end point.

neuroscience↗

bioRxiv2025

A Bayesian decision-making model of implicit motor learning from internal and external errors

A key challenge for the sensorimotor system is deciding which errors to learn from and which to ignore. Recent work has shown that humans are remarkably precise in parsing movement errors into internally- and externally-generated components for this purpose: Participants automatically ignore internally-generated reaching errors caused by motor noise, yet implicitly adapt to size-matched externally-generated errors caused by visuomotor rotations (Ranjan & Smith 2018, 2022). Following replication of these results with 16 neurotypical adults, we formalized our understanding of this behavior with a novel Bayesian decision-making model. The Parsing of Internal and External Causes of Error (PIECE) model frames adaptation as a process of causal inference regarding the source of error, with the magnitude of motor corrections reflecting a combination of state estimation and the observers degree-of-belief that their movement was externally perturbed. Thus, PIECE presents a challenge to a class of computational models that frames adaptation as a process of re-aligning the perceived hand position with the movement goal. We show that only PIECE can capture the precise parsing of internal versus external errors observed. Combined, this work provides a normative explanation of how the nervous system discounts intrinsic motor noise and adapts to perturbations, keeping movements finely-calibrated.

neuroscience↗

bioRxiv2024

Evidence for an efferent-based prediction contributing to implicit motor adaptation

Models of sensorimotor adaptation have proposed that implicit adaptation is driven by error signals created by discrepancies between various sensory information sources. While proprioception has been suggested as a critical source for the error signals driving adaptation, the role of an efferent-based motor prediction has largely been neglected. In this study, we examined the effect of dissociating the afferent and efferent information available during implicit adaptation. Participants moved a visual cursor towards targets by applying horizontal forces to a stationary handle at a central home location. During perturbation trials, the cursor followed an invariant path rotated relative to the target. Participants were instructed to ignore this task-irrelevant cursor feedback and to isometrically "reach" towards the target. Participants implicitly adapted in the isometric task, even when the hand never actually moved to the target. Moreover, the level of adaptation surpassed that of a typical clamped reaching paradigm by nearly twofold. This was confirmed in a secondary experiment where participants performed actual reaching movements and demonstrated significantly less adaptation. Our findings suggest that while afferent proprioceptive feedback of hand position around the target most likely plays a role in adaptation, it is not necessary to induce adaptation.

neuroscience↗

bioRxiv2023

Interactome Analysis of Visceral Adipose Tissue Elucidates Gene Regulatory Networks and Novel Gene Candidates in Obesity

ObjectiveVisceral adiposity is associated with increased proinflammatory activity, insulin resistance, diabetes risk and mortality rate. Numerous individual genes have been associated with obesity, but studies investigating gene-regulatory networks in human visceral obesity are lacking. MethodsWe analyzed gene-regulatory networks in human visceral adipose tissue (VAT) from 48 obese and 11 non-obese Chinese subjects using gene co-expression and network construction with RNA-sequencing data. We also conducted RNA interference-based tests on selected genes for adipocyte differentiation effects. ResultsA scale-free gene co-expression network was constructed from 360 differentially expressed genes between obese and non-obese VAT (absolute log fold-change >1, FDR<0.05) with edge probability >0.8. Gene regulatory network analysis identified candidate transcription factors associated with differentially expressed genes. Fifteen subnetworks (communities) displayed altered connectivity patterns between obese and non-obese networks. Genes in pro-inflammatory pathways showed increased network connectivities in obese VAT whereas the oxidative phosphorylation pathway displayed reduced connections (enrichment FDR<0.05). Functional screening via RNA interference identified SOX30 and OSBPL3 as potential network-derived gene candidates influencing adipocyte differentiation. ConclusionsThis interactome-based approach highlights the network architecture, identifies novel candidate genes, and leads to new hypotheses regarding network-assisted gene regulation in obese vs. non-obese VAT. What is already known about this subject?O_LIVisceral adipose tissue (VAT) is associated with increased levels of proinflammatory activity, insulin resistance, diabetes risk and mortality rate. C_LIO_LIGene expression studies have identified candidate genes associated with proinflammatory function in VAT. C_LI What are the new findings in your manuscript?O_LIUsing integrative network-science, we identified co-expression and gene regulatory networks that are differentially regulated in VAT samples from subjects with and without obesity C_LIO_LIWe used functional testing (adipocyte differentiation) to validate a subset of novel candidate genes with minimal prior reported associations to obesity C_LI How might your results change the direction of research or the focus of clinical practiceO_LINetwork biology-based investigation provides a new avenue to our understanding of gene function in visceral adiposity C_LIO_LIFunctional validation screen allows for the identification of novel gene candidates that may be targeted for the treatment of adipose tissue dysfunction in obesity C_LI

genomics↗

bioRxiv2023

An optimized method for gene knockdown in differentiating human and mouse adipocyte cultures

Adipocyte cultures are a mainstay of metabolic disease research, yet loss-of-function studies in differentiating adipocytes is complicated by the refractoriness of lipid-containing adipocytes to standard siRNA transfections. Alternative methods, such as electroporation or adenovirus/lentivirus-based delivery systems are complex, expensive and often accompanied with unacceptable levels of cell death. To address this problem, we have tested two commercially available siRNA delivery systems in this study using a multi-parameter optimization approach. Our results identified a uniform siRNA transfection protocol that can be applied to human and mouse adipocyte cultures throughout the time course of differentiation, beginning with pre-differentiated cells and continuing up to lipid-accumulated differentiated adipocytes. Our findings allow for efficient transfection of human and mouse adipocyte cultures using standard and readily available methodologies, and should help significantly expand the scope of gene manipulation studies in these cell types.

molecular biology↗

bioRxiv2023

Implicit motor adaptation and perceived hand position without proprioception: A kinesthetic error may be derived from efferent signals

Implicit sensorimotor adaptation keeps our movements well-calibrated amid changes in the body and environment. We have recently postulated that implicit adaptation is driven by a perceptual error: the difference between the desired and perceived movement outcome. According to this perceptual re-alignment model, implicit adaptation ceases when the perceived movement outcome - a multimodal percept determined by a prior belief conveying the intended action, the motor command, and feedback from proprioception and vision - is aligned with the desired movement outcome. Here, we examined the role of proprioception in implicit motor adaptation and perceived movement outcome by examining individuals who lack proprioception. We used a modified visuomotor rotation task designed to isolate implicit adaptation and probe perceived outcome throughout the experiment. Surprisingly, implicit adaptation and perceived outcome were minimally impacted by deafferentation, posing a challenge to the perceptual re-alignment model of implicit adaptation.

neuroscience↗

bioRxiv2019

The influence of kinesthetic motor imagery and effector specificity on the long-latency stretch response

The long-latency \"reflexive\" response (LLR) following an upper-limb mechanical disturbance is generated by neural circuitry shared with voluntary control. This feedback response supports many task-dependent behaviours and permits the expression of goal-directed corrections at latencies shorter than voluntary reaction time. An extensive body of literature has demonstrated that the LLR shows flexibility akin to voluntary control, but it has never been tested whether instruction-dependent LLR changes can also occur in the absence of an overt voluntary response. The present study used kinesthetic motor imagery (Experiment 1) and instructed participants to execute a voluntary response in a non-stretched contralateral muscle (Experiment 2) to explore the relationship between the overt production of a voluntary response and LLR facilitation. Activity in stretched right wrist flexors were compared to standard \"not-intervene\" and \"compensate\" conditions. Our findings revealed that on ~40% of imagery and ~50% of contralateral trials, a partial voluntary response \"leaked-out\" into the stretched right wrist flexor muscle. On these \"leaked\" trials, the early portion of the LLR (R2) was facilitated and displayed a similar increase to compensate trials. The latter half of the LLR (R3) showed further modulation, mirroring the patterns of voluntary response activity. By contrast, the LLR on \"non-leaked\" imagery and contralateral trials did not modulate. We suggest that even though a hastened voluntary response cannot account for all instruction-dependent LLR modulation, the overt execution of a voluntary response in the same muscle(s) as the LLR is a pre-requisite for facilitation of this rapid feedback response.\n\nKey Points SummaryO_LIThe long-latency \"reflexive\" response (LLR) in the upper-limb modulates based on volitional intent.\nC_LIO_LIWe used two novel approaches, kinesthetic motor imagery and execution of a contralateral movement, to examine the relationship between the overt production of a voluntary response and LLR facilitation.\nC_LIO_LIOur findings reveal an indissociable link between LLR facilitation and the appearance of a voluntary response in stretched muscle; specifically, the LLR was only facilitated on imagery or contralateral trials when a voluntary response \"leaked-out\" into the same muscle.\nC_LIO_LIThe first half of the LLR (R2) displayed a general increase on all trials with a voluntary response, while the latter portion (R3) mirrored the patterns of voluntary response activity.\nC_LIO_LIWe suggest that a voluntary response specific to the same muscle (as the LLR) is a pre-requisite for LLR facilitation\nC_LI

neuroscience↗