Biology subjects

Constant, M.

Publications and source records attributed to Constant, M..

4 recordsLinked to original sources

bioRxiv2025

Epithelial miR-149-5p up-regulation is associated with immune evasion in progressive bronchial premalignant lesions

The molecular drivers bronchial premalignant lesion progression to invasive lung squamous cell carcinoma are not well defined. Prior work profiling longitudinally collected bronchial premalignant lesion biopsies by RNA sequencing defined a proliferative subtype, enriched with bronchial dysplasia. We found that a gene co-expression module associated with interferon gamma signaling and antigen processing/presentation was down-regulated in progressive/persistent versus regressive lesions within the proliferative subtype, suggesting a functional impact of these genes on immune evasion. RNA from these same premalignant lesions was profiled by microRNA (miRNA) sequencing and a miRNA-gene network analysis identified hsa-miR-149-5p as a potential regulator of this antigen presentation gene co-expression module associated with lesion progression. hsa-miR-149-5p was found to be predominantly expressed in the epithelium and up-regulated in progressive/persistent versus regressive proliferative lesions while targets of this miRNA, the transcriptional coactivator of MHC-I gene expression, NLRC5, and the genes it regulates were down-regulated. MicroRNA in situ hybridization of hsa-miR-149-5p in tissue from adjacent fixed biopsies showed that hsa-miR-149-5p was increased in areas of bronchial dysplasia in progressive/persistent versus regressive lesions. Imaging mass cytometry showed that NLRC5 protein expression was decreased in progressive/persistent versus regressive lesions within areas of hyperplasia, metaplasia, and dysplasia. Additionally, basal cells with high versus low levels of NLRC5 were found to be in close spatial proximity to CD8 T cells, suggesting that these cells exhibit increased functional MHC-I gene expression in lesions with low hsa-miR-149-5p expression. Collectively, our data suggests a functional role for hsa-miR-149-5p in bronchial premalignant lesions and may serve as a therapeutic target for PML immunomodulation. STATEMENT OF SIGNIFICANCEIntegrative analysis across bronchial premalignant lesions has identified and localized a potential regulator of immune evasion in progressive/persistent lesions that could be a novel therapeutic target.

cancer biology↗

bioRxiv2024

Long-term perceptual priors drive confidence bias which favors prior-congruent evidence

According to the Bayesian framework, both our perceptual decisions and confidence about those decisions are based on the precision-weighted integration of prior expectations and incoming sensory information. While it is generally assumed that priors influence both decisions and confidence in the same way, previous work has found priors to have a stronger impact at the confidence level, challenging this assumption. However, these patterns were found for high-level probabilistic expectations that are flexibly induced in the task context. It remains unclear whether this generalizes to low-level perceptual priors that are naturally formed through long term exposure. Here we investigated human participants confidence in decisions made under the influence of a long-term perceptual prior: the slow-motion prior. Participants viewed tilted moving-line stimuli for which the slow-motion prior biases the perceived motion direction. On each trial, they made two consecutive motion direction decisions followed by a confidence decision. We contrasted two conditions - one in which the prior impacted discrimination performance, and one in which it did not. We found a confidence bias favoring the condition in which the prior influenced discrimination decisions, even after accounting for performance differences. Computational modeling revealed this effect to be best explained by confidence using the prior-congruent evidence as an additional cue, beyond the posterior evidence used in the perceptual decision. This is in agreement with a confirmatory confidence bias favoring evidence congruent with low-level perceptual priors, revealing that, in line with high-level expectations, even long-term priors have a greater influence on the metacognitive level than on perceptual decisions. Author SummaryPrior expectations play a critical role in shaping not only the perceptual inferences that we make, but also how confident we feel about those inferences. Bayesian confidence models capture that role, but assume priors to influence both decisions and confidence in the same way. Against this assumption, previous work has found dissociations in the influence of priors on decisions and confidence. However, that work has focussed only on high-level probabilistic priors, rather than the low-level perceptual priors that constrain our processing across many naturalistic situations. Here, we examine whether such dissociations arise under the influence of a low-level perceptual prior that naturally affects humans perception of motion, namely, the expectation that objects move slowly. We reveal evidence for such a dissociation: prior-congruent evidence impacts confidence to a greater extent than perceptual decisions. This suggests the existence of an implicit confidence bias favoring information that confirms prior beliefs, even in the case of long-term perceptual priors.

neuroscience↗

bioRxiv2022

Prior information differentially affects discrimination decisions and subjective confidence reports

According to Bayesian models, both decisions and confidence are based on the same precision-weighted integration of prior expectations ("priors") and incoming information ("likelihoods"). This assumes that priors are integrated optimally and equally in decisions and confidence, which has not been tested. In two experiments, we quantitatively assessed how priors inform both decisions and confidence. With a gamified dual-decision task we controlled the strength of priors and likelihoods to create pairs of conditions that were matched in posterior information, but differed on whether the prior or likelihood was more informative. We found that priors were underweighted in discrimination decisions, but used to a greater extent in confidence about those decisions, and this was not due to differences in processing time. With a Bayesian model we quantified the weighting parameters for the prior at both levels, and confirmed that priors are more optimally used in explicit confidence, even when underused in decisions.

neuroscience↗

bioRxiv2021

Judgments of agency are affected by sensory noise without recruiting metacognitive processing

Judgments of agency, our sense of control over our actions and the environment, often occur in noisy conditions. We examined the computations underlying judgments of agency, in particular under the influence of sensory noise. Building on previous literature, we studied whether judgments of agency incorporate uncertainty in the same way that confidence judgments do, which would imply that the former share computational mechanisms with metacognitive judgments. In two tasks, participants rated agency, or confidence in a decision about their agency, over a virtual hand that tracked their movements, either synchronously or with a delay and either under high or low noise. We compared the predictions of two computational models to participants ratings and found that agency ratings, unlike confidence, were best explained by a model involving no estimates of sensory noise. We propose that agency judgments reflect first-order measures of the internal signal, without involving metacognitive computations, challenging the assumed link between the two cognitive processes.

neuroscience↗