Biology subjects

Yeung, N.

Publications and source records attributed to Yeung, N..

11 recordsLinked to original sources

bioRxiv2026

Conditions and properties of non-Mendelian transmission of recombinants in female meiosis

In female meiosis, each of the four chromatids in a tetrad has a 25% chance to be selected for transmission through the pronucleus, realizing Mendel's second law. Here, we characterize a cheating but unselfish behaviour that has documented cases across diverse animal taxa including humans and flies, whereby chromatids with crossovers (COs) have a transmission advantage, resulting in increased production of recombinant offspring. Taking advantage of Drosophila ovarian physiology, we show that this form of meiotic cheating which we call recombinant drive occurs on the autosomes when females are under nutrient stress, potentially as a mechanism for recombination plasticity, while curiously, the effect is suppressed on the X by the distributive system. We explored recombinant drive using simulations and identified unique quantitative signatures that are at odds with several intrinsic properties of linkage. One violation is the production of more offspring with recombinant versus parental allele combinations, which we empirically demonstrated to be possible. Further, we show that recombinant drive can appear to modify CO patterning effectively acting as assurance and interference mechanisms, even when it has no influence on and acts downstream of CO spacing. We discuss the potential benefits and consequences of having a conserved method that can rapidly increase recombination in response to stress, and speculate on a mechanism for the preferential transmission of COs at meiosis II. Overall, our study revealed distinct properties and behaviours of a poorly understood, but potentially widespread, conserved phenomenon and offers avenues for broad detection and mechanistic dissection.

genetics↗

bioRxiv2025

A Validated Method for Detection of Bifidobacterium infantis Bi-26™ DNA in Stool by Quantitative Real-Time PCR

BackgroundBifidobacterium longum subspecies infantis (B. infantis) is a commensal bacterium enriched in the microbiota of breastfed infants and associated with beneficial effects on infant gut health. Clinical studies evaluating B. infantis supplementation in infants have reported increased colonization, reduced inflammation, enhanced vaccine responsiveness, and improved growth outcomes. To support rigorous evaluation of these effects in further clinical trials, reliable and validated methods for quantifying B. infantis in stool are needed. MethodsWe validated a quantitative real-time PCR (qPCR) assay against a conserved B. infantis genomic target. Assay performance was evaluated using DNA from the B. infantis strain Bi-26TM, spiked infant stool pools, and matrix controls. Validation parameters included linearity, sensitivity, accuracy, within- and between-run reproducibility, recovery, and matrix interference, with acceptance criteria informed by bioanalytical best practices. ResultsThe assay demonstrated robust performance across validation parameters. Linearity was confirmed over at least six orders of magnitude (R2 > 0.99; mean efficiency 96.4%), with a lower limit of quantification of 37.36 genome equivalents / reaction. Analytical sensitivity was high, with a 95% limit of detection of 4.67 genome equivalents / reaction. Accuracy across multiple stool pools met acceptance criteria, with mean deviation from nominal values of 0.39 log10. Reproducibility was strong, with within-run variability of 0.37% and between-run variability of 1.78%. Recovery averaged 41.3%, exceeding the predefined minimum threshold, and matrix interference was minimal. ConclusionsThis study reports a validated qPCR assay suitable for quantifying B. infantis Bi-26 DNA in stool samples collected in stabilized formats. Its robust analytical performance supports its use in clinical and translational research evaluating B. infantis colonization and its health impacts in early infant life.

microbiology↗

bioRxiv2025

Growth Arrest of Thoracic Aortic Aneurysms in Aging Marfan Mice

There is a pressing need to identify pathologic mechanisms that render a thoracic aortic aneurysm susceptible to continued enlargement, dissection, or rupture, but additional insight can be gleaned by understanding potential compensatory mechanisms that prevent disease progression and thereby stabilize a lesion. Our biomechanical data suggest that the ascending aorta within a common mouse model of Marfan syndrome, Fbn1C1041G/+, exhibits progressive disease from 12 weeks to 1 year of age, but near growth arrest from 1 to 2 years of age. Comparison of the biomechanical phenotype, histological characteristics, proteomic signature, and transcriptional profile from 12 weeks to 1 year to 2 years suggests that numerous differentially expressed genes (including downregulated Ilk, Ltbp3, and Rictor) and associated proteins may contribute to late-term growth arrest. There is also a conspicuous absence of proteins associated with inflammation from 1 to 2 years of age. Although there is a need to understand better the interconnected roles of temporal changes in differential gene expression and protein abundance, reducing mTOR signaling and reducing excessive inflammation appears to merit increased attention in preventing continued aneurysmal expansion in Marfan syndrome.

bioengineering↗

bioRxiv2025

Postnatal Pulmonary Artery Development from Transcript to Tissue

Many congenital conditions and surgical interventions perturb the hemodynamics experienced by proximal pulmonary arteries during early postnatal development, thus leading to differential gene expression and associated changes in vascular structure and function. Among these, pathologic conditions include patent ductus arteriosus, pulmonary atresia and stenosis, and hypoxemia-induced pulmonary hypertension while surgical interventions include the placement of a Blalock-Taussig shunt as well as Glenn, Fontan, and Norwood procedures. Despite the significant morbidity associated with these diverse conditions, there has been little attention directed towards understanding natural postnatal development of pulmonary arteries from both biological and mechanical perspectives. With-out such information, we cannot truly understand the phenotype of the affected pulmonary artery, which is fundamental to improving diagnosis, treatment, and prognosis. In this paper, we present novel data from wild-type mice that document normal postnatal changes in select gene expression, vascular wall composition, and biomechanical properties of proximal pulmonary arteries. These findings enabled the establishment of a novel, data-informed computational model of pulmonary artery development capable of simulating outcomes in response to perturbations in the pulmonary artery hemodynamic environment.

bioengineering↗

bioRxiv2024

An automatic domain-general error signal is shared across tasks and predicts confidence in different sensory modalities

Understanding the ability to self-evaluate decisions is an active area of research. This research has primarily focused on the neural correlates of self-evaluation during visual-tasks, and whether pre- or post-decisional neural correlates capture subjective confidence in that decision. This focus has been useful, yet also precludes an investigation of key every-day features of metacognitive self-evaluation: that decisions are rapid, must be evaluated without explicit feedback, and unfold in a multisensory world. These considerations lead us to hypothesise that an automatic domain-general metacognitive signal may be shared between sensory modalities, which we tested in the present study with multivariate decoding of electroencephalographic (EEG) data. Participants (N=21, 12 female) first performed a visual task with no request for self-evaluations of performance, prior to an auditory task that included rating decision confidence on each trial. A multivariate classifier trained to predict errors in the speeded visual-task generalised to predict errors in the subsequent non-speeded auditory discrimination. This generalisation was unique to classifiers trained on the visual response-locked data, and further predicted subjective confidence on the subsequent auditory task. This evidence of overlapping neural activity across the two tasks provides evidence for automatic encoding of confidence independent of any explicit request for metacognitive reports, and a shared basis for metacognitive evaluations across sensory modalities.

neuroscience↗

bioRxiv2022

Role of human HSPE1 for OPA1 processing independent of HSPD1

The mtHSP60/HSPD1-mtHSP10/HSPE1 system prevents protein misfolding and maintains proteostasis in the mitochondrial matrix. Altered activities of this chaperonin system have been implicated in human diseases, such as cancer and neurodegeneration. However, how defects in HSPD1 and HSPE1 affect mitochondrial structure and dynamics remains elusive. In the current study, we address this fundamental question in a human cell line, HEK293T. We found that the depletion of HSPD1 or HSPE1 results in fragmentation of mitochondria, suggesting a decrease in mitochondrial fusion. Supporting this notion, HSPE1 depletion led to proteolytic inactivation of OPA1, a dynamin-related GTPase that fuses the mitochondrial membrane. This OPA1 inactivation was mediated by a stress-activated metalloprotease, OMA1. In contrast, HSPD1 depletion did not induce OMA1 activation or OPA1 cleavage. These data suggest that HSPE1 controls mitochondrial morphology through a mechanism separate from its chaperonin activity.

cell biology↗

bioRxiv2021

Alpha power and stimulus-evoked activity dissociate metacognitive reports of attention, visibility and confidence in a visual detection task

Variability in the detection and discrimination of weak visual stimuli has been linked to oscillatory neural activity. In particular, the amplitude of activity in the alpha-band (8-12 Hz) has been shown to impact upon the objective likelihood of stimulus detection, as well as measures of subjective visibility, attention, and decision confidence. We aimed to clarify how preparatory alpha influences performance and phenomenology, by recording simultaneous subjective measures of attention and confidence (Experiment 1), or attention and visibility (Experiment 2) on a trial-by-trial basis in a visual detection task. Across both experiments, alpha amplitude was negatively and linearly correlated with the intensity of subjective attention. In contrast to this linear relationship, we observed a quadratic relationship between the strength of alpha oscillations and subjective ratings of confidence and visibility. We find that this same quadratic relationship links alpha amplitude to the strength of stimulus evoked responses. Visibility and confidence judgements corresponded to the strength of evoked responses, but confidence, uniquely, incorporated information about attentional state. As such, our findings reveal distinct psychological and neural correlates of metacognitive judgements of attentional state, stimulus visibility, and decision confidence.

neuroscience↗

bioRxiv2020

Bayesian confidence for drift diffusion observers in dynamic stimuli tasks

We introduce a new approach to modelling decision confidence, with the aim of enabling computationally cheap predictions while taking into account, and thereby exploiting, trial-by-trial variability in dynamic stimuli. Using the framework of the drift diffusion model of decision making, along with time-dependent thresholds and the idea of a Bayesian confidence readout, we derive expressions for the probability distribution over confidence reports. In line with current models of confidence, the derivations allow for the accumulation of "pipeline" evidence that has been received but not processed by the time of response, the effect of drift rate variability, and metacognitive noise. The expressions are valid for stimuli that change over the course of a trial with normally-distributed fluctuations in the evidence they provide. A number of approximations are made to arrive at the final expressions, and we test all approximations via simulation. The derived expressions contain only a small number of standard functions, and require evaluating only once per trial, making trial-by-trial modelling of confidence data in dynamic stimuli tasks more feasible. We conclude by using the expressions to gain insight into the confidence of optimal observers, and empirically observed patterns.

animal behavior and cognition↗

bioRxiv2018

I knew that! Confidence in outcome prediction and its impact on feedback processing and learning

Influential theories emphasize the importance of predictions in learning: we learn from feedback to the extent that it is surprising, and thus conveys new information. Here we explore the hypothesis that surprise depends not only on comparing current events to past experience, but also on online evaluation of performance via internal monitoring. Specifically, we propose that people leverage insights from response-based performance monitoring - outcome predictions and confidence - to control learning from feedback. In line with predictions from a Bayesian inference model, we find that people who are better at calibrating their confidence to the precision of their outcome predictions learn more quickly. Further in line with our proposal, EEG signatures of feedback processing are sensitive to the accuracy of, and confidence in, post-response outcome predictions. Taken together, our results suggest that online predictions and confidence serve to calibrate neural error signals to improve the efficiency of learning.

neuroscience↗

bioRxiv2018

A post-decisional neural marker of confidence predicts information-seeking

Theoretical work predicts that decisions made with low confidence should lead to increased information-seeking. This is an adaptive strategy because it can increase the quality of a decision, and previous behavioral work has shown that decision-makers engage in such confidence-driven information seeking. The present study aimed to characterize the neural markers that mediate the relationship between confidence and information-seeking. A paradigm was used in which human participants made an initial perceptual decision, and then decided whether or not they wanted to sample more evidence before committing to a final decision and confidence judgment. Pre-decisional and post-decisional ERP components were similarly modulated by the level of confidence and by information-seeking choices. Time-resolved multivariate decoding of scalp EEG signals first revealed that information-seeking choices could be decoded from the time of the initial decision to the time of the subsequent information-seeking choice (within-condition decoding). No above-chance decoding was visible in the pre-response time window. Crucially, a classifier trained to decode high versus low confidence predicted information-seeking choices after the initial perceptual decision (across-condition decoding). This time window corresponds to that of a post-decisional neural marker of confidence. Collectively, our findings demonstrate for the first time that neural indices of confidence are functionally involved in information-seeking decisions.

neuroscience↗

bioRxiv2018

Identification of a post-transcriptional regulatory element that responds to glucose in the African trypanosome

The ability to adapt to varying nutrient availability in changing environments is critical for successful parasitism. The lifecycle stages of the African trypanosome, Trypanosoma brucei, that infect the host mammalian bloodstream utilize glucose exclusively for ATP production. The finding that trypanosomes also inhabit other tissues that frequently contain lower glucose concentrations suggests blood stage parasites may have to respond to a dynamic environment with changing nutrient availability in order to survive. However, little is known about how the parasites coordinate gene expression with nutrient availability. Through transcriptome analysis, we have found blood stage parasites deprived of glucose alter gene expression in a pattern similar to transcriptome changes triggered by other stresses. A surprisingly low concentration of glucose (<10 M) was required to initiate the response. To further understand the dynamic regulation of gene expression that occurs in response to altered glucose availability in the environment, we have interrogated the 3UTR of cytochrome c oxidase subunit VI, a known lifecycle stage regulated gene, and have identified a stem-loop structure that confers glucose-responsive regulation at the translational level.

genetics↗