Biology subjects

Ngo, T. T.

Publications and source records attributed to Ngo, T. T..

12 recordsLinked to original sources

bioRxiv2025

Deliberation is a controllable process governed by desirability and cognitive effort

Humans spend a lifetime making decisions based on incoming sensory information and goals. Prominent theories of perceptual decision-making have described the components of deliber-ation process, yet they lack a unifying principle that governs how the nervous system tunes the deliberation process across multiple contexts. Desirability (reward) and effort (energy) are major determinants in governing a broad range of human and animal behaviour, such as for-aging, walking, and decisions. Here we develop a theory where desirability and cognitive effort tune the control gains that govern deliberation. Several hallmark features of decision behaviour simply emerge from the model, with the deliberation process closely resembling low-dimensional neural dynamics. We also predict and provide a novel mechanistic explanation for choking-under-pressure, where extremely large rewards lead to performance deficits. Our principled framework explains both behavioural and neural phenomena while providing a path to unify disparate fields.

neuroscience↗

bioRxiv2025

Loss of cell cycle gatekeeping by 1 CNOT3 impairs hematopoietic stem and progenitor cell division and repopulating activity

Adult mammalian hematopoietic stem cells (HSCs) constitute a heterogeneous population responsible for generating various cell types in the blood throughout adulthood. Gene expression programs underlying regulation of self-renewal and differentiation of HSCs are tightly regulated. However, how post-transcriptional regulation of gene expression influences HSCs and hematopoiesis remains largely unexplored. Here, we report the critical role of CNOT3, a subunit of the CCR4-NOT complex, in regulating hematopoietic stem cells (HSCs) function in adult hematopoiesis. We observed that Cnot3 mRNA is highly expressed in HSCs and CNOT3 ablation in the murine Cnot3 conditional knockout mouse model resulted in anemia, reduced bone marrow cellularity and enhanced extramedullary hematopoiesis in spleen. Deletion of Cnot3 resulted in the early expansion of immunophenotypic HSCs which were then progressively lost over time. Cnot3 knockout hematopoietic stem/progenitor cells (HSPCs) failed to reconstitute hematopoietic systems of recipient animals in transplantation assays. Single-cell RNA sequencing (scRNA-seq) analysis of HSPCs revealed disruptions in lineage development and loss of HSCs. Transcriptomic profiling and cell cycle analysis demonstrated that Cnot3 deletion led to increased cycling activity in HSCs. Our results indicate that CNOT3 is critical for maintenance of homeostasis in HSCs and the hematopoietic system.

developmental biology↗

bioRxiv2025

Involuntary feedback responses reflect a representation of partner actions

We have a remarkable ability to seamlessly and rapidly coordinate actions with others, from double dutch to dancing. Humans use high-level partner representations to jointly control voluntary actions, while other work shows lower-level involuntary feedback responses to sudden visual perturbations. Yet, it is unknown if a high-level partner representation can be rapidly expressed through lower-level involuntary sensorimotor circuitry. Here we test the idea that a partner representation influences involuntary visuomotor feedback responses during a cooperative sensorimotor task. Using two experiments and dynamic game theory predictions, we show that involuntary visuomotor feedback responses reflect a partner representation and consideration of a partners movement cost (i.e., accuracy and energy). Collectively, our results suggest there is top-down modulation from high-level partner representations to lower-level sensorimotor circuits, enabling fast and flexible feedback responses during jointly coordinated actions. Significance StatementHumans have an adept ability to rapidly coordinate their movements with others. Yet it is unknown how fast the sensorimotor system can use a representation of others to jointly control movement. Remarkably, intelligent reflexes (i.e., involuntary visuomotor feedback responses) consider high-level partner representations within 180 - 230 ms. Further, these involuntary visuomotor feedback responses show that the sensorimotor system is willing sacrifice energy to help a partner.

neuroscience↗

bioRxiv2024

Alternatives to Friction Coefficient: Fine Touch Perception Relies on Frictional Instabilities

Fine touch perception is often correlated to material properties and friction coefficients, but the inherent variability of human motion has led to low correlations and contradictory findings. Instead, we hypothesized that humans use frictional instabilities to discriminate between objects. Here, we constructed a set of coated surfaces with minimal physical differences, but due to differences in surface chemistry, generated different types of instabilities depending on how quickly a finger is slid and pressed during sliding. In one experiment, we used a mechanical mock finger to quantify and classify differences in instability formation from different coated surfaces. In a second experiment, participants perform a discrimination task using the same coated surfaces. Using the data from these two experiments, we found that human discrimination response times were faster with surfaces where the mock finger produced more stiction spikes and discrimination accuracy was higher where the mock finger produced more steady sliding. Conversely, traditional metrics like surface roughness or average friction coefficient did not relate to tactile discriminability. In fact, the typical method of averaging friction coefficients led to a spurious correlation which erroneously suggests that distinct objects should feel identical and identical objects should feel distinct--similar to findings by others. Friction instabilities may offer a more predictive and tractable framework of fine touch perception than friction coefficients, which would accelerate the design of tactile interfaces.

neuroscience↗

bioRxiv2024

Online movements reflect ongoing deliberation

From navigating a crowded hallway to skiing down a treacherous hill, humans are constantly making decisions while moving. Insightful past work has provided a glimpse of decision deliberation at the moment of movement onset. Yet it is unknown whether ongoing deliberation can be expressed during movement, following movement onset and prior to any decision. Here we tested the idea that an ongoing deliberation continually influences motor processes--prior to a decision--directing online movements. Over three experiments, we manipulated evidence to influence deliberation during movement. The deliberation process was manipulated by having participants observe evidence in the form of tokens that moved into a left or right target. Supporting our hypothesis we found that lateral hand movements reflected deliberation, prior to a decision. We also found that a deliberation urgency signal, which more heavily weighs later evidence, was fundamental to predicting decisions and explains past movement behaviour in a new light. Our paradigm promotes the expression of ongoing deliberation through movement, providing a powerful new window into understanding the interplay between decision and action.

neuroscience↗

bioRxiv2023

Shh from mossy cells contributes to preventing NSC pool depletion after seizure-induced neurogenesis and in aging

Epileptic seizures induce aberrant neurogenesis from resident neural stem cells (NSCs) in the dentate gyrus of the adult mouse hippocampus, which has been implicated in depletion of the NSC pool and impairment of hippocampal function. However, the mechanisms regulating neurogenesis after seizures remain unknown. Here we demonstrate that Shh from mossy cells is a major source of Shh signaling activity after seizures, by which mossy cells contribute to seizure-induced neurogenesis and maintenance of the NSC pool. Deletion of Shh from mossy cells attenuates seizure-induced neurogenesis. Moreover, in the absence of Shh from mossy cells, NSCs pool are prematurely depleted after seizure-induced proliferation, and NSCs have impaired self-renewal. Likewise, lack of Shh from mossy cells accelerates age-related decline of the NSC pool with accompanying reduction of self-renewal of NSCs outside the context of pathology such as seizures. Together, our findings indicate that Shh from mossy cells is critical to maintain NSCs and to prevent exhaustion from excessive consumption in aging and after seizures.

neuroscience↗

bioRxiv2022

Sentinel Cards Provide Practical SARS-CoV-2 Monitoring in School Settings

Accurate, high-resolution environmental monitoring of SARS-CoV-2 traces indoors through sentinel cards is a promising approach to help students safely return to in-person learning. Because SARS-CoV-2 RNA can persist for up to a week on several indoor surface types, there is a need for increased temporal resolution to determine whether consecutive surface positives arise from new infection events or continue to report past events. Cleaning sentinel cards after sampling would provide the needed resolution, but might interfere with assay performance. We tested the effect of three cleaning solutions (BZK wipes, wet wipes, RNase Away) at three different viral loads: "high" (4 x 104 GE/mL), "medium" (1 x 104 GE/mL), and "low" (2.5 x 103 GE/mL). RNAse Away, chosen as a positive control, was the most effective cleaning solution on all three viral loads. Wet wipes were found to be more effective than BZK wipes in the medium viral load condition. The low viral load condition was easily reset with all three cleaning solutions. These findings will enable temporal SARS-CoV-2 monitoring in indoor environments where transmission risk of the virus is high and the need to avoid individual-level sampling for privacy or compliance reasons exists. ImportanceBecause SARS-CoV-2, the virus that causes COVID-19, persists on surfaces, testing swabs taken from surfaces is useful as a monitoring tool. This approach is especially valuable in school settings, where there are cost and privacy concerns that are eliminated by taking a single sample from a classroom. However, the virus persists for days to weeks on surface samples, so it is impossible to tell whether positive detection events on consecutive days are persistent signal or new infectious cases, and therefore whether the positive individuals have been successfully removed from the classroom. We compare several methods for cleaning "sentinel cards" to show that this approach can be used to identify new SARS-CoV-2 signals day to day. The results are important for determining how to monitor classrooms and other indoor environments for SARS-CoV-2 virus.

bioinformatics↗

bioRxiv2021

Comparison of heat-inactivated and infectious SARS-CoV-2 across indoor surface materials shows comparable RT-qPCR viral signal intensity and persistence

Environmental monitoring in public spaces can be used to identify surfaces contaminated by persons with COVID-19 and inform appropriate infection mitigation responses. Research groups have reported detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) on surfaces days or weeks after the virus has been deposited, making it difficult to estimate when an infected individual may have shed virus onto a SARS-CoV-2 positive surface, which in turn complicates the process of establishing effective quarantine measures. In this study, we determined that reverse transcription-quantitative polymerase chain reaction (RT-qPCR) detection of viral RNA from heat-inactivated particles experiences minimal decay over seven days of monitoring on eight out of nine surfaces tested. The properties of the studied surfaces result in RT-qPCR signatures that can be segregated into two material categories, rough and smooth, where smooth surfaces have a lower limit of detection. RT-qPCR signal intensity (average quantification cycle (Cq)) can be correlated to surface viral load using only one linear regression model per material category. The same experiment was performed with infectious viral particles on one surface from each category, with essentially identical results. The stability of RT-qPCR viral signal demonstrates the need to clean monitored surfaces after sampling to establish temporal resolution. Additionally, these findings can be used to minimize the number of materials and time points tested and allow for the use of heat-inactivated viral particles when optimizing environmental monitoring methods. ImportanceEnvironmental monitoring is an important tool for public health surveillance, particularly in settings with low rates of diagnostic testing. Time between sampling public environments, such as hospitals or schools, and notifying stakeholders of the results should be minimal, allowing decisions to be made towards containing outbreaks of coronavirus disease 2019 (COVID-19). The Safer At School Early Alert program (SASEA) [1], a large-scale environmental monitoring effort in elementary school and child care settings, has processed > 13,000 surface samples for SARS-CoV-2, detecting viral signals from 574 samples. However, consecutive detection events necessitated the present study to establish appropriate response practices around persistent viral signals on classroom surfaces. Other research groups and clinical labs developing environmental monitoring methods may need to establish their own correlation between RT - qPCR results and viral load, but this work provides evidence justifying simplified experimental designs, like reduced testing materials and the use of heat-inactivated viral particles.

microbiology↗

bioRxiv2020

Inter-species variation in number of bristles on forewings of tiny insects does not impact clap-and-fling aerodynamics

Flight-capable miniature insects of body length (BL) < 2 mm typically possess wings with long bristles on the fringes. Though their flight is challenged by needing to overcome significant viscous resistance at chord-based Reynolds number (Rec) on the order of 10, these insects use clap-and-fling mechanism coupled with bristled wings for lift augmentation and drag reduction. However, inter-species variation in the number of bristles (n) and inter-bristle gap (G) to bristle diameter (D) ratio (G/D) and their effects on clap-and-fling aerodynamics remain unknown. Forewing image analyses of 16 species of thrips and 21 species of fairyflies showed that n and maximum wing span were both positively correlated with BL. We conducted aerodynamic force measurements and flow visualization on simplified physical models of bristled wing pairs that were prescribed to execute clap-and-fling kinematics at Rec=10 using a dynamically scaled robotic platform. 23 bristled wing pairs were tested to examine the isolated effects of changing dimensional (G, D, span) and non-dimensional (n, G/D) geometric variables on dimensionless lift and drag. Within biologically observed ranges of n and G/D, we found that: (a) increasing G provided more drag reduction than decreasing D; (b) changing n had minimal impact on lift generation; and (c) varying G/D produced minimal changes in aerodynamic forces. Taken together with the broad variation in n (32-161) across the species considered here, the lack of impact of changing n on lift generation suggests that tiny insects may experience reduced biological pressure to functionally optimize n for a given wing span. SUMMARY STATEMENTIntegrating morphological analysis of bristled wings seen in miniature insects with physical model experiments, we find that aerodynamic forces are unaffected across the broad biological variation in number of bristles.

bioengineering↗

bioRxiv2020

Measuring DNA mechanics on the genome scale

Mechanical deformations of DNA such as bending are ubiquitous and implicated in diverse cellular functions1. However, the lack of high-throughput tools to directly measure the mechanical properties of DNA limits our understanding of whether and how DNA sequences modulate DNA mechanics and associated chromatin transactions genome-wide. We developed an assay called loop-seq to measure the intrinsic cyclizability of DNA - a proxy for DNA bendability - in high throughput. We measured the intrinsic cyclizabilities of 270,806 50 bp DNA fragments that span the entire length of S. cerevisiae chromosome V and other genomic regions, and also include random sequences. We discovered sequence-encoded regions of unusually low bendability upstream of Transcription Start Sites (TSSs). These regions disfavor the sharp DNA bending required for nucleosome formation and are co-centric with known Nucleosome Depleted Regions (NDRs). We show biochemically that low bendability of linker DNA located about 40 bp away from a nucleosome edge inhibits nucleosome sliding into the linker by the chromatin remodeler INO80. The observation explains how INO80 can create promoter-proximal nucleosomal arrays in the absence of any other factors2 by reading the DNA mechanical landscape. We show that chromosome wide, nucleosomes are characterized by high DNA bendability near dyads and low bendability near the linkers. This contrast increases for nucleosomes deeper into gene bodies, suggesting that DNA mechanics plays a previously unappreciated role in organizing nucleosomes far from the TSS, where nucleosome remodelers predominate. Importantly, random substitution of synonymous codons does not preserve this contrast, suggesting that the evolution of codon choice has been impacted by selective pressure to preserve sequence-encoded mechanical modulations along genes. We also provide evidence that transcription through the TSS-proximal nucleosomes is impacted by local DNA mechanics. Overall, this first genome-scale map of DNA mechanics hints at a mechanical code with broad functional implications.

biophysics↗

bioRxiv2020

Genetic, lifestyle and environmental risk factors for chronic pain revealed through GWAS

Chronic pain (CP) is a leading cause of disability worldwide with complex aetiologies that remain elusive. Here we addressed this issue by performing a GWAS on a large UK Biobank sample (N=188,352 cases & N=69,627 controls) which identified two independent loci associated with CP near ADAMTS6 and LEMD2. Gene-based tests revealed additional CP-associated genes (DCAKD, NMT1, MLN, IP6K3). Across 1328 complex traits, 548 (41%) were genetically correlated with CP, of which 175 (13%) showed genetic causal relationships using the latent causal variable approach and Mendelian randomization. In particular, major depressive disorder, anxiety, smoking, body fat & BMI were found to increase the risk of CP, whereas diet, walking for pleasure & higher educational attainment were associated with a reduced risk (i.e., protective effect). This data-driven hypothesis-free approach has uncovered several specific risk factors that warrant further examination in longitudinal trials to help deliver effective early screening & management strategies for CP.

genetics↗

bioRxiv2017

A Noninvasive Molecular Clock for Fetal Development Predicts Gestational Age and Preterm Delivery

We performed a high time-resolution, longitudinal study of normal pregnancy development by measuring cell-free RNA (cfRNA) in blood from women during each week of pregnancy. Analysis of tissue-specific transcripts in these samples enabled us to follow fetal and placental development with high resolution and sensitivity, and also to detect gene-specific responses of the maternal immune system to pregnancy. We established a \"clock\" for normal pregnancy development and enabled a direct molecular approach to determine expected delivery dates with comparable accuracy to ultrasound, creating the basis for a portable, inexpensive fetal dating method. We also identified a related gene set that accurately discriminated women at risk for spontaneous preterm delivery up to two months in advance of labor, forming the basis of a potential screening test for risk of preterm delivery.

bioengineering↗