Biology subjects

Truong, V. H.

Publications and source records attributed to Truong, V. H..

6 recordsLinked to original sources

bioRxiv2026

A two-oscillator SCN model with period adaptation and systemic feedback captures photoperiod and T-cycle aftereffects in vivo and in explants

Light history leaves persistent changes in circadian period, but where this history is stored remains unresolved. Suprachiasmatic nucleus (SCN) network models have often approached photoperiodic encoding through phase organization or coupling strength. We computationally tested slow adaptation of subregion-specific intrinsic periods as an alternative memory mechanism. The model asymmetrically couples dorsal (D) and ventral (V) SCN oscillators and adds a systemic oscillator (X) representing putative circadian feedback present in vivo but lost ex vivo. With a single parameter set, period adaptation captured the direction and approximate magnitude of behavioral aftereffects across photoperiod and T-cycle conditions. Adapting coupling strength instead of period failed to reproduce the V-leading-D phase order reported after T22. Removing systemic feedback preserved the photoperiod-dependent period ordering but inverted the T22 and T26 aftereffects, an inversion that matched SCN explant observations. The model also yielded distinct D-V phase organization for each of 18:6 LD, T23, and T25. These results suggest that subregion-specific period plasticity provides a parsimonious substrate for encoding light history, while the dependence on systemic feedback indicates that behavioral period may not be a readout of the SCN alone. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=160 SRC="FIGDIR/small/743784v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@d48266org.highwire.dtl.DTLVardef@1bd15bdorg.highwire.dtl.DTLVardef@de3d9forg.highwire.dtl.DTLVardef@9fbc39_HPS_FORMAT_FIGEXP M_FIG C_FIG A model with dorsal period adaptation and phenomenological systemic feedback accounts for behavioral and explanted SCN aftereffects. (A) During T22 entrainment, dorsal (D), ventral (V), and systemic (X) oscillators remain phase-locked. After release into constant darkness, systemic coupling maintains a unified in vivo rhythm, whereas removing X feedback in the explant simulation allows the D-V network to express a distinct ex vivo period aftereffect. (B) The SCN model is modeled as an asymmetrically coupled attractive-repulsive oscillator network with stronger photic input to V. Light history is encoded via plasticity of the intrinsic period in D, while X represents putative systemic circadian feedback available in vivo and lacking direct photic input. (C) The model reproduces concordant period changes in behavior and SCN explants across photoperiods, but opposing period changes following T-cycle entrainment.

neuroscience↗

bioRxiv2026

Chronotype asymmetry arises from stochastic sleep homeostasis under circadian entrainment

Study ObjectivesChronotype, typically defined by the mid-sleep phase on free days, is often interpreted as a direct proxy for circadian phase. However, a fundamental paradox challenges this assumption: worldwide chronotype distributions show a heavy right skew, whereas circadian period distributions show a slight left skew. We investigated whether fast, noisy cortical processes in homeostatic sleep pressure dynamics could resolve this paradox. MethodsDrawing upon the classical two-process model of sleep regulation, we simulated how interindividual differences in sleep homeostasis (Process S), combined with realistic circadian period distributions (Process C), interact to shape chronotype variability. We introduce stochasticity into sleep pressure build-up to test whether homeostatic variance generates the empirically observed right-skew in chronotype distributions. ResultsExploring the parameter space reveals that stable sleep-wake cycles are constrained within physiological limits of entrainment in an Arnold tongue-like structure. While our simulations confirm a general positive correlation between intrinsic period and chronotype, the heavy right tail of the chronotype distribution arises from interindividual variability in homeostatic sleep dynamics operating near the unstable boundaries of entrainment. This mechanism preserves the individual-level correlation but inverts the population-level skew from left to right. ConclusionsBehavioral chronotype emerges from the nonlinear interaction between fluctuating homeostatic sleep pressure and a hierarchically entrained circadian system. We caution against inferring the intrinsic circadian period solely from chronotype, particularly in clinical contexts where accurate assessment of circadian rhythmicity is critical for targeted therapies.

biophysics↗

bioRxiv2025

Differential Effects of Sex and Age on Daily and Infradian Rhythms of Mice Running Title: Sex and Age Differences in Mouse Rhythms

Intrinsic biological rhythms regulate key physiological and behavioural processes, yet the influence of sex and age on these rhythms is not fully understood. We comprehensively examined 24-hour (circadian) and >24-hour (infradian; 5-day and 10-day) rhythms in wheel-running and ingestive behaviours in single-housed young and middle-aged male and female mice. Circadian analysis revealed that middle-aged mice, particularly females, exhibited more precise daily rhythms and shifted a greater proportion of activity and feeding to the lights-on phase compared to young female mice. Middle-aged animals also ran for longer durations per day, suggesting age-related changes in activity regulation. Analysis of infradian rhythms further highlighted sex- and age-specific differences. Young female mice displayed robust 5-day rhythms in wheel-running activity, which were absent in middle-aged females. In contrast, few males (young or middle-aged) showed significant 5-day rhythms. Ten-day rhythms were most prominent in male mice, while females rarely expressed this periodicity. Physiologically, middle-aged mice lost more body weight in response to single housing, with middle-aged females being most affected. Interactions among behavioural rhythms in females also showed greater complexity, which increased with age. These findings reveal distinct sex- and age-dependent patterns in circadian and infradian rhythms as well as in physiological responses to isolation. Our work highlights the need to account for sex and age in chronobiological research, with broader implications for understanding vulnerability to age-related metabolic and behavioural disorders.

animal behavior and cognition↗

bioRxiv2025

Choroid Plexus Hosts the Earliest Detectable Circadian Clock in the Brain

Maternal chronodisruption is linked to miscarriages and neurodevelopmental risks, yet the earliest brain circadian oscillator in the embryo and the mechanism of its emergence remain unknown. Using bioluminescent reporters for PER2 and Bmal1, we tracked the onset of autonomous [~]24 h oscillations ex vivo. While the suprachiasmatic nucleus (SCN) is widely considered the first circadian structure at embryonic day (E) 14.5-15.5, we find that the fourth ventricle choroid plexus (4VCP) exhibits PER2 oscillations by E11.5-E12.5. These oscillations show hallmarks of a saddle-node on an invariant circle (SNIC) bifurcation, characterized by an initially long period converging toward 24 h and pronounced sensitivity to sub-degree temperature cycles mimicking physiological maternal cues. Transcriptional profiling of maternal and embryonic 4VCPs unveiled three epochs in clock gene expression that parallel tissue differentiation. We identify the 4VCP as the earliest detectable brain circadian oscillator, and demonstrate how its bifurcation dynamics allow the nascent clock to couple to maternal rhythms.

developmental biology↗

bioRxiv2024

Gag proteins encoded by endogenous retroviruses are required for zebrafish development

Transposable elements (TEs) make up the bulk of eukaryotic genomes and examples abound of TE-derived sequences repurposed for organismal function. The process by which TEs become coopted remains obscure because most cases involve ancient, transpositionally inactive elements. Reports of active TEs serving beneficial functions are scarce and often contentious due to difficulties in manipulating repetitive sequences. Here we show that recently active TEs in zebrafish encode products critical for embryonic development. Knockdown and rescue experiments demonstrate that the endogenous retrovirus family BHIKHARI-1 (Bik-1) encodes a Gag protein essential for mesoderm development. Mechanistically, Bik-1 Gag associates with the cell membrane and its ectopic expression in chicken embryos alters cell migration. Similarly, depletion of BHIKHARI-2 Gag, a relative of Bik-1, causes defects in neural crest development in zebrafish. We propose an "addiction" model to explain how active TEs can be integrated into conserved developmental processes.

developmental biology↗

bioRxiv2022

Structures of the holo CRISPR RNA-guided transposon integration complex

CRISPR-associated transposons (CAST) are programmable mobile elements that insert large DNA cargo by an RNA-guided mechanism. Multiple conserved components act in concert at the target site through formation of an integration complex (transpososome). We reconstituted the type V-K CAST transpososome from Scytonema hofmannii (ShCAST) and determined the structure using cryo-EM. Transpososome architecture ensures orientation-specific association: AAA+ regulator TnsC has defined polarity and length, with dedicated interaction interfaces for other CAST components. Interestingly, transposase (TnsB)-TnsC interactions we observe contribute to stimulating TnsCs ATP hydrolysis activity. TnsC deviates from previously observed helical configurations of TnsC, and target DNA does not track with TnsC protomers. Consequently, TnsC makes new, functionally important protein-DNA interactions throughout the transpososome. Finally, two distinct transpososome populations suggests that associations with the CRISPR effector are flexible. These ShCAST transpososome structures significantly enhances our understanding of CAST transposition systems and suggests avenues for improving CAST transposition for precision genome-editing applications.

biophysics↗