bioRxiv Science⌕ Search

bioRxiv · 10.64898/2026.08.07.743459

Differential routing of spectral light inputs separates circadian timing from energetic responsiveness

Abstract

Light simultaneously provides phototrophic organisms with energy and with information about environmental time. These two functions need not impose the same response to fluctuations in irradiance: photosynthetic outputs should remain amplitude-sensitive, whereas circadian phase should reject changes that do not alter dawn, dusk, or photoperiod. We formulate this problem for two spectral inputs by decomposing their logarithmic intensities into a common-irradiance coordinate a and a spectral-contrast coordinate r. The contribution of channel i to phase is Qi = ZiGi, where the non-negative gate Gi determines when the pathway is active and the signed phase-response projection Zi determines whether this activity advances or delays the oscillator. For a locked oscillator, robustness to common irradiance together with retained contrast sensitivity requires two non-zero cycle-averaged contributions of opposite sign, A1 [~=] -A2 = 0. Energetic responsiveness is preserved only when the physiological projection of the same inputs is not proportional to their phase projection. A canonical repressilator provides an explicit nonlinear realization of these conditions. Positive gates placed on opposite lobes of its infinitesimal phase-response curve strongly attenuate common-mode phase shifts while preserving contrast sensitivity. A minimal photosynthetic-capacity model then shows how this organization protects temporal alignment under day-to-day irradiance fluctuations. At the largest variability tested, differential routing reduced the mean phase displacement by more than one half and the associated alignment loss by approximately 82%, whereas the resulting production advantage remained small, approximately 0.1%. Thus, multichannel light sensing can stabilize circadian timing without suppressing the energetic response to irradiance. HighlightsO_LIAnalytical routing conditions separate common irradiance from spectral contrast. C_LIO_LIPositive temporal gates can generate opposite signed phase contributions. C_LIO_LIPhase robustness requires a projection distinct from the energetic projection. C_LIO_LIA canonical oscillator provides a constructive illustration of the mechanism. C_LIO_LIThe functional benefit is improved temporal alignment rather than a large growth gain. C_LI

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Thommen, Q.. 2026-08-17. Differential routing of spectral light inputs separates circadian timing from energetic responsiveness. https://doi.org/10.64898/2026.08.07.743459

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Concentration limits and localization of hydrogen peroxide in the extracellular space of solid tissues

H2O2 released to the extracellular space (ECS) regulates diverse physiological processes, yet its concentrations and spatial distribution in tissues remain poorly defined. This uncertainty hampers mechanistic understanding of redox signaling. Here, we used reaction-diffusion modeling to estimate extracellular H2O2 concentrations and transport ranges in various scenarios. Idealized analytical models were combined with numerical models incorporating localized NADPH oxidase (NOX) clusters, ECS microstructure, membrane permeability, and the thioredoxin- and GSH-dependent clearance systems. Using maximal neutrophil and NOX superoxide/H2O2 release rates, we obtained upper bounds for extracellular H2O2. Adjacent to isolated average-sized, fully active NOX2 clusters H2O2 peaked at ~540 nM at adhesion cell-cell separations, and decreased radially over ~50-100 nm. At the receptor cell surface, peak concentration decreased inversely with intercellular separation, to <5 nM at 1 m separation. Radial decrease here, for this wide separation, was over ~2.5 m. Even the former maximal extracellular concentrations induce just a minimal, highly localized oxidation of the intracellular Prdx, Trx and GSH pools. In turn, maximally activated neutrophils carry ~2000 such NOX2 clusters, inducing 10s of M peak ECS H2O2 concentrations. These cause extensive Prdx and Trx oxidation near the exposed membranes. However, the GSH-dependent system still sustains a strong transmembrane gradient if the permeation barrier remains intact, and ECS H2O2 concentrations decay to sub-M within a few m of the source cell. Extracellular H2O2 concentrations scaled linearly with source flux in all the examined conditions. These results establish stringent constraints on autocrine, juxtacrine and next-cell paracrine H2O2 signaling.

systems biology↗

LSD-pipeline: Causal Inference of miRNA Network Effects in Alzheimer's Disease

MicroRNAs (miRNAs) are implicated in Alzheimer's disease (AD), but research has focused on individual miRNAs and direct targets. Existing approaches to miRNA regulation in AD identify associations rather than causal effects, and few methods estimate multi-stage chains from miRNAs through target genes to target transcription factor (TF) cascades. We developed the LSD pipeline (LASSO-SEM-DoWhy), integrating LASSO feature selection, multi-stage structural equation modeling, and DoWhy causal inference to identify and validate miRNA causal pathways in AD. Applying LSD to six blood miRNA and brain mRNA datasets, we identified four LSD-validated miRNAs (miR-30d-5p, miR-92a-3p, miR-296-5p, miR-193a-5p) as AD biomarkers, achieving >86% ROC accuracy in an independent validation cohort. Several miRNAs with no significant direct association with AD showed significant effects when estimated through their target networks, while others significant in direct analysis were not supported at the network level, underscoring the value of network-level analysis. Extending to the TF layer revealed complete miRNA [->] targets [->] TF cascades [->] AD causal chains, with HMGA1, NKX2-3, and PRRX2 as key intermediaries. Confirmed classic pathways converge primarily on tau pathology and synaptic dysfunction. miRNA effects were largely age-independent, suggesting miRNAs act as early initiators of AD pathogenesis. Beyond AD, the LSD pipeline provides a generalizable framework for uncovering causal regulatory mechanisms in other diseases.

systems biology↗

PyKappa: Rule-based modeling in Python

Rule-based languages have proven effective for modeling systems of interacting structured entities as typically encountered in chemistry and molecular biology. We present PyKappa, a rule-based modeling package written in Python whose interpreted nature enables interactive simulation and analysis, including by agentic AI. The package seeks to broaden the base of developers by utilizing a widely known programming language and serves as an easy-to-deploy teaching tool. Using PyKappa, we conduct a case study of phase separation.

systems biology↗