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At least 397 records · Page 22Linked to original sources

bioRxiv2026

Linking reaction time variability to physiological markers of arousal across timescales

Reaction time is a measure of the speed of our response to stimuli in the environment. Even for a well-trained task, a subjects reaction time varies. One source of this variability is internal state fluctuations (such as changes in arousal). There are few studies that systematically quantify the extent to which reaction time varies across different timescales and link this to measures of systemic physiology associated with arousal. In much of the literature, it is assumed but not demonstrated that behavioral and systemic measurements associated with arousal will be consistently linked because both estimate a common underlying arousal process. In this work, we examined this assumption by simultaneously measuring reaction time, heart rate, and pupil diameter in rhesus macaque monkeys performing several visual tasks over hours and across hundreds of sessions. We found a portion of the variability in reaction time could be linked to systemic physiological signatures of arousal on fast timescales from second to second and slower timescales from minute to minute. This link between reaction time and systemic physiology was also present for different biomarkers of arousal (heart rate and pupil). However, the strength of this relationship varied depending on the arousal biomarker. Our findings support the conclusion that there are multiple arousal mechanisms that act simultaneously to influence behavior and multiple timescales at which they operate.

neuroscience↗

bioRxiv2026

Physiological perfusion of human vasculature reveals a YAP/TAZ-Apelin switch linking intraluminal flow to endothelial state transitions and vessel remodeling

Vascular flow delivers nutrients and imposes hemodynamic forces that govern vessel behavior in health and disease, yet fully human systems that recapitulate and tune physiological intraluminal flow in three-dimensional (3D) tissues are lacking. We developed VIVOS (Vascularized In Vitro Organ Systems), a platform that couples perfused human vascular beds to tunable pumps, generating continuous intraluminal flow through millimetre-scale vessels and 3D tissues at physiological shear stresses and pressures. VIVOS supports integration and perfusion of diverse human organoids and tissues, including lung organoids, cerebral organoids, vascular organoids, breast spheroids, and human retinal explants, as well as enables direct measurement and control of pressure, shear stress, and perfusion-dominant compound transport over extended culture periods. By tuning intraluminal flow and applying single-cell transcriptomics, we uncover a remodeling program in which laminar shear stress acts through a YAP/TAZ-TEAD "switch" to rewire an Apelin ligand-receptor axis and bias tip-stalk endothelial states, reshaping human vascular networks and linking hemodynamic cues to cell state transitions. We further model fast-flow arteriovenous malformations (AVMs) from Hereditary Hemorrhagic Telangiectasia and show that BMP9 constrains vessel caliber and perfusion while antagonizing a VEGF-driven angiogenic program, generating flow-quantified AVM-like lesions in a fully human 3D context. Together, these findings establish VIVOS as a generalizable platform that links physiological intraluminal flow to endothelial state transitions and vessel remodeling, enabling preclinical testing and mechanistic dissection of flow-regulated vascular pathologies in perfused 3D human tissues under defined hemodynamic conditions.

bioengineering↗

bioRxiv2026

Integrated heart rate variability and physiological profiling reveals autonomic phenotypes in older adults from a high-southern-latitude population

Heart rate variability (HRV) is widely used to assess autonomic regulation, but its interpretation in older adults is influenced by age, sex, body composition, and hemodynamic status, particularly in underrepresented populations living in geographically extreme environments. We analyzed 530 community-dwelling older adults from the Magallanes region in southern Chile using an integrated framework that combined HRV indices with demographic, anthropometric, and cardiovascular descriptors. After quality-controlled preprocessing, we characterized the distribution and association structure of autonomic and physiological variables and then performed a large-scale unsupervised clustering benchmark across multiple feature spaces, dimensionality-reduction strategies, and clustering algorithms. Conventional descriptors explained only a limited proportion of HRV variability, whereas integrated multivariate analysis revealed a structured continuum of autonomic heterogeneity. A six-cluster solution provided the best compromise between separation, balance, and physiological interpretability, identifying profiles that differed in HRV magnitude, blood pressure burden, body composition, sex distribution, and age structure. These findings indicate that autonomic regulation in older adults cannot be adequately summarized by isolated descriptors such as age, body mass index, or blood pressure alone. Instead, it is better represented as a multidimensional physiological organization that supports future hypothesis generation for risk stratification and longitudinal monitoring in aging populations.

neuroscience↗

bioRxiv2026

Genomic Prediction Enables Provenance-Aware Selection in 1 Sessile Oak (Quercus petraea) using Foliar Physiological Traits

Climate change is reshaping the adaptive landscape of forest ecosystems, demanding more efficient strategies to identify and deploy resilient tree genotypes. Genomic prediction offers a powerful framework to accelerate selection for complex physiological traits underlying climate adaptability in long-lived species such as sessile oak (Quercus petraea (Matt.) Liebl.). Here, we conducted genomic prediction for three key physiological traits carbon isotope composition, nitrogen isotope composition, and the carbon-to-nitrogen content ratio (C/N ratio) measured in 746 trees genotyped with dense genome-wide markers ([~]580,000 SNPs). High genomic heritabilities were estimated across traits, with within-year prediction accuracies (Pearsons r between genomic estimated values and observed phenotypes) reaching 0.77. Notably, across-year and across-provenance predictions remained substantial (0.41 < r < 0.82), with predictability declining with increasing genetic distance (FST) between training and test provenances for nitrogen isotope composition and C/N ratio. In addition, GWAS-guided SNP preselection increased heritability capture by [~]15% relative to random SNP subsets. And, the pronounced provenance-by-environment interactions observed indicated substantial phenotypic plasticity in these traits. These results demonstrate the strong potential of applying genomic prediction to foliar physiological traits as polygenic predictors for climate adaptation in plants, support provenance-aware breeding to improve forest establishment, and provide practical strategies for deploying genomic prediction in long-lived species.

genetics↗

bioRxiv2026

Improving Emotion Classification by Combining fNIRS-Derived Hemodynamic Responses with Peripheral Physiological Signals

We investigated whether multimodal sensing that combines functional near-infrared spectroscopy (fNIRS) with peripheral physiological signals can improve subject-independent classification of arousal and valence, the fundamental affective dimensions in Russells circumplex model. We developed Japanese emotion-inducing music-video stimuli (60 seconds each) and recorded subjects central nervous system activity using fNIRS, alongside peripheral physiological measures, specifically electrodermal activity (EDA) and photoplethysmography (PPG), during video viewing. To prioritize reproducibility and methodological transparency, we extracted simple, easily computed features from each modality and performed binary (high vs. low) classification separately for arousal and valence using a support vector machine. The combination of fNIRS and EDA yielded the highest performance, with a macro-averaged F1 score of 0.73 for arousal and 0.64 for valence. These findings underscore the utility of integrating fNIRS with peripheral physiological signals for subject-independent emotion classification.

neuroscience↗

bioRxiv2026

Complex microbial consortia improve yield and physiological performance of leafy greens under deficit irrigation

O_LIWater scarcity is an increasing constraint on agricultural productivity, particularly for high-value vegetable crops. Deficit irrigation strategies can reduce water use but frequently compromise yield and crop physiological status. Scalable, biologically based tools are needed to sustain crop performance under reduced water input without reliance on additional agrochemical inputs. C_LIO_LIFive functionally diverse microbial consortia were assembled from taxa selected to support rhizosphere colonization, soil structural stabilization, and fungal-mediated nutrient and water foraging. Consortia were evaluated in greenhouse trials with lettuce (Lactuca sativa) and spinach (Spinacia oleracea) grown under full irrigation or a 30% deficit irrigation regime (70% of crop water requirement). Crop responses were assessed using yield, harvest delay, root length, wilting incidence, chlorophyll content, and Water Band Index. C_LIO_LIAcross both crops, microbial consortium treatments improved performance under deficit irrigation relative to untreated water-stressed controls. In lettuce, yield increased by 3-9%; in spinach, yield increased by 4-13%, with several treatments restoring performance to levels not significantly different from fully irrigated controls. C_LIO_LIMicrobial treatments reduced harvest delay by an average of three to four days, improved root length, lowered wilting incidence, and reduced WBI, indicating attenuation of plant water stress. In several cases, physiological responses under deficit irrigation approached those observed under full irrigation despite 30% lower water input. Higher application rates generally produced stronger responses, though this trend was not always statistically significant. C_LIO_LISynthesis and applications. Complex microbial consortia can buffer the physiological and yield penalties of deficit irrigation in leafy green crops. These findings demonstrate the potential of soil microbiome-based inoculants as scalable, biologically derived tools to improve agricultural water-use efficiency and resilience under increasing water scarcity. Practical adoption of such consortia could reduce irrigation demand in intensive vegetable production systems without proportional yield loss, supporting both economic and environmental sustainability goals in water-limited agricultural contexts. C_LI

microbiology↗

bioRxiv2026

Differentiating the Physiological Signatures of Cochlear Synaptopathy and Inner Hair Cell Damage in a Chinchilla Model

Aging and noise over-exposure lead to complex mixtures of cochlear degradation that impair the structure and function of outer hair cells, inner hair cells (IHCs), and the cochlear nerve. However, IHC damage and cochlear synaptopathy (CS) remain pathologies "hidden" from the audiogram. This study aimed to identify and differentiate the physiological signatures of these two distinct pathologies using promising non-invasive assays: Envelope Following Responses (EFRs), Auditory Brainstem Response (ABRs), Wideband middle-ear reflexes (WB-MEMRs), and Distortion Product Otoacoustic Emissions (DPOAEs). We utilized chinchilla models of carboplatin-induced (CA) IHC damage (N = 4) and temporary threshold shift (TTS) noise-induced CS (N = 4) to compare the physiological signatures of each pathology. While both groups showed unchanged ABR thresholds two weeks after exposure, EFRs, ABR Wave V/I ratios, and MEMRs showed distinct effects of exposure. Despite non-elevated ABR-derived audiometric thresholds after exposure, both CA and TTS exposure resulted in severe in EFR "peakiness", particularly for sharp, short-duty-cycle stimuli and significant elevations in ABR Wave V/I ratios. However, these findings were less-pronounced in the TTS-exposed animals. WB-MEMR amplitudes were decreased with elevated thresholds in both groups; this effect was more pronounced in the TTS group. Opposite trends in DPOAE amplitudes indicated that while both IHC damage and CS result in similar suprathreshold temporal coding deficits, effects on outer-hair-cell integrity and auditory efferent physiology may differ between the two pathologies. Future work and novel diagnostics should aim to distinguish these specific cochlear pathologies in clinical populations, or at the very least consider their overlap. HighlightsO_LIA multi-metric diagnostic approach was used with chinchilla models of inner-hair-cell (IHC) damage and cochlear synaptopathy (CS). C_LIO_LIIHC damage and synaptopathy both cause suprathreshold deficits "hidden" from the audiogram. C_LIO_LIIHC damage results in more severe temporal envelope coding degradation than does synaptopathy. C_LIO_LIA combination of EFR "peakiness", ABR Wave V/I ratio, and Wideband Middle Ear Muscle Reflex (WB-MEMR) appear to be useful measures for profiling IHC damage and CS. C_LI

neuroscience↗

bioRxiv2026

Dynamic visualization of physiological CaMKII activity using sensitive FRET biosensors

Calcium-calmodulin (CaM)-dependent protein kinase II (CaMKII) is a key mediator of complex physiological processes throughout the body, from the brain to the reproductive system, where CaMKII translates spatiotemporally dynamic calcium elevations into specific biological functions. Directly visualizing CaMKII activity dynamics in living cells using genetically encoded fluorescent biosensors can thus provide crucial insights into the molecular regulation of health and disease. Yet the ability to sensitively and specifically monitor endogenous CaMKII activity in physiologically relevant contexts is limited by the lack of sensors that can achieve robust, quantitative visualization of CaMKII responses. Here, we leveraged a recent serine/threonine kinome-wide substrate atlas to rationally engineer a powerful suite of Forster resonance energy transfer (FRET)-based CaMKII kinase activity reporters with high specificity, sensitivity, and signal-to-noise ratio. Using these biosensors, we were able to sensitively and robustly visualize endogenous CaMKII activity dynamics in both cultured cell lines and primary cells, including cardiomyocytes, oocytes, and neurons. We further utilized 2pFLIM imaging of organotypic hippocampal slices to quantitatively track LTP-induced CaMKII activity within single dendritic spines, highlighting a major advance in the study of physiological CaMKII signaling.

bioengineering↗

bioRxiv2026

A Cone-Plate Bioreactor for Applying Physiologically Derived Shear Stress Waveforms to Study Endothelial Mechanotransduction and Cardiac Cell Signaling

Fluid shear stress is a critical regulator of endothelial cell function and cardiovascular development, yet in vitro platforms often lack the ability to reproduce physiologically relevant, time-dependent flow environments with quantitative precision. Here, we present the design and validation of a macro-scale cone-plate bioreactor engineered to deliver controlled steady and pulsatile shear stress waveforms to endothelial monolayers and engineered tissues. The system integrates a geometry optimized to minimize secondary flow effects, a feedback-controlled motor capable of reproducing complex waveforms, and a viscosity-informed control framework to account for shear-dependent fluid behavior. Using this platform, endothelial cells were exposed to steady and physiologically derived pulsatile shear stresses. Cells exhibited increased alignment and eccentricity under shear, confirming biologically relevant mechanical stimulation. While pulsatile shear did not significantly alter endothelial neuregulin-1 expression, exogenous administration studies revealed a nonlinear, dose-dependent increase in cardiomyocyte proliferation. Furthermore, co-culture experiments demonstrated that shear-conditioned endothelial cells promote cardiomyocyte proliferation, suggesting a mechanotransduction-mediated paracrine signaling mechanism. Together, these results establish a versatile and quantitatively controlled platform for studying cardiovascular mechanobiology. This device enables systematic investigation of shear-dependent cellular responses and provides a foundation for integrating co-culture systems and three-dimensional engineered tissues under physiologically relevant hemodynamic conditions.

bioengineering↗

bioRxiv2026

Cross-Sectional Physiological and Neuromuscular Profiling of Elite and Recreational University Badminton Athletes: Preliminary Benchmarks for Exercise-Based Injury Risk Stratification

Background and PurposeBadminton imposes considerable cardiovascular and musculoskeletal stress. Physiological profiling can identify modifiable injury risk factors and inform exercise-based prevention and rehabilitation. This study compared cardiovascular recovery, neuromuscular activation, and limb strength between elite and recreational male university badminton players to derive preliminary physiological benchmarks for injury risk stratification and exercise rehabilitation guidance. MethodsForty male athletes (20 elite: national/university representatives with [≥]5 years of competitive experience; 20 recreational: <3 years of experience) completed assessments of heart rate recovery (HRR), biceps brachii surface electromyography (sEMG; SENIAM protocol), handgrip strength (JAMAR dynamometry), and maximal bodyweight squat repetitions. Independent-sample t-tests with Cohens d ( = 0.05) and Pearson correlations were applied. ResultsElite players demonstrated significantly greater handgrip strength (49.00{+/-}6.12 vs. 39.00{+/-}5.45 kg, p = 0.001, d = 1.72) and lower-limb (LL) strength (60.35{+/-}11.29 vs. 41.75{+/-}6.72 repetitions, p < 0.001, d = 1.96). Normalized sEMG root mean square (RMS) was higher in elite athletes during flexion (11.56{+/-}4.16% vs. 7.26{+/-}5.15%, p = 0.004, d = 0.94) and extension (12.67{+/-}4.56% vs. 7.85{+/-}5.73%, p = 0.003, d = 0.94). HRR did not differ significantly between groups (p = 0.17, d = 0.43, observed power = 0.34). Elite players nonetheless showed a more favorable recovery distribution. sEMG -HRR correlations were weak and non-significant in both groups. ConclusionsElite badminton players exhibit a distinct physiological profile of greater strength and more efficient neuromuscular activation. These preliminary cross-sectional findings may support the design of exercise-based injury-prevention and rehabilitation in university badminton.

biophysics↗

bioRxiv2026

Physiologically Informed PCA-Partial Correlation for highly Collinear Brainstem fMRI Networks

Functional connectivity (FC) approaches from resting-state fMRI (rs-fMRI) are amply spread to investigate the cortical organization, yet the brainstem remains relatively underexplored despite its pivotal roles in both physiological and pathological conditions. The highly collinear network, in which the strongly interconnected nodes and the widespread neuromodulatory influences induce indirect or mediated interactions, make the estimation of direct brainstem FC challenging. Standard bivariate methods fail to recover the true network structure in such complex topologies, causing false positive interactions. On the other hand, partial correlation can potentially estimate the direct FC, but multicollinearity issues and collider-induced spurious correlations limit its application in high-dimensional scenarios. Here, we propose a physiologically informed framework in which the conditioning strategy for partial correlation estimation is tailored for the investigation of the brainstem and its direct interactions within the network and with whole-brain regions. Specifically, we employed a PCA-regularized partial correlation (PCA - {rho}PC) approach, where PCA is applied to the brainstem covariates to mitigate multicollinearity and model shared modulatory variance. We show that PCA - {rho}PC improves the robustness and interpretability of brainstem FC, yielding sparser and more physiologically plausible connectomes compared with conventional (regularized) approaches. Both simulation and real fMRI data raise the possibility that Pearsons and PCA-regularized approaches may complement each other in an effort to unravel the pattern of direct vs. indirect effects in highly collinear settings, paving the way for future extensions in a wide range of multivariate neuroimaging applications.

bioengineering↗

bioRxiv2026

Expanding The Algal Hydrogen Toolbox: A Non-GMO Platform Reveals Multiple Physiological Routes To Sustained Hydrogen Production Across Microalgae

Sustainable hydrogen production from microalgae remains limited by intrinsic physiological constraints and the need to preserve biomass value for food and feed applications. Transgenic approaches to overcome these limitations were proven successful, yet result in genetically modified (GMO) strains that face major regulatory and deployment barriers. Here, we present a non-GMO experimental platform that enables systematic isolation of hydrogen-producing phenotypes through high-throughput UV mutagenesis pipline coupled with targeted physiological screening. Applying this approach across phylogenetically distinct algal species, including the industrial strain Chlorella vulgaris and the extremophile Chlorella ohadii, we achieve high discovery efficiency, recovering 0.4-0.6% validated hydrogen-producing mutants and achieving 6.7-25% validation rates among screen-positive candidates, indicating strong enrichment at the primary screening stage. We show that sustained hydrogen production represents a physiologically accessible state emerging across diverse genetic backgrounds. This state is consistently associated with reorganization of photosynthetic electron partitioning, yet arises through multiple distinct configurations that differentially balance hydrogen production, oxygen metabolism, and carbon fixation. This framework provides a scalable route to identify hydrogen-producing strains in industrially relevant algae without introducing foreign DNA and expands the accessible design space for photobiological hydrogen production.

plant biology↗

bioRxiv2026

Scalable biophysical constraints for physiologically consistent metabolic states

Systems biology aims to develop predictive models that connect molecular mechanisms to cellular behavior. Genome-scale metabolic models are among the most widely used frameworks for integrating stoichiometric, thermodynamic, and omics-derived information to predict feasible metabolic phenotypes. However, cellular metabolism operates on timescales governed by enzyme kinetics and by the relationship between metabolic fluxes and metabolite pool sizes. In steady-state metabolic models, this relationship can be expressed in terms of metabolite turnover rates, defined as flux-to-pool-size ratios that quantify how rapidly metabolite pools are renewed. As a result, physiologically consistent steady-state solutions should not only satisfy mass-balance and thermodynamic constraints but also exhibit turnover rates consistent with enzyme-mediated cellular dynamics. Current constraint-based approaches can admit many steady-state flux-concentration states that do not account for turnover rates, resulting in phenotypes incompatible with realistic metabolic dynamics, even when multiple types of data are imposed. Here, we present METEOR-K, an optimization framework that links steady-state metabolic fluxes to metabolite concentrations via turnover rate constraints to identify dynamically plausible flux-concentration reference states. Because these constraints reshape the feasible solution space, we also introduce turnover-rate-aware sampling strategies to efficiently explore the resulting feasible region. We applied METEOR-K to models of increasing scope and scale, including a reduced glycolysis pathway, anaerobic E. coli, and near-genome-scale ovarian cancer models. METEOR-K narrowed the admissible steady-state solution space, reduced uncertainty in feasible flux-concentration states, and improved local dynamic behavior. In nonlinear ODE simulations of bioreactor cultivation and drug-response scenarios, METEOR-K-derived states produced intracellular response times compatible with growth-supporting metabolic operation and perturbation recovery. Overall, these results establish metabolite turnover rates as scalable biophysical constraints that improve the physiological consistency of steady-state metabolic modeling. Because turnover rates encode flux-to-pool-size timescale constraints, METEOR-K moves part of physiological-consistency assessment upstream of kinetic parameterization, yielding better-suited flux-concentration reference states for kinetic modeling and dynamic prediction.

systems biology↗

bioRxiv2026

Dichloroacetate improves animal survival, growth, neuromuscular activity, mitochondrial stress and physiology, and elevated lactate in C. elegans pdha-1 and dld-1 RNAi models of pyruvate dehydrogenase complex deficiency (PDCD)

Pyruvate dehydrogenase complex (PDHc) deficiency (PDCD) is a primary mitochondrial disorder characterized by neurodevelopmental disability, altered intermediary metabolism and early mortality. Dichloroacetate (DCA), a pyruvate analogue, is a well-described PDHc activator that remains under clinical investigation for treatment of PDCD. Here, we studied the in vivo efficacy of a 5-point log concentration range of DCA on animal health and metabolism in C. elegans with feeding RNA interference (RNAi) expression knockdown of either PDHA-1 or DLD-1 homologues at graded degrees to model variable disease severity. These worm models recapitulate phenotypic features of PDCD observed in human patients, including reduced survival, delayed growth, locomotor impairment, and elevated lactate and/or pyruvate tissue levels. DCA treatment appeared well-tolerated, with no gross morphologic toxicity seen at doses up to 25 mM. Significantly improved health, survival, tissue lactate levels, and mitochondrial physiology were observed at 25 mM in pdha-1(RNAi) knockdown animals. DCA treatment in dld-1(RNAi) C. elegans models (undiluted, 1:20 dilution, and 1:100 dilution) showed significant therapeutic benefits on survival, neuromuscular function and metabolic phenotypes primarily in the moderate (1:20) and/or mild (1:100) dld-1(RNAi) deficiency strains, but not in full-dose dld-1(RNAi). Importantly, linear growth, neuromuscular activity, and mitochondrial physiology were significantly improved with DCA treatment even in the most severe dld-1(RNAi) undiluted model. Overall, preclinical modeling provides objective evidence of DCA therapeutic efficacy in C. elegans expression knockdown strains for two well-conserved homologues of PDHA1 and DLD that represent distinct genetic etiologies of PDHc deficiency, with demonstrated beneficial effects on survival, healthspan, tissue lactate, and mitochondrial physiology. These data further confirm that DCAs therapeutic effect correlates with PDHc disease phenotype severity in dld-1(RNAi) animals. SYNOPSIS: Dichloroacetate (DCA) treatment demonstrated significant preclinical beneficial effect on survival, neuromuscular function, linear growth, tissue lactate, and mitochondrial metabolism in two C. elegans models with variable degrees of pyruvate dehydrogenase complex (PDHc) deficiency (PDCD), providing confirmatory evidence to support its therapeutic potential in human PDCD patients.

cell biology↗

bioRxiv2026

Genomic and biochemical contexts determine the physiological role of a horizontally acquired gene

The horizontally acquired mgtC gene from Salmonella enterica confers this bacterium the abilities to survive episodes of magnesium (Mg2+) starvation, and to replicate in mammalian macrophages. The former property allows bacteria to persist in the environment through periods of Mg2+ depletion, whereas the latter allows S. enterica to overcome self-limiting intestinal colonization and cause an invasive systemic infection in susceptible mammalian hosts. Even though the biochemical function of MgtC is not completely understood, this protein is thought to function primarily by preventing the production of toxic levels of Mg2+-chelating adenosine triphosphate (ATP). In the current work, we investigated the physiological roles of mgtC homologs from an array of bacterial species, by probing the processes controlled by this gene during replication in low Mg2+ medium and in macrophages. We determined that MgtC homologs that do not participate in Pi homeostasis during Mg2+ starvation and do not promote intramacrophage replication in their resident species can partake in these processes when expressed in S. enterica. This indicates that the function of this protein is context dependent. Accordingly, we show that the physiological processes affected by S. enterica MgtC vary, depending on whether the bacteria replicate in low Mg2+ medium or inside macrophages. While these results suggest that MgtC is a regulator, they also demonstrate that horizontally acquired genes can assume different roles, depending on the genome and the biochemical context into which they are inserted. ImportanceThe mgtC gene encodes an inner membrane protein that has been horizontally acquired by multiple bacterial species, including several mammalian pathogens. In Salmonella enterica, MgtC promotes replication in mammalian macrophages and allows this bacterium to survive cytoplasmic magnesium (Mg2+) starvation. These phenotypes are thought to result from MgtCs inhibition of Pi metabolism and ATP production, which prevents the accumulation of toxic levels of Mg2+-chelating ATP and disrupts other physiological processes that are strictly dependent on Mg2+, such as ribosome assembly and translation. In the current study, we show that processes that are controlled by MgtC vary with the genetic and biochemical contexts in which this protein is expressed. While establishing a broader role for MgtC as a regulator, our findings illustrate how horizontally acquired regulatory genes can potentiate regulatory interactions, facilitating the evolution of new traits.

microbiology↗

bioRxiv2026

Sex Differences in Physiological Hair Cycling and Adhesive Material-Induced Hair Regeneration in Mice

Sex differences in hair growth are clinically evident, but sex-dependent regulation of physiological hair cycling and injury-induced hair regeneration remains incompletely understood. We compared physiological dorsal hair-cycle progression and adhesive material-induced localized hair regeneration in male and female C3H/He mice. Males entered the second and third anagen phases earlier than females, indicating longer telogen phases in females. In contrast, localized hair regrowth after application and removal of a cyanoacrylate adhesive material appeared earlier in females. Ovariectomy induced widespread telogen-to-anagen transition and therefore did not permit isolation of ovarian-hormone effects on the localized response. RNA sequencing of intact dorsal skin identified sex-dependent baseline expression profiles involving inflammation, wound response, and tissue repair. Independent time-course quantitative PCR further demonstrated sex-dependent expression of inflammatory and reparative genes after adhesive material application. Local clodronate liposome administration alone induced delayed perifocal hair growth. When combined with adhesive material application, clodronate treatment markedly delayed wound healing and localized hair regrowth in males, whereas these responses were comparatively preserved in females. These findings show that physiological hair cycling and adhesive material-induced hair regeneration exhibit distinct sex differences and suggest that the localized regenerative response is more macrophage-dependent in males than in females.

developmental biology↗

bioRxiv2026

Assessing the physiological S nitrosoproteome reveals nitric oxide mediated regulatory networks in rice

Nitric oxide metabolism-based protein post-translational modifications, such as reversible S- nitrosylation, have been at the pinnacle of plant redox research owing to their significant correlation with seed dormancy, interaction with other signaling molecules, plant development and metabolism, biotic and abiotic plant stress responses, immune defense responses against plant pathogens, and senescence. The rapid interconversion of reactive nitrogen species, the abrogation of nitric oxide homeostasis by exogenous supplementation of NO donors and scavengers, the lack of spatio-temporal specificity of NO signaling, and the limited bioavailability or assay sensitivity for detection often limit the effectiveness of identifying and characterizing S-nitrosothiols in plants. Hitherto unknown, we report the first experimental evidence of the total in vivo S-nitrosoproteome in Oryza sativa L. subsp. indica, comprising 134 PSNOs, enriched with 169 putative sites susceptible to S-nitrosylation, without any exogenous supplementation of NO donors. In the present study, mercuric salt- driven facile decomposition of S-nitrosoproteins in the presence of nitrone spin trap 5,5- dimethyl-1-pyrroline N-oxide, resulting in the synthesis of DMPO-nitrone adducts with PSNO-derived protein thiyl radicals in O. sativa, has been demonstrated as an efficient and novel strategy for characterizing the PSNOs using mass spectrometry analysis. The evidence of physiological levels of PSNOs was further re-examined in a bi-directional qualitative and quantitative approach involving the 2,3-diaminonaphthalene assay in tandem with fluorescence-based visualization and fluorometric quantification. In silico analyses, involving both functional enrichment and pathway prediction analyses, have furthermore revealed unique protein-protein interaction networks and signaling pathways among the S- nitrosoproteome candidates and their predictable physiological roles in O. sativa indica, awaiting further in vitro validation for their functional correlation in response to S- nitrosylation. In conclusion, the present study provides novel evidence of nitric oxide signaling in rice cultivars under physiological conditions, bringing new insights into the potential in vivo transnitrosylation of regulatory or active-site cysteine thiols.

biochemistry↗

bioRxiv2026

Denoising the central autonomic network: characterizing processes jointly associated with arousal and non-neuronal physiological artefacts in dynamic fMRI analyses

Using a multimodal dataset including fMRI, EEG-fMRI and concurrent physiological recordings, we investigated the effect of denoising systemic low frequency oscillations (sLFOs) on the characterization of dynamic signatures of central autonomic regulation and their relation to ongoing physiological states. We demonstrated that the time-frequency profiles of couplings between BOLD time series and cardiac and respiratory processes were statistically comparable between regions of the brain associated with autonomic function and non-autonomic motor regions, suggesting that these couplings largely do not reflect neuronal activation related to autonomic activity. We further showed that model-based (via physiological response functions) and data-driven (via CompCor nuisance regressors extracted from cerebrospinal fluid) methods of sLFO denoising had a statistically similar effect on these frequency profiles. We novelly applied co-activation pattern analysis to assess state dynamics of autonomic-associated regions of the brain, finding that such brain states interrelate decreases in vigilance and increases in heart rate, respiratory flow, and head motion, thus providing evidence for global arousal processes affecting BOLD signal in autonomic-associated regions. Lastly, we modelled sliding-window dynamic functional connectivity within the central autonomic network (CAN) as modulated by heart rate variability, showing significant differences in model outcomes linked to each denoising pipeline. With these findings, we provide a comprehensive discussion of the implications for the application of denoising techniques to the CAN and comment on the origins of dynamic components of the BOLD signal linked to autonomic regulation, highlighting the global role played by arousal.

neuroscience↗