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bioRxiv2024

Relationship Between Circulating FGF21 and Physiological and Lifestyle Characteristics, an Exploratory Study

Fibroblast growth factor 21 (FGF21) is a biomarker that has been linked to metabolic health. This study was conducted to examine the relationship between FGF21 and its purported upstream regulators and downstream targets in healthy humans. Male and female participants completed three study visits. During visit 1 anthropometrics were measured and a VO2peak test was conducted on a stationary bike. During visits 2 and 3 resting metabolic rate, heart rate, and blood pressure were recorded and a blood sample was taken. Results from visits 2 and 3 were averaged before statistical analysis. Additionally, participants completed a food frequency questionnaire to detail typical diet over the previous month and had three days of measured physical activity and sleep. Moderate correlations between FGF21 and measured sleep (r = 0.34, p = 0.05), saturated fat intake (r = -0.37, p = 0.04), and blood urea nitrogen levels (r = -0.47, p = 0.01) were observed. Additionally, greater intensities of daily physical activity were associated with lower FGF21 levels. Serum FGF21 levels may be influenced by lifestyle variables such as sleep and physical activity, diet, and other circulating biomarkers. Highlights- FGF21 is positively correlated with sleep in healthy humans. - Sugar intake is positively correlated with FGF21 concentrations in humans. - Blood urea nitrogen concentrations are negatively correlated with FGF21 in humans.

physiology↗

bioRxiv2025

CFTR High Expresser BEST4+ cells are pH-sensing neuropod cells: new implications for intestinal physiology and Cystic Fibrosis disease

Single-cell RNA sequencing (scRNA-seq) studies identified a novel subpopulation of epithelial cells along the rostrocaudal axis of human intestine specifically marked by bestrophin 4 (BEST4) that are enriched for genes regulating pH, GPCR acid-sensing receptors, satiety, cGMP signaling, HCO3- secretion, ion transport, neuropeptides, and paracrine hormones. Interestingly, BEST4+ cells in the proximal small intestine express CFTR but have not been linked to the previously described CFTR High Expresser Cell (CHE) subpopulation in rat and human intestine. ScRNA-seq studies in rat jejunum identified CHEs and a gene expression profile consistent with human small intestinal BEST4+ and neuropod cells. Protein immunolocalization confirmed that CHEs express CFTR, BEST4, neuropod proteins, high levels of intracellular uroguanylin (UGN), guanylyl cyclase-C (GC-C), and the proton channel otopetrin 2 (OTOP2), and display long basal processes connecting to neurons. OTOP2, GC-C, and CFTR traffic robustly into the apical domain of CHEs in response to acidic luminal conditions, indicating their roles in luminal pH regulation. In the {Delta}F508 cystic fibrosis (CF) rat jejunum, the loss of apical CFTR did not affect BEST4 protein expression in CHEs. However, there was an increased abundance of CHE cells in the {Delta}F508 rat jejunum compared to wild-type animals. Furthermore, {Delta}F508 rat CHEs expressed higher levels of GC-C at the apical domain compared to wild-type. These data implicate CHEs in intestinal CF disease pathogenesis. NEW & NOTEWORTHYThis is the first study to identify CFTR High Expresser cells in the rat small intestine as neuropod cells capable of sensing and responding to luminal pH. This study also provides the first characterization of CFTR and relevant mRNA and proteins in CHEs in CF rat models that provide insights into the significance of CHEs to CF intestinal disease.

physiology↗

bioRxiv2025

Temperature outweighs diet in shaping developmental performance in two cricket species via growth delays and physiological limits

Understanding how chronic environmental stressors shape animal development is essential for predicting ecological responses and optimizing rearing systems. This perspective complements the use of short-term tolerance assays, which overlook the cumulative effects of sustained stress. Temperature and nutrition affect key life-history traits such as growth, development rate, and survival, which are closely tied to reproductive success and fitness. While both factors have been widely studied, their relative impacts arent clearly defined. We investigated how constant temperature (26- 41{degrees}C) and dietary protein-to-carbohydrate (P:C) ratio (0.15-2.18) influence development in two cricket species, Acheta domesticus and Gryllodes sigillatus. Growth trajectories were modelled using a unified-logistic equation to estimate asymptotic mass and relative growth rate. This approach captures the growth trajectory in a simplified and interpretable way, enabling comparisons across treatments. Asymptotic mass was combined with developmental rate and survival to calculate a composite metric of developmental performance. Developmental performance peaked at 35{degrees}C but fell at thermal extremes due to delayed development (in cold) or reduced mass and survival (in heat). Diet had more modest effects. Performance was stable across most P:C ratios, declining only at extreme imbalances. Notably, the performance cost of the most unbalanced diets was comparable to a 4-5{degrees}C shift from thermal optimum. Our results demonstrate that temperature, more than diet, drives variation in developmental performance during ad libitum feeding. This integrative framework provides a robust approach to quantify environmental sensitivity, define performance limits, and guide us toward the mechanisms underlying those limits and/or performance trade-offs. Summary statementTemperature more strongly influences growth trajectories and developmental performance than diet, due to delayed development and reduced survival at thermal extremes.

physiology↗

bioRxiv2025

Aging Leads to Altered Physiological Reactivity in Response to Repeated Social Separation Stress in a Nonhuman Primate Model

Social relationships are critical for maintaining physical health and psychological wellbeing. Since nearly 1 in 4 adults aged 65 years or older are socially isolated, there is a strong need to understand how repeated social stress negatively impacts health outcomes. Using a nonhuman primate model of social aging (i.e., marmosets), we examined whether individuals transitioning into old age ("peri-geri") or individuals who were already geriatric ("very-geri") showed differences in measures of hypothalamic-pituitary axis (HPA) activity, markers of metabolic and immune function, and reunion social behavior in response to repeated social separation challenges (SSC). We found female marmosets, especially peri-geri females, had higher HPA reactivity and better HPA recovery than male marmosets, but this difference diminished in older, very-geri marmosets. HPA activity was correlated with multiple outcomes including locomotive behavior and grooming, changes in blood glucose levels, and neutrophil counts. Moreover, marmosets who approached their partner more and were groomed less during reunions had higher cortisol levels the following day. Interestingly, we found two distinct HPA profiles among our marmosets with half showing strong HPA responses (reactors) and the other half showing little or no HPA response (non-reactors). Non-reactors had less weight gain/more weight loss; elevated levels of calcium, phosphorus, and white blood cells; and received less grooming and social contact time during reunion. Overall, old-aged marmosets who show attenuated HPA responses may have different vulnerabilities to negative health and behavioral outcomes during social stress, and male marmosets appear more likely to present with this HPA non-reactor phenotype earlier in aging.

physiology↗

bioRxiv2025

Normalized Raman Imaging for Studies of Tissue Physiology of the Kidney

Conventional histological relies on fixation, embedding, sectioning, and staining methods that distort cellular architecture, extract lipids, and introduces variability, limiting reproducibility. We present Normalized Stimulated Raman Imaging (NoRI) that enables quantitative, label-free protein and lipid measurements at high-spatial resolution. NoRI computationally corrects protein, lipid, and water Raman signals, allowing quantitative biomass measurements while preserving tissue architecture, facilitating analysis by convolutional neural networks. Applied to mouse kidney, NoRI accurately classified tubule types (F1-[harmonic mean of precision and recall against manual annotation]=0.93), anatomical regions (F1=0.91), and biological sex (F1=0.97), revealing greater cytoplasmic lipid (+6.9mg/mL; p=0.028) and nuclear protein (+26.3mg/mL; p<0.001) in female tubules. In acute kidney injury, NoRI captured dynamic lipid and protein organization and quantified brush border remodelling and lipid droplet changes over 25 days. Spatial lipid quantification was central for feature classification in AKI (F1=1.0). These results establish NoRI as a reproducible, quantitative method for diagnostics, histopathology, and feature discovery.

physiology↗

bioRxiv2025

Aging Alters Hair Cell Physiological Properties in Mice with Late-Onset Age-Related Hearing Loss.

Cochlear hair cells convert sound stimuli into electrical signals. Age-related hearing loss (ARHL) is characterized by the progressive reduction of these hair cells and their synapses, but the underlying mechanisms remain poorly understood. In this study, we tested the hypothesis that hair cell function declines with age in CBA/CaJ mice, a strain known for its very slow ARHL progression. We found that hair cell size began to decrease from 10 months of age, before hearing loss was detectable. This structural change was associated with a significant decrease in the total current response and a distinct reduction in the expression of large conductance calcium-activated potassium (BK) channel currents (IK,f). However, the magnitude of the mechanoelectrical transducer (MET) currents at the hair cell stereociliary bundles remained unaffected. This observation challenges the common conception that stereocilia are the most fragile component of sensory cells in aging. Our results provide clear evidence of an early decline in hair cell function with age, which precedes measurable hearing loss, suggesting that these cellular deficits define a distinct pathological route to ARHL in the CBA/CaJ mouse model.

physiology↗

bioRxiv2025

Reduced-order modeling of solute transport within physiologically realistic solid tumor microenvironment

AO_SCPLOWBSTRACTC_SCPLOWSolid tumors are characterized by densely packed extracellular matrices and limited vascularization, creating significant resistance to both diffusive and convective transport. In this study, we developed an integration of numerical computations with a theoretical modeling framework that couples three phase viscous-laminar transient simulations of glycocalyx-patched tumor vessel resolving plasma, red blood cells (RBCs), and white blood cells (WBCs) and tracking their volume fractions to a calibrated reverse advection-diffusion (RAD) model for intratumoral plasma transport. The reduced-order tumor microenvironment model uses histology-informed extracellular matrix (ECM) tumor domain and packing fraction, together with explicit glycocalyx-patch electrohydrodynamics (EHD) at the tumor vessel wall. At the fenestra, EHD increases inlet plasma intensity relative to a non-EHD framework across all models (means: 0.576 non-EHD vs 0.722 EHD; gain 25.34%). Numerical simulations of plasma perfusion in both the tumor ECM domain and a microfluidic benchmark exhibit two-stage kinetics, with an initial advection-dominated regime. The RAD model reproduces this behavior and, after a simple temporal calibration to account for pore-scale hydrodynamic acceleration resolved by computational fluid dynamics (CFD), matches the observed propagation. By using fully resolved, EHD-inclusive multiphase CFD simulations to calibrate a reduced-order RAD model parameterized by measurable geometric features, we bridge the gap between classical Darcy-Starling tissue perfusion models and fully resolved CFD. The resulting framework provides a tractable, mechanism-grounded tool for quantifying plasma progression in dense solid tumors.

physiology↗

bioRxiv2018

Gradual repression of selenoprotein W ensures physiological bone remodelling

Selenoproteins containing selenium in the form of selenocysteine are critical for bone remodelling. However, their mechanism of action is not well understood. Here, we report the identification of selenoprotein W (SELENOW) through large-scale mRNA profiling of receptor activator of nuclear factor (NF)-{kappa}B ligand (RANKL)-induced osteoclast differentiation, as a protein that is downregulated via RANKL/RANK/tumour necrosis factor receptor-associated factor 6/p38 signalling. RNA sequencing analysis revealed that SELENOW regulates osteoclastogenic genes. SELENOW overexpression enhanced osteoclastogenesis in vitro via nuclear translocation of NF-{kappa}B and nuclear factor of activated T-cells cytoplasmic 1, whereas its loss suppressed osteoclast formation. SELENOW-deficient and SELENOW-overexpressing mice exhibited osteopetrosis and osteoporosis, respectively. Ectopic SELENOW expression stimulated cell-cell fusion critical for osteoclast maturation as well as bone resorption. Thus, RANKL-dependent repression of SELENOW maintains proper osteoclast differentiation and blocks osteoporosis caused by overactive osteoclasts. These findings demonstrate a biological link between selenium and bone metabolism.

physiology↗

bioRxiv2018

Integrative Transcription Start Site Analysis and Physiological Phenotyping Reveal Torpor-Specific Expressions in Mouse Skeletal Muscle

Mice enter an active hypometabolic state, called daily torpor, when they experience a lowered caloric intake under cool ambient temperature (TA). During torpor, the oxygen consumption rate (VO2) drops to less than 30% of the normal rate without harming the body. This safe but severe reduction in metabolism is attractive for various clinical applications; however, the mechanism and molecules involved are unclear. Therefore, here we systematically analyzed the expression landscape of transcription start sites (TSS) in mouse skeletal muscles under various metabolic states to identify torpor-specific transcription patterns. We analyzed the soleus muscles from 38 mice in torpid, non-torpid, and torpor-deprived conditions, and identified 287 torpor-specific promoters. Furthermore, we found that the transcription factor ATF3 was highly expressed during torpor deprivation and that the ATF3-binding motif was enriched in torpor-specific promoters. Our results demonstrate that the mouse torpor has a distinct hereditary genetic background and its peripheral tissues are useful for studying active hypometabolism.

physiology↗

bioRxiv2018

Effects of dietary replacement of broiler litter with Mucuna pruriens utilis forage and seed meal on performance, carcass characteristics, blood biochemical and physiological parameters in indigenous goats

The productivity of indigenous goats in Africa is constrained by shortage of protein-rich feed especially in winter. This study investigated the nutritional value of mucuna forage (MF) and seed meal (MSM) as alternative protein sources for indigenous goats. Mucuna was planted in 3 parallel and adjacent fields and its foliage nutritional composition determined at 4, 8, 12 and 16 weeks after planting (WAP). MF was harvested at 14 WAP whilst mucuna pods were harvested at 28 - 30 WAP, shelled and the MSM chemically analysed. In a completely randomised design (CRD), 20 indigenous goats were randomly offered 5 treatment diets with, respectively, 0%, 25%, 50% and 100% MF and 100% MSM replacing broiler litter (BL), each with 4 replicates, for 82 days. Both mucuna foliage DM and CF contents increased (P < 0.001) whilst foliage CP, EE and ash contents decreased (P<0.001) with maturity. On the other hand, MSM contained high DM (90.7%), EE (3.7% DM) and CP (26.0% DM) but low CF (9.7% DM) and ash (5.5% DM) contents. Both body weight gain (BWG) and feed conversion efficiency (FCE) were not influenced by dietary mucuna incorporation (P > 0.05). However, dietary MF, particularly at the 100% level, decreased goat feed intake (FI) (P < 0.001) whilst 100% MSM increased (P < 0.001) this parameter. Mucuna had no effect on all carcass characteristics (P > 0.05) but increased (P < 0.05), particularly at the 100% MSM level, hot carcass weight and dressing percentage. There were no effects of mucuna on all biochemical and haematological indices (P > 0.05), except for the increase in serum glucose (P < 0.05). In conclusion, the optimal stage for harvesting and utilisation of MF is between 12 and 16 WAP and both MF and MSM, particularly the latter, are rich alternative protein sources for indigenous goats.

physiology↗

bioRxiv2018

Physiological and transcriptome analysis of indica rice ‘MH86’ overexpressing OsSPL14

OsSPL14, identified as IDEAL PLANT ARCHITECTURE1 (IPA1) or WEALTHY FARMERS PANICLE (WFP) gene, plays a critical role in regulating rice plant architecture. Here, the study showed that OsSPL14-overexpression transgenic rice plants had shorter growth period, short-narrow flag leaves, and thick-green leaves. Compared with wild type plant MH86, transgenic plants had higher chlorophyll a (Ca), chlorophyll b (Cb) and carotenoid (Cx) content at both seedling and maturity stage. Meanwhile, transcriptome analysis identified 473 up-regulated and 103 down-regulated genes in transgenic plant. The expression of differentially expressed genes (DEGs) involved in carotenoid biosynthesis, abscisic acid (ABA) metabolism and lignin biosynthesis increased significantly. Most of DEGs participated in \"plant hormone signal transduction\" and \"starch and sucrose metabolism\" are also up-regulated in transgenic plant. In addition, there were higher levels of ABA and gibberellin acid (GA3) in OsSPL14-overexpression transgenic plants. Moreover, the content of culm lignin, cellulose, silicon and potassium all increased dramatically. Thus, these results demonstrate that overexpression of OsSPL14 has influence on leaf development, hormone level and culm composition in rice, which provide more insight into understanding the function of OsSPL14.\n\nHighlightOsSPL14-overexpression transgenic plants showed shorter growth period, short-narrow flag leaves, and thick-green leaves. Transcript profile, abscisic acid (ABA) and gibberellin acid (GA3) level, and culm composition also changed obviously.

physiology↗

bioRxiv2018

The Influence of Magnetic Fields on Selected Physiological Parameters of Blood and Tissues in Mice

This study aimed to highlight the influence of exposure to different applied magnetic fields (MFs) on SOD, MDA and GSH levels in the liver, LDH and CPK activities in the muscle and {gamma}-aminobutyric acid levels in the brain, as well as some haematological parameters. Adult male albino Swiss mice were divided into 5 equal groups (n = 6), the control group (untreated) and four exposure groups that were exposed to MFs of 20, 40, 60 and 80 Gauss for 5 min/day for 5 days.: Exposure to MFs induced significant decreases in total GSH levels and SOD activity but a significant increase in MDA levels in the liver. By contrast, SMF exposure significantly increased total LDH and total CPK activities in the muscle. The results revealed a significant increase in GABA levels in the brain, as well as decreases in haemoglobin, haematocrit, and red blood cell counts, in addition to platelet counts, after exposure to 20, 40, 60 and 80 Gauss MFs. After exposure to a 40 Gauss MF, the mice showed pathological changes in red blood cells, including changes to the outer membrane of the red blood cells (micronucleus and a serrated edge, with a mild incidence of echinocytes). In the group exposed to a 60 Gauss MF, examination of blood smears clearly showed changes in cell size, with the emergence of abnormal forms, including many areas with no red blood cells (rouleaux formation). With increasing intensity of exposure (80 Gauss), the red blood cells appeared completely different from their natural form and took the form of ovalocytes and bi-micronucleated erythrocytes, which appear in patients with anaemia. MF exposure caused different metabolic and haematological effects, which appeared to be related to the intensity of SMF exposure. The changes in the biochemical parameters of SMF-exposed mice probably reflect hepatic damage and anaemia caused by kidney failure. Further studies are needed to obtain a better understanding of the effects of MF on biological systems.

physiology↗

bioRxiv2019

Sox6: A new modulator of renin expression during physiological conditions

Juxtaglomerular (JG) cells, major sources of renin, differentiate from metanephric mesenchymal cells which give rise to JG cells or a subset of smooth muscle cells of the renal afferent arteriole. During periods of dehydration and salt deprivation JG cells undergo expansion. Gene expression profiling comparing resident renal Mesenchymal Stromal Cells (MSCs) with JG cells indicate that the transcription factor Sox6 is highly expressed in JG cells in the adult kidney. In vitro, loss of Sox6 expression reduces differentiation of renal MSCs to renin producing cells. In vivo, Sox6 expression is up-regulated during JG cell expansion. Importantly, knockout of Sox6 in Ren1d+ cells halts the increase in renin expressing cells normally seen during JG cell expansion as well as the typical increase in renin. These results support a previously undefined role for Sox6 in renin expression during normal and pathophysiological conditions.

physiology↗

bioRxiv2019

Time course of the physiological stress response to an acute stressor and its associations with the primacy and recency effect of the serial position curve

Whether stress affects memory depends on which stress pathway becomes activated and which specific memory system is involved. The activation of the sympathetic nervous system (SNS), leads to a release of catecholamines. The activation of the hypothalamic-pituitary-adrenal (HPA) axis, leads to a release of glucocorticoids. In thus study, it was investigated whether SNS and/or HPA axis activation are associated with long-term memory (LTM) and/or working memory (WM) performance in humans. Thirty-three participants underwent the socially evaluated cold-pressor test. Salivary alpha-amylase (sAA) was used as a marker for the activation of the SNS and cortisol as marker for HPA axis activation. Memory was assessed by means of word lists with 15 words each. The primacy effect (i.e., the correctly recalled words from the beginning of the lists) of the serial position curve was considered as indicator for LTM. The recency effect (i.e., the correctly recalled words from the end of the lists) were used as estimator for WM performance. In sAA responders, the recency effect and, therefore, WM performance increased immediately after the stressor. This was not found in sAA non-responders. In cortisol responders, the primacy effect and, thus, LTM performance decreased 20 minutes after the stressor. No change in LTM performance was found in cortisol non-responders. Our study supports the assumptions that 1) SNS activation is associated with WM processes via stimulation of the prefrontal cortex, and 2) HPA axis activation is associated with LTM processes through interactions with the hippocampus.

physiology↗

bioRxiv2019

Circadian time series proteomics reveals daily dynamics in cartilage physiology

ObjectivesArticular cartilage undergoes cyclical heavy loading and low load recovery during the 24-hour day/night cycle. We investigated the daily changes of protein abundance in mouse femoral head articular cartilage by performing 24-hour time-series proteomics study.\n\nMethodsTandem mass spectrometry analysis was used to quantify proteins extracted from mouse cartilage. Bioinformatics analysis was performed to quantify rhythmic changes in protein abundance. Primary chondrocytes were isolated and cultured for independent validation of selected rhythmic proteins.\n\nResults145 rhythmic proteins were detected. Among these were key cartilage molecules including CCN2, MATN1, PAI-1 and PLOD1 & 2. Pathway analysis revealed that proteins related to protein synthesis, cytoskeleton and glucose metabolism exhibited time-of-day dependent peaks in their abundance. Meta-analysis of published proteomics datasets from articular cartilage revealed that numerous rhythmic proteins were dysregulated in osteoarthritis and/or ageing.\n\nConclusionsOur circadian proteomics study revealed that articular cartilage is a much more dynamic tissue than previously thought. Chondrocytes exhibit circadian rhythms not only in gene expression but also in protein abundance. Our results clearly call for the consideration of circadian timing in understanding cartilage biology, osteoarthritis pathogenesis, treatment strategies and biomarker detection.

physiology↗

bioRxiv2019

Perlin Noise Generation of Physiologically Realistic Patterns of Fibrosis

Fibrosis, the pathological excess of fibroblast activity, is a significant health issue that hinders the function of many organs in the body, in some cases fatally. However, the severity of fibrosis-derived conditions depends on both the positioning of fibrotic affliction, and the microscopic patterning of fibroblast-deposited matrix proteins within afflicted regions. Variability in an individuals manifestation of a type of fibrosis is an important factor in explaining differences in symptoms, optimum treatment and prognosis, but a need for ex vivo procedures and a lack of experimental control over conflating factors has meant this variability remains poorly understood. In this work, we present a computational methodology for the generation of patterns of fibrosis microstructure, demonstrating the technique using histological images of four types of cardiac fibrosis. Our generator and automated tuning method prove flexible enough to capture each of these very distinct patterns, allowing for rapid generation of new realisations for high-throughput computational studies. We also demonstrate via simulation, using the generated fibrotic patterns, the importance of micro-scale variability by showing significant differences in electrophysiological impact even within a single class of fibrosis.

physiology↗

bioRxiv2026

Obstructive Sleep Apnea Syndrome Disrupts Glymphatic-Related Physiological Brain Pulsations

BackgroundObstructive sleep apnea (OSA) affects over one billion people and increases neurodegenerative risk. Brain vasomotor, respiratory, and cardiac pulsations are thought to drive glymphatic clearance during sleep, yet OSAs effect on these pulsations remains poorly understood. MethodsWe studied 20 healthy controls (HC; 39.7{+/-}8.0 y) and 12 patients with OSA (PWOSA; 53.0{+/-}11.0 y) using a four wavelength (690-980 nm) functional near-infrared spectroscopy (fNIRS) measuring oxygenated, deoxygenated and total hemoglobin, water and cerebrospinal fluid (HbO, HbR, HbT, H2O, CSF). Polar devices provided heart rate variability (HRV). Spectral power, coherence and phase transfer entropy analysis was performed for very low frequency (VLF), respiratory, and cardiac bands from 30 min sleep segments and event-based whole-night analysis assessed autonomic responses. ResultsOSA patients exhibited lower fNIRS spectral entropy for HbO, HbT, H2O & CSF (p<0.05), with increased VLF and respiratory band power across all concentrations (HbO, HbR, HbT, H2O & CSF, p<0.05). Signal coherence was reduced in respiratory and cardiac bands. Phase transfer entropy revealed disrupted directional coupling toward HbR (cardiac) and CSF-to-HbO (respiratory). HRV showed parallel VLF amplification (p <0.05), elevated heart rate during event-free and respiratory-event periods (p<0.001) and reduced Root Mean Square of Successive Differences (RMSSD, 32.5 vs 43.0 ms, p<0.001). Hypoxic burden correlated with cardiac band power of HbO, HbT and CSF (r>0.73). ConclusionsOSA reorganizes cortical pulsatile dynamics - reducing complexity, amplifying low frequency power and suppfdsfsdfsdfsdisrupting directed coupling. This state may compromise sleep-related glymphatic clearance. fNIRS-based spectral analysis offers a promising bedside tool for monitoring brain pulsatility.

physiology↗

bioRxiv2026

OrganScaleR: An Open Shiny Tool for Principled Organ-Weight Inference in Mouse Physiology

BackgroundOrgan weights are often divided by body weight to report "relative" organ size. Yet ratios usually stay size-dependent and become misleading. We built a simple decision path for size adjustment and wrapped it in a Shiny application so physiologists can get correct answers without coding. MethodsWe reused liver and body-weight data from a mouse nutrition study for confirmatory examples in two common cases: when diet groups shared a wide body-size range, and when diet produced much smaller animals with little overlap. We compared liver-to-body-weight ratios with size-adjusted regression when the body-size overlap allowed comparisons, and with causal Bayesian mediation when it did not. The full workflow was implemented in OrganScaleR, a guided R Shiny application. ResultsThe ratio-normalized organ weight is still associated with body weight, leading to misleading comparisons. Modeling liver weight against body weight gave more cautious, size-adjusted effects when groups shared a common size range. When diets shifted body size strongly and overlap was limited, causal mediation showed that most organ differences followed the change in body weight rather than an organ-specific action. Simulations confirmed that ratios can generate false positives and biased estimates under allometric scaling, while model-based approaches remained reliable. OrganScaleR implements this decision workflow in a guided Shiny application that returns interpretable effects. ConclusionsOrganScaleR selects scale, enforces common support, and routes the analysis to size-adjusted ANCOVA or causal Bayesian mediation depending on body-weight overlap. It reports adjusted effects in original units through a point-and-click workflow, removing the statistical barrier to abandoning ratio normalization. HighlightsO_LIBody-weight ratios remain size-dependent and distort organ-weight comparisons. C_LIO_LIANCOVA at a common reference body weight removes ratio bias when groups overlap. C_LIO_LICausal mediation separates organ-specific from body-weight-mediated diet effects. C_LIO_LISimulations confirm ratios inflate false-positive rates under allometric scaling. C_LIO_LIOrganScaleR guides size adjustment without coding via a point-and-click workflow. C_LI

physiology↗