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bioRxiv2019

PHYSIOLOGICAL DIFFERENCES BETWEEN ADVANCED CROSSFIT ATHLETES, RECREATIONAL CROSSFIT PARTICIPANTS, AND PHYSICALLY-ACTIVE ADULTS

This investigation examined anthropometric, hormonal, and physiological differences between advanced (ADV; n = 8, 27.8 {+/-} 4.2 years, 170 {+/-} 11 cm, 79.8 {+/-} 13.3 kg) and recreational (REC; n = 8, 33.5 {+/-} 8.1 years, 172 {+/-} 14 cm, 76.3 {+/-} 19.5 kg) CrossFit (CF) trained participants in comparison to physically-active controls (CON; n = 7, 27.5 {+/-} 6.7 years, 171 {+/-} 14 cm, 74.5 {+/-} 14.3 kg). ADV and REC were distinguished by their past competitive success. REC and CON were resistance-trained (>2 years) and exercised on 3-5 days{middle dot}wk-1 for the past year, but CON utilized traditional resistance and cardiovascular exercise. All participants provided a fasted, resting blood sample and completed assessments of resting metabolic rate, body composition, muscle morphology, isometric mid-thigh pull strength, peak aerobic capacity, and a 3-minute maximal cycle ergometer sprint across two separate occasions (separated by 3-7 days). Blood samples were analyzed for testosterone, cortisol, and insulin-like growth factor-1. One-way analysis of variance revealed ADV to possess lower body fat percentage (6.7-8.3%, p = 0.007), greater bone and non-bone lean mass (12.5-26.8%, p [≤] 0.028), muscle morphology characteristics (14.2-59.9%, p < 0.05), isometric strength characteristics (15.4-41.8%, p < 0.05), peak aerobic capacity (18.8-19.1%, p = 0.002), and anaerobic performance (15.4-51.1%, p [≤] 0.023) compared to both REC and CON. No differences were seen between REC and CON, or between all groups for resting metabolic rate or hormone concentrations. These data suggest ADV possess several physiological advantages over REC and CON, whereas similar physiological characteristics were present in individuals who have been regularly participating in either CF or resistance and cardiovascular training for the past year.

physiology↗

bioRxiv2026

Physiological consequences of acute heat exposure in mid-gestation on placental, foetal and maternal blood flow using a mouse model.

Pregnant women are particularly susceptible to adverse outcomes from environmental heat, yet the physiological effects of acute heat exposure during pregnancy remain poorly understood. Some physiological changes are monitored in humans; however, investigation of underlying molecular mechanisms requires invasive methods that can only be ethically applied in mammalian models. Moreover, research with animal models has largely focused on early and lethal teratogenic effects of heat exposure and lacks longitudinal physiological monitoring, detailed parameterisation of heating regimes and in-depth investigation of underlying mechanisms. Here we used a mouse model to investigate the impact of a controlled acute heat exposure at mid-gestation (E12{middle dot}5), slowly elevating core body temperature (CBT) over 210mins to raise CBT by [~]1{degrees}C. Using high-frequency ultrasound and morphological analyses, we observed delayed alterations in placental and foetal cerebral blood flow indicative of a brain-sparing response, alongside reduced placental labyrinth zone size. Additionally, maternal cardiac function was impaired, accompanied by cardiac and renal fibrosis and elevated circulating soluble Flt-1 levels, an anti-angiogenic biomarker of gestational hypertension. These findings demonstrate that brief heat stress at mid-gestation can induce lasting effects on placental function and maternal cardiovascular health in a mammalian model, highlighting potential risks for pregnancy outcomes under increasing global temperatures. Together this data suggests that an acute exposure to heat elevating core body temperature by 1{middle dot}2{degrees}C can induce a long-term impact on both placenta and maternal health in a mouse model. It will be important to understand the molecular changes which underpin the pathophysiology and whether this is translated to humans.

physiology↗

bioRxiv2026

Pannexin 1 phosphorylation sites differentially modulate channel activity and physiological outcomes

Within the vasculature, pannexin 1 (PANX1) channels in smooth muscle cells (SMCs) regulate -adrenergic constriction and blood pressure. PANX1 channel activity is regulated by phosphorylation at Y198, S205 and Y308 residues, but the physiological significance of these modifications is unknown. Here, we utilize newly developed PANX1 Y198F, S205A and Y308F phospho-dead mutant mice to test physiological changes related to hemodynamics. Radiotelemetry-measured blood pressure was decreased in Y198F, increased in Y308F, but unchanged in S205A mice at baseline. Clonidine-sensitive sympathetic-driven hypertension was observed in all mouse lines except Y198F. Pressure myography of third-order mesenteric arteries revealed -adrenergic contractile responses were decreased in Y198F, slightly enhanced in Y308F, but unchanged in S205A, with responses in Y198F vessels mimicking controls treated with PANX1 inhibitors. To understand signaling changes driving these phenotypes, we performed mesenteric artery bulk RNA sequencing, but found a minimal number of differentially expressed genes between phospho-dead mutants and controls. Similarly, co-immunoprecipitation-mass spectrometry of wildtype or phospho-dead mutant-expressing vascular SMCs revealed few interacting proteins distinct to each PANX1 variant. However, PANX1 channel activity assessments in HEK293T cells expressing the 1D-adrenergic receptor as well as each phospho-dead mutant PANX1 showed that phenylephrine-induced ATP release from Y198F channels was significantly decreased compared to wildtype, but current was unaffected. Conversely, basal and phenylephrine-induced S205A and Y308F currents were reduced, but ATP release resembled controls. Taken together, these findings indicate that distinct PANX1 phosphorylation determines PANX1 metabolite release versus current conducting properties and in turn, regulates physiological outcomes in the vasculature. One Sentence SummaryPANX1 Y198 phosphorylation-mediated ATP release is a major driver of -adrenergic vasoconstriction in vascular smooth muscle cells.

physiology↗

bioRxiv2026

Fetal Twin: a mechanistic computational model of fetal physiology for heart-rate-variability biomarker research

Fetal-monitoring biomarkers for neonatal hypoxic-ischemic brain injury face a structural gap: the mechanistic ground truth that would label a training set -- perfusion pressure, the moment of decompensation, the injury time course -- cannot be measured at scale or ethically in human pregnancy or labor, and generative synthetic data carry no mechanistic labels. We address this with a mechanistic computational model of the fetal cardiovascular, autonomic, and metabolic response to controlled hypoxic stress, and use it to test how beat detection and acquisition fidelity alter the interpretation of fetal-heart-rate-variability (HRV) biomarkers. The model integrates these systems forward in time across antepartum development (gestational-age growth scaling) and intrapartum stress (umbilical-cord occlusions), emitting synthetic monitoring signals (fetal heart rate, RR intervals) co-registered with model-computed latent labels (pH, base deficit, lactate, perfusion pressure, decompensation and injury states). In a fetal-sheep-derived autonomic-loop configuration we report three results. First, a phase-accumulator beat detector shows that the apparently physiologic baseline HRV of an earlier build was largely a detector artifact, and a noise-off control shows beat-to-beat variability requires an explicit stochastic driver rather than self-sustained autonomic oscillation. Second, a sampling-fidelity sweep yields a fidelity-matched selection rule: a deceleration-area biomarker is preserved at CTG-grade 4 Hz whereas RMSSD is corrupted there (inflated about 8-fold by timing quantization) and recovers only at fetal-ECG rates. Third, autonomic modulation alone does not reproduce the published RMSSD rise-then-collapse -- a negative result that motivates, but does not prove, an intrinsic sinoatrial-pacemaker contribution as a testable hypothesis. This is an in-silico, hypothesis-generating study: the model is not validated for individual fetal prediction, clinical risk estimation, or clinical decision-making. The model is implemented as Fetal Twin (engine fetaltwin), a source-available research instrument released under a noncommercial license, together with all figure configurations, so that these controlled experiments are reproducible. Key PointsO_LIProgress on fetal-monitoring biomarkers for neonatal brain-injury risk is constrained by a structural gap: the mechanistic ground truth that would label a training set -- perfusion pressure, the moment of cardiovascular decompensation, the time course of injury -- cannot be measured at scale or ethically during human pregnancy or labor. C_LIO_LIWe present Fetal Twin (source-available engine fetaltwin), a publicly available, noncommercially-licensed mechanistic testbed for fetal physiological development. It integrates the fetal cardiovascular, metabolic, and autonomic systems forward in time across antepartum development (gestational-age growth scaling) and intrapartum stress (umbilical-cord occlusions), and emits synthetic monitoring signals (fetal heart rate, RR intervals) co-registered with model-computed latent labels (pH, lactate, perfusion pressure, decompensation and injury states). C_LIO_LIThe names digital-twin connotation is deliberate but bounded: Fetal Twin is a mechanistic, population-level twin of fetal physiology used as a research instrument -- not a validated, patient-specific clinical digital twin or predictor. Its purpose is to interrogate what candidate biomarkers can and cannot mean, via in-silico controls impossible in vivo -- swapping the beat detector, turning a noise source off, ablating a reflex, or quantizing the signal to a monitors sampling grid. C_LIO_LIDemonstrations in a fetal-sheep-derived autonomic-loop configuration show that beat-to-beat HRV amplitude can be a numerical artifact of the beat detector, and that in this model class beat-to-beat variability requires an explicit stochastic driver -- it does not arise as a self-sustained oscillation of the deterministic autonomic loop. C_LIO_LIA further demonstration establishes a fidelity-matched biomarker-selection rule -- a deceleration-area biomarker survives CTG-grade 4 Hz sampling whereas RMSSD is corrupted at that rate and needs fetal-ECG timing -- and a negative result shows the published RMSSD "rise-then-collapse" is not reproducible from autonomic modulation in this model class, motivating (but not proving) an intrinsic-pacemaker hypothesis. C_LI

physiology↗

bioRxiv2026

The king of stress? Exploring the physiological resilience and resistance of adult king penguins to chronic glucocorticoid exposure

To better understand how animals cope with increasingly variable and challenging environments, there is a need to study how prolonged exposure to elevated glucocorticoid hormones (i.e. one mediator of the stress response) affects their physiology. While glucocorticoid elevation is known to increase oxidative stress and accelerate cellular ageing, there is evidence that king penguins (Aptenodytes patagonicus) can prevent oxidative stress during acute stress exposure, suggesting that species may differ in their sensitivity to glucocorticoids downstream negative effects. As king penguins thrive in a seemingly harsh environment, we hypothesized that they may be able to limit the deleterious effects usually associated with chronic glucocorticoid elevation, either through resistance (i.e. prevention of downstream negative effect) or resilience (i.e. rapid recovery following transient negative effect). To test this hypothesis, we experimentally elevated corticosterone levels in incubating king penguins and quantified treatment effects on a suite of physiological traits at multiple time points across incubation and early chick-rearing, up to ca. 2 months after implantation. Corticosterone-treated individuals showed a prolonged increase in corticosterone and decrease in body condition, confirming our treatment likely mimicked sustained stress exposure. Heterophil-to-lymphocyte ratio was only increased transiently, and there was no clear evidence that treatment influenced oxidative stress or telomere length maintenance. Plasma energy metabolites were mainly affected early after implantation, with rapid recovery over time. Overall, our results suggest that adult king penguins show at least moderate resistance and resilience to chronic corticosterone elevation, especially in preventing cellular integrity loss, though at-sea physiological effects remain to be determined.

physiology↗

bioRxiv2026

Green algal symbionts are stably retained and provisioned in the dark despite a clear physiological cost

Photosymbioses, or associations between heterotrophs and photoautotrophs, are widespread and indispensable in today's ecosystems. The chloroplasts of algae and land plants, which are at the heart of most of earth's primary production, stem from ancient photosymbioses. Photosymbioses often combine heterotrophy and autotrophy and must thus efficiently allocate resources between these two costly cellular processes. We currently lack a clear picture of how photosymbioses allocate their valuable cellular resources in response to environmental change. In this study, we combine growth assays, automated fluorescence microscopy, transmission electron microscopy, and mass spectrometry-based proteomics to explore the physiology and cellular resource allocation of the ciliate-green alga photosymbiosis of Paramecium bursaria. In nutrient-rich environments that resemble P. bursaria's natural habitat, the maximum growth rate attained saturates regardless of light intensity. The green algae thus do not provide a benefit in nutrient-replete conditions, and the photosymbiosis primarily functions heterotrophically. The green algae occupy a remarkably similar and constant volume fractions across contrasting light environments despite displaying clear photo-physiological adaptation. This is true regardless of a clear physiological cost of the photosymbionts; aposymbiotic hosts always display higher growth rates in the dark. The host does not decrease 'symbiont load' in environments where green algae are not beneficial. Moreover, in the dark, the green algae are fully dependent on their hosts and take up a larger proteome mass fraction that increases with prey abundance. Differential protein expression analyses suggest that acetate and amino acids are the preferred sources of carbon and nitrogen for the green algae in the dark. The stable persistence and higher resource uptake by the photosymbionts in the dark argue against a view where hosts have full control over and selfishly exploit their symbionts.

physiology↗

bioRxiv2014

Rapid transcriptional response to physiological neuronal activity in vivo revealed by transcriptome sequencing

Neuronal activity serves as a gateway between external stimulus from environment and the brain, often inducing gene expression changes. Alternative splicing (AS) is a widespread mechanism of increasing the number of transcripts produced from a single gene and has been shown to alter properties of neuronal genes, such as ion channels (Xie and Black 2001) and neurotransmitter receptors (Mu et al. 2003). Patterns of neural tissue-specific AS have been identified, often regulated by neuron-specific splicing factors that are essential for survival (Jensen et al. 2000; Li et al. 2007), demonstrating the importance of AS in neurons. In vitro studies of neuronal activity found AS changes in response to neuronal activity in addition to transcriptional ones, raising the question of whether such changes are recapitulated in vivo on behaviorally relevant timescales. We developed a paradigm for studying physiological neuronal activity through controlled stimulation of the olfactory bulb, and performed RNA-Seq transcriptome analysis of olfactory bulbs from odor-deprived and stimulated mice. We found that physiological stimulation induces large, rapid and reproducible changes in transcription in vivo, and that the activation of a core set of activity-regulated factors is recapitulated in an in vitro model of neuronal stimulation. However, physiological activity did not induce global changes in post-transcriptional mRNA processing, such as AS or alternative cleavage and polyadenylation. In contrast, analysis of RNA-Seq from in vitro stimulation models showed rapid activity-dependent changes in both transcription and mRNA processing. Our results provide the first genome-wide look at neuronal activity-dependent mRNA processing and suggest that rapid changes in AS might not be the dominant form of transcriptome alterations that take place during olfactory rodent behavior.

Neuroscience↗

bioRxiv2016

Deconstructing cell size control into physiological modules in Escherichia coli

It is generally assumed that the allocation and synthesis of total cellular resources in microorganisms are uniquely determined by the growth conditions. Adaptation to a new physiological state leads to a change in cell size via reallocation of cellular resources. However, it has not been understood how cell size is coordinated with biosynthesis and robustly adapts to physiological states. We show that cell size in Escherichia coli can be predicted for any steady-state condition by projecting all biosynthesis into three measurable variables representing replication initiation, replication-division cycle, and the global biosynthesis rate. These variables can be decoupled by selectively controlling their respective core biosynthesis using CRISPR interference and antibiotics, verifying our predictions that different physiological states can result in the same cell size. We performed extensive growth inhibition experiments, and discovered that cell size at replication initiation per origin, namely the initiation mass or \"unit cell,\" is remarkably invariant under perturbations targeting transcription, translation, ribosome content, replication kinetics, fatty acid and cell-wall synthesis, cell division, and cell shape. Based on this invariance and balanced resource allocation, we explain why the total cell size is the sum of all unit cells. These results provide an overarching framework with quantitative predictive power over cell size in bacteria.

microbiology↗

bioRxiv2017

Liver physiological T1rho dynamics associated with age and gender

PurposeUsing a single breathhold black blood sequence, the current study aims to understand the physiological ranges of liver T1rho relaxation for women and men.\n\nMaterials and MethodsThis volunteer study was conducted with institutional ethics committee approval, and included 62 females (age mean: 38.9 years; range: 18-75 years) and 34 males (age mean: 44.7 years, range: 24-80 years). MRI was conducted with a 3.0 T scanner, with six spin-lock times of 0, 10, 20, 25, 35, 50msec and a single breathhold of 12 seconds. Six slices were acquired for each examination.\n\nResultsFemale liver T1rho value ranged between 35.07 to 51.97ms, showed an age-dependent decrease with younger women had a higher measurement. Male Liver T1rho values ranged between 34.94 to 43.39 ms, and there was no evidential age-dependence. For females, there was a trend that liver T1rho value could be 4%-5% lower during menstrual phase than nonmenstrual phase. For both females and males, no evidential association was seen between body mass index and liver T1rho.\n\nConclusionLiver T1rho physiological value for males have relatively narrow distribution, while physiological value for females have wider distribution, and decreases with age.\n\nKey points1. Liver T1rho shows an age-dependency in women, with young women showing higher measurement. This age-dependency of liver T1rho measurement is not evidential in men. Post-menopausal women have similar liver T1rho value as men.\n\n2. Women at menstrual phase may have slight lower liver T1rho measurement.\n\n3. No association was noted between body mass index and liver T1rho\n\n4. When blood signal suppression sequence is used, in a population of 62 healthy women and 34 healthy men, the highest measured liver T1rho was 52 msec for young women, 44.7 msec for post-menopausal women, and 43.4 msec for men.

biophysics↗

bioRxiv2019

Physiological and genomic analysis of Candidatus Nitrosocosmicus agrestis, an ammonia tolerant ammonia-oxidizing archaeon from vegetable soil

The presences of ammonia tolerant ammonia-oxidizing archaea (AOA) in environments are always underestimated and their adaption to complex habitats has also rarely been reported. Here we present the physiological and genomic characteristics of an ammonia tolerant soil AOA strain Candidatus Nitrosocosmicus agrestis. This strain was able to form aggregates and adhere on the surface of hydrophobic matrix. Ammonia-oxidizing activities were still observed at 200 mM NH4+ (> 1500 M of free ammonia) and 50 mM NO2-. Urea could be used as sole energy source but exogenous organics had no significant effect on the ammonia oxidation. Besides the genes involving in ammonia oxidation, carbon fixation and urea hydrolysis, the genome also encodes a full set of genes (GTs, GHs, CEs, MOP, LPSE, etc) that responsible for polysaccharide metabolism and secretion, suggesting the potential production of extracellular polymeric substances (EPS). Moreover, a pathway connecting urea cycle, polyamines synthesis and excretion was identified in the genome, which indicates the NH4+ in cytoplasm could potentially be converted into polyamines and excreted out of cell, and then contributes to the high ammonia tolerance. Genes encoding the cytoplasmic carbonic anhydrase and putative polyamine exporter are unique in Ca. Nitrosocosmicus agrestis or the genus Ca. Nitrosocosmicus, suggesting the prevalence of ammonia tolerance in this clade. The proposed mechanism of ammonia tolerance via polyamines synthesis and export was verified by using transcriptional gene regulation and polyamines determination. IMPORTANCEAOA are ubiquitous in different environments and play a major role in nitrification. Though AOA have higher affinities for ammonia, their maximum specific cell activity and ammonia tolerance are usually much lower than AOB, resulting in low contribution to the global ammonia oxidation and N2O production. However, in some agricultural soils, the AOA activity would not be suppressed by the fertilization with high concentration of ammonium nitrogen, suggesting the presence of some ammonia tolerant species. This study provides some physiological and genomic characteristics for an ammonia tolerant soil AOA strain Ca. Nitrosocosmicus agrestis and proposes some mechanisms of this AOA adapting to a variety of environments and tolerating to high ammonia. Ammonia tolerance of AOA was always underestimated in many previous studies, physiological and genomic analyses of this AOA clade are benefit to uncover the role of AOA playing in global environmental patterns.

microbiology↗

bioRxiv2020

Acute Stress Desensitizes Hypothalamic CRH Neurons to Norepinephrine and Physiological Stress

Noradrenergic afferents to corticotropin releasing hormone (CRH) neurons of the hypothalamic paraventricular nucleus (PVN) provide a major excitatory drive to the hypothalamic-pituitary-adrenal (HPA) axis via 1 adrenoreceptor activation. The ascending noradrenergic afferents are recruited preferentially by physiological, rather than psychological, stress modalities. Glucocorticoids secreted in response to HPA activation feed back onto the hypothalamus to negatively regulate the HPA axis, providing a critical autoregulatory constraint that prevents glucocorticoid overexposure. Whether differential negative feedback mechanisms target stress modality-specific HPA activation is not known. Here, we reveal a desensitization of the 1 adrenoreceptor activation of the HPA axis following acute stress that is mediated by rapid glucocorticoid regulation of adrenoreceptor trafficking. Prior stress desensitized the HPA axis to subsequent physiological, but not psychological, stress. Our findings demonstrate rapid glucocorticoid suppression of adrenoreceptor signaling in CRH neurons that is specific to physiological stress activation, and reveal, therefore, a rapid, modality-selective glucocorticoid feedback mechanism.

neuroscience↗

bioRxiv2020

Dysregulation of neural excitability replicates physiological and functional changes in aging visual cortex

The mammalian visual system has been the focus of countless experimental and theoretical studies designed to elucidate principles of neural computation and sensory coding. Most theoretical work has focused on networks intended to reflect developing or mature neural circuitry, in both health and disease. Few computational studies have attempted to model changes that occur in neural circuitry as an organism ages non-pathologically. In this work we contribute to closing this gap, studying how physiological changes correlated with advanced age impact the computational performance of a spiking network model of primary visual cortex (V1). Our results demonstrate that deterioration of homeostatic regulation of excitatory firing, coupled with long-term synaptic plasticity, is a sufficient mechanism to reproduce features of observed physiological and functional changes in neural activity data, specifically declines in inhibition and in selectivity to oriented stimuli. This suggests a potential causality between dysregulation of neuron firing and age-induced changes in brain physiology and performance. While this does not rule out deeper underlying causes or other mechanisms that could give rise to these changes, our approach opens new avenues for exploring these underlying mechanisms in greater depth and making predictions for future experiments.

neuroscience↗

bioRxiv2020

The physiological adaptation for the 'fore-mid' four-legged walking behavior of the pygmy mole cricket Xya latreille

Animals have developed numerous specialized biological characteristics due to selective pressure from the environment. The pygmy mole cricket Xya sichuanensis has well-developed saltatorial hind legs for jumping and benefits for its survival, but these legs cannot be used for walking. Therefore, the typical tripedal gait used by most insects with six legs is not possible, and X. sichuanensis walks exclusively using its fore and mid legs. In this study, we describe a "fore-mid" walking pattern in X. sichuanensis. Further, we sought to deepen our understanding of the biological and physiological adaptations of this "four-legged" insect. We found the positions of tarsi points relative to the ground, integrated hind leg-abdomen structure, thickened ventral cuticle, and leg movements during walking to all show a unique biological adaptation. Of interest, X. sichuanensis was observed to demonstrate four-legged walking, underlining the general theme that insects have strong plasticity at both physiological and behavioral levels. We suggest that on an evolutionary timescale, X. sichuanensis has developed behavioral characteristics such as optimized jumping behavior and a unique walking pattern alongside specialized anatomical adaptations to enable survival in a competitive environment. This study could help explain biological and physiological adaptations for insects behaviors with important implications for the study of diversity in insect locomotion.

evolutionary biology↗

bioRxiv2020

Physiological characterization of nitrate ammonifying bacteria isolated from rice paddy soils via a newly developed high-throughput screening method

Dissimilatory nitrate/nitrite reduction to ammonium (DNRA) has recently gained attention as a nitrogen retention pathway that may potentially be harnessed to alleviate nitrogen loss resulting from denitrification. Until recently, ecophysiology of DNRA bacteria inhabiting agricultural soils has remained largely unexplored, due to the difficulty in targeted enrichment and isolation of DNRA microorganisms. In this study, >100 microbial isolates capable of DNRA have been isolated from rice paddy soil with apparent dominance of denitrification using a novel high-throughput screening method. Six of these isolates, each assigned to a disparate genus, was examined to improve understanding of DNRA physiology. All isolates carried nrfA and/or nirB, and an isolate affiliated to Bacillus possessed a clade II nosZ gene and was capable of N2O reduction. A common prominent physiological feature observed in all DNRA isolates was NO2- accumulation observed before NH4+ production, which was further examined with Citrobacter sp. DNRA3 (possessing nrfA and nirB) and Enterobacter sp. DNRA5 (possessing only nirB). In both organisms, NO2--to-NH4+ reduction was inhibited by submillimolar NO3-, and nrfA or nirB transcription was down-regulated when NO3- was being reduced to NO2-. Both batch and chemostat incubations of these isolates with excess organic electron donors produced NH4+ from reduction of NO3-; however, incubation with excess NO3- resulted in NO2- buildup but no substantial NH4+ production, presumably due to NO3- presence. This previously overlooked link between NO3- repression of NO2--to-NH4+ reduction and the C-to-N ratio regulation of DNRA activity may be a key mechanism underpinning denitrification-vs-DNRA competition in soil. IMPORTANCEDissimilatory nitrate/nitrite reduction to ammonium (DNRA) is an anaerobic microbial pathway that competes with denitrification for common substrates NO3- and NO2-. Unlike denitrification leading to nitrogen loss and N2O emission, DNRA reduces NO3- and NO2- to NH4+, a reactive nitrogen with higher tendency to be retained in soil matrix. Therefore, stimulation of DNRA has often been proposed as a strategy to improve fertilizer efficiency and reduce greenhouse gas emissions. Such attempts have been hampered by lack of insights into soil DNRA ecophysiology. Here, we have developed a novel high-throughput screening method for isolating DNRA-catalyzing organisms from agricultural soils without apparent DNRA activity. Physiological characteristics of six DNRA isolates were closely examined, disclosing a previously overlooked link between NO3- repression of NO2--to-NH4+ reduction and the C-to-N ratio regulation of DNRA activity, which may be key to understanding why significant DNRA activity is rarely observed in nitrogen-rich agricultural soils.

microbiology↗

bioRxiv2020

Probing the functions of microglial cyclin-dependent kinase 5 under physiological and pathological conditions

Cyclin dependent kinase 5 (Cdk5) regulates various developmental and physiological processes in the central nervous system. Deregulation of Cdk5 activity in neurons induces severe neurodegeneration and has been implicated in Alzheimers disease (AD) and other neurodegenerative conditions. A large fraction of AD risk genes are highly expressed in microglia, highlighting an important role for these cells in AD pathogenesis. While Cdk5 function in neurons is well characterized, our understanding of its roles in microglial function under physiological and neurodegenerative conditions remain rudimentary. Here, we investigate the roles of Cdk5 in microglia using myeloid-specific Cdk5 conditional knockout mice. Using microglia-specific transcriptome profiling, histological analyses, and behavioral assessments, we found that knockout of Cdk5 in microglia for 1 month induced transcriptional changes characterized by upregulation of cell cycle processes and type I interferon signaling genes in both physiological conditions and AD-related amyloidogenesis. In contrast to the robust transcriptional changes, conditional loss of microglial Cdk5 produced minimal effects on the density and morphology of microglia and their phagocytic activity toward myelin debris. Moreover, Cdk5cKO mice exhibited little change in synaptic density and tasks associated with locomotor, anxiety-like, and memory-related behaviors. Our findings indicate that the conditional loss of Cdk5 in microglia induces rapid alterations of microglial transcriptome with minimal or delayed effects on histological and behavioral responses.

neuroscience↗

bioRxiv2020

TAZ inhibits GR and coordinates hepatic glucose homeostasis in normal physiologic states

The elucidation of the mechanisms whereby the liver maintains glucose homeostasis is crucial for the understanding of physiologic and pathologic states. Here, we show a novel role of hepatic transcriptional co-activator with PDZ-binding motif (TAZ) in the inhibition of glucocorticoid receptor (GR). TAZ interacts via its WW domain with the ligand-binding domain of GR to limit the binding of GR to gluconeogenic gene promoters. Therefore, liver-specific TAZ knockout mice show increases in glucose production and blood glucose concentration. Conversely, the overexpression of TAZ in mouse liver reduces the binding of GR to gluconeogenic gene promoters and glucose production. Thus, our findings demonstrate distinct roles of the hippo pathway effector proteins yes-associated protein 1 (YAP) and TAZ in liver physiology: while deletion of hepatic YAP has little effect on glucose homeostasis, hepatic TAZ protein expression decreases upon fasting and coordinates gluconeogenesis in response to physiologic fasting and feeding.

biochemistry↗

bioRxiv2020

Predicting Collaborative Learning Quality through Physiological Synchrony Recorded by Wearable Biosensors

Interpersonal physiological synchrony has been consistently found during collaborative tasks. However, few studies have applied synchrony to predict collaborative learning quality in real classroom. This study collected electrodermal activity (EDA) and heart rate (HR) in naturalistic class sessions, and compared the physiological synchrony between independent task and group discussion task. Since each student learn differently and not everyone prefers collaborative learning, participants were sorted into collaboration and independent dyads based on collaborative behaviors before data analysis. The result showed that during groups discussions, high collaboration pairs produced significantly higher synchrony than low collaboration dyads (p = 0.010). Given the equivalent engagement level during independent and collaborative tasks, the difference of physiological synchrony between high and low collaboration dyads was triggered by collaboration quality. Building upon this result, the classification analysis was conducted, indicating that EDA synchrony can predict collaboration quality (AUC = 0.767, p = 0.015).

neuroscience↗

bioRxiv2020

Temporal proteomic profiling reveals insight into critical developmental processes and temperature-influenced physiological response differences in a bivalve mollusc

BackgroundProtein expression patterns underlie physiological processes and phenotypic differences including those occurring during early development. The Pacific oyster (Crassostrea gigas) undergoes a major phenotypic change in early development from free-swimming larval form to sessile benthic dweller while proliferating in environments with broad temperature ranges. Despite the economic and ecological importance of the species, physiological processes occurring throughout metamorphosis and the impact of temperature on these processes have not yet been mapped out. ResultsTowards this, we comprehensively characterized protein abundance patterns for 7978 proteins throughout metamorphosis in the Pacific oyster at different temperature regimes. We used a multi-statistical approach including principal component analysis, ANOVA-simultaneous component analysis, and hierarchical clustering coupled with functional enrichment analysis to characterize these data. We identified distinct sets of proteins with time-dependent abundances generally not affected by temperature. Over 12 days, adhesion and calcification related proteins acutely decreased, organogenesis and extracellular matrix related proteins gradually decreased, proteins related to signaling showed sinusoidal abundance patterns, and proteins related to metabolic and growth processes gradually increased. Contrastingly, different sets of proteins showed temperature-dependent abundance patterns with proteins related to immune response showing lower abundance and catabolic pro-growth processes showing higher abundance in animals reared at 29{degrees}C relative to 23{degrees}C. ConclusionAlthough time was a stronger driver than temperature of metamorphic proteome changes, temperature-induced proteome differences led to pro-growth physiology corresponding to larger oyster size at 29{degrees}C, and to altered specific metamorphic processes and possible pathogen presence at 23{degrees}C. These findings offer high resolution insight into why oysters may experience high mortality rates during this life transition in both field and culture settings. The proteome resource generated by this study provides data-driven guidance for future work on developmental changes in molluscs. Furthermore, the analytical approach taken here provides a foundation for effective shotgun proteomic analyses across a variety of taxa.

developmental biology↗