SEARCH · Search bioRxiv

Results for “Physiology”

Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,477 records · Page 82Linked to original sources

bioRxiv2024

Physiologic Regulation of Lipid Oxidation and Ferroptosis By Vitamin E, High-Density Lipoprotein, and Scavenger Receptor Class B Type 1

Ferroptosis is a form of cell death caused by oxidative (-OOH) damage to phospholipids (PL) that comprise the cell membrane. Understanding mechanisms of ferroptosis is important because of the role it plays in human disease, including cancer and neurodegeneration. Previous work has focused on the intracellular antioxidant enzyme glutathione peroxidase 4 (GPx4), which detoxifies PL-peroxides (PL-OOH) and prevents ferroptosis. Studies also show that alpha-tocopherol (-toc), the active form of Vitamin E, is an exogenous lipophilic antioxidant that inhibits ferroptosis in cancer cells in vitro and in neurons and hematopoietic stem cells in vivo. The mechanisms by which -toc engages cells to manipulate PL redox balance and ferroptosis are unknown. Lipoproteins, like high- and low-density lipoproteins (HDL and LDL), carry -toc in the circulation, which compelled our investigation of their role in -toc delivery and ferroptosis. Using cancer and neuronal cell models, here we show that lipoproteins, particularly HDL, deliver -toc by binding the cell membrane receptor scavenger receptor class B type 1 (SR-B1) to prevent ferroptosis. Additionally, we synthesized SR-B1 targeted HDL-like particles that contained -toc to validate data obtained with native lipoproteins. We reveal here a tunable cellular redox axis whereby native and synthetic HDLs containing -toc target SR-B1 to reduce PL-OOH and prevent ferroptosis.

cell biology↗

bioRxiv2024

Post-Critical Period Transcriptional and Physiological Adaptations of Thalamocortical Connections after Sensory Loss

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=95 SRC="FIGDIR/small/624130v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@100f64aorg.highwire.dtl.DTLVardef@29907corg.highwire.dtl.DTLVardef@cccd63org.highwire.dtl.DTLVardef@1c02318_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO C_FIG Unilateral whisker denervation activates plasticity mechanisms and circuit adaptations in adults. Single nucleus RNA sequencing and multiplex fluorescence in situ hybridization revealed differentially expressed genes related to altered glutamate receptor distributions and synaptogenesis in thalamocortical (TC) recipient layer 4 (L4) neurons of the sensory cortex, specifically those receiving input from the intact whiskers after whisker denervation. Electrophysiology detected increased spontaneous excitatory events at L4 neurons, confirming an increase in synaptic connections. Elevated expression levels of Gria2 mRNA and functional GluA2 subunit of AMPA receptors at the TC synapse indicate the presence of stabilized and potentiated TC synapses to L4 excitatory neurons along the intact pathway after unilateral whisker denervation. These adaptations likely underlie the increased cortical activity observed in rodents during intact whisker sensation after unilateral whisker denervation. Our findings provide new insights into the mechanisms by which the adult brain supports recovery after unilateral sensory loss.

neuroscience↗

bioRxiv2024

Physiological, transcriptomic and metabolomic responses of the marine diatom Phaeodactylum tricornutum to auxin

Auxin, an essential phytohormone, is widely used to promote plant growth and development. However, the effect of auxin on diatoms and its mechanism remain underexplored. Here, we studied the impact of auxin 3-indoleacetic acid (IAA) on the marine diatom Phaeodactylum tricornutum and the underlying molecular mechanisms. We found that 5 g L-1 of IAA promotes the growth of P. tricornutum in a time- dependent manner. Treatment with IAA resulted in significant changes in photosynthetic pigments and malondialdehyde, chlorophyll fluorescence, and antioxidant enzyme activities. In addition, transcriptomics showed that IAA exposure leads to upregulation of a large number of differential genes (DEGs) in carbon fixation and porphyrin metabolism, several of which were verified by qPCR. Furthermore, corresponding metabolites of these pathways were also validated by metabolomic analysis. Thus, IAA exhibits growth-promotion effect on the diatom mainly through increasing photosynthetic carbon sequestration and the expression of genes in porphyrin synthesis. Our results provide key data on the action mechanism of IAA in promoting the growth of a diatom.

plant biology↗

bioRxiv2024

Exploring mitonuclear interactions in the regulation of cell physiology: insights from interspecies cybrids

Brown hares (Lepus europaeus) and mountain hares (Lepus timidus) frequently hybridize in regions where their range overlaps, producing fertile offspring and enabling gene flow between the species. Despite this, no hybrid species has emerged, suggesting that hybrid backcrosses may incur fitness costs. One potential mechanism for such costs involves the interactions between mitochondrial and nuclear gene products, where incompatibilities between species-specific alleles may reinforce species barriers and lead to hybrid breakdown. However, direct experimental evidence for this hypothesis remains limited. In this study, we used fibroblasts derived from skin biopsies of wild-caught hares to generate cytoplasmic hybrid (cybrid) cell lines, wherein mitochondria and mtDNA from one species were transferred to mitochondria-depleted cells of the other species, creating novel mitonuclear gene combinations while preserving the original diploid nuclear background. Employing a range of techniques - including transcriptomics, metabolomics, microscopy, and respirometry - we explored the consequences of mitochondrial transfer between these hare species. Our results reveal that in the studied species mitonuclear incompatibilities exhibit strong effects on cellular fitness but are limited to specific genotypes. We propose mechanisms of cellular-level incompatibility and their potential consequences for interspecific hybrids, offering new insights into the complexity of mitonuclear interactions.

cell biology↗

bioRxiv2024

Disruptions in Primary Visual Cortex Physiology and Function in a Mouse Model of Timothy Syndrome

Timothy syndrome (TS) is a rare genetic disorder caused by mutations in the CACNA1C gene which encodes the L-type calcium channel -1 CaV1.2 subunit. While it is expressed throughout the body the most serious symptoms are cardiac and neurological. Classical TS1 and TS2 mutations cause prolonged action potentials (APs) in cardiomyocytes and in induced neurons derived from pluripotent stem cells taken from TS patients, but effects of TS mutations on neuronal function in vivo are not fully understood. TS is frequently associated with autistic traits, which in turn have been linked to altered sensory processing. Using the TS2-neo mouse model we analysed effects of the TS2 mutation on the visual system. We observed a widening of APs of pyramidal cells in ex vivo patch-clamp recordings and an increase in the density of parvalbumin positive (PV+) cells in the primary visual cortex. Neurons recorded extracellularly in vivo were less likely to respond to visual stimuli of low spatial frequency, but more likely to respond to visual stimuli of mid-to-high spatial frequency, compared to WT mice. These results point to a basic processing abnormality in the visual cortex of TS2-neo mice.

neuroscience↗

bioRxiv2024

Dissecting the functional heterogeneity of glutamatergic synapses with high-throughput optical physiology

Fluorescent reporters for glutamate release and postsynaptic Ca2+ signaling are essential tools for quantifying synapse functional heterogeneity across neurons and circuits. However, leveraging these probes for neuroscience requires scalable experimental frameworks. Here, we devised a high-throughput approach to efficiently collect and analyze hundreds of optical recordings of glutaamate release activity at presynaptic boutons in cultured rat hippocampal neurons. Boutons exhibited remarkable functional heterogeneity and could be separated into multiple functional classes based on their iGluSnFR3 responses to single action potentials, paired stimuli, and synaptic parameters derived from mean-variance analysis. Finally, we developed a novel all-optical assay of pre- and postsynaptic glutamatergic synapse function. We deployed iGluSnFR3 with a red-shifted, postsynaptically-targeted Ca2+ sensor, enabling direct imaging and analysis of NMDA receptor-mediated synaptic transmission at large numbers of dendritic spines. This work enables direct observation of the flow of information at single synapses and should speed detailed investigations of synaptic functional heterogeneity.

neuroscience↗

bioRxiv2025

Physiologically-relevant light exposure and light behaviour in Switzerland and Malaysia

Light synchronises the internal clock with the external light-dark cycle. Keeping this alignment benefits health and prevents diseases. Quantifying light exposure is, therefore, vital for effective prevention. Since light exposure depends on photoperiod, culture, and behaviour, we investigated objective light exposure and individual light-related behaviour in Switzerland and Malaysia. In this observational field study, participants (N=39) wore a calibrated melanopic light logger at chest level for 30 consecutive days. At baseline and study end, the Pittsburgh Sleep Quality Index was assessed, and every 3 to 4 days, the Light Exposure Behaviour Assessment (LEBA) was filled. Our pre-registered analyses reveal that participants in Switzerland experienced brighter days (+3.16 times the average mel EDI) and spent more time (x1.9 times the duration) in daylight levels per hour of daylight, had [~]1.5h later bright light exposure in the afternoon, and stayed over 1h longer in dim light conditions before bedtime. LEBA scores did not differ between Malaysia and Switzerland, and LEBA items were stable over time. LEBA items also correlated with objective light exposure variables in Switzerland but not Malaysia, with a medium effect size (range of absolute r=0.32-0.48). These results highlight cultural and geographical differences in light exposure. We showed that LEBA can be related to actual light exposure and is ecologically informative, but this varies by culture.

neuroscience↗

bioRxiv2025

Aggregation of HAPLN2, a component of the perinodal extracellular matrix, is a hallmark of physiological brain aging in mice

Protein aggregation is a hallmark of neurodegenerative diseases and is also observed in the brains of elderly individuals without such conditions, suggesting that aging drives the accumulation of protein aggregates. However, the comprehensive understanding of age-dependent protein aggregates involved in brain aging remains unclear. Here, we investigated proteins that become sarkosyl-insoluble with age and identified hyaluronan and proteoglycan link protein 2 (HAPLN2), a hyaluronic acid-binding protein of the extracellular matrix at the nodes of Ranvier, as an age-dependent aggregating protein in mouse brains. Elevated hyaluronic acid levels and impaired microglial function reduced the clearance of HAPLN2, leading to its accumulation. HAPLN2 oligomers induced microglial inflammatory responses both in vitro and in vivo. Furthermore, age-associated HAPLN2 aggregation was also observed in the human cerebellum. These findings suggest that HAPLN2 aggregation results from age-related decline in brain homeostasis and may exacerbate the brain environment by activating microglia. This study provides new insights into the mechanisms underlying cerebellar aging and highlights the role of HAPLN2 in age-associated changes in the brain. Author SummaryTo identify age-dependent protein aggregates unrelated to disease, we analyzed the sarkosyl-insoluble proteome of young and aged mouse brains. We discovered that hyaluronan and proteoglycan link protein 2 (HAPLN2), a hyaluronic acid-binding protein existing in the nodal extracellular matrix, accumulated with age. Age-dependently accumulated HAPLN2 formed large protein aggregates that cannot be solubilized by the anionic detergent sarkosyl or by hyaluronidase digestion. In addition, HAPLN2 formed irregularly shaped puncta that were mislocalized from the nodes of Ranvier in the cerebellar white matter of not only aged mice but also aged human brains. Oligomers of full-length HAPLN2 specifically induced microglial activation in vitro and in vivo. Our findings suggest that the accumulation of HAPLN2 aggregates is a new hallmark of brain aging and a possible factor contributing to brain inflammation.

biochemistry↗

bioRxiv2025

Autoimmune regulator deficiency causes sterile epididymitis and impacts male fertility through disruption of inorganic physiology

Autoimmune regulator (AIRE), a transcription factor expressed by medullary thymic epithelial cells, is required for shaping the self-antigen tolerant T cell receptor repertoire. Humans with mutations in AIRE suffer from Autoimmune Polyglandular Syndrome Type 1 (APS-1). Among many symptoms, men with APS-1 commonly experience testicular insufficiency and infertility, but the mechanisms causing infertility are unknown. Using an Aire-deficient mouse model, we demonstrate that male subfertility is caused by sterile epididymitis characterized by immune cell infiltration and extensive fibrosis. In addition, we reveal that the presence of autoreactive immune cells and inflammation in epididymides of Aire-deficient mice are required for iron (Fe) deposition in the interstitium, which is brought on by macrophages. We further demonstrate that male subfertility is associated with a decrease in metals zinc (Zn), copper (Cu), and selenium (Se) which serve as cofactors in several antioxidant enzymes. We also show increase in DNA damage of epididymal sperm of Aire-/- animals as a key contributing factor to subfertility. The absence of Aire results in autoimmune attack of the epididymis leading to fibrosis, Fe deposition, and Cu, Zn and Se imbalance, ultimately resulting in sperm DNA damage and subfertility. These results highlight the requirement of Aire to promote immune tolerance throughout the epididymis, disruption of which causes an imbalance of inorganic elements with resulting consequence on male fertility. Key pointsBreakdown of epididymal self-tolerance promotes disruption of inorganic elements. Autoimmunity causes interstitial fibrosis resulting in sperm DNA damage and subfertility. Elevated interstitial iron and macrophages contribute to fibrosis.

pathology↗

bioRxiv2025

Arousal State Control of Physiological Human Brain Pulsations

Sleep promotes cerebrospinal fluid (CSF) to interstitial fluid (ISF) exchange in brain facilitated by brain pulsations. Especially brain vasomotion and arterial pulsations modulated by noradrenaline drive the intracranial fluid dynamics. Narcolepsy type 1 (NT1) entails lessened hypocretinergic output to wake-promoting systems including the noradrenergic locus coeruleus. As arousal state and noradrenergic signaling affect CSF-ISF clearance, we chose patients with NT1 as a human hypocretin-targeted model of sleep-related pathology bridging the gap between healthy awake and sleep with respect to CSF flow pulsations. We also investigated the sensitivity of MREG to detect flow with a phantom model and sought to replicate earlier pulsation findings in sleep. In this case-control study, we used fast fMRI to map brain pulsations in groups of healthy sleeping controls (n=13), healthy awake controls (n=79) and awake NT1 (n=21) patients. We measured the very low frequency (0.008-0.1) and cardiorespiratory frequencies and calculated in each frequency band the coefficient of variation, spectral power, and full band spectral entropy to obtain brain pulsation maps. We uncovered a brain pulsation profile from healthy waking to sleep to a sleep-related pathology NT1 prominently affected in the vascular-related vasomotor and brain arterial pulsations. Our results established how drivers of brain hydrodynamics are affected by a specific loss of key neurotransmitter governing arousal compared to healthy sleep. We also showed with a phantom model that MREG is sensitive to flow-related signal changes and solidified evidence of brain pulsations in the healthy states of sleep and wakefulness. Significance statementThis study establishes how a specific depletion of arousal state controlling neurotransmitter hypocretin-1 affects brain fluid dynamics by comparing patients with narcolepsy type 1 (NT1) to healthy wake and sleeping controls. We used fast fMRI to reveal that reduced hypocretinergic activity and following postulated inconsistent noradrenergic signaling in NT1 leads to high vasomotor and low brain arterial pulsations compared to healthy wakefulness while healthy sleep produces brain arterial and respiratory pulsations that dominate over those observed in NT1. The water flow biometrics we verified in this study with a phantom model indicate that deficient hypocretin-noradrenaline axis in humans leads to opposing changes in vasomotor and arterial induced brain pulsation that may propagate to altered glymphatic solute transportation.

neuroscience↗

bioRxiv2025

Global Transcriptomics and Targeted Metabolite Analysis Reveal the Involvement of the AcrAB Efflux Pump in Physiological Functions by Exporting Signaling Molecules in Photorhabdus laumondii

In Gram-negative bacteria, resistance-nodulation-division-type efflux pumps, particularly AcrAB-TolC, play a critical role in mediating resistance to antimicrobial agents and toxic metabolites, contributing to multidrug resistance. Photorhabdus laumondii is an entomopathogenic bacterium that has garnered significant interest due to its production of bioactive specialized metabolites with anti-inflammatory, antimicrobial, and scavenger deterrents properties. In previous work, we demonstrated that AcrAB confers self-resistance to stilbenes in P. laumondii TT01. Here, we explore the pleiotropic effects of AcrAB in this bacterium. RNA sequencing of {Delta}acrA compared to wild-type revealed growth-phase-specific gene regulation, with stationary-phase cultures showing significant downregulation of genes involved in stilbenes, fatty acid, and anthraquinone pigment biosynthesis, as well as genes related to cellular clumping and fimbrial pilin formation. Genes encoding putative LuxR regulators, type VI secretion systems, two-partner secretion systems, and contact dependent growth inhibition systems were upregulated in {Delta}acrA. Additionally, exponential-phase cultures revealed reduced expression of genes related to motility in {Delta}acrA. The observed transcriptional changes were consistent with phenotypic assays, demonstrating that the {Delta}acrA mutant had altered bioluminescence and defective orange pigmentation due to disrupted anthraquinone production. These findings confirm the role of stilbenes as signaling molecules involved in gene expression, thereby shaping these phenotypes. Furthermore, we showed that AcrAB contributes to swarming and swimming motilities independently of stilbenes. Collectively, these results highlight that disrupting acrAB causes transcriptional and metabolic dysregulation in P. laumondii, likely by impeding the export of key signaling molecules such as stilbenes, which may serve as a ligand for global transcriptional regulators. ImportanceRecent discoveries have highlighted Photorhabdus laumondii as a promising source of novel anti-infective compounds, including non-ribosomal peptides and polyketides. One key player in the self-resistance of this bacterium to stilbene derivatives is the AcrAB-TolC complex, which is also a well-known contributor to multidrug-resistance. Here, we demonstrate the pleiotropic effects of the AcrAB efflux pump in P. laumondii TT01, impacting secondary metabolite biosynthesis, motility, and bioluminescence. These effects are evident at transcriptional, metabolic, and phenotypic levels and are likely mediated by the efflux of signaling molecules such as stilbenes. These findings shed light on the multifaceted roles of efflux pumps and open avenues to better explore the complexity of RND pump-mediated signaling pathways in bacteria, thereby aiding combat multidrug resistant infections.

microbiology↗

bioRxiv2025

The Endo-GeneScreen Platform Identifies Drug-Like Probes that Regulate Endogenous Protein Levels within Physiological Contexts

Traditional phenotypic drug discovery platforms have suffered from poor scalability and a lack of mechanistic understanding of newly discovered phenotypic probes. To address this, we created Endo-GeneScreen (EGS), a high-throughput enabled screening platform that identifies bioactive small molecules capable of regulating endogenous protein expression encoded by any preselected target gene within a biologically appropriate context. As a proof-of-concept, EGS successfully identified drug candidates that up-regulate endogenous expression of neuronal Syngap1, a gene that causes a neurodevelopmental disorder when haploinsufficient. For example, SR-1815, a previously unknown and undescribed kinase inhibitor, alleviated major cellular consequences of Syngap1 loss-of-function by restoring normal SynGAP protein levels and dampening neuronal hyperactivity within haploinsufficient neurons. Moreover, we demonstrate that EGS assays accelerate preclinical development of identified drug candidates and facilitate mode-of-action deconvolution studies. Thus, EGS identifies first-in-class bioactive small molecule probes that promote biological discovery and precision therapeutic development.

neuroscience↗

bioRxiv2025

Oocyte exposure to low levels of triclosan has a significant impact on subsequent embryo physiology.

Triclosan (TCS) is an anti-microbial agent in a wide range of health care products. It has been found in various human bodily fluids and is a potential reproductive toxicant. However, the effect of TCS on early embryo development in mammalian species is limited. We therefore asked whether exposure to TCS affects mammalian cumulus-oocyte-complexes (COCs), and if so, whether the effects persist into the early embryo. COCs, isolated from abattoir-derived bovine ovaries were exposed to two environmentally relevant doses of TCS (1 nM and 10 nM) during in vitrao maturation. When exposed to 1 nM TCS during in vitro maturation, progesterone release from bovine oocytes was elevated. Furthermore, altered pyruvate metabolism and mitochondrial dysfunction also observed; specifically, O2 consumption coupled to ATP production was significantly decreased in COCs after acute exposure of TCS prior to maturation, whereas proton leak from the respiratory chain was increased. Subsequently, TCS-exposed COCs were fertilised. Fewer oocytes were able to develop to blastocyst when exposed to 1 nM TCS during maturation compared to the Control group (12.22{+/-}% vs 29.11{+/-}% n=5; p=0.02) and those that did reach the blastocyst displayed impaired glycolytic and amino acid metabolic activity. These findings indicate for the first time that oocytes exposed to TCS during the final stages of maturation give rise to embryos with impaired mitochondria function, altered steroidogenesis and disrupted metabolic activity.

developmental biology↗

bioRxiv2025

Exploring the diversity and physiological characteristics of RubisCO-mediated carbon fixation in culturable prokaryotes

The utilization of microbial resources requires their relevant reproducible characteristics, and genome analysis plays a crucial role in discovering valuable strains for future applications. In this study, we analyzed potential carbon-fixing microorganisms via Calvin-Benson-Bassham (CBB) cycle using 6,262 bacterial and 487 archaeal genomes from available cultures in Japan Collection of Microorganisms (JCM), one of the well-established culture collections today. A total of 306 strains (147 genera, eight phyla) carried CBB cycle genes and a literal survey showed that 74 genera had reported evidence of their autotrophic growth, although 73 lacked supporting information. Phylogenetic analysis of RubisCO large subunit (RbcL) identified diverse forms (IA, IB, IC, IE, I+, II, and III) with distinct metabolic associations: form IA associated with sulfur oxidation and form IC with hydrogen oxidation. Genome-based metabolic predictions suggested potential carbon fixation in numerous strains lacking experimental evidence. Our analyses showed members of Actinomycetota harboring form IE RubisCO tend to associate with hydrogen oxidation possibly using oxygen or nitrate as an electron acceptor. Additionally, 12 strains in Pseudomonadota contained pufL and pufM genes, suggesting possible phototrophic capabilities, although some failed to predict their electron donors and they possibly use CBB cycle to regulate intracellular redox balance under photoheterotrophic growth. Our findings highlight unrecognized autotrophic potentials in JCM strains and expand our knowledge of carbon fixation diversity. Future experimental validation will deepen our understanding of these microbes roles in the global carbon cycle, with potential applications in carbon sequestration and environmental sustainability.

microbiology↗

bioRxiv2025

Physiological mechanisms underlying coral acclimatization capacity to novel, multi-stressor conditions

Reef-building corals are under pressure to acclimatize and/or adapt to multiple co-occurring stressors, including climate change and declines in water quality. However, their capacity to do so is largely unknown. Yet, some corals naturally persist in habitats with multi-stressor conditions which can provide crucial insight into coral adaptive capacity under future ocean conditions. To assess the role of phenotypic plasticity and local adaptation in coral acclimatory responses to novel conditions, we reciprocally transplanted two coral species (Siderastrea siderea, branching Porites) between a multi-stressor, highly variable inland bay and a more stable fringing reef, and measured key phenotypic traits after 0, 4, and 12 months. Reef-origin corals demonstrated high plasticity when transplanted to the bay, as both species maintained high survival and calcification, and matched bay natives phenotypic traits. Yet, both species had reduced photosynthesis-to-respiration ratios, highlighting the risk of metabolic tradeoffs unless compensated for through increased heterotrophy. Conversely, bay-origin corals had enhanced photosynthetic performance but lower calcification on the reef. Reaction norms provided stronger evidence for environmental specialization in bay-origin than reef-origin corals, which could limit their use as stress-tolerant source corals for reef restoration. Overall, our findings suggest multi-stressor variability may promote specialized genotypes, rather than increased phenotypic plasticity.

ecology↗

bioRxiv2025

Candida auris Metabolism and Growth Preferences in Physiologically Relevant Skin-like Conditions

Candida auris is an opportunistic, multidrug-resistant yeast with high capacity of skin colonization in healthcare settings, which can lead to subsequent infections with high mortality rates. Given the recent emergence of at least four distinct clades at the global scale, little remains known about how C. auris is so adept at growing on skin and the key genes and pathways it utilizes to metabolize the scarce nutrients available. Here, we identify the roles that conventional and alternative carbon metabolism genes and metabolic pathways have in facilitating C. auris growth through laboratory-based experiments and bioinformatics analyses. In artificial skin-like media, all four clades of C. auris were more capable of growing than C. albicans SC5314, a clinically relevant counterpart. By investigating the differential regulation of C. auris when growing in skin-like media as compared to rich fungal media, we uncovered hundreds of genes in multiple metabolic pathways. To further test the mechanisms of these metabolic pathways, we deleted several non-essential gene candidates including FOX2 (B9J08_002847), CAT2 (B9J08_000010), and ICL1 (B9J08_003374). The mutant strains all exhibited abrogated growth in skin-like media and demonstrated nutrient preferences that differed from the wild type. Thus, we propose a model of how C. auris has the capacity to metabolize nutrients that are naturally available on skin by changing its metabolic profile. Targeting these metabolic pathways to mitigate C. auris growth on skin is a potential avenue to explore in controlling the spread of this emerging human fungal pathogen. IMPORTANCECandida auris is an emerging fungal pathogen with skin as its primary site of colonization and subsequent transmission. Here, we show the importance of conventional and alternative carbon metabolism for C. auris ability to grow in artificial skin-like media. This knowledge provides a better understanding of C. auris metabolism and sheds light on genes and pathways that could be targeted to interfere with persistent skin colonization.

microbiology↗

bioRxiv2025

Prevalence of sympathetic fibers within the rat cervical vagus, and functional consequence on physiological effects mediated by vagus nerve stimulation (VNS).

IntroductionElectrical stimulation of the vagus nerve (VNS) is an FDA approved therapy for epilepsy, depression and rehabilitation after stroke, with recent clinical trials to treat heart failure and inflammation. VNS is often assumed to activate either parasympathetic efferents projecting to visceral organs, and/or sensory afferents projecting from these organs, for its therapeutic effects. Recent studies in humans, swine and dogs have shown that sympathetic nerve fibers from the sympathetic trunk (ST) can frequently be found within the cervical vagus nerve (VN). However, the prevalence and functional consequence of sympathetic fibers on VNS have yet to be elucidated in the most common high throughput animal model to study disease, the rodent. MethodsWe carefully traced ST from sympathetic cervical ganglion (SCG) to find its location in the carotid sheath with reference to the VN in a cohort of Long Evans rats. We then assessed the prevalence of ST fibers with the cervical VN across the cohort using microCT and immunohistochemistry. Finally, we stimulated the VN and the ST in isolation, and where they were conjoined, to evaluate the ST contribution to changes in heart rate. VNS induced heart rate changes are a commonly used surrogate for changes in sympathetic/parasympathetic tone. ResultsThe ST frequently runs in very close proximity to the VN in rats when traced caudally from the SCG. The ST is even conjoined with the VN for stretches within the carotid sheathe at the most common location to place an epineural cuff. Cross-connecting branches were found between the ST and the VN. VNS performed at locations where there was minimal ST crossover induced dose-dependent bradycardia (decrease in heart rate) across the cohort, with detectable bradycardia across the cohort beginning at 50 A (n=8 right, n=3 left). Conversely, stimulation of the isolated ST induced tachycardia (increase in heart rate) across the cohort beginning at [~]200 A (n=7 right, n=3 left). ConclusionThese data suggest that studies of VNS in the rodent model may also be stimulating sympathetic fibers from the ST in addition to canonical VN pathways. Concurrent sympathetic activation has profound implications for dissecting mechanisms of VNS for a host of diseases/disorders. As such, careful post-mortem assessment of the presence of hitchhiking sympathetic fibers within the VN is critical for understanding sources of variability in VNS outcomes.

neuroscience↗

bioRxiv2025

A Minimal Physiological Model of Perceptual Suppression and Breakthrough in Visual Rivalry

Visual rivalry paradigms provide a powerful tool for probing the mechanisms of visual awareness and perceptual suppression. While the dynamics and determinants of perceptual switches in visual rivalry have been extensively studied and modeled, recent advances in experimental design - particularly those that quantify the depth and variability of perceptual suppression - have outpaced the development of computational models. Here we extend an existing dynamical model of binocular rivalry to encompass two novel experimental paradigms: a threshold detection variant of binocular rivalry, and tracking continuous flash suppression. Together, these tasks provide complementary measures of the dynamics and magnitude of perceptual suppression. Through numerical simulation we demonstrate that a single mechanism, competitive (hysteretic) inhibition between slowly adapting monocular populations, is sufficient to account for the suppression depth findings across both paradigms. This unified model offers a foundation for the development of a quantitative theory of perceptual suppression in visual rivalry.

neuroscience↗