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 Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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At least 217 records · Page 12Linked to original sources

bioRxiv2021

Key metabolic pathways involved in seed primary physiological dormancy maintenance of Korean pine seed

The metabolic changes that occurred during either cold stratification or after-ripen treatment, and in both dormant seeds and after-ripened seeds either under the dry state or during imbibition have been extensively explored. Much less is known about those present in both dormant seeds and cold stratified seeds during the same period of incubation under favorable germination conditions. Metabolite composition was investigated in both embryo and megagametophyte of primary physiological dormant seeds (PPDS) of Pinus Koreansis collected at 0 week, 1 week, 2 weeks, 4 weeks and 6 weeks of incubation, and of cold stratified seeds with released primary physiological dormancy (RPPDS) sampled at 0 week and 1 week of incubation, seed coat rupture stage and radicle protrusion stage. Embryo contained higher levels of most metabolites compared to megagametophyte. Strong metabolic changes occurred at 1 week and 4 weeks of incubation in PPDS, with most metabolites were significantly accumulated in 4-weeks-incubated PPDS. A larger metabolic switch was found in RPPDS between 1-week-incubation and seed coat rupture stage. Especially, there was a significant major decrease in the relative levels of most phosphorylated sugars and amino acids. The carbohydrate metabolism, especially pentose phosphate pathway and tricarboxylic acid cycle were more active pathways in the embryos of 4-weeks-incubated PPDS, but the operation rate of most amino acid metabolism was lower compared to 1-week-incubated RPPDS. We suggest that a larger metabolic switch in the embryo of PPDS after 4 weeks of incubation may assist in maintaining primary dormancy. One-sentence summaryA larger metabolic switch in dormant seeds after 4 weeks of incubation under favorable conditions for germination may maintain primary physiological dormancy of Korean pine seeds.

physiology↗

bioRxiv2023

Corticosterone exposure causes long-term changes in DNA methylation, physiology, and breeding decisions in a wild bird.

When facing challenges, vertebrates activate an evolutionarily conserved hormonal stress response that can dramatically alter behavior and physiology. Although this response can be costly, conceptual models suggest that it can also recalibrate the stress response system, priming more effective responses to future challenges. Little is known about whether this process occurs in wild animals, particularly in adulthood, and if so, how information about prior experience with stressors is encoded. One potential mechanism is hormonally-mediated changes to DNA methylation. We simulated the spikes in corticosterone that accompany an acute stress response using non-invasive dosing in female tree swallows (Tachycineta bicolor) and monitored the phenotypic effects one year later, and DNA methylation both shortly after treatment and a full year later. The year after treatment, experimental females had stronger negative feedback and initiated breeding earlier - traits that are associated with stress resilience and reproductive performance in our population - and higher baseline corticosterone. We also found that natural variation in stress-induced corticosterone predicted patterns of DNA methylation, including methylation of the MC2R gene, which encodes the adrenocorticotropic hormone receptor. Finally, corticosterone treatment causally influenced methylation on short (1-2 weeks) and long (1 year) time scales; however, many of these changes did not have clear links to functional regulation of the stress response. Taken together, our results are consistent with corticosterone-induced priming of future stress resilience, and support DNA methylation as a potential mechanism. Uncovering the mechanisms linking experience with the response to future challenges has implications for understanding the drivers of stress resilience. SIGNIFICANCEA stress response to an environmental challenge can preserve an individuals fitness and may even prime them to survive similar challenges in the future. What mechanisms underlie priming is unclear, but epigenetic alterations to stress-related genes are one possibility. We experimentally tested whether increasing corticosterone in free-living swallows had lasting phenotypic or epigenetic effects. A year after treatment, females who received corticosterone had altered stress physiology and bred earlier than control birds, traits that are associated with higher fitness. Treatment also altered DNA methylation and methylation of the MC2R gene was correlated with stress physiology. This study adds to a growing body of literature suggesting that epigenetic changes are key to animals response to a changing environment.

physiology↗

bioRxiv2023

A Genetically Encoded Actuator Selectively Boosts L-type Calcium Channels in Diverse Physiological Settings

L-type Ca2+ channels (CaV1.2/1.3) convey influx of calcium ions (Ca2+) that orchestrate a bevy of biological responses including muscle contraction and gene transcription. Deficits in CaV1 function play a vital role in cardiac and neurodevelopmental disorders. Yet conventional pharmacological approaches to upregulate CaV1 are limited, as excessive Ca2+ influx leads to cytotoxicity. Here, we develop a genetically encoded enhancer of CaV1.2/1.3 channels (GeeC) to manipulate Ca2+ entry in distinct physiological settings. Specifically, we functionalized a nanobody that targets the CaV macromolecular complex by attaching a minimal effector domain from a CaV enhancer--leucine rich repeat containing protein 10 (Lrrc10). In cardiomyocytes, GeeC evoked a 3-fold increase in L-type current amplitude. In neurons, GeeC augmented excitation-transcription (E-T) coupling. In all, GeeC represents a powerful strategy to boost CaV1.2/1.3 function in distinct physiological settings and, in so doing, lays the groundwork to illuminate new insights on neuronal and cardiac physiology and disease.

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bioRxiv2023

Physiological Profiles of Male and Female CrossFit Athletes

ObjectiveTo 1) establish extensive physiological profiles of highly-trained CrossFit athletes using gold-standard tests and 2) investigate which physiological markers best correlate with CrossFit(R) Open performance. MethodsThis study encompassed sixty participants (30 males and 30 females), all within the top 5% of the CrossFit(R) Open, including 7 CrossFit(R) Semi-finalists and 3 Games finalists. Isokinetic dynamometers were employed to measure maximum isometric and isokinetic leg and trunk strength. Countermovement jump height and maximum isometric mid-thigh pull strength were assessed on a force plate. V{square}O2peak was measured by a cardiopulmonary exercise test, while critical power and W were evaluated during a 3-minute all-out test, both on a cycle ergometer. ResultsMale and female athletes median (IQR) V{square}O2peak was 4.64 (4.43, 4.80) and 3.21 (3.10, 3.29) (L{middle dot}min-1), critical power 314.5 (285.9, 343.6) and 221.3 (200.9, 238.9) (W) and mid-thigh pull 3158 (2690, 3462) and 2035 (1728, 2347) (N). Linear regression analysis shows strong evidence for associations between different anthropometric variables and CrossFit(R) Open performance in men and women, whereas for markers of cardiorespiratory fitness such as V{square}O2peak this was only true for women but not men. Conventional laboratory evaluations of strength, however, manifest minimal evidence for associations with Open performance across both sexes. ConclusionsThis study provides the first detailed insights into the physiology of high-performing CrossFit(R) athletes and informs training optimization. Further the results emphasize the advantage of athletes with shorter limbs and suggests potential modifications to Open workout designs to level the playing field for athletes across different anthropometrics characteristics.

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bioRxiv2023

Comparative phenotyping of mice reveals canonical and noncanonical physiological functions of TRα and TRβ

Thyroid hormone (TH) effects are mediated through TH receptors (TRs) TR1, TR{beta}1, and TR{beta}2. The TRs bind to thyroid hormone responsive elements on the DNA and regulate expression of TH target genes as ligand dependent transcription factors (canonical signaling). In addition, the TRs and {beta} mediate activation of signaling pathways, e.g. the PI3K/AKT and MAPK/ERK pathways (noncanonical signaling). Whether such DNA-binding independent TR action contributes to the spectrum of physiological TH effects is largely unknown. The aim of this study was to attribute physiological effects to the two TR isoforms and {beta} and their canonical and noncanonical signaling. We conducted multi-parameter phenotyping in male and female TR knockout mice (TRKO, TR{beta}KO), mice with disrupted canonical signaling due to a mutation in the TR DNA-binding domain (TRGS, TR{beta}GS) and their respective wild-type littermates. Perturbations in senses, especially hearing (mainly TR{beta} with a lesser impact of TR), visual acuity and retinal thickness (TR and TR{beta}), in muscle metabolism (TR) and in heart rate (TR) highlighted the role of canonical TR action. Strikingly, selective abrogation of canonical TR action often had little to no phenotypic consequence, suggesting that noncanonical TR action sufficed to maintain the wild-type phenotype for specific effects. For instance, macrocytic anemia, reduced retinal vascularization or increased anxiety related behavior were only observed in TRKO, but not TRGS mice. Noncanonical TR action increased the efficiency of energy utilization and prevented hyperphagia observed in TRKO mice. In summary, by examining the phenotypes of TR and TR{beta} knockout models alongside their DNA-binding-deficient GS mutants and wildtype counterparts, we could establish that the independent noncanonical actions of TR and TR{beta} play a crucial role in modulating sensory, behavioral, and metabolic functions. This comparison underscores the significance of the TRs in orchestrating a spectrum of physiological processes beyond their traditional genomic pathways.

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bioRxiv2024

The deep-sea ecosystem engineer Geodia barretti (Porifera, Demospongiae) maintains basic physiological functions under simulated future ocean pH and temperature conditions

Global ocean warming and acidification will alter the physicochemical conditions in the deep North-Atlantic Ocean. Here, extensive sponge grounds, often dominated by the demosponge species Geodia barretti, provide three-dimensional structure, habitat and significantly contribute to benthic-pelagic coupling and nutrient cycling processes in the deep sea. It is unknown if G. barretti remains physiologically functional under the future physicochemical properties of an Anthropocene ocean. In this study, individuals of G. barretti collected from 300 m water depth in the Barents Sea, were exposed to four treatments resembling future ocean conditions (no treatment, 4 {degrees}C increase in seawater temperature, decrease of seawater pH by 0.3, and a combination of the high temperature, low pH). Over the course of 39 weeks, oxygen consumption, dissolved inorganic nutrient fluxes, and bacterioplankton clearance rates were measured as indicators of metabolic activity. We found that all indicators within each sponge individual and per treatment were highly variable over time and no effect of manipulated seawater treatments on these parameters could be demonstrated. Oxygen consumption rates in all groups closely followed a seasonal pattern, potentially caused by (a)biotic cues in the seawater flowing through the experimental aquaria. While similar metabolic rates across all treatments suggest that G. barretti physiologically coped with simulated future ocean conditions, observed tissue necrosis in experimental animals might indicate that the response of the complex, high microbial G. barretti sponge (i.e., sponge host and microbial symbionts) to future ocean conditions may not be reflected in basic physiological processes.

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bioRxiv2024

Molecular characterization, localization, and physiological roles of ITP and ITP-L in the mosquito, Aedes aegypti

The insect ion transport peptide (ITP) and its alternatively spliced variant, ITP-like peptide (ITP-L), belong to the crustacean hyperglycemic hormone family of peptides and are widely conserved among insect species. While limited, studies have characterized the ITP/ITP-L signaling system within insects, and putative functions including regulation of ion and fluid transport, ovarian maturation, and thirst/excretion have been proposed. Herein, we aimed to molecularly investigate Itp and Itp-l expression profiles in the mosquito Aedes aegypti, examine peptide immunolocalization and distribution within the adult central nervous system, and elucidate physiological roles for these neuropeptides. Transcript expression profiles of both AedaeItp and AedaeItp-l revealed distinct enrichment patterns in adults, with AedaeItp expressed in the brain and AedaeItp-l expression predominantly within the abdominal ganglia. Immunohistochemical analysis within the central nervous system revealed expression of AedaeITP peptide in a number of cells in the brain and in the terminal ganglion. Comparatively, AedaeITP-L peptide was localized solely within the pre-terminal abdominal ganglia of the central nervous system. Interestingly, prolonged desiccation stress caused upregulation of AedaeItp and AedaeItp-l levels in adult mosquitoes, suggesting possible functional roles in water conservation and feeding-related activities. RNAi-mediated knockdown of AedaeItp caused an increase in urine excretion, while knockdown of both AedaeItp and AedaeItp-l reduced blood feeding and egg-laying in females as well as hindered egg viability, suggesting roles in reproductive physiology and behaviour. Altogether, this study identifies AedaeITP and AedaeITP-L as key pleiotropic hormones, regulating various critical physiological processes in the disease vector, A. aegypti.

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bioRxiv2024

Genome composition predicts physiological response to environmental change in polyploid salamanders

Multi-trait analyses can be used to measure the differential performance of phenotypic traits in species complexes. Hybridization within these complexes can result in a mismatch between mitochondrial and nuclear DNA that may lead to reduced performance and acclimation capacity in hybrids. To test the effect of this mismatch on physiology, we compared physiological performance and acclimation capacity of metabolic rate (VCO2) and total resistance to water loss (rT) between two sexual Ambystoma species and a closely related unisexual lineage. We also separated unisexuals by their unique biotypes to determine how physiology varies with subgenomic composition. We found that unisexual biotypes exhibited phenotypes more like their related sexual species than to other unisexuals. We also found a trade-off between rT and VCO2, with increasing rT resulting in a decrease in VCO2. Although we did not find evidence for mitonuclear mismatch, our results indicate that genomic composition of hybrids may be a suitable predictor of hybrid trait performance. Multi-trait analyses are imperative for understanding variation in phenotypic diversity, providing insight into how this diversity affects species responses to environmental change.

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bioRxiv2025

Deep learning approach to parameter optimization for physiological models

The inference of nonlinear dynamics and parameters in biological data modeling is challenging. Conventional methodologies, based on hypothetical underlying mechanisms, complicate inference because standard parameter optimization methods are difficult to constrain to biological ranges. Here, we propose a novel method to evaluate and improve putative models using neural networks to simultaneously address biological modeling, parametrization, and parameter inference. As an example, utilizing data from clinical frequently sampled intravenous glucose tolerance testing, we introduce two physiological lipolysis models (with parameters) of the dynamics of glucose, insulin, and free fatty acids (FFA). Parameter values are obtained via optimization from the limited clinical data. We then generate large quantities of simulated data from the model by sampling parameters within physiological ranges. A convolutional neural network is trained to take the simulated data time courses of glucose, insulin, and FFA as input and output the model parameters. The performance of the trained neural network is evaluated for both parameter inference and reconstruction of trajectories over a testing dataset and from optimized model-fitting curves. We show that our methodology enables accurate parameter inference and trajectory reconstruction over the testing dataset and optimized model-fitting curves. The trained neural network produces consistently high R2 values and low p-values across different feature engineering strategies and training dataset sizes. We assess the impact of feature engineering choices and training dataset size on inference performance, demonstrating that appropriately designed feature transformations and certain activation function improve accuracy. Our results establish a deep learning framework for parameter inference in mathematical models, which can be adapted to various physiological systems.

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bioRxiv2025

A physiology-based mathematical model of the renin-angiotensin system, bone remodeling, and calcium homeostasis: Effects of estrogen and renin-angiotensin system inhibitors

During menopause, estrogen levels decline significantly, leading to substantial physiological changes due to estrogens regulatory role in various systems. In particular, estrogen helps prevent excessive bone resorption by its impact on bone remodeling. When estrogen levels decrease, bone resorption increases, often resulting in weakened bones and osteoporosis in post-menopausal women. Experimental studies have also shown that estrogen regulates the renin-angiotensin system (RAS), a hormone system involved in many physiological processes, including blood pressure regulation. Additionally, the RAS has an interconnected relationship with calcium regulatory and bone remodeling systems. Given these dynamic interplays, how would perturbations in one system affect the others? To answer that question, we developed a physiology-based mathematical model that simulates the interactions of estrogen, key RAS components, calcium regulation, and bone remodeling. Through sensitivity analysis and model simulations, we investigated how declining estrogen levels affect the RAS and bone mineral density. Furthermore, we quantified how RAS inhibitors, specifically angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, may increase bone density during post-menopausal estrogen decline.

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bioRxiv2025

A method for analyzing physiological data with multiple non-independent observations

Physiological studies often involve recording multiple observations (e.g., repeated muscle contractions or cardiac cycles) from the same subject. To compare groups of subjects, observations from one subject are then sometimes pooled with observations from other subjects in the same group, and analyses are performed on these pooled data. This approach presents a number of potential problems, including over-or under-representing certain subjects in the sample and non-independence of measurements. There are statistical methods available to deal with repeated measures, but many make assumptions about the distribution and completeness of data. Instead, we developed a method to deal with multiple observations from physiological data that ensures that each subject is represented only once in the analysis (i.e. it avoids pseudoreplication), and makes no assumptions about the distribution of the data. We demonstrate this method using two different physiological datasets: (1) muscle recordings taken from Drosophila melanogaster larvae during fictive crawling, and (2) electrocardiogram recordings taken from human volunteers before, during, and after exercise. Our results show the broad applicability and validity of this method.

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bioRxiv2025

A decision matrix to better identify repeatable physiological variation within individuals

The performance of an individual has remained at the heart of evolutionary biology since the time of Darwin. Physiologists are equally drawn to the implications of individual variation for health and sporting endeavours, and specifically, whether or not a physiological trait is repeatable within an individual. Experimental biologists are especially interested in temporally stable physiological traits that are relevant to an individuals lifetime fitness for natural selection to act upon. Experimental noise, however, confounds the measurement of such repeatability, even though validated protocols exist for measuring many meaningful physiological performance traits. Missing is a decision matrix that helps distinguish individual variation from experimental noise. We propose a precision-&-repeatability assessment matrix (PRAM) that integrates established assessments of individual variability and repeatability. This matrix places metrics that are more repeatable and precise in the quadrant closest to the origins of Cartesian coordinates; those farthest away are less acceptable in terms of both repeatability and precision. As a case study, PRAM is applied to whole-organism aerobic and non-aerobic metabolic performance metrics from fish that were measured with the same protocols. The analysis illustrates that aerobic metabolic metrics can be more repeatable and precise than non-aerobic ones. Consequently, PRAM helps physiologists to better understand whether the observed variability is due to non-repeatable metrics or true individual variation.

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bioRxiv2017

Detecting pathogen exposure during the non-symptomatic incubation period using physiological data

Early pathogen exposure detection allows better patient care and faster implementation of public health measures (patient isolation, contact tracing). Existing exposure detection most frequently relies on overt clinical symptoms, namely fever, during the infectious prodromal period. We have developed a robust machine learning based method to better detect asymptomatic states during the incubation period using subtle, sub-clinical physiological markers. Starting with high-resolution physiological waveform data from non-human primate studies of viral (Ebola, Marburg, Lassa, and Nipah viruses) and bacterial (Y. pestis) exposure, we processed the data to reduce short-term variability and normalize diurnal variations, then provided these to a supervised random forest classification algorithm and post-classifier declaration logic step to reduce false alarms. In most subjects detection is achieved well before the onset of fever; subject cross-validation across exposure studies (varying viruses, exposure routes, animal species, and target dose) lead to 51h mean early detection (at 0.93 area under the receiver-operating characteristic curve [AUCROC]). Evaluating the algorithm against entirely independent datasets for Lassa, Nipah, and Y. pestis exposures un-used in algorithm training and development yields a mean 51h early warning time (at AUCROC=0.95). We discuss which physiological indicators are most informative for early detection and options for extending this capability to limited datasets such as those available from wearable, non-invasive, ECG-based sensors.

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bioRxiv2018

Physiologically driven, altitude-adaptive model for the interpretation of pediatric oxygen saturation at altitudes above 2000 m a.s.l.

Measuring peripheral oxygen saturation (SpO2) with pulse oximeters at the point of care is widely established. However, since SpO2 is dependent on ambient atmospheric pressure, the distribution of SpO2 values in populations living above 2000 m a.s.l. is largely unknown. Here, we propose and evaluate a computer model to predict SpO2 values for pediatric permanent residents living between 0 and 4000 m a.s.l. Based on a sensitivity analysis of oxygen transport parameters, we created an altitude-adaptive SpO2 model that takes physiological adaptation of permanent residents into account. From this model, we derived an altitude-adaptive abnormal SpO2 threshold using patient parameters from literature. We compared the obtained model and threshold against a previously proposed threshold derived statistically from data and two empirical datasets independently recorded from Peruvian children living at altitudes up to 4100 m a.s.l. Our model followed the trends of empirical data, with the empirical data having a narrower healthy SpO2 range below 2000 m a.s.l., but the medians did never differ more than 2.29% across all altitudes. Our threshold estimated abnormal SpO2 in only 17 out of 5981 (0.3%) healthy recordings, whereas the statistical threshold returned 95 (1.6%) recordings outside the healthy range. The strength of our parametrised model is that it is rooted in physiology-derived equations and enables customisation. Furthermore, as it provides a reference SpO2, it could assist practitioners in interpreting SpO2 values for diagnosis, prognosis, and oxygen administration at higher altitudes.\n\nNew & NoteworthyOur model describes the altitude-dependent decrease of SpO2 in healthy pediatric residents based on physiological equations and can be adapted based on measureable clinical parameters. The proposed altitude-specific abnormal SpO2 threshold might be more appropriate than rigid guidelines for administering oxygen that currently are only available for sea level patients. We see this as a starting point to discuss and adapt oxygen administration guidelines.

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bioRxiv2019

Agronomic, physiological and molecular characterization of rice mutants revealed key role of ROS and catalase in high temperature stress tolerance

Plants adapt to harsh environments particularly high temperature stress by regulating their physiological and biochemical processes, which are key tolerance mechanisms. Thus, identification of heat-tolerant rice genotypes and reliable selection indices are crucial for rice improvement programs. Here, we evaluated the response of a rice mutant population for high-temperature stress at the seedling and reproductive stages based on agronomic, physiological and molecular traits. The estimate of variance components revealed significant differences (P<0.001) among genotypes, treatments and their interaction for almost all traits. Principal component analysis showed significant diversity among the genotypes and traits under high-temperature stress. The mutant HTT-121 was identified as the most heat tolerant mutant with higher grain yield, panicle fertility, cell membrane thermo-stability (CMTS) and antioxidant enzyme levels under heat stress conditions. Various seedling-based morpho-physiological traits (leaf fresh weight, relative water contents, malondialdehyde, CMTS) and biochemical traits (superoxide dismutase, catalase and hydrogen peroxide) explained variations in grain yield that could be used as selection indices for heat tolerance in rice at early growth stages. Notably, heat sensitive mutants showed a significant accumulation of ROS level, reduced activities of catalase and upregulation of OsSRFP1 expression under heat stress, suggesting their key role in regulating heat tolerance in rice. The heat-tolerant mutants identified in this study could be used in breeding programs and the development of mapping populations to unravel the underlying genetic architecture for heat-stress adaptability.\n\nSummary text for table of contentsHeat stress probably due to changing climate scenario has become a serious threat for global rice production. On the other side, efforts to develop high yielding cultivars have led to the reduced genetic variability to withstand harsh environmental conditions. This study aimed to identify novel heat tolerant mutants developed through gamma irradiation which will provide a unique genetic resource for breeding programs. Further, we have identified reliable selection indices for screening heat-tolerant rice germplasm at early growth stages.

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bioRxiv2019

The choreography of human attraction: physiological synchrony in a blind date setting

Humans are social animals whose mental wellbeing is shaped by the ability to attract and connect with each other. In a dating world, in which success can be determined by brief interactions, apart from physical features, there is a whole choreography of movements, physical reactions and subtle expressions that drive humans sexual attraction. To determine what drives attraction, we measured nonverbal dynamics between people during real-life interactions outside the laboratory, where dating is most relevant. Participants wore eye-tracking glasses with embedded cameras, and devices to measure physiological signals including heart rate and skin conductance. Crucially, visible signals that can be controlled, such as facial expressions or gaze, did not predict attraction. Instead, attraction was predicted by synchrony in heart rate and skin conductance between partners, which are unconscious and difficult to regulate. Our findings suggest that shared emotionality is vital for mutual attraction. Moreover, physiological synchrony may provide a medium for translating visible expressions into embodied emotions, which can turn into intentions via somatosensory simulation. Significance StatementIn our modern world where millions of people meet online without interacting face-to-face, the question "what defines attraction" has become very relevant. In this study, we used modern technologies to lay down a foundation for the processes that drive human attraction during real-life interactions. Contrary to common belief, we found that attraction is not predicted by a frequency of expression or eye fixation duration, nor is linearly related to the participants autonomic nervous system activity. Importantly, we found that the more a participant synchronized their heart rate and skin conductance with their partner, the more they felt attracted toward that person. This study reveals a fundamental physiological process that plays a role in the formation of romantic relations.

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bioRxiv2019

The impact of pH on Clostridioides difficile sporulation and physiology

Clostridioides difficile is a pathogenic bacterium that infects the human colon to cause diarrheal disease. Growth of the bacterium is known to be dependent on certain bile acids, oxygen levels and nutrient availability in the intestine, but how the environmental pH can influence C. difficile is mostly unknown. Previous studies indicated that C. difficile modulates the intestinal pH, and prospective cohort studies have found a strong association between a more alkaline fecal pH and C. difficile infection. Based on these data we hypothesized that C. difficile physiology can be affected by various pH conditions. In this study, we investigated the impact of a range of pH conditions on C. difficile to assess potential effects on growth, sporulation, motility and toxin production in the strains 630{triangleup}erm and R20291. We observed pH-dependent differences in sporulation rate, spore morphology and viability. Sporulation frequency was lowest under acidic conditions, and differences in cell morphology were apparent at low pH. In alkaline environments, C. difficile sporulation was greater for strain 630{triangleup}erm, whereas R20291 produced relatively high levels of spores in a broad range of pH conditions. Rapid changes in pH during exponential growth impacted sporulation similarly among the strains. Furthermore, we observed an increase in C. difficile motility with increases in pH, and strain-dependent differences in toxin formation under acidic conditions. The data demonstrate that pH is an important parameter that affects C. difficile physiology and may reveal relevant insights into the growth and dissemination of this pathogen.\n\nIMPORTANCEClostridioides difficile is an anaerobic bacterium that causes gastrointestinal disease. C. difficile forms dormant spores, which can survive harsh environmental conditions, allowing their spread to new hosts. In this study, we determine how intestinally relevant pH conditions impact C. difficile physiology in the two divergent strains, 630{triangleup}erm and R20291. Our data demonstrate that low pH conditions reduce C. difficile growth, sporulation, and motility. However, toxin formation and spore morphology are differentially impacted in the strains at low pH. In addition, we observed that alkaline environments reduced C. difficile growth, but increased cell motility. When pH was adjusted rapidly during growth, we observed similar impacts on both strains. This study provides new insights into the phenotypic diversity of C. difficile grown under the diverse pH conditions present in the intestinal tract, and demonstrates similarities and differences in the pH responses of different C. difficile isolates.

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bioRxiv2019

Life out of water: Genomic and physiological mechanisms underlying skin phenotypic plasticity

The Devonian radiation of vertebrates from aquatic into terrestrial habitats required behavioral, physiological, and morphological adaptations. Changes to skin structure and function were likely crucial, but adaptations were needed to resolve contrasting demands of maintaining a mechanical and physiological barrier while also facilitating ion and gas transport. Little is known of the mechanisms that underlie skin plasticity and adaptation between water and air. We performed experiments using two isogenic lineages of an amphibious killifish (Kryptolebias marmoratus from brackish and freshwater habitats) and used transcriptional and morphological data to reveal mechanisms recruited to resolve the dual challenges of skin providing both a barrier and an exchange interface during terrestrial acclimation. Transcriptional regulators of skin morphogenesis were quickly activated upon emersion. Regulation of cell-cell adhesion complexes, coupled with pathways homologous with those that regulate stratum corneum formation, was consistent with barrier function and mechanical reinforcement. Cutaneous respiration was associated with regulation of angiogenesis pathways and with blood vessel architecture that facilitated extremely short diffusion distances and direct delivery to ionocyotes. Evolutionary analyses revealed directional selection operating on proteins involved in barrier and respiratory functions, reinforcing the importance of these mechanisms for enabling the amphibious lifestyle of K. marmoratus. Fish from brackish niches were more resilient to emersion and also differed from freshwater fish in ionoregulatory responses to emersion. We conclude that plasticity of barrier, respiratory, and ionoregulatory functions in skin evolved to support the amphibious lifestyle of K. marmoratus; similar processes may have facilitated the terrestrial radiation of ancient fishes.\n\nSignificance statementThe transition of vertebrate life from water to land coincided with solving multiple physiological challenges including avoiding drying out while also exchanging gases and ions with the environment. Though changes in the skin were likely important, little is known of the mechanisms that underlie skin flexibility and adaptation between water and air. We performed air exposure experiments with an amphibious killifish; gene expression profiling, microscopy, and evolutionary analysis of proteins revealed cell structures, proteins, and molecular pathways that support skin flexibility and adaptations during air exposure, and ion regulation contributed to differences in killifish abilities to adjust to air. Amphibious killifish are useful models to help us understand changes that enable water to air transitions in contemporary and ancient fishes.

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