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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 Read source abstracts and check manuscript versions; preprints are not peer reviewed.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 595 records · Page 33Linked to original sources

bioRxiv2023

Automatic sleep stage classification using physiological signals acquired by Dreem headband

In this paper, we aim to propose a model for automatic sleep stage classification based on physiological signals acquired by Dreem Headband and extreme gradient boosting (XGBoost) method. The dataset used in this study belongs to a challenge competition, namely as "Challenge Data", held in 2017-2018, and is publicly available on their website. Recordings, includes 4 EEG channels (FpZ-O1, FpZ-O2, FpZ-F7, F8-F7), 2 Pulse oximeter (RED & infra-red), and 3 accelerometer channels (X, Y, Z). In this work, sleep stages have been scored according to the AASM standard. Different features were extracted from the physiological signals after applying a preprocessing step. Each of the elicited features from EEG and PPG signals is falling into one of the three categories: time-domain, frequency domain, or non-linear features. Moreover, ancillary features including body movement, frequency features, breathing frequency, and respiration rate variability were also extracted from the accelerometer signal. Significance of the extracted features was examined through the Kruskal Wallis test, and features with P-value>0.01 were discarded from features set. Finally, significant features were classified by using support vector machine (SVM), K-nearest neighbors (KNN), random forest (RF), and XGBoost classifiers. Due to the class imbalance problem, repeated stratified 5-fold cross-validation was performed in order to tune systems parameters. Results show that among the four above-mentioned models, XGBoost has the best performance for the 5-class classification problem with accuracy: 81.34%{+/-}0.76% and Kappa 0.7388{+/-}0.0101. The proposed model shows promising results, therefore the model can be implemented in Dreem headband to differentiate between sleep states efficiently and be applicable in clinical trial.

bioengineering↗

bioRxiv2023

Zaxinone Synthase overexpression modulates rice physiology and metabolism, improving growth and productivity under normal and low phosphate supply

The rice Zaxinone Synthase (ZAS) gene encodes a carotenoid cleavage dioxygenase (CCD) that forms the apocarotenoid growth regulator zaxinone. Here, we generated and characterized constitutive ZAS-overexpressing rice lines, to better understand ZAS role in determining zaxinone content and regulating growth and architecture. ZAS overexpression enhanced endogenous zaxinone level, promoted root growth and meristem size, and increased the number of productive tillers, leading to an up to 30% higher grain yield per plant. Hormone analysis revealed a decrease in strigolactone (SL) content, which we confirmed by rescuing the high-tillering phenotype through application of a SL analog. Metabolomics analysis revealed that ZAS overexpressing plants accumulate higher amounts of monosaccharide sugars, in line with transcriptome analysis. Moreover, transgenic plants showed higher carbon (C) assimilation rate and elevated root phosphate, nitrate and sulfate level, enhancing the tolerance towards low phosphate (Pi) and indicating a generally better nutrient uptake. Our study shows that ZAS regulates hormone homeostasis and a combination of physiological processes to promote growth and grain yield, which makes this gene an excellent candidate for sustainable crop improvement. TeaserZaxinone Synthase overexpression modulates rice metabolism and physiology and improves growth and phosphate uptake.

plant biology↗

bioRxiv2023

Maize (Zea mays L.) interaction with the arbuscular mycorrhizal fungus Rhizophagus irregularis allows mitigation of nitrogen deficiency stress: physiological and molecular characterization

Maize is currently the most productive cereal crop in the world (www.faostat.org). Maize can form a symbiotic relationship with the Arbuscular Mycorrhizal Fungus (AMF), Rhizophagus irregularis. In this relationship, the fungus provides the plant with additional water and mineral nutrients, while the plant supplies carbon compounds to the fungus. Little is known about the N metabolism disruption during symbiosis in both partners. To address this issue, two genetically distant maize lines were studied in terms of physiological and molecular responses to AMF inoculation by dual RNA-seq, metabolomics and phenotyping. Interestingly, the beneficial effects of the AMF were observed mainly under conditions of limited N fertilization. Under such conditions, the AMF helped maintain plant biomass production. The availability of nitrogen was found to be a crucial factor influencing all the traits studied showing that the level of N supply plays a pivotal role in determining how maize plants interact with the AMF. Despite the two maize lines showing different transcriptomic and metabolomic responses to R. irregularis, their agro-physiological traits remained similar. Both the plant and fungal transcriptomes were more significantly influenced by the level of N nutrition rather than the specific maize genotype. This suggests that N availability has a more profound impact on gene expression in both organisms than the genetic makeup of the maize plant. To understand the metabolic implications of this symbiotic relationship, we integrated transcriptomic data into our recently built multi-organ Genome-scale metabolic model (GSM) called iZMA6517. Remarkably, this modelling approach was supported by metabolomics profiling, in particular increased leaf pyrimidine levels in response to AMF inoculation under limiting N supply. Consistently, fungal genes involved in pyrimidine de novo synthesis and salvage were found to be expressed in symbiotic roots. Our work highlights nucleotide and ureides metabolism as previously unrecognized factors contributing to the symbiotic N nutrition facilitated by R. irregularis, thereby enhancing maize growth. This study demonstrates the effectiveness of integrating multi-omics approaches with mathematical modelling to uncover novel metabolic mechanisms associated with AM symbiosis, without a priori.

plant biology↗

bioRxiv2023

An Evaluation of Physiological Responses Towards Variant Respiratory Function

The respiratory system is listed among the most critical systems that sustain lives. Numerous studies have explored respiratory system mechanisms and developed models to understand its responses to external stimuli in recent years. However, the relationship between the function and other physiological appearances must be well-established. In this study, the respiratory function was evaluated as inspiratory capacity (IC), and various physiological responses were linked to the variance of such function. Paired t-tests confirmed significant inter-posture variations on IC. A positive linear correlation was observed between MEP and IC, while a weaker was observed between abdominal muscle shortening and IC, particularly during the end exhalation. The lung inflation reflex investigation noted a strong linear correlation between heart rate and breath level. This study could shed light on understanding the respiratory system and its applications in various fields.

biophysics↗

bioRxiv2023

Global Sensitivity Analysis of the Onset of Nasal Passage Infection by SARS-CoV-2 With Respect to Heterogeneity in Host Physiology and Host Cell-Virus Kinetic Interactions

Throughout the COVID-19 pandemic, positive nasal swab tests have revealed dramatic population heterogeneity in viral titers spanning 6 orders-of-magnitude. Our goal here is to probe potential drivers of infection outcome sensitivity arising from (i) physiological heterogeneity between hosts and (ii) host-variant heterogeneity in the detailed kinetics of cell infection and viral replication. Toward this goal, we apply global sensitivity methods (Partial Rank Correlation Coefficient analysis and Latin Hypercube Sampling) to a physiologically faithful, stochastic, spatial model of inhaled SARS-CoV-2 exposure and infection in the human respiratory tract. We focus on the nasal passage as the primary origin of respiratory infection and site of clinical testing, and we simulate the spatial and dynamic progression of shed viral load and infected cells in the immediate 48 hours post infection. We impose immune evasion, i.e., suppressed immune protection, based on the preponderance of clinical evidence that nasal infections occur rapidly post exposure, largely independent of immune status. Global sensitivity methods provide the de-correlated outcome sensitivities to each source of within-host heterogeneity, including the dynamic progression of sensitivities at 12, 24, 36, and 48 hours post infection. The results reveal a dynamic rank-ordering of the drivers of outcome sensitivity in early infection, providing insights into the dramatic population-scale outcome diversity during the COVID-19 pandemic. While we focus on SARS-CoV-2, the model and methods are applicable to any inhaled virus in the immediate 48 hours post infection.

immunology↗

bioRxiv2024

Dynamic coexistence driven by physiological transitions in microbial communities

AO_SCPLOWBSTRACTC_SCPLOWMicrobial ecosystems are commonly modeled by fixed interactions between species in steady exponential growth states. However, microbes often modify their environments so strongly that they are forced out of the exponential state into stressed or non-growing states. Such dynamics are typical of ecological succession in nature and serial-dilution cycles in the laboratory. Here, we introduce a phenomenological model, the Community State model, to gain insight into the dynamic coexistence of microbes due to changes in their physiological states. Our model bypasses specific interactions (e.g., nutrient starvation, stress, aggregation) that lead to different combinations of physiological states, referred to collectively as "community states", and modeled by specifying the growth preference of each species along a global ecological coordinate, taken here to be the total community biomass density. We identify three key features of such dynamical communities that contrast starkly with steady-state communities: increased tolerance of community diversity to fast growth rates of species dominating different community states, enhanced community stability through staggered dominance of different species in different community states, and increased requirement on growth dominance for the inclusion of late-growing species. These features, derived explicitly for simplified models, are proposed here to be principles aiding the understanding of complex dynamical communities. Our model shifts the focus of ecosystem dynamics from bottom-up studies based on idealized inter-species interaction to top-down studies based on accessible macroscopic observables such as growth rates and total biomass density, enabling quantitative examination of community-wide characteristics.

ecology↗

bioRxiv2024

A genetic and physiological model of renal dysfunction in Lowe syndrome

Lowe syndrome (LS) is an X-linked recessive genetic disorder characterized by renal dysfunction, neurodevelopmental defects, and cataract. The affected gene, OCRL encodes for a polyphosphoinositide 5-phosphatase. OCRL is localized to multiple sub-cellular locations in the endolysosomal system and defects in these organelles have been described in human cells depleted of OCRL. However, the relationship of the endolysosomal defects in OCRL depleted cells to the altered physiology of kidney cells of LS patients has not been completely determined. Here we model the kidney phenotypes of LS using a Drosophila nephrocyte model. Using this model system, we demonstrate that OCRL plays a cell-autonomous role in nephrocyte function. Deletion of the only OCRL ortholog in Drosophila (dOCRL) leads to cell-autonomous defects in larval nephrocyte structure and function. Null mutants of dOCRL (dOCRLKO) show defects in the endolysosomal system of larval nephrocytes that are associated with physiological defects in nephrocyte function. These defects could be rescued by reconstitution with a human OCRL transgene but not with a phosphatase dead version or a human LS patient derived mutation. Overall, this work provides a model system to understand the mechanisms by which the sub-cellular changes from loss of OCRL leads to defects in kidney function in human patients.

cell biology↗

bioRxiv2024

Altered physiological, affective, and functional connectivity responses to acute stress in patients with alcohol use disorder

BackgroundThere is evidence that the processing of acute stress is altered in alcohol use disorder (AUD), but little is known about how this is manifested simultaneously across different stress parameters and which neural processes are involved. The present study examined physiological and affective responses to stress and functional connectivity in AUD. MethodsSalivary cortisol samples, pulse rate, and affect ratings were collected on two days from 34 individuals with moderate or severe AUD and 34 controls. On one day, stress was induced, and on the other day, a non-stressful control task was performed. Following the intervention, participants underwent fMRI to assess functional connectivity, focusing on cortical and subcortical seed regions previously reported to be involved in AUD and/or stress. ResultsFor pulse rate and cortisol, stress responses were blunted in AUD, whereas negative affect was increased. Furthermore, stress-related changes in pulse rate, cortisol, and affect were only correlated in healthy controls. Neuroimaging analyses revealed stress-related group differences in functional connectivity, involving the connectivity of striatal seeds with the posterior DMN, cerebellum and midcingulate cortex, and of the posterior DMN seed with the striatum and thalamus. ConclusionsThe results suggest a dissociation between subjective experienced distress and the physiological stress response in AUD as well as stress-related alterations in functional connectivity. These findings highlight the complex interplay between chronic alcohol use and acute stress regulation, offering valuable considerations for the development of therapeutic strategies.

neuroscience↗

bioRxiv2024

Developmental order, fibre caliber, and vascularization predict tract-wise declines: Testing retrogenesis and physiological predictions in white matter aging

To understand the consistently observed spatial distribution of white-matter (WM) aging, developmentally driven theories termed "retrogenesis" have gained traction, positing that the order of WM tract development predicts the order of declines. Regions that develop first are expected to deteriorate the last, i.e. "last-in-first-out". Alternatively, regions which develop most rapidly may also decline most rapidly in aging, or "gains-predict-loss". The validity of such theories remains uncertain, in part due to lack of clarity on the definition of developmental order. Importantly, our recent findings suggest that WM aging is also associated with physiological parameters such as perfusion, which may be linked to fibre metabolic need, which in turn varies with fibre size. Here we address the extent to which the degree of WM aging is determined by development trajectory (i.e. retrogenesis) and/or by physiological state. We obtained microstructural and perfusion measures using data from the Human Connectome Project in Aging (HCP-A), complemented by a meta-analysis involving maps of fibre calibre and macrovascular volume. Our results suggest that (1) while tracts that appear last or finish myelinating first in development display the slowest aging, the pattern of aging is not fully explained by retrogenesis; in fact, time courses of tract emergence and myelination give rise to opposite associations with WM decline; (2) tracts that appear earlier also have higher mean axon calibre and are also associated with lower degrees of WM microstructural aging; (3) such tracts also tend to exhibit relatively sustained CBF with a higher rate of lengthening of the arterial transit times (ATT), suggestive of collateral blood supply. These findings were also sex dependent in a tract-specific manner. Future work will investigate whether these are ultimately influenced by each tracts metabolic demand and the role of macrovascular collateral flow.

neuroscience↗

bioRxiv2024

When the tap runs dry: The multi-tissue gene expression and physiological responses of water deprived Peromyscus eremicus

The harsh and dry conditions of desert environments have resulted in genomic adaptations, allowing for desert organisms to withstand prolonged drought, extreme temperatures, and limited food resources. Here, we present a comprehensive exploration of gene expression across five tissues (kidney, liver, lung, gastrointestinal tract, and hypothalamus) and 19 phenotypic measurements to explore the whole-organism physiological and genomic response to water deprivation in the desert-adapted cactus mouse (Peromyscus eremicus). The findings encompass the identification of differentially expressed genes and correlative analysis between phenotypes and gene expression patterns across multiple tissues. Specifically, we found robust activation of the vasopressin renin-angiotensin-aldosterone system (RAAS) pathways, whose primary function is to manage water and solute balance. Animals reduce food intake during water deprivation, and upregulation of PCK1 highlights the adaptive response to reduced oral intake via its actions aimed at maintained serum glucose levels. Even with such responses to maintain water balance, hemoconcentration still occurred, prompting a protective downregulation of genes responsible for the production of clotting factors while simultaneously enhancing angiogenesis which is thought to maintains tissue perfusion. In this study, we elucidate the complex mechanisms involved in water balance in the desert-adapted cactus mouse, P. eremicus. By prioritizing a comprehensive analysis of whole-organism physiology and multi-tissue gene expression in a simulated desert environment, we describe the complex and successful response of regulatory processes.

genomics↗

bioRxiv2024

Sustaining healthy long-term host-microbiome interactions in a physiologically relevant dynamic gingival tissue model

Host-oral microbiome interactions are known to be critical in maintaining local and systemic health of the human body, although they are difficult to study in both clinical and in vitro applications. Despite efforts, recapitulation of gingival architecture and physiological characteristics of the periodontal niche cannot be achieved by traditional tissue engineering strategies. Here, we advanced our humanized three-dimensional gingival model by co-culturing it with a healthy patient-derived microbiomes for seven days within an oral bioreactor that mimics native salivary dynamics. Our results indicated long-term host and microbiome viability, host barrier integrity and physiological response, and preservation of healthy microbial populations and interbacterial dialogues. The model has proven useful in successfully mimicking tissue homeostasis at the interface of the periodontal niche and suitable for the introduction of immune cells. Future studies will focus on using the model as a comparator of periodontal inflammation and identifying biomarkers associated with eubiotic/dysbiotic profiles. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=137 SRC="FIGDIR/small/577629v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@1bc808aorg.highwire.dtl.DTLVardef@9b0ef8org.highwire.dtl.DTLVardef@1f3fbb1org.highwire.dtl.DTLVardef@11135f5_HPS_FORMAT_FIGEXP M_FIG Created partially in biorender.com. C_FIG

bioengineering↗

bioRxiv2024

Examining motor evidence for the pause-then-cancel model of action-stopping: Insights from motor system physiology

Stopping initiated actions is fundamental to adaptive behavior. Longstanding, single-process accounts of action-stopping have been challenged by recent, two-process, pause-then-cancel models. These models propose that action-stopping involves two inhibitory processes: 1) a fast Pause process, which broadly suppresses the motor system as the result of detecting any salient event, and 2) a slower Cancel process, which involves motor suppression specific to the cancelled action. A purported signature of the Pause process is global suppression, or the reduced corticospinal excitability (CSE) of task-unrelated effectors early on in action-stopping. However, unlike the Pause process, few (if any) motor system signatures of a Cancel process have been identified. Here, we used single- and paired-pulse TMS methods to comprehensively measure the local physiological excitation and inhibition of both responding and task-unrelated motor effector systems during action-stopping. Specifically, we measured CSE, short-interval intracortical inhibition (SICI), and the duration of the cortical silent period (CSP). Consistent with key predictions from the pause-then-cancel model, CSE measurements at the responding effector indicated that additional suppression was necessary to counteract Go-related increases in CSE during-action-stopping, particularly at later timepoints. Increases in SICI on Stop-signal trials did not differ across responding and non-responding effectors, or across timepoints. This suggests SICI as a potential source of global suppression. Increases in CSP duration on Stop- signal trials were more prominent at later timepoints. SICI and CSP duration therefore appeared most consistent with the Pause and Cancel processes, respectively. Our study provides further evidence from motor system physiology that multiple inhibitory processes influence action-stopping.

neuroscience↗

bioRxiv2024

The effect of constitutive root isoprene emission on root phenotype and physiology under control and salt stress conditions

ABSTRACTIsoprene, a volatile hydrocarbon, is typically emitted from the leaves and other aboveground plant organs; isoprene emission from roots is not well studied. Given its well-known function in plant growth and defense aboveground, isoprene may also be involved in shaping root physiology to resist belowground stress. We used isoprene-emitting transgenic lines (IE) and a non-emitting empty vector and/or wild type lines (NE) of Arabidopsis to elucidate the roles of isoprene in root physiology and salt stress resistance. We assessed root phenotype and metabolic changes, hormone biosynthesis and signaling, and stress-responses under normal and saline conditions of IE and NE lines. We also analyzed the root transcriptome in the presence or absence of salt stress. IE lines emitted isoprene from roots, which was associated with higher primary root growth, root biomass, and root/shoot biomass ratio under both control and salt stress conditions. Transcriptome data indicated that isoprene altered the expression of key genes involved in hormone metabolism and plant responses to stress factors. Our findings reveal that root constitutive isoprene emission sustains root growth also under salinity by regulating and/or priming hormone biosynthesis and signaling mechanisms, amino acids biosynthesis, and expression of key genes relevant to salt stress defense.

plant biology↗

bioRxiv2024

Discovering genotype-phenotype relationships with machine learning and the Visual Physiology Opsin Database (VPOD)

BackgroundPredicting phenotypes from genetic variation is foundational for fields as diverse as bioengineering and global change biology, highlighting the importance of efficient methods to predict gene functions. Linking genetic changes to phenotypic changes has been a goal of decades of experimental work, especially for some model gene families including light-sensitive opsin proteins. Opsins can be expressed in vitro to measure light absorption parameters, including {lambda}max - the wavelength of maximum absorbance - which strongly affects organismal phenotypes like color vision. Despite extensive research on opsins, the data remain dispersed, uncompiled, and often challenging to access, thereby precluding systematic and comprehensive analyses of the intricate relationships between genotype and phenotype. ResultsHere, we report a newly compiled database of all heterologously expressed opsin genes with {lambda}max phenotypes called the Visual Physiology Opsin Database (VPOD). VPOD_1.0 contains 864 unique opsin genotypes and corresponding {lambda}max phenotypes collected across all animals from 73 separate publications. We use VPOD data and deepBreaks to show regression-based machine learning (ML) models often reliably predict {lambda}max, account for non-additive effects of mutations on function, and identify functionally critical amino acid sites. ConclusionThe ability to reliably predict functions from gene sequences alone using ML will allow robust exploration of molecular-evolutionary patterns governing phenotype, will inform functional and evolutionary connections to an organisms ecological niche, and may be used more broadly for de-novo protein design. Together, our database, phenotype predictions, and model comparisons lay the groundwork for future research applicable to families of genes with quantifiable and comparable phenotypes. Key PointsO_LIWe introduce the Visual Physiology Opsin Database (VPOD_1.0), which includes 864 unique animal opsin genotypes and corresponding {lambda}max phenotypes from 73 separate publications. C_LIO_LIWe demonstrate that regression-based ML models can reliably predict {lambda}max from gene sequence alone, predict non-additive effects of mutations on function, and identify functionally critical amino acid sites. C_LIO_LIWe provide an approach that lays the groundwork for future robust exploration of molecular-evolutionary patterns governing phenotype, with potential broader applications to any family of genes with quantifiable and comparable phenotypes. C_LI

bioinformatics↗

bioRxiv2024

Reflection confocal microscopy for quantitative assessment of airway surface liquid dysregulation and pharmacological rescue in cystic fibrosis under near-physiological conditions

Proper regulation of airway surface liquid (ASL) is essential for effective mucociliary clearance (MCC) in healthy airways, and ASL depletion due to deficient cystic fibrosis transmembrane conductance regulator (CFTR)-mediated anion/fluid secretion plays an important role in the pathogenesis of mucociliary dysfunction and chronic muco-obstructive lung disease in patients with cystic fibrosis (CF). The current standard for quantitative measurements of ASL height is confocal fluorescence microscopy that has the disadvantage that it requires apical addition of volume for fluorescent staining, and hence perturbation of the ASL. Therefore, our aim was to develop a method that enables studies of ASL regulation under unperturbed conditions using reflected light by confocal microscopy of primary airway epithelial cultures grown at air-liquid interface (ALI). After apical volume addition to primary tracheal mouse cultures, confocal reflection microscopy yielded comparable ASL height as confocal fluorescence microscopy on cultures of wild-type mice, and was sensitive to detect ASL depletion on cultures of {beta}ENaC-Tg mice. Under unperturbed conditions, ASL determined by confocal reflection microscopy was significantly higher in wild-type and {beta}ENaC-Tg mice compared to values obtained by confocal fluorescence microscopy. Studies in normal and CF primary human airway epithelial cultures showed that confocal reflection microscopy was sensitive to detect effects of low temperature rescue and pharmacological modulation including improvement of CFTR function by VX-809 and VX-770 in cultures from CF patients with the F508del mutation. Our results support confocal reflection microscopy as a novel sensitive technique for quantitative studies of ASL regulation and response to therapeutic intervention under unperturbed near-physiological conditions in healthy and CF airways. NEW & NOTEWORTHYMeasurement of airway surface liquid (ASL) height by confocal fluorescence microscopy is an important tool to investigate ASL dysregulation and effects of therapeutic strategies aiming at restoring ASL volume to improve mucociliary clearance and lung function in patients with cystic fibrosis. However, confocal fluorescence microscopy has the disadvantage that it requires apical addition of volume for fluorescent staining of the ASL leading to perturbation of its height and composition. Here, we developed confocal reflection microscopy as a new method that enables quantitative assessment of ASL on highly-differentiated primary airway epithelial cultures under unperturbed near-physiological conditions by detection of refracted light.

cell biology↗

bioRxiv2024

Physiologic media renders human iPSC-derived macrophages permissive for M. tuberculosis by rewiring organelle function and metabolism

In vitro studies are crucial for our understanding of the human macrophage immune functions. However, traditional in vitro culture media poorly reflect the metabolic composition of blood, potentially affecting the outcomes of these studies. Here, we analysed the impact of a physiological medium on human induced pluripotent stem cell (iPSC)-derived macrophages (iPSDM) function. Macrophages cultured in a human plasma-like medium (HPLM) were more permissive to Mycobacterium tuberculosis (Mtb) replication and showed decreased lipid metabolism with increased metabolic polarisation. Functionally, we discovered that HPLM-differentiated macrophages showed different metabolic organelle content and activity. Specifically, HPLM-differentiated macrophages displayed reduced lipid droplet and peroxisome content, increased lysosomal proteolytic activity, and increased mitochondrial activity and dynamics. Inhibiting or inducing lipid droplet formation revealed that lipid droplet content is a key factor influencing macrophage permissiveness to Mtb. These findings underscore the importance of using physiologically relevant media in vitro for accurately studying human macrophage function.

cell biology↗

bioRxiv2024

Physics and physiology determine strategies of bacterial investment in flagellar motility

Regulatory strategies that allow microorganisms to balance their investment of limited resources in different physiological functions remain poorly understood, particularly for numerous cellular functions that are not directly required for growth. Here, we investigate the allocation of resources to flagellar swimming, the most prominent and costly behavior in bacteria that is not directly required for growth. We show that the dependence of motile behavior on gene expression in Escherichia coli is determined by the hydrodynamics of propulsion, which limits the ability of bacteria to increase their swimming by synthesizing more than a critical number of flagellar filaments. Together with the fitness cost of flagellar biosynthesis, this defines the physiologically relevant range of investment in motility. Gene expression in all E. coli isolates tested falls within this range, with many strains maximizing motility under nutrient-rich conditions, particularly when grown on a porous medium. The hydrodynamics of swimming may further explain the bet-hedging behavior observed at low levels of motility gene expression.

microbiology↗

bioRxiv2024

Physiological bias governs neutrophil inflammatory threat perception

Background and PurposeThe functional G protein-coupled receptor (GPCR) signalling unit consists of an agonist acting on a receptor that is coupled to a G protein that transduces the signals to effectors within a complex cellular environment. While much attention is given to GPCR-agonist or GPCR-transducer relationships, the contribution of the cellular environment remains significantly unexplored. Experimental ApproachHere, we juxtaposed the signalling responses triggered by the activation of two GPCR pattern recognition receptors, Formyl peptide receptor 1 and Formyl peptide receptor 2, in a recombinant cell system against their signalling dynamics in the native neutrophilic environment. Key resultsWe observed that agonist activation leads to cell context-dependent substantial differences in the receptor signalling texture. While the impact of receptor activation on de novo cAMP formation varied depending on the cell type, MAPK activation was similar in both systems. This physiological bias was conserved across species. Expression analysis unveiled the absence of the Gi-sensitive adenylyl cyclases ADCY5 and ADCY6 in neutrophils, implying that cAMP de novo synthesis cannot be inhibited by Gi-coupled receptors. The signalling behaviour of the Gi-coupled LTB4 high-affinity receptor BLT1 in neutrophils corroborated our findings. Conclusion and ImplicationsOur data underscore the profound impact of the specific cellular environment on GPCR signalling, causing physiological bias in GPCR signalling, thereby affecting drug efficacy and therapeutic targeting.

systems biology↗