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bioRxiv2025

Source-sink reduction and improvement in rapeseed (Brassica napus L.) during the exponential grain filling phase and responses of grain yield, its components and grain quality traits

Rapeseed (Brassica napus L.) final grain weight and in turn grain yield, results from the interaction between assimilate supply (source) and sink capacity; however, the extent to which source limitation constrains yield formation during grain filling remains under debate. Understanding how the manipulation of the source-sink ratio (S-S ratio) affects yield and grain traits is critical for elucidating the physiological mechanisms behind yield stability in high-yield environments. This study aimed to evaluate how variations in the S-S ratio during the grain-filling phase influence grain weight and yield, biomass allocation, grain-filling dynamics, and grain quality traits in rapeseed. A field experiment was conducted during two seasons in Valdivia, Chile. One high-yield potential and adapted hybrid (Click CL) was evaluated under three radiation regimes in a randomized complete block design: control, -50% incident radiation (shading), and +50 % incident radiation (reflected radiation pannels, PET). S-S ratio treatments were applied from the beginning of grain filling (BBCH 71) to physiological maturity (BBCH 89) aimed at modify the S-S ratio during the actual grain filling period. The reduced S-S ratio increased thousand-grain weight (TGW), particularly in basal siliques, resulting in yield compensation and demonstrating a strong structural and physiological buffering capacity. Conversely, increasing the S-S ratio enhanced grain number and grain yield, while TGW remained stable. Grain quality traits responded asymmetrically: under reduced S-S, oil concentration slightly declined whereas protein concentration increased. The increased S-S ratio, had no effect on grain oil and protein concentrations, remaining similar to the control. Sieving analyses revealed a shift toward larger grain size classes under reduced S- S, whereas the distribution under increased S-S resembled the control. Overall, these findings indicate that rapeseed maintains yield stability through compensatory adjustments in grain weight and size distribution under contrasting assimilate availabilities. Under high-radiation temperate conditions, rapeseed productivity during grain filling is predominantly governed by sink capacity, highlighting its physiological plasticity and resilience to variations in source-sink balance HighlightsO_LIIn high-yield conditions without structural changes, grain filling depends on sink capacity. C_LIO_LIA 50% reduction in radiation increases grain weight and maintains grain yield. C_LIO_LIA 50% increase in radiation raises grain number and yield via more grains per plant. C_LIO_LISource reduction shifts grains to larger sizes; source increase maintains stability. C_LIO_LIOil in grain is stable with increased radiation, declines when it is reduced. C_LI

physiology↗

bioRxiv2025

Revisiting Humidity Ramp Protocols for Assessing Human Heat Tolerance

BackgroundHumidity ramp protocols are widely used to estimate human heat tolerance limits, yet reported critical environmental limits (CELs) vary markedly across studies. Whether this variability reflects true physiological differences or systematic methodological artifacts related to ramp design remains unresolved. MethodsWe combined first-order thermal modeling with controlled physiological trials to examine how ramp temporal structure (step dwell time) influences apparent rectal temperature (Tcr) inflection points. Twenty-six healthy young adults completed randomized trials at 42 {degrees}C under two protocols: an aggressive-ramp (30-min equilibration followed by humidity increases every 5 min) and a slow-ramp (4-h equilibration followed by hourly humidity increments). CELs derived from ramp protocols were further evaluated using prolonged fixed-condition exposures in independent cohorts (n=14 per sex). ResultsShort-step dwell times ({Delta}t/{tau} <<1) prevented rectal temperature from approaching its step-specific equilibrium, resulting in kinetically constrained, non-equilibrium dynamics and earlier Tcr inflection points. Consequently, aggressive-ramp protocols yielded substantially lower CELs than slow-ramp protocols in both sexes ({approx}3.5 {degrees}C difference). CELs derived from the slow ramp closely matched those obtained from prolonged fixed-condition exposures, whereas aggressive ramps misclassified physiologically compensable conditions as uncompensable. ConclusionRapid humidity increments systematically underestimate heat tolerance because environmental forcing outpaces physiological response kinetics. Accurate CEL determination requires either prolonged fixed-condition exposures (benchmark approach) or sufficiently slow ramps that allow near-equilibrium responses ({Delta}t/{tau} {gtrsim}0.3-0.5).

physiology↗

bioRxiv2018

Exploring the mechanistic link between corticosterone and insulin-like growth factor-1 in a wild passerine bird

BackgroundPhysiological regulators of life history trade-offs need to be responsive to sudden changes of resource availability. When homeostasis is challenged by unpredictable stressors, vertebrates respond through a set of physiological reactions, which can promote organismal survival. Glucocorticoids have been traditionally recognized as one of the main regulators of the physiological stress response, but the role of an evolutionarily more conserved pathway, the hypothalamic-pituitary-somatotropic (HPS) axis producing insulin-like growth factor-1 (IGF-1) has received much less attention. Although IGF-1 is known to affect several life history traits, little is known about its role in the physiological stress response and it has never been studied directly in adult wild animals.\n\nMethodsIn this study, we combined field observations with a controlled experiment to investigate how circulating levels of IGF-1 change in response to stress and whether this change is due to concomitant change in glucocorticoids in a free-living songbird, the bearded reedling Panurus biarmicus. We used a standard capture-restraint protocol in field observation, in which we took first and second (stress induced: 15 minutes later) samples. In a follow-up experiment, we used a minimally invasive oral corticosterone manipulation.\n\nResultsWe showed that corticosterone levels significantly increased while IGF-1 levels significantly decreased during capture and handling stress. However, change in corticosterone levels were not related to change in IGF-1 levels. We found that experimentally elevated corticosterone levels did not affect IGF-1 levels.\n\nDiscussionOur results are the first to highlight that circulating IGF-1 levels are responsive to stress independently from glucocorticoids and suggest that the HPS axis is an autonomous physiological pathway that may play an important role as regulator of life-history decisions.

physiology↗

bioRxiv2018

Instant Automated Inference of Perceived Mental Stress through Smartphone PPG and Thermal Imaging

BackgroundA smartphone is a promising tool for daily cardiovascular measurement and mental stress monitoring. Photoplethysmography (PPG) and low-cost thermography can be used to create cheap, convenient and mobile systems. However, to achieve robustness, a person has to remain still for several minutes while a measurement is being taken. This is very cumbersome, and limits the usage in applications such producing instant measurements of stress.\n\nObjectiveWe propose to use smartphone-based mobile PPG and thermal imaging to provide a fast binary measure of stress responses to an event using dynamical physiological changes which occur within 20 seconds of the event finishing.\n\nMethodsWe propose a system that uses a smartphone and its physiological sensors to reliably and continuously measure over a short window of time a persons blood volume pulse, the time interval between heartbeats (R-R interval) and the 1D thermal signature of the nose tip. 17 healthy participants, involved in a series of stress-inducing mental activities, measured their physiological response to stress in the 20 second-window immediately following each activity. A 10-cm Visual Analogue Scale was used by them to self-report their level of mental stress. As a main labeling strategy, normalized K-means clustering is used to better treat interpersonal differences in ratings. By taking an array of the R-R intervals and thermal directionality as a low-level feature input, we mainly use an artificial neural network to enable the automatic feature learning and the machine learning inference process. To compare the automated inference performance, we also extracted widely used high level features from HRV (e.g., LF/HF ratio) and the thermal signature and input them to a k-nearest neighbor to infer perceived stress levels.\n\nResultsFirst, we tested the physiological measurement reliability. The measured cardiac signals were considered highly reliable (signal goodness probability used, Mean=0.9584, SD=0.0151). The proposed 1D thermal signal processing algorithm effectively minimized the effect of respiratory cycles on detecting the apparent temperature of the nose tip (respiratory signal goodness probability Mean=0.8998 to Mean=0). Second, we tested the 20 seconds instant perceived stress inference performance. The best results were obtained by using automatic feature learning and classification using artificial neural networks rather than using pre-crafted features. The combination of both modalities produced higher accuracy on the binary classification task using 17-fold leave-one-subject-out (LOSO) cross-validation (accuracy: HRV+Thermal: 76.96%; HRV: 60.29%; Thermal: 61.37%). The results are comparable with the state of the art automatic stress recognition methods requiring long term measurements (a minimum of 2 minutes for up to around 80% accuracy from LOSO). Lastly, we explored the impact of different data labeling strategies used in the field on the sensitivity of our inference methods and the need for normalization within individual.\n\nConclusionsResults demonstrate the capability of smartphone biomedical imaging in instant mental stress recognition. Given that this approach does not require long measurements requiring attention and reduced mobility, it is more feasible for mobile mental healthcare solution in the wild.

physiology↗

bioRxiv2025

Sex- and age-differences in cellular hallmarks of aging in a species with female-biased longevity and environmental sex determination

Cellular hallmarks of aging have been discovered and characterized in a number of model species for studying aging biology - such as humans, mice, fruit flies, and nematodes. Whether these canonical age-related changes to cellular physiology are present across diverse species that have variable rates of demographic aging remains less studied. Here, we tested whether several ubiquitous cellular hallmarks of aging - mitochondrial function, reactive oxygen species generation, and inducible DNA damage - change with age and in a sex-dependent manner in a species with indeterminate growth and reproduction (painted turtles, Chrysemys picta). A further feature of their biology that recommends them for an ecological model of vertebrate aging is their female-biased longevity, despite an absence of genotypic sex determination. Thus lifespan and aging may be reliable features of sex-specific life-histories. We measured aspects of mitochondrial health (cellular basal, maximal, and spare oxygen consumption rates), cellular levels of reactive oxygen species, and aspects of DNA damage and repair from exposure to UVB. We used these measures across several physiological axes as proxies for age-related physiological dysfunction. We further assessed our measures across several populations of painted turtles. We found that sex explained the largest proportion of variation, with males differing from females in mitochondrial function, reactive oxygen species production, and inducible DNA damage. In several cases, age significantly interacted with sex, but the effect size was small relative to sex alone. Thus, we found that sex, rather than age or size, was a consistent predictor of cellular aging physiological in this species with where females live longer and age slower.

physiology↗

bioRxiv2026

Multiday rhythms modulate human heart rate: an observational study in healthy adults

BackgroundChronobiology research has historically focused on circadian rhythms; however, longer infradian rhythms are prevalent in human physiology and may have important implications for health and wellbeing. Previous studies have identified widespread infradian rhythms across human physiology, often in the context of hormonal regulation and disease. Despite growing evidence of their ubiquity, the mechanisms, significance, and clinical relevance of these rhythms remain poorly understood, largely due to lack of longitudinal datasets and robust detection methods. The emergence of new wearable technologies enables rich, continuous data capture within individuals, allowing physiological rhythms to be studied at scale. MethodsThis study analyzed a cohort of healthy, young adults (N=623), with up to four years of wearable and questionnaire data collected through the University of Notre Dames (USA) NetHealth project. Participants who recorded at least three months of continuous (>80% adherence) heart rate data were included and significant infradian rhythms were identified using wavelet analysis. Unsupervised non-negative matrix factorization was performed to cluster similar wavelet power spectrum distributions. Individuals heart rate rhythms were compared to known environmental cycles (day-of-week, lunar, seasonal) and considering demographics and social networks. A second, smaller cohort (N=70) with heart rate and menstrual timing were included to analyze the interplay of hormonal regulation on monthly cycles. Multinomial logistic regression, and statistical tests (i.e., one-way ANOVA) were applied to quantify the effects of environmental, behavioral and demographic factors on heart rate rhythms. FindingsSignificant infradian rhythms of heart rate were detected in 69.7% (365/523) of the cohort and 35.9% (188/523) had two or more rhythms. Annual, biannual and 10-week rhythms were the most common. Within the 4-45-day band, individuals clustered into four multiday chronotypes based on dominant periodicities in their wavelet power spectra: weekly ([~]7 days), shorter-monthly ([~]25 days), longer-monthly ([~]35 days), and multi-month (>35 days). Heart rate rhythms were influenced by environmental cycles (day-of-week and seasonality) but were not tightly correlated to external cues. Additionally, heart rate rhythms were synchronized to the menstrual cycle in most menstruating females, although monthly rhythms were also observed in males and menopausal women. InterpretationThe prevalence of infradian, or multiday heart rate rhythms in healthy young people motivates further scientific investigation to understand the mechanisms of these rhythms and their potential association with autonomic function, and risk of disease or disease-specific symptoms. Characterizing physiological rhythms can drive new insights into how multiscale fluctuations modulate disease symptoms across neurological, psychiatric, and broader health conditions.

physiology↗

bioRxiv2026

Human decompression in real time: programmable ultrasound imaging during hyperbaric exposure

The formation of inert gas bubbles during decompression can lead to decompression sickness (DCS), a major operational risk for divers, compressed-gas workers, astronauts, and high-altitude aviators. In diving, DCS risk is typically inferred from post-dive ultrasound detection of venous gas emboli (VGE), precluding modification of decompression schedules based on real-time physiological feedback. Two-dimensional ultrasound imaging could provide additional insight into decompression-related physiological changes; however, its use in hyperbaric environments has been largely precluded by fire risk associated with elevated oxygen partial pressures (ppO2) in enclosed spaces. Here, we developed a workflow for operating a programmable ultrasound system under hyperbaric conditions and acquiring ultrasound data from the subclavian vein and calf muscle during decompression. A total of 42 dives were conducted by 26 individuals using a previously characterized dive profile to 132 feet seawater (FSW) for 20 min with 9 min of decompression. Three exposure conditions were evaluated: non-exercising, exercising, and a brief pause at 20 FSW during compression. Twelve dives included programmable ultrasound imaging during decompression. Post-dive VGE responses were consistent with prior reports while demonstrating substantial inter-individual variability and sensitivity to modest profile modifications. VGE were detected in the subclavian vein during decompression in two participants and subsequently confirmed by post-dive echocardiography. Calf muscle ultrasound brightness typically increased from pre-dive to decompression measurements, before decreasing below baseline in the 120 min post dive measurement period. These findings demonstrate the feasibility of programmable ultrasound imaging during human decompression and establish a practical framework for ultrasound operation under hyperbaric conditions. This approach may support future physiological studies and development of automated decompression monitoring technologies. New and NoteworthyThis study demonstrates the first use of a programmable ultrasound system to acquire and quantitatively analyze ultrasound data during human decompression. The approach enabled direct visualization of venous gas emboli during decompression and revealed calf muscle ultrasound signal changes, providing a new tool for investigating physiological responses during decompression that are not accessible through conventional post-dive monitoring.

physiology↗

bioRxiv2026

Tamoxifen transiently disrupts estrous cyclicity without altering long-term ovarian aging trajectories

The ovary is both one of the earliest organs to functionally age in the body, with declines emerging well before reproductive failure and contributing to systemic aging. Since ovarian function depends on tightly regulated hormonal and inflammatory cycles, even subtle disruptions can confound aging-related phenotypes. Tamoxifen-inducible Cre systems are widely used to study ovarian biology, however, tamoxifen is a selective estrogen receptor modulator capable of disturbing ovarian physiology. This introduces a critical and often overlooked concern that tamoxifen-based models may produce lasting effects that obscure true biological signals, particularly in ovarian aging studies. To address this, we tested the hypothesis that tamoxifen induces transient physiological disruption without altering long-term transcriptional outcomes. Female mice were treated with tamoxifen or vehicle at 3 months of age, and estrous cyclicity was monitored longitudinally by vaginal cytology at 3 days, 2 months, 3 months, 6 months, and 12 months post-induction. Ovaries were collected at young (6 months) and aged (12 months) time points for bulk RNA sequencing, followed by differential gene expression and pathway-level analyses. We found that tamoxifen treatment disrupted estrous cyclicity shortly after administration, confirming short term physiological effects. However, normal cycling was restored by 3 months post-treatment, indicating recovery of ovarian function. At the transcriptional level, minimal differences were observed between tamoxifen and vehicle treated groups at both young and aged time points. In contrast, aging-associated transcriptional programs were conserved across treatment conditions with shared alterations in pathways related to extracellular matrix remodeling, senescence, and cellular homeostasis. Together these findings demonstrated that while tamoxifen disturbs ovarian physiology in the short term, it does not produce lasting transcriptional effects or aging associated phenotypes. These results resolve a critical methodological concern and provide validation for the use of tamoxifen-inducible systems in ovarian research, supporting their application in studies of reproductive aging and systemic female health when proper controls are integrated into study design.

physiology↗

bioRxiv2017

Migration Of Human Mesenchymal Stem Cells Stimulated With Pulsed Electric Field And The Dynamics Of The Cell Surface Glycosylation

The objective of our study was to develop novel techniques for investigations of cell motility, and to assess whether the electric field of the therapeutic spinal cord stimulation system used in vivo contributes to the migration of human mesenchymal stem cells (hMSCs) in vitro.\n\nWe have investigated electrotaxis of bone marrow-derived MSCs using pulsed electric field (PEF) in range 16-80 mV/mm and frequency 130 Hz and 240 Hz. The PEF-related dynamics of the cell surface glycosylation was evaluated using six plant lectins.\n\nPEF at physiological levels (10mV/mm; 130 Hz) did not influence cellular motility in vitro, what may correspond to the maintenance of the transplanted cells at the lesion site in vivo. Increase of the PEF intensity and frequency above physiological levels resulted in the increase in the cellular migration rate in vitro. PEF elevated above physiological intensity and frequency (40-80 mV/mm; 240 Hz), but not at physiological levels, resulted in changes of the cell surface glycosylation.\n\nWe find the described approach as convenient for investigations and for the in vitro modeling of the cellular systems intended for the regenerative cell transplantations in vivo. Probing cell surface glycomes may provide valuable biomarkers to assess competence of transplanted cells.

cell biology↗

bioRxiv2017

Recording action potential propagation in single axons using multi-electrode arrays

The small caliber of central nervous system (CNS) axons makes routine study of axonal physiology relatively difficult. However, while recording extracellular action potentials from neurons cultured on planer multi-electrode arrays (MEAs) we found activity among groups of electrodes consistent with action potential propagation in single neurons. Action potential propagation was evident as widespread, repetitive cooccurrence of extracellular action potentials (eAPs) among groups of electrodes. These eAPs occurred with invariant sequences and inter-electrode latencies that were consistent with reported measures of action potential propagation in unmyelinated axons. Within co-active electrode groups, the inter-electrode eAP latencies were temperature sensitive, as expected for action potential propagation. Our data are consistent with these signals primarily reflecting axonal action potential propagation, from axons with a high density of voltage-gated sodium channels. Repeated codetection of eAPs by multiple electrodes confirmed these eAPs are from individual neurons and averaging these eAPs revealed sub-threshold events at other electrodes. The sequence of electrodes at which eAPs co-occur uniquely identifies these neurons, allowing us to monitor spiking of single identified neurons within neuronal ensembles. We recorded dynamic changes in single axon physiology such as simultaneous increases and decreases in excitability in different portions of single axonal arbors over several hours. Over several weeks, we measured changes in inter-electrode propagation latencies and ongoing changes in excitability in different regions of single axonal arbors. We recorded action potential propagation signals in human induced pluripotent stem cell-derived neurons which could thus be used to study axonal physiology in human disease models.\n\nSignificance StatementStudying the physiology of central nervous system axons is limited by the technical challenges of recording from axons with pairs of patch or extracellular electrodes at two places along single axons. We studied action potential propagation in single axonal arbors with extracellular recording with multi-electrode arrays. These recordings were non-invasive and were done from several sites of small caliber axons and branches. Unlike conventional extracellular recording, we unambiguously identified and labelled the neuronal source of propagating action potentials. We manipulated and quantified action potential propagation and found a surprisingly high density of axonal voltage-gated sodium channels. Our experiments also demonstrate that the excitability of different portions of axonal arbors can be independently regulated on time scales from hours to weeks.

neuroscience↗

bioRxiv2017

Recent Advancement in Biosensors Technology for Animal and Livestock Health Management

The term biosensors encompasses devices that have the potential to quantify physiological, immunological and behavioural responses of livestock and multiple animal species. Novel biosensing methodologies offer highly specialised monitoring devices for the specific measurement of individual and multiple parameters covering an animals physiology as well as monitoring of an animals environment. These devices are not only highly specific and sensitive for the parameters being analysed, but they are also reliable and easy to use, and can accelerate the monitoring process. Novel biosensors in livestock management provide significant benefits and applications in disease detection and isolation, health monitoring and detection of reproductive cycles, as well as monitoring physiological wellbeing of the animal via analysis of the animals environment. With the development of integrated systems and the Internet of Things, the continuously monitoring devices are expected to become affordable. The data generated from integrated livestock monitoring is anticipated to assist farmers and the agricultural industry to improve animal productivity in the future. The data is expected to reduce the impact of the livestock industry on the environment, while at the same time driving the new wave towards the improvements of viable farming techniques. This review focusses on the emerging technological advancements in monitoring of livestock health for detailed, precise information on productivity, as well as physiology and well-being. Biosensors will contribute to the 4th revolution in agriculture by incorporating innovative technologies into cost-effective diagnostic methods that can mitigate the potentially catastrophic effects of infectious outbreaks in farmed animals

bioengineering↗

bioRxiv2017

Side Effects And The Need For Secrecy: Characterising Discontinuation Of Modern Contraception And Its Causes In Ethiopia Using Mixed Methods

BackgroundContraceptive discontinuation is a major barrier to reducing global unmet needs for family planning, but the reasons why women discontinue contraception are poorly understood. Here we use data from Ethiopia to investigate (i) the magnitude of contraceptive discontinuation in 2005-2011, (ii) how the risk of discontinuation varies with method type and education level and (iii) the barriers to continuation. Our main hypothesis is that contraceptive discontinuation is driven by the experience of physiological side-effects associated with the use of hormonal contraception, rather than a lack of education.\n\nMethodsWe used a mixed methods explanatory sequential design to explain the quantitative results in more details through the qualitative data. First, we analysed quantitative data from the 2011 Ethiopian Demographic and Health Survey to study patterns of contraceptive discontinuation and method choice using multilevel multiprocess models. Second, we conducted semi-structured interviews and focus group discussions in the 3 most populated regions of Ethiopia with individuals of reproductive age and health professionals.\n\nResultsThe analysis of EDHS data shows that the rate of discontinuation has not reduced in the period 2005-2011 and remains high. Discontinuation mainly takes the form of abandonment, and is a function of method type and wealth but not of educational level. Interviews with women and health professionals reveal that the experience of debilitating physiological side effects, the need for secrecy and poverty are important barriers to continuation.\n\nConclusionsOur findings together suggest that physiological and social side-effects of contraceptive use, not education, are the root causes of contraceptive discontinuation in Ethiopia. We argue that to tackle discontinuation due to side-effects, dispelling misconceptions through educating women is not addressing the root causes of discontinuation, and that priority should be given to both engaging men and questioning the appropriateness of medical technology to the physiology of Ethiopian women, especially those living in poverty.

epidemiology↗

bioRxiv2017

To Beard, Or Not To Beard: Linking Sexual Selection On Masculinity, Embryonic Neural Crest Cells, And Human Self-Domestication

ObjectivesPre-historic decline in human craniofacial masculinity has been proposed as evidence of selection for elevated sociability and a process of human self-domestication thought to have promoted complex capacities including language, culture, and cumulative technological development. This follows experimental observation of similar changes in non-human animals under selection for reduced aggression. Two distinct domestication hypotheses posit developmental explanations, involving hypoplasia of embryonic neural crest cells (NCCs), and declining androgen influence, respectively. Here, I assess the operation and potential interactions between these two mechanisms and consider their role in enhanced human adaptation to a cooperative sociocultural niche. MethodsI provide a review and synthesis of related literature with a focus on physiological mechanisms effecting domesticated reductions in masculinity and sexual dimorphism. Further, I examine pre-historic modes of socio-sexual selection likely to drive human self-domestication via reduced aggression and masculinity. ResultsI find pluripotent NCCs provide progenitors for a wide range of vertebrate masculine features, acting as regular targets for sexually driven evolutionary change; suggesting domesticated hypoplasia of NCC-derived tissues would be sufficient to explain declines in masculine traits and features. However, lineage specific androgen receptor variability likely moderates these NCC-based effects. ConclusionsThese findings extend theorised mechanisms driving noted physiological, morphological, and behavioural changes thought to indicate enhanced sociability and human and self-domestication. Multiple current explanations for human sociability are consistent with physiological domestication under socio-sexual selection favouring dampened masculine physiology and behaviour as adaptations to an enhanced sociocultural niche. The analysis highlights multiple avenues for further investigation.

evolutionary biology↗

bioRxiv2020

Optimal microbial pathway variants can be determined by large-scale bioenergetic evaluation in syntrophic propionate oxidation

The complete understanding of microbial propionate oxidation in syntrophy with hydrogenotrophic methanogenesis remains elusive due to uncertainties in pathways and mechanisms for interspecies electron transfer (IET). Possible pathway variants differ in their intermediate metabolites, on which electron carriers are involved and in which steps are coupled to (and to how many) proton translocations. In this work, a systematic methodology was developed (based on sound biochemical, physiological and bioenergetic principles) to evaluate the feasibility and net ATP yield of large sets of pathway variants under different physiological and environmental conditions. A pathway variant is deemed feasible under given conditions only if all pathway reaction steps have non-positive Gibbs energy change and if all the metabolite concentrations remain within an acceptable physiological range (10-6 to 10-2 M). Several million combinations of pathway variants and parameters/conditions were evaluated for propionate oxidation, providing an unprecedented mechanistic insight into its biochemical and bioenergetic landscape. Propionate oxidation via lactate appeared as the most ATP yielding pathway under most of the conditions evaluated. Results under typical methanogenic conditions indicate that syntrophic propionate oxidation can sustain life only at hydrogen partial pressures within the range of 1.2 to 4 Pa. These extremely low concentrations constitute a kinetic impossibility and strongly suggest for IET mechanisms other than dissolved hydrogen. ImportanceIn this work an original methodology was developed that quantifies the bioenergetically and physiologically feasible net ATP yields for large numbers of microbial metabolic pathways and their variants under different conditions. This ensures global optimality in finding the pathway variant(s) leading to the highest ATP yield. The methodology is especially relevant to hypothesise which microbial pathway variants are most likely to prevail in microbial ecosystems under high selective pressure for efficient metabolic energy conservation. Syntrophic microbial oxidation of propionate to acetate has extremely low energy available and requires very high metabolic efficiency in order to sustain life. Our results bring mechanistic insights into the optimum pathway variants and the impact of environmental conditions on the ATP yields and other metabolic bottlenecks. Additionally, our results conclude that IET mechanisms other than hydrogen must exist to simultaneously sustain the growth of both propionate oxidisers and hydrogenotrophic methanogens.

bioengineering↗

bioRxiv2020

Dynamic changes in tRNA modifications and abundance during T-cell activation

The tRNA pool determines the efficiency, throughput, and accuracy of translation. Previous studies have identified dynamic changes in the tRNA supply and mRNA demand during cancerous proliferation. Yet, dynamic changes may occur also during physiologically normal proliferation, and these are less characterized. We examined the tRNA and mRNA pools of T-cells during their vigorous proliferation and differentiation upon triggering their antigen receptor. We observe a global signature of switch in demand for codons at the early proliferation phase of the response, accompanied by corresponding changes in tRNA expression levels. In the later phase, upon differentiation, the response of the tRNA pool is relaxed back to basal level, potentially restraining excessive proliferation. Sequencing of tRNAs allowed us to also evaluate their diverse base-modifications. We found that two types of tRNA modifications, wybutosine and ms2t6A, are reduced dramatically during T-cell activation. These modifications occur in the anti-codon loops of two tRNAs that decode "slippery codons", that are prone to ribosomal frameshifting. Attenuation of these frameshift-protective modifications is expected to increase the potential for proteome-wide frameshifting during T-cell proliferation. Indeed, human cell lines deleted of a wybutosine writer showed increased ribosomal frameshifting, as detected with a HIV gag-pol frameshifting site reporter. These results may explain HIVs specific tropism towards proliferating T-Cells since it requires ribosomal frameshift exactly on the corresponding codon for infection. The changes in tRNA expression and modifications uncover a new layer of translation regulation during T-cell proliferation and exposes a potential trade-off between cellular growth and translation fidelity. Significance statementThe tRNA pool decodes genetic information during translation. As such, it is subject to intricate physiological regulation in all species, across different physiological conditions. Here we show for the first time a program that governs the tRNA pool and its interaction with the transcriptome upon a physiological cellular proliferation- T-cells activation. We found that upon antigenic activation of T-cells, their tRNA and mRNA pools undergo coordinated and complementary changes, which are relaxed when cells reduce back their proliferation rate and differentiate into memory cells. We found a reduction in two particular tRNA modifications that have a role in governing translation fidelity and frameshift prevention. This exposes a vulnerability in activated T-cells that may be utilized by HIV for its replication. ClassificationBIOLOGICAL SCIENCES; cell biology

genomics↗

bioRxiv2020

Modular genetic control of social status in a cichlid fish

Social hierarchies are ubiquitous in social species and profoundly influence physiology and behavior. Androgens like testosterone have been strongly linked to social status, yet the molecular mechanisms regulating social status are not known. The African cichlid fish Astatotilapia burtoni is a powerful model species for elucidating the role of androgens in social status given their rich social hierarchy and genetic tractability. Dominant A. burtoni males possess large testes, bright coloration, and perform aggressive and reproductive behaviors while non-dominant males do not. Social status in A. burtoni is in flux, however, as males alter their status depending on the social environment. Due to a teleost-specific whole-genome duplication, A. burtoni possess two androgen receptor (AR) paralogs, ARα and ARβ, providing a unique opportunity to disentangle the role of gene duplication in the evolution of social systems. Here, we used CRISPR/Cas9 gene editing to generate AR mutant A. burtoni and performed a suite of experiments to interrogate the mechanistic basis of social dominance. We find that ARβ, but not ARα, is required for testes growth and bright coloration, while ARα, but not ARβ, is required for the performance of reproductive behavior and aggressive displays. Both receptors are required to reduce flees from females and either AR is sufficient for attacking males. Thus, social status in A. burtoni is inordinately dissociable and under the modular control of two AR paralogs. This type of non-redundancy may be important in facilitating social plasticity in A. burtoni and other species whose social status relies on social experience.Significance Statement Social rank along a hierarchy determines physiological state and behavioral performance. A ubiquitous feature of social hierarchies is the communication of rank through non-physical signaling systems (e.g., coloration) and aggression, traits that correlate with the reproductive status of an individual. Despite the links identified between social status, physiology, and behavior, the molecular basis of social status is not known. Here, we genetically dissect social status in the African cichlid fish Astatotilapia burtoni using CRISPR/Cas9 gene editing. We show that two distinct androgen receptor (AR) genes control social status in a highly modular manner. This type of coordination of social status may be fundamental across species that rely on social information to optimally guide physiology and behavior.Competing Interest StatementThe authors have declared no competing interest.View Full Text

animal behavior and cognition↗

bioRxiv2020

Systematic hormone-metabolite network provides insights of high salinity tolerance in Pongamia pinnata (L.) pierre

Salinity stress results significant losses in plant productivity, and loss of cultivable lands. Although Pongamia pinnata is reported to be a salt tolerant semiarid tree crop, the adaptive mechanisms to saline environment are elusive. The present investigation describes alterations in hormonal and metabolic responses in correlation with physiological and molecular variations in leaves and roots of Pongamia at sea salinity level (3% NaCl) for 8 days. At physiological level, salinity induced adjustments in plant morphology, leaf gas exchange and ion accumulation patterns were observed. Our study also revealed that phytohormones including JAs and ABA play crucial role in promoting the salt adaptive strategies such as apoplasmic Na+ sequestration and cell wall lignification in leaves and roots of Pongamia. Correlation studies demonstrated that hormones including ABA, JAs and SA showed a positive interaction with selective compatible metabolites (sugars, polyols and organic acids) to aid in maintaining osmotic balance and conferring salt tolerance to Pongamia. At the molecular level, our data showed that differential expression of transporter genes as well as antioxidant genes regulate the ionic and ROS homeostasis in Pongamia. Collectively, these results shed new insights on an integrated physiological, structural, molecular and metabolic adaptations conferring salinity tolerance to Pongamia. High lightOur data, for the first time, provide new insights for an integrated molecular and metabolic adaptation conferring salinity tolerance in Pongamia. The present investigation describes alterations in hormonal and metabolic responses in correlation with physiological and molecular variations in Pongamia at sea salinity level (3% NaCl) for 8 days.

plant biology↗

bioRxiv2020

Tau forms oligomeric complexes on microtubules that are distinct from pathological oligomers in disease

Tau is a microtubule-associated protein, which promotes neuronal microtubule assembly and stability. Accumulation of tau into insoluble aggregates known as neurofibrillary tangles (NFTs) is a pathological hallmark of several neurodegenerative diseases. The current hypothesis is that small, soluble oligomeric tau species preceding NFT formation cause toxicity. However, thus far visualizing the spatial distribution of tau monomers and oligomers inside cells under physiological or pathological conditions has not been possible. Here, using single molecule localization microscopy (SMLM), we show that, in vivo, tau forms small oligomers on microtubules under physiological conditions. These physiological oligomers are distinct from those found in cells exhibiting tau aggregation and could be pre-cursors of aggregated tau in pathology. Further, using an unsupervised shape classification algorithm that we developed, we show that different tau phosphorylation states are associated with distinct tau aggregate species. Our work elucidates taus nanoscale composition under physiological and pathological conditions in vivo.

cell biology↗