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bioRxiv2026

Physiological levels of 3-hydroxykynurenine alter mitochondrial function and morphology in neuronal cells

Mitochondrial morphology and function are critical determinants of neuronal function and survival, with disruptions in mitochondrial dynamics often preceding the overt neuronal dysfunction seen in neurodegenerative diseases such as Alzheimers disease, Huntingtons disease and Parkinsons disease. The kynurenine pathway accounts for 95% of dietary tryptophan catabolism and many of the metabolites are neuroactive, including redox-active 3-hydroxykynurenine (3-HK). 3-HK is present under normal physiological conditions in the central nervous system (CNS) and is elevated during inflammation. While supraphysiological levels of 3-HK have been associated with neurotoxicity, the effects of physiological concentrations on neuronal cells, and specifically their mitochondria, remain poorly understood. Here we assessed viability, ATP levels and redox status to determine cellular health and function in neuronal cells exposed to physiological levels of 3-HK, alongside confocal imaging and transcriptomic profiling, finding significant alterations in mitochondrial function and morphology. Interestingly, a biphasic influence of 3-HK on mitochondrial morphology was observed, with an elongated network as well as decreased surface area and volume being observed only at the lowest concentration of 3-HK, reflecting normal physiological levels. At the highest 3-HK concentration tested, reflecting an inflammatory situation, an increased number of mitochondria were present, accompanied by increased activation of caspase-3/7 and enhanced production of mitochondrial superoxide. These results highlight a previously unknown role for 3-HK in regulating mitochondrial function and structure, possibly through altered fission and fusion events, suggesting that subtle changes in kynurenine pathway metabolism may contribute to early mitochondrial dysfunction in neurological disease.

cell biology↗

bioRxiv2026

A Conserved Obg-type GTPase sustains protein synthesis and its physiological roles in eukaryotic cells

Translation is regulated both temporally and spatially to ensure that proteins are synthesized at the correct time and delivered to the proper subcellular location. Temporary slowing or halting of ribosomal movement along an mRNA, a physiological pausing, allows cells to coordinate protein production with internal cues and external signals. However, how cells distinguish such constructive pauses from harmful pathological stalls remains a fundamental unresolved question in molecular biology. Here, we report that a ribosome-binding GTPase (Rbg in yeast, and so-called Developmentally Regulated GTP-binding (Drg) in human) promotes protein biosynthesis in halted ribosomes in an evolutionarily conserved manner. We show that the essential bacterial Obg GTPase rescues cell growth and translation in Saccharomyces cerevisiae and human cells lacking their endogenous Rbg/Drg proteins in a GTPase-dependent manner. Furthermore, Obg enhances puromycin incorporation into stalled ribosomes in a manner requiring GTP hydrolysis. We reason that Rbg/Drg proteins act to prevent premature engagement of ribosome-associated quality-control or stress-response pathways. Under physiological conditions, proteomic analyses of Rbg1-bound ribosomes in yeast reveal that Rbg GTPases associate with ribosomes translating proteins essential for diverse functions, including those of the nucleus, ER, Golgi, mitochondria, and protein transport pathways. Finally, loss of even one of the two eukaryotic Rbg/Drg paralogs impedes cell-cycle progression, disrupts DNA replication, and compromises mitochondrial function. Together, these findings suggest that Rbg/Drg proteins enable cells across different domains of life to protect physiological ribosomal pauses, revealing a previously unrecognized layer of regulation in gene expression. Significance StatementHow cells distinguish productive ribosomal pauses from harmful stalls remains unclear. We identify a ribosome-binding GTPase--Rbg in yeast and Drg in humans--as a conserved regulator that protects physiological pauses and sustains protein synthesis. Remarkably, bacterial Obg functionally substitutes for eukaryotic Rbg/Drg in both yeast and human cells, revealing deep evolutionary conservation of this mechanism. Our data show that Obg promotes continued peptide-bond formation in a GTPase-dependent manner. Positioned near the ribosomal GTPase-associated center, these GTPases are also poised to compete with stringent-response and stress-activation factors that trigger translation shutdown. Together, the findings suggest that translation is controlled not only by GTPases that drive protein synthesis forward but also by Rbg/Drg GTPases that protect the catalytic cycle against premature arrest.

biochemistry↗

bioRxiv2026

An ice-bucket challenge: investigating ice algae physiology in laboratory microcosms.

John Raven pioneered the field of algae ecophysiology, advancing our understanding of cellular resource economics, carbon acquisition, and energy allocation. His work laid the foundation for investigating integrative physiology, linking growth-survival trade-offs across diverse environments. The sea ice habitat provides an excellent framework to continue the research John championed. With steep temperature-salinity gradients, algae survival requires a shift in physiology that we are only beginning to understand. We developed two small scale, reproducible icecosms to investigate physiological changes associated with incorporation into sea ice and survival potential post-melt. Fragilariopsis cylindrus and Nitzschia frigida, known for their association with the ice environment, and Porosira glacialis, known for its association with the ice edge, were used to mechanistically link physical properties with algal physiology and post-melt survival. We observe incorporation into the ice of F. cylindrus and N. frigida alongside vertical photophysiological profiles of F. cylindrus revealing inhospitable conditions in the top compared to the bottom layers of ice. N. frigida and P. glacialis remain viable within the ice and retain the capacity to seed populations following melt. Our results establish icecosms as experimental framework to investigate ecophysiological responses of sea ice algae and provide a foundation toward ecological and evolutionary questions.

ecology↗

bioRxiv2026

The Unlabeled Organ: Adipose tissue and normativity in anatomy and physiology texts

Adipose tissue is a dynamic and essential organ system with roles in metabolism, endocrine signaling, immune function, thermoregulation, and structural support. Despite this, it has historically been framed as inert or pathological, raising questions about how it is represented in biomedical education. We evaluated the visual and textual representation of adipose tissue across widely used anatomy, physiology, and combined anatomy-physiology textbooks. Images were coded for presence, labeling, and degree of representation, and text mentions of "adipose" and "fat" were quantified across functional contexts. In anatomy textbooks, adipose tissue was frequently present (6.6-21.7% of images) but rarely labeled (<5% of all images; <25% of adipose-containing images). Representation was often minimal or incidental, and text descriptions were predominantly non-functional, with a preference for the term "fat." In physiology textbooks, adipose tissue was more often described in functional terms and more frequently referred to as "adipose," particularly in metabolic contexts, but appeared in relatively few images (<5%) and was typically minimally depicted. Combined anatomy-physiology texts showed intermediate patterns but retained low labeling rates and limited integration of structure and function. Across all textbook types, terminology varied by context, with "fat" more common in non-functional and obesity-related descriptions and "adipose" associated with metabolic functions, suggesting context-dependent bias in terminology. Overall, adipose tissue is present but inconsistently framed across visual and textual domains. This fragmentation may limit recognition of adipose tissue as an integrated organ system and may reinforce reductive or stigmatizing interpretations. Aligning educational representations with current scientific understanding is therefore essential to support a more accurate and integrated view of adipose tissue as a dynamic organ system.

scientific communication and education↗

bioRxiv2026

A nutrient-derived dietary gradient links gut microbiome composition, network structure, and host physiology

Diet is an important determinant of gut microbiome composition and host physiology. However, dietary exposure is often represented using categorical groups that may not fully capture variation in nutrient intake or its associations with gut microbiome and host biomarkers. Here, we analyzed diet-microbiome-host physiology relationships in healthy adults with long-term adherence ([≥]2 years) to omnivore, vegetarian, or vegan diets. We integrated four-day weighed dietary records, blood biomarkers, and 16S rRNA gene sequencing to characterize dietary intake, host physiology, and gut microbiome composition. We derived nutrient intake gradients by dimensionality reduction of representative nutrients and identified the second nutrient intake gradient (NIG2) as a quantitative axis reflecting variation between animal- and plant-leaning nutrient profiles, broadly recapitulating categorical dietary groups. While NIG2 showed no association with microbiome within-sample diversity, it explained gut microbiome compositional variation that was not detected using categorical dietary groups. Mediation analyses identified nominal candidate microbiome-mediated diet-biomarker relationships involving thyroid-related, hematological, and vitamin-related biomarkers. Network analyses of NIG2-defined animal-leaning and plant-leaning subsets identified subset-specific microbial associations and differences in microbial community structure and potential interactions. Overall, this continuous nutrient-derived dietary gradient provides a quantitative exposure metric for characterizing diet-microbiome-host physiology relationships. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=97 SRC="FIGDIR/small/740531v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@104a825org.highwire.dtl.DTLVardef@bb2b33org.highwire.dtl.DTLVardef@114171org.highwire.dtl.DTLVardef@df9c38_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2026

The Principal Component Life Trajectory (PCLT): Mapping Sex-Specific Physiological Change Across the Human Lifespan

Age- and sex-related variation in physiological biomarkers is well documented, yet how coordinated systemic physiology unfolds across life stages at the population level remains unclear. Here, we introduce the Principal Component Life Trajectory (PCLT), reconstructing physiological trajectories via multivariate analysis of 54 blood-based biomarkers from 11,124 participants in the National Health and Nutrition Examination Survey (NHANES). Quantifying year-on-year progression with Euclidean Trajectory Distance (ETD), we identify five distinct phases in an unbiased manner: Early adolescence, Sexual Divergence, Sexual Convergence, Late Adulthood, and Advanced Aging. Trajectories show early, pronounced sexual divergence validated in an ethnically distinct, independent cohort. Chronic disease is associated with PCLT displacement and increased ETD progression, whereas metabolic, behavioral, and psychosocial factors generate graded, phase-specific perturbations. Together, these findings establish PCLT as a reproducible framework for characterizing structured physiological change across the lifespan and for monitoring population-level health dynamics.

systems biology↗

bioRxiv2026

Physiological landmarks reveal the laminar organization of the primate hippocampus

The laminar anatomy of the hippocampal microcircuit is conserved across mammals, and its physiology has been characterized extensively in rodents, yet how this circuitry is organized physiologically in the primate brain remains poorly understood. Here we used high-density Neuropixels probes to record simultaneously across the subfields of CA1, CA3 and the dentate gyrus in two awake macaques. Sharp-wave ripples and dentate spikes produced current source density signatures that provided physiological landmarks for CA1 and the dentate gyrus, enabling alignment of recordings to hippocampal cytoarchitecture. Theta-band (3-7 Hz) oscillatory activity occurred in discrete bouts whose prevalence peaked in the stratum lacunosum-moleculare. In CA1, gamma-band amplitude was modulated by theta-band phase, with fast and slow gamma preferentially coupled to distinct phases of the theta cycle. Putative principal cells and two interneuron classes differed systematically in firing rate, burstiness, and rhythmic modulation, with principal cells showing theta-rhythmic firing and wide-waveform interneurons showing alpha- and beta-rhythmic firing. Cross-correlogram analyses revealed sparse, distance-dependent functional coupling with a consistent directional hierarchy in which principal cells led interneurons. Together, these results identify the laminar microcircuit organization of the primate hippocampus in vivo and provide a new physiological framework for interpreting primate hippocampal recordings.

neuroscience↗

bioRxiv2026

Interspecific faecal microbiota transplantation tests microbial contributions to thermal physiology in lizards

While the influence of microorganisms in the thermal physiology of animals is increasingly recognised, the role of the gut microbiome in enhancing phenotypic plasticity remains underexplored, particularly in ectotherms. Here, we tested the effect of gut microbiomes in modulating the physiological response of lizards to sudden temperature fluctuations. In captivity, we conducted an experiment with wild-caught Podarcis lizards: Mediterranean Podarcis liolepis (n=9) adapted to warm and dry environments, and Atlantic P. muralis (n=18) adapted to cooler and wetter conditions. Animals were assigned to three groups (intervention, control-cold and control-warm) and subjected to microbiota manipulations using antibiotics and faecal microbiota transplants (FMT). In the intervention group, cold-adapted P. muralis received faecal suspension from warm-adapted P. liolepis, while control-cold and control-warm groups received intraspecific transplants. Microbiome variation was analysed through genome-resolved metagenomics of 162 faecal samples, yielding 313 MAGs across 15 phyla, containing almost 1M annotated genes. One week after transplantation, microbiomes of control animals differed from their original state, whereas those of the intervention group (P. muralis), transitioned to a state resembling P. liolepis. After two weeks, both control groups showed trends of reversing their microbiomes to their original states. However, the intervention group displayed a distinct trajectory, resembling the microbial donors'. Although potentially relevant trends were observed, these microbiome alterations did not translate into detectable significant differences in their thermal physiology. Nevertheless, our results provide proof of concept for microbial transplants in lizards, and opportunities to further explore the link between gut microbes and host physiological responses in ectotherms.

zoology↗

bioRxiv2026

The effect of the consumption of toxic prey on avian predator physiology

Many insects sequester plant toxic metabolites as a chemical defence against predators. Predators are predicted to include chemically defended prey in their diet if the benefits of gaining nutrients outweigh the costs of ingesting toxins. However, the physiological costs associated with the consumption of prey toxins remain largely unknown, especially when using ecologically relevant predators and naturally occurring levels of toxins. Here, we investigated whether the consumption of chemically-defended wood tiger moths (Arctia plantaginis) influences the physiological state of an avian predator, the great tit (Parus major). We manipulated the moth toxicity by first rearing the larvae in two different diets that varied in pyrrolizidine alkaloid (PA) content, and then manually extracting part of the defensive secretions from half of the moths in both diet groups. This led to four treatments with different moth PA profiles, which were fed to great tits for six consecutive days. After the bird diet manipulation, we collected fecal and blood samples for various physiological analyses of stress and metabolism. We found no significant effects of PA consumption on corticosterone or serotonin concentrations, nor on oxidative stress biomarkers. However, birds exposed to higher PA doses used more of their mitochondrial maximal capacity, which might result from increased metabolic stress. Overall, our results suggest that incorporating some PA-defended insects in the diet does not incur high physiological costs to avian predators, but further studies are needed to explore the costs of consuming a higher number of defended prey and the interactive effects of different prey toxins.

ecology↗

bioRxiv2026

Thalamo-insular basis for updating physiological needs

Physiological needs, such as thirst and hunger, produce powerful motivation for behaviors that are essential for survival. Yet, how the brain estimates these needs remains unknown. It is unclear whether the brain continuously monitors bodily signals to create real-time representations, or if existing internal representations are only updated when meaningful changes occur. To address this question, we manipulated thalamic internal sensory inputs to the interoceptive insular cortex. We found that inhibiting internal sensory inputs prevents the updating of insular cortex representations of thirst and hunger, thereby keeping its activity closer to its initial physiological need state. Consequently, cued feeding and drinking, as well as free consumption of food and water, persist beyond the current physiological need. We further show that insular cortex activity normally represents both predictions and sensory information. However, violating learned expectations evokes widespread need-specific prediction error signals. Our results thus reveal a thalamo-cortical basis for updating physiological needs in the brain.

neuroscience↗

bioRxiv2017

Non-contact measurement of emotional and physiological changes in heart rate from a webcam

Heart rate, measured in beats per minute (BPM), can be used as an index of an individuals physiological state. Each time the heart beats, blood is expelled and travels through the body. This blood flow can be detected in the face using a standard webcam that is able to pick up subtle changes in color that cannot be seen by the naked eye. Due to the light absorption spectrum of blood, we are able to detect differences in the amount of light absorbed by the blood traveling just below the skin (i.e., photoplethysmography). By modulating emotional and physiological stress--i.e., viewing arousing images and sitting vs. standing, respectively--to elicit changes in heart rate, we explored the feasibility of using a webcam as a psychophysiological measurement of autonomic activity. We found a high level of agreement between established physiological measures, electrocardiogram (ECG), and blood pulse oximetry, and heart rate estimates obtained from the webcam. We thus suggest webcams can be used as a non-invasive and readily available method for measuring psychophysiological changes, easily integrated into existing stimulus presentation software and hardware setups.

physiology↗

bioRxiv2020

EYES ABSENT and TIMELESS integrate photoperiodic and temperature cues to regulate seasonal physiology in Drosophila

Organisms possess photoperiodic timing mechanisms to anticipate variations in day length and temperature as the seasons progress. The nature of the molecular mechanisms interpreting and signaling these environmental changes to elicit downstream neuroendocrine and physiological responses are just starting to emerge. Here, we demonstrate that in Drosophila melanogaster, EYES ABSENT (EYA) acts as a seasonal sensor by interpreting photoperiodic and temperature changes to trigger appropriate physiological responses. We observed that tissue-specific genetic manipulation of eya expression is sufficient to disrupt the ability of flies to sense seasonal cues, thereby altering the extent of female reproductive dormancy. Specifically we observed that EYA proteins, which peak at night in short photoperiod and accumulate at higher levels in the cold, promote reproductive dormancy in female D. melanogaster. Furthermore, we provide evidence indicating that the role of EYA in photoperiodism and temperature sensing is aided by the stabilizing action of the light-sensitive circadian clock protein TIMELESS (TIM). We postulate that increased stability and level of TIM at night under short photoperiod together with the production of cold-induced and light-insensitive TIM isoforms facilitate EYA accumulation in winter conditions. This is supported by our observations that tim null mutants exhibit reduced incidence of reproductive dormancy in simulated winter conditions, while flies overexpressing tim show an increased incidence of reproductive dormancy even in long photoperiod. Significance StatementExtracting information on calendar time from seasonal changes in photoperiod and temperature is critical for organisms to maintain circannual cycles in physiology and behavior. Here we found that in flies, EYES ABSENT (EYA) protein act as a seasonal sensor by adjusting its abundance and circadian phase in response to changes in photoperiod and temperature. We show that the manipulation of EYA levels is sufficient to impair the ability of female Drosophila to regulate seasonal variation in reproductive dormancy. Finally, our results suggest an important role of the circadian clock protein TIMELESS (TIM) in modulating EYA level through its ability to measure night length, linking the circadian clock to seasonal timing.

physiology↗

bioRxiv2020

Early-life hypoxia alters adult physiology and reduces stress resistance and lifespan in Drosophila

In many animals, short-term fluctuations in environmental conditions in early life often exert long-term effects on adult physiology. In Drosophila, one ecologically relevant environmental variable is hypoxia. Drosophila larvae live on rotting, fermenting food rich in microorganisms - an environment characterized by low ambient oxygen. They have therefore evolved to tolerate hypoxia. While the acute effects of hypoxia in larvae have been well studied, whether early-life hypoxia affects adult physiology and fitness is less clear. Here we show that Drosophila exposed to hypoxia during their larval period subsequently show reduced starvation stress resistance and shorter lifespan as adults, with these effects being stronger in males. We find that these effects are associated with reduced whole-body insulin signaling but elevated TOR kinase activity, a manipulation known to reduce lifespan. We also identify a sexually dimorphic effect of larval hypoxia on adult nutrient storage and mobilization. Thus, we find that males, but not females, showing elevated levels of lipids and glycogen. Moreover, we see that both males and females exposed to hypoxia as larvae show defective lipid mobilization upon starvation stress as adults. These data show how early-life hypoxia can exert persistent, sexually dimorphic, long-term effects on Drosophila adult physiology and lifespan.

physiology↗

bioRxiv2020

Impact of Advanced Maternal Age on Physiologic Adaptations to Pregnancy in Vervet Monkeys

ContextThe trend to delay pregnancy in the United States has resulted in the number of advanced maternal age (AMA) pregnancies to also increase. In humans, AMA is associated with a variety of pregnancy-related pathologies such as preeclampsia (PE). While AMA is known to be a factor which contributes to the development of pregnancy-induced diseases, the molecular and cellular mechanisms giving rise to this phenomenon are still very limited. This is due in part to lack of a pre-clinical model which has physiologic relevance to human pregnancy while also allowing control of environmental and genetic variability inherent in human studies. ObjectiveTo determine potential physiologic relevance of the vervet/African green monkey (Chlorocebus aethiops sabaeus) as a pre-clinical model to study the effects of AMA on adaptations to pregnancy. DesignThirteen age-diverse pregnant vervet monkeys (3-16 y.o.) were utilized to measure third trimester blood pressure (BP), complete blood count, iron measurements and hormone levels. ResultsSignificant associations were observed between third trimester diastolic BP and maternal age. Furthermore, the presence of leukocytosis with enhanced circulating neutrophils was observed in AMA mothers compared to younger mothers. Moreover, we observed a negative relationship between maternal age and estradiol, progesterone and cortisol levels. Finally, offspring born to AMA mothers displayed a postnatal growth retardation phenotype. ConclusionsThese studies demonstrate physiologic impairment in the adaptation to pregnancy in AMA vervet/African green monkeys. Our data indicate the vervet/African green monkey may serve as a useful pre-clinical model and tool for deciphering pathological mediators of maternal disease in AMA pregnancy.

physiology↗

bioRxiv2020

Different protein metabolic strategies for growth during food-induced physiological plasticity

Food-induced morphological plasticity, a type of developmental plasticity, is a well-documented phenomenon in larvae of the echinoid echinoderm, Dendraster excentricus. A recent study in our lab has shown that this morphological plasticity is associated with significant physiological plasticity for growth. The goal of the current study was to measure several aspects of protein metabolism in larvae growing at different rates to understand the mechanistic basis for this physiological growth plasticity. Larvae of D. excentricus were fed rations of 1,000 (low-fed) or 10,000 (high-fed) algal cells mL−1. Primary measurements of protein growth, algal ingestion, aerobic metabolism, alanine transport and protein synthesis were used to model growth and protein metabolism. Relative protein growth rates were 6.0 and 12.2 % day−1 for low- and high-fed larvae, respectively. The energetic cost of protein synthesis was similar between both treatments at 4.91 J (mg protein synthesized)−1. Larvae in both treatments used about 50% of their metabolic energy production to fuel protein synthesis. Mass-specific rates of protein synthesis were also similar. The most important difference between low- and high-fed larvae were mass-specific rates of protein degradation. Low-fed larvae had relatively low rates of degradation early in development that increased with larval age, surpassing high-fed degradation rates at 20 days post-fertilization. Changes in protein depositional efficiency during development were similar to those of larval growth efficiency, indicating that differences in protein metabolism are largely responsible for whole-organism growth plasticity. Mass-specific alanine transport rates were about 2-times higher in low-fed larvae, demonstrating that the longer arms of low-fed larvae may be a mechanism for acquiring more dissolved nutrients from their environment. In total, these results provide an explanation for the differences in growth efficiency between low- and high-fed larvae and demonstrate the importance of protein degradation pathways in establishing these growth differences. These observations, together with previous studies measuring morphological and physiological plastic responses, allow for a more integrated understanding of developmental plasticity in echinoid larvae.AbbreviationsDPFdays post-fertilizationPOpostoral armAEassimilation efficiencyGGEgross growth efficiencyNGEnet growth efficiencyPGEprotein growth efficiencyPDEprotein depositional efficiencyMBLmidline body lengthFAAfree amino acid poolRGRrelative growth rateBCAbicinchoninic assayBSAbovine serum albuminTCAtrichloroacetic acidBODbiological oxygen demandTORtarget of rapamycinDOMdissolved organic materialView Full Text

physiology↗

bioRxiv2020

Delay-Induced Uncertainty in Physiological Systems

AO_SCPLOWBSTRACTC_SCPLOWMedical practice in the intensive care unit is based on the supposition that physiological systems such as the human glucose-insulin system are reliabile. Reliability of dynamical systems refers to response to perturbation: A dynamical system is reliable if it behaves predictably following a perturbation. Here, we demonstrate that reliability fails for an archetypal physiological model, the Ultradian glucose-insulin model. Reliability failure arises because of the presence of delay. Using the theory of rank one maps from smooth dynamical systems, we precisely explain the nature of the resulting delay-induced uncertainty (DIU). We develop a recipe one may use to diagnose DIU in a general dynamical system. Guided by this recipe, we analyze DIU emergence first in a classical linear shear flow model and then in the Ultradian model. Our results potentially apply to a broad class of physiological systems that involve delay.

physiology↗

bioRxiv2020

An absence of temporal filling-in at the physiological blind-spot.

Visual objects that extend across physiological blind spots seem to encapsulate the extent of blindness, due to a process commonly referred to as a perceptual filling-in of spatial vision. It is unclear if temporal perception is similar, so we examined temporal relationships governing causality perception across the blind spot. We found the human brain does not allow for the time an object should take to traverse the blind-spot when engaging in a causal interaction. We also used electroencephalogram (EEG), to examine temporal signatures of elements flickering on and off in tandem, or in counter-phase. At a control site, we found more brain activity was entrained at the duty cycle by flicker relative to counter-phase changes, whereas these conditions were indistinguishable about blind spots. Our data suggest a common pool of neurons might encode temporal properties on either side of physiological blind-spots. This would explain the absence of any allowance for the extent of blindness in causality perception, and the weakened differences between temporal representations of flicker and counter-phased changes about the blind spot. Overall, our data suggest that, unlike spatial vision, there is no temporal filling-in for perceptual representations about physiological blind spots.

physiology↗

bioRxiv2020

Pharmacological but not physiological GDF15 suppresses feeding and the motivation to exercise

Growing evidence supports that pharmacological application of growth differentiation factor 15 (GDF15) suppresses appetite but also promotes sickness-like behaviors in rodents via GDNF family receptor -like (GFRAL)-dependent mechanisms1,2. Conversely, the endogenous regulation and secretion of GDF15 and its physiological effects on energy homeostasis and behavior remain elusive. Here we show, in four independent studies that prolonged, moderate- to high-intensity endurance exercise substantially increases circulating GDF15, in a time-dependent and reversible fashion, to peak levels otherwise only observed in pathophysiological conditions. This exercise-induced increase can be recapitulated in mice following forced treadmill running and is accompanied by increased Gdf15 expression in the liver, skeletal muscle, and heart muscle. Compared to other metabolic stressors, like fasting, acute high-fat diet feeding, severe caloric excess and temperature changes, exercise has a greater impact on circulating GDF15 levels. However, whereas pharmacological GDF15 inhibits appetite and suppresses wheel running activity via GFRAL, in response to exercise, the physiological induction of GDF15 does not. In summary, exercise-induced circulating GDF15 correlates with the duration of endurance exercise. However, higher GDF15 levels after exercise are not sufficient to evoke canonical pharmacological GDF15 effects on appetite or responsible for exercise aversion/fatigue. Thus, the physiological effects of GDF15 as an exerkine remain elusive.

physiology↗