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bioRxiv2021

Highly accurate retinotopic maps of the physiological blind spot in human visual cortex

The physiological blind spot is a naturally occurring scotoma corresponding with the optic disc in the retina of each eye. Even during monocular viewing, observers are usually oblivious to the scotoma, in part because the visual system extrapolates information from the surrounding area. Unfortunately, studying this visual field region with neuroimaging has proven difficult, as it occupies only a small part of retinotopic cortex. Here we used functional magnetic resonance imaging and a novel data-driven method for mapping the retinotopic organization in and around the blind spot representation in V1. Our approach allowed for highly accurate reconstructions of the extent of an observers blind spot, and out-performed conventional model-based analyses. This method opens exciting opportunities to study the plasticity of receptive fields after visual field loss, and our data add to evidence suggesting that the neural circuitry responsible for impressions of perceptual completion across the physiological blind spot most likely involves regions of extrastriate cortex - beyond V1.

neuroscience↗

bioRxiv2021

Leveraging a physiologically based quantitative translational modeling platform for designing bispecific T cell engagers for treatment of multiple myeloma

Bispecific T cell engager (TCE) is an emerging anti-cancer modality which redirects cytotoxic T cells to tumor cells expressing tumor-associated antigen (TAA) thereby forming immune synapses to exerts anti-tumor effects. Considering the protein engineering challenges in designing and optimizing size and pharmacokinetically acceptable TCEs in the context of the complexity of intercellular bridging between T cells and tumor cells, a physiologically relevant and clinically verified computational modeling framework is of crucial importance to guide the process to understand the protein engineering trade offs. In this study, we developed a quantitative, physiologically based computational framework to predict immune synapse formation for a variety of molecular format of TCEs in tumor tissue. Our model incorporated the molecular size dependent biodistribution using the two pore theory, extra-vascularization of T cells and hematologic cancer cells, mechanistic bispecific intercellular binding of TCEs and competitive inhibitory interaction by shed targets. The biodistribution of TCE was verified by positron emission tomography imaging of [89Zr]AMG211 (a carcinoembryonic antigen-targeting TCE) in patients. Parameter sensitivity analyses indicated that immune synapse formation was highly sensitive to TAA expression, degree of target shedding and binding selectivity to tumor cell surface TAA over shed target. Interestingly, the model suggested a "sweet spot" for TCEs CD3 binding affinity which balanced the trapping of TCE in T cell rich organs. The final model simulations indicated that the number of immune synapses is similar ([~]50/tumor cell) between two distinct clinical stage B cell maturation antigen (BCMA)-targeting TCEs, PF-06863135 in IgG format and AMG420 in BiTE format, at their respective efficacious dose in multiple myeloma patients, demonstrating the applicability of the developed computational modeling framework to molecular design optimization and clinical benchmarking for TCEs. This framework can be employed to other targets to provide a quantitative means to facilitate the model-informed best in class TCE discovery and development. Author summaryCytotoxic T cells play a crucial role in eliminating tumor cells. However, tumor cells develop mechanisms to evade from T cell recognition. Bispecific T cell engager (TCE) is designed to overcome this issue with bringing T cells to close proximity of tumor cells through simultaneous bivalent binding to both tumor-associated antigen and T cells. After successful regulatory approval of blinatumomab (anti-CD19 TCE), more than 40 TCEs are currently in clinical development with a variety of molecular size and protein formats. In this study, we developed a quantitative computational modeling framework for molecular design optimization and clinical benchmarking of TCEs. The model accounts for molecular size dependent biodistribution of TCEs to tumor tissue and other organs as well as following bispecific intercellular bridging of T cells and tumor cells. The model simulation highlighted the importance of binding selectivity of TCEs to tumor cell surface target over shed target. The model also demonstrated a good agreement in predicted immune synapse number for two distinct molecular formats of TCEs at their respective clinically efficacious dose levels, highlighting the usefulness of developed computational modeling framework for best in class TCE discovery and development.

pharmacology and toxicology↗

bioRxiv2021

Molecular liver fingerprint reflects the seasonal physiology of the grey mouse lemur (Microcebus murinus) during winter

Grey mouse lemurs (Microcebus murinus) are a primate species exhibiting strong physiological seasonality in response to environmental energetic constraint. They notably store large amounts of lipids during early winter (EW), which are thereafter mobilized during late winter (LW), when food availability is low. In addition, they develop glucose intolerance in LW only. To decipher how the hepatic mechanisms may support such metabolic flexibility, we analyzed the liver proteome of adult captive male mouse lemurs, which seasonal regulations of metabolism and reproduction are comparable to their wild counterparts, during the phases of either constitution or use of fat reserves. We highlight profound changes that reflect fat accretion in EW at the whole-body level, however, without triggering an ectopic storage of fat in the liver. Moreover, molecular regulations would be in line with the lowering of liver glucose utilization in LW, and thus with reduced tolerance to glucose. However, no major regulation was seen in insulin signaling/resistance pathways, which suggests that glucose intolerance does not reach a pathological stage. Finally, fat mobilization in LW appeared possibly linked to reactivation of the reproductive system and enhanced liver detoxification may reflect an anticipation to return to summer levels of food intake. Altogether, these results show that the physiology of mouse lemurs during winter relies on solid molecular foundations in liver processes to adapt fuel partitioning while avoiding reaching a pathological state despite large lipid fluxes. This work emphasizes how the mouse lemur is of primary interest for identifying molecular mechanisms relevant to biomedical field.

molecular biology↗

bioRxiv2021

Enhanced microvasculature formation and patterning in iPSC-derived kidney organoids cultured in physiological hypoxia

Functional kidney organoids have the potential to be used in implantable kidney grafts for patients with end-stage kidney disease, because they have been shown to self-organize from induced pluripotent stem cells into most important renal structures. To date, however, long-term kidney organoid culture has not succeeded, as nephrons lose their phenotype after approximately 25 days. Furthermore, the renal structures remain immature with diminishing endothelial networks with low connectivity and limited organoid invasion. We hypothesized that introducing long-term culture at physiological hypoxia, rather than the normally applied non-physiological, hyperoxic 21% O2, could initiate angiogenesis, lead to enhanced growth factor expression and improve the endothelial patterning. We therefore cultured the kidney organoids at 7% O2 instead of 21% O2 for up to 25 days and evaluated nephrogenesis, VEGF-A expression and vascularization. Whole mount imaging revealed a homogenous morphology of the endothelial network with enhanced sprouting and interconnectivity when the kidney organoids were cultured in hypoxia. Three-dimensional quantification confirmed that the hypoxic culture led to an increased average vessel length, likely due to the observed upregulation of proangiogenic VEGF-A189 mRNA and downregulation of the antiangiogenic protein VEGF-A165b measured in hypoxia. This research indicates the importance of optimization of oxygen availability in organoid systems and the potential of hypoxic culture conditions in improving the vascularization of organoids. Significance statementCulturing kidney organoids in a hypoxic environment improved patterning of the endothelial network and improved vascularization. These findings may help improve the quality of kidney organoids, and could eventually improve the kidney graft for transplantation in patients with end-stage kidney disease. Furthermore, the organoids will be more suitable for drug testing and in developmental biology. The findings might also be translatable to other organoid models containing endothelial cells. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=199 SRC="FIGDIR/small/473849v1_ufig1.gif" ALT="Figure 1"> View larger version (61K): org.highwire.dtl.DTLVardef@d5cde7org.highwire.dtl.DTLVardef@c0ff46org.highwire.dtl.DTLVardef@b76191org.highwire.dtl.DTLVardef@166823d_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2021

Testing and Validation of Reciprocating Positive Displacement Pump for Benchtop Pulsating Flow Model of Cerebrospinal Fluid Production and Other Physiologic Systems

BackgroundThe flow of physiologic fluids through organs and organs systems is an integral component of their function. The complex fluid dynamics in many organ systems are still not completely understood, and in-vivo measurements of flow rates and pressure provide a testament to the complexity of each flow system. Variability in in-vivo measurements and the lack of control over flow characteristics leave a lot to be desired for testing and evaluation of current modes of treatments as well as future innovations. In-vitro models are particularly ideal for studying neurological conditions such as hydrocephalus due to their complex pathophysiology and interactions with therapeutic measures. The following aims to present the reciprocating positive displacement pump, capable of inducing pulsating flow of a defined volume at a controlled beat rate and amplitude. While the other fluidic applications of the pump are currently under investigation, this study was focused on simulating the pulsating cerebrospinal fluid production across profiles with varying parameters. MethodsPumps were manufactured using 3D printed and injection molded parts. The pumps were powered by an Arduino-based board and proprietary software that controls the linear motion of the pumps to achieve the specified output rate at the desired pulsation rate and amplitude. A range of [Formula] to [Formula] was tested to evaluate the versatility of the pumps. The accuracy and precision of the pumps output were evaluated by obtaining a total of 150 one-minute weight measurements of degassed deionized water per output rate across 15 pump channels. In addition, nine experiments were performed to evaluate the pumps control over pulsation rate and amplitude. Resultsvolumetric analysis of a total of 1200 readings determined that the pumps achieved the target output volume rate with a mean absolute error of -0.001034283 [Formula] across the specified domain. It was also determined that the pumps can maintain pulsatile flow at a user-specified beat rate and amplitude. ConclusionThe validation of this reciprocating positive displacement pump system allows for the future validation of novel designs to components used to treat hydrocephalus and other physiologic models involving pulsatile flow. Based on the promising results of these experiments at simulating pulsatile CSF flow, a benchtop model of human CSF production and distribution could be achieved through the incorporation of a chamber system and a compliance component.

bioengineering↗

bioRxiv2022

Physiological responses of plants to in vivo XRF radiation damage: insights from elemental, histochemical, anatomical and ultrastructural analyses

X-ray fluorescence spectroscopy (XRF) is a powerful technique for the in vivo assessment of plant tissues. However, the potential X-ray exposure damages might affect the structure and elemental composition of living plant tissues leading to artefacts in the recorded data. Herein, we exposed soybean (Glycine max (L.) Merrill) leaves to several X-ray doses through a polychromatic benchtop microprobe X-ray fluorescence spectrometer, modulating the photon flux by adjusting either the beam size, focus, or exposure time. The structure, ultrastructure and physiological responses of the irradiated plant tissues were investigated through light and transmission electron microscopy (TEM). Depending on the dose, the X-ray exposure induced decreased K and X-ray scattering intensities, and increased Ca, P, and Mn signals on soybean leaves. Anatomical analysis indicated necrosis of the epidermal and mesophyll cells on the irradiated spots, where TEM images revealed the collapse of cytoplasm and cell-wall breaking. Furthermore, the histochemical analysis detected the production of reactive oxygen species, as well as inhibition of chlorophyll autofluorescence in these areas. Under certain X-ray exposure conditions, e.g., high photon flux and exposure time, XRF measurements may affect the soybean leaves structures, elemental composition, and cellular ultrastructure, and induce programmed cell death. These results shed light on the characterization of the radiation damage, and thus, help to assess the X-ray radiation limits and strategies for in vivo for XRF analysis. HighlightBy exposing soybean leaves to several X-ray doses, we show that the characteristic X-ray induced elemental changes stem from plants physiological signalling or responses rather than only sample dehydration.

plant biology↗

bioRxiv2022

Navigation of Ultrasound-controlled Swarmbots under Physiological Flow Conditions

Navigation of microrobots in living vasculatures is essential in realizing targeted drug delivery and advancing non-invasive surgeries. We developed acoustically-controlled "swarmbots" based on the self-assembly of clinically-approved microbubbles. Ultrasound is noninvasive, penetrates deeply into the human body, and is well-developed in clinical settings. Our propulsion strategy relies in two forces: the primary radiation force and secondary Bjerknes force. Upon ultrasound activation, the microbubbles self-assemble into microswarms, which migrate towards and anchor at the containing vessels wall. A second transducer, which produces an acoustic field parallel to the channel, propels the swarms along the wall. We demonstrated cross- and upstream navigation of the swarmbots at 3.27 mm/s and 0.53 mm/s, respectively, against physiologically-relevant flow rates of 4.2 - 16.7 cm/s. Additionally, we showed swarm controlled manipulation within mice blood and under pulsatile flow conditions of 100 beats per minute. This capability represents a much-needed pathway for advancing preclinical research. TeaserNavigation of ultrasound-guided microrobots inside artificial blood vessels overcoming physiological conditions, including high flow rates, pulsatile flow regimes, and high cell concentrations of blood.

bioengineering↗

bioRxiv2022

Transition to siblinghood causes substantial and long-lasting physiological stress reactions in wild bonobos

In mammals with a slow ontogeny, the birth of a sibling marks a major developmental transition. Behavioral studies suggest that this event is stressful for the older offspring, but physiological evidence for this is lacking, and it remains unknown whether the birth of a sibling is stressful beyond mere weaning stress. Studying transition to siblinghood in wild bonobos, we investigated physiological changes in urinary cortisol (stress response), neopterin (cell-mediated immunity), and total triiodothyronine (metabolic rate), and related them to behavioral changes in mother-infant relationship and feeding (suckling, riding, proximity, body contact, independent foraging). With siblings birth, cortisol levels increased fivefold in the older offspring and remained elevated for seven months, independent of age. This was associated with diminished immunity but not with behavioral or metabolic changes. Our results indicate that transition to siblinghood is stressful beyond nutritional and social weaning and suggest that this effect is evolutionary old.

evolutionary biology↗

bioRxiv2022

Pleiotropic effects on E. coli physiology of the AraC-like regulator from prophage origin, AppY

Bacterial genome diversity is largely due to prophages, which are viral genomes integrated into the genomes of bacteria. Most prophage genes are silent, but those that are expressed can provide unexpected properties to their host. Using as a model E. coli K-12, that carries 9 defective prophages in its genome, we aimed at highlighting the impact of viral genes on host physiology. We focused our work on AppY, a transcriptional regulator encoded on the DLP12 prophage. By performing RNA-Seq experiments, we showed that AppY production modulates the expression of more than 200 genes; among them, 13 were identified by ChIP-Seq as direct AppY targets. AppY directly and positively regulates several genes involved in the acid stress response including the master regulator gene gadE, but also nhaR and gadY, two genes involved in biofilm formation. Moreover, AppY indirectly and negatively impacts bacterial motility by favouring the degradation of FlhDC, the master regulator of the flagella biosynthesis. As a consequence of these regulatory effects, AppY increased acid stress resistance and biofilm formation while also causing a strong defect in motility. We therefore demonstrate here that AppY is a central regulator from phage origin that controls the expression of bacterial master regulators to provide benefits to E. coli under stress conditions. Our research shed light on the importance to consider the genetic dialogue occurring between prophages and bacteria to fully understand bacterial physiology.

microbiology↗

bioRxiv2022

Pharmacological manipulations of physiological arousal and sleep-like slow waves modulate sustained attention

Sustained attention describes our ability to keep a constant focus on a given task. This ability is modulated by our physiological state of arousal. Although lapses of sustained attention have been linked with dysregulations of arousal, the underlying physiological mechanisms remain unclear. An emerging body of work proposes that the intrusion during wakefulness of sleep-like slow waves, a marker of the transition toward sleep, could mechanistically account for attentional lapses. This study aimed to expose, via pharmacological manipulations of the monoamine system, the relationship between the occurrence of sleep-like slow waves and the behavioural consequences of sustained attention failures. In a double-blind, randomised-control trial, 32 healthy human male participants received methylphenidate, atomoxetine, citalopram or placebo during four separate experimental sessions. During each session, electroencephalography (EEG) was used to measure neural activity whilst participants completed a visual task requiring sustained attention. Methylphenidate, which increases wake-promoting dopamine and noradrenaline across cortical and subcortical areas, improved behavioural performance whereas atomoxetine, which increases dopamine and noradrenaline predominantly over frontal cortices, led to more impulsive responses. Additionally, citalopram, which increases sleep-promoting serotonin, led to more missed trials. Based on EEG recording, citalopram was also associated with an increase in sleep-like slow waves. Importantly, compared to a classical marker of arousal such as alpha power, only slow waves differentially predicted both misses and faster responses in a region-specific fashion. These results suggest that a decrease in arousal can lead to local sleep intrusions during wakefulness which could be mechanistically linked to impulsivity and sluggishness. Significance StatementWe investigated whether the modulation of attention and arousal could not only share the same neuromodulatory pathways but also rely on similar neuronal mechanisms; for example, the intrusion of sleep-like activity within wakefulness. To do so, we pharmacologically manipulated noradrenaline, dopamine, and serotonin in a four-arm, randomised, placebo-controlled trial and examined the consequences on behavioural and EEG indices of attention and arousal. We showed that sleep-like slow waves can predict opposite behavioural signatures: impulsivity and sluggishness. Slow waves may be a candidate mechanism for the occurrence of attentional lapses since the relationship between slow-wave occurrence and performance is region-specific and the consequences of these local sleep intrusions are in line with the cognitive functions carried by the underlying brain regions.

neuroscience↗

bioRxiv2022

A metabolic labeling-based chemoproteomic platform unravels the physiological roles of choline metabolites

Choline is an essential nutrient for mammalian cells. Our understanding of the cellular functions of choline and its metabolites, independent of their roles as choline lipid metabolism intermediates, remains limited. In addition to fundamental cellular physiology, this knowledge has implications for cancer biology because elevated choline metabolite levels are a hallmark of cancer. Here, we establish the mammalian choline metabolite-interacting proteome by utilizing a photocrosslinkable choline probe. To design this probe, we performed metabolic labeling experiments with structurally diverse choline analogs that resulted in the serendipitous discovery of a choline lipid headgroup remodeling mechanism involving sequential dealkylation and methylation steps. We demonstrate that phosphocholine inhibits the binding of one of the proteins identified, the attractive anticancer target, p32, to its endogenous ligands and to the promising p32-targeting anticancer agent, Lyp-1. Our results reveal that choline metabolites play vital roles in cellular physiology by serving as modulators of protein function.

biochemistry↗

bioRxiv2022

Oxidative Stress Induced Senescence Gives Rise to Transcriptionally Distinct Physiological States

As people age, the risk of cardiovascular disease, diabetes, cancer, and Alzheimers disease increases, making age itself the greatest risk factor for many human diseases. Thus, understanding the aging process can have profound consequences for human health. One striking feature of the aging process is the accumulation of senescent cells with age. When cells become damaged, they can enter a state of senescence which is a permanent cell cycle exit associated with the secretion of inflammatory cytokines. In mouse models of aging, the destruction of senescent cells with senolytic drugs delays age-associated decline and extends healthy lifespan. Yet, despite the wealth of accumulated knowledge, we do not entirely understand the biology of senescent cells. Prior work has shown that senescence is associated with increased variation in gene expression, suggesting that there may exist distinct transcriptional signatures of senescence. Understanding the different transcriptional physiological states of senescent cells would allow us to better treat them with cell-type-specific senolytic drugs. Here, we performed large-scale single-cell RNA-sequencing time series experiments to understand the development of transcriptional heterogeneity among senescent cell types. Our approach allowed us to observe and classify different transcriptional signatures of senescent cells as they emerged through time. We found that upon entering oxidative stress-induced senescence, separate subpopulations of cells were reproducibly adopting two distinct transcriptional states, one of which was associated with stress response and the second one with tissue remodeling. Our data suggest that a combination of senolytic drugs may be needed to more effectively eliminate senescent cells by targeting physiologically distinct sub-populations.

cell biology↗

bioRxiv2022

Sex-specific transgenerational effects of diet on offspring life history and physiology

Dietary variation in males and females can shape the expression of offspring life histories and physiology. However, the relative contributions of maternal and paternal dietary variation to phenotypic expression of latter generations is currently unknown. We provided male and female Drosophila melanogaster diets differing in sucrose concentration prior to reproduction, and similarly subjected grandoffspring to the same treatments. We then investigated the phenotypic consequences of this dietary variation among grandsons and granddaughters. We demonstrate transgenerational effects of dietary sucrose, mediated through the grandmaternal lineage, which mimic the direct effects of sucrose on lifespan, with opposing patterns across sexes; low sucrose increased female, but decreased male, lifespan. Dietary mismatching of grandoffspring-grandparent diets increased lifespan and reproductive success, and moderated triglyceride levels, of grandoffspring, providing insights into the physiological underpinnings of the complex transgenerational effects on life histories.

evolutionary biology↗

bioRxiv2022

A genetic strategy to measure insulin signaling regulation and physiology in Drosophila

Insulin regulation is a hallmark of health, and impaired insulin signaling promotes metabolic diseases like diabetes mellitus. However, current assays for measuring insulin signaling in all animals remain semi-quantitative and lack the sensitivity, tissue-specificity or temporal resolution needed to quantify in vivo physiological signaling dynamics. Insulin signal transduction is remarkably conserved across metazoans, including insulin-dependent phosphorylation and regulation of Akt/Protein kinase B. Here, we generated transgenic fruit flies permitting tissue-specific expression of an immunoepitope-labelled Akt (AktHF). We developed enzyme-linked immunosorption assays (ELISA) to quantify picomolar levels of phosphorylated (pAktHF) and total AktHF in single flies, revealing dynamic tissue-specific physiological regulation of pAktHF in response to fasting and re-feeding, exogenous insulin, or targeted genetic suppression of established insulin signaling regulators. Genetic screening revealed Pp1-87B as an unrecognized regulator of Akt and insulin signaling. Tools and concepts here provide opportunities to discover tissue-specific regulators of in vivo insulin signaling responses. Author SummaryInsulin is an essential hormone that controls metabolism in all animals, by regulating energy use and growth of target tissues. Impaired insulin signaling ("resistance") in humans underlies development of type 2 diabetes, a pandemic disease causing significant morbidity and mortality. The genetic risk for insulin resistance is complex, and studies of diabetes are limited by a lack of tools to measure insulin resistance in a sensitive, quantitative, and tissue-specific way. Here, we describe a new technique to measure the strength of insulin signaling in fruit flies. By combining fruit fly genetics with antibody-based assays, we can quantify phosphorylated Akt, an evolutionarily conserved target of insulin signaling, in specific tissues of the adult fly. We show this technique can detect changes in insulin signaling after fasting and refeeding, addition of exogenous insulin, or genetic disruption of the insulin signaling pathway. We used this method to discover a new regulator of insulin signaling, a phosphatase enzyme encoded by Pp1-87B. This exciting new tool should advance our ability to study and discover additional regulators of insulin signaling and resistance.

genetics↗

bioRxiv2022

Variation in morpho-physiological and metabolic responses to low nitrogen stress across the sorghum association panel

Access to biologically available nitrogen is a key constraint on plant growth in both natural and agricultural settings. Variation in tolerance to nitrogen deficit stress and productivity in nitrogen limited conditions exists both within and between plant species. Here we quantified variation in the metabolic, physiological, and morphological responses of a sorghum association panel assembled to represent global genetic diversity to long term, moderate, nitrogen deficit stress and the relationship of these responses to grain yield under both conditions. Grain yield exhibits substantial genotype by environment interaction while many other morphological and physiological traits exhibited consistent responses to nitrogen stress across the population. Large scale nontargeted metabolic profiling for a subset of lines in both conditions identified a range of metabolic responses to long term nitrogen deficit stress as well as several metabolites associated with variation in the degree of yield plasticity specific sorghum genotypes exhibited in response to nitrogen deficit stress.

plant biology↗

bioRxiv2022

Adaptation shapes local cortical reactivity: from bifurcation diagram and simulations to human physiological and pathological responses

Human studies employing intracerebral and transcranial perturbations suggest that the input-output properties of cortical circuits are dramatically affected during sleep in healthy subjects as well as in awake patients with multifocal and focal brain injury. In all these conditions, cortical circuits react to direct stimulation with an initial activation followed by suppression of activity (Off-period) that disrupts the build-up of sustained causal interactions typically observed in healthy wakefulness. The transition to this stereotypical response is of clinical relevance, being associated with loss of consciousness or loss of function. Here, we provide a mechanistic explanation of these findings by means of mean-field theory and simulations of a cortical-like module endowed with activity-dependent adaptation. First, we show that fundamental aspects of the local responses elicited in humans by direct cortical stimulation can be replicated by systematically varying the relationships between adaptation strength and excitation level in the network. Then, we reveal a region in the adaptation-excitation parameter space of key relevance for both physiological and pathological conditions, where spontaneous activity and responses to perturbation diverge in their ability to reveal Off-periods. Finally, we substantiate through simulations of connected cortical-like modules the role of adaptation mechanisms in preventing cortical neurons from engaging in reciprocal causal interactions, as suggested by empirical studies. These modeling results provide a general theoretical framework and a mechanistic interpretation for a body of neurophysiological measurements that bears key relevance for physiological states as well as for the assessment and rehabilitation of brain-injured patients. Significance StatementSuppression of cortical activity following an initial activation is a defining feature of deep sleep in healthy subjects and wakefulness in patients affected by focal and multifocal brain injuries. Experimental findings suggest that these bimodal responses disrupt the emergence of complex interactions among cortical regions, leading to loss of consciousness or functional impairments. Given their practical implications, it is important to study the mechanisms involved within a general theoretical framework. Using a neuronal network model, we provide evidence for a key role of activity-dependent adaptation mechanisms in shaping the responses to perturbation and in affecting the build-up of complex cortical interactions. Overall, this work provides a mechanistic interpretation relevant for the stratification, follow-up, and rehabilitation of brain-injured patients.

neuroscience↗

bioRxiv2022

The Saccharina latissima microbiome: algal tissue matters more than region, season, and physiology

Saccharina latissima is a canopy-forming species of brown algae and, as such, is considered an ecosystem engineer. Several populations of this alga are exploited worldwide, and a decrease in the abundance of S. latissima at its southern distributional range limits has been observed. Despite its economic and ecological interest, only a few data are available on the composition of microbiota associated with S. latissima and its role in algal physiology. We studied the whole bacterial community composition associated with S. latissima samples from three locations (Brittany, Helgoland, and Skagerrak) by 16S metabarcoding analyses at different scales: algal blade part, regions, season, and physiologic state. We have shown that the difference in bacterial composition is driven by factors of decreasing importance: (i) the algal tissues (apex/meristem), (ii) the geographical area, (iii) the seasons, and (iv) the algal hosts condition (healthy vs. symptoms). Overall, Alphaproteobacteria, Gammaproteobacteria, and Bacteroidota dominated the general bacterial communities. Almost all individuals hosted bacteria of the genus Granulosicoccus, accounting for 12% of the total sequences, and eight additional core genera were identified. Our results also highlight a microbial signature characteristic for algae in poor health independent of the disease symptoms. Thus, our study provides a comprehensive overview of the S. latissima microbiome, forming a basis for understanding holobiont functioning.

microbiology↗

bioRxiv2022

Aesthetic and physiological effects of naturalistic multimodal music listening

Compared to audio only (AO) conditions, audiovisual (AV) information can enhance the aesthetic experience of a music performance. However, such beneficial multimodal effects have yet to be studied in naturalistic music performance settings. Further, peripheral physiological correlates of aesthetic experiences are not well-understood. Here, participants were invited to a concert hall for piano performances of Bach, Messiaen, and Beethoven, which were presented in two conditions: AV and AO. They rated their aesthetic experience (AE) after each piece (Experiment 1 and 2), while peripheral signals (cardiorespiratory measures, skin conductance, and facial muscle activity) were continuously measured (Experiment 2). Factor scores of AE were significantly higher in the AV condition in both experiments. LF/HF ratio, a heart rhythm that represents activation of the sympathetic nervous system, was higher in the AO condition, suggesting increased arousal, likely caused by less predictable sound onsets in the AO condition. We present partial evidence that breathing was faster and facial muscle activity was higher in the AV condition, suggesting that observing a performers movements likely enhances motor mimicry in these more voluntary peripheral measures. Further, zygomaticus ( smiling) muscle activity was a significant predictor of AE. Thus, we suggest physiological measures are related to AE, but at different levels: the more involuntary measures (i.e., heart rhythms) may reflect more sensory aspects, while the more voluntary measures (i.e., muscular control of breathing and facial responses) may reflect the liking aspect of an AE. In summary, we replicate and extend previous findings that AV information enhances AE in a naturalistic music performance setting. We further show that a combination of self-report and peripheral measures benefit a meaningful assessment of AE in naturalistic music performance settings.

neuroscience↗