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Queen loss fails to elicit physiological and transcriptional responses in workers of the invasive garden ant Lasius neglectus

Insect colonies with morphologically distinct castes have been called superorganisms because their queens and workers are functionally analogous to the germline and soma in metazoan bodies. In the haplodiploid ants, workers typically lost the sperm storage organ but retained ovaries so they can lay unfertilized eggs. Worker reproduction often occurs after queen loss and is accompanied by a number of physiological changes. However, in some evolutionarily derived ants, workers have become functionally sterile and in many of these species colonies contain multiple queens and can readily raise replacement queens - a syndrome characteristic for invasive ants. We hypothesized that the combination of full worker sterility and regular queen replacement should have eliminated important aspects of the physiological interdependence between queens and workers. We tested this hypothesis by analysing fat body gene expression and worker resistance to oxidative stress in colonies of the invasive ant Lasius neglectus with and without queens. We found age-related transcriptional shifts between young and old queens and young and old workers, suggesting rapid ageing in all castes. However, the removal of any queens in controlled experiments failed to elicit changes in the transcriptional activity and oxidative stress resistance of workers, consistent with our hypothesis. The invasive syndrome of this ant may thus have led to a somatic work force that evolved to be physiologically independent of queen presence.

evolutionary biology↗

Ion-channel degeneracy and heterogeneities in the emergence of signature physiological characteristics of dentate gyrus granule cells

Complex systems are neither fully determined nor completely random. Biological complex systems, including single neurons, manifest intermediate regimes of randomness that recruit integration of specific combinations of functionally segregated subsystems. Such emergence of biological function provides the substrate for the expression of degeneracy, the ability of disparate combinations of subsystems to yield similar function. Here, we present evidence for the expression of degeneracy in morphologically realistic models of dentate gyrus granule cells (GC) through functional integration of disparate ion-channel combinations. We performed a 45-parameter randomized search spanning 16 active and passive ion channels, each biophysically constrained by their gating kinetics and localization profiles, to search for valid GC models. Valid models were those that satisfied 17 sub- and supra-threshold cellular-scale electrophysiological measurements from rat GCs. A vast majority (>99%) of the 15,000 random models were not electrophysiologically valid, demonstrating that arbitrarily random ion-channel combinations wouldnt yield GC functions. The 141 valid models (0.94% of 15,000) manifested heterogeneities in and cross-dependencies across local and propagating electrophysiological measurements, which matched with their respective biological counterparts. Importantly, these valid models were widespread throughout the parametric space and manifested weak cross-dependencies across different parameters. These observations together showed that GC physiology could neither be obtained by entirely random ion-channel combinations nor is there an entirely determined single parametric combination that satisfied all constraints. The complexity, the heterogeneities in measurement and parametric spaces, and degeneracy associated with GC physiology should be rigorously accounted for, while assessing GCs and their robustness under physiological and pathological conditions. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC="FIGDIR/small/580453v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@1fe6e90org.highwire.dtl.DTLVardef@10cc473org.highwire.dtl.DTLVardef@135732dorg.highwire.dtl.DTLVardef@1caec0_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Opposing roles of physiological and pathological amyloid-β on synapses in live human brain slice cultures

In Alzheimers disease, it is theorised that amyloid beta (A{beta}) and tau pathology contribute to synapse loss. However, there is limited information on how endogenous levels of tau and A{beta} protein relate to patient characteristics, or how manipulating physiological levels of A{beta} impacts synapses, in living adult, human brain. Here, we employed live human brain slice cultures as a translational tool to assess endogenous tau and A{beta} release, pathology, and response to experimental manipulation. We found that the levels of A{beta}1-40 and tau detected in the culture medium depend on donor age, and brain region, respectively. Pharmacologically raising physiological A{beta} concentration enhanced levels of synaptic transcripts. Treatment of slices with A{beta}-containing Alzheimers disease brain extract resulted in postsynaptic A{beta} uptake and loss of presynaptic puncta. These data indicate that physiological and pathological A{beta} can have opposing effects on synapses in living human brain tissue.

neuroscience↗

Changes in plant physiology during cultivation periods influence the hydrogen isotope ratio of the water-insect relationship

O_LIThe hydrogen stable isotope ratios ({delta}2H) in tissues of terrestrial insects are widely applied to estimate natal origins in field populations. The hydrogen isotopes of insect tissues incorporate those of environmental waters through the insects metabolic processes. Water sources and abiotic environmental factors reflect changes in plant physiology, as indicated by the {delta}2H values of plants. However, the influence of plant physiology on the assimilation of hydrogen in insect tissues derived from water through feeding diets is still unknown. C_LIO_LIWe experimentally examined the influence of water on the {delta}2H values of maize leaf and of forewings of Mythimna separata (Lepidoptera: Noctuidae) and Spodoptera frugiperda (Noctuidae). We prepared five specific water samples for cultivating maize, aiming to replicate the gradient of {delta}2H values observed in environmental waters across the Japanese archipelago. C_LIO_LIThe mean-percentage contribution of water to hydrogen in maize leaves was 17.6% (July-August) and 25.1% (September-October). Linear analyses indicated that 17.4% and 32.7% of hydrogen in M. separata and S. frugiperda forewings were derived from water through the consumption of maize leaves. The slope values of linear regression between the insect forewings and the maize leaves supplied in the final instar were closest to 1.0. These results indicated that the {delta}2H values of maize leaves and insect forewings reflected those of water resources. C_LIO_LIThis study presented the seasonal changes in climate conditions that affected the {delta}2H values of host plants and insect tissues. Changes in plant physiology with seasonal variations may influence the interpretation of the linear relationship between water and insect tissues on the estimation of natal origins. C_LI

ecology↗

Cool ocean temperatures fail to buffer the impacts of heat exposure during low tide on the behaviour and physiology of a keystone predator

Air temperatures are warming at faster rates than ocean temperatures, and this "land-sea warming contrast" may create reprieves from thermal stress by providing cool underwater refugia during extreme heat events. Here we tested the impacts of the "land-sea warming contrast" on physiology (metabolism) and behaviour (feeding) in the juvenile life stage of a keystone intertidal predator, Pisaster ochraceus, by experimentally manipulating air ([~]20, 25, 30) and water ([~]15, 20) temperatures (at independent rates) representing early summer, late summer, and heatwave conditions in Barkley Sound (British Columbia, Canada). We further made observations of air temperatures, sea surface temperatures, and Pisaster moribundity at our study location to support interpretation of our results. We predicted metabolism and feeding would increase with early and late summer temperatures, but decrease during heatwave conditions as animals surpass their thermal optimum. We observed the greatest mortality and lowest feeding in juvenile Pisaster exposed to cool ocean temperatures ([~]15) and high aerial temperatures typical of extreme heat events ([~]30). Feeding rates increased with heat stress duration, indicating animals may be compensating for elevated metabolism. Metabolic rates did not differ between air temperatures, but oxygen consumption was higher in animals with access to mussels than for Pisaster that were fasted. The highest levels of experimental and field moribundity were observed in August, indicating Pisaster may have accumulated physiological stress damage following elevated air and ocean temperatures throughout the summer. Our research implicates shifts in community dynamics due to the loss of this keystone species as air temperatures warm. Summary StatementCooler ocean temperatures, rather than creating thermal refugia, may cause physiological stress for juvenile Pisaster ochraceus exposed to warm air during low tide.

ecology↗

Loss of LasR function leads to decreased repression of Pseudomonas aeruginosa PhoB activity at physiological phosphate concentrations

While the Pseudomonas aeruginosa LasR transcription factor plays a role in quorum sensing (QS) across phylogenetically-distinct lineages, isolates with loss-of-function mutations in lasR (LasR- strains) are commonly found in diverse settings including infections where they are associated with worse clinical outcomes. In LasR- strains, the transcription factor RhlR, which is controlled by LasR, can be alternately activated in low inorganic phosphate (Pi) concentrations via the two-component system PhoR-PhoB. Here, we demonstrate a new link between LasR and PhoB in which the absence of LasR increases PhoB activity at physiological Pi concentrations and raises the Pi concentration necessary for PhoB inhibition. PhoB activity was also less repressed by Pi in mutants lacking different QS regulators (RhlR and PqsR) and in mutants lacking genes required for the production of QS-regulated phenazines suggesting that decreased phenazine production was one reason for decreased PhoB repression by Pi in LasR- strains. In addition, the CbrA-CbrB two-component system, which is elevated in LasR- strains, was necessary for reduced PhoB repression by Pi and a {Delta}crc mutant, which lacks the CbrA-CbrB-controlled translational repressor, activated PhoB at higher Pi concentrations than the wild type. The {Delta}lasR mutant had a PhoB-dependent growth advantage in a medium with no added Pi and increased virulence-determinant gene expression in a medium with physiological Pi, in part through reactivation of QS. This work suggests PhoB activity may contribute to the virulence of LasR- P. aeruginosa and subsequent clinical outcomes. ImportanceLoss-of-function mutations in the gene encoding the Pseudomonas aeruginosa quorum sensing (QS) regulator LasR occur frequently and are associated with worse clinical outcomes. We have found that LasR- P. aeruginosa have elevated PhoB activity at physiological concentrations of inorganic phosphate (Pi). PhoB activity promotes Pi acquisition as well as the expression of QS and virulence-associated genes. Previous work has shown that PhoB induce RhlR, another QS regulator, in a LasR-mutant in low Pi conditions. Here, we demonstrate a novel relationship wherein LasR represses PhoB activity, in part through the production of phenazines and Crc-mediated translational repression. This work suggests PhoB activity may contribute to the increased virulence of LasR- P. aeruginosa.

microbiology↗

Physiological and transcriptional changes associated with obligate aestivation in the cabbage stem flea beetle (Psylliodes chrysocephala)

1Aestivation is a form of seasonal dormancy observed in various insect species, usually coinciding with the summer season. Psylliodes chrysocephala (Coleoptera: Chrysomelidae), the cabbage stem flea beetle, is a key pest of oilseed rape and obligatorily aestivates as adult in late summer. At present, our understanding of the physiological and transcriptional changes linked to aestivation in P. chrysocephala is still limited. In this study, physiological parameters and RNA-seq analyses were performed with laboratory-reared beetles at pre-aestivation, aestivation, and post-aestivation stages. Measurements of CO2 production supported the notion that aestivating beetles dramatically reduce their metabolic rate and, together with assessments of reproductive maturation, allowed precise discrimination between the three adult stages. Aestivating beetles showed a reduction in carbohydrate reserves and an increase in lipid reserves compared to pre-aestivating beetles, indicating that aestivation is associated with drastic changes in energy metabolism. In agreement with these findings, we found that genes involved in carbohydrate and lipid metabolism, digestion, and mitochondrial activity are differentially expressed between the three stages. Furthermore, RNA-seq analysis suggested the regulation of transcription factors associated with aestivation maintenance and the involvement of cytochrome P450s in conferring a summer-resistant phenotype during the aestivation period. In conclusion, this study represents the first exploration of the transcriptomic and physiological aspects of the aestivation response in P. chrysocephala. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/588545v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@10d486forg.highwire.dtl.DTLVardef@10e9e1corg.highwire.dtl.DTLVardef@ae63aforg.highwire.dtl.DTLVardef@112985c_HPS_FORMAT_FIGEXP M_FIG C_FIG O_LIP. chrysocephala obligatorily aestivate as sexually immature adults in summer C_LIO_LIAestivation entails metabolic suppression, body composition changes and resistance C_LIO_LIAccordingly, metabolism and stress genes were differentially expressed C_LIO_LIThe findings can support the development of innovative pest management strategies C_LI

zoology↗

A 3D whole-face movement analysis system to uncover underlying physiology in mice

Facial expressions and movements, from a subtle and ephemeral grimace, to vigorous and rapid chewing, offer direct insights into the moment-to-moment change of neural and physiological processes. Mice, with discernible facial responses and evolutionarily conserved mammalian facial movement control circuits, provide an ideal model to unravel the link between facial movement and underlying physiological states. However, existing frameworks lack the spatial or temporal resolution to sensitively track all movements of the mouse face, due to its small and conical form factor. We introduce Cheese3D, a computer vision system that captures high-speed 3D motion of the entire mouse face (including ears, eyes, whisker pad, and jaw, while covering both sides of the face) using a calibrated six-camera array. The interpretable framework extracts dynamics of anatomically-meaningful 3D facial features in absolute world units at sub-millimeter precision. The precise face-wide motion data generated by Cheese3D provides clear physiological insights, as shown by proof-of-principle experiments predicting time under general anesthesia from changing facial patterns, inferring tooth and muscle anatomy from fast ingestion motions across the entire face, measuring minute differences in movements evoked by brainstem stimulation, and relating neural activity to spontaneous facial movements, including expressive features only measurable in 3D (e.g., angles of ear motion). Cheese3D can serve as a discovery tool that renders subtle mouse facial movements highly interpretable as a readout of otherwise hidden internal states.

animal behavior and cognition↗

Physiological role and mechanisms of action for a long noncoding haplotype region

Most common sequence variants associated with human traits are in noncoding regions of the genome, form haplotypes with other noncoding variants, and exhibit small effect sizes in the general population. Determining the physiological roles and mechanisms of action for these noncoding variants, particularly large haplotypes containing multiple variants, is both critical and challenging. To address this challenge, we developed an approach that integrates physiological studies in genetically engineered and phenotypically permissive animal models, precise editing of large haplotypes in human induced pluripotent stem cells (hiPSCs), and targeted chromatin conformation analysis. We applied this approach to examine the blood pressure associated rs1173771 locus, which includes a haplotype containing 11 single nucleotide polymorphisms (SNPs) spanning 17.4 kbp. Deleting the orthologous noncoding region in the genome of the Dahl salt-sensitive rat attenuated the salt-induced increase in systolic blood pressure by nearly 10 mmHg. This attenuation of hypertension appeared to be mediated by upregulation of the adjacent gene Npr3 (natriuretic peptide receptor 3) in arteries, enhancing vasodilation. The blood pressure-elevating and -lowering haplotypes were precisely reconstituted in hiPSCs using an efficient, two-step genome editing technique. The blood pressure-elevating haplotype decreased NPR3 expression in endothelial cells and vascular smooth muscle cells derived from the edited, isogenic hiPSCs. The influence of the haplotype was partially recapitulated by the sentinel SNP rs1173771. Additionally, the blood pressure-elevating haplotype showed significantly greater chromatin interactions with the NPR3 promoter region. This study illustrates the feasibility of ascertaining the physiological roles and mechanisms of action for large noncoding haplotypes. Our efficient, integrated, and targeted approach can be applied to investigate other noncoding variants.

genetics↗

Using physiologically-based models to predict in vivo skeletal muscle energetics

Understanding how muscles use energy is essential for elucidating the role of skeletal muscle in animal locomotion. Yet, experimental measures of in vivo muscle energetics are challenging to obtain, so physiologically-based muscle models are often used to estimate energy use. These predictions of individual muscle energy expenditure are not often compared to indirect whole body measures of energetic cost. Here, we examined and illustrated the capability of physiologically-based muscle models to predict in vivo measures of energy use. To improve model predictions and ensure a physiological basis for model parameters, we refined our model to include data from isolated muscle experiments. Simulations were performed to capture three different experimental protocols, which involved varying contraction frequency, duty cycle, and muscle fascicle length. Our results demonstrated that these models are able capture the general features of whole body energetics across contractile conditions, but tended to under predict the magnitude of energetic cost. Our analysis revealed that when predicting in vivo energetic rates across contractile conditions, the model was most sensitive to the force-velocity parameters and the data informing the energetic rates when predicting in vivo energetic rates across contractile conditions. This work highlights it is the mechanics of skeletal muscle contraction that govern muscle energy use.

bioengineering↗

Physiological Roles of an Acinetobacter-specific σ Factor

The Gram-negative pathogen Acinetobacter baumannii is considered an "urgent threat" to human health due to its propensity to become antibiotic resistant. Understanding the distinct regulatory paradigms used by A. baumannii to mitigate cellular stresses may uncover new therapeutic targets. Many {gamma}-proteobacteria use the extracytoplasmic function (ECF) {sigma} factor, RpoE, to invoke envelope homeostasis networks in response to stress. Acinetobacter species contain the poorly characterized ECF "SigAb;" however, it is unclear if SigAb has the same physiological role as RpoE. Here, we show that SigAb is a metal stress-responsive ECF that appears unique to Acinetobacter species and distinct from RpoE. We combine promoter mutagenesis, motif scanning, and ChIP-seq to define the direct SigAb regulon, which consists of sigAb itself, the stringent response mediator, relA, and the uncharacterized small RNA, "sabS." However, RNA-seq of strains overexpressing SigAb revealed a large, indirect regulon containing hundreds of genes. Metal resistance genes are key elements of the indirect regulon, as CRISPRi knockdown of sigAb or sabS resulted in increased copper sensitivity and excess copper induced SigAb-dependent transcription. Further, we found that two uncharacterized genes in the sigAb operon, "aabA" and "aabB", have anti-SigAb activity. Finally, employing a targeted Tn-seq approach that uses CRISPR-associated transposons, we show that sigAb, aabA, and aabB are important for fitness even during optimal growth conditions. Our work reveals new physiological roles for SigAb and SabS, provides a novel approach for assessing gene fitness, and highlights the distinct regulatory architecture of A. baumannii. ImportanceAcinetobacter baumannii is a hospital-acquired pathogen, and many strains are resistant to multiple antibiotics. Understanding how A. baumannii senses and responds to stress may uncover novel routes to treat infections. Here, we examine how the Acinetobacter-specific transcription factor, SigAb, mitigates stress. We find that SigAb directly regulates only a small number of genes, but indirectly controls hundreds of genes that have substantial impacts on cell physiology. We show that SigAb is required for maximal growth, even during optimal conditions, and is acutely required during growth in the presence of elevated copper. Given that copper toxicity plays roles in pathogenesis and on copper-containing surfaces in hospitals, we speculate that SigAb function may be important in clinically-relevant contexts.

microbiology↗

Thermal preconditioning modulates coral physiology and heat tolerance: A multi-species perspective

Global warming threatens reef-building corals by challenging their natural adaptive capacity. Therefore, interventions such as stress hardening by thermal preconditioning could become crucial for their survival. Stress-hardening approaches recognize that organisms living in thermally variable environments are better able to withstand marine heat waves. However, a systematic assessment of preconditioning effects on the baseline physiology and thermal tolerance across coral species is lacking. We assessed the changes of thermal tolerance in six stony coral species (Galaxea fascicularis, Porites rus, Acropora muricata, Montipora digitata, and Stylophora pistillata) in three thermal preconditioning treatments of stable-high 29 {degrees}C and variable-high 29 {degrees}C with a daily oscillation of {+/-} 1.5 {degrees}C, compared to corals in stable-ambient 26 {degrees}C. We quantified changes in photosynthetic efficiency and coral bleaching intensity before and after a short-term heat stress assay and up to 30 days later. Stress-hardening success after preconditioning was observed in nearly all preconditioned corals, but the increases in thermal tolerance were species-specific. The greatest increase was recorded in G. fascicularis and A. muricata, with stress responses reduced by over 80 %. In contrast, preconditioning regimes had minor effects on stress tolerance of S. pistillata, making it least receptive to this intervention. After 30 days, most stress-hardened species demonstrated higher survival and recovery rates than their conspecifics from the stable-ambient regime. Notably, both preconditioning regimes affected baseline physiology, especially in the branching species, as indicated by minor tissue paling and decreased photosynthetic efficiency. We conclude that implementing thermal stress hardening protocols will require careful consideration of the species-specific receptiveness and evaluation of the potential trade-offs that can be inflicted with the post-conditioning shifts in physiological baselines.

ecology↗

Single cell multiome profiling of pancreatic islets reveals physiological changes in cell type-specific regulation associated with diabetes risk

Physiological variability in pancreatic cell type gene regulation and the impact on diabetes risk is poorly understood. In this study we mapped gene regulation in pancreatic cell types using single cell multiomic (joint RNA-seq and ATAC-seq) profiling in 28 non-diabetic donors in combination with single cell data from 35 non-diabetic donors in the Human Pancreas Analysis Program. We identified widespread associations with age, sex, BMI, and HbA1c, where gene regulatory responses were highly cell type- and phenotype-specific. In beta cells, donor age associated with hypoxia, apoptosis, unfolded protein response, and external signal-dependent transcriptional regulators, while HbA1c associated with inflammatory responses and gender with chromatin organization. We identified 10.8K loci where genetic variants were QTLs for cis regulatory element (cRE) accessibility, including 20% with lineage- or cell type-specific effects which disrupted distinct transcription factor motifs. Type 2 diabetes and glycemic trait associated variants were enriched in both phenotype- and QTL-associated beta cell cREs, whereas type 1 diabetes showed limited enrichment. Variants at 226 diabetes and glycemic trait loci were QTLs in beta and other cell types, including 40 that were statistically colocalized, and annotating target genes of colocalized QTLs revealed genes with putatively novel roles in disease. Our findings reveal diverse responses of pancreatic cell types to phenotype and genotype in physiology, and identify pathways, networks, and genes through which physiology impacts diabetes risk.

genomics↗

A physiologically inspired hybrid CPG/Reflex controller for cycling simulations that generalizes to walking

Predictive simulations based on explicit, physiologically inspired, control policies, can be used to test theories on motor control and to evaluate the effect of interventions on the different components of control. Several control architectures have been proposed for simulating locomotor tasks, based on fully feedback, reflex-based, controllers, or on feedforward architectures mimicking the Central Pattern Generators. Recently, hybrid architectures integrating both feedback and feedforward components have been shown to represent a viable alternative to fully feedback or feedforward controllers. Current literature on controller-based simulations, however, almost exclusively presents task-specific controllers that do not generalize across different tasks. The task-specificity of current controllers limits the generalizability of the neurophysiological principles behind such controllers. Here we propose a hybrid controller for predictive simulations of cycling based where the feedforward component is based on a well-known theoretical model, the Unit Burst Generation model, and the feedback component includes a limited set of reflex pathways, expected to be active during submaximal steady cycling. We show that this controller can simulate physiological cycling patterns at different desired speeds. We also show that the controller can generalize to walking behaviors by just adding an additional control component for accounting balance needs. The controller here proposed, although simple in design, represent an instance of physiologically inspired generalizable controller for cyclical lower limb tasks. Author SummaryPredictive simulations allow to synthesize human movements and their associated biomechanical quantities without using experimental data. Such simulations can help understand how humans may perform movement tasks in different scenarios and could provide useful information in fields like rehabilitation. One of the methodologies used for developing predictive simulations is based on creating models of the neural control architectures that generate the activation of the muscles. In this work we propose the first neural control architecture for cycling behaviors. We show that our architecture can be used to develop predictive simulations of cycling at different speeds and that the associated biomechanical quantitites are consistent with experimental data. Moreover, we show that our control architecture can also replicate walking behaviors with minimal modifications.

neuroscience↗

Comparison of morphological and physiological response to drought stress among temperate forest understory forbs and graminoids

O_LIDrought stress can profoundly affect plant growth and physiological vitality, yet there is a notable scarcity of controlled drought experiments focused on herbaceous species of the forest understory. C_LIO_LIIn this study, we collected seeds from five forb and four graminoid species growing in the temperate forest understory of the Czech Republic. These seeds were germinated under controlled glasshouse conditions and subjected to moderate drought stress for five weeks. We assessed biomass partitioning, stomatal and leaf morphology, leaf gas exchange, minimum leaf conductance (gmin), and chlorophyll fluorescence parameters. C_LIO_LIThe comparison of two ecological guilds revealed that graminoids exhibited a higher root-to-shoot ratio, improved water-use efficiency, greater carboxylation efficiency, and enhanced non-photochemical quenching under drought conditions compared to forbs. In contrast, forbs had significantly lower gmin, along with higher total biomass and total leaf area. Despite these differences in morpho-physiological functional traits, both groups experienced a similar relative reduction in biomass during drought stress. Key predictors of biomass accumulation under drought included photochemical quenching, stomatal traits, total leaf area and gmin. A negative correlation between biomass and gmin suggests that plants with lower residual water losses after stomatal closure can accumulate more biomass under drought stress. Additionally, gmin was positively correlated with guard cell length, suggesting that larger stomata contribute to higher residual water loss. C_LIO_LIGraminoids exhibited morpho-physiological modifications that enhanced drought resistance, indicating a greater emphasis on stress tolerance as a survival strategy. In contrast, forbs maintained higher biomass and total leaf area, reflecting a competitive strategy for maximizing resource acquisition. C_LI

plant biology↗

Synthetic chaperone based on Hsp90-Tau interaction inhibits pathological Tau aggregation and rescues physiological Tau-Microtubule interaction

The accumulation of intracellular aggregates of Tau protein is one main hallmark of Alzheimers disease (AD) and is the consequence of Tau conformational changes, increased phosphorylation, and self-association to form fibrillar aggregates. This pathological process prevents the physiological interaction of Tau with microtubules to the detriment of the structural integrity of neurons. In healthy cells, aberrant protein misfolding and aggregation are counteracted by chaperone proteins whose protective capacity decreases with age. The role of the chaperone Hsp90 and the mechanism by which it can prevent Tau aggregation toxicity are controversial. The innovative strategy of mimicking Hsp90 through the design of the {beta}-hairpin like peptidomimetic {beta}-Hsp90, inspired by two Hsp90/Tau interaction sequences, is presented here. {beta}-Hsp90 inhibits Tau aggregation both in vitro and in cells, restoring Taus physiological interaction with microtubules. {beta}-Hsp90, which interacts with the P1 region of Tau, is more effective than individual peptide sequences from the chaperone HSP90 and another {beta}-hairpin mimic based on Tau sequences. Moreover, {beta}-Hsp90 dramatically reduces AD-associated A{beta}1-42 aggregation, offering the development of a dual inhibitor. This work paves the way for the design of new drugs targeting devastating untreated amyloid diseases, by mimicking physiological chaperones with small synthetic peptide drugs.

pharmacology and toxicology↗

Repeated presentation of visual threats drives innate fear habituation and is modulated by environmental and physiological factors

To survive predation, animals must be able to detect and appropriately respond to predator threats in their environment. Such defensive behaviors are thought to utilize hard-wired neural circuits for threat detection, sensorimotor integration, and execution of ethologically relevant behaviors. Despite being hard-wired, defensive behaviors (i.e. fear responses) are not fixed, but rather show remarkable flexibility, suggesting that extrinsic factors such as threat history, environmental contexts, and physiological state may alter innate defensive behavioral responses. The goal of the present study was to examine how extrinsic and intrinsic factors influence innate defensive behaviors in response to visual threats. In the absence of a protective shelter, our results indicate that mice showed robust freezing behavior following both looming (proximal) and sweeping (distal) threats, with increased behavioral vigor in response to looming stimuli, which represent a higher threat imminence. Repeated presentation of looming or sweeping stimuli at short inter-trial intervals resulted in robust habituation of freezing, which was accelerated at longer inter-trial intervals, regardless of contextual cues. Finally, physiological factors such as acute stress further disrupted innate freezing habituation, resulting in a delayed habituation phenotype, consistent with a heightened fear state. Together, our results indicate that extrinsic factors such as threat history, environmental familiarity, and physiological stressors have robust and diverse effects on defensive behaviors, highlighting the behavioral flexibility in how mice respond to predator threats.

animal behavior and cognition↗

Circadian regulation of key physiological processes by the RITMO1 clock protein in the marine diatom Phaeodactylum tricornutum

O_LIPhasing biological and physiological processes to periodic light-dark cycles is crucial for the life of most organisms. Marine diatoms, as many phytoplanktonic species, exhibit biological rhythms, yet their molecular timekeepers remain largely uncharacterized. Recently, the bHLH-PAS protein RITMO1 has been proposed to act as a regulator of circadian rhythms. C_LIO_LIIn this study, we first determined the physiological conditions to monitor circadian clock activity and its perturbation in the diatom model species Phaeodactylum tricornutum by using cell fluorescence as a circadian output. Employing ectopic overexpression, targeted gene mutagenesis, and functional complementation, we then investigated the role of RITMO1 in various circadian processes. C_LIO_LIOur findings reveal that RITMO1 significantly influences the P. tricornutum circadian rhythms not only of cellular fluorescence, but also of photosynthesis and of the expression of clock-controlled genes, including transcription factors and putative clock input/output components. RITMO1 effects on rhythmicity are unambiguously detectable under free running conditions. C_LIO_LIBy uncovering the complex regulation of biological rhythms in P. tricornutum, these results provide a key step in understanding the endogenous regulators of phytoplankton physiological responses to environmental changes. Furthermore, these studies position diatoms as instrumental and novel model systems for elucidating key mechanistic principles of oscillator functions in marine ecosystems. C_LI

molecular biology↗