Biology subjects

Martel, A.

Publications and source records attributed to Martel, A..

At least 19 recordsLinked to original sources

bioRxiv2026

Calibrated ADAMTS13 inhibition prevents cardiovascular shear coagulopathy

Mechanical circulatory support essential for managing severe heart failure frequently triggers bleeding complications, driven by shear stress-induced over-proteolysis of von Willebrand factor (VWF) by ADAMTS13. Inhibiting ADAMTS13 presents a rationale to treat this condition, known as acquired von Willebrand syndrome (AVWS). However, conventional therapeutic strategies remain limited due to the risk of triggering thrombotic thrombocytopenic purpura. Here we show that HA10, a humanized anti-ADAMTS13 antibody, preserves a residual level of ADAMTS13 activity above the thrombosis-associated threshold. Multimodal structural and biophysical analyses--including NMR, SAXS, and SANS--revealed that HA10 bound to the disintegrin-like domain of ADAMTS13, dynamically competing with VWF while leaving 10- 20% residual enzymatic activity. The therapeutic efficacy and safety of HA10 were verified in non-human primate models of AVWS. Our findings establish a novel paradigm of enzymatic calibration rather than complete blockade, offering a mechanistically targeted and safe therapeutic approach for cardiovascular bleeding.

biochemistry↗

bioRxiv2026

Caenorhabditis becei recombinant inbred lines (beRILs) reveal the scope of heritable variation within a gonochoristic nematode population.

Caenorhabditis nematodes are a powerful model clade for evolutionary genetics. Isogenic lines and panels of recombinant inbred lines (RILs) are among the most essential tools for genetic studies in these species. While most Caenorhabditis species are gonochoristic, large RIL panels have only been developed for self-fertilizing species. This gap biases our understanding and limits our ability to address questions related to the genetic architecture of traits in outbred populations, which have radically higher genetic diversity, heterozygosity, and effective recombination than selfers. Having previously identified Caenorhabditis becei as a tractable gonochoristic species due to its moderate inbreeding depression, we generated two panels of advanced-intercross RILs derived from three individual outbred C. becei worms collected from a single locality on Barro Colorado Island, Panama. One panel derives from a pair of worms sampled from a single rotting fig; the other derives from a cross between worms from two different figs. The panels share one founder in common, yielding two half-sib RIL panels. We sequenced and haplotyped the lines, identifying millions of variants and thousands of recombination breakpoints. Using simulations, we demonstrate the suitability of these lines for quantitative genetics studies and QTL mapping. In our single-fig panel, we observe abundant heritable variation in population growth rate, individual body size, and sexual dimorphism for body size. We detected four QTLs associated with population growth rate and show that estimated allelic effects are good predictors of selection that occurred during panel derivation.

genetics↗

bioRxiv2026

Post-fledging space use and survival in hand-reared versuswild juvenile herring gulls

Parental care can shape post-fledging behaviour through provisioning, guidance and social information, yet its absence may alter how young birds establish space use and habitat preferences. We tested the consequences of absent parental care by comparing, hand-reared juvenile herring gulls released without parents with wild, parent-reared conspecifics, focusing on the first two months after fledging. Wild juveniles frequently revisited their natal nest during the first month, whereas hand-reared birds rarely returned to the release site; revisits declined in both groups by the second month but remained more common in wild birds. Wild juveniles used smaller ranges that subsequently expanded, while hand-reared birds began with larger ranges that later contracted, leading to convergence. Contrary to expectation, wild juveniles occurred in areas with higher human population density than hand-reared birds. Habitat use also differed between groups and changed over time. Early on, wild juveniles concentrated activity in anthropogenic and marine habitats, whereas hand-reared birds used rural green habitats more. Later, both groups shifted away from marine areas towards rural green habitats, reducing but not eliminating between-group differences. Short-term survival, did not differ between hand-reared and wild juveniles, indicating that parental care primarily reshaped early space use and habitat choice rather than immediate survival.

animal behavior and cognition↗

bioRxiv2026

Integrating Segmental Deuteration iCM-SANS with SAXS and MD for Dynamical Analysis of Multi-domain Proteins

Multi-domain proteins (MDPs) adopt diverse conformations arising from cooperative inter-domain motions, and such dynamics are intimately coupled to their biological functions. Quantitative characterization of these motions is crucial for elucidating their functional mechanisms. Although small-angle X-ray scattering (SAXS) provides information on overall domain arrangement, the limited experimental constraints hinder reliable discrimination of conformational ensembles derived from molecular dynamics (MD) simulations. To address this limitation, complementary experimental constraints that enable to observe domain-selective structural information are required. Inverse contrast-matching small-angle neutron scattering (iCM-SANS), combined with segmental deuteration, enables selective visualization of individual domains and thus provides such complementary information. However, practical strategies for preparing segmentally deuterated MDPs with arbitrary domain labelling have yet to be established. Here, we develop an experimental protocol that integrates controlled protein deuteration with high-efficiency multi-step protein ligation to generate a segmentally deuterated MDP in high yield. The combined use of SAXS and iCM-SANS yields complementary structural constraints that enhance discrimination of MD-derived conformational ensembles. This protocol expands the applicability of segment-selective visualization and also provides an opportunity for high-precision analysis of dynamics in complex MDPs. SynopsisSegmental deuteration enabled by high-efficiency multi-step protein ligation, combined with inverse contrast-matching SANS and SAXS, provides structural constraints that improve discrimination of molecular dynamics ensembles of multi-domain proteins. IMPORTANTthis document contains embedded data - to preserve data integrity, please ensure where possible that the IUCr Word tools (available from http://journals.iucr.org/services/docxtemplate/) are installed when editing this document.

biophysics↗

bioRxiv2026

Imminent invasion of the chytrid fungus threatens the last naive amphibian biodiversity hotspots

While the amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd) is driving catastrophic biodiversity loss worldwide, some amphibian communities persist seemingly unaffected despite occurring in climates conducive to pathogen establishment. These amphibian communities may remain epidemiologically naive. As mitigation of Bd is rarely successful after establishment, identifying remaining Bd-free refuges is imperative. Presently, the only known large-scale Bd-free refuge is the island of New Guinea (NG), safeguarding Australasias amphibian phylogenetic diversity otherwise devastated by Bd. Following extensive multi-year disease surveillance, we here uncover a second large-scale Bd-free refuge in the Sierra Nevada de Santa Marta (SNSM), a Neotropical biodiversity hotspot in northern Colombia. We detected no evidence of Bd in SNSM-wide screening, while we uncovered the presence of hypervirulent Bd-GPL in adjacent areas of the tropical Andes. Population genomic analyses in an SNSM-endemic anuran found no evidence for demographic bottlenecks indicative of cryptic epizootic decline. Niche modelling highlights the high risk for Bd establishment and Bd-induced declines in both the SNSM and NG, and the important role of lowland environmental barriers in restricting Bd invasion. Infection trials using three SNSM-endemic amphibians reveal varying disease susceptibility. Together, these data identify the SNSM as an epidemiologically naive refuge likely facing imminent Bd invasion, which could result in the loss of at least 25 endemic amphibian species. We highlight the urgent need for proactive conservation action and strict implementation of biosecurity to safeguard the unique and vast amphibian diversity of the worlds last major Bd-free refuges. Significance StatementAmphibian chytridiomycosis caused by Batrachochytrium dendrobatidis (Bd) has driven unprecedented global biodiversity loss. The Neotropics and Australasia comprise epicenters of declines. Identifying remaining Bd-free refuges is crucial to curb further amphibian extinctions, but so far contemporary absence of Bd has only been demonstrated for New Guinea. Here we identify the last known major Bd-free biodiversity hotspot in the Neotropics: the Sierra Nevada de Santa Marta (SNSM) in Colombia. Our results show that amphibian communities in this hotspot are immunologically naive despite occurrence of hypervirulent Bd lineages nearby and climatic conditions within the SNSM conducive to Bd-induced declines. This creates an imminent risk for Bd-driven declines and highlights the urgent need for preventive actions to avert another wave of biodiversity loss.

ecology↗

bioRxiv2026

Decline of Common Toad populations in Flanders is not linked to surrounding landscape

AimWe aim to quantify population trends of Common Toad in Flanders and assess to which extent population trends depend on general landscape variables (land use identity, structure and change). LocationFlanders, Belgium MethodsUsing standardized time series obtained from citizen science and spanning over four decades, we used an end-begin contrast to get a trend value for 234 populations. Next, we developed a testing strategy to find associations between these trend values and the surrounding landscape ResultsAcross the study region, 40% of the populations have declined significantly, while only 10% show an increase. Declines were not associated with landscape characteristics in our study area, which is one of the most fragmented regions in Europe. Main conclusionsWe discuss how the research region, spatial and temporal resolution, as well as the generalist nature of the species, may explain these findings. Our study suggests limited effects of general landscape characteristics on the decline of Common Toad populations, indicating that other major drivers are likely responsible.

ecology↗

bioRxiv2025

Early-life social instability affects aggression, but not response inhibition, in chickens

Living in complex social environments presents behavioural and cognitive challenges. A key challenge is the regulation of aggression, which may be facilitated by response inhibition, the ability to suppress inappropriate actions. In more complex social environments, greater variability in interactions may increase demands for aggression regulation, promoting the development of response inhibition. However, social instability, a form of complexity characterised by frequent changes in group composition, can elevate aggression and may instead impair inhibition. To test these competing predictions we raised 144 chickens (Gallus gallus domesticus) in either stable or unstable social groups for five weeks. We observed the aggression within their enclosures following the final manipulation, and assessed their response inhibition using a thwarting task and a cylinder task. Unstable groups initially showed more aggression than stable groups following regrouping, but this declined rapidly to the same lower level of aggression as the stable groups. Contrary to our predictions, there were no differences between birds raised in stable and unstable groups for any measure of response inhibition, and individual variation in aggression did not correlate with inhibitory performance. These findings suggest that social instability influences aggression but does not affect the development of response inhibition in chickens, highlighting the potential context- and species-specific nature of social effects on cognition.

animal behavior and cognition↗

bioRxiv2025

Multitaxon assessment reveals inconsistent biodiversity responses to forest structural complexity in temperate forests

Increasing forest structural complexity is a key objective of future-proof forest management, with potential benefits for biodiversity. However, empirical evidence for consistent biodiversity-structure relationships across taxa is still limited. We investigated whether structurally more complex forests support greater species richness and higher multidiversity across taxonomic and functional groups in 19 mature forest plots in Flanders, Belgium. As one of the most densely populated and urbanized regions in Europe, with limited and highly fragmented forest cover, Flanders provides a particularly informative and policy-relevant context to test structure-biodiversity relationships. Its forests, often dominated by a few tree species and subject to long-term anthropogenic pressures and management, represent a realistic gradient of structural complexity. Structural complexity was quantified using a Structural Complexity Index (SCI), and biodiversity was assessed using a multidiversity index integrating scaled species richness across five taxonomic and seven arthropod functional groups. Using mixed-effects models and multivariate Bayesian analyses, we tested both direct effects of SCI on biodiversity and the covariation in species richness among groups. Contrary to expectations, SCI was not a consistent predictor of multidiversity, and most groups showed weak or inconsistent responses. These findings might suggest that structural complexity alone may be insufficient to enhance biodiversity in simplified forests. HighlightsO_LIForest structural complexity does not consistently predict biodiversity. C_LIO_LIResponses vary among taxonomic and functional groups. C_LIO_LICross-taxon congruence in diversity is limited and scale-dependent. C_LIO_LIKeywords: Forest structural complexity; Multidiversity, Species richness; Functional groups; Sustainable forest management C_LI

ecology↗

bioRxiv2025

Evaluating wildlife rehabilitation: Successful return of rehabilitated gulls in the wild

The expansion of human activities has increased the need for animal rehabilitation, especially for urban-breeding species such as herring gulls (Larus argentatus) and lesser black-backed gulls (L. fuscus), which now commonly nest on buildings and industrial sites. This study evaluates rehabilitation effectiveness by comparing survival and post-release reintegration, measured through habitat use and the degree of association with human-dominated environments, between rehabilitated and wild juvenile gulls along the Belgian coast. From 2012 to 2023, 3443 juveniles were ringed and monitored. Estimated survival rates varied significantly with age, but there was no difference between rehabilitated and wild birds. Differences in habitat use and association with local human population density were largely confined to juveniles: rehabilitated juveniles were resighted more often in rural green areas with lower human population densities, with patterns converging in older age classes. Our results suggest rehabilitation can support urban gull populations by yielding wild-like survival and space use.

ecology↗

bioRxiv2025

Up-to-date MALDI-TOF MS based identification of the complete Corynebacterium diphtheriae species complex for improved diagnostics

The Corynebacterium (C.) diphtheriae species complex (CdSC) comprises the closely related pathogenic species C. diphtheriae, C. belfantii, C. rouxii, C. ulcerans, C. silvaticum, C. ramonii and C. pseudotuberculosis according to the taxonomic revisions after 2018. Due to their close relationship, reliable species identification within the CdSC is also challenging using MALDI-TOF mass spectrometry (MS) for fast and reliable identification of bacteria. However, the most commonly used commercial databases for MALDI-TOF MS do not reflect the current CdSC taxonomy. Therefore, the objective of the present study is to expand the Bruker MALDI-Biotyper database version K (MBTK) in order to achieve reliable identification for all currently known Corynebacterium species within the CdSC. Furthermore, the database extensions were verified with a systematic formal validation procedure in accordance with the German guideline for species identification by MALDI- TOF MS. For this, 321 strains including all seven valid species of the CdSC were identified with a set of 328 spectra using the commercial MBTK database and a customer-supplemented modified MBTK. This custom database version included 33 reference spectra of the CdSC and representatives of all four recently described species. The results of the formal validations for both, the commercial and the extended database, combined partly with a single signal analysis, provide a substantiated basis for the identification of bacteria of the CdSC. A key element for a fast up-to-date identification has been the exchange of user-generated sets of MSPs on the open access MALDI-UP catalogue that includes reference spectra for all members of the CdSC. HighlightsO_LIUsing MALDI-TOF MS, all current species of the C. diphtheriae species complex are accurately identified according to the current taxonomy C_LIO_LIValidation was performed using spectra from different institutions and an approved gold standard protocol C_LIO_LIThe extension and exchange of user created reference spectra via the MALDI User Platform proved to be a key tool for precise identification of bacteria C_LI Importance StatementBacteria belonging to the Corynebacterium (C.) diphtheriae complex are important pathogens for humans and animals. Identification of the species of this complex described since 2018, i.e. C. belfantii, C. rouxii, C. ramonii, and C. silvaticum, using the widely approved MALDI-TOF mass spectrometry is possible. This has been achieved by improved identification using supplemented MALDI reference databases. Comprehensive validation meets the requirements for accurate pathogen identification in accordance with recognised guidelines. This approach of identification is certainly a model for other bacterial species of interest to react on current taxonomic revisions in a short time frame.

microbiology↗

bioRxiv2025

Deciphering the dynamics of Cyanobacteria-Phage in a natural lake: Insights from a decade-long investigation

Phages - viruses that infect bacteria - are often seen as key players in bacterial community dynamics and the ecosystem services those communities support. However, much of our understanding of phage-bacteria interactions comes from in vitro studies, which provide limited insights into how these interactions occur in natural environments. In this study, we used cyanobacterial blooms as a model microbial community to evaluate the potential role of phages in driving cyanobacterial populations. These blooms are characterized by massive and usually rapid accumulation of cyanobacterial biomass and occur worldwide, threatening aquatic systems. The frequency and intensity of cyanobacterial blooms are increasing over time, likely due to human activities, and, until now, the role of predators like phages has remained unclear. We used a deep amplicon sequencing approach targeting the g20 capsid gene to profile the cyanophage community in eutrophic Lake Champlain over time, comparing their dynamics and diversity with bacterial communities and examining their associations. We evaluated whether phages simply followed bacterial dynamics, with limited impact on bacterial composition, or instead whether they played an active role in drving bacterial community structure. We found that phages exhibited similar dynamics to their potential bacterial hosts and shared environmental niches. However, we also observed strong differences specific to the phage community, such as inter-annual variation and an increase in Shannon diversity over time. Phage-bacteria and phage-cyanobacteria co-variance uncovered potential interactions that resulted in strongly modular networks. However, while the network structure remained modular, the composition of the modules differed significantly between environmental and temporal conditions. Lastly, viral phylogeny partially explained phage-bacteria co-variance, but only for a small proportion of bacterial ASVs. Our results indicate that phage-bacterial interactions are partly genetically structured and vary within modules across environmental conditions.

ecology↗

bioRxiv2024

To Peck or Not To Peck: The influence of early-life social environment on response inhibition and impulsive aggression in Japanese quails

Deficits in response inhibition (i.e., the ability to suppress inappropriate responses) may contribute to increased impulsive aggression (i.e., unplanned behaviors that harm others). Since early-life environment might influence the development of response inhibition, it could also indirectly affect impulsive aggression. However, this relationship has rarely been directly examined. Here, we investigated whether response inhibition is associated with impulsive aggression and whether this relationship explains the effects of early-life social environments on impulsive aggression in juvenile Japanese quails (Coturnix japonica). Quails (n = 120) were raised in two social conditions: Small groups of five birds or Large groups of 15 birds. Response inhibition was assessed using the Barrier and Cylinder tasks, while impulsive aggression was measured in two contexts - within a group of five familiar individuals and in a dyad with an unfamiliar individual. We found that some aspects of response inhibition were related to impulsive aggression. Furthermore, quails reared in small groups showed significantly poorer response inhibition than those reared in large groups. Yet, impulsive aggression did not significantly differ between the two conditions. These findings suggest that, while impulsive aggression is partly related to response inhibition, other factors mitigate the effects of early social environments on its expression.

animal behavior and cognition↗

bioRxiv2024

Local ionic conditions modulate the aggregation propensity and influence the structural polymorphism of alpha-synuclein

Parkinsons Disease (PD) is characterized by the aggregation of alpha-synuclein (aSyn), a presynaptic protein that transitions from a disordered monomer into beta-sheet rich amyloid fibrils. The precise triggers and mechanisms underlying aSyn misfolding and aggregation remain unclear, hindering the development of effective therapeutics. Monomeric aSyn is an intrinsically disordered protein (IDP) with high conformational flexibility. Local environmental factors, such as ion concentrations, can influence the conformational ensemble of aSyn, impacting its aggregation propensity and resulting in fibril polymorphism. In this study, we explore the impact of physiologically relevant ions, mainly Ca2+ and Na+, on the aggregation kinetics, monomer structural dynamics, and fibril polymorphism of aSyn. Using ThT fluorescence assays, we demonstrate that all ions accelerate aSyn aggregation, with Ca2+ having the most significant effect. Using Heteronuclear Single Quantum Correlation Nuclear Magnetic Resonance (1H-15NHSQC NMR) spectroscopy, we validate the specific binding of Ca2+ ions at the C-terminus, whereas Na+ ions display non-specific interactions along the sequence of aSyn. Small-angle neutron scattering (SANS) and hydrogen-deuterium exchange mass spectrometry (HDX-MS) further reveal that Na+ and Ca2+ induce distinct conformational changes in the aSyn monomer, with Na+ leading to more extended structures and Ca2+ promoting a moderate extension of the protein. Molecular dynamics simulations (MD) corroborate these findings, showing that Na+ ions increase the proteins extension, particularly between the non-amyloid beta component (NAC) region and the C-terminus, whereas Ca2+ ions bias the ensemble towards a more moderately elongated structure. Using MD, we further investigate the local environment and in particular the solvent effect and show the water persistence times in the hydration shell are also increased in the presence of Ca2+ ions, indicating that the aggregation propensity of the monomer is due to a combination of conformational bias of the monomer and solvent mobility. Atomic force microscopy (AFM) of aSyn fibrils formed under these different ionic conditions reveal distinct fibril polymorphs, suggesting that ion-induced conformational biases in the monomer contribute to the diversity of fibril structures. Collectively, these findings underscore the pivotal influence of the local ionic milieu in shaping the structure and aggregation propensity of aSyn, thus offering valuable insights into the molecular underpinnings of PD and potential therapeutic avenues aimed at manipulating aSyn conformational dynamics.

biophysics↗

bioRxiv2024

Ixodes ricinus nymphs prefer blood with Borrelia infection and low corticosteroid concentration

Ticks play a significant role in the transmission of various pathogens, impacting both human and animal health. Understanding the factors influencing tick feeding preferences is crucial for mitigating the risk of tick-borne diseases. This study investigates the blood preference of Ixodes ricinus nymphs, focusing on host species, stress hormone levels (glucocorticoids), and the presence of Borrelia burgdorferi bacteria. Three series of in vitro experiments were conducted. The setup involved placing individual blood drops (15 {micro}l) on filter paper over a 37{degrees}C plate. Ticks were placed in the center, and their movements were tracked for two minutes to record preferences. The first experiment evaluated the ticks preference for blood from different hosts (mouse, bird, sheep). The second experiment explored the role of stress hormones by assessing the ticks response to blood with varying levels of supplemented cortisol and corticosterone (0, 10, 100 and 1000 ng/ml). The third experiment examined the potential influence of Borrelia infection, combined with elevated stress hormone levels, on blood preference. Our results show that I. ricinus nymphs show a significant preference for blood without added glucocorticoids and, in mice, blood with Borrelia infection. No clear preference for a specific host species was observed. These findings provide valuable insights into the complex interactions between ticks, blood characteristics, and Borrelia infection status, highlighting the potential importance of host physiological state in tick host selection. Future studies should explore the mechanisms behind these preferences, which could lead to the development of new methods to control the spread of tick-borne diseases. HIGHLIGHTSO_LIIn vitro experiments with nymphs can reveal insights into their blood preferences C_LIO_LITicks displayed no difference in preference towards bird, mouse, or sheep blood C_LIO_LITicks prefer blood with baseline stress levels over increased stress levels C_LIO_LIMouse blood infected with Borrelia burgdorferi was preferred by ticks C_LI

ecology↗

bioRxiv2024

Structural characterization of the Pseudomonas Aeruginosa MexR-mexR repressor-operator complex: a small-angle X-ray and neutron scattering perspective

The rapid spread of acquired multidrug resistance (MDR) in bacteria is a world-wide health threat. The MexR protein regulates the expression of the MexAB-OprM efflux pump, which actively extrudes chemical compounds with high toxicity to the host organism Pseudomonas Aeruginosa. In repression mode, two MexR dimers bind to an operator with two homologous pseudo-palindromic boxes located in proximity (named PI and PII). Here we report a first structural characterization of the complex in solution using small angle X-ray scattering (SAXS), small-angle neutron scattering (SANS) and rigid body modelling. The spacing between the PI and PII boxes is rich in AT base pairs indicate possible flexibility between the two MexR dimer binding sites. In agreement, our best modelling fits show a requirement for DNA bending between the two MexR binding sites to optimally fit SAS data as well as known biological properties of the MexR operons. Taken together, this study contributes to better understanding of the structural properties of bacterial operators and their repressor proteins.

biophysics↗

bioRxiv2024

Beyond a unitary construct: Dissecting stopping behaviour in two bird species

The ability to stop behaviour is essential for adapting to changes in the environment, a principle that holds true across various species. While traditionally considered a unitary psychological construct, recent studies indicate that this ability is multifaceted. Our research evaluates this multifaceted nature using three tasks that measure stopping in different contexts in two related gull species: herring gulls (Larus argentatus) and lesser black-backed gulls (L. fuscus). These species were selected for their distinct migration and foraging strategies, offering a unique lens through which to examine behavioural adaptations. Across tasks and species, we conceptualised stopping as a race between a go and a stop runner, and predicted correlations based on the type of stop stimulus, the relative timing of the go and the stop stimuli, and the type of action that needed to be stopped. We found correlations between measures of going across tasks, but there was less consistency in measures of stopping. Furthermore, we observed significant differences in going and stopping behaviours that were specific to each species, which may be linked to their migration and foraging strategies. These findings highlight the importance of considering the multifaceted nature of stopping in evolutionary and behavioural studies.

animal behavior and cognition↗

bioRxiv2023

Distinct Electrophysiological Signatures of Intentional and Unintentional Mind-Wandering Revealed by Low-Frequency EEG Markers

Mind-wandering is typically characterized by the common experience wherein attention veers off into thoughts unrelated to the task at hand. Recent research highlights the intentionality dimension of mind-wandering as a key predictor of adverse functional outcomes with intentional and unintentional task-unrelated thought (TUT) differentially linked to neural, behavioral, clinical, and functional correlates. We here aimed to elucidate the electrophysiological underpinnings of intentional and unintentional TUT by systematically examining the individual and collective discriminative power of a large set of EEG markers to distinguish between attentional states. Univariate and multivariate analyses were conducted on 54 predefined markers belonging to four conceptual families: ERP, spectral, information theory and connectivity measures, extracted from scalp EEG recordings prior to multidimensional reports of ongoing thought from participants performing a sustained attention task. We report here that on-task, intentional and unintentional TUT exhibit distinct electrophysiological signatures in the low frequency range. More specifically, increased features of the theta frequency range were found to be most discriminative between on-task and off-task states, while features within the alpha band were characteristic of intentional TUT when compared to unintentional TUT. This result is theoretically well aligned with contemporary accounts describing alpha activity as an index of internally oriented attention and a potential mechanism to shield internal processes from sensory input. Our study verifies the validity of the intentionality dimension of mind-wandering and represents a step forward towards real-time detection and mitigation of maladaptive mind-wandering.

neuroscience↗

bioRxiv2022

Biophysical characterization of calcium-binding and modulatory-domain dynamics in a pentameric ligand-gated ion channel

Pentameric ligand-gated ion channels (pLGICs) perform electrochemical signal transduction in organisms ranging from bacteria to humans. Among the prokaryotic pLGICs there is architectural diversity involving N-terminal domains (NTDs) not found in eukaryotic relatives, exemplified by the calcium-sensitive channel (DeCLIC) from a Desulfofustis deltaproteobacterium, which has an NTD in addition to the canonical pLGIC structure. Here we have characterized the structure and dynamics of DeCLIC through cryo-electron microscopy (cryo-EM), small-angle neutron scattering (SANS), and molecular dynamics (MD) simulations. In the presence and absence of calcium, cryo-EM yielded structures with alternative conformations of the calcium binding site. SANS profiles further revealed conformational diversity at room temperature beyond that observed in static structures, shown through MD to be largely attributable to rigid body motions of the NTD relative to the protein core, with expanded and asymmetric conformations improving the fit of the SANS data. This work reveals the range of motion available to the DeCLIC NTD and calcium binding site, expanding the conformational landscape of the pLGIC family. Further, these findings demonstrate the power of combining low-resolution scattering, high-resolution structural, and MD-simulation data to elucidate interfacial interactions that are highly conserved in the pLGIC family.

biophysics↗