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Costa, A. C.

Publications and source records attributed to Costa, A. C..

14 recordsLinked to original sources

Unraveling phenotypic variation in multiscale behavioral dynamics

Behavioral variability reflects differences in internal and external parameters and provides a substrate for natural selection. However, uncovering its structure is challenging because behavior evolves nonlinearly across multiple timescales. Our goal is to reconstruct phenotypic variation from finite behavioral observations without prescribing the scales at which individuals should be compared. To achieve this, we introduce a multiscale dissimilarity that compares dynamics across all statistically resolvable resolutions by constructing reduced transfer operators at progressively finer scales and weighting their differences by finite-sampling uncertainty. This dissimilarity defines a geometry of dynamical phenotypes, which we reconstruct using diffusion maps. We show that the resulting phenotypic coordinates locally follow the parameter directions to which dynamics are most sensitive. We validate our approach in a stochastic model and apply it to bacterial and larval zebrafish behavior. In bacteria, we identify run speed as a major component of inter-individual variability, associated with the chemotaxis protein CheB. In zebrafish, we find that prior prey experience reshapes behavioral dynamics and phenotypic variability, with paramecia experience concentrating fish in a prey-capture-associated region of phenotypic space. Together, these results provide a framework for identifying internal and environmental variables that structure dynamical phenotypes across scales.

biophysics↗

In vitro programming and pseudounipolarization of human iPSC-derived sensory neurons

Ectopic expression of NGN1, BRN3A and ISLET1 (NBI) from a safe harbor locus in induced pluripotent stem cells (iPSCs) yielded robust differentiation into functional sensory neurons (iNBI-SNs) within seven days. Single nucleus transcriptomics identified peripheral sensory neuron profiles of nociceptors and mechanoreceptors. Electrophysiological studies showed that more than 98 % of iNBI-SNs display TTX-resistant sodium currents and that they establish functional connections to excitatory CNS neurons. iNBI-SNs derived from patients with inherited erythromelalgia, a pain disorder associated with gain-of-function mutations in the Nav1.7 sodium channel showed pathologically increased firing rates which could be partially rescued with a Nav1.7 inhibitor. Notably, iNBI-SNs acquire a characteristic pseudounipolar morphology upon co-culture with embryonic rodent DRG cells. Taken together, NBI-based forward programming of iPSCs represents a robust approach for the generation of human sensory neurons suitable for developmental, disease- and therapy-related studies.

neuroscience↗

Body-segment coordination as a new predictor of freezing of gait in people with Parkinson disease

Freezing of gait (FOG) in Parkinsons disease (PD) involves impaired integration of posture and locomotion with altered body-segment coordination. We measured coordination using gait kinematics during walking in 16 PD patients with FOG, preoperatively with and without dopaminergic medication (OFF/ON-DOPA), and postoperatively with and without subthalamic deep brain stimulation (OFF/ON-DBS). Body-segment coordination was modeled from acceleration-based intersegmental correlations across trunk, pelvis, and limbs. We tested whether coordination metrics predict individual postoperative FOG severity using LASSO regression with nested cross-validation, including preoperative demographics, clinical scores, gait and coordination metrics. Preoperatively, DOPA decreased trunk-pelvis-upper-limb coordination but increased crossed upper-lower-limbs coupling; while STN-DBS selectively increased inter-upper-limb coordination, with DOPA- and STN-DBS-induced changes being correlated. Whole-body coordination predicted individual postoperative FOG severity, with the most important couplings being the trunk-pelvis and pelvis-lower-limb. Body-segment coordination captures clinically relevant gait metrics in PD, highlighting coordination as a potential biomarker for patient stratification and treatment response.

neuroscience↗

Ports of Entry: Tracking Marine Invaders in Portuguese Mari-nas with DNA Metabarcoding from Coast to Archipelagos

Marine non-indigenous species (NIS), introduced primarily through shipping in marinas and ports, pose significant threats to coastal biodiversity and ecosystem functioning, requiring effective management strategies, especially for monitoring aimed at early detection. This study aimed to capture a comprehensive snapshot of the geographic variation of marine invertebrate assemblages and NIS occurrence, across 10 recreational marinas in Portugal (6 on the mainland - Viana do Castelo, Porto, Aveiro (2 marinas), and Lisbon (2 marinas) - and 2 in each archipelago, Madeira and the Azores). In each marina, hard substrates, zooplankton, and water samples (for eDNA) were collected in triplicate during summertime for metabarcoding profiling, adding up to a total of 111 samples. Using Illumina MiSeq sequencing of the mitochondrial cytochrome c oxidase subunit I (COI) gene (313 bp) and the V4 region of the small subunit 18S rRNA gene (18S, approximately 400 bp), we detected 645 species from 21 phyla, 40 of which were NIS (7 phyla). Only 5% of the species and 5% of NIS were detected in all marinas. The highest numbers of both exclusive native species and NIS were recorded in the Azores (100 and 7, respectively), and the lowest numbers of exclusive native species were recovered in Aveiro (39) while the lowest numbers of exclusive NIS were detected in the North and Aveiro regions (1 in each). A Principal Coordinate Analysis indicated a distinct separation among communities forming three main groups: 1) Viana do Castelo, Porto, and Aveiro; 2) Lisbon; and 3) Madeira and the Azores. Similarity between these groups is negatively correlated with geographic distance and overlaps with ecoregions previously identified within Lusitania. In the Azores 9 NIS were recorded for the first time, and one in Madeira. We also recorded a considerable number of potential range expansions of NIS, predominantly along the mainland coast, in both North (N) - South (S) or S-N directions, which shows promising results of the high potential of DNA metabarcoding to be included in future national marine biomonitoring campaigns.

ecology↗

Natural variation in Caenorhabditis elegans collective behavior reveals potential adaptation to novel environments

Animal behavior can diverge in natural populations in response to different environmental conditions, but if and how natural selection also shapes the evolution of collective behavior in groups of animals remains underexplored. With their cosmopolitan distribution and known collective behaviours, wild populations of Caenorhabditis elegans provide a powerful system to address how collective behavior could evolve across natural habitats on a global scale. We screened a panel of 196 genetically diverse C. elegans strains sampled from around the world, conducting aggregation behavior experiments and analysis to quantify natural variation among these populations. We found substantial variation in the spatial magnitude and the temporal dynamics of aggregation across strains, which were significantly explained by the elevation of the source habitats. Accounting for neutral evolutionary processes, our maximum likelihood population effects (MLPE) models further support a role of selection on aggregation. Furthermore, the two behavioral traits are highly heritable, and genome-wide association studies (GWAS) revealed a quantitative trait locus (QTL) containing several candidate genes associated with oxygen response and foraging behaviors. Our results showcase C. elegans aggregation as a collective behavior that has diverged globally across elevational gradients, and support that natural selection has shaped the evolution of this collective behavior.

evolutionary biology↗

Axon-specific microtubule regulation drives asymmetric regeneration of sensory neuron axons

Sensory dorsal root ganglion (DRG) neurons have a unique pseudo-unipolar morphology in which a stem axon bifurcates into a peripheral and a central axon, with different regenerative abilities. Whereas peripheral DRG axons regenerate, central axons are unable to regrow. Central axon regeneration can however be elicited by a prior conditioning lesion to the peripheral axon. How DRG axon asymmetry is established, remains unknown. Here we developed a rodent in vitro system replicating DRG pseudo-unipolarization and asymmetric axon regeneration. Using this model, we observed that from early development, central DRG axons have a higher density of growing microtubules. This asymmetry was also present in vivo and was abolished by a conditioning lesion that decreased microtubule polymerization of central DRG axons. An axon-specific microtubule-associated protein (MAP) signature, including the severases spastin and katanin and the microtubule regulators CRMP5 and tau, was found and shown to adapt upon conditioning lesion. Supporting its significance, interfering with the DRG MAP signature either in vitro or in vivo, readily abolished central-peripheral asymmetries in microtubule dynamics and regenerative ability. In summary, our data unveil that axon-specific microtubule regulation drives asymmetric regeneration of sensory neuron axons. Impact statementSensory neurons have a stem axon that bifurcates originating two axons with different properties. This work shows that DRG axons have a specific protein signature underlying microtubule and regeneration asymmetries. It also provides an in vitro system replicating DRG biology.

neuroscience↗

Uncovering multiscale structure in the variability of larval zebrafish navigation

Animals chain movements into long-lived motor strategies, resulting in variability that ultimately reflects the interplay between internal states and environmental cues. To reveal structure in such variability, we build models that bridges across time scales that enable a quantitative comparison of behavioral phenotypes among individuals. Applied to larval zebrafish exposed to diverse sensory cues, we uncover a hierarchy of long-lived motor strategies, dominated by changes in orientation distinguishing cruising and wandering strategies. Environmental cues induce preferences along these modes at the population level: while fish cruise in the light, they wander in response to aversive (dark) stimuli or in search for prey. Our method enables us to encode the behavioral dynamics of each individual fish in the transitions among coarse-grained motor strategies. By doing so, we uncover a hierarchical structure to the phenotypic variability that corresponds to exploration-exploitation trade-offs. Within a wide range of sensory cues, a major source of variation among fish is driven by prior and immediate exposure to prey that induces exploitation phenotypes. However, a large degree of variability is unexplained by environmental cues, pointing to hidden states that override the sensory context to induce contrasting exploration-exploitation phenotypes. Altogether, our approach extracts the timescales of motor strategies deployed during navigation, exposing undiscovered structure among individuals and pointing to internal states tuned by prior experience.

animal behavior and cognition↗

A Markovian dynamics for C. elegans behavior across scales

How do we capture the breadth of behavior in animal movement, from rapid body twitches to aging? Using high-resolution videos of the nematode worm C. elegans, we show that a single dynamics connects posture-scale fluctuations with trajectory diffusion, and longer-lived behavioral states. We take short posture sequences as an instantaneous behavioral measure, fixing the sequence length for maximal prediction. Within the space of posture sequences we construct a fine-scale, maximum entropy partition so that transitions among microstates define a high-fidelity Markov model, which we also use as a means of principled coarse-graining. We translate these dynamics into movement using resistive force theory, capturing the statistical properties of foraging trajectories. Predictive across scales, we leverage the longest-lived eigenvectors of the inferred Markov chain to perform a top-down subdivision of the worms foraging behavior, revealing both "runs-and-pirouettes" as well as previously uncharacterized finer-scale behaviors. We use our model to investigate the relevance of these fine-scale behaviors for foraging success, recovering a trade-off between local and global search strategies. SIGNIFICANCE STATEMENTComplex phenotypes, such as an animals behavior, generally depend on an overwhelming number of processes that span a vast range of scales. While there is no reason that behavioral dynamics permit simple models, by subsuming inherent nonlinearities and memory into maximally-predictive microstates, we find one for C. elegans foraging. The resulting "Markov worm" is effectively indistinguishable from real worm motion across a range of timescales, and we can decompose our model dynamics both to recover and discover behavioral states. Employing a simple form of substrate interactions, we connect postures to trajectories, illuminating how worms explore the environment. In more complex organisms, our approach can also link behaviors across time, from rapid muscular control to neuromodulation.

animal behavior and cognition↗

Emergent complexity in slowly driven stochastic processes

Animal behavior is shaped by a myriad of mechanisms acting on a wide range of scales. This immense variability hampers quantitative reasoning and renders the identification of universal principles elusive. Through data analysis and theory, we here show that slow non-ergodic drives generally give rise to heavy-tailed statistics in behaving animals. We leverage high-resolution recordings of C. elegans locomotion to extract a self-consistent reduced order model for an inferred reaction coordinate, bridging from sub-second chaotic dynamics to long-lived stochastic transitions among metastable states. The slow mode dynamics exhibits heavy-tailed first passage time distributions and correlation functions, and we show that such heavy tails can be explained by dynamics on a time-dependent potential landscape. Inspired by these results, we introduce a generic model in which we separate faster mixing modes that evolve on a quasi-stationary potential, from slower non-ergodic modes that drive the potential landscape, and reflect slowly varying internal states. We show that, even for simple potential landscapes, heavy tails emerge when barrier heights fluctuate slowly and strongly enough. In particular, the distribution of first passage times and the correlation function can asymptote to a power law, with related exponents that depend on the strength and nature of the fluctuations. We support our theoretical findings through direct numerical simulations.

biophysics↗

A deep learning approach to capture the essence of Candida albicans morphologies

We present deep learning-based approaches for exploring the complex array of morphologies exhibited by the opportunistic human pathogen C. albicans. Our system entitled Candescence automatically detects C. albicans cells from Differential Image Contrast microscopy, and labels each detected cell with one of nine vegetative, mating-competent or filamentous morphologies. The software is based upon a fully convolutional one-stage object detector and exploits a novel cumulative curriculum-based learning strategy that stratifies our images by difficulty from simple vegetative forms to more complex filamentous architectures. Candescence achieves very good performance on this difficult learning set which has substantial intermixing between the predicted classes. To capture the essence of each C. albicans morphology, we develop models using generative adversarial networks and identify subcomponents of the latent space which control technical variables, developmental trajectories or morphological switches. We envision Candescence as a community meeting point for quantitative explorations of C. albicans morphology.

microbiology↗

Maximally predictive ensemble dynamics from data

We leverage the interplay between microscopic variability and macroscopic order to connect physical descriptions across scales directly from data, without underlying equations. We reconstruct a state space by concatenating measurements in time, building a maximum entropy partition of the resulting sequences, and choosing the sequence length to maximize predictive information. Trading non-linear trajectories for linear, ensemble evolution, we analyze reconstructed dynamics through transfer operators. The evolution is parameterized by a transition time{tau} : capturing the source entropy rate at small{tau} and revealing timescale separation with collective, coherent states through the operator spectrum at larger{tau} . Applicable to both deterministic and stochastic systems, we illustrate our approach through the Langevin dynamics of a particle in a double-well potential and the Lorenz system. Applied to the behavior of the nematode worm C. elegans, we derive a "run-and-pirouette" navigation strategy directly from posture dynamics. We demonstrate how sequences simulated from the ensemble evolution capture both fine scale posture dynamics and large scale effective diffusion in the worms centroid trajectories and introduce a top-down, operator-based clustering which reveals subtle subdivisions of the "run" behavior. POPULAR SUMMARYComplex structure is often composed from a limited set of relatively simple building blocks; such as novels from letters or proteins from amino acids. In musical composition, e.g., sounds and silences combine to form longer time scale structures; motifs form passages which in turn form movements. The challenge we address is how to identify collective variables which distinguish structures across such disparate time scales. We introduce a principled framework for learning effective descriptions directly from observations. Just as a musical piece transitions from one movement to the next, the collective dynamics we infer consists of transitions between macroscopic states, like jumps between metastable states in an effective potential landscape. The statistics of these transitions are captured compactly by transfer operators. These operators play a central role, guiding the construction of maximally-predictive short-time states from incomplete measurements and identifying collective modes via eigenvalue decomposition. We demonstrate our analysis in both stochastic and deterministic systems, and with an application to the movement dynamics of an entire organism, unravelling new insight in long time scale behavioral states directly from measurements of posture dynamics. We can, in principle, also make connections to both longer or shorter timescales. Microscopically, postural dynamics result from the fine scale interactions of actin and myosin in the muscles, and from electrical impulses in the brain and nervous system. Macroscopically, behavioral dynamics may be extended to longer time scales, to moods or dispositions, including changes during aging, or over generations due to ecological or evolutionary adaptation. The generality of our approach provides opportunity for insights on long term dynamics within a wide variety of complex systems.

biophysics↗

Free-living marine nematodes diversity at Ponta Delgada-Sao Miguel (Azores archipelago, North-East Atlantic Ocean): first results from shallow soft-bottom habitats

Contrasting (sand, algae, rocky-dominated, mixed) benthic habitats were sampled to characterize marine nematode diversity inhabiting surface sediments in Sao Miguel (Azores, North-East Atlantic Ocean) in July 2019. Nematodes were extracted from the surface layer of sediments and morphologically identified using light microscopy. Nematode taxonomy was based on living/fresh specimens) to ensure a suitable recognition of morphological traits. Our results provide a preliminary checklist of free-living marine nematode genera from 21 intertidal and sublittoral sandy beach sites along the coast of Sao Miguel island, Azores archipelago, Portugal. The nematode fauna was represented by 4 orders, 21 families, and 43 genera. Cyatholaimus, Desmodora and Daptonema had two morphospecies each. Enoplida was represented by 8 families and 13 genera, while Chromadorida by 7 families and 18 genera, the latter corresponding to the most diverse nematode group. Monhysterida had 5 families and 10 genera and Araeolaimida was represented by a single 1 family and 2 genera. The most common genera (i.e., accounting for 75% of all organisms) included Adoncholaimus (most abundant genus, 32 specimens), Axonolaimus (18), Cyatholaimus (17), Enoploides (13), Rhabdocoma, and Acanthopharynx (11). Viscosia and Enoplolaimus were represented by 7 specimens, whilst Halalaimus, Desmoscolex, Monophostia, Daptonema, and Theristus obtained only 6 each. The dominant nematode taxa of Sao Miguel island have been commonly previously reported in other coastal habitats including sandy beaches. They can be considered typical meiofaunal components of intertidal sandy beaches. Many of the nematode morphotypes found in Sao Miguel island could represent new species to science. As far as we know, this is the first report on free-living nematodes for Sao Miguel Island and for marine shallow water in the Azores. Our findings will serve as an import baseline for future research aiming to improve our understating of nematode communities in volcanic islands such as Sao Miguel in the Azores archipelago.

ecology↗

Capturing the Continuous Complexity of Behavior in C. elegans

Animal behavior is often quantified through subjective, incomplete variables that may mask essential dynamics. Here, we develop a behavioral state space in which the full instantaneous state is smoothly unfolded as a combination of short-time posture dynamics. Our technique is tailored to multivariate observations and extends previous reconstructions through the use of maximal prediction. Applied to high-resolution video recordings of the roundworm C. elegans, we discover a low-dimensional state space dominated by three sets of cyclic trajectories corresponding to the worms basic stereotyped motifs: forward, backward, and turning locomotion. In contrast to this broad stereotypy, we find variability in the presence of locally-unstable dynamics, and this unpredictability shows signatures of deterministic chaos: a collection of unstable periodic orbits together with a positive maximal Lyapunov exponent. The full Lyapunov spectrum is symmetric with positive, chaotic exponents driving variability balanced by negative, dissipative exponents driving stereotypy. The symmetry is indicative of damped, driven Hamiltonian dynamics underlying the worms movement control.

animal behavior and cognition↗

Modeling the ballistic-to-diffusive transition in nematode motility reveals variation in exploratory behavior across species

A quantitative understanding of organism-level behavior requires predictive models that can capture the richness of behavioral phenotypes, yet are simple enough to connect with underlying mechanistic processes. Here we investigate the motile behavior of nematodes at the level of their translational motion on surfaces driven by undulatory propulsion. We broadly sample the nematode behavioral repertoire by measuring motile trajectories of the canonical lab strain C. elegans N2 as well as wild strains and distant species. We focus on trajectory dynamics over timescales spanning the transition from ballistic (straight) to diffusive (random) movement and find that salient features of the motility statistics are captured by a random walk model with independent dynamics in the speed, bearing and reversal events. We show that the model parameters vary among species in a correlated, low-dimensional manner suggestive of a common mode of behavioral control and a trade-off between exploration and exploitation. The distribution of phenotypes along this primary mode of variation reveals that not only the mean but also the variance varies considerably across strains, suggesting that these nematode lineages employ contrasting \"bet-hedging\" strategies for foraging.

biophysics↗