Biology subjects

Salles, A.

Publications and source records attributed to Salles, A..

13 recordsLinked to original sources

bioRxiv2026

Rapid repurposing of microvillar content drives a flagellate-to-amoeboid switch in the closest relative of animals

Animal cells extensively remodel their cytoskeleton during differentiation and can notably switch between two major motility modes: flagellum-based swimming and actin-based crawling. We previously showed that choanoflagellates, the closest living relatives of animals and classically viewed as obligate flagellated swimmers, can retract their collar complex and adopt an amoeboid form within seconds under spatial confinement, independently of regulated gene expression. Here, using live imaging, ultrastructural expansion microscopy, and cryo-electron tomography in Salpingoeca rosetta, we identify rapid, cell-wide cytoskeletal remodeling as the ultrastructural basis of this switch. Unconfined choanoflagellates lack a detectable actin cortex but display an apical flagellum and cortical microtubules, with F-actin being largely restricted to microvilli. Confinement triggers calcium release from intracellular stores, which induces microvillar retraction and absorption of microvillar material into the cell body, including actin, ezrin-radixin-moesin 1, and plasma membrane. Remodeling of the internalized F-actin and repurposing of associated proteins supports de novo actin cortex formation, which is necessary for amoeboid motility. In parallel, cortical microtubules are disassembled, and the reabsorbed microvillar plasma membrane increases the surface area of the cell body, allowing the cell to flatten under confinement. Cryo-electron tomography reveals stepwise actin reorganization from internalized microvillar bundles to a cortical contractile meshwork combining bundles and scattered filaments. This work reveals considerable ultrastructural plasticity in the cytoskeletal architecture of choanoflagellates and supports an ancestral role for microvilli as reservoirs of membrane and cytoskeleton to potentiate cell phenotypic transitions.

evolutionary biology↗

bioRxiv2026

Passive Physiological Responses Fail to Predict Context-Dependent Action Selection in Bats

How social animals encode vocalizations, assign them value, and formulate behavioral responses remains largely unknown. We asked whether physiological signatures of social-call perception predict behavioral responses across contexts, using the Egyptian Fruit Bat (Rousettus aegyptiacus), an auditory specialist with a rich repertoire of social calls. Using heart rate monitoring during playback of conspecific vocalizations, we found that females showed larger heart rate responses than males to social calls (aggression and distress), whereas non-social echolocation calls evoked no sex difference. In vivo recordings from primary auditory cortex (A1) revealed call-selective units whose selectivity was independent of frequency tuning, with the largest selective fraction for distress calls. In a behavioral assay, female bats approached a distress-call playback only when a live conspecific was coupled with it. However, in isolation, the same calls elicited interest (grooming, pointing) but no approach. Together, the neural and autonomic signatures of social-call perception are present across contexts, whereas the behavioral response is not. Social context, therefore, does not modulate the behavioral readout of social calls; rather, it gates it. Significance StatementHow a social animal converts the perception of a vocalization into behavior remains poorly understood. Using the Egyptian Fruit Bat (Rousettus aegyptiacus), we show that physiological and neural responses to social calls are present in isolation, whereas approach behavior is not. We conclude that social context acts as a necessary gate between sensory representation and action, not a modulator that adjusts an existing response.

neuroscience↗

bioRxiv2025

Ultrastructural changes at auditory nerve synapses following moderate noise exposure

Moderate noise exposure is a common experience, yet its impact on central auditory synapses remains poorly understood. We study this issue at the first synapses in the central auditory pathway formed by auditory nerve afferents onto bushy cells in the cochlear nucleus, called endbulbs of Held. Non-traumatic noise exposure alters endbulb properties, decreasing the probability of vesicle release and enlarging the pool of releasable vesicles as assessed using electrophysiological methods and immunolabelling. These changes appear homeostatic, to maintain synaptic efficacy during periods of high activity. To identify structural changes underlying the larger vesicle pool, we used serial blockface electron microscopy of endbulbs from control and noise-exposed mice to quantitatively assess synaptic morphology. We observed no differences in the juxtapositional area between endbulbs and bushy cells, nor in the number or density of active zones and postsynaptic densities. Images of endbulb terminals were significantly darker after noise exposure, indicating an increase in the density of synaptic vesicles. These results suggest that moderate noise exposure induces an activity-dependent increase in presynaptic vesicle numbers, consistent with the observed physiological changes in neurotransmitter release. This work sets the stage for high-resolution studies to quantify docked and reserve vesicles. Significance statementNoise exposure is a fact of everyday life, and it is important to understand how noise affects function in the auditory pathway in the brain to understand the full consequences of noise exposure. Electrophysiological experiments indicate that noise triggers a homeostatic increase in the releasable pool of vesicles at auditory nerve synapses. We examined the cellular basis for this change using serial blockface electron microscopy of auditory nerve synapses with and without noise exposure. We reconstructed a number of bushy cells and their presynaptic auditory nerve terminals. After noise exposure, there was no significant increase in the area of synaptic contact or the number or density of synaptic release sites. There was an increase in the number of vesicles near release sites, which may account for the physiological changes. These results emphasize the importance of detailed anatomical studies to study the effects of noise exposure and thus determine the best mechanistic approach for therapies and treatments of noise-induced hearing loss.

neuroscience↗

bioRxiv2025

'The ship is going down and we are powerless'- The Impact of Federal Funding Changes on Researchers Training the Next Generation of Scientists

IntroductionHistorically, federal grant terminations have been rare and almost exclusively used in cases of misconduct. Under the current presidential administration, however, grant terminations have been common, with thousands of grants terminated across federal agencies such as the National Institutes of Health (NIH) and the National Science Foundation. Although there have been scattered reports of the impact of these terminations on individual researchers, there has not yet been a systematic investigation of the impact on the overall scientific community. MethodsAs part of a survey for a larger study, we asked researchers involved in T32 training programs how likely they would be to go into science if they were a graduate student now (Likert-type item) and how federal funding changes have affected them and their labs (open-ended). We report mean and standard deviation for the Likert-type item (1=Not at all likely, 5=Extremely likely), and we performed inductive thematic analysis to analyze the open-ended responses. Two independent raters coded responses, developed a codebook, and applied the codebook to all responses. The interrater reliability was high, {kappa}=0.84. ResultsOf the 490 researchers invited to participate in the survey, 277 (response rate 56.5%) completed it in full. Participants were relatively unlikely to choose to pursue science again, with only about one-third being somewhat or more likely to do so. Two hundred twenty-three people responded to the open-ended item about how federal funding changes have affected them. Coding resulted in 48 unique codes which fell into four themes: Impact on Finances, Impact on Trainees, Impact on Science, and Well-being. Participants described instability in their labs, concern for trainees well-being and careers, concern about the future of the entire scientific enterprise, and negative impacts on their and others well-being. DiscussionOur data demonstrates the significant, overwhelmingly negative impact of the changes in federal funding on researchers involved in training the next generation of scientists. Not only are they concerned about how they can continue to do the work they have dedicated their lives to, but they are also worried about the future of science in the United States. This latter concern stems not only from the decreasing availability and reliability of federal funding but also due to the impact all this is having on trainees ability to do their research and find jobs where they can do science. These data are a call to action to our federal agencies, institutions, other agencies, and donors who understand the value of science to support researchers through these uncertain times. Otherwise, what has taken decades to build will be eliminated by a few anti-scientific decisions.

scientific communication and education↗

bioRxiv2025

HTRA3 protease-chaperone stabilizes cathepsin B for mitochondrial POLG1 depletion in human cell ageing

The maintenance of mitochondrial proteins homeostasis, which is essential for proper cell function, is affected in pathophysiological ageing, yet several underlying mechanisms remain unexplored. We show that in normal and accelerated ageing cells, POLG1, the enzyme responsible for mitochondrial DNA replication, is degraded by the protease cathepsin B, which is overexpressed, escapes from lysosomes, and is stabilized by the chaperone activity of another protease, HTRA3. This degradation is in part counteracted by RAC1, a small GTPase also stabilized by HTRA3. POLG1 depletion, that occurs in progeroid Cockayne syndrome and senescent cells, is linked respectively to impairment or downregulation of the CSB protein, which promote cellular senescence. Our experiments in engineered cells, demonstrate that senescence itself, and not the absence of CSB, triggers the accumulation of cathepsin B and HTRA3, leading to POLG1 degradation. In summary, we uncover a complex, multi-step process that controls the degradation of POLG1 in mitochondria, a process that is activated by cell senescence and becomes more pronounced in Cockayne syndrome cells, providing new insight in the regulation of mitochondrial proteostasis in ageing and progeroid disorders.

cell biology↗

bioRxiv2024

HIV-1 budding requires cortical actin disassembly by the oxidoreductase MICAL1

Many enveloped viruses bud from the plasma membrane that is tightly associated with a dense and thick actin cortex. This actin network represents a significant challenge for membrane deformation and scission, and how it is remodeled during the late steps of the viral cycle is largely unknown. Using super-resolution microscopy, we show that HIV-1 buds in areas of the plasma membrane with low cortical F-actin levels. We find that the cellular oxidoreductase MICAL1 locally depolymerizes actin at budding sites to promote HIV-1 budding and release. In the absence of MICAL1, F-actin abnormally remains at viral budding sites, incompletely budded viruses accumulate at the plasma membrane and viral release is impaired. Remarkably, normal viral release can be restored in MICAL1-depleted cells by inhibiting Arp2/3-dependent branched actin networks. Mechanistically, we find that MICAL1 directly disassembles branched-actin networks and controls the timely recruitment of the ESCRT scission machinery during viral budding. In addition, the MICAL1 activator Rab35 is recruited at budding sites, functions in the same pathway as MICAL1 and is also required for viral release. This work reveals a role for oxidoreduction in triggering local actin depolymerization to control HIV-1 budding, a mechanism that may be widely used by other viruses. The debranching activity of MICAL1 could be involved beyond viral budding in various other cellular functions requiring local plasma membrane deformation.

cell biology↗

bioRxiv2023

MiniBAR/KIAA0355 is a dual Rac and Rab effector required for ciliogenesis

Cilia protrude from the cell surface and play critical roles in in-tracellular signaling, environmental sensing and development. Actin-dependent contractility and intracellular trafficking are both required for ciliogenesis, but little is known about how these processes are coordinated. Here, we identified a Rac1-and Rab35-binding protein with a truncated BAR domain that we named MiniBAR (aka KIAA0355/GARRE) which plays a key role in ciliogenesis. MiniBAR colocalizes with Rac1 and Rab35 at the plasma membrane and on intracellular vesicles traffick-ing to the ciliary base and exhibits remarkable fast pulses at the ciliary membrane. MiniBAR depletion leads to short cilia resulting from abnormal Rac-GTP/Rho-GTP levels, increased acto-myosin-II-dependent contractility together with defective trafficking of IFT88 and ARL13B into cilia. MiniBAR-depleted zebrafish embryos display dysfunctional short cilia and hall-marks of ciliopathies including left-right asymmetry defects. Thus, MiniBAR is a unique dual Rac and Rab effector that con-trols both actin cytoskeleton and membrane trafficking for cili-ogenesis.

cell biology↗

bioRxiv2022

Caveolae govern plasma membrane mechanics to protect cells against EDIN B-induced transcellular tunnel formation and lethality from S. aureus septicaemia

Large transcellular pores elicited by bacterial mono-ADP-ribosyltransferase (mART) exotoxins inhibiting the small RhoA GTPase compromise the endothelial barrier. Recent advances in biophysical modeling point towards membrane tension and bending rigidity as the minimal set of mechanical parameters determining the nucleation and maximal size of transendothelial cell macroaperture (TEM) tunnels induced by bacterial RhoA-targeting mART exotoxins. We report that cellular depletion of caveolin-1, the membrane-embedded building block of caveolae, and depletion of cavin-1, the master regulator of caveolae invaginations, increase the number of TEMs per cell. The enhanced occurrence of TEM nucleation events correlates with a reduction of cell height, due to the increase of cell spreading and decrease of cell volume, which, together with the disruption of RhoA-driven F-actin meshwork, favor membrane apposition for TEM nucleation. Strikingly, caveolin-1 specifically controls the opening speed of TEMs leading to their dramatic 5.4-fold larger widening. Consistent with the increase of TEM density and width in siCAV1 cells, we record a higher lethality in caveolin-1-deficient mice subjected to a catalytically active mART exotoxin targeting RhoA during staphylococcal bloodstream infection. Combined theoretical modeling with independent biophysical measurements of plasma membrane bending rigidity point toward a specific contribution of caveolin-1 to membrane stiffening in addition to the role of cavin-1/caveolin-1-dependent caveolae in the control of membrane tension homeostasis.

biophysics↗

bioRxiv2020

Inflight head stabilization associated with wingbeat cycle and sonar emissions in the Egyptian fruit bat.

Sensory processing of environmental stimuli during locomotion is critical for the successful execution of goal-directed behaviors and navigating around obstacles. The outcome of these sensorimotor processes can be challenged by head movements that perturb the sensory coordinate frames directing behaviors. In the case of visually-guided behaviors, visual gaze stabilization results from the integrated activity of the vestibuloocular reflex and motor efference copy originating within circuits driving locomotor behavior. A recent videographic study showed that echolocating bats exhibit inflight head stabilization during a target identification and landing task, though compensatory timing of the bats sonar signals was not reported. In the present investigation we tested hypotheses that head stabilization is more broadly implemented during epochs of exploratory flight, and is temporally associated with emitted sonar signals, which would optimize acoustic gaze. This was achieved by measuring head and body kinematics with motion sensors secured to the head and body of free-flying Egyptian fruit bats. These devices were integrated with ultrasonic microphones to record the bats sonar emissions and elucidate their temporal association with periods of head stabilization. Head accelerations in the Earth-vertical axis were asymmetric with respect to wing downbeat and upbeat relative to body accelerations. This indicated that inflight head and body accelerations were uncoupled, outcomes consistent with the implementation of head movements that limit vertical acceleration during wing downbeat. Furthermore, sonar emissions during stable flight occurred most often during wing downbeat and head stabilization, supporting the conclusion that head stabilization behavior optimized sonar gaze and environmental interrogation via echolocation. Summary statementDirect measurements of head and body kinematics from affixed motion sensors revealed head stabilization behaviors during exploratory flights in bats. Most sonar emissions were temporally correlated with this behavior, thereby contributing to the optimization of acoustic gaze.

animal behavior and cognition↗

bioRxiv2018

Adhesion to nanofibers drives cell membrane remodeling through 1D wetting

The shape of cellular membranes is highly regulated by a set of conserved mechanisms. These mechanisms can be manipulated by bacterial pathogens to infect cells. Human endothelial cell plasma membrane remodeling by the bacterium Neisseria meningitidis is thought to be essential during the blood phase of meningococcal infection, but the underlying mechanisms are unknown. Here we show that plasma membrane remodeling occurs independently of F-actin, along meningococcal type IV pili fibers, by a novel physical mechanism we term \" onedimensional\" membrane wetting. We provide a theoretical model that gives the physical basis of 1D wetting and show that this mechanism occurs in model membranes interacting with model nanofibers, and in human cells interacting with model extracellular matrices. It is thus a new general principle driving the interaction of cells with their environment at the nanoscale that is diverted by meningococcus during infection.

cell biology↗

bioRxiv2017

Bayesian Selection Of Grammar Productions For The Language Of Thought

Probabilistic proposals of Language of Thoughts (LoTs) can explain learning across different domains as statistical inference over a compositionally structured hypothesis space. While frameworks may differ on how a LoT may be implemented computationally, they all share the property that they are built from a set of atomic symbols and rules by which these symbols can be combined. In this work we show how the set of productions of a LoT grammar can be effectively selected from a broad repertoire of possible productions by an inferential process starting from experimental data. We then test this method in the language of geometry, a specific LoT model (Amalric et al., 2017). Finally, despite the fact of the geometrical LoT not being a universal (i.e. Turing-complete) language, we show an empirical relation between a sequences probability and its complexity consistent with the theoretical relationship for universal languages described by Levins Coding Theorem.

neuroscience↗

bioRxiv2017

Variability in prior expectations explains biases in confidence reports

Confidence in a decision is defined statistically as the probability of that decision being correct. Humans, however, display systematic confidence biases, as has been exposed in various experiments. Here, we show that these biases vanish when taking into account participants' prior expectations, which we measure independently of the confidence report. We use a wagering experiment to show that modeling subjects' choices allows for classifying individuals according to their prior biases, which fully explain from first principles the differences in their later confidence reports. Our parameter-free confidence model predicts two counterintuitive patterns for individuals with different prior beliefs: pessimists should report higher confidence than optimists, and, for the same task difficulty, the confidence of pessimists should increase with the generosity of the task. These findings show how systematic confidence biases can be simply understood as differences in prior expectations.

animal behavior and cognition↗

bioRxiv2017

Decision Confidence As A Mapping Of Bayesian Posterior Belief

We study the confidence response distributions for several two alternative forced choice tasks with different structure, and assess whether their behavioral responses are accurately accounted for as a mapping from bayesian inferred probability of having made a correct choice. We propose an extension to an existing bayesian decision making model that allows us to quantitatively compare the relative quality of different function mappings from bayesian belief onto responded confidence. We find that a simple linear rescaling from bayesian belief best fits the observed response distributions. Furthermore, the parameter values allow us to study how task structure affects differently the decision policy and confidence mapping, highlighting a dissociable effect between confidence and perceptual performance.

neuroscience↗