Biology subjects

Pons, J. L.

Publications and source records attributed to Pons, J. L..

8 recordsLinked to original sources

bioRxiv2026

DSF signalling integrates c-di-GMP and σ54 pathways with metabolic reprogramming to control Stenotrophomonas maltophilia pathogenicity and antibiotic resistance

Stenotrophomonas maltophilia is an opportunistic, multidrug-resistant pathogen whose pathogenicity is mainly driven by biofilm formation, extracellular enzyme production, surface adhesins and motility. In addition, a diffusible signal factor (DSF)-mediated quorum sensing (QS) system encoded by the rpf gene cluster coordinates collective behaviours and contributes to pathogenicity. While DSF signalling has been extensively studied in plant-pathogenic xanthomonads, its integration with transcriptional and metabolic regulation in human pathogens remains poorly defined. Here, we investigate how the DSF/Rpf system shapes virulence and adaptation in S. maltophilia by modulating downstream regulatory and metabolic pathways. Cell density-dependent activation of the RpfC-RpfG two-component system reduces intracellular c-di-GMP levels, promoting a growth phase-dependent switch between biofilm formation and motile lifestyle. This transition requires the global transcriptional regulator Clp, which functions as a transcriptional activator when unbound to c-di-GMP. Clp controls genes involved in motility, adhesion, and the alternative sigma factor {sigma} RpoN2, which inversely regulates flagellar motility and type IV pilus-mediated adhesion. Transcriptomic profiling uncovered additional DSF-dependent regulatory circuits linking quorum sensing to metabolism and antibiotic resistance. Notably, at the onset of stationary phase, the {sigma} paralog RpoN1 acts together with RpfF and RpfB to fine-tune DSF production through fatty acid and central carbon metabolism, coupling QS output to cellular metabolic state. This metabolic control constrains DSF output and impacts colistin susceptibility, highlighting clinically relevant consequences of DSF homeostasis. Together, these findings define a species-specific DSF regulatory architecture in S. maltophilia that integrates quorum sensing, second-messenger signalling, transcriptional regulation, and metabolic reprogramming to promote survival and pathogenicity. Author SummaryStenotrophomonas maltophilia is a bacterial pathogen that causes infections, particularly in hospitalized and immunocompromised patients. Its clinical impact is driven by intrinsic multidrug resistance and the ability to switch between a free-swimming state and a surface-attached biofilm state. Biofilms protect bacteria from antibiotics and the immune system, making infections persistent, while motility promotes spread and colonization. Understanding how S. maltophilia controls this balance is critical for combating infection. Like many bacteria, S. maltophilia uses chemical communication, known as quorum sensing, to sense population density and coordinate behaviours linked to virulence and survival. This system is based on the autoinducer DSF, allowing bacteria to decide when to move, attach, or alter metabolism. In this work, we show that DSF-based quorum sensing activates a regulatory cascade that modulates levels of the signalling molecule c-di-GMP, triggering a switch between biofilm formation and motility. This switch relies on global regulators that control genes involved in movement, adhesion, metabolism, and antibiotic resistance. We also uncover a metabolic feedback mechanism that fine-tunes DSF concentration, impacting bacteria state and antibiotic susceptibility. These findings reveal how bacterial communication, metabolism, and pathogenic behaviour are linked in S. maltophilia, highlighting opportunities for antimicrobial intervention.

microbiology↗

bioRxiv2024

Modulation of Common Synaptic Inputs and Motor Unit Recruitment Threshold in TricepsSurae Muscles: Effects of Ankle Position

The objective of this study was to investigate how altering muscle length by changing ankle position affects force control, motor unit recruitment, and motor unit coherence within and across triceps surae muscles. Sixteen healthy young adults performed isometric plantarflexion (PF) at three ankle positions with the ankle plantarflexed at 20{degrees} (PF20{degrees}), at the neural position (PF0{degrees}) and dorsiflexed at 20{degrees} (DF20{degrees}). High-density surface electromyography was used to record the medial and lateral heads of the gastrocnemius muscle (GM and GL), and the medial and lateral portions of the soleus muscle (SL and SM). Motor unit cumulative spike trains (MUCST) were used to calculate intramuscular, intermuscular, and Force-MUCST coherence in the delta (0-5 Hz), alpha (5-15 Hz), and beta (15-35 Hz) frequency bands. Changing the ankle position from a shortened to lengthened position resulted in increased GM-SM coherence in the delta and alpha bands and improved force steadiness, while intramuscular coherence and Force-MUCST coherence decreased in the alpha band. However, there were minimal changes in beta band coherence. Motor unit recruitment thresholds of GM and SL were reduced with muscle lengthening, while GL showed greater thresholds at lengthened positions, and SM was unaffected by ankle position. These findings highlight the role of inhibitory inputs associated with changes in muscle length and the modulation of these inputs by neighboring synergistic muscles. This study reveals a neuromuscular control strategy that modulates common synaptic inputs and motor unit recruitment of triceps surae to maintain force output during isometric plantarflexions at varying muscle lengths. Key pointsO_LIWhen comparing isometric contractions at different ankle joint angles, a lengthened position resulted in greater shared common inputs between the medial head of the gastrocnemius and the medial compartment of the soleus in delta and alpha frequency bands during submaximal force production. C_LIO_LIIncreased muscle length resulted in improved force steadiness, as well as reduced common synaptic inputs within each triceps surae muscle and coupling between force output and neural drive in the alpha band. C_LIO_LIShifting the ankle position from a shortened to a lengthened position resulted in a reduced motor unit recruitment threshold of GM and SL. However, GL exhibited an opposite pattern, showing higher recruitment thresholds at lengthened positions, while SM was not affected by changes in muscle length. C_LIO_LIThis study reveals a neuromuscular control strategy that integrates afferent feedback and muscle mechanical properties while modulating common descending inputs to synergistic plantarflexors. C_LI

neuroscience↗

bioRxiv2024

Effects of Uni- and Bidirectional Interaction During Dyadic Ankle and Wrist Tracking

Haptic human-robot-human interaction allows users to feel and respond to one anothers forces while interfacing with separate robotic devices, providing customizable infrastructure for studying physical interaction during motor tasks (i.e., physical rehabilitation). For both upper- and lower-limb tasks, previous work has shown that virtual interactions with a partner can improve motor performance and enhance individual learning. However, whether the mechanism of these improvements generalizes across different human systems is an open question. In this work, we investigate the effects of haptic interaction between healthy individuals during a trajectory tracking task involving single-joint movements at the wrist and ankle. We compare tracking performance and muscle activation during haptic conditions where pairs of participants were uni- and bidirectionally connected, in order to investigate the contribution of real-time responses from a partner during the interaction. Findings indicate similar improvements in tracking performance during the bidirectional interaction for both the wrist and ankle, despite significant differences in how individuals modulated co-contraction. For each joint, bidirectional and unidirectional interaction resulted in similar improvements for the worse partner in the dyad. For the better partner, bidirectional interaction outperformed unidirectional interaction, likely due to changes in movement planning that were not observed in the unidirectional condition. While these results suggest that unidirectional interaction is sufficient for error correction of less skilled individuals during simple motor tasks, they also highlight the mutual benefits of bidirectional interaction which are consistent across the upper and lower limbs.

bioengineering↗

bioRxiv2022

Transcutaneous electrical nerve stimulation acutely impacts motor unit firing activity during isometric contractions

A low intensity electrical current delivered transcutaneously at a high frequency over a muscle can acutely recruit motor units in a physiological order by activating peripheral sensory pathways. This method has been used in patients to reduce tremor or supplement motor function, leading to the development of therapies and products. We aimed to better understand how the stimulation of the median nerve, the contralateral first dorsal interosseus muscle (FDI), and the combination of these two paradigms impact the motor unit activity from the FDI muscle. We identified and tracked the same motor units across the conditions and compared the electromyographic amplitude, motor unit discharge rates, and the degree of correlation between fast and slow oscillations of motor unit discharge rates. We found that the stimulation of the FDI muscle can acutely increase the electromyographic amplitude of the homonymous muscle on the contralateral side (F = 20.4; p < 0.001) while the discharge rate of motor units did not differ between the control and the stimulation condition (F = 0.2; p = 0.806). We did not observe any significant effect of the stimulation on the ratio of pairs of motor units with a significant correlation, showing that the stimulation barely impacted the distribution of correlated inputs to the pool of motor units. We did not observe short-term effects of the stimulation once it was discontinued. Overall, these results showed that the specific stimulation of peripheral sensory pathways can acutely impact motor unit firing activity without disturbing the neural control of force. New & NoteworthyWe identified and tracked the same motor units across stimulation and control conditions using high-density electromyography. We found that the specific stimulation of peripherial sensory pathways can acutely impact motor unit firing activity, likely due to the recruitment of additional motor units. At the same time, the degree of correlation between fast and slow oscillations of motor unit discharge rates was stable, limiting the disturbance of the neural control of force.

physiology↗

bioRxiv2022

Two motor neuron synergies, invariant across ankle joint angles, activate the triceps surae during plantarflexion

Recent studies have suggested that the nervous system generates movements by controlling groups of motor neurons (synergies) that do not always align with muscle anatomy. In this study, we determined whether these synergies are robust across tasks with different mechanical constraints. We identified motor neuron synergies using principal component analysis (PCA) and cross-correlations between smoothed discharge rates of motor neurons. In Part 1, we used simulations to validate these methods. The results suggested that PCA can accurately identify the number of common inputs and their distribution across active motor neurons. Moreover, the results confirmed that cross-correlation can separate pairs of motor neurons that receive common inputs from those that do not receive common inputs. In Part 2, sixteen individuals performed plantarflexion at three ankle angles while we recorded electromyographic signals from the gastrocnemius lateralis (GL) and medialis (GM) and the soleus (SOL) with grids of surface electrodes. PCA revealed two motor neuron synergies. These motor neuron synergies were relatively stable with no significant differences in the distribution of motor neuron weights across ankle angles (p=0.62). When the cross-correlation was calculated for pairs of motor units tracked across ankle angles, we observed that only 13.0% of pairs of motor units from GL and GM exhibited significant correlations of their smoothed discharge rates across angles, confirming the low level of common inputs between these muscles. Overall, these results highlight the modularity of movement control at the motor neuron level, suggesting a sensible reduction of computational resources for movement control. Key points summaryO_LIThe central nervous system may generate movements by activating groups of motor neurons (synergies) with common inputs. C_LIO_LIWe show here that two main sources of common inputs drive the motor neurons innervating the triceps surae muscles during isometric ankle plantarflexions. C_LIO_LIWe report that the distribution of these common inputs is globally invariant despite changing the mechanical constraints of the tasks, i.e., the ankle angle. C_LIO_LIThese results suggest the functional relevance of the modular organization of the central nervous system to control movements. C_LI

neuroscience↗

bioRxiv2022

Modulation of spinal circuits following phase-dependent electrical stimulation of afferent pathways

Peripheral electrical stimulation (PES) of afferent pathways is a tool commonly used to induce neural adaptations in some neural disorders such as pathological tremor or stroke. However, the neuromodulatory effects of stimulation interventions synchronized with physiological activity (closed-loop strategies) have been scarcely researched in the upper-limb. Here, the short-term spinal effects of a 20-minute stimulation of afferent pathways protocol applied with a closed-loop strategy named Selective and Adaptive Timely Stimulation (SATS) was explored. The SATS strategy was applied to the radial nerve in-phase (INP) or out-of-phase (OOP) with respect to the muscle activity of the extensor carpi radialis (ECR). The neural adaptations at the spinal cord level were assessed for the flexor carpi radialis (FCR) by measuring disynaptic Group I inhibition, Ia presynaptic inhibition, and Ib facilitation from the H-reflex, and estimation of the neural drive before, immediately after, and 30 minutes after the intervention. SATS strategy was proved to deliver synchronous stimulation with the real-time measured muscle activity with an average delay of 17{+/-}8 ms. SATS-INP induced an increase of the disynaptic Group I inhibition (77{+/-}23 % of baseline conditioned FCR H-reflex), while SATS-OOP elicited the opposite effect (125{+/-}46 %). Not all the subjects maintained the changes after 30 minutes. Additionally, no other significant specific neural adaptations were found for the rest of measurements. These results suggest that the short-term modulatory effects of phase-dependent PES occur at the specific targeted spinal pathways for the wrist muscles in healthy individuals. Overall, timely recruitment of afferent pathways with the muscle activity is a fundamental principle which should be considered in tailoring PES protocols for the specific neural circuits to be modulated.

neuroscience↗

bioRxiv2022

Transcutaneous electrical nerve stimulation modulates corticospinal excitability while preserving motor unit discharge properties during isometric contractions

AimTranscutaneous electrical nerve stimulation (TENS) aims to supplement sensory feedback to improve force steadiness or motor function. In this study, we directly assessed potential changes in corticospinal excitability and motor unit discharge characteristics from the first dorsal interosseous (FDI) muscle due to TENS by using transcranial magnetic stimulation (TMS) and high-density surface electromyography (HDsEMG). MethodsEleven healthy young adults performed a series of submaximal isometric index abductions. We estimated i) motor evoked potential (MEP) amplitudes, ii) persistent inward current amplitudes (PIC, i.e., delta F), iii) motor unit recruitment thresholds and discharge rates, and iv) common synaptic input to motor units before and after TENS. ResultsTENS did not affect force steadiness (2.5 {+/-} 0.9% and 3.3 {+/-} 1.9% (p = 0.010)). MEP amplitudes decreased at 110% of the resting motor threshold (rMT; 0.72 {+/-} 0.66 mV vs. 0.59 {+/-} 0.63 mV; p < 0.001), increased at 130% rMT (1.18 {+/-} 1.10 mV vs. 1.41 {+/-} 1.29 mV; p < 0.001). Delta F increased after TENS (3.7 {+/-} 2.2 pps vs. 4.5 {+/-} 2.6 pps; p = 0.010). We did not find a change in the level of common synaptic input or in the temporal variability of motor unit discharge rates after the session of TENS. ConclusionThese results suggest that TENS can modulate corticospinal excitability through supraspinal and spinal processes and, thus act as a priming technique. At the same time, TENS does not generate short-term changes in the neural control of force in young, healthy adults.

physiology↗

bioRxiv2022

A deep CNN framework for neural drive estimation from HD-EMG across contraction intensities and joint angles

ObjectivePrevious studies have demonstrated promising results in estimating the neural drive to muscles, the net output of all motoneurons that innervate the muscle, using high-density electromyography (HD-EMG) for the purpose of interfacing with assistive technologies. Despite the high estimation accuracy, current methods based on neural networks need to be trained with specific motor unit action potential (MUAP) shapes updated for each condition (i.e., varying muscle contraction intensities or joint angles). This preliminary step dramatically limits the potential generalization of these algorithms across tasks. We propose a novel approach to estimate the neural drive using a deep convolutional neural network (CNN), which can identify the cumulative spike train (CST) through general features of MUAPs from a pool of motor units. MethodsWe recorded HD-EMG signals from the gastrocnemius medialis muscle under three isometric contraction scenarios: 1) trapezoidal contraction tasks with different intensities, 2) contraction tasks with a trapezoidal or sinusoidal torque target, and 3) trapezoidal contraction tasks at different ankle angles. We applied a convolutive blind source separation (BSS) method to decompose HD-EMG signals to CST and segmented both signals into windows to train and validate the deep CNN. Then, we optimized the structure of the deep CNN and validated its generalizability across contraction tasks within each scenario. ResultsWith the optimal configuration for the HD-EMG data window (overlap of 20 data points and window length of 40 data points), the deep CNN estimated the CST close to that from BSS, with a correlation coefficient higher than 0.96 and normalized root-mean-square-error lower than 7% with respect to the BSS (golden standard) within each scenario. ConclusionThe proposed deep CNN framework can utilize data from different contraction tasks (e.g., different intensities), learn general features of MUAP variants, and estimate the neural drive for other contraction tasks. SignificanceWith the proposed deep CNN, we could potentially build a neuraldrive-based human-machine interface that is generalizable to different contraction tasks without retraining.

bioengineering↗