Biology subjects

Muralidharan, V.

Publications and source records attributed to Muralidharan, V..

At least 19 recordsLinked to original sources

bioRxiv2026

Modulation of the speed of Intrinsic Alpha Frequency (IAF) with tACS modulates variability of illusory speech perception

Navigating the world requires our brains to constantly process a massive influx of information from the environment. One of the most remarkable yet complex feats the human brain performs daily is speech perception. It is a multifaceted, hierarchical process that relies heavily on the integration of auditory and visual cues, particularly in noisy environments. Neural integration of these streams is hypothesized to depend on temporal mechanisms governed by individual alpha frequency (IAF, 8-12 Hz), which serves as a key neural correlate of the temporal binding window (TBW). While IAF has been linked to multisensory integration, its role in shaping multisensory illusions remains largely unexplored. Here, we tested this directly using transcranial alternating current stimulation (tACS) to modulate occipital activity during multisensory conflict. In a two-day protocol involving 27 healthy participants, resting-state EEG was recorded to determine IAF. On Day 2, participants then performed a multisensory speech task involving congruent (pa/, /ta/, /ka/) and incongruent McGurk stimuli (auditory /pa/, visual /ka/), both at baseline and during tACS applied at IAF and offset frequencies (IAF +/- 2 Hz) over occipital electrodes. While accuracy for congruent syllables remained high across conditions, results revealed that tACS significantly reduced the perception of illusory /ta/ percepts during McGurk trials. Finally, using a phenomenological model based on Kuramoto oscillators, we provided a mechanistic explanation for the percentage of illusory responses observed across participants under the influence of tACS at IAF and offsets. This study highlights the potential for targeted neuromodulatory interventions to influence multisensory processing in clinical or professional settings.

neuroscience↗

bioRxiv2026

Impaired value estimation over space explains turn-induced freezing of gait in Parkinson's disease: A cortico-basal ganglia-inspired reinforcement learning model

Parkinson's disease (PD) gait is characterized by reduced walking speed, short shuffling steps, increased double stance time, and increased step time variability. The most debilitating symptom in PD is freezing of gait (FOG), a context-dependent locomotion arrest, mostly occurring while encountering turns, obstacles, and narrow pathways. FOG is more pronounced during turning, a complex task that challenges motor planning and execution. Here, we simulate this phenomenon using a computational model inspired by the cortico-basal ganglia circuitry, based on reinforcement learning (RL) principles. In the model, the agent was trained to learn a value profile while navigating a path that involved turning. To simulate PD conditions, we clamped the temporal difference (TD) error, typically associated with dopaminergic signaling. Our model results show that compared to healthy controls (HC), PD non-freezers and PD freezers exhibit a reduction in turning velocity and step length, alongside an attenuated compensatory step-width widening at the sharpest turn, more pronounced in PD freezers, who additionally show increased step time variability. These kinematic impairments worsen during tighter turns. Ultimately, this model implicates FOG as a problem of impaired estimation of value over space and could potentially represent a generalized deficit in gait impairments in PD.

neuroscience↗

bioRxiv2026

NANHA - Neurostimulation in Atypical Neurodevelopment: a Harmonized Atlas

Non-invasive brain stimulation (NIBS) has become an important tool for investigating brain function and exploring therapeutic intervention in neurodevelopmental disorders (NDDs). Nevertheless, relevant studies are scattered across different NDDs, stimulation modalities, target regions, and experimental designs, which makes systematic exploration and comparative analysis challenging. Therefore, we present NANHA, a manually curated, harmonized and freely accessible resource of published NIBS studies in NDDs. The database was constructed using systematic PubMed searches covering 22 NDDs and five NIBS modalities. NANHA captures participant characteristics, study design, stimulation purpose and parameters, targeted brain regions, behavioral, cognitive, and neurophysiological outcomes, safety information, and follow-up assessments, whenever available. The NANHA web platform (https://cb.imsc.res.in/nanha/) provides searchable and downloadable records, advanced filtering options, and interactive visualizations to support data exploration. Overall, NANHA is a standardized resource for evidence synthesis, comparative analyses, identification of research gaps, and the development of disease-specific stimulation protocols for NDDs.

neuroscience↗

bioRxiv2026

Investigating sensorimotor beta burst dynamics as a robust biomarker for graded force modulation in humans

The most prominent signature associated with motor execution and motor imagery is the event-related desynchronisation and synchronisation (ERD/S) in the mu and beta bands (8-30 Hz). In the context of brain-computer interfaces (BCI), this ERD/S signature is helpful for binary decisions, such as left vs. right imagery, but it is not a robust biomarker for continuous prediction, such as precisely decoding different levels of force application. This is essential for developing better BCI applications with precise dynamic force outputs. Recent studies have revealed that sensorimotor beta bursts have a stronger relationship with motor control, even at a single-trial level, than mu and beta frequency band power. We, therefore, investigated whether the transient nature of beta bursts provide an alternative, but robust biomarker for BCI force decoding. Here, we designed an experiment where human participants (N = 16) performed both motor execution (ME) at four force levels (10%, 25%, 50%, and 75% of maximum voluntary contraction) and followed by imagination of the same, i.e. a motor imagery (MI) task, as their electroencephalogram (EEG) was recorded. We observed a clear and classical ERD pattern in the motor cortex region during the ME task, whereas it was less pronounced during the MI task. To explore the robust biomarkers for explanation of the force modulation we moved beyond classic trial average ERD/S and analysed the role of beta burst. After extracting sensorimotor beta bursts, we observed differences in spectral burst features between motor execution and imagery including burst amplitude, spectral width, and temporal width. Moreover, different force levels were correlated with changes in the burst amplitude and burst spectral width, specifically during motor execution. Interestingly, we found that different beta burst waveforms are associated with the different force levels and conditions. This suggests that the bursts-level features could be driven by changes in the underlying beta burst waveforms. Overall, our study shows that sensorimotor beta burst can be an important piece of the puzzle to implementing precise force control in brain-computer interface based prosthetics.

neuroscience↗

bioRxiv2025

Meditation as a Bioactive Intervention: Molecular and Neurophysiological Mechanisms Revealed by Connectivity Mapping

Meditation practices are often used as non-pharmacological adjunct therapy for managing stress and well-being benefits. We propose that beneath their non-pharmacological facade, meditation practices might operate via drug target modulation having profound neurophysiological effects. Firstly, we leverage the Connectivity Map (CMap) to investigate (a) the overlap between meditation-induced molecular signatures and established drug responses, and (b) the pathways and mechanisms contributing to meditation potential therapeutic effects. This was studied in a comprehensive temporal RNAseq dataset comprising premeditation, meditation, and follow-up stages from a clinical trial involving 106 participants practising inner engineering meditation. Meditation signatures overlapped with over 438 drugs, but predominantly with drugs targeting the neuroactive ligand receptor pathways, capable of modulating the brains excitation-inhibition (E/I) balance. Next, to bridge the meditation-induced molecular changes to measurable neurophysiological effects, we performed a comprehensive meta-analysis of drugs affecting E/I balance through the lens of non-invasive brain stimulation, i.e., transcranial magnetic stimulation (TMS-EMG and TMS-EEG). Using multiple correspondence analysis, we then clustered the CMap informed neuroactive drugs and their E/I effects on the same latent space. We found that meditations effects mimic drugs targeting the GABAergic, Glutametergic and other neuromodulatory system pathways. Our findings lead to a working model to objectively test neurophysiological changes resulting from meditation that can lead to evidence-based clinical applications. Overall, these findings support the view that meditation acts as a biologically active intervention capable of modulating molecular pathways and cortical excitability, rather than functioning solely as a psychological or contemplative practice.

systems biology↗

bioRxiv2025

The inner membrane complex protein, IMC55, is dispensable for intra-erythrocytic development of Plasmodium falciparum

Plasmodium falciparum, an obligate intracellular Apicomplexan parasite and the causative agent of malaria must reside and replicate within a host cell during the intra-erythrocytic stage. The parasite utilizes a specialized double-membraned organelle, called the inner membrane complex for schizont-stage segmentation and merozoite motility during subsequent re-invasion. In this study, we investigate the function of IMC55, a multi-transmembrane inner membrane complex protein, which we identified as a putative interacting partner of the P. falciparum ER-resident calcium binding protein, PfERC. We have previously shown that PfERC is essential for parasite egress and our data shows that PfERC may also function in parasite invasion into the RBC. The whole genome transposon mutagenesis screen predicts that IMC55 is essential for the intra-erythrocytic asexual cycle. In this work, we show that IMC55 is not required for asexual replication. Following inducible expression of this gene using two conditional systems, we find there is no defect in replicative fitness during the asexual blood stage. Taken together, these data demonstrate that the function of IMC55 is either dispensable or redundant for the Plasmodium falciparum asexual blood stage.

cell biology↗

bioRxiv2025

Spatiotemporal dynamics of signal dependent exocytosis and parasitophorous vacuolar membrane rupture during Plasmodium falciparum egress.

Malaria, caused by intracellular Plasmodium parasites, remains a major global health concern. These parasites reside and replicate within a vacuole in host red blood cells. Egress of daughter parasites out of the vacuolar and host membranes is tightly regulated via a complex mechanism. Prior studies have suggested that a cyclic-GMP driven calcium signaling pathway leads to the signal-dependent exocytosis of egress-specific vesicles that discharge several proteases into the parasitophorous vacuole. However, signal-dependent exocytosis during egress has not yet been observed in live parasitized RBCs. We targeted the exocytosis reporter, superecliptic pHlourin or SEP, to these egress-specific vesicles and utilized time-lapse imaging to observe exocytosis in live P. falciparum parasites. The spatiotemporal relationship between exocytosis and the breakdown of the parasitophorous vacuolar membrane (PVM) as well as parasite egress was also determined using a fluorescent reporter targeted to the PVM. Our data showed that exocytosis is triggered as early as 3 hours prior to merozoite egress. These data suggest that the PVM rupture occurs at a single site and rapidly expands from that initial site of rupture, releasing the merozoites into the RBC. This is followed by RBC membrane rupture and egress of merozoites. Using conditional mutants of the P. falciparum endoplasmic reticulum calcium-binding protein (PfERC), we demonstrate that knockdown of PfERC inhibits signal-dependent exocytosis of egress-specific vesicles. Together, these data demonstrate that signal-dependent exocytosis of egress-specific vesicles starts well before merozoites are formed via cytokinesis, PVM ruptures at a single site, and that PfERC is required for exocytosis of egress-specific vesicles.

cell biology↗

bioRxiv2024

Plasmodium RON11 triggers biogenesis of the merozoite rhoptry pair and is essential for erythrocyte invasion

Malaria is a global and deadly human disease caused by the apicomplexan parasites of the genus Plasmodium. Parasite proliferation within human red blood cells (RBC) is associated with the clinical manifestations of the disease. This asexual expansion within human RBCs, begins with the invasion of RBCs by P. falciparum, which is mediated by the secretion of effectors from two specialized club-shaped secretory organelles in merozoite-stage parasites known as rhoptries. We investigated the function of the Rhoptry Neck Protein 11 (RON11), which contains seven transmembrane domains and calcium-binding EF-hand domains. We generated conditional mutants of the P. falciparum RON11. Knockdown of RON11 inhibits parasite growth by preventing merozoite invasion. The loss of RON11 did not lead to any defects in processing of rhoptry proteins but instead led to a decrease in the amount of rhoptry proteins. We utilized ultrastructure expansion microscopy (U-ExM) to determine the effect of RON11 knockdown on rhoptry biogenesis. Surprisingly, in the absence of RON11, fully developed merozoites had only one rhoptry each. The single rhoptry in RON11 deficient merozoites were morphologically typical with a bulb and a neck oriented into the apical polar ring. Moreover, rhoptry proteins are trafficked accurately to the single rhoptry in RON11 deficient parasites. These data show that in the absence of RON11, the first rhoptry is generated during schizogony but upon the start of cytokinesis, the second rhoptry never forms. Interestingly, these single-rhoptry merozoites were able to attach to host RBCs but are unable to invade RBCs. Instead, RON11 deficient merozoites continue to engage with RBC for prolonged periods eventually resulting in echinocytosis, a result of secreting the contents from the single rhoptry into the RBC. Together, our data show that RON11 triggers the de novo biogenesis of the second rhoptry and functions in RBC invasion.

cell biology↗

bioRxiv2023

Atlas of Plasmodium falciparum intraerythrocytic development using expansion microscopy

Apicomplexan parasites exhibit tremendous diversity in much of their fundamental cell biology, but study of these organisms using light microscopy is often hindered by their small size. Ultrastructural expansion microscopy (U-ExM) is a microscopy preparation method that physically expands the sample [~]4.5x. Here, we apply U-ExM to the human malaria parasite Plasmodium falciparum during the asexual blood stage of its lifecycle to understand how this parasite is organized in three-dimensions. Using a combination of dye-conjugated reagents and immunostaining, we have catalogued 13 different P. falciparum structures or organelles across the intraerythrocytic development of this parasite and made multiple observations about fundamental parasite cell biology. We describe that the outer centriolar plaque and its associated proteins anchor the nucleus to the parasite plasma membrane during mitosis. Furthermore, the rhoptries, Golgi, basal complex, and inner membrane complex, which form around this anchoring site while nuclei are still dividing, are concurrently segregated and maintain an association to the outer centriolar plaque until the start of segmentation. We also show that the mitochondrion and apicoplast undergo sequential fission events while maintaining an association with the outer centriolar plaque during cytokinesis. Collectively, this study represents the most detailed ultrastructural analysis of P. falciparum during its intraerythrocytic development to date, and sheds light on multiple poorly understood aspects of its organelle biogenesis and fundamental cell biology. IMPACT STATEMENTUsing ultrastructure-expansion microscopy we explore the fundamental cell biology of malaria parasites, providing new insights into processes including establishment of cell polarity and organelle fission.

cell biology↗

bioRxiv2022

RAPID, TIME-RESOLVED PROXIMITY LABELING BY SBP1 IDENTIFIES A PORIN DOMAIN PROTEIN AT THE MALARIA PARASITE PERIPHERY

The deadly human malaria-causing parasite, Plasmodium falciparum relies on its capacity to completely remodel its host red blood cell (RBC) through the export of hundreds of parasite proteins across several membranes to the RBC. Among these exported proteins are numerous membrane proteins that are inserted into the parasite plasma membrane (PPM) during their transport via the secretory pathway. It is not known how these exported membrane proteins are extracted from the PPM for export. To answer this question, we fused the exported membrane protein skeleton binding protein 1 (SBP1) with the rapid, efficient, and promiscuous biotin ligase known as TurboID (SBP1TbID). Our data show that the SBP1TbID fusion protein was exported efficiently to the host RBC and was able to rapidly biotinylate proteins at the host-parasite interface during its export as well as at its final destination in the host RBC. Using time-resolved proximity biotinylation and label-free quantitative proteomics, we identified early (pre-export) interactors and late (post-export) interactors of SBP1TbID. This led to the identification of 24 proteins that were 10-fold or more enriched in the pre-export time point compared to the post-export time point. Among these early interactors were two promising membrane-associated proteins, one of which has a predicted porin domain, that could potentially act as a translocon at the PPM for exported membrane proteins (Plasmodium translocon of exported membrane proteins or PTEM). Both proteins localize to the host-parasite interface during early stages of the intraerythrocytic cycle and conditional knockdown of these candidates show that they play essential roles in the asexual lifecycle of the parasite. Taken together, our data suggest that these two proteins may play a role in extracting membrane proteins from the PPM for export to the host RBC.

cell biology↗

bioRxiv2022

Two modes of mid-frontal theta suggest a role in conflict and error processing

Mid-frontal theta increases during scenarios when conflicts are successfully resolved. Often considered as a generic signal of cognitive control, its temporal nature has hardly been investigated. Using advanced spatiotemporal techniques, we uncover that mid-frontal theta occurs as a transient oscillation or "event" at single trials with their timing reflecting computationally distinct modes. Single-trial analyses of electrophysiological data from participants performing the Flanker (N = 28) and Simon task (N = 18) were used to probe the relationship between theta and metrics of response conflict. We specifically investigated "partial errors", in which a small burst of muscle activity in the incorrect response effector occurred, quickly followed by a correction. We found that transient theta events in single trials could be categorized into two distinct theta modes based on their relative timing to different task events. Theta events from the first mode occurred briefly after the task stimulus and might reflect conflict-related processing of the stimulus. In contrast, theta events from the second mode were more likely to occur around the time partial errors were committed, suggesting they were elicited by a potential upcoming error. Importantly, in trials in which a full error was committed, this "error-related theta" occurred too late with respect to the onset of the erroneous muscle response, supporting a role of theta also in error correction. We conclude that different modes of transient mid-frontal theta can be adopted in single trials not only to process stimulus conflict, but also to correct erroneous responses.

neuroscience↗

bioRxiv2021

Transient beta modulates decision thresholds during human action-stopping

Action-stopping in humans involves bursts of beta oscillations in prefrontal-basal ganglia regions. To determine the functional role of these beta bursts we took advantage of the Race Model framework describing action-stopping. We incorporated beta bursts in three race model variants, each implementing a different functional contribution of beta to action-stopping. In these variants, we hypothesized that a transient increase in beta could 1) modulate decision thresholds, 2) change stop accumulation rates, or 3) promote the interaction between the Stop and the Go process. We then tested the model predictions using EEG recordings in humans performing a Stop-signal task. We found that the model variant in which beta increased decision thresholds for a brief period of time best explained the empirical data. The model parameters fitted to the empirical data indicated that beta bursts involve a stronger decision threshold modulation for the Go process than for the Stop process. This suggests that prefrontal beta influences stopping by temporarily holding the response from execution. Our study further suggests that human action-stopping could be multi-staged with the beta acting as a pause, increasing the response threshold for the Stop process to modulate behavior successfully. Our novel approach of introducing transient oscillations into the race model and testing against human neurophysiological data allowed us to discover potential mechanisms of prefrontal beta, possibly generalizing its role in situations requiring executive control over actions.

neuroscience↗

bioRxiv2020

A druggable oxidative folding pathway in the endoplasmic reticulum of human malaria parasites

Malaria remains a major global health problem, and there exists a constant need to identify druggable weaknesses in P. falciparum biology. The endoplasmic reticulum (ER) has many essential roles in the asexual lifecycle and may offer new drug targets, but it remains critically understudied. We generated conditional mutants of the putative redox-active, ER chaperone PfJ2, and show that it is essential for parasite survival. Using a redox-active cysteine crosslinker, we identify its substrates to be other mediators of oxidative folding, PfPDI8 and PfPDI11, suggesting a redox-regulatory role for PfJ2. Knockdown of these protein disulfide isomerases in PfJ2 conditional mutants show that PfPDI11 is not essential, while PfPDI8 is essential for asexual growth and may work in a complex with PfJ2 and other ER chaperones. Finally, we show that these redox interactions in the parasite ER are sensitive to small molecule inhibition. Together these data build a model for how oxidative folding occurs in the P. falciparum ER and demonstrate its suitability for antimalarial drug development.

microbiology↗

bioRxiv2019

Temporally-precise disruption of prefrontal cortex informed by the timing of beta bursts impairs human action-stopping

Human action-stopping is thought to rely on a prefronto-basal ganglia-thalamocortical network, with right inferior frontal cortex (rIFC) posited to play a critical role in the early stage of implementation. Here we sought causal evidence for this idea in experiments involving healthy human participants. We first show that action-stopping is preceded by bursts of electroencephalographic activity in the beta band over prefrontal electrodes, putatively rIFC, and that the timing of these bursts correlates with the latency of stopping at a single-trial level: earlier bursts are associated with faster stopping. From this we reasoned that the integrity of rIFC at the time of beta bursts might be critical to successful stopping. We then used fMRI-guided transcranial magnetic stimulation (TMS) to disrupt rIFC at the approximate time of beta bursting. Stimulation prolonged stopping latencies and, moreover, the prolongation was most pronounced in individuals for whom the pulse appeared closer to the presumed time of beta bursting. These results help validate a model of the neural architecture and temporal dynamics of action-stopping. They also highlight the usefulness of prefrontal beta bursts to index an apparently important sub-process of stopping, the timing of which might help explain within- and between-individual variation in impulse control.

neuroscience↗

bioRxiv2019

The Clp proteolytic system acts as an essential nexus for Plasmodium plastid biogenesis

The human malaria parasite, Plasmodium falciparum, contains an essential plastid called the apicoplast. Most of apicoplast proteins are encoded by the nuclear genome and it is unclear how the plastid proteome is regulated. Here, we study an apicoplast-localized caseinolytic-protease (Clp) system and how it regulates organelle proteostasis. Using null and conditional mutants, we demonstrated that the Clp protease (PfClpP) has robust enzymatic activity that is essential for apicoplast biogenesis. We developed a CRISPR/Cas9 based system to express catalytically-dead PfClpP, which showed that PfClpP oligomerizes as a zymogen and matured via trans-autocatalysis. The expression of a Clp chaperone (PfClpC) mutant led to the discovery of a functional chaperone-protease interaction essential for plastid function. Conditional mutants of the substrate-adaptor (PfClpS) demonstrated its essential function in plastid biogenesis. A combination of multiple affinity purification screens identified the Clp complex composition as well as putative Clp substrates. This comprehensive study reveals the molecular composition and interactions influencing the proteolytic function of the apicoplast Clp system and demonstrates its central role in the biogenesis of the plastid in malaria parasites.

microbiology↗

bioRxiv2019

Temporal cascade of frontal, motor and muscle processes underlying human action-stopping

Action-stopping is a canonical executive function thought to involve top-down control over the motor system. Here we aimed to validate this stopping system using high temporal resolution methods in humans. We show that, following the requirement to stop, there was an increase of right frontal beta ([~]13 to 30 Hz) at [~]120 ms, likely a proxy of right inferior frontal gyrus; then, at 140 ms, there was a broad skeletomotor suppression, likely reflecting the impact of the subthalamic nucleus on basal ganglia output; then, at [~]160 ms, suppression was detected in the muscle, and, finally, the behavioral time of stopping was [~]220 ms. This temporal cascade confirms a detailed model of action-stopping, and partitions it into subprocesses that are isolable to different nodes and are more precise than the behavioral speed of stopping. Variation in these subprocesses, including at the single-trial level, could better explain individual differences in impulse control.

neuroscience↗

bioRxiv2019

Metabolomic profiling reveals developmentally regulated biosynthesis of polyprenols and dolichols in the malaria parasite

The cis-polyisoprenoid lipids namely polyprenols, dolichols and their derivatives are linear polymers of several isoprene units. In eukaryotes, polyprenols and dolichols are synthesized as a mixture of four or more homologues of different length with one or two predominant species with sizes varying among organisms. Polyprenols have been hardly detectable in eukaryotic cells under normal conditions with the exception of plants and sporulating yeast. Our metabolomics studies revealed that cis-polyisoprenoids are more prevalent and diverse in the parasite Plasmodium falciparum than previously postulated as we uncovered active de novo biosynthesis and substantial levels of accumulation of polyprenols and dolichols of 15 to 19 isoprene units. A distinctive polyprenol and dolichol profile both within the intraerythrocytic asexual cycle and between asexual and gametocyte stages was also observed suggesting that cis-polyisoprenoid biosynthesis changes throughout parasites development. In addition, we confirmed the presence of an active cis-prenyltransferase (PfCPT) and that dolichol biosynthesis occurs via reduction of the polyprenol to dolichol by an active polyprenol reductase (PfPPRD) in the malaria parasite. Isotopic labeling and metabolomic analyses of a conditional mutant of PfCPT or PfPPRD suggest that polyprenols may be able to substitute dolichols in their biological functions when dolichol synthesis is impaired in Plasmodium.

biochemistry↗

bioRxiv2018

An ER-resident calcium binding protein modulates egress of malaria parasites from erythrocytes

The endoplasmic reticulum (ER) is thought to play an essential role during egress of malaria parasites because the ER is assumed to be the calcium (Ca2+) signaling hub and required for biogenesis of egress-related organelles. However, no proteins localized to the parasite ER have been shown to play a role in egress of malaria parasites. In this study, we generated conditional mutants of the Plasmodium falciparum Endoplasmic Reticulum-resident Calcium-binding protein (PfERC), a member of the CREC family. Knockdown of PfERC shows that this gene is essential for asexual growth of P. falciparum. Analysis of the intraerythrocytic lifecycle revealed that PfERC is essential for parasite egress but not required for protein trafficking or Ca2+ storage. We found that PfERC knockdown prevents the rupture of the parasitophorous vacuole membrane. This is because PfERC knockdown inhibited the proteolytic maturation of the subtilisin-like serine protease, SUB1. Using double mutant parasites, we show that PfERC is required for the proteolytic maturation of the essential aspartic protease, Plasmepsin X, which cleaves SUB1. Further, we show that processing of substrates downstream of the proteolytic cascade is inhibited by PfERC knockdown. Thus, these data establish the ER-resident CREC family protein, PfERC, as a key early regulator of the egress proteolytic cascade of malaria parasites.

cell biology↗