Biology subjects

Kumar, N.

Publications and source records attributed to Kumar, N..

At least 19 recordsLinked to original sources

bioRxiv2026

Evaluating Brain Flow Index from a temple-worn wearable against depth-resolved time-domain NIRS during head-down tilt and postural transitions in healthy young men

Significance: Wearable optical sensors could make continuous cerebral hemodynamic monitoring practical in daily life. Because any surface head sensor also samples extracerebral tissue, demonstrating cerebral relevance requires a reference that separates deep from superficial hemodynamics. Aim: We evaluated whether the Temple Brain Flow Index (Temple-BF), derived from a temple-worn photoplethysmographic wearable, covaried more strongly with the deeper (brain-assigned) than the superficial (scalp-assigned) hemodynamics recovered from time-domain near-infrared spectroscopy (TD-NIRS) during controlled postural challenges. Approach: Sixty sessions from 44 healthy young adult men were analyzed across three physiological challenges: 30{degrees} head-down tilt, stand-to-squat, and stand-to-supine transitions. Optical density and mean time of flight from a three-module TD-NIRS system were inverted with a Monte Carlo-derived two-layer model to obtain scalp- and brain-layer hemoglobin time series. Temple-BF was compared with these model-derived signals using lag-adjusted and zero-lag correlations, paired brain-versus-scalp comparisons, heart rate and short-separation-HbO adjusted partial correlations. Results: Median lag-adjusted correlations between Temple-BF and brain-layer {Delta}HbO traces were 0.912, 0.843, and 0.839 for head-down tilt, stand-to-squat, and stand-to-supine transitions, respectively; corresponding scalp-layer medians were 0.494, 0.700, and 0.767. Paired brain-minus-scalp differences were significant for head-down tilt (median 0.333, p < 0.001) and stand-to-squat (0.110, p < 0.001) but not for stand-to-supine (0.036, p = 0.082) transitions. Zero-lag brain-layer medians were 0.826, 0.701, and 0.796, and the association persisted after adjustment for heart rate (partial r = 0.832, 0.850, 0.654) and for short-separation superficial HbO (0.649, 0.570, 0.438). Transition-window correlations had medians of 0.878, 0.861, and 0.876, with directionally concordant transition responses in 59 of 60 sessions. Conclusions: Temple-BF tracked model-derived brain-layer TD-NIRS {Delta}HbO across all three postural challenges, with larger median correlations against the brain-layer than the scalp compartment in all three protocols, and transition responses in the same direction for almost all sessions. These results support Temple-BF as a relative marker of cerebral hemodynamic change during postural perturbations. Establishing cerebral specificity at the temple, and excluding residual systemic and superficial contributions, will require flow-sensitive references and fuller systemic monitoring.

neuroscience↗

bioRxiv2026

Nutritional history affects stress-resistance architecture across ageing and sex

Diet can influence lifespan and age-dependent physiological function, but how nutrition during development and adulthood affects relationships among stress resistance traits across age remains unclear. Using an isocaloric full-factorial larval x adult diet design in outbred Drosophila melanogaster, we tested how protein- and carbohydrate-biased diets affected starvation, desiccation, cold, osmotic, and heat resistance across the adult life course and sex. We also measured whole-body triacylglyceride, protein, body weight, and water content, and compared responses with matched lifespan and reproductive-output data. Resistance declined across the adult life course, but the traits did not vary as a single phenotype: among the traits included in the covariance analysis, desiccation, osmotic, and heat resistance formed a tightly correlated core, whereas starvation resistance remained comparatively peripheral in both sexes. Developmental diet produced trait-specific effects, whereas protein-biased adult diet favoured heat and osmotic resistance, paralleling effects on lifespan and reproductive output, but had opposite effects on starvation and cold resistance in specific contexts. Thus, nutrition alters rather than uniformly improves stress resistance, and covariance among resistance traits does not necessarily predict how those traits respond to nutritional perturbation.

ecology↗

bioRxiv2026

nf_xpatial: A Reproducible Framework for Standardized Preprocessing and Clustering of Xenium Data

Recent advances in spatial transcriptomics have enabled the profiling of increasingly larger numbers of genes while retaining single-cell and subcellular resolution in situ. However, standardized bioinformatics workflows for analyzing these datasets have lagged behind, with existing pipelines focusing primarily on image processing and cell segmentation. To address this gap, we present nf_xpatial, a best-practices Nextflow pipeline for the downstream analysis of 10x Genomics Xenium data. The pipeline performs quality control, filtering, log and cell area normalization, multi-sample integration, and both expression-driven and spatially informed clustering across systematic parameter sweeps, allowing users to evaluate and compare clustering resolutions and spatial modeling parameters within a single reproducible run. Overall, nf_xpatial streamlines the processing of Xenium data from platform outputs to integrated single-cell and spatial clustering datasets, providing a standardized starting point from which biologists can fine-tune parameters and proceed to hypothesis-driven spatial analyses.

bioinformatics↗

bioRxiv2026

Contextual Inference Drives Motor Memory Protection and Disruption

Newly acquired memories are initially fragile and are consolidated into long-term memory over time. Although consolidated memories were once thought to be resistant to interference, accumulating evidence shows that memory reactivation renders them transiently labile, making them susceptible to modification or interference before reconsolidation. Crucially, however, there is substantial variation in whether reactivated memories are disrupted by new information, remain protected from it, or even strengthened by it. The factors that guide this modification are largely unknown. To systematically investigate this, we examined motor memory interference using a classic A-B-A visuomotor rotation paradigm. Participants adapted to a 30-degree clockwise rotation (A) on Day1. On Day2, an interfering 30-degree counter-clockwise rotation (B) was introduced under varied conditions: directly without reactivation, after brief reactivation of A, after expression of A without feedback, or following a gradual transition from A to B. The final experiment used explicit contextual cues (a secondary follow-through target) to distinguish A and B trials. Contrary to the simple prediction that reactivation should increase vulnerability to interference, reactivating the original memory before introducing interference protected it, as evidenced by significant savings during relearning on Day3. In contrast, introducing interference directly, without reactivation, disrupted the original memory. This protection was consistent with a contextual-inference account: the large sensory prediction error experienced during the abrupt transition from A to B served as a latent contextual cue, signaling a new context and thereby shielding the original memory from being overwritten. Eliminating this prediction error through an immediate washout session with a similar error profile or through a gradual A-to-B transition abolished the protective effect and disrupted the original memory. Furthermore, when explicit contextual cues distinguished the two perturbations, memories were protected even in the absence of a salient prediction error. Our findings are consistent with a contextual inference account in which the fate of a consolidated memory, whether it is modified or protected, is shaped by the availability of explicit cues or latent signals such as sensory prediction error at the time when interference is introduced.

neuroscience↗

bioRxiv2026

Mitigation of Parkinson's Disease Pathology in C. elegans by Marine Bacterium Kocuria rhizophila via Ferroptosis Suppression

Parkinson's disease (PD) is a progressive neurodegenerative condition characterized by the loss of dopaminergic (DA) neurons and alpha-synuclein aggregation, with ferroptosis playing a critical pathological role. This study investigated the neuroprotective potential of Kocuria rhizophila strain CDMP12, a marine bacterium isolated from the Gulf of Mannar, India, using Caenorhabditis elegans models of PD. Dietary supplementation with K. rhizophila (CDMP12) significantly preserved DA neuron structure, rescued neuro-sensory and motor deficits, and attenuated both alpha-synuclein expression in the C. elegans models. Transcriptomic and qRT-PCR analyses revealed that CDMP12 systematically suppressed ferroptosis by significantly downregulating iron and lipid regulatory genes such as smf-3, ftn-1, and acs-4, while upregulating the protective antioxidant gene gpx-1. Furthermore, BODIPY staining demonstrated that CDMP12 treatment markedly reduced lipid peroxidation, lowering the oxidized-to-non-oxidized lipid ratio in PD worms. Collectively, these findings identify K. rhizophila (CDMP12) as a promising marine-derived neuroprotective candidate that mitigates PD-associated pathology, accompanied by reduced alpha-synuclein burden, preservation of DA neuronal function, and attenuation of ferroptosis-associated molecular and lipid peroxidation signatures.

neuroscience↗

bioRxiv2026

A human monoclonal antibody from hybrid immunity exhibits exceptional neutralization breadth against antigenically divergent contemporary Omicron JN.1 lineage variants

Hybrid immunity offers stronger and more durable antibody-mediated protection against symptomatic SARS-CoV-2 infection. In the present study, we report the development of a durable antibody response in an individual with hybrid immunity who also received three doses of the prototype COVID-19 vaccine. Polyclonal plasma antibody obtained from this donor also showed extraordinary neutralization breadth against contemporary Omicron variants. One of the functional monoclonal antibodies (ATHS-C30) isolated from this individual, representing the IGHV4-30 lineage-specific B cell with strong binding affinity to JN.1 spike protein, showed extraordinary neutralization breadth, including variants of Omicron lineages that emerged beyond JN.1, such as KP.2, KP.3.1.1, KP.3.2, KP.3.3, LB.1 and XEC. ATHS-C30 was found to bind RBD with high affinity and showed distinct epitope specificity to the other neutralizing mAbs isolated from the same donor through the epitope binning assay. Molecular modelling of the CDHR3 sequence using existing structures indicated that ATHSC-30 belongs to the class 4 antibody, a feature that contributes to breadth, while epitope conservation analysis indicated that the majority of RBD-interacting residues of ATHSC-30 are evolutionarily conserved. Taken together, our study indicate that ATHS-C30 forms the basis of development of a robust and broadly neutralizing antibody response in this individual with hybrid immunity, which overcomes the antigenic variation by targeting highly conserved and cryptic epitopes in destabilizing the spike structure. ImportanceSARS-CoV-2 continues to pose a significant public health threat, particularly to immunocompromised individuals and older adults with underlying comorbidities. Hybrid immunity to SARS-CoV-2 in vaccinated individuals leads to the development of B cells that are qualitatively superior to those that are expected to develop in only vaccinated individuals. In the present study, we found that among individuals with hybrid immunity who developed robust, durable antigen-specific antibody responses, one developed antibody response capable of broadly cross-neutralising contemporary Omicron variants. This was correlated with development of antigen-specific B cell lineage, such as IGHV4-30, that produced antibodies with potent and extraordinary neutralisation breadth against contemporary Omicron lineages, such as KP.2, KP.3.1.1, KP.3.2, KP.3.3, LB.1 and XEC. This is believed to be due to heterologous antigen exposures driving the development of an antigen-specific B cell repertoire that, in turn, facilitates immune imprinting capable of overcoming the ineffectiveness of antibodies to effectively neutralize newly emerging Omicron variants.

immunology↗

bioRxiv2026

HSV-1 hijacks the DNA repair protein RAD51 at gene promoters to drive viral transcription

Productive infection by Herpes Simplex Virus type 1 (HSV-1) requires initiation of efficient viral gene expression. Upon nuclear entry, HSV-1 genomes are associated with several cellular factors, including DNA repair proteins. It is unclear how these cellular factors impact viral processes at early stages of infection. In this study, we investigate the role of RAD51, a core homologous recombination (HR) factor. We measured nascent viral transcription and show that RAD51 plays a pro-viral role in infection by promoting immediate-early viral gene expression. We demonstrate that RAD51 binds GC-rich gene promoter of ICP4 and directly promotes gene expression. We also reveal a previously unknown interaction between RAD51 and ADNP, a subunit of the ChAHP complex, known for its role in transcription regulation. We propose a model where RAD51 binds incoming genomes at promoter regions regulating the genome landscape and allowing for efficient transcription initiation.

cell biology↗

bioRxiv2026

Therapeutic targeting of MYC- and MYCN-driven medulloblastoma with a novel MYC degrader molecule

BackgroundMedulloblastoma (MB) is the most common malignant brain tumour in children, and aggressive subgroups are frequently driven by the oncoproteins MYC or MYCN. Direct therapeutic targeting of MYC/MYCN has been challenging because of their intrinsically disordered protein structures. The aim of this study was to determine whether novel SE486-11 analogues (UNSW-SCs) can therapeutically target MYC/MYCN-driven MB. MethodsThe anticancer activity of UNSW-SCs was assessed in MB cell lines with differential MYC/MYCN expression. Target engagement was evaluated using surface plasmon resonance and drug affinity responsive target stability assays. Blood-brain barrier penetration, MYC/MYCN protein degradation, cell cycle effects, apoptosis, DNA damage, and synergy with histone deacetylase (HDAC) inhibitors were examined. Therapeutic efficacy was evaluated in murine models of MYC- and MYCN-driven human MB. ResultsUNSW-SCs showed potent anticancer activity, with preferential selectivity toward MB cells expressing high MYC/MYCN levels and IC50 values ranging from 0.22 to 1.18 M. The lead molecule, UNSW-SC-22, directly bound MYC, crossed the blood-brain barrier, and achieved a brain-to-plasma ratio of 1.44 at peak concentrations. UNSW-SC-22 induced MYC/MYCN-dependent cytotoxicity associated with enhanced proteasomal degradation, cell cycle arrest, apoptosis, and DNA damage. Combined treatment with HDAC inhibitors further reduced MYC/MYCN protein levels, increased DNA damage, and enhanced apoptosis. In vivo, UNSW-SC-22, either alone or with entinostat, significantly suppressed intracranial tumour growth and prolonged survival. ConclusionsUNSW-SC-22 is a brain-penetrant MYC/MYCN-targeting molecule with potent preclinical activity in MYC/MYCN-driven MB, supporting its development as a monotherapy or combination strategy with HDAC inhibition. Key PointsO_LIUNSW-SC-22 directly targets MYC/MYCN in medulloblastoma. C_LIO_LIUNSW-SC-22 crosses the blood-brain barrier and prolongs survival. C_LIO_LIHDAC inhibition enhances UNSW-SC-22 activity in MYC-driven cells. C_LI Importance of the StudyMYC- and MYCN-driven medulloblastomas remain among the most aggressive paediatric brain tumours, yet direct pharmacological targeting of MYC/MYCN has historically been difficult. This study identifies UNSW-SC-22 as a novel brain-penetrant small molecule that directly engages MYC/MYCN and promotes proteasomal degradation, leading to tumour cell death. Compared with prior MYC-directed approaches, UNSW-SC-22 combines direct target engagement, blood-brain barrier penetration, and in vivo efficacy in orthotopic MYC- and MYCN-driven medulloblastoma models. The study further demonstrates that combining UNSW-SC-22 with histone deacetylase inhibition enhances MYC/MYCN suppression, DNA damage, apoptosis, and survival benefit. These findings provide a translational framework for developing MYC/MYCN degradation as a therapeutic strategy for high-risk medulloblastoma and support future pharmacological optimisation, biomarker-guided patient selection, and combination therapy development.

cancer biology↗

bioRxiv2026

Multiple coexisting pathways to synchronization shape seizure dynamics in a mesoscale mouse brain model

The computational study of epileptic seizure dynamics has primarily focused on the identification of seizure onset zones and propagation pathways. Here, we present a network dynamical model implemented on the empirically measured mesoscale mouse brain network that reveals previously unresolved organizational principles underlying seizure propagation. Rather than the conventional assumption of a single dominant pathway to synchronization, the model reveals multiple competing pathways to synchronization with distinct dynamical properties including transition propensity, recruitment speed, spatial coverage, synchronization stability and transition kinetics. Consequently, node ablation does not uniformly suppress synchronization across pathways, but instead selectively alters pathway occupancy, producing non-trivial alterations to seizure dynamics with potential implications for resection and network-targeted intervention strategies. Biologically, the olfactory and limbic sub-networks emerge as key mesoscale regulators of synchronization dynamics, with olfactory recruitment preferentially constraining global synchronization while limbic-driven pathways preferentially support seizure generalization. More broadly, these findings extend transient explosive synchronization theory by demonstrating that synchronization in biologically constrained networks may emerge through competing mesoscale recruitment programs rather than a single transition process. Together, these findings introduce a new conceptual framework for seizure propagation, suggesting that pathological synchronization emerges not through a single dominant route, but through competing mesoscale dynamical pathways whose accessibility depends on both network architecture and ongoing network state. Significance statementEpileptic seizure propagation is conventionally understood as progressing through a dominant pathway that recruits increasingly larger portions of the brain into pathological synchronization. Using a network dynamical model implemented on the empirical mesoscale mouse connectome, we show that seizure-like synchronization instead emerges through multiple competing pathways with distinct spatial and temporal characteristics. These pathways differ in their propensity for generalization, synchronization stability and sensitivity to node perturbation, such that network interventions selectively reshape pathway accessibility rather than uniformly suppressing seizure dynamics. Our findings introduce a new framework for understanding seizure propagation, identify mesoscale mechanisms linking network architecture to synchronization dynamics and suggest that competing synchronization pathways may represent an important organizing principle in complex brain networks. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=97 SRC="FIGDIR/small/730931v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@7c4076org.highwire.dtl.DTLVardef@16c0961org.highwire.dtl.DTLVardef@1dbd8a0org.highwire.dtl.DTLVardef@6b06de_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2026

Age Dependent Immunopathology Drives Pneumonia-Associated Cardiac Dysfunction During Streptococcus pneumoniae Infection

Aging is a major risk factor for severe Streptococcus pneumoniae (Spn) infection and pneumonia-associated - major adverse cardiac events (PA-MACE), yet underlying mechanisms remain unclear. Using young and aged murine models, we show that aging exacerbates bacterial burden, mortality, and cardiac dysfunction following Spn infection, associated with impaired macrophage bacterial killing. Single-cell RNA sequencing infected hearts revealed extensive age-dependent remodeling across immune and stromal compartments. Aged mice exhibited heightened pro-inflammatory myeloid responses, with increased neutrophil infiltration characterized by elevated S100A8/9 and LCN2 and reduced antimicrobial programs. Macrophages displayed defective efferocytosis, including disruption of the GAS6-AXL axis. Aging also drove expansion of an infection-responsive fibroblast population with inflammatory signatures and reduced extracellular matrix gene expression. These changes were linked to oxidative stress and impaired glucose oxidation. Notably, anti-inflammatory treatment rescued cardiac dysfunction, implicating excessive inflammation as a central driver of PA-MACE. Together, these findings define mechanisms linking aging to pneumococcal cardiac complications and identify potential therapeutic targets.

immunology↗

bioRxiv2026

Engaging working memory following skill reactivation has implications for interlimb skill generalization

Interlimb skill generalization, defined as the transfer of a newly learned skill from the trained to the untrained limb, represents a fundamental aspect of human motor behavior with significant implications for rehabilitation and athletic training. Skill generalization is influenced by processes that drive learning and interact with the newly acquired memory. For instance, in our recent work, we reported that performing a secondary, cognitively demanding task immediately after a short skill-training session impaired skill generalization when the untrained arm was tested 24-hour later. This suggests that working memory (WM) interacts with the early stage of skill memory consolidation processes and thereby impacts skill generalization. Motivated by this finding, in the current study, we investigate how WM interacts with reactivated skill memory and its subsequent impact on skill generalization, tested 24 or 48-hour post skill training. We recruited right-handed young participants (n=95) who performed a fast, accurate reaching task with their dominant right arm during a short training session (50 trials) on Day-1. After 24-hour on Day-2, depending on the group type, participants had a brief skill reactivation session (10 trials or no reactivation) and then performed the WM task (or a control task) with their right arm. Interlimb generalization to the untrained left arm was assessed either immediately after the WM/control task on Day-2 or after a 24-hour gap on Day-3. We found that, engaging in the WM task (compared to the control task) after skill reactivation on Day-2 enhanced immediate generalization. Conversely, when generalization was tested 24-hour later on Day-3, the same WM engagement impaired skill generalization. These findings demonstrate that WM engagement during the post-reactivation phase has a time-dependent influence on interlimb generalization. WM can facilitate immediate generalization, possibly by sustaining neural processes that promote skill memory generalization across effectors. However, when a 24-hours time gap is introduced, generalization is disrupted following WM engagement, possibly because of interference between underlying neural processes involved in WM and reactivation-induced (re)consolidation of the skill memory. This study highlights the delicate interplay among WM, motor memory reactivation dynamics, and skill generalization and suggests a time-dependent interplay of neural processes critical for optimizing outcomes in motor learning and clinical rehabilitation protocols. NEW & NOTEWORTHYThis study reveals that working memory engagement following skill memory reactivation exerts a time-dependent dual effect on interlimb generalization. When tested immediately, WM engagement enhances generalization by prolonging the labile state of reactivated memory, which is needed to transfer abstract/effector-independent features to the untrained arm. When tested 24-hour after a delay, the same intervention impairs generalization by possibly engaging reconsolidation processes that interfere with effector-independent features. These findings establish a unified framework in which the temporal dynamics of the reconsolidation window determine whether a cognitive intervention strengthens or weakens a motor memory, with implications for understanding memory plasticity and for designing effective rehabilitation protocols.

neuroscience↗

bioRxiv2026

HAIRpred2: Human Host-Specific Prediction of Antibody-Interacting Residues Using Hybrid Physicochemical and Structural Features

1.Prediction of conformational B-cell epitopes is critical for vaccine design, immunotherapy, and antibody engineering. To date, several host-independent computational methods have been developed for predicting antibody-interacting residues in antigen structures. However, it is well established that antigen-antibody (Ag-Ab) interactions vary depending on the host immune system indicating the importance of developing host-specific prediction models. In this study, we present, for the first time, a human host-specific method, HAIRpred2, that predicts antibody-interacting residues in an antigen from its tertiary structure. The dataset was derived from HAIRpred and comprises 277 human Ag-Ab complexes, with 221 structures used for training and 56 for independent testing. Preliminary analysis revealed that residues with a relative surface accessibility (RSA) below 0.05, corresponding to buried regions, are highly likely to be non-interacting, underscoring the importance of structural accessibility in antibody recognition. To identify the most informative features, we evaluated multiple feature representations, including RSA, large language model (LLM)-based embeddings, distance-based features, and physicochemical properties. A model trained on single-residue RSA features achieved an AUC of 0.72. Incorporating a sliding window of 15 residues to capture local structural context improved performance to an AUC of 0.75. The best performance (AUC = 0.78 on the independent test set) was achieved by integrating RSA with physicochemical descriptors. Benchmarking against existing antibody-interaction prediction methods on the same independent dataset demonstrated that HAIRpred2 outperforms current tools, further highlighting the advantage of host-specific modeling. HAIRpred2 is freely available as a web server at https://webs.iiitd.edu.in/raghava/hairpred2/. HighlightsO_LIDevelopment of HAIRpred2, the first human host-specific method for predicting antibody-interacting residues. C_LIO_LIAnalysis of 277 human antigen-antibody complexes to capture host-dependent interaction patterns. C_LIO_LIRelative surface accessibility (RSA) identified as a key determinant, with buried residues rarely participating in interactions. C_LIO_LIIntegration of RSA with physicochemical features achieved the best performance (AUC = 0.78) on an independent dataset. C_LIO_LIHAIRpred2 outperforms existing methods and is available as a web server for epitope prediction. C_LI

bioinformatics↗

bioRxiv2026

Antiviral Potential of Lauric Acid against Dengue Virus 2: Evidence from a Luciferase-Based Replicon Assay

Dengue virus (DENV) infection generates a significant health burden throughout the world, and there are no clinically approved antiviral drugs, as of now. The virus also depends on lipid metabolism in the host to conduct effective replication and this makes lipid-directed compounds promising as therapeutic options. We assessed the antiviral effect of lauric acid, a 12-carbon medium-chain fatty acid, against DENV serotype 2 (DV2) in the presence of a stable cell line, DV2-replicon, expressing all the non-structural proteins (NS1-NS5) and a luciferase reporter. Active viral replication in replicon cells was established by morphological examination and immunofluorescence of cells. The MTT assay was used to determine the cytotoxicity of lauric acid revealing the LD50 of 2.52 uM, so higher concentrations were toxic as the effect of the drug is dose-related. The antiviral effect was tested through replicon inhibition (luciferase) assay which showed an incredible inhibition of viral RNA replication with a IC50 of 1.70 uM and this is equivalent to antiviral mycophenolphycic acid. The cytopathic effects, as well as a decrease in the activity of luciferase, proved the presence of viral translation and replication inhibition within the process of the treatment of the lauric acid. These results propose that lauric acid has cytotoxic and antiviral dual effect and can be a possible inhibitor of DENV replication. The toxicity needs to be reduced and future research is necessary to explain its molecular pathway and also to come up with the best delivery methods. IMPORTANCEDengue virus (DENV) remains a significant health challenge to the world since there are no effective antiviral agents. This work will recognize lauric acid as a possible dengue virus replication inhibitor in a model of a DV2 replicon, exhibiting antiviral action that is similar to that of mycophenolic acid. These results support lipid-directed compounds as potential dengue antiviral targets, but more research is needed to minimize toxicity and better understand the molecular mechanism of action.

molecular biology↗

bioRxiv2026

Causal Dissociation of Frontoparietal Control Mechanisms in Automatic Alcohol Approach Tendencies Using Continuous Theta Burst Stimulation

Compulsive alcohol intake is often sustained by approach tendencies that automatically orient individuals toward alcohol-related cues, even when they intend to avoid them. Converging evidence implicates the frontoparietal regions in regulating such automatic behavior; however, the specific contributions of the right dorsolateral prefrontal cortex (rDLPFC) and right posterior parietal cortex (rPPC), and the underlying neurocognitive mechanisms, remain unclear. To determine the specific contributions of these regions, we applied continuous theta burst stimulation (cTBS) to the rDLPFC or rPPC in separate groups of non-clinical alcohol users (rDLPFC: n = 29; rPPC: n = 28) using a within-subject, active-sham counterbalanced design. Alcohol approach tendencies were assessed using the Alcohol Approach-Avoidance Task at baseline and following active and sham stimulation. Active rDLPFC cTBS selectively slowed alcohol push responses without affecting pull responses, whereas rPPC cTBS produced a bidirectional, alcohol-specific shift in which push responses slowed and pull responses simultaneously accelerated. Although stimulation at either site shifted automatic tendencies toward greater alcohol approach, the behavioral profiles were dissociable. The findings suggest that rDLPFC contributes to sustaining the regulatory signal that drives avoidance over prepotent alcohol approach responses, whereas rPPC determines whether that signal is successfully expressed in behavior when competing cue-driven influences are present. These findings provide node-specific evidence for functional specialization within the frontoparietal network and identify a potential parietal mechanism linking cue salience to overt alcohol approach behavior.

neuroscience↗

bioRxiv2026

Consolidation Separates Implicit and Explicit Components of Compound Motor Memories

Motor adaptation involves the parallel operation of implicit recalibration and explicit re-aiming processes. During naturalistic learning, these systems interact, producing compound behavioral outputs that reflect their combined contributions. It remains unclear whether simultaneously engaged implicit and explicit processes form a single unified representation, or generate parallel memory representations that are merely co-expressed, and how consolidation transforms such representations. We addressed these questions across three visuomotor adaptation experiments (n = 120), in which the implicit process was engaged via gradual cursor rotation and the explicit process via target jump, by systematically manipulating the sequence of learning and the timing of expression. Immediately after learning, behavior reflected an inflexible, integrated memory that could not be decomposed by changing task demands. Following 24-hour consolidation, however, expression became component-selective, with implicit or explicit contributions retrieved in response to task demand. This reorganization had direct consequences on relearning, producing facilitation when the expressed and relearned components matched and interference when they mismatched. Moreover, when implicit adaptation was stabilized prior to compound learning, consolidation preserved the updated state rather than the original implicit representation. Together, these findings demonstrate that consolidation does not merely stabilize compound motor memories. Instead, it actively reorganizes them, transforming the initially integrated representations into independent, context-dependent components.

neuroscience↗

bioRxiv2026

Modulation of Automatic Alcohol Approach Tendencies using Single-Session 10 Hz rTMS over the Right dLPFC

BackgroundMaladaptive drinking is often sustained by automatic approach tendencies toward alcohol cues that override conscious self-control. While cognitive and behavioral modification techniques show some promise, their effects remain limited, highlighting the need for alternative neuromodulatory strategies. The current study examined the feasibility of a single session of 10 Hz repetitive transcranial magnetic stimulation (rTMS) to the right dorsolateral prefrontal cortex (dLPFC) as a targeted approach to reduce automatic alcohol approach tendencies. MethodForty-five healthy alcohol-using participants completed an alcohol approach- avoidance task (A-AAT) with concurrent electroencephalographic recording before and after active or sham stimulation. Primary analyses focused on participants with baseline alcohol approach tendencies (n = 35). ResultsAt baseline, individuals with approach tendencies exhibited attenuated N2 and P3b amplitudes to alcohol relative to non-alcohol cues, indicating reduced cognitive control and attentional mechanisms irrespective of group. Following stimulation, active rTMS selectively facilitated alcohol avoidance responses and enhanced prefrontal N2 amplitudes, suggesting strengthened top-down control and protection against repetition-induced automaticity, which was evident in the sham group. ConclusionThese findings suggest that high-frequency rTMS over the right dLPFC can modulate automatic alcohol-related action tendencies by strengthening neural control mechanisms, supporting its further evaluation as a neuromodulatory adjunct for maladaptive drinking. Baseline motivational profiles may additionally influence rTMS response and warrant consideration when tailoring such approaches.

neuroscience↗

bioRxiv2026

Integration of QTL Mapping, Transcriptomics, and Genome Resequencing Identifies Yield-Associated Genes for Salt Stress in Rice

Salinity and sodicity stresses adversely affect rice growth and yield. To overcome yield losses, suitable tolerant rice cultivars can be developed through a marker-assisted breeding (MAB) program. In the present study, genomic regions associated with sodicity stress tolerance at the reproductive stage were identified using a high-density 50kSNP array in a recombinant inbred line (RIL) population derived from the contrasting rice genotypes CSR11 and MI48. A total of 50 QTLs were detected for various yield-related traits; further, 19 QTLs with [≥]15% of phenotypic variance were selected for integrated (omics) analysis. RNA sequencing of leaves and panicles at the reproductive stage under sodic stress conditions was employed to find differentially expressed genes. A total of 1368 and 1410 SNPs; 104 and 144 indels were found for MI48 and CSR11, respectively, within the QTL regions from resequencing. At chromosomes 1 and 6, colocalized QTLs (qPH1-1/qGP1-1 and qGP6-2/qSSI6-2) were discovered. Differentially expressed genes (DEGs) were mapped over the QTL regions selected, and SNP variations and indels were screened for colocalized QTLs. Potential candidate genes, namely Os-pGlcT1 (Os01g0133400), OsHKT2;1 (Os06g0701600) and OsHKT2;4 (Os06g0701700), OsANTH12 (Os06g0699800), and OsPTR2 (Os06g0706400), were identified as being responsible for glucose transport, ion homeostasis, pollen germination, and nitrogen use efficiency, respectively, under salt stress. Finally, our study provides important insights into the genes and potential mechanisms affecting grain yield under sodic stress in rice, which will contribute to the development of molecular markers for rice breeding programs.

plant biology↗

bioRxiv2026

Integrative Omics and Network Biology Reveal Transcriptional Changes of Amino Acid Transport in Arabidopsis Susceptibility to Pseudomonas syringae

Plant amino acids function as both pathogen nutrients and essential drivers of systemic immunity. The regulation of amino acid homeostasis through transporters is a essential for mounting a robust and coordinated immune response in plants during pathogen infection. Using systems biology and integrative network science, we investigated bacterial virulence in Arabidopsis. By comparing gene coexpression networks of effector-triggered susceptibility (ETS) and pattern-triggered immunity (PTI), we uncovered a plant amino acid-related processes specifically linked to ETS. Integrating time-series transcriptomics, protein-DNA interactions, and mathematical simulations, we identified ANAC046 as a transcriptional regulator of amino acid processes during ETS. Single-cell RNA-Seq revealed that amino acid transporters are primarily expressed in companion and mesophyll cells, while functional validation confirmed ANAC046s roles in promoting susceptibility. Further integration of transcriptome and interactome data showed that amino acid-related genes interact with key immune hub proteins. Network topology analysis enabled the characterization of seven additional genes involved in plant defense. To support community-wide research, we developed MIData, an open-access platform for pre-analyzed Arabidopsis networks. Together, our findings demonstrate the power of systems-level approaches in uncovering hierarchical regulatory mechanisms underlying plant susceptibility to bacterial pathogens.

plant biology↗