Biology subjects

Tripathi, V.

Publications and source records attributed to Tripathi, V..

At least 19 recordsLinked to original sources

bioRxiv2026

The scaffold nucleoporin Nup188 undergoes liquid-liquid phase separation

Components of nuclear pore complexes are broadly classified into two categories: intrinsically disordered FG-repeat nucleoporins such as Nup98, which can undergo liquid-liquid phase separation, and scaffold nucleoporins, which form the NPC's structural framework. The basis for crosstalk of these nucleoporins within NPC and beyond is poorly understood. Here we show that human Nup188, a helical inner-ring scaffold protein, forms condensates both in purified form as well as at endogenous level. This condensate exhibits fusion, dissolved in 1,6-hexanediol and recovered after photobleaching, with dynamics and material properties comparable to those of hNup98 condensates. Moreover, these condensates are not colocalized to annulate lamellae. Our analysis also revealed that hNup188CTD is sufficient to form condensates and MD simulations revealed the key roles of IDR1-3 for condensation. Notably, hNup93 expression along with hNup188 suppressed the condensate formation. Together, these findings indicate that a structured scaffold nucleoporin can adopt a condensate-forming state via its CTD and Nup93 binding can suppress this phenomenon.

biochemistry↗

bioRxiv2026

The Choreography of Coupled Brains: Coordinated Movement and Multi-Scale Neural Synchrony in Musical Theater for Individuals with Developmental Disabilities

Performing together, which demands moving, singing, and coordinating in real time, is among the most social things people do, yet whether such coordination synchronizes not only behavior but brain activity, within and between performers, has rarely been examined during genuine performance. In this pilot study, we used mobile electroencephalography, including dual-brain hyperscanning of co-performing partners, to resolve neural change over a 16-week musical-theater program in adolescents and adults with developmental disabilities, the majority autistic. We examined four levels: behavior, spectral power, within-brain (source-space) connectivity, and between-brain synchrony, framing all estimates as effect sizes. Anxiety decreased from pre- to post-intervention, consistently across participant and parent reports. During performance, high-beta and gamma power and within-brain amplitude connectivity rose broadly across the cortex, with maximal effects seen in parieto-occipital regions. Between-brain coupling was similarly carried by amplitude co-fluctuation rather than phase; however, it was graded by the degree of interpersonal movement coordination (strongest when partners mirrored one another) and scaled with movement vigor. Local and within-brain changes were thus broad and state-like, whereas coupling between brains was specific to interpersonal coordination. Coordinated movement may organize neural synchrony across scales, positioning musical theater as a tractable model for studying the social brain in motion.

neuroscience↗

bioRxiv2026

Gradients of function between sensory drive and working memory in human frontal cortex

The coordination of sensory processing and working memory (WM) is fundamental to cognition. Spatial organization of sensory processing and WM is known to be broadly distributed across the cortex, but finer-scale organization at the interfaces between these functions remains understudied. Although the notion of sharp parcellations of cortex into distinct functional modules dominates the field, a growing body of works support graded changes in function and anatomy in some cortical zones. Based on this and potential advantages of gradient organizational structure in frontal cortex, we hypothesized that sensory-WM interfaces in the frontal cortex are gradient-like, not boundary-like. We examined twenty bilateral cortical regions that participate in visual/auditory WM tasks. In five frontal cortical regions, group-level WM activation overlapped with sensory drive, but was spatially shifted. We compared subject-level (N=20) boundary and gradient models of change in function. Strong individual-level evidence for sensory-WM gradients was observed in pre-supplementary motor area, ventral premotor cortex, and anterior insula in both modalities and in dorsal premotor cortex for visual WM. Conversely, dorsolateral pre-frontal cortex yielded mixed results, favored distinct WM and sensory regions in the left hemisphere, and gave some evidence for gradients in the right hemisphere. These results provide evidence that sensory and WM regions in frontal cortex are largely not distinct with sharp boundaries at their interfaces but instead bleed into each other to form local rostral-caudal sensory-WM gradients. We speculate these gradients may allow efficient interfacing between sensory and WM representations, and/or fine-grained, task-dependent shifting between bottom-up sensory and top-down influences.

neuroscience↗

bioRxiv2026

Persistent Staphylococcus aureus in human musculoskeletal tissues despite targeted antibiotic therapy

Staphylococcus aureus is a leading cause of musculoskeletal infection with frequent recurrence despite surgery and antibiotic therapy. Its persistence in human tissues under antibiotic pressure remains unclear. We performed longitudinal in situ analyses of matched tissue samples before and during therapy from patients undergoing repeated surgery using advanced imaging and tissue-based metagenomics. S. aureus remained detectable in all samples--including culture-negative specimens--and whole-genome sequencing confirmed persistence of the infecting strain. Antibiotic initiation reduced bacterial burden by 1.0Slog10 bacteria/mm3 but residual loads stabilized thereafter. Quantitative imaging identified a culture detection threshold ([~]103bacteria/mm3), indicating that culture negativity reflects diagnostic sensitivity limits rather than true bacterial clearance. Persistence under antibiotic therapy was associated with high baseline burden and intracellular sequestration, whereas long-term persistence was characterized by predominantly extracellular bacteria capable of driving relapse. These findings reveal sustained tissue persistence despite apparent microbiological clearance and guide precision strategies to target resilient bacterial reservoirs.

microbiology↗

bioRxiv2026

Mutational and functional heterogeneity of homology-directed repair deficiency and clinical implications

Homology-directed repair deficiency (HRd) encompasses mutations in multiple genes yet is treated clinically as a single entity. Here, through parallel analyses of isogenic knockouts of multiple HR pathway genes, integrating multi-omic analyses with genome-wide CRISPR-Cas9-dependency and resistance screens, we show that HRd is not a single entity but exists along a molecular and functional continuum. BRCA1, BRCA2, PALB2, RAD51C, and RAD51D mutants shared many HRd-associated mutational signatures, while RAD51B, BRIP1, CDK12 exhibited distinct genomic patterns. Functional heterogeneity was equally apparent: synthetic lethal interactions including CIP2A and a novel dependency on PRDX1 were penetrant across most HRd genotypes, whereas FANCM dependency was linked to HRd subtypes characterized by tandem duplications. PARPi resistance screens in distinct HRd contexts uncovered BRIP1 and RECQL5 as new BRCA2-specific resistance genes. HRd is thus a complex continuum, underscoring why modernizing the molecular taxonomy utilizing all genomic features available per patient is crucial to informing precision interventions.

genomics↗

bioRxiv2026

Sephin1 rewires proteostasis through actin-dependent signaling

The maintenance of protein homeostasis is vital for all cells. Alteration in protein handling underlies several diseases. The small molecule sephin1 is a promising clinical candidate against proteostasis disruption, but its mechanism of action is still uncertain. Our experimental evidence shows that sephin1 binds G-actin and drives actin cytoskeleton misfolding, and eventually, Golgi disintegration. At first, sephin1 impairs the autophagic flux and elicits the phosphorylation of the subunit of eIF2 and the ER-stress independent expression of CHOP via GCN2 kinase. Sephin1 also inhibits the mammalian target of rapamycin (mTORC1), activates the transcription Factor EB (TFEB), drives the expression of TFEB-direct target genes, and eventually stimulates the autophagy lysosomal pathway. Our results reveal that the actin cytoskeleton may regulate autophagy via mTORC1-TFEB complemented with the GCN2-eIF2-CHOP signaling pathway.

cell biology↗

bioRxiv2026

FOXO3 regulated MIR503HG safeguards cellular quiescence by modulating PI3K/Akt pathway via miR-508/PTEN axis

Long noncoding RNAs (LncRNAs) have emerged as a class of important regulatory ncRNAs and are known to fine-tune numerous cellular processes including proliferation, differentiation and development; however, their role in quiescence still remains largely unexplored. A miRNA host gene lncRNA, MIR503HG, has been reported to play important role in cancer development. Here, we demonstrate the role of MIR503HG lncRNA in regulating cellular quiescence. MIR503HG displays elevated levels in human diploid fibroblasts induced to undergo quiescence. Depletion of MIR503HG in HDFs affects the entry of cells into quiescence but has no effect on cell cycle progression, suggesting its role in quiescence attainment and/or maintenance. Additionally, MIR503HG depletion led to a drastic decrease in the levels of miR508 target, PTEN with a concomitant increase in pAkt levels, indicating its role in negative regulation of miR508. Further, we demonstrate that the lncRNA MIR503HG regulates PTEN levels by acting as a ceRNA for miR508 to maintain cellular quiescence. Our studies illustrate that MIR503HG can function synergistically with miR503 to maintain cells under quiescence and both the miRNA-HG and the miRNA encoded by its gene locus synergistically control the same biological process in different ways by regulating different downstream genes.

cell biology↗

bioRxiv2026

lncRNA NORM is essential for proper chromosome segregation through the Plk1-Bub1 and Nsun2 axis.

The cell cycle comprises different phases and is a tightly regulated process at the molecular level. During the cell cycle, two key events occurred: DNA duplication during the S phase and chromosome segregation during mitosis. Accurate cell cycle progression, achieved through faithful chromosome segregation, is essential for maintaining cell fidelity. Long noncoding RNAs are a subclass of noncoding RNA that are longer than 200 bp and form RNA protein complexes (RNPs) to regulate various biological processes. Herein, we demonstrate that lncRNA NORM is involved in regulating the cell cycle by maintaining proper chromosome segregation. NORM exhibited G2 phase-specific expression, and the depletion of NORM resulted in a significant G2/M arrest. NORM-depleted cells failed to progress in mitosis and showed defects in chromosome segregation. We further demonstrated that NORM binds to proteins such as Plk1 and Nsun2. Depletion of NORM hindered the interaction between Plk1 and Bub1, resulting in reduced kinetochore localization of Plk1 during prometaphase. Our results also show that the depletion of NORM affects the binding of Nsun2 protein to CDK1 mRNA and, consequently, the stabilization of CDK1 at the protein level. Altogether, our results demonstrate that NORM regulates chromosome segregation by mediating the interaction between Plk1 and Bub1.

cell biology↗

bioRxiv2025

Microgeography of staphyloccoci in human tissue explains antibiotic failure

Summary paragraphBacterial infections remain a major health threat, yet pathogen biology in human tissues is poorly understood. Using AI-guided imaging, we mapped [~]15,500 Staphylococcus aureus cells in biopsies from 33 patients undergoing surgery for musculoskeletal infections. Despite substantial interindividual variability, consistent patterns emerged. Most bacteria resided within non-classical monocytes/macrophages, challenging models of primarily extracellular pathogenesis. Both intra- and extracellular bacteria were predominantly isolated single cells or doublets with low rRNA content, suggesting limited replication. Complementary proteomics implicated inflammation-associated hypoxia and host glucose-to-lactate metabolism as growth constraints. Preoperative antibiotic therapy failed to clear bacteria across microenvironments and cluster sizes, challenging assumptions that antibiotic tolerance is confined to intracellular niches or biofilms and underscoring the clinical need for debridement. In vitro models replicating diverse tissues conditions impaired antibiotic activity, indicating multifactorial resilience. Together, these findings redefine S. aureus infection biology in musculoskeletal infections and establish a framework for mechanism-based prevention and therapy.

microbiology↗

bioRxiv2025

Dynamic task-based reorganization of sensory-biased and supramodal working memory networks in the human cerebral cortex

Human working memory is supported by a broadly distributed set of brain networks. Content-specific networks communicate with a domain-general, supramodal network that is recruited regardless of the type of content. Here, we contrasted visual and auditory working memory tasks to examine interactions between the supramodal network and two content-specific networks. Functional connectivity among visual-biased, auditory-biased, and supramodal working memory networks was assayed by collecting task and resting-state fMRI data from 24 human participants (age 18-43; 11 men and 13 women). At rest, as found previously, the supramodal network exhibited stronger functional connectivity with the visual-biased network than with the auditory-biased network. This asymmetry raises questions about how networks communicate to support robust performance across modalities. However, during auditory task performance, dynamic changes increased auditory network connectivity with supramodal and visual-biased frontal regions, while decreasing connectivity from posterior visual areas to supramodal and frontal visual regions. In contrast, the visual task produced weak changes. Across individuals, auditory working memory precision correlated with the strength of auditory network connectivity changes, while no such brain-behavior link was observed for visual working memory. These results demonstrate an asymmetry in working memory network organization and reveal that dynamic reorganization accompanies performance of working memory tasks.

neuroscience↗

bioRxiv2025

Temporal Synchronization Analysis: A Model-Free Method for Detecting Robust and Nonlinear Brain Activation in fMRI Data

The sluggishness of the fMRI blood oxygenation level dependent (BOLD) signal has motivated the use of block or trial-based experimental designs that rely on the assumption of linearity, typically modeled using the General Linear Model (GLM). But many non-sensory brain regions and subcortical areas do not correspond to such linearities. We introduce a model-free estimation method called Temporal Synchronization Analysis (TSA) which detects significant brain activations across trials and subjects at an individual time point. We validate it across multiple cognitive tasks (combined n=1600). In constrained task stimuli like visual checkerboard paradigms, we discovered novel nonlinearities not reported previously. In model-free task paradigms like listening to naturalistic auditory stimuli, TSA can detect unique stimuli linked quasi-temporal activations across default mode and language networks. Our user-friendly Python toolkit enables cognitive neuroscience researchers to identify stable and robust brain activation across various cognitive paradigms that are challenging to model with current methods.

neuroscience↗

bioRxiv2024

Inclusivity in fNIRS Studies: Quantifying the Impact of Hair and Skin Characteristics on Signal Quality with Practical Recommendations for Improvement

Functional Near-Infrared Spectroscopy (fNIRS) holds transformative potential for research and clinical applications in neuroscience due to its non-invasive nature and adaptability to real-world settings. However, despite its promise, fNIRS signal quality is sensitive to individual differences in biophysical factors such as hair and skin characteristics, which can significantly impact the absorption and scattering of near-infrared light. If not properly addressed, these factors risk biasing fNIRS research by disproportionately affecting signal quality across diverse populations. Our results quantify the impact of various hair properties, skin pigmentation as well as head size, sex and age on signal quality, providing quantitative guidance for future hardware advances and methodological standards to help overcome these critical barriers to inclusivity in fNIRS studies. We provide actionable guidelines for fNIRS researchers, including a suggested metadata table and recommendations for cap and optode configurations, hair management techniques, and strategies to optimize data collection across varied participants. This research paves the way for the development of more inclusive fNIRS technologies, fostering broader applicability and improved interpretability of neuroimaging data in diverse populations.

neuroscience↗

bioRxiv2023

Brain Connectivity Changes in Meditators and Novices during Yoga Nidra: A Novel fMRI Study

Yoga Nidra practice aims to induce a deeply relaxed state akin to sleep while maintaining heightened awareness. Despite the growing interest in its clinical applications, a comprehensive understanding of the underlying neural correlates of the practice of Yoga Nidra (YN) remains largely unexplored. In this novel fMRI investigation, we aim to discover the differences between wakeful resting states and states attained during YN practice. The study included individuals experienced in meditation and/or yogic practices, referred to as meditators (n=30), and novice controls (n=31). The GLM analysis, based on audio instructions, demonstrated activation related to auditory cues without concurrent Default Mode Network (DMN) deactivation. Additionally, meditators exhibited heightened bilateral thalamic activation compared to novices. DMN seed based Functional connectivity (FC) analysis revealed significant reductions in connectivity among meditators during YN as compared to controls. We did not find differences between the two groups during the pre and post resting state scans. Moreover, when DMN-FC was compared between the YN state and resting state, meditators showed distinct decoupling, whereas controls showed increased DMN-FC. Finally, meditators exhibit a remarkable correlation between reduced DMN connectivity during Yoga Nidra and self-reported hours of cumulative meditation and yoga practice. Together, these results suggest a unique neural modulation of the DMN in meditators during Yoga Nidra which results in being restful yet aware, aligned with their subjective experience of the practice. The study deepens our understanding of the neural mechanisms of Yoga Nidra, revealing distinct DMN connectivity decoupling in meditators and its relationship with meditation and yoga experience. These findings have interdisciplinary implications for neuroscience, psychology, and yogic disciplines.

neuroscience↗

bioRxiv2023

A Far-Red Fluorescent Probe to Visualize Staphylococcus aureus in Patient Samples

Staphylococcus aureus (S. aureus) is the leading bacterial cause of death in high-income countries and can cause invasive infections at various body sites. These infections are associated with prolonged hospital stays, a large economic burden, considerable treatment failure, and mortality rates. So far, there is only limited knowledge about the specific locations where S. aureus resides in the human body during various infections. Hence, the visualization of S. aureus holds significant importance in microbiological research. Herein, we report the development and validation of a far-red-fluorescent probe to detect S. aureus in human biopsies from deep-seated infections. This probe displays strong fluorescence and low background in human tissues, outperforming current tools for S. aureus detection. Several applications are demonstrated, including fixed- and live-cell imaging, flow cytometry, and super-resolution bacterial imaging. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=124 SRC="FIGDIR/small/556223v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@1bcf4e4org.highwire.dtl.DTLVardef@71bf45org.highwire.dtl.DTLVardef@1c468fdorg.highwire.dtl.DTLVardef@1c8baf3_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2023

Predicting an Individual's Cerebellar Activity from Functional Connectivity Fingerprints

The cerebellum is gaining scientific attention as a key neural substrate of cognitive function; however, individual differences in the cerebellar organization have not yet been well studied. Individual differences in functional brain organization can be closely tied to individual differences in brain connectivity. Connectome Fingerprinting is a modeling approach that predicts an individuals brain activity from their connectome. Here, we extend Connectome Fingerprinting (CF) to the cerebellum. We examined functional MRI data from 160 subjects (98 females) of the Human Connectome Project young adult dataset. For each of seven cognitive task paradigms, we constructed CF models from task activation maps and resting-state cortico-cerebellar functional connectomes, using a set of training subjects. For each model, we then predicted task activation in novel individual subjects, using their resting-state functional connectomes. In each cognitive paradigm, the CF models predicted individual subject cerebellar activity patterns with significantly greater precision than did predictions from the group average task activation. Examination of the CF models revealed that the cortico-cerebellar connections that carried the most information were those made with the non-motor portions of the cerebral cortex. These results demonstrate that the fine-scale functional connectivity between the cerebral cortex and cerebellum carries important information about individual differences in cerebellar functional organization. Additionally, CF modeling may be useful in the examination of patients with cerebellar dysfunction, since model predictions require only resting-state fMRI data which is more easily obtained than task fMRI.

neuroscience↗

bioRxiv2023

Default Mode and Dorsal Attention Network functional connectivity associated with alpha and beta peak frequency in individuals.

Alpha- and Beta-frequency oscillatory waves are evident in resting-state electro- and magneto-encephalography (EEG, MEG). Higher peak frequencies for Alpha and Beta are associated with greater cognitive health. Aging slows down the alpha and beta waves which are also affected by mental states, disorders such as ADHD, and sleep deprivation. Functional magnetic resonance imaging (fMRI) of resting-state brain activity reveals anti-correlation of very low frequency (< 0.1 Hz) fluctuations between two distributed cerebral cortical networks, the Dorsal Attention Network (DAN) and the Default Mode Network (DMN). DAN activation is related to attentional demands in extrinsic tasks, whereas DMN is associated with mind wandering, episodic memory retrieval, and intrinsic processing. Prior research has found that higher DAN-DMN anticorrelation is related to greater cognitive and mental health. Here, we investigated whether these two measures of cognitive and mental health are related to each other within individuals. We investigated resting-state Functional Connectivity (rsFC) between the DMN and DAN using fMRI and alpha and beta peaks from MEG using two large datasets (n=89 and n=189). We found that more robust anti-correlations between DMN and DAN regions are related to higher peak frequencies of alpha and beta rhythms in the brain. Subjects with higher alpha peak frequencies also show stronger positive within-network connectivity in both the DMN and DAN networks. Females show stronger correspondence between the two measures as compared to males. This association between two non-invasive cognitive neuroscience modalities adds to the growing literature on the biomarkers of cognitive and mental health. Key pointsO_LIMEG/EEG biomarker of brain health is correlated with rs-fMRI biomarker of brain health C_LIO_LIAlpha and beta peak frequency correlated with DMN-DAN functional connectivity C_LIO_LIStronger within-network connectivity for subjects with a high alpha peak frequency C_LIO_LIFemales have a stronger association between peak frequency and DMN-DAN connectivity C_LI

neuroscience↗

bioRxiv2022

Electroencephalographic dynamics of rhythmicbreath-based meditation

Meditation has been practised for millennia but the neuroscientific understanding of the dynamics is still lacking. Sudarshan Kriya Yoga (SKY) is an evidence based breathing based meditation technique that utilizes rhythmic breathing to induce a deep state of relaxation and calm. Multiple studies have found benefits of the SKY technique from genetic, physiological, psychological to behaviour levels. We collected Electroencephalographic (EEG) data in 43 subjects who underwent the SKY technique and analysed the brain rhythms at different stages of the technique namely preparatory breathing (Pranayama), rhythmic breathing (Kriya) and meditation (Yoga Nidra) using newly developed methods to analyse periodic and aperiodic components. Alpha waves amplitude in the parieto-occipital region decreased as the rhythmic breathing progressed and dropped sharply during the meditation period. Theta amplitudes and peak frequency increased in the centro-frontal region during the rhythmic breathing period but were marked by sustained low theta waves during the meditation period. The delta wave amplitude was not affected by breathing but both delta band power and peak frequency increased during the meditation period in the centro-frontal region. We also saw a decrease in the 1/f aperiodic signal across the brain during the meditation period suggesting a modification of excitation-inhibition balance. We see an overall slowing down of brain oscillations from alpha to theta to delta as the meditation progressed. The paper studies in depth the transitional dynamics of the SKY technique analysing the alpha, theta, delta waves and aperiodic signals and demonstrates that each phase in a breathing based meditation has a unique electrophysiological signature.

neuroscience↗

bioRxiv2022

Linking Dynamic DNA Secondary Structures to Genome Instability

Genomic double-stranded DNA (dsDNA) becomes single-stranded (ssDNA) during replication, transcription, and DNA repair. ssDNA is therefore believed to be transient, occurring in only a fraction of the genome at a given time, and variable amongst a population of cells. These transiently formed ssDNA segments can also adopt alternative, dynamic DNA conformations, such as cruciform DNA, triplexes, quadruplexes and others. To determine whether there are stable and conserved regions of ssDNA, we utilized our previously developed method S1-END-seq 1 to convert ssDNA to DNA double strand breaks (DSBs), which are then processed for high-throughput sequencing. This approach revealed two predominant dynamic DNA structures: cruciform DNA formed by expanded (TA)n repeats that accumulated uniquely in microsatellite unstable human cancer cell lines, and DNA triplexes (H-DNA) formed by homopurine/homopyrimidine (hPu/hPy) mirror repeats common across a variety of human cell lines. Triplex-forming repeats accumulated during replication, blocked DNA synthesis and were hotspots of somatic mutation. In contrast, pathologically expanded (hPu/hPy) repeats in Friedreichs ataxia patient cells formed a replication-independent and transcription-inducible DNA secondary structure. Our results identify dynamic DNA secondary structures in vivo that contribute to elevated genome instability.

molecular biology↗