Biology subjects

Ganesh, G.

Publications and source records attributed to Ganesh, G..

7 recordsLinked to original sources

bioRxiv2025

Criticality-driven enhancer-promoter dynamics in Drosophila chromosomes

Recent live imaging in Drosophila embryonic nuclei revealed anomalous dynamics of synthetic enhancer promoter locus pairs, challenging classical polymer models. To identify the physical mechanisms underlying this behavior, we performed coarse-grained polymer simulations exploring three chromatin organization modes: an ideal polymer, loop extrusion, and compartmental segregation. We found that genome compartments, when tuned near the coil globule phase transition, best captured both structural and dynamical observables. Importantly, we demonstrate that the agreement with experimental data is maximized in a narrow regime characterized by near critical polymer behavior. Incorporating loop extrusion does not markedly improve the overall fit, suggesting that the mechanism plays a limited role in shaping chromatin organization and dynamics in the Drosophila embryo. These results support a picture in which chromatin operates in a near-critical physical regime, enabling efficient exploration of nuclear space and frequent long-range interactions.

biophysics↗

bioRxiv2024

Chromatin folding motifs define the basic grammar of TAD architecture in single alleles

Chromatin folding exhibits extensive cell-to-cell variability, yet whether this variability is dominated by continuously varying conformations or by recurrent organizational patterns remains unclear. Here, we combined high-resolution chromatin tracing with a novel machine learning algorithm to show that chromatin organization can be compactly represented by a limited repertoire of recurrent folding motifs. Using polymer simulations and cohesin depletion experiments, we further show that these motifs arise primarily from loop extrusion. Analysis of distinct tissues reveals that a shared motif repertoire is sufficient to describe diverse structural ensembles, with biological differences arising primarily through changes in motif occupancy and combinatorial usage. More generally, rather than generating entirely new conformations, transcriptional and disease-associated changes, including those occurring during disease onset, act primarily by redistributing motif occupancy within this common repertoire. In particular, gene activation is associated with a shift toward decompacted states and reduced contact frequencies, revealing a quantitative link between transcription and chromatin organization at the single-allele level. Together, these findings reveal that single-allele chromatin variability is structured by a constrained repertoire of recurrent folding motifs whose usage is modulated by regulatory context, providing a new framework to interpret how chromatin organization relates to gene activity.

genomics↗

bioRxiv2023

Background environment modulates motor contagions in humans

Motor contagions refer to implicit effects in ones actions induced by the observation of actions made by others. A plethora of studies over the last two decades have exhibited that observed, as well as predicted, actions can induce various kinds of motor contagions in a human observer. However, motor contagion has always been investigated in regard to different features of an observed action and it remains unclear whether the environment, in which an observed action takes place, modulates motor contagions as well. Here we investigated the effect of the observed environment on motor contagions using an empirical hand steering task in which the participants were required to move a cursor through visual channels of different shapes. We observed the movement time of observers to be influenced by both the movement of the cursor they observed, as well as the background (channel shape) in which the cursor movement was observed. Observers consistently made faster movements after observing steering movements in a narrowing channel compared to a widening channel. These results show a distinct effect of the environment, in which an observed action occurs, on ones own movement.

neuroscience↗

bioRxiv2022

Trans-synaptic dwelling of SARS-CoV-2 particles perturbs neural synapse organization and function

SARS-CoV-2 infection is associated with short- and long-term neurological and psychiatric complications, referred to as neuroCOVID. These symptoms are relatively heterogenous and fluctuating, hampering the discovery of molecular mechanisms underlying viro-induced brain perturbations. Here, we show that the human cerebral cortex poorly supports SARS-CoV-2 dissemination using post-mortem COVID-19 patient samples, ex vivo organotypic cultures of human brain explants and stem cell-derived cortical organoids. Despite restricted infection, the sole exposure of neural cells to SARS-CoV-2 particles is sufficient to induce significant perturbations on neural synapse organization associated to electrical activity dysfunction. Single-organoid proteomics revealed that exposure to SARS-CoV-2 is associated to trans-synaptic proteins upregulation and unveiled that incoming virions dwell at LPHN3/FLRT3-containing synapses. Our study provides new mechanistic insights on the origin of SARS-CoV-2-induced neurological disorders. One-Sentence SummarySARS-CoV-2 modulates neural plasticity and electrical activity as viral particles lodge at the trans-synaptic interface.

microbiology↗

bioRxiv2021

Bodily ownership of an independent supernumerary limb: An exploratory study

Can our brain perceive a sense of ownership towards an independent supernumerary limb; one that can be moved independently of any other limb and provides its own independent movement feedback? Following the rubberhand illusion experiment, a plethora of studies has shown that the human representation of self is very plastic. But previous studies have almost exclusively investigated ownership towards substitute artificial limbs, which are controlled by the movements of a real limb and/or limbs from which non-visual sensory feedback is provided on an existing limb. Here, to investigate whether the human brain can own an independent artificial limb, we first developed a novel independent robotic sixth finger. We allowed participants to train using the finger and examined whether it induced changes in the body representation using behavioral as well as cognitive measures. Our results suggest that unlike a substituted artificial limb (like in the rubber hand experiment), it is more difficult for humans to perceive a sense of ownership towards an independent limb. However, ownership does seem possible, as we observed clear tendencies of changes in the body representation that correlated with the cognitive reports of the sense of ownership. Our results provide the first evidence to show that an independent supernumerary limb can be embodied by the human brain.

neuroscience↗

bioRxiv2020

Hierarchical motor adaptations negotiate failures during force field learning

Humans have the amazing ability to learn the dynamics of the body and environment to develop motor skills. Traditional motor studies using arm reaching paradigms have viewed this ability as the process of internal model adaptation. However, the behaviors have not been fully explored in the case when reaches fail to attain the intended target. Here we examined human reaching under two force fields types; one that induces failures (i.e., target errors), and the other that does not. Our results show the presence of a distinct failure-driven adaptation process that enables quick task success after failures, and before completion of internal model adaptation, but that can result in persistent changes to the undisturbed trajectory. These behaviors can be explained by considering a hierarchical interaction between internal model adaptation and the failure-driven adaptation of reach direction. Our findings suggest that movement failure is negotiated using hierarchical motor adaptations by humans.

neuroscience↗

bioRxiv2017

Prediction error induced motor contagions in human behaviors

Motor contagions refer to implicit effects on ones actions induced by observation of others actions. Motor contagions are believed to be induced simply by action observation and cause an observers action to become similar to the observed action. In contrast, here we report a new motor contagion that is induced only when the observation is accompanied by prediction errors-differences between actions one observes and those he/she predicts or expects. Moreover, this contagion may not manifest as a similarity between ones own and observed actions. In our experiment, observation of the same action induced distinct motor contagions, depending on whether prediction errors are present or not. In the absence of prediction errors, similarly to previous reports, participants actions changed to become similar to the observed action, while in the presence of prediction errors, their actions changed to diverge away from it. Our results suggest distinct effects of action observation and action prediction on human actions.

neuroscience↗