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Biology subjects

Bhattacharyya, K.

Publications and source records attributed to Bhattacharyya, K..

10 recordsLinked to original sources

Cnidarian oocytes reveal conserved actin-driven mechanisms of female meiosis

Oocyte meiosis is a specialized form of cell division adapted to produce a single haploid egg for fertilization. Diverse actin-driven mechanisms have essential roles in supporting these highly asymmetric divisions of the large oocyte. Whether these represent exotic adaptations in individual species or whether actin has broadly conserved functions in animal oocytes remains unclear. To address this, we established live-imaging assays, combined with targeted perturbations and biophysical modeling, in the non-bilaterian jellyfish Clytia hemisphaerica. We show that in Clytia, a nuclear F-actin network stabilizes the large oocyte nucleus. Upon meiotic entry, a transient F-actin shell forms to facilitate nuclear envelope rupture, followed by chromosome congression driven by the collapse of the nuclear F-actin network and capture by microtubules. Finally, the forming spindle is transported to the cell periphery by cytoplasmic flows produced by a wave of cortical contraction. Together, the presence of these actin-driven mechanisms in a basal metazoan evidence their ancient origin, establishing a metazoan complement of conserved molecular modules required for oocyte divisions.

cell biology↗

Interactions between single actin and vimentin filaments

The cytoskeleton determines cell shape, mechanical properties, and motility by interconnected networks of protein filaments - actin filaments, microtubules and intermediate filaments. Their collective function relies on crosstalk between these filament systems, yet the physical basis of interactions between the filaments remains insufficiently understood. Actin and vimentin filaments and networks frequently co-localize within cells and jointly regulate contractility, force transmission and mechanical resilience, indicating functional cooperation. However, it remains unclear whether these interactions arise from direct filament-filament interactions or are mediated exclusively by accessory crosslinking proteins. Studies of reconstituted composite networks probing direct interactions by rheology have yielded inconsistent results. Here, we show that single actin filaments and vimentin intermediate filaments do indeed interact directly, forming force-bearing contacts in the absence of crosslinking proteins, with interaction strengths comparable to other previously reported cytoskeletal filament pairs. Using quadruple optical tweezers combined with microfluidics and confocal microscopy, we systematically probe these interactions under controlled conditions across a range of ionic environments. We find that, in contrast to other filament pairs, variations in ionic strength do not appreciably affect the interaction breaking forces between actin and vimentin filaments. However, the interaction geometry determines the achievable interaction strengths, because the limited stretchability of the actin filaments sets an upper bound to the measurable force range. This limit also imposes a restriction on direct quantification of interaction parameters, which we circumvent by a Bayesian unmasking strategy that allows us to infer bond parameters despite the breaking of actin filaments. Furthermore, actin bundling enhances the stability against breaking, enabling the detection of higher interaction forces. These findings demonstrate that actin and vimentin form a mechanically interacting system through direct filament bonds, and our work establishes a minimal, protein-linker-independent physical basis for actin-vimentin crosstalk and quantifies the interaction forces between the two filament types.

biophysics↗

A common connectome-based neural reference space across affective, autonomic, and wakefulness arousal

Arousal is often invoked to explain state-dependent variability in attention, emotion, memory, and decision-making. However, the term is used inconsistently, referring variously to affective experience, autonomic activation, and states of wakefulness. The extent to which different operationalizations of arousal reflect a shared neurobiological basis remains unclear, limiting efforts to unify findings across studies. We applied dynamic connectome predictive models to five fMRI datasets spanning naturalistic movie watching, story listening, wakeful rest, and sleep. We derived measures of affective, autonomic, and wakefulness arousal from subjective ratings, pupil dilation, and EEG, respectively. Models trained to predict arousal in one dataset generalized across datasets, indicating that dynamic connectivity captures shared arousal-related dynamics across measures and task contexts. The models also predicted manually scored sleep stages, suggesting that they capture arousal dynamics that extend to the graded fluctuations in arousal during sleep. Decoded arousal dynamics during movie-viewing predicted how well participants later recalled movie events, reproducing classic arousal-dependent memory enhancement effects. Model predictions were supported by overlapping functional connections, including a subset shared across all models. The largest proportion of shared connections was between the salience and somatomotor networks, suggesting that increased coordination between salience detection and action readiness may be a common feature across multiple operationalizations of arousal. Together, these results are consistent with a connectome-based neural reference space for arousal, in which different varieties share a core set of predictive connections. Our findings offer a quantitative framework for integrating arousal-related findings across tasks and modalities.

neuroscience↗

Digital Twins for Fungal Computing: Viable XOR Regimes, Parameter Inference, and Waveform-Guided Rediscovery

Fungal substrates are promising candidates for unconventional computing, but specimen-to-specimen variability makes logic-gate fabrication difficult to reproduce. This paper presents a digital-twin workflow for fungal excitable networks and evaluates three components needed for computeraided design: identifying parameter regimes that support XOR computation, inferring latent biophysical parameters from electrical characterization data, and refining those inferred parameters by waveform matching. The model represents mycelium as a random geometric graph with FitzHugh-Nagumo node dynamics and memristive edge conductances. A systematic optimization study over 160 simulated specimens identifies a viable XOR subspace defined by tuned biophysical parameters, electrode geometry, and stimulus timing. A characterization study over 400 simulated specimens uses step-response, paired-pulse, and triangle-sweep protocols to extract 94 response features. Random forest regressors recover several latent parameters reliably (R2 = 0.912 for{tau} v, 0.816 for{tau} w, 0.717 for a), while vscale, Ron, and Roff remain weakly identifiable. On a preliminary rediscovery validation using 15 optimized specimens (20-50 nodes), ML initialization followed by local waveform-matching refinement reduces mean waveform mismatch from 1.070 to 0.042 (96.0%; one-sided Wilcoxon p = 3.1 x 10-5) and reduces mean core-parameter error from 16.6% to 8.8% (p = 6.1 x 10-5). A sensitivity analysis on 72 viable specimens reveals that{tau} w and are the most consequential parameters for XOR twin accuracy, while vscale and Roff are both hard to identify and tolerant to error. These results show that fungal digital twins can already narrow the search for viable computational substrates, partially recover the excitable dynamics that govern them, and support small-scale specimen-specific refinement without yet claiming full XOR transfer.

bioengineering↗

Viscoelasticity Analysis of Coarse-grained Cytoskeletal Simulations with Cytosim and Cytocalc

Computational modeling has emerged as a powerful approach to studying cytoskeletal dynamics. The simulation software Cytosim provides intuitive yet flexible simulations of filament polymerization, cross-linking, and motor activity. Here, we present Cytocalc, a lightweight Python toolkit designed to streamline and standardize the analysis of Cytosim simulation output, supporting studies of biological functionality and physical properties of cytoskeletal systems. After introducing Cytocalc and validating it, we use it to establish a new workflow for quantifying network viscoelasticity from Cytosim simulations. Specifically, we determine the complex shear modulus of cross-linked networks and quantify how the storage modulus increases with cross-linker density. The cross-linker dependence of the networks elasticity exhibits two regimes, a scaling regime consistent with elasticity arising from the suppression of thermal bending fluctuations of filaments as well as a much weaker dependence at high cross-linker concentration.

biophysics↗

Human PRE-PIK3C2B exhibits long-range intra- and inter-chromosomal interactions with genomic regions enriched in repressive marks.

Human PRE-PIK3C2B is a dual nature polycomb response element that interacts with both polycomb as well as trithorax members. In the current study, using 4C-Seq (Capturing Circular Chromosomal Conformation-Sequencing), we identified long-range chromatin interactions associated with PRE-PIK3C2B and validated them with 3C-PCR. We identified both intra-as well as inter-chromosomal interactions, a large proportion of which were found to be closely distributed around transcriptional start sites (TSS). A significant number of interactions were also found to be associated with heterochromatic regions. Meta-analysis of ENCODE ChIP-Seq data identified an overall enrichment of YY1, CTCF as well as histone modification such as H3K4me3 and H3K27me marks in different cell lines. Almost 90% interactions were derived from either intronic or intergenic regions. among which large proportions of intronic interactors were either unique sequences or LINE/SINE derived. In case of intergenic interactions, majority of the interaction were associated with LINE/SINE repeats. We further found that genes proximal to the interactor sequences were co-expressed, they showed reduced expression. To the best of our knowledge this is one of the early demonstrations of long-range interaction of PRE sequences in human genome.

genetics↗

Modulation of macrophage defense responses by Mycobacterial persistence protein MprA (Rv0981) in human THP-1 cells: effect of single amino acid variation on host-pathogen interactions

M. tuberculosis is one of the most successful human pathogens causing tuberculosis that leads to highest daily morbidity worldwide. The evasion of the host immune responses is an important strategy that M. tuberculosis adopts. MprA (Rv0981), the response regulator of two component system is known for DNA binding activity in the pathogen and its role in persistent infection in the host. MprA is recognized as a late stage antigen during infection. A variant form of the protein MprA with G70S polymorphism (MprA*) is observed in one of our local and in several global clinical isolates of M. tuberculosis. Here we report the nuclear localization of MprA and MprA* in differentiated macrophages. MprA and MprA* increase the expression of TGF-{beta} and IL-10, the immune suppressive cytokines in THP-1 derived macrophage cells. Concurrently the phago-lysosome fusion is significantly reduced as shown by infection with M.bovis BCG. We show that single nucleotide variation in clinical isolates lead to quantitative variations resulting in host immune suppression and support the survival and persistence of the pathogen.

microbiology↗

Correlation of drug resistance with Single Nucleotide Variations through genome analysis and experimental validation in a multi-drug resistant clinical isolate of M.tuberculosis.

BackgroundGenome sequencing and genetic polymorphism analysis of clinical isolates of M.tuberculosis is carried out to gain further insight into molecular pathogenesis and host-pathogen interaction. Therefore the functional evaluation of the effect of single nucleotide variation (SNV) is essential. At the same time, the identification of invariant sequences unique to M.tuberculosis contributes to infection detection by sensitive methods. In the present study, genome analysis is accompanied by evaluation of the functional implication of the SNVs in a MDR clinical isolate VPCI591. ResultBy sequencing and comparative analysis of VPCI591 genome with 1553 global clinical isolates of M.tuberculosis, we identified 143 unique strain specific SNVs. A novel intergenic variation in VPCI591 in the putative promoter/regulatory region mapping between embC (Rv3793) and embA (Rv3794) genes was found to enhance the expression of embAB, which correlates with the high resistance of the VPCI591 to ethambutol. Similarly, the unique combination of three genic SNVs in RNA polymerase {beta} gene (rpoB) in VPCI591 was evaluated for its effect on rifampicin resistance through molecular docking analysis. The comparative genomics also showed that along with variations, there are genes that remain invariant. 173 such genes were identified in our analysis. ConclusionWe have demonstrated that SNVs are not always benign and can also have functional effect. We show that variations bring about quantitative changes in transcription. Our results show the collective effect of SNVs on the structure of protein, impacting the interaction between the target protein and the drug molecule, with rpoB as an example.

microbiology↗

Intersection of motor volumes predicts the outcome of predator-prey interactions

The escape maneuvers of animals are key determinants of their survival. Consequently these maneuvers are under intense selection pressure. Current work indicates that a number of escape maneuver parameters contribute to survival including response latency, escape speed, and direction. This work has found that the relative importance of these parameters is context dependent, suggesting that interactions between escape maneuver parameters and the predatory context together determine the likelihood of escape success. However, it is unclear how escape maneuver parameters interact to contribute to escape success across different predatory contexts. To clarify these issues, we investigated the determinants of successful escape maneuvers by analyzing the responses of larval zebrafish to the attacks of dragonfly nymphs. We found that the strongest predictor of the outcome was the time needed for the nymph to reach the fishs initial position at the onset of the attack, measured from the time that the fish initiates its escape response. We show how this result is related to the intersection of the swept volume of the nymphs grasping organs with the volume containing all possible escape trajectories of the fish. By analyzing the intersection of these volumes, we compute the survival benefit of recruiting the Mauthner cell, a neuron in anamniotes devoted to producing escapes. We discuss how escape maneuver parameters interact in determining escape response. The intersection of motor volume approach provides a framework that unifies the influence of many escape maneuver parameters on the likelihood of survival.

animal behavior and cognition↗

Switchable amplification of fluoresence from a photosynthetic microbe

One known attribute of the photosynthetic apparatus is photon capture and generation of metabolic energy. The thermodynamic implications of fluorescence, invariably associated with the photosynthetic components is however poorly understood. In this paper we report a density dependent amplification of such fluorescence which can be interpreted as a thermodynamic strategy of controlled energy release by the cell. We show in support of this hypothesis that prolonged photo-exitation of cell free extract of Rhodobacter capsulatus SB1003 at 395 nm, induces fluorescence emission amplifying with time as long as the fluorophore density is above a critical level. The fact that the amplification disappears at low temperature and at dilute condition, is in accordance with the thermodynamic interpretation that energy is released as per requirement. Live cell imaging is also validation of the phenomenon even at the cellular level. Single cells of Rhodobacter capsulatus SB1003 shows time dependent loss of fluorescence, the process being reversed for cellular clusters. To explain the mechanism of this bistable fluorescence (F) amplification, variation of the scale free kinetic constant k=1/F (dF/dt) is studied at varying temperatures in presence and absence of static magnetic field. The sign of k shifts from positive to negative if T is lowered or if the system is diluted. But at low T, k again switches from negative to positive value, if static magnetic field is applied. The chain of events can be explained by a simple model assuming excretion of a porphyrin by the microbe and possible photon dependent aggregation behavior of such porphyrin complex, differential temperature and magnetic field sensitivity of the monomeric or aggregated forms of porphyrin being reported earlier.

biophysics↗