Biology subjects

Ghosh, I.

Publications and source records attributed to Ghosh, I..

14 recordsLinked to original sources

bioRxiv2026

A network-based framework for detecting communities of similar neural spike trains

Recent advances in large-scale electrophysiological recording technologies now allow simultaneous measurement of spike trains from ensembles of neurons. A central challenge in mathematical neuroscience is therefore to identify functional assemblies and their collective organisation directly from this data. The goal of this work is to devise a method to infer the collective organisation of the neurons from their spiking activity. We construct weighted functional networks from neural spike trains using the van Rossum distance to quantify pairwise similarity. The functional network captures similarities in neuron firing patterns and provides a representation of their collective organisation. We hypothesise that similar neuronal assemblies will appear as clustered communities in the network, and employ the Louvain algorithm to detect such assemblies. We validate our approach using synthetic spike train data and simulated data from a stochastic block model of Leaky Integrate and Fire neurons subjected to external Poisson drives, where the ground truth is known. Finally, we apply our approach to large-scale recordings from the Allen Institute Visual Coding: Neuropixels dataset. We find that our methodology works well as long as a sufficient amount of data is available and the temporal structure is strong relative to the noise.

neuroscience↗

bioRxiv2026

Preserved CD4+ T cell helper function and coordinated antiviral immunity in people with HBV/HIV co-infection on long-term therapy

Background & AimsPeople with HBV/HIV co-infection on antiretroviral therapy achieve higher rates of HBV functional cure than those with HBV mono-infection, yet the immunological basis remains poorly characterised. HBV-specific CD4+ T cell responses are critical for viral control and functional cure but have been scarcely examined in HBV/HIV co-infection. Our previous studies in HBV/HIV co-infection demonstrated preserved stem-like CD8+ T cells and NK cell functional responses, but whether CD4+ T cell helper function is similarly maintained is unknown. MethodsWe analysed CD4+ T cell responses in 72 participants (HBV n=26, HBV/HIV n=24, HIV n=22) on suppressive antiviral therapy, using multiparameter flow cytometry, virus-specific CD4+ T cell functional assays and proliferation assays. ResultsPeople with HBV/HIV co-infection had significantly higher HBV envelope- and core-specific CD4+ T cell responses, with IL-2 production particularly discriminating between groups. CD4+ T cell responses to CEF (CMV, EBV, and Influenza) were comparable, confirming antigen specificity. Granzyme B-expressing cytotoxic CD4+ T cells and TCF-1+CD127+PD-1+CD4+ T cells were enriched in co-infection. CD4+ and CD8+ T cell responses were more frequently coordinated within donors in co-infection than in mono-infection (envelope 83% vs 50%; core 94% vs 60%), where they were more often uncoupled. IL-2 producing CD4+ T cells correlated with CD8+ T cell responses and the CD4:CD8 ratio in co-infection. HBV-specific proliferative capacity was enhanced in co-infection. ConclusionsPeople with HBV/HIV co-infection mount functional HBV-specific CD4+ T helper responses that are coordinated with CD8+ T cell immunity at the individual level. Together with our prior findings of preserved NK and CD8+ T cell responses in this cohort, these data identify treated HBV/HIV co-infection as a setting of integrated, rather than compromised, antiviral immunity. Impact and ImplicationsPeople with HBV/HIV co-infection can achieve HBV functional cure more frequently than people with HBV mono-infection, but the immune mechanisms remain unclear. This study shows that treated HBV/HIV co-infection is characterised by functional HBV-specific CD4 helper responses and coordinated CD4/CD8 antiviral immunity. These responses were most strongly associated with the CD4:CD8 ratio, a routinely available clinical marker, rather than with CD4 count alone. These findings argue that people with HBV/HIV co-infection should be prioritised in, not excluded from, HBV cure immunotherapy trials. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=90 SRC="FIGDIR/small/730166v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@89be79org.highwire.dtl.DTLVardef@13836bborg.highwire.dtl.DTLVardef@1915698org.highwire.dtl.DTLVardef@cc286c_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2025

Efficacy of immunostimulant feed additive ShrimpGuard, for the preventive management of White Spot Syndrome Virus (WSSV) infection in shrimps

White spot syndrome virus (WSSV) is a virulent lethal viral pathogen affecting shrimp aquaculture worldwide. Current solutions for WSSV management can be divided into three categories; farm management, selective breeding or genetic engineering to get WSSV resistant varieties of shrimp, and developing vaccine or drug-like solutions specifically targeting WSSV. At present, farm management or good farming practice is the most reliable way of managing the problem, anti-WSSV vaccine, or anti-WSSV drugs that are reliable and scalable in the market are not available. We have developed a feed additive named "ShrimpGuard" using our SOLAQ (Solutions for Agriculture and Aquaculture) platform that specifically provides Shrimp protection against the WSSV infection. Here we report protection observed in both laboratory and farm demonstrations, in Penaeus vannamei. Collectively, these studies show that Shrimp-Guard does not cause any adverse effects on shrimp health and is able to provide significant protection to shrimp against WSSV infection. Briefly, the immune parameters of shrimp respond to ShrimpGuard treatment with increase observed in Total haemocyte count, and activity of prophenoloxidase. Further, survival rates of shrimp treated with ShrimpGuard after WSSV infection was between 80-100 % compared to 0% survival observed in untreated shrimp. The ShrimpGuards performance was tested in production farms and it was found that ShrimpGuard is safe for farm-based applications and the data obtained shows a positive impact on shrimp yield after ShrimpGuard treatment.

immunology↗

bioRxiv2025

Mitochondria structurally remodel near synapses to fuel the sustained energy demands of plasticity

Brain synapses are hotspots of energy consumption, and the synaptic plasticity underlying learning sharply increases this demand. Because most synapses lie far from their cell body, their energy demands must be met locally. A dendritic mitochondrion can extend ~30 m and span many spines, yet ramps up ATP synthesis only near spines undergoing plasticity, providing immediate and sustained energy. Whether structural changes in these juxtaspinal mitochondrial regions (2 m segments at spine bases) support this response is unknown; resolving their energy-producing architecture poses substantial challenges. Compared with the lamellar cristae of axonal mitochondria, dendritic mitochondrial cristae form complex, tubular, and interconnected networks that require multiple high-resolution tomograms to characterize. We therefore developed a correlative light and electron microscopy (CLEM) pipeline with a custom deep-learning model that simultaneously segments five distinct 3D suborganellar structures from limited training data, enabling quantitative analysis across 42 tomograms at 2 nm pixel resolution. We find that juxtaspinal mitochondrial regions are larger than non-juxtaspinal regions within the same mitochondrion and enlarge further during synaptic plasticity. Juxtaspinal mitochondrial ATP synthesis and spine ATP levels rise in parallel; during single-spine plasticity, ATP rises within minutes, before detectable enlargement, indicating that juxtaspinal mitochondrial enlargement sustains rather than initiates the local energy response. The enlarged regions exhibit increased cristae membrane surface area, crista junction number, and membrane area with high curvature, together with increased MIC60 and ATP synthase copies, endoplasmic reticulum contacts, and more proximal ribosomes. Matrix-targeted PKA inhibition reduces MIC60 phosphorylation and impairs juxtaspinal mitochondrial enlargement, plasticity-associated ATP increase, and single-spine plasticity. Together, our findings support a model in which spine-specific remodeling within an individual mitochondrion boosts local metabolic capacity to sustain ATP synthesis and fuel synaptic plasticity.

neuroscience↗

bioRxiv2025

Tumor-Educated-Platelets interact with Breast Cancer-Stem-Cells via P-selectin- PSGL1 and ensure stemness and metastasis through WNT-β-Catenin-VEGF-VEGFR2 intra-cellular signaling: Therapeutic modulation by aspirin

BackgroundProtagonistic role of platelets promote capillary infiltration of tumors for distant metastasis along with immunosurveillance. Despite existing reports highlighting role of platelets in tumorigenesis, its impact on breast cancer stem cells (BCSCs) remain underexplored. Our first ever report on murine and human system, accentuate that, tumor educated platelets (TEPs) of luminal A and TNBC subtypes are distinct from healthy counterparts, collaborating with BCSCs to generate sub-variants that elevate tumor aggressiveness. MethodsImpact of TEPs on BCSCs was evaluated from primary breast tumor and blood samples of luminal A/TNBC patients along with EC/4T1 murine breast tumor models and MCF-7/MDA-MB-231 cell lines. For downstream assays, TEPs were co-cultured with breast tumor samples or cell lines, followed by magnetic sorting of lin-CD44+CD24- BCSCs. TEP induced alterations of BCSCs were evaluated from 3D tumorsphere, colony formation, transwell migration, scratch-wound healing, matrigel invasion, in-vitro tube formation assays. Fluorescence-confocal microscopy, RT-PCR, flow-cytometry, western-blotting was utilized to decipher the role of genes and protein involved in stemness, metastasis along with the transcription factors in the downstream signaling cascade, followed by verifications by RNAi. ResultsTEPs have elevated expression of P-selectin and interacts with BCSCs via P-selectin and PSGL1 on BCSCs surface. Treatment with aspirin had restorative impact on P-selectin level, converting TEPs from active to resting platelet (RP) state. Under TEPs influence, BCSCs were tumorigenic, clonogenic, multidrug resistant, invasive with numerous invadopodia and remained skewed towards mesenchymal phenotype. Administration of RP reduced TEP associated BCSC virulence both in-vivo and in-vitro. P-selectin-PSGL1 interaction results in binding of WNT to FRIZZLED followed by stabilization and nuclear translocation of {beta}-Catenin. Nuclear {beta}-Catenin promotes stemness-EMT (Epithelial to mesenchymal transition)- metastasis, along with stimulation of autocrine VEGF-VEGFR2 cascade. Inhibition of WNT and VEGFR2 by RNAi confirmed the critical role of this axis in regulating TEPs influence on BCSCs. ConclusionThese insights into TEPs-BCSC interplay, acknowledges TEPs, as-well-as unveils novel receptor-ligand signaling cascade between TEPs and BCSCs, that could be a beneficial therapeutic strategy to target cancer metastasis. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=122 SRC="FIGDIR/small/657784v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@11db5d0org.highwire.dtl.DTLVardef@18b7270org.highwire.dtl.DTLVardef@64c2borg.highwire.dtl.DTLVardef@172d68f_HPS_FORMAT_FIGEXP M_FIG C_FIG Cellular interaction between TEPs P-selectin and BCSCs PSGL1 to regulate stemness, EMT, metastasis and angiogenesis via WNT-{beta}-Catenin-VEGF-VEGFR2 cascade: Modulation by pharmacological inhibitor and RNAi.

cancer biology↗

bioRxiv2025

Synapses drive local mitochondrial ATP synthesis to fuel plasticity

Our brain constantly forms new memories and stabilizes existing memories. To achieve such cognitive flexibility, the brain is wired by plastic synapses that are hotspots of energy consumption. Supplying energy to distant synapses is challenging as they are distributed throughout dendrites and axons, spanning hundreds of microns from their cell body. Synapses, therefore, require an instant and local energy supply provided by mitochondria stabilized near dendritic spines. However, the mechanisms by which synapses communicate their energy demands to locally stable mitochondria to drive local energy production and sustain synaptic plasticity is unknown. Using highly sensitive spine- and mitochondrial ATP reporters and two-photon glutamate uncaging to stimulate individual spines, we find that synaptic plasticity input drives instant and sustained increase in spine ATP levels, provided by local ATP synthesis in [~]10-20 m spatially confined compartments within mitochondria. This spatially localized mitochondrial ATP generation is driven by a spatially localized mitochondrial calcium influx independent of the endoplasmic reticulum. Notably, the initial spine ATP increase, supported by local mitochondrial ATP synthesis, is independent of CaMKII and the energy demands of spine structural plasticity. Without local calcium signaling and mitochondrial stabilization, synapses do not meet their instant and sustained energy needs, resulting in synaptic plasticity defects, as observed in neurological disorders.

neuroscience↗

bioRxiv2023

NEK1-Mediated Phosphorylation of YAP1 is key to Prostate Cancer Progression

Understanding how Androgen-dependent PCa cells progress to independence and modify accordingly their transcriptional repertoire is the key to preventing mCRPC progression. We recently identified a novel axis of the Hippo pathway characterized by the sequential kinase cascade induced by androgen deprivation: AR->TLK1B>NEK1>pYAP1-Y407 leading to CRPC adaptation. Phosphorylation of YAP-Y407 increases upon ADT or induction of DNA damage, correlated with the known increase in NEK1 expression/activity, and this is suppressed in the Y407F mutant. Dominant expression of YAP1-Y407F in Hek293 cells reprograms the YAP1-mediated transcriptome to reduced TEAD- and P73-regulated gene expression and mediates sensitivity to MMC. NEK1 haploinsufficient TRAMP mice display reduced YAP1 expression and if castrated fail to progress to overt prostate carcinomas, even while displaying reduced E-CAD expression in hyperplastic ductules. YAP1 overexpression, but not the Y407F mutant, transforms LNCaP cells to androgen independent growth and a mesenchymal morphology. Immunohistochemical examination of Prostate Cancer biopsies revealed that pYAP1-Y407 nuclear signal is low in samples of low-grade cancer but elevated in high GS specimens. We also found that J54, pharmacological inhibitor of the TLK1>NEK1>YAP1 nexus, leading to degradation of YAP1 can suppress the transcriptional reprogramming of LNCaP cells to Androgen-Independent growth and EMT progression even when YAP1-WT is overexpressed.

cancer biology↗

bioRxiv2022

TLK1-mediated RAD54 phosphorylation spatio-temporally regulates Homologous Recombination Repair

Environmental agents like ionizing radiation (IR) and chemotherapeutic drugs can cause severe damage to the DNA, often in the form of double-strand breaks (DSBs). Remaining unrepaired, DSBs can lead to chromosomal rearrangements, and cell death. One major error-free pathway to repair DSBs is homologous recombination repair (HRR). Tousled-like kinase 1 (TLK1), a Ser/Thr kinase that regulates the DNA damage checkpoint, has been found to interact with RAD54, a central DNA translocase in HRR. To determine how TLK1 regulates RAD54, we inhibited or depleted TLK1 and tested how this impacts HRR in human cells using a ISce-I-GR-DsRed fused reporter endonuclease. Our results show that TLK1 phosphorylates RAD54 at three threonines (T41, T59, and T700), two of which are located within its N-terminal domain (NTD) and one is located within its C-terminal domain (CTD). Phosphorylation at both T41 and T59 supports HRR and protects cells from DNA DSB damage. In contrast, phosphorylation of T700 leads to impaired HRR and engenders no protection to cells from cytotoxicity and rather results in repair delay. Further, our work enlightens the effect of RAD54-T700 (RAD54-CTD) phosphorylation by TLK1 in mammalian system and reveals a new site of interaction with RAD51.

molecular biology↗

bioRxiv2022

Evidence that Nek1 does not phosphorylate Rad54-S572 during recovery from IR

A main focus of the work in our lab is on the activity of Tousled Like Kinase 1 (TLK1) in the area of DNA Damage and Repair. As one of its key interactor, TLK1 phosphorylates NIMA related kinase 1 (Nek1), and Nek1 was reported by Spies et al. to phosphorylate and regulate the activity of the key HRR protein Rad541, which suggested an intriguing signal transduction pathway: TLK1>Nek1>Rad54. In an effort to confirm such relations, we now report that we have not been able to reproduce key findings from that study. Specifically, we found that Nek1 does not phosphorylate RAD54-S572 as was reported. We generated Nek1-KO mouse NT1 cells2 and Nek1-Knock-down in Hek293 (same cells as in Spies et al.), and the pRAD54-S572 signal does not change with our custom Ab, with or w/o IR. When we used an Ab from the Lobrich lab, it detected an immunoreactive band of wrong size for RAD54, which also did not change after IR even in synchronized G2 cells, contrary to their report. We also note that their P-assignment was based on guessing a weak consensus Nek1 sequence, and that site-directed mutagenesis of RAD54-S572 failed to yield biological effects in their in in vitro studies1. To conclusively establish that S572 is not a site of phosphorylation of Nek1, we carried out a IVK with purified Nek1 and RAD54 followed by MS analysis of the phosphatides, which revealed several but not S572. We also could not reproduce their copurification of Nek1-RAD54 by coIP, calling into question this interaction. Neither we could reproduce their results demonstrating the importance of Nek1 for HRR using the same SceI-mediated DR-GFP conversion assays.

molecular biology↗

bioRxiv2022

Exploring repeats in rice genomes: Identification, Characterization and its Applications

Biodiversity is a fundamental property of all natural systems existing in the field biology. It refers to the underlying heterogeneity at different levels of ecology, genetics and evolution. In case of plant systems, dramatic variability has been observed during the Anthropocene at different spatial scales. Environmental stress is one of the major influencing factors behind this plant biodiversity. Huge genetic diversity has been also demonstrated across varieties of important crop species like rice. Repetitive sequences which are a major contributor of genomic diversity in polyploidy plants have been found to occur ubiquitously in their genomes. To date diverse repeat types have been characterized in the plant genomes performing various functions starting from qualitative trait markers to genome evolution and stress management. With an objective to identify of plant stress associated genes using DNA repeat probes, a robust method has been developed. The method has been modularized into three distinct sections. First part is dedicated for identification of different types of repeats. Earlier review has suggested building a pipeline of multiples tools for capturing different types of repeats from the genome sequences. Specialized tools like TROLL, Tandem repeat finder (TRF), PHOBOS and database like REPBASE have been selected for performing this job. Second module is intended for screening of stress related genes from the published articles and databases and the last module has been designed for the association mining between genomic repetitive patterns with stress phenotypes. The method has been used to explore stress associated repeats from 9 Oryza species from different continents and other plants like Arabidopsis and Brachypodium. In case of Oryza species distribution repeats has been found to be significantly different between stress associated and housekeeping genes. More than 55% of the repeats are found to be in positive association (nPMI > 0) whereas 26% of the repeats are false-positives. These repetitive probes have been utilized in several applications. Firstly, using as molecular markers to identify stress related genes in different Oryza species where availability is limited. Secondly, using as a probe to reanalyzing the evolutionary lineage of Oryza species etc.

bioinformatics↗

bioRxiv2021

Benchmarking tools for DNA repeat identification in diverse genomes

Continuous progression in genomics shows that repeats are important elements of genomes that perform many regulatory and other functions. Eventually, to date, many computational tools have been developed and frequently used for the identification and analysis of genomic repeats. A single tool cannot detect all different types of repeats in diverse species rather pipeline of tools is more effective. But, the choice of such rigorous and robust tools is highly challenging. A method has been implemented to select a set of optimal tools for finding all available classes of perfect and imperfect tandem repeats including microsatellites, minisatellites, and interspersed CRISPRs in genomes. A total of 11 tools have been shortlisted using rule-based selection and then ranked by analyzing rigorousness in searching in diverse species and execution time. Tool comparison shows consistency in perfect microsatellite detection performance but significantly differ for long and imperfect repeats. A web-server has been built which provides a generic platform for various classes of repeat identification from the diverse genome using multiple tools and comparison.

bioinformatics↗

bioRxiv2018

Forecasting dengue epidemics using a hybrid methodology

Dengue case management is an alarmingly important global health issue. The effective allocation of resources is often difficult due to external and internal factors imposing nonlinear fluctuations in the prevalence of dengue fever. We aimed to construct an early-warning system that could accurately forecast subsequent dengue cases in three dengue endemic regions, namely San Juan, Iquitos, and the Philippines. The problem is solely regarded as a time series forecasting problem ignoring the known epidemiology of dengue fever as well as the other meteorological variables. Autoregressive integrated moving average (ARIMA) model is a popular classical time series model for linear data structures whereas with the advent of neural networks, nonlinear structures in the dataset can be handled. In this paper, we propose a novel hybrid model combining ARIMA and neural network autoregressive (NNAR) model to capture both linearity and nonlinearity in the datasets. The ARIMA model filters out linear tendencies in the data and passes on the residual values to the NNAR model. The proposed hybrid approach is applied to three dengue time-series data sets and is found to give better forecasting accuracy in comparison to the state-of-the-art. The results of this study indicate that dengue cases can be accurately forecasted over a sufficient time period using the proposed hybrid methodology.

bioinformatics↗

bioRxiv2018

Global dynamics of a general vector-borne disease model with two transmission routes

In this paper, we study the dynamics of a vector-borne disease model with two transmission paths: direct transmission through contact and indirect transmission through vector. The direct transmission is considered to be a non-monotone incidence function to describe the psychological effect of some severe diseases among the population when the number of infected hosts is large and/or the disease possesses high case fatality rate. The system has a disease-free equilibrium which is locally asymptomatically stable when the basic reproduction number (R0) is less than unity and may have up to four endemic equilibria. Analytical expression representing the epidemic growth rate is obtained for the system. Sensitivity of the two transmission pathways were compared with respect to the epidemic growth rate. We numerically find that the direct transmission coefficient is more sensitive than the indirect transmission coefficient with respect to R0 and the epidemic growth rate. Local stability of endemic equilibria is studied. Further, the global asymptotic stability of the endemic equilibrium is proved using Li and Muldowney geometric approach. The explicit condition for which the system undergoes backward bifurcation is obtained. The basic model also exhibits the hysteresis phenomenon which implies diseases will persist even when R0 < 1 although the system undergoes a forward bifurcation and this phenomenon is rarely observed in disease models. Consequently, our analysis suggests that the diseases with multiple transmission routes exhibit bi-stable dynamics. However, efficient application of temporary control in bi-stable regions will curb the disease to lower endemicity. In addition, increase in transmission heterogeneity will increase the chance of disease eradication.

epidemiology↗

bioRxiv2017

ProLego: tool for extracting and visualizing topological modules in protein structures

BackgroundIn protein design, correct use of topology is among the initial and most critical feature. Meticulous selection of backbone topology aids in drastically reducing the structure search space. With ProLego, we present a server application to explore the component aspect of protein structures and provide an intuitive and efficient way to scan the protein topology space.\n\nResultWe have implemented in-house developed \"topological representation\" in an automated-pipeline to extract protein topology from given protein structure. Using the topology string, ProLego, compares topology against a non-redundant extensive topology database (ProLegoDB) as well as extracts constituent topological modules. The platform offers interactive topology visualization graphs.\n\nConclusionProLego, provides an alternative but comprehensive way to scan and visualize protein topology along with an extensive database of protein topology.\n\nProLego can be found at http://www.proteinlego.com

bioinformatics↗