Biology subjects

Sikdar, S.

Publications and source records attributed to Sikdar, S..

16 recordsLinked to original sources

bioRxiv2026

Frequency modulated semi-continuous wave Doppler ultrasound: A novel method for the detection of scatterer velocity and range using wearable ultrasound instrumentation

Doppler ultrasound imaging has become a key tool for clinicians and researchers to measure the velocity of blood and tissues within the human body. Presently pulsed wave and continuous wave Doppler imaging dominate the space as the two most prominent methods and are considered distinct from one another. However, these two techniques can also be considered as ends of a continuum along which Doppler imaging and phase tracking techniques exist. At the midpoint between these methods exists another underexplored Doppler imaging technique we refer to as frequency modulated semi-continuous wave (FMSCW) Doppler. We present a full technical overview of this technique, simulations exploring the impact of selected imaging parameters as well as how noise impacts imaging, and present three exemplary imaging sessions collected from human participants using FMSCW Doppler collected from a wearable ultrasound system. The results of the simulations evaluating the impact of imaging parameters demonstrate the trade-off between resolution in the range and velocity axis as well as the impact of scatterer range and speed on the measurement error. The three sets of images collected from human participants serve to demonstrate FMSCW Doppler used in a variety of wearable ultrasound applications including cardiovascular monitoring, rehabilitation assessment, and prosthetic device control. Furthermore, we discuss the relationship between FMSCW Doppler and isomorphic techniques from radar as well as potential inspiration for improvements for FMSCW Doppler inspired by the echolocation of bats.

bioengineering↗

bioRxiv2026

Microbiome-derived hydroxyphenyl propanoates enhance antitumour immunity by potentiating gasdermin D activity in tumour-associated myeloid cells

The microbiome plays a critical role in immune health and response to immune-stimulating treatments, including cancer immunotherapy. However, the molecular mechanisms by which commensal microbes influence cancer immunology remain poorly understood. Here, we report a class of microbiome-derived metabolites called hydroxyphenyl propanoates (HPP) that enhance tumour immune surveillance and response to immune checkpoint blockade (ICB) therapy in mice. HPPs function as potentiators of innate immune signalling in tumour-associated myeloid cells by promoting cleavage of the pore-forming protein gasdermin D (GSDMD), a critical effector of inflammasome function. This enhances the secretion of proinflammatory cytokines, such as IL-1 family members, while simultaneously protecting against pyroptosis. Secreted IL-1 family cytokines in turn elicit autocrine and paracrine inflammatory signaling in tumour-infiltrating leukocytes. HPP supplementation increases anticancer T cell function, improves disease control and extends overall survival (OS) in tumour-bearing mice harboring complex microbiomes or those treated with broad-spectrum antibiotics. In humans, GSDMD activation is associated with a favourable response to PD-1 blockade therapy in patients with advanced stage melanoma. Our study uncovers a molecular mechanism of regulation over host antitumour immunity that is modifiable and can be harnessed for improved cancer immunotherapy in a broad spectrum of patients.

cancer biology↗

bioRxiv2026

STEQ: A statistically consistent quartet distance based species tree estimation method

Accurate estimation of large-scale species trees from multilocus data in the presence of gene tree discordance remains a major challenge in phylogenomics. Although maximum likelihood, Bayesian, and statistically consistent summary methods can infer species trees with high accuracy, most of these methods are slow and not scalable to large number of taxa and genes. One of the promising ways for enabling large-scale phylogeny estimation is distance based estimation methods. Here, we present STEQ, a new statistically consistent, fast, and accurate distance based method to estimate species trees from a collection of gene trees. We used a quartet based distance metric which is statistically consistent under the multi-species coalescent (MSC) model. The running time of STEQ scales as [O] (kn2 log n), for n taxa and k genes, which is asymptotically faster than the leading summary based methods such as ASTRAL. We evaluated the performance of STEQ in comparison with ASTRAL and wQFM-TREE - two of the most popular and accurate coalescent-based methods. Experimental findings on a collection of simulated and empirical datasets suggest that STEQ enables significantly faster inference of species trees while maintaining competitive accuracy with the best current methods. STEQ is publicly available at https://github.com/prottoysaha99/STEQ.

bioinformatics↗

bioRxiv2026

Gum Odina, a novel prebiotic, promotes the expression of sealing tight junction proteins in colon organoids developed from the C57BL/6 mice model

Maintaining gut-microbiome homeostasis is the biggest issue worldwide as per public health concerns. Gut probiotics not only inhibit pathogen invasion in the systemic circulation but also help us metabolize complex food. Therefore, for decades, gut dysbiosis has been proven to be the gateway to several diseases, leading to comorbidity and even mortality. Prebiotics are natural products, mainly nondigestible food ingredients, that help the selective growth of probiotic bacteria in the gut. This study focuses on the novel Gum-Odina (GO) prebiotic and its efficacy on gut microbial metabolite modulation and maintaining gut barrier integrity. Gut wall enterocytes are integrated by a series of tight junctional (TJ) proteins. This study explains the effect of GO prebiotic-modulated gut metabolites on tight-junctional (TJ) protein expression in a murine colon Organoid model. Fecal microbiota from a colitis patient were used to inoculate the SHIME gut simulator, comprising a colitis control run and a Gum-Odina-supplemented run to enrich commensal bacteria selectively. Metabolites from both groups were then applied to healthy colon organoids. According to the mRNA expression analysis, tight junctional sealing proteins such as Zonula occludens, or ZO-1, Occludin, Claudin-1, 4, and 5 were significantly upregulated in the colon organoids upon Gum-Odina administration, whereas no change in the Junctional Adhesion Molecule-A or JAM-A was observed. Downregulation of sealing TJ proteins is the Hallmark of Leaky gut, which was successfully reversed using the Gum-Odina supplement. Hence, Gum-Odina prebiotics have a promising capability to reduce colitis-induced gut permeability and can be considered to be a therapeutic agent in the future.

cell biology↗

bioRxiv2025

Mitigating Enterotoxigenic Escherichia coli (ETEC) infection with Probiotic and Synbiotic Treatments: A murine and in vitro study

Background & AimsEnterotoxigenic Escherichia coli (ETEC) strain H10407 is a major causative agent of Diarrhoeal diseases. This study investigates the inhibitory effects of selected probiotics (Lactobacillus casei, Lactococcus lactis, and Bifidobacterium bifidum) and their synbiotic combinations with inulin on ETEC proliferation, adhesion, intestinal colonization, and host immune response. MethodsETEC H10407 was cultured in Luria-Bertani broth and co-cultured with probiotic strains to assess growth dynamics. Adhesion and competitive inhibition assays were performed using INT 407 intestinal epithelial cells. A murine infection model (C57BL/6) was employed to evaluate pathogen colonization, diarrheal severity, stool consistency, histopathological changes, and immune modulation. Synbiotic efficacy was further tested by combining probiotics with the prebiotic inulin. Additionally, fecal microbiota transfer (FMT) was conducted to examine microbiome-mediated protective effects. ResultsProbiotic co-culture significantly inhibited ETEC growth from 2 h onward without impairing probiotic viability. All probiotics markedly reduced ETEC adhesion to INT 407 small intestinal cells. In vivo, probiotics lowered ETEC colonization by 81.34%, while synbiotics conferred an additional 29.68% reduction. Synbiotics prevent watery stool and preserve ileal architecture, with reduced goblet cell loss and neutrophil infiltration. Synbiotics significantly (p<0.0001) decreased CD3+/CD4+ Th1 cells in spleen and mesenteric lymph nodes, reduced pro-inflammatory cytokines and chemokines, and restored tight junctional proteins. ConclusionSynbiotic supplementation offered superior protection against ETEC-induced diarrhea compared to probiotics or prebiotics alone, highlighting its potential as a non-antibiotic prophylactic strategy. These findings support the role of microbiome-targeted interventions within the One Health framework to address enteric infections and antimicrobial resistance.

microbiology↗

bioRxiv2023

ASPSCR1-TFE3 reprograms transcription by organizing enhancer loops around hexameric VCP/p97

The t(X,17) chromosomal translocation, generating the ASPSCR1-TFE3 fusion oncoprotein, is the singular genetic driver of alveolar soft part sarcoma (ASPS) and some Xp11-rearranged renal cell carcinomas (RCC), frustrating efforts to identify therapeutic targets for these rare cancers. Proteomic analysis showed that VCP/p97, an AAA+ ATPase with known segregase function, was strongly enriched in co-immunoprecipitated nuclear complexes with ASPSCR1-TFE3. We demonstrate that VCP is a likely obligate co-factor of ASPSCR1-TFE3, one of the only such fusion oncoprotein co-factors identified in cancer biology. Specifically, VCP co-distributed with ASPSCR1-TFE3 across chromatin in association with enhancers genome-wide. VCP presence, its hexameric assembly, and its enzymatic function orchestrated the oncogenic transcriptional signature of ASPSCR1-TFE3, by facilitating assembly of higher-order chromatin conformation structures as demonstrated by HiChIP. Finally, ASPSCR1-TFE3 and VCP demonstrated co-dependence for cancer cell proliferation and tumorigenesis in vitro and in ASPS and RCC mouse models, underscoring VCPs potential as a novel therapeutic target.

cancer biology↗

bioRxiv2023

The pore-forming apolipoprotein APOL7C drives phagosomal rupture and antigen cross-presentation by dendritic cells

Type I conventional dendritic cells (cDC1s) are essential for the generation of protective cytotoxic T lymphocyte (CTL) responses against many types of viruses and tumours. They do so by internalizing antigens from virally infected or tumour cells and presenting them to CD8+ T cells in a process known as cross-presentation (XP). Despite the obvious biological importance of XP, the molecular mechanism(s) driving this process remain unclear. Here, we show that a cDC-specific pore-forming protein called apolipoprotein 7C (APOL7C) is upregulated in response to innate immune stimuli and is recruited to phagosomes. Strikingly, the association of APOL7C with phagosomes leads to phagosomal rupture, which in turn allows for the escape of engulfed protein antigens to the cytosol where they can be processed via the endogenous major histocompatibility complex (MHC) class I antigen processing pathway. We show that APOL7C recruitment to phagosomes is voltage-dependent and occurs in response to NADPH oxidase-induced depolarization of the phagosomal membrane. Our data indicate the presence of dedicated pore-forming apolipoproteins that mediate the delivery of phagocytosed proteins to the cytosol of activated cDC1s to facilitate MHC class I presentation of exogenous antigen and to regulate adaptive immunity.

cell biology↗

bioRxiv2023

Correlation between antimicrobial structural classes and membrane partitioning: Role of emerging lipid packing defects

In this study, a combination of bioinformatics and molecular dynamics simulations is employed to investigate the partitioning behavior of different classes of antimicrobial peptides (AMPs) into model membranes. The main objective is to identify any correlations between the structural characteristics of AMPs and their membrane partitioning mechanisms. The simulation results reveal distinct membrane interactions among the various structural classes of AMPs, particularly in relation to the generation and subsequent interaction with lipid packing defects. Notably, AMPs with a structure-less coil conformation generate a higher number of deep and shallow defects, which are larger in size compared to other classes of AMPs. AMPs with helical component demonstrated the deepest insertion into the membrane. On the other hand, AMPs with a significant percentage of beta sheets tend to adsorb onto the membrane surface, suggesting a potentially distinct partitioning mechanism attributed to their structural rigidity. These findings highlight the diverse membrane interactions and partitioning mechanisms exhibited by different structural classes of AMPs.

biophysics↗

bioRxiv2022

SonoMyoNet: A Convolutional Neural Network for Predicting Isometric Force From Highly Sparse Ultrasound Images

Ultrasound imaging or sonomyography has been found to be a robust modality for sensing muscle activity due to its ability to directly image deep-seated muscles while providing superior spatiotemporal specificity compared to surface electromyography-based techniques. Quantifying the morphological changes during muscle activity involves computationally expensive approaches to track muscle anatomical structures or extracting features from B-mode images and A-mode signals. In this paper an offline regression convolutional neural network (CNN) called SonoMyoNet for estimating continuous isometric force from sparse ultrasound scanlines has been presented. SonoMyoNet learns features from a few equispaced scanlines selected from B-mode images and utilizes the learned features to accurately estimate continuous isometric force. The performance of SonoMyoNet was evaluated by varying the number of scanlines to simulate the placement of multiple single element ultrasound transducers in a wearable system. Results showed that SonoMyoNet could accurately predict isometric force with just four scanlines and is immune to speckle noise and shifts in the scanline location. Thus, the proposed network reduces the computational load involved in feature tracking algorithms and estimates muscle force from global features of sparse ultrasound images.

bioengineering↗

bioRxiv2022

Role of lipid packing defects in determining membraneinteractions of antimicrobial polymers

Understanding the emergence and role of lipid packing defects in the detection and subsequent partitioning of antimicrobial agents into bacterial membranes is essential for gaining insights into general antimicrobial mechanisms. Herein, using methacrylate polymers as a model platform, we investigate the effects of inclusion of various functional groups in the biomimetic antimicrobial polymer design on the aspects of lipid packing defects in model bacterial membranes. Two antimicrobial polymers are considered: ternary polymers composed of cationic, hydrophobic and polar moieties and binary polymers with only cationic and hydrophobic moieties. We find that differing modes of insertion of these two polymers lead to different packing defects in the bacterial membrane. While insertion of both binary and ternary polymers leads to an enhanced number of deep defects in the upper leaflet, shallow defects are moderately enhanced upon interaction with ternary polymers only. We provide conclusive evidence that insertion of antimicrobial polymers in bacterial membrane is preceded by sensing of interfacial lipid packing defects. Our simulation results show that the hydrophobic groups are inserted at a single co-localized deep defect site for both binary and ternary polymers. However, the presence of polar groups in the ternary polymers use the shallow defects close to the lipid-water interface, in addition, to insert into the membrane, which leads to a more folded conformation of the ternary polymer in the membrane environment, and hence a different membrane partitioning mechanism compared to the binary polymer, which acquires an amphiphilic conformation.

biophysics↗

bioRxiv2021

Role of Disulfide Bonds in Membrane Partitioning of a Viral Peptide

The importance of disulfide bond in mediating viral peptide entry into host cells is well known. In the present work, we elucidate the role of disulfide (SS) bond in partitioning mechanism of membrane active Hepatitis A Virus-2B (HAV-2B) peptide, which harbours three cysteine residues promoting formation of multiple SS-bonded states. The inclusion of SS-bond not only results in a compact conformation but also induces distorted -helical hairpin geometry in comparison to SS-free state, resulting in reduced hydrophobic exposure. Owing to this, the partitioning of HAV-2B peptide is completely or partly abolished. In a way, the disulfide bond regulates the partitioning of HAV-2B peptide, such that the membrane remodelling effects of this viral peptide are significantly reduced. The current findings may have potential implications in drug designing, targeting the HAV-2B protein by promoting disulfide bond formation within its membrane active region.

biophysics↗

bioRxiv2021

Sparse Sonomyography-based Estimation of Isometric Force: A Comparison of Methods and Features

Noninvasive methods for estimation of joint and muscle forces have widespread clinical and research applications. Surface electromyography or sEMG provides a measure of the neural activation of muscles which can be used to estimate the force produced by the muscle. However, sEMG based measures of force suffer from poor signal-to-noise ratio and limited spatiotemporal specificity. In this paper, we propose an ultrasound imaging or sonomyography-based approach for estimating continuous isometric force from a sparse set of ultrasound scanlines. Our approach isolates anatomically relevant features from A-mode ultrasound signals, greatly reducing the dimensionality of the feature space and the computational complexity involved in traditional ultrasound-based methods. We evaluate the performance of four regression methodologies for force prediction using the reduced feature set. We also evaluate the feasibility of a practical wearable sonomyography-based system by simulating the effect of transducer placement and varying the number of transducers used in force prediction. Our results demonstrate that Gaussian process regression models outperform other regression methods in predicting continuous force levels from just four equispaced transducers and are tolerant to speckle noise. These findings will aid in the design of wearable sonomyography-based force prediction systems with robust, computationally efficient operation.

bioengineering↗

bioRxiv2020

Effect of Cholesterol on Membrane Partitioning Dynamics of Hepatitis A Virus-2B peptide

Understanding the viral peptide detection, partitioning and subsequent host membrane composition-based response is required for gaining insights into viral mechanism. Here, we probe the crucial role of presence of membrane lipid packing defects, depending on the membrane composition, in allowing the viral peptide belonging to C-terminal Hepatitis A Virus-2B (HAV-2B) to detect, attach and subsequently partition into the host cell membrane mimics. We conclusively show that the hydrophobic residues in the viral peptide detect the transiently present lipid packing defects, insert themselves into such defects, form anchor points and facilitate the partitioning of the peptide. We also show that the presence of cholesterol significantly alters such lipid packing defects, both in size and in number, thus mitigating the partitioning of the membrane active viral peptide into cholesterol-rich membranes. These results show differential ways in which presence and absence of cholesterol can alter the permeability of the host membranes to the membrane active viral peptide component of HAV-2B virus, via lipid packing defects, and can possibly be a part of general membrane detection mechanism for the viroporin class of viruses.

biophysics↗

bioRxiv2019

Spring-loaded inverted pendulum goes through two contraction-extension cycles during the single stance phase of walking

Despite the overall complexity of legged locomotion, the motion of the center of mass (COM) itself is relatively simple, and can be qualitatively described by simple mechanical models. The spring-loaded inverted pendulum (SLIP) is one such model, and describes both the COM motion and the ground reaction forces (GRFs) during running. Similarly, walking can be modeled by two SLIP-like legs (double SLIP or DSLIP). However, DSLIP has many limitations and is unlikely to serve as a quantitative model for walking. As a first step to obtaining a quantitative model for walking, we explored the ability of SLIP to model the single stance phase of walking across the entire range of walking speeds. We show that SLIP can be employed to quantitatively model the single stance phase except for two exceptions: first, it predicts larger horizontal GRFs than empirically observed. A new model - angular and radial spring-loaded inverted pendulum (ARSLIP) can overcome this deficit. Second, even the single stance phase has active elements, and therefore a quantitative model of locomotion would require active elements. Surprisingly, the leg spring undergoes a contraction-extension-contraction-extension (CECE) during walking; this cycling is partly responsible for the M-shaped GRFs produced during walking. The CECE cycle also lengthens the stance duration allowing the COM to travel passively for a longer time, and decreases the velocity redirection between the beginning and end of a step. A combination of ARSLIP along with active mechanisms during transition from one step to the next is necessary to describe walking.

bioengineering↗

bioRxiv2018

Proprioceptive Sonomyographic Control: A novel method of intuitive proportional control of multiple degrees of freedom for upper-extremity amputees

Technological advances in multi-articulated prosthetic hands have outpaced the methods available to amputees to intuitively control these devices. Amputees often cite difficulty of use as a key contributing factor for abandoning their prosthesis, creating a pressing need for improved control technology. A major challenge of traditional myoelectric control strategies using surface electromyography electrodes has been the difficulty in achieving intuitive and robust proportional control of multiple degrees of freedom. In this paper, we describe a new control method, proprioceptive sonomyographic control that overcomes several limitations of myoelectric control. In sonomyography, muscle mechanical deformation is sensed using ultrasound, as compared to electrical activation, and therefore the resulting control signals can directly control the position of the end effector. Compared to myoelectric control which controls the velocity of the end-effector device, sonomyographic control is more congruent with residual proprioception in the residual limb. We tested our approach with 5 upper-extremity amputees and able-bodied subjects using a virtual target achievement and holding task. Amputees and able-bodied participants demonstrated the ability to achieve positional control for 5 degrees of freedom with an hour of training. Our results demonstrate the potential of proprioceptive sonomyographic control for intuitive dexterous control of multiarticulated prostheses.

bioengineering↗

bioRxiv2018

Stimulus statistics and HCN current mediated resonance sets the scale of input-output mapping in Stellate cells of the Medial Entorhinal Cortex

Grid cell spatial period is thought to be dictated by a mapping between the speed-direction modulated excitatory inputs, and consequent modulation of the firing rate, yet, the exact underlying mechanisms are not known. Here, through experiments on the medial entorhinal cortex stellate cells, subjected to in-vivo like stochastic synaptic activity through the dynamic clamp, we show that such mapping can emerge from a theta-frequency resonance in the signal gain, which is HCN sensitive, robust to noise, and is potent enough to modulate the synaptic responses in the theta frequency. This modulation also extends to the corresponding theta-gamma modulation of the firing rate, the slope of whose excitation mediated increase is steeper in the presence of HCN channels. We also show that in the cells devoid of HCN channels, inhibition can emulate their role. Considering the dorso-ventral gradients of HCN and inhibition, which are present aligned to the grid spacing gradient in the medial entorhinal cortex, these findings should be noteworthy.

neuroscience↗