Biology subjects

Patra, P.

Publications and source records attributed to Patra, P..

10 recordsLinked to original sources

bioRxiv2026

Gut bacterium of Leishmania donovani-non-transmitting sand fly induces IL-23~Th17 axis to protect hosts from drug-resistant visceral leishmaniasis

Background: Visceral leishmaniasis (VL) is caused by Leishmania donovani and differentiates under the influence of biotope-specific gut bacteria in the Leishmania donovani-transmitting sand fly vector, Phlebotomus argentipes, which coexists with the Leishmania donovani-non-transmitting Sergentomyia species in the Indian subcontinent. Hypothesis: Sergentomyia are primarily herpetophilic. Interestingly, we identified a specific population of anthropophilic Sergentomyia babu babu, a proven naturally non-competent vector for transmitting Leishmania donovani, with high abundance and human-bite incidences in VL-non-endemic regions, compared with VL-endemic regions of India. Thus, the possibility of egesting gut bacteria to humans from VL-non-transmitting Sergentomyia and inducing downstream immune cascades remains undeniable. Innovation: We characterized gut bacteria from anthropophilic Sergentomyia babu babu in both VL-endemic and VL-non-endemic regions of India and found that a heat-inactivated formulation of Heyndrickxia sporothermodurans [NCBI Sequence Read Archive (SRA): PRJNA1403236], isolated from anthropophilic Sergentomyia babu babu from a VL-non-endemic region, prevented and cured L. donovani infection by inducing IL-23~Th17. More importantly, it also prevented the initial parasite establishment by inducing phagocytosis, ROS, and TNF- in circulatory Ly6G-CD11b+Ly6Chi monocytes. To the best of our knowledge, this is the first report confirming that the gut bacteria of VL-non-transmitting sand flies are critical and need to be investigated in depth for developing therapeutics and/or prophylactics against visceral leishmaniasis (VL), and suggests that possible bite-transfer of gut bacteria from disease-non-transmitting vectors to hosts may restrict disease pathogenicity. Further clinical trials are needed to warrant (Indian patent: 202511041013, April 28, 2025).

immunology↗

bioRxiv2026

Super-Resolution Visual ProteomEx for Hard Tissues and Clinical Samples

Correlating nanoscale tissue architecture with unbiased molecular composition within the same specimen remains a fundamental challenge in spatial biology. Current spatial proteomics methods either lack the imaging resolution required to resolve nanoscale tissue architecture or achieve only limited proteome coverage, and untargeted approaches capable of deep protein identification have yet to be integrated with super-resolution imaging within a single workflow. Here, we present microProteomEx, an integrated platform that combines hydrogel-assisted tissue expansion with mass spectrometry-compatible fluorescence imaging, laser capture microdissection, and bottom-up proteomics to achieve simultaneous three-dimensional super-resolution imaging (effective lateral resolution down to [~]47 nm on conventional diffraction-limited microscopes) and spatially resolved proteomics at a scalable lateral resolution of 29-100 {micro}m (0.02-0.28 nL volumetric resolution). By optimizing fixation, protein anchoring, and a secondary re-embedding strategy, we extend the method to mechanically resilient tissues, including mouse kidney and heart, as well as to formalin-fixed, paraffin-embedded clinical specimens. We demonstrate single-glomerulus and single-plaque proteomics (450-1,000 proteins per structure), resolve proteomic differences between malignant melanoma and giant congenital melanocytic nevus in a rare pediatric case, and characterize the morphology-resolved molecular heterogeneity of cored versus diffuse amyloid-beta plaques in a mouse model of Alzheimers disease across two disease stages. microProteomEx establishes a broadly accessible framework for correlating tissue ultrastructure with deep spatial proteomics, with direct implications for disease biology, biomarker discovery, and precision medicine.

biochemistry↗

bioRxiv2026

Nanoscale visualization of ribonucleoprotein condensates with ultrastructure RNA expansion microscopy

Superresolution imaging of RNAs in their native cellular context is crucial for investigating RNA biology. Here, we develop Ultrastructure RNA Expansion (UREx) microscopy, an expansion microscopy approach, that retains cellular RNAs and RNP granule condensates. We demonstrate that UREx retains the highly ordered core-shell architecture of Neat1 RNA in the paraspeckles, confirming RNA ultrastructure preservation. In addition to robust RNA retention, UREx also preserves protein epitopes and overall cellular protein ultrastructure thus enabling context-dependent visualization of RNAs in cells as well as intact tissues. Employing UREx, we visualize RNP condensates in the intact Drosophila germline and resolve diffraction-limited oskar granules into RNP nanoclusters. Together, our findings establish UREx as a broadly applicable and cost-effective resource to interrogate the nanoscale spatial organization of RNAs and proteins within diffraction-limited RNP assemblies.

cell biology↗

bioRxiv2025

Fano factor as a key measure of sensitivity in biological networks

Sensitivity of a biological process is vital for its proper function and regulation. Biological networks in equilibrium display such sensitivity mainly through cooperative binding of ligands to network elements comprised of multiple sites of an oligomeric protein. The classical measure of binding cooperativity is the Hill slope obtained empirically from binding isotherm data, known as the Hill plot. Hill slope value greater (less) than unity indicates positive (negative) cooperativity. In this study, we have shown that the Hill slope is actually a combination of two Fano factors associated with the number of bound and empty sites of the network, respectively. Taking a ladder network capable of showing positive cooperativity only, we have analytically proved that if the variation of Fano factors with fractional saturation of the network is non-linear, the binding is cooperative and if the variation is linear, the binding is non-cooperative with Hill slope equal to unity. Further, through numerical analyses of a linear network that can exhibit both positive and negative cooperativity, it is established that the curves of Fano factor for the positive (negative) cooperative cases reside above (below) the line representing the non-cooperative case. Our results, thus, confirm the role of Fano factor as the crucial measure of sensitivity in biological networks.

biophysics↗

bioRxiv2022

Water-Quality analysis and Fish diversity of Southern West Part of the West-Bengal

Marine fishes are one of the important factors to stabilize the local aquatic ecosystem and regulating socio-economy of local fishermen. In this study we emphasized upon finding out the interrelationship in the water quality, anthropogenic activity, and fish habitat through the 31km stretch of East Medinipur coast in West Bengal, India which is known for its tourist destinations. The study was conducted monthly on different trawler fish landing sites from Dec 2018 to Dec 2021. During this period, we took fish samples and identified them. We took water quality data such as SST, Concentration of Chl-a, Turbidity, and DO for further correlation between the water quality and species diversity. Total 154 numbers of commercially important marine fish species were documented. Among them, 12 species are from Elasmobranch and the rest is Actinopterygii. As per the IUCN database, 13% of the total fish species are under the red list category and 16% of the species showing decreasing population trend. After analyzing the water quality data, we found out that DO, SST, Turbidity, and Chlorophyll-A correlate with the species richness and it also differs during the seasons.

ecology↗

bioRxiv2021

A particle-based computational model to analyse remodelling of the red blood cell cytoskeleton during malaria infections

Red blood cells can withstand the harsh mechanical conditions in the vasculature only because the bending rigidity of their plasma membrane is complemented by the shear elasticity of the underlying spectrin-actin network. During an infection by the malaria parasite Plasmodium falciparum, the parasite mines host actin from the junctional complexes and establishes a system of adhesive knobs, whose main structural component is the knob-associated histidine rich protein (KAHRP) secreted by the parasite. Here we aim at a mechanistic understanding of this dramatic transformation process. We have developed a particle-based computational model for the cytoskeleton of red blood cells and simulated it with Brownian dynamics to predict the mechanical changes resulting from actin mining and KAHRP-clustering. Our simulations include the three-dimensional conformations of the semi-flexible spectrin chains, the capping of the actin protofilaments and several established binding sites for KAHRP. For the healthy red blood cell, we find that incorporation of actin protofilaments leads to two regimes in the shear response. Actin mining decreases the shear modulus, but knob formation increases it. We show that dynamical changes in KAHRP binding affinities can explain the experimentally observed relocalization of KAHRP from ankyrin to actin complexes and demonstrate good qualitative agreement with experiments by measuring pair cross-correlations both in the computer simulations and in super-resolution imaging experiments. Author summaryMalaria is one of the deadliest infectious diseases and its symptoms are related to the blood stage, when the parasite multiplies within red blood cells. In order to avoid clearance by the spleen, the parasite produces specific factors like the adhesion receptor PfEMP1 and the multifunctional protein KAHRP that lead to the formation of adhesive knobs on the surface of the red blood cells and thus increase residence time in the vasculature. We have developed a computational model for the parasite-induced remodelling of the actin-spectrin network to quantitatively predict the dynamical changes in the mechanical properties of the infected red blood cells and the spatial distribution of the different protein components of the membrane skeleton. Our simulations show that KAHRP can relocate to actin junctions due to dynamical changes in binding affinities, in good qualitative agreement with super-resolution imaging experiments. In the future, our simulation framework can be used to gain further mechanistic insight into the way malaria parasites attack the red blood cell cytoskeleton.

biophysics↗

bioRxiv2021

KAHRP dynamically relocalizes to remodeled actin junctions and associates with knob spirals in P. falciparum-infected erythrocytes

The knob-associated histidine-rich protein (KAHRP) plays a pivotal role in the pathophysiology of Plasmodium falciparum malaria by forming membrane protrusions in infected erythrocytes, which anchor parasite-encoded adhesins to the membrane skeleton. The resulting sequestration of parasitized erythrocytes in the microvasculature leads to severe disease. Despite KAHRP being an important virulence factor, its physical location within the membrane skeleton is still debated, as is its function in knob formation. Here, we show by super-resolution microscopy that KAHRP initially associates with various skeletal components, including ankyrin bridges, but eventually co-localizes with remnant actin junctions. We further present a 35[A] map of the spiral scaffold underlying knobs and show that a KAHRP-targeting nanoprobe binds close to the spiral scaffold. Single-molecule localization microscopy detected [~]60 KAHRP molecules per knob. We propose a dynamic model of KAHRP organization and a function of KAHRP in attaching other factors to the spiral scaffold.

microbiology↗

bioRxiv2021

Role of bacterial persistence in spatial population expansion

Bacterial persistence, tolerance to antibiotics via stochastic phenotype switching provides a survival strategy and a fitness advantage in temporally fluctuating environments. Here we study its possible benefit in spatially varying environments using a Fisher wave approach. We study the spatial expansion of a population with stochastic switching between two phenotypes in spatially homogeneous conditions and in the presence of an antibiotic barrier. Our analytical results show that the expansion speed in growth-supporting conditions depends on the fraction of persister cells at the leading edge of the population wave. The leading edge contains a small fraction of persister cells, keeping the effect on the expansion speed minimal. The fraction of persisters increases gradually in the interior of the wave. This persister pool benefits the population when it is stalled by an antibiotic environment. In that case, the presence of persister enables the population to spread deeper into the antibiotic region and to cross an antibiotic region more rapidly. The interplay of population dynamics at the interface separating the two environments and phenotype switching in the antibiotic region results in a optimal switching rate. Overall, our results show that stochastic switching can promote population expansion in the presence of antibiotic barriers or other stressful environments.

biophysics↗

bioRxiv2019

Graphene Quantum Dot Oxidation Governs Noncovalent Biopolymer Adsorption

The graphene quantum dot (GQD) is a carbon allotrope with a planar surface amenable for functionalization and nanoscale dimensions that confer photoluminescent properties. Collectively, these properties render GQDs an advantageous platform for nanobiotechnology applications, including as optical biosensors and delivery platforms. In particular, noncovalent functionalization offers a route to reversible modification and preservation of the pristine GQD substrate. However, a clear paradigm for GQD noncovalent functionalization has yet to be realized. Herein, we demonstrate the feasibility of noncovalent polymer adsorption to the GQD surface, with a specific focus on single-stranded DNA (ssDNA). We study how GQD oxidation level affects the propensity for polymer adsorption by synthesizing and characterizing four types of GQD substrates and investigating noncovalent polymer association to these substrates. Distinct adsorption methods are developed for successful ssDNA attachment based upon the GQDs initial level of oxidation. ssDNA adsorption to the GQD is confirmed by atomic force microscopy, by inducing ssDNA desorption, and with molecular dynamics simulations. ssDNA is determined to adsorb strongly to no-oxidation GQDs, weakly to low-oxidation GQDs, and not at all for heavily oxidized GQDs. We hypothesize that high GQD oxygen content disrupts the graphitic carbon domains responsible for stacking with the aromatic ssDNA bases, thus preventing the formation of stable polymer-GQD complexes. Finally, we develop a more generic adsorption platform and assess how the GQD system is tunable by modifying both the polymer sequence and type.

bioengineering↗

bioRxiv2018

Systematic analysis of the Myxococcus xanthus developmental gene regulatory network supports posttranslational regulation of FruA by C-signaling

Upon starvation Myxococcus xanthus undergoes multicellular development. Rod-shaped cells move into mounds in which some cells differentiate into spores. Cells begin committing to sporulation at 24-30 h poststarvation, but the mechanisms governing commitment are unknown. FruA and MrpC are transcription factors that are necessary for commitment. They bind cooperatively to promoter regions and activate developmental gene transcription, including that of the dev operon. Leading up to and during the commitment period, dev mRNA increased in wild type, but not in a mutant defective in C-signaling, a short-range signaling interaction between cells that is also necessary for commitment. The C-signaling mutant exhibited [~]20-fold less dev mRNA than wild type at 30 h poststarvation, despite a similar level of MrpC and only twofold less FruA. Boosting the FruA level twofold in the C-signaling mutant had little effect on the dev mRNA level, and dev mRNA was not less stable in the C-signaling mutant. Neither did high cooperativity of MrpC and FruA binding upstream of the dev promoter explain the data. Rather, our systematic experimental and computational analyses support a model in which C-signaling activates FruA at least ninefold posttranslationally in order to commit a cell to spore formation.\n\nGraphical abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=169 HEIGHT=200 SRC=\"FIGDIR/small/415331_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (28K):\norg.highwire.dtl.DTLVardef@c16410org.highwire.dtl.DTLVardef@909252org.highwire.dtl.DTLVardef@17668a8org.highwire.dtl.DTLVardef@d126c3_HPS_FORMAT_FIGEXP M_FIG C_FIG Abbreviated summaryStarvation promotes MrpC accumulation, whereas nutrients favor proteolysis. MrpC activates transcription of fruA, but FruA protein appears to be activated by short-range C-signaling in a cycle leading to mound formation and lysis of some cells. Activated FruA* and MrpC are proposed to cooperatively stimulate transcription of the dev operon and genes that commit starving rod-shaped cells to form spores, while Dev proteins slow commitment, resulting in a spore-filled fruiting body surrounded by peripheral rods.

molecular biology↗