Biology subjects

Jana, K.

Publications and source records attributed to Jana, K..

8 recordsLinked to original sources

bioRxiv2026

Emerging combinations of climatic parameters for dengue proliferation in urban landscapes

Ectotherm insects growth and development are dictated by temperature and humidity. Conducive habitats and the availability of resources set ideal conditions for insect population growth. Mosquitoes require water, favorable temperature, and blood meal to survive. In this research, we picked a rapidly growing megacity, Ahmedabad, in western India, to explore and establish potential linkages between disease spread and meteorological conditions. Ahmedabad, with a population of over 8 million, is experiencing changes in rain and humidity patterns, pushing the city towards changing vector-borne disease dynamics. We examined dengue cases over ten years, 2012-22, and explored their connections with two prominent climatic variables, temperature and relative humidity. Our findings indicate that stable temperature (25-27.5 {degrees}C) and humidity (> 60%) interaction is a ruling factor in spikes in dengue cases in the city. While stable temperature ranges triggers the dengue cases, RH drives the explosive phases and sustainability of such episodes. Statistically significant increasing trends in temperatures, narrowing down of the day-night temperature ranges, and increasing night temperatures provide more stable temperature regimes in a warming world thereby likely to extend the dengue season beyond the usual monsoon season. Plain Language SummaryDengue incidences have been found to be associated with mosquito population outbreaks. Every year, thousands of lives are lost due to this deadly virus spread by mosquitoes. Particularly in the Indian subcontinent, a large proportion of these cases is associated with the monsoon season and rain patterns. In recent years, there have been abrupt spikes in dengue cases across Indian cities, particularly in western India. To understand this complex interaction of viral proliferation and local environmental conditions, the last ten years of dengue case patterns have been scanned in parallel to the climate data. Our findings suggest that stable temperature windows and humidity levels above certain thresholds trigger a rise in dengue cases. While stable temperature ranges trigger dengue cases, humidity drives such episodes explosive phases and sustainability. Our work pinpoints specific temperature-humidity combinations and suggests that local municipal corporations use them as warning indicators to initiate preventive measures.

ecology↗

bioRxiv2025

Azadiradione regulates Heat Shock Factor 1 function by interacting with its DNA-binding domain independent of the oligomerization domain

Heat shock factor 1 (HSF1) masters cellular proteostasis under stress by upregulating the expression of molecular chaperones that help refold or degrade the misfolded proteins. HSF1 activation involves a monomer-to-oligomer transition and binding to its recognition sequence, the heat shock elements (HSEs) on its target gene promoters. HSF1 activity declines with age as well as in neurodegenerative disorders (NDs) such as Parkinsons disease, highlighting the need for strategies to restore its function. Azadiradione (AZD), a limonoid isolated from Azadirachta indica seeds, directly activates HSF1 in cellular and preclinical ND models, unlike other small-molecule activators reported elsewhere. We investigated the molecular basis of AZD-mediated HSF1 activation using purified variants of this protein including those without its oligomerization and transactivation domain. Fluorescence polarization and dynamic light scattering assays revealed that AZD promotes the oligomerization of monomeric HSF1 to enhance its HSE-binding affinity by engaging with its DNA-binding domain (DBD). The oligomerization domain known to be required for stress-induced activation, appears redundant in AZD-mediated activation. Furthermore, evidence suggests AZD-induced conformational alterations in the HSE facilitate its binding to the HSF1 monomer. Notably, AZD reduces the DNA-binding ability of pre-assembled oligomeric HSF1 by triggering its amyloid-like aggregation. This finding also highlighted a potential anticancer effect of AZD, as cancer cells heavily depend on this HSF1 population for rapid proliferation and survival. Overall, these findings offer novel insights into the functional regulation of HSF1 and suggest a framework for developing small-molecule HSF1 activators with therapeutic potential for protein conformation disorders.

biochemistry↗

bioRxiv2024

Polyphenol-rich fraction of Bergenia ligulata (Wall.) Engl. sensitizes colon and breast cancer metastasis in vivo: Evidence of cell-type specific mechanism

BackgroundColon and breast cancer are one of the leading causes of mortality worldwide. Limited efficacies of present treatments highlighted an urgent need for improvement. Bergenia ligulata is known for its anticancer properties in Indian traditional and folk medicine though the molecular basis of its effects, particularly its anti-metastatic properties, is not well understood. Anti-prostate cancer activity of a LCMS defined polyphenol-rich fraction from Bergenia ligulata (PFBL) rhizome extract has already been published showing promising results in preclinical models. PurposeThe present study aims to explore anti-cancer activity and anti-metastatic potentials of PFBL against colon and breast cancers in both in vitro and preclinical settings. Study design and methodsPFBL alone or in synergy with standard chemotherapeutic drugs was tasted in CT26 and 4T1 subcutaneous solid tumors in BALB/c mice. The effect of PFBL was analyzed in terms of changes in tumor mass and different molecular marker levels. Anti-metastatic potential of PFBL was evaluated in CT26 and 4T1 lung metastasis model in mice focusing on the number of lung nodules and lung size. ResultsOur results evidenced that PFBL efficiently regressed both CT26 and 4T1-induced solid tumors alone and in combination with 5FU/doxorubicin without affecting the health of normal host. Notably, PFBL suppressed lung metastasis of 4T1 and CT26 cells in mice with great efficacy. Analysis of tumor and cell extracts suggested that colon cancer cells died by autophagy, while breast cancer cells majorly died by caspase-dependent apoptosis. PFBL actions involved AMPK-dependent inhibition of mTORC1 and subsequent increase in LC3II, PARP1, CDK4 and Cyclin D1 levels in both HCT116 and MCF7 cells; an elevation of intracellular ROS level was the major cause of death in both the cancer types. PFBL treatment also reversed the EMT marker expressions in in vivo and in vitro. ConclusionPFBL regressed colon and breast cancer metastasis through distinct mechanisms with little effect on healthy mice. The present study underscored PFBL as a novel anti-tumor and anti-metastasis candidate warranting further testing in clinical settings.

cancer biology↗

bioRxiv2024

The binary protein interactome mapping of the Giardia lamblia proteasome lid reveals extra proteasomal functions of GlRpn11

Giardia lamblia does not encode Rpn12 and Sem1, two proteins crucial for assembling the proteasome lid. To understand how the interactions between the giardial proteasome lid subunits may have changed to compensate for their absence, we used the yeast two-hybrid assay to generate a binary protein interaction map of the Giardia lid subunits. Most interactions within the Giardia proteasome lid are stronger than those within the Saccharomyces cerevisiae lid. These may compensate for the absence of Rpn12 and Sem1. A notable exception was the weaker interaction between GlRpn11 and GlRpn8, compared to the strong interaction between Rpn11-Rpn8 of yeast. The Rpn11-Rpn8 dimer provides a platform for lid assembly and their interaction involves the insertion of a methionine residue of Rpn11 into a hydrophobic pocket of Rpn8. Molecular modeling indicates that GlRpn8s pocket is wider, reconciling the experimental observation of its weak interaction with GlRpn11. This weaker interaction may have evolved to support extra proteasomal functions of GlRpn11, which localizes to multiple subcellular regions where other proteasome subunits have not been detected. One such location is the mitosome. Functional complementation in yeast shows that GlRpn11 can influence mitochondrial function and distribution. This, together with its mitosomal localization, indicates that GlRpn11 functions at the mitosome. Thus, this parasites proteasome lid has a simpler subunit architecture and structural attributes that may support dual functionalities for GlRpn11. Such parasite-specific proteasome features could provide new avenues for controlling the transmission of Giardia. 1 Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/613619v1_ufigs1.gif" ALT="Figure 0"> View larger version (33K): org.highwire.dtl.DTLVardef@989e69org.highwire.dtl.DTLVardef@1c8134aorg.highwire.dtl.DTLVardef@6a9794org.highwire.dtl.DTLVardef@5ac20_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIGiardia genome does not encode two proteasomal lid subunits: Rpn12 and Sem1 C_LIO_LIUnique interactions within the lid may compensate for the absence of these two C_LIO_LIGlRpn8:GlRpn11 weakly interacts to support GlRpn11s extra-proteasomal distribution C_LIO_LIGlRpn11 localizes at mitosomes, OZ of VD, and to the VFP C_LIO_LIThe 182-218 fragment of GlRpn11 may regulate mitosomal function C_LI

cell biology↗

bioRxiv2024

Two paralogues of N-ethylmaleimide sensitive factor: An exception to the minimal vesicular trafficking machinery of Giardia

Vesicular trafficking plays a critical role in the survival of the human gut pathogen Giardia lamblia as it drives nutrient uptake and morphological stage transition. Unlike most eukaryotes, Giardia has a minimal vesicular trafficking machinery. Herein, we report a rare exception to this minimalism wherein two paralogues of NSF, a crucial factor driving vesicular trafficking by uncoupling the cis-SNARE bundle, are present in this unicellular parasite. While GlNSF114776 and GlNSF112681 share very high sequence homology, they are likely to have distinct cellular roles as they exhibit differences in their affinities towards the Gl-SNAPs and display non-overlapping distribution in encysting trophozoites. Under multiple stress conditions (nutritional, oxidative and nitrosative), while GlNSF112681 remains at peripheral vesicles, GlNSF114776 relocalizes to the anterior flagella-associated striated fibres, indicating a possible role in regulating flagellar motility. At this location, GlNSF114776 is likely to perform a 20S complex independent function as neither Gl-SNAPs nor GlSNAREs are present there. The two paralogues are likely needed for stress adaptation as both copies have also been retained in Giardia genomes isolated from clinical samples. This non-canonical function of the GlNSF114776 may have evolved to support the unique architecture and motility of the anterior flagella.

cell biology↗

bioRxiv2022

BtuB TonB-dependent transporters and BtuG surface lipoproteins form stable complexes for vitamin B12 uptake in gut Bacteroides.

Vitamin B12 (cobalamin) is the most complex vitamin and essential for many human gut microbes. However, cobalamin is synthesised only by a limited number of bacteria, making many gut microbes dependent on scavenging to meet their cobalamin requirements. Since bacterial densities in the gut are extremely high, competition for cobalamin is severe, making it a keystone micronutrient that shapes human gut microbial communities. Contrasting with Enterobacteria like Escherichia coli which only have one outer membrane (OM) transporter dedicated to B12 uptake (BtuB), members of the dominant genus Bacteroides often encode several vitamin B12 OM transporters together with a conserved array of surface-exposed B12-binding lipoproteins. Here we show, via X-ray crystallography, cryogenic electron microscopy (cryoEM) and molecular dynamics (MD) simulations, that the BtuB1 and BtuB2 transporters from the prominent human gut bacterium Bacteroides thetaiotaomicron form stable complexes with the surface-exposed lipoproteins BtuG1 and BtuG2. The lipoproteins cap the external surface of their cognate BtuB transporter and, when open, capture B12 via electrostatic attraction. After B12 capture, the BtuG lid closes, with concomitant transfer of the vitamin to the BtuB transporter and subsequent transport. We propose that TonB-dependent, lipoprotein-assisted small molecule uptake is a general feature of Bacteroides spp. that is important for the success of this genus in colonising the human gut.

microbiology↗

bioRxiv2020

Force-Field Benchmarking by Alternatives: A Systematic Study of Ten Small α- and β-Proteins

Predicting protein structure from sequence is a central challenge of biochemistry, yet different force fields feature distinct structural biases that are hard to quantify, preventing clear assessment of results. Since structural transitions occur on milliseconds to seconds, sampling is out of reach in almost all routine studies, we inherently rely on local sampled structures, and benchmarks have emphasized the ability to reproduce these local structures. Here we approach the force field bias problem in a different way, via alternatives, by revisiting the old question: How unique is the sequence-structure relationship when studied computationally? To circumvent the sampling problem, the system-bias (specific structure choices affect apparent force field structural preference) and the complexity of tertiary structure, we studied ten small - and {beta}-proteins (20-35 amino acids) with one helix or sheet. For each of the ten sequences, we then designed alternative {beta}- or -structures and subjected all 20 proteins to molecular dynamics simulations. We apply this "alternative structure" benchmark to five of the best modern force fields: Amber ff99SB-ILDN, Amber ff99SB*-ILDN, CHARMM22*, CHARMM36, and GROMOS54A8. Surprisingly, we find that all sequences with reported {beta}-structures also feature stable native-like -structures with all five force fields. In contrast, only the alternative {beta}-1T5Q and to some extent {beta}-1CQ0 and {beta}-1V1D resembled native {beta}-proteins. With full phase space sampling being impossible in almost all cases, our benchmark by alternatives, which samples another local part of phase space in direct comparison, is a useful complement to millisecond benchmarks when these become more common.

biophysics↗

bioRxiv2019

Detection and quantification of house mouse Eimeria at the species level - challenges and solutions for the assessment of Coccidia in wildlife

Detection and quantification of coccidia in studies of wildlife can be challenging. Therefore, the prevalence of coccidia is often not assessed at the parasite species level in non-livestock animals. Parasite species-specific prevalences are especially important when studying evolutionary questions in wild populations. We tested whether increased host population density increases the prevalence of individual Eimeria species at the farm level, as predicted by epidemiological theory. We studied free-living commensal populations of the house mouse (Mus musculus) in Germany and established a strategy to detect and quantify Eimeria infections. We show that a novel diagnostic primer targeting the apicoplast genome (Ap5) and coprological assessment after flotation provide complementary detection results increasing sensitivity. Genotyping PCRs confirm detection in a subset of samples and cross-validation of different PCR markers does not indicate a bias towards a particular parasite species in genotyping. We were able to detect double infections and to determine the preferred niche of each parasite species along the distal-proximal axis of the intestine. Parasite genotyping from tissue samples provides an additional indication for the absence of species bias in genotyping amplifications. Three Eimeria species were found infecting house mice at different prevalences: Eimeria ferrisi (16.7%; 95% CI 13.2 - 20.7), E. falciformis (4.2%; 95% CI 2.6 - 6.8) and E. vermiformis (1.9%; 95% CI 0.9 - 3.8). We also find that mice in dense populations are more likely to be infected with E. falciformis and E. ferrisi.\n\nWe provide methods for the assessment of prevalences of coccidia at the species level in rodent systems. We show and discuss how such data can help to test hypotheses in ecology, evolution and epidemiology on a species level.

microbiology↗