Biology subjects

Haque, S.

Publications and source records attributed to Haque, S..

12 recordsLinked to original sources

bioRxiv2026

phyB photobodies display molecular memory, regulating light signaling transcriptional states through phase separation.

Phytochrome B is a crucial red and far-red light sensor, which controls plant development and environmental responses to light and temperature. In the nucleus, phyB forms phase separated condensates, also called photobodies, consisting of various transcriptional regulators and transcription factors. phyB photobodies can form or disperse depending on the amount of light, the light quality, or ambient temperature. However, the biological relevance for forming photobodies is still unclear. In recent years the study of condensates has given rise to the idea that condensates can act as molecular memory, either due to long equilibration timescales arising from strong interactions can kinetically trap a mixture in a phase-separated state beyond the equilibrium coexistence line, or from phase-separation dependent modification processes or transcriptional regulation. Here, we hypothesize that the formation of phyB photobodies and the associated sequestration of signaling molecules allows for the formation of cell-type specific memory about light conditions. To address this hypothesis, we first developed a live imaging setup of phyB photobodies which shows that they do not follow classic liquid-liquid phase separation dynamics, but instead have a restriction on their size, intensity and minimum number. Fluorescence recovery after photobleaching (FRAP) then showed that photobodies between cell types have different levels of mobilities and diffusivities, suggesting that they are more stable in darkness or high red light, versus low red light. These differences in phyB photobody stability between cell types were also confirmed through whole-mount confocal imaging and single-nucleus transcriptomics in the same light-perturbation series. Through sci-Seq single nucleus spatial transcriptomics of the cotyledon in this light perturbation series, we identify a photobody-associated transcriptional cluster of nuclei that regulates photosynthesis, circadian rhythm, and RNA processing; the phyB photobody likely promotes its own stability by regulating TZP and PCH1 expression. The correlation between photobodies and transcriptional regulation shows how phyB condensates can provide cell-type specific light responses and exhibit signaling memory in changing environmental conditions.

cell biology↗

bioRxiv2026

Cytokinin-mediated repression of jacalin lectins reinforces root immunity

The root cap is essential for perceiving environmental cues surrounding the root. However, the molecular mechanisms underlying root cap-mediated immunity and how it defends against invading pathogens remain largely unresolved. Our results indicate that cytokinin plays a major role in regulating soil-borne pathogen such as Ralstonia pseudosolanacearum load around the root and root cap. As Ralstonia populations increase, cytokinin signalling is activated and represses the expression of its downstream signalling targets such as root cap-specific proteins JAL10 and JAL20, to impart the tolerance against the Ralstonia. The functional analysis jacalin-associated lectin family proteins JAL10 and JAL20, revealed that loss-of-function leads to enhance tolerance to Ralstonia whereas gain-of-function leads to susceptibility compared to Col-0. Our Glycoproteomic and metabolomic analyses indicate that JAL10 and JAL20 act as negative regulators of cell wall remodelling and likely to promotes cell wall thickening, thereby enhancing resistance to soil-borne infections. The knockdown of ortholog of JAL protein in Tomato also revealed its conserved function in imparting tolerance to Ralstonia pseudosolanacearum. Further we also show downregulation of JALs by other soil-borne pathogen infection, suggesting that cytokinin might protecting the vulnerable areas of root tip regions by regulating the expression of root cap-specific JALs and thereby fortifying the cell wall.

plant biology↗

bioRxiv2026

Landscape viromics of introduced honeybees and bumblebees reveal distinct environmental and host-specific effects

Understanding how viral communities vary across co-occurring hosts and environments is essential for assessing species-specific viral risks under changing land use and climate. This is particularly relevant for managing introduced bees, which face persistent viral threats themselves, as well as transmitting plant viruses. Here, we compare RNA viromes of the long-established honeybee (Apis mellifera, introduced to Tasmania in 1831) and the more recent invader, the bumblebee (Bombus terrestris, invasive since 1992), across 14 Tasmanian sites - an island still free of the viral vector, Varroa destructor. Using a metatranscriptomic approach on total RNA from whole bees, we identified insect- and plant-associated viruses and inferred phylogenetic patterns of insect viral sharing, divergence, and potential cross-species transmission. We also assessed spatial and environmental drivers of viral composition, diversity, and richness. Geographic longitude, precipitation, temperature, and pasture percentage influenced the total, insect-, and plant-associated viromes of B. terrestris. In contrast, for A. mellifera, only precipitation and temperature were associated with insect and plant viral alpha diversity and community composition. Phylogenetic analyses revealed that Black Queen Cell virus in A. mellifera from Tasmania has diverged from mainland Australian sequences, and two distinct sub-strains of Lake Sinai virus 1 were shared by both bee species. Lake Sinai virus 3 showed evidence of interspecies transmission between A. mellifera and B. terrestris. Notably, this study provides the first detection of Moku virus in Australian bees and globally in bumblebees, suggesting potential interspecies transmission among social Hymenoptera. Overall, our findings demonstrate local viral diversification and reveal that B. terrestris viromes are more strongly shaped by environmental factors than those of A. mellifera, underscoring the importance of monitoring invasive pollinators as reservoirs and vectors of viral emergence.

evolutionary biology↗

bioRxiv2026

Metabolic Repression of Autophagy Drives Inflammation, Pain, and Malodor in Hidradenitis Suppurativa

Hidradenitis suppurativa (HS) is a debilitating and underdiagnosed inflammatory skin disease with limited therapeutic options due to an incomplete understanding of its molecular and immunopathogenic basis. Using an integrated multi-omics approach, we delineate convergent pathways linking dysregulated autophagy, malodour, and pain in HS. Lesional tissues exhibited sustained autophagy repression, marked by increased expression and activation of mTOR and ZKSCAN3, reduced levels of autolysosome-promoting metabolites {beta}-hydroxybutyrate and nicotinamide riboside, and accumulation of fructose-1,6-bisphosphate, a negative regulator of AMPK. Transcriptomic analyses identified cadaverine derivatives as key metabolic drivers of keratinocyte reprogramming, inducing gene networks associated with hyperproliferation, inflammation, fibrosis, nociception, and the characteristic carrion-like odour of HS. Concordantly, ATAC-seq revealed increased chromatin accessibility at loci encoding TRP channels and histamine receptors, consistent with heightened nociceptive signalling. Multi-layered proteomics, phospho-proteomics, kinomics, and spatial proteomics analyses, validated by high-resolution confocal imaging, demonstrated elevated mTOR (Ser2448), ZKSCAN3, and P62, alongside reduced LAMP1, across keratinocytes and immune cell populations including CD4 T cells, CD56 NK cells, and CD68 macrophages. Inhibition of mTOR normalized transcriptional programs and cytokine production linked to NLRP3 inflammasome, restoring tissue homeostasis. Collectively, these findings identify a metabolically reinforced mTOR-ZKSCAN3 axis in autophagy dysregulation and cadaverine-driven epithelial reprogramming as central mechanisms sustaining inflammation, pain, and fibrosis in HS. HighlightsO_LIWe identified BCAAs, BHB, NR, and FBP as key metabolites linked to mTOR activation and autophagy dysregulation in HS. C_LIO_LIPolyamines like cadaverine and putrescine, their acetylated derivatives, LPCs, and endocannabinoid dysregulation likely drive malodor and pain in HS. C_LIO_LICadaverine treatment of Ker-CT cells induces HS-associated gene signatures of inflammation, fibrosis, and pain. C_LIO_LIIdentification of an HS macrophage subpopulation expressing ZKSCAN3 with activated mTOR and impaired autophagy. C_LI

immunology↗

bioRxiv2025

Activated fatty acid synthesis pathway in macrophages propagates pathogenic fibroblast expansion after myocardial infarction

Metabolic pathways, such as fatty acid oxidation and oxidative phosphorylation, can modulate inflammatory cells. However, little is known about the effects of the fatty acid synthesis pathway in macrophages on inflammation and cardiac remodeling after myocardial infarction (MI). Using spatial metabolomics, here we show that cardiac macrophages residing in the infarct synthesize de novo fatty acids and increase the production of fatty acid enzymes including ACLY and FASN. Mice deficient in myeloid Acly and Fasn have improved cardiac function after MI and reduced fibrosis. Combining Cleavage Under Targets and Release Using Nuclease (CUT&RUN), RNA sequencing analysis of Acly-/-macrophages, and macrophage-specific in vivo gene silencing, we demonstrate that ACLY acetylates the promoter region of the upstream regulator Krt17, which drives the production of pro-fibrotic cytokines, including IL-33. Single-cell RNA sequencing of cardiac fibroblasts shows that the expansion of a population of fibroblasts (Fibroblast 5) expressing high levels of extracellular matrix genes after MI is confined in the absence of macrophage Acly. Finally, the analysis of spatial multi-omics data of human hearts with MI uncovers myofibroblasts with the Fibroblast 5 gene signature. These myofibroblasts are located near cardiac macrophages expressing high levels of ACLY. In summary, we show that macrophage ACLY and FASN are deleterious in MI pathogenesis.

immunology↗

bioRxiv2024

Landscape-wide metabarcoding of the invasive bumblebee (Bombus terrestris) shows interactions among the gut microbiome and pollenbiome

Many species of social insects introduced to regions beyond their native ranges have become highly invasive. The introduction of the eusocial European buff-tailed bumblebee, Bombus terrestris, to the island of Tasmania (Australia) [~]30 years ago is of concern due to its ecological impacts and its potential to spill over pathogens to native bees or commercially important honeybees. The health of B. terrestris is intricately connected with its gut microbiome and diet; however, environmental variables may also interact, particularly during invasion into novel environments. Using landscape-wide sampling and a metabarcoding approach to characterize the gut bacteria (16S rRNA) and diet composition from foraged pollen (ITS2: floristic diversity of pollen baskets), this study investigates how the gut microbiota of B. terrestris workers is affected by nutritional diversity ( pollenbiome) and environmental variation across diverse landscapes of its invasive range in Tasmania. Gut bacterial community composition and diversity were significantly predicted by site annual precipitation and percentage of pasture. Further, a positive interaction between site annual precipitation and site annual temperature significantly predicted gut bacterial diversity. The interaction effect of pollen diversity and average summer wind velocity was also significantly and positively related to gut bacterial diversity. Following comparison of Akaike information criterion (AIC) and sum of weights, the percentage of pasture was identified as the most strongly weighted variable, which, along with pollen diversity, had a negative impact on gut bacterial diversity. These insights help to uncover how environmental interactions affect the gut microbiome of B. terrestris in an invaded landscape with novel nutritional resources. This knowledge contributes to understanding the factors that predict the spread and persistence of invasive bumblebees.

ecology↗

bioRxiv2023

Anti-nuclear antibody (ANA) detection in culture supernatant of cloned B cells

Anti-nuclear antibodies (ANA) of individuals with SLE contribute to disease pathogenesis and tissue injury. Systematic analysis of the fine specificity of ANA produced by individual B cells has been limited, in part, to the low concentration of immunoglobulin in single B cell cultures. We modified single B cell culture methods and developed an ANA ELISA to detect ANA at very low levels (15.0 ng/ml) of IgM in the supernatant of clonally expanded B cell cultures. This approach allows for the analysis of ANA reactivity of the IgM produced by approximately 60% of the single sorted naive B cells expanded in culture and permits a relatively high throughput evaluation at the single cell level of the ANA reactivity of naive B cells of healthy individuals and patients with autoimmune diseases.

immunology↗

bioRxiv2021

Metformin-mediated mitochondrial protection post-cardiac arrest improves EEG activity and confers neuroprotection and survival benefit

Cardiac arrest (CA) produces global ischemia/reperfusion injury resulting in substantial multiorgan damage. There are limited efficacious therapies to save lives despite CA being such a lethal disease process. Surviving patients suffer extensive brain damage with mitochondrial dysfunction implicated as a major source of injury. Metformin, a first-line treatment for diabetes, has also shown promising results in other diseases and is known to interact with mitochondria. In the present study, we evaluated the therapeutic benefits of metformin administration immediately after resuscitation using a 10 min asphxyial-CA rat model. This is the first study to show that metformin treatment post-CA a) improves survival and neurologic function, b) potentiates early normalization of brain electrophysiologic activity, and c) protects mitochondrial function with a reduction in apoptotic brain injury. Overall, as an effective and safe drug, metformin has the potential to be an easily translatable intervention for improving survival and preventing brain damage after CA. SummaryBrain damage post-cardiac arrest is a major cause of death; metformin protects brain mitochondria and improved survival and brain function.

neuroscience↗

bioRxiv2020

Exosomes are predominantly loaded with mRNA transcript encoding cytoplasmic proteins and exclude mRNA transcript encoding nuclear proteins

Exosomes are nanovesicles ([~]30-150 nm diameters) released via an endocytic pathway in almost all mammalian cell types. Exosomes are composed of a lipid bilayer membrane that encloses RNA, miRNA, proteins and DNA. This manuscript unravels how exosome cargo is collected by a highly precise process delineating two separate mRNA transcript entities encoding cytoplasmic and nuclear proteins separately. Ultracentrifuge isolated exosomes were directly converted into cDNA (Exo-cDNA), by a method developed in our laboratory. Cellular RNA was extracted from each cell line and cDNA was prepared (Cell-cDNA). We amplified mRNA transcripts translating cytoplasmic proteins CD10 and CXCR4 and mRNA transcripts translating nuclear proteins such as proliferating cell nuclear antigen (PCNA), CREB-BP, activation induced cytidine deaminase (AID), and terminal deoxynucleotidyl transferase (TdT). We amplified all four different mRNA transcripts (PCNA, CREB-BP, AID, and TdT) from cellular cDNA but none from exosomal cDNA (Exo-cDNA). These findings suggest that exosomes carry mRNA transcripts encoding cytoplasmic proteins only but mRNA transcripts encoding nuclear proteins could not be detected. This important observation could prove to be crucial for the exosome research community since it sheds light on one of the limitations relating to the use of exosomes as biomarkers in cancer biology and other diseases. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=118 SRC="FIGDIR/small/227223v2_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@102c790org.highwire.dtl.DTLVardef@17bcabdorg.highwire.dtl.DTLVardef@3b5ac0org.highwire.dtl.DTLVardef@c303c8_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2020

Computer vision approach to characterize size and shape phenotypes of horticultural crops using high-throughput imagery

For many horticultural crops, variation in quality (e.g., shape and size) contribute significantly to the crops market value. Metrics characterizing less subjective harvest quantities (e.g., yield and total biomass) are routinely monitored. In contrast, metrics quantifying more subjective crop quality characteristics such as ideal size and shape remain difficult to characterize objectively at the production-scale due to the lack of modular technologies for high-throughput sensing and computation. Several horticultural crops are sent to packing facilities after having been harvested, where they are sorted into boxes and containers using high-throughput scanners. These scanners capture images of each fruit or vegetable being sorted and packed, but the images are typically used solely for sorting purposes and promptly discarded. With further analysis, these images could offer unparalleled insight on how crop quality metrics vary at the industrial production-scale and provide further insight into how these characteristics translate to overall market value. At present, methods for extracting and quantifying quality characteristics of crops using images generated by existing industrial infrastructure have not been developed. Furthermore, prior studies that investigated horticultural crop quality metrics, specifically of size and shape, used a limited number of samples, did not incorporate deformed or non-marketable samples, and did not use images captured from high-throughput systems. In this work, using sweetpotato (SP) as a use case, we introduce a computer vision algorithm for quantifying shape and size characteristics in a high-throughput manner. This approach generates 3D model of SPs from two 2D images captured by an industrial sorter 90 degrees apart and extracts 3D shape features in a few hundred milliseconds. We applied the 3D reconstruction and feature extraction method to thousands of image samples to demonstrate how variations in shape features across sweetptoato cultivars can be quantified. We created a sweetpotato shape dataset containing sweetpotato images, extracted shape features, and qualitative shape types (U.S. No. 1 or Cull). We used this dataset to develop a neural network-based shape classifier that was able to predict Cull vs. U.S. No. 1 sweetpotato with 84.59% accuracy. In addition, using univariate Chi-squared tests and random forest, we identified the most important features for determining qualitative shape (U.S. No. 1 or Cull) of the sweetpotatoes. Our study serves as the first step towards enabling big data analytics for sweetpotato agriculture. The methodological framework is readily transferable to other horticultural crops, particularly those that are sorted using commercial imaging equipment.

bioengineering↗

bioRxiv2020

Silencing of Exosomal miR-181a reverses Pediatric Acute Lymphocytic Leukemia Cell Proliferation

Exosomes are cell-generated nano-vesicles (30-150 nm) found in most biological fluids. Major components of their cargo are lipids, proteins, RNA, DNA, and non-coding RNAs. Exosomes carry the fingerprint of the parental tumor and as such, may regulate tumor growth, progression and metastasis. We investigated the impact of exosomes on cell proliferation in pediatric acute lymphocytic leukemia and its reversal by silencing of exo-miR-181a.We isolated exosomes from serum of acute lymphocytic leukemia pediatric patients (Exo-PALL) and conditioned medium of leukemic cell lines (Exo-CM) by ultracentrifugation. Gene expression was carried out by q-PCR. We found that Exo-PALL promote cell proliferation in leukemic B cell lines as well as in the control B cell line. This exosome-induced cell proliferation is a precise event with up-regulation of proliferative (PCNA, Ki-67) and pro-survival genes (MCL-1, and BCL2), and suppression of pro-apoptotic genes (BAD, BAX). Exo-PALL and Exo-CM both show over expression of miR-181a compared to controls (Exo-HD). Specific silencing of exosomal miR-181a using a miR-181a inhibitor confirms that miR-181a inhibitor treatment reverses Exo-PALL/Exo-CM-induced leukemic cell proliferation in vitro. Altogether, this study suggests that exosomal miR-181a inhibition can be a novel target for growth suppression in pediatric lymphatic leukemia.

cancer biology↗

bioRxiv2019

Quantitative assessment of fecal contamination in multiple environmental sample types in urban communities in Dhaka, Bangladesh using SaniPath microbial approach

Rapid urbanization has led to a growing sanitation crisis in urban areas of Bangladesh and potential exposure to fecal contamination in the urban environment due to inadequate sanitation and poor fecal sludge management. Limited data are available on environmental fecal contamination associated with different exposure pathways in urban Dhaka. We conducted a cross-sectional study to explore the magnitude of fecal contamination in the environment in low-income, high-income, and transient/floating neighborhoods in urban Dhaka. Ten samples were collected from each of 10 environmental compartments in 10 different neighborhoods (4 low-income, 4 high-income and 2 transient/floating neighborhoods). These 1,000 samples were analyzed with the IDEXX-Quanti-Tray technique to determine most-probable-number (MPN) of E. coli. Samples of open drains (6.91 log10 MPN/100 mL), surface water (5.28 log10 MPN/100 mL), floodwater (4.60 log10 MPN/100 mL), produce (3.19 log10 MPN/serving), soil (2.29 log10 MPN/gram), and street food (1.79 log10 MPN/gram) had the highest mean log10 E. coli contamination compared to other samples. The contamination concentrations did not differ between low-income and high-income neighborhoods for shared latrine swabs, open drains, municipal water, produce, and street foodsamples. E. coli contamination were significantly higher (p <0.05) in low-income neighborhoods compared to high-income for soil (0.91 log10 MPN/gram, 95% CI, 0.39, 1.43), bathing water (0.98 log10 MPN/100 mL, 95% CI, 0.41, 1.54), non-municipal water (0.64 log10 MPN/100 mL, 95% CI, 0.24, 1.04), surface water (1.92 log10 MPN/100 mL, 95% CI, 1.44, 2.40), and floodwater (0.48 log10 MPN/100 mL, 95% CI, 0.03, 0.92) samples. E. coli contamination were significantly higher (p<0.05) in low-income neighborhoods compared to transient/floating neighborhoods for drain water, bathing water, non-municipal water and surface water. Future studies should examine behavior that brings people into contact with the environment and assess the extent of exposure to fecal contamination in the environment through multiple pathways and associated risks.

microbiology↗