Biology subjects

Chakrabarti, M.

Publications and source records attributed to Chakrabarti, M..

8 recordsLinked to original sources

bioRxiv2026

Integrative transcriptome analysis reveals distinct and common stress-responsive regulatory networks driving drought and heat responses in sorghum

Drought and heat are key abiotic stresses that severely affect crop production. Sorghum (Sorghum bicolor L. Moench), a drought-resilient cereal, serves as a model for studying abiotic stress responses in cereals. To elucidate the molecular responses to individual drought and heat stress, we conducted a transcriptome analysis of sorghum seedlings subjected to individual drought and heat treatment for 1h and 6h. Our analysis revealed distinct as well as overlapping patterns of gene expression between the two stresses at two time points, with a larger transcriptional shift observed at 6h of drought and heat treatment. We identified 410 and 4,136 differentially expressed genes (DEGs) in response to 1 and 6 h of drought treatments, respectively, whereas 1,807 and 2,776 DEGs were identified under 1 and 6 h of heat treatments. Among all four stress conditions, 32 common DEGs were identified. Genes encoding ion transporters were enriched among DEGs common in both 1h stress treatments. Genes involved in ribosome biogenesis were enriched among the common DEGs in both 6 h stress treatments. Specifically, drought-regulated genes were involved in ribosome biogenesis, whereas heat-induced genes were involved in protein folding and histone modifications. Enrichment of ribosome biogenesis in different sets of DEGs suggests that maintaining a balance between growth and survival by regulating protein synthesis may play a role in defining early stress response in sorghum. 6h of drought resulted in strong upregulation of abscisic acid and jasmonate-associated genes. Genes encoding bZIP, MYB, and HSF transcription factors displayed both stress-specific and common temporal regulation, suggesting vital regulatory roles of these transcription factors in mediating responses to drought and heat treatments. Extensive downregulation of genes encoding core histone proteins, in response to both 6h of drought and heat stress, was detected, indicating possible roles of chromatin structure and accessibility in mediating early responses to drought and heat treatments in sorghum.

plant biology↗

bioRxiv2026

Alternative polyadenylation and the sex-specific gene expression program in hemp

Hemp (Cannabis sativa) produces a wide array of medicinally significant compounds, including cannabidiol (CBD). These compounds are predominantly synthesized in female hemp inflorescences. The proposed research utilizes next-generation sequencing-based transcriptome analysis using a 3{square}-end-directed approach to identify differentially expressed genes between male and female hemp plants at the early vegetative stage. 886 differentially expressed genes (DEGs) were identified, a majority of which were upregulated in males compared to females. We hypothesized that alternative RNA processing contributes to sex-specific gene expression. To this end, 932 genes were identified that exhibited significant changes in poly(A) site usage when comparing males and females. These genes were much more likely to be differentially expressed, supportive of this hypothesis. Males tend to have longer 3 UTRs with canonical motifs found in the Near-Upstream Elements (NUE), compared to the shorter 3 UTRs in females, which have A-rich motifs near the cleavage site. This suggests that polyadenylation remodels hemp mRNAs with distal poly(A) sites being preferred in males. To further investigate when this sex-specific gene expression program is established, RNA was isolated from plants at various developmental stages, such as developing seeds, four-day-old seedlings, and different developmental stages up to four weeks after sowing. Diagnostic male-specific genes were analyzed using RT/PCR. The results indicate that sex-specific gene expression is not evident in seeds but rather is set during or after germination. SignificanceO_LIHemp males tend to have longer 3 UTRs with canonical motifs found in the Near-Upstream Elements (NUE), compared to the shorter 3 UTRs in females, which have A-rich motifs near the cleavage site. C_LIO_LIThe sex-specific gene expression program is not yet established in mature seed but is set in the time between germination and 4 days of growth. C_LI

plant biology↗

bioRxiv2026

Diet-Associated Differences in the Rumen Microbiome and Resistome of Bangladeshi Cattle

Diet influences the composition, diversity, and functional capacity of the cattle gut microbiome. However, the extent to which feeding practices affect the microbial community and resistome under real-world conditions remains poorly understood, particularly in low- and middle-income settings. Here, we applied metagenomics to fecal samples from Bangladeshi cattle fed either a natural or a mixed diet to examine differences in microbial composition, functional potential, and resistome associated with feed type. Natural-fed cattle harbored higher microbial diversity and distinct bacterial phyla, including Bacteroidota, Campylobacteriota, and Mycoplasmatota. Acinetobacter, Aliarcobacter, Comamonas, Dysosmobacter, and Sharpea were enriched in natural-fed cattle, whereas Anaerotignum, Aristaeella, Oscillibacter, and Clostridium were more abundant in the mixed-fed group. Notably, the emerging zoonotic genus Aliarcobacter was detected in the natural-fed cohort. Alpha diversity analysis showed higher richness and evenness in natural-fed cattle, and a clear separation between dietary groups in beta diversity analysis (PERMANOVA, p = 0.01). Differential analysis identified Oscillibacter ruminantium as a biomarker of natural feeding, while Succinivibrio faecicola and Anaerovibrio slackiae for mixed feeding. Resistome profiles demonstrated clear differences. Mixed-fed cattle showed a consistent enrichment of tetracycline resistance genes, whereas the natural-fed group displayed a more variable resistome. Functional analysis suggested diet-associated differences in metabolic potential, with glutathione metabolism enriched in natural-fed cattle (p<0.05) and bile secretion and fatty acid metabolism moderately enriched in the mixed-fed group. These findings indicate that feeding practices are associated with differences in rumen microbial communities and resistome profiles in Bangladeshi cattle, providing baseline insights into microbiome-resistome relationships under field conditions.

microbiology↗

bioRxiv2025

Smooth Muscle Cell-Specific TGFβ2 Protects Against Thoracic Aortic Aneurysm and Dissection in Mice

ObjectiveThoracic aortic aneurysm and dissection (TAAD) are major complications of Loeys- Dietz syndrome caused by heterozygous TGFB2 mutations. While Tgfb2 knockout mice die at birth and adult heterozygotes develop late, non-dissecting or non-rupturing aneurysms, the role of vascular smooth muscle cell (SMC)-derived TGF{beta}2 in postnatal aortic homeostasis and disease remains undefined. Approach and ResultsWe generated tamoxifen-inducible, SMC-specific Tgfb2 conditional knockout mice (Tgfb2cKO) by crossing Tgfb2flox alleles with Myh11CreERT2 and ROSAmT/mG lineage reporter mice. Tgfb2 deletion was induced at 4 weeks of age. Tgfb2cKO mice developed rapidly progressive aneurysms involving both ascending and descending aortas, with intramural dissection and/or rupture at the proximal descending aorta. Lineage tracing confirmed loss of Tgfb2-deficient SMCs during disease progression. Histological and morphometric analyses revealed elastic fiber fragmentation, SMC loss and de-differentiation, medial thickening, adventitial fibrosis, and accumulation of collagen and proteoglycans. Molecular profiling demonstrated reduced expression of SMC contractile genes (Acta2, Myh11), increased fibrillar collagen (Col1a1) expression, early suppression of SMAD2/3 phosphorylation and increased non-canonical TGF{beta} signaling via p38 and pERK1/2 MAPK pathways. ConclusionsThese findings demonstrate that TGF{beta}2 derived from vascular SMCs is essential for postnatal aortic wall homeostasis by preserving SMC differentiation, maintaining extracellular matrix integrity, and supporting and preserving a proper balance of both canonical and non-canonical TGF{beta} signaling. Loss of SMC-specific Tgfb2 precipitates medial degeneration, aneurysm formation, dissection, and rupture, providing direct mechanistic insight into TGFB2-associated aortopathy and establishing a robust novel genetic mouse model for evaluating targeted therapies in TAAD. HighlightsO_LIPostnatal, SMC-specific Tgfb2 deletion in mice caused rapidly progressive thoracic aortic aneurysms, dissections, and fatal rupture. C_LIO_LILoss of Tgfb2 disrupts SMC contractile phenotype and ECM homeostasis, leading to medial degeneration, elastin fragmentation, and abnormal collagen/proteoglycan accumulation. C_LIO_LICanonical TGF{beta}-SMAD signaling is suppressed, while MAPK pathways are activated, indicating ligand-specific signaling imbalance. C_LIO_LIFindings highlight TGF{beta}2 as a central regulator of postnatal aortic homeostasis and suggest that targeted ligand-specific therapeutic strategies may better preserve aortic wall stability. C_LI SignificanceThis study identifies smooth muscle cell-derived TGF{beta}2 as a critical, nonredundant regulator of postnatal aortic wall integrity, linking its loss to thoracic aortic aneurysm, dissection, and rupture, and highlighting TGF{beta}2 ligand-specific signaling as a targeted therapeutic target. Graphical AbstractSmooth muscle cell-derived TGF{beta}2 maintains postnatal aortic wall homeostasis by preserving contractile gene expression, elastin architecture, and balanced ECM remodeling. Conditional deletion of Tgfb2 in SMCs shifts signaling from canonical SMAD2/3 to MAPK pathways, leading to medial degeneration, progressive aneurysm, dissection, and rupture--highlighting TGF{beta}2 as a nonredundant, ligand-specific regulator and potential therapeutic target in thoracic aortopathy. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=163 SRC="FIGDIR/small/679917v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@1ef41d3org.highwire.dtl.DTLVardef@ca8feborg.highwire.dtl.DTLVardef@aebce4org.highwire.dtl.DTLVardef@1f3599b_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2025

Nucleotide-resolution Mapping of RNA N6-Methyladenosine (m6A) modifications and comprehensive analysis of global polyadenylation events in mRNA 3' end processing in malaria pathogen Plasmodium falciparum

Plasmodium falciparum is an obligate human parasite of the phylum Apicomplexa and is the causative agent of the most lethal form of human malaria. Although N6-methyladenosine modification is thought to be one of the major post-transcriptional regulatory mechanisms for stage-specific gene expression in apicomplexan parasites, the precise base position of m6A in mRNAs or noncoding RNAs in these parasites remains unknown. Here, we report global nucleotide-resolution mapping of m6A residues in P. falciparum using DART-seq technology, which quantitatively displayed a stage-specific, dynamic distribution pattern with enrichment near mRNA 3 ends. In this process we identified 894, 788, and 1,762 m6A-modified genes in Ring, Trophozoite and Schizont stages respectively, with an average of 5-7 m6A sites per-transcript at the individual gene level. Notably, several genes involved in malaria pathophysiology, such as KAHRP, ETRAMPs, SERA and stress response genes, such as members of Heat Shock Protein (HSP) family are highly enriched in m6A and therefore could be regulated by this RNA modification. Since we observed preferential methylation at the 3 ends of P. falciparum transcripts and because malaria polyadenylation specificity factor PfCPSF30 harbors an m6A reader YTH domain, we reasoned that m6A might play an important role in 3-end processing of malaria mRNAs. To investigate this, we used two complementary high-throughput RNA 3-end mapping approaches, which provided an initial framework to explore potential roles of m6A in the regulation of alternative polyadenylation (APA) during malaria development in human hosts.

genomics↗

bioRxiv2024

Cryo-EM Structure of AAA + ATPase Thorase Reveals Novel Helical Filament Formation

The AAA+ (ATPases associated with a variety of cellular activities) ATPase, Thorase, also known as ATAD1, plays multiple roles in synaptic plasticity, mitochondrial quality control and mTOR signaling through disassembling protein complexes like AMPAR and mTORC1 in an ATP-dependent manner. The Oligomerization of Thorase is crucial for its disassembly and remodeling functions. We show that wild-type Thorase forms long helical filaments in vitro, dependent on ATP binding but not hydrolysis. We report the Cryogenic Electron Microscopy (cryo-EM) structure of the Thorase filament at a resolution of 4 [A], revealing the dimeric arrangement of the basic repeating unit that is formed through a distinct interface compared to the hexameric MSP1/ATAD1E193Q assembly. Structure-guided mutagenesis confirms the role of critical amino acid residues required for filament formation, oligomerization and disassembly of mTORC1 protein complex. Together, our data reveals a novel filament structure of Thorase and provides critical information that elucidates the mechanism underlying Thorase filament formation and Thorase-mediated disassembly of the mTORC1 complex.

biochemistry↗

bioRxiv2022

NIS metastable intermediates provide insights into conformational transition between principal thermodynamic states

The Sodium/Iodide Symporter (NIS), a thirteen-helix transmembrane protein found in the thyroid and other tissues, transports iodide, a required constituent of thyroid hormones T3 and T4. Despite extensive experimental information and clinical data, structural details of the intermediate microstates comprising the conformational transition of NIS between its inwardly and outwardly open states remain unresolved. We present data from a combination of enhanced sampling and transition path molecular dynamics (MD) simulations that elucidate the nature of the principal intermediate states comprising the transition between the inwardly and outwardly open metastable states of fully bound and unbound NIS under an enforced ionic gradient. Our findings suggest that in both the absence and presence of bound physiological ions, NIS principally occupies a proximally inward to inwardly open state, whereas when fully bound, it also occupies a rare but thermodynamically favorable inward occluded state. The results of this work provide novel insight into the populations of NIS intermediates and the free energy landscape comprising the conformational transition, adding to a mechanistic understanding of NIS ion transport. Moreover, the knowledge gained from this approach can serve as a basis for studies of NIS mutants to target therapeutic interventions. O_FIG O_LINKSMALLFIG WIDTH=192 HEIGHT=200 SRC="FIGDIR/small/512170v1_ufig1.gif" ALT="Figure 1"> View larger version (80K): org.highwire.dtl.DTLVardef@e826e0org.highwire.dtl.DTLVardef@1504d00org.highwire.dtl.DTLVardef@ef7104org.highwire.dtl.DTLVardef@1e4c95f_HPS_FORMAT_FIGEXP M_FIG For Table of Contents Only C_FIG

biophysics↗

bioRxiv2021

Effects of Emodin, a Plant-Derived Anthraquinone, on TGFβ1-Induced Cardiac Fibroblast Activation and Function

Cardiac fibrosis accompanies a number of pathological conditions and results in altered myocardial structure, biomechanical properties and function. The signaling networks leading to fibrosis are complex, contributing to the general lack of progress in identifying effective therapeutic approaches to prevent or reverse this condition. Several studies have shown protective effects of emodin, a plant-derived anthraquinone, in animal models of fibrosis. A number of questions remain regarding the mechanisms whereby emodin impacts fibrosis. TGF-{beta}1 is a potent stimulus of fibrosis and fibroblast activation. In the present study, experiments were performed to evaluate the effects of emodin on activation and function of cardiac fibroblasts following treatment with TGF-{beta}1. We demonstrate that emodin attenuates TGF-{beta}1-induced fibroblast activation and collagen accumulation in vitro. Emodin also inhibits activation of several canonical (SMAD2/3) and non-canonical (Erk1/2) TGF-{beta} signaling pathways, while activating the p38 pathway. These results suggest that emodin may provide an effective therapeutic agent for fibrosis that functions via specific TGF-{beta} signaling pathways.

cell biology↗