Biology subjects

Talukdar, S.

Publications and source records attributed to Talukdar, S..

6 recordsLinked to original sources

bioRxiv2026

Mechanistic insights into proteolytic activation ofmembrane-bound NAC transcription factor SlNACMTF3 intomato plants under heat stress

Stress is perceived at the cellular membrane, where membrane-bound transcription factors (MTFs) are activated, initiating a rapid gene-regulation cascade. We previously demonstrated the multifaceted role of tomato MTF, SlNACMTF3, in regulating expression of biotic and abiotic stress responsive genes. However, the molecular mechanism underlying its activation following stress perception remained unknown. Here, we show that the membrane rhomboid protease SlRP3 recognizes an ISK motif near the transmembrane domain of SlNACMTF3 for cleavage and releasing the transcription factor from the membrane. SlRP3 and SlNACMTF3 co-localize within the same plasma membrane microdomain and interact directly. Molecular dynamics simulations supported the proposed mechanism, in which heat-induced conformational switching of SlRP3, driven by reorientation of the L5 loop, enhances substrate accessibility and proteolytic activity. Furthermore, mutation of key SlRP3 residues involved in substrate interaction impaired SlNACMTF3 activation and reduced the expression of stress33 responsive genes. Analysis with SlNACMTF3-overexpressing tomato lines and SlRP3 transient knockdown leaves further revealed that transcription factor activation, stress35 responsive gene regulation, and cellular ROS detoxification occur coordinately. Collectively, these findings provide mechanistic insight into stress-triggered SlNACMTF3 activation and identify SlRP3 as a novel membrane-associated stress sensor that activates a major transcriptional regulator to enhance stress preparedness in economically important tomato plants.

plant biology↗

bioRxiv2026

Influenza A virus H5N1 genotypes B3.13 and D1.1 show temperature-dependent restriction of replication in primary human respiratory epithelial cell cultures derived from the upper and lower respiratory tract.

H5N1 clade 2.3.4.4b avian influenza A viruses pose a significant threat to wild animal populations, domesticated animals, and potentially, the human population. For H5N1s to infect and transmit among mammalian species, mutations for improved utilization of mammalian receptors and enhanced replication at the lower temperatures of the upper respiratory tract need to be acquired. A human H1N1pdm09-like virus was compared to H5N1 genotypes B3.13 and D1.1 for replication at 33{o}C, 37{o}C, and 39{o}C - temperatures consistent with the upper and lower respiratory tract in humans, and dairy cow udder tissue. All H5N1 viruses had increased plaque sizes on MDCK cells at 37{o}C and 39{o}C compared to H1N1pdm09. In primary, differentiated human nasal and bronchial epithelial cultures, all H5N1 viruses show restricted infectious virus production compared to H1N1 at 33{o}C. While H5N1 D1.1 also showed restricted replication at 37{o}C and 39{o}C, the H5N1 B3.13 replicated to nearly equivalent titers as H1N1pdm09. All H5N1 viruses demonstrated similar cell tropism in cells from the upper and lower respiratory tract, infecting more ciliated than non-ciliated cells relative to H1N1pdm09. H1N1, H5N1 B3.13 D1.1 infection induced similar innate immune factors, with nasal epithelial cells producing higher levels compared to bronchial epithelial cells. These data suggest that genotype B3.13 and D1.1 H5N1 viruses show different temperature dependent replication patterns compared to H1N1pdm09.

microbiology↗

bioRxiv2024

CLCC1 promotes hepatic neutral lipid flux and nuclear pore complex assembly

Imbalances in lipid storage and secretion lead to the accumulation of hepatocyte lipid droplets (LDs) (i.e., hepatic steatosis). Our understanding of the mechanisms that govern the channeling of hepatocyte neutral lipids towards cytosolic LDs or secreted lipoproteins remains incomplete. Here, we performed a series of CRISPR-Cas9 screens under different metabolic states to uncover mechanisms of hepatic neutral lipid flux. Clustering of chemical-genetic interactions identified CLIC-like chloride channel 1 (CLCC1) as a critical regulator of neutral lipid storage and secretion. Loss of CLCC1 resulted in the buildup of large LDs in hepatoma cells and knockout in mice caused liver steatosis. Remarkably, the LDs are in the lumen of the ER and exhibit properties of lipoproteins, indicating a profound shift in neutral lipid flux. Finally, remote homology searches identified a domain in CLCC1 that is homologous to yeast Brl1p and Brr6p, factors that promote the fusion of the inner and outer nuclear envelopes during nuclear pore complex assembly. Loss of CLCC1 lead to extensive nuclear membrane herniations, consistent with impaired nuclear pore complex assembly. Thus, we identify CLCC1 as the human Brl1p/Brr6p homolog and propose that CLCC1-mediated membrane remodeling promotes hepatic neutral lipid flux and nuclear pore complex assembly.

cell biology↗

bioRxiv2024

Mycobacterium tuberculosis exploits SIRT2 for iron acquisition to facilitate its intracellular survival

Iron availability is a critical factor for both bacteria and humans, and its availability significantly influences host-pathogen dynamics. As Mtb has coevolved with the human race, Mtb relentlessly tries to exploit iron from the tightly regulated iron machinery of host. Sirtuins are evolutionary conserved NAD+-dependent deacetylases involved in various cellular processes including infection. Notably, the cytosolic protein, Sirtuin 2 regulates cellular iron homeostasis in hepatocytes and after Mtb infection, SIRT2 translocates to the nucleus leading to decreased protective immune response. However, the underlying mechanism as to how Mtb exploits SIRT2 for iron acquisition remains unknown. In the current study, we observe that the decreased bacillary load in SIRT2 inhibited or knock down cells is due to low availability of iron to the bacilli. Inhibition or knockdown of SIRT2 in Mtb infected cells displays differential modulation of iron import and export proteins suggesting ongoing tussle by host to limit the bioavailability of iron to pathogen. More specifically, by flow cytometry analysis, we show significant upregulation of cell surface Apo Tf and GAPDH in infected SIRT2 inhibited macrophages. Thus, in SIRT2 depleted state, we delineate a different mechanism of iron export occurring through Apo Tf and GAPDH during infection in contrast to the classical iron exporter Fpn1. Collectively, our findings showed the importance of SIRT2-mediated iron regulation in Mtb pathogenesis and can encourage designing of novel host-targeted therapeutics.

cell biology↗

bioRxiv2020

Discovery of A New Class of Integrin Antibodies for Fibrosis

Lung fibrosis, or the scarring of the lung, is a devastating disease with huge unmet medical need. There are limited treatment options and its prognosis is worse than most types of cancer. We previously discovered that MK-0429 is an equipotent pan-inhibitor of all v integrins that reduces proteinuria and kidney fibrosis in a preclinical model. In the present study, we further demonstrated that MK-0429 significantly inhibits fibrosis progression in a bleomycin-induced lung injury model. In search of newer integrin inhibitors for fibrosis, we characterized monoclonal antibodies discovered using Adimabs yeast display platform. We identified several potent neutralizing integrin antibodies with unique human and mouse cross-reactivity. Among these, Ab-31 blocked the binding of multiple v integrins to their ligands with IC50s comparable to those of MK-0429. Furthermore, both MK-0429 and Ab-31 suppressed integrin-mediated cell adhesion and latent TGF{beta} activation. In IPF patient lung fibroblasts, TGF{beta} treatment induced profound SMA expression in phenotypic imaging assays and Ab-31 demonstrated superior in vitro activity at inhibiting SMA expression, suggesting that the integrin antibody is able to modulate TGF{beta} action though mechanisms beyond the inhibition of latent TGF{beta} activation. Together, our results highlight the potential to develop newer integrin therapeutics for the treatment of fibrotic lung diseases. One Sentence Summarytargeting integrin in lung fibrosis

pharmacology and toxicology↗

bioRxiv2019

The Impact of a Wireless Audio System on Communication in Robotic-Assisted Laparoscopic Surgery: A Prospective Controlled Trial

BackgroundRobotic surgery presents a challenge to effective teamwork and communication in the operating theatre (OR). Our objective was to evaluate the effect of using a wireless audio headset device on communication, efficiency and patient outcome in robotic surgery.\n\nMethods and findingsA prospective controlled trial of team members participating in gynecologic and urologic robotic procedures between January and March 2015. In the first phase, all surgeries were performed without headsets (control), followed by the intervention phase where all team members used the wireless headsets. Noise levels were measured during both phases. After each case, all team members evaluated the quality of communication, performance, teamwork and mental load using a validated 14-point questionnaire graded on a 1-10 scale. Higher overall scores indicated better communication and efficiency. Clinical and surgical data of all patients in the study were retrieved, analyzed and correlated with the survey results.\n\nThe study included 137 procedures, yielding 843 questionnaires with an overall response rate of 89% (843/943). Self-reported communication quality was better in cases where headsets were used (113.0 {+/-} 1.6 vs. 101.4 {+/-} 1.6; p < .001). Use of headsets reduced the percentage of time with a noise level above 70 dB at the console (8.2% {+/-} 0.6 vs. 5.3% {+/-} 0.6, p < .001), but had no significant effect on length of surgery nor postoperative complications.\n\nConclusionsThe use of wireless headset devices improved quality of communication between team members and reduced the peak noise level in the robotic OR.

scientific communication and education↗