Biology subjects

Bose, K.

Publications and source records attributed to Bose, K..

6 recordsLinked to original sources

bioRxiv2026

Remodelling of chromatin architecture and super-enhancer landscape in lamin A/C depleted HGSOC

Lamins are nuclear intermediate filament proteins that maintain nuclear architecture through interactions with the chromatin. The A- and B-type lamins tether the genome at the peripheral lamina underlying the inner nuclear membrane in the form of heterochromatic lamina-associated domains (LADs). However, LADs associated with A-type lamins are confined not only to lamina but also to the nuclear core, thereby pointing to their distinct and multifarious roles in chromatin organisation and regulation. Previous studies involving lamin B1 depletion depicted the detachment of LADs from the nuclear periphery, accompanied by alteration of chromatin distribution while preserving the topologically associating domains (TADs) in structurally intact form. In this piece of work, we have shown, for the first time in HGSOC, the effects of lamin A/C knockdown on chromatin organisation, which was characterised by significant detethering of gene-poor chromatin from the periphery along with active (A) to inactive (B) compartment switching. This was associated with a rewiring of oncogenic super-enhancer elements corroborated by the differential gene expression profile. Overall analysis tipped the scale in favour of reduced cellular proliferation upon lamin A/C knockdown. This finding was strengthened by the observed proliferative potential of spheroids ex vivo and tumours in a mouse xenograft model.

cancer biology↗

bioRxiv2025

Multimodal sensory overload in dopamine-deficient larval zebrafish leads to paradoxical kinesia

Paradoxical kinesia--the temporary alleviation of motor deficits by powerful, urgent stimuli in Parkinsons disease (PD)--remains poorly understood at the neural circuit level. Through chemo-genetic ablation of tyrosine hydroxylase-expressing neurons in larval zebrafish and brain-wide calcium imaging under head-fixed, tail-free conditions, we uncovered a neural mechanism underlying this phenomenon. While catecholamine (CA)-deficient larvae exhibited severe locomotor deficits during free swimming, they showed paradoxical recovery of tail movements during whole-brain neural activity imaging. This locomotor recovery was accompanied by a significantly increased number of active neurons in the midbrain and hindbrain, but with reduced firing rates. Further analyses across 2158 anatomically defined regions allowed us to uncover a subset of regions, genes, and neurotransmitter types. GABAergic neurons were found to primarily account for the hyperactivity in the hindbrain, while glutamatergic neurons accounted for the hyperactivity in the midbrain. Hierarchical clustering of neuronal activity with tail movements revealed distinct motor- and non-motor-associated hyperactive clusters in the hindbrain and midbrain, respectively. We identified the Mesencephalic Locomotor Region (MLR) sandwiched between these domains, with enhanced glutamatergic firing rate and cholinergic activation. Furthermore, we found that Telencephalic corticotropin-releasing factor b (crhb) expressing neurons play a crucial role in mediating stress-response to the tectum, which in turn triggers a cascade of neuronal hyperactivity downstream via MLR. These findings reveal a neural mechanism that links stress-induced sensory processing with motor control systems in the absence of regulatory feedback from catecholaminergic neurons, suggesting a direct, unmodulated pathway that bypasses typical inhibitory controls.

neuroscience↗

bioRxiv2025

FACED 2.0 enables large-scale voltage and calcium imaging in vivo

Monitoring neuronal activity at large scale and high spatiotemporal resolution is crucial for understanding information processing within the brain. We optimized a kilohertz-frame-rate two-photon fluorescence microscope with all-optical megahertz line-scan rate to achieve ultrafast imaging across large areas and volumes at subcellular resolution. Applying this technique to voltage and calcium imaging in vivo, we demonstrated simultaneous recording of voltage activity over 200 neurons and calcium activity over 14,000 neurons.

neuroscience↗

bioRxiv2023

Scalable, flexible carbon fiber electrode thread arrays for three-dimensional spatial profiling of neurochemical activity in deep brain structures of rodents

We developed a flexible "electrode-thread" array for recording dopamine neurochemical activity from a lateral distribution of subcortical targets (up to 16) transverse to the axis of insertion. Ultrathin ([~] 10 {micro}m diameter) carbon fiber (CF) electrode-threads (CFETs) are clustered into a tight bundle to introduce them into the brain from a single entry point. The individual CFETs splay laterally in deep brain tissue during insertion due to their innate flexibility. This spatial redistribution allows navigation of the CFETs towards deep brain targets spreading horizontally from the axis of insertion. Commercial "linear" arrays provide single entry insertion but only allow measurements along the axis of insertion. Horizontally configured neurochemical recording arrays inflict separate penetrations for each individual channel (i.e., electrode). We tested functional performance of our CFET arrays in vivo for recording dopamine neurochemical dynamics and for providing lateral spread to multiple distributed sites in the striatum of rats. Spatial spread was further characterized using agar brain phantoms to measure electrode deflection as a function of insertion depth. We also developed protocols to slice the embedded CFETs within fixed brain tissue using standard histology techniques. This method allowed extraction of the precise spatial coordinates of the implanted CFETs and their recording sites as integrated with immunohistochemical staining for surrounding anatomical, cytological, and protein expression labels. Neurochemical recording operations tested here can be integrated with already widely established capabilities of CF-based electrodes to record single neuron activity and local field potentials, to enable multi-modal recording functions. Our CFET array has the potential to unlock a wide range of applications, from uncovering the role of neuromodulators in synaptic plasticity, to addressing critical safety barriers in clinical translation towards diagnostic and adaptive treatment in Parkinsons disease and major mood disorders.

bioengineering↗

bioRxiv2021

Inter-subunit Crosstalk via PDZ Synergistically Governs Allosteric Activation of Proapoptotic HtrA2

Mitochondrial serine protease - High temperature requirement A2 (HtrA2), is associated with various diseases including neurodegenerative disorders and cancer. Despite availability of structural details, the reports on HtrA2s mechanistic regulation that varies with the type of activation signals still remain non-concordant. To expound the role of regulatory PDZ domains in promoting synergistic coordination between HtrA2 subunits, we generated heterotrimeric HtrA2 variants comprising different numbers of PDZs and/or active-site mutations. Sequential deletion of PDZs from the trimeric ensemble significantly affected its residual activity in a way that proffered a hypothesis advocating intermolecular allosteric crosstalk via PDZ domains in trimeric HtrA2. Furthermore, structural and computational snapshots affirmed the role of PDZs in secondary structural element formation and coordinated reorganization of the N-terminal region and regulatory loops. Therefore, apart from providing cues for devising structure-guided therapeutic strategies, this study establishes a physiologically relevant working model of complex allosteric regulation through a multifaceted trans-mediated cooperatively-shared energy landscape.

biochemistry↗

bioRxiv2021

Simultaneous Control of Infection and Inflammation by Keratin-Derived Antimicrobial Peptides (KAMPs) Targeting TLRs and Co-receptors

The use and the timing of initiation of steroids for controlling unwanted infectious inflammation are major clinical dilemmas due to their possible adverse effects including delayed microbial clearance and wound healing. Compounding this difficulty is the continued emergence of drug-resistant bacteria; yet anti-infective strategies aiming at augmenting inflammatory responses to facilitate bacterial killing cannot be used to treat infections involving vulnerable tissues. As is the case with bacterial keratitis, excessive inflammation jeopardizes corneal transparency leading to devastating vision loss. Hence, a two-pronged remedy possessing both anti-infective and anti-inflammatory properties would be helpful for tackling antibiotic resistance and enabling prompt inflammation control at once. Using murine primary neutrophils, macrophages and sterile corneal inflammation models, we found that non-toxic and pro-healing human keratin 6a-derived antimicrobial peptides (KAMPs) with a native 10-or 18-amino-acid sequence suppress LTA- and LPS-induced NF-[kcy]B and IRF3 activation, proinflammatory cytokine production, as well as phagocyte recruitment, independently of their bactericidal function. Mechanistically, direct binding of KAMPs to cell surface TLR2 and TLR co-receptors CD14 and MD-2 not only blocks their bacterial ligand docking sites, but also reduces cell surface availability of TLR2 and TLR4 through promotion of receptor endocytosis. Benefitting from the dual functions of topical KAMPs, experimental bacterial keratitis caused was effectively prevented or controlled, as evidenced by significant reductions of corneal opacification and inflammatory cell infiltration in addition to enhanced bacterial clearance. These findings reveal multiple TLR-targeting activities of KAMPs and demonstrate their therapeutic potential as a multifunctional drug for managing sterile and infectious inflammatory diseases. One Sentence SummaryBifunctional native keratin peptides allow concurrent alleviation of inflammation and infection to avoid functional damages in vulnerable tissues.

immunology↗