Biology subjects

Dutta, K.

Publications and source records attributed to Dutta, K..

8 recordsLinked to original sources

bioRxiv2026

A Dual-Function Guanidinium Scaffold that Couples Copper Sequestration with Redox Protection in Wilson disease

Wilson disease (WD) is caused due to mutations in the copper ATPase gene ATP7B, that result in accumulation of labile copper pools and the consequent disruption of cellular redox homeostasis through uncontrolled copper-mediated reactive oxygen species generation. Current therapies mainly depend on high-affinity copper chelation to lower metal burden which sometimes also strip copper from cuproproteins and may disturb physiological copper-dependent processes. It also does not directly suppress pathological copper reactivity i.e., free radical generation, a major driver of WD progression. To overcome these limitations, we have rationally designed Gua-Cu-3, a C-symmetric guanidinium-based molecule that can chelate labile copper without metal stripping from cuproproteins due to moderate binding affinity and it has intrinsic antioxidant activity within a single nanosheet-forming supramolecular self-assembly. Spectroscopic, calorimetric, and computational analyses revealed controlled multivalent copper coordination (Kd = 95.4 M) while radical-scavenging and hydroxyl-radical inhibition assays further revealed potent redox-regulatory activity. In cellular models of copper overload, Gua-Cu-3 treatment reduces ATP7B trafficking from trans-Golgi network, confirming effective intracellular copper sequestration. This was accompanied by a marked reduction in oxidative stress, reduction of translocation of Nrf2 in nucleus and of HO-1 expression, thereby limiting lipid peroxidation which leads to restoration of cellular homeostasis, including improved lysosomal integrity, reduced endoplasmic reticulum stress, decreased mitochondrial superoxide levels, and diminished apoptosis. Importantly, the protective effects extended, beyond cultured cells, Gua-Cu-3 attenuates oxidative stress in ATP7B-homolog-deficient C. elegans and rescues copper-induced developmental defects in zebrafish, outperforming D-penicillamine, which is currently in use for Wilson disease management. These findings establish Gua-Cu-3 as a molecularly designed supramolecular copper-reactivity buffer that couples-controlled copper sequestration with redox regulation which is distinct from conventional copper depletion and provides a framework for treating Wilson disease and other disorders associated with metal dyshomeostasis and oxidative stress.

Cell Biology↗

bioRxiv2024

Temporal-Coherence Induces Binding in Responses to Sound Sequences in Ferret Auditory Cortex

Binding the attributes of a sensory source is necessary to perceive it as a unified entity, one that can be attended to and extracted from its surrounding scene. In auditory perception, this is the essence of the cocktail party problem in which a listener segregates one speaker from a mixture of voices, or a musical stream from simultaneous others. It is postulated that coherence of the temporal modulations of a sources features is necessary to bind them. The focus of this study is on the role of temporal-coherence in binding and segregation, and specifically as evidenced by the neural correlates of rapid plasticity that enhance cortical responses among synchronized neurons, while suppressing them among asynchronized ones. In a first experiment, we find that attention to a sound sequence rapidly binds it to other coherent sequences while suppressing nearby incoherent sequences, thus enhancing the contrast between the two groups. In a second experiment, a sequence of synchronized multi-tone complexes, embedded in a cloud of randomly dispersed background of desynchronized tones, perceptually and neurally pops-out after a fraction of a second highlighting the binding among its coherent tones against the incoherent background. These findings demonstrate the role of temporal-coherence in binding and segregation.

neuroscience↗

bioRxiv2023

Molecular dynamic investigation for ROCO-4 kinase inhibitor as treatment options for parkinsonism

Parkinsons disease (PD) is a neurodegenerative condition that degenerates dopaminergic neurons and is characterized by motor disabilities like rigidity, bradykinesia, postural instability, and resting tremors. Although the etiology of PD remains uncertain, familial and sporadic forms of PD are known to be predominately caused by the G2019S mutation present in the kinase domain of LRRK2. Therefore, it might be possible to treat Parkinsons by inhibiting the kinase action of the mutated LRRK2 protein. In order to find possible inhibitors, 3069 phytochemicals were examined for their ability to bind ROCO4 kinase, which has structural and functional similarities to the LRRK2 protein. Open-source bioinformatics tools were used to determine the binding affinities of phytochemicals to the native and mutant variants of the protein. Mongolicain-A exhibited high specificity and selectivity towards the G2019S mutation of the ROCO4 protein with -12.3 Kcal/mol binding affinity, whereas Bacoside-A displayed high affinity (11.4 Kcal/mol) for the target protein, but lacked specificity towards the mutant form of the protein. Based on molecular simulation studies., RMSD, RMSF, SASA, potential energy, and hydrogen bond analysis, it was suggested that Mongolicain-A may be an effective inhibitor of the G2019S mutation and a promising drug molecule to address PD.

neuroscience↗

bioRxiv2022

Biomechanical influence of plate configurations on mandible subcondylar fracture fixation: a finite element study

Mandible subcondylar fractures have very high complication rate, yet there is no consensus in a suitable plate design for optimal patient outcomes. The present study is aimed at understanding the subcondylar fracture fixation by comparing load transfer in intact and reconstructed fractured mandibles with five different plates: single mini, trapezoid, lambda, strut, and double-mini plates under the complete mastication cycle. Under contralateral molar occlusion (LMOL), the single mini plate resulted in the highest strains. On the contrary, during ipsilateral molar clenching (RMOL), the tensile and compressive strain distributions were found to be reversed, with the tensile strains at the posterior border resulting in lesser strain in reconstructed mandible with single mini plate. Owing to the reduced strains in the reconstructed mandibles, the contralateral molar clenching task is preferred during the immediate post-surgery period for patients. Under this contralateral molar clenching, the peak von Mises stresses in the plate decreased with increase in the number of screws. Furthermore, the presence of two arms seems beneficial to neutralise the tensile and compressive strains across load cases. Consequently, double mini and trapezoid plates were found to perform better as compared to single mini plate during the entire mastication cycle for subcondylar fracture fixation.

bioengineering↗

bioRxiv2020

Multi valent DNA vaccine against group A human rotavirus: an in-silico investigation

Gastroenteritis due to single rotavirus causes huge economic loss annually. Severity of rotaviral diarrhoea among children is primarily manifested by different combinations of G and P types. Rotavirus surveillance studies resulted in two ambitious globally licensed vaccine namely, Rotarix and RotaTaq and a few other. However, post-vaccination surveillance studies indicate, vaccine failure and other complications such as intussusception, environmental enteric dysfunction, etc. Herein, we design a multivalent DNA vaccine against rotavirus and tested its efficiency by using in silico tools. Two main neutralizing rotaviral antigens i.e, VP7 and VP8 were taken into account and respectively 390, 450 known sequences of different serogroup have been analyzed to obtain a consensus sequence for epitope prediction. Epitopes specific for MHC-I and -II were predicted using IEDB and chosen based on their best IC50 value and CPR. A good binding profile with a monoclonal antibody specific for B-cell antigens is displayed by all epitopes they were found to be non-allergenic in the human host. Ethnic specificity of the epitopes is also within acceptable range except for South African and Central American populations. We use pBI-CMV1 bidirectional mammalian expression vector to design the DNA vaccine, where we stapled manually integrated epitopes for VP7 and VP8 at MCS1 and 2 respectively. In conclusion, this study provides a new set of data for a new DNA vaccine against rotavirus.

immunology↗

bioRxiv2019

Optimal Multichannel Artifact Prediction and Removal for Brain Machine Interfaces and Neural Prosthetics

Neural implants that electrically stimulate neural tissue such as deep brain stimulators, cochlear implants (CI), and vagal nerve stimulators are becoming the routine treatment options for various diseases. Optimizing electrical stimulation paradigms requires closed-loop stimulation using simultaneous recordings of evoked neural activity in real time. Stimulus-evoked artifacts at the recording site are generally orders of magnitude larger than the neural signals, which challenge the interpretation of evoked neural activity. We developed a generalized artifact removal algorithm that can be applied in a variety of neural recording modalities. The procedure leverages known electrical stimulation currents to derive optimal filters that are used to predict and remove artifacts. We validated the procedure using paired recordings and electrical stimulation from sciatic nerve axons, high-rate bilateral CI stimulation, and concurrent multichannel stimulation in auditory midbrain and recordings in auditory cortex. We demonstrate a vast enhancement in the quality of recording even for high-throughput multi-site stimulation with typical improvements in the signal-to-noise ratio between 20-40 dB. The algorithm is efficient, can be scaled to arbitrary number of sites, and is applicable in range of recording modalities. It has numerous benefits over existing approaches and thus should be valuable for emerging neural recording and stimulation technologies.

neuroscience↗

bioRxiv2019

Enhanced biodegradation of naphthalene by Pseudomonas sp. consortium immobilized in calcium alginate beads

Polycyclic aromatic hydrocarbons (PAHs) belong to a large group of organic pollutant which considers as a potential health hazard to living beings. Herein, naphthalene biodegradation potential by free and immobilized Pseudomonas putida strain KD10 and Pseudomonas sp. consortium were studied. Additionally, naphthalene 1, 2-dioxygenase (nahAc) was sequenced and analyzed, which reveals two altered amino acid residues. However, the altered amino acid residues are not present in the vicinity of the active site. The gas-phase binding free energy ({Delta}GLondon) of the mutant variant of naphthalene 1, 2-dioxygenase was -7.10 kcal mol-1 which closely resembles the wild type variant. Naphthalene biodegradation rate by Pseudomonas putida strain KD10 was 79.12 mg L-1 day-1 and it was significantly elevated up to 123 mg L-1 day-1 by the immobilized Pseudomonas sp. consortium. The half-life (t1/2) for naphthalene biodegradation was 3.1 days with the inhibition constant (ki), substrate saturation constant (ks) and maximum specific degradation rate constant (qmax) of 1268 mg L-1, 395.5 mg L-1 and 0.65 h-1, respectively, for the Pseudomonas putida strain KD10. However, the t1/2 value was significantly reduced to 2 days along with ki, ks and qmaxvalues of 1475 mg L-1, 298.8 mg L-1 and 0.71 h-1, respectively, by the immobilized Pseudomonas sp. consortium. The GC-MS data suggest that KD10 might follow D-gluconic acid mediated meta-cleavage pathway of catechol biodegradation. It is concluded that naphthalene biodegradation performance by immobilized Pseudomonas sp. consortium was superior to free or immobilized Pseudomonas putida KD10. Microbial consortium immobilization could be a useful tool for water quality management and environmental remediation.\n\nHighlightsO_LISuperior naphthalene biodegradation by Pseudomonas sp. consortium immobilized in calcium alginate beads.\nC_LIO_LIA common mutation prone amino acid stretch inside chain A of naphthalene 1, 2-dioxygenase has been identified.\nC_LIO_LIA new naphthalene biodegradation pathway by Pseudomonas putida strain KD10 has been proposed.\nC_LI

microbiology↗

bioRxiv2019

Adaptive efficient coding of correlated acoustic properties

Natural sounds such as vocalizations often have co-varying acoustic attributes where one acoustic feature can be predicted from another, resulting in redundancy in neural coding. It has been proposed that sensory systems are able to detect such covariation and adapt to reduce redundancy, leading to more efficient neural coding. Results of recent psychoacoustic studies suggest that, following passive exposure to sounds in which temporal and spectral attributes covaried in a correlated fashion, the auditory system adapts to efficiently encode the two co-varying dimensions as a single dimension, at the cost of lost sensitivity to the orthogonal dimension. Here we explore the neural basis of this psychophysical phenomenon by recording single-unit responses from primary auditory cortex (A1) in awake ferrets exposed passively to stimuli with two correlated attributes in the temporal and spectral domain similar to that utilized in the psychoacoustic experiments. We found that: (1) the signal-to-noise (SNR) ratio of spike rate coding of cortical responses driven by sounds with correlated attributes was reduced along the orthogonal dimension; while the SNR ratio remained intact along the exposure dimension; (2) Mutual information of spike temporal coding increased only along the exposure dimension; (3) correlation between neurons tuned to the two covarying attributes decreased after exposure; (4) these exposure effects still occurred if sounds were correlated along two acoustic dimensions, but varied randomly along a third dimension. These neurophysiological results are consistent with the Efficient Learning Hypothesis and may deepen our understanding of how the auditory system represents acoustic regularities and covariance. SignificanceIn the Efficient Coding (EC) hypothesis, proposed by Barlow in 1961, the neural code in sensory systems efficiently encodes natural stimuli by minimizing the number of spikes to transmit a sensory signal. Results of recent psychoacoustic studies are consistent with the EC hypothesis, showing that following passive exposure to stimuli with correlated attributes, the auditory system adapts so as to more efficiently encode the two co-varying dimensions as a single dimension. In the current neurophysiological experiments, using a similar stimulus design and experimental paradigm to the psychoacoustic studies of Stilp and colleagues (2010, 2011, 2012, 2016), we recorded responses from single neurons in the auditory cortex of the awake ferret, showing adaptive efficient neural coding of correlated acoustic properties.

neuroscience↗