Biology subjects

Konar, A.

Publications and source records attributed to Konar, A..

7 recordsLinked to original sources

bioRxiv2026

Magnetic Field Enhanced Docosahexaenoic Acid Delivery for Acetylcholine Restoration in Alzheimers Disease an In Silico Study

Alzheimers Disease (AD) is characterised by the progressive depletion of Acetylcholine (ACh), a neurotransmitter essential for cognition and synaptic communication. Docosahexaenoic acid (DHA), the predominant omega 3 polyunsaturated fatty acid in neuronal membranes, raises cerebral ACh and supports cholinergic transmission, but its therapeutic efficacy is limited by poor blood brain barrier permeability and slow passive diffusion. This work addresses these limitations through a closed form mathematical model coupling the spatiotemporal dynamics of DHA diffusion and ACh synthesis under an externally applied static magnetic field. Because DHA is diamagnetically anisotropic, it aligns along the field axis through diamagnetic torque while body cells form field aligned linear arrays; together these effects raise the effective diffusion coefficient of DHA. At a representative observation point, 0.5cm, magnetic field assisted transport reduces the time for ACh to reach a therapeutic threshold by 83.3%, from 10.55 s to 1.76 s. This reduction is spatially uniform across the modelled range of 0 to 3.0 cm from the source, with the absolute saving growing from 6.71 s at the source to 19.21 s at 3.0 cm. Co-evolution analysis reveals the mechanism: by the end of a 2.0 s window the field elevates DHA 7.39 fold relative to baseline, driving ACh to 133.7% of threshold versus only 18.1% without the field. A Brain Computer Interface (BCI)-based closed loop dosing framework is additionally proposed for future clinical validation. These findings establish a quantitatively grounded theoretical basis for magnetically enhanced DHA therapy as an approach to cholinergic restoration in AD.

neuroscience↗

bioRxiv2026

Hypothalamic Interleukin 6 linked to sex-specific behavioral deficits following adolescent social isolation

Social isolation refers to an extreme form of social deprivation that has enduring effects on the brain and behavior. Adolescents show selective vulnerability to such heightened social stress, displaying aberrant behavior and psychiatric ailments. The post-weaning social isolation rodent model has been widely used to recapitulate such behavioral anomalies and delineate their mechanistic bases. Here, we aim to identify how prolonged social isolation during adolescence affects neuroimmune responses in both sexes and the implications for behavioral outcomes, particularly aggression. While males subjected to adolescent isolation were hyper-aggressive with pathological signs, females showed reduced social exploration and inactivity. Cytokine profiling in core brain regions implicated in aggression revealed reduced interleukin 6 (IL6) levels, specifically in the hypothalamus, in both sexes. Other proinflammatory cytokines, including interferon-gamma and interleukin-1beta, were unaltered. IL6-responsive genes, SOCS3 and TIMP1, were also downregulated in the hypothalamus of both socially isolated males and females. The hypothalamus is crucial for stress responsiveness and the expression of excessive aggression. Despite behavioral dimorphism, reduced IL6 levels in both sexes may indicate differences in downstream signaling and roles beyond classical immune responses. Our findings suggest that hypothalamic IL6 may be a key mediator of adolescent social isolation, which is associated with aberrant behavior, including aggression.

neuroscience↗

bioRxiv2025

A Highly Thermostable and Novel GH5 Endoglucanase from Bacillus sp. Strain BS with Enhanced Biomass Saccharification Potential in Seawater

The efficient enzymatic conversion of lignocellulosic biomass to glucose is crucial for biofuel production, with enzyme costs being a significant barrier to commercialization. Multifunctional enzymes that reduce enzyme components can improve efficiency. In this study, we amplified and sequenced a gene from Bacillus sp. strain BS, which showed 89.8% identity with bacterial endoglucanase Q6YK34. This putative novel endoglucanase, BsEG2, is a GH5-like endoglucanase, with optimal activity at pH 6.0 and 55 {square}, and efficiently hydrolyzes amorphous and crystalline cellulose, including pre-treated and untreated sugarcane bagasse. Kinetics on carboxymethyl cellulose (CMC) indicate high substrate binding efficiency (apparent Vmax of 148.9 {micro}M min-1, a Km of 24.9 mg mL-1, and a kcat of 517 s-1). BsEG2 hydrolyzes long cellulosic chains, oligosaccharides, and cellobiose to produce glucose, demonstrating multifunctionality. It exhibits remarkable thermal stability, retaining over 90% activity after 15 days at 55 {degrees}C. BsEG2 also retains activity in high salts and ionic liquids, and is not inhibited by cellobiose, even at 200 mM, unlike other endoglucanases and cellobiohydrolases. Furthermore, BsEG2 functions in seawater, reducing freshwater footprint in biofuel production. BsEG2 is a promising candidate for a cost-effective enzyme formulation for glucose production from lignocellulosic biomass, supporting downstream glucose-fed metabolic pathways.

biochemistry↗

bioRxiv2025

Domain Compatibility and Linker Design Dictate the Success of Chimeric Cellulase Engineering

Efficient conversion of lignocellulosic biomass into fermentable sugars remains a major challenge due to individual cellulases limited synergy and catalytic efficiency. Engineering chimeric enzymes provides a promising strategy to streamline biomass hydrolysis by combining complementary catalytic activities in a single protein, thereby enhancing efficiency and lowering process costs. In this study, we constructed chimeric cellulases by fusing a thermophilic GH1 {beta}-glucosidase (TsBG) with endoglucanases from the GH5 (BsEG2) or GH9 (BlEG) families through flexible peptide linkers. Constructs containing BsEG2 exhibited a pronounced loss of {beta}-glucosidase activity and reduced endoglucanase activity, whereas substitution with the full-length BlEG restored dual functionality under identical design conditions. The optimized chimera (BlEG+(G4S)2+TsBG) demonstrated enhanced catalytic performance, with a 4.8-fold lower Km, a 1.7-fold higher Vmax, and an increased kcat (from 1088 to 1454 s-1). The chimera also exhibited enhanced stability, retaining [~]10 % higher activity under elevated cellobiose (up to 300 mM) and >90 % specific activity in 2.5 M NaCl. Molecular dynamics simulations further revealed that activity loss in non-optimized constructs arose from C-terminal structural instability and steric clashes, underscoring the critical role of domain orientation and linker flexibility in chimera design. These findings establish a chimeric cellulase that integrates endoglucanase and {beta}-glucosidase activities in a single polypeptide, offering a robust and cost-effective biocatalyst for lignocellulosic biomass conversion.

biochemistry↗

bioRxiv2025

In Vitro and Viral Evolution Convergence Reveal the Selective Pressures Driving Omicron Emergence

In vitro protein evolution provides powerful insights into the amino acid sequences that underlie key biological functions. Here, we used this approach to explore the evolutionary trajectories of the SARS-CoV-2 spike protein receptor-binding domain (RBD) constrained to engage the human ACE2 receptor--an essential first step in viral infection. Applying mild (LSS) or stringent (HSS) selection pressures starting from the ancestral Wuhan strain, we found that HSS, but not LSS rapidly converged on mutations characteristic of the Omicron variant. HSS resulted in fewer, but dominant, non-synonymous mutations mirroring Omicron mutations and its advanced sub-lineages. Conversely, LSS produced only some Omicron-like mutations at much lower frequencies and with incomplete representation. Notably, initiating evolution from Omicron itself resulted in high-fidelity maintenance of Omicron-defining mutations under both HSS and LSS conditions. This evolutionary pattern parallels global SARS-CoV-2 mutation trends as well as in silico simulations, emphasizing the critical role of receptor-binding constraints in shaping viral adaptation, which may be a frequent driver during zoonosis. Predominantly immune evasion associated mutations not selected in vitro. Our findings demonstrate the predictive capacity of in vitro evolution, suggesting Omicrons abrupt emergence resulted from rare, high-stringency selection, superimposed on a background of broader, milder pressures, with Omicron being the humanized SARS-CoV-2.

evolutionary biology↗

bioRxiv2022

Preclinical efficacy of bacosides-lauric acid nano-herbal formulation incomparison to rivastigmine for treatment of Alzheimer's disease

Despite decades of rigorous scientific endeavors for Alzheimers disease (AD) drug development, massive failures in clinical trials is continuously posing healthcare and societal burden. Currently recommended single targeted drugs including rivastigmine with limited bioavailability can alleviate AD symptoms only for a limited period of time but unable to reverse the disease progression. Recent evidences consider poly-pharmacological and multi-targeted agents aiming at amyloid and tau burden, neuroinflammation, neuroprotection and cognitive enhancement as potential treatment options. In this regard, bioactive herbal compounds with holistic action and minimal adversities have gained prominence, though lacunae in their scientific validation and limited bio-permeability to cross BBB represent major hurdles. Previously, we showed that lactoferrin conjugated PEG-S-S-PLA-PCL-OH efficaciously delivered herbal compounds to brain and such nano-herbal formulation of bacosides-lauric acid (BAN-LAN) attenuated neuronal damages induced by scopolamine in vitro. Here, we tested the preclinical potential of BAN-LAN in reversal of AD pathologies in 5XFAD transgenic mice. Our nano-herbal formulation substantially reduced amyloid burden by clearing A{beta} plaques in the hippocampus of 5XFAD mice and also attenuated a{beta}42 induced alterations in AD associated gene expression in hippocampal neurons in vitro. It showed neuroprotection by rescuing neuronal damage and promoting neurogenesis in the hippocampus of AD transgenic mice. Anti-neuroinflammatory properties were also exhibited by the formulation as evident from inhibition of hippocampal astrocytic and microglial activation in 5XFAD mice. BAN-LAN showed cognitive efficacy by restoring memory impairment in AD transgenic mice and effects were more pronounced than unconjugated natural form and rivastigmine. These findings suggest that BAN-LAN may serve as a promising therapeutic agent for AD with better brain penetration and targeting multiple AD pathways.

pharmacology and toxicology↗

bioRxiv2021

Early life trauma leads to violent behavior and its inheritance by impairing local thyroid hormone availability in brain

Escalated and inappropriate levels of aggressive behavior referred to as pathological in psychiatry can lead to violent outcomes with detrimental impact on health and society. Early life trauma triggers adulthood violence and criminality, though molecular mechanisms remain elusive. Here, we provide prefrontal cortex and hypothalamus specific transcriptome profiles of peripubertal stress (PPS) exposed Balb/c adult male mice exhibiting escalated aggression and adult female mice resilient to such aberrant behavioral responses. We identify transthyretin (TTR) as a key regulator of PPS induced escalated aggression and its intergenerational inheritance. TTR mediated long-term perturbation in hypothalamic thyroid hormone (TH) availability contributed to male aggressive behavior without affecting circulating hormone. Ttr gene ablation in hypothalamus impaired local TH signaling including levels of TH transporters (Mct8, Oatp1c1), deiodinase 2(DIO2) and TH responsive genes (Nrgn, Trh and Hr). Escalated aggressive behavior and impaired TTR-TH signaling was also inherited in F1 male progenies. Further, we deciphered Ttr promoter hyper methylation in hypothalamus of such abnormally aggressive males across generations. Interestingly prefrontal cortex showed opposite pattern of Ttr expression as well as long term epigenetic changes. Also, T4 increase by levothyroxine in PFC did not produce any behavioral changes. Our findings reveal that trauma during puberty trigger lasting escalated aggression by epigenetic programming of TTR and consequent impaired thyroid availability in brain. TTR-TH signaling in brain can serve as potential target in reversal of escalated aggression and related psychopathologies.

neuroscience↗