Biology subjects

Bhatt, T.

Publications and source records attributed to Bhatt, T..

6 recordsLinked to original sources

bioRxiv2026

Biogenic flavonoid capping converts a cytotoxic Carica papaya fraction into a selective, cross-serotype Dengue entry inhibitor

Plant-derived flavonoids show measurable anti-dengue activity in cell culture, but their translational value is limited by a narrow therapeutic window: the concentrations that inhibit the virus approach or exceed those that are cytotoxic. Whether nanoparticle formulation can resolve this constraint, rather than simply add potency, remains untested for a chemically defined fraction. Here we show that biogenic silver nanoparticle (AgNP) formation using a flavonoid-enriched fraction of Carica papaya inverts an unusable selectivity profile into a viable one. The unformulated fraction was cytotoxic below the concentrations required for antiviral activity: its 50% cytotoxic concentration (CC50 = 134.9 ug/mL) lay below its 50% effective concentration against dengue virus serotype 2 (DENV-2; EC50 = 254.4 ug/mL), giving a Selectivity Index (SI) of 0.53. Using the same flavonoids as sole reducing and capping agents produced AgNPs (Z-average 128.4 nm; PDI 0.232; zeta potential -28.4 mV) that moved both parameters simultaneously. CC50 rose approximately 8.6-fold to 1,165.74 ug/mL while EC50 fell approximately 8.8-fold to 29.05 ug/mL, raising the SI to 40.12, an approximately 75-fold shift. Time-of-addition analysis localised the effect to the extracellular phase: inhibition was significant under pre-treatment and co-treatment but not after viral adsorption, identifying the AgNPs as entry inhibitors rather than replication inhibitors. Consistent with a serotype-independent physical mechanism, AgNP treatment at 30 ug/mL reduced viral RNA across all four serotypes, using inocula standardised against WHO-traceable NAAT reference reagents. These findings identify capping chemistry, rather than silver content alone, as a determinant of the therapeutic window in phytosynthesised nanoantivirals.

microbiology↗

bioRxiv2025

MkAtt-SDN2GO: Multi-kernel Attentive-SDN2GO Network for Protein Function Prediction in Humans

Accurately annotating the functions of uncharacterised human proteins remains a major bottleneck in biology. We present MkAtt-SDN2GO, a neural architecture that extends SDN2GO by integrating adaptive multi-kernel convolution and attention mechanisms to predict Gene Ontology terms from protein sequences, domains, and protein-protein interaction (PPI) context. The sequence stream employs a learnable multi-kernel convolution layer that combines features from multiple kernel sizes through attention-based gating, enabling adaptive motif detection without relying on a fixed receptive field. A self-attention layer models long-range dependencies, while cross-attention integrates sequence, domain, and PPI representations into a unified prediction space. On a CAFA-style benchmark, MkAtt-SDN2GO improves Molecular Function (MF) Fmax by 14.8% (0.657 vs 0.572) and Recallmax by 18.8% over SDN2GO. Across Homo sapiens, the fused model achieves top Fmax scores in Biological Process (BP) (0.441), MF (0.657), and Cellular Component (CC) (0.522) compared with other methods. Although the domain-only stream performs strongly, the cross-attention fusion enhances robustness and interpretability when individual modalities are weak or missing. Overall, adaptive multi-scale convolution combined with attention thus advances large-scale protein annotation and offers a scalable and potential tool for functional genomics and disease research.

bioinformatics↗

bioRxiv2025

Drought and methyl jasmonate memory interact to determine plant functioning under current drought stress in a perennial grass

As droughts become more common due to climate change, survival may rely not only on a plants immediate response but also on what it has learned from past challenges. However, we still know little about how plants integrate different types of experiences, such as recurrent drought and hormonal cues, from previous generations. In this study, we examined whether clonal offspring of Festuca rubra plants previously exposed to drought or the stress hormone methyl jasmonate (MeJA) inherited biological memories that help them tolerate new drought stress. Using a factorial design, we combined untargeted LC- MS metabolomics with morpho-physiological measurements to evaluate these memory effects. We found that each type of memory changed plant metabolism and physiology, but the most notable changes occurred when both memories were present, and plants faced recurrent drought conditions again. This interaction between drought memory, MeJA memory, and current stress did not just add effects, it created entirely new metabolic responses, not seen in any single treatment. These combined memories fine-tuned water conservation, photosynthesis, and extensive metabolomic reshuffling, revealing a deeper level of drought resilience. Our results uncover a layered memory system in plants where past stresses do not act in isolation but interact to reshape future responses. This offers new insight into how plants prepare for stress and suggests practical strategies for priming drought tolerance across plant generations.

plant biology↗

bioRxiv2025

12-Hydroxystearic acid induces epidermal keratinocytes to secrete antimicrobial peptides that are potent inhibitors of viral infection.

Epidermal keratinocytes produce antimicrobial peptides (AMPs) that serve as a crucial component of the skins innate immune barrier. These peptides effectively target a broad spectrum of pathogenic microorganisms while preserving commensal microbiota essential for skin barrier homeostasis and overall skin health. Regulating the release of these AMPs presents a promising approach to enhancing the skin barriers defense mechanisms with minimal side effects. We have identified 12-hydroxystearic acid (12-HSA) as a potent stimulator of AMP secretion from primary epidermal keratinocytes. Mechanistic investigations revealed that, akin to bacterial stimulation, 12-HSA induces AMP release through the downregulation of caspase-8, which subsequently activates the inflammasome. Notably, we discovered that 12-HSA mediates caspase-8 downregulation via the acute activation of DNA methyltransferase 3A (DNMT3A), leading to transcriptional silencing of the caspase-8 locus. Importantly, 12-HSA is widely utilized in the cosmetic industry for its several skin beneficial properties including hydration and emolliency. Our findings suggest that this compound can be leveraged to enhance innate immune defenses in the skin, effectively mobilizing stored AMPs from keratinocytes to counteract microbial threats. This discovery highlights the potential for 12-HSA as a novel agent in dermatological applications aimed at fortifying skin barrier immunity.

cell biology↗

bioRxiv2022

Niacinamide enhances cathelicidin mediated SARS-CoV-2 membrane disruption

The continual emergence of new SARS-CoV-2 variants threatens the effectiveness of worldwide vaccination programs and highlights the need for complementary strategies for a sustainable containment plan. A promising approach is to mobilize the bodys own antimicrobial peptides (AMPs), to combat SARS-CoV-2 infection and propagation. We have found that human cathelicidin (LL37), an AMP found at epithelial barriers as well as in various bodily fluids, has the capacity to neutralise multiple strains of SARS-CoV-2. Biophysical and computational studies indicate that LL37s mechanism of action is through the disruption of the viral membrane. This antiviral activity of LL37 is enhanced by the hydrotropic action of niacinamide, which may increase the bioavailability of the AMP. Interestingly, we observed inverse correlation between LL37 levels and disease severity of COVID-19 positive patients, suggesting enhancement of AMP response would be an effective therapeutic avenue to mitigate disease severity and overcome vaccine escape.

pathology↗

bioRxiv2021

The initiation of the wound healing program is regulated by the convergence of mechanical and epigenetic cues

Wound healing in the skin is a complex physiological process that is a product of a cell state transition from homeostasis to repair. Mechanical cues are increasingly being recognized as important regulators of cellular reprogramming, but the mechanism by which it is translated to changes in gene expression and ultimately cellular behavior remains largely a mystery. To probe the molecular underpinnings of this phenomenon further, we used the downregulation of caspase-8 as a biomarker of a cell entering the wound-healing program. We found that the wound-induced release of tension within the epidermis leads to the alteration of gene expression via the nuclear translocation of the DNA methyltransferase 3A (DNMT3a). This enzyme then methylates promoters of genes that are known to be downregulated in response to wound stimuli as well as potentially novel players in the repair program. Overall, these findings illuminate the convergence of mechanical and epigenetic signaling modules that are important regulators of the transcriptome landscape required to initiate the tissue repair process in the differentiated layers of the epidermis. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=107 SRC="FIGDIR/small/463764v2_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@1b5b182org.highwire.dtl.DTLVardef@198e646org.highwire.dtl.DTLVardef@1361f4forg.highwire.dtl.DTLVardef@418a84_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗