Biology subjects

Haque, M. E.

Publications and source records attributed to Haque, M. E..

10 recordsLinked to original sources

bioRxiv2026

Recombinant SIRT1 expression and SIRT1 METTL3 interaction analysis with computational identification of phytochemical SIRT1 activators and inhibitors

Sirtuin 1 (SIRT1), a NAD{+/-}dependent histone deacetylase, regulates diverse biological processes including aging, stress response, and cancer progression. Owing to its dual roles in tumor suppression and promotion, selective modulators of SIRT1 have attracted considerable therapeutic interest. This study explored the interaction of SIRT1 with METTL3 and screened phytochemicals from Indian medicinal plants for potential SIRT1 activation or inhibition. Human SIRT1 (residues 183-665) was cloned, expressed in E. coli, purified, and validated by isothermal titration calorimetry (ITC) to confirm binding with METTL3. Computational approaches, including molecular docking, ADMET profiling, molecular dynamics (MD) simulations, MM-PBSA free energy estimation, and frontier molecular orbital (FMO) analysis, were employed to characterize ligand interactions. Docking revealed Catechin, Epicatechin, Kaempferol, and Bisdemethoxycurcumin as potent inhibitors, showing stronger binding than the reference inhibitor Selisistat by stabilizing the catalytic pocket via key hydrogen bonds and {pi}-{pi} stacking interactions. Among activators, Ginsenosides and Carnosol demonstrated higher affinities than resveratrol, binding the allosteric site through hydrophobic and electrostatic interactions. MD simulations highlighted Catechin and Ginsenosides as the most stable modulators, supported by reduced RMSD, compact Rg values, and favorable hydrogen bond occupancy. MM-PBSA confirmed their strong binding free energies, while ADMET analysis predicted favorable pharmacokinetic properties and low toxicity, particularly for Catechin and Ginsenosides. Overall, this study integrates expression and purification of the protein and computational modeling to identify phytochemicals as potential SIRT1 modulators and provides novel insights into the SIRT1-METTL3 regulatory axis. These findings highlight Catechin and Ginsenosides as promising scaffolds for therapeutic strategies targeting cancer and metabolic disorders.

molecular biology↗

bioRxiv2026

AI-Driven Design of Next-Generation Immunoinformatics Multi-Epitope Subunit Vaccine Targeting the Most Virulent Mpox Proteome: A Structural and Kinetic Validation Framework

The resurgence of the Mpox virus (MPXV) highlights the urgent need for scalable, mutation-resistant countermeasures. Slow development timelines hinder traditional empirical vaccine discovery, while conventional vaccinology often yields high false-positive rates because it relies on static, linear sequence-based screening. These classical informatics filters consistently fail to predict physical structural stability or the dynamic presentation of immune cells under physiological conditions, creating a distinct translational gap between computational design and in vitro efficacy. To address these limitations, here we engineered an advanced, AI-augmented vaccine discovery pipeline targeting the most virulent components of the MPXV proteome. We systematically screened eight critical viral targets essential for replication, membrane morphogenesis, and host-cell entry to map highly conserved T-cell and B-cell epitopes. Moving beyond standard heuristic filtering, we implemented a high-fidelity deep learning validation layer: ESM-2 protein language models (pLMs) were deployed to calculate pseudo-perplexity scores across chimeric linker junctions (EAAAK, GPGPG) to guarantee structural naturalness, MHCflurry ensemble models successfully verified active intracellular antigen presentation, and structure-informed graph neural networks (GNNs) simulated the physical node-attention dynamics of the immune synapse. Finally, recurrent neural networks (RNNs)-driven mRNA kinetic modeling optimized translation initiation rates and minimum free energy profiles during in silico cloning. This multi-layered pipeline successfully yielded three structurally refined, multi-epitope vaccine constructs optimized for maximum global population coverage. ESM-2 structural validation confirmed exceptionally low perplexity scores at structural junctions, indicating that the engineered chimaeras have native-like stability and a minimized risk of proteolysis. GNN-based immune synapse modeling demonstrated highly stable binding kinetics and robust binding free energies between the target epitopes and human HLA alleles. Furthermore, RNN kinetic optimizations established that the cDNA sequences are optimized for high-yield expression in heterologous expression hosts without risk of ribosomal stalling or translational bottlenecks. This study establishes a deep learning-augmented framework that bridges the gap between theoretical sequence optimization and biopharmaceutical scalability. By validating the structural naturalness, real-world immunogenicity, and manufacturing kinetics of our vaccine chimeras, this framework presents a robust, proactive paradigm for rapid vaccine architecture against emerging orthopoxvirus threats.

bioinformatics↗

bioRxiv2026

Computational Structure Modeling, Functional Characterization, and Identification of Potential Inhibitors for the cyclic-di-GMP Mediated Biofilm Forming Membrane Protein in Vibrio cholerae

Cholera, caused by Vibrio cholerae, continues to pose a serious global public health challenge, with its impact worsened by rising antibiotic resistance associated with bacterial biofilm formation. This study reveals the role of the hypothetical protein (HP) TYC33605.1 in cyclic-di-GMP (c-di-GMP)-mediated biofilm regulation and identifies natural inhibitors that disrupt this mechanism. Functional annotation revealed TYC33605.1 as a membrane-associated diguanylate cyclase (DGC) with GGDEF and sensory domains, critical for c-di-GMP synthesis and biofilm persistence. Homology modelling and molecular dynamics (MD) simulations validated its stable 3D structure (C-score: -1.22, Ramachandran favoured regions: 91.1%) and dynamic behaviour (average RMSD: 8.55 [A]). Virtual molecular docking screening of 1,092 natural compounds identified Luteolin (CID 5280445) and Sativanone (CID 13886678) as top candidates, exhibiting strong binding affinities (-9.1 and -9.0 kcal/mol, respectively) and forming hydrogen bonds, {pi}-cation, and hydrophobic interactions with key residues (Glu293, Arg364, Ala176). MD simulations (100 ns) confirmed complex stability, with Luteolin and Sativanone showing lower RMSD fluctuations (7.78 [A] and 8.13 [A]) compared to the control and apoprotein. The ADME/Tox profiles highlighted favourable pharmacodynamics (PD), pharmacokinetics (PK), high gastrointestinal absorption, no hepatotoxicity, and drug-likeness (Lipinski compliance). Principal component, probability density function, and binding free energy analyses underscore ligand-induced conformational stability. This study proposes the molecular characterisation of the HP and the bioactive compounds Luteolin and Sativanone as promising inhibitors targeting TYC33605.1, offering a novel strategy to combat biofilm-mediated antibiotic resistance and a framework for analogous antimicrobial discovery in Vibrio cholerae.

bioinformatics↗

bioRxiv2022

A microfluidic finger-actuated blood lysate preparation device enabled by rapid acoustofluidic mixing

For many blood-based diagnostic tests, including prophylactic drug analysis and malaria assays, red blood cells must be lysed effectively prior to their use in an analytical workflow. We report on a finger-actuated blood lysate preparation device, which utilises a previously reported acoustofluidic micromixer module. The integrated device includes a range of innovations from a sample interface, to the integration of blisters on a laser engraved surface and a large volume (130 L) one-stroke manual pump which could be useful in other low-cost microfluidic-based point-of-care devices. The adaptability of the acoustic mixer is demonstrated on highly viscous fluids, including whole blood, with up to 65% percent volume fraction of red blood cells. Used in conjunction with a lysis buffer, the micromixer unit is also shown to lyse a finger-prick (20 L) blood sample in 30 seconds and benchmarked across ten donor samples. Finally, we demonstrate the ease of use of the fully integrated device. Cheap, modular, but reliable, finger-actuated microfluidic functions could open up opportunities for the development of diagnostics with minimal resources.

bioengineering↗

bioRxiv2022

Evaluation of Three Forms of Rhizoctonia solani Mediated Pathogenicity to Sugar Beet Cultivars in Greenhouse Studies

Rhizoctonia solani causes damping-off, as well as crown and root rot of sugar beet (Beta vulgaris L). This pathogen overwinters as sclerotia or melanized mycelia. Traditionally, the resistance of cultivars to R. solani is evaluated by scoring disease reactions of the crowns and roots of older seedlings, instead of evaluating at seed germination. Most studies that have evaluated cultivar resistance to R. solani have used colonized whole barley grains as artificial inocula. Colonized grains are prone to contamination with other pathogens and are often lost to rodents/birds when applied in the field. Considering those limitations, a study was undertaken (1) to develop in vitro methods to generate natural sclerotia of R. solani on a large scale, (2) to compare pathogenic potentials of R. solani sclerotia, mycelia, and colonized barley grains for optimization of damping-off assays, and (3) to evaluate resistance of selected commercial cultivars to R. solani. Of the six-culture media, amended clarified V8 (ACV8) was the most suitable culture medium to grow and produce sclerotia on a large scale and 10% PDA was the least suitable. Three testing sizes of sclerotia were found to be equally effective in causing plant losses. Sclerotia inocula were comparable with mycelial discs and colonized barley grains in causing pre-emergence damping off under aseptic in vitro conditions. Sclerotia also were equally or more effective than mycelia plug or barley grain inocula in reducing seedling emergence, inducing damping off, and increased root rot under greenhouse in vivo conditions. To conclude, sclerotia can be prepared on a feasible scale and used as natural inocula to screen response to R. solani on sugar beet.

plant biology↗

bioRxiv2022

Heterosis and Combining Ability in Pumpkin Inbreds (Cucurbita moschata Duch. ex Poir.)

Twenty hybrids along with five parents evaluated in the study were mainly contemplated to find out the best cross combinations and the best general and specific combiners as well as to estimate the nature and magnitude of the gene action for different qualitative traits. Using Griffings and Haymans approach through a 5 x 5 full diallel cross fashion, an investigation on heterosis and combining ability in pumpkin was undertaken following RCBD design with three replications at the experimental field. Both positive and negative significant GCA and SCA variances were obtained from few parents and hybrids. Predominance of additive-additive gene action was noted for most of the characters except hollowness and dry matter content, where additive-dominance gene action was predominant; flesh thickness and brix (%), where dominance-dominance gene action were predominant. A single parent was not found as good combiner for more than two characters. The best specific combiners were IBD 40 X IBD 47 for beta carotene, total sugar and fruit yield; IBD23 X IBD40 for brix (%), hollowness and flesh thickness; IBD40 X IBD57 for fruit breadth; IBD47 X IBD50 for non reducing sugar; and IBD47 X IBD57 for reducing sugar. The Vr-Wr graphs exhibited complete, partial and over dominance effect of genes for different characters. Complete dominance was observed only for beta carotene whereas over dominance was noticed for hollowness and flesh thickness. Partial dominance was ensured for fruit breadth, dry matter, brix (%), reducing sugar, non-reducing sugar, total sugar and fruit yield. Significant heterosis of some crosses against mid parent and better parents were observed for some characters.

plant biology↗

bioRxiv2022

In Vitro and In Vivo Pathogenicity of A. alternata to Sugar beet and Assessment of Sensitivity to Fungicides

A. alternata is a weak and opportunistic pathogen, but recently this pathogen has been reported in major sugar beet growing regions in the US. Therefore, we were interested to investigate the in-vitro and in-vivo pathogenesis of A. alternata to sugar beet seed, seedlings, tissue slices, stecklings, and roots. The in-vitro study demonstrated that A. alternata reduces seed germination, causes damping-off of seedlings, and decomposes beet tissue. The in-vivo study showed the same inoculum responsible for Alternaria leaf spots, and black circular spots on beetroot. Furthermore, we did a preliminary study to determine in vitro sensitivities of some fungicides to determine the effective concentration that inhibited 50% of radial mycelial growth (EC50 values) of A. alternata. The results indicated that EC50 values ranged from 0.0023 to 0.0058 for PROLINE, from 0.0004 to 0.0021 for OMEGA, and from 0.0027 to 0.0053 for Super TIN. Among the potential fungicides, the efficiency of quinone outside inhibitors (QoI- PRIAXOR) was relatively higher to inhibit the radial growth of A. alternata, irrespective of concentrations.

plant biology↗

bioRxiv2021

Design, 3D-printing, and characterisation of a low-cost, open-source centrifuge adaptor for separating large volume clinical blood samples

Blood plasma separation is a prerequisite in numerous biomedical assays involving low abundance plasma-borne biomarkers and thus is the fundamental step before many bioanalytical steps. Conventionally, plasma separation is performed using high-capacity refrigerated centrifuges which have the advantage of handling large volume blood samples. These centrifuges are bulky, and prohibitively expensive for low-resource settings, with prices starting from $1,500. Although commercial and existing open-source micro-centrifuges are relatively low-cost, they cannot handle large volume blood samples. Microfluidic blood plasma separation also has been adopted by many researchers to enable low-cost plasma separation, however, these systems still present yield and purity issues for extremely low abundance biomarker detection such as the detection of various fractions of circulating cell-free DNA. To overcome this, we customised the rotor of a commercially available micro-centrifuge [~]$125) using fused filament fabrication to enable centrifugation of large clinical blood samples in resource poor-settings. Our designed adaptor ($15) can hold two 9 mL S-Monovette tubes and maintain the same separation performance (yield, cell count, hemolysis, albumin levels) as the control benchtop refrigerated centrifuge. This low-cost open-source centrifugation system capable of processing clinical blood tubes could be valuable to low-funded laboratories or low-resource settings where centrifugation is required immediately after blood withdrawal for further testing.

bioengineering↗

bioRxiv2020

Isolation and characterization of two bacterial strains from textile effluents having Malachite Green dye degradation ability

Water pollution from textile effluent is now one of the major issues all over the world. Malachite Green dye of the triphenylmethane group is a key component of textile effluents. This study aimed to isolate and identify potential Malachite Green dye degrading bacteria from textile effluents. Different growth and culture parameters such as temperature, pH, inoculum-size and dye concentration were optimized to perform the dye-degradation assay using different concentrations of Malachite Green dye in mineral salt medium. A photo-electric-colorimeter was used to measure the decolorizing activity of bacteria at different time intervals after aerobic incubation. Two competent bacterial strains of Enterobacter spp. (CV-S1 and CM-S1) were isolated from textile effluents showing potential degradation efficiency against Malachite Green dye. The RAPD analysis and 16S rRNA sequencing confirmed the genetical difference of the isolated strains Enterobacter sp. CV-S1 and Enterobacter sp. CM-S1. The two bacterial strains CV-S1 and CM-S1 showed complete Malachite Green dye degradation up to 15 mg/l under shaking condition with 5% (v/v) inoculums at pH 6.50 and temperature 35{degrees}C within 72 and 144 hours respectively. These findings indicate that the two potential bacterial strains can be used in large scale treatment of textile effluents in the future.

microbiology↗

bioRxiv2019

Attenuation of epigenetic regulator SMARCA4 and ERK-ETS signaling suppresses aging-related dopaminergic degeneration

Parkinsons disease (PD) is a complex disease with high heterogeneity. How complex interactions of genetic, environmental factors and aging jointly contribute to dopaminergic degeneration in PD is largely unclear. Here, we applied frequent gene co-expression analysis on human patient substantia nigra-specific microarray datasets to identify potential novel disease-related genes. In vivo Drosophila studies validated two of 32 candidate genes, a chromatin remodeling factor SMARCA4 and a biliverdin reductase BLVRA. Inhibition of SMARCA4 was able to prevent dopaminergic degeneration not only caused by overexpression of BLVRA but also in four most common Drosophila PD models. Mechanistically, aberrant SMARCA4 and BLVRA converged on elevated ERK-ETS activity, attenuation of which by either genetic or pharmacological manipulation effectively suppressed dopaminergic degeneration in vivo. Drug inhibition of MEK/ERK also mitigated mitochondrial defects in PD gene-deficient human cells. Our findings underscore the important role of epigenetic regulators and implicate a common signaling axis for therapeutic intervention in a broad range of aging-related disorders including PD.

neuroscience↗