Biology subjects

Ullah, M. A.

Publications and source records attributed to Ullah, M. A..

15 recordsLinked to original sources

bioRxiv2026

Biodiversity Dimensions in Mangroves: Uncovering Interactions and Spatial Drivers in the Sundarbans

Mangroves play a crucial role in supporting global biodiversity and ecosystem functioning, yet how their multidimensional diversity interact and respond under diverse stress conditions remains underexplored. To address this gap, using species, environmental, functional trait and forest structural data collected from the permanent sample plot (PSP) network (110 PSPs) of the worlds largest mangrove ecosystem, the Sundarbans, we answer three key questions: (Q1) How are structural, functional, taxonomic, and phylogenetic diversities interconnected? We hypothesized that these diversity components are positively correlated (H1). (Q2) What are the key environmental stressors and how the diversity components are influenced by multiple stressors? We hypothesized that these stressors negatively affect all diversity components (H2). (Q3) What spatial patterns emerge in the distributions of these diversity components? Here we hypothesized that these diversity components vary across space under changing environmental conditions (H3). Our results show that taxonomic, functional, structural, and phylogenetic diversity have varying degrees of interconnection. While taxonomic and structural diversity are strongly correlated, functional and phylogenetic diversity exhibit more independent patterns, suggesting distinct ecological processes shape each dimension. Salinity, elevation, silt, community structure and downstream-upstream gradient (i.e., upriver position) have strong influences on all the diversity components although the magnitude of the influence varies. GAM results reveal that salinity and siltation act as the primary negative drivers for most dimensions; however, functional richness and divergence show a unique positive response to salinity. Furthermore, we found that community structure and upriver position significantly influence diversity patterns, often in a non-linear fashion. Though taxonomic, structural, and phylogenetic diversity show higher values mainly in the moderate and low saline areas, functional richness shows higher values in high saline areas. Overall, our results provide strong support for all the hypotheses. Our findings highlight the importance of holistic approach integrating taxonomic, structural, functional, and phylogenetic dimensions for maintaining biodiversity and ecosystem functions in dynamic mangrove ecosystems and emphasize the need for conservation efforts that target moderate-stress zones to preserve both ecological and evolutionary diversity. HighlightsO_LIExplored the interconnection between four dimensions of biodiversity (taxonomic, structural, functional, and phylogenetic) and how they respond to multiple stressors in the worlds largest mangrove forest. C_LIO_LIHigh salinity and siltation act as the primary environmental stressors that negatively affect overall biodiversity. C_LIO_LIStructural diversity is strongly related to species richness, serving as a key indicator of ecosystem health. C_LIO_LIFunctional and phylogenetic diversity follow independent spatial patterns, promoting the need for multi-dimensional monitoring. C_LI

ecology↗

bioRxiv2025

Assessment of the Genetic Architecture at Early-Stage Drought Tolerance in Wheat Using UAV-Based Multispectral Imaging

Recent advances in unmanned aerial vehicles (UAVs) and multispectral sensor technologies have transformed high-throughput phenotyping as an efficient alternative to traditional approaches. In this study, we employed UAV-based multispectral imaging to monitor early-stage drought stress in wheat. A panel of 221 historical spring wheat cultivars from Pakistan, representing over a century of breeding history, were evaluated under irrigated and drought conditions. UAV flights were conducted twice at early growth stages to capture multispectral imagery, which was processed in Pix4D mapper for image alignment and orthomosaic generation. Plot segmentation and trait extraction were performed in QGIS. Eight drought-responsive vegetative indices (VIs) were analyzed to assess genotypic variation. Significant to highly significant differences were observed among genotypes, treatments, and their interactions across all VIs. Broad-sense heritability estimates were moderate to high for most traits, with predominantly additive gene action. Vegetative indices such as NDVI, GNDVI, EVI, and SAVI showed strong correlations with each other and effectively detected early canopy stress under drought. Principal component analysis based on 23.897K SNPs indicated a mixed genetic population. Genome-wide association studies identified 115 significant QTNs linked to VIs under both conditions, corresponding to 74 loci, including 26 pleiotropic loci. Of these, 10 pleiotropic loci detected under drought were annotated and six putative candidate genes were identified which showed expression in multiple tissues based on transcriptome data. Two genes i.e., TraesCS1D01G217600.1 (HSP70) and TraesCS6D01G254000.1 (ZmMDAR3), showed differential expression pattern among control and drought treatment. These findings highlight the potential of UAV-based phenotyping for early drought detection and provide candidate genes for improving drought tolerance in wheat. Future research should focus on the functional roles of these genes under drought stress.

molecular biology↗

bioRxiv2024

A maternal high-fat diet predisposes to infant lung disease via increased neutrophil-mediated IL-6 trans-signaling

Poor maternal diet during pregnancy predisposes to severe lower respiratory tract infections (sLRI) in infancy, which in turn, increases childhood asthma risk, however the underlying mechanisms remain poorly understood. Here, we show that the offspring of high fat diet (HFD)-fed mothers ( HFD-reared pups) developed a sLRI following pneumovirus inoculation in early-life and subsequent asthma in later-life upon allergen exposure. Prior to infection, HFD-reared pups developed microbial dysbiosis and low-grade systemic inflammation (LGSI), characterized by hyper-granulopoiesis in the liver and elevated inflammatory cytokine expression, most notably IL-17A, IL-6 and sIL-6R (indicative of IL-6 trans-signaling) in the circulation and multiple organs, but most prominently the liver. Inhibition of IL-6 trans-signaling, using sgp130Fc transgenic mice or via specific genetic deletion of IL-6Ra on neutrophils, conferred protection against both diseases. Taken together, our findings suggest that a maternal HFD induces neonatal LGSI that predisposes to sLRI and subsequent asthma via neutrophil-mediated IL-6 trans-signaling.

immunology↗

bioRxiv2023

Accelerating Cancer Vaccine Development for Human T-Lymphotropic Virus (HTLV) Using a High-Throughput Molecular Dynamics Approach

Human T-lymphotropic virus (HTLV), a retrovirus belonging to the oncovirus family, has long been linked to be associated with various inflammatory and immunosuppressive disorders. To combat the devastating impact of this virus, our study employed a reverse vaccinology approach to design a multi-epitope-based vaccine targeting the highly virulent subtypes of HTLV. We conducted a comprehensive analysis of the molecular interactions between the vaccine and Toll-like receptors (TLRs), providing valuable insights for future research on preventing and managing HTLV-related diseases and any possible outbreaks. The vaccine was designed by focusing on the envelope glycoprotein gp62, a crucial protein involved in the infectious process and immune mechanisms of HTLV inside the human body. Epitope mapping identified T cell and B cell epitopes with low binding energies, ensuring their immunogenicity and safety. Linkers and adjuvants were incorporated to enhance the vaccines stability, antigenicity, and immunogenicity. Two vaccine constructs were developed, both exhibiting high antigenicity and conferring safety. Vaccine construct 2 demonstrated expected solubility and structural stability after disulfide engineering. Molecular docking analyses revealed strong binding affinity between the vaccine construct 2 and both TLR2 and TLR4. Molecular dynamics simulations indicated that the TLR2-vaccine complex displayed enhanced stability, compactness, and consistent hydrogen bond formation, suggesting a favorable affinity. Contact analysis, Gibbs free energy landscapes, and DCC analysis further supported the stability of the TLR2-vaccine complex, while DSSP analysis confirmed stable secondary structures. MM-PBSA analysis revealed a more favorable binding affinity of the TLR4-vaccine complex, primarily due to lower electrostatic energy. In conclusion, our study successfully designed a multi-epitope-based vaccine targeting HTLV subtypes and provided valuable insights into the molecular interactions between the vaccine and TLRs. These findings should contribute to the development of effective preventive and treatment approaches against HTLV-related diseases.

bioinformatics↗

bioRxiv2023

Unravelling the Oncogenic Potential and Prognostic Significance of CKS1B in Human Lung Adenocarcinoma and Squamous Cell Carcinoma: A Comprehensive Computational Analysis

Lung cancer (LC) confers to radical malignancy with a limited recourse of therapy worldwide. Consequently, LC has become the leading cause of cancer deaths in both men and women globally. Non-small cell lung cancer (NSCLC), one of the major LC types and accountable for a greater share of these cancer-associated deaths, further branches out to adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC). A dearth of evident clinical symptoms coupled with the diagnosis feasibility only after advanced metastasis raises the need for precision in treatment apart from the existing chemical drug treatments. Precise guidance can be entailed by targeted therapies, utilizing the potential and thoroughly evaluated differentially expressed genes of cancer under speculation for tumor treatments. Cyclin-dependent kinase regulatory subunit 1B (CKS1B), a member of the conserved cyclin kinase subunit 1 (CKS1) protein family, regulates the cell cycle. Increasing evidence revealed that up-regulation of the CKS1B gene is associated with multiple human-related cancers, indicates its potential use as a targeted therapeutic for early detection and treatment. CKS1B has been found to be associated with poor prognosis in both LUAD and LUSC, while the prognostic significance of CKS1B in other types of cancer is not well established. Herein, we have performed a comprehensive bioinformatics analysis of factors involved in LUAD and LUSC with CKS1B and discussed its role as a potential biomarker for early lung cancer detection and treatment. While these evaluations demonstrate the immunotherapeutic features and prognostic value of CKS1B, further in vivo and in vitro studies are required to determine the accuracy of final applications.

cancer biology↗

bioRxiv2023

The maternal microbiome regulates infant respiratory disease susceptibility via intestinal Flt3L expression and plasmacytoid dendritic cell hematopoiesis

Severe lower respiratory infection (sLRI) are a major cause of infant morbidity and mortality, and predispose to later chronic respiratory diseases such as asthma. Poor maternal diet during pregnancy is a risk factor for sLRI in the offspring. Here we demonstrate in mice that a maternal low-fibre diet (LFD) disrupts plasmacytoid and conventional dendritic cell (DC) hematopoiesis in the offspring, predisposing to sLRI and subsequent asthma. The LFD alters the composition of the maternal milk microbiome and assembling infant gut microbiome, ablating the induction of a developmental wave of the non-redundant DC growth factor Flt3L by neonatal intestinal epithelial cells. Therapy with a propionate-producing bacteria isolated from the milk of high-fibre diet-fed mothers, or supplementation with propionate, confers protection against sLRI by restoring gut Flt3L expression and pDC hematopoiesis. Our findings identify a microbiome-dependent Flt3L axis in the gut that regulates pDC hematopoiesis in early life and confers disease resistance. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=51 SRC="FIGDIR/small/522516v1_ufig1.gif" ALT="Figure 1"> View larger version (15K): org.highwire.dtl.DTLVardef@1a39990org.highwire.dtl.DTLVardef@1b6fe67org.highwire.dtl.DTLVardef@f8440dorg.highwire.dtl.DTLVardef@13bc67e_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2022

A Multi-omics Study on the Oncogenic Roles and Clinical Significance of Dynactin Family Gene (DCTN1-6) Expression in Liver Hepatocellular Carcinoma

In this study, we employed a comprehensive database mining approach to examine the possible oncogenic roles and clinical relevance of Dynactin family genes (DCTN1-6) in Liver Hepatocellular Carcinoma (LIHC). All the DCTNs were observed to be differentially expressed in LIHC tissues compared to the adjacent normal liver tissues. Most of the DCTNs were discovered to be aberrantly methylated (less methylated) and contain multiple somatic mutations (alteration frequency: 0.2-2.5%) in LIHC tissues. Overexpression of DCTNs was mostly associated with poor overall and relapse-free survival of LIHC patients. Alongside, all the DCTN genes were reported to be overexpressed across different demographic and clinical conditions, i.e., age, cancer stage, tumor grades, and metastatic stages of LIHC patients. DCTN expression was also associated with the infiltration levels of different immune cells, i.e., B cell, T cell, and macrophages in LIHC microenvironment. The co-expressed genes of DCTNs in the LIHC tissues were previously found to be involved in oncogenic processes in different cancer types and control crucial biological processes, i.e., nucleotide metabolism, RNA degradation, and chromosome organization. Later, the expression pattern of DCTNs was validated in two independent microarray datasets (i.e., GSE17856, GSE98383), which also supported our initial findings. All these findings suggest that DCTNs and their transcriptional and translational products are potential prognostic and therapeutic targets for LIHC diagnosis and treatment. This study will help further the development of DCTN-based diagnostic and therapeutic measures for LIHC and translate them into clinical implications.

genomics↗

bioRxiv2022

Identifying Proteasome 26S Subunit, ATPase (PSMC) Family Genes as the Prognostic Indicators and Therapeutic Targets in Lung Adenocarcinoma

This study explored the prognostic and therapeutic potentials of multiple Proteasome 26S Subunit, ATPase (PSMC) family of genes (PSMC1-5) in lung adenocarcinoma (LUAD) diagnosis and treatment. All the PSMCs were found to be differentially expressed (upregulated) at the mRNA and protein levels in LUAD tissues. The promoter and multiple coding regions of PSMCs were reported to be differentially and distinctly methylated, which may serve in the methylation-sensitive diagnosis of LUAD patients. Multiple somatic mutations (alteration frequency: 0.6-2%) were observed along the PSMCs coding regions in LUAD tissues that could assist in the high-throughput screening of LUAD patients. A significant association between PSMCs overexpression and LUAD patients poor overall and relapse-free survival (p<0.05, HR:>1.3) and individual cancer stages (p<0.001) was discovered, which justifies PSMCs as the ideal targets for LUAD diagnosis. Multiple immune cells and modulators (i.e., CD274, IDO1) were found to be associated with PSMCs expression in LUAD tissues that could aid in formulating PSMC-based diagnostic measures and therapeutic interventions for LUAD. Functional enrichment analysis of neighbor genes of PSMCs in LUAD tissues revealed different genes (i.e., SLIRP, PSMA2, NUDSF3) previously known to be involved in oncogenic processes and metastasis co-expressed with PSMCs, which could also be investigated further. Overall, this study recommends that PSMCs and their transcriptional and translational products are potential candidates for LUAD diagnostic and therapeutic measure discovery. However, further laboratory research is needed to validate the findings of this experiment.

cancer biology↗

bioRxiv2022

Expression Analysis, Molecular Characterization and Prognostic Evaluation on TMED4 and TMED9 Gene Expression in Glioma

Here, we utilized a database mining approach to unfold the prognostic and therapeutic potentials of Transmembrane EmP24 Trafficking Protein 4 (TMED4) and 9 (TMED) coding gene expressions in glioma. Both the genes were found to be overexpressed at the mRNA and protein level in low grade glioma (LGG) and glioblastoma multiforme (GBM) tissues including different glioma cell lines. Significant increase in the expression level of these genes with advancing glioma patients age, glioma grades and histological subtypes was observed. Differential and distinct promoter and coding sequence methylation pattern of TMED4 and TMED9 was observed in LGG and GBM tissues that may aid in methylation-sensitive diagnosis of glioma patients. The presence of multiple heterozygous genetic alterations (frequency: 0.4-1.1%) in those genes unveiled their potentials in high-throughput screening of glioma patients. The overexpression of TMED4 and TMED9 genes was associated with poor overall survival (OS) of LGG and GBM patients (HR:>1.6). Association of the expression levels of these genes with different immune cell infiltration levels i.e., B cell and T cell and modulators like CD274 and IL10RB was observed providing assurance in TMED-based diagnostic measure and therapeutic intervention discovery. Furthermore, functional enrichment analysis of the neighbor genes of TMED4 and TMED9 revealed that they are involved in metal ion binding, focal adhesion of cells and protein processing, and the deregulation of these activities are associated with gliomagenesis. Altogether, this study suggests that TMED4 and TMED9 are potential prognostic and therapeutic targets for glioma. However, further laboratory research is warranted.

cancer biology↗

bioRxiv2022

Exploring different virulent proteins of human respiratory syncytial virus for designing a novel epitope-based polyvalent vaccine: Immunoinformatics and molecular dynamics approaches

Human Respiratory Syncytial Virus (RSV) is one of the most prominent causes of lower respiratory tract infections (LRTI), contributory to infecting people from all age groups - a majority of which comprises infants and children. The implicated severe RSV infections lead to numerous deaths of multitudes of the overall population, predominantly the children, every year. Consequently, despite several distinctive efforts to develop a vaccine against the RSV as a potential countermeasure, there is no approved or licensed vaccine available yet, to control the RSV infection effectively. Therefore, through the utilization of immunoinformatics tools, a computational approach was taken in this study, to design and construct a multi-epitope polyvalent vaccine against the RSV-A and RSV-B strains of the virus. Potential predictions of the T-cell and B-cell epitopes were followed by extensive tests of antigenicity, allergenicity, toxicity, conservancy, homology to human proteome, transmembrane topology, and cytokine-inducing ability. The most promising epitopes (i.e. 13 CTL epitopes, 9 HTL epitopes, and 10 LBL epitopes) exhibiting full conservancy were then selected for designing the peptide fusion with appropriate linkers, having hBD-3 as the adjuvant. The peptide vaccine was modeled, refined, and validated to further improve the structural attributes. Following this, molecular docking analysis with specific TLRs was carried out which revealed excellent interactions and global binding energies. Additionally, molecular dynamics (MD) simulation was conducted which ensured the stability of the interactions between vaccine and TLR. Furthermore, mechanistic approaches to imitate and predict the potential immune response generated by the administration of vaccines were determined through immune simulations. Owing to an overall evaluation, in silico cloning was carried out in efforts to generate recombinant pETite plasmid vectors for subsequent mass production of the vaccine peptide, incorporated within E.coli. However, more in vitro and in vivo experiments can further validate its efficacy against RSV infections.

immunology↗

bioRxiv2020

Synergism and antagonism of bacterial-viral co-infection in the upper respiratory tract

Streptococcus pneumoniae (the pneumococcus) is a leading cause of pneumonia in children under five years old. Co-infection by pneumococci and respiratory viruses enhances disease severity. Little is known about pneumococcal co-infections with Respiratory Syncytial Virus (RSV). Here, we developed a novel infant mouse model of co-infection using Pneumonia Virus of Mice (PVM), a murine analogue of RSV, to examine the dynamics of co-infection in the upper respiratory tract, an anatomical niche that is essential for host-to-host transmission and progression to disease. Coinfection increased damage to the nasal tissue and increased production of the chemokine CCL3. Pneumococcal nasopharyngeal density and shedding in nasal secretions were increased by co-infection. In contrast, co-infection reduced PVM loads in the nasopharynx, an effect that was independent of pneumococcal strain and the order of infection. We showed this antagonistic effect was abrogated using a pneumococcal mutant deficient in capsule production and incapable of nasopharyngeal carriage. The pneumococcal-mediated reduction in PVM loads was caused by accelerated viral clearance from the nasopharynx. Although these synergistic and antagonistic effects occurred with both wild-type pneumococcal strains used in this study, the magnitude of the effects was strain dependent. Lastly, we showed that pneumococci can also antagonize influenza virus. Taken together, our study has uncovered multiple novel facets of bacterial-viral co-infection. Our findings have important public health implications, including for bacterial and viral vaccination strategies in young children.

microbiology↗

bioRxiv2020

The Essential Facts of Wuhan Novel Coronavirus Outbreak in China and Epitope-based Vaccine Designing against 2019-nCoV

Wuhan Novel Coronavirus disease (COVID-19) outbreak has become a global outbreak which has raised the concern of scientific community to design and discover a definitive cure against this deadly virus which has caused deaths of numerous infected people upon infection and spreading. To date, no antiviral therapy or vaccine is available which can effectively combat the infection caused by this virus. This study was conducted to design possible epitope-based subunit vaccines against the SARS-CoV-2 virus using the approaches of reverse vaccinology and immunoinformatics. Upon continual computational experimentation three possible vaccine constructs were designed and one vaccine construct was selected as the best vaccine based on molecular docking study which is supposed to effectively act against SARS-CoV-2. Later, molecular dynamics simulation and in silico codon adaptation experiments were carried out in order to check biological stability and find effective mass production strategy of the selected vaccine. Hopefully, this study will contribute to uphold the present efforts of the researches to secure a definitive treatment against this lethal virus.

immunology↗

bioRxiv2020

Curcumin Analogues as the Inhibitors of TLR4 Pathway in Inflammation and Their Drug Like Potentialities: A Computer-based Study

In this study Curcumin and their different analogues have been analyzed as the inhibitors of signaling proteins i.e., Cycloxygenase-2 (COX-2), Inhibitor of Kappa{beta} Kinase (IKK) and TANK binding kinase-1 (TBK-1) of Toll Like Receptor 4 (TLR4) pathway involved in inflammation using computational tools. Multiple analogues showed better binding affinity than the approved drugs for the respective targets. Upon continuous computational exploration 6-Gingerol, Yakuchinone A and Yakuchinone B were identified as the best inhibitors of COX-2, IKK and TBK-1 respectively. Then their drug like potentialities were analyzed in different experiments where they also performed sound and similar. Hopefully, this study will uphold the efforts of researchers to identify anti-inflammatory drugs from natural sources.

pharmacology and toxicology↗

bioRxiv2020

In Silico Analysis of Some Phytochemicals as Potential Anti-cancer Agents Targeting Cyclin Dependent Kinase-2, Human Topoisomerase IIa and Vascular Endothelial Growth Factor Receptor-2

Cancer is caused by a variety of pathways, involving numerous types of enzymes, among them three enzymes: Cyclin dependent kinase-2 (CDK-2), Human topoisomerase II and Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) are three most common enzymes that are involved in the cancer development. Although many chemical drugs are available in the market, plant sources are known to contain a wide variety of agents that are known to possess anticancer activity. In this experiment, total thirty compounds were analysed against the mentioned enzymes using different tools of bioinformatics and in silico biology like molecular docking study, druglikeness property experiment, ADME/T test, PASS prediction and P450 site of metabolism prediction as well as DFT calculations to determine three best ligands that have the capability to inhibit the mentioned enzymes. Form the experiment, Epigallocatechin gallate was found to be the best ligand to inhibit CDK-2, Daidzein showed best inhibitory activities towards Human topoisomerase II and Quercetin was predicted to be the best agent against VEGFR-2. They were also predicted to be quite safe and effective agents to treat cancer. However, more in vivo and in vitro analysis are required to confirm their safety and efficacy in this regard.

bioinformatics↗

bioRxiv2020

Designing Novel Subunit Vaccines against Herpes Simplex Virus-1 using Reverse Vaccinology Approach

Herpes Simplex Virus (HSV) is an infectious virus that is responsible for various types of orofacial and genital infections. Two types of HSV viruses, HSV-1 and HSV-2, are the most dangerous HSV viruses. Every year, millions of people get infected with this menacing virus, however, no satisfactory treatment or vaccine has not yet been discovered to fight against HSV. Although there are some anti-viral therapies, however, studies have showed that such anti-viral therapies may also fail to provide good impact. In this study, a possible subunit vaccine against HSV-1, strain-17, was designed using the tools and reverse vaccinology and bioinformatics. Three potential antigenic envelope glycoproteins were selected from nine envelope glycoproteins, for possible vaccine construction. Potential epitopes capable of inducing high immunogenic response and at the same time have non-allergenicity and conservancy across other strains and species, were selected by some robust analysis, for vaccine construction. Finally, three possible vaccines were designed. Each of the vaccine construct differ from each other only in their adjuvant sequences and based on molecular docking analysis, one best vaccine construct was selected for molecular dynamics simulation study and in silico codon adaptation. The experiment showed that the selected best vaccine should be good candidate against HPV-1, strain-17. However, wet lab study should be conducted on the suggested vaccine(s) for confirming their potentiality, safety and efficacy.

bioinformatics↗