Biology subjects

Ahmed, I.

Publications and source records attributed to Ahmed, I..

At least 37 records · Page 2Linked to original sources

bioRxiv2023

In vivo and in silico experiment on Mitragyna speciosa offers new insight of antidiabetic potentials

Diabetes Mellitus (DM) is a serious metabolic disease with several treatments available for managing it, however, they can be expensive and have side effects. Medicinal plants have been used for many years to treat numerous diseases. Mitragyna speciosa (M. speciosa) plant has been shown to have anti-diabetic properties in preclinical studies. Hence, this study aimed to investigate the phytochemical compositions and anti-diabetic effects of M. speciose, using both in vivo and in silico approaches. In the in vivo study, experimental diabetes was induced in Swiss albino mice using the drug alloxan (150 mg/kg). Four groups of diabetic mice were taken. Two of the groups were given extracts at doses of 200 mg/kg and 400 mg/kg respectively. Diabetic mice treated with the reference drug, glibenclamide (5mg/kg) were chosen as a positive control, and mice with only vehicles were considered as a negative control. The Oral Glucose Tolerance Test (OGTT) and the acute toxicity test were performed. In the in silico study, molecular docking and dynamics were performed for the identification of the plant compounds that could effectively bind with the DPP4 receptor. Analysis of the study suggested that the lethal dose (LD50) values were greater than 2000 mg/kg, indicating that a dose below this level can be selected. The OGTT results showed that both doses of M. speciose extracts significantly reduced blood glucose levels (P<0.0001). However, neither dose exhibited a significantly higher blood glucose reduction compared to glibenclamide (5 mg/kg) (P > 0.05). Phytochemical screening and the ADMET profile analysis suggested four key compounds: Mitragynine, Corynantheidine, Corynoxine, and Speciociliatine in M. speciosa. The molecular docking analysis revealed these four compounds as potential antidiabetic agents considering their high binding affinity to the DPP4 receptor. These compounds were also found to be stable in the DPP4 binding pocket, as evidenced by the molecular dynamics simulation. Lastly, it can be demonstrated that the in silico experiments confirmed M. speciosa extracts to be capable of reducing blood glucose levels because of the presence of compounds.

pharmacology and toxicology↗

bioRxiv2023

Clonal fitness decline in somatic differentiation hierarchies

The concept of clonal fitness is fundamental to describe the evolutionary dynamics in somatic tissues. It is now well established that otherwise healthy somatic tissues become increasingly populated by expanding clones with age. However, the dynamic properties and respective fitnesses of these clones are less well understood. Here we show, that in somatic tissues organised as a differentiation hierarchy, theory predicts a natural decline of effective clonal fitness over time in the absence of additional driver events. This decline is intrinsic to the tissue organisation and can be captured quantitatively by a simple heuristic equation that is proportional to 1/time. We also show that the expected fitness decline is directly observable in human haematopoiesis. The predicted short and long term dynamics agree with in vivo observations using data of Neutrophil recovery after bone marrow transplants and naturally progressing Chronic Lymphocyte Leukemia (CLL). We further show that theory predicts the existence of a long term equilibrium fitness. All CLL patients transition into a stable equilibrium fitness eventually. We find significant inter-patient variation of long term fitness and a strong correlation with disease aggressiveness. Interestingly, CLL long term fitness can be forecast based on the early stages of disease progression, suggesting a Big Bang like model for CLL evolution.

cancer biology↗

bioRxiv2023

GAGA Factor Overcomes 1D Diffusion Barrier by 3D Diffusion in Search of Nucleosomal Targets

To elucidate how eukaryotic sequence-specific transcription factors (TFs) search for gene targets on chromatin, we used multi-color smFRET and single-particle imaging to track the diffusion of purified GAGA-Associated Factor (GAF) on DNA and nucleosomes. Monomeric GAF DNA-binding domain (DBD) bearing one zinc finger finds its cognate site by 1D or 3D diffusion on bare DNA and rapidly slides back-and-forth between naturally clustered motifs for seconds before escape. Multimeric, full-length GAF also finds clustered motifs on DNA by 1D-3D diffusion, but remains locked on target for longer periods. Nucleosome architecture effectively blocks GAF-DBD 1D-sliding into the histone core but favors retention of GAF-DBD when targeting solvent-exposed sites by 3D-diffusion. Despite the occlusive power of nucleosomes, 1D-3D facilitated diffusion enables GAF to effectively search for clustered cognate motifs in chromatin, providing a mechanism for navigation to nucleosome and nucleosome-free sites by a member of the largest TF family.

biophysics↗

bioRxiv2023

Repurposing Remdesivir for COVID-19: Computational Drug Design Targeting SARS-CoV-2 RNA Polymerase and Main Protease using Molecular Dynamics Approach

The coronavirus disease of 2019 (COVID-19) is a highly contagious respiratory illness that has become a global health crisis with new variants, an unprecedented number of infections, and deaths and demands urgent manufacturing of potent therapeutics. Despite the success of vaccination campaigns around the globe, there is no particular therapeutics approved to date for efficiently treating infected individuals. Repositioning or repurposing previously effective antivirals against RNA viruses to treat COVID-19 patients is a feasible option. Remdesivir is a broad-spectrum antiviral drug that the Food and Drug Administration (FDA) licenses for treating COVID-19 patients who are critically ill patients. Remdesivirs low efficacy, which has been shown in some clinical trials, possible adverse effects, and dose-related toxicities are issues with its use in clinical use. Our study aimed to design potent derivatives of remdesivir through the functional group modification of the parent drug targeting RNA-dependent RNA polymerase (RdRp) and main protease (MPro) of SARS-CoV-2. The efficacy and stability of the proposed derivatives were assessed by molecular docking and extended molecular dynamics simulation analyses. Furthermore, the pharmacokinetic activity was measured to ensure the safety and drug potential of the designed derivatives. The derivatives were non-carcinogenic, chemically reactive, highly interactive, and stable with the target proteins. D-CF3 is one of the designed derivatives that finally showed stronger interaction than the parent drug, according to the docking and dynamics simulation analyses, with both target proteins. However, in vitro and in vivo investigations are guaranteed to validate the findings in the future.

bioinformatics↗

bioRxiv2022

Optopharmacological tools for precise spatiotemporal control of oxytocin signaling in the central nervous system and periphery

Oxytocin is a neuropeptide critical for maternal physiology and social behavior, and is thought to be dysregulated in several neuropsychiatric disorders. Despite the biological and neurocognitive importance of oxytocin signaling, methods are lacking to activate oxytocin receptors with high spatiotemporal precision in the brain and peripheral mammalian tissues. Here we developed and validated caged analogs of oxytocin which are functionally inert until cage release is triggered by ultraviolet light. We examined how focal versus global oxytocin application affected oxytocin-driven Ca2+ wave propagation in mouse mammary tissue. We also validated the application of caged oxytocin in the hippocampus and auditory cortex with electrophysiological recordings in vitro, and demonstrated that oxytocin uncaging can accelerate the onset of mouse maternal behavior in vivo. Together, these results demonstrate that optopharmacological control of caged peptides is a robust tool with spatiotemporal precision for modulating neuropeptide signaling throughout the brain and body.

neuroscience↗

bioRxiv2022

Oncogenic ERRB2 signals through the AP-1 transcription factor to control mesenchymal-like properties of oesophageal adenocarcinoma

Oesophageal adenocarcinoma (OAC) is a deadly disease with poor survival statistics and few targeted therapies available. One of the most common molecular aberrations in OAC is amplification or activation of the gene encoding the receptor tyrosine kinase ERBB2, and ERBB2 is targeted in the clinic for this subset of patients. However, the downstream consequences of these ERBB2 activating events are not well understood. Here we used a combination of phosphoproteomics, open chromatin profiling and transcriptome analysis on cell line models and patient-derived datasets to interrogate the molecular pathways operating downstream from ERBB2. Integrated analysis of these data sets converge on a model where dysregulated ERBB2 signalling is mediated at the transcriptional level by the transcription factor AP-1. AP-1 in turn controls cell behaviour by acting on cohorts of genes that regulate cell migration and adhesion, features often associated with EMT. Our study therefore provides a valuable resource for the cancer cell signalling community and reveals novel molecular determinants underlying the dysregulated behaviour of OAC cells.

cancer biology↗

bioRxiv2022

eRNA profiling uncovers the enhancer landscape of oesophageal adenocarcinoma and reveals new deregulated pathways

Cancer is driven by both genetic and epigenetic changes that impact on gene expression profiles and the resulting tumourigenic phenotype. Enhancers are transcriptional regulatory elements that are key to our understanding of how this rewiring of gene expression is achieved in cancer cells. Here we have harnessed the power of RNA-seq data from hundreds of patients with oesophageal adenocarcinoma (OAC) or its precursor state Barretts oesophagus (BO) coupled with open chromatin maps to identify potential enhancer RNAs (eRNAs) and their associated enhancer regions in this cancer. We identify [~]1000 OAC-specific enhancers and use this data to uncover new cellular pathways that are operational in OAC. Among these are enhancers for JUP, MYBL2 and CCNE1, and we show that their activity is required for cancer cell viability. We also demonstrate the clinical utility of our dataset for identifying disease stage and patient prognosis. Our data therefore identify an important set of regulatory elements that enhance our molecular understanding of OAC and point to potential new therapeutic directions.

cancer biology↗

bioRxiv2022

Honey bee flights under ethanol-exposure show changes in body and wing kinematics

Flying social insects can provide model systems for inflight interactions in computationally-constrained aerial robot swarms, whose interactions may be chemically modulated under recent measurement advancements provide a capability to simultaneously make precise measurements of insect wing and body motions. This paper presents the first quantitative measurements of ethanol-exposed honey bee flight body and wing kinematic parameters. Four high speed cameras (9000 fps) were used to track the wing and body motions of insects (Apis mellifera). Digitization, consisting of data association, hull reconstruction, and segmentation, achieved the first high speed measurements of ethanol exposed honey bees wing and body motions. Kinematic changes induced by exposure to ethanol concentrations from 0% to 5% were studied using statistical analysis tools. Analysis considered trial wide mean and maximum values and gross wingstroke parameters, and tested deviations for statistical significance using Welchs t-test and Cohens d test. The results indicate a decrease in maximal heading and pitch rates of the body, and that roll rate is affected at high concentrations (5%). The wingstroke effects include a stroke frequency decrease, stroke amplitude increase, stroke inclination angle increase, and a more planar wingstroke. These effects due to ethanol exposure are valuable tools to separate from interaction effects.

animal behavior and cognition↗

bioRxiv2022

High Speed Visual Insect Swarm Tracker (Hi-VISTA) used to identify the effects of confinement on individual insect flight

Individual insects flying in crowded assemblies perform complex aerial maneuvers by sensing and feeding back neighbor measurements to small changes in their wing motions. To understand the individual feedback rules that permit these fast, adaptive behaviors in group flight, a high-speed tracking system is needed capable of tracking both body motions and more subtle wing motion changes for multiple insects in simultaneous flight. This capability extends tracking beyond the previous focus on individual insects to multiple insects. This paper presents Hi-VISTA, which provides a capability to track wing and body motions of multiple insects using high speed cameras (9000 fps). Processing steps consist of automatic background identification, data association, hull reconstruction, segmentation, and feature measurement. To improve the biological relevance of laboratory experiments and develop a platform for interaction studies, this paper applies the Hi-VISTA measurement system to Apis mellifera foragers habituated to transit flights through a transparent tunnel. Binary statistical analysis (Welchs t-test, Cohens d effect size) of 95 flight trajectories is presented, quantifying the differences between flights in an unobstructed tunnel and in a confined tunnel volume. The results indicate that body pitch angle, heading rate, flapping frequency, and vertical speed (heave) are all affected by confinement, and other flight variables show minor or statistically insignificant changes. These results form a baseline as swarm tracking and analysis begins to isolate the effects of neighbors from environment.

animal behavior and cognition↗

bioRxiv2021

Pseudogenization of trnT-GGU in chloroplast genomes of the plant family Asteraceae

The chloroplast genome evolves through the course of evolution. Various types of mutational events are found within the chloroplast genome, including insertions-deletions (InDels), substitutions, inversions, gene rearrangement, and pseudogenization of genes. The pseudogenization of the trnT-GGU gene was previously reported in the Cryptomeria japonica (Cupressaceae), Pelargonium x hortorum (Geraniaceae), and in the two species of the tribe Gnaphalieae (Asteroideae, Asteraceae). Here, we performed a broad analysis of the trnT-GGU gene among the species of twelve subfamilies of Asteraceae and found pseudogenization of this gene is not limited to the two species of Gnaphalieae or the tribe Gnaphalieae. We report for the first time that this gene is pseudo in the species of three subfamilies of Asteraceae, including Gymnarrhenoideae, Cichorioideae and Asteroideae. The analyses of the species of 78 genera of Asteroideae revealed that this pseudogenization event is linked to the insertion within the 5' acceptor stem and not linked to the habit, habitat, and geographical distribution of the plant.

evolutionary biology↗

bioRxiv2021

The GASA Gene Family in Theobroma cacao: Genome Wide Identification and Expression Analyses

The gibberellic acid-stimulated Arabidopsis (GASA/GAST) gene family is widely distributed in plants. The role of the GASA gene family has been reported previously in various physiological and biological processes, such as cell division, root and seed development, stem growth, and fruit ripening. These genes also provide resistance to abiotic and biotic stresses including antimicrobial, antiviral, and antifungal. Here, we report 17 tcGASA genes in Theobroma cacao L. distributed on six chromosomes. The gene structure, promoter-region sequences, protein structure, and biochemical properties, expression, and phylogenetics of all tcGASAs were analyzed. Phylogenetic analyses divided tcGASA proteins into five groups. The nine segmentally duplicating genes form four pairs and cluster together in phylogenetic tree. Purifying selection pressure was recorded on tcGASA, including duplicated genes. Several stress/hormone-responsive cis-regulatory elements were also recognized in the promoter region of tcGASAs. Differential expression analyses revealed that most of the tcGASA genes showed elevated expression in the seeds (cacao food), implying their role in seed development. The black rod disease of genus Phytophthora caused up to 20-25% loss (700,000 metric tons) in world cacao production. The role of tcGASA genes in conferring fungal resistance was also explored based on RNAseq data against Phytophthora megakarya. The differential expression of tcGASA genes was recorded between the tolerant and susceptible cultivars of cacao plants, which were inoculated with the fungus for 24h and 72h. This differential expression indicating possible role of tcGASA genes to fungal resistant in cacao. Our findings provide new insight into the function, evolution, and regulatory system of the GASA family genes in T. cacao and provide new target genes for development of fungi-resistant cacao varieties in breeding programs.

plant biology↗

bioRxiv2021

Human leukocyte antigen class II gene diversity tunes antibody repertoires to common pathogens

Allelic diversity of HLA class II genes may help maintain humoral immunity against infectious diseases. We investigated the relative contribution of specific HLA class II alleles, haplotypes and genotypes on the variation of antibody responses to a variety of common pathogens in a cohort of 800 adults representing the general Arab population. We found that classical HLA class II gene heterozygosity confers a selective advantage. Moreover, we demonstrated that multiple HLA class II alleles play a synergistic role in shaping the antibody repertoire. Interestingly, associations of HLA-DRB1 genotypes with specific antigens were identified. Our findings suggest that HLA class II gene polymorphisms confer specific humoral immunity against common pathogens, which may have contributed to the genetic diversity of HLA class II loci during hominine evolution.

genetics↗

bioRxiv2020

Novel Mutations in NSP1 and PLPro of SARS-CoV-2 NIB-1 Genome Mount for Effective Therapeutics

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the etiologic agent of Coronavirus Disease-2019 (COVID-19), is rapidly accumulating new mutations. Analysis of these mutations is necessary for gaining knowledge regarding different aspects of therapeutic development. Recently, we have reported a Sanger method based genome sequence of a viral isolate named SARS-CoV-2 NIB-1, circulating in Bangladesh. The genome has four novel mutations in V121D, V843F, A889V and G1691C positions. V121D substitution has the potential to destabilize the Non-Structural Protein (NSP-1) which inactivates the type-1 Interferon-induced antiviral system hence this mutant could be the basis of attenuated vaccines against SARS-CoV-V843F, A889V and G1691C are all located in NSP3. G1691C can decrease the flexibility of the protein while V843F and A889V changed the binding pattern of SARS-CoV-2 Papain-Like protease (PLPro) inhibitor GRL0617. V843F PLPro showed reduced affinity for Interferon Stimulating Gene-15 (ISG-15) protein whereas V843F+A889V double mutants exhibited the same binding affinity as wild type PLPro. Here, V843F is a conserved position of PLPro that damaged the structure but A889V, a less conserved residue, most probably neutralized that damage. Mutants of NSP1 could provide attenuated vaccines against coronavirus. Also, these mutations of PLPro could be targeted to develop anti-SARS therapeutics.

bioinformatics↗

bioRxiv2020

Profiles of Expression pattern and tissue distribution of host defense peptides genes in different chicken (Gallus gallus) breeds related to body weight

Host defense peptides (HDPs) are an important first line of defense with antimicrobial and immunomodulatory properties. Selection for increased body weight is suggested to be related to reduced immune response. We studied the relationships among body weight, age, and the HDP expression patterns in intestine and immune organs. We used chickens with marked differences of body sizes. The non-selected Daweishan mini chickens showed the highest indexes of immune organs and the lowest concentrations of the plasma immune parameters C3, C4, IgA, and IgY, while the commercial Avian broiler showed the opposite results. The Daweishan mini chickens showed the highest mRNA expressions of HDP genes in small intestine followed by the semi-selected Wuding chickens. Compared with local breeds, broiler chickens showed higher mRNA expression of HDP genes in spleen, thymus, and bursa. Body weight and HDP expression levels were negatively correlated in the intestine and positively in the immune organs. These results indicated that the HDP immune regulatory roles in small intestine acted as first line of defense in innate immunity in local breeds, and as an adaptive immunity in broiler chickens. Selection was associated with the expression profiles of HDP genes in a chicken, age, and organ-specific manner.

immunology↗

bioRxiv2020

Agro-morphological, yield, and genotyping-by-sequencing data of selected wheat germplasm

Wheat (Triticum aestivum) is the most important staple food in Pakistan. Knowledge of its genetic diversity is critical for designing effective crop breeding programs. Here we report agro-morphological and yield data for 112 genotypes (including 7 duplicates) of wheat (Triticum aestivum) cultivars, advance lines, landraces and wild relatives, collected from several research institutes and breeders across Pakistan. We also report genotyping-by-sequencing (GBS) data for a selected sub-set of 52 genotypes. Sequencing was performed using Illumina HiSeq 2500 platform using the PE150 run. Data generated per sample ranged from 1.01 to 2.5 Gb; 90% of the short reads exhibited quality scores above 99.9%. TGACv1 wheat genome was used as a reference to map short reads from individual genotypes and to filter single nucleotide polymorphic loci (SNPs). On average, 364,074{+/-}54479 SNPs per genotype were recorded. The sequencing data has been submitted to the SRA database of NCBI (accession number SRP179096). The agro-morphological and yield data, along with the sequence data and SNPs will be invaluable resources for wheat breeding programs in future.

genetics↗

bioRxiv2020

Comparison among the first representative chloroplast genomes of Orontium, Lisa, Zamioculcas, and Stylochaeton of the plant family Araceae: inverted repeat dynamics are not linked to phylogenetic signaling

The chloroplast genome provides insight into the evolution of plant species. We de novo assembled and annotated chloroplast genomes of the first representatives of four genera representing three subfamilies: Lasia spinosa (Lasioideae), Stylochaeton bogneri, Zamioculcas zamiifolia (Zamioculcadoideae), and Orontium aquaticum (Orontioideae), and performed comparative genomics using the plastomes. The size of the chloroplast genomes ranged from 163,770-169,982 bp. These genomes comprise 114 unique genes, including 80 protein-coding, 4 rRNA, and 30 tRNA genes. These genomes exhibited high similarities in codon usage, amino acid frequency, RNA editing sites, and microsatellites. The junctions JSB (IRb/SSC) and JSA (SSC/IRa) are highly variable, as is oligonucleotide repeats content among the genomes. The patterns of inverted repeats contraction and expansion were shown to be homoplasious and therefore unsuitable for phylogenetic analyses. Signatures of positive selection were shown for several genes in S. bogneri. This study is a valuable addition to the evolutionary history of chloroplast genome structure in Araceae.

plant biology↗

bioRxiv2020

Complete chloroplast genomes of Anthurium huixtlense and Pothos scandens (Pothoideae, Araceae): unique inverted repeat expansion and contraction affect rate of evolution

The subfamily Pothoideae belongs to the ecologically important plant family Araceae. Here, we report the chloroplast genomes of two species of the subfamily Pothoideae: Anthurium huixtlense (163,116 bp) and Pothos scandens (164,719 bp). The chloroplast genome of P. scandens showed unique inverted repeats (IRs) contraction and expansion, which increases the size of the large single copy (102,956) region and decreases the size of the small single-copy (6779 bp) region. This led to duplication of many single-copy genes due to transfer to IR regions from the small single-copy (SSC) region, whereas some duplicate genes became single copy due to transfer to large single-copy regions. The rate of evolution of protein-coding genes was affected by the contraction and expansion of IRs; we found higher mutation rates for genes that exist in single-copy regions as opposed to IRs. We found a 2.3-fold increase of oligonucleotide repeats in P. scandens when compared with A. huixtlense, whereas amino acid frequency and codon usage revealed similarities. We recorded higher transition substitutions than transversion substitutions. The transition/transversion ratio was 2.26 in P. scandens and 2.12 in A. huixtlense. We also found a higher rate of transversion substitutions linked with non-synonymous substitutions than synonymous substitutions. The phylogenetic inference of the limited species showed the monophyly of the Araceae subfamilies. Our study provides insight into the molecular evolution of chloroplast genomes in the subfamily Pothoideae and family Araceae.

genomics↗

bioRxiv2020

Plastid genomics of Nicotiana (Solanaceae): insights into molecular evolution, positive selection and the origin of the maternal genome of Aztec tobacco (Nicotiana rustica)

The genus Nicotiana of the family Solanaceae, commonly referred to as tobacco plants, are a group cultivated as garden ornamentals. Besides their use in the worldwide production of tobacco leaves, they are also used as evolutionary model systems due to their complex development history, which is tangled by polyploidy and hybridization. Here, we assembled the plastid genomes of five tobacco species, namely N. knightiana, N. rustica, N. paniculata, N. obtusifolia and N. glauca. De novo assembled tobacco plastid genomes showed typical quadripartite structure, consisting of a pair of inverted repeats (IR) regions (25,323-25,369 bp each) separated by a large single copy (LSC) region (86,510 -86,716 bp) and a small single copy (SSC) region (18,441-18,555 bp). Comparative analyses of Nicotiana plastid genomes showed similar GC content, gene content, codon usage, simple sequence repeats, oligonucleotide repeats, RNA editing sites and substitutions with currently available Solanaceae genomes sequences. We identified twenty highly polymorphic regions mostly belonging to intergenic spacer regions (IGS), which could be appropriate for the development of robust and cost-effective markers to infer the phylogeny of genus Nicotiana and family Solanaceae. Our comparative plastid genome analysis revealed that the maternal parent of the tetraploid N. rustica was the common ancestor of N. paniculata and N. knightiana, and the later species is more closely related to N. rustica. The relaxed molecular clock analyses estimated that the speciation event between N. rustica and knightiana appeared 0.56 Ma (HPD 0.65-0.46). The biogeographical analysis showed a south-to-north range expansion and diversification for N. rustica and related species, where N. undulata and N. paniculata evolved in North/Central Peru, while N. rustica developed in Southern Peru and separated from N. knightiana, which adapted to the Southern coastal climatic regimes. We further inspected selective pressure on protein-coding genes among tobacco species to determine if this adaptation process affected the evolution of plastid genes. These analyses indicated that four genes involved in different plastid functions, such as DNA replication (rpoA) and photosynthesis (atpB, ndhD and ndhF), came under positive selective pressure as a result of specific environmental conditions. Genetic mutations of the following genes might have contributed to the survival and better adaptation during the evolutionary history of tobacco species.

genomics↗