Biology subjects

Ahmed, I.

Publications and source records attributed to Ahmed, I..

At least 19 recordsLinked to original sources

bioRxiv2026

CASC15 dictates vascular smooth muscle cell growth fate and pathological vascular remodeling through post-transcription regulation of mitotic fidelity

Vascular smooth muscle cell (SMC) growth, whether hyperplastic or hypertrophic, is a central determinant of vascular remodeling in cardiovascular disease, yet the molecular regulators that direct SMC toward a specific growth fate remain poorly understood. Here, we identify the long non-coding RNA CASC15 as a critical regulator of SMC growth and vascular remodeling. CASC15 is enriched in the vasculature and SMC-rich tissues in humans and mice, and its locus harbors SNPs significantly associated with coronary artery disease and blood pressure. We identify a novel SMC-selective CASC15 isoform (S-CASC15) whose expression level determines SMC growth fate: elevated S-CASC15 promotes proliferation, while its loss drives hypertrophy, polyploidization, and binucleation. In vivo depletion of CASC15 limits vascular injury-induced neointima formation and atherosclerotic lesion expansion. Conversely, CASC15 overexpression exacerbates injury-induced neointimal hyperplasia. However, CASC15 KO mice exhibit spontaneous medial hypertrophy and vascular hypercontractility. Mechanistically, loss of S-CASC15 expression causes mitotic defects, followed by arrest in the G1 phase of hypertrophic and polyploid cells. We found that S-CASC15 pro-proliferative function is mediated through its interaction with RNA-binding proteins, including Nucleolin, and by regulating the stability of cell cycle checkpoint gene transcripts, thereby ensuring mitotic fidelity. Together, these findings establish CASC15 as a pivotal molecular switch governing the balance between hyperplastic and hypertrophic vascular remodeling and as a potential therapeutic target in cardiovascular disease.

Cell Biology↗

bioRxiv2026

Isolation and Characterization of Extracellular Vesicles from Mouse Retina Tissue

This protocol provides a standardized workflow for the isolation of extracellular vesicles (EVs) from mouse retinal tissue, and includes an assessment of EV size and concentration, marker expression, and EV visualization in accordance with the International Society for Extracellular Vesicles Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines. Most retinal EV studies rely on cell culture, which may not fully capture in vivo biology. Our approach more accurately reflects physiological and pathological EV states in vivo by enabling the extraction of EVs from intact retinal tissue. This method addresses a key gap in the field by providing a reproducible and rigorous protocol for studying retinal EVs in a biologically relevant context.

cell biology↗

bioRxiv2026

Biochemical and kinetic properties of a Type III restriction-modification enzyme Mbo45V from the host-adapted pathogen Mycoplasma bovis

Type III restriction-modification (RM) enzymes are prominent bacterial defense against bacteriophage and invading foreign DNA that also modulate the hosts epigenetic landscape. Genome analysis of the host-adapted Mycoplasma bovis PG45 that has a very small genome revealed a Type III RM locus comprising one res and three mod genes. We characterized Mbo45V, a representative enzyme encoded by this locus. The enzyme forms a heterotrimeric complex consisting of two Mod subunits and one Res subunit. Mbo45V recognizes the asymmetric sequence 5'-YAATC-3' (Y = T/C) and cleaves DNA having at least two head-to-head oriented sites [~]26-28 bp away from the recognition site. Methylation of the second adenine of the target site using cofactor S-adenosylmethionine (SAM) protects DNA from restriction, while the SAM analogue sinefungin enhances DNA binding and cleavage. Kinetic studies reveal that Mbo45V exhibits relatively weak DNA binding affinity and an unusually high Km for SAM, indicating low cofactor affinity compared to prototypical enzymes such as EcoP15I. ATPase activity is strongly stimulated by cognate DNA and is inhibited upon methylation of the substrate, suggesting a regulatory interplay between methylation and restriction functions. Comparative analysis indicates that, although Mbo45V shares core mechanistic features with prototypes from Escherichia coli, its kinetic parameters are distinct. These differences likely reflect adaptation to the stable intracellular environment of M. bovis, in contrast to the fluctuating conditions encountered by the enteric bacteria.

biochemistry↗

bioRxiv2026

Comparative Mapping of Functional and Structural Homologies in the Pig and Human Brain

Comparative mapping of functional and structural homologies across humans, small animals, and nonhuman primates has been extensively pursued due to its strong translational relevance. However, these experimental models possess inherent limitations in fully recapitulating the complexity of human cortical organization. The porcine model has recently emerged as a promising alternative, given its neuroanatomical and physiological similarities to the human brain. Despite these advantages, systematic cross-species characterization of functional and structural homologies between humans and pigs remains largely understudied. In the present study, we acquired resting-state functional MRI and diffusion MRI data from pigs and analyzed them alongside corresponding human datasets to investigate cross-species correspondence in large-scale brain organization. First, to enhance functional network alignment across species, group independent component analysis was performed separately within each species to identify intrinsic large-scale functional networks. Our results demonstrated that multiple canonical human resting-state networks are represented in the porcine brain, including sensorimotor, default mode, cerebellar, frontal, and central executive networks. Moreover, we observed significant cross-species concordance in intrinsic functional architecture across multiple distributed networks, both in spatial distribution and temporal patterns, indicating homologous large-scale brain organization between pigs and humans. Second, we conducted comparative structural analyses using diffusion MRI-based fiber tractography, color-encoded fractional anisotropy maps, and structural connectivity analyses to examine and compare white matter organization in pigs and humans. Cross-species comparison revealed substantial similarities in major white matter pathways and their spatial organization, supporting structural correspondence at the level of tract geometry. Together, these findings underscore the translational value of the porcine model as a robust and neurobiologically relevant platform for investigating human brain function, structural organization, and related neurological disorders.

neuroscience↗

bioRxiv2026

Assessment of Coupled Phase Oscillators-Based Modeling in Swine Brain Connectome

Linking structural connectivity (SC) to functional connectivity (FC) through mechanistic models remains challenging in network neuroscience. In this study, empirical data of diffusion magnetic resonance imaging (dMRI) and resting-state functional MRI (rs-fMRI) were used to reconstruct SC and FC of a swine connectome. We evaluated a structurally constrained Kuramoto phase-oscillator framework to reproduce resting-state FC and then assessed the models sensitivity to traumatic brain injury (TBI) and its longitudinal progression post-TBI. A joint tuning procedure was implemented to calibrate data-informed natural frequencies and global coupling strength. The tuned Kuramoto model was then used to evolve oscillator phases constrained by the SC, followed by a Balloon-Windkessel hemodynamic model. The optimized model produced significant edge-wise correspondence between averaged simulated FC and the empirical FC (r = 0.61, p < 0.001). Graph-theoretical analysis across network densities (30-50%) showed strong agreement for global efficiency, characteristic path length, and clustering coefficient, while modularity and small-worldness exhibited deviations. Longitudinal analysis of the swine TBI dataset revealed modest reductions in structure-function coupling over time but no significant differences across injury severities. These results demonstrate that optimized Kuramoto models can reproduce key functional network features while preserving inter-subject variability.

neuroscience↗

bioRxiv2026

Fluorometric DNA Polymerase Activity Assay for Resource-Limited Enzyme Manufacturing

BackgroundDNA polymerase activity assays are required for enzyme quality control in biotechnology and diagnostics, but standard methods rely on specialist reagents, radioactivity and other hazardous materials, or real-time PCR instruments that are not widely accessible in resource-limited settings. This constrains local production of high quality, validated reagents and increases dependence on imported enzymes. MethodsBased on experiences derived from partnerships with scientists in several low and middle-income countries (LMICs) and stakeholder consultations, we adapted a commercial EvaGreen-based fluorometric DNA polymerase activity assay for isothermal operation using minimal equipment. Assay conditions were optimized using Design of Experiments (DOE) methodology, varying temperature, reaction volume, and MgCl2 concentration. To address reagent cost and supply-chain constraints, we developed detailed protocols for in-house synthesis of the off-patent AOAO-12 DNA dye (sold commercially as EvaGreen) and generation of single-stranded DNA templates via asymmetric PCR. ResultsOptimized isothermal assay conditions (40{degrees}C, 7.75 mM MgCl2) reliably quantified activity across multiple DNA polymerase families. In-house synthesized AOAO-12 dye exhibited comparable DNA-binding performance to commercial alternatives (R{superscript 2} = 0.95), reducing costs by more than an order of magnitude when normalized to working concentrations, enabling assay costs of approximately {pound}0.001 per reaction. The assay is effective across multiple polymerases (Bst-LF, OpenVent, Taq, Q5) and is compatible with both plate readers and qByte, a low-cost, open-source fluorometric device. ConclusionsThis stakeholder-informed assay provides an accessible, cost-effective solution for DNA polymerase quality control in resource-limited settings. The combination of optimized commercial protocols and in-house reagent synthesis offers flexibility for different resource contexts, potentially improving access to molecular biology tools globally.

biochemistry↗

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

From Scattered to Focused: Task-Dependent Connectivity in Honey Bees, with Midge Swarms and Bird Flocks

Collective motions in biological organisms such as honey bees, midges, and birds exhibit remarkable coordination and adaptability, emerging from local interactions among individuals, including those with tight constraints on neural material. Understanding the underlying mechanisms behind the collective behavior of biological swarms informs the dynamics of decentralized systems, including engineered aerial swarms. This study provides a systematic graph network extraction formulation applicable to physical domains trajectories including the practical effects of data dropouts, multiple agents, and multiple degrees of freedom. The analysis uses graph network modeling (in which nodes represent agents and edges denote interactions) to uncover the connectivity patterns governing swarm dynamics and quantify their differences. Three network identification methods, including sparse regression, Granger-causality, and crosscorrelation, are applied to determine the underlying graph from measured animal trajectories. An additional geometric anisotropy analysis used in bird flocks is also applied. The methods are applied to experimental recordings of honey bees involving scattered and focused "return-to-hive" behaviors, to midges in reproductive-related aggregations, and to flocking passerine birds. Across these studies, the number of agents a focal agent receives information from was quantified by analyzing the connectivity of identified interaction graphs. The results reveal honey bees show significant differences in connectivity and slight differences in anisotropy between experiments involving scattered and focused "return-to-hive" behaviors. In particular, scattered honey bees showed causal relationships up to 10 neighbors (consistent with flocking jackdaw data), while focused honey bees showed connections with up to 2-3 agents, and midges showed slightly lower connectivity. Finally, cross-correlation analysis indicated honey bees exhibit distance-sensitivity in close proximity, while flocking birds exhibit a distance-dependent correlation decline. Together, these results provide evidence for task-dependent in-degree modulation in honey bees, and provide a systematic analysis formulation that highlights the variety of approaches to coordinated motion, including those with and without geometric anisotropy. These results inform the design of bioinspired networked systems.

animal behavior and cognition↗

bioRxiv2025

Reversible DNA condensation drives natural transformation

Natural transformation drives the spread of antibiotic resistance among bacteria. The DNA receptor ComEA is essential for transporting external transforming DNA into the periplasm by an unknown mechanism. Here, single-molecule optical tweezers and electron microscopy approaches show that Geobacillus stearothermophilus ComEA forms dynamic oligomers on DNA that can switch between two conformations depending on local concentration. When ComEA sparsely decorates DNA, it forms bridging oligomers that condense the DNA to generate sub-pN pulling forces. When ComEA more fully decorates DNA, it forms non-bridging oligomers that decondense DNA and cannot generate force. Mutating ComEA to favor either bridging or non-bridging conformations causes transformation deficiency in Bacillus subtilis, meaning condensation and decondensation are separately essential. Our results show that ComEA reversibly condenses DNA during natural transformation, first producing force to pull DNA into the periplasm and then abating force production to promote transport into the cytoplasm.

biophysics↗

bioRxiv2025

Impacts of wastewater treatment and the exposome on antibiotic resistance gene dynamics: Insights from Guadeloupe, a French Caribbean Island

Wastewater treatment plants (WWTPs) are global hotspots for the dissemination of antibiotic resistance genes (ARGs), primarily driven by different anthropogenic activities. Chemical compounds commonly found in wastewater, including antibiotics, biocides, non-steroidal anti-inflammatory drugs (NSAIDs), and heavy metals, along with environmental factors such as temperature and precipitation, might enhance the selection of antibiotic-resistant bacteria (ARB) even at low concentrations, inadvertently promoting the proliferation of ARGs. Since WWTPs can vary in their removal efficiency and influent compositions, it is important to assess their impact in influencing the relative abundance of ARGs and pollutant concentrations in discharged effluent. We analyzed data collected in Guadeloupe, French Caribbean, using random forest and lasso to investigate changes in the resistome and exposome within untreated wastewater influents and treated effluents from three WWTPs. These WWTPs represented three distinct wastewater continuums--hospital-based, urban non-touristic, and urban touristic--each with unique influent compositions. The study, which spanned four sampling campaigns from September 2021 to January 2023, revealed that the reduction in ARG abundance by the WWTPs was lower than expected. Of the 16 clinically relevant genes and mobile genetic elements examined, the relative abundance of aph(3)-III, blaOXA, blaSHV, blaTEM, ermB, intI1, qnrS, and tetM was reduced by 59.8% to 89.9% across the three WWTPs. An increasing trend in the relative abundance of the mcr-1 gene was observed, showing a 9.52-fold increase in the treated effluent in the hospital continuum. Of the nine antibiotics tested, trimethoprim levels dropped by 70.8% in the touristic continuum and 78.8% in the non-touristic, while ciprofloxacin saw a significant 64.4% reduction only in the touristic continuum, while no other antibiotics or biocides among the eight tested were effectively removed. Regarding heavy metals, significant reductions were observed only in the non-touristic continuum, with cadmium (Cd), copper (Cu), and mercury (Hg) concentrations reduced by 32.5%, 21.1%, and 36.2%, respectively. Our findings provide insights into the associations between environmental factors and the relative abundance of ARGs in Guadeloupe. Generally, depending on the continuum, biocides, the antibiotic erythromycin, certain heavy metals (As, Cd, Cu, Cr, and Hg) and water temperature were associated with the relative abundance of clinically relevant ARGs. This study was not able to assess the impact of climate. Future research should include longitudinal studies with more frequent sampling to better investigate the evolution of antibiotic resistance in bacterial species and its associated drivers, including pollutants and climate-related factors.

microbiology↗

bioRxiv2025

Immune Cells Infiltration of Patient Derived Glioblastoma Cells spheroids in Acoustic Levitation in Bulk Acoustic Wave devices

We describe an acoustofluidic device that allows scaffold-free structuration and culture of multi-cellular tumoroids composed of patient-derived glioblastoma cells only or in combination with non-cancerous cell. A PDMS chip of controlled height was created to allow acoustic levitation of cells using a 2 MHz transducer held on top of the chip. Cells are introduced into the chip through a dedicated inlet upstream of the resonant cavity. The specific design of the cavity together with the acoustic field allow the formation of tumoroids of cells in a precise and controlled manner within the levitation chamber. The acoustic and fluidic environment of the device was determined through experiments confronted with numerical simulations. The control of the flow within the chip was optimized to allow long-term culture of tumoroids and injection of cell culture media without disturbing the tumoroids in levitation. The tumoroids can be also structured, with sequential injections of the different cell types. Using microglia, we show that the acoustofluidic device allows the formation and culture in acoustic levitation of tumoroids mixing cancer cells with other cells populating the tumor as well as immune cell infiltration within the tumoroids. These results demonstrate the suitability of acoustofluidic levitation as an original 3D culture method adapted to the exploration of cancer growth at multiple levels.

bioengineering↗

bioRxiv2025

Persistent glycolysis defines the foreign body response to polymeric implants.

Non-degradable polymeric implantable medical devices are a mainstay of modern healthcare but can frequently lead to severe complications. These complications are largely attributable to the foreign body response (FBR), which is characterized by excessive inflammation and fibrosis in response to implanted materials. The pathologic mechanisms underpinning the FBR remain elusive; however, metabolism is increasingly regarded as a critical regulator of innate immune function. We conducted comprehensive metabolic profiling of implant-associated macrophages and multinucleated giant cells in response to the subcutaneous implantation of clinically relevant implantable materials in a mouse model of implant fibrosis. Leveraging novel metabolic characterization methods for analysis of both metabolic dependence and enzyme expression in heterogeneous peri-implant tissues, we demonstrate that peri-implant macrophages are glycolytic at least up to six weeks post-implantation. Glycolytically dependent peri-implant macrophages expression of glucose transporter 1 (GLUT1) increased temporally and with proximity to the implant-tissue interface. Paired rate-limiting metabolic enzyme expression analysis showed notable increases in biosynthetic pathways (G6PD and ACC1), matched with increased mitochondrial staining intensity in GLUT1Hi cells at chronic timepoints, which were not notable at early timepoints. Notably, we identified a glycolytic dependence of multinucleated macrophages associated with polymeric materials: these cells expressed higher levels of GLUT1 than mononuclear macrophages of comparable metabolic phenotype. Our findings highlight GLUT1-dependent glycolysis as the definitive metabolic system used by peri-implant macrophages and multinucleated cells in the FBR, highlighting this pathway as a potential target for the development of novel therapeutic approaches.

immunology↗

bioRxiv2024

A novel membrane stress-response that blocks chromosomal replication by targeting the DnaA initiator via the ClpP protease

In Escherichia coli, membrane-stress due to interrupted lipoprotein (Lpp) maturation impairs DNA replication and arrests cell growth. How the two disparate processes of Lpp maturation and DNA replication are connected remains unclear. We demonstrate that upon membrane-stress the Rcs stress-response pathway is activated and the replication initiator DnaA is lost, which explains the replication block. However, the Lon protease, a key regulator of the Rcs pathway, is not required for the DnaA loss. We further ruled out the involvement of (p)ppGpp, one of the major mediators of stress-response in bacteria. However, upon deletion of the ClpP protease gene, DnaA was stable, replication initiated, and there was no cell-growth arrest. In wildtype cells, overexpression of DnaA was lethal even without the membrane-stress apparently from hyper-initiation. The hyper-initiation was restrained in {Delta}crp cells, and overexpression of DnaA was able to overcome the growth-arrest. {Delta}fis cells, which were earlier found resistant to the membrane-stress, showed DnaA stability and normal replication upon induction of the membrane-stress. We conclude that DnaA loss suffices to explain the growth-arrest upon the membrane-stress. The stress-response pathway described here appears novel because of its independence from Lon and (p)ppGpp, which have been implicated in other stress-responses that block DNA replication. SignificanceThe seminal observation that DNA replication-stress can block cell division in E. coli (SOS response), introduced the concept of checkpoint control in the cell cycle. Here, we describe a novel checkpoint control that functions in the opposite direction: membrane-stress causing replication block. We show how two apparently unrelated outcomes of reducing a membrane phospholipid, accumulation of a precursor lipoprotein (pLpp) and block of replication initiation, could be linked. The pLpp accumulation stresses the membrane that causes a response culminating in activating the ClpP protease that blocks replication by targeting the initiator DnaA. DnaA being vital and highly conserved, the detail understanding of the response pathway is likely to open new avenues to treat bacterial infection.

microbiology↗

bioRxiv2024

Characterization and molecular insights of a chromium-reducing bacterium Bacillus tropicus

Environmental pollution from metal toxicity is a widespread concern. Certain bacteria hold promise for bioremediation that converts toxic chromium into a less harmful form, promoting environmental cleanup. In this study, we report the isolation and detailed characterization of a highly chromium-tolerant bacterium, Bacillus tropicus CRB14. The isolate is capable of growing on 5000 mg/l Cr (VI) in LB agar plate while on 900 mg/l Cr (VI) in LB broth with an 86.57% reduction ability within 96 hours of culture. It can also tolerate high levels of As, Cd, Co, Fe, Zn, and Pb. The plant growth-promoting potential of the isolate was demonstrated by a significant activity of nitrogen fixation, phosphate solubilization, IAA, and siderophore production. Whole-genome sequencing revealed that the isolate lacks plasmids for Cr resistance, suggesting genes reside on its chromosome. The presence of the chrA gene points towards Cr (VI) transport, while the absence of ycnD suggests alternative reduction pathways. The genome harbors features like genomic islands and CRISPR-Cas systems, potentially aiding adaptation and defense. Analysis suggests a robust metabolism, potentially involved in Cr detoxification. Notably, genes for siderophore and NRP-metallophore production were identified. Whole Genome Sequencing (WGS) data also provides the basis for molecular validation of various genes. Findings from this study highlight the potential application of Bacillus tropicus CRB14 for bioremediation while plant growth promotion can be utilized as an added benefit.

microbiology↗

bioRxiv2024

Exploring Effector Protein Dynamics and Natural Fungicidal Potential in Rice Blast Pathogen Magnaporthe oryzae

Rice blast, caused by Magnaporthe oryzae, is a severe agricultural disease leading to significant global economic losses. Genetic and genomic investigations have identified crucial genes and pathways involved in its pathogenesis, particularly highlighting effector proteins like AvrPik variants and MAX proteins. These proteins interact with specific Pik alleles on rice chromosome 11, influencing host immune responses. This study focused on 35 plant-derived metabolites known for their antifungal properties, evaluating their potential as fungicidal agents against M. oryzae. Molecular docking analyses identified Hecogenin and Cucurbitacin E as highly effective binders to MAX40 and APIKL2A proteins, respectively, which are pivotal for fungal virulence and immune evasion. Molecular dynamics simulations further validated strong and stable interactions, affirming the therapeutic potential of these compounds. Additional assessments including Lipinskis rule of five criteria and toxicity predictions indicated their suitability for agricultural use. These findings underscore the promise of Hecogenin and Cucurbitacin E as lead candidates in developing novel fungicidal strategies against rice blast, offering prospects for enhanced crop protection and agricultural sustainability.

bioinformatics↗

bioRxiv2024

Massively Parallel Reporter Assays identify enhancer elements in Oesophageal Adenocarcinoma.

Cancer is a disease underpinned by aberrant gene expression. Enhancers are regulatory elements that play a major role in transcriptional control and changes in active enhancer function are likely critical in the pathogenesis of oesophageal adenocarcinoma (OAC). Here, we utilise STARR-seq to profile the genome-wide enhancer landscape in OAC and identify hundreds of high-confidence enhancer elements. These regions are enriched in enhancer-associated chromatin marks, are actively transcribed and exhibit high levels of associated gene activity in OAC cells. These characteristics are maintained in human patient samples, demonstrating their disease relevance. This relevance is further underlined by their responsiveness to oncogenic ERBB2 inhibition and increased activity compared to the pre-cancerous Barretts state. Mechanistically, these enhancers are linked to the core OAC transcriptional network and in particular KLF5 binding is associated with high level activity, providing further support for a role of this transcription factor in defining the OAC transcriptome. Our results therefore uncover a set of enhancer elements with physiological significance, that widen our understanding of the molecular alterations in OAC and point to mechanisms through which response to targeted therapy may occur.

molecular biology↗

bioRxiv2023

Mice Models to Bioinformatics Methods Led to the Discovery of Antidiabetic Compounds in the F. racemosa Plant Extracts

One of the primary health issues caused by inadequate blood sugar regulation is Diabetes Mellitus (DM). Diabetes and its consequences remain clinically significant even with the development of oral hypoglycemic medications. Therefore, Ficus racemosa (F. racemosa) plant has been studied for assessing of its antidiabetic potential coupling with animal model and in silico experiments. Drug Alloxan (150 mg/kg) was injected to induce the experimental diabetes in Swiss Albino mice, and two doses methanol extract of the F. racemosa fruit (300 and 500 mg/kg) along with glibenclamide (5 mg/kg) were given orally. Oral Glucose Tolerance Test (OGTT) and acute toxicity were performed as well in both diabetic and non-diabetic mice. Later, in silico experiments including ADMET profiling, molecular docking and simulations were performed. The administration of a dosage less than 3000 mg/kg has been observed to be well-tolerated by mice, with no reported instances of mortality or adverse effects. Following oral administration for 7 days, the blood glucose level (BGL) was significantly decreased in mice model in both doses of extracts, indicating the effect of F. racemosa. Subsequent to this, molecular docking and simulations have indicated that the SIRT1 receptor exhibits a higher binding affinity towards four specific compounds, namely Friedelin, Lupeol Acetate, Gluanol, and Ferulic Acid, as indicated by the dynamics parameters and interacting residues. The current investigation provided evidence that the fruit extract of F. racemosa significantly mitigated the hyperglycemic impact. Moreover, a total of four substances have been found that play a crucial role in the mechanisms behind the reduction of diabetic effects. Hence, the current investigation could potentially serve as a viable therapeutic approach in the treatment of diabetes.

microbiology↗

bioRxiv2023

From Sequence to Significance: A Thorough Investigation of the Distinctive Genome Traits Uncovered in C. werkmanii strain NIB003

Citrobacter werkmanii (C. werkmanii) is an opportunistic bacterium that has received very little investigation in Bangladesh, even though it is thought to be capable of causing diseases including diarrhea and urinary tract infections. Therefore, the present study focuses on the exploration of genomic features, including antibiotic resistance genes, virulent genes, and their distinctive nature in the pathogenesis of diseases. A complete genome was sequenced for the first time in Bangladesh after the morphological, biochemical and molecular identification of this bacteria. A total of 47,65,861 nucleotide base pairs makes up the genome, which contains 4669 genes, and many of the protein-coding genes can be classified into various ontological frameworks, including COG and KEGG pathways. Notably, C. werkmanii has the capability to have interactions with Escherichia coli, Salmonella, and Klebsiella while they possess the same domains and motifs, indicating a causal role in the development of diarrhea. Furthermore, the Bangladeshi isolate of C. werkmaii has observed genetic heterogeneity when compared to other strains of C. werkmanii: C. werkmanii FDAARGOS_616, C. werkmanii LCU-V21, and C. werkmanii BF-6. This identified genetic variation of sequenced C. werkmanii could drive the functional aberration in body homeostasis of bacteria. Later, molecular dynamics studies have proven the impact of their genetic variation on the protein structure, as indicated by the SASA, RMSD, Rg, and RMSF values. Finally, the findings of C. werkmanii from the sequenced genome might provide us with a better understanding of C. werkmanii and their possible role as opportunistic bacteria in diseases including diarrhea and urinary tract infections.

genomics↗