Biology subjects

Ahmadi, A.

Publications and source records attributed to Ahmadi, A..

11 recordsLinked to original sources

bioRxiv2026

A Neuronally Active Bacterial Siderophore Manipulates Host Behavior and Longevity

Aging populations face a growing burden of neurodegenerative disease and behavioral decline. The microbiota is increasingly implicated in host physiology, highlighting an urgent need to understand how gut microbes modulate brain function and late life health. Here, we develop a high-throughput microbe-host screening platform to systematically dissect how bacterial genes shape organismal behavior. Using the Escherichia coli Keio library of 3,985 distinct non-essential single-gene deletion mutants in combination with Caenorhabditis elegans, we quantitatively profiled 768 behavioral features per bacterial clone and uncovered a coherent module of bacterial genes involved in iron homeostasis that robustly reprogrammed host behavior. Bacterial omics analyses revealed that alterations in iron homeostasis amplify siderophore production in a TCA cycle-dependent manner, and loss of enterobactin biosynthesis abolished the bacteria-induced changes in worm movement. Transcriptional, molecular and functional studies demonstrated that bacterial enterobactin activates host neuromuscular responses to shape both lifespan and healthspan in a manner dependent on the mitochondrial unfolded protein response. Thermal proteome profiling identified mitochondrial glutaryl-CoA dehydrogenase and the electron-transfer flavoproteins A and B as enterobactin-binding targets that control mitochondrial function. Finally, genetic manipulation of neuronal mitochondrial and cytosolic reactive oxygen species via superoxide dismutase and catalase revealed that redox state modulates enterobactin-driven changes in movement and lifespan through the secretin-family GPCR neuropeptide receptor PDFR-1. Together, these findings establish microbial enterobactin as a non-canonical neurotransmitter regulating neuronal mitochondrial function, behavior and aging, defining a gut bacteria-brain axis with broad implications for maintaining late-life health.

animal behavior and cognition↗

bioRxiv2026

STING dampens the unfolded protein response to enable the presentation of self-antigens on MHC-I during inflammation.

A growing body of evidence supports the contribution of the long-lasting adaptive immune system in Parkinsons disease (PD). We showed that the PD-associated protein PINK1 negatively regulates the presentation of mitochondrial antigens (MitAP) on MHC-I molecules. In vivo evidence indicated that MitAP activation in mice, in the absence of PINK1, led to cytotoxic CD8+ T cell stimulation and severe motor impairments, reversible by L-DOPA. We show here that following TLR4 activation, MitAP is engaged through a pathway involving cGAS-STING, which acts as a rheostat to dampen the unfolded protein response (UPR). Without STING, the stress response is amplified, leading to a translational attenuation that inhibits the expression of XBP1s, a transcription factor required for MitAP. STING activity also regulates the repertoire of peptides displayed at the cell surface during inflammation, highlighting a potential role in immunosurveillance. These findings establish STING and the UPR as key immune regulators targetable for therapeutic intervention during autoimmune diseases and PD.

immunology↗

bioRxiv2026

More Efficient Walking via Temporal and Spatial Energy Transfer in a Passive Biarticular Exosuit

Evaluating bioinspired design principles in wearable assistive devices provides a unique opportunity to interrogate our understanding of the critical factors that enable agile, stable, and economical human movement. We introduce the BiArticular Thigh EXosuit (BATEX), a wearable device integrating two morphological features found in biological legged systems: biarticular muscles and elastic tissues. BATEX employs two biarticular springs spanning the hip and knee to emulate the human rectus femoris and hamstring muscles, creating beneficial synergy to enhance walking economy. This design enables two energy-shuffling mechanisms: temporal (spring-like storage/return at a joint) and spatial (strut-like transfer across joints). In walking experiments at 1.3 m/s with N = 9 participants, a single compliant biarticular spring yielded a 7% metabolic cost reduction compared to walking without BATEX. Individually optimized configurations further improved metabolic reduction to 9%. BATEX morphology allowed users not only to off-load biological joint power (Assist) but also to increase total power (Augment). Across all exosuit configurations, the mechanical impact of the exosuit was reflected by a significant correlation between changes in users biarticular muscles activity and changes in net metabolic rate. In sum, compliant-biarticular exosuit architectures can concurrently assist and augment human lower-limb joint function, providing significant metabolic savings during walking.

bioengineering↗

bioRxiv2025

Epigenomic and transcriptomic germ-free ageing atlas reveals sterile inflammation as an intrinsic ageing feature

Inflammageing is a hallmark of ageing. Commensal microbiota plays crucial roles in maintaining tissue homeostasis, yet its impact on cellular ageing and inflammageing remains poorly understood. Here we present a comprehensive single-cell epigenomic and transcriptomic atlas of tissues from mice aged under specific pathogen-free (SPF) or germ-free (GF) conditions. Microbiota conferred beneficial effects in young mice but accelerated various ageing features in old, such as age-related AP-1 pathway upregulation, senescence and transcriptomic alterations, likely due to age-associated dysbiosis. Strikingly, inflammatory signatures persisted across cell types in aged GF mouse tissues, establishing sterile inflammation as an intrinsic feature of ageing. Age-associated B cells expanded equally under GF and SPF conditions, raising the possibility that they function as intrinsic, microbiota-independent drivers of inflammageing and potential therapeutic targets. The atlas provides a resource for distinguishing intrinsic ageing features from those modulated by the microbiota, illuminating mechanisms of cellular ageing and potential anti-ageing interventions. HighlightsSterile inflammation and age-associated B cell expansion are prominent intrinsic ageing features The upregulation of age-associated AP-1 pathways and senescence of alveolar macrophages are attenuated in germ-free condition Germ-free condition induces premature ageing-like features in young mouse tissues but delays ageing features in old mice across multiple cell types

genomics↗

bioRxiv2025

Evaluating exon-skipping therapies targeting the central nervous system in Duchenne muscular dystrophy using high-resolution spatial transcriptomics

Duchenne muscular dystrophy (DMD) is marked by progressive muscle degeneration due to dystrophin deficiency. Despite cognitive impairments in up to one-third of patients, central nervous system (CNS)-targeted dystrophin restoration remains relatively underexplored compared to muscle-focused therapies. Since dystrophin is expressed in the brain during development and postnatally, it is important to assess which aspects of CNS pathology could be rescued. However, studying Dmd is difficult due to its size, low-abundance transcripts, and with multiple isoforms, limiting the sensitivity and isoform resolution of standard sequencing methods. To overcome these limitations, we applied Xenium spatial transcriptomics to target splice junctions, enabling isoform-specific and exon 51 skipping events detection across brain regions and cell types. Using this approach, we analyzed mdx52 mice lacking the full-length and Dp140 isoforms, treated with two exon 51 skipping therapies (antisense oligonucleotides or AAV-U7ex51). We observed distinct spatial expression patterns in the wild type brain between the full-length isoforms (Dp427c/m/p1) and shorter isoforms (Dp71 and Dp40). The full-length isoforms were predominantly expressed in cortex layers 2/3-6b and the CA1 region, while the shorter isoforms were localized to cortex layer 1 and the dentate gyrus. Among the exon skipping therapies tested, U7ex51 delivered neonatally induced broad exon skipping in neurons and effectively restored full-length isoforms in the targeted cells. This study introduces the first subcellular-resolution spatial transcriptomic atlas of dystrophin presence and rescue in the CNS and demonstrates a framework for evaluating gene therapies in spatially and transcriptionally complex tissues such as the brain.

neuroscience↗

bioRxiv2025

Mustard-DB: The Database of Cellular, Molecular, and Phenotypic Data in Sulphur Mustard Exposure

1The significance of sulfur mustard as a chemical hazard cannot be overstated. Its potential for causing severe morbidity and long-term health issues makes understanding its effects crucial. Mustard-DB is an essential database that consolidates extensive cellular, molecular, and clinical data on sulfur mustard exposure. It stands as a critical tool for the scientific community, shedding light on the pathophysiological mechanisms and potential therapeutic interventions for those affected by this noxious agent. The database provides a detailed account of the acute and chronic cellular responses, and clinical outcomes associated with sulfur mustard in in vitro, ex vivo and in vivo studies. By offering a multidimensional view of the data, Mustard-DB enables a comprehensive understanding of the agents impact on human health. This manuscript presents the development, structure, and application of Mustard-DB (www.Mustard-DB.com), emphasizing its role in enhancing our response to chemical threats and improving patient outcomes.

bioinformatics↗

bioRxiv2025

TrackRefiner: A tool for refinement of bacillus cell tracking data

MotivationSingle-cell resolution time-lapse microscopy of bacterial populations is a powerful tool for assessing cellular behavior and interaction dynamics. Realizing the full potential of this approach requires accurate image analysis: segmentation of individual cell objects, tracking of persistent cells from frame to frame, and connecting of mother cells to daughters when division events occur. In particular, accurate tracking is needed to produce longitudinal datasets for analysis of interactions and features that develop through time. Tracking is challenging when populations are densely packed or when cells undergo significant motion between frames. The leading software packages struggle to provide accurate data in such cases. ResultTo address this problem, we present TrackRefiner, a tool for refinement of bacillus cell tracking data. This package was specifically designed to refine the tracking outputs of CellProfiler, a commonly used image processing tool. TrackRefiner is built with a modular and publicly accessible structure, making it adaptable for integration with other image processing software. To assess the packages performance, we manually determined ground truth tracking results for eight datasets from four research groups, comprising a total of 159,349 object links. This curated dataset, the first of its kind, serves as a valuable benchmark for assessing the performance of bacillus cell tracking algorithms. For timelapses with frequent imaging, TrackRefiner consistently achieved, with one exception, over 98% detection accuracy and corrected 57-100% of tracking errors. Accuracy was reduced for images sampled at lower frequency. Availability and implementationFor easy access, TrackRefiner has been published on PyPI and Anaconda. Source code and user manuals can be accessed via Github and OSF. The manually curated benchmark dataset is also posted at these sites.

microbiology↗

bioRxiv2023

A benchmarked comparison of software packagesfor time-lapse image processing of monolayerbacterial population dynamics

Time-lapse microscopy offers a powerful approach for analysing cellular activity. In particular, this technique is valuable for assessing the behaviour of bacterial populations, which can exhibit growth and intercellular interactions in monolayer. Such time-lapse imaging typically generates large quantities of data, limiting the options for manual investigation. Several of image processing software packages have been developed to facilitate analysis. It can thus be a challenge to identify the software package best suited to a particular research goal. Here, we compare four software packages that support analysis of 2D time-lapse images of cellular populations: CellProfiler, SuperSegger-Omnipose, DeLTA, and FAST. We compare their performance against benchmarked results on time-lapse observations of E. coli populations. Performance varies across the packages, with each of the four out-performing the others in at least one aspect of the analysis. Not surprisingly, the packages that have been in development for longer showed the strongest performance. We found that deep-learning based approaches to object segmentation outperformed traditional approaches, but the opposite was true for frame-to-frame object tracking. We offer these comparisons, together with insight on usability, computational efficiency, and feature availability, as a guide to researchers seeking image processing solutions. Significance StatementTime-lapse microscopy provides a detailed window into the world of bacterial behavior. However, the vast amount of data produced by these techniques is difficult to analyze manually. We have analysed four software tools designed to process such data and compared their performance, using populations of commonly studied bacterial species as our test subjects. Our findings offer a roadmap to scientists, helping them choose the right tool for their research. This comparison bridges a gap between microbiology and computational analysis, streamlining research efforts.

microbiology↗

bioRxiv2023

LRRK2 regulates the activation of the unfolded protein response and antigen presentation in macrophages during inflammation

While the contribution of inflammation in the pathological process leading to Parkinsons disease (PD) is well established, a growing body of evidence supports a role for the long-lasting adaptive immune system in the disease. We showed that, in inflammatory conditions, the PD-proteins PINK1 and Parkin negatively regulate the presentation of mitochondrial antigens on MHC I molecules, a process referred to as MitAP (Mitochondrial Antigen Presentation). In the absence of PINK1, over-activation of this pathway in antigen-presenting cells (APCs) engages autoimmune mechanisms leading to the establishment of cytotoxic CD8+ T cells. Co-culture of dopaminergic neurons (DNs) with these T cells led to neuronal cell death, suggesting that the MitAP in DNs made them susceptible to T cell-mediated destruction. In the present study, we used a pharmacological and genetic approach to characterize the MitAP pathway at the molecular level. We showed that this antigen presentation pathway is induced in APCs in response to inflammatory signals through the sequential activation of TLR4, cGAS-STING and the Unfolded Protein Response (UPR). A "UPR motif" present on a STING cytoplasmic domain was shown to specifically activate the UPR sensor IRE1. Remarkably, the PD-related protein LRRK2, acted with STING upstream of the UPR to regulate the transition from innate to adaptive immunity, thereby identifying this PD-related protein as a key player in the immune response during inflammation.

immunology↗

bioRxiv2019

Identification of new inhibitors of the Toxoplasma gondii by using in-silico drug repurposing

IntroductionThe common treatment for toxoplasmosis was pyrimethamine. In recent years, it has been found that this parasite is getting resistant to this treatment, therefore urgent alternative treatments are needed. Material and MethodsIn this study, by using drug repurposing and in silico methods we tried to make a selective treatment by inhibiting the Calcium-Dependent Protein Kinase 1 from Toxoplasma gondii which doesnt exist in mammalians. We screened the FDA approved drugs by molecular docking and after ranking them by their binding energies and inspecting the top scored ones, we chose Cefpiramide, Ceftriaxone and Cefotiam as the hit compounds. After that, we used molecular dynamics simulations to test the hit compounds in a much more realistic environment. ResultsBy analyzing the results, we found that all of the hit compounds and good and can bind strongly to the active site of the protein. Therefore, they can be potential candidates for inhibiting Calcium-Dependent Protein Kinase 1 from Toxoplasma gondii. ConclusionMoreover, because the predicted compounds are FDA approved drugs, their toxicity profiles are well known and their newly predicted use can be tested in clinical trials.

bioinformatics↗

bioRxiv2018

miR-216b-5p is Down-Regulated in Human Breast Cancer and Inhibits Proliferation and Progression by Targeting HDAC8 Oncogene

BackgroundPrevious studies showed the role of histone deacetylases (HDACs) on the progression of some malignancies. Recently, there is more attention to therapeutic applications of epigenetic factors such as microRNAs (miRs). To the best of our knowledge, there are no other results regarding the contribution of miR-216b-5p and its potential target, HDAC8, in progression of cancer.\n\nAimIn the present study, we investigated the role of miR-216b-5p on HDAC8 and there following impacts on breast cancer (BC) progression.\n\nMethodsHuman BC specimens and noncancerous tissues were acquired from Iran Tumor Bank (I.T.B). The MDA-MB-231, MCF-7 and MCF-10A BC cell lines were also prepared. The tissue and cell line expression levels of miR-216b-5p and HDAC8 were determined by quantitative real-time PCR (qPCR). Protein levels of HDAC8 were also measured by Western blotting assay. The cell cycle, cell proliferation and colony formation assay were determined and the role of HDAC8 was investigated using a knockout vector. Targeting the 3' untranslated region (3'UTR) of HDAC8 by miR-216b-5p were confirmed using a luciferase reporter assay.\n\nResultsOur results show the significant decline in miR-216b-5p and highly increase in HDAC8 levels in human breast cancer tissues and cell lines. Overexpression of miR-216b-5p in BC cell lines inhibited cellular proliferation and progression and inhibition of miR-216b-5p reverse these effects. We also confirmed that HDAC8 is directly down-regulated by miR-216b-5p. Knockout of HDAC8 had also the effects as miR-216b-5p overexpression. Furthermore, we found that lower levels of miR-216b-5p are negatively correlated with lymph node metastasis and advanced tumor size.\n\nConclusionTaken together, our data shown that targeted overexpression of miR-216b-5p can suppress the growth of BC cells down-regulation of HDAC8. Therefore, inhibition of HDAC8 by miR-216b-5p will be helpful developing newer therapies for the effective treatment of BC.

cancer biology↗