bioRxiv Preprints

{
  "doi": "10.64898/2026.07.24.740456",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.24.740456v1",
  "title": "Microbial Metabolites Potentiate MAIT Cell Anti-Tumor Immunity Against Solid Tumors",
  "source": "biorxiv",
  "authors": "Zhu, Y.; Shen, X.; Chen, Y.; Ma, N.; Zhang, C.; Zhao, A. S.; Tian, Y.; Gumate, S.; Huang, J.; Lin, S.; Wang, A.; Agopian, V. G.; Li, Y.-R.; Yang, L.",
  "version": "1",
  "abstract": "Mucosal-associated invariant T (MAIT) cells sense riboflavin metabolites through the monomorphic antigen-presenting molecule MR1, providing a unique opportunity to therapeutically mobilize a broadly shared T cell population without genetic engineering. Here, we show that the highly potent microbial metabolites, 5-OP-RU and 5-OE-RU, can be exploited as pharmacologic precision immune activators to drive human MAIT cell responses against solid tumors. Ligand stimulation in human co-culture systems elicited robust MAIT cell cytotoxicity, inflammatory cytokine secretion, and transcriptional states transformation. In vivo administration of riboflavin ligands 5-OP-RU significantly suppressed tumor growth in xenograft liver cancer models. Metabolite-driven MAIT activation also reprogrammed the local immune landscape, enhancing effector function and overcoming features of the immunosuppressive niche by markedly eliminating tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) within the tumor microenvironment (TME). These findings reveal that microbial riboflavin metabolites can power and redirect MAIT cells to solid tumors, establishing MR1-metabolite signaling a",
  "category": "cancer biology",
  "published_at": "2026-07-25T00:00:00.000Z",
  "corresponding_author": "Yichen Zhu",
  "journal_published_doi": null,
  "corresponding_institution": "University of California, Los Angeles"
}

{
  "doi": "10.64898/2026.07.23.739635",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.23.739635v1",
  "title": "Deletion of Ferritin Heavy Chain Limits Tumor Growth and Promotes Iron-Dependent Stress in Medulloblastoma",
  "source": "biorxiv",
  "authors": "Segui, F.; Durivault, J.; Pagnuzzi, M.; Vial, V.; Bernini, A.; Filipponi, D.; Harayama, T.; Perne, P.; Debayle, D.; Muller, K.; Pasquier, E.; Le Grand, M.; Parks, S. K.; Cormerais, Y.; Pouyssegur, J.; Vucetic, M.; Picco, V.",
  "version": "1",
  "abstract": "Iron is essential for tumor proliferation and metabolic adaptation but becomes cytotoxic when unbuffered, creating a potential metabolic vulnerability. Ferritin, a conserved iron-storage complex, limits labile iron and establishes the upper threshold of iron tolerance in cancer cells. Here, we report the first ferritin heavy chain (FTH) knockout in a brain tumor model system. Although FTH loss was tolerated under basal conditions through adaptive remodeling of iron metabolism, it exposed profound vulnerabilities under iron stress. FTH deficiency lowered the threshold for iron toxicity, sensitizing medulloblastoma (MB) cells to both canonical ferroptosis and a mechanistically distinct iron-dependent cell death pathway. Oxidative iron stress impaired tumor growth and prolonged survival in orthotopic xenografts, whereas vitamin C-induced iron reduction triggered a selective, iron-dependent, but non-ferroptotic elimination of MB-like cells in tumor organoids. Notably, sensitivity to iron toxicity correlated strongly with cellular phenotype, with mesenchymal-like cells displaying greater susceptibility than epithelial-like counterparts. Collectively, these findings identify ferritin as ",
  "category": "cancer biology",
  "published_at": "2026-07-25T00:00:00.000Z",
  "corresponding_author": "Milica Vucetic",
  "journal_published_doi": null,
  "corresponding_institution": "Medical Biology Department, Centre Scientifique de Monaco (CSM), 98 000 Monaco, Principality of Monaco"
}

{
  "doi": "10.64898/2026.07.23.740329",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.23.740329v2",
  "title": "Imprinted regulatory networks reveal the molecular cross-talk between paternal and maternal genomes in the endosperm of Arabidopsis arenosa",
  "source": "biorxiv",
  "authors": "Budinsky, T.; Kovacik, M.; Cermak, V.; Pribylova, A.; Salony, S.; Iltas, O.; Pecinka, A.; Lafon Placette, C.",
  "version": "2",
  "abstract": "Imprinted genes do not act alone to shape seed development, but as a complex network - just like any other gene. Yet, the molecular context in which they are embedded, i.e. their gene network, remains largely understudied. To address this knowledge gap, we characterized the imprintome of Arabidopsis arenosa at the species-level and used gene regulatory network analyses. We show that genomic imprinting preferentially affects only a few pathways, offering candidates for dosage sensitive processes and the molecular arena of parental conflict. In these pathways, some imprinted genes act as hub genes, among which NRPE1, highlighting the importance of epigenetics in endosperm development. The interaction between parental genomes was rather one-sided: paternally expressed regulators preferentially targeted PEGs, while maternally expressed regulators targeted both PEGs and MEGs indiscriminately. This aligns with a self-promoting paternal influence and a maternal buffer under a parental conflict scenario. Shared paternal and maternal regulation of downstream targets was nevertheless common, and we reveal novel molecular interactions between imprinted regulators. Overall, our work shows how ",
  "category": "plant biology",
  "published_at": "2026-07-25T00:00:00.000Z",
  "corresponding_author": "Clement Lafon Placette",
  "journal_published_doi": null,
  "corresponding_institution": "Charles University"
}

{
  "doi": "10.64898/2026.07.07.736934",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.07.736934v2",
  "title": "Glycine molecule radical: Predicted properties and dipeptide formation",
  "source": "biorxiv",
  "authors": "Synak, J.; Blazewicz, J.",
  "version": "2",
  "abstract": "The formation of the first peptide bonds under prebiotic conditions remains an open question. We used density functional theory calculations with the B3LYP functional to predict a novel pathway of peptide bond formation, which could have taken place without the sophisticated catalysts used by modern biological systems, utilising only radical chemistry. To make our investigation more extensive, the properties of intermediates (glycine-derived radicals) were thoroughly analysed, using the DFT, resonance hybrid model and orbital hybridisation. These methods shed more light on the exact nature of processes which should take place, explaining why this pathway could be favoured by the system. The result is a series of reactions, which without any sophisticated catalysts and with relatively low electronic energy barrier (<20 kcal/mol) can lead to formation of dipeptides, suggesting also a possible starting point for further peptide chain extension.",
  "category": "bioinformatics",
  "published_at": "2026-07-25T00:00:00.000Z",
  "corresponding_author": "Jaroslaw Synak",
  "journal_published_doi": null,
  "corresponding_institution": "Poznan University of Technology"
}

{
  "doi": "10.64898/2025.12.12.694034",
  "url": "https://www.biorxiv.org/content/10.64898/2025.12.12.694034v2",
  "title": "Molecular basis of tRNA substrate recognition and modification by the atypical SPOUT methyltransferase Trm10",
  "source": "biorxiv",
  "authors": "Nandi, S.; Strassler, S. E.; Dey, D.; Whitney, C. B.; Roumaya, O. B.; Krishnamohan, A.; Harris, G. M.; Comstock, L. R.; Jackman, J. E.; Conn, G. L.",
  "version": "2",
  "abstract": "The evolutionarily conserved methyltransferase Trm10 catalyzes N1 methylation of guanosine 9 (G9) in select tRNAs, but the basis of specific substrate recognition and modification has remained unclear. Using an S-adenosyl-L-methionine analog, we trapped a post-catalytic state of the Trm10-tRNAGly complex for structure determination by cryogenic electron microscopy. Three distinct complexes were captured: two monomeric Trm10-tRNA complexes with distinct tRNA acceptor stem orientations (\"closed\" and \"open\"), and a minor dimeric complex with two Trm10s bound to the same tRNA. The monomeric structures identify conserved residues involved in tRNA interactions across a positively charged surface that guide G9 into the catalytic site and stabilize the flipped nucleotide. In the tRNAopen conformation, acceptor stem rotation weakens tRNA-protein contacts, consistent with a product-release state. The dimeric complex, supported by tRNA-dependent protein crosslinking and molecular dynamics (MD) simulations, positions one Trm10 on G9 similarly to the monomeric complexes, while the other contacts distal tRNA regions, suggesting a functional role in promoting functionally critical conformational ",
  "category": "biochemistry",
  "published_at": "2026-07-25T00:00:00.000Z",
  "corresponding_author": "Graeme L. Conn",
  "journal_published_doi": null,
  "corresponding_institution": "Emory University School of Medicine"
}

{
  "doi": "10.64898/2026.06.25.734463",
  "url": "https://www.biorxiv.org/content/10.64898/2026.06.25.734463v2",
  "title": "The BPI-like TULIP domain proteins of Drosophila melanogaster: a novel class of candidate odorant transporters.",
  "source": "biorxiv",
  "authors": "Dupas, S.; Chauvel, I.; Bousquet, F.; Cortot, J.; Kelle, N.; Bourgeois, M.; Boichot, V.; Bonnotte, A.; Avoscan, L.; Musso, P.-Y.; Fraichard, S.; Briand, L.; Neiers, F.; CHARLES, J.-P.",
  "version": "2",
  "abstract": "TULIP (TUbular LIPid binding) domain proteins (TDPs) are found in all living organisms including bacteria. They have various documented functions, some of which clearly related to their intra- or extracellular lipid transfer activities. Extracellular, BPI-related TDPs of insects (B-TDPs, also known as Takeout-related proteins), are often found in chemosensory organs, but little is known regarding their exact location or how they could contribute to olfaction or gustation. We have surveyed and updated the full set of Drosophila B-TDPs and found that roughly 50% are overexpressed in chemosensory organs. Focusing on three genes clustered on the third chromosome, we provide evidence that at least one of the encoded proteins is secreted in the lymph cavity housing the dendrites of olfactory neurons. Biochemical data give support for a putative function of B-TDPs as odorant transporters, but loss-of-function analyses also hint to a potential role as a barrier against plant-emitted terpenoids.",
  "category": "animal behavior and cognition",
  "published_at": "2026-07-25T00:00:00.000Z",
  "corresponding_author": "Jean-Philippe CHARLES",
  "journal_published_doi": null,
  "corresponding_institution": "UniversitÁ Bourgogne Europe, Institut Agro, CNRS, INRAE, UMR CSGA, 21000 Dijon, France."
}

{
  "doi": "10.64898/2026.07.23.740440",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.23.740440v2",
  "title": "Identification of the Down syndrome critical region 3 gene as a mammalian cell size regulator",
  "source": "biorxiv",
  "authors": "Kimura, K.; Souda, M.; Mori, R.; Kato, Y.; Kurahashi, H.; Asai, M.; Yamamoto, K.",
  "version": "2",
  "abstract": "Using a genetic screening approach based on an inducible gene-activating system and cell sorting, Down syndrome critical region 3 (DSCR3) was isolated as a gene whose overexpression increased cell size. Fibroblasts derived from individuals with Down syndrome (DS) exhibit elevated DSCR3 expression at both the mRNA and protein levels, correlating with increased cell volume compared to fibroblasts from healthy donors. Despite a slower proliferation rate, DS fibroblasts demonstrate higher basal and maximal mitochondrial respiration, suggesting enhanced metabolic activity associated with increased cell size. siRNA-mediated knockdown of DSCR3 reduces cell size in both DS and normal fibroblasts, indicating its general role in cell size regulation. As DSCR3 is a component of the retriever complex involved in endosomal cargo recycling, these findings position membrane protein trafficking as a novel module for cell size control.",
  "category": "cell biology",
  "published_at": "2026-07-25T00:00:00.000Z",
  "corresponding_author": "Masashi Asai",
  "journal_published_doi": null,
  "corresponding_institution": "Department of Genome-Based Drug Discovery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan"
}

{
  "doi": "10.64898/2026.03.03.708097",
  "url": "https://www.biorxiv.org/content/10.64898/2026.03.03.708097v2",
  "title": "Endosome motility controls light-responsive reproductive development and secondary metabolite production in Aspergillus",
  "source": "biorxiv",
  "authors": "Kumar, G.; Allen, J. L.; Oster, L. D.; Amir Rawa, M. S.; Ramirez, E. A.; Bok, J. W.; Suen, P. H.; Driscoll, B. E.; Salogiannis, J.; Keller, N. P.; Reck-Peterson, S. L.",
  "version": "2",
  "abstract": "Filamentous fungi, such as Aspergillus species, use microtubule transport to move early endosomes. Other cargos, such as peroxisomes and mRNAs, \"hitchhike\" on early endosomes to move throughout the long hyphae of these organisms. In Aspergillus nidulans, peroxisomes hitchhike on early endosomes using the endosomal protein PxdA and the peroxisomal protein AcbdA. The HookA adaptor protein links endosomes to microtubule motors. Here, we set out to explore the physiological functions of peroxisome hitchhiking and endosome motility. Aspergillus nidulans has a complex life cycle that includes asexual and sexual reproduction. A. nidulans and other fungi within the Pezizomycotina subphylum are also notable for the vast number of secondary metabolites they produce. Light and other environmental conditions influence developmental decisions and secondary metabolite production. Here, we found that sexual reproduction is favored in the absence of endosome motility, even in the light, which normally promotes asexual reproduction. RNA sequencing of strains lacking PxdA-marked motile early endosomes showed altered expression of genes involved in development. Unexpectedly, we also observed altered ",
  "category": "cell biology",
  "published_at": "2026-07-25T00:00:00.000Z",
  "corresponding_author": "Samara L Reck-Peterson",
  "journal_published_doi": null,
  "corresponding_institution": "1. Department of Biochemistry and Biophysics, Weill Cornell Medicine, New York, NY ,    2. Howard Hughes Medical Institute, Chevy Chase, MD"
}

{
  "doi": "10.64898/2026.05.17.725321",
  "url": "https://www.biorxiv.org/content/10.64898/2026.05.17.725321v2",
  "title": "Unveiling Gloriosine as a Dual-Acting Regulator of Glutamine Metabolism and Ferroptosis in Triple-Negative Breast Cancer: Insights from Network Pharmacology and Experimental Validation",
  "source": "biorxiv",
  "authors": "Dey, B.; Chatterjee, E.; Goel, B.; Jain, S. K.; Naik, P. K.; Guru, S. K.",
  "version": "2",
  "abstract": "Abstract Background TNBC lacks clearly defined molecular targets, so chemotherapy remains the standard approach despite resistance, toxicity, and high relapse rates. New, less toxic therapeutic options are urgently needed. This study evaluated the anticancer potential of gloriosine, a plant-derived alkaloid known to inhibit tumor cell growth with minimal effect on normal breast cells. Methods Putative targets of gloriosine were predicted using SwissTargetPrediction, TargetNet, and PharmMapper, then intersected with gene sets linked to TNBC and glutamine metabolism. The resulting network was characterized through protein-protein interaction mapping and Gene Ontology/KEGG enrichment analysis. Molecular docking assessed binding affinity to top targets, and predictions were validated experimentally using cell viability, colony formation, and wound-healing assays. Oxidative stress and ferroptosis were assessed via ROS (DCFDA), glutathione, and lipid peroxidation (MDA) assays, along with Western blotting and FerroOrange staining. Results Network analysis identified 100 predicted targets, 60 overlapping with TNBC/glutamine-metabolism genes; SRC, EGFR, mTOR, and HSP90AA1 emerged as hub pro",
  "category": "cancer biology",
  "published_at": "2026-07-25T00:00:00.000Z",
  "corresponding_author": "Santosh Kumar Guru",
  "journal_published_doi": null,
  "corresponding_institution": "Department of Biological Sciences, National Institute of Pharmaceutical Education and Research, Balanagar, Hyderabad 500037, India."
}

{
  "doi": "10.64898/2026.07.21.739882",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.21.739882v1",
  "title": "Bidirectional Electron Transfer in Far-Red-Light Adapted Photosystem I. Implications for the Photosystem's Functionality",
  "source": "biorxiv",
  "authors": "Calcinoni, A.; Casazza, A. P.; Agostini, A.; Bortolus, M.; Carbonera, D.; Santabarbara, S.",
  "version": "1",
  "abstract": "Far-Red (FR) Light Photoacclimation (FaRLiP) enables cyanobacteria to extend photosynthetic activity into the far-red region by extensively remodelling Photosystem I (PSI), including the replacement of several core subunits with paralogs that coordinate the red-shifted chlorophyll f (Chl f). The binding positions of Chls f are still a matter of debate, with the most recent structural findings supporting the location of a single Chl f molecule within the reaction centre (RC) at the so-called A-1B site. This was in turn suggested to strongly affect electron transfer (ET) directionality leading to an almost monodirectional transfer along the B branch in FR-PSI RC. Here, we directly probe ET in FR-PSI by characterising the photogenerated [P700A1-] spin-correlated radical pair using complementary pulse and Time-Resolved (TR) Electron Paramagnetic Resonance (EPR) spectroscopy at cryogenic temperature. Electron spin-echo decay kinetics are distinctly biexponential, indicating the formation of two charge-separated states. Consistently, out-of-phase ESEEM traces are quantitatively described by two modulation frequencies arising from different dipolar interactions, while TR-EPR spectra are a",
  "category": "biophysics",
  "published_at": "2026-07-25T00:00:00.000Z",
  "corresponding_author": "Stefano Santabarbara",
  "journal_published_doi": null,
  "corresponding_institution": "Photosynthesis Research Unit, Consiglio Nazionale delle Ricerche, Via A. Corti 12, 20133, Milano, Italy."
}