bioRxiv Preprints

{
  "doi": "10.64898/2026.07.27.740930",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.27.740930v1",
  "title": "New histone deposition recruits the DNA methylation maintenance machinery at sites of DNA damage repair",
  "source": "biorxiv",
  "authors": "Mori, M.; Piquet, S.; Girard, L.; Ferry, L.; Yamaguchi, K.; Farshchi, M.; Bethouel, E.; Kirsh, O.; Hennion, M.; Defossez, P.-A.; Polo, S. E.",
  "version": "1",
  "abstract": "Faithful inheritance of DNA methylation contributes to the memory of epigenetic states and protects against disease. While the mechanisms underlying DNA methylation maintenance at replication forks are well characterized, whether and how DNA methylation is altered or maintained at sites of DNA damage repair is still poorly understood. Here, by exploiting sequencing, imaging and proteomic approaches in mammalian cells exposed to UV radiation, we show that the majority of DNA methylation marks are maintained during UV damage repair and we dissect the molecular machinery involved in DNA methylation control. We detect the recruitment to sites of repair synthesis of the DNMT1 and DNMT3A DNA methylating enzymes, driven by the DNMT1 cofactor UHRF1 and by UV damage repair endonucleases. We also uncover a crosstalk with histone dynamics, whereby newly deposited H3.3 histones at UV damage sites promote the recruitment of DNMT1. Functionally, we reveal the importance of the DNA methylation maintenance machinery for the transcriptional response to UV damage and sustained cell proliferation. This work provides a comprehensive picture of DNA methylation control mechanisms following DNA damage, w",
  "category": "molecular biology",
  "published_at": "2026-07-28T00:00:00.000Z",
  "corresponding_author": "Sophie E Polo",
  "journal_published_doi": null,
  "corresponding_institution": "Laboratory of Epigenome Integrity, Epigenetics & Cell Fate Centre, UMR7216 CNRS, Universite Paris Cite, Paris, 75013, France"
}

{
  "doi": "10.64898/2026.07.01.735277",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.01.735277v2",
  "title": "Wobble Vaccines: Complex Vaccine Antigen Pools Promote Increased Antibody Breadth and Cross-Strain Viral Targeting in SARS-CoV-2",
  "source": "biorxiv",
  "authors": "McIlroy, P. R.; Zinzow-Kramer, W. M.; Ellis, M. L.; Melief, E.; Ali, M.; Peck, H. E.; Sasser, L. E.; Vanover, D.; Santangelo, P. J.; Suthar, M. S.; Voigt, E. A.; Woodruff, M. C.",
  "version": "2",
  "abstract": "Vaccination remains the most successful preventative measure against viral infection, but methods to stably deter rapidly-evolving pathogens have remained elusive. Vaccines capable of incorporating and anticipating viral evolution could address current challenges in seasonal vaccination efforts against SARS-CoV-2 and influenza where economic and disease burdens remain high despite decades of combined study. Rare epitope suppression (RES) is an underutilized concept within vaccine design, where humoral epitope targeting can be molded using complex antigen pools. Based in mRNA vaccine technology, wobble vaccines represent the novel application of RES to human pathogens designed to anticipate and resist viral evolution. To establish this platform, public SARS-CoV-2 sequencing data was compiled from the first two years of the COVID-19 pandemic to identify high-diversity sites across the receptor binding domain (RBD) of the spike protein. Wobble RBD (WobbRBD) libraries reflecting that entropy were synthesized and incorporated into established self-amplifying (SA) vaccine constructs. Animals immunized with these complex antigen pools showed no obvious adverse effects. By three days-post ",
  "category": "immunology",
  "published_at": "2026-07-28T00:00:00.000Z",
  "corresponding_author": "Matthew C Woodruff",
  "journal_published_doi": null,
  "corresponding_institution": "Emory University"
}

{
  "doi": "10.1101/2025.11.20.689413",
  "url": "https://www.biorxiv.org/content/10.1101/2025.11.20.689413v2",
  "title": "Gelsolin Counteracts ER Stress-Driven Inflammatory Circuits in Psoriasis-like Dermatitis",
  "source": "biorxiv",
  "authors": "Ori, D.; Okude, H.; Konishi, R.; Murase, M.; Hiroki, S.; Takahara, S.; Tanaka, T.; Toyodome, R.; Kano, N.; Kawasaki, T.; Ishii, K.; Kobiyama, K.; Nakashima, H.; Nakashima, K.; Sasai, M.; Yamamoto, M.; Kumagai, Y.; Tsuru, A.; Kohno, K.; Kawai, T.",
  "version": "2",
  "abstract": "Psoriasis is a chronic inflammatory skin disorder driven by amplified communication between immune cells and keratinocytes. Here, we show that imiquimod (IMQ) triggers organelle stress responses that directly contribute to this pathogenic circuit. In dendritic cells (DCs), IMQ promotes formation of ER-mitochondria contact sites (MAMs), inducing ER stress and activation of the unfolded protein response (UPR). These pathways act independently of, yet converge with, TLR7/MyD88 signaling to enhance IL-23 expression. IMQ also increases cytosolic Ca{superscript 2}+, facilitating NLRP3 inflammasome activation and release of mitochondrial DNA (mtDNA). In parallel, keratinocytes exposed to IMQ activate UPR-dependent genes, including Defb14 (mBD14), a psoriasis-associated antimicrobial peptide. Extracellular mtDNA and mBD14 then cooperatively stimulate plasmacytoid DCs through TLR9, establishing a feed-forward inflammatory loop. We further identify Gelsolin as a direct IMQ-binding protein that mitigates IMQ-induced ER stress; its loss amplifies ER stress, UPR activation, and oxidative stress, and its expression is reduced in human psoriatic lesions. Thus, MAM-UPR signaling links intracellula",
  "category": "immunology",
  "published_at": "2026-07-28T00:00:00.000Z",
  "corresponding_author": "Taro Kawai",
  "journal_published_doi": null,
  "corresponding_institution": "Nara Institute of Science and Technology"
}

{
  "doi": "10.64898/2026.07.27.740322",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.27.740322v1",
  "title": "Language-aligned models and structured scene descriptions reveal sensitivity to compositional scene structure in the high-level visual cortex",
  "source": "biorxiv",
  "authors": "Rajaei, K.; Afshar, A.; Cichy, R. M.; Soltanian-Zadeh, H.",
  "version": "1",
  "abstract": "Natural scenes are defined not only by their contained objects, but also by the structured relations among those objects. Using 7T fMRI data from the Natural Scenes Dataset, we tested whether the high-level visual cortex is sensitive to this compositional scene structure. We related narrative scene descriptions to cortical responses in an encoding framework, contrasting intact narrative descriptions with lexical control descriptions that preserved word content while disrupting compositional structure via word randomization. Intact narrative descriptions better predicted cortical responses in high-level visual cortex, indicating sensitivity to structured scene information beyond lexical content alone. This advantage was particularly pronounced for scenes with richer compositional structure. Further, a language-aligned vision model outperformed a self-supervised vision-only model, and this advantage showed a similar high-level cortical distribution. These findings suggest that the high-level visual cortex represents structured scene information beyond simple entity co-occurrence and language supervision may help induce similar representations in artificial vision models.",
  "category": "neuroscience",
  "published_at": "2026-07-28T00:00:00.000Z",
  "corresponding_author": "Karim Rajaei",
  "journal_published_doi": null,
  "corresponding_institution": "Institute for Research in Fundamental Sciences (IPM)"
}

{
  "doi": "10.64898/2026.07.26.740824",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.26.740824v1",
  "title": "Seasonal hepatic plasticity follows a temporal response hierarchy in a Neotropical frog",
  "source": "biorxiv",
  "authors": "Franco-Belussi, L. B.; Moraes, L. T.; de Oliveira, C.; Fernandes, C. E.; Provete, D. B.",
  "version": "1",
  "abstract": "BackgroundSeasonal climate variation drives physiological change across levels of biological organization in ectotherms, yet whether these responses follow a predictable temporal hierarchy remains untested in wild populations. In a year-round field study of the Lesser Treefrog (Dendropsophus minutus, Anura: Hylidae) in Sao Jose do Rio Preto, southeastern Brazil, we sampled 40 to 68 adult males across a full annual cycle to quantify seasonal variation in four hepatic phenotypic modules spanning multiple organizational levels: liver histochemistry (pigments and glycogen; intracellular), cell and nucleus morphometry (cellular), tissue volumetric composition of hepatocytes, sinusoids, melanomacrophage centres and portal structures (tissue), and whole-body somatic indices of liver mass and body condition (organismal). We asked whether lower organizational levels respond faster to seasonal climate, as predicted by the bottom-up cascade framework originally proposed for toxicant exposure, or whether alternative hierarchies emerge when climate acts first through whole-organism physiology. To test whether climatic change precedes each biological response, we extended Procrustean superimposi",
  "category": "zoology",
  "published_at": "2026-07-28T00:00:00.000Z",
  "corresponding_author": "Lilian B. Franco-Belussi",
  "journal_published_doi": null,
  "corresponding_institution": "UNESP"
}

{
  "doi": "10.64898/2026.07.26.740836",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.26.740836v1",
  "title": "Proteome-wide QTL mapping enables gene-protein-phenotype metabolic network construction in a genetically diverse MASLD mouse model",
  "source": "biorxiv",
  "authors": "Robinson, M. L.; Benegiamo, G.; Liu, W.; Williams, M. T.; Smith, G. I.; Klein, S.; Auwerx, J.; Coon, J. J.",
  "version": "1",
  "abstract": "The limited treatment options available for the estimated 38% of adults worldwide affected by Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) are largely due to an incomplete understanding of the complex molecular networks underlying disease pathogenesis. To dissect the genetic architecture and proteomic regulation underlying MASLD, we generated a genetically diverse mouse cohort through a four-way cross of founder strains with varying susceptibility to liver disease, producing 444 F2 mice with a spectrum of phenotypes and genotypes. Utilizing deep proteomic profiling of the livers of this population, we identified quantitative trait loci (QTL) for 2,652 proteins, spanning over 4,000 unique genomic loci, and distinguished cis- and trans-acting regulatory mechanisms. Integrating proteomic, genomic, and phenotypic data reveals key regulatory loci and candidate proteins influencing disease progression, creating a mineable proteogenomic resource for MASLD research. We utilize this resource to identify the E3 ubiquitin ligase Ubr1 as a candidate central regulator connecting proteostasis and lipid metabolism, with genetic polymorphisms that may alter its abundance and pr",
  "category": "systems biology",
  "published_at": "2026-07-28T00:00:00.000Z",
  "corresponding_author": "Joshua J Coon",
  "journal_published_doi": null,
  "corresponding_institution": "University of Wisconsin - Madison"
}

{
  "doi": "10.64898/2026.07.27.740924",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.27.740924v1",
  "title": "Cross-Species Efficacy of Combinatorial Gene Therapy for Osteoarthritis and Correction of Neuro-Inflammatory Pain Mechanisms",
  "source": "biorxiv",
  "authors": "Secor, E.; Wang, J.; Dou, Z.; Yan, J.; Majano, C.; Woodman, M.; Ruiz, O.; Al Azaat, J.; Crosby, D.; Cela, R.; Pownder, S.; Engiles, J. B.; Palmer, D.; Jiang, M.; Leynes, C.; Yaman, I.; Jeong, M.; Sponder, G.; Plutziki, S.; Yuva, L.; Veeragavan, S.; Ray, R. S.; Wythe, J. D.; Arenkiel, B. R.; Chen, R.; Worley, K. C.; Consortium, R.-J.; Ng, P.; Suzuki, M.; Guse, K.; Bae, Y.; Haelterman, N. A.; Reesink, H.; Lee, B.",
  "version": "1",
  "abstract": "Osteoarthritis is a leading cause of chronic pain and disability, which lacks disease-modifying treatment. Given the complex multi-tissue and multifactorial drivers behind disease progression, effective treatments will require simultaneously targeting several mechanisms underlying joint degeneration and pain. Here, we developed and evaluated a combinatorial gene therapy, consisting of a high-capacity adenoviral vector carrying two therapeutic genes to target distinct pathological mechanisms: inflammation (IL-1Ra) and chondrocyte health (PRG4). Intra-articular delivery of this treatment improved functional, structural, and pain outcomes in murine and equine osteoarthritis models. In addition, treatment normalized inflammatory environments in joint tissues, as well as in the dorsal root ganglia (DRG) known to harbor joint-innervating sensory neurons. Moreover, gene therapy reversed OA-induced molecular signatures of neural hyperexcitability, suggesting amelioration of peripheral sensitization. Collectively, these findings support combinatorial gene therapy as a promising treatment for osteoarthritis, while identifying neuroinflammatory signatures for correction of disease progression",
  "category": "systems biology",
  "published_at": "2026-07-28T00:00:00.000Z",
  "corresponding_author": "Brendan Lee",
  "journal_published_doi": null,
  "corresponding_institution": "Department of Molecular and Human Genetics, Baylor College of Medicine; Houston, USA."
}

{
  "doi": "10.64898/2026.07.27.740914",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.27.740914v1",
  "title": "Unlocking substrate specificities of human solute carrier proteins using untargeted metabolomics",
  "source": "biorxiv",
  "authors": "Zhang, Y.; Stanchev, L. D.; Schulz, F. C.; Rago, D.; Acevedo-Rocha, C. G.; Santos Delgado, A.; Kell, D. B.; Borodina, I.",
  "version": "1",
  "abstract": "The limited understanding of transporter substrate spectra constrains our ability to interpret cell and membrane function, highlighting the need for methods that enable transporter deorphanization and characterization of promiscuous transport activities. Here, we present a Xenopus oocyte-based platform for unbiased transporter substrate discovery. Oocytes expressing heterologous solute carrier proteins (SLC) were incubated in human blood serum, a chemically complex metabolite library containing thousands of endogenous metabolites and xenobiotics, followed by paired untargeted LC-MS/MS profiling of intracellular extracts and surrounding medium to capture metabolite exchange events. Across the five human SLC transporters, viz. SLC10A2, SLC10A6, SLC13A2, SLC16A10, and SLC46A1, metabolite exchange signatures were detected, and automated feature annotation was refined by manual chromatographic peak inspection. The workflow recovered known substrates of SLC10A2 and SLC16A10 and identified additional transported metabolites with MS/MS confirmation. This method provides a scalable framework for transporter substrate profiling and prioritization of candidates for targeted validation.",
  "category": "systems biology",
  "published_at": "2026-07-28T00:00:00.000Z",
  "corresponding_author": "Irina Borodina",
  "journal_published_doi": null,
  "corresponding_institution": "The Novo Nordisk Foundation Biotechnology Research Institute for the Green Transition, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark"
}

{
  "doi": "10.64898/2026.07.27.739389",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.27.739389v1",
  "title": "Beige/brown fat-mediated cardiac protection from high-fat diet is dependent on adipocyte beta3-adrenergic receptor",
  "source": "biorxiv",
  "authors": "Cascarano, L.; Michel, L.; Esfahani, H.; De Mulder, D.; Melecchi, A.; Bouzin, C.; Loriot, A.; Ambroise, J.; Pezzica, S.; Carli, F.; Sabatini, S.; Gatto, L.; Dessy, C.; Gastaldelli, A.; Balligand, J.-L.",
  "version": "1",
  "abstract": "Cardiometabolic diseases associated with obesity are continuously increasing worldwide. Yet, current therapeutic strategies remain insufficient to improve patient outcomes. The beta3-adrenergic receptor ({beta}3AR) promotes lipolysis in adipose tissue (AT) and thermogenesis specifically in brown adipose tissue (BAT). In mice, BAT activation also improves systemic metabolism and limits cardiometabolic damage. While BAT is limited in humans (e.g., with ageing and obesity), {beta}3AR activation induces beige adipocytes within white adipose depots with similar thermogenic properties. To study the role of adipocyte {beta}3AR in the regulation of cardiac metabolism and remodeling, mice with/without adipocyte-specific {beta}3AR genetic deletion were fed a high-fat-sucrose (HF-S) diet and treated with the selective {beta}3AR agonist CL316,243 (CL). The metabolic and cardiac protection following {beta}3AR activation was abrogated upon {beta}3AR deletion in adipocytes, together with the beiging of the epididymal (visceral) AT, highlighting a critical role of adipose {beta}3AR signalling in mediating these benefits. Multi-omic analysis of AT and cardiac samples identified CL-induced secreted ",
  "category": "systems biology",
  "published_at": "2026-07-28T00:00:00.000Z",
  "corresponding_author": "Lorena Cascarano",
  "journal_published_doi": null,
  "corresponding_institution": "Institute of Experimental and Clinical Research (IREC), Universite Catholique de Louvain, Belgium"
}

{
  "doi": "10.64898/2026.07.27.740543",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.27.740543v1",
  "title": "Leaf hydraulics is a core component of plant immunity",
  "source": "biorxiv",
  "authors": "Marty, S.; Bellenot, C.; vasselon, d.; Goussot, M.; Boulanger, A.; Audran, C.; Savourat, P.; Sarthou, A.-S.; Pouzet, C.; Routaboul, J.-M.; Laufs, P.; NOEL, L. D.",
  "version": "1",
  "abstract": "Hydathodes at leaf margins mediate guttation of xylem-derived fluids and serve as primary entry sites for adapted vascular bacterial pathogens such as Xanthomonas campestris. Infection of Arabidopsis mutants with fewer hydathodes resulted in spontaneous mesophyll water-soaking and revealed unexpectedly-large pathogen populations explained by direct infection of the mesophyll niche through stomata and subsequent proliferation. Physical blockage of hydathodes also induced mesophyll water-soaking and enhanced bacterial growth in both Arabidopsis and cauliflower leaves. These findings reveal a dual role for hydathodes as primary sites of infection while being essential to restrict pathogen proliferation in nonvascular tissues. More broadly, our study identifies leaf hydraulics and guttation as central components of water immunity in vascular plants.",
  "category": "plant biology",
  "published_at": "2026-07-28T00:00:00.000Z",
  "corresponding_author": "Laurent D NOEL",
  "journal_published_doi": null,
  "corresponding_institution": "LIPME"
}