bioRxiv Preprints

{
  "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."
}

{
  "doi": "10.64898/2026.07.21.739890",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.21.739890v1",
  "title": "Optimized cryo-FIB milling strategy to generate thin, minimally damaged biological lamellae",
  "source": "biorxiv",
  "authors": "Hall, L. N.; Paul, J.; Ngo, P.; Lucas, B. A.",
  "version": "1",
  "abstract": "Focused ion beam (FIB)-milling has been adapted to thin frozen cells for visualization of macromolecular structures in situ with cryogenic electron microscopy. However, only a few large and abundant complexes have been annotated to date. FIB-milling introduces damage which limits the recoverable information from cellular sections. Here, we present Nilas, a low-energy milling strategy optimized to minimize damage and produce thin lamellae. Nilas-milled lamellae show minimal FIB-milling damage, contain areas at or below 50 nm and produce higher resolution in situ 3D reconstructions. Nilas improves the recovery of ribosomal subunits and reduces the predicted minimal detectable molecular mass with two-dimensional template matching (2DTM) to approximately 220 kDa. Consistently, we recover additional non-ribosomal complexes including RNA polymerase III with 2DTM in Nilas-milled lamellae. Nilas is compatible with common milling hardware, making it accessible to diverse users. By extending the size limit for in situ structural biology we bring visual proteomics closer to reality.",
  "category": "biophysics",
  "published_at": "2026-07-25T00:00:00.000Z",
  "corresponding_author": "Bronwyn A Lucas",
  "journal_published_doi": null,
  "corresponding_institution": "University of California Berkeley"
}

{
  "doi": "10.64898/2026.07.21.739736",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.21.739736v2",
  "title": "Phenotype-driven de novo molecular design from gene expression signatures",
  "source": "biorxiv",
  "authors": "Xu, Y.; Kuang, T.; Ge, S.; Wu, H.; Wang, M.; Xu, H.; An, F.; Ma, Z.; Cheng, Q.; Ren, Z.",
  "version": "2",
  "abstract": "Target-based and structure-guided drug design remain central to modern drug discovery, but complementary strategies are needed when predefined targets or binding pockets do not fully capture disease biology. Gene-expression signatures provide scalable system-level readouts of disease and perturbation states, making them attractive inputs for phenotype-guided molecular design. However, preserving phenotypic information during molecular generation remains challenging, and chemically plausible molecules may lose connection to the intended biological response. Here, we present Tx2Mol, a transcriptome-guided framework that translates gene-expression signatures into candidate molecules while maintaining biological guidance throughout generation. We evaluated Tx2Mol across three biological settings: bulk gene perturbation, single-cell perturbation, and patient-derived disease signatures; and three validation dimensions: chemical plausibility, structural compatibility, and phenotypic preservation. Across 10 cancer-relevant bulk gene-perturbation benchmarks, Tx2Mol outperformed 9 transcriptome-guided baselines, improving maximum Tanimoto similarity to known ligands by 24.10% on average and ",
  "category": "bioinformatics",
  "published_at": "2026-07-25T00:00:00.000Z",
  "corresponding_author": "Zhixiang Ren",
  "journal_published_doi": null,
  "corresponding_institution": "Shanghai Smart Logic Technology Co., Ltd."
}

{
  "doi": "10.64898/2026.07.21.739920",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.21.739920v1",
  "title": "Characterization of NPR-14 in the Regulation of Sleep-Like Behaviour in Caenorhabditis elegans",
  "source": "biorxiv",
  "authors": "Chin-Sang, I.; Torki, F.; Bendena, W. G.",
  "version": "1",
  "abstract": "Sleep-like quiescence is an evolutionarily conserved state essential for physiological homeostasis; however, its dysregulation can lead to sleep disorders such as narcolepsy, which can be caused by abnormal neuropeptide signaling. In Caenorhabditis elegans, the G-protein-coupled receptor NPR-14 belongs to the orexin/allatotropin receptor family and has been proposed as a homolog of mammalian orexin receptors. Using npr-14 loss-of-function (lf) mutants, we demonstrate that NPR-14 promotes arousal and inhibits sleep-like quiescence. npr-14(lf) mutants exhibit prolonged quiescence, reduced locomotion, impaired sensory responses, and metabolic defects including elevated fat accumulation and decreased feeding and egg-laying. NPR-14 is expressed in ASH and ASI sensory neurons and in GABAergic DD, VD, and VC motor neurons, positioning it to modulate both sensory-motor integration and motor output directly. Genetic epistasis analysis revealed that NPR-14 functions upstream of EGL-4/protein kinase G (PKG): egl-4 loss-of-function suppressed the enhanced quiescence of npr-14 mutants, while egl-4 gain-of-function phenotypes were not enhanced by loss of npr-14. Caffeine treatment partially supp",
  "category": "genetics",
  "published_at": "2026-07-25T00:00:00.000Z",
  "corresponding_author": "Ian Chin-Sang",
  "journal_published_doi": null,
  "corresponding_institution": "Queen's University"
}

{
  "doi": "10.64898/2026.07.24.740579",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.24.740579v1",
  "title": "Outbreak of Dermatophilus congolensis skin infection among contact sport practitioners, Norway, summer 2025",
  "source": "biorxiv",
  "authors": "Pape, K.; Javnes, S.; Aas, C. G.; Sagvik, E. O.; Larssen, K. W.; Jore, S.",
  "version": "1",
  "abstract": "Dermatophilus congolensis is a zoonotic gram-positive bacterium causing dermatophilosis, a skin infection primarily affecting animals and uncommonly reported in humans. Although human infections have traditionally been associated with animal contact, recent reports suggest alternative transmission pathways. We investigated an outbreak among contact sport athletes in Trondheim, Norway, during July to September 2025, using structured interviews and whole-genome sequencing. Nine confirmed cases were identified. Symptoms were mild and consisted mainly of pustular lesions affecting the face, arms, back, and chest. None of the cases reported animal contact. Genomic analysis confirmed species identity and showed that outbreak isolates were highly related, differing by only 0-7 core-genome single nucleotide polymorphisms. The Trondheim isolates clustered with strains from recent outbreaks in Spain and France, suggesting international dissemination of a shared clone. These findings identify contact sports as a potential setting for transmission of human dermatophilosis and highlight the value of genomic surveillance for outbreak investigation.",
  "category": "microbiology",
  "published_at": "2026-07-25T00:00:00.000Z",
  "corresponding_author": "Kristine Pape",
  "journal_published_doi": null,
  "corresponding_institution": "Municipality of Trondheim, Department of Infectious Disease Control, Trondheim, Norway"
}

{
  "doi": "10.64898/2026.07.24.740542",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.24.740542v1",
  "title": "Intrafilament nucleotide exchange in a prokaryotic actin homolog",
  "source": "biorxiv",
  "authors": "Adriaans, I. E.; Billaudeau, C.; Cornilleau, C.; Lim, K. S.; Dinet, C.; Renner, L. D.; Peron-Cane, C.; Jegou, A.; Wong, R. W.; Chastanet, A.; Michelot, A.; Carballido-Lopez, R.",
  "version": "1",
  "abstract": "Polymerisation and disassembly govern the cellular functions of cytoskeletal proteins. In canonical nucleotide-dependent polymers such as actin and tubulin, nucleotide exchange occurs in soluble subunits but not within intact protofilaments. By contrast, the assembly dynamics and nucleotide dependency of the prokaryotic actin homolog MreB, whose polymerization into membrane associated filaments is essential for bacterial cell morphogenesis, remain poorly understood. We used total internal reflection fluorescence microscopy and high-speed atomic force microscopy to monitor the assembly of MreB on supported lipid bilayers in real time. ATP binding triggers MreB polymerization into symmetrically elongating pairs of filaments on cardiolipin-containing membranes. While ATP hydrolysis occurs within filaments and contributes to endwise disassembly, continuous nucleotide exchange within filaments tunes their stability on the membrane. Nucleotide cycling within MreB filaments defines a new class of biological polymer behavior and highlights the evolutionary divergence of mechanisms governing actin homologs assembly dynamics.",
  "category": "microbiology",
  "published_at": "2026-07-25T00:00:00.000Z",
  "corresponding_author": "Rut Carballido-Lopez",
  "journal_published_doi": null,
  "corresponding_institution": "Universite Paris-Saclay, INRAE, AgroParisTech, Micalis Institute"
}

{
  "doi": "10.64898/2026.07.24.740629",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.24.740629v1",
  "title": "Structural and Stereochemical Elucidation of Cyanochelin C, a Siderophore Associated with Novel Class of Cyanobacterial Acyl Hydrolases",
  "source": "biorxiv",
  "authors": "Di Matteo, V.; Stenclova, L. M.; Falcao, B. P.; Hrouzek, P.; Urajova, P.; Mares, J.; Esposito, G.; Mangoni, A.; Costantino, V.; Galica, T.",
  "version": "1",
  "abstract": "Iron is a key micronutrient that constrains microbial growth and productivity in many aquatic and terrestrial environments due to its limited bioavailability. Microorganisms evolved sophisticated acquisition strategies, including the production of siderophores, high-affinity iron-chelating molecules that facilitate iron solubilisation and uptake. Cyanobacteria, photosynthetic prokaryotes and major contributors to global primary production, also depend on iron as a cofactor to their core metabolic enzymes. However, very few cyanobacterial siderophores were described so far, and cyanobacteria remain an underxplored source of possibly novel siderophores. Here we report a novel cyanobacterial siderophore, cyanochelin C, that employs two {beta}-hydroxyaspartate residues for iron chelation. We provide extensive nuclear magnetic resonance (NMR) and mass spectrometry (MS) evidence on the molecular structure and identify the corresponding biosynthetic gene cluster (BGC). Bioinformatic analysis of the BGC further revealed the presence of an acylase CcsQ clustering with a broader cyanobacteria-specific family of acylases associated with predicted siderophore-encoding BGCs. Discovery of cyanoc",
  "category": "microbiology",
  "published_at": "2026-07-25T00:00:00.000Z",
  "corresponding_author": "Tomáš Galica",
  "journal_published_doi": null,
  "corresponding_institution": "Centre Algatech, Institute of Microbiology of the Czech Academy of Sciences"
}

{
  "doi": "10.64898/2026.07.24.740633",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.24.740633v1",
  "title": "Prevalent phenotypic mutation impairs binding of broadly neutralizing antibodies to influenza hemagglutinin",
  "source": "biorxiv",
  "authors": "Barriga, M.; Barranco-Gomez, O.; Garcia-Corzo, L.; Fernandez-Fernandez, A.; Vizcaino, A.; Ramilo, P.; Osuna, A.; Risso, V. A.; Sanchez-Ruiz, J. M.",
  "version": "1",
  "abstract": "Mistakes during protein synthesis, such as transcription errors, occur often and lead to non-inheritable amino acid replacements generally known as phenotypic mutations. We recently used a consensus approach in high-throughput sequencing to determine the error landscape for influenza-hemagglutinin mRNA. We found single-site errors to occur with widely different frequencies. Here we show that the most prevalent transcription error encodes a phenotypic mutation that impairs binding of broadly neutralizing antibodies. The error occurs in 0.2-0.5% of mRNA molecules and, consequently, many virions will expose hemagglutinin variants bearing the encoded amino acid replacement. Our results point to a mechanism of antibody evasion, akin to programmed recoding, in which evading mutations are encoded by transcription errors promoted by inheritable RNA sequence/structure patterns.",
  "category": "microbiology",
  "published_at": "2026-07-25T00:00:00.000Z",
  "corresponding_author": "Jose M. Sanchez-Ruiz",
  "journal_published_doi": null,
  "corresponding_institution": "University of Granada"
}

{
  "doi": "10.64898/2026.07.24.740622",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.24.740622v1",
  "title": "Cryo-electron microscopy structure of Jabs, a bacteriophage infecting the multidrug-resistant pathogen Mycobacterium abscessus",
  "source": "biorxiv",
  "authors": "Cambillau, C.; Liew, J. H.; Tan, B. S. Y.; Kremer, L.; Bifani, P.; Goulet, A.",
  "version": "1",
  "abstract": "Exploring bacteriophage structural diversity is essential for understanding phage biology and for advancing phage-based therapies. Here, we determine the cryo-electron microscopy structure of Jabs, providing, to our knowledge, the first high-resolution view of a phage infecting the multidrug-resistant human pathogen Mycobacterium abscessus. Although Jabs displays the canonical organization of a siphophage, its virion combines several unusual architectural features. The T=9 icosahedral capsid is assembled from two distinct major capsid proteins, with one forming the hexons and the other the pentons, revealing an unprecedented capsid assembly strategy among icosahedral phages. An extensive network of ~1,700 disulfide bonds stabilize individual structural components and covalently links the capsid, connector, tail, and adhesion device into a continuous assembly. At the distal end of the tail, an elaborate and conformationally dynamic adhesion device comprises multiple candidate receptor-binding proteins organized into complex multidomain architectures, including carbohydrate-binding modules and {beta}-sandwich hetero- and homotrimers resembling the receptor-binding proteins of phages ",
  "category": "microbiology",
  "published_at": "2026-07-25T00:00:00.000Z",
  "corresponding_author": "Adeline Goulet",
  "journal_published_doi": null,
  "corresponding_institution": "CNRS"
}

{
  "doi": "10.64898/2026.07.21.739902",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.21.739902v1",
  "title": "Intracellular pathogen targeting by IL32 elicits cell-autonomous immunity",
  "source": "biorxiv",
  "authors": "Reitano, J. R.; Walsh, S. C.; Dickinson, M. S.; Johnston, E. A.; Cortina, M. E.; Adcox, H.; Alto, N.; Derre, I.; Hybiske, K.; Suchland, R.; Kim, S. Y.; Coers, J.",
  "version": "1",
  "abstract": "Interferon gamma safeguards humans against intracellular pathogens, yet how most interferon-stimulated genes protect host cells, and how human-adapted pathogens evade these defenses is unclear. Here, we discover a potent immune surveillance and effector circuit executed by an intracellularly acting cytokine, IL32, that targets and restricts phylogenetically distinct vacuolar pathogens, including the bacterium Chlamydia and the microsporidian Encephalitozoon. Quantitative proteomics coupled to a tailored CRISPR screen, uncovered components of the cysteine/Arg N-degron pathway that modify IL32 through oxidation-dependent arginylation, thereby enabling the recruitment of the autophagy machinery to pathogen-containing vacuoles. A forward genetics screen in Chlamydia trachomatis, the leading cause of sexually transmitted bacterial infection, identified the secreted virulence factor IncS as an evasion factor that blocks IL32 targeting and shields this human pathogen from xenophagy. These findings establish an IL32-dependent intracellular sensing mechanism linking IFN gamma signaling to N-degron-mediated xenophagy, revealing a broadly relevant axis of human host-pathogen conflict",
  "category": "immunology",
  "published_at": "2026-07-25T00:00:00.000Z",
  "corresponding_author": "Jorn Coers",
  "journal_published_doi": null,
  "corresponding_institution": "Duke University School of Medicine"
}