bioRxiv Preprints

{
  "doi": "10.64898/2026.07.24.740376",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.24.740376v1",
  "title": "IL-13 Induces a Tuft Cell-Intrinsic CD45 Checkpoint to Limit Intestinal Type 2 Immunity",
  "source": "biorxiv",
  "authors": "Sochen, C.; Lebon, S.; Habshush-Menachem, A.; Sarusi-Portuguez, A.; Holiar, V.; Rudenko, V.; Toval, B.; Liu, J.; Levin, Y.; Vaaknin, E.; Rosenthal, N.; Tiferet, N.; Orr, I.; Ben-Dor, S.; Haffner-Krausz, R.; Grencis, R.; Munitz, A.; Karo-Atar, D.; Shulman, Z.; Biton, M.",
  "version": "1",
  "abstract": "Tuft cells initiate intestinal type 2 immunity, yet the mechanisms that restrain excessive tuft cell activation remain poorly understood. Here, we identify the receptor tyrosine phosphatase CD45 (Ptprc), previously considered a hematopoietic marker, as a regulator of intestinal tuft cell function. CD45 expression is restricted to a subset of tuft cells and is induced by helminth infection and IL-13. Epithelial-specific deletion of Ptprc activated a tuft cell inflammatory program, promoted an epithelial inflammatory state, and increased eosinophil accumulation at homeostasis. During Heligmosomoides polygyrus bakeri infection, CD45 deficiency enhanced ILC2 and Th2 responses and reduced parasite burden, demonstrating that epithelial CD45 limits type 2 immunity in vivo. Accordingly, in intestinal organoids, CD45 was dispensable for IL-13-driven tuft cell differentiation but restrained IL-13-responsive transcriptional programs. Mechanistically, CD45-deficient tuft cells exhibited altered protein abundance of STAT5 and IL17RB, implicated in tuft cell immune regulation. Together, these findings identify CD45 as a tuft cell-intrinsic regulatory checkpoint that restrains intestinal type 2 i",
  "category": "immunology",
  "published_at": "2026-07-26T00:00:00.000Z",
  "corresponding_author": "Moshe Biton",
  "journal_published_doi": null,
  "corresponding_institution": "Department of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot, Israel"
}

{
  "doi": "10.64898/2026.06.10.731461",
  "url": "https://www.biorxiv.org/content/10.64898/2026.06.10.731461v3",
  "title": "An information-bottleneck theory of suboptimal human inference",
  "source": "biorxiv",
  "authors": "Parker, J. A.; Filipowicz, A. L. S.; Li, K.; Balasubramanian, V.; Kable, J. W.; Gold, J. I.",
  "version": "3",
  "abstract": "Human inference is often suboptimal in ways that vary across individuals and tasks. We propose that this variability reflects information processing limits and develop a task-general application of the information bottleneck framework to quantify how much information individuals use (information capacity) and how effectively they use it (efficiency). Applying this framework to human choice behavior across two distinct inference tasks, we identify two principal axes of individual variation: 1) the choice of inference strategy (optimal versus heuristic), and 2) the information capacity used to implement that strategy. Despite substantial variability along these axes, participants largely achieve near-maximal accuracy given their strategy and capacity. Moreover, they can adjust information capacity while maintaining efficiency as task demands change. We interpret these findings in terms of new analytical results linking optimal capacity-limited inference to evidence-based choice noise, which suggests that a hallmark of human behavior may reflect rational adaptation to information processing costs.",
  "category": "neuroscience",
  "published_at": "2026-07-26T00:00:00.000Z",
  "corresponding_author": "Jacob A Parker",
  "journal_published_doi": null,
  "corresponding_institution": "University of Pennsylvania"
}

{
  "doi": "10.64898/2026.01.30.702896",
  "url": "https://www.biorxiv.org/content/10.64898/2026.01.30.702896v3",
  "title": "Efficient and low-impact enzymatic glycosylation with robust sucrose synthase variants",
  "source": "biorxiv",
  "authors": "Mejia-Otalvaro, F.; Delima, D.; Hobusch, M.; Lax, B. M.; Mendonca, C.; Bidart, G.; Matera, A.; Branger, A.; Escorial Garcia, M.; Rovira, C.; Welner, D. H.",
  "version": "3",
  "abstract": "Glycosyltransferase-driven glycosylation enables environmentally mild synthesis of high-value chemicals, but industrial implementation is constrained by the cost of UDP-glucose. Sucrose synthase (SuSy) offers an attractive route for UDP-glucose recycling, yet inadequate operational stability has limited its use. Here, we report an integrated engineering workflow that overcomes the longstanding trade-off between efficiency and robustness in glycosyl donor recycling enzymes. We engineered GmSuSy wild-type and obtained variants combining supra-wildtype activity (178%) with enhanced thermostability ({Delta}Tmapp = 13.3 {degrees}C), solvent tolerance (70% retained activity in 25% DMSO) and a 123-fold longer half-life. The variants achieved total turnover numbers of ~1 million (60 {degrees}C), supporting their industrial relevance. Mechanistic analyses revealed that long-range residue communication networks couple oligomeric interfaces with active sites, shifting conformational populations toward stable, catalytically competent states while increasing hydrophobic packing and reducing solvent accessibility. This enhanced robustness enabled significant process-level gains, including >90% c",
  "category": "biochemistry",
  "published_at": "2026-07-26T00:00:00.000Z",
  "corresponding_author": "Ditte Hededam Welner",
  "journal_published_doi": null,
  "corresponding_institution": "Technical University of Denmark"
}

{
  "doi": "10.64898/2026.05.27.726245",
  "url": "https://www.biorxiv.org/content/10.64898/2026.05.27.726245v2",
  "title": "Pansoma, a machine learning tool for identifying somatic variants using pangenome graphs",
  "source": "biorxiv",
  "authors": "Shen, J.; Fu, Q.; Macias, J. F.; Human Pangenome Reference Consortium,  ; Li, D.; Wang, T.",
  "version": "2",
  "abstract": "Somatic variant calling, the identification of mutations in non-germline cells acquired over an individual's lifetime, is critical for studying diseases, including cancer, and for developing precision oncology strategies. Traditional somatic variant calling methods rely on linear reference genomes, which do not adequately capture human genetic diversity and result in reference bias, compromising the accuracy of somatic variant detection. The recently developed graph-based human pangenome reference represents diverse genetic variants across human populations and has promised to drive advances in many genetics and genomics studies. In this study, we introduce Pansoma, a novel pangenome-native and machine learning-based tool specifically designed for somatic variant calling using a pangenome graph reference. Pansoma performs somatic variant detection from both short- and long-read sequencing data by learning tensor representations of alignment on graph nodes rather than on a linear reference. Pansoma outputs variant representations anchored to the pangenome graph paths and conventional somatic variant calls remapped to the linear reference. Additionally, we provide a suite of bioinfor",
  "category": "genomics",
  "published_at": "2026-07-26T00:00:00.000Z",
  "corresponding_author": "Ting Wang",
  "journal_published_doi": null,
  "corresponding_institution": "Washington University in St. Louis"
}

{
  "doi": "10.64898/2026.07.24.740504",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.24.740504v1",
  "title": "A GSK3-dependent phosphorylation switch licenses BNIP3-mediated mitophagy",
  "source": "biorxiv",
  "authors": "Hurd, T. R.; Philip, R. R.; Minenkova, A. V.; Li, Y.",
  "version": "1",
  "abstract": "The turnover of mitochondria through mitophagy is essential for maintaining mitochondrial function and matching mitochondrial content to cellular demand. In many cells, this process is mediated by the paralogous mitochondrial receptors BNIP3 and BNIP3L, which recruit WIPI-family autophagy effectors to initiate mitophagosome formation. However, the mechanisms that activate BNIP3/L remain poorly understood. Here, we show that the kinase GSK3 directly phosphorylates BNIP3, licensing receptor activity and activating mitophagy. Phosphorylation promotes BNIP3 recruitment of WIPI proteins, thereby initiating mitophagosome formation. We identify the critical phosphorylation sites required for this regulation and demonstrate that disruption of these sites abolishes BNIP3-dependent mitophagy. Together, our findings identify phosphorylation as a molecular switch controlling BNIP3/L activity and suggest that receptor phosphorylation may temporally and spatially license mitophagosome formation and mitochondrial clearance.",
  "category": "cell biology",
  "published_at": "2026-07-26T00:00:00.000Z",
  "corresponding_author": "Thomas Ryan Hurd",
  "journal_published_doi": null,
  "corresponding_institution": "University of Toronto"
}

{
  "doi": "10.64898/2026.07.24.740573",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.24.740573v1",
  "title": "Rapid motility arrest of the Lyme disease spirochete, Borrelia burgdorferi, by vaccine-induced OspA antibodies",
  "source": "biorxiv",
  "authors": "Bhattacharyya, A.; Yau, R.; Bartlett, T. M.; MANTIS, N. J.",
  "version": "1",
  "abstract": "Outer surface protein A (OspA)-based Lyme disease vaccines elicit antibodies that inhibit transmission of infectious Borrelia burgdorferi spirochetes from ticks to humans, although the mechanism by which this occurs is unclear. Here we demonstrate using high-resolution, single-cell fluorescence video microscopy that B. burgdorferi motility is arrested within minutes by human OspA-specific monoclonal antibodies and polyclonal OspA antisera from mice immunized with a candidate OspA mRNA lipid nanoparticle vaccine.",
  "category": "immunology",
  "published_at": "2026-07-26T00:00:00.000Z",
  "corresponding_author": "Nicholas J MANTIS",
  "journal_published_doi": null,
  "corresponding_institution": "Wadsworth Center, New York State Department of Health"
}

{
  "doi": "10.64898/2026.05.06.723392",
  "url": "https://www.biorxiv.org/content/10.64898/2026.05.06.723392v2",
  "title": "Convergent gene family evolution underpins repeated transitions to metamorphic development across Pancrustacea",
  "source": "biorxiv",
  "authors": "Campli, G.; Chipman, A. D.; Robinson-Rechavi, M.; Waterhouse, R. M.",
  "version": "2",
  "abstract": "Arthropod developmental modes are highly diverse, ranging from direct development with little morphological change between moults to metamorphic life-stage progressions characterised by profound transformations. Metamorphosis can be defined as a post-embryonic life-stage progression event leading to adulthood that is characterised by major morphological changes and modifications of the adaptive landscape. Within this framework, we compare four independent evolutionary life history transitions to metamorphic development across Pancrustacea. Using a phylogenomic dataset of 54 species spanning 26 orders, we investigated gene family evolutionary dynamics associated with the inferred origins of metamorphosis in Insecta, Copepoda, Eucarida, and Thecostraca. Compared with non-metamorphic sister lineages as well as descendent and ancestral nodes, transitions to metamorphic development were consistently associated with elevated gene family births and expansions. Although these expansions predominantly involved different gene families in each lineage, they repeatedly converged on shared biological functions, particularly those related to embryonic and post-embryonic development, morphogenesi",
  "category": "evolutionary biology",
  "published_at": "2026-07-26T00:00:00.000Z",
  "corresponding_author": "Robert M. Waterhouse",
  "journal_published_doi": null,
  "corresponding_institution": "SIB Swiss Institute of Bioinformatics"
}

{
  "doi": "10.64898/2026.05.22.727092",
  "url": "https://www.biorxiv.org/content/10.64898/2026.05.22.727092v2",
  "title": "Evidence of thermal selection from experimental evolution in the arboviral vector Aedes albopictus",
  "source": "biorxiv",
  "authors": "Khorramnejad, A.; Palatini, U.; Da Re, D.; Lozada-Chavez, I.; Bahrami, R.; Perdomo, H. D.; Di Castri, S.; Rosa, R.; Aronson, H.; Lahondere, C.; Bonizzoni, M.",
  "version": "2",
  "abstract": "The extent and the pace to which plasticity and adaptation interact during ectotherm thermal evolution are unclear. We exposed the invasive arboviral vector Aedes albopictus to thermal experimental evolution for three years. Within 10-15 generations, mosquitoes exhibited major changes in fitness, metabolism and transcriptome, marking the consolidation of a temperature-dependent trade-off between reproduction and lifespan. Most phenotypic and gene expression changes reverted to control levels when thermal selection was relaxed, demonstrating a predominant plastic response after prolonged evolution. Also, 250 genes displayed an opposite association in expression changes in warm- versus relaxed-evolved mosquitoes, consistent with selection operating on a polygenic architecture. Ecological modelling identified egg-to-adult viability as the primary driver of thermal reproductive success, highlighting juvenile stages as a crucial control target under continued warming.",
  "category": "evolutionary biology",
  "published_at": "2026-07-26T00:00:00.000Z",
  "corresponding_author": "Mariangela Bonizzoni",
  "journal_published_doi": null,
  "corresponding_institution": "Universita degli Studi di Pavia"
}

{
  "doi": "10.64898/2026.05.25.727646",
  "url": "https://www.biorxiv.org/content/10.64898/2026.05.25.727646v2",
  "title": "Dual lineages of Langerhans cells cooperate to restore the immune barrier after skin injury",
  "source": "biorxiv",
  "authors": "Schmitter-Sanchez, A. D.; Basista, N.; Mishra, S.; Kim, H.; Bench, A.; Matte-Martone, C.; Seo, M.-S.; Lee, G. W.; Park, S.",
  "version": "2",
  "abstract": "Langerhans cells (LCs) are key immune sentinels of the epidermis. How this network reorganizes to safeguard epidermal immunity after injury has remained unclear. Here, we uncover a previously unrecognized two-lineage program of LC repopulation during wound repair. Classically, tissue-resident embryonically derived LCs (eLCs) migrate to lymph nodes in response to antigens. In contrast, we find that injury triggers nearby eLCs to migrate into wounds, providing immediate coverage. In parallel, circulating monocytes infiltrate the skin and differentiate into long-lived monocyte-derived LCs (mLCs) that integrate stably into the network. We identify the chemokine receptor CXCR2 as a novel regulator of eLC migration into wounds, distinct from the CXCR4/CCR7 pathways mediating LC egress to lymph nodes. Pharmacological inhibition of CXCR2 impairs directional eLC migration and is accompanied by increased mLC infiltration, preserving immune barrier density. These findings reveal a coordinated and flexible two-lineage repair program that ensures robust restoration of epidermal immunity.",
  "category": "cell biology",
  "published_at": "2026-07-26T00:00:00.000Z",
  "corresponding_author": "Sangbum Park",
  "journal_published_doi": null,
  "corresponding_institution": "Michigan State University"
}

{
  "doi": "10.64898/2026.07.23.740331",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.23.740331v3",
  "title": "A significant enrichment that is not: spatial nulls, co-expression, and the imaging transcriptomics of EEG alpha-power genetics",
  "source": "biorxiv",
  "authors": "Schenetti, J.",
  "version": "3",
  "abstract": "Background. Imaging transcriptomics routinely asks whether a trait-associated gene set is over-expressed in a region of interest, and the field standard is to guard that inference with a spatial-autocorrelation-preserving spin test. Electroencephalographic (EEG) oscillatory power is among the most heritable human neurophysiological traits, and the cortical generators of the alpha rhythm have been characterised independently from resting-state magnetoencephalography - making this a natural test bed both for asking whether trait genetics is regionally organised, and for asking what such a test actually establishes. Objective. To test whether alpha-associated genetic signal is spatially enriched in the cortical generators of the alpha rhythm, and to evaluate that inference against complementary null models. Methods. MAGMA gene-based analysis of ENIGMA-EEG summary statistics for six phenotypes: central and occipital alpha power, occipital alpha peak frequency, and theta, beta and delta power. Regional transcription was obtained from the Allen Human Brain Atlas (AHBA) with abagen in the Glasser HCP-MMP1.0 atlas, with Schaefer-100 and Yan-600 as sensitivity analyses. Enrichment in the 41",
  "category": "neuroscience",
  "published_at": "2026-07-26T00:00:00.000Z",
  "corresponding_author": "Jacopo Schenetti",
  "journal_published_doi": null,
  "corresponding_institution": "University of Trento"
}