@unpublished{21968,
  abstract     = {Balancing selection, a form of selection that maintains genetic diversity, is difficult to detect, and the importance of balancing selection for the maintenance of genetic variation may be larger than often assumed. We model the possibility that the diversity-promoting effects of balancing selection extend to other loci that show sign epistasis with a locus under balancing selection. Rather than focusing on overdominance, as was done in previous efforts, we explore the effects of negative frequency dependence and show that this has important effects on the conditions under which the diversity-promoting effect of epistasis can occur in diploids. Our results show that not only recombination rate but also the dominance of sign epistasis are key parameters that determine the maintenance of polymorphism beyond the locus under direct balancing selection. We suggest that the effect we explore may play a significant role, especially when balancing selection acts on major effect loci.},
  author       = {Khudiakova, Kseniia and Barton, Nicholas H and Arnqvist, Goran},
  booktitle    = {bioRxiv},
  title        = {{Sign epistasis extends the effects of balancing selection on genetic diversity}},
  doi          = {10.1101/2025.04.09.647826},
  year         = {2026},
}

@misc{21971,
  abstract     = {A Rust library for analyzing dendritic structures using quadric matrices. This project provides efficient tools for representing dendritic trees, computing quadric error metrics, and visualizing eigenvalue distributions on hexagonal plots.

This library implements quadric-based geometric analysis of dendritic structures, commonly found in neuroscience applications. Key features include:

Tree data structures: Hierarchical vertex and edge representations for dendritic trees
Quadric matrices: Computation of quadric error metrics for edges and vertices
Visualisation: Hexagonal plot generation using NormPolar transformations
Interactive tools: Desktop application with plotting capabilities},
  author       = {Bleile, Yossi and Cortinovis, Emanuele},
  keywords     = {quadratics, mathematics, dendrites, geometry, topology},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Quadrix}},
  doi          = {10.15479/AT-ISTA-21971},
  year         = {2026},
}

@article{21980,
  abstract     = {Despite significant progress in the field of molecular electronics over the last two decades, the quantitative prediction of metal-molecule-metal junction conductance remains a challenge. The standard computational framework combines density functional theory (DFT) with nonequilibrium Green’s functions (NEGF) using low-rung exchange-correlation functionals such as PBE, which overestimate the conductances. More advanced correction methods exist but require complex workflows and high computational cost, limiting their accessibility. Here, we introduce a physically motivated approach that approximates results obtained with high-rung functionals. Our method fits the PBE-calculated transmission to a Breit-Wigner form and subsequently refines the fit parameters using molecular orbital energies and metal densities of states computed for the isolated subsystems with high-rung functionals. This approach is applicable to a broad range of molecular junctions yielding conductance values in quantitative agreement with experiments. Our approach is simple, low-cost, and accurate, making it well-suited for routine and large-scale prediction of single-molecule junction conductance.},
  author       = {Gulyaev, Artem and Hazarika, Jyotisman and Liu, Zhen-Fei and Venkataraman, Latha},
  issn         = {1530-6992},
  journal      = {Nano Letters},
  number       = {22},
  pages        = {7429–7434},
  publisher    = {American Chemical Society},
  title        = {{A computationally efficient and accurate method for predicting conductance of single-molecule junctions}},
  doi          = {10.1021/acs.nanolett.6c01462},
  volume       = {26},
  year         = {2026},
}

@article{21981,
  abstract     = {For Hamiltonian actions of semidirect products G = FxH, we study 2-cocycles arising from residual Hamiltonian actions of F on Hamiltonian reductions for H. The motivation comes from the study of Teichmüller spaces for surfaces with boundary, which carry Hamiltonian actions of the Virasoro algebra. In this paper, we give a general setup for the problem, and we suggest an easier way to obtain the Gelfand-Fuchs 2-cocycles for Hamiltonian actions on Teichmüller spaces.},
  author       = {Goncharov, Viacheslav},
  issn         = {1879-1662},
  journal      = {Journal of Geometry and Physics},
  publisher    = {Elsevier},
  title        = {{An easier way to compute 2-cocycles coming from a reduction for semidirect products}},
  doi          = {10.1016/j.geomphys.2026.105878},
  volume       = {227},
  year         = {2026},
}

@article{21982,
  abstract     = {A floating Leidenfrost droplet exhibits curvature inversion of its underside, due to the balance of vapor pressure and surface tension. Using interferometric imaging, we find different behavior for a levitated hydrogel sphere. Curvature inversion is observed briefly just after deposition, but quickly gives way to a steady state with no inversion. We show the essential role of vaporization in shaping the underbelly of the hydrogel, where changes due to direct mass loss are more significant than the balance of vapor pressure and elastic forces.},
  author       = {Diaz Melian, Vicente L and Lenton, Isaac C and Binysh, Jack and Souslov, Anton and Waitukaitis, Scott R},
  issn         = {2470-0053},
  journal      = {Physical Review E},
  number       = {5},
  publisher    = {American Physical Society},
  title        = {{Geometry of the vapor layer under a Leidenfrost hydrogel sphere}},
  doi          = {10.1103/m7gr-2t6j},
  volume       = {113},
  year         = {2026},
}

@article{21983,
  abstract     = {Promoters and enhancers are cis-regulatory elements (CREs), DNA sequences that bind transcription factor (TF) proteins to up- or down-regulate target genes. Decades-long efforts yielded TF-DNA interaction models that predict how strongly an individual TF binds arbitrary DNA sequences and how individual binding events on the CRE combine to affect gene expression. These insights can be synthesized into a global, biophysically realistic, and quantitative genotype–phenotype map for gene regulation, a ‘holy grail’ for the application of evolutionary theory. A global map provides a rare opportunity to simulate the long-term evolution of regulatory sequences and pose several fundamental questions: How long does it take to evolve CREs de novo? How many non-trivial regulatory functions exist in sequence space? How connected are they? For which regulatory architecture is CRE evolution most rapid and evolvable? In this article, the first of a two-part series, we briefly review the pertinent modeling and simulation efforts for a unique system that enables close, quantitative, and mechanistic links between biophysics, as well as systems, synthetic, and evolutionary biology.},
  author       = {Mascolo, Elia and Körei, Reka E and Herrera-Álvarez, Santiago and Guet, Calin C and Crocker, Justin and Tkačik, Gašper},
  issn         = {1879-0380},
  journal      = {Current Opinion in Genetics & Development},
  publisher    = {Elsevier},
  title        = {{Long-term evolution of regulatory DNA sequences. Part 1: Simulations on global, biophysically-realistic genotype–phenotype maps}},
  doi          = {10.1016/j.gde.2026.102483},
  volume       = {99},
  year         = {2026},
}

@article{21985,
  abstract     = {Upon infecting a bacterial cell, temperate phages make a decision between lysis and lysogeny. While research has previously explored how phages sense environmental information to make this choice, most studies have focused on modelling known mechanisms that impact the decision. These mechanisms tell us what environmental information the phage does respond to, but not what it should respond to, as the signals sensed by the phage may serve as proxies for other sources of information. Here, using a mechanism-agnostic population dynamics model, we find that irreversible phage binding to lysogens protects sensitive host cells from infection. This results in lysogens being an additional environmental factor that the phage should sense while making its decision to undergo lysis or lysogeny. Using this model, we derive a responsive lysogeny probability for phages that respond to both cell and lysogen densities optimized towards invading phage-occupied systems, and show that it is more capable of invading and resisting invasion than phage with fixed lysogeny probabilities across different environmental conditions.},
  author       = {Wu, Bryan and Guet, Calin C},
  issn         = {1558-5646},
  journal      = {Evolution},
  number       = {6},
  pages        = {1365--1373},
  publisher    = {Oxford University Press},
  title        = {{Responsive lysogeny under nonproductive phage binding}},
  doi          = {10.1093/evolut/qpag061},
  volume       = {80},
  year         = {2026},
}

@article{21986,
  abstract     = {Over the past two decades, molecular electronics has made significant progress toward discovering nanoscale analogues of conventional electronic components, largely enabled by the development of the scanning tunneling microscope-based break-junction (STM-BJ) technique. The STM-BJ technique enables precise and highly reproducible measurement of a molecule’s electronic transport properties, making it a powerful technique to explore physiochemical and electrochemical phenomena that are otherwise difficult to access. It has gained substantial popularity in the past 20 years, with experiments becoming increasingly diverse and sophisticated. Despite the wealth of literature, an accessible, practical guide to performing STM-BJ experiments and interpreting the data is largely absent. This tutorial includes a brief background into the development of STM-BJ measurements, followed by detailed explanations of instrumentation, data collection, statistical analysis, variations on standard experiments, and some troubleshooting methods. It is aimed at researchers looking to begin or improve STM-BJ studies in their laboratories, graduate students and postdoctoral researchers learning the technique, and readers seeking to critically evaluate the growing body of STM-BJ literature.},
  author       = {York, Emma and Venkataraman, Latha},
  issn         = {2694-2445},
  journal      = {ACS Physical Chemistry Au},
  number       = {3},
  pages        = {408--424},
  publisher    = {American Chemical Society},
  title        = {{Scanning tunneling microscope-based break-junction technique - A tutorial}},
  doi          = {10.1021/acsphyschemau.6c00026},
  volume       = {6},
  year         = {2026},
}

@article{21987,
  abstract     = {We introduce JODIE, a genetic joint modeling approach that estimates how DNA loci influence human traits by partitioning genetic effects into four components: direct effects (from a child’s alleles), indirect maternal and paternal effects (from parents’ alleles), and parent-of-origin (PofO) effects (dependent on parental transmission of alleles), while uniquely accounting for assortative mating. We analyze 30,000 child-mother-father trios from the Estonian Biobank and the Norwegian Mother, Father, and Child Cohort, focusing on height, body mass index, and childhood educational test scores. We find direct effects to be the largest contributor to trait variation, but combined, indirect parental and PofO effects are similarly substantial. We support our results by within-family genome-wide association testing and identify 276 independently associated DNA regions with a complex interplay between direct, indirect, and PofO effects. By joint modeling, we show that direct, indirect, and PofO effects collectively shape human phenotypic variation across loci genome-wide.},
  author       = {Krätschmer, Ilse and Hegemann, Laura and Hofmeister, Robin J. and Corfield, Elizabeth C. and Mahmoudi, Mahdi and Delaneau, Olivier and Andreassen, Ole A. and Campbell, Archie and Hayward, Caroline and Marioni, Riccardo E. and Ystrom, Eivind and Havdahl, Alexandra and Robinson, Matthew Richard},
  issn         = {2666-979X},
  journal      = {Cell Genomics},
  publisher    = {Elsevier},
  title        = {{Separating direct, indirect, and parent-of-origin genetic effects in the human population}},
  doi          = {10.1016/j.xgen.2026.101277},
  year         = {2026},
}

@unpublished{21994,
  abstract     = {Adaptive plant development is orchestrated, among others, by directional, intercellular transport of the phytohormone auxin. Self-organizing development, such as flexible vasculature formation, depends on so-called auxin canalization, manifested by the gradual formation of auxin transport channels through feedback between auxin signalling and transport. Herein, we identify MAKR6 as an important, novel component in this feedback. MAKR6 expression accumulates strongly in vascular cells and is tightly regulated by auxin via the Aux/IAA-ARF-WRKY23 transcriptional network. MAKR6 is required for auxin canalization-dependent processes, including leaf venation, vasculature regeneration, and de novo auxin channel formation from local auxin sources. Mechanistically, MAKR6 interacts with the PIN1 auxin transporter, modulating its trafficking and polarization. MAKR6 also associates with and integrates two key receptor-like kinase complexes involved in canalization, TMK1/4 and the CAMEL-CANAR. Together, our study establishes MAKR6 as a multifaceted regulator that couples transcriptional auxin signalling to PIN1 repolarization and coordinates multiple RLK-mediated signalling pathways during canalization. This provides mechanistic insights into auxin canalization and exemplifies a framework for exploring similar regulatory nodes in other developmental contexts.},
  author       = {Ge, Zengxiang and Koczka, Lilla and Mazur, Ewa and Molnar, Gergely and Vladimirtsev, Dmitrii and Kassem, Nada and Ait Ikene, Sara and Fiedler, Lukas and Friml, Jiří},
  booktitle    = {bioRxiv},
  title        = {{MAKR6 integrates TMK and CAMEL/CANAR signalling for auxin canalization in Arabidopsis}},
  doi          = {10.1101/2025.10.07.680881},
  year         = {2026},
}

@article{21997,
  abstract     = {The massive binary common envelope (CE) phase plays a pivotal role in the formation of close black hole (BH)/neutron star binaries, yet significant uncertainties remain in our understanding of this process. In this study, we aim to constrain the massive binary CE phase by systematically reconstructing three observed BH X-ray binaries (BHXBs): GRO J1655-40, SAX J1819.3-2525, and 4U 1543-47. Through comprehensive binary evolution simulations and parametric supernova modeling, we establish lower limits for the CE efficiency parameters under different energy considerations within the standard energy formalism. Specifically, we derive minimum values for three cases: α0.5U and αU, representing CE efficiencies with half and all of the internal energy contributing to the envelope ejection, respectively, and αH, accounting for the envelope’s enthalpy. Our analysis reveals that the self-consistent formation of these three BHXBs requires CE efficiency parameters satisfying α0.5U ≳ 6.7, αU ≳ 4.2, and αH ≳ 1.7. Notably, we find no viable solutions with CE efficiency values below unity, even when considering the most extreme scenarios, in which the envelope binding energy is significantly reduced through enthalpy inclusion. Our results strongly imply that either additional energy sources are required or the formalism itself must be revised. Furthermore, we quantitatively assess the impact of BH natal kicks on our results. A key finding is that 4U 1543-47’s formation requires substantial natal kicks (≳50 km s−1), as lower kick velocities are incompatible with isolated binary evolution.},
  author       = {Li, Zhenwei and Wei, Dandan and Jia, Shi and Chen, Hailiang and Ge, Hongwei and Chen, Zhuo and Zhang, Yangyang and Chen, Xuefei and Han, Zhanwen},
  issn         = {1538-4357},
  journal      = {The Astrophysical Journal},
  number       = {1},
  publisher    = {IOP Publishing},
  title        = {{A path to constraints on common envelope ejection in massive binaries: Full evolutionary reconstruction of three Black Hole X-ray binaries}},
  doi          = {10.3847/1538-4357/ae66fd},
  volume       = {1004},
  year         = {2026},
}

@article{21998,
  abstract     = {Little Red Dots (LRDs), among the most enigmatic high-redshift discoveries by JWST, are commonly believed to be powered by accreting supermassive black holes. Here, we explore the possibility that these sources are globular clusters in formation, with rest-frame UV arising from a very young stellar population and rest-frame optical from a short-lived supermassive (>104 M⊙) star. The spectral profiles of LRDs are broadly consistent with this scenario, though the observed temperatures and bolometric luminosities favor emission reprocessed by optically thick continuum-driven winds not fully captured by current models. The LRD z ∼ 5−7 UV luminosity function naturally evolves, under standard evolutionary and mass-loss prescriptions, into a present-day mass function with a turnover at log10(M*/M⊙) = 5.3 and an exponential cutoff at high masses, consistent with local globular cluster populations. We estimate the total present-day number density of LRDs formed across all redshifts to be ≈0.3 Mpc−3, similar within uncertainties to local globular clusters. The observed LRD redshift range matches the age distribution of metal-poor globular clusters, without current LRD counterparts to the metal-rich population. If LRDs are globular clusters in formation, we predict chemical abundance patterns characteristic of multiple stellar populations, including enhanced He and N, and potential Na–O and Al–Mg anticorrelations. These results offer a local perspective to explore this surprisingly abundant population of distant sources, and a potential new window into extreme stellar astrophysics in the early Universe.},
  author       = {Chisholm, John and Berg, Danielle A. and Boylan-Kolchin, Michael and De Graaff, Anna and Furtak, Lukas J. and Kokorev, Vasily and Matthee, Jorryt J and Muñoz, Julian B. and Naidu, Rohan P. and Sander, Andreas A.C.},
  issn         = {2041-8213},
  journal      = {The Astrophysical Journal Letters},
  number       = {1},
  publisher    = {IOP Publishing},
  title        = {{Little Red Dots as globular clusters in formation}},
  doi          = {10.3847/2041-8213/ae6dae},
  volume       = {1004},
  year         = {2026},
}

@article{20328,
  abstract     = {We consider the standard overlap (math formular) of any bi-orthogonal family of left and right eigenvectors of a large random matrix X with centred i.i.d. entries and we prove that it decays as an inverse second power of the distance between the corresponding eigenvalues. This extends similar results for the complex Gaussian ensemble from Bourgade and Dubach [15], as well as Benaych-Georges and Zeitouni [13], to any i.i.d. matrix ensemble in both symmetry classes. As a main tool, we prove a two-resolvent local law for the Hermitisation of X uniformly in the spectrum with optimal decay rate and optimal dependence on the density near the spectral edge.},
  author       = {Cipolloni, Giorgio and Erdös, László and Xu, Yuanyuan},
  issn         = {0022-1236},
  journal      = {Journal of Functional Analysis},
  number       = {1},
  publisher    = {Elsevier},
  title        = {{Optimal decay of eigenvector overlap for non-Hermitian random matrices}},
  doi          = {10.1016/j.jfa.2025.111180},
  volume       = {290},
  year         = {2026},
}

@article{20422,
  abstract     = {We show that if n is odd and p>=Clog n/n, then with high probability Hamilton cycles in G(n,p) span its cycle space. More generally, we show this holds for a class of graphs satisfying certain natural pseudorandom properties. The proof is based on a novel idea of parity-switchers, which can be thought of as analogues of absorbers in the context of cycle spaces. As another application of our method, we show that Hamilton cycles in a near-Dirac graph G, that is, a graph G with odd n vertices and minimum degree n/2+C for sufficiently large constant C, span its cycle space.
},
  author       = {Christoph, Micha and Nenadov, Rajko and Petrova, Kalina H},
  issn         = {1096-0902},
  journal      = {Journal of Combinatorial Theory Series B},
  pages        = {254--267},
  publisher    = {Elsevier},
  title        = {{The Hamilton space of pseudorandom graphs}},
  doi          = {10.1016/j.jctb.2025.09.002},
  volume       = {176},
  year         = {2026},
}

@article{20456,
  abstract     = {Given a locally finite set A⊆Rd and a coloring χ:A→{0,1,…,s}, we introduce the chromatic Delaunay mosaic of χ, which is a Delaunay mosaic in Rs+d that represents how points of different colors mingle. Our main results are bounds on the size of the chromatic Delaunay mosaic, in which we assume that d and s are constants. For example, if A is finite with n=#A, and the coloring is random, then the chromatic Delaunay mosaic has O(n⌈d/2⌉) cells in expectation. In contrast, for Delone sets and Poisson point processes in Rd, the expected number of cells within a closed ball is only a constant times the number of points in this ball. Furthermore, in R2 all colorings of a dense set of n points have chromatic Delaunay mosaics of size O(n). This encourages the use of chromatic Delaunay mosaics in applications.},
  author       = {Biswas, Ranita and Cultrera di Montesano, Sebastiano and Draganov, Ondrej and Edelsbrunner, Herbert and Saghafian, Morteza},
  issn         = {1432-0444},
  journal      = {Discrete and Computational Geometry},
  pages        = {24--47},
  publisher    = {Springer Nature},
  title        = {{On the size of chromatic Delaunay mosaics}},
  doi          = {10.1007/s00454-025-00778-7},
  volume       = {75},
  year         = {2026},
}

@article{20482,
  abstract     = {In his study of graph codes, Alon introduced the concept of the odd-Ramsey number of a family of graphs H in Kn, defined as the minimum number of colours needed to colour the edges of K so that every copy of a graph H E H intersects some colour class in an odd number of edges. In this paper, we focus on complete bipartite graphs. First, we completely resolve the problem when H is the family of all spanning complete bipartite graphs on n vertices. We then focus on its subfamilies, that is, {Kt,n-t : t E T} for a fixed set of integers T c [[n/2]]. We prove that the odd-Ramsey problem is equivalent to determining the maximum dimension of a linear binary code avoiding codewords of given weights, and leverage known results from coding theory to deduce asymptotically tight bounds in our setting. We conclude with bounds for the odd-Ramsey numbers of fixed (that is, non-spanning) complete bipartite subgraphs.},
  author       = {Boyadzhiyska, Simona and Das, Shagnik and Lesgourgues, Thomas and Petrova, Kalina H},
  issn         = {0195-6698},
  journal      = {European Journal of Combinatorics},
  publisher    = {Elsevier},
  title        = {{Odd-Ramsey numbers of complete bipartite graphs}},
  doi          = {10.1016/j.ejc.2025.104235},
  volume       = {131},
  year         = {2026},
}

@misc{20833,
  abstract     = {Sex-chromosome systems are highly variable across animals, but how they transition from one to another is not well understood. Diptera have undergone multiple sex-chromosome turnovers and expansions while maintaining their general chromosomal content, which makes them an ideal clade to study such transitions. We analysed more than 100 dipteran whole-genome assemblies and identified 4 new lineages that underwent sex-chromosome turnover (in addition to the 5 previously reported). We find the majority of turnovers happened in the group Schizophora, which tend to have fewer genes on the F element (the chromosome homologous to the ancestral insect X chromosome) than lower dipterans, a factor previously hypothesized to facilitate turnover. Most derived X chromosomes have higher GC content than autosomes, consistent with a high prevalence of male-achiasmy in Diptera. In addition, an excess of gene movement out of the X is detected for most of these new X chromosomes, and many of these moved genes have high testis expression in Drosophila, suggesting that out-of-X gene movement contributes to the long-term demasculinization of X chromosomes.},
  author       = {Layana Franco, Lorena Alexandra and Toups, Melissa A and Vicoso, Beatriz},
  keywords     = {Schizophora, sex chromosomes, sex-chromosome turnover, Diptera, genomic features, out-of-X movement.},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Research Data for 'Causes and consequences of sex-chromosome turnovers in Diptera'}},
  doi          = {10.15479/AT-ISTA-20833},
  year         = {2026},
}

@article{20840,
  abstract     = {Probing the possibility of entanglement generation through gravity offers a path to tackle the question of whether gravitational fields possess a quantum mechanical nature. A potential realization necessitates systems with low-frequency dynamics at an optimal mass scale, for which the microgram-to-milligram range is a strong contender. Here, after refining a figure-of-merit for the problem, we present a 1-milligram torsional pendulum operating at 18 Hz. We demonstrate laser cooling its motion from room temperature to 240 microkelvins, surpassing by over 20-fold the coldest motions attained for oscillators ranging from micrograms to kilograms. We quantify and contrast the utility of the current approach with other platforms. The achieved performance and large improvement potential highlight milligram-scale torsional pendulums as a powerful platform for precision measurements relevant to future studies at the quantum-gravity interface.},
  author       = {Agafonova, Sofya and Rosello, Pere and Mekonnen, Manuel and Hosten, Onur},
  issn         = {2399-3650},
  journal      = {Communications Physics},
  publisher    = {Springer Nature},
  title        = {{One-milligram torsional pendulum toward experiments at the quantum-gravity interface}},
  doi          = {10.1038/s42005-026-02514-w},
  volume       = {9},
  year         = {2026},
}

@article{20865,
  abstract     = {We prove the convergence of a modified Jordan–Kinderlehrer–Otto scheme to a solution
to the Fokker–Planck equation in Ω e R^d with general—strictly positive and temporally
constant—Dirichlet boundary conditions. We work under mild assumptions on the domain,
the drift, and the initial datum. In the special case where Ω is an interval in R1, we prove
that such a solution is a gradient flow—curve of maximal slope—within a suitable space of
measures, endowed with a modified Wasserstein distance. Our discrete scheme and modified
distance draw inspiration from contributions by A. Figalli and N. Gigli [J. Math. Pures
Appl. 94, (2010), pp. 107–130], and J. Morales [J. Math. Pures Appl. 112, (2018), pp. 41–88]
on an optimal-transport approach to evolution equations with Dirichlet boundary conditions.
Similarly to these works, we allow the mass to flow from/to the boundary ∂Ω throughout
the evolution. However, our leading idea is to also keep track of the mass at the boundary
by working with measures defined on the whole closure Ω . The driving functional is a
modification of the classical relative entropy that also makes use of the information at the
boundary. As an intermediate result, when Ω is an interval in R1, we find a formula for the
descending slope of this geodesically nonconvex functional.},
  author       = {Quattrocchi, Filippo},
  issn         = {1432-0835},
  journal      = {Calculus of Variations and Partial Differential Equations},
  number       = {1},
  publisher    = {Springer Nature},
  title        = {{Variational structures for the Fokker-Planck equation with general Dirichlet boundary conditions}},
  doi          = {10.1007/s00526-025-03193-1},
  volume       = {65},
  year         = {2026},
}

@article{20963,
  abstract     = {In all domains of life, tRNAs mediate the transfer of genetic information from mRNAs to proteins. As their depletion suppresses translation and, consequently, viral replication, tRNAs represent long-standing and increasingly recognized targets of innate immunity1,2,3,4,5. Here we report Cas12a3 effector nucleases from type V CRISPR–Cas adaptive immune systems in bacteria that preferentially cleave tRNAs after recognition of target RNA. Cas12a3 orthologues belong to one of two previously unreported nuclease clades that exhibit RNA-mediated cleavage of non-target RNA, and are distinct from all other known type V systems. Through cell-based and biochemical assays and direct RNA sequencing, we demonstrate that recognition of a complementary target RNA by the CRISPR RNA triggers Cas12a3 to cleave the conserved 5′-CCA-3′ tail of diverse tRNAs to drive growth arrest and anti-phage defence. Cryogenic electron microscopy structures further revealed a distinct tRNA-loading domain that positions the tRNA tail in the RuvC active site of the nuclease. By designing synthetic reporters that mimic the tRNA acceptor stem and tail, we expanded the capacity of current CRISPR-based diagnostics for multiplexed RNA detection. Overall, these findings reveal widespread tRNA inactivation as a previously unrecognized CRISPR-based immune strategy that broadens the application space of the existing CRISPR toolbox.},
  author       = {Dmytrenko, Oleg and Yuan, Biao and Crosby, Kadin T. and Krebel, Max and Chen, Xiye and Nowak, Jakub S. and Chramiec-Głąbik, Andrzej and Filani, Bamidele and Gribling-Burrer, Anne-Sophie and van der Toorn, Wiep and von Kleist, Max and Achmedov, Tatjana and Smyth, Redmond P. and Glatt, Sebastian and Bravo, Jack Peter Kelly and Heinz, Dirk W. and Jackson, Ryan N. and Beisel, Chase L.},
  issn         = {1476-4687},
  journal      = {Nature},
  publisher    = {Springer Nature},
  title        = {{RNA-triggered Cas12a3 cleaves tRNA tails to execute bacterial immunity}},
  doi          = {10.1038/s41586-025-09852-9},
  year         = {2026},
}

