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    Mathematica notebook and Fortran code for 'Effect of assortative mating and sexual selection on polygenic barriers to gene flow'

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    This file contains the code associated with the manuscript 'Effect of assortative mating and sexual selection on polygenic barriers to gene flow'

    DNA targeting by compact Cas9d and its resurrected ancestor

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    Type II CRISPR endonucleases are widely used programmable genome editing tools. Recently, CRISPR-Cas systems with highly compact nucleases have been discovered, including Cas9d (a type II-D nuclease). Here, we report the cryo-EM structures of a Cas9d nuclease (747 amino acids in length) in multiple functional states, revealing a stepwise process of DNA targeting involving a conformational switch in a REC2 domain insertion. Our structures provide insights into the intricately folded guide RNA which acts as a structural scaffold to anchor small, flexible protein domains for DNA recognition. The sgRNA can be truncated by up to ~25% yet still retain activity in vivo. Using ancestral sequence reconstruction, we generated compact nucleases capable of efficient genome editing in mammalian cells. Collectively, our results provide mechanistic insights into the evolution and DNA targeting of diverse type II CRISPR-Cas systems, providing a blueprint for future re-engineering of minimal RNA-guided DNA endonucleases

    Altruistic disease signalling in ant colonies

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    Sick individuals often conceal their disease status to group members, thereby preventing social exclusion or aggression. Here we show by behavioural, chemical, immunological and infection load analyses that sick ant pupae instead actively emit a chemical signal that in itself is sufficient to trigger their own destruction by colony members. In our experiments, this altruistic disease-signalling was performed only by worker but not queen pupae. The lack of signalling by queen pupae did not constitute cheating behaviour, but reflected their superior immune capabilities. Worker pupae suffered from extensive pathogen replication whereas queen pupae were able to restrain their infection. Our data suggest the evolution of a finely-tuned signalling system in which it is not the induction of an individual’s immune response, but rather its failure to overcome the infection, that triggers pupal signalling for sacrifice. This demonstrates a balanced interplay between individual and social immunity that efficiently achieves whole-colony health

    Tissue active matter: Integrating mechanics and signaling into dynamical models

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    The importance of physical forces in the morphogenesis, homeostatic function, and pathological dysfunction of multicellular tissues is being increasingly characterized, both theoretically and experimentally. Analogies between biological systems and inert materials such as foams, gels, and liquid crystals have provided striking insights into the core design principles underlying multicellular organization. However, these connections can seem surprising given that a key feature of multicellular systems is their ability to constantly consume energy, providing an active origin for the forces that they produce. Key emerging questions are, therefore, to understand whether and how this activity grants tissues novel properties that do not have counterparts in classical materials, as well as their consequences for biological function. Here, we review recent discoveries at the intersection of active matter and tissue biology, with an emphasis on how modeling and experiments can be combined to understand the dynamics of multicellular systems. These approaches suggest that a number of key biological tissue-scale phenomena, such as morphogenetic shape changes, collective migration, or fate decisions, share unifying design principles that can be described by physical models of tissue active matter

    Combining REBOUND and MESA: Dynamical evolution of planets orbiting interacting binaries

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    Although planets have been found orbiting binary systems, whether they can survive binary interactions is debated. While the tightest-orbit binaries should host the most dynamically stable and long-lived circumbinary planetary systems, they are also the systems that are expected to experience mass transfer, common envelope evolution, or stellar mergers. In this study, we explore the effect of stable non-conservative mass transfer on the dynamical evolution of circumbinary planets. We present a new script that seamlessly integrates binary evolution data from the 1D binary stellar evolution code MESA into the N-body simulation code REBOUND. This integration framework enables a comprehensive examination of the dynamical evolution of circumbinary planets orbiting mass-transferring binaries, while simultaneously accounting for the detailed stellar structure evolution. In addition, we introduce a recalibration method to mitigate numerical errors from updates of binary properties during the system's dynamical evolution. We construct a reference binary model in which a 2.21M⊙ star loses its hydrogen-rich envelope through non-conservative mass transfer to the 1.76M⊙ companion star, creating a 0.38M⊙ subdwarf. We find the tightest stable orbital separation for circumbinary planets to be ≃2.5 times the binary separation after mass transfer. Accounting for tides by using the interior stellar structure, we find that tidal effects become apparent after the rapid mass transfer phase and start to fade away during the latter stage of the slow mass transfer phase. Our research provides a new framework for exploring circumbinary planet dynamics in interacting binary systems

    The semi-random tree process

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    The online semi-random graph process is a one-player game which starts with the empty graph on n vertices. At every round, a player (called Builder) is presented with a vertex v chosen uniformly at random and independently from previous rounds, and constructs an edge of their choice that is incident to v. Inspired by recent advances on the semi-random graph process, we define a family of generalized online semi-random models. We analyse a particular instance that shares similar features with the original semi-random graph process and determine the hitting times of the classical graph properties minimum degree k,k-connectivity, containment of a perfect matching, a Hamiltonian cycle and an H-factor for a fixed graph H possessing an additional tree-like property. Along the way, we derive a few consequences of the famous Aldous-Broder algorithm that may be of independent interest

    Multilevel Monte Carlo methods for the Dean–Kawasaki equation from fluctuating hydrodynamics

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    Stochastic PDEs of fluctuating hydrodynamics are a powerful tool for the description of fluctuations in many-particle systems. In this paper, we develop and analyze a multilevel Monte Carlo (MLMC) scheme for the Dean–Kawasaki equation, a pivotal representative of this class of SPDEs. We prove analytically and demonstrate numerically that our MLMC scheme provides a significant reduction in computational cost (with respect to a standard Monte Carlo method) in the simulation of the Dean–Kawasaki equation. Specifically, we link this reduction in cost to having a sufficiently large average particle density and show that sizeable cost reductions can be obtained even when we have solutions with regions of low density. Numerical simulations are provided in the two-dimensional case, confirming our theoretical predictions. Our results are formulated entirely in terms of the law of distributions rather than in terms of strong spatial norms: this crucially allows for MLMC speed-ups altogether despite the Dean–Kawasaki equation being highly singular

    All-optical superconducting qubit readout

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    The rapid development of superconducting quantum hardware is expected to run into substantial restrictions on scalability because error correction in a cryogenic environment has stringent input–output requirements. Classical data centres rely on fibre-optic interconnects to remove similar networking bottlenecks. In the same spirit, ultracold electro-optic links have been proposed and used to generate qubit control signals, or to replace cryogenic readout electronics. So far, these approaches have suffered from either low efficiency, low bandwidth or additional noise. Here we realize radio-over-fibre qubit readout at millikelvin temperatures. We use one device to simultaneously perform upconversion and downconversion between microwave and optical frequencies and so do not require any active or passive cryogenic microwave equipment. We demonstrate all-optical single-shot readout in a circulator-free readout scheme. Importantly, we do not observe any direct radiation impact on the qubit state, despite the absence of shielding elements. This compatibility between superconducting circuits and telecom-wavelength light is not only a prerequisite to establish modular quantum networks, but it is also relevant for multiplexed readout of superconducting photon detectors and classical superconducting logic

    Reduced efficacy of selection on a young Z chromosome region of schistosoma japonicum

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    Sex-linked and autosomal loci experience different selective pressures and evolutionary dynamics. X (or Z) chromosomes are often hemizygous in males (or females), as Y (or W) chromosomes often degenerate. Such hemizygous regions can be under greater efficacy of selection, as recessive mutations are immediately exposed to selection in the heterogametic sex leading to faster adaptation and faster divergence on the X chromosome (the so-called Faster-X or Faster-Z effect). However, in young nonrecombining regions, Y/W chromosomes often have many functional genes, and many X/Z-linked loci are therefore diploid. The sheltering of recessive mutations on the X/Z by the Y/W homolog is expected to drive slower adaptation for diploid X/Z loci, i.e. a reduction in the efficacy of selection. While the Faster-X effect has been studied extensively, much less is known empirically about the evolutionary dynamics of diploid X or Z chromosomes. Here, we took advantage of published population genomic data in the female-heterogametic human parasite Schistosoma japonicum to characterize the gene content and diversity levels of the diploid and hemizygous regions of the Z chromosome. We used different metrics of selective pressures acting on genes to test for differences in the efficacy of selection in hemizygous and diploid Z regions, relative to autosomes. We found consistent patterns suggesting reduced Ne, and reduced efficacy of purifying selection, on both hemizygous and diploid Z regions. Moreover, relaxed selection was particularly pronounced for female-biased genes on the diploid Z, as predicted by recent theoretical work

    Renormalized Bogoliubov theory for the Nelson model

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    We consider the time evolution of the renormalized Nelson model, which describes N bosons linearly coupled to a quantized scalar field, in the mean-field limit of many particles N≫1 with coupling constant proportional to N^−1/2. First, we show that initial states exhibiting Bose–Einstein condensation for the particles and approximating a coherent state for the quantum field retain their structure under the many-body time evolution. Concretely, the dynamics of the reduced densities are approximated by solutions of two coupled PDEs, the Schrödinger–Klein–Gordon equations. Second, we construct a renormalized Bogoliubov evolution that describes the quantum fluctuations around the Schrödinger–Klein–Gordon equations. This evolution is used to extend the approximation of the evolved many-body state to the full norm topology. In summary, we provide a comprehensive analysis of the Nelson model that reveals the role of renormalization in the mean-field Bogoliubov theory

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