TY - JOUR AB - Inositol hexakisphosphate (IP6) is an assembly cofactor for HIV-1. We report here that IP6 is also used for assembly of Rous sarcoma virus (RSV), a retrovirus from a different genus. IP6 is ~100-fold more potent at promoting RSV mature capsid protein (CA) assembly than observed for HIV-1 and removal of IP6 in cells reduces infectivity by 100-fold. Here, visualized by cryo-electron tomography and subtomogram averaging, mature capsid-like particles show an IP6-like density in the CA hexamer, coordinated by rings of six lysines and six arginines. Phosphate and IP6 have opposing effects on CA in vitro assembly, inducing formation of T = 1 icosahedrons and tubes, respectively, implying that phosphate promotes pentamer and IP6 hexamer formation. Subtomogram averaging and classification optimized for analysis of pleomorphic retrovirus particles reveal that the heterogeneity of mature RSV CA polyhedrons results from an unexpected, intrinsic CA hexamer flexibility. In contrast, the CA pentamer forms rigid units organizing the local architecture. These different features of hexamers and pentamers determine the structural mechanism to form CA polyhedrons of variable shape in mature RSV particles. AU - Obr, Martin AU - Ricana, Clifton L. AU - Nikulin, Nadia AU - Feathers, Jon-Philip R. AU - Klanschnig, Marco AU - Thader, Andreas AU - Johnson, Marc C. AU - Vogt, Volker M. AU - Schur, Florian KM AU - Dick, Robert A. ID - 9431 IS - 1 JF - Nature Communications KW - General Biochemistry KW - Genetics and Molecular Biology KW - General Physics and Astronomy KW - General Chemistry TI - Structure of the mature Rous sarcoma virus lattice reveals a role for IP6 in the formation of the capsid hexamer VL - 12 ER - TY - JOUR AB - Turbulence in the flow of fluid through a pipe can be suppressed by buoyancy forces. As the suppression of turbulence leads to severe heat transfer deterioration, this is an important and undesirable phenomenon in both heating and cooling applications. Vertical flow is often considered, as the axial buoyancy force can help drive the flow. With heating measured by the buoyancy parameter 𝐶, our direct numerical simulations show that shear-driven turbulence may either be completely laminarised or it transitions to a relatively quiescent convection-driven state. Buoyancy forces cause a flattening of the base flow profile, which in isothermal pipe flow has recently been linked to complete suppression of turbulence (Kühnen et al., Nat. Phys., vol. 14, 2018, pp. 386–390), and the flattened laminar base profile has enhanced nonlinear stability (Marensi et al., J. Fluid Mech., vol. 863, 2019, pp. 50–875). In agreement with these findings, the nonlinear lower-branch travelling-wave solution analysed here, which is believed to mediate transition to turbulence in isothermal pipe flow, is shown to be suppressed by buoyancy. A linear instability of the laminar base flow is responsible for the appearance of the relatively quiescent convection driven state for 𝐶≳4 across the range of Reynolds numbers considered. In the suppression of turbulence, however, i.e. in the transition from turbulence, we find clearer association with the analysis of He et al. (J. Fluid Mech., vol. 809, 2016, pp. 31–71) than with the above dynamical systems approach, which describes better the transition to turbulence. The laminarisation criterion He et al. propose, based on an apparent Reynolds number of the flow as measured by its driving pressure gradient, is found to capture the critical 𝐶=𝐶𝑐𝑟(𝑅𝑒) above which the flow will be laminarised or switch to the convection-driven type. Our analysis suggests that it is the weakened rolls, rather than the streaks, which appear to be critical for laminarisation. AU - Marensi, Elena AU - He, Shuisheng AU - Willis, Ashley P. ID - 9467 JF - Journal of Fluid Mechanics SN - 00221120 TI - Suppression of turbulence and travelling waves in a vertical heated pipe VL - 919 ER - TY - JOUR AB - A key step in understanding the genetic basis of different evolutionary outcomes (e.g., adaptation) is to determine the roles played by different mutation types (e.g., SNPs, translocations and inversions). To do this we must simultaneously consider different mutation types in an evolutionary framework. Here, we propose a research framework that directly utilizes the most important characteristics of mutations, their population genetic effects, to determine their relative evolutionary significance in a given scenario. We review known population genetic effects of different mutation types and show how these may be connected to different evolutionary outcomes. We provide examples of how to implement this framework and pinpoint areas where more data, theory and synthesis are needed. Linking experimental and theoretical approaches to examine different mutation types simultaneously is a critical step towards understanding their evolutionary significance. AU - Berdan, Emma L. AU - Blanckaert, Alexandre AU - Slotte, Tanja AU - Suh, Alexander AU - Westram, Anja M AU - Fragata, Inês ID - 9470 IS - 12 JF - Molecular Ecology SN - 09621083 TI - Unboxing mutations: Connecting mutation types with evolutionary consequences VL - 30 ER - TY - JOUR AB - Motivated by the successful application of geometry to proving the Harary--Hill conjecture for “pseudolinear” drawings of $K_n$, we introduce “pseudospherical” drawings of graphs. A spherical drawing of a graph $G$ is a drawing in the unit sphere $\mathbb{S}^2$ in which the vertices of $G$ are represented as points---no three on a great circle---and the edges of $G$ are shortest-arcs in $\mathbb{S}^2$ connecting pairs of vertices. Such a drawing has three properties: (1) every edge $e$ is contained in a simple closed curve $\gamma_e$ such that the only vertices in $\gamma_e$ are the ends of $e$; (2) if $e\ne f$, then $\gamma_e\cap\gamma_f$ has precisely two crossings; and (3) if $e\ne f$, then $e$ intersects $\gamma_f$ at most once, in either a crossing or an end of $e$. We use properties (1)--(3) to define a pseudospherical drawing of $G$. Our main result is that for the complete graph, properties (1)--(3) are equivalent to the same three properties but with “precisely two crossings” in (2) replaced by “at most two crossings.” The proof requires a result in the geometric transversal theory of arrangements of pseudocircles. This is proved using the surprising result that the absence of special arcs (coherent spirals) in an arrangement of simple closed curves characterizes the fact that any two curves in the arrangement have at most two crossings. Our studies provide the necessary ideas for exhibiting a drawing of $K_{10}$ that has no extension to an arrangement of pseudocircles and a drawing of $K_9$ that does extend to an arrangement of pseudocircles, but no such extension has all pairs of pseudocircles crossing twice. AU - Arroyo Guevara, Alan M AU - Richter, R. Bruce AU - Sunohara, Matthew ID - 9468 IS - 2 JF - SIAM Journal on Discrete Mathematics SN - 08954801 TI - Extending drawings of complete graphs into arrangements of pseudocircles VL - 35 ER - TY - JOUR AB - We consider a system of N trapped bosons with repulsive interactions in a combined semiclassical mean-field limit at positive temperature. We show that the free energy is well approximated by the minimum of the Hartree free energy functional – a natural extension of the Hartree energy functional to positive temperatures. The Hartree free energy functional converges in the same limit to a semiclassical free energy functional, and we show that the system displays Bose–Einstein condensation if and only if it occurs in the semiclassical free energy functional. This allows us to show that for weak coupling the critical temperature decreases due to the repulsive interactions. AU - Deuchert, Andreas AU - Seiringer, Robert ID - 9462 IS - 6 JF - Journal of Functional Analysis SN - 0022-1236 TI - Semiclassical approximation and critical temperature shift for weakly interacting trapped bosons VL - 281 ER - TY - JOUR AB - In this paper, we consider reflected three-operator splitting methods for monotone inclusion problems in real Hilbert spaces. To do this, we first obtain weak convergence analysis and nonasymptotic O(1/n) convergence rate of the reflected Krasnosel'skiĭ-Mann iteration for finding a fixed point of nonexpansive mapping in real Hilbert spaces under some seemingly easy to implement conditions on the iterative parameters. We then apply our results to three-operator splitting for the monotone inclusion problem and consequently obtain the corresponding convergence analysis. Furthermore, we derive reflected primal-dual algorithms for highly structured monotone inclusion problems. Some numerical implementations are drawn from splitting methods to support the theoretical analysis. AU - Iyiola, Olaniyi S. AU - Enyi, Cyril D. AU - Shehu, Yekini ID - 9469 JF - Optimization Methods and Software SN - 1055-6788 TI - Reflected three-operator splitting method for monotone inclusion problem ER - TY - JOUR AB - The hexameric AAA-ATPase Drg1 is a key factor in eukaryotic ribosome biogenesis and initiates cytoplasmic maturation of the large ribosomal subunit by releasing the shuttling maturation factor Rlp24. Drg1 monomers contain two AAA-domains (D1 and D2) that act in a concerted manner. Rlp24 release is inhibited by the drug diazaborine which blocks ATP hydrolysis in D2. The mode of inhibition was unknown. Here we show the first cryo-EM structure of Drg1 revealing the inhibitory mechanism. Diazaborine forms a covalent bond to the 2′-OH of the nucleotide in D2, explaining its specificity for this site. As a consequence, the D2 domain is locked in a rigid, inactive state, stalling the whole Drg1 hexamer. Resistance mechanisms identified include abolished drug binding and altered positioning of the nucleotide. Our results suggest nucleotide-modifying compounds as potential novel inhibitors for AAA-ATPases. AU - Prattes, Michael AU - Grishkovskaya, Irina AU - Hodirnau, Victor-Valentin AU - Rössler, Ingrid AU - Klein, Isabella AU - Hetzmannseder, Christina AU - Zisser, Gertrude AU - Gruber, Christian C. AU - Gruber, Karl AU - Haselbach, David AU - Bergler, Helmut ID - 9540 IS - 1 JF - Nature Communications KW - General Biochemistry KW - Genetics and Molecular Biology KW - General Physics and Astronomy KW - General Chemistry TI - Structural basis for inhibition of the AAA-ATPase Drg1 by diazaborine VL - 12 ER - TY - JOUR AB - AMPA receptors (AMPARs) mediate the majority of excitatory transmission in the brain and enable the synaptic plasticity that underlies learning1. A diverse array of AMPAR signalling complexes are established by receptor auxiliary subunits, which associate with the AMPAR in various combinations to modulate trafficking, gating and synaptic strength2. However, their mechanisms of action are poorly understood. Here we determine cryo-electron microscopy structures of the heteromeric GluA1–GluA2 receptor assembled with both TARP-γ8 and CNIH2, the predominant AMPAR complex in the forebrain, in both resting and active states. Two TARP-γ8 and two CNIH2 subunits insert at distinct sites beneath the ligand-binding domains of the receptor, with site-specific lipids shaping each interaction and affecting the gating regulation of the AMPARs. Activation of the receptor leads to asymmetry between GluA1 and GluA2 along the ion conduction path and an outward expansion of the channel triggers counter-rotations of both auxiliary subunit pairs, promoting the active-state conformation. In addition, both TARP-γ8 and CNIH2 pivot towards the pore exit upon activation, extending their reach for cytoplasmic receptor elements. CNIH2 achieves this through its uniquely extended M2 helix, which has transformed this endoplasmic reticulum-export factor into a powerful AMPAR modulator that is capable of providing hippocampal pyramidal neurons with their integrative synaptic properties. AU - Zhang, Danyang AU - Watson, Jake AU - Matthews, Peter M. AU - Cais, Ondrej AU - Greger, Ingo H. ID - 9549 JF - Nature SN - 0028-0836 TI - Gating and modulation of a hetero-octameric AMPA glutamate receptor VL - 594 ER - TY - JOUR AB - We prove that the energy of any eigenvector of a sum of several independent large Wigner matrices is equally distributed among these matrices with very high precision. This shows a particularly strong microcanonical form of the equipartition principle for quantum systems whose components are modelled by Wigner matrices. AU - Bao, Zhigang AU - Erdös, László AU - Schnelli, Kevin ID - 9550 JF - Forum of Mathematics, Sigma TI - Equipartition principle for Wigner matrices VL - 9 ER - TY - JOUR AB - We present conductance-matrix measurements in long, three-terminal hybrid superconductor-semiconductor nanowires, and compare with theoretical predictions of a magnetic-field-driven, topological quantum phase transition. By examining the nonlocal conductance, we identify the closure of the excitation gap in the bulk of the semiconductor before the emergence of zero-bias peaks, ruling out spurious gap-closure signatures from localized states. We observe that after the gap closes, nonlocal signals and zero-bias peaks fluctuate strongly at both ends, inconsistent with a simple picture of clean topological superconductivity. AU - Puglia, Denise AU - Martinez, E. A. AU - Ménard, G. C. AU - Pöschl, A. AU - Gronin, S. AU - Gardner, G. C. AU - Kallaher, R. AU - Manfra, M. J. AU - Marcus, C. M. AU - Higginbotham, Andrew P AU - Casparis, L. ID - 9570 IS - 23 JF - Physical Review B SN - 24699950 TI - Closing of the induced gap in a hybrid superconductor-semiconductor nanowire VL - 103 ER - TY - JOUR AB - We extend the notion of the minimal volume ellipsoid containing a convex body in Rd to the setting of logarithmically concave functions. We consider a vast class of logarithmically concave functions whose superlevel sets are concentric ellipsoids. For a fixed function from this class, we consider the set of all its “affine” positions. For any log-concave function f on Rd, we consider functions belonging to this set of “affine” positions, and find the one with the minimal integral under the condition that it is pointwise greater than or equal to f. We study the properties of existence and uniqueness of the solution to this problem. For any s∈[0,+∞), we consider the construction dual to the recently defined John s-function (Ivanov and Naszódi in Functional John ellipsoids. arXiv preprint: arXiv:2006.09934, 2020). We prove that such a construction determines a unique function and call it the Löwner s-function of f. We study the Löwner s-functions as s tends to zero and to infinity. Finally, extending the notion of the outer volume ratio, we define the outer integral ratio of a log-concave function and give an asymptotically tight bound on it. AU - Ivanov, Grigory AU - Tsiutsiurupa, Igor ID - 9548 JF - Journal of Geometric Analysis SN - 1050-6926 TI - Functional Löwner ellipsoids VL - 31 ER - TY - GEN AB - Data for the manuscript 'Closing of the Induced Gap in a Hybrid Superconductor-Semiconductor Nanowire' ([2006.01275] Closing of the Induced Gap in a Hybrid Superconductor-Semiconductor Nanowire (arxiv.org)) We upload a pdf with extended data sets, and the raw data for these extended datasets as well. AU - Puglia, Denise AU - Martinez, Esteban AU - Menard, Gerbold AU - Pöschl, Andreas AU - Gronin, Sergei AU - Gardner, Geoffrey AU - Kallaher, Ray AU - Manfra, Michael AU - Marcus, Charles AU - Higginbotham, Andrew P AU - Casparis, Lucas ID - 13080 TI - Data for 'Closing of the Induced Gap in a Hybrid Superconductor-Semiconductor Nanowire ER - TY - JOUR AB - We report the synthesis and characterization of graphene functionalized with iron (Fe3+) oxide (G-Fe3O4) nanohybrids for radio-frequency magnetic hyperthermia application. We adopted the wet chemical procedure, using various contents of Fe3O4 (magnetite) from 0–100% for making two-dimensional graphene–Fe3O4 nanohybrids. The homogeneous dispersal of Fe3O4 nanoparticles decorated on the graphene surface combined with their biocompatibility and high thermal conductivity make them an excellent material for magnetic hyperthermia. The morphological and magnetic properties of the nanohybrids were studied using scanning electron microscopy (SEM) and a vibrating sample magnetometer (VSM), respectively. The smart magnetic platforms were exposed to an alternating current (AC) magnetic field of 633 kHz and of strength 9.1 mT for studying their hyperthermic performance. The localized antitumor effects were investigated with artificial neural network modeling. A neural net time-series model was developed for the assessment of the best nanohybrid composition to serve the purpose with an accuracy close to 100%. Six Nonlinear Autoregressive with External Input (NARX) models were obtained, one for each of the components. The assessment of the accuracy of the predicted results has been done on the basis of Mean Squared Error (MSE). The highest Mean Squared Error value was obtained for the nanohybrid containing 45% magnetite and 55% graphene (F45G55) in the training phase i.e., 0.44703, which is where the model achieved optimal results after 71 epochs. The F45G55 nanohybrid was found to be the best for hyperthermia applications in low dosage with the highest specific absorption rate (SAR) and mean squared error values. AU - Dar, M. S. AU - Akram, Khush Bakhat AU - Sohail, Ayesha AU - Arif, Fatima AU - Zabihi, Fatemeh AU - Yang, Shengyuan AU - Munir, Shamsa AU - Zhu, Meifang AU - Abid, M. AU - Nauman, Muhammad ID - 9569 IS - 35 JF - RSC Advances TI - Heat induction in two-dimensional graphene–Fe3O4 nanohybrids for magnetic hyperthermia applications with artificial neural network modeling VL - 11 ER - TY - JOUR AB - We show that turbulent dynamics that arise in simulations of the three-dimensional Navier--Stokes equations in a triply-periodic domain under sinusoidal forcing can be described as transient visits to the neighborhoods of unstable time-periodic solutions. Based on this description, we reduce the original system with more than 10^5 degrees of freedom to a 17-node Markov chain where each node corresponds to the neighborhood of a periodic orbit. The model accurately reproduces long-term averages of the system's observables as weighted sums over the periodic orbits. AU - Yalniz, Gökhan AU - Hof, Björn AU - Budanur, Nazmi B ID - 9558 IS - 24 JF - Physical Review Letters SN - 0031-9007 TI - Coarse graining the state space of a turbulent flow using periodic orbits VL - 126 ER - TY - JOUR AB - While high risk of failure is an inherent part of developing innovative therapies, it can be reduced by adherence to evidence-based rigorous research practices. Numerous analyses conducted to date have clearly identified measures that need to be taken to improve research rigor. Supported through the European Union's Innovative Medicines Initiative, the EQIPD consortium has developed a novel preclinical research quality system that can be applied in both public and private sectors and is free for anyone to use. The EQIPD Quality System was designed to be suited to boost innovation by ensuring the generation of robust and reliable preclinical data while being lean, effective and not becoming a burden that could negatively impact the freedom to explore scientific questions. EQIPD defines research quality as the extent to which research data are fit for their intended use. Fitness, in this context, is defined by the stakeholders, who are the scientists directly involved in the research, but also their funders, sponsors, publishers, research tool manufacturers and collaboration partners such as peers in a multi-site research project. The essence of the EQIPD Quality System is the set of 18 core requirements that can be addressed flexibly, according to user-specific needs and following a user-defined trajectory. The EQIPD Quality System proposes guidance on expectations for quality-related measures, defines criteria for adequate processes (i.e., performance standards) and provides examples of how such measures can be developed and implemented. However, it does not prescribe any pre-determined solutions. EQIPD has also developed tools (for optional use) to support users in implementing the system and assessment services for those research units that successfully implement the quality system and seek formal accreditation. Building upon the feedback from users and continuous improvement, a sustainable EQIPD Quality System will ultimately serve the entire community of scientists conducting non-regulated preclinical research, by helping them generate reliable data that are fit for their intended use. AU - Bespalov, Anton AU - Bernard, René AU - Gilis, Anja AU - Gerlach, Björn AU - Guillén, Javier AU - Castagné, Vincent AU - Lefevre, Isabel A. AU - Ducrey, Fiona AU - Monk, Lee AU - Bongiovanni, Sandrine AU - Altevogt, Bruce AU - Arroyo-Araujo, María AU - Bikovski, Lior AU - De Bruin, Natasja AU - Castaños-Vélez, Esmeralda AU - Dityatev, Alexander AU - Emmerich, Christoph H. AU - Fares, Raafat AU - Ferland-Beckham, Chantelle AU - Froger-Colléaux, Christelle AU - Gailus-Durner, Valerie AU - Hölter, Sabine M. AU - Hofmann, Martine Cj AU - Kabitzke, Patricia AU - Kas, Martien Jh AU - Kurreck, Claudia AU - Moser, Paul AU - Pietraszek, Malgorzata AU - Popik, Piotr AU - Potschka, Heidrun AU - Prado Montes De Oca, Ernesto AU - Restivo, Leonardo AU - Riedel, Gernot AU - Ritskes-Hoitinga, Merel AU - Samardzic, Janko AU - Schunn, Michael AU - Stöger, Claudia AU - Voikar, Vootele AU - Vollert, Jan AU - Wever, Kimberley E. AU - Wuyts, Kathleen AU - Macleod, Malcolm R. AU - Dirnagl, Ulrich AU - Steckler, Thomas ID - 9607 JF - eLife TI - Introduction to the EQIPD quality system VL - 10 ER - TY - JOUR AB - In mammalian genomes, differentially methylated regions (DMRs) and histone marks including trimethylation of histone 3 lysine 27 (H3K27me3) at imprinted genes are asymmetrically inherited to control parentally-biased gene expression. However, neither parent-of-origin-specific transcription nor imprints have been comprehensively mapped at the blastocyst stage of preimplantation development. Here, we address this by integrating transcriptomic and epigenomic approaches in mouse preimplantation embryos. We find that seventy-one genes exhibit previously unreported parent-of-origin-specific expression in blastocysts (nBiX: novel blastocyst-imprinted expressed). Uniparental expression of nBiX genes disappears soon after implantation. Micro-whole-genome bisulfite sequencing (µWGBS) of individual uniparental blastocysts detects 859 DMRs. We further find that 16% of nBiX genes are associated with a DMR, whereas most are associated with parentally-biased H3K27me3, suggesting a role for Polycomb-mediated imprinting in blastocysts. nBiX genes are clustered: five clusters contained at least one published imprinted gene, and five clusters exclusively contained nBiX genes. These data suggest that early development undergoes a complex program of stage-specific imprinting involving different tiers of regulation. AU - Santini, Laura AU - Halbritter, Florian AU - Titz-Teixeira, Fabian AU - Suzuki, Toru AU - Asami, Maki AU - Ma, Xiaoyan AU - Ramesmayer, Julia AU - Lackner, Andreas AU - Warr, Nick AU - Pauler, Florian AU - Hippenmeyer, Simon AU - Laue, Ernest AU - Farlik, Matthias AU - Bock, Christoph AU - Beyer, Andreas AU - Perry, Anthony C.F. AU - Leeb, Martin ID - 9601 IS - 1 JF - Nature Communications TI - Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3 VL - 12 ER - TY - JOUR AB - An ordered graph is a graph with a linear ordering on its vertex set. We prove that for every positive integer k, there exists a constant ck > 0 such that any ordered graph G on n vertices with the property that neither G nor its complement contains an induced monotone path of size k, has either a clique or an independent set of size at least n^ck . This strengthens a result of Bousquet, Lagoutte, and Thomassé, who proved the analogous result for unordered graphs. A key idea of the above paper was to show that any unordered graph on n vertices that does not contain an induced path of size k, and whose maximum degree is at most c(k)n for some small c(k) > 0, contains two disjoint linear size subsets with no edge between them. This approach fails for ordered graphs, because the analogous statement is false for k ≥ 3, by a construction of Fox. We provide some further examples showing that this statement also fails for ordered graphs avoiding other ordered trees. AU - Pach, János AU - Tomon, István ID - 9602 JF - Journal of Combinatorial Theory. Series B SN - 0095-8956 TI - Erdős-Hajnal-type results for monotone paths VL - 151 ER - TY - JOUR AB - Sound propagation is a macroscopic manifestation of the interplay between the equilibrium thermodynamics and the dynamical transport properties of fluids. Here, for a two-dimensional system of ultracold fermions, we calculate the first and second sound velocities across the whole BCS-BEC crossover, and we analyze the system response to an external perturbation. In the low-temperature regime we reproduce the recent measurements [Phys. Rev. Lett. 124, 240403 (2020)] of the first sound velocity, which, due to the decoupling of density and entropy fluctuations, is the sole mode excited by a density probe. Conversely, a heat perturbation excites only the second sound, which, being sensitive to the superfluid depletion, vanishes in the deep BCS regime and jumps discontinuously to zero at the Berezinskii-Kosterlitz-Thouless superfluid transition. A mixing between the modes occurs only in the finite-temperature BEC regime, where our theory converges to the purely bosonic results. AU - Tononi, A. AU - Cappellaro, Alberto AU - Bighin, Giacomo AU - Salasnich, L. ID - 9606 IS - 6 JF - Physical Review A SN - 24699926 TI - Propagation of first and second sound in a two-dimensional Fermi superfluid VL - 103 ER - TY - JOUR AB - Perineuronal nets (PNNs), components of the extracellular matrix, preferentially coat parvalbumin-positive interneurons and constrain critical-period plasticity in the adult cerebral cortex. Current strategies to remove PNN are long-lasting, invasive, and trigger neuropsychiatric symptoms. Here, we apply repeated anesthetic ketamine as a method with minimal behavioral effect. We find that this paradigm strongly reduces PNN coating in the healthy adult brain and promotes juvenile-like plasticity. Microglia are critically involved in PNN loss because they engage with parvalbumin-positive neurons in their defined cortical layer. We identify external 60-Hz light-flickering entrainment to recapitulate microglia-mediated PNN removal. Importantly, 40-Hz frequency, which is known to remove amyloid plaques, does not induce PNN loss, suggesting microglia might functionally tune to distinct brain frequencies. Thus, our 60-Hz light-entrainment strategy provides an alternative form of PNN intervention in the healthy adult brain. AU - Venturino, Alessandro AU - Schulz, Rouven AU - De Jesús-Cortés, Héctor AU - Maes, Margaret E AU - Nagy, Balint AU - Reilly-Andújar, Francis AU - Colombo, Gloria AU - Cubero, Ryan J AU - Schoot Uiterkamp, Florianne E AU - Bear, Mark F. AU - Siegert, Sandra ID - 9642 IS - 1 JF - Cell Reports TI - Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain VL - 36 ER - TY - JOUR AB - Mosaic analysis with double markers (MADM) offers one approach to visualize and concomitantly manipulate genetically defined cells in mice with single-cell resolution. MADM applications include the analysis of lineage, single-cell morphology and physiology, genomic imprinting phenotypes, and dissection of cell-autonomous gene functions in vivo in health and disease. Yet, MADM can only be applied to <25% of all mouse genes on select chromosomes to date. To overcome this limitation, we generate transgenic mice with knocked-in MADM cassettes near the centromeres of all 19 autosomes and validate their use across organs. With this resource, >96% of the entire mouse genome can now be subjected to single-cell genetic mosaic analysis. Beyond a proof of principle, we apply our MADM library to systematically trace sister chromatid segregation in distinct mitotic cell lineages. We find striking chromosome-specific biases in segregation patterns, reflecting a putative mechanism for the asymmetric segregation of genetic determinants in somatic stem cell division. AU - Contreras, Ximena AU - Amberg, Nicole AU - Davaatseren, Amarbayasgalan AU - Hansen, Andi H AU - Sonntag, Johanna AU - Andersen, Lill AU - Bernthaler, Tina AU - Streicher, Carmen AU - Heger, Anna-Magdalena AU - Johnson, Randy L. AU - Schwarz, Lindsay A. AU - Luo, Liqun AU - Rülicke, Thomas AU - Hippenmeyer, Simon ID - 9603 IS - 12 JF - Cell Reports TI - A genome-wide library of MADM mice for single-cell genetic mosaic analysis VL - 35 ER -