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 -