TY - GEN AB - All polyN tracts of length 5 or more nucleotides in sequences of genes from OG1. Sequences were extracted and scanned prior to automatic correction for frameshifts implemented in the RAST pipeline. (CSV 133 kb) AU - Sigalova, Olga M. AU - Chaplin, Andrei V. AU - Bochkareva, Olga AU - Shelyakin, Pavel V. AU - Filaretov, Vsevolod A. AU - Akkuratov, Evgeny E. AU - Burskaia, Valentina AU - Gelfand, Mikhail S. ID - 9898 TI - Additional file 21 of Chlamydia pan-genomic analysis reveals balance between host adaptation and selective pressure to genome reduction ER - TY - GEN AB - Clusters of Orthologous Genes (COGs) and corresponding functional categories assigned to OGs. (CSV 117 kb) AU - Sigalova, Olga M. AU - Chaplin, Andrei V. AU - Bochkareva, Olga AU - Shelyakin, Pavel V. AU - Filaretov, Vsevolod A. AU - Akkuratov, Evgeny E. AU - Burskaia, Valentina AU - Gelfand, Mikhail S. ID - 9901 TI - Additional file 9 of Chlamydia pan-genomic analysis reveals balance between host adaptation and selective pressure to genome reduction ER - TY - GEN AB - Summary of orthologous groups (OGs) for 227 genomes of genus Chlamydia. (CSV 362 kb) AU - Sigalova, Olga M. AU - Chaplin, Andrei V. AU - Bochkareva, Olga AU - Shelyakin, Pavel V. AU - Filaretov, Vsevolod A. AU - Akkuratov, Evgeny E. AU - Burskaia, Valentina AU - Gelfand, Mikhail S. ID - 9899 TI - Additional file 2 of Chlamydia pan-genomic analysis reveals balance between host adaptation and selective pressure to genome reduction ER - TY - GEN AB - Pan-genome statistics by species. (CSV 3 kb) AU - Sigalova, Olga M. AU - Chaplin, Andrei V. AU - Bochkareva, Olga AU - Shelyakin, Pavel V. AU - Filaretov, Vsevolod A. AU - Akkuratov, Evgeny E. AU - Burskaia, Valentina AU - Gelfand, Mikhail S. ID - 9900 TI - Additional file 5 of Chlamydia pan-genomic analysis reveals balance between host adaptation and selective pressure to genome reduction ER - TY - JOUR AB - A key challenge for community ecology is to understand to what extent observational data can be used to infer the underlying community assembly processes. As different processes can lead to similar or even identical patterns, statistical analyses of non‐manipulative observational data never yield undisputable causal inference on the underlying processes. Still, most empirical studies in community ecology are based on observational data, and hence understanding under which circumstances such data can shed light on assembly processes is a central concern for community ecologists. We simulated a spatial agent‐based model that generates variation in metacommunity dynamics across multiple axes, including the four classic metacommunity paradigms as special cases. We further simulated a virtual ecologist who analysed snapshot data sampled from the simulations using eighteen output metrics derived from beta‐diversity and habitat variation indices, variation partitioning and joint species distribution modelling. Our results indicated two main axes of variation in the output metrics. The first axis of variation described whether the landscape has patchy or continuous variation, and thus was essentially independent of the properties of the species community. The second axis of variation related to the level of predictability of the metacommunity. The most predictable communities were niche‐based metacommunities inhabiting static landscapes with marked environmental heterogeneity, such as metacommunities following the species sorting paradigm or the mass effects paradigm. The most unpredictable communities were neutral‐based metacommunities inhabiting dynamics landscapes with little spatial heterogeneity, such as metacommunities following the neutral or patch sorting paradigms. The output metrics from joint species distribution modelling yielded generally the highest resolution to disentangle among the simulated scenarios. Yet, the different types of statistical approaches utilized in this study carried complementary information, and thus our results suggest that the most comprehensive evaluation of metacommunity structure can be obtained by combining them. AU - Ovaskainen, Otso AU - Rybicki, Joel AU - Abrego, Nerea ID - 6936 IS - 11 JF - Ecography SN - 0906-7590 TI - What can observational data reveal about metacommunity processes? VL - 42 ER - TY - JOUR AB - Gene Drives are regarded as future tools with a high potential for population control. Due to their inherent ability to overcome the rules of Mendelian inheritance, gene drives (GD) may spread genes rapidly through populations of sexually reproducing organisms. A release of organisms carrying a GD would constitute a paradigm shift in the handling of genetically modified organisms because gene drive organisms (GDO) are designed to drive their transgenes into wild populations and thereby increase the number of GDOs. The rapid development in this field and its focus on wild populations demand a prospective risk assessment with a focus on exposure related aspects. Presently, it is unclear how adequate risk management could be guaranteed to limit the spread of GDs in time and space, in order to avoid potential adverse effects in socio‐ecological systems. The recent workshop on the “Evaluation of Spatial and Temporal Control of Gene Drives” hosted by the Institute of Safety/Security and Risk Sciences (ISR) in Vienna aimed at gaining some insight into the potential population dynamic behavior of GDs and appropriate measures of control. Scientists from France, Germany, England, and the USA discussed both topics in this meeting on April 4–5, 2019. This article summarizes results of the workshop. AU - Giese, B AU - Friess, J L AU - Schetelig, M F AU - Barton, Nicholas H AU - Messer, Philip AU - Debarre, Florence AU - Meimberg, H AU - Windbichler, N AU - Boete, C ID - 6857 IS - 11 JF - BioEssays TI - Gene Drives: Dynamics and regulatory matters – A report from the workshop “Evaluation of spatial and temporal control of Gene Drives”, 4 – 5 April 2019, Vienna VL - 41 ER - TY - JOUR AB - We study the effect of a linear tunneling coupling between two-dimensional systems, each separately exhibiting the topological Berezinskii-Kosterlitz-Thouless (BKT) transition. In the uncoupled limit, there are two phases: one where the one-body correlation functions are algebraically decaying and the other with exponential decay. When the linear coupling is turned on, a third BKT-paired phase emerges, in which one-body correlations are exponentially decaying, while two-body correlation functions exhibit power-law decay. We perform numerical simulations in the paradigmatic case of two coupled XY models at finite temperature, finding evidences that for any finite value of the interlayer coupling, the BKT-paired phase is present. We provide a picture of the phase diagram using a renormalization group approach. AU - Bighin, Giacomo AU - Defenu, Nicolò AU - Nándori, István AU - Salasnich, Luca AU - Trombettoni, Andrea ID - 6940 IS - 10 JF - Physical Review Letters SN - 0031-9007 TI - Berezinskii-Kosterlitz-Thouless paired phase in coupled XY models VL - 123 ER - TY - JOUR AU - Qi, Chao AU - Minin, Giulio Di AU - Vercellino, Irene AU - Wutz, Anton AU - Korkhov, Volodymyr M. ID - 6919 IS - 9 JF - Science Advances TI - Structural basis of sterol recognition by human hedgehog receptor PTCH1 VL - 5 ER - TY - JOUR AB - Malaria, a disease caused by parasites of the Plasmodium genus, begins when Plasmodium-infected mosquitoes inject malaria sporozoites while searching for blood. Sporozoites migrate from the skin via blood to the liver, infect hepatocytes, and form liver stages which in mice 48 h later escape into blood and cause clinical malaria. Vaccine-induced activated or memory CD8 T cells are capable of locating and eliminating all liver stages in 48 h, thus preventing the blood-stage disease. However, the rules of how CD8 T cells are able to locate all liver stages within a relatively short time period remains poorly understood. We recently reported formation of clusters consisting of variable numbers of activated CD8 T cells around Plasmodium yoelii (Py)-infected hepatocytes. Using a combination of experimental data and mathematical models we now provide additional insights into mechanisms of formation of these clusters. First, we show that a model in which cluster formation is driven exclusively by T-cell-extrinsic factors, such as variability in “attractiveness” of different liver stages, cannot explain distribution of cluster sizes in different experimental conditions. In contrast, the model in which cluster formation is driven by the positive feedback loop (i.e., larger clusters attract more CD8 T cells) can accurately explain the available data. Second, while both Py-specific CD8 T cells and T cells of irrelevant specificity (non-specific CD8 T cells) are attracted to the clusters, we found no evidence that non-specific CD8 T cells play a role in cluster formation. Third and finally, mathematical modeling suggested that formation of clusters occurs rapidly, within few hours after adoptive transfer of CD8 T cells, thus illustrating high efficiency of CD8 T cells in locating their targets in complex peripheral organs, such as the liver. Taken together, our analysis provides novel insights into and attempts to discriminate between alternative mechanisms driving the formation of clusters of antigen-specific CD8 T cells in the liver. AU - Kelemen, Réka K AU - Rajakaruna, H AU - Cockburn, IA AU - Ganusov, VV ID - 6983 JF - Frontiers in Immunology SN - 1664-3224 TI - Clustering of activated CD8 T cells around Malaria-infected hepatocytes is rapid and is driven by antigen-specific cells VL - 10 ER - TY - JOUR AB - We give fault-tolerant algorithms for establishing synchrony in distributed systems in which each of thennodes has its own clock. Our algorithms operate in a very strong fault model: we require self-stabilisation, i.e.,the initial state of the system may be arbitrary, and there can be up to f> r eff and show that these systems obey universal scaling laws different from neutral particles. An accurate description of these states requires both the Coulomb-modified scattering length and the effective range unless the Coulomb interaction is very weak (D -> ). Our findings are relevant for bound states whose spatial extent is significantly larger than the range of the attractive potential. These states enjoy universality – their character is independent of the shape of the short-range potential. AU - Schmickler, C.H. AU - Hammer, H.-W. AU - Volosniev, Artem ID - 6955 JF - Physics Letters B SN - 0370-2693 TI - Universal physics of bound states of a few charged particles VL - 798 ER - TY - JOUR AB - Activity-dependent bulk endocytosis generates synaptic vesicles (SVs) during intense neuronal activity via a two-step process. First, bulk endosomes are formed direct from the plasma membrane from which SVs are then generated. SV generation from bulk endosomes requires the efflux of previously accumulated calcium and activation of the protein phosphatase calcineurin. However, it is still unknown how calcineurin mediates SV generation. We addressed this question using a series of acute interventions that decoupled the generation of SVs from bulk endosomes in rat primary neuronal culture. This was achieved by either disruption of protein–protein interactions via delivery of competitive peptides, or inhibition of enzyme activity by known inhibitors. SV generation was monitored using either a morphological horseradish peroxidase assay or an optical assay that monitors the replenishment of the reserve SV pool. We found that SV generation was inhibited by, (i) peptides that disrupt calcineurin interactions, (ii) an inhibitor of dynamin I GTPase activity and (iii) peptides that disrupt the phosphorylation-dependent dynamin I–syndapin I interaction. Peptides that disrupted syndapin I interactions with eps15 homology domain-containing proteins had no effect. This revealed that (i) calcineurin must be localized at bulk endosomes to mediate its effect, (ii) dynamin I GTPase activity is essential for SV fission and (iii) the calcineurin-dependent interaction between dynamin I and syndapin I is essential for SV generation. We therefore propose that a calcineurin-dependent dephosphorylation cascade that requires both dynamin I GTPase and syndapin I lipid-deforming activity is essential for SV generation from bulk endosomes. AU - Cheung, Giselle T AU - Cousin, Michael A. ID - 7005 IS - 5 JF - Journal of Neurochemistry SN - 0022-3042 TI - Synaptic vesicle generation from activity‐dependent bulk endosomes requires a dephosphorylation‐dependent dynamin–syndapin interaction VL - 151 ER - TY - JOUR AB - The main contributions of this paper are the proposition and the convergence analysis of a class of inertial projection-type algorithm for solving variational inequality problems in real Hilbert spaces where the underline operator is monotone and uniformly continuous. We carry out a unified analysis of the proposed method under very mild assumptions. In particular, weak convergence of the generated sequence is established and nonasymptotic O(1 / n) rate of convergence is established, where n denotes the iteration counter. We also present some experimental results to illustrate the profits gained by introducing the inertial extrapolation steps. AU - Shehu, Yekini AU - Iyiola, Olaniyi S. AU - Li, Xiao-Huan AU - Dong, Qiao-Li ID - 7000 IS - 4 JF - Computational and Applied Mathematics SN - 2238-3603 TI - Convergence analysis of projection method for variational inequalities VL - 38 ER - TY - JOUR AB - In pipes and channels, the onset of turbulence is initially dominated by localizedtransients, which lead to sustained turbulence through their collective dynamics. In thepresent work, we study numerically the localized turbulence in pipe flow and elucidate astate space structure that gives rise to transient chaos. Starting from the basin boundaryseparating laminar and turbulent flow, we identify transverse homoclinic orbits, thepresence of which necessitates a homoclinic tangle and chaos. A direct consequence ofthe homoclinic tangle is the fractal nature of the laminar-turbulent boundary, which wasconjectured in various earlier studies. By mapping the transverse intersections between thestable and unstable manifold of a periodic orbit, we identify the gateways that promote anescape from turbulence. AU - Budanur, Nazmi B AU - Dogra, Akshunna AU - Hof, Björn ID - 6978 IS - 10 JF - Physical Review Fluids TI - Geometry of transient chaos in streamwise-localized pipe flow turbulence VL - 4 ER - TY - JOUR AB - Effective design of combination therapies requires understanding the changes in cell physiology that result from drug interactions. Here, we show that the genome-wide transcriptional response to combinations of two drugs, measured at a rigorously controlled growth rate, can predict higher-order antagonism with a third drug in Saccharomyces cerevisiae. Using isogrowth profiling, over 90% of the variation in cellular response can be decomposed into three principal components (PCs) that have clear biological interpretations. We demonstrate that the third PC captures emergent transcriptional programs that are dependent on both drugs and can predict antagonism with a third drug targeting the emergent pathway. We further show that emergent gene expression patterns are most pronounced at a drug ratio where the drug interaction is strongest, providing a guideline for future measurements. Our results provide a readily applicable recipe for uncovering emergent responses in other systems and for higher-order drug combinations. A record of this paper’s transparent peer review process is included in the Supplemental Information. AU - Lukacisin, Martin AU - Bollenbach, Tobias ID - 7026 IS - 5 JF - Cell Systems SN - 2405-4712 TI - Emergent gene expression responses to drug combinations predict higher-order drug interactions VL - 9 ER - TY - JOUR AB - We find a graph of genus 5 and its drawing on the orientable surface of genus 4 with every pair of independent edges crossing an even number of times. This shows that the strong Hanani–Tutte theorem cannot be extended to the orientable surface of genus 4. As a base step in the construction we use a counterexample to an extension of the unified Hanani–Tutte theorem on the torus. AU - Fulek, Radoslav AU - Kynčl, Jan ID - 7034 IS - 6 JF - Combinatorica SN - 0209-9683 TI - Counterexample to an extension of the Hanani-Tutte theorem on the surface of genus 4 VL - 39 ER - TY - JOUR AB - BAX, a member of the BCL2 gene family, controls the committed step of the intrinsic apoptotic program. Mitochondrial fragmentation is a commonly observed feature of apoptosis, which occurs through the process of mitochondrial fission. BAX has consistently been associated with mitochondrial fission, yet how BAX participates in the process of mitochondrial fragmentation during apoptosis remains to be tested. Time-lapse imaging of BAX recruitment and mitochondrial fragmentation demonstrates that rapid mitochondrial fragmentation during apoptosis occurs after the complete recruitment of BAX to the mitochondrial outer membrane (MOM). The requirement of a fully functioning BAX protein for the fission process was demonstrated further in BAX/BAK-deficient HCT116 cells expressing a P168A mutant of BAX. The mutant performed fusion to restore the mitochondrial network. but was not demonstrably recruited to the MOM after apoptosis induction. Under these conditions, mitochondrial fragmentation was blocked. Additionally, we show that loss of the fission protein, dynamin-like protein 1 (DRP1), does not temporally affect the initiation time or rate of BAX recruitment, but does reduce the final level of BAX recruited to the MOM during the late phase of BAX recruitment. These correlative observations suggest a model where late-stage BAX oligomers play a functional part of the mitochondrial fragmentation machinery in apoptotic cells. AU - Maes, Margaret E AU - Grosser, J. A. AU - Fehrman, R. L. AU - Schlamp, C. L. AU - Nickells, R. W. ID - 7095 JF - Scientific Reports TI - Completion of BAX recruitment correlates with mitochondrial fission during apoptosis VL - 9 ER - TY - JOUR AB - Early endosomes, also called sorting endosomes, are known to mature into late endosomesvia the Rab5-mediated endolysosomal trafficking pathway. Thus, early endosome existence isthought to be maintained by the continual fusion of transport vesicles from the plasmamembrane and thetrans-Golgi network (TGN). Here we show instead that endocytosis isdispensable and post-Golgi vesicle transport is crucial for the formation of endosomes andthe subsequent endolysosomal traffic regulated by yeast Rab5 Vps21p. Fittingly, all threeproteins required for endosomal nucleotide exchange on Vps21p arefirst recruited to theTGN before transport to the endosome, namely the GEF Vps9p and the epsin-relatedadaptors Ent3/5p. The TGN recruitment of these components is distinctly controlled, withVps9p appearing to require the Arf1p GTPase, and the Rab11s, Ypt31p/32p. These resultsprovide a different view of endosome formation and identify the TGN as a critical location forregulating progress through the endolysosomal trafficking pathway. AU - Nagano, Makoto AU - Toshima, Junko Y. AU - Siekhaus, Daria E AU - Toshima, Jiro ID - 7097 IS - 1 JF - Communications Biology SN - 2399-3642 TI - Rab5-mediated endosome formation is regulated at the trans-Golgi network VL - 2 ER - TY - JOUR AU - Kasugai, Yu AU - Vogel, Elisabeth AU - Hörtnagl, Heide AU - Schönherr, Sabine AU - Paradiso, Enrica AU - Hauschild, Markus AU - Göbel, Georg AU - Milenkovic, Ivan AU - Peterschmitt, Yvan AU - Tasan, Ramon AU - Sperk, Günther AU - Shigemoto, Ryuichi AU - Sieghart, Werner AU - Singewald, Nicolas AU - Lüthi, Andreas AU - Ferraguti, Francesco ID - 7099 IS - 4 JF - Neuron SN - 0896-6273 TI - Structural and functional remodeling of amygdala GABAergic synapses in associative fear learning VL - 104 ER -