@article{145, abstract = {Aged proteins can become hazardous to cellular function, by accumulating molecular damage. This implies that cells should preferentially rely on newly produced ones. We tested this hypothesis in cultured hippocampal neurons, focusing on synaptic transmission. We found that newly synthesized vesicle proteins were incorporated in the actively recycling pool of vesicles responsible for all neurotransmitter release during physiological activity. We observed this for the calcium sensor Synaptotagmin 1, for the neurotransmitter transporter VGAT, and for the fusion protein VAMP2 (Synaptobrevin 2). Metabolic labeling of proteins and visualization by secondary ion mass spectrometry enabled us to query the entire protein makeup of the actively recycling vesicles, which we found to be younger than that of non-recycling vesicles. The young vesicle proteins remained in use for up to ~ 24 h, during which they participated in recycling a few hundred times. They were afterward reluctant to release and were degraded after an additional ~ 24–48 h. We suggest that the recycling pool of synaptic vesicles relies on newly synthesized proteins, while the inactive reserve pool contains older proteins.}, author = {Truckenbrodt, Sven M and Viplav, Abhiyan and Jähne, Sebsatian and Vogts, Angela and Denker, Annette and Wildhagen, Hanna and Fornasiero, Eugenio and Rizzoli, Silvio}, issn = {0261-4189}, journal = {The EMBO Journal}, number = {15}, publisher = {Wiley}, title = {{Newly produced synaptic vesicle proteins are preferentially used in synaptic transmission}}, doi = {10.15252/embj.201798044}, volume = {37}, year = {2018}, } @article{146, abstract = {The root cap protects the stem cell niche of angiosperm roots from damage. In Arabidopsis, lateral root cap (LRC) cells covering the meristematic zone are regularly lost through programmed cell death, while the outermost layer of the root cap covering the tip is repeatedly sloughed. Efficient coordination with stem cells producing new layers is needed to maintain a constant size of the cap. We present a signalling pair, the peptide IDA-LIKE1 (IDL1) and its receptor HAESA-LIKE2 (HSL2), mediating such communication. Live imaging over several days characterized this process from initial fractures in LRC cell files to full separation of a layer. Enhanced expression of IDL1 in the separating root cap layers resulted in increased frequency of sloughing, balanced with generation of new layers in a HSL2-dependent manner. Transcriptome analyses linked IDL1-HSL2 signalling to the transcription factors BEARSKIN1/2 and genes associated with programmed cell death. Mutations in either IDL1 or HSL2 slowed down cell division, maturation and separation. Thus, IDL1-HSL2 signalling potentiates dynamic regulation of the homeostatic balance between stem cell division and sloughing activity.}, author = {Shi, Chun Lin and Von Wangenheim, Daniel and Herrmann, Ullrich and Wildhagen, Mari and Kulik, Ivan and Kopf, Andreas and Ishida, Takashi and Olsson, Vilde and Anker, Mari Kristine and Albert, Markus and Butenko, Melinka A and Felix, Georg and Sawa, Shinichiro and Claassen, Manfred and Friml, Jirí and Aalen, Reidunn B}, journal = {Nature Plants}, number = {8}, pages = {596 -- 604}, publisher = {Nature Publishing Group}, title = {{The dynamics of root cap sloughing in Arabidopsis is regulated by peptide signalling}}, doi = {10.1038/s41477-018-0212-z}, volume = {4}, year = {2018}, } @article{147, abstract = {The trafficking of subcellular cargos in eukaryotic cells crucially depends on vesicle budding, a process mediated by ARF-GEFs (ADP-ribosylation factor guanine nucleotide exchange factors). In plants, ARF-GEFs play essential roles in endocytosis, vacuolar trafficking, recycling, secretion, and polar trafficking. Moreover, they are important for plant development, mainly through controlling the polar subcellular localization of PIN-FORMED (PIN) transporters of the plant hormone auxin. Here, using a chemical genetics screen in Arabidopsis thaliana, we identified Endosidin 4 (ES4), an inhibitor of eukaryotic ARF-GEFs. ES4 acts similarly to and synergistically with the established ARF-GEF inhibitor Brefeldin A and has broad effects on intracellular trafficking, including endocytosis, exocytosis, and vacuolar targeting. Additionally, Arabidopsis and yeast (Sacharomyces cerevisiae) mutants defective in ARF-GEF show altered sensitivity to ES4. ES4 interferes with the activation-based membrane association of the ARF1 GTPases, but not of their mutant variants that are activated independently of ARF-GEF activity. Biochemical approaches and docking simulations confirmed that ES4 specifically targets the SEC7 domain-containing ARF-GEFs. These observations collectively identify ES4 as a chemical tool enabling the study of ARF-GEF-mediated processes, including ARF-GEF-mediated plant development.}, author = {Kania, Urszula and Nodzyński, Tomasz and Lu, Qing and Hicks, Glenn R and Nerinckx, Wim and Mishev, Kiril and Peurois, Francois and Cherfils, Jacqueline and De, Rycke Riet Maria and Grones, Peter and Robert, Stéphanie and Russinova, Eugenia and Friml, Jirí}, issn = {1040-4651}, journal = {The Plant Cell}, number = {10}, pages = {2553 -- 2572}, publisher = {Oxford University Press}, title = {{The inhibitor Endosidin 4 targets SEC7 domain-type ARF GTPase exchange factors and interferes with sub cellular trafficking in eukaryotes}}, doi = {10.1105/tpc.18.00127}, volume = {30}, year = {2018}, } @article{18, abstract = {An N-superconcentrator is a directed, acyclic graph with N input nodes and N output nodes such that every subset of the inputs and every subset of the outputs of same cardinality can be connected by node-disjoint paths. It is known that linear-size and bounded-degree superconcentrators exist. We prove the existence of such superconcentrators with asymptotic density 25.3 (where the density is the number of edges divided by N). The previously best known densities were 28 [12] and 27.4136 [17].}, author = {Kolmogorov, Vladimir and Rolinek, Michal}, issn = {0381-7032}, journal = {Ars Combinatoria}, number = {10}, pages = {269 -- 304}, publisher = {Charles Babbage Research Centre}, title = {{Superconcentrators of density 25.3}}, volume = {141}, year = {2018}, } @article{180, abstract = {In this paper we define and study the classical Uniform Electron Gas (UEG), a system of infinitely many electrons whose density is constant everywhere in space. The UEG is defined differently from Jellium, which has a positive constant background but no constraint on the density. We prove that the UEG arises in Density Functional Theory in the limit of a slowly varying density, minimizing the indirect Coulomb energy. We also construct the quantum UEG and compare it to the classical UEG at low density.}, author = {Lewi, Mathieu and Lieb, Élliott and Seiringer, Robert}, issn = {2270-518X}, journal = {Journal de l'Ecole Polytechnique - Mathematiques}, pages = {79 -- 116}, publisher = {Ecole Polytechnique}, title = {{Statistical mechanics of the uniform electron gas}}, doi = {10.5802/jep.64}, volume = {5}, year = {2018}, } @article{181, abstract = {We consider large random matrices X with centered, independent entries but possibly di erent variances. We compute the normalized trace of f(X)g(X∗) for f, g functions analytic on the spectrum of X. We use these results to compute the long time asymptotics for systems of coupled di erential equations with random coe cients. We show that when the coupling is critical, the norm squared of the solution decays like t−1/2.}, author = {Erdös, László and Krüger, Torben H and Renfrew, David T}, journal = {SIAM Journal on Mathematical Analysis}, number = {3}, pages = {3271 -- 3290}, publisher = {Society for Industrial and Applied Mathematics }, title = {{Power law decay for systems of randomly coupled differential equations}}, doi = {10.1137/17M1143125}, volume = {50}, year = {2018}, } @inproceedings{182, abstract = {We describe a new algorithm for the parametric identification problem for signal temporal logic (STL), stated as follows. Given a densetime real-valued signal w and a parameterized temporal logic formula φ, compute the subset of the parameter space that renders the formula satisfied by the signal. Unlike previous solutions, which were based on search in the parameter space or quantifier elimination, our procedure works recursively on φ and computes the evolution over time of the set of valid parameter assignments. This procedure is similar to that of monitoring or computing the robustness of φ relative to w. Our implementation and experiments demonstrate that this approach can work well in practice.}, author = {Bakhirkin, Alexey and Ferrere, Thomas and Maler, Oded}, booktitle = {Proceedings of the 21st International Conference on Hybrid Systems}, isbn = {978-1-4503-5642-8 }, location = {Porto, Portugal}, pages = {177 -- 186}, publisher = {ACM}, title = {{Efficient parametric identification for STL}}, doi = {10.1145/3178126.3178132}, year = {2018}, } @inproceedings{183, abstract = {Fault-localization is considered to be a very tedious and time-consuming activity in the design of complex Cyber-Physical Systems (CPS). This laborious task essentially requires expert knowledge of the system in order to discover the cause of the fault. In this context, we propose a new procedure that AIDS designers in debugging Simulink/Stateflow hybrid system models, guided by Signal Temporal Logic (STL) specifications. The proposed method relies on three main ingredients: (1) a monitoring and a trace diagnostics procedure that checks whether a tested behavior satisfies or violates an STL specification, localizes time segments and interfaces variables contributing to the property violations; (2) a slicing procedure that maps these observable behavior segments to the internal states and transitions of the Simulink model; and (3) a spectrum-based fault-localization method that combines the previous analysis from multiple tests to identify the internal states and/or transitions that are the most likely to explain the fault. We demonstrate the applicability of our approach on two Simulink models from the automotive and the avionics domain.}, author = {Bartocci, Ezio and Ferrere, Thomas and Manjunath, Niveditha and Nickovic, Dejan}, location = {Porto, Portugal}, pages = {197 -- 206}, publisher = {Association for Computing Machinery}, title = {{Localizing faults in simulink/stateflow models with STL}}, doi = {10.1145/3178126.3178131}, year = {2018}, } @inproceedings{184, abstract = {We prove that for every d ≥ 2, deciding if a pure, d-dimensional, simplicial complex is shellable is NP-hard, hence NP-complete. This resolves a question raised, e.g., by Danaraj and Klee in 1978. Our reduction also yields that for every d ≥ 2 and k ≥ 0, deciding if a pure, d-dimensional, simplicial complex is k-decomposable is NP-hard. For d ≥ 3, both problems remain NP-hard when restricted to contractible pure d-dimensional complexes.}, author = {Goaoc, Xavier and Paták, Pavel and Patakova, Zuzana and Tancer, Martin and Wagner, Uli}, location = {Budapest, Hungary}, pages = {41:1 -- 41:16}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Shellability is NP-complete}}, doi = {10.4230/LIPIcs.SoCG.2018.41}, volume = {99}, year = {2018}, } @inproceedings{185, abstract = {We resolve in the affirmative conjectures of A. Skopenkov and Repovš (1998), and M. Skopenkov (2003) generalizing the classical Hanani-Tutte theorem to the setting of approximating maps of graphs on 2-dimensional surfaces by embeddings. Our proof of this result is constructive and almost immediately implies an efficient algorithm for testing whether a given piecewise linear map of a graph in a surface is approximable by an embedding. More precisely, an instance of this problem consists of (i) a graph G whose vertices are partitioned into clusters and whose inter-cluster edges are partitioned into bundles, and (ii) a region R of a 2-dimensional compact surface M given as the union of a set of pairwise disjoint discs corresponding to the clusters and a set of pairwise disjoint "pipes" corresponding to the bundles, connecting certain pairs of these discs. We are to decide whether G can be embedded inside M so that the vertices in every cluster are drawn in the corresponding disc, the edges in every bundle pass only through its corresponding pipe, and every edge crosses the boundary of each disc at most once.}, author = {Fulek, Radoslav and Kynčl, Jan}, isbn = {978-3-95977-066-8}, location = {Budapest, Hungary}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Hanani-Tutte for approximating maps of graphs}}, doi = {10.4230/LIPIcs.SoCG.2018.39}, volume = {99}, year = {2018}, } @inproceedings{186, abstract = {A drawing of a graph on a surface is independently even if every pair of nonadjacent edges in the drawing crosses an even number of times. The ℤ2-genus of a graph G is the minimum g such that G has an independently even drawing on the orientable surface of genus g. An unpublished result by Robertson and Seymour implies that for every t, every graph of sufficiently large genus contains as a minor a projective t × t grid or one of the following so-called t-Kuratowski graphs: K3, t, or t copies of K5 or K3,3 sharing at most 2 common vertices. We show that the ℤ2-genus of graphs in these families is unbounded in t; in fact, equal to their genus. Together, this implies that the genus of a graph is bounded from above by a function of its ℤ2-genus, solving a problem posed by Schaefer and Štefankovič, and giving an approximate version of the Hanani-Tutte theorem on orientable surfaces.}, author = {Fulek, Radoslav and Kynčl, Jan}, location = {Budapest, Hungary}, pages = {40.1 -- 40.14}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{The ℤ2-Genus of Kuratowski minors}}, doi = {10.4230/LIPIcs.SoCG.2018.40}, volume = {99}, year = {2018}, } @article{13, abstract = {We propose a new method for fabricating digital objects through reusable silicone molds. Molds are generated by casting liquid silicone into custom 3D printed containers called metamolds. Metamolds automatically define the cuts that are needed to extract the cast object from the silicone mold. The shape of metamolds is designed through a novel segmentation technique, which takes into account both geometric and topological constraints involved in the process of mold casting. Our technique is simple, does not require changing the shape or topology of the input objects, and only requires off-the- shelf materials and technologies. We successfully tested our method on a set of challenging examples with complex shapes and rich geometric detail. © 2018 Association for Computing Machinery.}, author = {Alderighi, Thomas and Malomo, Luigi and Giorgi, Daniela and Pietroni, Nico and Bickel, Bernd and Cignoni, Paolo}, journal = {ACM Trans. Graph.}, number = {4}, publisher = {ACM}, title = {{Metamolds: Computational design of silicone molds}}, doi = {10.1145/3197517.3201381}, volume = {37}, year = {2018}, } @misc{13055, abstract = {Dataset for manuscript 'Social network plasticity decreases disease transmission in a eusocial insect' Compared to previous versions: - raw image files added - correction of URLs within README.txt file }, author = {Stroeymeyt, Nathalie and Grasse, Anna V and Crespi, Alessandro and Mersch, Danielle and Cremer, Sylvia and Keller, Laurent}, publisher = {Zenodo}, title = {{Social network plasticity decreases disease transmission in a eusocial insect}}, doi = {10.5281/ZENODO.1322669}, year = {2018}, } @misc{13059, abstract = {This dataset contains a GitHub repository containing all the data, analysis, Nextflow workflows and Jupyter notebooks to replicate the manuscript titled "Fast and accurate large multiple sequence alignments with a root-to-leaf regressive method". It also contains the Multiple Sequence Alignments (MSAs) generated and well as the main figures and tables from the manuscript. The repository is also available at GitHub (https://github.com/cbcrg/dpa-analysis) release `v1.2`. For details on how to use the regressive alignment algorithm, see the T-Coffee software suite (https://github.com/cbcrg/tcoffee).}, author = {Garriga, Edgar and di Tommaso, Paolo and Magis, Cedrik and Erb, Ionas and Mansouri, Leila and Baltzis, Athanasios and Laayouni, Hafid and Kondrashov, Fyodor and Floden, Evan and Notredame, Cedric}, publisher = {Zenodo}, title = {{Fast and accurate large multiple sequence alignments with a root-to-leaf regressive method}}, doi = {10.5281/ZENODO.2025846}, year = {2018}, } @article{131, abstract = {XY systems usually show chromosome-wide compensation of X-linked genes, while in many ZW systems, compensation is restricted to a minority of dosage-sensitive genes. Why such differences arose is still unclear. Here, we combine comparative genomics, transcriptomics and proteomics to obtain a complete overview of the evolution of gene dosage on the Z-chromosome of Schistosoma parasites. We compare the Z-chromosome gene content of African (Schistosoma mansoni and S. haematobium) and Asian (S. japonicum) schistosomes and describe lineage-specific evolutionary strata. We use these to assess gene expression evolution following sex-linkage. The resulting patterns suggest a reduction in expression of Z-linked genes in females, combined with upregulation of the Z in both sexes, in line with the first step of Ohno’s classic model of dosage compensation evolution. Quantitative proteomics suggest that post-transcriptional mechanisms do not play a major role in balancing the expression of Z-linked genes. }, author = {Picard, Marion A and Cosseau, Celine and Ferré, Sabrina and Quack, Thomas and Grevelding, Christoph and Couté, Yohann and Vicoso, Beatriz}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Evolution of gene dosage on the Z-chromosome of schistosome parasites}}, doi = {10.7554/eLife.35684}, volume = {7}, year = {2018}, } @article{132, abstract = {Pancreas development involves a coordinated process in which an early phase of cell segregation is followed by a longer phase of lineage restriction, expansion, and tissue remodeling. By combining clonal tracing and whole-mount reconstruction with proliferation kinetics and single-cell transcriptional profiling, we define the functional basis of pancreas morphogenesis. We show that the large-scale organization of mouse pancreas can be traced to the activity of self-renewing precursors positioned at the termini of growing ducts, which act collectively to drive serial rounds of stochastic ductal bifurcation balanced by termination. During this phase of branching morphogenesis, multipotent precursors become progressively fate-restricted, giving rise to self-renewing acinar-committed precursors that are conveyed with growing ducts, as well as ductal progenitors that expand the trailing ducts and give rise to delaminating endocrine cells. These findings define quantitatively how the functional behavior and lineage progression of precursor pools determine the large-scale patterning of pancreatic sub-compartments.}, author = {Sznurkowska, Magdalena and Hannezo, Edouard B and Azzarelli, Roberta and Rulands, Steffen and Nestorowa, Sonia and Hindley, Christopher and Nichols, Jennifer and Göttgens, Berthold and Huch, Meritxell and Philpott, Anna and Simons, Benjamin}, journal = {Developmental Cell}, number = {3}, pages = {360 -- 375}, publisher = {Cell Press}, title = {{Defining lineage potential and fate behavior of precursors during pancreas development}}, doi = {10.1016/j.devcel.2018.06.028}, volume = {46}, year = {2018}, } @article{198, abstract = {We consider a class of students learning a language from a teacher. The situation can be interpreted as a group of child learners receiving input from the linguistic environment. The teacher provides sample sentences. The students try to learn the grammar from the teacher. In addition to just listening to the teacher, the students can also communicate with each other. The students hold hypotheses about the grammar and change them if they receive counter evidence. The process stops when all students have converged to the correct grammar. We study how the time to convergence depends on the structure of the classroom by introducing and evaluating various complexity measures. We find that structured communication between students, although potentially introducing confusion, can greatly reduce some of the complexity measures. Our theory can also be interpreted as applying to the scientific process, where nature is the teacher and the scientists are the students.}, author = {Ibsen-Jensen, Rasmus and Tkadlec, Josef and Chatterjee, Krishnendu and Nowak, Martin}, issn = {1742-5662}, journal = {Journal of the Royal Society Interface}, number = {140}, publisher = {The Royal Society}, title = {{Language acquisition with communication between learners}}, doi = {10.1098/rsif.2018.0073}, volume = {15}, year = {2018}, } @article{199, abstract = {Sex-biased genes are central to the study of sexual selection, sexual antagonism, and sex chromosome evolution. We describe a comprehensive de novo assembled transcriptome in the common frog Rana temporaria based on five developmental stages and three adult tissues from both sexes, obtained from a population with karyotypically homomorphic but genetically differentiated sex chromosomes. This allows the study of sex-biased gene expression throughout development, and its effect on the rate of gene evolution while accounting for pleiotropic expression, which is known to negatively correlate with the evolutionary rate. Overall, sex-biased genes had little overlap among developmental stages and adult tissues. Late developmental stages and gonad tissues had the highest numbers of stage-or tissue-specific genes. We find that pleiotropic gene expression is a better predictor than sex bias for the evolutionary rate of genes, though it often interacts with sex bias. Although genetically differentiated, the sex chromosomes were not enriched in sex-biased genes, possibly due to a very recent arrest of XY recombination. These results extend our understanding of the developmental dynamics, tissue specificity, and genomic localization of sex-biased genes.}, author = {Ma, Wen and Veltsos, Paris and Toups, Melissa A and Rodrigues, Nicolas and Sermier, Roberto and Jeffries, Daniel and Perrin, Nicolas}, journal = {Genes}, number = {6}, publisher = {MDPI}, title = {{Tissue specificity and dynamics of sex biased gene expression in a common frog population with differentiated, yet homomorphic, sex chromosomes}}, doi = {10.3390/genes9060294}, volume = {9}, year = {2018}, } @article{20, abstract = {Background: Norepinephrine (NE) signaling has a key role in white adipose tissue (WAT) functions, including lipolysis, free fatty acid liberation and, under certain conditions, conversion of white into brite (brown-in-white) adipocytes. However, acute effects of NE stimulation have not been described at the transcriptional network level. Results: We used RNA-seq to uncover a broad transcriptional response. The inference of protein-protein and protein-DNA interaction networks allowed us to identify a set of immediate-early genes (IEGs) with high betweenness, validating our approach and suggesting a hierarchical control of transcriptional regulation. In addition, we identified a transcriptional regulatory network with IEGs as master regulators, including HSF1 and NFIL3 as novel NE-induced IEG candidates. Moreover, a functional enrichment analysis and gene clustering into functional modules suggest a crosstalk between metabolic, signaling, and immune responses. Conclusions: Altogether, our network biology approach explores for the first time the immediate-early systems level response of human adipocytes to acute sympathetic activation, thereby providing a first network basis of early cell fate programs and crosstalks between metabolic and transcriptional networks required for proper WAT function.}, author = {Higareda Almaraz, Juan and Karbiener, Michael and Giroud, Maude and Pauler, Florian and Gerhalter, Teresa and Herzig, Stephan and Scheideler, Marcel}, issn = {1471-2164}, journal = {BMC Genomics}, number = {1}, publisher = {BioMed Central}, title = {{Norepinephrine triggers an immediate-early regulatory network response in primary human white adipocytes}}, doi = {10.1186/s12864-018-5173-0}, volume = {19}, year = {2018}, } @inproceedings{188, abstract = {Smallest enclosing spheres of finite point sets are central to methods in topological data analysis. Focusing on Bregman divergences to measure dissimilarity, we prove bounds on the location of the center of a smallest enclosing sphere. These bounds depend on the range of radii for which Bregman balls are convex.}, author = {Edelsbrunner, Herbert and Virk, Ziga and Wagner, Hubert}, location = {Budapest, Hungary}, pages = {35:1 -- 35:13}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Smallest enclosing spheres and Chernoff points in Bregman geometry}}, doi = {10.4230/LIPIcs.SoCG.2018.35}, volume = {99}, year = {2018}, }