TY - DATA
AB - The data stored here is used in Murat Tugrul's PhD thesis (Chapter 3), which is related to the evolution of bacterial RNA polymerase binding.
Magdalena Steinrueck (PhD Student in Calin Guet's group at IST Austria) performed the experiments and created the data on de novo promoter evolution. Fabienne Jesse (PhD Student in Jon Bollback's group at IST Austria) performed the experiments and created the data on lac promoter evolution.
AU - Tugrul, Murat
ID - 5554
KW - RNAP binding
KW - de novo promoter evolution
KW - lac promoter
TI - Experimental Data for Binding Site Evolution of Bacterial RNA Polymerase
ER -
TY - THES
AU - Morri, Maurizio
ID - 1124
TI - Optical functionalization of human class A orphan G-protein coupled receptors
ER -
TY - JOUR
AB - Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping with other neurological conditions. We previously described abnormalities in the branched-chain amino acid (BCAA) catabolic pathway as a cause of ASD. Here, we show that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter localized at the blood brain barrier (BBB), has an essential role in maintaining normal levels of brain BCAAs. In mice, deletion of Slc7a5 from the endothelial cells of the BBB leads to atypical brain amino acid profile, abnormal mRNA translation, and severe neurological abnormalities. Furthermore, we identified several patients with autistic traits and motor delay carrying deleterious homozygous mutations in the SLC7A5 gene. Finally, we demonstrate that BCAA intracerebroventricular administration ameliorates abnormal behaviors in adult mutant mice. Our data elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for the BCAA in human brain function.
AU - Tarlungeanu, Dora-Clara
AU - Deliu, Elena
AU - Dotter, Christoph
AU - Kara, Majdi
AU - Janiesch, Philipp
AU - Scalise, Mariafrancesca
AU - Galluccio, Michele
AU - Tesulov, Mateja
AU - Morelli, Emanuela
AU - Sönmez, Fatma
AU - Bilgüvar, Kaya
AU - Ohgaki, Ryuichi
AU - Kanai, Yoshikatsu
AU - Johansen, Anide
AU - Esharif, Seham
AU - Ben Omran, Tawfeg
AU - Topcu, Meral
AU - Schlessinger, Avner
AU - Indiveri, Cesare
AU - Duncan, Kent
AU - Caglayan, Ahmet
AU - Günel, Murat
AU - Gleeson, Joseph
AU - Novarino, Gaia
ID - 1183
IS - 6
JF - Cell
TI - Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder
VL - 167
ER -
TY - JOUR
AB - Most migrating cells extrude their front by the force of actin polymerization. Polymerization requires an initial nucleation step, which is mediated by factors establishing either parallel filaments in the case of filopodia or branched filaments that form the branched lamellipodial network. Branches are considered essential for regular cell motility and are initiated by the Arp2/3 complex, which in turn is activated by nucleation-promoting factors of the WASP and WAVE families. Here we employed rapid amoeboid crawling leukocytes and found that deletion of the WAVE complex eliminated actin branching and thus lamellipodia formation. The cells were left with parallel filaments at the leading edge, which translated, depending on the differentiation status of the cell, into a unipolar pointed cell shape or cells with multiple filopodia. Remarkably, unipolar cells migrated with increased speed and enormous directional persistence, while they were unable to turn towards chemotactic gradients. Cells with multiple filopodia retained chemotactic activity but their migration was progressively impaired with increasing geometrical complexity of the extracellular environment. These findings establish that diversified leading edge protrusions serve as explorative structures while they slow down actual locomotion.
AU - Leithner, Alexander F
AU - Eichner, Alexander
AU - Müller, Jan
AU - Reversat, Anne
AU - Brown, Markus
AU - Schwarz, Jan
AU - Merrin, Jack
AU - De Gorter, David
AU - Schur, Florian
AU - Bayerl, Jonathan
AU - De Vries, Ingrid
AU - Wieser, Stefan
AU - Hauschild, Robert
AU - Lai, Frank
AU - Moser, Markus
AU - Kerjaschki, Dontscho
AU - Rottner, Klemens
AU - Small, Victor
AU - Stradal, Theresia
AU - Sixt, Michael K
ID - 1321
JF - Nature Cell Biology
TI - Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes
VL - 18
ER -
TY - JOUR
AB - During metazoan development, the temporal pattern of morphogen signaling is critical for organizing cell fates in space and time. Yet, tools for temporally controlling morphogen signaling within the embryo are still scarce. Here, we developed a photoactivatable Nodal receptor to determine how the temporal pattern of Nodal signaling affects cell fate specification during zebrafish gastrulation. By using this receptor to manipulate the duration of Nodal signaling in vivo by light, we show that extended Nodal signaling within the organizer promotes prechordal plate specification and suppresses endoderm differentiation. Endoderm differentiation is suppressed by extended Nodal signaling inducing expression of the transcriptional repressor goosecoid (gsc) in prechordal plate progenitors, which in turn restrains Nodal signaling from upregulating the endoderm differentiation gene sox17 within these cells. Thus, optogenetic manipulation of Nodal signaling identifies a critical role of Nodal signaling duration for organizer cell fate specification during gastrulation.
AU - Sako, Keisuke
AU - Pradhan, Saurabh
AU - Barone, Vanessa
AU - Inglés Prieto, Álvaro
AU - Mueller, Patrick
AU - Ruprecht, Verena
AU - Capek, Daniel
AU - Galande, Sanjeev
AU - Janovjak, Harald L
AU - Heisenberg, Carl-Philipp J
ID - 1100
IS - 3
JF - Cell Reports
TI - Optogenetic control of nodal signaling reveals a temporal pattern of nodal signaling regulating cell fate specification during gastrulation
VL - 16
ER -
TY - CONF
AB - We study algorithmic questions for concurrent systems where the transitions are labeled from a complete, closed semiring, and path properties are algebraic with semiring operations. The algebraic path properties can model dataflow analysis problems, the shortest path problem, and many other natural problems that arise in program analysis. We consider that each component of the concurrent system is a graph with constant treewidth, a property satisfied by the controlflow graphs of most programs. We allow for multiple possible queries, which arise naturally in demand driven dataflow analysis. The study of multiple queries allows us to consider the tradeoff between the resource usage of the one-time preprocessing and for each individual query. The traditional approach constructs the product graph of all components and applies the best-known graph algorithm on the product. In this approach, even the answer to a single query requires the transitive closure (i.e., the results of all possible queries), which provides no room for tradeoff between preprocessing and query time. Our main contributions are algorithms that significantly improve the worst-case running time of the traditional approach, and provide various tradeoffs depending on the number of queries. For example, in a concurrent system of two components, the traditional approach requires hexic time in the worst case for answering one query as well as computing the transitive closure, whereas we show that with one-time preprocessing in almost cubic time, each subsequent query can be answered in at most linear time, and even the transitive closure can be computed in almost quartic time. Furthermore, we establish conditional optimality results showing that the worst-case running time of our algorithms cannot be improved without achieving major breakthroughs in graph algorithms (i.e., improving the worst-case bound for the shortest path problem in general graphs). Preliminary experimental results show that our algorithms perform favorably on several benchmarks.
AU - Chatterjee, Krishnendu
AU - Goharshady, Amir
AU - Ibsen-Jensen, Rasmus
AU - Pavlogiannis, Andreas
ID - 1437
TI - Algorithms for algebraic path properties in concurrent systems of constant treewidth components
VL - 20-22
ER -
TY - CONF
AB - We consider nondeterministic probabilistic programs with the most basic liveness property of termination. We present efficient methods for termination analysis of nondeterministic probabilistic programs with polynomial guards and assignments. Our approach is through synthesis of polynomial ranking supermartingales, that on one hand significantly generalizes linear ranking supermartingales and on the other hand is a counterpart of polynomial ranking-functions for proving termination of nonprobabilistic programs. The approach synthesizes polynomial ranking-supermartingales through Positivstellensatz's, yielding an efficient method which is not only sound, but also semi-complete over a large subclass of programs. We show experimental results to demonstrate that our approach can handle several classical programs with complex polynomial guards and assignments, and can synthesize efficient quadratic ranking-supermartingales when a linear one does not exist even for simple affine programs.
AU - Chatterjee, Krishnendu
AU - Fu, Hongfei
AU - Goharshady, Amir
ID - 1386
TI - Termination analysis of probabilistic programs through Positivstellensatz's
VL - 9779
ER -
TY - JOUR
AB - A class of valued constraint satisfaction problems (VCSPs) is characterised by a valued constraint language, a fixed set of cost functions on a finite domain. Finite-valued constraint languages contain functions that take on rational costs and general-valued constraint languages contain functions that take on rational or infinite costs. An instance of the problem is specified by a sum of functions from the language with the goal to minimise the sum. This framework includes and generalises well-studied constraint satisfaction problems (CSPs) and maximum constraint satisfaction problems (Max-CSPs).
Our main result is a precise algebraic characterisation of valued constraint languages whose instances can be solved exactly by the basic linear programming relaxation (BLP). For a general-valued constraint language Γ, BLP is a decision procedure for Γ if and only if Γ admits a symmetric fractional polymorphism of every arity. For a finite-valued constraint language Γ, BLP is a decision procedure if and only if Γ admits a symmetric fractional polymorphism of some arity, or equivalently, if Γ admits a symmetric fractional polymorphism of arity 2.
Using these results, we obtain tractability of several novel and previously widely-open classes of VCSPs, including problems over valued constraint languages that are: (1) submodular on arbitrary lattices; (2) bisubmodular (also known as k-submodular) on arbitrary finite domains; (3) weakly (and hence strongly) tree-submodular on arbitrary trees.
AU - Kolmogorov, Vladimir
AU - Thapper, Johan
AU - Živný, Stanislav
ID - 2271
IS - 1
JF - SIAM Journal on Computing
TI - The power of linear programming for general-valued CSPs
VL - 44
ER -
TY - JOUR
AB - We show that a non-singular integral form of degree d is soluble over the integers if and only if it is soluble over ℝ and over ℚp for all primes p, provided that the form has at least (d - 1/2 √d)2d variables. This improves on a longstanding result of Birch.
AU - Timothy Browning
AU - Prendiville, Sean M
ID - 256
IS - 731
JF - Journal fur die Reine und Angewandte Mathematik
TI - Improvements in Birch's theorem on forms in many variables
VL - 2017
ER -
TY - JOUR
AB - For suitable pairs of diagonal quadratic forms in eight variables we use the circle method to investigate the density of simultaneous integer solutions and relate this to the problem of estimating linear correlations among sums of two squares.
AU - Timothy Browning
AU - Munshi, Ritabrata
ID - 257
IS - 4
JF - Forum Mathematicum
TI - Pairs of diagonal quadratic forms and linear correlations among sums of two squares
VL - 27
ER -