@article{514, abstract = {Orientation in space is represented in specialized brain circuits. Persistent head direction signals are transmitted from anterior thalamus to the presubiculum, but the identity of the presubicular target neurons, their connectivity and function in local microcircuits are unknown. Here, we examine how thalamic afferents recruit presubicular principal neurons and Martinotti interneurons, and the ensuing synaptic interactions between these cells. Pyramidal neuron activation of Martinotti cells in superficial layers is strongly facilitating such that high-frequency head directional stimulation efficiently unmutes synaptic excitation. Martinotti-cell feedback plays a dual role: precisely timed spikes may not inhibit the firing of in-tune head direction cells, while exerting lateral inhibition. Autonomous attractor dynamics emerge from a modelled network implementing wiring motifs and timing sensitive synaptic interactions in the pyramidal - Martinotti-cell feedback loop. This inhibitory microcircuit is therefore tuned to refine and maintain head direction information in the presubiculum.}, author = {Simonnet, Jean and Nassar, Mérie and Stella, Federico and Cohen, Ivan and Mathon, Bertrand and Boccara, Charlotte and Miles, Richard and Fricker, Desdemona}, issn = {20411723}, journal = {Nature Communications}, publisher = {Nature Publishing Group}, title = {{Activity dependent feedback inhibition may maintain head direction signals in mouse presubiculum}}, doi = {10.1038/ncomms16032}, volume = {8}, year = {2017}, } @article{515, abstract = {The oxidative phosphorylation electron transport chain (OXPHOS-ETC) of the inner mitochondrial membrane is composed of five large protein complexes, named CI-CV. These complexes convert energy from the food we eat into ATP, a small molecule used to power a multitude of essential reactions throughout the cell. OXPHOS-ETC complexes are organized into supercomplexes (SCs) of defined stoichiometry: CI forms a supercomplex with CIII2 and CIV (SC I+III2+IV, known as the respirasome), as well as with CIII2 alone (SC I+III2). CIII2 forms a supercomplex with CIV (SC III2+IV) and CV forms dimers (CV2). Recent cryo-EM studies have revealed the structures of SC I+III2+IV and SC I+III2. Furthermore, recent work has shed light on the assembly and function of the SCs. Here we review and compare these recent studies and discuss how they have advanced our understanding of mitochondrial electron transport.}, author = {Letts, James A and Sazanov, Leonid A}, issn = {15459993}, journal = {Nature Structural and Molecular Biology}, number = {10}, pages = {800 -- 808}, publisher = {Nature Publishing Group}, title = {{Clarifying the supercomplex: The higher-order organization of the mitochondrial electron transport chain}}, doi = {10.1038/nsmb.3460}, volume = {24}, year = {2017}, } @article{513, abstract = {We present an experimental setup that creates a shear flow with zero mean advection velocity achieved by counterbalancing the nonzero streamwise pressure gradient by moving boundaries, which generates plane Couette-Poiseuille flow. We obtain experimental results in the transitional regime for this flow. Using flow visualization, we characterize the subcritical transition to turbulence in Couette-Poiseuille flow and show the existence of turbulent spots generated by a permanent perturbation. Due to the zero mean advection velocity of the base profile, these turbulent structures are nearly stationary. We distinguish two regions of the turbulent spot: the active turbulent core, which is characterized by waviness of the streaks similar to traveling waves, and the surrounding region, which includes in addition the weak undisturbed streaks and oblique waves at the laminar-turbulent interface. We also study the dependence of the size of these two regions on Reynolds number. Finally, we show that the traveling waves move in the downstream (Poiseuille) direction.}, author = {Klotz, Lukasz and Lemoult, Grégoire M and Frontczak, Idalia and Tuckerman, Laurette and Wesfreid, José}, journal = {Physical Review Fluids}, number = {4}, publisher = {American Physical Society}, title = {{Couette-Poiseuille flow experiment with zero mean advection velocity: Subcritical transition to turbulence}}, doi = {10.1103/PhysRevFluids.2.043904}, volume = {2}, year = {2017}, } @article{520, abstract = {Cyanobacteria are mostly engineered to be sustainable cell-factories by genetic manipulations alone. Here, by modulating the concentration of allosteric effectors, we focus on increasing product formation without further burdening the cells with increased expression of enzymes. Resorting to a novel 96-well microplate cultivation system for cyanobacteria, and using lactate-producing strains of Synechocystis PCC6803 expressing different l-lactate dehydrogenases (LDH), we titrated the effect of 2,5-anhydro-mannitol supplementation. The latter acts in cells as a nonmetabolizable analogue of fructose 1,6-bisphosphate, a known allosteric regulator of one of the tested LDHs. In this strain (SAA023), we achieved over 2-fold increase of lactate productivity. Furthermore, we observed that as carbon is increasingly deviated during growth toward product formation, there is an increased fixation rate in the population of spontaneous mutants harboring an impaired production pathway. This is a challenge in the development of green cell factories, which may be countered by the incorporation in biotechnological processes of strategies such as the one pioneered here.}, author = {Du, Wei and Angermayr, Andreas and Jongbloets, Joeri and Molenaar, Douwe and Bachmann, Herwig and Hellingwerf, Klaas and Branco Dos Santos, Filipe}, issn = {21615063}, journal = {ACS Synthetic Biology}, number = {3}, pages = {395 -- 401}, publisher = {American Chemical Society}, title = {{Nonhierarchical flux regulation exposes the fitness burden associated with lactate production in Synechocystis sp. PCC6803}}, doi = {10.1021/acssynbio.6b00235}, volume = {6}, year = {2017}, } @article{521, abstract = {Let X and Y be proper metric spaces. We show that a coarsely n-to-1 map f:X→Y induces an n-to-1 map of Higson coronas. This viewpoint turns out to be successful in showing that the classical dimension raising theorems hold in large scale; that is, if f:X→Y is a coarsely n-to-1 map between proper metric spaces X and Y then asdim(Y)≤asdim(X)+n−1. Furthermore we introduce coarsely open coarsely n-to-1 maps, which include the natural quotient maps via a finite group action, and prove that they preserve the asymptotic dimension.}, author = {Austin, Kyle and Virk, Ziga}, issn = {01668641}, journal = {Topology and its Applications}, pages = {45 -- 57}, publisher = {Elsevier}, title = {{Higson compactification and dimension raising}}, doi = {10.1016/j.topol.2016.10.005}, volume = {215}, year = {2017}, } @article{534, abstract = {We investigate the complexity of finding an embedded non-orientable surface of Euler genus g in a triangulated 3-manifold. This problem occurs both as a natural question in low-dimensional topology, and as a first non-trivial instance of embeddability of complexes into 3-manifolds. We prove that the problem is NP-hard, thus adding to the relatively few hardness results that are currently known in 3-manifold topology. In addition, we show that the problem lies in NP when the Euler genus g is odd, and we give an explicit algorithm in this case.}, author = {Burton, Benjamin and De Mesmay, Arnaud N and Wagner, Uli}, issn = {01795376}, journal = {Discrete & Computational Geometry}, number = {4}, pages = {871 -- 888}, publisher = {Springer}, title = {{Finding non-orientable surfaces in 3-Manifolds}}, doi = {10.1007/s00454-017-9900-0}, volume = {58}, year = {2017}, } @article{538, abstract = {Optogenetik und Photopharmakologie ermöglichen präzise räumliche und zeitliche Kontrolle von Proteinwechselwirkung und -funktion in Zellen und Tieren. Optogenetische Methoden, die auf grünes Licht ansprechen und zum Trennen von Proteinkomplexen geeignet sind, sind nichtweitläufig verfügbar, würden jedoch mehrfarbige Experimente zur Beantwortung von biologischen Fragestellungen ermöglichen. Hier demonstrieren wir die Verwendung von Cobalamin(Vitamin B12)-bindenden Domänen von bakteriellen CarH-Transkriptionsfaktoren zur Grünlicht-induzierten Dissoziation von Rezeptoren. Fusioniert mit dem Fibroblasten-W achstumsfaktor-Rezeptor 1 führten diese im Dunkeln in kultivierten Zellen zu Signalaktivität durch Oligomerisierung, welche durch Beleuchten umgehend aufgehoben wurde. In Zebrafischembryonen, die einen derartigen Rezeptor exprimieren, ermöglichte grünes Licht die Kontrolle über abnormale Signalaktivität während der Embryonalentwicklung. }, author = {Kainrath, Stephanie and Stadler, Manuela and Gschaider-Reichhart, Eva and Distel, Martin and Janovjak, Harald L}, journal = {Angewandte Chemie}, number = {16}, pages = {4679 -- 4682}, publisher = {Wiley}, title = {{Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen}}, doi = {10.1002/ange.201611998}, volume = {129}, year = {2017}, } @article{540, abstract = {RNA-dependent RNA polymerases (RdRps) play a key role in the life cycle of RNA viruses and impact their immunobiology. The arenavirus lymphocytic choriomeningitis virus (LCMV) strain Clone 13 provides a benchmark model for studying chronic infection. A major genetic determinant for its ability to persist maps to a single amino acid exchange in the viral L protein, which exhibits RdRp activity, yet its functional consequences remain elusive. To unravel the L protein interactions with the host proteome, we engineered infectious L protein-tagged LCMV virions by reverse genetics. A subsequent mass-spectrometric analysis of L protein pulldowns from infected human cells revealed a comprehensive network of interacting host proteins. The obtained LCMV L protein interactome was bioinformatically integrated with known host protein interactors of RdRps from other RNA viruses, emphasizing interconnected modules of human proteins. Functional characterization of selected interactors highlighted proviral (DDX3X) as well as antiviral (NKRF, TRIM21) host factors. To corroborate these findings, we infected Trim21-/-mice with LCMV and found impaired virus control in chronic infection. These results provide insights into the complex interactions of the arenavirus LCMV and other viral RdRps with the host proteome and contribute to a better molecular understanding of how chronic viruses interact with their host.}, author = {Khamina, Kseniya and Lercher, Alexander and Caldera, Michael and Schliehe, Christopher and Vilagos, Bojan and Sahin, Mehmet and Kosack, Lindsay and Bhattacharya, Anannya and Májek, Peter and Stukalov, Alexey and Sacco, Roberto and James, Leo and Pinschewer, Daniel and Bennett, Keiryn and Menche, Jörg and Bergthaler, Andreas}, issn = {15537366}, journal = {PLoS Pathogens}, number = {12}, publisher = {Public Library of Science}, title = {{Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein}}, doi = {10.1371/journal.ppat.1006758}, volume = {13}, year = {2017}, } @article{466, abstract = {We consider Markov decision processes (MDPs) with multiple limit-average (or mean-payoff) objectives. There exist two different views: (i) the expectation semantics, where the goal is to optimize the expected mean-payoff objective, and (ii) the satisfaction semantics, where the goal is to maximize the probability of runs such that the mean-payoff value stays above a given vector. We consider optimization with respect to both objectives at once, thus unifying the existing semantics. Precisely, the goal is to optimize the expectation while ensuring the satisfaction constraint. Our problem captures the notion of optimization with respect to strategies that are risk-averse (i.e., ensure certain probabilistic guarantee). Our main results are as follows: First, we present algorithms for the decision problems which are always polynomial in the size of the MDP. We also show that an approximation of the Pareto-curve can be computed in time polynomial in the size of the MDP, and the approximation factor, but exponential in the number of dimensions. Second, we present a complete characterization of the strategy complexity (in terms of memory bounds and randomization) required to solve our problem. }, author = {Chatterjee, Krishnendu and Křetínská, Zuzana and Kretinsky, Jan}, issn = {18605974}, journal = {Logical Methods in Computer Science}, number = {2}, publisher = {International Federation of Computational Logic}, title = {{Unifying two views on multiple mean-payoff objectives in Markov decision processes}}, doi = {10.23638/LMCS-13(2:15)2017}, volume = {13}, year = {2017}, } @article{467, abstract = {Recently there has been a significant effort to handle quantitative properties in formal verification and synthesis. While weighted automata over finite and infinite words provide a natural and flexible framework to express quantitative properties, perhaps surprisingly, some basic system properties such as average response time cannot be expressed using weighted automata or in any other known decidable formalism. In this work, we introduce nested weighted automata as a natural extension of weighted automata, which makes it possible to express important quantitative properties such as average response time. In nested weighted automata, a master automaton spins off and collects results from weighted slave automata, each of which computes a quantity along a finite portion of an infinite word. Nested weighted automata can be viewed as the quantitative analogue of monitor automata, which are used in runtime verification. We establish an almost-complete decidability picture for the basic decision problems about nested weighted automata and illustrate their applicability in several domains. In particular, nested weighted automata can be used to decide average response time properties.}, author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Otop, Jan}, issn = {15293785}, journal = {ACM Transactions on Computational Logic (TOCL)}, number = {4}, publisher = {ACM}, title = {{Nested weighted automata}}, doi = {10.1145/3152769}, volume = {18}, year = {2017}, }