TY - JOUR
AB - Optogenetics and photopharmacology enable the spatio-temporal control of cell and animal behavior by light. Although red light offers deep-tissue penetration and minimal phototoxicity, very few red-light-sensitive optogenetic methods are currently available. We have now developed a red-light-induced homodimerization domain. We first showed that an optimized sensory domain of the cyanobacterial phytochrome 1 can be expressed robustly and without cytotoxicity in human cells. We then applied this domain to induce the dimerization of two receptor tyrosine kinases—the fibroblast growth factor receptor 1 and the neurotrophin receptor trkB. This new optogenetic method was then used to activate the MAPK/ERK pathway non-invasively in mammalian tissue and in multicolor cell-signaling experiments. The light-controlled dimerizer and red-light-activated receptor tyrosine kinases will prove useful to regulate a variety of cellular processes with light. Go deep with red: The sensory domain (S) of the cyanobacterial phytochrome 1 (CPH1) was repurposed to induce the homodimerization of proteins in living cells by red light. By using this domain, light-activated protein kinases were engineered that can be activated orthogonally from many fluorescent proteins and through mammalian tissue. Pr/Pfr=red-/far-red-absorbing state of CPH1.
AU - Gschaider-Reichhart, Eva
AU - Inglés Prieto, Álvaro
AU - Tichy, Alexandra-Madelaine
AU - Mckenzie, Catherine
AU - Janovjak, Harald L
ID - 1441
IS - 21
JF - Angewandte Chemie - International Edition
TI - A phytochrome sensory domain permits receptor activation by red light
VL - 55
ER -
TY - JOUR
AB - The accuracy of interdisciplinarity measurements is directly related to the quality of the underlying bibliographic data. Existing indicators of interdisciplinarity are not capable of reflecting the inaccuracies introduced by incorrect and incomplete records because correct and complete bibliographic data can rarely be obtained. This is the case for the Rao–Stirling index, which cannot handle references that are not categorized into disciplinary fields. We introduce a method that addresses this problem. It extends the Rao–Stirling index to acknowledge missing data by calculating its interval of uncertainty using computational optimization. The evaluation of our method indicates that the uncertainty interval is not only useful for estimating the inaccuracy of interdisciplinarity measurements, but it also delivers slightly more accurate aggregated interdisciplinarity measurements than the Rao–Stirling index.
AU - Calatrava Moreno, Maria
AU - Auzinger, Thomas
AU - Werthner, Hannes
ID - 1446
IS - 1
JF - Scientometrics
TI - On the uncertainty of interdisciplinarity measurements due to incomplete bibliographic data
VL - 107
ER -
TY - JOUR
AB - We develop a new and systematic method for proving entropic Ricci curvature lower bounds for Markov chains on discrete sets. Using different methods, such bounds have recently been obtained in several examples (e.g., 1-dimensional birth and death chains, product chains, Bernoulli–Laplace models, and random transposition models). However, a general method to obtain discrete Ricci bounds had been lacking. Our method covers all of the examples above. In addition we obtain new Ricci curvature bounds for zero-range processes on the complete graph. The method is inspired by recent work of Caputo, Dai Pra and Posta on discrete functional inequalities.
AU - Fathi, Max
AU - Maas, Jan
ID - 1448
IS - 3
JF - The Annals of Applied Probability
TI - Entropic Ricci curvature bounds for discrete interacting systems
VL - 26
ER -
TY - JOUR
AB - The actin cytoskeleton plays important roles in the formation and internalization of endocytic vesicles. In yeast, endocytic vesicles move towards early endosomes along actin cables, however, the molecular machinery regulating interaction between endocytic vesicles and actin cables is poorly understood. The Eps15-like protein Pan1p plays a key role in actin-mediated endocytosis and is negatively regulated by Ark1 and Prk1 kinases. Here we show that pan1 mutated to prevent phosphorylation at all 18 threonines, pan1-18TA, displayed almost the same endocytic defect as ark1Δ prk1Δ cells, and contained abnormal actin concentrations including several endocytic compartments. Early endosomes were highly localized in the actin concentrations and displayed movement along actin cables. The dephosphorylated form of Pan1p also caused stable associations between endocytic vesicles and actin cables, and between endocytic vesicles and endosomes. Thus Pan1 phosphorylation is part of a novel mechanism that regulates endocytic compartment interactions with each other and with actin cables.
AU - Toshima, Junko
AU - Furuya, Eri
AU - Nagano, Makoto
AU - Kanno, Chisa
AU - Sakamoto, Yuta
AU - Ebihara, Masashi
AU - Siekhaus, Daria E
AU - Toshima, Jiro
ID - 1475
IS - February 2016
JF - eLife
TI - Yeast Eps15-like endocytic protein Pan1p regulates the interaction between endocytic vesicles, endosomes and the actin cytoskeleton
VL - 5
ER -
TY - JOUR
AB - The dynamic assembly and disassembly of actin filaments is essential for the formation and transport of vesicles during endocytosis. In yeast, two types of actin structures, namely cortical patches and cytoplasmic cables, play a direct role in endocytosis, but how their interaction is regulated remains unclear. Here, we show that Srv2/CAP, an evolutionarily conserved actin regulator, is required for efficient endocytosis owing to its role in the formation of the actin patches that aid initial vesicle invagination and of the actin cables that these move along. Deletion of the SRV2 gene resulted in the appearance of aberrant fragmented actin cables that frequently moved past actin patches, the sites of endocytosis. We find that the C-terminal CARP domain of Srv2p is vitally important for the proper assembly of actin patches and cables; we also demonstrate that the N-terminal helical folded domain of Srv2 is required for its localization to actin patches, specifically to the ADP-actin rich region through an interaction with cofilin. These results demonstrate the in vivo roles of Srv2p in the regulation of the actin cytoskeleton during clathrin-mediated endocytosis
AU - Toshima, Junko
AU - Horikomi, Chika
AU - Okada, Asuka
AU - Hatori, Makiko
AU - Nagano, Makoto
AU - Masuda, Atsushi
AU - Yamamoto, Wataru
AU - Siekhaus, Daria E
AU - Toshima, Jiro
ID - 1476
IS - 2
JF - Journal of Cell Science
TI - Srv2/CAP is required for polarized actin cable assembly and patch internalization during clathrin-mediated endocytosis
VL - 129
ER -
TY - JOUR
AB - We consider partially observable Markov decision processes (POMDPs) with ω-regular conditions specified as parity objectives. The class of ω-regular languages provides a robust specification language to express properties in verification, and parity objectives are canonical forms to express them. The qualitative analysis problem given a POMDP and a parity objective asks whether there is a strategy to ensure that the objective is satisfied with probability 1 (resp. positive probability). While the qualitative analysis problems are undecidable even for special cases of parity objectives, we establish decidability (with optimal complexity) for POMDPs with all parity objectives under finite-memory strategies. We establish optimal (exponential) memory bounds and EXPTIME-completeness of the qualitative analysis problems under finite-memory strategies for POMDPs with parity objectives. We also present a practical approach, where we design heuristics to deal with the exponential complexity, and have applied our implementation on a number of POMDP examples.
AU - Chatterjee, Krishnendu
AU - Chmelik, Martin
AU - Tracol, Mathieu
ID - 1477
IS - 5
JF - Journal of Computer and System Sciences
TI - What is decidable about partially observable Markov decision processes with ω-regular objectives
VL - 82
ER -
TY - JOUR
AB - We consider the Tonks-Girardeau gas subject to a random external potential. If the disorder is such that the underlying one-particle Hamiltonian displays localization (which is known to be generically the case), we show that there is exponential decay of correlations in the many-body eigenstates. Moreover, there is no Bose-Einstein condensation and no superfluidity, even at zero temperature.
AU - Seiringer, Robert
AU - Warzel, Simone
ID - 1478
IS - 3
JF - New Journal of Physics
TI - Decay of correlations and absence of superfluidity in the disordered Tonks-Girardeau gas
VL - 18
ER -
TY - JOUR
AB - Most entropy notions H(.) like Shannon or min-entropy satisfy a chain rule stating that for random variables X,Z, and A we have H(X|Z,A)≥H(X|Z)−|A|. That is, by conditioning on A the entropy of X can decrease by at most the bitlength |A| of A. Such chain rules are known to hold for some computational entropy notions like Yao’s and unpredictability-entropy. For HILL entropy, the computational analogue of min-entropy, the chain rule is of special interest and has found many applications, including leakage-resilient cryptography, deterministic encryption, and memory delegation. These applications rely on restricted special cases of the chain rule. Whether the chain rule for conditional HILL entropy holds in general was an open problem for which we give a strong negative answer: we construct joint distributions (X,Z,A), where A is a distribution over a single bit, such that the HILL entropy H HILL (X|Z) is large but H HILL (X|Z,A) is basically zero.
Our counterexample just makes the minimal assumption that NP⊈P/poly. Under the stronger assumption that injective one-way function exist, we can make all the distributions efficiently samplable.
Finally, we show that some more sophisticated cryptographic objects like lossy functions can be used to sample a distribution constituting a counterexample to the chain rule making only a single invocation to the underlying object.
AU - Krenn, Stephan
AU - Pietrzak, Krzysztof Z
AU - Wadia, Akshay
AU - Wichs, Daniel
ID - 1479
IS - 3
JF - Computational Complexity
TI - A counterexample to the chain rule for conditional HILL entropy
VL - 25
ER -
TY - JOUR
AB - Exponential varieties arise from exponential families in statistics. These real algebraic varieties have strong positivity and convexity properties, familiar from toric varieties and their moment maps. Among them are varieties of inverses of symmetric matrices satisfying linear constraints. This class includes Gaussian graphical models. We develop a general theory of exponential varieties. These are derived from hyperbolic polynomials and their integral representations. We compare the multidegrees and ML degrees of the gradient map for hyperbolic polynomials.
AU - Michałek, Mateusz
AU - Sturmfels, Bernd
AU - Uhler, Caroline
AU - Zwiernik, Piotr
ID - 1480
IS - 1
JF - Proceedings of the London Mathematical Society
TI - Exponential varieties
VL - 112
ER -
TY - JOUR
AB - Plants have the ability to continously generate new organs by maintaining populations of stem cells throught their lives. The shoot apical meristem (SAM) provides a stable environment for the maintenance of stem cells. All cells inside the SAM divide, yet boundaries and patterns are maintained. Experimental evidence indicates that patterning is independent of cell lineage, thus a dynamic self-regulatory mechanism is required. A pivotal role in the organization of the SAM is played by the WUSCHEL gene (WUS). An important question in this regard is that how WUS expression is positioned in the SAM via a cell-lineage independent signaling mechanism. In this study we demonstrate via mathematical modeling that a combination of an inhibitor of the Cytokinin (CK) receptor, Arabidopsis histidine kinase 4 (AHK4) and two morphogens originating from the top cell layer, can plausibly account for the cell lineage-independent centering of WUS expression within SAM. Furthermore, our laser ablation and microsurgical experiments support the hypothesis that patterning in SAM occurs at the level of CK reception and signaling. The model suggests that the interplay between CK signaling, WUS/CLV feedback loop and boundary signals can account for positioning of the WUS expression, and provides directions for further experimental investigation.
AU - Adibi, Milad
AU - Yoshida, Saiko
AU - Weijers, Dolf
AU - Fleck, Christian
ID - 1482
IS - 2
JF - PLoS One
TI - Centering the organizing center in the Arabidopsis thaliana shoot apical meristem by a combination of cytokinin signaling and self-organization
VL - 11
ER -