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A phytochrome sensory domain permits receptor activation by red light
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
Yeast Eps15-like endocytic protein Pan1p regulates the interaction between endocytic vesicles, endosomes and the actin cytoskeleton
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
A practical method for high-resolution embedded liquid surfaces
Combining high-resolution level set surface tracking with lower resolution physics is an inexpensive method for achieving highly detailed liquid animations. Unfortunately, the inherent resolution mismatch introduces several types of disturbing visual artifacts. We identify the primary sources of these artifacts and present simple, efficient, and practical solutions to address them. First, we propose an unconditionally stable filtering method that selectively removes sub-grid surface artifacts not seen by the fluid physics, while preserving fine detail in dynamic splashing regions. It provides comparable results to recent error-correction techniques at lower cost, without substepping, and with better scaling behavior. Second, we show how a modified narrow-band scheme can ensure accurate free surface boundary conditions in the presence of large resolution mismatches. Our scheme preserves the efficiency of the narrow-band methodology, while eliminating objectionable stairstep artifacts observed in prior work. Third, we demonstrate that the use of linear interpolation of velocity during advection of the high-resolution level set surface is responsible for visible grid-aligned kinks; we therefore advocate higher-order velocity interpolation, and show that it dramatically reduces this artifact. While these three contributions are orthogonal, our results demonstrate that taken together they efficiently address the dominant sources of visual artifacts arising with high-resolution embedded liquid surfaces; the proposed approach offers improved visual quality, a straightforward implementation, and substantially greater scalability than competing methods
Dissipative preparation of antiferromagnetic order in the Fermi-Hubbard model
The Fermi-Hubbard model is one of the key models of condensed matter physics, which holds a
potential for explaining the mystery of high-temperature superconductivity. Recent progress in
ultracold atoms in optical lattices has paved the way to studying the model's phase diagram using
the tools of quantum simulation, which emerged as a promising alternative to the numerical
calculations plagued by the infamous sign problem. However, the temperatures achieved using
elaborate laser cooling protocols so far have been too high to show the appearance of
antiferromagnetic (AF) and superconducting quantum phases directly. In this work, we demonstrate
that using the machinery of dissipative quantum state engineering, one can observe the emergence of
the AF order in the Fermi-Hubbard model with fermions in optical lattices. The core of the approach
is to add incoherent laser scattering in such a way that the AF state emerges as the dark state of
the driven-dissipative dynamics. The proposed controlled dissipation channels described in this work
are straightforward to add to already existing experimental setups
Activity dependent plasticity of hippocampal place maps
Hippocampal neurons encode a cognitive map of space. These maps are thought to be updated during learning and in response to changes in the environment through activity-dependent synaptic plasticity. Here we examine how changes in activity influence spatial coding in rats using halorhodopsin-mediated, spatially selective optogenetic silencing. Halorhoposin stimulation leads to light-induced suppression in many place cells and interneurons; some place cells increase their firing through disinhibition, whereas some show no effect. We find that place fields of the unaffected subpopulation remain stable. On the other hand, place fields of suppressed place cells were unstable, showing remapping across sessions before and after optogenetic inhibition. Disinhibited place cells had stable maps but sustained an elevated firing rate. These findings suggest that place representation in the hippocampus is constantly governed by activity-dependent processes, and that disinhibition may provide a mechanism for rate remapping
Infinite-dimensional calculus under weak spatial regularity of the processes
Two generalizations of Itô formula to infinite-dimensional spaces are given.
The first one, in Hilbert spaces, extends the classical one by taking advantage of
cancellations when they occur in examples and it is applied to the case of a group
generator. The second one, based on the previous one and a limit procedure, is an Itô
formula in a special class of Banach spaces having a product structure with the noise
in a Hilbert component; again the key point is the extension due to a cancellation. This
extension to Banach spaces and in particular the specific cancellation are motivated
by path-dependent Itô calculus
Asymmetric power boosts extortion in an economic experiment
Direct reciprocity is a major mechanism for the evolution of cooperation. Several classical studies have suggested that humans should quickly learn to adopt reciprocal strategies to establish mutual cooperation in repeated interactions. On the other hand, the recently discovered theory of ZD strategies has found that subjects who use extortionate strategies are able to exploit and subdue cooperators. Although such extortioners have been predicted to succeed in any population of adaptive opponents, theoretical follow-up studies questioned whether extortion can evolve in reality. However, most of these studies presumed that individuals have similar strategic possibilities and comparable outside options, whereas asymmetries are ubiquitous in real world applications. Here we show with a model and an economic experiment that extortionate strategies readily emerge once subjects differ in their strategic power. Our experiment combines a repeated social dilemma with asymmetric partner choice. In our main treatment there is one randomly chosen group member who is unilaterally allowed to exchange one of the other group members after every ten rounds of the social dilemma. We find that this asymmetric replacement opportunity generally promotes cooperation, but often the resulting payoff distribution reflects the underlying power structure. Almost half of the subjects in a better strategic position turn into extortioners, who quickly proceed to exploit their peers. By adapting their cooperation probabilities consistent with ZD theory, extortioners force their co-players to cooperate without being similarly cooperative themselves. Comparison to non-extortionate players under the same conditions indicates a substantial net gain to extortion. Our results thus highlight how power asymmetries can endanger mutually beneficial interactions, and transform them into exploitative relationships. In particular, our results indicate that the extortionate strategies predicted from ZD theory could play a more prominent role in our daily interactions than previously thought
Conditionally optimal algorithms for generalized Büchi Games
Games on graphs provide the appropriate framework to study several central problems in computer science, such as verification and synthesis of reactive systems. One of the most basic objectives for games on graphs is the liveness (or Büchi) objective that given a target set of vertices requires that some vertex in the target set is visited infinitely often. We study generalized Büchi objectives (i.e., conjunction of liveness objectives), and implications between two generalized Büchi objectives (known as GR(1) objectives), that arise in numerous applications in computer-aided verification. We present improved algorithms and conditional super-linear lower bounds based on widely believed assumptions about the complexity of (A1) combinatorial Boolean matrix multiplication and (A2) CNF-SAT. We consider graph games with n vertices, m edges, and generalized Büchi objectives with k conjunctions. First, we present an algorithm with running time O(k*n^2), improving the previously known O(k*n*m) and O(k^2*n^2) worst-case bounds. Our algorithm is optimal for dense graphs under (A1). Second, we show that the basic algorithm for the problem is optimal for sparse graphs when the target sets have constant size under (A2). Finally, we consider GR(1) objectives, with k_1 conjunctions in the antecedent and k_2 conjunctions in the consequent, and present an O(k_1 k_2 n^{2.5})-time algorithm, improving the previously known O(k_1*k_2*n*m)-time algorithm for m > n^{1.5}
Environmental and endogenous control of cortical microtubule orientation
Plant growth requires a tight coordination of cell shape and anisotropic expansion. Owing to their immobility, plant cells determine body architecture through the orientation of cell division and cell expansion. Microtubule cytoskeleton represents a versatile cellular structure essential for coordinating flexible cell morphogenesis. Previous studies have identified a large number of microtubule-associated regulators that control microtubule dynamics; however, the mechanisms by which microtubule reorientation responds to exogenous and environmental stimuli are largely unknown. In this review, we describe the molecular details of microtubule dynamics that are required for cortical microtubule array pattern formation, and recapitulate current knowledge on the mechanisms by which various environmental and endogenous stimuli control cortical microtubule reorientation. Microtubule reorientation requires the activity of microtubule-associated proteins, including regulators of microtubule nucleation, severing, polymerization (and depolymerization), bundling, and interactions with cellulose microfilaments.Predominant cortical microtubule orientations determine plant cell morphology and the direction of organ outgrowth.In response to endogenous and environmental signals, cortical microtubules reorient and form various array patterns
Cytokinins influence root gravitropism via differential regulation of auxin transporter expression and localization in Arabidopsis
Redirection of intercellular auxin fluxes via relocalization of the PIN-FORMED 3 (PIN3) and PIN7 auxin efflux carriers has been suggested to be necessary for the root gravitropic response. Cytokinins have also been proposed to play a role in controlling root gravitropism, but conclusive evidence is lacking. We present a detailed study of the dynamics of root bending early after gravistimulation, which revealed a delayed gravitropic response in transgenic lines with depleted endogenous cytokinins (Pro35S:AtCKX) and cytokinin signaling mutants. Pro35S:AtCKX lines, as well as a cytokinin receptor mutant ahk3, showed aberrations in the auxin response distribution in columella cells consistent with defects in the auxin transport machinery. Using in vivo real-time imaging of PIN3-GFP and PIN7-GFP in AtCKX3 overexpression and ahk3 backgrounds, we observed wild-type-like relocalization of PIN proteins in the columella early after gravistimulation, with gravity-induced relocalization of PIN7 faster than that of PIN3. Nonetheless, the cellular distribution of PIN3 and PIN7 and expression of PIN7 and the auxin influx carrier AUX1 was affected in AtCKX overexpression lines. Based on the retained cytokinin sensitivity in pin3 pin4 pin7 mutant, we propose the AUX1-mediated auxin transport rather than columella-located PIN proteins as a target of endogenous cytokinins in the control of root gravitropism