TY - JOUR AB - Lymphatic endothelial cells (LECs) release extracellular chemokines to guide the migration of dendritic cells. In this study, we report that LECs also release basolateral exosome-rich endothelial vesicles (EEVs) that are secreted in greater numbers in the presence of inflammatory cytokines and accumulate in the perivascular stroma of small lymphatic vessels in human chronic inflammatory diseases. Proteomic analyses of EEV fractions identified > 1,700 cargo proteins and revealed a dominant motility-promoting protein signature. In vitro and ex vivo EEV fractions augmented cellular protrusion formation in a CX3CL1/fractalkine-dependent fashion and enhanced the directional migratory response of human dendritic cells along guidance cues. We conclude that perilymphatic LEC exosomes enhance exploratory behavior and thus promote directional migration of CX3CR1-expressing cells in complex tissue environments. AU - Brown, Markus AU - Johnson, Louise AU - Leone, Dario AU - Májek, Peter AU - Vaahtomeri, Kari AU - Senfter, Daniel AU - Bukosza, Nora AU - Schachner, Helga AU - Asfour, Gabriele AU - Langer, Brigitte AU - Hauschild, Robert AU - Parapatics, Katja AU - Hong, Young AU - Bennett, Keiryn AU - Kain, Renate AU - Detmar, Michael AU - Sixt, Michael K AU - Jackson, David AU - Kerjaschki, Dontscho ID - 275 IS - 6 JF - Journal of Cell Biology TI - Lymphatic exosomes promote dendritic cell migration along guidance cues VL - 217 ER - TY - JOUR AB - The angiosperm seed is composed of three genetically distinct tissues: the diploid embryo that originates from the fertilized egg cell, the triploid endosperm that is produced from the fertilized central cell, and the maternal sporophytic integuments that develop into the seed coat1. At the onset of embryo development in Arabidopsis thaliana, the zygote divides asymmetrically, producing a small apical embryonic cell and a larger basal cell that connects the embryo to the maternal tissue2. The coordinated and synchronous development of the embryo and the surrounding integuments, and the alignment of their growth axes, suggest communication between maternal tissues and the embryo. In contrast to animals, however, where a network of maternal factors that direct embryo patterning have been identified3,4, only a few maternal mutations have been described to affect embryo development in plants5–7. Early embryo patterning in Arabidopsis requires accumulation of the phytohormone auxin in the apical cell by directed transport from the suspensor8–10. However, the origin of this auxin has remained obscure. Here we investigate the source of auxin for early embryogenesis and provide evidence that the mother plant coordinates seed development by supplying auxin to the early embryo from the integuments of the ovule. We show that auxin response increases in ovules after fertilization, due to upregulated auxin biosynthesis in the integuments, and this maternally produced auxin is required for correct embryo development. AU - Robert, Hélène AU - Park, Chulmin AU - Gutièrrez, Carla AU - Wójcikowska, Barbara AU - Pěnčík, Aleš AU - Novák, Ondřej AU - Chen, Junyi AU - Grunewald, Wim AU - Dresselhaus, Thomas AU - Friml, Jirí AU - Laux, Thomas ID - 158 IS - 8 JF - Nature Plants TI - Maternal auxin supply contributes to early embryo patterning in Arabidopsis VL - 4 ER - TY - JOUR AB - Complex I has an essential role in ATP production by coupling electron transfer from NADH to quinone with translocation of protons across the inner mitochondrial membrane. Isolated complex I deficiency is a frequent cause of mitochondrial inherited diseases. Complex I has also been implicated in cancer, ageing, and neurodegenerative conditions. Until recently, the understanding of complex I deficiency on the molecular level was limited due to the lack of high-resolution structures of the enzyme. However, due to developments in single particle cryo-electron microscopy (cryo-EM), recent studies have reported nearly atomic resolution maps and models of mitochondrial complex I. These structures significantly add to our understanding of complex I mechanism and assembly. The disease-causing mutations are discussed here in their structural context. AU - Fiedorczuk, Karol AU - Sazanov, Leonid A ID - 152 IS - 10 JF - Trends in Cell Biology TI - Mammalian mitochondrial complex I structure and disease causing mutations VL - 28 ER - TY - CONF AB - A model of computation that is widely used in the formal analysis of reactive systems is symbolic algorithms. In this model the access to the input graph is restricted to consist of symbolic operations, which are expensive in comparison to the standard RAM operations. We give lower bounds on the number of symbolic operations for basic graph problems such as the computation of the strongly connected components and of the approximate diameter as well as for fundamental problems in model checking such as safety, liveness, and coliveness. Our lower bounds are linear in the number of vertices of the graph, even for constant-diameter graphs. For none of these problems lower bounds on the number of symbolic operations were known before. The lower bounds show an interesting separation of these problems from the reachability problem, which can be solved with O(D) symbolic operations, where D is the diameter of the graph. Additionally we present an approximation algorithm for the graph diameter which requires Õ(n/D) symbolic steps to achieve a (1 +ϵ)-approximation for any constant > 0. This compares to O(n/D) symbolic steps for the (naive) exact algorithm and O(D) symbolic steps for a 2-approximation. Finally we also give a refined analysis of the strongly connected components algorithms of [15], showing that it uses an optimal number of symbolic steps that is proportional to the sum of the diameters of the strongly connected components. AU - Chatterjee, Krishnendu AU - Dvorák, Wolfgang AU - Henzinger, Monika H AU - Loitzenbauer, Veronika ID - 310 TI - Lower bounds for symbolic computation on graphs: Strongly connected components, liveness, safety, and diameter ER - TY - JOUR AB - There has been significant interest recently in using complex quantum systems to create effective nonreciprocal dynamics. Proposals have been put forward for the realization of artificial magnetic fields for photons and phonons; experimental progress is fast making these proposals a reality. Much work has concentrated on the use of such systems for controlling the flow of signals, e.g., to create isolators or directional amplifiers for optical signals. In this Letter, we build on this work but move in a different direction. We develop the theory of and discuss a potential realization for the controllable flow of thermal noise in quantum systems. We demonstrate theoretically that the unidirectional flow of thermal noise is possible within quantum cascaded systems. Viewing an optomechanical platform as a cascaded system we show here that one can ultimately control the direction of the flow of thermal noise. By appropriately engineering the mechanical resonator, which acts as an artificial reservoir, the flow of thermal noise can be constrained to a desired direction, yielding a thermal rectifier. The proposed quantum thermal noise rectifier could potentially be used to develop devices such as a thermal modulator, a thermal router, and a thermal amplifier for nanoelectronic devices and superconducting circuits. AU - Barzanjeh, Shabir AU - Aquilina, Matteo AU - Xuereb, André ID - 436 IS - 6 JF - Physical Review Letters TI - Manipulating the flow of thermal noise in quantum devices VL - 120 ER -