Growth and Scaling during Development and Regeneration

Life presents fascinating examples of self-organization and emergent phenomena. In multi-cellular organisms, a multitude of cells interact to form and maintain highly complex body plans of well-defined size. In this thesis, we investigate theoretical feedback mechanisms for both self-organized body plan patterning and size control. The thesis is inspired by the astonishing scaling and regeneration abilities of flatworms. These worms can perfectly regrow their entire body plan even from tiny amputation fragments like the tip of the tail. Moreover, they can grow and actively de-grow by more than a factor of 40 in length depending on feeding conditions. These capabilities prompt for remarkable physical mechanisms of self-organized pattern formation and scaling. First, we explore the basic principles and challenges of pattern scaling in mechanisms previously proposed to describe biological pattern formation. Next, we present a novel class of patterning mechanisms yielding entirely self-organized and self-scaling patterns. This framework captures essential features of body plan regeneration and scaling in flatworms. Further, we analyze shape and motility of flatworms. By applying principal component analysis, we characterize shape dynamics during different motility modes and also identify shape variations between different flatworm species. Finally, we investigate the metabolic control of cell turnover and growth. We identify three mechanisms of metabolic energy storage; theoretical descriptions thereof can explain the measured organism growth by rules on the cellular scale. In a close collaboration with experimental biologists, we combine minimal theoretical descriptions with state-of-the-art experiments and data analysis. This allows us to identify generic principles of scalable body plan patterning and growth control in flatworms.Comment: PhD thesis, TU Dresden, German

Interaction of NO-sensitive guanylyl cyclase with Src-like kinases

Poster presentation NO-sensitive guanylyl cyclases (soluble guanylyl cyclase, sGC) are among the key regulators of intracellular cGMP concentration. The mechanisms underlying NO-mediated activation of sGC are quite well understood, however, little is known about the fine-tuning of sGC activity through alternative mechanisms such as protein phosphorylation. Several reports have demonstrated the reversible phosphorylation of sGC on serine/threonine residues, and it has been speculated, though not experimentally proven, that sGC might also be phosphorylated on tyrosine residues. Using broad-spectrum phosphatase inhibitors we were able to demonstrate tyrosine phosphorylation at Tyr192 of the beta 1 subunit of human sGC in COS1 cells. This residue forms part of a sequence segment (YEDL) representing a preferential binding site for SH2 domains of Src-like kinases. Pull-down assays and co-immunoprecipitation experiments showed that Src can indeed bind via its SH2 domain to pTyr192 of beta 1 indicating that tyrosine phosphorylation of sGC may be followed by recruitment of Src-like kinases to the phosphorylated beta 1 subunit. In support of this hypothesis, immunofluorescence studies showed a colocalization of overexpressed sGC and Src at the plasma membrane of COS1 and Hela cells. Together, our results point to an unexpected crosstalk between tyrosine kinase pathway(s) and the NO/cGMP signalling cascade which may result in translocation of the predominantly cytosolic sGC to the cytosolic face of the plasma membrane

Characterization of MRIP2 as a NO-sensitive guanylyl cyclase-associated protein

Poster presentation: NO-sensitive guanylyl cyclases (sGCs) are cytosolic receptors for nitric oxide (NO) catalyzing the conversion of GTP to cGMP. sGCs are obligate heterodimers composed of one alpha and beta subunit each. The allosteric mechanism of sGC activation via NO is well understood, however, our knowledge about alternative mechanisms such as protein-protein interactions regulating activity, availability, translocation and expression of sGC is rather limited. In a search by the yeast two-hybrid system using the catalytic domain of the alpha1 subunit as the bait, we have identified two structurally related proteins AGAP1 [1] and MRIP2 as novel sGC interacting proteins. MRIP2 is a multi-domain protein of 75 kDa comprising a single PH and ArfGAP domain each and two ankyrin repeats. Co-immunoprecipitation experiments using COS1 cells overexpressing both proteins demonstrated the interaction of MRIP2 with both subunits of the sGC alpha1beta1. Confocal microscopical analysis showed a prominent plasma membrane staining of MRIP2. This membrane association is mediated through an N-terminal myristoylation site and through binding of its PH domain to phospholipids such as phosphatidylinositol-3,5-bisphosphate (PI(3,5)P2). We hypothesize that MRIP2 may represent an acceptor protein for sGC that mediates recruitment of cytosolic sGC to the plasma membrane or other subcellular compartments

Hubble flow variations as a test for inhomogeneous cosmology

Context. Backreactions from large-scale inhomogeneities may provide an elegant explanation for the observed accelerated expansion of the universe without the need to introduce dark energy. Aims. We propose a cosmological test for a specific model of inhomogeneous cosmology, called timescape cosmology. Using large-scale galaxy surveys such as SDSS and 2MRS, we test the variation of expansion expected in the $\Lambda$-CDM model versus a more generic differential expansion using our own calibrations of bounds suggested by timescape cosmology. Method. Our test measures the systematic variations of the Hubble flow towards distant galaxies groups as a function of the matter distribution in the lines of sight to those galaxy groups. We compare the observed systematic variation of the Hubble flow to mock catalogues from the Millennium Simulation in the case of the $\Lambda$-CDM model, and a deformed version of the same simulation that exhibits more pronounced differential expansion. Results. We perform a series of statistical tests, ranging from linear regressions to Kolmogorov-Smirnov tests, on the obtained data. They consistently yield results preferring $\Lambda$-CDM cosmology over our approximated model of timescape cosmology. Conclusions. Our analysis of observational data shows no evidence that the variation of expansion differs from that of the standard $\Lambda$-CDM model.Comment: 20 pages, 21 figures, accepted for publication in A&

Electric quantum walks with individual atoms

We report on the experimental realization of electric quantum walks, which mimic the effect of an electric field on a charged particle in a lattice. Starting from a textbook implementation of discrete-time quantum walks, we introduce an extra operation in each step to implement the effect of the field. The recorded dynamics of such a quantum particle exhibits features closely related to Bloch oscillations and interband tunneling. In particular, we explore the regime of strong fields, demonstrating contrasting quantum behaviors: quantum resonances vs. dynamical localization depending on whether the accumulated Bloch phase is a rational or irrational fraction of 2\pi.Comment: 5 pages, 4 figure

Heavy-flavor observables at RHIC and LHC

We investigate the charm-quark propagation in the QGP media produced in ultrarelativistic heavy-ion collisions at RHIC and the LHC. Purely collisional and radiative processes lead to a significant suppression of final $D$-meson spectra at high transverse momentum and a finite flow of heavy quarks inside the fluid dynamical evolution of the light partons. The $D$-meson nuclear modification factor and the elliptic flow are studied at two collision energies. We further propose to measure the triangular flow of $D$ mesons, which we find to be nonzero in non-central collisions.Comment: Proceedings of the 24th Quark Matter conference, 19-24 May 2014, Darmstadt, Germany. 4 p

Shape mode analysis exposes movement patterns in biology: flagella and flatworms as case studies

We illustrate shape mode analysis as a simple, yet powerful technique to concisely describe complex biological shapes and their dynamics. We characterize undulatory bending waves of beating flagella and reconstruct a limit cycle of flagellar oscillations, paying particular attention to the periodicity of angular data. As a second example, we analyze non-convex boundary outlines of gliding flatworms, which allows us to expose stereotypic body postures that can be related to two different locomotion mechanisms. Further, shape mode analysis based on principal component analysis allows to discriminate different flatworm species, despite large motion-associated shape variability. Thus, complex shape dynamics is characterized by a small number of shape scores that change in time. We present this method using descriptive examples, explaining abstract mathematics in a graphic way.Comment: 20 pages, 6 figures, accepted for publication in PLoS On

Die Berücksichtigung der Gemeindefinanzen im Länderfinanzausgleich: Zwischen Verfassungsrecht und Ökonomie

Das Verfassungsrecht räumt dem Gesetzgeber für die einzelgesetzliche Umsetzung der Regelungen des Art. 107 Abs. 1 S. 4 GG und Art. 107 Abs. 2 S. 1 GG weite Definitions- und Gestaltungsspielräume ein, die erheblich weiter sind, als dies in der rechts- und finanzwissenschaftlichen Literatur häufig angenommen wird. Die Klagen von Bayern, Baden-Württemberg und Hessen geben keinen Anlaß, warum das Bundesverfassungsgericht bei dem jetzt anstehenden Urteil von dieser Rechtsprechung, die es zuletzt im Urteil des Jahres 1992 bestätigt hat, abweichen sollte. Die ökonomische Theorie will zu einer Objektivierung des politischen Handelns beitragen, indem sie sich für wissenschaftlich tragfähige Vorgaben für die Gewichtung der kommunalen Einwohnerzahl und die Einbeziehung der kommunalen Finanzkraft im LFA ausgesprochen hat. Damit soll präjudiziert werden, wie die politischen Entscheidungsträger die Handlungsspielräume auszufüllen haben, die ihnen das Grundgesetz und die Rechtsprechung des BVerfG einräumt. Einen so formulierten Anspruch auf wissenschaftliche Politikberatung kann die ökonomische Theorie jedoch nicht einlösen. Sowohl bzgl. der Einwohnerzahlwertung als auch bzgl. der Einbeziehung der kommunalen Finanzkraft lassen sich aus den verschiedenen Theorieansätzen keine eindeutigen, vom Gesetzgeber bedenkenlos verwertbaren Aussagen ableiten. --

Die Anreizwirkungen des Finanzausgleichs

Der durch die Solidarpaktgesetzgebung des Jahres 1993 neugeordnete Länderfinanzausgleich ist seit den Verfassungsklagen von Bayern und Baden- Württemberg Gegenstand öffentlicher Auseinandersetzungen geworden. Dabei stehen mögliche negative Anreizwirkungen des Finanzausgleichs im Mittelpunkt. Kann es einen anreizkompatiblen solidarischen Finanzausgleich geben? --