IST Austria Thesis

The development and growth of Arabidopsis thaliana is regulated by a combination of genetic programing and also by the environmental influences. An important role in these processes play the phytohormones and among them, auxin is crucial as it controls many important functions. It is transported through the whole plant body by creating local and temporal concentration maxima and minima, which have an impact on the cell status, tissue and organ identity. Auxin has the property to undergo a directional and finely regulated cell-to-cell transport, which is enabled by the transport proteins, localized on the plasma membrane. An important role in this process have the PIN auxin efflux proteins, which have an asymmetric/polar subcellular localization and determine the directionality of the auxin transport. During the last years, there were significant advances in understanding how the trafficking molecular machineries function, including studies on molecular interactions, function, subcellular localization and intracellular distribution. However, there is still a lack of detailed characterization on the steps of endocytosis, exocytosis, endocytic recycling and degradation. Due to this fact, I focused on the identification of novel trafficking factors and better characterization of the intracellular trafficking pathways. My PhD thesis consists of an introductory chapter, three experimental chapters, a chapter containing general discussion, conclusions and perspectives and also an appendix chapter with published collaborative papers. The first chapter is separated in two different parts: I start by a general introduction to auxin biology and then I introduce the trafficking pathways in the model plant Arabidopsis thaliana. Then, I explain also the phosphorylation-signals for polar targeting and also the roles of the phytohormone strigolactone. The second chapter includes the characterization of bar1/sacsin mutant, which was identified in a forward genetic screen for novel trafficking components in Arabidopsis thaliana, where by the implementation of an EMS-treated pPIN1::PIN1-GFP marker line and by using the established inhibitor of ARF-GEFs, Brefeldin A (BFA) as a tool to study trafficking processes, we identified a novel factor, which is mediating the adaptation of the plant cell to ARF-GEF inhibition. The mutation is in a previously uncharacterized gene, encoding a very big protein that we, based on its homologies, called SACSIN with domains suggesting roles as a molecular chaperon or as a component of the ubiquitin-proteasome system. Our physiology and imaging studies revealed that SACSIN is a crucial plant cell component of the adaptation to the ARF-GEF inhibition. The third chapter includes six subchapters, where I focus on the role of the phytohormone strigolactone, which interferes with auxin feedback on PIN internalization. Strigolactone moderates the polar auxin transport by increasing the internalization of the PIN auxin efflux carriers, which reduces the canalization related growth responses. In addition, I also studied the role of phosphorylation in the strigolactone regulation of auxin feedback on PIN internalization. In this chapter I also present my results on the MAX2-dependence of strigolactone-mediated root growth inhibition and I also share my results on the auxin metabolomics profiling after application of GR24. In the fourth chapter I studied the effect of two small molecules ES-9 and ES9-17, which were identified from a collection of small molecules with the property to impair the clathrin-mediated endocytosis. In the fifth chapter, I discuss all my observations and experimental findings and suggest alternative hypothesis to interpret my results. In the appendix there are three collaborative published projects. In the first, I participated in the characterization of the role of ES9 as a small molecule, which is inhibitor of clathrin- mediated endocytosis in different model organisms. In the second paper, I contributed to the characterization of another small molecule ES9-17, which is a non-protonophoric analog of ES9 and also impairs the clathrin-mediated endocytosis not only in plant cells, but also in mammalian HeLa cells. Last but not least, I also attach another paper, where I tried to establish the grafting method as a technique in our lab to study canalization related processes

A Review of Frailty Syndrome and Its Physical, Cognitive and Emotional Domains in the Elderly

Peer reviewedPublisher PD

Optimizing Electrode Configuration for Electrical Impedance Measurements of Muscle via the Finite Element Method

Electrical impedance myography (EIM) is a technique for the evaluation of neuromuscular diseases, including amyotrophic lateral sclerosis and muscular dystrophy. In this study, we evaluated how alterations in the size and conductivity of muscle and thickness of subcutaneous fat impact the EIM data, with the aim of identifying an optimized electrode configuration for EIM measurements. Finite element models were developed for the human upper arm based on anatomic data; material properties of the tissues were obtained from rat and published sources. The developed model matched the frequency-dependent character of the data. Of the three major EIM parameters, resistance, reactance, and phase, the reactance was least susceptible to alterations in the subcutaneous fat thickness, regardless of electrode arrangement. For example, a quadrupling of fat thickness resulted in a 375% increase in resistance at 35 kHz but only a 29% reduction in reactance. By further optimizing the electrode configuration, the change in reactance could be reduced to just 0.25%. For a fixed 30 mm distance between the sense electrodes centered between the excitation electrodes, an 80 mm distance between the excitation electrodes was found to provide the best balance, with a less than 1% change in reactance despite a doubling of subcutaneous fat thickness or halving of muscle size. These analyses describe a basic approach for further electrode configuration optimization for EIM

The Cultural Contours of Democracy: Indigenous Epistemologies Informing South African Citizenship

Drawing upon the African concept of ubuntu, this article examines the epistemic orientations toward individual-society relations that inform democratic citizenship and identity in South Africa. Findings from focus group interviews conducted with 50 Xhosa teachers from all seven primary and intermediate schools in a township outside Cape Town depict the cultural contours of democracy and how the teachers reaffirm and question the dominant Western-oriented democratic narrative. Through ubuntu, defined as the virtue of being human premised upon respect, the Xhosa teachers interrupt the prevailing rights-and-responsibilities discourse to interpose a conception of democracy based on rights, responsibilities, and respect. Society and schools, in their view, fall short in educating young learners for democratic citizenship in South Africa; their insights offer ways for formal schooling to improve upon its democratic mission

Inverse seesaw mechanism, leptogenesis, observable proton decay, and Δ<SUB>R</SUB><SUP>±±</SUP> in supersymmetric SO(10) with heavy W<SUB>R</SUB>

We explore the prospects of low-scale leptogenesis in a class of supersymmetric SO(10) models using extra singlet neutrinos (Ti, i=1, 2, 3) and the Higgs representations 126H&#8853; 126&#x0305;H as well as 16H&#8853;16&#x0305;H. A singlet neutrino, which we show can be as light as 105-106 GeV, decays through its small mixings with right-handed (RH) neutrinos creating a lepton asymmetry which is explicitly shown to be flavor dependent. While the doublet vacuum expectation value in 16&#x0305;H triggers the generation of desired mixings, it also induces a large RH-triplet vacuum expectation value that breaks the left-right intermediate gauge symmetry and gives large right-handed neutrino masses. Manifest unification of gauge couplings and generation of heavy RH neutrino masses are achieved by purely renormalizable interactions. The canonical (Type-I) seesaw contributions to the light neutrino mass matrix cancel out while the Type-II seesaw contribution is negligible. Determining the parameters of the dominant inverse seesaw formula by using the underlying quark-lepton symmetry and neutrino oscillation data, we show how leptogenesis under the gravitino constraint is successfully implemented. New formulas for the decay rate and the asymmetry parameter are derived leading to baryon asymmetry within the observed range without invoking a resonant condition on RH neutrinos. The model is found to work for hierarchical as well as inverted hierarchical light neutrino masses. Testable predictions of the model are RH doubly charged Higgs bosons which may be leptophilic and accessible to the Tevatron, LHC or a linear collider. In a model-independent manner, the Drell-Yan pair production cross section at the Tevatron or LHC is shown to be bounded between 59%-79% of their left-handed counterparts with same mass. In contrast to single-step breaking supersymmetric grand unified theories, which predict a long proton lifetime for the decay p&#8594;e+&#960;0, here this lifetime is substantially reduced, bringing it within one order of the current experimental limit

Type II Seesaw Dominance in Non-supersymmetric and Split Susy SO(10) and Proton Life Time

Recently type II seesaw dominance in a supersymmetric SO(10) framework has been found useful in explaining large solar and atmospheric mixing angles as well as larger values of $theta_{13}$ while unifying quark and lepton masses. An important question in these models is whether there exists consistency between coupling unification and type II seesaw dominance. Scenarios where this consistency can be demonstrated have been given in a SUSY framework. In this paper we give examples where type II dominance occurs in SO(10) models without supersymmetry but with additional TeV scale particles and also in models with split-supersummetry. Grand unification is realized in a two-step process via breaking of SO(10) to SU(5) and then to a TeV scale standard model supplemented by extra fields and an SU(5) Higgs multiplet ${15}_H$ at a scale about $10^{12}$ GeV to give type-II seesaw. The predictions for proton lifetime in these models are in the range $\tau_p^0 = 2\times 10^{35}$ yrs. to $\tau_p^0 = 6\times 10^{35}$ yrs.. A number of recent numerical fits to GUT-scale fermion masses can be accommodated within this model.Comment: 7 pages LaTeX, 3 figures, related areas: hep-ex, hep-th, astro-ph; Reference added, typo corrected, version to appear in Physical Review

Entrainment and Control of Bacterial Populations: An in Silico Study over a Spatially Extended Agent Based Model

This is the author accepted manuscript. The final version is available from American Chemical Society via the DOI in this record.We extend a spatially explicit agent based model (ABM) developed previously to investigate entrainment and control of the emergent behavior of a population of synchronized oscillating cells in a microfluidic chamber. Unlike most of the work in models of control of cellular systems which focus on temporal changes, we model individual cells with spatial dependencies which may contribute to certain behavioral responses. We use the model to investigate the response of both open loop and closed loop strategies, such as proportional control (P-control), proportional-integral control (PI-control) and proportional-integral-derivative control (PID-control), to heterogeinities and growth in the cell population, variations of the control parameters and spatial effects such as diffusion in the spatially explicit setting of a microfluidic chamber setup. We show that, as expected from the theory of phase locking in dynamical systems, open loop control can only entrain the cell population in a subset of forcing periods, with a wide variety of dynamical behaviors obtained outside these regions of entrainment. Closed-loop control is shown instead to guarantee entrainment in a much wider region of control parameter space although presenting limitations when the population size increases over a certain threshold. In silico tracking experiments are also performed to validate the ability of classical control approaches to achieve other reference behaviors such as a desired constant output or a linearly varying one. All simulations are carried out in BSim, an advanced agent-based simulator of microbial population which is here extended ad hoc to include the effects of control strategies acting onto the population.The authors declare no competing interests. We thank Dr. Nigel J. Savery at the University of Bristol for useful discussions around the subject of GRNs and for his help in developing the original ABM model. We also wish to thank Dr Gianfranco Fiore at the University of Bristol and the anonymous reviewers for reading the revised manuscript carefully and providing insightful comments that led to a consistent revision of the original manuscript. P.M. was supported by EPSRC Grant EP/E501214/1 and K.T.-A. by EPSRC Grant EP/I018638/1. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. This work was carried out using the computational facilities of the Advanced Computing Research Centre, University of Bristol, http://www.bris.ac.uk/acrc/