Neuronal basis for directed walking in Drosophila melanogaster

Insekten zeigen eine bemerkenswerte Anpassungsfähigkeit und Flexibilität in ihrem Laufverhalten. Die Mechanismen motorischer Kontrolle und die Funktionsweise von „central pattern generators“ sind vergleichsweise gut erforscht. Sehr wenig ist jedoch bekannt darüber, wie neuronale Zentren höherer Ordnung motorische Schaltkreise kontrollieren, zielgerichtetes Laufverhalten steuern und die Laufrichtung bestimmen. Ziel der vorliegenden Arbeit war es, mit Hilfe genetischer Methoden in Drosophila Komponenten diese neuronalen Zentren höherer Ordnung zu identifizieren und zu untersuchen. In der erste Hälfte der Arbeit wird die Erstellung einer Bibliothek von „enhancer tile“ GAL4 Linien beschrieben, mit der spezifische Neuronengruppen im Drosophila Nervensystem manipuliert werden können. Diese Sammlung von GAL4 Linien wurde mit Aktivierungs- und Deaktivierungsscreens getestet, um Neuronen zu identifizieren, deren Aktivität Einfluss auf die Laufrichtung der Fliege hat. Gruppen von Neuronen wurden mit dem thermosensitiven Kationenkanal dTrpA1 aktiviert bzw.mit Tetanustoxin (TNT) deaktiviert. In den beiden Screens wurden mehrere, zum Teil überlappende GAL4 Linien identifiziert, die nach der jeweiligen Manipulation Veränderungen in der Laufrichtung aufweisen, während die Laufkoordination oder die Laufgeschwindigkeit unbeeinträchtigt ist. Besonderes Interesse galt im Weiteren solchen GAL4 Linien, die Neuronen markierten, deren Aktivierung Rückwärtslaufen herbeiführt oder deren Deaktivierung Rückwärtslaufen verhindert. Mit Hilfe von intersektioneller genetischer Methoden und stochastischer Markierung von Zellen war es in der Tat möglich, solche spezifischen Neuronenklassen zu identifizieren und zu untersuchen. Im letzten Teil der Arbeit wurde der gesamte Datensatz des Deaktivierungsscreens systematisch analysiert, was eine wichtige Grundlage dafür legte, weitere Neuronen zu finden, die eine Rolle für den Vorwärts- und Rückwärtslauf spielen. In der vorliegenden Arbeit konnten Komponenten neuronaler Zentren höherer Ordnung identifiziert werden, die Einfluss auf die Laufrichtung haben. Letzteres eröffnet neue Möglichkeiten, den neuronalen Schaltkreis für die umfassende Kontrolle des Laufverhaltens in Drosophila melanogaster mit zellulärer Auflösung zu entschlüsseln und funktional zu charakterisieren.Insects show remarkable adaptability and flexibility in their walking behavior. Although considerable progress has been made in understanding the mechanisms of motor control and central pattern generators, very little is known about how higher order neuronal centers control these motor circuits to determine the walking direction. The objective of the current work was to exploit the power of Drosophila genetics in order to identify these higher order neuronal centers. The first part of this work focused on generation of an enhancer GAL4 library which would enable targeting small populations of neurons in the Drosophila melanogaster nervous system. This GAL4 library was used to conduct screens for flies in which walking direction is altered upon activation or silencing of specific neurons. These screens employ either the thermosensitive cation channel dTrpA1 or tetanus toxin light chain (TNT), respectively, which are expressed in subsets of neurons using the enhancer GAL4 lines. Several GAL4 lines have been identified in each screen, some in both, that result in altered walking direction without a dramatic effect on the coordination or pace of walking. Further work was focused on lines that label neurons which on activation induce backward walking, and on silencing abolish backward walking. Using intersectional genetics and stochastic labeling approaches, it was possible to pinpoint specific neurons involved in backward directed walking. The last part of the work focused on systematically analyzing behavioral data from the silencing screen and resulted in providing a foundation for finding additional neurons involved in backward and forward directed walking. Thus, in this project, potential higher order neurons responsible for directional control of walking could be identified. These studies provide an entry point into mapping and ultimately characterizing the neuronal circuitry responsible for higher order control of walking behavior in Drosophila melanogaster

Analyzing the effects of surface distribution of pores in cell electroporation for a cell membrane containing cholesterol

This paper presents a model and numerical analysis (simulations) of transmembrane potential induced in biological cell membrane under the influence of externally applied electric field (i.e., electroporation). This model differs from the established models of electroporation in two distinct ways. Firstly, it incorporates the presence of cholesterol (~20% mole-fraction) in biological membrane. Secondly, it considers the distribution of pores as a function of the variation of transmembrane potential from one region of the cell to another. Formulation is based on the role of membrane tension and electrical forces in the formation of pores in a cell membrane, which is considered as an infinitesimally thin insulator. The model has been used to explore the process of creation and evolution of pores and to determine the number and size of pores as a function of applied electric field (magnitude and duration). Results show that the presence of cholesterol enhances poration by changing the membrane tension. Analyses indicate that the number of pores and average pore radii differ significantly from one part of the cell to the other. While some regions of the cell membrane undergo rapid and dense poration, others remain unaffected. The method can be a useful tool for a more realistic prediction of pore formation in cells subjected to electroporation.Comment: 11 pages, 3 figures. v2: added new references, grammatical changes, corrected typo

Fluctuation-Driven Neural Dynamics Reproduce Drosophila Locomotor Patterns.

The neural mechanisms determining the timing of even simple actions, such as when to walk or rest, are largely mysterious. One intriguing, but untested, hypothesis posits a role for ongoing activity fluctuations in neurons of central action selection circuits that drive animal behavior from moment to moment. To examine how fluctuating activity can contribute to action timing, we paired high-resolution measurements of freely walking Drosophila melanogaster with data-driven neural network modeling and dynamical systems analysis. We generated fluctuation-driven network models whose outputs-locomotor bouts-matched those measured from sensory-deprived Drosophila. From these models, we identified those that could also reproduce a second, unrelated dataset: the complex time-course of odor-evoked walking for genetically diverse Drosophila strains. Dynamical models that best reproduced both Drosophila basal and odor-evoked locomotor patterns exhibited specific characteristics. First, ongoing fluctuations were required. In a stochastic resonance-like manner, these fluctuations allowed neural activity to escape stable equilibria and to exceed a threshold for locomotion. Second, odor-induced shifts of equilibria in these models caused a depression in locomotor frequency following olfactory stimulation. Our models predict that activity fluctuations in action selection circuits cause behavioral output to more closely match sensory drive and may therefore enhance navigation in complex sensory environments. Together these data reveal how simple neural dynamics, when coupled with activity fluctuations, can give rise to complex patterns of animal behavior

Tropologies of Indianness in Anglophone Colonial and Postcolonial South Asian Fiction

While previous studies have explored the literary representation of "India" as a place, a colony, or a modern nation-state, this dissertation focuses on the idea of Indianess as a civilizational essence within the field of Anglophone colonial and postcolonial South Asian fiction. The central finding of this project is that Indianness is often imagined in fiction through a system of recurrent tropes. These tropes include the Neo-Vedantic concept of metaphysical oneness (brahman); the centripetal dynamics of Sanskritization; the ontological modes of "impersonal" being; the Hegelian allegory of "History"; and most importantly, the rhetoric of caste subjectivity (varna). The use of these tropes in fiction reveals a critical disassociation with contemporary grand narratives of "India" as a postcolonial nation-state as well as the fascist Hindutva ideology of purified Hindu-ness. For these reasons, this project uses the term "Indutva" to classify the unique tropologies of Indianness within colonial and postcolonial South Asian literature. The primary texts of this study are E. M. Forster's A Passage to India (1924), Raja Rao's The Serpent and the Rope (1960), and Arundhati Roy's The God of Small Things (1997). In Passage, Forster illustrates his idea of Indianness through the rituals of the Gokul Ashtami festival, its Brahminical agents of varnic order and its heterotopic confrontations with History. In Serpent, Indianness is explored through the marital crises of Rao's Brahminical protagonist and the symbolic rebirth of varnic Indianness in post-imperial Europe. Finally, in Small Things, Roy engages an allegorical, counter-Indutva critique of civilizational Indianness, as represented by the "History" of violence against lower-caste "Untouchables." This study of Indianness in fiction is grounded in a historical and theoretical framework that takes late eighteenth-century British Orientalism as a starting point for the modernity of Indianness, and it also draws on Sanskrit and vernacular Indian discourses of religion, caste, and metaphysics. The methodology of this project thus draws equally from postcolonial and pre-colonial sources.Ph.D.2016-11-30 00:00:0

Studies on the chlorination of zircon: Part I. Static bed investigations

Carbochlorination is an important unit operation in the processing of zirconium resources. In the article, the use of different reducing agents in zircon chlorination, to produce zirconium tetrachloride, has been examined on thermodynamic and other considerations. While numerous workers have investigated zircon chlorination, a literature survey shows that there is a wide variation in the reported effect of various process parameters on the chlorination rate and a wide scatter in the values for kinetic parameters such as order of reaction, activation energy, rate constant as also the rate law expression. This work is an extensive study on zircon chlorination and the article discusses the effect of process parameters such as charge particle size, gas and solid composition, gas flow rate, temperature, reaction duration, etc, on the chlorination rate, over a much wider range of the parameter values. During investigations in the static bed chlorinator, it was noticed that the initial rate and the total extent of chlorination are proportional to the exposed surface of the solid zircon-coke charge but independent of the depth or amount of the charge. Further, the stalled chlorination could be reactivated by remixing the solid charge. Also, while the reaction rate in general increased as the charge became finer, the effect of zircon particle size was much more predominant. The activation energy value for the chlorination showed a wide variation with other operating conditions. Likewise, the order of reaction with respect to chlorine decreased from two to zero as the chlorine concentration in the gaseous atmosphere increased. Interestingly, the chlorination rate initially increased with gas flow rate, then decreased, before finally becoming independent of the gas flow rate. Results also indicated that there is an optimum charge composition that yields the maximum chlorination rate and the article discusses the effect of the zircon to coke particle number ratio in the initial charge on the chlorination kinetics. With the help of these observations, it is possible to explain the wide variation in the reported effect of the various process parameters on zircon chlorination

Peritonsillar abscess drainage: using oropharyngeal endoscopy as a therapeutic adjunct and training tool.

BACKGROUND Peritonsillar abscess, or quinsy, is one of the most common emergency presentations to ENT departments, and is the most common deep tissue infection of the head and neck. In the UK, junior members of the ENT team are regularly required to independently assess, diagnose and treat patients with peritonsillar aspiration or incision and drainage. ISSUE Inexperienced practitioners can stumble at several obstacles: poor access due to trismus; poor lighting; difficulty in learning the therapeutic procedure; and difficulty in accurately documenting findings and treatment. SOLUTION To counter these and other difficulties, the authors describe the routine use of video endoscopy as a training tool and therapeutic adjunct in the management of quinsy

Kinetic studies on the chlorination of zircon

This paper reports on an investigation on the zircon chlorination process. The chlorination was conducted (i) with static zircon-coke powder mixtures in horizontal and vertical reactors, (ii) with zircon-coke mixed powder compacts in the two reactors, and (iii) with a sintered zircon disc and a grooved carbon disc. Experiments with the zircon and carbon discs clearly revealed that physical contact between zircon and coke was mandatory for the chlorination to occur. It was also observed that a faster chlorination rate and a higher extent of chlorination with static charge were achieved if the charge was compacted prior to chlorination. This was explained as being due to the formation of fine zircon and coke particles in intimate contact with each other. Due to the complexity of zircon carbo-chlorination, system specific rate expressions have been proposed. For a loose charge in a horizontal static bed reactor, the rate expression was linear, while for a compacted (and crumbled) zircon-coke mixture held in a vertical pipe reactor the reduced time plots technique was used to arrive at the rate expression, which turned out to be the Ginstling-Brounshtein expression

Six-legged walking in insects: how CPGs, peripheral feedback, and descending signals generate coordinated and adaptive motor rhythms

Walking is a rhythmic locomotor behavior of legged animals, and its underlying mechanisms have been the subject of neurobiological research for more than 100 years. In this article, we review relevant historical aspects and contemporary studies in this field of research with a particular focus on the role of central pattern generating networks (CPGs) and their contribution to the generation of six-legged walking in insects. Aspects of importance are the generation of single-leg stepping, the generation of interleg coordination, and how descending signals influence walking. We first review how CPGs interact with sensory signals from the leg in the generation of leg stepping. Next, we summarize how these interactions are modified in the generation of motor flexibility for forward and backward walking, curve walking, and speed changes. We then review the present state of knowledge with regard to the role of CPGs in intersegmental coordination and how CPGs might be involved in mediating descending influences from the brain for the initiation, maintenance, modification, and cessation of the motor output for walking. Throughout, we aim to specifically address gaps in knowledge, and we describe potential future avenues and approaches, conceptual and methodological, with the latter emphasizing in particular options arising from the advent of neurogenetic approaches to this field of research and its combination with traditional approaches