Characterization of YisK, a Cell Shape Modifier and Enzyme in Bacillus subtilis

Bacterial growth and division requires the careful coordination of peptidoglycan (PG) synthesis and PG hydrolysis, allowing the insertion of new cell wall material at sites of active growth. In many rod-shaped bacteria, the bacterial actin homolog MreB is thought to coordinate this balance of synthesis and hydrolysis, particularly during cell elongation, and the current model is that MreB-like proteins act as a scaffold, directing the PG synthesis machinery to sites of active growth. Despite their importance, very little is known about how MreB-like proteins in prokaryotes are regulated. Using a Bacillus subtilis misexpression screen, we identified yisK and yodL, which cause a loss of cell shape and viability when misexpressed. Suppressors resistant to YisK’s killing activity primarily occur in mbl (the structural gene for an MreB paralog in B. subtilis), while suppressors resistant to YodL’s activity primarily occur in MreB. Consistent with the idea that YisK targets Mbl activity and YodL targets MreB activity, deletion of mbl confers resistance to YisK, while deletion of MreB confers resistance to YodL. In an mbl deletion background, YisK expressing cells also become 20% shorter, suggesting that YisK activity affects at least one other target integral to cell shape. Using a bacterial 2-hybrid assay, we detected an interaction between YisK and FtsE (the ATPase of the ABC Transporter FtsEX). Interestingly, published data indicates that FtsEX, which is important for regulating the activity of the D,L-endopeptidase CwlO, appears to act in the same pathway as Mbl, and both ftsE and cwlO mutants exhibit short-cell phenotypes. Our data suggest that ftsE is required for YisK-dependent cell shortening, but not cell widening. YisK shows ~40% amino acid identity to an FAH from Mycobacterium abcsessus, and we have obtained a preliminary crystal structure for YisK, with a dicarboxylic acid, most likely L-tartrate, bound in the active site. Surprisingly, introducing mutations in YisK’s active site has no effect on its ability to perturb cell shape. Our current model is that YisK is an enzyme, possibly involved in the dicarboxylate pathway, that utilizes interactions with Mbl and possibly FtsE to localize its enzymatic activity to specific regions within the cell

swMATH - a new information service for mathematical software

An information service for mathematical software is presented. Publications and software are two closely connected facets of mathematical knowledge. This relation can be used to identify mathematical software and find relevant information about it. The approach and the state of the art of the information service are described here.Comment: see also: http://www.swmath.or

Computer-Assisted Lighting Design and Control

This dissertation shows that computer-based lighting control systems can support the lighting design process considerably better than traditional consoles. It describes the Lula Project, a new software package for lighting design and control, that implements this level of support. Lula's focus is on the conceptual ideas behind a lighting design rather than the concrete lighting fixtures used to put it on stage. Among the innovative aspects of the system are its model for designing static lighting looks and its subsystem for programmable continuous animated lighting. Lula's application design is centered around the idea of componential lighting design that allows the user to express a lighting design as a hierarchy of components. Lula is a result of the rigorous application of high-level software engineering techniques and implementation technology from the general realm of functional programming. The high-level structure of the application rests upon stratified design, algebraic modelling, and domain-specific languages. Among the implementation techniques instrumental to Lula are automatic memory management, higher-order programming, functional data structures, data-directed programming, parametric inheritance, and concurrent programming.Computer-basierte Systeme für Beleuchtungssteuerung sind in der Lage, den Lichtdesigner weitaus besser zu unterstützen als es derzeit marktübliche Steuerkonsolen tun. Das Thema dieser Dissertation ist ein solches System, das Projekt Lula. Lula ist eine neue Software für Lichtregie und Beleuchtungssteuerung, welche die Modellierung der konzeptuellen Elemente eines Lichtdesigns ermöglicht, unabhängig von der konkreten Realisierung auf der Bühne. Unter den innovativen Aspekten des Systems ist das Modell für den Entwurf statischer Beleuchtungsszenen sowie das Subsystem für programmierbare, stetig animierte Beleuchtung. Das übergeordnete Prinzip bei Lula ist komponentenbasierte Lichtregie, die es dem Benutzer erlaubt, ein Lichtdesign als eine Hierarchie von Komponenten auszudrücken. Lula ist das Resultat konsequenter Anwendung von Entwurfs- und Implementierungs-Techniken aus dem Bereich der funktionalen Programmierung. Die High-Level-Struktur des Systems baut auf stratifiziertes Design, algebraische Modellierung und anwendungsspezifische Programmiersprachen. Unter den Implementationstechniken, die entscheidend bei der Entwicklung von Lula waren, befinden sich automatische Speicherverwaltung, Higher-Order-Programmierung, funktionale Datenstrukturen, datengesteuerte Programmierung, parametrische Vererbung und nebenläufige Programmierung

Characterization of YisK, a Cell Shape Modifier and Enzyme in Bacillus subtilis

Bacterial growth and division requires the careful coordination of peptidoglycan (PG) synthesis and PG hydrolysis, allowing the insertion of new cell wall material at sites of active growth. In many rod-shaped bacteria, the bacterial actin homolog MreB is thought to coordinate this balance of synthesis and hydrolysis, particularly during cell elongation, and the current model is that MreB-like proteins act as a scaffold, directing the PG synthesis machinery to sites of active growth. Despite their importance, very little is known about how MreB-like proteins in prokaryotes are regulated. Using a Bacillus subtilis misexpression screen, we identified yisK and yodL, which cause a loss of cell shape and viability when misexpressed. Suppressors resistant to YisK’s killing activity primarily occur in mbl (the structural gene for an MreB paralog in B. subtilis), while suppressors resistant to YodL’s activity primarily occur in MreB. Consistent with the idea that YisK targets Mbl activity and YodL targets MreB activity, deletion of mbl confers resistance to YisK, while deletion of MreB confers resistance to YodL. In an mbl deletion background, YisK expressing cells also become 20% shorter, suggesting that YisK activity affects at least one other target integral to cell shape. Using a bacterial 2-hybrid assay, we detected an interaction between YisK and FtsE (the ATPase of the ABC Transporter FtsEX). Interestingly, published data indicates that FtsEX, which is important for regulating the activity of the D,L-endopeptidase CwlO, appears to act in the same pathway as Mbl, and both ftsE and cwlO mutants exhibit short-cell phenotypes. Our data suggest that ftsE is required for YisK-dependent cell shortening, but not cell widening. YisK shows ~40% amino acid identity to an FAH from Mycobacterium abcsessus, and we have obtained a preliminary crystal structure for YisK, with a dicarboxylic acid, most likely L-tartrate, bound in the active site. Surprisingly, introducing mutations in YisK’s active site has no effect on its ability to perturb cell shape. Our current model is that YisK is an enzyme, possibly involved in the dicarboxylate pathway, that utilizes interactions with Mbl and possibly FtsE to localize its enzymatic activity to specific regions within the cell

Mental flexibility depends on a largely distributed white matter network: Causal evidence from connectome-based lesion-symptom mapping.

Mental flexibility (MF) refers to the capacity to dynamically switch from one task to another. Current neurocognitive models suggest that since this function requires interactions between multiple remote brain areas, the integrity of the anatomic tracts connecting these brain areas is necessary to maintain performance. We tested this hypothesis by assessing with a connectome-based lesion-symptom mapping approach the effects of white matter lesions on the brain's structural connectome and their association with performance on the trail making test, a neuropsychological test of MF, in a sample of 167 first unilateral stroke patients. We found associations between MF deficits and damage of i) left lateralized fronto-temporo-parietal connections and interhemispheric connections between left temporo-parietal and right parietal areas; ii) left cortico-basal connections; and iii) left cortico-pontine connections. We further identified a relationship between MF and white matter disconnections within cortical areas composing the cognitive control, default mode and attention functional networks. These results for a central role of white matter integrity in MF extend current literature by providing causal evidence for a functional interdependence among the regional cortical and subcortical structures composing the MF network. Our results further emphasize the necessity to consider connectomics in lesion-symptom mapping analyses to establish comprehensive neurocognitive models of high-order cognitive functions

Schreibe dein Programm!

Schreibe Dein Programm! ist eine Einführung in die Entwicklung von Programmen und die dazugehörigen Grundlagen. Im Zentrum stehen Konstruktionsanleitungen, welche die systematische Konstruktion von Programmen fördern, sowie Techniken zur Abstraktion, welche die Umsetzung der Konstruktionsanleitungen ermöglichen. In der Betonung systematischer Konstruktion unterscheidet sich dieses Buch drastisch von den meisten anderen Einführungen in die Programmierung. Die vermittelten Grundlagen und Techniken sind unabhängig von einer bestimmten Programmiersprache. Zur Illustration und zum Training der Programmierung dienen speziell für die Anfängerausbildung entwickelte Sprachebenen. Diese erleichtern den Einstieg und erlauben, die Konzepte der Programmierung zu präsentieren, ohne Zeit mit der Konstruktvielfalt anderer Programmiersprachen zu verlieren. Entsprechend vermittelt dieses Buch fortgeschrittene Techniken. Schreibe Dein Programm! ist aus der Praxis der Informatik-Grundausbildung an den Universitäten Tübingen, Freiburg und Kiel entstanden: Über mehrere Vorlesungszyklen wurden Stoffauswahl und Präsentation stetig verbessert. Gegenüber dem Vorgängerbuch Vom Problem zum Programm wurde ein Großteil des Materials neu entwickelt. Das Buch enthält viele Beispiele und Übungsaufgaben. Alle nötigen mathematischen Grundlagen werden vermittelt

The Semantic Multilingual Glossary of Mathematics (SMGloM) project or why do we need a semantic glossary of mathematics

In this overview, we describe a new terminological and notational base for mathematics: The Semantic Multilingual Glossary of Mathematics (shortly SMGloM) is an ontology for mathematical concepts, objects or models. The terminological and notational data can be applied, e.g. in a more semantic text and formula search and the disambiguation of symbols and formulae in mathematical publications or the translation of mathematical terms. The paper is focused to present the intention, the needs, the framework, and user scenarios of the SMGloM concept, not the technical details of the data model and its implementation