The Autodepalmitoylating activity of APT maintains the spatial organization of Palmitoylated membrane proteins

The localization and signaling of S-palmitoylated peripheral membrane proteins is sustained by an acylation cycle in which acyl protein thioesterases (APTs) depalmitoylate mislocalized palmitoylated proteins on endomembranes. However, the APTs are themselves reversibly S-palmitoylated, which localizes thioesterase activity to the site of the antagonistc palmitoylation activity on the Golgi. Here, we resolve this conundrum by showing that palmitoylation of APTs is labile due to autodepalmitoylation, creating two interconverting thioesterase pools: palmitoylated APT on the Golgi and depalmitoylated APT in the cytoplasm, with distinct functionality. By imaging APT-substrate catalytic intermediates, we show that it is the depalmitoylated soluble APT pool that depalmitoylates substrates on all membranes in the cell, thereby establishing its function as release factor of mislocalized palmitoylated proteins in the acylation cycle. The autodepalmitoylating activity on the Golgi constitutes a homeostatic regulation mechanism of APT levels at the Golgi that ensures robust partitioning of APT substrates between the plasma membrane and the Golgi.Fil: Vartak, Nachiket. Institut Max Planck Fur Molekulare Physiologie; AlemaniaFil: Papke, Bjoern. Institut Max Planck Fur Molekulare Physiologie; AlemaniaFil: Grecco, Hernan Edgardo. Institut Max Planck Fur Molekulare Physiologie; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rossmannek, Lisaweta. Institut Max Planck Fur Molekulare Physiologie; AlemaniaFil: Waldmann, Herbert. Institut Max Planck Fur Molekulare Physiologie; AlemaniaFil: Hedberg, Christian. Institut Max Planck Fur Molekulare Physiologie; AlemaniaFil: Bastiaens, Philippe I. H.. Institut Max Planck Fur Molekulare Physiologie; Alemani

Uncovering distinct protein-network topologies in heterogeneous cell populations

Background: Cell biology research is fundamentally limited by the number of intracellular components, particularly proteins, that can be co-measured in the same cell. Therefore, cell-to-cell heterogeneity in unmeasured proteins can lead to completely different observed relations between the same measured proteins. Attempts to infer such relations in a heterogeneous cell population can yield uninformative average relations if only one underlying biochemical network is assumed. To address this, we developed a method that recursively couples an iterative unmixing process with a Bayesian analysis of each unmixed subpopulation. Results: Our approach enables to identify the number of distinct cell subpopulations, unmix their corresponding observations and resolve the network structure of each subpopulation. Using simulations of the MAPK pathway upon EGF and NGF stimulations we assess the performance of the method. We demonstrate that the presented method can identify better than clustering approaches the number of subpopulations within a mixture of observations, thus resolving correctly the statistical relations between the proteins. Conclusions: Coupling the unmixing of multiplexed observations with the inference of statistical relations between the measured parameters is essential for the success of both of these processes. Here we present a conceptual and algorithmic solution to achieve such coupling and hence to analyze data obtained from a natural mixture of cell populations. As the technologies and necessity for multiplexed measurements are rising in the systems biology era, this work addresses an important current challenge in the analysis of the derived data.Fil: Wieczorek, Jakob. Universitat Dortmund; AlemaniaFil: Malik Sheriff, Rahuman S.. Institut Max Planck fur Molekulare Physiologie; Alemania. Imperial College London; Reino Unido. European Bioinformatics Institute. European Molecular Biology Laboratory; Reino UnidoFil: Fermin, Yessica. Universitat Dortmund; AlemaniaFil: Grecco, Hernan Edgardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina. Institut Max Planck fur Molekulare Physiologie; AlemaniaFil: Zamir, Eli. Institut Max Planck fur Molekulare Physiologie; AlemaniaFil: Ickstadt, Katja. Universitat Dortmund; Alemani

Emil du Bois-Reymond vs Ludimar Hermann

This essay recounts a controversy between a pioneer electrophysiologist, Emil du Bois-Reymond (1818–1896), and his student, Ludimar Hermann (1838–1914). Du Bois-Reymond proposed a molecular explanation for the slight electrical currents that he detected in frog muscles and nerves. Hermann argued that du Bois-Reymond's ‘resting currents’ were an artifact of injury to living tissue. He contested du Bois-Reymond's molecular model, explaining his teacher's observations as electricity produced by chemical decomposition. History has painted Hermann as the wronged party in this dispute. I seek to set the record straight

Notes de mission en Thaïlande visite du 6 au 9 juillet 1990

Typescript (photocopy).The study was designed to investigate the relationship between selective and self concept. The relationship between self concept and the D score; the relationship of locus of control and self concept; the correlation between the D score and self acceptance were also evaluated. The subjects in this project were 231 student volunteers from Educational Psychology classes at Texas A&M University. The research procedures allowed the subjects to work at their own pace on a test booklet. This booklet contained the Self Rating Scale, Rotter's Locus of Control Inventory and the Self Report Scale, as well as, a selective exposure paradigm. The results of this project suggest that a difference in self concept seems to exist between male and female subjects. For females as the difference in their self and ideal self images decreases their level of self acceptance increases. While for males self acceptance appears to be related to their locus of control. In conjunction with these findings the results of this project indicate a significant difference in the locus of control scores between males and females. However, self concept does not appear to be related to locus of control for either sex. Even so, self concept appears to be related to the D score. Finally, self concept does not appear to be related to the degree of resolution in the selective exposure paradigm. However, the research methodology employed in this project may not have been able to induce the subjects to feel a sense of responsibility and commitment for their actions. Previous research has indicated that it is this sense of commitment and responsibility which is essential to the creation of selective exposure (Frey & Wickland, 1978)

Form and Data - from linear Calculus to cybernetic Computation and Interaction

Digital architecture developed in the 1960s and, supported by CAAD the 1990s, has created the path towards an architecture produced by computer and architect in a mutual relationship. The evolution of architecture since the 1970s led to the beginning of the first digital turn in the 1990s, and subsequently to the emergence of new typologies of buildings, architects and design tools; atom-based, bit-based (virtual) [1], and cyber-physical as a combination of both. The paper provides an insight into historical foundations of CAAD insofar as it engages with complexity in mechanics, geometry, and space between the 1600s and 1950s. I will address a selection of principles discovered, and mechanisms invented before computer-aided-architectural-design; those include the typewriter, the Cartesian grid and a pre-cyber-physical system by Hermann von Helmholtz. The paper concludes with a summary and an outlook to the future of CAAD challenged by the variety of correlations of disparate data sets