Impaired protein translation in Drosophila models for Charcot–Marie–Tooth neuropathy caused by mutant tRNA synthetases

Dominant mutations in five tRNA synthetases cause Charcot–Marie–Tooth (CMT) neuropathy, suggesting that altered aminoacylation function underlies the disease. However, previous studies showed that loss of aminoacylation activity is not required to cause CMT. Here we present a Drosophila model for CMT with mutations in glycyl-tRNA synthetase (GARS). Expression of three CMT-mutant GARS proteins induces defects in motor performance and motor and sensory neuron morphology, and shortens lifespan. Mutant GARS proteins display normal subcellular localization but markedly reduce global protein synthesis in motor and sensory neurons, or when ubiquitously expressed in adults, as revealed by FUNCAT and BONCAT. Translational slowdown is not attributable to altered tRNA[superscript Gly] aminoacylation, and cannot be rescued by Drosophila Gars overexpression, indicating a gain-of-toxic-function mechanism. Expression of CMT-mutant tyrosyl-tRNA synthetase also impairs translation, suggesting a common pathogenic mechanism. Finally, genetic reduction of translation is sufficient to induce CMT-like phenotypes, indicating a causal contribution of translational slowdown to CMT.National Institutes of Health (U.S.) (Grant GM17151

Impact of St. John’s wort extract Ze 117 on stress induced changes in the lipidome of PBMC

Abstract Background Membrane lipids have an important function in the brain as they not only provide a physical barrier segregating the inner and outer cellular environments, but are also involved in cell signaling. It has been shown that the lipid composition effects membrane fluidity which affects lateral mobility and activity of membrane-bound receptors. Methods Since changes in cellular membrane properties are considered to play an important role in the development of depression, the effect of St. John’s wort extract Ze 117 on plasma membrane fluidity in peripheral blood mononuclear cells (PBMC) was investigated using fluorescence anisotropy measurements. Changes in fatty acid residues in phospholipids after treatment of cortisol-stressed [1 μM] PBMCs with Ze 117 [10–50 µg/ml] were analyzed by mass spectrometry. Results Cortisol increased membrane fluidity significantly by 3%, co-treatment with Ze 117 [50 µg/ml] counteracted this by 4.6%. The increased membrane rigidity by Ze 117 in cortisol-stressed [1 μM] PBMC can be explained by a reduced average number of double bonds and shortened chain length of fatty acid residues in phospholipids, as shown by lipidomics experiments. Conclusion The increase in membrane rigidity after Ze 117 treatment and therefore the ability to normalize membrane structure points to a new mechanism of antidepressant action of the extract

Identitat : Versuche bildhafter Selbstdefinition : Arbeiten von Christian Boltanski, Anna Oppermann, Bernhard Praesent, Martin Rosz und Roger Welch, sovie von 42 Schülen der Klassen 5a, b und c des Gymnasiums i.E. Köln -Höhenhaus

Pointing to the growing consciousness of the importance of the theme of self definition, the authors introduce an exhibition project on the theme of personal identity which brings together five international artists. Texts in German only. Artists' statements. Biographical notes

Towards Autonomous Planetary Exploration: The Lightweight Rover Unit (LRU), its Success in the SpaceBotCamp Challenge, and Beyond

Planetary exploration poses many challenges for a robot system: From weight and size constraints to extraterrestrial environment conditions, which constrain the suitable sensors and actuators. As the distance to other planets introduces a significant communication delay, the efficient operation of a robot system requires a high level of autonomy. In this work, we present our Lightweight Rover Unit (LRU), a small and agile rover prototype that we designed for the challenges of planetary exploration. Its locomotion system with individually steered wheels allows for high maneuverability in rough terrain and stereo cameras as its main sensors ensure the applicability to space missions. We implemented software components for self-localization in GPS-denied environments, autonomous exploration and mapping as well as computer vision, planning and control modules for the autonomous localization, pickup and assembly of objects with its manipulator. Additional high-level mission control components facilitate both autonomous behavior and remote monitoring of the system state over a delayed communication link. We successfully demonstrated the autonomous capabilities of our LRU at the SpaceBotCamp challenge, a national robotics contest with focus on autonomous planetary exploration. A robot had to autonomously explore an unknown Moon-like rough terrain, locate and collect two objects and assemble them after transport to a third object - which the LRU did on its first try, in half of the time and fully autonomously. The next milestone for our ongoing LRU development is an upcoming planetary exploration analogue mission to perform scientific experiments at a Moon analogue site located on a volcano

First Results of the ROBEX Analogue Mission Campaign: Robotic Deployment of Seismic Networks for Future Lunar Missions

This paper presents first results of the analog mission campaign which was performed between the 12th of June and the 10th of July 2017 on Mount Etna in Europe, Italy. The aim of the ROBEX demonstration mission is to test and validate a complex robotic mission. This includes highly autonomous tasks with supervision from scientists to guarantee measurement of real and scientifically relevant data. The main scientific objective of the ROBEX mission, the detailed analysis of the lunar crust layers, that is replaced by the analysis of Etna lava layers in the demo mission, has been guiding the developments of the last four years. As key missions, a seismic network has been deployed and a seismic profile measurement has been conducted using only robots on the landing site. Additional experiments consisted of long term autonomous navigation, multi-robot mapping and exploration of craters as well as experiments with the aim of geological analyses and probe selection. During the one month analog campaign, a realistic mission scenario has been built up, including a control station approximately 30 km from the remote site

In Vivo Analysis Reveals a Highly Stereotypic Morphogenetic Pathway of Vascular Anastomosis

Organ formation and growth requires cells to organize into properly patterned three-dimensional architectures. Network formation within the vertebrate vascular system is driven by fusion events between nascent sprouts or between sprouts and pre-existing blood vessels. Here, we describe the cellular activities that occur during blood vessel anastomosis in the cranial vasculature of the zebrafish embryo. We show that the early steps of the fusion process involve endothelial cell recognition, de novo polarization of endothelial cells, and apical membrane invagination and fusion. These processes generate a unicellular tube, which is then transformed into a multicellular tube via cell rearrangements and cell splitting. This stereotypic series of morphogenetic events is typical for anastomosis in perfused sprouts. Vascular endothelial-cadherin plays an important role early in the anastomosis process and is required for filopodial tip cell interactions and efficient formation of a single contact site

MOSES: A Novel Observation System to Monitor Dynamic Events across Earth Compartments

Modular Observation Solutions of Earth Systems (MOSES) is a novel observation system that is specifically designed to unravel the impact of distinct, dynamic events on the long-term development of environmental systems. Hydrometeorological extremes such as the recent European droughts or the floods of 2013 caused severe and lasting environmental damage. Modeling studies suggest that abrupt permafrost thaw events accelerate Arctic greenhouse gas emissions. Short-lived ocean eddies seem to comprise a significant share of the marine carbon uptake or release. Although there is increasing evidence that such dynamic events bear the potential for major environmental impacts, our knowledge on the processes they trigger is still very limited. MOSES aims at capturing such events, from their formation to their end, with high spatial and temporal resolution. As such, the observation system extends and complements existing national and international observation networks, which are mostly designed for long-term monitoring. Several German Helmholtz Association centers have developed this research facility as a mobile and modular “system of systems” to record energy, water, greenhouse gas, and nutrient cycles on the land surface, in coastal regions, in the ocean, in polar regions, and in the atmosphere—but especially the interactions between the Earth compartments. During the implementation period (2017–21), the measuring systems were put into operation and test campaigns were performed to establish event-driven campaign routines. With MOSES’s regular operation starting in 2022, the observation system will then be ready for cross-compartment and cross-discipline research on the environmental impacts of dynamic events