Higher-order structural organization of the mitochondrial proteome charted by in situ cross-linking mass spectrometry

Mitochondria are densely packed with proteins, of which most are involved physically or more transiently in protein-protein interactions (PPIs). Mitochondria host among others all enzymes of the Krebs cycle and the oxidative phosphorylation (OXPHOS) pathway and are foremost associated with cellular bioenergetics (1, 2). However, mitochondria are also important contributors to apoptotic cell death (3) and contain their own genome (4) indicating that they play additionally an eminent role in processes beyond bioenergetics (5). Despite intense efforts in identifying and characterizing mitochondrial protein complexes by structural biology and proteomics techniques, many PPIs have remained elusive. Several of these (membrane embedded) PPIs are less stable in-vitro hampering their characterization by most contemporary methods in structural biology. Particularly in these cases, cross-linking mass spectrometry (XL-MS) has proven valuable for the in-depth characterization of mitochondrial protein complexes in situ. Here, we highlight experimental strategies for the analysis of proteome-wide protein-protein interactions in mitochondria using XL-MS. We showcase the ability of in situ XL-MS as a tool to map sub-organelle interactions and topologies, and aid in refining structural models of protein complexes. We describe some of the most recent technological advances in XL-MS that may benefit the in situ characterization of PPIs even further, especially when combined with electron microscopy and structural modelling

Reflecting open practices on digital infrastructures. Functionalities and implications of knowledge. [Preprint]

Open practices in education focus on the actions of learners and teachers regarding openness. The sharing and collaborative creation of open educational resources is at the core of such practices. Digital infrastructures do not only provide environments for these kinds of practices but reflect ide-as and implications of open practices through the functionalities they offer. Those infrastructures can be seen as drivers for enabling open practices to become default. However, a common understanding of open practices has yet to be defined. As such, designing digital infrastructures that foster open prac-tices might be a challenge. This chapter shows the relation between open practices and digital infrastructures. (DIPF/Orig.

Extensive air shower simulations at the highest energies

Air shower simulation programs are essential tools for the analysis of data from cosmic ray experiments and for planning the layout of new detectors. They are used to estimate the energy and mass of the primary particle. Unfortunately the model uncertainties translate directly into systematic errors in the energy and mass determination. Aiming at energies > 1019 eV, the models have to be extrapolated far beyond the energies available at accelerators. On the other hand, hybrid measurement of ground particle densities and calorimetric shower energy, as will be provided by the Pierre Auger Observatory, will strongly constrain shower models. While the main uncertainty of contemporary models comes from our poor knowledge of the (soft) hadronic interactions at high energies, also electromagnetic interactions, lowenergy hadronic interactions and the particle transport influence details of the shower development. We review here the physics processes and some of the computational techniques of air shower models presently used for highest energies, and discuss the properties and limitations of the models.Facultad de Ciencias Exacta

Potenziale von Open Educational Resources in der Informationswissenschaft?

Open Educational Resources (OER) werden durch ihre offene Lizenzierung und den damit verbundenen Möglichkeiten zur Nachnutzung Potenziale zur Verbes- serung von Lern-/Lehrsituationen zugeschrieben. In unserer Mixed-Methods-Studie erheben wir die Einschätzung zum Nutzen von OER für die Lehrpraxis von Lehrenden der deutschsprachigen Informationswissenschaft. Außerdem fragen wir nach Umsetzungsmöglichkeiten eines gemeinsamen OER-Pools und den Einstellungen zu gemeinschaftlichen Erstellungsprozessen von Lern-/Lehrmaterial. Im folgenden Posterbeitrag werden erste Ergebnisse einer qualitativen Befragung ausgewählter Lehrender vorgestellt, die Basis für eine darauf aufbauende quantitative Befragung unter Lehrenden der deutschsprachigen Informationswissenschaft ist

Who are Leibniz PostDocs and what is it like to work at a Leibniz institute? Report of the first Leibniz PostDoc Survey 2020

Postdoctoral researchers play a critical role in scientific research. This is the case not only for the Leibniz Association but for research worldwide. However, postdoctoral researchers are often overlooked or misrepresented as a homogeneous group of researchers. The principal aim of the Leibniz PostDoc Survey was to understand who Leibniz PostDocs are and to provide some insight into their experiences, interests, and needs. This report summarizes the results of the first Leibniz PostDoc Survey, which was open for submission from July to October 2020. The report includes a summary of the key findings and recommendations as well as a comprehensive description of all results from each survey question

Extensive air shower simulations at the highest energies

Air shower simulation programs are essential tools for the analysis of data from cosmic ray experiments and for planning the layout of new detectors. They are used to estimate the energy and mass of the primary particle. Unfortunately the model uncertainties translate directly into systematic errors in the energy and mass determination. Aiming at energies > 1019 eV, the models have to be extrapolated far beyond the energies available at accelerators. On the other hand, hybrid measurement of ground particle densities and calorimetric shower energy, as will be provided by the Pierre Auger Observatory, will strongly constrain shower models. While the main uncertainty of contemporary models comes from our poor knowledge of the (soft) hadronic interactions at high energies, also electromagnetic interactions, lowenergy hadronic interactions and the particle transport influence details of the shower development. We review here the physics processes and some of the computational techniques of air shower models presently used for highest energies, and discuss the properties and limitations of the models.Facultad de Ciencias Exacta

Site-specific Activity-based Protein Profiling Using Phosphonate Handles

Most drug molecules target proteins. Identification of the exact drug binding sites on these proteins is essential to understand and predict how drugs affect protein structure and function. To address this challenge, we developed a strategy that uses immobilized metal-affinity chromatography-enrichable phosphonate affinity tags, for efficient and selective enrichment of peptides bound to an activity-based probe, enabling the identification of the exact drug binding site. As a proof of concept, using this approach, termed PhosID-ABPP (activity-based protein profiling), over 500 unique binding sites were reproducibly identified of an alkynylated afatinib derivative (PF-06672131). As PhosID-ABPP is compatible with intact cell inhibitor treatment, we investigated the quantitative differences in approachable binding sites in intact cells and in lysates of the same cell line and observed and quantified substantial differences. Moreover, an alternative protease digestion approach was used to capture the previously reported binding site on the epidermal growth factor receptor, which turned out to remain elusive when using solely trypsin as protease. Overall, we find that PhosID-ABPP is highly complementary to biotin-based enrichment strategies in ABPP studies, with PhosID-ABPP providing the advantage of direct activity-based probe interaction site identification