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Ribosomes decode mRNA to synthesize proteins. Ribosomes, once considered static, executing machines, are now viewed as dynamic modulators of translation. Increasingly detailed analyses of structural ribosome heterogeneity led to a paradigm shift toward ribosome specialization for selective translation. As sessile organisms, plants cannot escape harmful environments and evolved strategies to withstand. Plant cytosolic ribosomes are in some respects more diverse than those of other metazoans. This diversity may contribute to plant stress acclimation. The goal of this thesis was to determine whether plants use ribosome heterogeneity to regulate protein synthesis through specialized translation. I focused on temperature acclimation, specifically on shifts to low temperatures. During cold acclimation, Arabidopsis ceases growth for seven days while establishing the responses required to resume growth. Earlier results indicate that ribosome biogenesis is essential for cold acclimation. REIL mutants (reil-dkos) lacking a 60S maturation factor do not acclimate successfully and do not resume growth. Using these genotypes, I ascribed cold-induced defects of ribosome biogenesis to the assembly of the polypeptide exit tunnel (PET) by performing spatial statistics of rProtein changes mapped onto the plant 80S structure. I discovered that growth cessation and PET remodeling also occurs in barley, suggesting a general cold response in plants. Cold triggered PET remodeling is consistent with the function of Rei-1, a REIL homolog of yeast, which performs PET quality control. Using seminal data of ribosome specialization, I show that yeast remodels the tRNA entry site of ribosomes upon change of carbon sources and demonstrate that spatially constrained remodeling of ribosomes in metazoans may modulate protein synthesis. I argue that regional remodeling may be a form of ribosome specialization and show that heterogeneous cytosolic polysomes accumulate after cold acclimation, leading to shifts in the translational output that differs between wild-type and reil-dkos. I found that heterogeneous complexes consist of newly synthesized and reused proteins. I propose that tailored ribosome complexes enable free 60S subunits to select specific 48S initiation complexes for translation. Cold acclimated ribosomes through ribosome remodeling synthesize a novel proteome consistent with known mechanisms of cold acclimation. The main hypothesis arising from my thesis is that heterogeneous/ specialized ribosomes alter translation preferences, adjust the proteome and thereby activate plant programs for successful cold acclimation.
Under Brazil's ex-president Bolsonaro, deforestation of the Amazon increased dramatically. An Austrian NGO filed a complaint to the Prosecutor of the International Criminal Court (ICC) against Bolsonaro in October 2021, accusing him of crimes against humanity against the backdrop of his involvement in environmental destruction. This paper deals with the question of whether this initi-ative constitutes a promising means of juridification to mitigate conflicts revolving around mass deforestation in Brazil. It thematizes attempts to juridify environmental destruction in international criminal law and examines the Climate Fund Case at the Brazilian Supreme Court. Finally, emerging problems and arguments in favour of starting preliminary examinations at the ICC against Bolsonaro are illuminated. This paper provides arguments as to why the initiative might be a promising undertaking, even though it is unlikely that Bolsonaro will be arrested.
When moral authority speaks
(2023)
In this work, binding interactions between biomolecules were analyzed by a technique that is based on electrically controllable DNA nanolevers. The technique was applied to virus-receptor interactions for the first time. As receptors, primarily peptides on DNA nanostructures and antibodies were utilized. The DNA nanostructures were integrated into the measurement technique and enabled the presentation of the peptides in a controllable geometrical order. The number of peptides could be varied to be compatible to the binding sites of the viral surface proteins.
Influenza A virus served as a model system, on which the general measurability was demonstrated. Variations of the receptor peptide, the surface ligand density, the measurement temperature and the virus subtypes showed the sensitivity and applicability of the technology. Additionally, the immobilization of virus particles enabled the measurement of differences in oligovalent binding of DNA-peptide nanostructures to the viral proteins in their native environment.
When the coronavirus pandemic broke out in 2020, work on binding interactions of a peptide from the hACE2 receptor and the spike protein of the SARS-CoV-2 virus revealed that oligovalent binding can be quantified in the switchSENSE technology. It could also be shown that small changes in the amino acid sequence of the spike protein resulted in complete loss of binding. Interactions of the peptide and inactivated virus material as well as pseudo virus particles could be measured. Additionally, the switchSENSE technology was utilized to rank six antibodies for their binding affinity towards the nucleocapsid protein of SARS-CoV-2 for the development of a rapid antigen test device.
The technique was furthermore employed to show binding of a non-enveloped virus (adenovirus) and a virus-like particle (norovirus-like particle) to antibodies. Apart from binding interactions, the use of DNA origami levers with a length of around 50 nm enabled the switching of virus material. This proved that the technology is also able to size objects with a hydrodynamic diameter larger than 14 nm.
A theoretical work on diffusion and reaction-limited binding interactions revealed that the technique and the chosen parameters enable the determination of binding rate constants in the reaction-limited regime.
Overall, the applicability of the switchSENSE technique to virus-receptor binding interactions could be demonstrated on multiple examples. While there are challenges that remain, the setup enables the determination of affinities between viruses and receptors in their native environment. Especially the possibilities regarding the quantification of oligo- and multivalent binding interactions could be presented.
The central gas in half of all galaxy clusters shows short cooling times. Assuming unimpeded cooling, this should lead to high star formation and mass cooling rates, which are not observed. Instead, it is believed that condensing gas is accreted by the central black hole that powers an active galactic nuclei jet, which heats the cluster. The detailed heating mechanism remains uncertain. A promising mechanism invokes cosmic ray protons that scatter on self-generated magnetic fluctuations, i.e. Alfvén waves. Continuous damping of Alfvén waves provides heat to the intracluster medium. Previous work has found steady state solutions for a large sample of clusters where cooling is balanced by Alfvénic wave heating. To verify modeling assumptions, we set out to study cosmic ray injection in three-dimensional magnetohydrodynamical simulations of jet feedback in an idealized cluster with the moving-mesh code arepo. We analyze the interaction of jet-inflated bubbles with the turbulent magnetized intracluster medium.
Furthermore, jet dynamics and heating are closely linked to the largely unconstrained jet composition. Interactions of electrons with photons of the cosmic microwave background result in observational signatures that depend on the bubble content. Those recent observations provided evidence for underdense bubbles with a relativistic filling while adopting simplifying modeling assumptions for the bubbles. By reproducing the observations with our simulations, we confirm the validity of their modeling assumptions and as such, confirm the important finding of low-(momentum) density jets.
In addition, the velocity and magnetic field structure of the intracluster medium have profound consequences for bubble evolution and heating processes. As velocity and magnetic fields are physically coupled, we demonstrate that numerical simulations can help link and thereby constrain their respective observables. Finally, we implement the currently preferred accretion model, cold accretion, into the moving-mesh code arepo and study feedback by light jets in a radiatively cooling magnetized cluster. While self-regulation is attained independently of accretion model, jet density and feedback efficiencies, we find that in order to reproduce observed cold gas morphology light jets are preferred.
N-of-1 trials are the gold standard study design to evaluate individual treatment effects and derive personalized treatment strategies. Digital tools have the potential to initiate a new era of N-of-1 trials in terms of scale and scope, but fully functional platforms are not yet available. Here, we present the open source StudyU platform, which includes the StudyU Designer and StudyU app. With the StudyU Designer, scientists are given a collaborative web application to digitally specify, publish, and conduct N-of-1 trials. The StudyU app is a smartphone app with innovative user-centric elements for participants to partake in trials published through the StudyU Designer to assess the effects of different interventions on their health. Thereby, the StudyU platform allows clinicians and researchers worldwide to easily design and conduct digital N-of-1 trials in a safe manner. We envision that StudyU can change the landscape of personalized treatments both for patients and healthy individuals, democratize and personalize evidence generation for self-optimization and medicine, and can be integrated in clinical practice.
The urge of light utilization in fabrication of materials is as encouraging as challenging. Steadily increasing energy consumption in accordance with rapid population growth, is requiring a corresponding solution within the same rate of occurrence speed. Therefore, creating, designing and manufacturing materials that can interact with light and in further be applicable as well as disposable in photo-based applications are very much under attention of researchers. In the era of sustainability for renewable energy systems, semiconductor-based photoactive materials have received great attention not only based on solar and/or hydrocarbon fuels generation from solar energy, but also successful stimulation of photocatalytic reactions such as water splitting, pollutant degradation and organic molecule synthesisThe turning point had been reached for water splitting with an electrochemical cell consisting of TiO2-Pt electrode illuminated by UV light as energy source rather than an external voltage, that successfully pursued water photolysis by Fujishima and Honda in 1972. Ever since, there has been a great deal of interest in research of semiconductors (e.g. metal oxide, metal-free organic, noble-metal complex) exhibiting effective band gap for photochemical reactions. In the case of environmental friendliness, toxicity of metal-based semiconductors brings some restrictions in possible applications. Regarding this, very robust and ‘earth-abundant’ organic semiconductor, graphitic carbon nitride has been synthesized and successfully applied in photoinduced applications as novel photocatalyst. Properties such as suitable band gap, low charge carrier recombination and feasibility for scaling up, pave the way of advance combination with other catalysts to gather higher photoactivity based on compatible heterojunction.
This dissertation aims to demonstrate a series of combinations between organic semiconductor g-CN and polymer materials that are forged through photochemistry, either in synthesis or in application. Fabrication and design processes as well as applications performed in accordance to the scope of thesis will be elucidated in detail. In addition to UV light, more attention is placed on visible light as energy source with a vision of more sustainability and better scalability in creation of novel materials and solar energy based applications.
Facing the environmental crisis, new technologies are needed to sustain our society. In this context, this thesis aims to describe the properties and applications of carbon-based sustainable materials. In particular, it reports the synthesis and characterization of a wide set of porous carbonaceous materials with high nitrogen content obtained from nucleobases. These materials are used as cathodes for Li-ion capacitors, and a major focus is put on the cathode preparation, highlighting the oxidation resistance of nucleobase-derived materials. Furthermore, their catalytic properties for acid/base and redox reactions are described, pointing to the role of nitrogen speciation on their surfaces. Finally, these materials are used as supports for highly dispersed nickel loading, activating the materials for carbon dioxide electroreduction.
Despite the popularity of thermoresponsive polymers, much is still unknown about their behavior, how it is triggered, and what factors influence it, hindering the full exploitation of their potential. One particularly puzzling phenomenon is called co-nonsolvency, in which a polymer is soluble in two individual solvents, but counter-intuitively becomes insoluble in mixtures of both. Despite the innumerous potential applications of such systems, including actuators, viscosity regulators and as carrier structures, this field has not yet been extensively studied apart from the classical example of poly(N isopropyl acrylamide) (PNIPAM) in mixtures of water and methanol. Therefore, this thesis focuses on evaluating how changes in the chemical structure of the polymers impact the thermoresponsive, aggregation and co-nonsolvency behaviors of both homopolymers and amphiphilic block copolymers. Within this scope, both the synthesis of the polymers and their characterization in solution is investigated. Homopolymers were synthesized by conventional free radical polymerization, whereas block copolymers were synthesized by consecutive reversible addition fragmentation chain transfer (RAFT) polymerizations. The synthesis of the monomers N isopropyl methacrylamide (NIPMAM) and N vinyl isobutyramide (NVIBAM), as well as a few chain transfer agents is also covered. Through turbidimetry measurements, the thermoresponsive and co-nonsolvency behavior of PNIPMAM and PNVIBAM homopolymers is then compared to the well-known PNIPAM, in aqueous solutions with 9 different organic co-solvents. Additionally, the effects of end-groups, molar mass, and concentration are investigated. Despite the similarity of their chemical structures, the 3 homopolymers show significant differences in transition temperatures and some divergences in their co-nonsolvency behavior. More complex systems are also evaluated, namely amphiphilic di- and triblock copolymers of PNIPAM and PNIPMAM with polystyrene and poly(methyl methacrylate) hydrophobic blocks. Dynamic light scattering is used to evaluate their aggregation behavior in aqueous and mixed aqueous solutions, and how it is affected by the chemical structure of the blocks, the chain architecture, presence of cosolvents and polymer concentration. The results obtained shed light into the thermoresponsive, co-nonsolvency and aggregation behavior of these polymers in solution, providing valuable information for the design of systems with a desired aggregation behavior, and that generate targeted responses to temperature and solvent mixture changes.
Anchored in ink
(2023)
This book serves as a gateway to the Elementa grammaticae Huronicae, an eighteenth-century grammar of the Wendat (‘Huron’) language by Jesuit Pierre-Philippe Potier (1708–1781). The volume falls into three main parts. The first part introduces the grammar and some of its contexts, offering information about the Huron-Wendat and Wyandot, the early modern Jesuit mission in New France and the Jesuits’ linguistic output. The heart of the volume is made up by its second part, a text edition of the Elementa. The third part presents some avenues of research by way of specific case studies.