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Trypanosoma brucei is the causal infectious agent of African trypanosomiasis in humans and Nagana in livestock. Both diseases are currently treated with a small number of chemotherapeutics, which are hampered by a variety of limitations reaching from efficacy and toxicity complications to drug-resistance problems. Here, we explore the forward design of a new class of synthetic trypanocides based on nanostructured, core-shell DNA-lipid particles. In aqueous solution, the particles self-assemble into micelle-type structures consisting of a solvent-exposed, hydrophilic DNA shell and a hydrophobic lipid core. DNA-lipid nanoparticles have membrane-adhesive qualities and can permeabilize lipid membranes. We report the synthesis of DNA-cholesterol nanoparticles, which specifically subvert the membrane integrity of the T. brucei lysosome, killing the parasite with nanomolar potencies. Furthermore, we provide an example of the programmability of the nanoparticles. By functionalizing the DNA shell with a spliced leader (SL)-RNA-specific DNAzyme, we target a second trypanosome-specific pathway (dual-target approach). The DNAzyme provides a backup to counteract the recovery of compromised parasites, which reduces the risk of developing drug resistance.

The assembly of high molecular mass ribonucleoprotein complexes typically relies on the binary interaction of defined RNA sequences or precisely folded RNA motifs with dedicated RNA-binding domains on the protein side. Here we describe a new molecular recognition principle of RNA molecules by a high molecular mass protein complex. By chemically probing the solvent accessibility of mitochondrial pre-mRNAs when bound to the Trypanosoma brucei editosome, we identified multiple similar but non-identical RNA motifs as editosome contact sites. However, by treating the different motifs as mathematical graph objects we demonstrate that they fit a consensus 2D-graph consisting of 4 vertices (V) and 3 edges (E) with a Laplacian eigenvalue of 0.5477 (λ2). We establish that synthetic 4V(3E)-RNAs are sufficient to compete for the editosomal pre-mRNA binding site and that they inhibit RNA editing in vitro. Furthermore, we demonstrate that only two topological indices are necessary to predict the binding of any RNA motif to the editosome with a high level of confidence. Our analysis corroborates that the editosome has adapted to the structural multiplicity of the mitochondrial mRNA folding space by recognizing a fuzzy continuum of RNA folds that fit a consensus graph descriptor.

Patientology traditionally signifies the scientific study of the patients through medical sociological and anthropological perspectives. The last decades have witnessed notable changes in the understanding of what it means to be a patient and what role patients play in healthcare processes, with the rise of concepts such as patient-centered care, patient empowerment, and patient participation. This article develops a reconceptualization of patientology, proposes a model hereof, and exemplifies its use through the application to an illustrative case. Our reconceptualization of patientology considers the patient as the central actor in a network of healthcare actors. Being a patient requires health capital that is comprised of health-relevant aspects of Bourdieusian forms of capitals: economic, social, and cultural capital. The patient role is constructed through the patient’s interaction with a range of healthcare actors such as health professionals, relatives, and other patients. The proposed model allows for understanding health inequalities as based on differences in (cultural) health capital, opening up new avenues of investigating and ameliorating patients’ challenges in health interactions. The model allows for a fresh take on the reciprocity of Parsons social sick role, allowing to clarify both how patients can contribute to their own health and healthcare and where and how health professionals ought to meet their patients.

The present chapter, much like the previous one, comprises a series of short sections, each focusing on a particular aspect arising from the interview discussions. The analyses adopt predominantly thematic qualitative approaches embedded within various theoretical perspectives and are meant to explore the ways in which young people perceive hate speech and matters associated with it. Again, it should be noted that even though each section is based on a particular national setting, the overall argumentation is of relevance to other contexts and to the wider discussion of the specific phenomenon in focus.

Spektrum Nord: Vielfalt der Ziele, Inhalte und Methoden in der Landeskunde : Beitrage zur 3. Konferenz des Netzwerks Landeskunde Nord in Odense am 21./22. Januar 2016

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Straipsnyje nagrinėjami konceptualieji lyginamosios vokiečių ir lietuvių kalbos gramatikos klausimai. Apžvelgiami pagrindiniai gramatikografijos ir lyginamosios kalbotyros darbai, į kuriuos reikia atsižvelgti renkantis teorinį lyginamosios gramatikos pagrindą. Straipsnio pradžioje trumpai aptariamas terminų lyginamasis (vergleichend), istorinis-lyginamasis (historisch-vergleichend), tipologinis (typologisch), kontrastyvinis (kontrastiv) ir gretinamasis (konfrontativ) metodas vartojimas. Keliami klausimai, kaip rašant lyginamąją vokiečių ir lietuvių kalbos gramatiką būtų galima taikyti įvairius lyginamuosius ar tipologinius bei kontrastyvinius aspektus. Toliau straipsnyje pristatoma diskusija, skirta pastaraisiais metais pasirodžiusioms vokiečių kalbos gramatikoms, kuriose vokiečių kalba lyginama su kitomis kalbomis, atkreipiamas dėmesys į šių gramatikų privalumus ir trūkumus. Be to, aptariamos gramatikų naudotojų grupės, gramatikų naudojimo ypatumai. Svarstoma, kokiai naudotojų grupei turėtų būti skirta vokiečių ir lietuvių kalbos lyginamoji gramatika. Straipsnyje taip pat pateikiama trumpa vokiečių ir lietuvių kalbų lyginamųjų darbų apžvalga. Straipsnio pabaigoje pristatoma vokiečių ir lietuvių kalbos lyginamosios gramatikos koncepcija ir brėžiama tolesnių darbų perspektyva. The paper analyses the conceptual issues of comparative German and Lithuanian grammar. The major works on grammaticography and comparative linguistics are reviewed, which should be taken into consideration when choosing the theoretical foundation of comparative grammar. The paper starts with a short discussion of the usage of the terms “comparative” (vergleichend), “historical-comparative” (historisch-vergleichend), “typological” (typologisch), “contrastive” (kontrastiv) and “confrontational” (konfrontativ) method. The paper raises questions how when writing the comparative German-Lithuanian grammar various comparative or typological and contrastive aspects could be applied. The paper further presents a discussion on recent German grammars which compare the German language with other languages, and notes the strengths and weaknesses of these grammars. Furthermore, it discusses the groups of grammar users and the peculiarities of using grammars. It considers which group of users the German-Lithuanian comparative grammar should be targeted at. The paper also presents a brief overview of German and Lithuanian comparative studies. The paper ends with the presentation of the conception of the German-Lithuanian comparative grammar and draws a perspective of further studies.