Foot-and-mouth disease virus 2C is a hexameric AAA+ protein with a coordinated ATP hydrolysis mechanism.

Foot-and-mouth disease virus (FMDV), a positive sense, single-stranded RNA virus, causes a highly contagious disease in cloven-hoofed livestock. Like other picornaviruses, FMDV has a conserved 2C protein assigned to the superfamily 3 helicases a group of AAA+ ATPases that has a predicted N-terminal membrane-binding amphipathic helix attached to the main ATPase domain. In infected cells, 2C is involved in the formation of membrane vesicles, where it co-localizes with viral RNA replication complexes, but its precise role in virus replication has not been elucidated. We show here that deletion of the predicted N-terminal amphipathic helix enables overexpression in Escherichia coli of a highly soluble truncated protein, 2C(34–318), that has ATPase and RNA binding activity. ATPase activity was abrogated by point mutations in the Walker A (K116A) and B (D160A) motifs and Motif C (N207A) in the active site. Unliganded 2C(34–318) exhibits concentration-dependent self-association to yield oligomeric forms, the largest of which is tetrameric. Strikingly, in the presence of ATP and RNA, FMDV 2C(34–318) containing the N207A mutation, which binds but does not hydrolyze ATP, was found to oligomerize specifically into hexamers. Visualization of FMDV 2C-ATP-RNA complexes by negative stain electron microscopy revealed hexameric ring structures with 6-fold symmetry that are characteristic of AAA+ ATPases. ATPase assays performed by mixing purified active and inactive 2C(34–318) subunits revealed a coordinated mechanism of ATP hydrolysis. Our results provide new insights into the structure and mechanism of picornavirus 2C proteins that will facilitate new investigations of their roles in infection

Structure-Activity Relationships of Triple-Action Platinum(IV) Prodrugs with Albumin-Binding Properties and Immunomodulating Ligands

Chemotherapy with platinum complexes is essential for clinical anticancer therapy. However, due to side effects and drug resistance, further drug improvement is urgently needed. Herein, we report on triple-action platinum­(IV) prodrugs, which, in addition to tumor targeting via maleimide-mediated albumin binding, release the immunomodulatory ligand 1-methyl-d-tryptophan (1-MDT). Unexpectedly, structure–activity relationship analysis showed that the mode of 1-MDT conjugation distinctly impacts the reducibility and thus activation of the prodrugs. This in turn affected ligand release, pharmacokinetic properties, efficiency of immunomodulation, and the anticancer activity in vitro and in a mouse model in vivo. Moreover, we could demonstrate that the design of albumin-targeted multi-modal prodrugs using platinum­(IV) is a promising strategy to enhance the cellular uptake of bioactive ligands with low cell permeability (1-MDT) and to improve their selective delivery into the malignant tissue. This will allow tumor-specific anticancer therapy supported by a favorably tuned immune microenvironment

An online platform supporting the analysis of water adaptation measures in the Alps

Climate change may result in reduced water supply from the Alps - an important water resource for Europe. This paper presents a multilingual platform that combines spatial and multi-criteria decision-support tools to facilitate stakeholder collaboration in the analysis of water management adaptation options. The platform has an interactive map interface that allows participants to select a location of their interest within the Alpine Arc. By utilising the decision-support tool, stakeholders can identify suitable adaptation solutions for different geographical units, according to their experience and preference. The platform was used to involve experts across Alpine borders, domains and decision-making levels, as well as a group of university students. The experts favoured the planning instruments for saving water, while the students inclined towards the measures that would improve water conservation. The initial results confirmed the suitability of the platform for future involvement of decision-makers in spatio-temporal analyses of adaptation pathways in the Alps

Eteokles in Spain? On Brecht’s Mein Bruder war ein Flieger

One of Bertolt Brecht’s most famous poems, Mein Bruder war ein Flieger, is often invoked as a manifesto for pacifist ideals, but some essential questions (who is the lyric I? what is the literal meaning of the poem?) have hardly received any attention. By evoking the poem’s nature as a Kinderlied, the context of its first publication, and its relationship with Brecht’s play Die Gewehre der Frau Carrar, this article tentatively identifies the source of its final pointe in a famous passage of Aeschylus’ Seven against Thebes, thereby suggesting—on the basis of textual comparisons—an example of far-reaching, ideological Antikerezeption in Brecht’s oeuvre, working all the way down to his Kalendergeschichten and to his Antigone

microbeMASST: a taxonomically informed mass spectrometry search tool for microbial metabolomics data

microbeMASST, a taxonomically informed mass spectrometry (MS) search tool, tackles limited microbial metabolite annotation in untargeted metabolomics experiments. Leveraging a curated database of >60,000 microbial monocultures, users can search known and unknown MS/MS spectra and link them to their respective microbial producers via MS/MS fragmentation patterns. Identification of microbe-derived metabolites and relative producers without a priori knowledge will vastly enhance the understanding of microorganisms' role in ecology and human health

microbeMASST: A Taxonomically-informed Mass Spectrometry Search Tool for Microbial Metabolomics Data

microbeMASST, a taxonomically informed mass spectrometry (MS) search tool, tackles limited microbial metabolite annotation in untargeted metabolomics experiments. Leveraging a curated database of >60,000 microbial monocultures, users can search known and unknown MS/MS spectra and link them to their respective microbial producers via MS/MS fragmentation patterns. Identification of microbe-derived metabolites and relative producers without a priori knowledge will vastly enhance the understanding of microorganisms’ role in ecology and human health

Pferdegest\ufctzte Supervision\u201eDas Pferd als Semiophor\u201c

Die vorliegende Masterarbeit besch\ue4ftigt sich mit dem Einsatz des Pferdes in derSupervision. Der Geschichte der Supervision sowie der gemeinsamen Geschichte vonMensch und Pferd wird Beachtung geschenkt und das Verhalten des Pferdes imAllgemeinen n\ue4her beschrieben. Zum besseren Verst\ue4ndnis von denWirkmechanismen in der pferdegest\ufctzten Supervision widmet sich ein Abschnitt derEntwicklungspsychologie, Neurobiologie und P\ue4dagogik.Vertiefend werden verschiedenen Wirkfaktoren beschrieben und der Versuchgestartet, dies in einen wissenschaftlichen Kontext zu stellen. Die verschiedenenFormate der Supervision im pferdegest\ufctzen Kontext werden n\ue4her beschrieben undes erfolgt eine Auseinandersetzung mit den besonderen Rahmenbedingungen sowieder speziellen Rolle des Pferdes. Ein gro fer Schwerpunkt wird dem Erfassen derAuswirkungen der pferdegest\ufctzten Supervision auf den/die Supervisand*ingewidmet.Der Fokus liegt dabei auf der Praxisn\ue4he. Gest\ufctzt durch viele Aussagen vonSupervisand*innen wird die Relevanz und die Nachhaltigkeit der pferdegest\ufctzenSupervision hervorgehoben, zugleich aber auch ein Augenmerk auf dieQualit\ue4tskriterien gelegt.Zum Abschluss wird ein kritischer Diskurs \ufcber die gewonnenen Kenntnisse gestartetund ein m\uf6glicher Ausblick in die Zukunft gestartet.The following master's thesis deals with the use of horses in supervision. To begin,attention is given to the history of supervision as well as the shared history of humansand horses. The behaviour of horses in general is described in more detail. In order tobetter understand the mechanisms at work in equine-assisted supervision, a section isdedicated to developmental psychology, neurobiology, and pedagogy.Various influencing factors in relation to equine supervision are described in depth, andan attempt is made to place them in a scientific context. The different formats ofsupervision in the context of equine-assisted activities are described in more detail,and consideration is given to the special framework conditions and the specific role ofthe horse. Special priority is given to understanding the effects of equine-assistedsupervision on the supervisee.The focus was on practical relevance. Supported by many statements fromsupervisees, the relevance and sustainability of equine-assisted supervision areemphasized, while simultaneously paying attention to quality criteria. Finally, a criticaldiscourse on the acquired knowledge in relation to equine supervision is initiated, anda possible outlook into the future of the use of horses in supervision is provided.Automatisch erstellte Titelanzeige \u2013 Daten nicht gepr\ufcftMasterarbeit Universit\ue4t Graz 202