Fabrication and Analysis of Bio-Inspired Smart Surfaces

This work introduces novel techniques for the fabrication of bio-inspired hierarchical micro- and nanostructures. The enormous potential of these techniques is demonstrated by presenting a synthetic gecko-like adhesive matching the adhesion and self-cleaning of geckos very closely and a nanofur which is superhydrophobic, superoleophilic, underwater air-retaining, and even self-healing when surface treated

Induction of tolerogenic lung CD4+ T cells by local treatment with a pSTAT-3 and pSTAT-5 inhibitor ameliorated experimental allergic asthma

Signal transducer and activator of transcription (STAT)-3 inhibitors play an important role in regulating immune responses. Galiellalactone (GL) is a fungal secondary metabolite known to interfere with the binding of phosphorylated signal transducer and activator of transcription (pSTAT)-3 as well of pSTAT-6 dimers to their target DNA in vitro. Intra nasal delivery of 50 μg GL into the lung of naive Balb/c mice induced FoxP3 expression locally and IL-10 production and IL-12p40 in RNA expression in the airways in vivo. In a murine model of allergic asthma, GL significantly suppressed the cardinal features of asthma, such as airway hyperresponsiveness, eosinophilia and mucus production, after sensitization and subsequent challenge with ovalbumin (OVA). These changes resulted in induction of IL-12p70 and IL-10 production by lung CD11c+ dendritic cells (DCs) accompanied by an increase of IL-3 receptor α chain and indoleamine-2,3-dioxygenase expression in these cells. Furthermore, GL inhibited IL-4 production in T-bet-deficient CD4+ T cells and down-regulated the suppressor of cytokine signaling-3 (SOCS-3), also in the absence of STAT-3 in T cells, in the lung in a murine model of asthma. In addition, we found reduced amounts of pSTAT-5 in the lung of GL-treated mice that correlated with decreased release of IL-2 by lung OVA-specific CD4+ T cells after treatment with GL in vitro also in the absence of T-bet. Thus, GL treatment in vivo and in vitro emerges as a novel therapeutic approach for allergic asthma by modulating lung DC phenotype and function resulting in a protective response via CD4+FoxP3+ regulatory T cells locall

Micro-rheological properties of lung homogenates correlate with infection severity in a mouse model of Pseudomonas aeruginosa lung infection

Lung infections caused by Pseudomonas aeruginosa pose a serious threat to patients suffering from, among others, cystic fibrosis, chronic obstructive pulmonary disease, or bronchiectasis, often leading to life-threatening complications. The establishment of a chronic infection is substantially related to communication between bacteria via quorum-sensing networks. In this study, we aimed to assess the role of quorum-sensing signaling molecules of the Pseudomonas quinolone signal (PQS) and to investigate the viscoelastic properties of lung tissue homogenates of PA-infected mice in a prolonged acute murine infection model. Therefore, a murine infection model was successfully established via intra-tracheal infection with alginate-supplemented Pseudomonas aeruginosa NH57388A. Rheological properties of lung homogenates were analyzed with multiple particle tracking (MPT) and quorum-sensing molecules were quantified with LC–MS/MS. Statistical analysis of bacterial load and quorum-sensing molecules showed a strong correlation between these biomarkers in infected lungs. This was accompanied by noticeable changes in the consistency of lung homogenates with increasing infection severity. Furthermore, viscoelastic properties of the lung homogenates strongly correlated with bacterial load and quorum sensing molecules. Considering the strong correlation between the viscoelasticity of lung homogenates and the aforementioned biomarkers, the viscoelastic properties of infected lungs might serve as reliable new biomarker for the evaluation of the severity of P. aeruginosa infections in murine models

Re-evaluation of phytohormone-independent division of tobacco protoplast-derived cells

We have used a [3H] thymidine incorporation assay and microscopic observation in order to reassess recently published data dealing with the response of tobacco protoplasts to phytohormones, lipochitooligosaccharides and peptides (Harling et al., 1997; Hayashi et al., 1992; Miklashevichs et al., 1996; Miklashevichs et al., 1997; Rohrig et al., 1995; Rohrig et al., 1996; van de Sande et al., 1996; Walden et al., 1994). These proliferation assays reveal that, in contrast to published data, isolated cells of the investigated mutant plant lines axi159 (Hayashi et al., 1992; Walden et al., 1994), axi4/1 (Harling et al., 1997) and cyil (Miklashevichs et al., 1997), which were generated by activation T-DNA tagging, were unable to grow in the absence of auxin or cytokinin. Furthermore, lipochitooligosaccharides which play a key role in the induction of nodules on roots of legumes were unable to promote auxin- or cytokinin-independent cell division in tobacco protoplasts as claimed by Rohrig et al. (1995, 1996). The finding of van de Sande et al. (1996) that ENOD40 confers tolerance of high auxin concentration to wild-type tobacco protoplasts was also reinvestigated. The results of our investigations show that we were unable to reproduce the proliferation data presented in this study, which were obtained by counting tobacco protoplast-derived cells undergoing division. In total, none of the published data on phytohormone-independent division of tobacco cells could be reproduced.Peer reviewe

A Federated and Distributed Data Management Infrastructure to Enable Public Health Surveillance from Intensive Care Unit Data

The Robert Koch Institute (RKI) monitors the actual number of COVID-19 patients requiring intensive care from aggregated data reported by hospitals in Germany. So far, there is no infrastructure to make use of individual patient-level data from intensive care units for public health surveillance. Adopting concepts and components of the already established AKTIN Emergency Department Data registry, we implemented the prototype of a federated and distributed research infrastructure giving the RKI access to patient-level intensive care data.Peer Reviewe

Nachgefragt: 25 Antworten zum Stand des Wissens rund um Öko-Landbau und Bio-Lebensmittel

Die Broschüre „Nachgefragt: 25 Antworten zum Stand des Wissens rund um Öko-Landbau und Bio-Lebensmittel“ wurde 2006 in Kooperation mit externen Experten ausgearbeitet, in zwei Auflagen gedruckt und 2008 durch 3 Fragen ergänzt, die derzeit nur Online verfügbar sind. Die erste Auflage mit 5.000 Stück hat der BÖLW kostenlos an Multiplikatoren verschickt. Die zweite Auflage – ebenfalls in einer Auflage von 5.000 Exemplaren gedruckt – wurde zu den Kosten für Druck und Versand verkauft. Der Argumentationsleitfaden ist nahezu vergriffen. Hauptabnehmer waren Verbände und Wirtschaft. So fragten den Leitfaden beispielsweise viele Einzelhändler und Einzelhandelsketten für die Schulung ihres Verkaufspersonals nach. Für Journalisten und Politiker ist der Argumentationsleitfaden eine prägnante Einführung in aktuelle Fragen der Ökologischen Lebensmittelwirtschaft und übersichtliches Nachschlagewerk. Gerade in der Politik kann damit Verständnis für die Leistungen und die Bedeutung des Ökologischen Landbaus erreicht werden. Auch viele Privatpersonen haben den Leitfaden bestellt, um sich fundiert über die Ökologische Landwirtschaft zu informieren. Der Argumentationsleitfaden hat eine Lücke bei den Informationsmaterialien und Nachschlagewerken zur Ökologischen Lebensmittelwirtschaft geschlossen. Dazu und zu der inhaltlichen Aufarbeitung der Themen haben wir sehr gute Resonanzen erhalten und sind davon überzeugt, dass auch eine Neuauflage gut angenommen würde. Der Leitfaden ist bereits in der kurzen Zeit seit der Erstauflage ein Grundlagenwerk zum Ökologischen Landbau geworden, sodass Aktualität gewährleistet werden muss. Zentrales Qualitätsmerkmal eines Argumentationsleitfadens ist seine Aktualität. Besonderes Merkmal des Argumentationsleitfadens ist, dass er kurze prägnante Antworten auf zentrale Fragen zur Ökologischen Lebensmittelwirtschaft gibt und dabei den aktuellen Stand des Wissens zur Grundlage hat. Einerseits hat sich seit der Erstauflage die gesetzliche Grundlage für die Bio-Branche wesentlich verändert, da die EU-Öko-Verordnung einer Totalrevision unterzogen wurde. Andererseits wurden seither zahlreiche neue wissenschaftliche Studien veröffentlicht – insbesondere auch im Rahmen des Bundesprogramms Ökologischer Landbau – die bei der Fragenbeantwortung im Leitfaden berücksichtigt werden müssten. Aus diesen Gründen ist es unerlässlich, den Leitfaden inhaltlich gründlich zu überarbeiten und neu aufzulegen, damit seine bisherige erfolgreiche Leistung weiter zur Verfügung stehen kann. Ziel des Projektes ist daher die Überarbeitung und Veröffentlichung einer 4. Auflage des Argumentationsleitfadens, der Antworten auf grundlegende und besonders kritische Fragen zum ökologischen Landbau gibt. Auf einen Blick wird Wissen verfügbar gemacht, das über das allgemeine Grundlagenwissen zum Ökologischen Landbau hinaus geht und auf aktuellsten wissenschaftlichen Erkenntnissen beruht. Der neue Argumentationsleitfaden soll sowohl in elektronischer, als auch in gedruckter Form der Zielgruppe zugänglich gemacht werden. Wie die zweite Auflage soll auch diese der Zielgruppe zu einem Preis, der Druck und Versand abdeckt, zu Verfügung gestellt werden, so dass veraltete Exemplare ausgetauscht werden können. Für Journalisten und Politiker soll der Argumentationsleitfaden kostenlos zur Verfügung gestellt werden

Towards an International Consensus on the Prevention, Treatment, and Management of High-Risk Substance Use and Overdose among Youth

Background and Objectives: Now more than ever, there is an obvious need to reduce the overall burden of disease and risk of premature mortality that are associated with mental health and substance use disorders among young people. However, the current state of research and evidence-based clinical care for high-risk substance use among youth is fragmented and scarce. The objective of the study is to establish consensus for the prevention, treatment, and management of high-risk substance use and overdose among youth (10 to 24 years old). Materials and Methods: A modified Delphi technique was used based on the combination of scientific evidence and clinical experience of a group of 31 experts representing 10 countries. A semi-structured questionnaire with five domains (clinical risks, target populations, intervention goals, intervention strategies, and settings/expertise) was shared with the panelists. Based on their responses, statements were developed, which were subsequently revised and finalized through three iterations of feedback. Results: Among the five major domains, 60 statements reached consensus. Importantly, experts agreed that screening in primary care and other clinical settings is recommended for all youth, and that the objectives of treating youth with high-risk substance use are to reduce harm and mortality while promoting resilience and healthy development. For all substance use disorders, evidence-based interventions should be available and should be used according to the needs and preferences of the patient. Involuntary admission was the only topic that did not reach consensus, mainly due to its ethical implications and resulting lack of comparable evidence. Conclusions: High-risk substance use and overdoses among youth have become a major challenge. The system’s response has been insufficient and needs substantial change. Internationally devised consensus statements provide a first step in system improvement and reform

A New PqsR Inverse Agonist Potentiates Tobramycin Efficacy to Eradicate Pseudomonas aeruginosa Biofilms

Pseudomonas aeruginosa (PA) infections can be notoriously difficult to treat and are often accompanied by the development of antimicrobial resistance (AMR). Quorum sensing inhibitors (QSI) acting on PqsR (MvfR) – a crucial transcriptional regulator serving major functions in PA virulence – can enhance antibiotic efficacy and eventually prevent the AMR. An integrated drug discovery campaign including design, medicinal chemistry-driven hit-to-lead optimization and in-depth biological profiling of a new QSI generation is reported. The QSI possess excellent activity in inhibiting pyocyanin production and PqsR reporter-gene with IC50 values as low as 200 and 11 × 10−9 m, respectively. Drug metabolism and pharmacokinetics (DMPK) as well as safety pharmacology studies especially highlight the promising translational properties of the lead QSI for pulmonary applications. Moreover, target engagement of the lead QSI is shown in a PA mucoid lung infection mouse model. Beyond that, a significant synergistic effect of a QSI-tobramycin (Tob) combination against PA biofilms using a tailor-made squalene-derived nanoparticle (NP) formulation, which enhance the minimum biofilm eradicating concentration (MBEC) of Tob more than 32-fold is demonstrated. The novel lead QSI and the accompanying NP formulation highlight the potential of adjunctive pathoblocker-mediated therapy against PA infections opening up avenues for preclinical development

Benefits from using mixed precision computations in the ELPA-AEO and ESSEX-II eigensolver projects

We first briefly report on the status and recent achievements of the ELPA-AEO (Eigenvalue Solvers for Petaflop Applications - Algorithmic Extensions and Optimizations) and ESSEX II (Equipping Sparse Solvers for Exascale) projects. In both collaboratory efforts, scientists from the application areas, mathematicians, and computer scientists work together to develop and make available efficient highly parallel methods for the solution of eigenvalue problems. Then we focus on a topic addressed in both projects, the use of mixed precision computations to enhance efficiency. We give a more detailed description of our approaches for benefiting from either lower or higher precision in three selected contexts and of the results thus obtained

Molecular Mechanism of a Green-Shifted, pH-Dependent Red Fluorescent Protein mKate Variant

Fluorescent proteins that can switch between distinct colors have contributed significantly to modern biomedical imaging technologies and molecular cell biology. Here we report the identification and biochemical analysis of a green-shifted red fluorescent protein variant GmKate, produced by the introduction of two mutations into mKate. Although the mutations decrease the overall brightness of the protein, GmKate is subject to pH-dependent, reversible green-to-red color conversion. At physiological pH, GmKate absorbs blue light (445 nm) and emits green fluorescence (525 nm). At pH above 9.0, GmKate absorbs 598 nm light and emits 646 nm, far-red fluorescence, similar to its sequence homolog mNeptune. Based on optical spectra and crystal structures of GmKate in its green and red states, the reversible color transition is attributed to the different protonation states of the cis-chromophore, an interpretation that was confirmed by quantum chemical calculations. Crystal structures reveal potential hydrogen bond networks around the chromophore that may facilitate the protonation switch, and indicate a molecular basis for the unusual bathochromic shift observed at high pH. This study provides mechanistic insights into the color tuning of mKate variants, which may aid the development of green-to-red color-convertible fluorescent sensors, and suggests GmKate as a prototype of genetically encoded pH sensors for biological studies