Development of an inhibiting antibody against equine interleukin 5 to treat insect bite hypersensitivity of horses

Insect bite hypersensitivity (IBH) is the most common allergic skin disease of horses. It is caused by insect bites of the Culicoides spp. which mediate a type I/IVb allergy with strong involvement of eosinophil cells. No specific treatment option is available so far. One concept could be the use of a therapeutic antibody targeting equine interleukin 5, the main activator and regulator of eosinophils. Therefore, antibodies were selected by phage display using the naïve human antibody gene libraries HAL9/10, tested in a cellular in vitro inhibition assay and subjected to an in vitro affinity maturation. In total, 28 antibodies were selected by phage display out of which eleven have been found to be inhibiting in the final format as chimeric immunoglobulin G with equine constant domains. The two most promising candidates were further improved by in vitro affinity maturation up to factor 2.5 regarding their binding activity and up to factor 2.0 regarding their inhibition effect. The final antibody named NOL226-2-D10 showed a strong inhibition of the interleukin 5 binding to its receptor (IC50 = 4 nM). Furthermore, a nanomolar binding activity (EC50 = 8.8 nM), stable behavior and satisfactory producibility were demonstrated. This antibody is an excellent candidate for in vivo studies for the treatment of equine IBH

Development of an inhibiting antibody against equine interleukin 5 to treat insect bite hypersensitivity of horses

Insect bite hypersensitivity (IBH) is the most common allergic skin disease of horses. It is caused by insect bites of the Culicoides spp. which mediate a type I/IVb allergy with strong involvement of eosinophil cells. No specific treatment option is available so far. One concept could be the use of a therapeutic antibody targeting equine interleukin 5, the main activator and regulator of eosinophils. Therefore, antibodies were selected by phage display using the naïve human antibody gene libraries HAL9/10, tested in a cellular in vitro inhibition assay and subjected to an in vitro affinity maturation. In total, 28 antibodies were selected by phage display out of which eleven have been found to be inhibiting in the final format as chimeric immunoglobulin G with equine constant domains. The two most promising candidates were further improved by in vitro affinity maturation up to factor 2.5 regarding their binding activity and up to factor 2.0 regarding their inhibition effect. The final antibody named NOL226-2-D10 showed a strong inhibition of the interleukin 5 binding to its receptor (IC50 = 4 nM). Furthermore, a nanomolar binding activity (EC50 = 8.8 nM), stable behavior and satisfactory producibility were demonstrated. This antibody is an excellent candidate for in vivo studies for the treatment of equine IBH

Towards Our Common Digital Future. Flagship Report.

In the report “Towards Our Common Digital Future”, the WBGU makes it clear that sustainability strategies and concepts need to be fundamentally further developed in the age of digitalization. Only if digital change and the Transformation towards Sustainability are synchronized can we succeed in advancing climate and Earth-system protection and in making social progress in human development. Without formative political action, digital change will further accelerate resource and energy consumption, and exacerbate damage to the environment and the climate. It is therefore an urgent political task to create the conditions needed to place digitalization at the service of sustainable development

Rethinking Land in the Anthropocene: from Separation to Integration

Nur wenn sich unser Umgang mit Land grundlegend ändert, können die Klimaschutzziele erreicht, der dramatische Verlust der biologischen Vielfalt abgewendet und das globale Ernährungssystem nachhaltig gestaltet werden. Der WBGU schlägt fünf exemplarische Mehrgewinnstrategien vor, um Konkurrenzen zwischen Nutzungsansprüchen zu überwinden. Diese sollten durch fünf Governance-Strategien vorangetrieben werden, darunter insbesondere die Setzung geeigneter Rahmenbedingungen, eine Neuorientierung der EUPolitik und die Errichtung von Gemeinschaften gleichgesinnter Staaten.Only if there is a fundamental change in the way we manage land can we reach the targets of climate-change mitigation, avert the dramatic loss of biodiversity and make the global food system sustainable. The WBGU proposes five multiple-benefit strategies illustrating ways of overcoming competition between rival claims to the use of land. These should be promoted by five governance strategies, especially by setting suitable framework conditions, reorienting EU policy and establishing alliances of like-minded states

Unsere gemeinsame digitale Zukunft

Das Gutachten „Unsere gemeinsame digitale Zukunft“ macht deutlich, dass Nachhaltigkeitsstrategien und -konzepte im Zeitalter der Digitalisierung grundlegend weiterentwickelt werden müssen. Nur wenn der digitale Wandel und die Transformation zur Nachhaltigkeit konstruktiv verzahnt werden, kann es gelingen, Klima- und Erdsystemschutz sowie soziale Fortschritte menschlicher Entwicklung voranzubringen. Ohne aktive politische Gestaltung wird der digitale Wandel den Ressourcen- und Energieverbrauch sowie die Schädigung von Umwelt und Klima weiter beschleunigen. Daher ist es eine vordringliche politische Aufgabe, Bedingungen dafür zu schaffen, die Digitalisierung in den Dienst nachhaltiger Entwicklung zu stellen

External auditory exostoses in wind-dependent water sports participants: German wind- and kitesurfers

Purpose!#!Cold water and wind are known to cause exostoses of the external auditory canal. Different prevalences in different sports have been described in the literature. The aim of this study was to investigate the prevalence of external auditory exostosis (EAE) and EAE severity in coastal German wind- and kitesurfers who are exposed to cold water and strong winds. Furthermore, influencing factors such as the total exposure time and frequency of activity as well as the correlations between symptoms and the severity of EAE were investigated.!##!Methods!#!In this retrospective cross-sectional study, German non-professional wind- and kitesurfers along the North and Baltic Sea coasts were recruited between September 2020 and November 2020. Each participant was interviewed about exposure time and otological symptoms and underwent bilateral video otoscopic examination to determine EAE severity.!##!Results!#!A total of 241 ears from 130 subjects were analysed. The prevalence of EAE was 75.1%. In 19.9% of the participants, severe EAE was found. Exposure time and the frequency of activity had significant effects on the severity of EAE. Compared to surfers, EAE growth seems to progress faster in wind- and kitesurfers. The number of symptoms requiring medical treatment increased when two-thirds of the external auditory canal was obstructed.!##!Conclusion!#!The prevalence of EAE in wind- and kitesurfers is high. Total exposure time and the frequency of activity influence EAE growth. EAE growth occurs faster in wind- and kitesurfers than in surfers. The additional influence of wind and the evaporative cooling of the EAC are thought to be responsible. The results of this study should increase awareness of the dynamics of EAE among ENT specialists and improve patient counselling

Digitales bürgerschaftliches Engagement

Fußballtrainer im Verein, einem älterem Herrn über die Straße helfen, bei OpenStreetMap Geoinformationen eintragen - alles freiwillig ausgeübte Tätigkeiten im Dienste des Gemeinwohls, die nicht auf materiellen Gewinn ausgerichtet sind. Die Tätigkeitsfelder dieses für die Gesellschaft so enorm wichtigen Engagements entwickeln sich immer ein bisschen fort. In unserer digitalen Gesellschaft findet bürgerschaftliches Engagement immer häufiger auch digital statt oder wird digital unterstützt. Dieses Whitepaper beleuchtet daher die Bedeutung der zunehmenden Digitalisierung der Gesellschaft für das bürgerschaftliche Engagement

Development of an inhibiting antibody against equine interleukin 5 to treat insect bite hypersensitivity of horses

Insect bite hypersensitivity (IBH) is the most common allergic skin disease of horses. It is caused by insect bites of the Culicoides spp. which mediate a type I/IVb allergy with strong involvement of eosinophil cells. No specific treatment option is available so far. One concept could be the use of a therapeutic antibody targeting equine interleukin 5, the main activator and regulator of eosinophils. Therefore, antibodies were selected by phage display using the naïve human antibody gene libraries HAL9/10, tested in a cellular in vitro inhibition assay and subjected to an in vitro affinity maturation. In total, 28 antibodies were selected by phage display out of which eleven have been found to be inhibiting in the final format as chimeric immunoglobulin G with equine constant domains. The two most promising candidates were further improved by in vitro affinity maturation up to factor 2.5 regarding their binding activity and up to factor 2.0 regarding their inhibition effect. The final antibody named NOL226-2-D10 showed a strong inhibition of the interleukin 5 binding to its receptor (IC50 = 4 nM). Furthermore, a nanomolar binding activity (EC50 = 8.8 nM), stable behavior and satisfactory producibility were demonstrated. This antibody is an excellent candidate for in vivo studies for the treatment of equine IBH