Substantiate a read-across hypothesis by using transcriptome data—A case study on volatile diketones

This case study explores the applicability of transcriptome data to characterize a common mechanism of action within groups of short-chain aliphatic α-, β-, and γ-diketones. Human reference in vivo data indicate that the α-diketone diacetyl induces bronchiolitis obliterans in workers involved in the preparation of microwave popcorn. The other three α-diketones induced inflammatory responses in preclinical in vivo animal studies, whereas beta and gamma diketones in addition caused neuronal effects. We investigated early transcriptional responses in primary human bronchiolar (PBEC) cell cultures after 24 h and 72 h of air-liquid exposure. Differentially expressed genes (DEGs) were assessed based on transcriptome data generated with the EUToxRisk gene panel of Temp-O-Seq®. For each individual substance, genes were identified displaying a consistent differential expression across dose and exposure duration. The log fold change values of the DEG profiles indicate that α- and β-diketones are more active compared to γ-diketones. α-diketones in particular showed a highly concordant expression pattern, which may serve as a first indication of the shared mode of action. In order to gain a better mechanistic understanding, the resultant DEGs were submitted to a pathway analysis using ConsensusPathDB. The four α-diketones showed very similar results with regard to the number of activated and shared pathways. Overall, the number of signaling pathways decreased from α-to β-to γ-diketones. Additionally, we reconstructed networks of genes that interact with one another and are associated with different adverse outcomes such as fibrosis, inflammation or apoptosis using the TRANSPATH-database. Transcription factor enrichment and upstream analyses with the geneXplain platform revealed highly interacting gene products (called master regulators, MRs) per case study compound. The mapping of the resultant MRs on the reconstructed networks, visualized similar gene regulation with regard to fibrosis, inflammation and apoptosis. This analysis showed that transcriptome data can strengthen the similarity assessment of compounds, which is of particular importance, e.g., in read-across approaches. It is one important step towards grouping of compounds based on biological profiles

Beiträge zum 28. Darmstädter Geotechnik-Kolloquium am 09. März 2022

Themenschwerpunkte: 1. Modell- und Feldversuche 2. Digitalisierung und künstliche Intelligenz in der Geotechnik 3. Nationale und internationale Großprojekte 4. Normung und Rechtliche

Beiträge zum 28. Darmstädter Geotechnik-Kolloquium am 09. März 2022

Themenschwerpunkte: 1. Modell- und Feldversuche 2. Digitalisierung und künstliche Intelligenz in der Geotechnik 3. Nationale und internationale Großprojekte 4. Normung und Rechtliche

Global data on earthworm abundance, biomass, diversity and corresponding environmental properties

Publisher Copyright: © 2021, The Author(s).Earthworms are an important soil taxon as ecosystem engineers, providing a variety of crucial ecosystem functions and services. Little is known about their diversity and distribution at large spatial scales, despite the availability of considerable amounts of local-scale data. Earthworm diversity data, obtained from the primary literature or provided directly by authors, were collated with information on site locations, including coordinates, habitat cover, and soil properties. Datasets were required, at a minimum, to include abundance or biomass of earthworms at a site. Where possible, site-level species lists were included, as well as the abundance and biomass of individual species and ecological groups. This global dataset contains 10,840 sites, with 184 species, from 60 countries and all continents except Antarctica. The data were obtained from 182 published articles, published between 1973 and 2017, and 17 unpublished datasets. Amalgamating data into a single global database will assist researchers in investigating and answering a wide variety of pressing questions, for example, jointly assessing aboveground and belowground biodiversity distributions and drivers of biodiversity change.Peer reviewe

Global data on earthworm abundance, biomass, diversity and corresponding environmental properties

Earthworms are an important soil taxon as ecosystem engineers, providing a variety of crucial ecosystem functions and services. Little is known about their diversity and distribution at large spatial scales, despite the availability of considerable amounts of local-scale data. Earthworm diversity data, obtained from the primary literature or provided directly by authors, were collated with information on site locations, including coordinates, habitat cover, and soil properties. Datasets were required, at a minimum, to include abundance or biomass of earthworms at a site. Where possible, site-level species lists were included, as well as the abundance and biomass of individual species and ecological groups. This global dataset contains 10,840 sites, with 184 species, from 60 countries and all continents except Antarctica. The data were obtained from 182 published articles, published between 1973 and 2017, and 17 unpublished datasets. Amalgamating data into a single global database will assist researchers in investigating and answering a wide variety of pressing questions, for example, jointly assessing aboveground and belowground biodiversity distributions and drivers of biodiversity change

Hematopoietic stem cell transplantation for adolescents and adults with inborn errors of immunity: an EBMT IEWP study.

peer reviewedAllogeneic hematopoietic stem cell transplantation (HSCT) is the gold standard curative therapy for infants and children with many inborn errors of immunity (IEI), but adolescents and adults with IEI are rarely referred for transplant. Lack of published HSCT outcome data outside small, single-center studies and perceived high risk of transplant-related mortality have delayed the adoption of HSCT for IEI patients presenting or developing significant organ damage later in life. This large retrospective, multicenter HSCT outcome study reports on 329 IEI patients (age range, 15-62.5 years at HSCT). Patients underwent first HSCT between 2000 and 2019. Primary endpoints were overall survival (OS) and event-free survival (EFS). We also evaluated the influence of IEI-subgroup and IEI-specific risk factors at HSCT, including infections, bronchiectasis, colitis, malignancy, inflammatory lung disease, splenectomy, hepatic dysfunction, and systemic immunosuppression. At a median follow-up of 44.3 months, the estimated OS at 1 and 5 years post-HSCT for all patients was 78% and 71%, and EFS was 65% and 62%, respectively, with low rates of severe acute (8%) or extensive chronic (7%) graft-versus-host disease. On univariate analysis, OS and EFS were inferior in patients with primary antibody deficiency, bronchiectasis, prior splenectomy, hepatic comorbidity, and higher hematopoietic cell transplant comorbidity index scores. On multivariable analysis, EFS was inferior in those with a higher number of IEI-associated complications. Neither age nor donor had a significant effect on OS or EFS. We have identified age-independent risk factors for adverse outcome, providing much needed evidence to identify which patients are most likely to benefit from HSCT

Biological Earth observation with animal sensors

Space-based tracking technology using low-cost miniature tags is now delivering data on fine-scale animal movement at near-global scale. Linked with remotely sensed environmental data, this offers a biological lens on habitat integrity and connectivity for conservation and human health; a global network of animal sentinels of environmen-tal change

Rechtspflichten im Verfassungsstaat | Verfassungs- und verwaltungsrechtliche Aspekte der Dogmatik öffentlich-rechtlicher Pflichten Privater

Der Begriff der Rechtspflicht hat umfassende rechts- und normtheoretische Behandlung erfahren, in der neueren staats- und verwaltungsrechtlichen Dogmatik aber wenig Beachtung gefunden. Matthias Wehr erörtert die systematische Funktion der Rechtspflicht im öffentlichen Recht und insbesondere öffentliche Pflichten Privater zum Schutz von Rechtsgütern Dritter.Als Grundbegriff (auch) des öffentlichen Rechts erweist sich die Rechtspflicht für den Begriff der Rechtswidrigkeit sowohl in Bezug auf staatliche Maßnahmen als auch für das Verhalten der Bürger. Rechtswidrigkeit ist stets nur in Relation zu einem Rechtssubjekt und einer dieses treffenden Rechtspflicht zu verstehen. Ergänzt wird dies durch das Postulat der Einheit der Pflichtwidrigkeit, was beispielhaft an der Akzessorietät des Strafrechts aufgezeigt wird.Am Beispiel allgemeiner Rechtsgüterschutzpflichten Privater untersucht der Autor den Zusammenhang zu gleichgerichteten, aus den Grundrechten folgenden staatlichen Pflichten. Freiheit und Gleichheit erweisen sich dabei als die zentralen Bezugspunkte dieser Pflichten. In einem allgemeinen Rechtfertigungsmodell werden diese Aspekte einer Pflichtendogmatik verarbeitet. Die hieraus gewonnenen Erkenntnisse werden sodann zur Bestimmung von Rechtsgrund, Inhalt und Umfang der gefahrenabwehrrechtlichen Verantwortlichkeit fruchtbar gemacht.Schließlich analysiert Wehr die Rückwirkungen der Pflichtendogmatik auf die Entscheidungsbefugnisse der Exekutive und eröffnet so eine weitere, nämlich kompetenzielle Perspektive. Zugleich werden die der verwaltungsrechtlichen Lehre geläufigen Begriffe "Opportunitäts-" bzw. "Legalitätsprinzip" auf ihren sachlichen Gehalt hin befragt und eine inhaltliche, nicht lediglich definitorische Reformulierung dieser Termini vorgeschlagen