Vision Lieferdrohnen: Aufruf zur Betrachtung aus Perspektive der Technikfolgenabschätzung

The vision of drone-based delivery is not without presuppositions. To fully realize this vision, it is imperative to overcome the many technical and regulatory obstacles. Given the considerable depth of engagement of this technology – the airspace around us, which has so far only been used by birds and the occasional helicopter, would change profoundly – a number of typical technology assessment (TA) questions are on the table: Are there any safety concerns? Are there any environmental risks? Could criminals or terrorists misuse the technology? Are we going to face societal conflict in view of divergent interests? Is the current regulatory framework sufficient, or do we need new rules? This article provides a broad outline of this topic, gives first answers to the above mentioned questions, and concludes that an encompassing participatory TA study is needed.Die Vision eines drohnenbasierten Lieferverkehrs ist nicht voraussetzungslos. Viele regulative und technische Hürden müssen noch genommen werden, um sie Wirklichkeit werden zu lassen. Aufgrund der großen Eingriffstiefe dieser Technologieentwicklung – immerhin würde sich der uns umgebende Luftraum, der bislang nur von Vögeln und gelegentlichen Hubschraubern benutzt wird, gravierend ändern – stellen sich eine Reihe von typischen Fragen der Technikfolgenabschätzung (TA): Bestehen Sicherheitsbedenken? Gibt es Umweltrisiken? Kann die Technologie für kriminelle oder terroristische Zwecke missbraucht werden? Besteht ein gesellschaftliches Konfliktpotenzial angesichts unterschiedlicher Interessen? Reicht die aktuelle Regulierung aus oder müssen neue Regeln geschaffen werden? Dieser Artikel stellt das Thema in groben Zügen dar, gibt erste Antworten auf die genannten Fragen und erkennt die Notwendigkeit einer umfassenden, partizipativen TA‑Studie

An in vivo evaluation of Brilliant Blue G in animals and humans

Background/Aims: To evaluate the retinal toxicity of Brilliant Blue G (BBG) following intravitreal injection in rat eyes and examine the biocompatibility and the staining properties in humans.Methods: BBG was injected into the 11 rat eyes to evaluate toxic effects with balanced salt solution (BSS) serving as control. Retinal toxicity was assessed by retinal ganglion cell (RGC) counts and by light microscopy 7 days later. In addition, BBG was applied during vitrectomy for macular hole (MH) (n = 15) or epiretinal membranes (ERM) (n = 3) in a prospective, non-comparative consecutive series of patients. Before and after surgery, all patients underwent a complete clinical examination including measurement of best corrected visual acuity (VA) and intraocular pressure, perimetry, fundus photography and optical coherence tomography. Patients were seen 1 day before surgery and then in approximately four weeks intervals.Results: No significant reduction in RGC numbers and no morphological alterations were noted. A sufficient staining of the internal limiting membrane (ILM) was seen in patients with MH, while the staining pattern in ERM cases was patchy, indicating that parts of the ILM were peeled off along with the ERM in a variable extent. All MHs could be closed successfully. VA improved in 10 eyes (56%; 8/15 MH patients, 2/3 ERM patients), was unchanged in four eyes (22%; all MH patients) and was reduced in four eyes (22%; 3/15 MH, 1/3 ERM). No toxic effects attributable to the dye were noted during patient follow-up. The ultrastructure of tissue harvested during surgery was unremarkable.Conclusion: Brilliant Blue provides a sufficient and selective staining of the ILM. No retinal toxicity or adverse effects related to the dye were observed in animal and human studies. The long-term safety of this novel dye will have to be evaluated in larger patient series and a longer follow-up

Allele-specific gene expression can underlie altered transcript abundance in zebrafish mutants.

In model organisms, RNA-sequencing (RNA-seq) is frequently used to assess the effect of genetic mutations on cellular and developmental processes. Typically, animals heterozygous for a mutation are crossed to produce offspring with different genotypes. Resultant embryos are grouped by genotype to compare homozygous mutant embryos to heterozygous and wild-type siblings. Genes that are differentially expressed between the groups are assumed to reveal insights into the pathways affected by the mutation. Here we show that in zebrafish, differentially expressed genes are often over-represented on the same chromosome as the mutation due to different levels of expression of alleles from different genetic backgrounds. Using an incross of haplotype-resolved wild-type fish, we found evidence of widespread allele-specific expression, which appears as differential expression when comparing embryos homozygous for a region of the genome to their siblings. When analysing mutant transcriptomes, this means that the differential expression of genes on the same chromosome as a mutation of interest may not be caused by that mutation. Typically, the genomic location of a differentially expressed gene is not considered when interpreting its importance with respect to the phenotype. This could lead to pathways being erroneously implicated or overlooked due to the noise of spurious differentially expressed genes on the same chromosome as the mutation. These observations have implications for the interpretation of RNA-seq experiments involving outbred animals and non-inbred model organisms

Allele-specific gene expression can underlie altered transcript abundance in zebrafish mutants.

In model organisms, RNA-sequencing (RNA-seq) is frequently used to assess the effect of genetic mutations on cellular and developmental processes. Typically, animals heterozygous for a mutation are crossed to produce offspring with different genotypes. Resultant embryos are grouped by genotype to compare homozygous mutant embryos to heterozygous and wild-type siblings. Genes that are differentially expressed between the groups are assumed to reveal insights into the pathways affected by the mutation. Here we show that in zebrafish, differentially expressed genes are often over-represented on the same chromosome as the mutation due to different levels of expression of alleles from different genetic backgrounds. Using an incross of haplotype-resolved wild-type fish, we found evidence of widespread allele-specific expression, which appears as differential expression when comparing embryos homozygous for a region of the genome to their siblings. When analysing mutant transcriptomes, this means that the differential expression of genes on the same chromosome as a mutation of interest may not be caused by that mutation. Typically, the genomic location of a differentially expressed gene is not considered when interpreting its importance with respect to the phenotype. This could lead to pathways being erroneously implicated or overlooked due to the noise of spurious differentially expressed genes on the same chromosome as the mutation. These observations have implications for the interpretation of RNA-seq experiments involving outbred animals and non-inbred model organisms

Satisfiability of constraint specifications on XML documents

Jose Meseguer is one of the earliest contributors in the area of Algebraic Specification. In this paper, which we are happy to dedicate to him on the occasion of his 65th birthday, we use ideas and methods coming from that area with the aim of presenting an approach for the specification of the structure of classes of XML documents and for reasoning about them. More precisely, we specify the structure of documents using sets of constraints that are based on XPath and we present inference rules that are shown to define a sound and complete refutation procedure for checking satisfiability of a given specification using tableaux.Peer ReviewedPostprint (author's final draft

The gene regulatory basis of genetic compensation during neural crest induction.

The neural crest (NC) is a vertebrate-specific cell type that contributes to a wide range of different tissues across all three germ layers. The gene regulatory network (GRN) responsible for the formation of neural crest is conserved across vertebrates. Central to the induction of the NC GRN are AP-2 and SoxE transcription factors. NC induction robustness is ensured through the ability of some of these transcription factors to compensate loss of function of gene family members. However the gene regulatory events underlying compensation are poorly understood. We have used gene knockout and RNA sequencing strategies to dissect NC induction and compensation in zebrafish. We genetically ablate the NC using double mutants of tfap2a;tfap2c or remove specific subsets of the NC with sox10 and mitfa knockouts and characterise genome-wide gene expression levels across multiple time points. We find that compensation through a single wild-type allele of tfap2c is capable of maintaining early NC induction and differentiation in the absence of tfap2a function, but many target genes have abnormal expression levels and therefore show sensitivity to the reduced tfap2 dosage. This separation of morphological and molecular phenotypes identifies a core set of genes required for early NC development. We also identify the 15 somites stage as the peak of the molecular phenotype which strongly diminishes at 24 hpf even as the morphological phenotype becomes more apparent. Using gene knockouts, we associate previously uncharacterised genes with pigment cell development and establish a role for maternal Hippo signalling in melanocyte differentiation. This work extends and refines the NC GRN while also uncovering the transcriptional basis of genetic compensation via paralogues

Transcriptional profiling of zebrafish identifies host factors controlling susceptibility to Shigella flexneri

Shigella flexneri is a human-adapted pathovar of Escherichia coli that can invade the intestinal epithelium, causing inflammation and bacillary dysentery. Although an important human pathogen, the host response to S. flexneri has not been fully described. Zebrafish larvae represent a valuable model to study human infections in vivo. Here we use a Shigella-zebrafish infection model to generate mRNA expression profiles of host response to Shigella infection at the whole animal level. Immune response-related processes dominate the signature of early Shigella infection (6 hours post-infection). Consistent with its clearance from the host, the signature of late Shigella infection (24 hours post-infection) is significantly changed, and only a small set of immune-related genes remain differentially expressed, including acod1 and gpr84. Using mutant lines generated by ENU, CRISPR mutagenesis and F0 Crispants, we show that acod1- and gpr84-deficient larvae are more susceptible to Shigella infection. Together, these results highlight the power of zebrafish to model infection by bacterial pathogens and reveal the mRNA expression of the early (acutely infected) and late (clearing) host response to Shigella infection