CHARGE syndrome and related disorders:A mechanistic link

CHARGE syndrome is an autosomal dominant malformation disorder caused by pathogenic variants in the chromatin remodeler CHD7. Affected are craniofacial structures, cranial nerves and multiple organ systems. Depending on the combination of malformations present, its distinction from other congenital disorders can be challenging. To gain a better insight into the regulatory disturbances in CHARGE syndrome, we performed RNA-Seq analysis on blood samples of 19 children with CHARGE syndrome and a confirmed disease-causing CHD7 variant in comparison to healthy control children. Our analysis revealed a distinct CHARGE syndrome pattern with downregulation of genes that are linked to disorders described to mimic the CHARGE phenotype, i.e. KMT2D and KDM6A (Kabuki syndrome), EP300 and CREBBP (Rubinstein-Taybi syndrome) and ARID1A and ARID1B (Coffin-Siris syndrome). Furthermore, by performing protein-protein interaction studies using co-immunoprecipitation, direct yeast-two hybrid and in situ proximity ligation assays, we could demonstrate an interplay between CHD7, KMT2D, KDM6A and EP300. In summary, our data demonstrate a mechanistic and regulatory link between the developmental disorders CHARGE-, Kabuki- and Rubinstein Taybi-syndrome providing an explanation for the overlapping phenotypes

Functional evolution of nuclear structure

The evolution of the nucleus, the defining feature of eukaryotic cells, was long shrouded in speculation and mystery. There is now strong evidence that nuclear pore complexes (NPCs) and nuclear membranes coevolved with the endomembrane system, and that the last eukaryotic common ancestor (LECA) had fully functional NPCs. Recent studies have identified many components of the nuclear envelope in living Opisthokonts, the eukaryotic supergroup that includes fungi and metazoan animals. These components include diverse chromatin-binding membrane proteins, and membrane proteins with adhesive lumenal domains that may have contributed to the evolution of nuclear membrane architecture. Further discoveries about the nucleoskeleton suggest that the evolution of nuclear structure was tightly coupled to genome partitioning during mitosis

Late 1920s film theory and criticism as a test-case for Benjamin’s generalizations on the experiential effects of editing

This article investigates Walter Benjamin’s influential generalization that the effects of cinema are akin to the hyper-stimulating experience of modernity. More specifically, I focus on his oft-cited 1935/36 claim that all editing elicits shock-like disruption. First, I propose a more detailed articulation of the experience of modernity understood as hyper-stimulation and call for distinguishing between at least two of its subsets: the experience of speed and dynamism, on the one hand, and the experience of shock/disruption, on the other. Then I turn to classical film theory of the late 1920s to demonstrate the existence of contemporary views on editing alternative to Benjamin’s. For instance, whereas classical Soviet and Weimar theorists relate the experience of speed and dynamism to both Soviet and classical Hollywood style editing, they reserve the experience of shock/disruption for Soviet montage. In order to resolve the conceptual disagreement between these theorists, on the one hand, and Benjamin, on the other, I turn to late 1920s Weimar film criticism. I demonstrate that, contrary to Benjamin’s generalizations about the disruptive and shock-like nature of all editing, and in line with other theorists’ accounts, different editing practices were regularly distinguished by comparison to at least two distinct hyper-stimulation subsets: speed and dynamism, and shock-like disruption. In other words, contemporaries regularly distinguished between Soviet montage and classical Hollywood editing patterns on the basis of experiential effects alone. On the basis of contemporary reviews of city symphonies, I conclude with a proposal for distinguishing a third subset – confusion. This is an original manuscript / preprint of an article published by Taylor & Francis in Early Popular Visual Culture on 02 Aug 2016 available online: https://doi.org/10.1080/17460654.2016.1199322

Multiple Sklerose Therapie Konsensus Gruppe (MSTKG): Positionspapier zur verlaufsmodifizierenden Therapie der Multiplen Sklerose 2021 (White Paper)

Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, Switzerland)

Editorial: Emotion and Behavior

No abstract available

Installation of BSL-3 Laboratories and ABSL-3 Animal Experimentation Rooms in a Preexisting BSL-3Ag Facility: Design, Implementation, Validation, Time Requirements, and Costs

The Institute of Virology and Immunoprophylaxis (IVI) in Switzerland is a governmental biosafety level 3 agricultural (BSL-3Ag) facility involved in the diagnosis, surveillance, and control of highly contagious epizootics, such as foot and mouth disease or classical swine fever. It consists of an animal unit and a laboratory unit, which are interconnected in the same building. Although the shell of the facility corresponds to a biosafety level 4 (BSL-4) facility with respect to the environment (BSL-3Ag), in most cases people inside work at BSL-1 and -2. When the avian influenza type A (H5N1) epidemics reached their climax in Europe a few years ago, the Swiss veterinary services needed a reference laboratory for diagnosis and research of avian influenza Type A virus strains. However, since some highly pathogenic strains for avian influenza belong to risk group 3, it was necessary to integrate a new BSL-3 laboratory into the existing facility. Furthermore, four stables originally used for large animal experiments had to be retrofitted to comply with the ABSL-3 (animal biosafety level) standard to perform in vivo studies with zoonotic agents, in particular with avian influenza H5N1. This article addresses the process, the new system, the validation, the encountered problems, the time requirement, and the personnel and financial resources for this reconstruction within a BSL-3Ag facility

Installation of BSL-3 Laboratories and ABSL-3 Animal Experimentation Rooms in a Preexisting BSL-3Ag Facility: Design, Implementation, Validation, Time Requirements, and Costs

The Institute of Virology and Immunoprophylaxis (IVI) in Switzerland is a governmental biosafety level 3 agricultural (BSL-3Ag) facility involved in the diagnosis, surveillance, and control of highly contagious epizootics, such as foot and mouth disease or classical swine fever. It consists of an animal unit and a laboratory unit, which are interconnected in the same building. Although the shell of the facility corresponds to a biosafety level 4 (BSL-4) facility with respect to the environment (BSL-3Ag), in most cases people inside work at BSL-1 and -2. When the avian influenza type A (H5N1) epidemics reached their climax in Europe a few years ago, the Swiss veterinary services needed a reference laboratory for diagnosis and research of avian influenza Type A virus strains. However, since some highly pathogenic strains for avian influenza belong to risk group 3, it was necessary to integrate a new BSL-3 laboratory into the existing facility. Furthermore, four stables originally used for large animal experiments had to be retrofitted to comply with the ABSL-3 (animal biosafety level) standard to perform in vivo studies with zoonotic agents, in particular with avian influenza H5N1. This article addresses the process, the new system, the validation, the encountered problems, the time requirement, and the personnel and financial resources for this reconstruction within a BSL-3Ag facility