Bridging the divide in language and approach between pedagogy and programming: the case of IMS Learning Design

Even though the IMS Learning Design (IMS LD) specification has offered a way for expressing multiple-learner scenarios, the language thus provided is far from the language, teaching practitioners use. To bridge this divide, we have developed IMS LD authoring software that translates from the learning designer perspective to the technical perspective. To aid adequate software developments, an analysis was performed to identify uses of level B properties in expert units of learning. In a second analysis, which is described in this paper, these uses were matched with demands of typical pedagogical methods. Some restrictions of the IMS LD specification are pointed out in this regard. As an outcome of the analyses, interfaces employing pedagogical language were integrated in the IMS LD authoring software in order to provide teaching practitioners access to level B functionalities despite their highly technical nature

Inflammatory events and their effect on neural stem cell differentiation

Inflammation plays a dual role in the central nervous system (CNS), serving as a defence mechanism to protect and restore neural tissue following injuries or infections, but also driving degeneration and aggravating damage. This study examines the intricate relationship between inflammation and neural stem cells (NSCs) within the CNS. NSCs are highly versatile cells capable of self-renewal and differentiation into various brain cell types, such as neurons, oligodendrocytes, and astrocytes, which are crucial for maintaining brain homeostasis. In Paper I we investigated the impact of NSC transplantation into an inflammatory environment following a spinal cord injury (SCI). The transplanted NSCs differentiated into oligodendrocytes and modulated the inflammatory environment, resulting in accelerated functional recovery after SCI. In Paper II we focused on the effect of irradiation on NSCs in young mice and their subsequent response to brain injuries. Irradiation poses an inflammatory challenge to the irradiated areas initiating for example microglial activation. Irradiated mice demonstrated a reduction in new neuron production post-stroke and a decrease in microglia cell numbers, indicating the influence of radiation on NSC behaviour during inflammation. In Paper III we delved into the role of secreted factors during an inflammatory reaction. We created a region-specific model by generating brain-stem specific astrocytes from embryonic stem cells (ESC) which, when exposed to inflammatory cues, exert neurotoxic effects on motor neurons. These findings present possibilities to recapitulate inflammatory scenarios using ESC. Finally, the Manuscript examines the impact of hydrogen peroxide (H2O2), a free radical released during inflammation, on the proliferation and differentiation of NSCs in vitro and in vivo. The results show that H2O2 increased NSC division and prompted a higher proportion of these cells to differentiate into oligodendrocytes. Moreover, this NSC behaviour was accompanied by transcriptional changes as seen in bulk RNA sequencing. Collectively, this doctoral thesis provided new cell-molecular insights into NSC biology in disease models of inflammatory responses involved in stroke, spinal cord injury or to inflammatory mediators. This is essential knowledge when developing therapeutic strategies aimed at mitigating harmful outcomes and promoting neurological health. Such insights may pave the way for future advancements in treating neurological disorders and injuries by leveraging the interaction between inflammation and NSC

Expression cloning screen for modifiers of amyloid precursor protein shedding

Ectodomain shedding of the amyloid precursor protein (APP) is a key regulatory step in the generation of the amyloid β peptide (Aβ), which is thought to provoke the pathogenesis of Alzheimer's disease. To better understand the cellular processes that regulate ectodomain shedding of APP we used human embryonic kidney 293 cells and applied a sib-selection expression cloning approach. In addition to a known activator of APP shedding – protein kinase A – the following cDNAs were identified: the endocytic proteins endophilin A1 and A3, the metabotropic glutamate receptor 3 (mGluR3), palmitoyl-protein thioesterase 1 (PPT1), Numb-like and the kinase MEKK2. Endophilins A1 and A3, as well as mGluR3 activated APP shedding relatively specifically. They had little or no effect on the shedding of the unrelated membrane proteins TNF receptor 2 and P-selectin glycoprotein ligand-1. In contrast, MEKK2 and PKA also increased shedding of TNF receptor 2, suggesting that these kinases contribute to a general program regulating ectodomain shedding. The strongest activator of APP shedding, endophilin A3, reduced the rate of APP endocytosis and specifically increased APP shedding by the protease α-secretase, as measured in an antibody uptake assay and by immunoblot analysis. This suggests that endophilin A3 is a novel modulator of APP trafficking affecting access of APP to α-secretase. In summary, this study shows that expression cloning is a suitable way to identify proteins controlling ectodomain shedding of membrane proteins

A novel activating mutation in transmembrane helix 6 of the thyrotropin receptor as cause of hereditary nonautoimmune hyperthyroidism

Constitutively-activating germline mutations of the thyrotropin receptor (TSHR) gene are very rare and are considered the cause of hereditary nonautoimmune hyperthyroidism. We describe four affected individuals from a Caucasian family: a mother and her three children, and an unaffected father. The mother and her first two children presented in a similar manner: lifelong histories of heat intolerance, hyperactivity, fast heart rate, reduced energy, increased appetite, and scrawny build. They all developed goiter in childhood and showed a suppressed TSH and elevated thyroxine (T(4)). The last child, a 12-year-old female, presented with no clinical symptoms or palpable neck mass, but with a suppressed TSH, elevated T(4) and thyromegaly detected by ultrasound. Mutation analysis of the TSHR gene in all family members revealed a novel heterozygous germline mutation resulting in the substitution of phenylalanine (TTC) by serine (TCC) at codon 631 in transmembrane helix 6 in the mother and all three children. Functional characterization of this germline mutation showed constitutive activation of the G(s)-mediated cyclic adenosine monophosphate (cAMP) pathway, which controls thyroid hormone production and thyroid growth. Molecular characterization of F631S demonstrates that this activating mutation plays a key role in the development of hereditary hyperthyroidism in this family although the timing of onset of clinical manifestations in the subjects may depend on other, as yet unidentified, factors

Cycloaddition Reactions of the Diphosphenyl Complex (η5-C5Me5)(CO)2Fe-P=P-Mes* (Mes* = 2,4,6-tBu3C6H2) with Hexafluoroacetone. X-Ray Structure Analyses of (η5-C5Me5)(CO) Fe P(=PMes*)OC(CF3)2CO and (η5-C5Me5)(CO)2FePP(Mes*)OC(CF3)2

Weber L, Buchwald S, Lentz D, Preugschat D, Stammler H-G, Neumann B. Cycloaddition Reactions of the Diphosphenyl Complex (η5-C5Me5)(CO)2Fe-P=P-Mes* (Mes* = 2,4,6-tBu3C6H2) with Hexafluoroacetone. X-Ray Structure Analyses of (η5-C5Me5)(CO) Fe P(=PMes*)OC(CF3)2CO and (η5-C5Me5)(CO)2FePP(Mes*)OC(CF3)2. Organometallics. 1992;11(7):2351-2353.The diphosphenyl complex (eta-5-C5Me5)-(CO)2Fe-P=P-Mes* (Mes* = 2,4,6-tBu3C6H2) undergoes a [3 + 2] dipolar cycloaddition with hexafluoroacetone to give the metalla heterocycle (eta-5-C5Me5)(CO)-Fe-P(=PMes*)OC(CF3)2C(O) with a remarkably short Fe-P bond (2.084 (4) angstrom) and an exocyclic P=P bond. When stored in solution at -40-degrees-C, this complex partly rearranges to the metalated 1-oxa-2,3-diphosphetane (eta-5-C5Me5)(CO)2Fe-P-P(Mes*)OC(CF3)2. The molecular structures of both isomers were elucidated by single-crystal X-ray analyses

The complex co-translational processing of glycoprotein GP5 of type 1 porcine reproductive and respiratory syndrome virus

GP5 and M, the major membrane proteins of porcine reproductive and respiratory syndrome virus (PRRSV), are the driving force for virus budding and a target for antibodies. We studied co-translational processing of GP5 from an European PRRSV-1 strain. Using mass spectrometry, we show that in virus particles of a Lelystad variant, the signal peptide of GP5 was absent due to cleavage between glycine-34 and asparagine-35. This cleavage site removes an epitope for a neutralizing monoclonal antibody, but leaves intact another epitope recognized by neutralizing pig sera. Upon ectopic expression of this GP5 in cells, signal peptide cleavage was however inefficient. Complete cleavage occurred when cysteine-24 was changed to proline or an unused glycosylation site involving asparagine-35 was mutated. Insertion of proline at position 24 also caused carbohydrate attachment to asparagine-35. Glycosylation sites introduced downstream of residue 35 were used, but did not inhibit signal peptide processing. Co-expression of the M protein rescued this processing defect in GP5, suggesting a novel function of M towards GP5. We speculate that a complex interplay of the co-translational modifications of GP5 affect the N-terminal structure of the mature proteins and hence its antigenicity

kontakt.los! Bildung und Beratung für Familien während der Corona-Pandemie

Die Corona-Pandemie mit den Maßnahmen zu ihrer Eindämmung ist für Familien eine besondere Herausforderung – im Alltag, bei der Erziehung und Betreuung von Kindern sowie bei der Vereinbarkeit von Familie und Beruf. Sie stellt auch Einrichtungen, die Eltern unterstützend und beratend zur Seite stehen, vor große Aufgaben. Das Projekt "kontakt.los! Bildung und Beratung für Familien während der Corona-Pandemie" untersucht, wie Fachkräfte trotz weitreichender Veranstaltungsverbote, Kontaktbeschränkungen und Abstandsgebote mit Eltern in Kontakt bleiben, sie mit bedarfsgerechten Angeboten und passgenauen Formaten stärken und begleiten können, und welche digitalen Formate und innovativen Ansätze gut angenommen werden