“In a Land of Myth and a Time of Magic”: The Role and Adaptability of the Arthurian Tradition in the Twentieth and Twenty-First Centuries

The story of King Arthur and his knights is a narrative that spans centuries, a myth recreated by a variety of people for a variety of purposes. This thesis, by investigating key moments in the history of the Arthurian tradition, seeks to reveal the fluidity of Arthurian tales and identify some of the features that make them prevalent and influential across time. Part I examines the development of the Arthurian tradition, identifying significant time periods and works of literature that contributed to the formation of the overarching legend. Part II discusses two key eras that illustrate how the myth has been appropriated and the ways it contributed to that particular time: the ideas of knighthood and the Holy Grail found in Nazi Germany, and the Camelot myth of John F. Kennedy’s presidency. Part III turns towards a contemporary work featuring Arthur and explores how it has been adapted for a modern audience, analyzing the British Broadcasting Corporation’s (BBC’s) television series Merlin. Considering the revisions and innovations made to the Arthurian myth in the show, I posit the contemporary issues it addresses and compare the role it serves today to the roles played by the myth in the past. In conclusion, I propose what makes the Arthurian narrative as adaptable and timeless as to be continually reinvented over thousands of years

Aetiology, course and treatment of acute tubulointerstitial nephritis in paediatric patients : A cross-sectional web-based survey

Publisher Copyright: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Background Acute tubulointerstitial nephritis (TIN) is a significant cause of acute renal failure in paediatric and adult patients. There are no large paediatric series focusing on the aetiology, treatment and courses of acute TIN. Patients, design and setting We collected retrospective clinical data from paediatric patients with acute biopsy-proven TIN by means of an online survey. Members of four professional societies were invited to participate. Results Thirty-nine physicians from 18 countries responded. 171 patients with acute TIN were included (54% female, median age 12 years). The most frequent causes were tubulointerstitial nephritis and uveitis syndrome in 31% and drug-induced TIN in 30% (the majority of these caused by non-steroidal anti-inflammatory drugs). In 28% of patients, no initiating noxae were identified (idiopathic TIN). Median estimated glomerular filtration rate (eGFR) rose significantly from 31 at time of renal biopsy to 86 mL/ min/1.73 m2 3-6 months later (p<0.001). After 3-6 months, eGFR normalised in 41% of patients (eGFR ≥90 mL/ min/1.73 m2), with only 3% having severe or end-stage impairment of renal function (<30 mL/min/1.73 m2). 80% of patients received corticosteroid therapy. Median eGFR after 3-6 months did not differ between steroid-treated and steroid-untreated patients. Other immunosuppressants were used in 18% (n=31) of patients, 21 of whom received mycophenolate mofetil. Conclusions Despite different aetiologies, acute paediatric TIN had a favourable outcome overall with 88% of patients showing no or mild impairment of eGFR after 3-6 months. Prospective randomised controlled trials are needed to evaluate the efficacy of glucocorticoid treatment in paediatric patients with acute TIN.Peer reviewe

Ran-dependent docking of importin-β to RanBP2/Nup358 filaments is essential for protein import and cell viability

RanBP2 captures RanGTP–importin-β complexes at cytoplasmic fibrils to ensure adequate classical NLS–mediated protein import and cell viability

Studies of synaptic proteins in an animal model for Alzheimer's disease

Die Alzheimer-Demenz (AD) ist eine schwere neurodegenerative Erkrankung und stellt die häufigste Ursache einer Demenz dar. Charakteristische neuropathologische Kennzeichen der AD sind extrazelluläre senile Plaques, neurofibrilläre Tangles sowie axonale und synaptische Degeneration. Gestörten axonalen Transportprozessen wird eine wesentliche pathogenetische Bedeutung für die AD beigemessen. Sie manifestieren sich auf morphologischer Ebene als axonale Auftreibungen oder Sphäroide, die axonal transportierte Zellbestandteile enthalten, und als dystrophe Neuriten, die in der Peripherie der Alzheimer-Plaques vorkommen. Der Verlust von Synapsen und das Auftreten dystropher Neuriten scheinen besser mit dem kognitiven Abbau im Krankheitsprozess der AD zu korrelieren als die Menge extrazellulärer Amyloidplaques. Gegenstand dieser Arbeit war die Markierung neuritischer Schädigung im doppelt-transgenen APPSLPS1KI-Mausmodell. Spezifische Enzym-markierte Antikörper gegen synaptisch exprimierte Proteine wurden für immunhistochemische Färbungen an Paraffinschnitten des Mausgehirns getestet. Es gelang der Nachweis pathologischer Akkumulationen der zum synaptischen SNARE-Komplex gehörenden Proteine Synaptobrevin, SNAP-25, Syntaxin 7, Syntaxin 13 und Vti1b sowie der Proteine α- und β-Synuclein, Synaptopodin und Proton-ATPase in dystrophen Neuriten in der Umgebung neuritischer Plaques. Die Mehrzahl dieser Proteine konnte ebenfalls in dystrophen Neuriten humaner AD-Fälle nachgewiesen werden. Die Ergebnisse der Arbeit zeigen, dass diverse synaptische Proteine in pathologische Veränderungen des AD-Gehirns einbezogen werden und aufgrund ihres Akkumulationsverhaltens als Marker neuritischer Schädigung eingesetzt werden können. Die morphologische und neurochemische Vielfalt der dystrophen Neuriten deutet auf den Schweregrad der neuritischen Schädigung im APPSLPS1KI-Mausmodell hin

Aetiology, course and treatment of acute tubulointerstitial nephritis in paediatric patients: a cross-sectional web-based survey

Background Acute tubulointerstitial nephritis (TIN) is a significant cause of acute renal failure in paediatric and adult patients. There are no large paediatric series focusing on the aetiology, treatment and courses of acute TIN. Patients, design and setting We collected retrospective clinical data from paediatric patients with acute biopsy-proven TIN by means of an online survey. Members of four professional societies were invited to participate. Results Thirty-nine physicians from 18 countries responded. 171 patients with acute TIN were included (54%female, median age 12 years). The most frequent causes were tubulointerstitial nephritis and uveitis syndrome in 31% and drug-induced TIN in 30% (the majority of these caused by non-steroidal anti-inflammatory drugs). In 28% of patients, no initiating noxae were identified (idiopathic TIN). Median estimated glomerular filtration rate (eGFR) rose significantly from 31 at time of renal biopsy to 86mL/min/1.73m(2) 3-6 months later (p90mL/min/1.73m(2)), with only 3% having severe or end-stage impairment of renal function (<30mL/min/1.73m(2)). 80% of patients received corticosteroid therapy. Median eGFR after 3-6 months did not differ between steroid-treated and steroid-untreated patients. Other immunosuppressants were used in 18% (n=31) of patients, 21 of whom received mycophenolate mofetil. Conclusions Despite different aetiologies, acute paediatric TIN had a favourable outcome overall with 88% of patients showing no or mild impairment of eGFR after 3-6 months. Prospective randomised controlled trials are needed to evaluate the efficacy of glucocorticoid treatment in paediatric patients with acute TIN.German Society of Pediatric Nephrology (GPN); European Society of Pediatric Nephrology (ESPN); European Network of Rare Kidney Diseases (ERKnet); Pediatric Nephrology Research Consortium (PNRC)We would like to thank the German Society of Pediatric Nephrology (GPN), the European Society of Pediatric Nephrology (ESPN), the European Network of Rare Kidney Diseases (ERKnet) and the Pediatric Nephrology Research Consortium (PNRC) for the support of this project

Nosological delineation of congenital ocular motor apraxia type Cogan : an observational study

Background: The nosological assignment of congenital ocular motor apraxia type Cogan (COMA) is still controversial. While regarded as a distinct entity by some authorities including the Online Mendelian Inheritance in Man catalog of genetic disorders, others consider COMA merely a clinical symptom. Methods: We performed a retrospective multicenter data collection study with re-evaluation of clinical and neuroimaging data of 21 previously unreported patients (8 female, 13 male, ages ranging from 2 to 24 years) diagnosed as having COMA. Results: Ocular motor apraxia (OMA) was recognized during the first year of life and confined to horizontal pursuit in all patients. OMA attenuated over the years in most cases, regressed completely in two siblings, and persisted unimproved in one individual. Accompanying clinical features included early onset ataxia in most patients and cognitive impairment with learning disability (n = 6) or intellectual disability (n = 4). Re-evaluation of MRI data sets revealed a hitherto unrecognized molar tooth sign diagnostic for Joubert syndrome in 11 patients, neuroimaging features of Poretti-Boltshauser syndrome in one case and cerebral malformation suspicious of a tubulinopathy in another subject. In the remainder, MRI showed vermian hypo-/dysplasia in 4 and no abnormalities in another 4 patients. There was a strong trend to more severe cognitive impairment in patients with Joubert syndrome compared to those with inconclusive MRI, but otherwise no significant difference in clinical phenotypes between these two groups. Conclusions: Systematical renewed analysis of neuroimaging data resulted in a diagnostic reappraisal in the majority of patients with early-onset OMA in the cohort reported here. This finding poses a further challenge to the notion of COMA constituting a separate entity and underlines the need for an expert assessment of neuroimaging in children with COMA, especially if they show cognitive impairment

Nosological delineation of congenital ocular motor apraxia type Cogan: an observational study

BACKGROUND: The nosological assignment of congenital ocular motor apraxia type Cogan (COMA) is still controversial. While regarded as a distinct entity by some authorities including the Online Mendelian Inheritance in Man catalog of genetic disorders, others consider COMA merely a clinical symptom. METHODS: We performed a retrospective multicenter data collection study with re-evaluation of clinical and neuroimaging data of 21 previously unreported patients (8 female, 13 male, ages ranging from 2 to 24 years) diagnosed as having COMA. RESULTS: Ocular motor apraxia (OMA) was recognized during the first year of life and confined to horizontal pursuit in all patients. OMA attenuated over the years in most cases, regressed completely in two siblings, and persisted unimproved in one individual. Accompanying clinical features included early onset ataxia in most patients and cognitive impairment with learning disability (n = 6) or intellectual disability (n = 4). Re-evaluation of MRI data sets revealed a hitherto unrecognized molar tooth sign diagnostic for Joubert syndrome in 11 patients, neuroimaging features of Poretti-Boltshauser syndrome in one case and cerebral malformation suspicious of a tubulinopathy in another subject. In the remainder, MRI showed vermian hypo-/dysplasia in 4 and no abnormalities in another 4 patients. There was a strong trend to more severe cognitive impairment in patients with Joubert syndrome compared to those with inconclusive MRI, but otherwise no significant difference in clinical phenotypes between these two groups. CONCLUSIONS: Systematical renewed analysis of neuroimaging data resulted in a diagnostic reappraisal in the majority of patients with early-onset OMA in the cohort reported here. This finding poses a further challenge to the notion of COMA constituting a separate entity and underlines the need for an expert assessment of neuroimaging in children with COMA, especially if they show cognitive impairment

Heterozygous truncating variants in SUFU cause congenital ocular motor apraxia

Purpose: This study aimed to delineate the genetic basis of congenital ocular motor apraxia (COMA) in patients not otherwise classifiable. Methods: We compiled clinical and neuroimaging data of individuals from six unrelated families with distinct clinical features of COMA who do not share common diagnostic characteristics of Joubert syndrome or other known genetic conditions associated with COMA. We used exome sequencing to identify pathogenic variants and functional studies in patient-derived fibroblasts. Results: In 15 individuals, we detected familial as well as de novo heterozygous truncating causative variants in the Suppressor of Fused (SUFU) gene, a negative regulator of the Hedgehog (HH) signaling pathway. Functional studies showed no differences in cilia occurrence, morphology, or localization of ciliary proteins, such as smoothened. However, analysis of expression of HH signaling target genes detected a significant increase in the general signaling activity in COMA patient-derived fibroblasts compared with control cells. We observed higher basal HH signaling activity resulting in increased basal expression levels of GLI1, GLI2, GLI3, and Patched1. Neuroimaging revealed subtle cerebellar changes, but no full-blown molar tooth sign. Conclusion: Taken together, our data imply that the clinical phenotype associated with heterozygous truncating germline variants in SUFU is a forme fruste of Joubert syndrome