Molecular clarification of brainstem astroblastoma with EWSR1-BEND2 fusion in a 38-year-old man

The majority of astroblastoma occur in a cerebral location in children and young adults. Here we describe the unusual case of a 38-year-old man found to have a rapidly growing cystic enhancing circumscribed brainstem tumor with high grade histopathology classified as astroblastoma, MN1-altered by methylome profiling. He was treated with chemoradiation and temozolomide followed by adjuvant temozolomide without progression to date over one year from treatment initiation. Astroblastoma most frequently contain a MN1-BEND2 fusion, while in this case a rare EWSR1-BEND2 fusion was identified. Only a few such fusions have been reported, mostly in the brainstem and spinal cord, and they suggest that BEND2, rather than MN1, may have a more critical functional role, at least in these regions. This unusual clinical scenario exemplifies the utility of methylome profiling and assessment of gene fusions in tumors of the central nervous system

WINDOWS

Creative writin

Banquet

Banquet by Anja Ziejewsk

Apoptosis

Apoptosis by Svea Türling

Specific immune modulation of experimental colitis drives enteric alpha-synuclein accumulation and triggers age-related Parkinson-like brain pathology

Background: In some people with Parkinson’s disease (PD), a-synuclein (αSyn) accumulation may begin in the enteric nervous system (ENS) decades before development of brain pathology and disease diagnosis. Objective: To determine how different types and severity of intestinal inflammation could trigger αSyn accumulation in the ENS and the subsequent development of αSyn brain pathology. Methods: We assessed the effects of modulating short- and long-term experimental colitis on αSyn accumulation in the gut of αSyn transgenic and wild type mice by immunostaining and gene expression analysis. To determine the long-term effect on the brain, we induced dextran sulfate sodium (DSS) colitis in young αSyn transgenic mice and aged them under normal conditions up to 9 or 21 months before tissue analyses. Results: A single strong or sustained mild DSS colitis triggered αSyn accumulation in the submucosal plexus of wild type and αSyn transgenic mice, while short-term mild DSS colitis or inflammation induced by lipopolysaccharide did not have such an effect. Genetic and pharmacological modulation of macrophage-associated pathways modulated the severity of enteric αSyn. Remarkably, experimental colitis at three months of age exacerbated the accumulation of aggregated phospho-Serine 129 αSyn in the midbrain (including the substantia nigra), in 21- but not 9-month-old αSyn transgenic mice. This increase in midbrain αSyn accumulation is accompanied by the loss of tyrosine hydroxylase-immunoreactive nigral neurons. Conclusions: Our data suggest that specific types and severity of intestinal inflammation, mediated by monocyte/macrophage signaling, could play a critical role in the initiation and progression of PD

[Die Combinations of] Unrelated Obverses and Reverses of Ancient Coins in Jacopo Strada’s Numismatic Works

Jacopo Strada beschreibt in seinen hinterlassenen numismatischen Manuskripten (i.e. Magnum ac Novum Opus, Diaskeué, Series Imperatorum Romanorum) Münzaverse und -reverse als zusammengehörig, die aber in Wirklichkeit mit jeweils anderen Vorder- und Rückseiten kombiniert sind. In einigen Bänden des MaNO und der Diaskeué ist die Anzahl solcher Münzen signifikant hoch (i.e. Augustus, Antoninus Pius, Mark Aurel). Durch die Besitzerangabe in der Diaskeué verleiht er ihnen eine vermeintlich sichere Authentizität. In dem Beitrag werden einige dieser Stempelkombinationen vorgestellt und es wird der Frage nachgegangen, was Strada zu diesen Zusammenstellungen veranlasst haben könnte. Hat er diese Münzen wirklich gesehen, d. h. existierten sie zu seiner Zeit und sind nicht auf uns gekommen oder hat er sie komplett ›erfunden‹? Dazu sollen auch die Werke seiner Zeitgenossen herangezogen werden (Pirro Ligorio, Sebastiano Erizzo, Antonio Agustín), um zu überprüfen, ob sich diese möglicherweise erfundenen Stempelkombinationen auch in deren Werken wiederfinden. Dadurch ergeben sich neue Einblicke in die Arbeits- und Vorgehensweise renaissancezeitlicher Antiquare.In his surviving numismatic manuscripts (i.e. Magnum ac Novum Opus, Diaskeué, Series Imperatorum Romanorum) Jacopo Strada describes coin obverses and reverses as belonging together, when in reality they had originally been part of coins displaying other obverses and reverses. In some volumes of the MaNO and Diaskeué, the occurence of such coins is very high (e.g. coins of Augustus, Antoninus Pius, Marcus Aurelius). By naming their sixteenth-century owners in the Diaskeué, Strada gave them a supposedly secure authenticity. My contribution presents some of these ›combinations‹ and examines what may have prompted Strada to create them. Did he really see these coins, i.e. did they exist in his time but have not been preserved, or did he completely ›invent‹ them? This investigation will also involve the works of his contemporaries (Pirro Ligorio, Sebastiano Erizzo, Antonio Agustín) to check whether such potentially invented ›combinations‹ can also be found in the works of other antiquarians. This investigation will also provide new insights into the work and approach of renaissance antiquarians

Neuromuscular disease: 2023 update

This review highlights ten important advances in the neuromuscular disease field that were reported in 2022. As with prior updates in this article series, the overarching topics include (i) advances in understanding of fundamental neuromuscular biology; (ii) new / emerging diseases; (iii) advances in understanding of disease etiology and pathogenesis; (iv) diagnostic advances; and (v) therapeutic advances. Within this general framework, the individual disease entities that are discussed in more detail include neuromuscular complications of COVID-19 (another look at the topic first covered in the 2021 and 2022 reviews), DNAJB4-associated myopathy, NMNAT2-deficient hereditary axonal neuropathy, Guillain-Barré syndrome, sporadic inclusion body myositis, and amyotrophic lateral sclerosis. In addition, the review highlights a few other advances (including new insights into mechanisms of fiber maturation during muscle regeneration and fiber rebuilding following reinnervation, improved genetic testing methods for facioscapulohumeral and myotonic muscular dystrophies, and the use of SARM1 inhibitors to block Wallerian degeneration) that will be of significant interest for clinicians and researchers who specialize in neuromuscular disease

What’s in a Name? Megarian apoikiai in the Black Sea: Common nomima and Local Traditions

The Megarians were one of the most active colonizers between the eighth and sixth centuries BCE, founding apoikiai ("colonies") in Sicily (Megara Hyblaia, Selinous), on the coasts of the Sea of Marmara (Astakos, Chalkedon, Selymbria, Byzantion), and along the Black Sea (Herakleia Pontike, Mesambria). At the same time, Megara was often not the only city who participated in the establishment of these settlements overseas: the literary and epigraphic sources attest the collaboration of Megarians with other groups of settlers from Greece (especially from Boiotia, Argos, and Corinth) and from their own colonies (Megara Hyblaia and Chalkedon), in the foundation and the development of their apoikiai. We may consider these foundations as the result of a synoikismos, or combination of several groups of settlers, often ethnically heterogeneous

Christian Social Ethics in the Benelux Countries: The Dynamics of European Unity in Diversity

Die Benelux-Länder werden eher in Reisebüchern als in der Wissenschaft als eine Einheit wahrgenommen. Dennoch verbindet Belgien, die Niederlande und Luxemburg eine spezielle historisch gewachsene Position innerhalb der EU mit Auswirkungen auf die Bedingungen und Themen Christlicher Sozialethik. Obwohl das Fach als eigenständige Disziplin nur an wenigen Orten existiert, bietet die gesellschaftliche Spannung z wischenUniversitäten mit großer auch  religiös geprägter Tradition und sehr weit fortgeschrittener Säkularisierung einen idealen Ausgangspunkt für innovative Forschung und Lehre mitten in Europa: mit Öffnungen zur anglophonen Welt und einer Brückenfunktion zwischen deutschen und französischen Einflüssen. Sozialethik ist überall in den Benelux-Ländern mit internationalem Profil und zugleich regionaler Verwurzelung verbunden.The Benelux countries are more frequently presented as a unity in tourist guides than in academic life. Belgium, the Netherlands and Luxembourg are nevertheless bound together by a specific historically founded position within the EU with consequences for the conditions and topics of Christian social ethics. Although it rarely exists as an autonomous discipline, the tension between old universities with religious traditions and a widely proceeded secularisation provides an ideal starting point for innovative research and teaching at the heart of Europe: with an access to the English speaking world and a bridge between German and French influences. All over the Benelux countries, social ethics combines an international profile with regional rooting