Sound Signalling in Orthoptera

The sounds produced by orthopteran insects are very diverse. They are widely studied for the insight they give into acoustic behaviour and the biophysical aspects of sound production and hearing, as well as the transduction of sound to neural signals in the ear and the subsequent processing of information in the central nervous system. The study of sound signalling is a multidisciplinary area of research, with a strong physiological contribution. This review considers recent research in physiology and the links with related areas of acoustic work on the Orthoptera

Mutations in ALK signaling pathways conferring resistance to ALK inhibitor treatment lead to collateral vulnerabilities in neuroblastoma cells

Background: Development of resistance to targeted therapies has tempered initial optimism that precision oncology would improve poor outcomes for cancer patients. Resistance mechanisms, however, can also confer new resistance-specific vulnerabilities, termed collateral sensitivities. Here we investigated anaplastic lymphoma kinase (ALK) inhibitor resistance in neuroblastoma, a childhood cancer frequently affected by activating ALK alterations. Methods: Genome-wide forward genetic CRISPR-Cas9 based screens were performed to identify genes associated with ALK inhibitor resistance in neuroblastoma cell lines. Furthermore, the neuroblastoma cell line NBLW-R was rendered resistant by continuous exposure to ALK inhibitors. Genes identified to be associated with ALK inhibitor resistance were further investigated by generating suitable cell line models. In addition, tumor and liquid biopsy samples of four patients with ALK-mutated neuroblastomas before ALK inhibitor treatment and during tumor progression under treatment were genomically profiled. Results: Both genome-wide CRISPR-Cas9-based screens and preclinical spontaneous ALKi resistance models identified NF1 loss and activating NRASQ61K mutations to confer resistance to chemically diverse ALKi. Moreover, human neuroblastomas recurrently developed de novo loss of NF1 and activating RAS mutations after ALKi treatment, leading to therapy resistance. Pathway-specific perturbations confirmed that NF1 loss and activating RAS mutations lead to RAS-MAPK signaling even in the presence of ALKi. Intriguingly, NF1 loss rendered neuroblastoma cells hypersensitive to MEK inhibition. Conclusions: Our results provide a clinically relevant mechanistic model of ALKi resistance in neuroblastoma and highlight new clinically actionable collateral sensitivities in resistant cells

House Sorting in “Harry Potter”: A Choice of Stereotypes?

Innerhalb dieser Arbeit wird der Einfluss des House Sorting, das Einteilen von Schülern in Häusern, in den „Harry Potter“-Romanen von J. K. Rowling untersucht. Es wird die These aufgestellt, dass im Zusammenhang mit den Hogwarts-Häusern Stereotypen gebildet werden, die einer klaren Abtrennung von Gut und Böse dienen und zum Ende der Buchreihe teilweise durchbrochen werden. Nach einer theoretischen Abhandlung über Stereotypen und ihrer Bildung wird auf die Struktur von Häusern innerhalb der Organisation von Internatsschulen eingegangen. Es wird gezeigt, wie die Häuser im Gleichklang zu britischen Boarding Schools auch im narrativen Text zu einem Gemeinschaftsgefühl, zu Rivalisierungen und zu einer gleichsamen Eintracht und Trennung von Schülern führen. Im Anschluss wird dargestellt, wie der narrative Text die Einstellungen gegenüber den Hogwarts-Häusern mithilfe von mehreren stilistischen Mitteln manipuliert, steuert und damit Stereotype hervorruft. Durch eine Analyse der Einführung jedes Hauses wird deutlich, wie Slytherin mit Voldemort, faschistischen Ideologien und dem Bösen assoziiert wird, während Gryffindor durch den symbolischen Gegensatz zu Slytherin zum endgültigen Gutem und Rechtmäßigem wird. Die Entwicklungen ausgesuchter, stereotypisierter Figuren, die sich in entscheidenden Momenten überraschend verhalten, brechen die Stereotype, die zu den Häusern gehören, leicht. Der Schwerpunkt liegt dabei auf Severus Snape und Peter Pettigrew, die mit unterschiedlichen Motivationen die Seite wechseln. Im Anschluss wird argumentiert, dass die Haus-Stereotypen am Ende der Buchreihe nicht abgelehnt werden, sondern weiterhin innerhalb der Zaubergesellschaft bestehen bleiben. Allerdings ist die Möglichkeit der Wahl ein wiederkehrendes Motiv in „Harry Potter“, welches deutlich macht, dass Lebensumstände keinen Einfluss auf moralische Entscheidungen haben.This work examines the influence of House Sorting – the act of dividing pupils into school houses – in the “Harry Potter” novels by J. K. Rowling. Within the novels, stereotypes in connection to Hogwarts houses are established. The stereotypes then serve as a clear distinction between good and evil and are partially rejected at the end of the series. After a theoretical investigation into stereotypes and their development, the work at hand focuses on the structure of houses within the organisation of boarding schools. It is shown how the houses in the narrative text lead to a sense of community and to rivalry among Hogwarts students – thus, similar to British boarding schools, both to unification and separation of students. Following this, it is outlined how the narrative text manipulates and guides the character’s and the reader’s attitudes towards the Hogwarts Houses with the help of stylistic means, thereby creating stereotypes. An analysis of the introduction of every house shows how Slytherin is associated with Voldemort, fascists ideologies and evil, while Gryffindor becomes the ultimate good and rightful by its symbolic opposition to Slytherin. The developments of selected, stereotypical characters who behave surprisingly in moments of choice partially break the stereotypes connected to the houses. The analysis focuses on Severus Snape and Peter Pettigrew who both change sides out of different motivations. Finally, it is argued that the house stereotypes as such are not rejected at the end of the book series but rather persist within the magical society. However, a recurring motif in “Harry Potter” is the possibility of choice, which shows how personal (living) conditions do not confine moral decisions