The relationship between performance on the Stanford Achievement Test and the Peabody Individual Achievement test for a group of hearing-impaired children

This paper discusses the Stanford and Peabody tests for achievement and which test is more efficient for hearing impaired children

The Drosophila functional Smad suppressing element fuss, a homologue of the human Skor genes, retains pro-oncogenic properties of the Ski/Sno family

Over the years Ski and Sno have been found to be involved in cancer progression e.g. in oesophageal squamous cell carcinoma, melanoma, oestrogen receptor-positive breast carcinoma, colorectal carcinoma, and leukaemia. Often, their prooncogenic features have been linked to their ability of inhibiting the anti-proliferative action of TGF-ß signalling. Recently, not only pro-oncogenic but also anti-oncogenic functions of Ski/Sno proteins have been revealed. Besides Ski and Sno, which are ubiquitously expressed other members of Ski/Sno proteins exist which show highly specific neuronal expression, the SKI Family Transcriptional Corepressors (Skor). Among others Skor1 and Skor2 are involved in the development of Purkinje neurons and a mutation of Skor1 has been found to be associated with restless legs syndrome. But neither Skor1 nor Skor2 have been reported to be involved in cancer progression. Using overexpression studies in the Drosophila eye imaginal disc, we analysed if the Drosophila Skor homologue Fuss has retained the potential to inhibit differentiation and induce increased proliferation. Fuss expressed in cells posterior to the morphogenetic furrow, impairs photoreceptor axon pathfinding and inhibits differentiation of accessory cells. However, if its expression is induced prior to eye differentiation, Fuss might inhibit the differentiating function of Dpp signalling and might maintain proliferative action of Wg signalling, which is reminiscent of the Ski/Sno protein function in cancer

The Mitochondrial Chaperone Protein TRAP1 Mitigates α-Synuclein Toxicity

Overexpression or mutation of α-Synuclein is associated with protein aggregation and interferes with a number of cellular processes, including mitochondrial integrity and function. We used a whole-genome screen in the fruit fly Drosophila melanogaster to search for novel genetic modifiers of human [A53T]α-Synuclein–induced neurotoxicity. Decreased expression of the mitochondrial chaperone protein tumor necrosis factor receptor associated protein-1 (TRAP1) was found to enhance age-dependent loss of fly head dopamine (DA) and DA neuron number resulting from [A53T]α-Synuclein expression. In addition, decreased TRAP1 expression in [A53T]α-Synuclein–expressing flies resulted in enhanced loss of climbing ability and sensitivity to oxidative stress. Overexpression of human TRAP1 was able to rescue these phenotypes. Similarly, human TRAP1 overexpression in rat primary cortical neurons rescued [A53T]α-Synuclein–induced sensitivity to rotenone treatment. In human (non)neuronal cell lines, small interfering RNA directed against TRAP1 enhanced [A53T]α-Synuclein–induced sensitivity to oxidative stress treatment. [A53T]α-Synuclein directly interfered with mitochondrial function, as its expression reduced Complex I activity in HEK293 cells. These effects were blocked by TRAP1 overexpression. Moreover, TRAP1 was able to prevent alteration in mitochondrial morphology caused by [A53T]α-Synuclein overexpression in human SH-SY5Y cells. These results indicate that [A53T]α-Synuclein toxicity is intimately connected to mitochondrial dysfunction and that toxicity reduction in fly and rat primary neurons and human cell lines can be achieved using overexpression of the mitochondrial chaperone TRAP1. Interestingly, TRAP1 has previously been shown to be phosphorylated by the serine/threonine kinase PINK1, thus providing a potential link of PINK1 via TRAP1 to α-Synuclein

fussel (fuss) - A Negative Regulator of BMP Signaling in Drosophila melanogaster

The TGF-β/BMP signaling cascades control a wide range of developmental and physiological functions in vertebrates and invertebrates. In Drosophila melanogaster, members of this pathway can be divided into a Bone Morphogenic Protein (BMP) and an Activin-ß (Act-ß) branch, where Decapentaplegic (Dpp), a member of the BMP family has been most intensively studied. They differ in ligands, receptors and transmitting proteins, but also share some components, such as the Co-Smad Medea (Med). The essential role of Med is to form a complex with one of the two activating Smads, mothers against decapentaplegic (Mad) or dSmad, and to translocate together to the nucleus where they can function as transcriptional regulators of downstream target genes. This signaling cascade underlies different mechanisms of negative regulation, which can be exerted by inhibitory Smads, such as daughters against decapentaplegic (dad), but also by the Ski-Sno family. In this work we identified and functionally analyzed a new member of the Ski/Sno-family, fussel (fuss), the Drosophila homolog of the human functional suppressing element 15 (fussel-15). fuss codes for two differentially spliced transcripts with a neuronal expression pattern. The proteins are characterized by a Ski-Sno and a SAND homology domain. Overexpression studies and genetic interaction experiments clearly reveal an interaction of fuss with members of the BMP pathway, leading to a strong repression of BMP-signaling. The protein interacts directly with Medea and seems to reprogram the Smad pathway through its influence upon the formation of functional Mad/Medea complexes. This leads amongst others to a repression of downstream target genes of the Dpp pathway, such as optomotor blind (omb). Taken together we could show that fuss exerts a pivotal role as an antagonist of BMP signaling in Drosophila melanogaster

The Appropriation of Nietzschean Thought by Donald Kuspit in the Critic Is Artist: The Intentionality of Art and the Existential Activist Painter: The Example of Leon Golub

The prolific scholar and art critic, Donald Kuspit has frequently cited the works of Friedrich Nietzsche as a means to elucidate his art critical theories. This paper is an investigation of these citations in two of his most important works, The Critic is Artist: The Intentionality of Art, published in 1984, and The Existential Activist Painter: The Example of Leon Golub, published in 1986. In each of these two works many citations revolve around two Nietzschean concepts, the will to power and ressentiment. This paper first explores the relevance of using the philosophical work of Nietzsche as a point of departure for art critical theories, and follows with a brief discussion of the application of Nietzsche\u27s theories to the visual arts. Finally, the citations used by Donald Kuspit are compared to Nietzsche\u27s text, demonstrating their use to be in conflict with Nietzsche\u27s theories

Die Bedeutung von oxidativem Stress bei hereditären und sporadischen Formen der Parkinson'schen Krankheit. Eine Studie an Drosophila melanogaster

Die Entstehung der Parkinson'schen Krankheit wird sowohl auf schädliche Umwelteinflüsse als auch auf genetische Prädisposition zurückgeführt. Einerseits führen diverse rezessive und dominante genetische Mutationen zum Auftreten der hereditären Form der Krankheit. Andererseits tritt sie auch sporadisch ohne erkennbaren genetischen Hintergrund auf oder wird erst durch Kontakt mit Neurotoxinen ausgelöst. In der vorliegenden Arbeit wurden nach Faktoren gesucht, die beiden Formen der Krankheit gemeinsam sind. Dafür wurden genetische und Neurotoxin-basierende Modellsysteme der Degeneration dopaminerger Neurone von Drosophila melanogaster etabliert. Es wurde beobachtet, dass die gezielte Expression humanem alpha-Synucleins zu altersabhängigem und spezifischem Verlust dopaminerger Neurone führt. Hereditäre Mutationen im alpha-Synuclein-Gen, beschleunigen die Degenerationsrate. Zumindest im Fall von alpha-SynA30P könnte die erhöhte Toxizität mit gestörtem axonalen Transport in Zusammenhang stehen. Außerdem sind dopaminerge Neurone anfällig gegenüber oxidativem Stress. Mittels Hyperoxie, Rotenon, Paraquat und genetisch bedingter Dysfunktion der zellulären Stressantwort war es möglich, Zellverluste am dopaminergen System auszulösen. Außerdem konnte beobachtet werden, dass die Toxizität von alpha-Syn, alpha-SynA30P und alpha-SynA53T unter Hyperoxie stark zunimmt. Daher erscheint es möglich, dass der Degeneration dieser Neurone bei den verschiedenen Modellsystemen ähnliche und synergetisch wirkende Mechanismen zugrunde liegen. Um diese Hypothese zu überprüfen wurde untersucht, ob die Neurodegeneration durch Verringerung der oxidativen Belastung der Zellen aufgehalten werden kann. Die Entfernung von Superoxid-Radikalen durch Expression humaner Zn/Cu- Superoxid-Dismutase war ausreichend, alpha-SynA30P-induzierte Neurodegeneration signifikant zu reduzieren. Allerdings war es dadurch nicht möglich, den Verlust der Neurone unter Rotenon- und Paraquatstress bedeutend zu verlangsamen. Alternativ zum Abfangen der Superoxid-Radikale wurde versucht, durch eine Reduktion der Dopamin-Produktion die Entstehung toxischer Dopamin- Metabolite zu verhindern. Durch die Unterdrückung des Dopamin-Stoffwechsels durch Silencing des Gens pale werden die dopaminergen Neurone vor der Toxizität von alpha-Synuclein und Rotenon geschützt. Die Paraquat-Neurotoxizität wurde wiederum nicht beeinflusst. Weiterhin wurde untersucht, ob auch die, bei der Parkinson'schen Krankheit auftretende alpha-Syn-Aggregation durch oxidativen Stress beeinflusst wird. Dafür wurde eine Fliegenlinie hergestellt, die C-terminal-modifiziertes alpha-Syn exprimiert. Die Expression dieses Konstrukts führte zu einem robusten Aggregations-Phänotyp in dopaminergen Neuronen. An diesem Modell konnte beobachtet werden, dass Rotenon und Paraquat den Aggregationsprozess des modifizierten alpha-Synucleins beschleunigen. Die Ergebnisse unterstützen die Hypothese, dass oxidativer Stress im Allgemeinen und oxidativer Stress aus dem Dopamin-Stoffwechsel im speziellen ein bedeutender Faktor bei der Entstehung und dem Fortschreiten der Parkinson'schen Krankheit sein könnte