dolls/puppets in threat scenarios

Puppen in Bedrohungsszenarien – so lautet der Themenschwerpunkt der ersten Ausgabe der interdisziplinären online-Zeitschrift "denkste: puppe / just a bit of: doll" zu Mensch-Puppen-Diskursen (Akronym: de:do). Die Bezeichnung ‚Puppe’ steht dabei für anthropomorphe ,Wesen’ und Artefakte in all ihren unterschiedlichen Erscheinungsformen und der Begriff der Bedrohung wird hier weit gefasst. Ausgangspunkt der Entscheidung für diesen Fokus war die Annahme, dass Puppen und puppenaffinen Artefakten sowohl in Zeiten existenzieller Bedrohung als auch in Phasen innerpsychischer Beunruhigung und Irritation eine besondere Bedeutung zukommt. Die hier einbezogenen Beiträge stammen aus unterschiedlichen Fachdisziplinen und eröffnen in der bewusst nicht disziplinär ausgerichteten Zusammenstellung reizvolle multiperspektivische Mensch-Puppen-Diskurse. Dabei sind nicht nur die hier angesprochenen Themenbezüge, sondern auch die jeweiligen methodischen Zugänge ausgesprochen heterogen. So werden Puppen-Narrative aufgegriffen, die beispielsweise innerhalb der Literaturwissenschaft an die lange Tradition von Puppen-Erzählungen anknüpfen, aber auch solche, die aktuell in den Diskursen über Zukunftsszenarien und neue Technologien mittels verschiedener medialer Formate und/oder künstlerischer Aktionen für Diskussionsstoff sorgen. Ein erster thematischer Fokus liegt auf der Bedeutung von Puppen im Zuge der Erfahrung von Bedrohung und Verlusten im Kontext von Krieg, Flucht und Verfolgung in politisch unsicheren Zeiten. Hier werden aus verschiedenen fachdisziplinären Perspektiven unterschiedliche Facetten von Bedrohungsszenarien angesprochen. So geht es aus theaterwissenschaftlicher Sicht um zwei Inszenierungen aus dem Bereich des Objekt- und Materialtheaters, in denen bedrohliche Kriegsdarstellungen mittels Plastikpuppen bzw. amorphen Materials aufbereitet werden. Aus psychologischer Perspektive kommen Rollen und Funktionen von Puppen als Übergangsobjekte im Kontext von Umbrüchen, Krieg und Gewalt zur Sprache. In zwei literaturwissenschaftlichen Beiträgen wird jeweils ein Roman aus der Kinder- und Jugendliteratur analysiert, in denen in einem Fall eine Puppe zur psychischen Stabilisierung der literarischen Protagonistin beiträgt und im anderen Fall das Schicksal der Puppe die Geschichte von Abschied und letztendlicher Vernichtung ihrer Besitzerin erzählt und symbolisiert. Und schließlich geht es um den Stellenwert von Puppen und Teddys in verschiedenen Kinderzeitschriften, die – in den politisch unsicheren Zeiten zwischen und nach den beiden Weltkriegen – Identifikationsfiguren und Interaktionspartner für Kinder sein können. Ein zweiter Fokus thematisiert Puppen und ihre Narrative im Kontext verschiedener aversiver Erfahrungen sowie in Zeiten psychischer Irritation. So geht es zum einen um die literaturwissenschaftliche Sicht auf die Bedeutung und Wirkung von Puppen in zwei ‚klassischen’ Puppenerzählungen: „"Nussknacker und Mausekönig" von E.T.A. Hoffmann und "Romeo und Julia auf dem Dorfe" von Gottfried Keller. Zum anderen werden in verschiedenen Beiträgen Entgrenzungs-, Transformations- und Identitätsfragen in Mensch-Puppen-Bezügen aus medien- und kunstwissenschaftlicher sowie kinderliterarischer Perspektive angesprochen, in denen Puppen in Gestalt von Androiden, Kunstwesen oder anthropomorphen Figuren agieren und dabei selber Irritationen auslösen oder Versuche darstellen, Antworten auf beunruhigende Fragen zu finden. Über den Themenschwerpunkt hinaus finden sich zudem eine Reihe weiterer Beitragsformen zu verschiedenen puppenbezogenen Themen und Praxen, die noch einmal das breite Spektrum unterschiedlicher Puppen-Narrative und Zugangsformen dokumentieren: So beschäftigt sich ein freier Beitrag mit dem Puppenspiel als strukturiertes Therapieangebot für Kinder, bei den Miszellen findet sich eine Skizze zu Marlene Dietrich und ihren Puppen sowie ein kurzer Essay zu einer biographischen Erinnerung, ein Interview mit der Begründerin des Berliner Puppentheaters bubales veranschaulicht Möglichkeiten der dramatischen und poetischen Umsetzung von Puppen-Themen, im Diskussionsforum wird ein kritischer Blick auf "Barbie als Diskursmaschine" geworfen und eine Rezension zum Ausstellungskatalog "From Her Wooden Sleep von Ydessa Hendels" lotet Chancen und Grenzen der künstlerischen Arbeit mit Puppen-Artefakten aus.Dolls / Puppets in Threat Scenarios – this is the topic focus of the first issue of the interdisciplinary online magazine "denkste: puppe / just a bit of: doll" on human-doll discourses (acronym: de: do). The term ’doll’ stands for anthropomorphic ’beings’ and artifacts of all kinds and the concept of threat is broadly defined. This focus was stimulated by the assumption that dolls and doll-related artifacts are of particular importance in times of existential threat as well as in phases of inner psychic anxiety and irritation. Yet, the basically ambiguous character of the doll does not necessarily determine a clear effect, so that its usability always involves a certain blurriness and ambivalence. In threatening and adverse situations dolls can act as companions and significant (transitional) objects, thus allowing psychic stabilization, security, and attachment as well as enabling (inner) autonomy, agency, and developmental processes. But dolls can also be a crucial component of threat scenarios themselves and act frightening in this function. All this applies not only to material and real existing dolls and puppets, but also to dolls as literary and / or media figures as well as to doll narratives of any kind. The articles included here come from different disciplines and open up an appealing and deliberately non-disciplinary oriented human-doll discourse from multiple perspectives. Accordingly, the relevant themes as well as the respective methodological approaches are highly heterogeneous. Thus, some contributions follow the long tradition of doll narratives in literature while others discuss currrent topics and discourses on future scenarios and new technologies by means of various doll-related media formats and / or art performances. A first thematic focus is on the significance of dolls in experiencing threats and losses in the context of war, flight and persecution in times of political uncertainty. Here, different facets of threat scenarios are addressed from different disciplinary perspectives. From the field of object and material theater two productions are introduced in which menacing war scenes are processed by means of plastic dolls or amorphous material. From a psychological perspective, dolls are discussed in their roles and functions as transitional objects within the context of upheaval, war and violence. Furthermore, two literary contributions analyze novels from children’s and youth literature. One story deals with a doll which contributes to the psychological stabilization of the literary protagonist. The other story tells of a girl and her doll which symbolizes the final farewell and eventual annihilation of the (Jewish) girl. Finally, the role of dolls and teddy bears in various children’s magazines is exemplified, which serve as identification figures and interaction partners for children in the politically unstable times between and after the two World Wars. A second focus deals with dolls and their narratives in the context of various aversive experiences as well as in times of psychological irritation. Two contributions analyze the meaning and effect of dolls in two ’classical’ doll narratives from a literary perspective: "Nussknacker und Mausekönig" by E.T.A. Hoffmann and "Romeo und Julia auf dem Dorfe" by Gottfried Keller. Further contributions address questions of ego dissolution, transformation and identity processes in human-doll relations from various perspectives such as media, art and children’s literature. Here, dolls appear as androids, artistic or anthropomorphic figures which cause irritation themselves or attempt to find answers to disturbing human-doll questions. In addition to the main topic, there are also a number of other sections and types of contributions on various doll-related topics and practices which once again document the wide range of doll narratives and possible forms of access: For example, a free contribution deals with doll play as a structured therapy for children, the miscellaneous section includes a portrait of Marlene Dietrich and her dolls as well as a short essay on a biographical reminiscence, an interview with the founder of the Berlin Puppet Theater bubales illustrates the possibilities of dramatic and poetic realization of puppet and doll narratives, a critical view on "Barbie as a discourse machine" is presented in the discussion forum and a review of the exhibition catalog "From Her Wooden Sleep by Ydessa Hendels" explores opportunities and limits of artistic work with doll artifacts

Role of mitochondrial raft-like microdomains in the regulation of cell apoptosis

Lipid rafts are envisaged as lateral assemblies of specific lipids and proteins that dissociate and associate rapidly and form functional clusters in cell membranes. These structural platforms are not confined to the plasma membrane; indeed lipid microdomains are similarly formed at subcellular organelles, which include endoplasmic reticulum, Golgi and mitochondria, named raft-like microdomains. In addition, some components of raft-like microdomains are present within ER-mitochondria associated membranes. This review is focused on the role of mitochondrial raft-like microdomains in the regulation of cell apoptosis, since these microdomains may represent preferential sites where key reactions take place, regulating mitochondria hyperpolarization, fission-associated changes, megapore formation and release of apoptogenic factors. These structural platforms appear to modulate cytoplasmic pathways switching cell fate towards cell survival or death. Main insights on this issue derive from some pathological conditions in which alterations of microdomains structure or function can lead to severe alterations of cell activity and life span. In the light of the role played by raft-like microdomains to integrate apoptotic signals and in regulating mitochondrial dynamics, it is conceivable that these membrane structures may play a role in the mitochondrial alterations observed in some of the most common human neurodegenerative diseases, such as Amyotrophic lateral sclerosis, Huntington's chorea and prion-related diseases. These findings introduce an additional task for identifying new molecular target(s) of pharmacological agents in these pathologies

Neuronal lysosomal dysfunction releases exosomes harboring APP C-terminal fragments and unique lipid signatures

Defects in endolysosomal and autophagic functions are increasingly viewed as key pathological features of neurodegenerative disorders. A master regulator of these functions is phosphatidylinositol-3-phosphate (PI3P), a phospholipid synthesized primarily by class III PI 3-kinase Vps34. Here we report that disruption of neuronal Vps34 function in vitro and in vivo impairs autophagy, lysosomal degradation as well as lipid metabolism, causing endolysosomal membrane damage. PI3P deficiency also promotes secretion of unique exosomes enriched for undigested lysosomal substrates, including amyloid precursor protein C-terminal fragments (APP-CTFs), specific sphingolipids, and the phospholipid bis(monoacylglycero)phosphate (BMP), which normally resides in the internal vesicles of endolysosomes. Secretion of these exosomes requires neutral sphingomyelinase 2 and sphingolipid synthesis. Our results reveal a homeostatic response counteracting lysosomal dysfunction via secretion of atypical exosomes eliminating lysosomal waste and define exosomal APP-CTFs and BMP as candidate biomarkers for endolysosomal dysfunction associated with neurodegenerative disorders.Fan Wang for the kind gift of the Pi3kc3flox/flox mice. We thank Basant Abdulrahman and Hermann Schaetzl for providing the gene-edited Atg5 KO N2a cells. We are also grateful to Zhenyu Yue, Ralph Nixon, and Jean Gruenberg for the kind gift of anti-Atg14L, Cathepsin D, and BMP antibodies, respectively. We thank Thomas Südhof for sharing Cre recombinase lentiviruses. We thank the OCS Microscopy Core of New York University Langone Medical Center for the support of the EM work and Rocio Perez-Gonzalez and Efrat Levy of New York University for their support during optimization of the brain exosome isolation technique. We thank Elizabeta Micevska for the maintenance and genotyping of the animal colony and Bowen Zhou for the preliminary lipidomic analysis of conditional Pi3kc3 cKO mice. We also thank Rebecca Williams and Catherine Marquer for critically reading the manuscript. This work was supported by grants from the Fundação para a Ciência e Tecnologia (PD/BD/105915/2014 to A.M.M.); the National Institute of Health (R01 NS056049 to G.D.P., transferred to Ron Liem, Columbia University; T32-MH015174 to Rene Hen (Z.M.L.)). Z.M.L. and R.B.C. received pilot grants from ADRC grant P50 AG008702 to S.A.S.info:eu-repo/semantics/publishedVersio

dolls/puppets as miniatures - more than small

Weitere Hrsg.: Jana Mikota, Philipp SchmerheimDer Themenschwerpunkt der zweiten Ausgabe von de:do lautet: Puppen als Miniaturen – mehr als klein. Puppen und ihre Kontexte beanspruchen hier, ’mehr’ als nur verkleinerte Varianten oder Repliken menschlicher Lebenswelten zu sein. Nicht von ungefähr gelten sie als ein ’Fundort der Größe’ (Bachelard). Als ’kleine Formate’ generieren sie Bilder und Narrative der eigenen Art, die in Funktion und Wirkung offen sind: so bewegen sie sich zwischen Abbildung, Verdichtung und Transformation von Realität, sind Ausdruck von Sehnsüchten und/oder Kontrollbedürfnissen ihrer ErschafferInnen, lösen Bezauberung, Verwunderung oder Befremden aus und ermöglichen ganzheitliche Weltzugänge und Erkenntnis über innere Zusammenhänge. Einmal mehr erweisen sich Puppen als Miniaturen und im Kontext miniaturisierter Welten als hybride Objekte, aufgeladen mit vielerlei Symbolik und Bedeutungsüberschuss. Die Zusammenschau der höchst unterschiedlichen Beiträge im vorliegenden Heft vermittelt eine Ahnung von möglichen Spannungsverhältnissen – zwischen ’klein’ und ’groß’, ’Sichtbarem’ und ’Verstecktem’, ’Realität’ und ’Fiktion’, ’Mimesis’ und ’Poetik’. Das heterogene Themenspektrum unterstreicht die subtile Bedeutung der Puppe als einem besonderen Markenzeichen der ’kleinen Form’ in vielerlei Disziplinen. Die Beiträge stammen aus so unterschiedlichen Fächern bzw. interdisziplinär offenen Fachkulturen wie Archäologie, Anthropologie, Volkskunde, Kinder- und Jugendliteratur, Kunstgeschichte, Spielzeugkunde, Animationsfilm, Bildende Kunst, Mode-Design, Forensik. Ein Interview mit einer jungen Künstlerin, Miszellen und Rezensionen ergänzen die Themenvielfalt.The focus topic of the second edition of the journal denkste: puppe / just a bit of: doll (de:do), a multidisciplinary, peer reviewed online journal for human-doll discourses is: dolls/puppets as miniatures - more than small. Dolls/puppets and their contexts claim to be ’more’ than just miniaturized variants or replicas of human worlds. Thus, it is not by chance that they are regarded as a ’place to find greatness’ (Bachelard). As ’small formats’, they generate images and narratives of their own kind which are open in function and effect: they oscillate between representation, condensation and transformation of reality, expressing longings and/or control needs of their creators and triggering enchantment, amazement or alienation while enabling a holistic access to the world and insight into inner contexts. Arguing in this line, dolls/puppets prove to be miniatures and – in the context of miniaturized worlds –hybrid objects, charged with all sorts of symbolism and excess of meaning. The synopsis of the highly diverse contributions in this issue gives us an idea of possible tensions – between ’small’ and ’large’, ’visible’ and ’hidden’, ’reality’ and ’fiction’, ’mimesis’ and ’poetics’. The heterogeneous range of topics underlines the subtle significance of the doll/puppet as a special trademark of the ’small form’ in many disciplines. The contributions come from subjects as diverse as diverse as archeology, anthropology, folklore, children’s and youth literature, art history, toy studies, animated film, fine arts, fashion design, forensics. An interview with a young artist, miscellaneous aspects as well as reviews complete the variety of topics

The role of phospholipase D in modulating the MTOR signaling pathway in polycystic kidney disease

The mammalian target of rapamycin (mTOR) signaling pathway is aberrantly activated in polycystic kidney disease (PKD). Emerging evidence suggests that phospholipase D (PLD) and its product phosphatidic acid (PA) regulate mTOR activity. In this study, we assessed in vitro the regulatory function of PLD and PA on the mTOR signaling pathway in PKD. We found that the basal level of PLD activity was elevated in PKD cells. Targeting PLD by small molecule inhibitors reduced cell proliferation and blocked mTOR signaling, whereas exogenous PA stimulated mTOR signaling and abolished the inhibitory effect of PLD on PKD cell proliferation. We also show that blocking PLD activity enhanced the sensitivity of PKD cells to rapamycin and that combining PLD inhibitors and rapamycin synergistically inhibited PKD cell proliferation. Furthermore, we demonstrate that targeting mTOR did not induce autophagy, whereas targeting PLD induced autophagosome formation. Taken together, our findings suggest that deregulated mTOR pathway activation is mediated partly by increased PLD signaling in PKD cells. Targeting PLD isoforms with pharmacological inhibitors may represent a new therapeutic strategy in PKD

Arf6 promotes autophagosome formation via effects on phosphatidylinositol 4,5-bisphosphate and phospholipase D

Macroautophagy (in this paper referred to as autophagy) and the ubiquitin–proteasome system are the two major catabolic systems in cells. Autophagy involves sequestration of cytosolic contents in double membrane–bounded vesicles called autophagosomes. The membrane source for autophagosomes has received much attention, and diverse sources, such as the plasma membrane, Golgi, endoplasmic reticulum, and mitochondria, have been implicated. These may not be mutually exclusive, but the exact sources and mechanism involved in the formation of autophagosomes are still unclear. In this paper, we identify a positive role for the small G protein Arf6 in autophagosome formation. The effect of Arf6 on autophagy is mediated by its role in the generation of phosphatidylinositol 4,5-bisphosphate (PIP(2)) and in inducing phospholipase D (PLD) activity. PIP(2) and PLD may themselves promote autophagosome biogenesis by influencing endocytic uptake of plasma membrane into autophagosome precursors. However, Arf6 may also influence autophagy by indirect effects, such as either by regulating membrane flow from other compartments or by modulating PLD activity independently of the mammalian target of rapamycin