In vitro impact of platinum nanoparticles on inner ear related cell culture models

So far, it was supposed that the increase of electrical impedance following cochlear implant (CI) insertion was due to technical defects of the electrode, inflammatory and/or formation of scar tissue along the electrode. However, it was recently reported that corrosion of the platinum electrode contacts may be the reason for high impedances. It could be shown that platinum particles were stripped from the electrode surfaces. Its potential cytotoxic effects within the inner ear remains to be examined. In this study in vitro cell culture models of the mouse organ of Corti cell line (HEI-OC1) and the spiral ganglion (SG) cells derived from the cochleae neonatal rats were used to investigate the effects of the polyvinylpyrrolidone coated platinum nanoparticles (Pt-NPPVP, 3 nm) on cell metabolism, neuronal survival and neurite outgrowth. Our data revealed no decrease of the metabolic activity of the HEI-OC1 cells at Pt-NPPVP concentrations between 50-150 μg/ml. Also, staining with Calcein AM/ EthD demonstrated prevalent presence of vital cells. As shown by transmission electron microscopy no Pt-NPPVP could be found at the cell surface or in the cytosol of the HEI-OC1 cells. Similarly, the SG cells exposed to 20-100 μg/ml Pt-NPPVP did not show any reduced survival rate and neurite outgrowth following staining of the neurofilament antigen even at the highest Pt-NPPVP concentration. Although the SG cells were exposed to Pt-NPPVP for further 72 h and 96 h immunocytochemical staining of the glial cells and fibroblasts presented normal cell morphology and growth independently of the cultivation period. Our data indicates that the used Pt-NPPVP do not trigger the cellular uptake and, thus, presumable do not initiate apoptotic pathways in cells of the organ of Corti cell line or the auditory nerve. The protection mechanisms to the Pt-NPPVP interactions remain to be clarified

Different cell populations are inducible by BMP-2 covalently covered Bioverit® II implants in rabbit subcutis and middle ear

To optimize the function of implants the formation of surrounding connective tissue should be adapted in dependence to the mechanical conditions. Therefore, with nanostructured silica coated Bioverit® II implants were only partly reacted with recombinant BMP-2. The histology was compared 28, 84 and 301 days after implantation in the rabbit middle ear and subcutis, respectively. The whole tissue blocks were embedded in Epon, sequentially grinded, stained with Toluidine Blue O and Eosin G. The granulation tissue covering the implants varies related to cell types, cell amounts, extracellular matrix and vessels. Whereas the high cell density and the angiogenesis predominated in the subcutis, the formation of new bone could only be recognized in the scar around the implants in the middle ear.SFB/599/project D1

Innovative 3D Model of the Human Middle Ear in High Resolution with a Histological Microgrinding Method: A Feasibility Study and Comparison with μCT

Conclusion. The development of a histological 3D model of the tympanic cavity visualizes the exact microanatomy of the sound conduction organ and is therefore essential for finite elements simulations and surgical training. Objectives. So far, no accurate histological 3D model of the sound conduction system existed in literature. For 3D reconstruction of the very fine structures inside and outside the auditory ossicles, a method based on histological slices allows a more differential analysis of both hard and soft tissues and could thus be superior to μCT. Method. A complete temporal bone was embedded in epoxy resin and microground in distances of about 34 μm. After photodocumentation of every plane, a 3D reconstruction was performed by using the Computer Aided Design (CAD) program Rhinoceros 5®. For comparison, a μCT of the same specimen resulted in a 3D model of the calcified structures in the middle ear. Results. The histological 3D model gives an excellent overview to all anatomical soft and bony tissues of the human auditory ossicles. Specifically the fine blood vessel system and the exact dimension of cartilage areas inside the ossicles can be illustrated much more precisely than with μCT data. The present technique also allows the evaluation of the fine connecting ligaments inside the tympanic cavity

Stabilizing A Vascularized Autologous Matrix with Flexible Magnesium Scaffolds to Reconstruct Dysfunctional Left Ventricular Myocardium in a Large-Animal Feasibility Study

The surgical reconstruction of dysfunctional myocardium is necessary for patients with severe heart failure. Autologous biomaterials, such as vascularized patch materials, have a regenerative potential due to in vivo remodeling. However, additional temporary mechanical stabilization of the biomaterials is required to prevent aneurysms or rupture. Degradable magnesium scaffolds could prevent these life-threatening risks. A left ventricular transmural defect was reconstructed in minipigs with a piece of the autologous stomach. Geometrically adaptable and degradable scaffolds made of magnesium alloy LA63 were affixed on the epicardium to stabilize the stomach tissue. The degradation of the magnesium structures, their biocompatibility, physiological remodeling of the stomach, and the heart’s function were examined six months after the procedure via MRI (Magnetic Resonance Imaging), angiography, µ-CT, and light microscopy. All animals survived the surgery. Stable physiological integration of the stomach patch could be detected. No ruptures of the grafts occurred. The magnesium scaffolds showed good biocompatibility. Regenerative surgical approaches for treating severe heart failure are a promising therapeutic alternative to the currently available, far from optimal options. The temporary mechanical stabilization of viable, vascularized grafts facilitates their applicability in clinical scenarios

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

LAMTOR2 (p14) Controls B Cell Differentiation by Orchestrating Endosomal BCR Trafficking

B-cell development and function depend on stage-specific signaling through the B-cell antigen receptor (BCR). Signaling and intracellular trafficking of the BCR are connected, but the molecular mechanisms of this link are incompletely understood. Here, we investigated the role of the endosomal adaptor protein and member of the LAMTOR/Ragulator complex LAMTOR2 (p14) in B-cell development. Efficient conditional deletion of LAMTOR2 at the pre-B1 stage using mb1-Cre mice resulted in complete developmental arrest. Deletion of LAMTOR2 using Cd19-Cre mice permitted analysis of residual B cells at later developmental stages, revealing that LAMTOR2 was critical for the generation and activation of mature B lymphocytes. Loss of LAMTOR2 resulted in aberrant BCR signaling due to delayed receptor internalization and endosomal trafficking. In conclusion, we identify LAMTOR2 as critical regulator of BCR trafficking and signaling that is essential for early B-cell development in mice

Spider Silk Constructs Enhance Axonal Regeneration and Remyelination in Long Nerve Defects in Sheep

BACKGROUND: Surgical reapposition of peripheral nerve results in some axonal regeneration and functional recovery, but the clinical outcome in long distance nerve defects is disappointing and research continues to utilize further interventional approaches to optimize functional recovery. We describe the use of nerve constructs consisting of decellularized vein grafts filled with spider silk fibers as a guiding material to bridge a 6.0 cm tibial nerve defect in adult sheep. METHODOLOGY/PRINCIPAL FINDINGS: The nerve constructs were compared to autologous nerve grafts. Regeneration was evaluated for clinical, electrophysiological and histological outcome. Electrophysiological recordings were obtained at 6 months and 10 months post surgery in each group. Ten months later, the nerves were removed and prepared for immunostaining, electrophysiological and electron microscopy. Immunostaining for sodium channel (NaV 1.6) was used to define nodes of Ranvier on regenerated axons in combination with anti-S100 and neurofilament. Anti-S100 was used to identify Schwann cells. Axons regenerated through the constructs and were myelinated indicating migration of Schwann cells into the constructs. Nodes of Ranvier between myelin segments were observed and identified by intense sodium channel (NaV 1.6) staining on the regenerated axons. There was no significant difference in electrophysiological results between control autologous experimental and construct implantation indicating that our construct are an effective alternative to autologous nerve transplantation. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that spider silk enhances Schwann cell migration, axonal regrowth and remyelination including electrophysiological recovery in a long-distance peripheral nerve gap model resulting in functional recovery. This improvement in nerve regeneration could have significant clinical implications for reconstructive nerve surgery

Interactions between Spider Silk and Cells – NIH/3T3 Fibroblasts Seeded on Miniature Weaving Frames

Native spider silk does not require any modification to its application as a biomaterial that can rival any artificial material in terms of cell growth promoting properties. We could show adhesion mechanics on intracellular level. Additionally, proliferation kinetics were higher than in enzymatically digested controls, indicating that spider silk does not require modification. Recent findings concerning reduction of cell proliferation after exposure could not be met. As biotechnological production of the hierarchical composition of native spider silk fibres is still a challenge, our study has a pioneer role in researching cellular mechanics on native spider silk fibres

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