Coating of upconversion nanoparticles with silica nanoshells of 5–250 nm thickness

A concept for the growth of silica shells with a thickness of 5–250 nm onto oleate-coated NaYF4:Yb3+/Er3+ upconversion nanoparticles (UCNP) is presented. The concept enables the precise adjustment of shell thicknesses for the preparation of thick-shelled nanoparticles for applications in plasmonics and sensing. First, an initial 5–11 nm thick shell is grown onto the UCNPs in a reverse microemulsion. This is followed by a stepwise growth of these particles without a purification step, where in each step equal volumes of tetraethyl orthosilicate and ammonia water are added, while the volumes of cyclohexane and the surfactant Igepal® CO-520 are increased so that the ammonia water and surfactant concentrations remain constant. Hence, the number of micelles stays constant, and their size is increased to accommodate the growing core–shell particles. Consequently, the formation of core-free silica particles is suppressed. When the negative zeta potential of the particles, which continuously decreased during the stepwise growth, falls below −40 mV, the particles can be dispersed in an ammoniacal ethanol solution and grown further by the continuous addition of tetraethyl orthosilicate to a diameter larger than 500 nm. Due to the high colloidal stability, a coalescence of the particles can be suppressed, and single-core particles are obtained. This strategy can be easily transferred to other nanomaterials for the design of plasmonic nanoconstructs and sensor systems

Effect of different silica coatings on the toxicity of upconversion nanoparticles on RAW 264.7 macrophage cells

Upconversion nanoparticles (UCNPs), consisting of NaYF4 doped with 18% Yb and 2% Er, were coated with microporous silica shells with thickness values of 7 +/- 2 and 21 +/- 3 nm. Subsequently, the negatively charged particles were functionalized with N-(6-aminohexyl)-3-aminopropyltrimethoxysilane (AHAPS), which provide a positive charge to the nanoparticle surface. Inductively coupled plasma optical emission spectrometry (ICP-OES) measurements revealed that, over the course of 24h, particles with thicker shells release fewer lanthanide ions than particles with thinner shells. However, even a 21 +/- 3 nm thick silica layer does not entirely block the disintegration process of the UCNPs. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and cell cytometry measurements performed on macrophages (RAW 264.7 cells) indicate that cells treated with amino-functionalized particles with a thicker silica shell have a higher viability than those incubated with UCNPs with a thinner silica shell, even if more particles with a thicker shell are taken up. This effect is less significant for negatively charged particles. Cell cycle analyses with amino-functionalized particles also confirm that thicker silica shells reduce cytotoxicity. Thus, growing silica shells to a sufficient thickness is a simple approach to minimize the cytotoxicity of UCNPs

Das peritoneale lymphatische System in gesundem vs. tumorösem Gewebe: eine morphologische und funktionelle ex-vivo Studie

Hintergrund: Das Omentum verfügt über einzigartige lymphatische Strukturen, die als Milky Spots (MS) bezeichnet werden. Dieses Gewebe ist für Immunprozesse äußerst attraktiv und zwar insbesondere im Hinblick auf Interaktionen mit der Bauchhöhle. MS sind die erste Verteidigungslinie in der frühen Phase der Peritonealmetastasierung (PM), bieten aber auch eine strukturelle und metabolische Grundlage für das Fortschreiten der PM. Aufgrund von Metastasierungsprozessen verändert sich die zelluläre Zusammensetzung des Omentums und die Expression verschiedener Chemokine, die als interzelluläre Botenstoffe fungieren. Diese Studie zielt darauf ab, neue Erkenntnisse über die MS-Subpopulationen, die Verteilung von Immunzellen und die damit verbundenen Chemokinspiegel im Omentum in verschiedenen Stadien der Tumorprogression zu charakterisieren und damit den Weg für neue Ansätze in der Immuntherapie bei PM zu eröffnen. Methoden: Die Charakterisierung der zellulären Subpopulationen von MS im Omentum wurde mittels Immunhistochemie, Multiplex-Immunfluoreszenz (MacSima) und Durchflusszytometrie (FACS) durchgeführt, während die Chemokine im Omentum mittels Enzyme-Linked Immunosorbent Assay (ELISA) analysiert wurden. Ergebnisse: Die durchschnittliche Zellmenge bei MS erwies sich während des Fortschreitens der PM im Gewebe von PM-Patienten als außergewöhnlich hoch, wobei die Zellmenge, ebenso wie die Größe der MS, im Vergleich zum Gewebe mit Kolonkarzinom ohne PM und zum Kontrollgewebe deutlich erhöht war. Die IHC-, MacSima und FACS-Ergebnisse zeigten, dass bei allen Methoden nur wenige Zellsubpopulationen im gesamten Omentum gefunden werden konnten (0,1 %–5 %). Die höchste Anzahl an Immunzellen, darunter auch M1-, M2- 84 Makrophagen und regulatorischen T-Zellen wurde jedoch jeweils im Gewebe von kolorektalen PM-Patienten nachgewiesen. Die Ergebnisse der ELISA-Analyse machten deutlich, dass die Konzentrationen aller drei tumorfördernden Chemokine (CCL2, CCL22, CXCL12) mit dem Fortschreiten des Karzinoms und der PM anstiegen. Im Gegensatz dazu nahm die Konzentration des tumorhemmenden Chemokins (CCL19) mit fortschreitender PM ab. Zudem konnten Korrelationen zwischen bestimmten Immunzellen und Chemokinen bestätigt werden. Schlussfolgerung: Nach unserem Kenntnisstand haben wir die Subpopulationen von MS-Immunzellen sowie die Verteilung dieser Immunzellen im Omentum mittels Immunhistochemie und FACS in menschlichen Omentalproben bei PM unterschiedlichen Ausmaßes zum ersten Mal beschrieben. Weiterhin wurden verschiedene Chemokine während der peritonealen Tumorprogression nachgewiesen, die die Immunzellen und damit die Tumorumgebung beeinflussen. Dies eröffnet ein neues Beobachtungsfenster zur Charakterisierung des peritonealen immunologischen Milieus bei Gesunden und bei tumorerkrankten Patienten

Beyond immune escape:a variant surface glycoprotein causes suramin resistance in Trypanosoma brucei

Suramin is one of the first drugs developed in a medicinal chemistry program (Bayer, 1916), and it is still the treatment of choice for the hemolymphatic stage of African sleeping sickness caused by Trypanosoma brucei rhodesiense. Cellular uptake of suramin occurs by endocytosis, and reverse genetic studies with T. b. brucei have linked downregulation of the endocytic pathway to suramin resistance. Here we show that forward selection for suramin resistance in T. brucei spp. cultures is fast, highly reproducible and linked to antigenic variation. Bloodstream-form trypanosomes are covered by a dense coat of variant surface glycoprotein (VSG), which protects them from their mammalian hosts' immune defenses. Each T. brucei genome contains over 2000 different VSG genes, but only one is expressed at a time. An expression switch to one particular VSG, termed VSGSur , correlated with suramin resistance. Reintroduction of the originally expressed VSG gene in resistant T. brucei restored suramin susceptibility. This is the first report of a link between antigenic variation and drug resistance in African trypanosomes

Lehrerin und Forscherin? Erfahrungen aus der Praxisforschung des Oberstufen-Kollegs Bielefeld

Ausgehend von einem Forschungs- und Entwicklungsprojekt zum Praxissemester im Unterrichtsfach Pädagogik stellen die Autorinnen ihre Erfahrungen als Lehrer-Forscherinnen dar. Dieses Forschungs- und Entwicklungsprojekt ist hierfür in besonderer Weise geeignet, da es sowohl die schulpädago-gischen Bemühungen um die Förderung einer forschenden Grundhaltung bei  Schüler*innen als auch in der Lehrerausbildung sowie in der berufsbegleitenden Professionalisierung von Lehrkräften thematisch werden lässt. Ihren Erfahrungsbericht systematisieren die Autorinnen entlang von drei aus der Literatur zu Forschendem Lernen und Lehrerprofessionalisierung extrahierten Dimensionen: der Professionalisierungsstrategie, der Entwicklungsstrategie und der Anregung zu kolle-gialer Lehrerfortbildung. Entlang des Abgleichs dieser Dimensionen mit ihren individuellen berufsbiografischen Erfahrungen zeigen sie auf, wie nachhaltig eine forschende Grundhaltung zur Professionalisierung beitragen und welche positiven Effekte für die kollegiale Fort- und Weiterbildung sowie die Unterrichts- und Schulentwicklung diese haben kann. Based on a research and development project on a long-term practical training for students in teacher education for the subject “pedagogy”, the authors present their experiences as teacher researchers. This research and development project is particularly suitable for this purpose, as it focuses on the efforts of schoolteachers to promote a basic research attitude among pupils, on teacher training and on the professionalization of teachers. The authors systematize their experience report along three dimensions extracted from the literature on research-based learning and teacher professionalization: the strategy for professionalization, for development and for stimulating collegial teacher training. By comparing these dimensions with their individual professional biographical experiences, they show how a research-oriented attitude can contribute to professionalization in the long term and what positive effects this can have on collegial continuing training as well as on teaching and school development

DoctorEye: A clinically driven multifunctional platform, for accurate processing of tumors in medical images

Copyright @ Skounakis et al.This paper presents a novel, open access interactive platform for 3D medical image analysis, simulation and visualization, focusing in oncology images. The platform was developed through constant interaction and feedback from expert clinicians integrating a thorough analysis of their requirements while having an ultimate goal of assisting in accurately delineating tumors. It allows clinicians not only to work with a large number of 3D tomographic datasets but also to efficiently annotate multiple regions of interest in the same session. Manual and semi-automatic segmentation techniques combined with integrated correction tools assist in the quick and refined delineation of tumors while different users can add different components related to oncology such as tumor growth and simulation algorithms for improving therapy planning. The platform has been tested by different users and over large number of heterogeneous tomographic datasets to ensure stability, usability, extensibility and robustness with promising results. AVAILABILITY: THE PLATFORM, A MANUAL AND TUTORIAL VIDEOS ARE AVAILABLE AT: http://biomodeling.ics.forth.gr. It is free to use under the GNU General Public License

Effects of Spinal Fusion for Idiopathic Scoliosis on Lower Body Kinematics During Gait

Objectives The purpose of this study was to compare gait among patients with scoliosis undergoing posterior spinal fusion and instrumentation (PSFI) to typically developing subjects and determine if the location of the lowest instrumented vertebra impacted results. Summary of Background Data PSFI is the standard of care for correcting spine deformities, allowing the preservation of body equilibrium while maintaining as many mobile spinal segments as possible. The effect of surgery on joint motion distal to the spine must also be considered. Very few studies have addressed the effect of PSFI on activities such as walking and even fewer address how surgical choice of the lowest instrumented vertebra (LIV) influences possible motion reduction. Methods Individuals with scoliosis undergoing PSFI (n = 38) completed gait analysis preoperatively and at postoperative years 1 and 2 along with a control group (n = 24). Comparisons were made with the control group at each time point and between patients fused at L2 and above (L2+) versus L3 and below (L3–). Results The kinematic results of the AIS group showed some differences when compared to the Control Group, most notably decreased range of motion (ROM) in pelvic tilt and trunk lateral bending. When comparing the LIV groups, only minor differences were observed, and the results showed decreased coronal trunk and pelvis ROM at the one-year visit and decreased hip rotation ROM at the two-year visit in the L3– group. Conclusions Patients with AIS showed decreased ROM preoperatively with further decreases postoperatively. These changes remained relatively consistent following the two-year visit, indicating that most kinematic changes occurred in the first year following surgery. Limited functional differences between the two LIV groups may be due to the lack of full ROM used during normal gait, and future work could address tasks that use greater ROM

Nicht förderungswürdig. Weshalb die Evaluation der Exzellenzinitiative gegen deren Fortsetzung spricht

Die deutsche Hochschulpolitik hat eine Verstetigung der Exzellenzinitiative auf den Weg gebracht. In Zukunft sollen nach einem Antragswettbewerb ca. fünfzig Exzellenzcluster und acht bis elf Exzellenz-Universitäten für jeweils sieben Jahre vom Bund gefördert werden. Grundlage der politischen Entscheidung ist die Evaluation der Exzellenzinitiative durch eine Expert_innenkommission(Imboden-Bericht). Der Beitrag kommentiert diesen Bericht kritisch und reflektiert problematische Folgen des Wettbewerbs um Fördermittel und ‚Exzellenz‘. Hohe Arbeitslasten, schlechte Betreuungsverhältnisse und die prekäre Lage im wissenschaftlichen Mittelbau an deutschen Hochschulen werden unterstrichen, die angestrebte vertikale Differenzierung des deutschen Hochschulsystems und die Forderung nach starken Hochschulleitungen kritisiert sowie die Verstärkung sozialer Ungleichheiten durch Elitehochschulen angesprochen. Schließlich wird die Grundsatzfrage gestellt, wieso es überhaupt Antrags- und Statuswettbewerbe geben muss

Stathmin is required for stability of the drosophila neuromuscular junction

Synaptic connections can be stably maintained for prolonged periods, yet can be rapidly disassembled during the developmental refinement of neural circuitry and following cytological insults that lead to neurodegeneration. To date, the molecular mechanisms that determine whether a synapse will persist versus being remodeled or eliminated remain poorly understood. Mutations in Drosophila stathmin were isolated in two independent genetic screens that sought mutations leading to impaired synapse stability at the Drosophila neuromuscular junction (NMJ). Here we demonstrate that Stathmin, a protein that associates with microtubules and can function as a point of signaling integration, is necessary to maintain the stability of the Drosophila NMJ. We show that Stathmin protein is widely distributed within motoneurons and that loss of Stathmin causes impaired NMJ growth and stability. In addition, we show that stathmin mutants display evidence of defective axonal transport, a common feature associated with neuronal degeneration and altered synapse stability. The disassembly of the NMJ in stathmin includes a predictable sequence of cytological events, suggesting that a common program of synapse disassembly is induced following the loss of Stathmin protein. These data define a required function for Stathmin during synapse maintenance in a model system in which there is only a single stathmin gene, enabling future genetic investigation of Stathmin function with potential relevance to the cause and progression of neuromuscular degenerative disease