Gap Junction Dependent Cell Communication Is Modulated During Transdifferentiation of Mesenchymal Stem/Stromal Cells Towards Neuron-Like Cells

In vitro transdifferentiation of patient-derived mesenchymal stem/stromal cells (MSCs) into neurons is of special interest for treatment of neurodegenerative diseases. Although there are encouraging studies, little is known about physiological modulations during this transdifferentiation process. Here, we focus on the analysis of gap junction dependent cell-cell communication and the expression pattern of gap junction-building connexins during small molecule-induced neuronal transdifferentiation of human bone marrow-derived MSCs. During this process, the MSC markers CD73, CD90, CD105, and CD166 were downregulated while the neuronal marker Tuj1 was upregulated. Moreover, the differentiation protocol used in the present study changed the cellular morphology and physiology. The MSCs evolved from a fibroblastoid morphology towards a neuronal shape with round cell bodies and neurite-like processes. Moreover, depolarization evoked action potentials in the transdifferentiated cells. MSCs expressed mRNAs encoding Cx43 and Cx45 as well as trace levels of Cx26, Cx37- and Cx40 and allowed transfer of microinjected Lucifer yellow. The differentiation protocol increased levels of Cx26 (mRNA and protein) and decreased Cx43 (mRNA and protein) while reducing the dye transfer. Cx36 mRNA was nearly undetectable in all cells regardless of treatment. Treatment of the cells with the gap junction coupling inhibitor carbenoxolone (CBX) only modestly altered connexin mRNA levels and had little effect on neuronal differentiation. Our study indicates that the small molecule-based differentiation protocol generates immature neuron-like cells from MSCs. This might be potentially interesting for elucidating physiological modifications and mechanisms in MSCs during the initial steps of differentiation towards a neuronal lineage

Rationality, Irrationality and Escalating Behavior in Lowest Unique Bid Auctions

Information technology has revolutionized the traditional structure of markets. The removal of geographical and time constraints has fostered the growth of online auction markets, which now include millions of economic agents worldwide and annual transaction volumes in the billions of dollars. Here, we analyze bid histories of a little studied type of online auctions – lowest unique bid auctions. Similarly to what has been reported for foraging animals searching for scarce food, we find that agents adopt Lévy flight search strategies in their exploration of “bid space”. The Lévy regime, which is characterized by a power-law decaying probability distribution of step lengths, holds over nearly three orders of magnitude. We develop a quantitative model for lowest unique bid online auctions that reveals that agents use nearly optimal bidding strategies. However, agents participating in these auctions do not optimize their financial gain. Indeed, as long as there are many auction participants, a rational profit optimizing agent would choose not to participate in these auction markets

Frameworks and tools for risk assessment of manufactured nanomaterials

Commercialization of nanotechnologies entails a regulatory requirement for understanding their environmental, health and safety (EHS) risks. Today we face challenges to assess these risks, which emerge from uncertainties around the interactions of manufactured nanomaterials (MNs) with humans and the environment. In order to reduce these uncertainties, it is necessary to generate sound scientific data on hazard and exposure by means of relevant frameworks and tools. The development of such approaches to facilitate the risk assessment (RA) of MNs has become a dynamic area of research. The aim of this paper was to review and critically analyse these approaches against a set of relevant criteria. The analysis concluded that none of the reviewed frameworks were able to fulfill all evaluation criteria. Many of the existing modelling tools are designed to provide screening-level assessments rather than to support regulatory RA and risk management. Nevertheless, there is a tendency towards developing more quantitative, higher-tier models, capable of incorporating uncertainty into their analyses. There is also a trend towards developing validated experimental protocols for material identification and hazard testing, reproducible across laboratories. These tools could enable a shift from a costly case-by-case RA of MNs towards a targeted, flexible and efficient process, based on grouping and read-across strategies and compliant with the 3R (Replacement, Reduction, Refinement) principles. In order to facilitate this process, it is important to transform the current efforts on developing databases and computational models into creating an integrated data and tools infrastructure to support the risk assessment and management of MNs.Commercialization of nanotechnologies entails a regulatory requirement for understanding their environmental, health and safety (EHS) risks. Today we face challenges to assess these risks, which emerge from uncertainties around the interactions of manufactured nanomaterials (MNs) with humans and the environment. In order to reduce these uncertainties, it is necessary to generate sound scientific data on hazard and exposure by means of relevant frameworks and tools. The development of such approaches to facilitate the risk assessment (RA) of MNs has become a dynamic area of research. The aim of this paper was to review and critically analyse these approaches against a set of relevant criteria. The analysis concluded that none of the reviewed frameworks were able to fulfill all evaluation criteria. Many of the existing modelling tools are designed to provide screening level assessments rather than to support regulatory RA and risk management Nevertheless, there is a tendency towards developing more quantitative, higher-tier models, capable of incorporating uncertainty into their analyses. There is also a trend towards developing validated experimental protocols for material identification and hazard testing, reproducible across laboratories. These tools could enable a shift from a costly case-by-case RA of MNs towards a targeted, flexible and efficient process, based on grouping and read-across strategies and compliant with the 3R (Replacement, Reduction, Refinement) principles. In order to facilitate this process, it is important to transform the current efforts on developing databases and computational models into creating an integrated data and tools infrastructure to support the risk assessment and management of MNs. (C) 2016 Elsevier Ltd. All rights reserved

Team 3: Analyzing Selected Questions in a Refugee Camp Scenario Using PAX3D

from Scythe : Proceedings and Bulletin of the International Data Farming Community, Issue 7 Workshop 19The Bundeswehr Transformation Center is examining how M&S can effectively support CD&E projects related to Peace Support Operations (PSO). Human Factors and Human Behavior analyses have proven to be highly relevant in this context. One study specifically examines possibilities to model scenarios in a PSO with PAX in which the military is tasked to assist in building and operating refugee camps, and especially to ensure order and security. PAX is planned to be used to support decision makers in assessing and evaluating ROE (Rules of Engagements) applying the basic use of force guidelines for the soldier in PSO missions

Neurofibromatosis type 2 tumor suppressor protein is expressed in oligodendrocytes and regulates cell proliferation and process formation.

The neurofibromatosis type 2 (NF2) tumor suppressor protein Merlin functions as a negative regulator of cell growth and actin dynamics in different cell types amongst which Schwann cells have been extensively studied. In contrast, the presence and the role of Merlin in oligodendrocytes, the myelin forming cells within the CNS, have not been elucidated. In this work, we demonstrate that Merlin immunoreactivity was broadly distributed in the white matter throughout the central nervous system. Following Merlin expression during development in the cerebellum, Merlin could be detected in the cerebellar white matter tract at early postnatal stages as shown by its co-localization with Olig2-positive cells as well as in adult brain sections where it was aligned with myelin basic protein containing fibers. This suggests that Merlin is expressed in immature and mature oligodendrocytes. Expression levels of Merlin were low in oligodendrocytes as compared to astrocytes and neurons throughout development. Expression of Merlin in oligodendroglia was further supported by its identification in either immortalized cell lines of oligodendroglial origin or in primary oligodendrocyte cultures. In these cultures, the two main splice variants of Nf2 could be detected. Merlin was localized in clusters within the nuclei and in the cytoplasm. Overexpressing Merlin in oligodendrocyte cell lines strengthened reduced impedance in XCELLigence measurements and Ki67 stainings in cultures over time. In addition, the initiation and elongation of cellular projections were reduced by Merlin overexpression. Consistently, cell migration was retarded in scratch assays done on Nf2-transfected oligodendrocyte cell lines. These data suggest that Merlin actively modulates process outgrowth and migration in oligodendrocytes

Merlin expression affects cell impedance in XCELLigence measurements.

<p>Cellular impedance was measured in RT4 (A, B), OLN93 (C, D) and TC620 cells (E, F), over-expressing <i>Nf2</i> and in control cells by XCELLigence. The cell index given as a measure of impedance of adhered cells, demonstrated a similar curve in all cell lines (A, C, E). Comparing cell indices over time by evaluating slopes of curves revealed a significant drop in <i>Nf2</i>-transfected (solid line) as compared to the <i>control-</i>transfected cells (dashed line) (B, D, F). Same symbols stand for replicates of one experiment. Lines connect corresponding average values of replicates within a single experiment. Significance values were calculated using the Wilcoxon signed rank test for independent samples (*p < 0.05; **p < 0.01; ***p < 0.001). Pictures in G represent typical images of Ki67 stainings (red). Mitotic figures are depicted by arrows. Total numbers of cells were visualized by Hoechst staining (blue, bar 10 μm). The relative Ki67/Hoechst staining was significantly decreased in <i>Nf2-</i>transfected versus <i>control</i>-transfected cells at 48 and more hours (H), but it was unchanged at shorter time periods (I, ns non-significant).</p