Mechanisms of oligodendrocyte precursor cell differentiation

Oligodendrozyten sind die Myelin produzierenden Zellen des Zentralen Nervensystems und stellen das Gegenstück zu den myelinierenden Schwann-Zellen des Peripheren Nervensystems dar. Neben der Produktion von Myelin für die Isolation von Axonen um die schnelle Weiterleitung von Nervenimpulsen zu gewährleisten, haben die Oligodendrozyten in den letzten Jahren immer größere Bedeutung für die Bewahrung der Integrität von Axonen erlangt. Diese Loslösung der bis dahin passiv gesehenen Aufgabe der Neuronenunterstützung hat die Oligodendrozyten zu aktiven Begleitern der Neuronen erhoben, die sich unverzichtbar für deren Erhalt herausgestellt haben. Weiters hat sich gezeigt, dass Oligodendrozyten das Ziel von neurodegenerativen Krankheiten wie Pelizaeus-Merzbacher oder Multipler Sclerose (MS) sind und beispielsweise chronische MS Läsionen auf Fehler in der Re-Myelinierung von Axonen hinweisen. Neue Therapien zur Vermeidung von De-Myelinierung oder zur Wiederherstellung von Myelin werden dringend benötigt, aber leider weiß man noch zu wenig über den Ablauf und Fehler von Myelinierungsvorgängen. Effiziente Forschung und neue Strategien sind demnach unerlässlich um detailreiches Wissen über die zellulären und molekularen Prozesse anzureichern, die der Differenzierung von Oligodendrozyten zugrunde liegen da sie sehr wahrscheinlich jenen der Re-Myelinierung ähneln. Kürzlich erbrachte Experimente, welche die Auswirkung von Eph-Rezeptoren und Ephrinen auf Oligodendrozyten untersucht haben, konnten eine rezeptorbasierende Blockierung der Differenzierung nachweisen. Da die Signalwege der Differenzierung von Oligodendrocyten-Vorläuferzellen (OPCs) bis hin zu myelinierenden Oligodendrozyten kaum bekannt sind, beschäftigt sich diese Studie mit Experimenten, welche die Mechanismen der Differenzierung von OPCs durch Eph-Rezeptoren vermittelte Signalwege und Gehirnproben von EphrinB3 Knock-Out Mäusen im Vergleich zu Kontrollen analysieren. Außerdem wurde versucht, etablierte Primär-Zellkultur Experimente zur Oligodendrozyten Differenzierung mit Zelllinien zu reproduzieren um sowohl die Anzahl der benötigten Tiere zu reduzieren, als auch eine schnellere Umsetzung dieser Experimente realisieren zu können. Die Ergebnisse haben jedoch gezeigt, dass die OLN-93 und OLI-Neu OPC Zelllinien dafür nicht geeignet sind und wahrscheinlich Frühstadien von Oligodendrozyten repräsentieren, die in dieser Entwicklungsphase konserviert sind. Von großer Bedeutung war jedoch ein Ergebnis, welches auf eine verfrühte Myelinierung von Axonen in zwei Tage alten Hirnen von EphrinB3 Knock-Out Mäusen hindeutet. Da sich EphrinB3 in in vitro Versuchen inhibierend auf die Oligodendrozyt-Vorläuferzellen Differenzierung auswirkt, unterstreicht dieses Ergebnis die wichtige Rolle von EphrinB3 in der Oligodendrozyten Entwicklung.Oligodendrocytes are the myelin-producing cells in the central nervous system (CNS) and constitute the pendant to the myelinating Schwann cells in the peripheral nervous system (PNS). Whilst myelin formation for axonal insulation to ensure rapid impulse propagation, oligodendrocytes have gained a prominent role in the maintenance of axonal integrity. Therefore, oligodendrocytes are detached from the former passive role as a supporter cell of neurons to an indispensable, active companion to assure neuronal preservation. Further, oligodendrocytes are the target in developmental defects like Pelizaeus-Merzbacher disease and devastating degenerative diseases like Multiple Sclerosis (MS). To understand the presumably failure of re-myelination in chronic MS lesions and for establishing new therapies to avoid de-myelination or enhance re-myelination, the efficient research in oligodendrocyte precursor cell (OPC) differentiation is constitutive. The mechanisms of myelination are thought to be related to those of re-myelination. Thus, detailed knowledge about the cellular and molecular processes that underlie myelination is necessary to provide insights into myelin regeneration. As recent experiments regarding the impact of Eph-receptors and Ephrins on oligodendrocyte differentiation suggest a receptor mediated differentiation block, new studies are needed to explore those pathways of OPC differentiation. Thus, this study focussed on experiments that investigate the mechanisms of oligodendrocyte precursor cell differentiation through analyzing of Eph-receptor mediated pathways as well as brain samples from EphrinB3 knockout mice compared to controls. In addition, established primary oligodendrocyte cell differentiation experiments were tried to be reproduced by the oligodendrocyte cell lines OLN-93 and OLI-Neu for both the reduction of animal sacrifices and a faster realization of experiments. The results revealed the OLN-93 and OLI-Neu cell lines to be not suitable for the simulation of OPC differentiation in vitro and to probably represent oligodendroglial cells conserved in earlier stages of development. However, the most important finding in this study indicated that EphrinB3 knock out in day 2 mice promotes premature myelination of axons compared to controls. As EphrinB3 was shown to act inhibitory on OPC differentiation in vitro, this result strengthens EphrinB3 to be a crucial element in oligodendrocyte development

Inheritable Effect of Unpredictable Maternal Separation on Behavioral Responses in Mice

The long-term impact of early stress on behavior and emotions is well documented in humans, and can be modeled in experimental animals. In mice, maternal separation during early postnatal development induces poor and disorganized maternal care, and results in behavioral deficits that persist through adulthood. Here, we examined the long-term effect of unpredictable maternal separation combined with maternal stress on behavior and its transmissibility. We report that unpredictable maternal separation from birth to postnatal day 14 in C57Bl/6J mice has mild behavioral effects in the animals when adult, but that its combination with maternal stress exacerbates this effect. Further, the behavioral deficits are transmitted to the following generation through females, an effect that is independent of maternal care and is not affected by cross-fostering. The combined manipulation does not alter basic components of the hypothalamic–pituitary–adrenal axis but decreases the expression of the corticotropin releasing factor receptor 2 (CRFR2) in several nuclei of the amygdala and the hypothalamus in the brain of maternal-separated females. These results suggest a non-genomic mode of transmission of the impact of early stress in mice

Queens Library HealthLink: Fighting Health Disparities through Community Engagement

Queens, New York is a diverse urban environment and home to many recent immigrants and low-income populations, which are known to have lower access to healthcare and are thus at higher risk for a wide range of negative health outcomes. Queens residents face serious cancer disparities, with late-stage cancer detection rates for breast, colorectal and prostate cancers far surpassing national averages. Developed to address such disparities, Queens Library HealthLink (HealthLink) is a four-way partnership that seeks to increase access to cancer screening, care and education in medically underserved neighborhoods in Queens. Through 20 of the 62 Queens Public Libraries, HealthLink organizes community members into Cancer Action Councils that develop and tailor interventions suited to community needs, assets and priorities, as well as perform evaluation of their work. This article describes the partnership, its program outcomes and case examples of successful initiatives in order to present HealthLink’s relevance to other urban public libraries as a model for reaching broad, underserved audiences with health information and services

Experimental determination of zinc isotope fractionation in complexes with the phytosiderophore 2′-deoxymugeneic acid (DMA) and its structural analogues, and implications for plant uptake mechanisms

The stable isotope signatures of zinc and other metals are increasingly used to study plant and soil processes. Complexation with phytosiderophores is a key reaction and understanding the controls of isotope fractionation is central to such studies. Here, we investigated isotope fractionation during complexation of Zn2+ with the phytosiderophore 2′-deoxymugeneic acid (DMA), and with three commercially available structural analogues of DMA: EDTA, TmDTA, and CyDTA. We used ion exchange chromatography to separate free and complexed zinc, and identified appropriate cation exchange resins for the individual systems. These were Chelex-100 for EDTA and CyDTA, Amberlite CG50 for TmDTA and Amberlite IR120 for DMA. With all the ligands we found preferential partitioning of isotopically heavy zinc in the complexed form, and the extent of fractionation was independent of the Zn:ligand ratio used, indicating isotopic equilibrium and that the results were not significantly affected by artifacts during separation. The fractionations (in ‰) were +0.33 ± 0.07 (1σ, n = 3), + 0.45 ± 0.02 (1σ, n = 2), + 0.62 ± 0.05 (1σ, n = 3) and +0.30 ± 0.07 (1σ, n = 4) for EDTA, TmDTA, CyDTA, and DMA, respectively. Despite the similarity in Zn-coordinating donor groups, the fractionation factors are significantly different and extent of fractionation seems proportional to the complexation stability constant. The extent of fractionation with DMA agreed with observed fractionations in zinc uptake by paddy rice in field experiments, supporting the possible involvement of DMA in zinc uptake by rice

Preface and acknowledgements

This collection is the outcome of a Maastricht Research Based Learning Project (MARBLE) that took place at the Faculty of Arts and Social Sciences at Maastricht University in spring 2011. Under the guidance of Jens Lachmund (who is a lecturer at that faculty) a group of nine students worked on eight distinct case-studies on the culture and politics of product labelling

A geometric morphometric relationship predicts stone flake shape and size variability

The archaeological record represents a window onto the complex relationship between stone artefact variance and hominin behaviour. Differences in the shapes and sizes of stone flakes-the most abundant remains of past behaviours for much of human evolutionary history-may be underpinned by variation in a range of different environmental and behavioural factors. Controlled flake production experiments have drawn inferences between flake platform preparation behaviours, which have thus far been approximated by linear measurements, and different aspects of overall stone flake variability (Dibble and Rezek J Archaeol Sci 36:1945-1954, 2009; Lin et al. Am Antiq 724-745, 2013; Magnani et al. J Archaeol Sci 46:37-49, 2014; Rezek et al. J Archaeol Sci 38:1346-1359, 2011). However, when the results are applied to archaeological assemblages, there remains a substantial amount of unexplained variability. It is unclear whether this disparity between explanatory models and archaeological data is a result of measurement error on certain key variables, whether traditional analyses are somehow a general limiting factor, or whether there are additional flake shape and size drivers that remain unaccounted for. To try and circumvent these issues, here, we describe a shape analysis approach to assessing stone flake variability including a newly developed three-dimensional geometric morphometric method (\u273DGM\u27). We use 3DGM to demonstrate that a relationship between platform and flake body governs flake shape and size variability. Contingently, we show that by using this 3DGM approach, we can use flake platform attributes to both (1) make fairly accurate stone flake size predictions and (2) make relatively detailed predictions of stone flake shape. Whether conscious or instinctive, an understanding of this geometric relationship would have been critical to past knappers effectively controlling the production of desired stone flakes. However, despite being able to holistically and accurately incorporate three-dimensional flake variance into our analyses, the behavioural drivers of this variance remain elusive

Schwann cell stimulation induces functional and structural changes in peripheral nerves

Signal propagation is the essential function of nerves. Lysophosphatidic acid 18:1 (LPA) allows the selective stimulation of calcium signaling in Schwann cells but not neurons. Here, the time course of slowing and amplitude reduction on compound action potentials due to LPA exposure was observed in myelinated and unmyelinated fibers of the mouse, indicating a clear change of axonal function. Teased nerve fiber imaging showed that Schwann cell activation is also present in axon-attached Schwann cells in freshly isolated peripheral rat nerves. The LPA receptor 1 was primarily localized at the cell extensions in isolated rat Schwann cells, suggesting a role in cell migration. Structural investigation of rat C-fibers demonstrated that LPA leads to an evagination of the axons from their Schwann cells. In A-fibers, the nodes of Ranvier appeared unchanged, but the Schmidt-Lanterman incisures were shortened and myelination reduced. The latter might increase leak current, reducing the potential spread to the next node of Ranvier and explain the changes in conduction velocity. The observed structural changes provide a plausible explanation for the functional changes in myelinated and unmyelinated axons of peripheral nerves and the reported sensory sensations such as itch and pain

Cenários: uma Análise da Produção Científica Brasileira entre 1980 e 2016

Este estudo investiga os cenários e desenvolvido com o objetivo de investigar as abordagens sobre cenários nas pesquisas publicadas em periódicos nacionais, o qual justifica-se pela importância do tema como ferramenta estratégica emergencial no ambiente organizacional. A principal contribuição que se pretende neste estudo é apresentaras pesquisas que vem sendo desenvolvidas e publicadas sobre o assunto, abrindo assim caminho para novas pesquisas. Realizou-se uma pesquisa bibliométrica e sociométrica, sem delimitação de tempo, em 84 artigos. A Pesquisa é caracterizada como descritiva quanto aos objetivos, documental quanto aos procedimentos e quantitativa quanto à abordagem do problema. A técnica utilizada foi bibliometria e análise de redes. Como resultado, destaca-se a existência de pesquisas sobre Cenários Prospectivos, sendo o primeiro artigo publicado em 1989, os autores que mais se destacam no cenário nacional são Claudio Antonio Rojo e James Terence Coulter Wright, sendo estes considerados atores centrais em sua rede, tendo em vista o número de laços deste em relação aos outros autores

Introducing platform surface interior angle (PSIA) and its role in flake formation, size and shape

Four ways archaeologists have tried to gain insights into how flintknapping creates lithic variability are fracture mechanics, controlled experimentation, replication and attribute studies of lithic assemblages. Fracture mechanics has the advantage of drawing more directly on first principles derived from physics and material sciences, but its relevance to controlled experimentation, replication and lithic studies more generally has been limited. Controlled experiments have the advantage of being able to isolate and quantify the contribution of individual variables to knapping outcomes, and the results of these experiments have provided models of flake formation that when applied to the archaeological record of flintknapping have provided insights into past behavior. Here we develop a linkage between fracture mechanics and the results of previous controlled experiments to increase their combined explanatory and predictive power. We do this by documenting the influence of Herztian cone formation, a constant in fracture mechanics, on flake platforms. We find that the platform width is a function of the Hertzian cone constant angle and the geometry of the platform edge. This finding strengthens the foundation of one of the more influential models emerging from the controlled experiments. With additional work, this should make it possible to merge more of the experimental results into a more comprehensive model of flake formation