1,721,035 research outputs found
Brevican, Neurocan, Tenascin-C and Tenascin-R Act as Important Regulators of the Interplay between Perineuronal Nets, Synaptic Integrity, Inhibitory Interneurons and Otx2
No full text
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Analysis of combinatorial variability reveals selective accumulation of the fibronectin type III domains B and D of tenascin-C in injured brain
No full textTenascin-C (Tnc) is a multimodular extracellular matrix glycoprotein that is markedly upregulated in CNS injuries where it is primarily secreted by reactive astrocytes. Different Tnc isoforms can be generated by the insertion of variable combinations of one to seven (in rats) alternatively spliced distinct fibronectin type III (FnIII) domains to the smallest variant. Each spliced FnIII repeat mediates specific actions on neurite outgrowth, neuron migration or adhesion. Hence, different Tnc isoforms might differentially influence CNS repair. We explored the expression pattern of Tnc variants after cortical lesions and after treatment of astrocytes with various cytokines. Using RT-PCR, we observed a strong upregulation of Tnc transcripts containing the spliced FnIII domains B or D in injured tissue at 2-4 days post-lesion (dpl). Looking at specific combinations, we showed a dramatic increase of Tnc isoforms harboring the neurite outgrowth-promoting BD repeat with both the B and D domains being adjacent to each other. Isoforms containing only the axon growth-stimulating spliced domain D were also dramatically enhanced after injury. Injury-induced increase of Tnc proteins comprising the domain D was confirmed by Western Blotting and immunostaining of cortical lesions. In contrast, the FnIII modules C and AD1 were weakly modulated after injury. The growth cone repulsive A1A2A4 domains were poorly expressed in normal and injured tissue but the smallest isoform, which is also repellant, was highly expressed after injury. Expression of the shortest Tnc isoform and of variants containing B, D or BD, was strongly upregulated in cultured astrocytes after TGFbeta1 treatment, suggesting that TGFbeta1 could mediate, at least in part, the injury-induced upregulation of these isoforms. We identified complex injury-induced differential regulations of Tnc isoforms that may well influence axonal regeneration and repair processes in the damaged CNS.</p
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
In vitro recapitulation of developmental transitions in human neural stem cells
No full textProgress made in pluripotent stem cell (PSC) technology potentially enables the production of almost any cell type in unlimited quantities for human specific models. This is particularly interesting for the generation of neuronal cells as the human brain differs considerably from commonly used animal models and human brain tissue samples are scarce, difficult to obtain and to propagate in vitro.
In recent years it has become possible to isolate and expand neural stem cells (NSCs) from different sources using growth factor-based protocols. However, a still open question is to what extent these diverse stem cell systems reflect physiological stem cell states observed in vivo (Conti et al. 2010).
During nervous system development, early neuroepithelial stem (NES) cells with a highly polarized morphology and responsiveness to regionalizing morphogens give rise to radial glia (RG) cells, which generate region-specific neurons. Stable neural cell populations reminiscent of NES cells have been obtained from pluripotent stem cells (lt-NES cells) and the fetal human hindbrain (hbNES cells) (Tailor et al. 2013; Koch et al. 2009b).
In this study a sequential differentiation protocol was developed enabling the in vitro generation of RG-like neural stem cells from NES-like cells (lt-NES and hbNES cells). By employing differentiating conditions NES-like cells were coaxed into following the in vivo developmental transition of neural stem cells into a RG-like phenotype. Indeed, this newly established NSC population exhibits important features of multipotent neuro- and gliogenic RG cells. These RG-like NS cells could be expanded for at least 25 passages and express classical NSC markers such as Nestin and SOX2 as well as markers typically associated with RG cells including SOX9, CD44, AQP4 and HOP, while the NES cell markers PLZF, DACH1, ZO1 and MMRN1 were down-regulated.
Importantly, RG-like cells generated from PSC-derived lt-NES cells and from primary hbNES cells showed similar properties as primary RG cells obtained from fetal tissue, indicating that conversion of NES-like cells into RG-like cells recapitulates the developmental progression of early NES cells into radial glia cells occurring in vivo.
Key challenges associated with the biomedical application of PSC-derived neural stem cells are their controlled patterning towards distinct regional subtypes and the maintenance of an acquired regional phenotype across multiple passages of in vitro expansion.
Previous studies have shown that lt-NES cells, shortly after their derivation from PSC, undergo gradual posteriorization into an anterior hindbrain phenotype, which might be due to regionalizing effects of the growth factors employed for in vitro proliferation (Bithell et al. 2008; Koch et al. 2009b). This behavior is in line with their in vivo role in which they respond to morphogens in order to establish different regions of the brain. In a second step this regional identity is consolidated in RG cells which can no longer be influenced by regionalizing factors.
In order to harness this property of RG cells, RG-like NS cells were generated from dorsal forebrain-, ventral forebrain-, hindbrain- and spinal cord-patterned NES-like cells. The resulting regionalized RG-like NS cell populations express transcription factors appropriate for their positional identity across multiple passages of in vitro expansion while maintaining their differentiation potential into neurons and glia. Reminiscent of heterotopic transplantation studies, even under the influence of strong rationalizing factors in vitro the positional identity of dorsal forebrain-like NS cells remained stable (Onorati et al. 2011). Following differentiation RG-like cells generated region-specific neurons appropriate for their positional identity. These results indicate that conversion into RG-like cells may provide a route for conserving the regional identity of pre-patterned early NES cells and establishing regionally stable neural stem cell lines for biomedical application.In den letzten Jahren erzielte Fortschritte in der pluripotenten Stammzelltechnologie ermöglichen es potentiell, alle Zelltypen des Körpers in nahezu unbegrenzter Menge für die Verwendung in humanspezifischen Modellen zu generieren. Insbesondere das menschliche Gehirn unterscheidet sich wesentlich von dem der üblicherweise eingesetzten Tiermodelle und zudem sind Gewebeproben des menschlichen Gehirns schwer zugänglich und die daraus gewonnenen Zellen nur unzureichend in vitro vermehrbar. Daher ist besonders die Aussicht, humane neuronale Zellen aus pluripotenten Stammzellen (PSZ) zu gewinnen, sehr attraktiv.
Neuste Entwicklungen in den letzten Jahren haben es ermöglicht neurale Stammzellen aus unterschiedlichen Quellen zu isolieren oder zu generieren und unter Einsatz von Wachstumsfaktor-basierten Protokollen zu vermehren. Eine noch offene Frage ist jedoch, inwieweit diese verschiedenen Stammzellsysteme in vitro physiologische, in vivo existierende Stammzellstadien nachbilden.
Während der physiologischen Entwicklung des Nervensystems entstehen aus frühen, neuroepithelialen Stammzellen (NES), welche eine hochgradig polarisierte Morphologie aufweisen und empfindlich auf sogenannte regionalisierende Morphogenen reagieren, späte radiale Gliazellen (RG), die dann wiederum regionalspezifische Neurone generieren.
In vitro konnten bislang stabil proliferierenden neurale Stammzellpopulationen, welche neuroepithelialen Stammzellen gleichen, sowohl von humanen pluripotenten Stammzellen (lt-NES Zellen) als auch direkt aus dem fetalen humanen Hinterhirn (hbNES Zellen) gewonnen werden.
Darauf aufbauend wurde in dieser Arbeit ein sequentielles Differenzierungsprotokoll entwickelt, das die Generierung von RG-ähnlichen neuralen Stammzellen (RG-ähnliche NS Zellen) aus NES-ähnlichen Zellen (lt-NES und hbNES Zellen) in vitro ermöglicht. Durch die zeitlich begrenzte Anwendung differenzierender Zellkulturbedingungen werden NES-ähnliche Zellen dazu gebracht, die Entwicklung neuraler Stammzellen in vivo nachzuvollziehen und RG-ähnliche Zellen zu generieren.
Tatsächlich weist diese neu etablierte neurale Stammzellpopulation wichtige Merkmale von neuro- und gliogenen RG Zellen auf. RG-ähnliche NS Zellen können für mindestens 25 Passagen expandiert werden und exprimieren klassische neurale Stammzellmarker wie NESTIN und SOX2 sowie typischerweise RG Zell-assoziierte Marker wie SOX9, CD44, AQP4 und HOP während die NES Zell Marker PLZF, DACH1, ZO-1 und MMRN1 herunterreguliert werden.
Eine wichtige Erkenntnis dieser Studie ist, dass RG-ähnliche NS Zellen - generiert von PSZ-abgeleiteten lt-NES Zellen oder primär isolierten hbNES Zellen - ähnliche Eigenschaften zeigen wie primär aus fetalem Gewebe gewonnene RG Zellen. Dies deutet darauf hin, dass der Übergang von NES-ähnlichen Zellen in RG-ähnliche Zellen in vitro in der Tat die Entwicklung von frühen NES Zellen in RG Zellen während der Neurogenese in vivo nachvollzieht.
Eine große Herausforderung, im Hinblick auf die biomedizinische Anwendung von aus PSZ-abgeleiteten neuralen Stammzellen, ist ihre kontrollierte Entwicklung in unterschiedliche regionale Subtypen und die Aufrechterhaltung eines erworbenen regionalen Phänotyps während ihrer Kultivierung und Expansion in vitro. Vorangegangenen Arbeiten haben gezeigt, dass lt-NES Zellen kurz nach ihrer Generierung aus PSZ einen anterioren Vorderhirn Phänotyp aufweisen und in der Folge eine sukzessive regionale Posteriorisierung in einen Phänotyp durchlaufen, welcher dem ventralen Hinterhirn entspricht. Dieses Phänomen ist vermutlich auf die regionalisierenden Effekte der für die Proliferation in vitro notwendigen Wachstumsfaktoren (FGF2 und EGF) zurückzuführen.
Dieses Verhalten entspricht auch der Rolle von NES Zellen in vivo, wo sie zunächst auf Morphogene ansprechen und auf diese Weise die verschiedenen Regionen des Gehirnes generieren. In einem zweiten Schritt wird diese regionale Identität durch den Übergang in RG Zellen, welche nicht mehr durch regionalisierend Faktoren beeinflussbar sind, konsolidiert.
Um die Eigenschaft von RG Zellen, eine stabile regionale Identität zu besitzen, nutzbar zu machen, wurden zunächst RG-ähnliche NS Zellen von NES-ähnlichen Zellen mit unterschiedlicher regionalen Phänotypen abgeleitet (ventrales Vorderhirn, dorsales Vorderhirn, Hinterhirn, Rückenmark). Die hieraus gewonnenen regionalisierten RG-ähnlichen NS Zellpopulationen exprimieren trotz Exposition zu Wachstumsfaktoren über zahlreiche Passagen stabil Transkriptionsfaktoren, welche ihrer regionalen Identität entsprechen ohne zu posteriorisieren und behalten über die Zeit, die Fähigkeit sowohl in Neurone, als auch in Gliazellen zu differenzieren. In Anlehnung an Studien zur heterotopen Transplantation von RG Zellen in Mäusen in vivo wird die regionale Identität von RG-ähnlichen Zellen selbst unter dem Einfluss starker regionalisierender Faktoren wie beispielweise Retinsäure aufrechterhalten. Werden diese regionalisierten RG-ähnliche NS Zellen differenziert, generieren sie zudem neuronale Subtypen, welche ihrer regionalen Identität entsprechen.
Die Ergebnisse dieser Studie deuten zusammenfassend darauf hin, dass die Überführung in RG-ähnliche NS Zellen eine Methode darstellt, die regionale Identität von frühen regionalisierten NES Zellen zu konservieren und so regional stabile neurale Stammzelllinien für biomedizinische Anwendungen zu etablieren
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
- …
