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The overall staining by GS clearly reveals astrocytes, including all cells of the astroglial family (1), i.e., Bergmann glia, Müller cells (2), tanycytes (3), and ependymal cells. The star shaped morphology from classical silver impregnations relates to cortical and hippocampal astrocytes, which display a comparable pattern in material stained for GFAP. However, the dense population of GS stained astrocytes found in all diencephalic and mesencephalic regions, known to display faint GFAP-labeling (unpublished observations) indicated that while apparently all astrocytes contain GS they have GFAP-ir filaments only in a region-dependent pattern. This is complicated by the emerging view that "astrocytes" constitute a heterogeneous population even within a given region. In the rat hippocampus, combined immunostainings have revealed that the "classical" GFAP-ir astrocyte constitutes a subpopulation of GS-ir astrocytes, which can also lack GFAP staining [direct double staining (4)]. In view of several astroglial subtypes and/or glial precursors present in the adult rodent brain, anti-GS appears to be the most general astrocyte marker, covering all subtypes. In addition, GS has been found early on to label exclusively astrocytic cells and no other glial or neuronal cell types in situ or in culture [reviewed by (5)]. GS has, thus, been applied as a reliable astrocyte marker in very many studies since.
"Complex cells" in rat hippocampus, initially assumed to be an astrocyte subtype (6) but now understood to belong to NG2 cells, a fourth glial type in the CNS (7), may display faint GS-ir in the soma but not its fine processes. Oligodendrocyte precursor cells, possibly also related to NG2 cells, were found to be devoid of GS-ir (8). The immunocytochemical profile and possible heterogeneity of NG2 cells is still under debate to date. Disputing the exclusion of non-astrocytic cells in GS staining, some authors have later reported GS+ oligodendrocytes, although this has not been investigated systematically. Reports on non-astrocytic GS will be discussed in detail here.
Wenn in Romanen Gerichte vorkommen, geht es meistens um Prozesse. Bei den populären Varianten halten diabolische Staatsanwälte gnadenlose Plädoyers gegen unschuldige Angeklagte (jung und weiblich), gutaussehende Strafverteidiger (jung und männlich), die immer gerade ihren ersten Fall haben, fallen ihnen heroisch ins Wort und tragen am Ende den Sieg und die Angeklagte davon. Bei den weniger populären gehen die Prozesse oft schlecht aus. Menschen werden verurteilt, ohne dass sie etwas Böses getan hätten, oder Rosshändler enden auf dem Schafott. ...
Recent studies have proven that Dimethylfumarate (DMF) has a marked anti-proliferative impact on diverse cancer entities e.g., on malignant melanoma. To explore its anti-tumorigenic potential, we examined the effects of DMF on human colon carcinoma cell lines and the underlying mechanisms of action. Human colon cancer cell line HT-29 and human colorectal carcinoma cell line T84 were treated with or without DMF. Effects of DMF on proliferation, cell cycle progression, and apoptosis were analyzed mainly by Bromodeoxyuridine (BrdU)- and Lactatdehydrogenase (LDH)-assays, caspase activation, flowcytometry, immunofluorescence, and immunoblotting. In addition, combinational treatments with radiation and chemotherapy were performed. DMF inhibits cell proliferation in both cell lines. It was shown that DMF induces a cell cycle arrest in G0/G1 phase, which is accompanied by upregulation of p21 and downregulation of cyclin D1 and Cyclin dependent kinase (CDK)4. Furthermore, upregulation of autophagy associated proteins suggests that autophagy is involved. In addition, the activation of apoptotic markers provides evidence that apoptosis is involved. Our results show that DMF supports the action of oxaliplatin in a synergetic manner and failed synergy with radiation. We demonstrated that DMF has distinct anti-tumorigenic, cell dependent effects on colon cancer cells by arresting cell cycle in G0/G1 phase as well as activating both the autophagic and apoptotic pathways and synergizes with chemotherapy.
Die Geschichte klingt bekannt: Ein Rechtssystem etabliert im 19. Jahrhundert eine liberale institutionelle Ordnung. Eine Verfassung garantiert mehr oder weniger verbindlich individuelle Rechte, flankiert von einer prinzipiell nach Vertragsfreiheit und Eigentumsfreiheit gestalteten Privatrechtskodifikation. Zu Beginn des 20. Jahrhunderts gerät das liberale Gleichgewicht jedoch ins Wanken. Arbeitende Menschen artikulieren ihre Interessen schärfer als zuvor, es entsteht revolutionärer Sprengstoff, die "soziale Frage" ist allgegenwärtig und das Privatrecht der alten Ordnung scheint keine Antworten darauf zu haben. Es beginnt ein Ringen zwischen neuen, zunehmend radikalen politischen Bekenntnissen, die den Gegensatz der Klassen entweder zugunsten einer Klasse – wenn nötig gewaltsam – entscheiden oder ihn beseitigen wollen, durch Harmonisierung widerstreitender Interessen. Die neuen politischen Richtungen beeinflussen entscheidend das Privatrecht. Das Arbeitsrecht, als neu entstehende Disziplin, gerät in das Spannungsfeld der politischen Glaubenskämpfe des neuen Jahrhunderts und gewinnt gerade durch sie an Relevanz. ...
Adipose-derived mesenchymal stem cells (ASCs) are considered to be a useful tool for regenerative medicine, owing to their capabilities in differentiation, self-renewal, and immunomodulation. These cells have become a focus in the clinical setting due to their abundance and easy isolation. However, ASCs from different depots are not well characterized. Here, we analyzed the functional similarities and differences of subcutaneous and visceral ASCs. Subcutaneous ASCs have an extraordinarily directed mode of motility and a highly dynamic focal adhesion turnover, even though they share similar surface markers, whereas visceral ASCs move in an undirected random pattern with more stable focal adhesions. Visceral ASCs have a higher potential to differentiate into adipogenic and osteogenic cells when compared to subcutaneous ASCs. In line with these observations, visceral ASCs demonstrate a more active sonic hedgehog pathway that is linked to a high expression of cilia/differentiation related genes. Moreover, visceral ASCs secrete higher levels of inflammatory cytokines interleukin-6, interleukin-8, and tumor necrosis factor α relative to subcutaneous ASCs. These findings highlight, that both ASC subpopulations share multiple cellular features, but significantly differ in their functions. The functional diversity of ASCs depends on their origin, cellular context and surrounding microenvironment within adipose tissues. The data provide important insight into the biology of ASCs, which might be useful in choosing the adequate ASC subpopulation for regenerative therapies.
In Germany, the termination of employment contracts is a central and often intensely debated legal issue today. This is not surprising since employment termination entails substantial risks for the person affected and threatens the very foundation of his or her economic existence. This is why both politics and legal dogmatics place the individual engaged in dependent work at the centre of concern as a subject requiring protection. In Germany, labour law ("Arbeitsrecht") emerged as an independent field of law focusing on the persona of the dependent worker ("Arbeitnehmer") and its typified normative ascriptions. This process took place in the course of the 20th century, as the concept of the principal requirement that employees be protected against unforeseen or unjustified dismissal became increasingly established, giving rise to very intricate regulations. Social security is a guiding motif of this legislation which regards contract termination primarily as a risk. It is often not considered that this constellation is a very new one. Defined conceptions of the interests of the parties to labour contracts also existed before 1900, but social security was then not a central criterion. At that time, many people perceived the termination of their employment as an opportunity rather than primarily as a risk. Employers, on the other hand, aimed to keep people in their service for as long as possible. In the late 19th century, the enforcement of labour performance by legal means and normative instruments, which no longer plays any role today, was still an important issue. This provides occasion to investigate the freedom of working people from the perspective of the history of law, whereby this article focuses on the history of the German-speaking territories. ...
IL-27 regulates inflammatory diseases by exerting a pleiotropic impact on immune cells. In cancer, IL-27 restricts tumor growth by acting on tumor cells directly, while its role in the tumor microenvironment is still controversially discussed. To explore IL-27 signaling in the tumor stroma, we used a mammary carcinoma syngraft approach in IL27Rα-deficient mice. Tumor growth in animals lacking IL27Rα was markedly reduced. We noticed a decrease in immune cell infiltrates, enhanced tumor cell death, and fibroblast accumulation. However, most striking changes pertain the tumor vasculature. Tumors in IL27Rα-deficient mice were unable to form functional vessels. Blocking IL-27-STAT1 signaling in endothelial cells in vitro provoked an overshooting migration/sprouting of endothelial cells. Apparently, the lack of the IL-27 receptor caused endothelial cell hyper-activation via STAT1 that limited vessel maturation. Our data reveal a so far unappreciated role of IL-27 in endothelial cells with importance in pathological vessel formation.
Ich möchte dem Direktor, Herrn Professor Thomas Duve, meinen aufrichtigsten Dank dafür sagen, dass ich die Rede zum Beginn einer neuen Phase im mittlerweile langen Leben des Frankfurter Instituts halten darf. Für einen Rechtshistoriker handelt es sich um eine wirkliche Ehre, hat doch das Max-Planck-Institut für europäische Rechtsgeschichte seit 1964, seinem Gründungsjahr, dank seiner Leiter – u.a. Helmut Coing, Dieter Simon, Michael Stolleis und Thomas Duve, die allesamt herausragende, allgemein anerkannte Wissenschaftler waren (und sind) – die Studien zur mittelalterlichen und neuzeitlichen Rechtsgeschichte wesentlich vorangetrieben und sich damit weltweit als wichtigstes Forschungszentrum durchgesetzt. ...
Chemotherapy, nerve injuries, or diseases like multiple sclerosis can cause pathophysiological processes of persistent and neuropathic pain. Thereby, the activation threshold of ion channels is reduced in peripheral sensory neurons to normally noxious stimuli like heat, cold, acid, or mechanical due to sensitization processes. This leads to enhanced neuronal activity, which can result in mechanical allodynia, cold allodynia, thermal hyperalgesia, spontaneous pain, and may initiate persistent and neuropathic pain. The treatment options for persistent and neuropathic pain patients are limited; for about 50% of them, current medication is not efficient due to severe side effects or low response to the treatment. Therefore, it is of special interest to find additional treatment strategies. One approach is the control of neuronal sensitization processes. Herein, signaling lipids are crucial mediators and play an important role during the onset and maintenance of pain. As preclinical studies demonstrate, lipids may act as endogenous ligands or may sensitize transient receptor potential (TRP)-channels. Likewise, they can cause enhanced activity of sensory neurons by mechanisms involving G-protein coupled receptors and activation of intracellular protein kinases. In this regard, oxidized metabolites of the essential fatty acid linoleic acid, 9- and 13-hydroxyoctadecadienoic acid (HODE), their dihydroxy-metabolites (DiHOMEs), as well as epoxides of linoleic acid (EpOMEs) and of arachidonic acid (EETs), as well as lysophospholipids, sphingolipids, and specialized pro-resolving mediators (SPMs) have been reported to play distinct roles in pain transmission or inhibition. Here, we discuss the underlying molecular mechanisms of the oxidized linoleic acid metabolites and eicosanoids. Furthermore, we critically evaluate their role as potential targets for the development of novel analgesics and for the treatment of persistent or neuropathic pain.
"Nothing is more soothing to the nerves than a detailed discussion of homage and lordship …" If William de Briwerr, fictional English knight and narrator in Alfred Duggan’s historical novel Lord Geoffrey’s Fancy, is right, then a conference held in April 2011 will have set the participants at ease. Following the call of the Konstanzer Arbeitskreis für mittelalterliche Geschichte and the conference organiser, Karl-Heinz Spieß, they had gathered to discuss the "Formation and dissemination of feudalism in the Empire and in Italy during the 12th and 13th century". The conference proceedings have now been published, and I suppose William de Briwerr would have approved of the intensity of discussion contained therein. ...
Introduction: MRI-targeted biopsy (TB) increases overall prostate-cancer (PCa) detection-rates and decreases the risk of insignificant PCa detection. However, the impact of these findings on the definite pathology after radical prostatectomy (RP) is under debate.
Materials and Methods: Between 01/2014 and 12/2018, 366 patients undergoing prostate biopsy and RP were retrospectively analyzed. The correlation between biopsy Gleason-score (highest Gleason-score in a core) and the RP Gleason-score in patients undergoing systematic biopsy (SB-group) (n = 221) or TB+SB (TB-group, n = 145) was tested using the ISUP Gleason-group grading (GGG, scale 1–5). Sub analyses focused on biopsy GGG 1 and GGG ≥ 2.
Results: Proportions of biopsy GGG 1–5 in the SB-group and TB-group were 24.4, 37.6, 19, 10.9, 8.1% and 13.8, 43.4, 24.2, 13.8, 4.8%, respectively (p = 0.07). Biopsy and pathologic GGG were concordant in 108 of 221 (48.9%) in SB- and 74 of 145 (51.1%) in TB-group (p = 0.8). Gleason upgrading was recorded in 33.5 and 31.7% in SB- vs. TB-group (p = 0.8). Patients with biopsy GGG 1 undergoing RP showed an upgrading in 68.5%(37/54) in SB- and 75%(15/20) in TB-group (p = 0.8). In patients with biopsy GGG ≥ 2 concordance increased for both biopsy approaches (54.5 vs. 55.2% for SB- vs. TB-group, p = 0.9).
Discussion: Irrespective of differences in PCa detection-rates between TB- and SB-groups, no significant differences in GGG concordance and upgrading between patients of both groups undergoing biopsy, followed by RP, were recorded. Concordance rates increased in men with biopsy GGG ≥ 2. TB seems to detect more patients with PCa without a difference in concordance with final pathology.
In the last few decades the concept of self-regulation accompanied the process of dismantling the welfare state. In this context, in central countries—Europe and North America—the importance given to private regulations versus public action increased, thus requiring new mechanisms of legitimacy. To this end, appeals to the principles of economy and technical efficiency to legitimate private regulations have been made by several researchers. However, these principles acquired a negative view in Argentina because they were used to use to legitimate processes that led to various crises, especially taking into consideration the neo-liberal experience of the 1990s. Against this historical background, this paper seeks to show a particular case of legitimizing the self-regulation of non-state organizations (social clubs) by using classic topoi, which had been historically used to legitimize state action. In order to do so, this text focuses on the analysis of “Luna de Avellaneda” Act of 2007, by which the government of Buenos Aires sought to legitimize the self-regulation of clubs appealing to the classical values of democracy, participation, and solidarity. For this, the historical experience of the Argentinean political community will be observed from the perspective of the history of these clubs, thus recovering the social function they played in the diverse political and economic crises.
Ziel der vorliegenden Arbeit ist der Aufbau von koaxialen Plasmabeschleunigern und deren Verwendung für die Untersuchung der Eigenschaften von kollidierenden Plasmen. Zukünftig sollen diese kollidierenden Plasmen als intensive Strahlungsquelle im Bereich der ultravioletten (UV-) und vakuumultravioletten (VUV-)Strahlung sowie in der Grundlagenforschung als Target zur Ionenstrahl-Plasma-Wechselwirkung Verwendung finden. Für diese Anwendungen steht dabei eine Betrachtung der physikalischen Grundlagen im Vordergrund. So sind neben der Kenntnis der Plasmadynamik auch Aussagen bezüglich der Elektronendichte, der Elektronentemperatur und der Strahlungsintensität von Bedeutung. Im Einzelnen konnte gezeigt werden, dass es möglich ist, durch eine Plasmakollision die Elektronendichte des Plasmas im Vergleich zu der eines einzelnen Plasmas deutlich zu erhöhen - im Maximalfall um den Faktor vier. Gleichzeitig stieg durch die Plasmakollision die Lichtintensität im Wellenlängenbereich der UV- und VUV-Strahlung um den Faktor drei an...
On February 20 at the Max Planck Institut für europäische Rechtsgeschichte, the Legal Historian and member of the Constitutional Court of Peru, Dr. Carlos Ramos Núñez, presented a crucial intervention on the problems that face the current constitutionalism in Latin America. Faced with a heterogeneous group of historians, philosophers and theoreticians of law, interested in the vicissitudes of Latin American juridical evolution, the political-juridical tensions of the Peruvian present served him as a framework to raise various constitutional problems and controversies. ...
Video and image data are regularly used in the field of benthic ecology to document biodiversity. However, their use is subject to a number of challenges, principally the identification of taxa within the images without associated physical specimens. The challenge of applying traditional taxonomic keys to the identification of fauna from images has led to the development of personal, group, or institution level reference image catalogues of operational taxonomic units (OTUs) or morphospecies. Lack of standardisation among these reference catalogues has led to problems with observer bias and the inability to combine datasets across studies. In addition, lack of a common reference standard is stifling efforts in the application of artificial intelligence to taxon identification. Using the North Atlantic deep sea as a case study, we propose a database structure to facilitate standardisation of morphospecies image catalogues between research groups and support future use in multiple front-end applications. We also propose a framework for coordination of international efforts to develop reference guides for the identification of marine species from images. The proposed structure maps to the Darwin Core standard to allow integration with existing databases. We suggest a management framework where high-level taxonomic groups are curated by a regional team, consisting of both end users and taxonomic experts. We identify a mechanism by which overall quality of data within a common reference guide could be raised over the next decade. Finally, we discuss the role of a common reference standard in advancing marine ecology and supporting sustainable use of this ecosystem.
A Borges, como es bien sabido, le interesaban más aquellos universos tejidos por las palabras que ese otro espacio teñido de desconfianza que algunos persistían en llamar realidad. Dicha pulsión creadora de mundos propios transfirió a sus lectores la risa profunda, el don de la ironía pero también, como algunos lo reconocen, un cierto malestar. Algo similar, pero con una pretensión centrada no ya en lo ficcional sino en las políticas del lenguaje y en los modos de reencontrar claves antropológicas de diversas codificaciones de lo inteligible, acaece con la reciente publicación colectiva «Tour du monde des concepts», dirigida por Pierre Legendre. ...
To date, there is insufficient insight into inflammatory bowel disease (IBD)-associated stress, recognized disability, and contact with the social care system. We aimed to assess these parameters in IBD patients and a non-IBD control group, who were invited to participate in an online survey developed specifically for this study (www.soscisurvey.de) with the help of IBD patients. 505 IBD patients and 166 volunteers (i.e., control group) participated in the survey. IBD patients reported significantly increased levels of stress within the last six months and five years (p<0.0001) and were more likely to have a recognized disability (p<0.0001). A low academic status was the strongest indicator of a disability (p = 0.006). Only 153 IBD patients (30.3%) reported contact with the social care system, and a disability was the strongest indicator for this (p<0.0001). Our study provides data on stress and disability in a large unselected German IBD cohort. We showed that patients with IBD suffer more often from emotional stress and more often have a recognized disability. As only about 1/3 of the patients had come into contact with the social care system and the corresponding support, this patient group is undersupplied in this area.
Ein blinder Fleck mag eine vereinzelte Fehlerquelle sein: ein weißer Fleck auf einer sonst gut kartographierten Fläche. Der blinde Fleck, mit dem es Christa Wolf zu tun hat, ist eher Teil und Makel der menschlichen Konstitution. Zu nahe(liegend), um in unseren Blickkreis treten zu können, gehört er der Anatomie unseres Wissens und Unwissens an; und was es mit diesem 'unser' und 'Un'- auf sich hat, liegt ebenfalls im Dunkeln. Wüssten wir, was und wo er ist, wäre er - wären wir - nicht mehr blind. Nicht, dass er uns ganz so unzugänglich ist wie Kants Ding an sich; er ist vielmehr 'an und für uns' da. Dank vor allem der breiten Rezeption der Psychoanalyse ist er uns, zumindest als Redensart, geläufig. Inwieweit er sich aufklären lässt, steht auf einem anderen Blatt. Dessen Erforschung stellt eine unabschließbare Aufgabe im Sinne von Freuds "unendlicher Analyse" dar. Als literarische Erbin deutsch-protestantischer Seelenprüfung ist Christa Wolf dieser 'Berufspflicht' beharrlich nachgegangen. Oder besser: sie wurde von ihr umgetrieben. Denn ihre Arbeit am blinden Fleck ist immer zugleich die daes blinden Flecks gewesen. Daher die böse Erfahrung, die sie eines Tages mit ihm machen sollte. Trotz einer jahrzehntelang geübten Gewissensforschung, die den Verhören der Stasi in nichts nachstand, stieß sie in deren Archiven eines Tages auf einen eigenen blinden Fleck. Und zwar einen, den sie am allerwenigsten an sich dulden konnte. Für solche Begegnungen hat Freud die Begriffe des "Unheimlichen" und der "Nachträglichkeit" geprägt. Es geht dabei immer um die "Arbeit" des Unbewussten.
In der heutigen Epoche von Radikalismen, politischer und existentieller Unbehaustheit und vermeintlich in die Krise geratener Männlichkeit wird die "vaterlose Gesellschaft" (Matthias Matussek) oft als Ursache für vielfache Fehlentwicklungen insbesondere der Söhne betrachtet und geradezu zur conditio humana der westlichen Welt erklärt. Zwar wird diese 'Vaterlosigkeit' vor allem im rechtskonservativen Lager immer wieder als Verlustgeschichte natürlicher männlicher Vorherrschaft bedauert, aber auch ein kritisch-engagierter Autor wie Milo Rau scheint in seinem Theaterstück Civil Wars ein (Ideal-)Bild normal-autoritärer väterlicher Männlichkeit zu vermitteln, insofern besonders das problematische Verhältnis zum Vater das Stück leitmotivisch durchzieht und als Ursache für die psychosoziale Fehlentwicklung der Figuren aufgeführt wird.
Um 1900 wurde diese heute so oft beklagte vaterlose Gesellschaft aber geradezu herbeigesehnt: Nicht nur die eben erst gegründete bürgerliche Jugendbewegung, sondern auch die reformwillige wilhelminische Elternschaft, die im morbiden Aufbruch der (männlichen) Jugend ihre eigenen politischen Hoffnungen zu realisieren wünschte, erhoben den Vatermord provokativ zum Teil ihres Programms.
Von Natur aus, so Döblin, kannte das Epische in seiner "unbegrenzten Form" kein bestimmtes Ende. Realität, Traum und Phantasie waren noch nicht voneinander geschieden; berichtet wurden "Elementarsituationen des menschlichen Daseins" in "immer neuen Abwandlungen", in der "Serienarbeit" der mündlichen und kollektiven Erzählungen und Nacherzählungen, im Grunde der "Wahrheit" ohne Begründung. Auf Einladung des Germanistikprofessors Julius Petersen hielt Döblin am 10. Dezember 1928 seinen Vortrag "Der Bau des epischen Werks" im Auditorium Maximum der Berliner Friedrich-Wilhelms-Universität. Darin erstellt er ein Programm zur Erneuerung des Romans unter den Bedingungen der modernen Kollektiverfahrungen von Masse, Technik und medialer Öffentlichkeit, in Verbindung mit den Wissensbeständen von Medizin, Psychiatrie und Soziologie und deren "Resonanz", wie er in seiner ganz persönlichen Universalschrift 'Unser Dasein' von 1933 schrieb, seiner letzten in Deutschland vor dem Exil erschienenen Publikation. Die Literatur hätte die Aufgabe, die neu entstandene Wirklichkeit zu "durchstoßen", das Menschenmögliche, auch die destruktiven Energien zur Sprache zu bringen: im Produktionsprozess eines als "dynamisches Netzwerk" zu begreifenden und plastisch zu gestaltenden Weltganzen, der Dinge und Vorgänge mit den in ihnen wirkenden Kräften. Die Vitalisierung und Elementarisierung der Sprache sollte den Ursprung des Epischen wiedergewinnen und die vorherrschende Repräsentationslogik der medialen Vermittlung außer Kraft setzen: "Das Buch ist der Tod der wirklichen Sprache."