Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells

Exposure of adult humans to manganese (Mn) has long been known to cause neurotoxicity. Recent evidence also suggests that exposure of children to Mn is associated with developmental neurotoxicity. Astrocytes are critical for the proper functioning of the nervous system, and they play active roles in neurogenesis, synaptogenesis and synaptic neurotransmission. In this report, to help elucidate the molecular events underlying Mn neurotoxicity, we systematically identified the molecular targets of Mn in primary human astrocytes at a genome-wide level, by using microarray gene expression profiling and computational data analysis algorithms. We found that Mn altered the expression of diverse genes ranging from those encoding cytokines and transporters to signal transducers and transcriptional regulators. Particularly, 28 genes encoding proinflammatory chemokines, cytokines and related functions were up-regulated, whereas 15 genes encoding functions involved in DNA replication and repair and cell cycle checkpoint control were down-regulated. Consistent with the increased expression of proinflammatory factors, analysis of common regulators revealed that 16 targets known to be positively affected by the interferon-γ signaling pathway were up-regulated by Mn2+. In addition, 68 genes were found to be similarly up- or down-regulated by both Mn2+ and hypoxia. These results from genomic analysis are further supported by data from real-time RT-PCR, Western blotting, flow cytometric and toxicological analyses. Together, these analyses show that Mn2+ selectively affects cell cycle progression, the expression of hypoxia-responsive genes, and the expression of proinflammatory factors in primary human astrocytes. These results provide important insights into the molecular mechanisms underlying Mn neurotoxicity

Die Transnationalisierung von Wirtschaftsorganisationen in der Perspektive der Économie des conventions

Mense-Petermann U. Die Transnationalisierung von Wirtschaftsorganisationen in der Perspektive der Économie des conventions. In: Knoll L, ed. Organisationen und Konventionen. Die Soziologie der Konventionen in der Organisationsforschung. Organisationssoziologie. Wiesbaden: VS Verlag für Sozialwissenschaften; 2014: 163-191

Queering and diversifying gender in equality work at European higher education institutions

Against the background of recent changes to EU legislation to meet the demands and needs of LGBTIQ* communities, the authors seek to situate a queered and diversified understanding of gender firmly at the centre of the gender equality discourse in higher education (HE). Based on case examples, the legal and discursive status quo in German and Dutch HE institutions as well as actors' motivations, challenges and opportunities are examined through a queer lens. The results highlight how differently EU legislation is transposed into national law. They also show that change is currently driven by highly motivated individual actors, be they students, gender equality and diversity officers, or individual institutions. We argue that queering and diversifying should be understood and used as modes to reflect on and analyse the processes that lead to heteronormative understandings of gender in HE and to develop strategies that take the complexities of gendered identities and discrimination into account.In den letzten Jahren hat die zunehmende Anerkennung von Forderungen und Bedürfnissen der LGBTIQ* Communities zu Änderungen im EU-Recht beigetragen. Vor diesem Hintergrund plädieren die Autor*innen für ein queeres und damit vielfältiges Verständnis von Gender in den Gleichstellungsdiskursen an Hochschulen. Anhand der Fallbeispiele Deutschland und den Niederlanden werden rechtliche und diskursive Bedingungen sowie die Motivationen, Herausforderungen und Chancen der Akteur*innen im jeweiligen Hochschulsystem aus einer queeren Perspektive betrachtet. Die Beispiele zeigen, wie unterschiedlich die Umsetzung von EU-Richtlinien in nationales Recht erfolgt ist. Sie machen ebenfalls deutlich, dass Veränderungen in den Hochschulen derzeit von hoch motivierten Akteur*innen wie Studierenden, Gleichstellungs- und Diversity-Beauftragten oder einzelnen Einrichtungen angestoßen werden. Als aufeinander aufbauende, analytische Konzepte können "queering" und "diversifying" dazu beitragen, heteronormative Vorannahmen und diskriminierende Prozesse im gleichstellungspolitischen Kontext an Hochschulen zu erkennen. Sie erlauben ferner die Entwicklung von Strategien, die die Komplexität von Geschlechteridentitäten und Diskriminierungen berücksichtigen

Der Weg in die Wissenschaft als gelebte Erfahrung

Schäfer S. Der Weg in die Wissenschaft als gelebte Erfahrung. In: Schlüter A, Metz-Göckel S, Mense L, Sabisch K, eds. Kooperation und Konkurrenz im Wissenschaftsbetrieb. Perspektiven aus der Genderforschung und -politik. Opladen ; Berlin ; Toronto: Verlag Barbara Budrich; 2020: 202-210

Pathophysiology of the Rhesus Macaque Model for Inhalational Brucellosis

The objective of this study was to characterize the rhesus macaque (RM) as a model for inhalational brucellosis in support of the U.S. Food and Drug Administration's (FDA) Animal Rule. The pathophysiology of chronic Brucella melitensis aerosol infection was monitored in two phases that each occurred over an 8-week time period; dose escalation (8 RMs; targeted doses of 5.0E+03, 5.0E+04, or 5.0E+05 CFU/animal or the unchallenged control) and natural history (12 RMs; targeted dose of 2.50E+05 CFU/animal or the unchallenged control). RMs given an aerosol challenge with B. melitensis developed undulating fevers (6/6 phase I; 8/9 phase II), positive enriched blood cultures (5/10; phase II), and bacterial burdens in tissues starting 14 to 21 days postchallenge (6/6 phase I; 10/10 phase II). In addition, 80% (8/10; phase II) of infected RMs seroconverted 14 to 21 days postchallenge. RMs developed elevations in certain liver enzymes and had an increased inflammatory response by 3 weeks postchallenge as shown by increases in C-reactive protein (6/8) and neopterin (4/8), which correlated with the onset of a fever. As early as 14 days postchallenge, positive liver biopsy specimens were detected (2/8), and ultrasound imaging showed the development of splenomegaly. Finally, histopathologic examination found lesions attributed to Brucella infection in the liver, kidney, lung, and/or spleen of all animals. The disease progression observed with the RMs in this study is analogous to human brucellosis pathophysiology. Thus, the results from this study support the use of the RM as an animal model for inhalational brucellosis to evaluate the efficacy of novel vaccines and therapeutics against B. melitensis