Human CLPP reverts the longevity phenotype of a fungal ClpP deletion strain

Mitochondrial maintenance crucially depends on the quality control of proteins by various chaperones, proteases and repair enzymes. While most of the involved components have been studied in some detail, little is known on the biological role of the CLPXP protease complex located in the mitochondrial matrix. Here we show that deletion of PaClpP, encoding the CLP protease proteolytic subunit CLPP, leads to an unexpected healthy phenotype and increased lifespan of the fungal ageing model organism Podospora anserina. This phenotype can be reverted by expression of human ClpP in the fungal deletion background, demonstrating functional conservation of human and fungal CLPP. Our results show that the biological role of eukaryotic CLP proteases can be studied in an experimentally accessible model organism

Auf dem Weg zur Kulturzeitschrift : die ersten Jahrgänge von Wielands "Teutschem Merkur"

Das Ganze des Teutschen Merkurs, d.h. 38 Jahrgänge, kann man nur quantitativ erfassen. Ich konnte in diesem Beitrag nur einen winzigen Bruchteil der möglichen quantitativen Auswertungen vorstellen. Ich hoffe, anhand des Fächerspektrums, der Beiträger, Wielands spezifischer Herausgebertätigkeit und der Programmatik, die vielfältige Angebote zur Kommunikation, zum Dialog und zur Selbst-Aufklärung beinhaltete, deutlich gemacht zu haben, daß die Verbindung von Kultur, Kommunikation und Aufklärung eine zentrale Rolle für diese Zeitschrift spielte. Umgekehrt hatte aber auch der weit rezipierte Teutsche Merkur eine entscheidende Rolle für die Kultur, Kommunikation und Aufklärung im gesamten deutschen Sprachraum inne

Wieland und das Weimarer Theater (1772-1774) : Prinzenerziehung durch das Theater als politisch-moralisches Institut

Die Theateraufführungen der Seyler-Ekhofschen Gesellschaft, die von 1771 bis 1774 dreimal pro Woche im Schloßtheater spielte, bildeten in diesen Jahren einen wesentlichen Bestandteil der Hofkultur. Hof und Bürgertum waren nicht nur regelmäßige Zuschauer, sondern das Theater konnte nur auf Grund der aktiven Teilnahme und Zusammenarbeit der Schauspieler, Komponisten und Weimarer Dichter sowie der großzügigen Unterstützung der Fürstenfamilie zu einem hohen Grad an künstlerischer Perfektion gelangen. Die gelungene Vereinigung von bürgerlichen und höfischen Kunstvorstellungen spiegelt sich am besten in dem Aufschwung der Gattung des Singspiels wider, das aus seinen bürgerlichen Anfängen auf eine neue Stufe mit Hilfe antiker Stoffe, einer dichterisch anspruchsvollen Behandlung „wie das regelmäßigste Trauerspiel“ und neuer Kompositionen gehoben wurde. Durch diese deutschen Singspiele und Opern wurde es möglich, deutsches Theater und Musiktheater am Weimarer Hof zu etablieren und zu fördern, nachdem die großen Höfe im 18. Jahrhundert bisher ausschließlich italienische Opern gepflegt hatten. Der Wunsch des Hofes nach musikalischer Unterhaltung sowie der aufklärerische Bildungs- und Erziehungsanspruch konnten von Wieland am Weimarer Theater mit Hilfe seiner Singspiele zu einer gelungenen Synthese geführt werden. Die kleine Residenzstadt erlangte Anfang der 70er Jahre durch zwei Dinge Berühmtheit: durch Wieland und durch das Theater. Und Wieland war derjenige, der aktiv - durch seine Dichtungen und seine einflußreiche Zeit-schrift - den Ruhm Weimars vermehrte und verbreitete. Weimar wurde somit, bevor Goethe eintraf, bereits durch Wieland erfolgreich zu einem Muster an "Hofkultur" bzw. zum "Musenhof" stilisiert

On Exiting from Commercial Sexual Exploitation: Insights from Sex Trade Experienced Persons

As a woman who exited after seven years in licensed commercial sexual exploitation in Canada, I share my reflections on my experience, which led to the development of the Insights from Sex Trade Experienced Persons (InSTEP) Model. The model was constructed based on interviews with “service providers” in the sex trade. Twelve exited women share their experiences inclusively. InSTEP is geared toward a population of quasi-autonomous providers who have alternate economic options. Three levels are introduced in the InSTEP model to describe the continuum of agency among service providers; Level 1: trafficked/controlled; Level 2: quasi-autonomous; Level 3: autonomous. The InSTEP Model focuses on Level 2 providers and identifies optimal times when helping professionals or agencies could be most effective in offering exit support. Opportunities for change are contextualized within Maslow’s Hierarchy of Needs (1943) and the Prochaska and DiClemente’s (1983) Stages of Change

A Mule for the Patriarchy: Waking Up to the Harm of Prostitution to Wives and Families

I exited from commercial sexual exploitation eight years ago. Here, I share my reflections on how my actions directly impacted other women. I describe how my participation in the sex trade adversely affected the wives and girlfriends of sex buyers. I posit that sex sellers negatively impact these vicarious victims by subscribing to and endorsing “sex work” ideology. I assert that the collective good of all women is diminished by viewing sexual services as a market commodity. I stress that the collective good of all women is enhanced by assuming responsibility and compassion for one another

A differential genome-wide transcriptome analysis : impact of cellular copper on complex biological processes like aging and development

The regulation of cellular copper homeostasis is crucial in biology. Impairments lead to severe dysfunctions and are known to affect aging and development. Previously, a loss-of-function mutation in the gene encoding the copper-sensing and copper-regulated transcription factor GRISEA of the filamentous fungus Podospora anserina was reported to lead to cellular copper depletion and a pleiotropic phenotype with hypopigmentation of the mycelium and the ascospores, affected fertility and increased lifespan by approximately 60% when compared to the wild type. This phenotype is linked to a switch from a copper-dependent standard to an alternative respiration leading to both a reduced generation of reactive oxygen species (ROS) and of adenosine triphosphate (ATP). We performed a genome-wide comparative transcriptome analysis of a wild-type strain and the copper-depleted grisea mutant. We unambiguously assigned 9,700 sequences of the transcriptome in both strains to the more than 10,600 predicted and annotated open reading frames of the P. anserina genome indicating 90% coverage of the transcriptome. 4,752 of the transcripts differed significantly in abundance with 1,156 transcripts differing at least 3-fold. Selected genes were investigated by qRT-PCR analyses. Apart from this general characterization we analyzed the data with special emphasis on molecular pathways related to the grisea mutation taking advantage of the available complete genomic sequence of P. anserina. This analysis verified but also corrected conclusions from earlier data obtained by single gene analysis, identified new candidates of factors as part of the cellular copper homeostasis system including target genes of transcription factor GRISEA, and provides a rich reference source of quantitative data for further in detail investigations. Overall, the present study demonstrates the importance of systems biology approaches also in cases were mutations in single genes are analyzed to explain the underlying mechanisms controlling complex biological processes like aging and development

Use of old and new media by ethnic minority youth in Europe with a special emphasis on Switzerland

The first part of this article summarizes research carried out during the last decade in the field of media use of ethnic minorities throughout Europe. Guiding research questions, underlying paradigms, and empirical evidence will be critically discussed in a comparative way. In the second part, empirical data of a Swiss survey among 1,600 adolescents aged 12 to 17 with migrant and Swiss backgrounds are presented. The comparative study points at similarities and differences in access to and use of old and new media such as the Internet as well as with the link between media use and social integration or cultural identity. Special emphasis is given to ethnic versus social factors as underlying explanatory factors. The results of the Swiss study are placed in the context of European research evidenc

Adenine Nucleotide Translocase 1 Expression is Coupled to the HSP27-Mediated TLR4 Signaling in Cardiomyocytes

The cardiac-specific overexpression of the adenine nucleotide translocase 1 (ANT1) has cardioprotective effects in various experimental heart disease models. Here, we analyzed the link between ANT1 expression and heat shock protein 27 (HSP27)-mediated toll-like receptor 4 (TLR4) signaling, which represents a novel communication pathway between mitochondria and the extracellular environment. The interaction between ANT1 and HSP27 was identified by co-immunoprecipitation from neonatal rat cardiomyocytes. ANT1 transgenic (ANT1-TG) cardiomyocytes demonstrated elevated HSP27 expression levels. Increased levels of HSP27 were released from the ANT1-TG cardiomyocytes under both normoxic and hypoxic conditions. Extracellular HSP27 stimulated TLR4 signaling via protein kinase B (AKT). The HSP27-mediated activation of the TLR4 pathway was more pronounced in ANT1-TG cardiomyocytes than in wild-type (WT) cardiomyocytes. HSP27-specific antibodies inhibited TLR4 activation and the expression of HSP27. Inhibition of the HSP27-mediated TLR4 signaling pathway with the TLR4 inhibitor oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) reduced the mitochondrial membrane potential (∆ψm) and increased caspase 3/7 activity, which are both markers for cell stress. Conversely, treating cardiomyocytes with recombinant HSP27 protein stimulated TLR4 signaling, induced HSP27 and ANT1 expression, and stabilized the mitochondrial membrane potential. The activation of HSP27 signaling was verified in ischemic ANT1-TG heart tissue, where it correlated with ANT1 expression and the tightness of the inner mitochondrial membrane. Our study shows a new mechanism by which ANT1 is part of the cardioprotective HSP27-mediated TLR4 signaling