Irisin – a myth rather than an exercise-inducible myokine

The myokine irisin is supposed to be cleaved from a transmembrane precursor, FNDC5 (fibronectin type III domain containing 5), and to mediate beneficial effects of exercise on human metabolism. However, evidence for irisin circulating in blood is largely based on commercial ELISA kits which are based on polyclonal antibodies (pAbs) not previously tested for cross-reacting serum proteins. We have analyzed four commercial pAbs by Western blotting, which revealed prominent cross-reactivity with non-specific proteins in human and animal sera. Using recombinant glycosylated and non-glycosylated irisin as positive controls, we found no immune-reactive bands of the expected size in any biological samples. A FNDC5 signature was identified at ~20 kDa by mass spectrometry in human serum but was not detected by the commercial pAbs tested. Our results call into question all previous data obtained with commercial ELISA kits for irisin, and provide evidence against a physiological role for irisin in humans and other species.

The Almost Person: Myth, Narrative and The Doctor

Paul Ricœur describes selfhood as the product of a communal narrative. Communal narratives structured as symbolic myths provide a narrative identity and an ethic of selfhood. The psychologist Jerome Bruner, for instance, places the source of such a narrative identity in the family, where ‘canonical stories’ are formed. ‘Home’ becomes a mode of discourse, a way of recognizing ourselves in the narratives given to us by others. This paper will draw on these concepts of narrative identity in order to investigate the problems to selfhood which face the character of The Doctor in the BBC series Doctor Who. I will identify The Doctor as a character who acts within a self-constructed narrative vacuum, reading the character by contrasting two types of personal myth-making, one ‘real’, as in a lived narrative, and one ‘counterfeit’; a conjured myth to replace and obscure the lived self. The paper will pay particular attention to the twenty-first century reincarnations of Doctor Who. I will argue that the writing of Russell T. Davis and later Steven Moffat in particular directly address this tension of myth and selfhood, as The Doctor struggles between his self-imposed role as a modern Prometheus and the insistent haunting and return of his own story. In these incarnations, his companions become mirrors to The Doctor, bringing with them their own narrative and ethical identities. In turn, it is through his companions that The Doctor is able to build his own lived narrative of sorts, which challenges his self-created ‘mythology’. In contrast to the weeping angels, whose horrific agency manifests only when not apprehended, the Doctor’s story continues to become more real the more he is ‘perceived’, both by the human race and by the viewer.

Standard cystectomy fits all: truth or myth?

Radical cystectomy (RC) with pelvic lymph node dissection (PLND) followed by urinary diversion is the treatment of choice for muscle-invasive bladder cancer (BC) and non-invasive BC refractory to transurethral resection of the bladder (TUR-B) and/or intravesical instillation therapies. Since the morbidity and possible mortality of this surgery are relevant, care must be taken in the preoperative selection of patients for the various organ-sparing procedures (e.g., bladder-sparing, nerve sparing, seminal vesicle sparing) and various types of urinary diversion. The patient’s performance status and comorbidities, along with individual tumor characteristics, determine possible surgical steps during RC. This individualized approach to RC in each patient can maximize oncological safety and minimize avoidable side effects, rendering ‘standard’ cystectomy a surgery of the past.

The American Myth of Markets in Social Policy: Ideological Roots of Inequality

The American Myth of Markets in Social Policy examines how implementing American tropes in policy design inadvertently frustrates policy goals. It investigates multiple market-oriented designs including funding for private organizations to deliver public services, funding for individuals to buy services, and policies incentivizing or mandating private actors to provide social policy. The author shows that these solutions often not only fail to achieve social goals, but, in fact, actively undermine them, for example saddling the poor with debt or encouraging discrimination. The book carefully details the mechanisms through which this occurs, for example a mismatch between program goals and either contract terms or individual preferences. The author examines several policies in depth, covering universal social insurance programs like healthcare and pensions, as well as smaller interventions like programs for the homeless. The author builds the argument using detailed empirical evidence as well as anecdote, keeping the book accessible and entertaining.

Monitoring protein-protein interactions between the mammalian integral membrane transporters and PDZ-interacting partners using a modified split-ubiquitin membrane yeast two-hybrid system

PDZ-binding motifs are found in the C-terminal tails of numerous integral membrane proteins where they mediate specific protein-protein interactions by binding to PDZ-containing proteins. Conventional yeast two-hybrid screens have been used to probe protein-protein interactions of these soluble C termini. However, to date no in vivo technology has been available to study interactions between the full-length integral membrane proteins and their cognate PDZ-interacting partners. We previously developed a split-ubiquitin membrane yeast two-hybrid (MYTH) system to test interactions between such integral membrane proteins by using a transcriptional output based on cleavage of a transcription factor from the C terminus of membrane-inserted baits. Here we modified MYTH to permit detection of C-terminal PDZ domain interactions by redirecting the transcription factor moiety from the C to the N terminus of a given integral membrane protein thus liberating their native C termini. We successfully applied this "MYTH 2.0" system to five different mammalian full-length renal transporters and identified novel PDZ domain-containing partners of the phosphate (NaPi-IIa) and sulfate (NaS1) transporters that would have otherwise not been detectable. Furthermore this assay was applied to locate the PDZ-binding domain on the NaS1 protein. We showed that the PDZ-binding domain for PDZK1 on NaS1 is upstream of its C terminus, whereas the two interacting proteins, NHERF-1 and NHERF-2, bind at a location closer to the N terminus of NaS1. Moreover NHERF-1 and NHERF-2 increased functional sulfate uptake in Xenopus oocytes when co-expressed with NaS1. Finally we used MYTH 2.0 to demonstrate that the NaPi-IIa transporter homodimerizes via protein-protein interactions within the lipid bilayer. In summary, our study establishes the MYTH 2.0 system as a novel tool for interactive proteomics studies of membrane protein complexes.

GABARAP deficiency modulates expression of NaPi-IIa in renal brush-border membranes

Renal reabsorption of inorganic phosphate (P(i)) is mainly mediated by the Na(+)-dependent P(i)-cotransporter NaPi-IIa that is expressed in the brush-border membrane (BBM) of renal proximal tubules. Regulation and apical expression of NaPi-IIa are known to depend on a network of interacting proteins. Most of the interacting partners identified so far associate with the COOH-terminal PDZ-binding motif (TRL) of NaPi-IIa. In this study GABA(A) receptor-associated protein (GABARAP) was identified as a novel interacting partner of NaPi-IIa applying a membrane yeast-two-hybrid system (MYTH 2.0) to screen a mouse kidney library with the TRL-truncated cotransporter as bait. GABARAP mRNA and protein are present in renal tubules, and the interaction of NaPi-IIa and GABARAP was confirmed by using glutathione S-transferase pulldowns from BBM and coimmunoprecipitations from transfected HEK293 cells. Amino acids 36-68 of GABARAP were identified as the determinant for the described interaction. The in vivo effects of this interaction were studied in a murine model. GABARAP(-/-) mice have reduced urinary excretion of P(i), higher Na(+)-dependent (32)P(i) uptake in BBM vesicles, and increased expression of NaPi-IIa in renal BBM compared with GABARAP(+/+) mice. The expression of Na(+)/H(+) exchanger regulatory factor (NHERF)1, an important scaffold for the apical expression of NaPi-IIa, is also increased in GABARAP(-/-) mice. The absence of GABARAP does not interfere with the regulation of the cotransporter by either parathyroid hormone or acute changes of dietary P(i) content.

Die Odyssee der Pygmäen. Eine prekäre Figur auf den neuzeitlichen Spieltischen anthropologischer Differenz

Due to the impacts of postcolonialism, social and cultural anthropology has been dealing intensively with the possibilities and limits of representing "other” human beings and their meaningful worlds. Scholars such as George Marcus, James Clifford or Clifford Geertz have discussed ways of improving anthropological methods of representation without, however, fully raising questions about the quality and validity of the objects represented and the very idea, that they could be “represented”. Thus, despite attempts to purify classical anthropological categories, substantialized presences (“Humans”, “Others”, “Pygmies” etc.), various forms of binary oppositions (us–them, culture–nature, human–animal) as well as certain epistemological modes/ logoi (representation, interpretation) have been rehearsed until today. The research aims to dissect and challenge the metaphysical outputs of the “anthropological machine” (Giorgio Agamben). I intended to solve these from their apparent familiarity as representable identities or differences in order to investigate their genealogy. In Derrida’s and Foucault’s understanding, genealogy becomes manifest mainly in the “blind spots” (Derrida) or “anomalies” (Foucault) between differences, at the borders of identities. As an analytical guideline, the research uses on one concrete metonym for the Derridean blind spot, one incorporation of a Foucauldian Other, namely pygmy narratives within early modern and 19th century imaginings. “Pygmies” have been part of both Western mythology and anthropological reflection since the antiquity and finally became “ethnographical facts” within an evolutionary anthropology in the 19th century during the European exploration of Africa. Throughout this veritable Odyssey, they were mostly precarious “category-jammers” (Timothy Beal), occupying the impossible middle grounds within (proto)anthropological classification. Thus, along with the early modern wild men, enfants sauvages or the apes of proto-primatology, the pygmies of the Homeric myth, as a catalyst for the negotiation of categories, played a decisive role in early modern and 19th century conceptions of the human. Through the precarious Pygmies, concrete socio-historical materializations of Identities (human, European), differences (human–animal etc.), as well as the accompanying logoi which vindicate these as pseudo-entities, appear evident. The research aims to read and write the history of early modern and 19th Century anthropology through one of its many classificatory constituting Others. It thus contributes to a discipline that for a long time has examined concrete systems of knowledge and the genealogy of classification in general. One might call it an “anthropologization” of anthropology.

Der erste Mord. Der Tod des Apsyrtos als Schlüsselmoment für moderne Interpretationen des Medea-Mythos: Jahnn, Pasolini, Wolf, Loher

Murderous Medea – following Euripides’ seminal tragedy countless authors and artists have depicted Medea as child-slaughtering outlaw and avenger. But the Medea myth is much more diverse and holds more depth than this. Medea’s path through her career as princess, magician, wife, mother and avengress opens with another abominable death: that of her brother Apsyrtos. This article focuses on how and why the death of Medea’s brother Apsyrtos has been examined and instrumentalised in modern adaptions of the myth by Hans Henny Jahnn, Pier Paolo Pasolini, Christa Wolf and Dea Loher. Whether guilty as charged but with sensible intentions to gain self-rule and show herself trustworthy or innocent of crime or murder but stricken with guilt and alienation, Medea’s involvement in her brother’s death seems to hold the key to modern interpretations of antiquity’s different strands of the Medea myth and its adaptability to modern concerns of subjectivity and emancipation.

Dein Gott ist ein Esel. Griechische und römische Tierkarikaturen als Spiegel antiker Wertvorstellungen

Die Doktorarbeit “Dein Gott ist ein Esel. Griechische und römische Tierkarikaturen als Spiegel antiker Wertvorstellungen” hat sowohl die lange und intensive Beziehung zwischen Mensch und Tier als auch das antike Humorverständnis zum Thema. Trotz seiner verschiedenen Rollen als Helfer und Freund blieb (und bleibt) das Tier der Stereotyp des ‚Anderen’, das Gegenbild, das alle Menschen teilen. Das Lachen und damit die Karikatur wiederum helfen uns, zu reflektieren und Distanz zu den Dingen und vielleicht zu uns selbst zu gewinnen. Tierkarikaturen sind deshalb besonders geeignet, ein Spiegel menschlicher Fehler und Schwächen zu sein. In der Regel handelt es sich bei den antiken Tierkarikaturen um Bilder von Menschen, die tiergestaltig ‚verzerrt’ sind, zum Beispiel ein Lehrer mit dem Äusseren eines Esels. Solche Darstellungen sind ab dem 6. Jh. v. Chr. zu finden und werden in hellenistischer und römischer Zeit häufiger, wo der Fokus der Arbeit liegt. Meist sind es Terrakotta- oder Bronzefiguren, die verschiedenen gesellschaftlichen Bereichen zugeordnet werden können wie Religion, Politik, Freizeit usw. Unter Berücksichtigung des spezifischen kulturellen und funktionalen Kontextes jedes Stückes sowie zeitgenössischen schriftlichen Quellen wird die Bedeutung dieser Karikaturen erarbeitet.

Le Grand Retour ou les Grands Adieux ? Le roman de l’exil chez Kundera

Milan Kundera, an intellectual born in Moravia who emigrated to France in 1975, in L’Ignorance leans on the myth of Ulysses to question contemporary realities of exile and return, nostalgia and oblivion. Does the hope of returning to the place of origin really haunt the modern émigré? To what extent does the notion of homeland still have meaning for him? And what happens when the émigré, unlike Ulysses the great nostalgic, prefers to stay with Calypso his lover rather than return to his native land and faithful wife Penelope? With some cynicism, Kundera in L’Ignorance offers scenarios of exile which desecrate and destabilize historically and culturally available standards while allowing us to reflect on new paradigmatic figures of contemporary exile.