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Witnessing the birth of a tiny RNA at brain synapses
Proteins are the building blocks of all cells. They are made from messenger RNA (mRNA) molecules, which are copied from DNA in the nuclei of cells. All cells, including brain cells, called neurons, carry out their functions by carefully regulating the amount and kind of proteins they make. An important feature of neurons is their ability to communicate with one another at synapses, the points of contact between two cells. Synapses use proteins that are synthesized close-by to fuel communication and the formation of memories.
In neurons and other cells, protein synthesis is regulated by microRNAs, very small “non-coding” RNAs that bind, using complementary sequences, to mRNA and prevent the mRNA from being made into protein. microRNAs are made from larger precursor RNA molecules by several processing steps in the nucleus and cytoplasm. In individual cells, copy numbers of most microRNAs in single cells are relatively low in contrast to potential mRNA targets within individual cells where copy numbers can be up to 10,000 molecules. As such, the absolute number of potential mRNA targets within a cell for a single microRNA species could be very high (e.g. millions), raising the question of how a microRNA can effectively regulate a particular target mRNA.
In the February 10th issue of Science, the Schuman and Heckel labs, from the Max Planck Institute for Brain Research and Goethe University, respectively, show that neurons have solved the abundance problem by moving the site of microRNA maturation (or “birth”) away from the cytoplasm out to the dendrites, thin processes, which are closer to where synapses are. This puts the newly born microRNA into much smaller environment with fewer mRNA target options.
“We tested this hypothesis by using a clever design of a fluorescent molecular reporter, modelled after an immature microRNA”, Heckel says. “We filled neurons with this probe and then stimulated individual synapses. To our surprise, we could then see bright fluorescent spots at the stimulated synapses, showing us the birth of the microRNA. We then saw that the microRNA target was downregulated in the neighborhood of the dendrite where the microRNA was born”.
Schuman: “By moving the birthplace of the microRNA to the dendrites and synapses where it is closer to its targets, neurons have solved the microRNA-mRNA numbers game and gained a way for external events-resulting in the activation of synapses, to control the local expression of important brain molecules which is important for neuronal communication and also for memory formation”.
Publication: Sambandan, S., Akbalik, G., Kochen, L., Rinne, J. Kahlstatt, J., Glock, C. Tushev, G., Alvarez-Castelao, B., Heckel, A. and Schuman, E.M. (2017). Activity-dependent spatially-localized miRNA maturation in neuronal dendrites. Science 355: 634-637 Contact: Prof. Dr. Erin M. Schuman, Max Planck Institute for Brain Research, Max-von-Laue Str. 4, 60438 Frankfurt am Main, Germany, Email: email@example.com, T: +49 69 850033 1001 (Ms. Nicole Thomsen).
Frankfurt School documents: 13 bequests already
FRANKFURT.The Archive Centre of theJohann Christian Senckenberg University Library has been able to expand its collection of material on critical theory thanks to the bequest of philosopher Hermann Schweppenhäuser (1928-2015). Schweppenhäuser earned his doctorate in 1956 at the Institute for Social Research, which by that time had reopened. He was Theodor W. Adorno’s assistant up until 1961 and one of the most influential philosophers of the Frankfurt School. His bequest comprises about 75,000 pages and extensive unpublished archive material, which is accessible for research purposes at the Archive Centre.
Dr. Mathias Jehn, director of the Archive Centre, is very pleased: “This expands our collection on critical theory and the Frankfurt School tremendously. Our stock already includes, amongst others, the bequests of Max Horkheimer, Herbert Marcuse and Ludwig von Friedeburg as well as lifetime contributions from Jürgen Habermas and Oskar Negt.” The Institute for Social Research is also home to the Adorno archive and valuable historic stock from the 1950s and 1960s. Some of the Schweppenhäuser bequest has yet to be processed: “It’s so vast that this is going to take at least another twelve months”, says Jehn. But the bequest, which comprises extensive correspondence with international experts from the field of philosophy, partly unpublished scientific manuscripts as well as a few private documents, is now entirely in Frankfurt and was entrusted to the library by Gerhard Schweppenhäuser, the philosopher’s son.
In 1961, Hermann Schweppenhäuser, who was born in Frankfurt, moved to Lüneburg where he had been called to the newly established chair of philosophy at the College of Education. What was originally supposed to be an intermezzo became a lifetime post accompanied by an honorary professorship at Goethe University Frankfurt. Adorno evidently had other ideas too: in a card dated 14 October 1960 from Graz, which is also part of the bequest, he congratulated Schweppenhäuser “most sincerely” on his appointment in Lüneburg and added: “I hope that you will accept the post, which will certainly allow you to gain considerable experience, and this hope goes hand in hand with the hope that you will complete your post-doctoral degreequicklyand stay with us!”
Yet the critical theory of the Frankfurt School, which never was or is seen by most of the researchers involved as a closed circle with a uniform theory, developed in another direction and so Schweppenhäuser was not called to Goethe University Frankfurt. Habermas, who became Horkheimer’s successor in Frankfurt in 1964, retaliated several times in public against “being categorized uninterruptedly as a critical theorist”, although he had worshipped Adorno, as his biographer Stefan Müller-Doohm notes. Habermas developed his own independent idea of a societal communication theory “which regards itself not as transformation but entirely as an alternative to the critical theory of society”, says Müller-Doohm in an article in the FAZ newspaper (2016).
Whilst Habermas indeed shared Adorno’s and Horkheimer’s criticism of the one-sided technical and economic rationalization of modern culture and society, he chose a different perspective and focused his diagnosis on a “problematic primacy of economics over democratically legitimized politics, with which societies influence themselves”, says Müller-Doohm.
In the obituary he wrote for the weekly “jungle world” newspaper (2015), Roger Behrens is critical of the fact that Goethe University Frankfurt did not give Schweppenhäuser a chance: “Schweppenhäuser’s philosophy is the attempt to justify critical theory […] without falling into the trap and postulating on normativity, as did Jürgen Habermas and the academics who followed him […]. In contrast, Hermann Schweppenhäuser – a year older than Habermas incidentally – vigorously pursued the postulate of critical theory, in line with Horkheimer and Adorno, in line with Karl Marx and in line with Kant – as radical enlightenment [and] critique of power.”
Although not all documents have yet been viewed, the bequest makes it clear that Schweppenhäuser significantly shaped the discourse on Adorno and Benjamin through numerous essays, which enjoyed international acclaim and were partly translated. Schweppenhäuser formulated a version of critical theory “which is closer to the prime intention of Horkheimer and Adorno than the Frankfurt School with its communication theory as reformed by Habermas and his successors”, says his son Gerhard Schweppenhäuser. His lectures, for example on the “Characteristics of Adornoesque Thinking” or the “Dialectics of Enlightenment” made “authentic study” of critical theory possible in both Lüneburg as well as Frankfurt.
In his philosophical writings, Schweppenhäuser dealt with the self-reflection of dialectical thinking, the philosophy of language, aesthetics and critique of culture and current times as well as with the relationship between philosophy and theology. In the 1970s, he published the Collected Works of Walter Benjamin (Suhrkamp Verlag) together with Rolf Tiedemann. The bequest, numbered as “Na 77 Nachlass Hermann Schweppenhäuser”, includes numerous unpublished texts of many different kinds: from subject-specific deliberations to elegantly formulated aphorisms and fragments to literary productions in the fields of poetry and short prose. Attempts at playwriting from his student days are also waiting in the archive to be discovered. A first small selection of aphorisms from the Schweppenhäuser bequest appeared in the commemorative volume “Image and Idea” (Bild und Gedanke) published in 2016.
The extensive correspondence, which is also part of the bequest, shows just how close the philosopher’s dialogue with international academics was. These included, amongst others, Giorgio Agamben (Italy), Siegfried Kracauer (USA), Herbert Marcuse (USA), Gerard Raulet (France), Gershom Scholem (Israel), Gary Smith (USA), Ulrich Sonnemann (Germany) and Moshe Zuckermann (Israel).
Photos and captions under: www.uni-frankfurt.de/65055989
Further information: Dr. Mathias Jehn, Archive Centre of Johann Christian Senckenberg University Library, Bockenheim Campus, Tel.: +49(69)798-39007, Email: firstname.lastname@example.org
Researchers from Goethe University discover a new clinical biomarker to improve treatment of leukaemia
Because it is impossible to predict which acute myeloid leukaemia (AML) patients will benefit, all patients are routinely treated with chemotherapy although only some will respond to the treatment. Researchers from Goethe-University Frankfurt have now discovered a novel biomarker that enables the detection of therapy responders and non-responders with high accuracy. In addition, their research reveals new hope for patients who currently cannot be effectively treated.
The anti-cancer drug cytarabine provides the basis of chemotherapies directed against AML. Cytarabine needs to be activated in cancer cells by the addition of phosphate groups to exert its anti-cancer effects. Prof Jindrich Cinatl (Institut für Medizinische Virologie, Goethe-Universität, Acting Director: Prof Volkhard Kempf) investigated with his research group (funded by the Frankfurter Stiftung fürkrebskranke Kinder) cytarabine-resistant AML cells from the Resistant Cancer Cell Line (RCCL) collection (www.kent.ac.uk/stms/cmp/RCCL/RCCLabout.html) that he runs together with Prof Martin Michaelis (University of Kent, Canterbury, UK). ProfCinatl discovered that the toxicity of cytarabine against AML cells correlates with the expression of the cellular enzyme SAMHD1, which enables to predict the sensitivity of AML cells to cytarabine.
Following this initial finding, a consortium led by Prof Cinatl together with Prof Oliver Keppler (who moved from the Institut für Medizinische Virologie, Goethe-Universität to Ludwig-Maximilians-Universität, München during the project) showed that SAMHD1 removes the phosphate residues from the active form of cytarabine and thereby reverses it into its inactive state. In a cooperation with clinicians (led by Prof Hubert Serve, Medizinische Klinik II, Goethe-Universität) it was shown that SAMHD1 levels determined in leukaemia cells also enabled the prediction of the response of AML patients to cytarabine-based chemotherapies with high accuracy. This introduces SAMHD1 as clinical biomarker that can guide cytarabine-based chemotherapies only to such patients that are very likely to respond and spares patients who are unlikely to respond from toxic side effects. In addition, the Frankfurt-led team showed that inhibition of SAMHD1 effectively sensitises cytarabine-resistant AML cells to cytarabine-based chemotherapies, opening future prospects for the treatment of patients for whom currently no effective therapy exists.
The research was published in the journal Nature Medicine on 19th December 2016 and can be found here:
Federal State of Hessen paves the way for shared professorship with Fritz Bauer Institute
FRANKFURT/WIESBADEN. Boris Rhein, Hessen’s Minister for Science and the Arts, announced on the 16th of December that historian Professor Dr. Sybille Steinbacher had been called to the first chair for Holocaust Studies in Germany. In their decision to appoint her, senate and president’s office of Goethe University Frankfurt followed the recommendation of a committee of international experts. The creation of a chair for research into the history and impact of the Holocaust was anchored in a financial agreement signed with Goethe University Frankfurt and the Fritz Bauer Institute back in July 2015, after which the formal procedure for filling the new position was launched. The Foundation Board of the Fritz Bauer Institute has confirmed its approval of Steinbacher’s appointment. The Federal State of Hessen is co-funding the professorship with an additional € 150,000 per year.
Boris Rhein, Minister for Science: “We are very happy that this important professorship can now be filled by a particularly renowned expert. This is a milestone on the route to a better understanding of Nazi crimes and the history of their impact up to the present day. This joint appointment by Goethe University Frankfurt and the Fritz Bauer Institute will also further enhance the integration of university and institute-based research.”
The historian, who currently still heads the Institute of Contemporary History at the University of Vienna, will take up her post on the 1st of May 2017. Steinbacher is a proven expert in the field of Holocaust Studies and has conducted extensive research on the subject. The professorship, which will be based at the Faculty of Philosophy and History of Goethe University Frankfurt, is shared with the Fritz Bauer Institute and sponsored by the Federal State of Hessen.
Professor Birgitta Wolff, President of the University: “Goethe University Frankfurt is particularly committed, not least due to its own chequered history, to the intellectual reappraisal of the Holocaust. Sybille Steinbacher will dedicate herself to this subject with our full support and fit in well as a colleague too.”
The new chair will also be in charge of the Fritz Bauer Institute, which the federal state government will continue to sponsor to the tune of about € 375,000 in 2017. That means a total sum of well over € 500,000 from federal state funds for the professorship and the institute in future.
“Linking the new professorship with the directorship of the Fritz Bauer Institute is a unique opportunity which we are using to advance the scientific reappraisal of the Holocaust to the greatest degree possible. The Fritz Bauer Institute is a centre of research and education of highest international acclaim and its importance radiates beyond the borders of Hessen too. Above all the confrontation with the ethical and moral structures with which the Holocaust is justified even up to the present day makes the research work so valuable and unique”, explained Boris Rhein, Minister for Science.
Jutta Ebeling, Chairwoman of the Foundation Board of the Fritz Bauer Institute: “With Sybille Steinbacher, the University and the Institute have appointed an internationally acknowledged scholar who combines the scientific investigation of Nazi crimes with tremendous sensitivity towards the subject’s significance in present times. We look forward to welcoming Sybille Steinbacher to Frankfurt am Main in the near future.”
Sybille Steinbacher already handled the subject of mass extermination in Nazi Germany in her Masters thesis at LMU Munich, which was also published in book form: “Dachau: The Town and the Concentration Camp in the Third Reich”. She then expanded her new approach in her doctoral dissertation, which she wrote at Ruhr-Universität Bochum and was entitled “‘Model Town’ Auschwitz. Germanisation Policy and Murder of Jews in East Upper Silesia”. This later formed the basis for an internationally much acclaimed standard reference work on the subject, which was translated into numerous languages. A second field in which Steinbacher is working is the social history of the early Federal Republic. Her monograph “How sex came to Germany. The struggle for morality and decency in the early Federal Republic” was based on her professorial thesis submitted at Friedrich Schiller University Jena in 2010.
Sybille Steinbacher has spent much of her career abroad: She was a scholar at the German Historical Institute Warsaw and Harvard University as well as a fellow at the United States Holocaust Memorial Museum. She was already visiting professor at Goethe University Frankfurt for the history and impact of the Holocaust in 2010 in conjunction with the Fritz Bauer Institute. Sybille Steinbacher has been professor of Contemporary History/Comparative Dictatorship, Violence and Genocide Studies at the University of Vienna since 2010 and Corresponding Member of the Austrian Academy of Sciences since 2014.
Universal behaviour detected in Mott metal-insulator transition
FRANKFURT. Whether water freezes to ice, iron is demagnetized or a material becomes superconducting – for physicists there is always a phase transition behind it. They endeavour to understand these different phenomena by searching for universal properties. Researchers at Goethe University Frankfurt and Technische Universität Dresden have now made a pioneering discovery during their study of a phase transition from an electrical conductor to an insulator (Mott metal-insulator transition).
According to Sir Nevill Francis Mott’s prediction in 1937, the mutual repulsion of charged electrons, which are responsible for carrying electrical current, can cause a metal-insulator transition. Yet, contrary to common textbook opinion, according to which the phase transition is determined solely by the electrons, it is the interaction of the electrons with the atomic lattice of the solid which is the determinant factor. The researchers have reported this in the latest issue of the “Science Advances” journal.
The research group, led by Professor Michael Lang of the Physics Institute at Goethe University Frankfurt, succeeded in making the discovery with the help of a homemade apparatus which is unique worldwide. It allows the measurement of length changes at low temperatures under variable external pressure with extremely high resolution. In this way, it was possible to prove experimentally for the first time that it is not just the electrons which play a significant role in the phase transition but also the atomic lattice - the solid’s scaffold.
“These experimental results will herald in a paradigm shift in our understanding of one of the key phenomena of current condensed matter research”, says Professor Lang. The Mott metal-insulator transition is namely linked to unusual phenomena, such as high-temperature superconductivity in copper oxide-based materials. These offer tremendous potential for future technical applications.
The theoretical analysis of the experimental findings is based on the fundamental notion that the many particles in a system close to a phase transition not only interact with their immediate neighbours but also “communicate” over long distances with all other particles. As a consequence, only overarching aspects are important, such as the system’s symmetry. The identification of such universal properties is thus the key to understanding phase transitions.
“These new insights open up a whole new perspective on the Mott metal-insulator transition and permit more sophisticated theoretical modelling of the phase transition”, explains Dr. Markus Garst, Senior Lecturer at the Institute of Theoretical Physics of Technische Universität Dresden.
The research work was funded by the German Research Foundation in the framework of the Collaborative Research Centre/Transregio “Condensed Matter Systems with Variable Many-Body Interactions” led by Professor Michael Lang.
Elena Gati, Markus Garst, Rudra S. Manna, Ulrich Tutsch, Bernd Wolf, Lorenz Bartosch, Harald Schubert, Takahiko Sasaki, John A. Schlueter, and Michael Lang, Breakdown of Hooke’s law of elasticity at the Mott critical endpoint in an organic conductor, Science Advances 2, e1601646 (2016).
A picture can be downloaded from: www.uni-frankfurt.de/64342454
Caption: Electrons embedded in the atomic lattice – the components of a solid. The mutual repulsion of the electrons prevents them from coming into close contact. This impedes the electron flow and the system can become an insulator (originator: Dr. Ulrich Tutsch)
Further information: Professor Dr. Michael Lang, Physics Institute, Riedberg Campus, Tel.: +49(0)69-798-47241, Michael.Lang@physik.uni-frankfurt.de.