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:
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
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).
Next exhibition at Goethe University’s Giersch Museum opens on March 19th
The 1950s represented an era of new beginnings. Abstraction dominated the art of the young Federal Republic of Germany. Featuring 74 works by 20 artists, Giersch Museum’s new exhibition is a tribute to the artistic diversity of that decade.
Organic and vegetal, rigorously geometrical, impulse and gesture-oriented or tentatively scriptural; bursting with colour, subdued in tone, even monochrome – the abstract art of the period was vastly heterogeneous in terms of form and colour alike. Yet the dissolving boundaries also granted new freedom in the definition of the painting as such and its various genres.
The exhibition at Goethe University’s Giersch Museum starts with the Darmstädter Gespräch (Darmstadt Dialogue) of 1950, which served to take stock of post-war contemporary art and its conflict between figuration and abstraction. The focus is on the most important artists’ groups of the time – “junger westen” in Recklinghausen, “ZEN 49” in Munich and “Quadriga” in Frankfurt – with their wide-ranging origins, venues and protagonists. Works by painters Gerhard Hoehme, Emil Schumacher and Heinrich Siepmann and the sculptor Ernst Hermanns testify to the new paths explored by the “junger westen” (“young west”). Rupprecht Geiger, K. R. H. Sonderborg, Fritz Winter and the sculptress Brigitte Meier-Denninghoff stand for the Munich group “ZEN 49”. The exhibition pays special attention to the painters of the Frankfurt “Quadriga” – K. O. Götz, Otto Greis, Heinz Kreutz and Bernard Schultze: a representative selection of their works from the 1950s sheds light on the four artists’ individual paths. Finally, with examples by Hermann Goepfert, Hans Haacke, Peter Roehr and Franz Erhard Walther, a look at Kassel’s documenta II of 1959 and the emerging generation of artists marks the transition to the 1960s, the age of the “ZERO” movement and object art.
Goethe University’s Giersch Museum perceives itself as the “university’s window” on the city of Frankfurt and the Rhine-Main region. For many years, the museum has been dedicated to the research and mediation of regional art – which is unique within Frankfurt’s rich museum landscape.
This profile will remain and at the same time a particular aspect will become more important: the museum as a location for exhibitions that show important elements of scientific and intellectual life at Goethe University and which allows suitable topics and exhibits to be presented to a wider audience.
Freedom at Last: Abstraction in the 1950s
Exhibition at Goethe University's GIERSCH MUSEUM
March 19th 2017 – July 9th 2017
Private guided tours in English (1 hour) by arrangement: +49(0)69-13821–010
Price on weekdays € 75 (plus admission)
Price on Saturdays, Sundays and holidays: € 80 (plus admission)
Schaumainkai 83 (Museumsufer)
60596 Frankfurt am Main
Household chaos makes bringing up children with ADHD more difficult
FRANKFURT. Researchers often observe inadequate parenting, a negative emotional climate and household chaos in families of children with ADHD. A research group at Goethe University Frankfurt and the universities of Bremen, Heidelberg, Tübingen and Kiel has now explored how these factors interrelate. The result is astounding.
“We assumed that the parents of children with ADHD found it difficult to maintain a structured family life and daily routines due to their children’s symptoms. In turn, household chaos has an adverse effect on emotional climate and parents’ behaviour”, explains Dr. Andrea Wirth, research associate at the Department of Educational Psychology of Goethe University Frankfurt.
The data of 84 children aged between 7 and 13 years was included in the study, of which 31 children were assigned to the ADHD group and 53 to the control group. Parental behaviour was assessed using a standardized questionnaire, which asked to what extent the parents looked after their children, praised or criticized them, how consistent they were in their parenting and whether they resorted to physical punishment. In order to document the emotional climate in the family, the psychologists asked one of the parents to talk about his or her child for five minutes and describe the child’s personality as well as his or her relationship to it. Household chaos was also recorded using a standardized test.
As expected, parenting by the parents of children with ADHD was less adequate, they criticized their children more often und reported more household chaos than the parents of the children in the control group. However and to the psychologists’ surprise, the parents of children with ADHD rated their relationship to their children more positively than the parents of children without ADHD. The researchers presume that a possible reason, amongst others, might be that some of the families involved were already undergoing therapy, since improvements in the parent-child relationship have already been proven both for interventions with medication as well as those based on behavioural therapy.
The exact relationship between the three constructs was examined with the help of statistical analyses (mediation analyses). “Household chaos seems to be some kind of mechanism through which the symptoms of children with ADHD have a negative impact on their parents’ behaviour towards them”, says Andrea Wirth. However, a chaotic environment does not appear to affect the emotional climate in the family. This contradicts earlier studies which had found a link between inadequate parenting and emotional climate. “A highly chaotic and unstructured household, to which the children’s ADHD symptoms are a contributing factor, makes it difficult for their parents to be authoritative in their upbringing. At the same time, it can be assumed that the parents - despite the prevailing chaos - are fond of their children, speak positively about them and enjoy spending time with them.”
The research group at the LOEWE centre IDeA, of which Andrea Wirth is a member, is drawing up recommendations for future research aimed at designing parent training which can help parents to plan family life better, establish fixed routines and rituals, and organize daily life more efficiently. These may include, for example, turning off the radio and the television when the child is doing its homework, leaving the room to make phone calls, only receiving guests at certain times and letting the child do its homework alone in a quiet room.
Wirth, A., Reinelt, T., Gawrilow, C., Schwenck, C., Freitag, C. M. & Rauch, W. A. (2017). Examining the relationship between children’s ADHD symptomatology and inadequate parenting: The role of household chaos. Journal of Attention Disorders. Advance online publication. doi:10.1177/1087054717692881
Further information: Dr. Andrea Wirth, Department of Educational Psychology, Faculty of Psychology and Sports Sciences, Westend Campus, Tel.: +49(0)69-798-35398, firstname.lastname@example.org.