Researchers from Frankfurt and Grenoble observe disulphide bridge formation in gamma-B crystalline for the first time in the ribosomal exit tunnel
Chemical bonds within the eye-lens protein gamma-B crystallin hold the protein together and are therefore important for the function of the protein within the lens. Contrary to previous assumptions, some of these bonds, called disulphide bridges, are already formed simultaneously with the synthesis of the protein in the cell. This is what scientists at Goethe University Frankfurt, Max Planck Institute of Biophysics and the French Institute de Biologie Structurale in Grenoble have discovered.
FRANKFURT. The lens of the human eye gets its transparency and refractive power from the fact that certain proteins are densely packed in its cells. These are mainly crystallines. If this dense packing cannot be maintained, for example due to hereditary changes in the crystallines, the result is lens opacities, known as cataracts, which are the most common cause of vision loss worldwide.
In order for crystallins to be packed tightly in lens fibre cells, they must be folded stably and correctly. Protein folding already begins during the biosynthesis of proteins in the ribosomes, which are large protein complexes. Ribosomes help translate the genetic code into a sequence of amino acids. In the process, ribosomes form a protective tunnel around the new amino acid chain, which takes on three-dimensional structures with different elements such as helices or folded structures immediately after the tunnel's formation. The gamma-B crystallines studied in Frankfurt and Grenoble also exhibit many bonds between two sulphur-containing amino acids, so-called disulphide bridges.
The production of these disulphide bridges is not easy for the cell, since biochemical conditions prevail in the cell environment that prevent or dissolve such disulphide bridges. In the finished gamma-B crystalline protein, the disulphide bridges are therefore shielded from the outside by other parts of the protein. However, as long as the protein is in the process of formation, this is not yet possible.
But because the ribosomal tunnel was considered too narrow, it was assumed - also on the basis of other studies - that the disulphide bridges of the gamma-B crystallins are formed only after the proteins have been completed. To test this assumption, the researchers from Frankfurt and Grenoble used genetically modified bacterial cells as a model system, stopped the synthesis of the gamma-B crystallins at different points in time and examined the intermediate products with mass spectrometric, nuclear magnetic resonance spectroscopic and electron microscopic methods, and supplemented these with theoretical simulation calculations. The result: The disulphide bridges are already formed on the not yet finished protein during the synthesis of the amino acid chain.
"We were thus able to show that disulphide bridges can already form in the ribosomal tunnel, which offers sufficient space for this and shields the disulphide bridges from the cellular milieu," says Prof. Harald Schwalbe from the Institute of Organic Chemistry and Chemical Biology at Goethe University. "Surprisingly, however, these are not the same disulphide bridges that are later present in the finished gamma-B crystallin. We conclude that at least some of the disulphide bridges are later dissolved again and linked differently. The reason for this probably lies in the optimal timing of protein production: the 'preliminary' disulphide bridges accelerate the formation of the 'final' disulphide bridges when the gamma-B crystallin is released from the ribosome."
In further studies, the researchers now want to test whether the synthesis processes in the slightly different ribosomes of higher cells are similar to those in the bacterial model system.
Publication: Linda Schulte, Jiafei Mao, Julian Reitz, Sridhar Sreeramulu, Denis Kudlinzki,
Victor-Valentin Hodirnau, Jakob Meier-Credo, Krishna Saxena, Florian Buhr, Julian D. Langer, Martin Blackledge, Achilleas S. Frangakis, Clemens Glaubitz, Harald Schwalbe: Cysteine oxidation and disulfide formation in the ribosomal exit tunnel. Nature Communications https://doi.org/10.1038/s41467-020-19372-x
Prof. Dr. Harald Schwalbe
Institute for Chemistry and Chemical Biology
Center for Biomolecular Magnetic Resonance (BMRZ)
Goethe University Frankfurt
Tel +49 69 798-29137
Goethe University honours patron, romantic arts lover and doctor Klaus Heyne
FRANKFURT. For the first time in 2021, innovative contributions to the study of Romanticism can be awarded the Goethe University’s Klaus Heyne-Award. The new award, endowed with 15,000 euros, is aimed at early-career scholars from Germany and abroad who are in a phase of academic qualification and have made an outstanding contribution to Romanticism research.
The new award has been made possible by a generous bequest from the paediatrician Professor Klaus Heyne (1937-2017), whose had a particular passion for the arts and literature of German Romanticism. Frankfurt literary scholar Professor Frederike Middelhoff says: "We are very grateful that we can support young scholars with this award which is also significantly benefits Romanticism research at Goethe University."
The Klaus Heyne-Award, which is meant to be conferred every two years, consists of two components: 5,000 euros will be awarded on a non-earmarked basis; 10,000 euros will be made available for the organisation of a conference on Romantic Studies to be hosted at Goethe University in 2022 and supported by the Frankfurt Chair of Modern German Literature with a Focus on Romantic Studies.
The award winner is to be honoured at a ceremony in October 2021 (currently planned as an in-person event but will be organised online if necessary).
Interested researchers please contact:
Prof. Dr. Frederike Middelhoff
Chair of Modern German Literature with a focus on Romantic Studies
Researchers develop robust approach for detecting market manipulation
Social media is increasingly used to spread fake news. The same problem can be found on the capital market – criminals spread fake news about companies in order to manipulate share prices. Researchers at the Universities of Göttingen and Frankfurt and the Jožef Stefan Institute in Ljubljana have developed an approach that can recognise such fake news, even when the news contents are repeatedly adapted. The results of the study were published in the Journal of the Association for Information Systems.
FRANKFURT. In order to detect false information – often fictitious data that presents a company in a positive light – the scientists used machine learning methods and created classification models that can be applied to identify suspicious messages based on their content and certain linguistic characteristics.
"Here we look at other aspects of the text that makes up the message, such as the comprehensibility of the language and the mood that the text conveys," says Professor Jan Muntermann from the University of Göttingen. The approach is already known in principle from its use by spam filters, for example. However, the key problem with the current methods is that to avoid being recognised, fraudsters continuously adapt the content and avoid certain words that are used to identify the fake news.
This is where the researchers' new approach comes in: to identify fake news despite such strategies to evade detection, they combine models recently developed by the researchers in such a way that high detection rates and robustness come together. So even if "suspicious" words disappear from the text, the fake news is still recognised by its linguistic features. "This puts scammers into a dilemma. They can only avoid detection if they change the mood of the text so that it is negative, for instance," explains Dr Michael Siering. "But then they would miss their target of inducing investors to buy certain stocks."
The new approach can be used, for example, in market surveillance to temporarily suspend the trading of affected stocks. In addition, it offers investors valuable information to avoid falling for such fraud schemes. It is also possible that it could be used for criminal prosecutions in the future.
Publication: Michael Siering, Jan Muntermann, Miha Grčar. Design Principles for Robust Fraud Detection: The Case of Stock Market Manipulations. Journal of the Association for Information Sys-tems (2021). https://aisel.aisnet.org/jais/vol22/iss1/4
Dr Michael Siering
Goethe University Frankfurt
Economics and Business Administration
Chair of e-Finance
Professor Jan Muntermann
University of Göttingen
Faculty of Business and Economics
Professor of Electronic Finance and Digital Markets
Tel: +49 (0)551 39 27062
Findings of the PREDICT study on acute decompensation and acute-on-chronic liver failure
Acute-on-chronic liver failure (ACLF) is a common cause of death in patients with cirrhosis. In ACLF the progressive loss of function of the scarred liver can no longer be compensated (acute decompensation). As a result, other organs such as the kidney or brain fail. The triggers for acute decompensation of liver cirrhosis and an ACLF are most frequently bacterial infections, liver inflammation caused by alcohol, or a combination of both factors. This was revealed by the evaluation of the PREDICT study, which was conducted by an international team of researchers led by Professor Jonel Trebicka from the University Hospital Frankfurt.
FRANKFURT. Chronic liver disease and even cirrhosis can go unnoticed for a long time because many patients have no symptoms: the liver suffers silently. When the body is no longer able to compensate for the liver's declining performance, the condition deteriorates dramatically in a very short time: tissue fluid collects in the abdomen (ascites), internal bleeding occurs in the oesophagus and elsewhere, and the brain is at risk of being poisoned by metabolic products. This acute decompensation of liver cirrhosis can develop into acute-on-chronic liver failure with inflammatory reactions throughout the body and failure of several organs.
In the PREDICT study, led by Professor Jonel Trebicka, scientists from 15 European countries observed 1273 patients who were hospitalized with acute decompensation of their liver cirrhosis. The current evaluation of the study focused on the question of what can trigger acute decompensation of liver cirrhosis. The result: in the vast majority of cases (>90%), a bacterial infection, liver inflammation caused by alcohol consumption, or both together could be identified as the trigger.
Bleeding in the digestive tract and brain dysfunction induced by painkillers or sedatives (drug-induced toxic encephalopathy) were identified as further trigger, although at a lower rate.
Lead investigator Professor Jonel Trebicka, gastroenterologist and hepatologist at the Medical Clinic I of the University Hospital Frankfurt, explains: "The acute decompensation of liver cirrhosis demands rapid and targeted action. In the PREDICT study, we therefore want to learn a lot about the triggering factors of this life-threatening disease in order to be able to derive recommendations for diagnostics and therapy. Knowing what the most likely triggers of acute decompensation are will help to further develop diagnostic and treatment strategies for patients with this life-threatening disease."
The pan-European PREDICT study has monitored the clinical course of acute decompensations of liver cirrhosis to find early signs of the development of acute-on-chronic liver failure (ACLF). PREDICT is funded by the European Foundation for the Study of Chronic Liver Failure. A total of 136 scientists from 47 centres and institutions in 15 European countries are participating in PREDICT.
Publication: Jonel Trebicka, Javier Fernandez, et al. for the PREDICT STUDY group of the EASL-CLIF CONSORTIUM: PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis. Journal of Hepatology (2020), https://doi.org/10.1016/j.jhep.2020.11.019
University Hospital Frankfurt, Goethe University Frankfurt
Medical Clinic I
Professor Jonel Trebicka
Section Translational Hepatology,
Medical Clinic I (Director: Professor Stefan Zeuzem)
Goethe University/University Hospital Frankfurt
Tel. +49 69 6301 80789 (Jennifer Biondo, secretarial office)
European Foundation for the Study of Chronic Liver Failure (EF Clif) is a private, non-profit Foundation whose mission is to promote study
and research on Acute-on-Chronic Liver Failure and thus, contribute to
improving both the quality of life and survival of patients with liver
The EF Clif was created in 2015 to support the research work carried out by the EASL Clif Consortium, a research network of more than 100 European University Hospitals and 200 clinical investigators. In 2013, the Consortium described a new syndrome: Acute-on-Chronic Liver Failure (ACLF), which is the most common cause of death in cirrhosis.
Currently, the research activity of the EF Clif is fostered through two chairs: the EASL Clif Chair, to promote observational, pathophysiological and therapeutic studies through the EASL-Clif Consortium's hospital network; and the Grifols Chair, which promotes the development of translational research projects with the creation of a network of centres across Europe: The European Network for Translational Research in Chronic Liver Failure (ENTR-CLIF).
To know more about the EF Clif: http://www.efclif.com Twitter: @ef_clif
Research project on East Asia led by Goethe University receives 2 million euros in funding
The economies of China and Singapore are among the most dynamic migration regions in the world. But Japan and Korea also rely on the immigration of skilled workers. The competition for qualified professionals sets several million people on the move in these regions every year. The role that skills and education play in mobility is now being investigated by scholars on East Asia from the universities of Frankfurt and Duisburg-Essen, the Free University of Berlin, and the Max Planck Institute for the Study of Multiethnic and Multireligious Societies in Göttingen. The junior research group coordinated by Goethe University will receive a total of more than 2 million euros from the Federal Ministry of Education and Research (BMBF) for the next four years as part of the "Small Subjects " funding initiative.
FRANKFURT. Aging societies in industrialised nations need skilled workers - specialists in the IT sector, in innovative start-ups, or from top universities. This applies to Germany as well as to the East Asian countries of South Korea, Singapore, China, and especially Japan. Because of their quality of life and lucrative renumeration, these countries are attractive for qualified migrants. But the recipe for success in the competition for the best brains is far from clear: What attracts well-trained specialists to Japan, South Korea, China, or Singapore? What facilitates, and what hinders the integration of skilled foreign workers? What social networks do skilled migrant workers develop? What role does their own initiative for further qualification, their ethnicity and nationality, their gender and multilingualism play? And what causes skilled workers to return to their home countries after years?
"If a country's immigration policy is to be sustainable," explains project leader Dr Ruth Achenbach from Goethe University, "then we need to know exactly what the perceptions of migrants are." The aim of the research project, which will receive funding by the BMBF of more than 2 million euros, is to examine the role of skills of migrant professionals. The researchers hope their findings will contribute to sustainable immigration policies in industrial nations.
In addition to Ruth Achenbach and Dr Joohyun Justine Park from the Interdisciplinary Centre for East Asian Studies (Goethe University), the academic team includes Dr Helena Hof (MPI Göttingen) as well as Dr Megha Wadhwa (Free University Berlin) and Dr Aimi Muranaka (University Duisburg-Essen). In addition, the researchers work with numerous external regional cooperation partners.
The research project will collect qualitative data in different East Asian countries over a period of three years. It will investigate the situation of East Asian start-ups in Japan and Singapore as well as East Asian professionals in South Korea; Chinese professionals in Japan, professionals who have returned to China, and Vietnamese IT workers and Indian professionals in Japan will also be interviewed. The Frankfurt sub-project also accompanies Chinese graduates of the 20 best Japanese universities from the beginning of their job-hunting to their first years on the labour market.
In the final year of funding, quantitative research will be conducted in the East Asin countries to test a theory developed from the qualitative research and previous migration research. In doing so, the researchers also aim to improve the dominant Western concepts of international migration research. Influenced by experiences of migration to America and Europe, these concepts assume that the economic situation in the country of origin and the country of immigration differ considerably. This is not necessarily the case anymore with East Asian labour migration and the project will differentiate between socioeconomic backgrounds of migrants.
The results of the empirical research as well as the development of theory will not only be published scientifically, but they will also be disseminated to the broader public. The project team’s dissemination activities include workshops for high school teachers in the subjects of politics and economics, and the release of a documentary film.
The researchers hope that their project will strengthen the "small subjects" by linking the researchers' knowledge of these regions with current research questions from sociology, political science and economics, thus increasing the visibility of the small subjects.
Dr Ruth Achenbach
Interdisciplinary Centre for East Asian Studies
Goethe University Frankfurt