Press releases

Whenever bats use echolocation when foraging for food or to communicate with other bats: sounds are omnipresent. How Seba's short-tailed bat, a species native to South America, filters out important signals from the wide diversity of ambient sound is being examined by researchers at the Institute of Cell Biology and Neuroscience at Goethe University Frankfurt. The most recent finding: the brain stem, which to date had been regarded as being solely responsible for very basic tasks, already processes the probabilities of acoustic signals.

FRANKFURT. Bats are renowned for their echolocation skills, navigation using sound therefore: they 'see' with their extremely sensitive hearing, by emitting ultrasonic calls and forming a picture of their immediate environment on the basis of the reflected sound. Thus, for instance, Seba's short-tailed bat (Carollia perspicillata) finds the fruit it prefers to eat using this echolocation system. At the same time bats use their voice to communicate with other bats, whereby they then utilise a somewhat lower frequency range. Seba's short-tailed bat has a vocal range which is otherwise only found among songbirds and humans. Just like humans it creates sound via its larynx.

In order to find out how Seba's short-tailed bat filters out particularly important signals from the wide diversity of different sounds – warning cries from other bats, the isolation calls of infant bats, as well as the reflections from pepper plants in the labyrinth of leaves and branches, for example – researchers at Goethe University Frankfurt recorded the brain waves of the bats.

To this end the researchers headed by Professor Manfred Kössl from the Institute of Cell Biology and Neuroscience inserted electrodes – as fine as acupuncture needles – under the scalp of the bats while the bats drowsed under anaesthetic. Ultimately this measuring method is so sensitive that even the slightest movement of a bat's head would interfere with the results of the measurements. Despite being anaesthetised, the bat's brain still reacts to sound.

Successions of two notes with differing pitches, corresponding to either echolocation calls or communication calls, were then played back to the bats. Initially a sequence was played back in which note 1 occurs much more frequently than note 2, for example “1-1-1-1-2-1-1-1-2-1-1-1-1-1-1...". This was reversed in the next sequence, with note 1 occurring rarely and note 2 frequently. In this manner the scientists wanted to establish whether the neuronal processing of a given sound depended on the probability of it occurring and not, for instance, on its pitch.

Ph.D. student Johannes Wetekam, lead author of the study, explains: “Indeed our research results show that a rare and thus unexpected sound leads to a stronger neuronal response than a frequent sound." In this respect the bat's brain regulates the strength of the neuronal response to frequent echolocation calls by downplaying these, and amplifies the response to infrequent communication calls. Wetekam: “This shows that the bats process unexpected sounds differently in dependence on their frequency in order to gather adequate sensory impressions."

The interesting aspect here, says Wetekam, is that the processing of the signals seemingly already occurs in the brain stem, which it has been assumed to date merely receives acoustic signals and transmits them to higher regions of the brain, where the signals are then offset against one another. The reason: “This probably saves the brain as a whole a lot of energy and allows for a very fast reaction," says Wetekam.

Professor Manfred Kössl believes: “We are all familiar with the party effect: we filter out the conversations of people in our immediate environment so we can concentrate totally on the person we are speaking with. These mechanisms are similar to those found in bats. If we can better understand how bats hear sound, in the future this could help us to understand what occurs with disorders such as ADHD (attention deficit hyperactivity disorder), which disrupt adequate processing of extraneous stimuli."

Publication: Johannes Wetekam, Julio Hechavarría, Luciana López-Jury, Manfred Kössl: Correlates of deviance detection in auditory brainstem responses of bats. Eur. J. Neurosci 2021, Nov 11 https://onlinelibrary.wiley.com/doi/10.1111/ejn.15527

Picture download: https://www.uni-frankfurt.de/112837573

Caption: Searching for fruit at night: Seba's short-tailed bat (Carollia perspicillata). Photo: Julio Hechavarría

Further Information:
Johannes Wetekam
Department of  Neurobiology and Biosensors
Phone +49 (0)69 798 42066
wetekam@bio.uni-frankfurt.de

Professor Manfred Kössl
Institute of Cell Biology and Neuroscience
Head of Department of Neurobiology and Biosensors
Goethe University Frankfurt, Germany
Phone. +49 (0)69 798 42052
Koessl@bio.uni-frankfurt.de
https://www.goethe-university-frankfurt.de/47091958/Department_of_Neurobiology_and_Biosensors

Editor: Dr. Markus Bernards, Science Editor, PR & Communication Office, Tel: +49 (0) 69 798-12498, Fax: +49 (0) 69 798-763 12531, bernards@em.uni-frankfurt.de.

With the early assessment of sustainable, newly developed chemicals and products it is possible to assess a potential risk of toxic substances being released at a later point in product cascades. This has been revealed in a proof-of-concept study jointly coordinated by Goethe University Frankfurt and RWTH Aachen University. In the course of the study the toxicity of sustainable biosurfactants, potentially applied in, e.g., bio-shampoos, and of a new technology for the economical deployment of plant protection agents were analysed using a combination of computer modelling and laboratory experiments. The study is the first step towards a safe bioeconomy from an eco-toxicological stance, and which uses sustainable resources and processes to reduce environmental burdens significantly.

FRANKFURT. The natural resources of the planet are running short, yet at the same time they are the basis for our prosperity and development. A dilemma which the EU intends to overcome with the aid of its revised bioeconomy strategy. Rather than relying on fossil-based materials, the economy is to be based on renewable materials. These include plants, wood, microorganisms and algae. At some point in time everything is to be found in closed loops, yet the implementation of a circular bioeconomy requires a shift in the manufacture of chemicals. These also have to be produced from bio-materials rather than crude oil. Based on these requirements the American chemists Paul Anastas and John C. Warner formulated their twelve principles of green chemistry in 1998. One of their principles has very much been neglected to date, however: the reduction of the environmental toxicity of newly developed substances.

It is precisely here that the interdisciplinary project “GreenToxiConomy", which is part of the scientific alliance Bioeconomy Science Center (BioSC), comes into play. The objective was to examine bio-based substances and innovative technologies with a view to their toxic impact on the environment at an early stage in product development and to incorporate the resulting findings into product design. Project partners from Aachen, Jülich and Düsseldorf provided two of their bio-based product candidates for the analyses: microgel containers for crop protection agents and biosurfactants.

The wash-active biosurfactants for use in shampoos and detergents at BioSC are based on the synthesis abilities of the Pseudomonas putida bacterium and the Ustilago maydis fungus, respectively, rather than on crude oil. The microgel technology allows for the controlled delivery of crop protection agents because the containers ensure that the active ingredients still adhere to the plants in the event of rain.

Dr. Sarah Johann, the lead author for the study and the head of a working group in the department of evolutionary ecology and environmental toxicology at the Institute for Ecology, Evolution and Diversity at Goethe University Frankfurt, explains: “For the analysis of novel substances and technologies we have selected a broad range of concentration to be able to adequately estimate potential hazards for humans and the environment. We wanted to examine whether the bio-based surfactants were more environmentally friendly than conventional chemical surfactants. In addition, we investigated whether the microgel containers per se induce any toxicity."

To ensure the ecotoxicological evaluation was as precise as possible, the project team combined two elements in the determination of the toxicity: computer-aided prognoses (in silico) and experiments in the laboratory (in vitro and in vivo). The computer models work with the toxicity data of known chemicals, whose structure they compared with the structure of the new bio-based substances to forecast the toxicity. The experiments were conducted on aquatic and terrestrial organisms that represent specific organism groups, among them earthworms, springtails, water fleas and zebrafish embryos at a very early stage.

The result: both biosurfactants and microgels are highly promising candidates for use in a future bioeconomy whose products must be sustainably manufactured while not causing any environmental damage or harm to humans both during and after their utilisation. “We can only make statements within certain limits, however, as the transfer of laboratory results to the reality in the open field or in other applications is complicated," says Johann. More research is necessary for a holistic assessment of the risk potential, which is why follow-up projects are planned.

Prof. Henner Hollert, head of the evolutionary ecology and environmental toxicology department at Goethe University Frankfurt, underlines the significance of the close interdisciplinary collaboration on “GreenToxiConomy". In the project biotechnologists and engineers jointly designed a new product, and this was evaluated during the development stages by eco-toxicologists from Goethe University together with a team at RWTH Aachen headed by Prof. Dr. Martina Roß-Nickoll. “This continuous process is the major strength of the project." Although it is only a first step towards a bioeconomy that is safe in eco-toxicological terms, for Hollert it is already clear that eco-toxicology and green toxicology will play a key role in the plans being drawn up by the EU. “Whenever it is a question of future bio-based product development and product design, we have to clarify the consequences for humans and the environment at an early stage. In this respect our approach can provide valuable results."

Publication: Sarah Johann, Fabian G. Weichert, Lukas Schröer, Lucas Stratemann, Christoph Kämpfer, Thomas-Benjamin Seiler, Sebastian Heger, Alexander Töpel, Tim Sassmann, Andrij Pich, Felix Jakob, Ulrich Schwaneberg, Peter Stoffels, Magnus Philipp, Marius Terfrüchte, Anita Loeschcke, Kerstin Schipper, Michael Feldbrügge, Nina Ihling, Jochen Büchs, Isabel Bator, Till Tiso, Lars M. Blank, Martina Roß-Nickoll, Henner Hollert. A plea for the integration of Green Toxicology in sustainable bioeconomy strategies – Biosurfactants and microgel-based pesticide release systems as examples. In: J. Hazard. Mat. 426 (2022) 127800. https://doi.org/10.1016/j.jhazmat.2021.127800

Further Information:
Prof. Dr. Henner Hollert
Institute of Ecology, Diversity and Evolution
Goethe University Frankfurt
Phone: +49 (0)69 798-42171
hollert@bio.uni-frankfurt.de
https://www.bio.uni-frankfurt.de/43970666/Abt__Hollert

In Germany, liver cirrhosis has the highest mortality rate of any chronic disease requiring hospital admission. When diagnosed as a comorbidity of other chronic diseases, liver cirrhosis at least doubles the mortality rate. Overall, the number of patients hospitalised with liver cirrhosis has increased throughout Germany despite the introduction of very effective drugs for treating hepatitis C, and alcohol abuse remains by far the most common cause. These are the results of a study headed by Prof. Jonel Trebicka at the University Hospital Frankfurt, which observed patients over a period of 14 years.

FRANKFURT. Cirrhosis, a disease of the liver in which tissue becomes dysfunctional and scarred, is the final stage of most chronic liver diseases and the fourth most frequent cause of death in central Europe. However, until now hardly any current findings have been available on its epidemiological profile in Germany. For this reason, Prof. Jonel Trebicka and his team of researchers investigated the data sets from the German Federal Statistical Office on the approx. 250 million hospital admissions taking place from 2005 to 2018 in Germany for any reason, and categorised them according to the Tenth Revision of the International Classification of Diseases (ICD-10). They found that 0.94 per cent of these hospitalised patients had been diagnosed with cirrhosis of the liver, which in the majority of cases occurred as a comorbidity and not the primary disease. In absolute figures, admissions of patients with liver cirrhosis rose from 151,108 to 181,688 during the observation period.

The primary end point of the study was the mortality rate from liver cirrhosis in hospital. This did indeed exhibit a welcome fall from 11.57% to 9.49% during the investigation period, but it is still much higher than the respective rates for other chronic diseases such as cardiac insufficiency (8.4%), renal failure (6.4%) and chronic obstructive pulmonary disease (5.2%). In cases where liver cirrhosis was comorbid with another chronic disease, it increased that disease's mortality rate two to three fold; the greatest effect was observed with infectious respiratory diseases.

Thanks to the introduction of direct-acting antivirals to combat Hepatitis C, the proportion of HCV-related cirrhosis fell during the observation period to around one third. On the other hand, the frequency of cirrhosis caused by non-alcoholic fatty liver disease quadrupled during the same period, in parallel with a rise in the number of obese patients. However, despite these etiological trends, cirrhosis caused by alcohol abuse continues to dominate. It accounts for 52 per cent of all cirrhoses in the study, and the absolute number is still rising.

Gastrointestinal bleeding is becoming increasingly rare as a complication of liver cirrhosis in hospital patients, presumably due to the treatment guidelines that continue to be applied in German hospitals, including endoscopic procedures or the administration of non-selective beta blockers. By 2018, bleeding from oesophageal varices had shrunk to one tenth of its original level in 2005. On the other hand, deterioration of symptoms owing to ascites or hepatic encephalopathy caused by insufficient detoxification by the liver has increased. The number of portal vein thromboses doubled in parallel with the intensified use of imaging diagnostics.

The patients admitted with cirrhosis were much younger than those with other chronic diseases: half of them were under the age of 64. Higher hospitalisation rates and in-hospital mortality rates were recorded in the eastern German states than in western Germany. Across the country, around two thirds of patients hospitalised with liver cirrhosis were men. Many of them died while in their fifties or younger, which explains the large number of disability-adjusted life years and the enormous socio-economic burden caused by liver cirrhosis, as men in this age group still account for the majority of the labour force.

“The results of our study show that the decision-makers and financing bodies in the health system should invest much more in the prevention of alcohol-related liver cirrhosis," Prof. Jonel Trebicka concludes. “They also point up how important it is to recognise and treat liver cirrhosis as a comorbidity of other chronic diseases."

Publication: Wenyi Gu, Hannah Hortlik, Hans-Peter Erasmus, Louisa Schaaf, Yasmin Zeleke, Frank E. Uschner, Philip Ferstl, Martin Schulz, Kai-Henrik Peiffer, Alexander Queck, Tilman Sauerbruch, Maximilian Joseph Brol, Gernot Rohde, Cristina Sanchez, Richard Moreau, Vicente Arroyo, Stefan Zeuzem, Christoph Welsch, Jonel Trebicka: Trends and the course of liver cirrhosis and its complications in Germany: Nationwide population-based study (2005 to 2018) The Lancet Regional Health - Europe 2022;12: 100240 https://doi.org/10.1016/j.lanepe.2021.100240

When light hits a material, electrons can be released from this material – the photoelectric effect. Although this effect played a major role in the development of the quantum theory, it still holds a number of secrets: To date it has not been clear how quickly the electron is released after the photon is absorbed. Jonas Rist, a Ph.D. student working within an international team of researchers at the Institute for Nuclear Physics at Goethe University Frankfurt, has now been able to find an answer to this mystery with the aid of a COLTRIMS reaction microscope which had been developed in Frankfurt: The emission takes place lightning fast, namely within just a few attoseconds – within a billionths of billionths of a second.

FRANKFURT. It is now exactly one hundred years ago that Albert Einstein was awarded the Nobel Prize in Physics for his work on the photoelectric effect. The jury had not yet really understood his revolutionary theory of relativity – but Einstein had also conducted ground-breaking work on the photoelectric effect. With his analysis he was able to demonstrate that light comprises individual packets of energy – so-called photons. This was the decisive confirmation of Max Planck's hypothesis that light is made up of quanta, and paved the way for the modern quantum theory.

Although the photoelectric effect in molecules has been studied extensively in the meantime, it has not yet been possible to determine its evolution over time in an experimental measurement. How long does it take after a light quantum has hit a molecule for an electron to be dislodged in a specific direction? “The length of time between photon absorption and electron emission is very difficult to measure because it is only a matter of attoseconds," explains Till Jahnke, the PhD-supervisor of Jonas Rist. This corresponds to just a few light oscillations. “It has so far been impossible to measure this duration directly, which is why we have now determined it indirectly." To this end the scientists used a COLTRIMS reaction microscope – a measuring device with which individual atoms and molecules can be studied in incredible detail.

The researchers fired extremely intense X-ray light – generated by the synchrotron radiation source BESSY II of Helmholtz-Zentrum Berlin – at a sample of carbon monoxide in the centre of the reaction microscope. The carbon monoxide molecule consists of one oxygen atom and one carbon atom. The X-ray beam now had exactly the right amount of energy to dislodge one of the electrons from the innermost electron shell of the carbon atom. As a result, the molecule fragments. The oxygen and carbon atoms as well as the released electron were then measured.

“And this is where quantum physics comes into play," explains Rist. “The emission of the electrons does not take place symmetrically in all directions." As carbon monoxide molecules have an outstanding axis, the emitted electrons, as long as they are still in the immediate vicinity of the molecule, are still affected by its electrostatic fields. This delays the release slightly – and to differing extents depending upon the direction in which the electrons are ejected.

As, in accordance with the laws of quantum physics, electrons not only have a particle character but also a wave character, which in the end manifests in form of an interference pattern on the detector. “On the basis of these interference effects, which we were able to measure with the reaction microscope, the duration of the delay could be determined indirectly with very high accuracy, even if the time interval is incredibly short," says Rist. “To do this, however, we had to avail of several of the possible tricks offered by quantum physics."

On the one hand the measurements showed that it does indeed only take a few dozen attoseconds to emit the electron. On the other hand, they revealed that this time interval is very heavily dependent on the direction in which the electron leaves the molecule, and that this emission time is likewise greatly dependent on the velocity of the electron.

These measurements are not only interesting for fundamental research in the field of physics. The models which are used to describe this type of electron dynamics are also relevant for many chemical processes in which electrons are not released entirely, but are transferred to neighbouring molecules, for instance, and trigger further reactions there. “In the future such experiments could also help to better understand chemical reaction dynamics therefore," says Jahnke.

Publication: Jonas Rist, Kim Klyssek, Nikolay M. Novikovskiy, Max Kircher, Isabel Vela-Pérez, Daniel Trabert, Sven Grundmann, Dimitrios Tsitsonis, Juliane Siebert, Angelina Geyer, Niklas Melzer, Christian Schwarz, Nils Anders, Leon Kaiser, Kilian Fehre, Alexander Hartung, Sebastian Eckart, Lothar Ph. H. Schmidt,1 Markus S. Schöffler, Vernon T. Davis, Joshua B. Williams, Florian Trinter, Reinhard Dörner,1 Philipp V. Demekhin, Till Jahnke: Measuring the photoelectron emission delay in the molecular frame. Nat Commun 12, 6657 (2021). https://doi.org/10.1038/s41467-021-26994-2

Picture download: 
https://www.uni-frankfurt.de/112731392

Captions:
COLTRIMS_atBESSYii_PhotoMiriamKeller.jpg:
High-tech: COLTRIMS reaction microscope at electron storage ring BESSY II, Helmholtz-Zentrum Berlin für Materialien und Energie (HZB). Photo: Miriam Weller, Goethe University Frankfurt

Rist_Jonas_PhotoAlexanderHartung.jpg:
Ph.D. student Jonas Rist, Goethe University Frankfurt. Photo: Alexander Hartung, Goethe University Frankfurt

Further Information:
Prof. Dr. Till Jahnke
European XFEL and
Institute for Nuclear Physics, Goethe University Frankfurt, Germany
Tel.: + 49 (0)69-798 47023 (Office)
till.jahnke@xfel.eu

Prof. Dr. Reinhard Dörner
Institute for Nuclear Physics
Goethe University Frankfurt, Germany
Tel. +49 (0)69 798-47003
doerner@atom.uni-frankfurt.de
https://www.atom.uni-frankfurt.de

Transforming Growth Factor beta (TGF-β) is a signalling protein whose dysregulation can cause developmental disorders and cancer. Dr Xinlai Cheng and his colleagues at the Goethe University Frankfurt have discovered how a tumour suppressor known as pVHL influences signal transmission involving TGF-β. Their findings suggest possible starting points for developing new drugs.

FRANKFURT/HEIDELBERG. Signal transmission inside cells is a complex process. TGF-β, for example, regulates many cell functions during the early development of both humans and animals, but also in adult organisms. The mechanisms involved are not yet fully understood. It is, however, clear that activated TGF-β initially binds to receptors located on the cell surface. Inside the cell, the TGF-β receptors in their turn activate a protein called SMAD3, which then forms complexes with SMAD4 that translocate to the cell nucleus. There the SMAD proteins mediate the extent to which genes are activated and translated into proteins and other gene products.

Researchers at the Goethe University Frankfurt, Heidelberg University, the German Cancer Research Center (DKFZ), Heidelberg University Hospital and the University Hospital in Jena have now discovered how the von Hippel-Lindau tumour suppressor protein (pVHL) intervenes in this signalling pathway. Tumour suppressors are proteins whose defects or reduced presence in multicellular organisms are associated with a high risk that cells will degenerate into tumour cells. In the Journal of Cell Biology the scientists report the first evidence that pVHL degrades the SMAD3 protein. This occurs before SMAD3 and SMAD4 associate. pVHL thus inhibits the signalling chain that starts with activated TGF-β. “We obtained evidence of this both in cultures of human cells and in Drosophila," says the last author, Dr Xinlai Cheng. “This suggests that at a very early stage in evolution pVHL assumed the regulatory function that we have now brought to light."

Xinlai Cheng has been leading a junior research group at the Buchmann Institute for Molecular Life Sciences at the Goethe University Frankfurt since 2019. He began the investigations at the Institute of Pharmacy and Molecular Biotechnology at Heidelberg University. His mentor, Professor Stefan Wölfl, explained an important finding that emerged from the new-found connection between pVHL and the TGF-β signalling pathway: “pVHL is known to be involved in how cells 'feel' oxygen and react to varying oxygen availability. As a result, a cell's oxygen supply also mediates TGF-β signal transmission."

The researchers' discovery opens up new opportunities for developing drugs to combat cancer. “If we could, for example, use a substance to specifically regulate pVHL activity, we would also influence the TGF-β signalling pathway, which in turn plays a major role in the formation of tumours, and metastases in particular," says Xinlai Cheng. Tumour cells are good at adapting to their environment inside the organism and to variations in oxygen availability. Their very flexible cellular activity helps them to do so. This activity is regulated by factors including the TGF-β signalling pathway.

Publication: Jun Zhou, Yasamin Dabiri, Rodrigo A. Gama-Brambila, Shahrouz Ghafoory, Mukaddes Altinbay, Arianeb Mehrabi, Mohammad Golriz, Biljana Blagojevic, Stefanie Reuter, Kang Han, Anna Seidel, Ivan Đikić, Stefan Wölfl, Xinlai Cheng: pVHL-mediated SMAD3 degradation suppresses TGF-β signaling. Journal of Cell Biology (2022) 221 (1): e202012097 https://doi.org/10.1083/jcb.202012097

Picture download:
https://www.uni-frankfurt.de/112400017

Caption: Stained liver tissue shows the complementary occurrence of pVHL and SMAD proteins: Where pVHL (green) is abundant, SMAD2/3 (red) is scarce, and vice versa. Cell nuclei are stained blue. The lower right picture shows all three colours combined. Photos: Xinglai Cheng/Goethe University

Further Information:
Dr. rer. nat. habil. Xinlai Cheng
Buchmann Institute for Molecular Life Sciences Chemical Biology
AK Cheng
Goethe University Frankfurt
Phone +49 69 798-42718
Cheng@pharmchem.uni-frankfurt.de

Professor Stefan Wölfl
Institut of Pharmacy and Molecular Biotechnology –
Pharmaceutical Biology, Pharmaceutical Bioanalytics and Molecular Cell Biology
Heidelberg University
Phone +49 6221-544880
wolfl@uni-hd.de