Goethe-Universit盲t 鈥� Press releases

51猎奇 PR & Communication Department聽

Aug 3 2022

13:12

A feedback loop sensitises the auditory cortex to acoustic reflections

How bat brains listen out for incoming signals during echolocation

Neuroscientists at 51猎奇, Frankfurt have discovered a feedback loop that modulates the receptivity of the auditory cortex to incoming acoustic signals when bats emit echolocation calls. In a study published in the journal 鈥淣ature Communications", the researchers show that information transfer in the neural circuits involved switched direction in the course of call production. It seems likely that this feedback prepares the auditory cortex for the expected echoes of the emitted calls. The researchers interpret their findings as indicating that the importance of feedback loops in the brain is currently still underestimated.

FRANKFURT. Bats famously have an ultrasonic navigation system: they use their extremely sensitive hearing to orient themselves by emitting ultrasonic sounds and using the echoes that result to build up a picture of their environment. For example, Seba's short-tailed bat (Carollia perspicillata) finds the fruits that are its preferred food using this echolocation system. At the same time, bats also use their vocalisations to communicate with other bats. They use a somewhat lower range of frequencies for this purpose.

Neuroscientist Julio C. Hechavarr铆a from the Institute of Cell Biology and Neuroscience at 51猎奇 and his team are investigating the brain activities associated with vocalisations in Seba's short-tailed bat. Their most recent study investigates how the auditory cortex and the frontal lobe work together in echolocation. The auditory cortex processes auditory information and the frontal lobe is a region in the forebrain that is associated, in humans, with tasks that include planning actions. To discover more about this, the researchers inserted tiny electrodes into the bats' brains to record neural activity in the frontal lobe and the auditory cortex.

The researchers succeeded in identifying a feedback loop that had previously been entirely unknown in the frontal lobe-auditory cortex network of bats emitting echolocation calls. Information normally flows from the frontal lobe, where call production is planned, to the auditory cortex to ready it to expect an acoustic signal. But it was observed that the flow of information from the frontal lobe to the auditory cortex diminished after the emission of an echolocation pulse until the direction of information transfer switched completely and information flowed from the auditory cortex back to the frontal lobe. Hechavarr铆a hypothesises that this feedback loop readies the auditory cortex to better receive the sounds reflected back from the echolocation call.

The neurobiologists simulated signals originating from the auditory cortex by electrically stimulating the frontal lobe. The activity this generated in the frontal lobe had the expected effect of prompting the auditory cortex to respond more strongly to acoustic reflections. 鈥淭his shows that the feedback loop we found is functional", neurobiologist Hechavarr铆a sums up. He takes up the metaphor of a highway to illustrate the significance of these findings: 鈥淯p to now, it was generally believed that the flow of data on this information superhighway mainly runs in one direction and that feedback loops are exceptions. Our data show that this view is most likely incorrect and that feedback loops in the brain are probably considerably more significant than has previously been hypothesised."

Surprisingly, no pronounced reversal of information flow was observed for bat vocalisations used for communication purposes. 鈥淭his may be because the bats were alone in a sound-proofed and electrically isolated chamber and therefore did not expect a response to their calls", Hechavarr铆a speculates before going on to note: 鈥淥ne of the aspects that makes our study so interesting is that it opens up new ways to study the social interactions of bats. We want to continue work in this area in the future."

Publication: Francisco Garc铆a-Rosales, Luciana L贸pez-Jury, Eugenia Gonzalez-Palomares, Johannes Wetekam, Yuranny Cabral-Calder铆n, Ava Kiai, Manfred K枚ssl, Julio C. Hechavarr铆a: Echolocation-related reversal of information flow in a cortical vocalisation network. Nature Communications 13, 3642 (2022)

An image to download:

Caption: Bats 鈥渟ee" with their ears. Researchers at 51猎奇 have discovered how the auditory cortex is readied for incoming acoustic signals. (Photo: Dr. Julio C. Hechavarr铆a)

Further information
Dr. Julio C. Hechavarr铆a (Ph.D.)
Auditory Computations Group (Group Leader)
Institute for Cell Biology and Neuroscience
Tel. +49 (0)69 798-42050
Hechavarria@bio.uni-frankfurt.de

Aug 3 2022

11:17

A research team with members from 51猎奇 Frankfurt and the University of Michigan in the USA is using bacterial biosynthesis to produce an antibiotic containing fluorine 鈥揟he technology is being commercialized by a startup

A New Biosynthesis Method Has Been Developed to Produce Antibiotics from Natural Substances

The use of the element fluorine to modify active substances is an important tool in modern drug development. A team at Goethe University Frankfurt has now achieved an important 鈥渇irst" by successfully fluorinating a natural antibiotic via targeted bioengineering. With this method, an entire substance class of medically relevant natural products can be modified. The method has enormous potential for the manufacture of new antibiotics against resistant bacterial pathogens and for the (further) development of other drugs. The startup kez.biosolutions GmbH will bring these research results to the application stage (Nature Chemistry, DOI 10.1038/s41557-022-00996-z).

FRANKFURT/MAIN. Active drug agents have been chemically modified with fluorine for decades, owing to its numerous therapeutic effects: Fluorine can strengthen the bonding of the active agent to the target molecule, make it more accessible to the body, and altering the time it spends in the body. Nearly half of the small-molecule drugs (molecules up to approx. 100 atoms) currently approved by the U.S. Food and Drug Administration (FDA) contain at least one chemically bound fluorine atom. These include such different drugs as cholesterol-lowering agents, antidepressants, anticancer agents and antibiotics.

Bacteria and fungi often manufacture complex natural compounds to obtain a growth advantage. One possible route for the development of drugs from natural compounds is to modify these substances by adding one or more fluorine atoms. In the case of the antibiotic erythromycin, for example, the attached fluorine atom confers important advantages. The new erythromycin manufactured via this process can be accessed more easily by the body and is more effective against pathogenic microorganisms that have developed resistance to this antibiotic. However, the synthetic-chemical methods for inserting fluorine into natural substances are very complicated. Owing to the chemical and reaction conditions that are necessary, these methods are frequently "brutal," says Martin Grininger, Professor for Organic Chemistry and Chemical Biology at 51猎奇. "This means, for example, that we are very limited in selecting the positions where the fluorine atom can be attached," he adds.

A German-U.S. scientific team headed by Prof. Martin Grininger and Prof. David Sherman, Professor of Chemistry at the University of Michigan, has now succeeded in utilizing the biosynthesis of an antibiotic-producing bacteria. In this process, the fluorine atom is incorporated as part of a small substrate during the biological synthesis of a macrolide antibiotic. 鈥淲e introduce the fluorinated unit during the natural manufacturing process, an approach that is both effective and elegant," stresses Grininger, "This gives us great flexibility when positioning the fluorine in the natural substance 鈥� and allows us to influence its efficacy."

To this end the project leaders Dr. Alexander Rittner and Dr. Mirko Joppe 鈥� both members of Grininger's research group in Frankfurt 鈥� inserted a subunit of an enzyme called fatty acid synthase into the bacterial protein. The enzyme is naturally involved in the biosynthesis of fats and fatty acids in mice. The fatty acid synthase is not very selective in processing the precursors, which are also important for the manufacture of antibiotics in bacteria, Rittner explains. With an intelligent product design, the team succeeded in integrating a subunit of the murine enzyme into the corresponding biosynthetic process for the antibiotic. "The exciting part is that, with erythromycin, we were able to fluorinate a representative of a gigantic substance class, the so-called polyketides," says Rittner. 鈥淭here are about 10,000 known polyketides, many of which are used as natural medicines 鈥揻or example, as antibiotics, immunosuppressives or cancer drugs. Our new method thus possesses a huge potential for the chemical optimization of this group of natural substances 鈥� in the antibiotics primarily to overcome antibiotic resistance." To exploit this potential, Dr. Alexander Rittner founded the startup kez.biosolutions GmbH.

Prof. Martin Grininger has been conducting research on the tailor-made biosynthesis of polyketides for several years. "Our success in fluorinating macrolide antibiotics is a breakthrough we worked hard to achieve and of which I am now very proud" he says. 鈥淭his success is also an impetus for the future. We are already testing the antibiotic effect of various fluorinated erythromycin compounds and additional fluorinated polyketides. We intend to expand this new technology to include additional fluorine motifs in collaboration with Prof. David Sherman and his team at the University of Michigan in the U.S."

The search for drugs that overcome antibiotic resistance is a long-term task: depending on how frequently they are used, all antibiotics naturally cause resistances sooner or later. Against this background Dr. Mirko Joppe also believes that his work has broader implications for society. "Research on antibiotics is not economically lucrative for various reasons. It is therefore the task of the universities to close this gap by developing new antibiotics in cooperation with pharmaceutical companies," he explains. "Our technology can be used to generate new antibiotics simply and quickly and now offers ideal contact points for projects with industrial partners."

The research work on polyketides described above was supported by the Volkswagen Foundation (within the framework of a Lichtenberg Professorship), the LOEWE MegaSyn research initiative funded by the Hessian Ministry for Science and the Arts, and the National Institute of Health in the U.S.

Publication: Alexander Rittner, Mirko Joppe, Jennifer J. Schmidt, Lara Maria Mayer, Simon Reiners, Elia Heid, Dietmar Herzberg, David H. Sherman, Martin Grininger: Chemoenzymatic synthesis of fluorinated polyketides. Nature Chemistry (2022)

Image to download:

Caption: Scientists working at 51猎奇 Frankfurt have created an enzyme capable of producing fluorinated antibiotics via a series of reactions. For clarity, the different regions of the hybrid that interact in this context are shown in different colors. (Graphic: Grininger)

Additional Information:
Prof. Dr. Martin Grininger
Institute for Organic Chemistry and Chemical Biology
Buchmann Institute for Molecular Life Sciences
51猎奇 Frankfurt
Frankfurt/Main, Germany
Tel.: +49 (0)69 798-42705
grininger@chemie.uni-frankfurt.de

Aug 2 2022

12:27

A study among students from 41 countries provides orientation for university education聽

Environmental students from poorer regions rate the UN鈥檚 Sustainable Development Goals as more important than those from richer regions do

Environmental students from countries with lower prosperity indicators rate the 17 Sustainable Development Goals of the United Nations as more important than environmental students from countries with higher prosperity indicators do. Moreover, they mostly assign the goals to only one pillar of sustainability, either social, economic or environmental sustainability. This is the conclusion drawn by a study by 51猎奇 Frankfurt, which is based on an online survey in 41 countries. Now, for the first time, findings are available about how a certain group of potential future decision-makers currently perceives the 17 goals. From this, specific recommendations can be derived for university education.

FRANKFURT. In 2015, the member states of the United Nations adopted the 2030 Agenda for Sustainable Development. The central element is the 17 Sustainable Development Goals (SDGs). These include 鈥淶ero Hunger", 鈥淐lean Water", 鈥淩esponsible Consumption" and 鈥淟ife Below Water". The SDGs relate to all three pillars of sustainability, i.e. social, economic and environmental sustainability. Achieving the goals should enable a life of dignity for everyone worldwide and conserve the planet's natural resources on a sustained basis. Yet how are the SDGs perceived in the first place, and what conclusions can be drawn from this? Until now, there has been a research gap in this area. The few international studies to date had mostly interviewed rather broad population groups. There was a lack of data that could deliver specific recommendations in certain realms of society, for example, how university practice could be improved in line with the 2030 Agenda.

A new study by 51猎奇 Frankfurt is now closing this research gap. It is based on an online survey in 41 countries in North America, South America, Africa, Asia, Oceania and Europe, which was conducted between September 2020 and July 2021. All 4,305 interviewees were exclusively students of environment-related subjects, such as environmental science, biology or nature management. They indicated on a scale of 1 to 5 how important they considered each individual SDG. 鈥淥ur study is the first to document and evaluate how the UN's Sustainable Development Goals are perceived among such a highly selected group of future decision-makers," says first author Dr Matthias Kleespies from the Department of Didactics in the Biological Sciences and Zoo Biology at 51猎奇 Frankfurt.

The data show, says Kleespies, that the SDGs have a high level of acceptance among environmental students worldwide, irrespective of the region. For Kleespies, this is a pleasing result: 鈥淭he major social, economic and environmental problems we're currently facing worldwide are also perceived as such."

Through factor analysis, a common statistical method, Kleespies was able to establish something else: the interviewees mainly assigned individual SDGs to only one of the three pillars of sustainability: for example, the goal 鈥淣o Poverty" exclusively to the first pillar (social) or the goal 鈥淐limate Action" exclusively to the third pillar (environmental). These assignments led to a further result, says Kleespies: 鈥淲e could see significant differences between countries in how they rate the three pillars." For example, interviewees from Germany considered the environmental pillar to be particularly important, while interviewees from Thailand rated all three pillars as more or less equally important.

To be able to evaluate the differences between countries even more accurately, a further statistical analysis followed: the results from the individual countries were compared with five prosperity indicators, including the Human Development Index (HDI) and the Environmental Performance Index (EPI). A similar picture emerged for all five indicators. In a direct comparison, countries with lower indices 鈥� such as the Philippines 鈥� rated the SDGs as more important than countries with higher indices did, such as Canada. 鈥淭his result surprised us, as older studies often showed that especially people in modern industrialised societies campaign more for environmental protection," says Kleespies.

Even if the study is not transferable to a country's entire population, it does, according to Professor Paul Dierkes, head of the Department of Didactics in the Biological Sciences and Zoo Biology, deliver important new insights. 鈥淭o be able to put the SDGs into practice in a country, there needs to be great acceptance not only among the population but also among the people at the social and political interfaces. As potential future decision-makers and multipliers, students in the environmental domain are particularly important in this context. Although a university education in this field is no guarantee of a decision-making position, universities teach important skills, abilities and knowledge that qualify for such positions."

What improvement measures for university education can be derived from the study? Kleespies says: 鈥淒egree programmes in the environmental sciences ought to address in greater depth the fact that the SDGs are multidimensional and that each of the goals contains a social, environmental and economic component." After all, he says, the study has shown that students mostly overlook this multidimensionality. For example, SDG 15 鈥� 鈥淟ife On Land" 鈥� was often categorised as a solely environmental goal. 鈥淏ut protecting terrestrial ecosystems also includes very important economic and social components." A second suggestion is directed specifically at more affluent countries, where the SDGs were rated as less important by comparison. Kleespies calls on the universities there to incorporate educational measures on the UN's Sustainable Development Goals into the present curriculum of degree programmes: 鈥淚n this way, students will be better informed than they are at the moment about the benefits and multidimensional nature of the SDGs."

Over 4,000 students took part in the online survey and emails were sent to institutes in more than 50 countries. For 41 countries, the datasets were ultimately sufficient for a statistical analysis.

Publication: 鈥淭he importance of the Sustainable Development Goals to students of environmental and sustainability studies 鈥� a global survey in 41 countries", Matthias Winfried Kleespies & Paul Wilhelm Dierkes;

Further information
Department of Didactics in the Biological Sciences and Zoo Biology
51猎奇 Frankfurt
Dr Matthias Kleespies
Tel.: +49 (0)69 798-42276
kleespies@em.uni-frankfurt.de

Professor Paul W. Dierkes
Tel.: +49 (0)69 798-42273
dierkes@bio.uni-frankfurt.de

Jul 28 2022

16:58

51猎奇 Frankfurt, the Institute of Ethnology, and the Frobenius Institute congratulate 鈥渢heir鈥� social and cultural anthropologist

Prof. Mamadou Diawara Now a Fellow of the British Academy

In recognition of his accomplishments in the humanities and the social sciences, Mamadou Diawara has been elected a Fellow of the British Academy. Diawara is Professor for Social and Cultural Anthropology at the Institute of Ethnology and Deputy Director of the Frobenius Institute at 51猎奇. He is also Director of Point Sud, the Center for Research on Local Knowledge in Bamako, Mali.

FRANKFURT/MAIN. Professor Mamadou Diawara has been elected a "Corresponding Fellow" of the British Academy at their Annual Meeting and is thus now a member of the Academy, where he will be responsible for the disciplinary section "Africa, Asia and the Middle East." Election to the "Corresponding Fellowship" is the highest scientific honor awarded by the Academy in the humanities and social sciences. According to the Academy statutes, only a person who has "achieved great international prestige" in one of the research areas to be promoted by the Academy may be elected. A permanent place of residence outside the United Kingdom, the Isle of Man or the Channel Islands is an additional criterion for appointment.

"The news caught me totally by surprise and made me very happy, of course," said Professor Diawara, adding that it was a great honor to be admitted to a circle containing so many luminaires. "The British Academy is an important authority which repeatedly voices its opinion in public debates, and its point of view carries great weight. He stated that he is personally looking forward to interesting lectures and a regular academic exchange with scholars in the humanities and social sciences from all over the world. He is now entitled to use the title "FBA" after his name for his entire life.

Mamadou Diawara, born in 1954, studied at the 脡cole Normale Sup茅rieure in Bamako and the 脡cole des hautes 茅tudes en sciences sociales in Paris. Diawara completed his doctorate in anthropology and history in Paris in 1985. This was followed, in 1998, by his habilitation at the University of Bayreuth in Germany and in 2004 by the call to 51猎奇 Frankfurt. Diawara has taught at universities in Europe and the Americas. He was a Henry Hart Rice Visiting Professor in Anthropology and History at Yale University in the USA and a Fellow at the Wissenschaftskolleg [Institute for Advanced Study] in Berlin. In 1998 Diawara founded Point Sud, the Center for Research on Local Knowledge in Bamako, Mali, together with Moussa Sissoko and other colleagues from Germany, Austria and Mali. Moreover, he was co-initiator of several research promotion projects aimed at the upcoming generation of scholars in Africa and played an active role in programs fostering cooperation between scientists in Africa and other parts of the world.

Mamadou Diawara's research deals with history, oral cultures, media, changing standards, mobility and migration in Africa. His regional focus is on Sub-Saharan Africa, in particular the Sahel countries, and relations between Africa and Southeast Asia, in particular Thailand, where he conducts research on trade, including trade in precious and semiprecious stones. He has received major support for this work from the Cluster of Excellence "The Formation of Normative Orders.鈥�

The British Academy was founded in 1902 and is the national academy for the humanities and social sciences of the United Kingdom. It is a community of more than 1,400 leading minds in these areas. The Academy views itself as an institution devoted to promoting research on the national and international level and as a forum for discussion and engagement. This year a total of 85 Fellows were elected including 52 from the United Kingdom, 29 Corresponding Fellows and four Honorary Fellows.

In her welcoming speech, Professor Julia Black, President of the British Academy, said: "I am delighted to welcome these distinguished and pioneering scholars to our Fellowship. (鈥�) With our new Fellows鈥� expertise and insights, the Academy is better placed than ever to open new seams of knowledge and understanding and to enhance the wellbeing and prosperity of societies around the world. I congratulate each of our new Fellows on their achievement and look forward to working with them.鈥濃€�

Portrait of Prof. Diawara for downloading:

Photo caption: The ethnologist Prof. Mamadou Diawara has been elected a Corresponding Fellow of the British Academy. (Photo: Normative Orders, Frankfurt/Main)

Further information
Institute of Ethnology
Administrative Office
Tel: +49 (0)69 798-33064
ethnologie@em.uni-frankfurt.de

PD Dr. Susanne Fehlings, Press and Public Relations, Frobenius Institute
Tel: +49 (0)69 798-33058
fehlings@uni-frankfurt.de

Jul 22 2022

20:50

Laboratory study: Lower level of protection as early as 3 months after a second vaccination or booster shot 鈥� monoclonal antibodies in part ineffective. However, results do not indicate how severely people fall ill

Neutralisation efficacy of antibodies against Omicron variants BA.1 and BA.2 declines quickly

The Omicron variants BA.1 and BA.2 of the SARS-CoV-2 virus, which dominated from about December to April, can already circumvent after three months the protection against infection offered by vaccinations and recovery from infection. This has been revealed in a study in Frankfurt lead-managed by University Hospital Frankfurt and 51猎奇. Moreover, according to the study, various pharmaceutical antibody preparations (monoclonal antibodies) have widely differing effects on the two virus variants. The study authors emphasise how important it is to align protective measures to the genetic changes in the virus, therefore.

FRANKFURT. The Omicron variant of the SARS-CoV-2 virus was first detected in South Africa in November 2021. The high level of infectiousness of the virus and its ability to quickly spawn additional variants has also been observed in Germany: Since January 2022 the Omicron variant BA.1 has dominated here, followed in subsequent months by the variant BA.2. In the meantime, the virus has mutated further, and since June the variants BA.4 and BA.5 have superseded their predecessors.

This poses major challenges for the immune system of the human body: antibodies are formed in the course of a SARS-CoV-2 infection and these attach themselves to the surface structures of the virus, thus preventing it from penetrating human cells. The viral spike protein plays the key role here. In the Omicron variants, this has changed in more than 50 sites compared to the first SARS-CoV-2 virus identified in Wuhan. The consequence: the antibodies formed after an infection or a vaccination do not recognise the variants less efficient. This is why despite having overcome an infection, people can again become infected with a new SARS-CoV-2 variant, or there are breakthrough infections. However, how good the immunity response is to an infection depends on more than just antibodies.

Researchers in Frankfurt headed by Marek Widera and Professor Sandra Ciesek from the Institute for Medical Virology at the University Hospital of the 51猎奇 Frankfurt have now examined how long the antibodies present in blood after a vaccination or recovery from an infection were still able to neutralise the virus variants Omicron BA.1 and BA.2. To this end, they collected blood samples from people who had been vaccinated twice or three times (booster shot), placed the liquid blood component (blood serum), which contains antibodies, together with SARS-CoV-2 viruses on cultivated cells and observed how many of the cells became infected. Furthermore, in each case they ascertained the quantity of antibodies in the samples that recognised the spike protein.

The result: six months after the second vaccination, the tested sera practically had no neutralising effect on the Omicron variants BA.1 and BA.2. The effect of a booster vaccination declined rapidly: although the sera still provided very good protection shortly after the booster vaccination, three months later the protective effect was merely very weak, with the effect that the tested sera were no longer capable of neutralising the two virus variants. 鈥淭his is due to the fact that the antibody titre in serum 鈥� the amount of antibodies, so to speak 鈥� after a vaccination or infection declines in the course of time," explains Widera. 鈥淏ecause the antibodies have a significantly lower ability to recognise newer virus variants, a lower level of antibodies is then no longer sufficient to neutralise the virus variants and prevent an infection of the cells in a cell culture. However, the data from this study does not allow any conclusions to be drawn regarding protection against the seriousness of the course of the disease." The decisive factor for the immune function is not just the antibody titre, but also the cellular immune response, which was not examined in this study, Widera adds.

These results are particularly problematic for the use of monoclonal antibodies, which are administered to patients with a compromised immune system as a precautionary measure, for example, says Professor Sandra Ciesek. Ciesek is the Director of the Institute for Medical Virology at the University Hospital Frankfurt and the senior author of the study. She explains: 鈥淎s an example we studied three such monoclonal antibodies in laboratory experiments and saw that their efficacy is very heavily dependent on the virus variant. So that we are able to protect vulnerable patients with such preparations, it is absolutely essential to also test in patients the extent to which such antibodies can neutralise the virus variants that are currently prevalent, therefore." Admittedly, the virus variants BA.1 and BA.2 examined in the study are no longer dominant in Germany in the meantime, adds the virologist. 鈥淥ur study shows, however, that we cannot afford to let up in adapting our protective measures in line with the genetic changes in the SARS-CoV-2 virus, at present to the Omicron variants BA.4 und BA.5, therefore."

Publication: Alexander Wilhelm, Marek Widera, Katharina Grikscheit, Tuna Toptan, Barbara Schenk, Christiane Pallas, Melinda Metzler, Niko Kohmer, Sebastian Hoehl, Rolf Marschalek, Eva Herrmann, Fabian A. Helfritz, Timo Wolf, Udo Goetsch, Sandra Ciesek: Limited Neutralisation of the SARS-CoV-2 Omicron Subvariants BA.1 and BA.2 by Convalescent and Vaccine Serum and monoclonal antibodies. eBioMedicine (2022) https://doi.org/10.1016/j.ebiom.2022.104158

Further information:
Professor Sandra Ciesek
Marek Widera, Ph.D.
Institute for Medical Virology
University Clinic Frankfurt via Press Office University Clinic Frankfurt
Christoph.Lunkenheimer@kgu.de
Tel. +49 (0)69 6301 鈥� 86442

51猎奇

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