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During the first lockdown people were a good 40 percent less active, as shown by an international study led by Goethe University Frankfurt. Psychological well-being sank as well; the portion of people at potential risk for depression tripled. The authors fear long-term consequences and urge that this be taken into account going forward.

FRANKFURT. Twenty scientists from 14 countries warn of a hidden “pandemic within the pandemic“ in two current publications. On the one hand, physical activity levels have gone down significantly, on the other hand, psychological well-being has suffered. “Governments and those responsible for health systems should take our findings seriously," emphasizes the author team, headed by Dr Jan Wilke from the Institute for Sport Sciences at Goethe University Frankfurt.

About 15,000 people in participating countries answered standardised questionaires as part of an international survey. In April/May 2020, they reported physical activity levels (13,500 participants) as well as their mental and physical well-being (15,000 participants) before and during the pandemic-related restrictions.

Older individuals especially affected

“The results show drastic reductions in physical activity and well-being," says Wilke. More than two thirds of those questioned were unable to maintain their usual level of activity. Moderate exercise decreased by an average of 41 percent according to self-reported data - this includes anything that increases heart rate and breathing, such as brisk walking, running, cycling or even strenuous gardening.

The proportion of vigorous exercise during which people sweat and clearly run out of breath fell by a similar amount (42 percent). The effects were somewhat higher among professional athletes and particularly active people, as well as comparatively young and old people. The decline in activity was particularly noticeable among people over 70 years of age, who were 56 to 67 percent less active than before. "We know that physical inactivity, especially in older people, can lead to changes that are difficult to reverse after only two weeks - for example, in body fat percentage or insulin sensitivity," warn the study authors.

Exercise helps prevents disease and reduces mortality

The WHO recommends at least 150 minutes of moderate or 75 minutes of intensive physical activity per week - 81 percent of the study participants achieved this before the pandemic, but only 63 percent during the lockdowns. Yet sufficient exercise can reduce mortality by up to 39 per cent, as a 2015 study showed. Data suggests that too little exercise plays a role in about one in ten premature deaths, because physical activity reduces the likelihood of, for example, high blood pressure, metabolic disorders such as type 2 diabetes, and cancer.

Exercise is known to activate the immune system because it promotes blood circulation and activates lymphocytes and messenger substances (cytokines) that are important for immune defence. Studies show that physically active people are less susceptible to influenza, rhino and herpes viruses and respiratory infections in general. So it may be that exercise also offers protection against severe COVID-19 by reducing risk factors such as obesity. Physical health and exercise also reduce the risk of mental health problems such as depression and anxiety disorders.

Mental well-being drastically reduced

In another part of the study, the team of authors asked about mental well-being during the pandemic restrictions. 73 percent of the study participants stated that their well-being had deteriorated. The perceived quality of life as measured by the WHO well-being Index, which measures mood, relaxation, activity, rest and interest, dropped on average from 68 percent before the pandemic to 52 percent during the first lockdown phase.

Above all, people felt less "active and full of energy" and led a life less "filled with interesting things". The proportion of very low scores indicating a possible risk of depression tripled from 15 to 45 percent. "These effects were stronger among women and younger people, " the study says. "More attention should be paid to the needs of women in particular, as they are significantly more vulnerable."

Nonetheless, 14 to 20 percent of the respondents also stated that their health had improved - the authors see more family time, greater work autonomy, fewer business trips or a changed perception of health as possible reasons. "But a large part of the population may still be suffering from barely visible health effects of the pandemic," the team of authors warns.

This could also translate into rising health costs: According to US data, the annual expenditure for inactive or insufficiently active people increases by 1200 and 600 euros respectively - this would add up to two to four million euros after one year just for the 3104 people from the survey who did not exercise enough during the lockdown.

The results of these first multinational studies are likely to be relevant for an estimated four billion people worldwide who were affected by the restrictions of the first coronavirus wave in the spring of 2020. However, the data was predominantly collected through electronic media, so populations without internet were not included. Also, no differentiation was made according to factors such as living environment, education and social status. In addition, the data is based on self-assessments, not measurements, which may distort retrospective perceptions in particular. "Nevertheless, our results show that the issues of physical activity and well-being belong on the policy agenda," Wilke emphasises.

"Governmental and health-related decison-makers need to develop strategies to mitigate the loss of physical activity," write the authors. They suggest better public education, creating exercise opportunities with a low likelihood of infection, or offering effective home exercise programmes. Among numerous other health facets, this would have a particularly positive effect on mental well-being.

Negative effects similar to those observed in these studies should be avoided at all costs in future pandemics. "Unfortunately, physical activity and exercise do not have a strong lobby and are usually neglected in public discourse," says Wilke. "Yet they can greatly help us to better cope with the pandemic."

Publications: Jan Wilke et al. A Pandemic within the Pandemic? Physical Activity Levels Substantially Decreased in Countries Affected by COVID-19. Int. J. Environ. Res. Public Health, Vol. 18, 5 (2021), https://www.mdpi.com/1660-4601/18/5/2235/htm#B11-ijerph-18-02235

Jan Wilke et al., Drastic Reductions in Mental Well-Being Observed Globally During the COVID-19 Pandemic: Results from the ASAP Survey. Front. Med. 8:578959 (2021), https://www.frontiersin.org/articles/10.3389/fmed.2021.578959/full

Further information
Dr Jan Wilke
Institute für Sport Sciences
Goethe University Frankfurt
Tel. +49 (69) 798-24588,
wilke@sport.uni-frankfurt.de
https://www.uni-frankfurt.de/50765300/Arbeitsbereich_Sportmedizin_und_Leistungsphysiologie

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

Theoretical physicists at Goethe University Frankfurt have analysed data from the black hole M87* as part of the Event Horizon Telescope (EHT) collaboration to test Albert Einstein's theory of general relativity. According to the tests, the size of the shadow from M87* is in excellent agreement being from a black hole in general relativity, but sets constraints on the properties of black holes in other theories. In 2019, the EHT collaboration published the first image of a black hole located at the centre of the galaxy M87.

FRANKFURT. As first pointed out by the German astronomer Karl Schwarzschild, black holes bend space-time to an extreme degree due to their extraordinary concentration of mass, and heat up the matter in their vicinity so that it begins to glow. New Zealand physicist Roy Kerr showed rotation can change the black hole's size and the geometry of its surroundings. The "edge" of a black hole is known as the event horizon, the boundary around the concentration of mass beyond which light and matter cannot escape and which makes the black hole “black". Black holes, theory predicts, can be described by a handful of properties: mass, spin, and a variety of possible charges.

In addition to black holes predicted from Einstein's theory of general relativity, one can consider those from models inspired by string theories, which describe matter and all particles as modes of tiny vibrating strings. String-inspired theories of black holes predict the existence of an additional field in the description of fundamental physics, which leads to observable modifications in the sizes of black holes as well as in the curvature in their vicinity.

Physicists Dr Prashant Kocherlakota and Professor Luciano Rezzolla from the Institute for Theoretical Physics at Goethe University Frankfurt, have now investigated for the first time how the different theories fit with the observational data of the black hole M87* at the centre of the galaxy Messier 87. The image of M87*, taken in 2019 by the international Event Horizon Telescope (EHT) collaboration, was the first experimental proof of the actual existence of black holes after the measurement of gravitational waves in 2015.

The result of these investigations: The data from M87* are in excellent agreement with the Einstein-based theories and to a certain extent with the string-based theories. Dr Prashant Kocherlakota explains: "With the data recorded by the EHT collaboration, we can now test different theories of physics with black hole images. Currently, we cannot reject these theories when describing the shadow size of M87*, but our calculations constrain the range of validity of these black hole models."

Professor Luciano Rezzolla says: “The idea of black holes for us theoretical physicists is at the same time a source of concern and of inspiration. While we still struggle with some of the consequences of black holes – such as the event horizon or the singularity – we seem always keen to find new black hole solutions also in other theories. It is therefore very important to obtain results like ours, which determine what is plausible and what is not. This was an important first step and our constraints will be improved as new observations are made".

In the Event Horizon Telescope collaboration, telescopes from around the globe are interconnected to form a virtual giant telescope with a dish as big as the Earth itself. With the precision of this telescope, a newspaper in New York could be read from a street café in Berlin.

Publication: Prashant Kocherlakota, Luciano Rezzolla, Heino Falcke, Christian M. Fromm, Michael Kramer,  Yosuke Mizuno, Antonios Nathanail, H´ector Olivares, Ziri Younsi et. al. (The Event Horizon Telescope collaboration), Constraints on black-hole charges with the 2017 EHT observations of M87*. Physical Review D, vol 103, https://journals.aps.org/prd/abstract/10.1103/PhysRevD.103.104047 DOI: 10.1103/PhysRevD.103.104047

Video: Testing different theories of gravity with the data obtained
https://youtu.be/Xf8He6Z1eQU

Images for download:
www.uni-frankfurt.de/101531130

Caption: Event horizon sizes for different theories of gravity. All of these black holes cast dark shadows that are distinguishable from each other in size, but only those that fall in the gray band are compatible with the 2017 EHT measurements of M87*, and in this image, the one represented in red at the bottom is too small to be a viable model for M87*. Credit: Prashant Kocherlakota, Luciano Rezzolla (Goethe University Frankfurt and EHT Collaboration/ Fiks Film 2021)

Scientific contact:
Dr Prashant Kocherlakota
Institute for Theoretical Physics
Goethe University Frankfurt
Tel. +49 69 798-47848
kocherlakota@itp.uni-frankfurt.de

Professor Luciano Rezzolla
Institute for Theoretical Physics
Goethe University Frankfurt
rezzolla@itp.uni-frankfurt.de

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

Whether bacteria are resistant to antibiotics is often decided at the cell membrane. This is where antibiotics can be blocked on their way into the cell interior or catapulted from the inside to the outside. Macrocyclic peptides, a novel class of antibiotics, bioactive cytotoxins and inhibitors, shed light on how this transport process occurs at the membrane, how it is influenced and how it can be used to circumvent the resistance of a malignantly transformed cell. The research results, which were developed under the direction of Professor Robert Tampé (Goethe University) and Professor Hiroaki Suga (University of Tokyo), have been published in the renowned journal eLife (20-02-2021-RA-eLife-67732). 

FRANKFURT. There are currently only a few synthetic agents that bind to and block the widespread membrane transport proteins, ATP-binding cassette transporters (ABC). Scientists at Goethe University and the University of Tokyo identified four of these macrocyclic peptides as models for a novel generation of active substances. They used methods for which the scientists involved are considered world leaders.

Thanks to deep sequencing, an extremely fast and efficient read-out procedure, the desired macrocyclic peptides could be filtered out of a "library" of macrocyclic peptides comprising trillions of variants (1 with 12 zeroes) - a number that exceeds the number of stars in the Milky Way. The fact that such an enormous amount exists at all is related to a novel procedure: By reprogramming the genetic code, amino acids can be used specifically as active components that are not otherwise used in the cell. In particular, their circular, closed structure distinguishes them from natural proteins. "Because these therapeutics are cyclic, they break down less rapidly in the cell," explains Robert Tampé, Director of the Institute of Biochemistry at Goethe University. "In addition, the ring-shaped active substances are restricted in their spatial structure, so they bind to the target molecule without major rearrangements." A third distinguishing feature makes macrocyclic peptides particularly attractive for scientists: When the active substances are produced, their building instructions are supplied as a "barcode". If certain therapeutics are selected from among a trillion synthetically produced ones, they carry their "name tags" with them, so to speak.

So what role do synthetic therapeutics play in antibiotic resistance in bacteria or multidrug resistance in tumour cells? What happens when they encounter the ATP-driven transport molecule that is responsible for resistance by carrying the chemotherapeutic agents out of the cell? In a nutshell: The drugs block the transporter by binding to it. This can happen at the beginning or at the end of a transport process, when the transporter is in a resting state. However, since the scientists can slow down the transport process so that it is carried out in slow motion, they can identify the agents that "enter" in the middle of the transport process and "hold" the membrane protein in its respective position. In this way, the researchers gain an insight into the choreography of the transport process as if through the images of a film strip.

These insights have already led to a "paradigm shift" in science, as Tampé explains: "Until now, we have assumed that ATP hydrolysis (note: an energy-releasing splitting process) provides the energy for transport through the membrane. However, this is only indirectly the case. It is the event of the binding of the ATP molecule that pushes substances out of the cell. The energy of hydrolysis, on the other hand, is used to return the ABC transporter to its initial state." The research groups at Goethe University and the University of Tokyo are convinced that these and other insights into membrane processes will point to the development of future medicines.

Basic research on cellular membranes and membrane proteins already has a long tradition in Frankfurt. Robert Tampé elucidated essential mechanisms of ATP-driven transport proteins and cellular machinery of adaptive immune response and quality control, which together with this new publication can provide approaches for applied drug research. Tampé was head of the Collaborative Research Centre "Transport and Communication across Biological Membranes" (SFB 807) which expired at the end of 2020. Meanwhile the concept for a new research centre on highly dynamic processes related to protein networks and machineries in cellular membranes is already under development. In the long term, the research results should reveal new possibilities for the therapy of molecular diseases, infections and cancer.

Publication:
Erich Stefan, Richard Obexer, Susanne Hofmann, Khanh Vu Huu, Yichao Huang, Nina Morgner, Hiroaki Suga, Robert Tampé: “De novo macrocyclic peptides dissect energy coupling of a heterodimeric ABC transporter by multimode allosteric inhibition“ (20-02-2021-RA-eLife-67732)

Stefan, Hofmann, and Tampé at the Institute of Biochemistry at Goethe University, Vu Huu and Morgner at the Institute for Physical and Theoretical Chemistry at Goethe University, and Obexer, Huang and Suga at the Department of Chemistry, University of Tokyo.

Images for download: www.uni-frankfurt.de/101026220
(Graphic: Robert Tampé, Institute for Biochemistry, Biocentre, Goethe University Frankfurt)
Caption: Synthetic therapeutics for antibiotic resistance in bacteria or multidrug resistance in tumour cells can block ATP-driven transport proteins that carries chemotherapeutics out of the cell 

Further information
Professor Robert Tampé
Institute of Biochemistry, Biocentre
Goethe University Frankfurt
tampe@em.uni-frankfurt.de

Professor Hiroaki Suga
Department of Chemistry
Graduate School of Science
The University of Tokyo
hsuga@chem.s.u-tokyo.ac.jp

Editor: Pia Barth, Public Relations, PR & Communication Department, Tel: -49 (0) 69 798-12481, Fax: +49 (0) 69 798-763 12531, p.barth@em.uni-frankfurt.de

When a cell is infected, SARS-CoV-2 not only causes the host cell to produce new virus particles. The virus also suppresses host cell defence mechanisms. The virus protein nsP3 plays a central role in this. Using structural analyses, researchers at Goethe University in cooperation with the Swiss Paul Scherrer Institute have now discovered that a decomposition product of the virostatic agent remdesivir binds to nsP3. This points to a further, previously unknown effective mechanism of remdesivir which may be important for the development of new drugs to combat SARS-CoV-2 and other RNA viruses.

FRANKFURT. The virostatic agent remdesivir was developed to disrupt an important step in the propagation of RNA viruses, to which SARS-CoV-2 also belongs: the reproduction of the virus's own genetic material. This is present as RNA matrices with which the host cell directly produces virus proteins. To accelerate the production of its own proteins, however, RNA viruses cause the RNA matrices to be copied. To do so, they use a specific protein of their own (an RNA polymerase), which is blocked by remdesivir. Strictly speaking, remdesivir does not do this itself, but rather a substance that is synthesized from remdesivir in five steps when remdesivir penetrates a cell.

In the second of these five steps, an intermediate is formed from remdesivir, a substance with the somewhat unwieldy name GS-441524 (in scientific terms: a remdesivir metabolite). GS-441524 is a virostatic agent as well. As the scientists in the group headed by Professor Stefan Knapp from the Institute for Pharmaceutical Chemistry at Goethe University Frankfurt have discovered, GS-441524 targets a SARS-CoV-2 protein called nsP3. nsP3 is a multifunctional protein, whose tasks include suppressing the host cell's defence response. The host cell is not helpless in the face of a virus attack, but activates inflammatory mechanisms, among other things, to summon the aid of the cell's endogenous immune system. nsP3 helps the viruses suppress the cell's calls for help.

Professor Stefan Knapp explains: “GS-441525 inhibits the activities of an nsP3 domain which is important for the reproduction of viruses, and which communicates with human cellular defence systems. Our structural analysis shows how this inhibition functions, allowing us to lay an important foundation for the development of new and more potent antiviral drugs – effective not only against SARS-CoV-2. The target structure of GS-441524 is very similar in other coronaviruses, for example SARS-CoV and MERS-CoV, as well in a series of alphaviruses, such as the chikungunya virus. For this reason, the development of such medicines could also help prepare for future virus pandemics."

Publication: Xiaomin Ni, Martin Schröder, Vincent Olieric, May E. Sharpe, Victor Hernandez-Olmos, Ewgenij Proschak, Daniel Merk, Stefan Knapp, Apirat Chaikuad: Structural Insights into Plasticity and Discovery of Remdesivir Metabolite GS-441524 Binding in SARS-CoV‑2 Macrodomain. ACS Med. Chem. Lett. 2021, 12, 603−609 https://pubs.acs.org/doi/10.1021/acsmedchemlett.0c00684

Further information
Professor Stefan Knapp
Institute for Pharmaceutical Chemistry and
Buchmann Institute for Molecular Life Sciences
Goethe University Frankfurt
Tel. +49 69 798-29871
knapp@pharmchem.uni-frankfurt.de
https://www.uni-frankfurt.de/53483664/Knapp

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

What happens when film leaves the cinema and becomes available everywhere – out and about on mobile devices, or in the living room at home? The Graduiertenkolleg (Research Training Group) “Configurations of Film" at Goethe University has been researching the current transformation of film and cinema culture since 2017. The German Research Foundation has now given the project the green light to continue.

FRANKFURT. “We are happy that the German Research Foundation's has kept their trust in us so that we can continue to our work in the Kolleg," says Vinzenz Hediger, professor for film studies and speaker of the Kolleg. In individual studies that include the participation of the disciplines of philosophy, literary studies and theatre studies, the Kolleg examines a fundamental problem in film studies: the transformation of its objects through the progressive digitalisation of the production, distribution and perception of moving images. "The medium of the moving image, which was standardised for global distribution in an international agreement as early as 1905, has always been a medium in motion," says Hediger. "With digitalisation, however, cinema itself as the privileged place of film is now being called into question, with far-reaching consequences for the aesthetics, as well as for the social impact and significance of films and other moving image formats."

The Graduiertenkolleg at the Institute for Theatre, Film and Media Studies started in 2017 with twelve doctoral candidates and two post-docs. Currently, the second group with a another twelve young sceintists from Germany, India and Nigeria is already at work. In close collaboration with the two postdocs of the Kolleg, they deal with topics as diverse as the interpenetration of film and video and computer games, the afterlife of Rainer Werner Fassbinder's work and reputation, the role of textiles in Nigerian historical films or the digital rediscovery of popular Bengali cinema of the 1950s and 1960s.

The Graduiertenkolleg is run in cooperation with the Universities of Mainz and Marburg and the University for Art and Design in Offenbach. The Kolleg builds on three Master's programmes at Goethe University as well as collaborations among the applicant researchers. It utilises the potential of Frankfurt as a location, where the university library and the German National Library have literature holdings of European standing and important non-university partners are available in the form of the German Film Institute, the Murnau Foundation and the Max Planck Institute for Empirical Aesthetics. The Kolleg is developing an international reputation through its cooperation with Yale University and Concordia University.

The Kolleg attracted attention among experts in autumn 2020 with the publication "Pandemic Media. Preliminary Notes towards an Inventory", in which 37 authors from the Kolleg and its international network reflect on global media culture under pandemic conditions. The book is available in open access at the academic publisher meson press (https://meson.press/books/pandemic-media/).

Further information:
Professor Vinzenz Hediger

Graduiertenkolleg „Configurations of Film“

Editor: Dr. Anke Sauter, Science and Humanities Editor, International Communication, PR & Communication Department, Phone: +49 69 798-13066, Fax  +49(0)69 798-761 12531, sauter@pvw.uni-frankfurt.de.