Researchers of Goethe University decode the mechanism of chemotherapy induced female infertility
FRANKFURT. One of the most significant impairments of the quality of life after a chemotherapy is infertility. Researchers of the Goethe University and the University Tor Vergata in Rome have now identified the mechanism of chemotherapy-induced infertility in females.
Many chemotherapeutics act by damaging the DNA. Since cancer cells divide more often than most normal cells, they react more sensitive to DNA damaging agents. One exception are oocytes. To prevent birth defects they initiate a cellular death program if DNA damage is detected. This process, called apoptosis, is triggered in oocytes by the protein p63. Oocytes contain a high concentration of an oocyte-specific isoform of p63 which plays a key role as a quality control factor in causing infertility.
In contrast to men who produce new sperm cells throughout their life women are born with a finite number of oocytes. When this pool is depleted menopause starts. This pool of oocytes can be depleted prematurely by chemotherapy resulting in early menopause. This results not only in infertility but also in hormone-based problems such as osteoporosis.
Scientists in the laboratory of Prof Volker Dötsch at the Institute for Biophysical Chemistry of Goethe University have now deciphered the mechanism leading to premature loss of the oocyte pool caused by treatment with chemotherapy. In non-damaged oocytes p63 exists in an inactive form. DNA damage caused by chemo- or radiotherapy results in the modification of p63 with phosphate groups which triggers a conformational change to the active form. Active p63 starts the cell death program which leads to the elimination of the oocyte. The scientists describe in the online edition of the journal „Nature Structural and Molecular Biology“ the molecular details of this activation mechanism and the enzymes responsible for it.
These results open new opportunities for developing a therapy for preserving oocytes of female cancer patients treated with chemotherapeutics. In experiments with mouse ovaries inhibiting the identified enzymes saved the oocytes from cell death despite treatment with chemotherapeutics.
Publication: Tuppi M., Kehrloesser S., Coutandin D.W. et al. Oocyte DNA damage quality control requires consecutive interplay of CHK2 and CK1 to activate p63, in: Nature Structural and Molecular Biology. DOI: 10.1038/s41594-018-0035-7
Astrophysicists at Goethe University Frankfurt answer this question by computing images of feeding non-Einsteinian black holes: At present it is hard to tell them apart from standard black holes.
FRANKFURT. One of the most fundamental predictions of Einstein's theory of relativity is the existence of black holes. In spite of the recent detection of gravitational waves from binary black holes by LIGO, direct evidence using electromagnetic waves remains elusive and astronomers are searching for it with radio telescopes. Astrophysicists at Goethe University Frankfurt, and collaborators in the ERC-funded project BlackHoleCam in Bonn and Nijmegen have created and compared self-consistent and realistic images of the shadow of an accreting supermassive black hole - such as the black-hole candidate Sagittarius A* (Sgr A*) in the heart of our galaxy - both in general relativity and in a different theory of gravity. The goal was to test if Einsteinian black holes can be distinguished from those in alternative theories of gravity.
Not all of the light rays (or photons) produced by matter falling into a black hole are trapped by the event horizon, a region of spacetime from which nothing can escape. Some of these photons will reach distant observers, so that when a black hole is observed directly a “shadow” is expected against the background sky. The size and shape of this shadow will depend on the black-hole’s properties but also on the theory of gravity.
Because the largest deviations from Einstein’s theory of relativity are expected very close to the event horizon and since alternative theories of gravity make different predictions on the properties of the shadow, direct observations of Sgr A* represent a very promising approach for testing gravity in the strongest regime. Making such images of the black-hole shadow is the primary goal of the international Event Horizon Telescope Collaboration (EHTC), which combines radio data from telescopes around the world.
Scientists from the BlackHoleCam team in Europe, who are part of the EHTC, have now gone a step further and investigated whether it is possible to distinguish between a "Kerr" black hole from Einstein’s gravity and a "dilaton" black hole, which is a possible solution of an alternative theory of gravity.
The researchers studied the evolution of matter falling into the two very different types of black holes and calculated the radiation emitted to construct the images. Furthermore, real-life physical conditions in the telescopes and interstellar medium were used to create physically realistic images. “To capture the effects of different black holes we used realistic simulations of accretion disks with near-identical initial setups. These expensive numerical simulations used state-of-the-art codes and took several months on the Institute’s supercomputer LOEWE,” says Dr. Yosuke Mizuno, lead author of the study.
Moreover, expected radio images obviously have a limited resolution and image fidelity. When using realistic image resolutions, the scientists found, to their surprise, that even highly non-Einsteinian black holes could disguise themselves as normal black holes.
“Our results show that there are theories of gravity in which black holes can masquerade as Einsteinian, so new techniques of analyzing EHT data may be needed to tell them apart,” remarks Luciano Rezzolla, professor at Goethe University and leader of the Frankfurt team. “While we believe general relativity is correct, as scientists we need to be open-minded. Luckily, future observations and more advanced techniques will eventually settle these doubts,” concludes Rezzolla.
“Indeed, independent information from an orbiting pulsar, which we are actively searching for, will help eliminate these ambiguities,” says Michael Kramer, director at the MPI for Radio Astronomy in Bonn. Heino Falcke (professor at Radboud University), who 20 years ago proposed using radio telescopes to image the shadow of black holes, is optimistic. “There is little doubt that the EHT will eventually obtain strong evidence of a black-hole shadow. These results encourage us to refine our techniques beyond the current state of the art and thus make even sharper images in the future."
Yosuke Mizuno1, Ziri Younsi1, Christian M. Fromm1, , Oliver Porth1, Mariafelicia De Laurentis1, Hector Olivares1, Heino Falcke2, Michael Kramer3 and Luciano Rezzolla1,4 'The current ability to test theories of gravity with black hole shadows, Nature Astronomy, doi: 10.1038/s41550-018-0449-5
1Institute for Theoretical Physics, Goethe University, Frankfurt, Germany
2Radboud University, Nijmegen, The Netherlands
3Max-Planck Institute for Radio Astronomy, Bonn, Germany
4Institute for Advanced Studies, Frankfurt, Germany
Contact phone numbers:
Mizuno: Mobile: +49 159 02104299, Office: +49 69 79847885
Falcke: Mobile: +49 151 23040365, Office: +31 24 3652020
Kramer: Mobile: +49 160 90747348, Office: +49 228 525278
Rezzolla: Mobile: +49 170 3022982, Office: +49 69 79847871
You can download a figure from: www.uni-frankfurt.de/71465647
Credit: Fromm/Younsi/Mizuno/Rezzolla (Frankfurt)
BlackHoleCam is an ERC-funded Synergy Grant that aims to image, measure and understand astrophysical black holes. Its PIs, Falcke, Kramer and Rezzolla, test fundamental predictions of Einstein’s theory of General Relativity. The BlackHoleCam team members are active partners of the international Event Horizon Telescope Collaboration (ETHC). Goethe University is a stakeholder institute and represented on the EHTC's executive board.
Scientists at Goethe University Frankfurt are awarded two ERC Advanced Grants/ € 2.5 million each for five years
FRANKFURT. Two Advanced Grants of the European Research Council (ERC) have been awarded to researchers at Goethe University Frankfurt. The sociologist Professor Thomas Lemke is researching the social impacts of cryobiology, i.e. the freezing and long-term preservation of organic material. The biochemist Professor Robert Tampé wants to unravel the winding pathways of the immune system inside the cell.
“Cryosocieties” project explores „suspended life“
Cryobiology has seen an enormous upturn over the last decades. More and more types of tissues and cellular material can be frozen, stored and thawed again without any detectable loss of vitality. Today, cryobiological practices are not only an important infrastructural prerequisite for many medical applications and a significant driver for innovations in the life sciences but also represent important options for personal family planning decisions as well as for the preservation of global biodiversity.
“In our ‘Cryosocieties’ project, I want to investigate the impact of cryopreservation on our understanding of life, starting with the hypothesis that cryobiological practices produce a specific form of life that I call „suspended life“ . They keep many vital processes in a suspended state between life and death, in which biological substances are neither completely alive nor completely dead,” explains Professor Thomas Lemke from the Institute of Sociology. The aim of the project, which lies at the interface between biology, sociology and technology, is to study how cryopreservation practices alter temporal and spatial relationships and configurations as well as our understanding of life and death, health and illness, (in)fertility and sustainability.
In three different scenarios, Lemke and his team will investigate how „suspended life“ is produced in current cryopreservation practices. These sub-projects deal with the freezing of umbilical cord blood as preparation for later regenerative therapies, the cryopreservation of egg cells for reproductive purposes and the setting up of cryobanks for the preservation of endangered or already extinct animal species.
Immune defence in the cell
Although the immune system is one of the most complex systems in the human body – with many different types of immune cells as well as transport and messenger molecules - pathogens and cancer cells manage to outwit it over and over again. Herpes and smallpox viruses, for example, have developed ingenious strategies to attack specific pathways in the body’s immune system.
A virus that has penetrated the cell is normally disassembled in a kind of molecule shredder (proteasome) and then transported to the cell’s surface where it is presented to the T cells of the immune system. Herpes and smallpox viruses manage, however, to remain hidden in the cell by attacking the transport molecule that is supposed to carry them to the surface.
What is known so far is that small pieces of proteins (peptides) from the proteasome are processed by a large macromolecular complex and many helper molecules in preparation for their journey to the cell’s surface. This is known as the peptide-loading complex and sits in the endoplasmic reticulum, the “cell’s engine room”. In this highly folded system of membrane-enclosed cavities, proteins are produced, folded, checked and prepared for their journey to the cell’s surface.
Professor Robert Tampé from the Institute of Biochemistry explains the project: “My goal is to study the antigen processing mechanism in detail. With this research, we are setting off along one of the thorniest paths in the life sciences because we’re dealing with large molecules with different assemblies which are moreover relatively rare in intercellular membranes.” However, since his research group has succeeded in recent years in shedding light on some important structures in the peptide-loading complex and their functions, he is well prepared for the new project. “We expect that our work will have a considerable influence on many areas of the life sciences, especially in the field of cancer research as well as infectious and autoimmune diseases,” says Tampé.
Pictures can be downloaded under: www.uni-frankfurt.de/71298300
Professor Thomas Lemke, Institute of Sociology, Faculty of Social Sciences, Westend Campus, Tel.: +49(0)69-798-36664, firstname.lastname@example.org
Professor Robert Tampé, Institute of Biochemistry, Faculty of Biochemistry, Chemistry and Pharmacy, Riedberg Campus, Tel.: +49(0)69-798-29475, email@example.com.
University Library Johann Christian Senckenberg is the first German library in the consortium
FRANKFURT. The University Library Johann Christian Senckenberg (UB JCS) in Frankfurt am Main just joined the Biodiversity Heritage Library (BHL) as an official Affiliate. BHL is an online library sustained by nearly 40 natural history libraries and museums from around the world. UB JCS is the first German library to join the consortium.
The University Library will enhance BHL’s corpus of biodiversity literature by contributing content from its rich Biology Collection. By enabling free access to Central European biodiversity literature, the Library will significantly enhance discoverability of knowledge contained in a segment of literature which is not yet satisfactorily represented online.
The University Library’s Biology Collection comprises excellent holdings of historic and modern biodiversity literature, representing some 400,000 volumes on the entire spectrum of biological science. UB JCS has a long history of collection digitization and provides access to a large corpus of digitized literature through its "Digitale Sammlungen" portal, including a notable collection of German botanical journals from 1753-1914. In 2017, the Specialised Information Service Biodiversity Research project (BIOfid; co-funded by the German Research Council DFG) was established to enhance access to the Biology Collection. Through continued digitization of literature and the development of new services including text mining tools to mobilize data within the literature, the project aims to build a bridge between historical holdings and modern biodiversity research. The BIOfid project is conducted by the Library in collaboration with the Senckenberg Gesellschaft für Naturforschung and the Text Technology Lab of the Goethe University of Frankfurt am Main.
For further information:
Information: Dr. Gerwin Kasperek, Subject Librarian for Biology and Head of BIOfid Project, University Library J. C. Senckenberg, Bockenheimer Landstraße 134-138, 60325 Frankfurt am Main, Germany, Tel: +49 (69) 798 39365, E-Mail: firstname.lastname@example.org
The brain processes weak visual stimuli better in the morning and evening than at noon
FRANKFURT. In the pre-industrial age, twilight was a dangerous time for humans since they were at risk of encountering nocturnal predators. Anyone still able to recognise things despite the weak light was at a clear evolutionary advantage. As neuroscientists at Goethe University Frankfurt have now discovered, the human brain prepares for dawn and dusk by shutting down resting activity in the visual cortex at these times so that weak visual stimuli do not disappear in the brain’s background noise.
The transition from night to day, light and dark, has a greater influence on perception that we realise. The time of day has a particularly significant impact on the quality of visual signals around us. In the course of evolution, our visual system has adapted perfectly to light conditions during the day. It has, however, also developed a strategy for twilight: Evidently it allows our inner clock to predict these periods and prepare our visual system for times when the quality of visual signals deteriorates.
“Whilst the cogs of our inner clock have already been studied in depth, it was not known to date which mechanism optimises visual perception at times when poor signal quality can be expected,” explains Dr. Christian Kell from the Brain Imaging Center of Goethe University Frankfurt. That is why Lorenzo Cordani, his doctoral researcher, examined how 14 healthy test persons reacted to visual stimuli at six different times of the day in the framework of a complex fMRI study.
The main idea of the study was to relate the perception of sensory signals to the brain’s resting activity. There is namely a certain “background noise” in the brain even in the complete absence of external stimuli. The international team led by Christian Kell, Lorenzo Cordani and Joerg Stehle was able to show that the body independently downregulates resting activity in the sensory areas during dawn and dusk. The more resting activity was reduced, the better the test persons were able to perceive weak visual signals when measured afterwards.
This means that humans can perceive weak visual stimuli during dawn and dusk better than at other times of the day. In other words: During twilight, the signal-to-noise ratio in the sensory areas of the brain improves. Since resting activity during twilight decreases not only in the visual but also in the auditory and somatosensory regions of the brain, the researchers assume that perception sharpens not only in the visual system. An earlier study already showed that weak auditory stimuli during twilight were perceived better. The mechanism now discovered, which was published in the latest issue of Nature Communications, could therefore represent a key evolutionary advantage that ensured survival in the pre-industrial era.
Publication: Lorenzo Cordani, Enzo Tagliazucchi, Céline Vetter, Christian Hassemer, Till Roenneberg, Jörg H. Stehle, Christian A. Kell: Endogenous Modulation of Human Visual Cortex Activity Improves Perception at Twilight, in: Nature Communications http://dx.doi.org/10.1038/s41467-018-03660-8
Information: Privatdozent Dr. Christian Kell, Brain Imaging Center der Goethe-Universität, Cognitive Neuroscience Group, Fachbereich Medizin, Campus Niederrad, Tel: (069) 6301 5739; email@example.com.