For a clear picture please hold your breath – Gentle diagnostics make early-stage heart disease visible
FRANKFURT. By no means are only elderly people at risk from heart diseases. Physically active individuals can also be affected, for example if a seemingly harmless flu bug spreads to the heart muscle. Should this remain undetected and if, for example, a builder continues with his strenuous job or an athlete carries on training, this can lead to chronic inflammation and in the worst case even to sudden death. The latest issue of the “Forschung Frankfurt” journal describes how modern non-invasive examinations using state-of-the-art imaging technology can reduce such risks.
Professor Eike Nagel and his 12 coworkers at the Institute for Experimental and Translational Cardio Vascular Imaging of Goethe University Frankfurt are developing better ways to predict and diagnose heart diseases. In recent years, the researchers have taken the lead in the development of a procedure that is still very new in heart scans. Nagel explains the advantages: “With the help of magnetic resonance imaging, we can look right inside the heart muscle.” Blood flow to the heart muscle is visualized and shows whether there are any constrictions of the arteries supplying the heart. Experts can also spot whether the heart muscle is scarred, inflamed or displays any other anomalies.
The comparatively fast method makes it possible to examine patients at an early stage and may prevent cardiac insufficiency or even a heart attack. “Diseases such as HIV, kidney damage, rheumatic diseases or tumours often affect the heart either directly or as a side effect of therapy,” says Nagel, describing groups potentially at risk. The cardiologist is convinced: “Nowadays we can treat or even cure so many diseases, but the heart suffers too and this should be carefully monitored as it mostly remains undetected.”
MRI is a non-invasive and gentle examination technique, which is less risky but just as efficient as an examination using a conventional heart catheter, where a thin tube is pushed in the direction of the heart through an artery. Nagel’s research group was recently able to demonstrate this in a large international multi-centre study that was met with international acclaim.
The Institute for Experimental and Translational Cardio Vascular Imaging also has state-of-the-art computer tomography equipment at its disposal that can produce three-dimensional images of the heart. These especially reveal calcium deposits and plaques in the artery walls which could rupture and trigger a sudden heart attack. “This allows us to determine the risk of a heart attack and the need for therapy fast and at an early stage, which can then be non-invasive,” says Nagel. Which technique is best for which patient is one of the research topics Nagel’s group is evaluating. In some patients, both may be needed and the Institute is optimally equipped to answer most aspects of heart disease thanks to its deep insight into the heart.
Nagel finds these rapid advances in imaging over the last decades fascinating: “Nowadays we can spot the slightest changes and literally get a clear picture of the heart’s condition.”
Many further articles on “Image and Imagery” can be found in the current issue of “Forschung Frankfurt” and show the fascinating use of image material in scientific applications.
Images and captions can be downloaded from: www.uni-frankfurt.de/69481709
Further information: Professor Eike Nagel, Institute for Experimental and Translational Cardio Vascular Imaging, University Hospital Frankfurt, Department of Medicine III / Cardiology (House 23 A), Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Tel.: +49-(0)69-6301-87200, Eike.Nagel@kgu.de
Journalists can order the current issue of “Forschung Frankfurt” free of charge from Helga Ott, firstname.lastname@example.org.
“Forschung Frankfurt” subscriptions: http://tinygu.de/ff-abonnieren
Study at Goethe University Frankfurt: In intelligent persons, some brain regions interact more closely, while others de-couple themselves
FRANKFURT. Differences in intelligence have so far mostly been attributed to differences in specific brain regions. However, are smart people’s brains also wired differently to those of less intelligent persons? A new study published by researchers from Goethe University Frankfurt (Germany) supports this assumption. In intelligent persons, certain brain regions are more strongly involved in the flow of information between brain regions, while other brain regions are less engaged.
Understanding the foundations of human thought is fascinating for scientists and laypersons alike. Differences in cognitive abilities – and the resulting differences for example in academic success and professional careers – are attributed to a considerable degree to individual differences in intelligence. A study just published in “Scientific Reports” shows that these differences go hand in hand with differences in the patterns of integration among functional modules of the brain. Kirsten Hilger, Christian Fiebach and Ulrike Basten from the Department of Psychology at Goethe University Frankfurt combined functional MRI brain scans from over 300 persons with modern graph theoretical network analysis methods to investigate the neurobiological basis of human intelligence.
Already in 2015, the same research group published a meta-study in the journal “Intelligence”, in which they identified brain regions – among them the prefrontal cortex – activation changes of which are reliably associated with individual differences in intelligence. Until recently, however, it was not possible to examine how such ‘intelligence regions’ in the human brain are functionally interconnected.
Earlier this year, the research team reported that in more intelligent persons two brain regions involved in the cognitive processing of task-relevant information (i.e., the anterior insula and the anterior cingulate cortex) are connected more efficiently to the rest of the brain (2017, “Intelligence”). Another brain region, the junction area between temporal and parietal cortex that has been related to the shielding of thoughts against irrelevant information, is less strongly connected to the rest of the brain network. “The different topological embedding of these regions into the brain network could make it easier for smarter persons to differentiate between important and irrelevant information – which would be advantageous for many cognitive challenges,” proposes Ulrike Basten, the study’s principle investigator.
In their current study, the researchers take into account that the brain is functionally organized into modules. “This is similar to a social network which consists of multiple sub-networks (e.g., families or circles of friends). Within these sub-networks or modules, the members of one family are more strongly interconnected than they are with people from other families or circles of friends. Our brain is functionally organized in a very similar way: There are sub-networks of brain regions – modules – that are more strongly interconnected among themselves while they have weaker connections to brain regions from other modules. In our study, we examined whether the role of specific brain regions for communication within and among brain modules varies with individual differences in intelligence, i.e., whether a specific brain region supports the information exchange within their own ‘family’ more than information exchange with other ‘families’, and how this relates to individual differences in intelligence.”
The study shows that in more intelligent persons certain brain regions are clearly more strongly involved in the exchange of information between different sub-networks of the brain in order for important information to be communicated quickly and efficiently. On the other hand, the research team also identified brain regions that are more strongly ‘de-coupled’ from the rest of the network in more intelligent people. This may result in better protection against distracting and irrelevant inputs. “We assume that network properties we have found in more intelligent persons help us to focus mentally and to ignore or suppress irrelevant, potentially distracting inputs,” says Basten. The causes of these associations remain an open question at present. “It is possible that due to their biological predispositions, some individuals develop brain networks that favor intelligent behaviors or more challenging cognitive tasks. However, it is equally as likely that the frequent use of the brain for cognitively challenging tasks may positively influence the development of brain networks. Given what we currently know about intelligence, an interplay of both processes seems most likely.”
Publication: Hilger, K., Ekman, M., Fiebach, C., & Basten, U. (2017). Intelligence is associated with the modular structure of intrinsic brain networks. Scientific Reports. (DOI:10.1038/s41598-017-15795-7)
Basten, U., Hilger, K., & Fiebach, C. J. (2015). Where smart brains are different: A quantitative meta-analysis of functional and structural brain imaging studies on intelligence. Intelligence, 51, 10-27.
Hilger, K., Ekman, M., Fiebach, C., & Basten, U. (2017). Efficient hubs in the intelligent brain: Nodal efficiency of hub regions in the salience network is associated with general intelligence. Intelligence, 60, 10-25.
Contact Information: Dr. Ulrike Basten, email@example.com, see also Laboratory for Neurocognitive Psychology, Department of Psychology, Goethe University Frankfurt, Germany; http://fiebachlab.org
Theoretician at Goethe University Frankfurt calculates effect of magnetic sails
FRANKFURT. With a miniaturised space probe capable of being accelerated to a quarter of the speed of light we could reach Alpha Centauri, our nearest star, in about 20 or up to 50 years. However, without a mechanism to slow it down the space probe could only collect data from the star and its planets as it would zoom past. A theoretical physicist at Goethe University Frankfurt has now examined whether interstellar spacecrafts can be decelerated using “magnetic sails”.
For a long time, the idea of sending unmanned space probes through the depths of interstellar space to distant stars was purely utopian. Recent research on new concepts - amongst others within the “Breakthrough Starshot” project – has shown that miniaturised space probes could be accelerated by means of powerful lasers. Slowing them down again seems more challenging, since they cannot be fitted with braking systems for weight reasons. However, according to Professor Claudius Gros from the Institute for Theoretical Physics at Goethe University Frankfurt, it would be possible to decelerate at least comparatively slow space probes with the help of magnetic sails.
“Slow would mean in this case a travel velocity of 1,000 kilometres per second, which is only 0.3 percent of the speed of light, but nevertheless about 50 times faster than the Voyager spacecraft,” explains Gros. According to Gros’ calculations, we require a magnetic sail in order to transfer the spacecraft’s momentum to the interstellar gas. The sail consists in a large, superconducting loop with a diameter of a about 50 kilometres. A lossless current induced in this loop then creates a strong magnetic field. The ionised hydrogen in the interstellar medium is then reflected off the probe’s magnetic field, slowing it down gradually. This concept works, as Gros was able to show, despite the extremely low particle density of interstellar space (0.005 to 0.1 particles per cubic centimetre).
Gros’ research shows that magnetic sails can decelerate ‘slow’ spacecrafts weighing up to 1,500 kilograms. However, the journey would take historical periods of time, for example about 12,000 years to reach the seven known planets of the TRAPPIST-1 system. Surprisingly, slower cruising probes of the size of a car could be launched by the same laser which would allow to send, according to current planing, high-speed space probes weighing just a few gram to Alpha Centauri.
Missions to distant stars taking thousands of years are out of the question for exploratory missions. But the situation is quite different in cases where the cruising time is irrelevant, such as missions that open up alternative possibilities for terrestrial life. Such missions, like Gros proposed in 2016 under the name of ‘The Genesis Project’, would carry single-celled organisms, either as deep-frozen spores or encoded in a miniaturised gene laboratory. For a Genesis probe, it is not the time of arrival which is important, but the possibility to decelerate and then orbit the target planet.
Publications: Claudius Gros: Universal scaling relation for magnetic sails: momentum braking in the limit of dilute interstellar media, Journal of Physics Communications 1, 045007 (2017)
Claudius Gros: Developing Ecospheres on Transiently Habitable Planets: The Genesis Project, in: Astrophysics and Space Science 361, 324 (2016)
Further information: Professor Claudius Gros, Faculty of Physics, Institute for Theoretical Physics, Riedberg Campus, phone: +49(0)69-798 47818, email: gros07[@]itp.uni-frankfurt.de
New Scientist, 13 November 2017: Should we seed life through the cosmos using laser-driven ships?
Biochemist Christian Münch awarded Emmy Noether grant of the German Research Foundation
FRANKFURT. Misfolded proteins cause many diseases including neurodegenerative conditions and cancer. To protect themselves from protein misfolding, cells have developed sophisticated quality control mechanisms. How these function in the case of protein misfolding in mitochondria is now the subject of research currently being conducted by Dr. Christian Münch at the Institute of Biochemistry II of Goethe University Frankfurt. The German Research Foundation is supporting his work with an Emmy Noether grant of up to € 2 million.
The misfolding of single or several cellular proteins is a constant danger. Even just a slight rise in body temperature is sufficient to disrupt the folding balance in cells. If this occurs in mitochondria, the cell’s usual control mechanisms do not come into action because the small organelles, also known as the cell’s “powerhouses”, are separated from the rest of the cell by two membranes. They therefore need their own control mechanisms to safeguard mitochondrial protein folding.
That is why mitochondria, when their proteins fail to fold correctly, activate a stress response which attempts to correct this folding. By activating certain genes in the cell nucleus, they induce the production of proteins that support folding in the mitochondria. “Especially in the case of mammalian cells, little is known about how information about misfolded mitochondrial proteins is relayed to the cell nucleus,” explains Dr. Christian Münch.
The research group, which Münch is currently building up with the help of the funds approved by the German Research Foundation, aims also to investigate how the stress response acts under chronic conditions and how programmed cell death is triggered if protein folding cannot be reinstated. The researchers hope in this way to discover which role these processes play in diseases and whether they can be modified for therapeutic purposes.
Dr. Münch studied biochemistry in Tübingen and Munich and completed his doctoral degree at Cambridge University, England, in 2011. He then spent several years as a researcher at Harvard Medical School in the USA. He has been a group leader at the Institute of Biochemistry II of the Faculty of Medical Science at Goethe University Frankfurt since December 2016.
In the framework of the Emmy Noether Programme, the German Research Foundation sponsors outstanding junior researchers so that they can lead their own independent junior research group and qualify for a university teaching career. The programme also especially endeavours to recruit excellent early career researchers back from abroad.
A photograph of Christian Münch can be downloaded under: www.uni-frankfurt.de/69177152 (Photo: Uwe Dettmar)
Further information: Dr. Christian Münch, Institute of Biochemistry II, Faculty of Medical Science, Niederrad Campus, Tel.: +49(0)69-6301-6599, firstname.lastname@example.org.
Publication in "Nature": Decision-making in immune response solved
FRANKFURT. Social media have become an indispensable part of our everyday life. We use them constantly to screen the latest news and share pre-selected information. The cells in our body do a similar thing. Information is pre-selected and transmitted to the immune system in order to fight against unwelcome invaders, such as viruses, bacteria, parasites or cancer. This pre-selection occurs by means of a highly complex molecular machine. Biochemists at Goethe University Frankfurt and the Max Planck Institute of Biophysics, in cooperation with researchers at Martin Luther University Halle-Wittenberg, have now unveiled the inner workings of this complex molecular machine.
Status updates of each cell are transmitted from the cell’s interior to the immune system in the form of small protein fragments. These fragments are presented on the cell surface by specific proteins, known as MHC-I molecules. Cancerous or infected cells can thus be quickly identified and eliminated. However, viruses and tumours can also trick the immune system and in so doing escape immune surveillance. In addition, ambiguous messages can lead to autoimmune diseases or chronic inflammation.
That is why it is particularly important to understand how this highly complex molecular machine in the cell’s interior selects the relevant protein fragments and coordinates the loading of MHC-I molecules. In the current issue of the renowned scientific journal NATURE, the researchers from Frankfurt and Halle provide first insights into the molecular architecture and inner workings of what is referred to as the MHC-I peptide-loading complex.
“We had to pull out all the stops to prepare this extremely fragile complex for structural analyses,” explains Dr. Simon Trowitzsch of the Institute of Biochemistry at Goethe University Frankfurt. “First of all, we expanded our biochemical toolbox and developed a viral molecular bait that allowed us to isolate the native MHC-I peptide-loading complex from the endoplasmic reticulum.”
“Thanks to groundbreaking advances in cryo-electron microscopy, which were recently awarded the Nobel Prize, we were able to look closely at the MHC-I peptide-loading complex - which is about a hundred thousand times smaller than a pinhead - and to determine its molecular structure,” reports Dr. Arne Möller from the Max Planck Institute of Biophysics.
The scientists can now deduce how the cell manages to generate information important for the immune system. Its structure shows how transport proteins in the membrane, folding enzymes and MHC-I molecules are working together precisely within a highly dynamic complex.
“Our research shows how the MHC-I peptide-loading complex filters out only those fragments of information which are actually needed by the immune system’s effector cells. These findings have solved a decades-old puzzle and allow us now to describe the antigen selection process with greater precision. This knowledge will help to further improve immunotherapies,” concludes Professor Robert Tampé from the Institute of Biochemistry.
Publication: Andreas Blees, Dovilė Janulienė, Tommy Hofmann, Nicole Koller, Carla Schmidt, Simon Trowitzsch, Arne Moeller & Robert Tampé: Structure of the human MHC-I peptide-loading complex, NATURE (Nov 6, 2017, First Release) doi:10.1038/nature24627
A picture can be downloaded from: www.uni-frankfurt.de/69093715
Caption: Structure of the MHC-I peptide-loading complex in the membrane of the endoplasmic reticulum.
Image rights: Arne Möller (Max Planck Institute of Biophysics), Simon Trowitzsch and Robert Tampé (Goethe University Frankfurt)
Further information: Professor Dr. Robert Tampé and Dr. Simon Trowitzsch, Institute of Biochemistry, Faculty of Biochemistry, Chemistry and Pharmacy, Riedberg Campus, Tel.: +49(0)69-798-29475, Tel.: +49(0)69-798-29273, email@example.com, Trowitzsch@biochem.uni-frankfurt.de; Dr. Arne Möller, Max Planck Institute of Biophysics, Tel.: +49(0)69-6303-3057, firstname.lastname@example.org.