Press releases – June 2015

 

Jun 25 2015
11:51

Higher brain regions are only activated when predictions are false.

How does the brain recognize faces from minimal information?

FRANKFURT Our brain recognizes objects within milliseconds, even if it only receives rudimentary visual information. Researchers believe that reliable and fast recognition works because the brain is constantly making predictions about objects in the field of view and is comparing these with  incoming information. Only if mismatches occur in this process do higher areas of the brain have to be notified of the error in order to make active corrections to the predictions. Now scientists at the Goethe University have confirmed this hypothesis. As they report in the current edition of the "Journal of Neuroscience", those brain waves that are sent to higher brain areas increase their activity when a predictive error occurs. These results also promise a better understanding of schizophrenia and autism spectrum disorders.

In order to induce predictive errors in their subjects, the researchers showed them so-called Mooney faces, named after their inventor Craig Mooney. These are photographs of faces which have been reduced entirely to black and white. We usually recognize these easily. We can even give details about the gender, age and facial expression – despite the fact that only the borders between black and white contain any information about the face. Moreover, even this minimal amount of information is ambiguous, because the boundaries either represent the transition between light and cast shadows or they confine the object itself.

"In our study, we used Mooney faces which intentionally violated two expectations: Firstly, that we always see faces oriented upright, and secondly, that light comes from above. The facial recognition performance became noticably poorer and slower as a result", Prof. Michael Wibral from the Brain Imaging Center at the Goethe University explained.

What happens in the brain in this situation? The current theory, the "Predictive Coding" theory, suggests that signals only have to be sent to higher brain areas for processing if predictions aren't met. Thus an increase in signal activity towards higher brain areas should occur. However, there are also competing theories which predict the exact opposite.

Testing the theory directly only became possible recently, when Frankfurt scientists at the Strüngmann Institute discovered that brain wave activity at about 90 Hertz increases when signals are sent from lower to higher brain areas. "If a predictive error is induced by generating images which contradict the everyday visual reality learned over the course of a lifetime, then we should see an increase in brain wave activity at 90 Hertz in response to an error. We were able to confirm this experimentally", Wibral explained. "And we were also able to show that the intensity of these 'error brain waves' increases along with the time necessary for recognition. This shows that these brain waves don't just initiate a correction, but also play a causal role in our perception", Wibral continued. The results are important specifically because these brain waves also appear to be significantly impaired in patients with schizophrenia and autism spectrum disorders. This was shown through measurements taken in the laboratory of the Frankfurt Brain Imaging Centre over the past few years. The researchers are now hoping to gain a better understanding of both illnesses and to find ways of helping patients to correct their predictive errors more effectively.

Publication
Alla Brodski, Georg-Friedrich Paasch, Saskia Helbling, and Michael Wibral: The Faces of Predictive Coding, in: Journal of Neuroscience, 17 June 2015 • 35(24):8997–9006 • 8997, DOI: 10.1523/JNEUROSCI.1529-14.2015;

Information: Prof. Michael Wibral, MEG Labor, Brain Imaging Center, Klinikum der Goethe Universität, Tel.: +49(0)69 6301 83193, Wibral@bic.uni-frankfurt.de.

An image for downloading is available here: www.uni-frankfurt.de/56080403

Caption: The black and white transitions which indicate shadow borders (red arrow) and those which are object edges (green arrow) are marked on the left Mooney face. The middle image shows an upside-down image lit from above, while the image on the right is inverted and lit from below.

 

Jun 10 2015
13:06

Luminescent blue boron-containing nanographenes are highly promising materials for portable electronic devices

New boron compounds for organic light-emitting diodes (OLEDs)

FRANKFURT. Major advances in the field of organic electronics are currently revolutionising previously silicon-dominated semiconductor technology. Customised organic molecules enable the production of lightweight, mechanically flexible electronic components that are perfectly adapted to individual applications. Chemists at the Goethe University have now developed a new class of organic luminescent materials through the targeted introduction of boron atoms into the molecular structures. The compounds described in the professional journal "Angewandte Chemie" (Applied Chemistry) feature an intensive blue fluorescence and are therefore of interest for use in organic light-emitting diodes (LED's).
 
Carbon in the form of graphite conducts the electrical current in a similar way to a metal. In addition, its two-dimensional shape, the graphene layer, has extremely attractive optical and electronic properties. In graphene, the discoverers of which were awarded the Nobel Prize for Physics in 2010, countless benzene rings are fused to form a honeycomb structure. Sections of this structure, so-called nanographenes or Polycyclic Aromatic Hydrocarbons (PAHs), constitute an important basis of organic electronics.

"For a long time, efforts were largely focused on affecting the properties of nanographenes by chemically manipulating their edges", according to Prof. Matthias Wagner of the Institute for Inorganic and Analytical Chemistry at the Goethe University. "However, in recent years, researchers have been increasingly capable of also modifying the inner structure by embedding foreign atoms in the carbon network. This is where boron assumes crucial significance."

A comparison of the new boron-containing nanographenes with the analogous boron-free hydrocarbons verifies the fact that the boron atoms have a decisive impact on two key properties of an OLED luminophore: the fluorescence colour shifts into the highly desirable blue spectral range and the capacity to transport electrons is substantially improved. To date, only limited use could be made of the full potential of boron-containing PAHs, since most of the exponents are sensitive to air and moisture. "This problem does not occur with our materials, which is important with regard to practical applications" explains Valentin Hertz, who synthesised the compounds within the scope of his doctoral dissertation.

Hertz and Wagner anticipate that materials such as the graphene flakes they have developed will be particularly suitable for use in portable electronic devices. As film displays for future generations of smartphones and tablets, even large-scale screens could be rolled up or folded to save space when the devices are not in use.


Publication
V. Hertz et al: Boron-Containing PAHs: Facile Synthesis of Stable, Redox-Active Luminophores, in: Angew. Chem. Int. Ed. 2015, DOI: 10.1002/anie.201502977;
http://onlinelibrary.wiley.com/doi/10.1002/anie.201502977/abstract

Information
Prof. Dr. Matthias Wagner, Institute for Anorganic and Analytic Chemistry, Riedberg Campus, Tel.: +49 (0) 69 798-29156, Matthias.Wagner@chemie.uni-frankfurt.de

 

Jun 3 2015
13:37

Frankfurt scientists discover new molecular mechanisms that eliminate intracellular damages – Mutations in this pathway trigger neurodegenerative diseases

Controller in the Cell

FRANKFURT. Quality control is important – this is not only applicable to industrial production but also true for all life processes. However, whereas an enterprise can start a large-scale recall in case of any doubt, defects in the quality control systems of cells are often fatal. This is seen in particular in neurodegenerative diseases such as Alzheimer's, Parkinson's, or amyotrophic lateral sclerosis (ALS), in which fundamental mechanisms of cellular quality control fail.

A Frankfurt research team led by Ivan Dikic, Professor for Biochemistry, now successfully decoded  molecular details enabling a better understanding  of two neurodegenerative diseases. Their work focuses on "autophagy" as a central element of cellular quality control. Autophagy literally means "self-eating", and refers to a sophisticated system in which cellular waste is specifically detected, surrounded by membranes, and removed. Typical targets are harmful or superfluous proteins or cell organelles, even pathogens such as bacteria or viruses can be eliminated via this pathway.

Together with colleagues from Jena, Aachen, and The Netherlands, the team of Ivan Dikic has now identified a new autophagy receptor, the so-called FAM134B protein. In the online issue of the renowned journal Nature, the researchers report a new function of FAM134B in the constant renewal of the endoplasmic reticulum (ER), an important cell organelle. FAM134B  ensures proper breakdown and disposal of dysfunctional ER.
"Too little FAM134B leads to an uncontrolled dilation and expansion of this organelle, which is harmful for the cell", explains Ivan Dikic. "The discovery of FAM134B as a new autophagy receptor is already a milestone. Even more exciting is the connection to a rare neuronal hereditary disease". Collaborators from the Human Genetics Department at the University Hospital of Jena, PD Ingo Kurth and Professor Christian Hübner, already demonstrated in 2009 that mutations in FAM134B cause the death of sensory neurons in a disorder called hereditary sensory and autonomic neuropathy type II (HSAN II). The exact function of FAM134B, however, remained unknown until now.

HSAN II is a very rare hereditary disease in which both pain and temperature sensitivity and perspiration are impaired. For example, affected patients burn and hurt themselves easily, because they cannot feel heat and pain signals. Mutation of FAM134B in a mouse model leads to a similar syndrome "The mutated protein cannot function as a receptor. With these discoveries we have taken a big step to understanding the molecular causes of this neuropathy. At the same time, the importance of autophagy in cellular quality control is underlined", explains Dikic.

His laboratories at the Institute for Biochemistry II (IBC II) and at the Buchmann Institute for Molecular Life Sciences (BMLS) recently participated in another groundbreaking study of a neurodegenerative disease, ALS. Typically, ALS leads to death after three to four years due to the massive loss of motor neurons ALS (Amyotrophic lateral sclerosis ) is a devastating disease characterized by loss of motor neurons and neurodegeneration, usually leading to death within 3-4 years. Despite being classified as rare disease, public awareness is very high, fueled by celebrity patients like Stephen Hawking and culminating in last years’ Ice Bucket Challenge, the first charity campaign with global impact. Still, there is no treatment for ALS, despite intensive research in the field.   

As reported in the title story of Nature Neuroscience’s May issue, an international team has now progressed significantly in understanding gene defects responsible for ALS. The scientists discovered that mutations in a specific enzyme, Tank-binding kinase (TBK1), occur more frequently in families with ALS. The Dikic lab was particularly involved in clarifying the function of TBK1 and was able to show that the mutations found in patients interrupt the interaction of TBK1 with the autophagy receptor optineurin. Optineurin is involved, for example, in the elimination of aggregated proteins and bacterial infection defense. Co-lead author Dr. Benjamin Richter comments: " For me as a medical doctor working in basic science this story represents the ideal case of explaining the pathophysiology of a disease by a collaborative effort across disciplines. ".

"The two studies show in an unparalleled way how general concepts can be developed from individual findings", emphasizes Ivan Dikic. When cellular quality control in neurons fails over a long time, the consequences for the overall organism are disastrous. "Autophagy has crystalized as a common central mechanism of cellular quality control in neurodegenerative disease", says Dikic.

Ivan Dikic (49) is leading his lab at the Goethe University in Frankfurt am Main since 2002; he is the director of Institute for Biochemistry II since 2009; and was the  Founding Director of the Buchmann Institute for Molecular Life Sciences at the Riedberg Campus. Born in Croatia, he studied medicine in Zagreb, followed by a doctorate in natural sciences at the University of New York and the establishment of his first independent research group at the Ludwig Institute for Cancer Research in Uppsala (Sweden). In 2013, he received the Leibniz Prize of the German Research Foundation (DFG), the most prestigious German scientific prize. Furthermore, he has been honored with numerous other awards, including the Ernst Jung Prize for Medicine (2013), the William C. Rose Award of the American Society for Biochemistry and Molecular Biology (2013), and the German Cancer Prize (2010). He is a member of the German National Academy of Sciences and EMBO (European Molecular Biology Organisation) In 2010 he won an advanced investigator grant from the European Research Council (ERC), and he is the spokesperson for the LOEWE focus project Ubiquitin Networks, in the context of which parts of the now published work were done.

Image for download:
www.uni-frankfurt.de/55863443

Publications:
A. Khaminets et al.: Regulation of endoplasmic reticulum turnover by selective autophagy. Nature, doi: 10.1038/nature14498, Advance Online Publication (AOP): http://www.nature.com/nature

A. Freischmidt et al.: Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia Natur Neuroscience, Nature Neuroscience
18,
631–636
(2015),
doi:10.1038/nn.4000http://www.nature.com/neuro/journal/v18/n5/full/nn.4000.html

Contact: Prof. Dr. Ivan Dikic, Goethe-Universität Frankfurt, Phone +49 (0)69 6301 5964, Email: dikic@biochem2.uni-frankfurt.de