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German-American team of researchers finds neurophysiological correlates for cognitive and emotional symptoms in a Schizophrenia mouse model
Schizophrenia is not only associated with positive symptoms such as hallucinations and delusions, but also with negative symptoms e.g. cognitive deficits and impairments of the emotional drive. Until now, the underlying mechanisms for these negative symptoms have not been well characterized. In the current edition of the Proceedings of the National Academy of Sciences (PNAS) a German-American team of researchers, with the cooperation of the Goethe University, reports that a selective dopamine midbrain population that is crucial for emotional and cognitive processing shows reduced electrical in vivo activity in a disease mouse model.
Schizophrenia is a severe and incurable psychiatric illness, which affects approximately one percent of the world population. While acute psychotic states of the disease have been successfully treated with psychopharmaceutical drugs (antipsychotic agents) for many decades, cognitive deficits and impairments of motivation do not respond well to standard drug therapy. This is a crucial problem, as the long-term prognosis of a patient is determined above all by the severity of these negative symptoms. Therefore, the shortened average life-span of about 25 years for schizophrenia patients remained largely unaltered in recent decades.
"In order to develop new therapy strategies we need an improved neurobiological understanding of the negative symptoms of schizophrenia" explains Prof. Roeper of the Institute for Neurophysiology of the Goethe University. His American colleagues, Prof. Eleanor Simpson and Prof. Eric Kandel at Columbia University in New York recently made an important initial step in this direction. They created a new transgenic mouse model based on striatal overexpression of dopamine typ 2 receptors, which displayed typical signs of cognitive and emotional negative symptoms similar to those occurring in patients with schizophrenia. The researchers detected typical impairment in working memory with corresponding neurochemical changes in dopamine in the prefrontal cortex. However, the underlying neurophysiological impairments of dopamine neurons remained unresolved.
Now, Prof. Eleanor Simpson and Prof. Jochen Roeper, in cooperation with the mathematician Prof. Gaby Schneider of the Goethe University and the physiologist Prof. Birgit Liss of the University of Ulm have succeeded in defining the neurophysiological impairments with the dopamine system. They were able to show, with single cell recordings in the intact brain of mice, that those dopamine midbrain neurons responsible for emotional and cognitive processing displayed altered patterns and frequencies of electrical activity. In contrast, adjacent dopamine neurons, which are involved in motor control, were not affected.
The researchers were also able to show that – in line with the persistence of cognitive deficits in mice and patients– the pathological discharge patterns of dopamine neurons persisted even after the causal transgene had been switched off in adult mice. "This result emphasizes the presence of a critical early phase for the development of cognitive deficits in schizophrenia" according to Roeper. He and his colleagues are currently examining how the neuronal activity of dopamine neurons changes during the working memory tasks. "Our results show that altered neuronal activity of selective dopamine neurons is crucial for schizophrenia", Jochen Roeper summarises the importance of the research work.
Krabbe et al.: Increased dopamine D2 receptor activity in the striatum alters the firing pattern of dopamine neurons in the ventral tegmental area, in PNAS 9.2.2015, www.pnas.org/cgi/doi/10.1073/pnas.1500450112
Information: Prof. Jochen Roeper, Institute for Neurophysiology, Campus Niederrad, Tel.: +49 (0)69 6301-84091, email@example.com.
The Volkswagen Foundation provides room for thought: The Frankfurt sociologist Thomas Lemke writes his "Magnum Opus"
FRANKFURT. Frankfurt Professor of Sociology, Thomas Lemke, has received funding from the Volkswagen Foundation for his "Magnum Opus". For the 51-year old scientist, who has dedicated himself to the subject of "Biotechnology, Nature and Society" for many years, this means eighteen months of freedom to devote himself solely to a larger scientific work. He already has a working title for his "Magnum Opus": "The Government of Things. Foundations and Perspectives of New Materialism". In his book, Lemke intends to examine the exploratory and innovative potential of New Materialism with a critical eye, and to take a systematic approach to this new area of research for the first time.
As part of its sponsorship programme, the Foundation will fund Lemke's substitute professor. This means that not only will the Professor benefit, but also Dr. Eva Sänger, who has just completed a research project in the Faculty of Social Sciences on the role of ultrasound images in prenatal diagnostics, funded by the German Research Association. During the upcoming summer semester, she will be lecturing to students on topics covering science and technology studies, medical sociology and feminist theory.
In his major work, Lemke wants to pick up on a striking new approach and a shift of emphasis that he has observed for some years in the Humanities and Social Sciences, and which has been given the term "New Materialism". "The hallmark of this materialism is that the concepts of self-organization and agency, which were traditionally reserved for human beings, have been extended to non-human entities", explains Lemke. By entities, philosophers and sociologists are referring to something that exists; an entity, which can be a tangible or abstract object. "It can be observed that things, artefacts and objects, are being increasingly debated and newly conceptualised." Whether it is stem cells, computers or the internet: they are all viewed as a hybrid between dead matter and living beings, between the factual and the normative.
The sociologist comments on his extensive project: "For me, on the one hand it is about exploring the differences compared to earlier versions of materialism, while on the other hand looking at the unsolved theoretical tensions and conceptual ambiguities of this research perspective." However, his aim is ultimately to achieve more than just to compile a critical inventory of the current situation within New Materialism. "My thesis is that within the idea of a "Government of Things", which occurs in the work of the French philosopher and historian, Michel Foucault, there are also elements of a post-humanist and relational concept of materialism, which could be usefully developed." In this sense, there are no "things as such", but instead things and their limitations are only created through interactive relationships, and human behaviour depends entirely on certain enabling conditions, devices and material arrangements.
The book will consider and expand on this historically informed and empirically oriented perspective, moving it towards that which Foucault refers to as the "intrication of men and things". Lemke adds: "To that end I intend to identify systematic links between Foucault's analysis of government and insights from science and technology studies." The conceptual suggestion of a "Government of Things", according to Lemke, avoids the narrow understanding of a concept of government focussed purely on human beings and furthermore aims to make a substantial contribution to a materialistic analysis of political processes and structures.
Since his appointment in 2008, Lemke has led a series of projects, funded by third parties, including an international collaborative research project on the social and political implications of the use of DNA analysis in immigration procedures in various European states. He has also been heavily involved in the University's own administration. Lemke was Managing Director of the Institute for the Basic Principles of Social Sciences and Vice-Dean of the Faculty of Social Sciences. The profile of Lemke fits perfectly with the "Magnum Opus" programme of the Volkswagen Foundation. The aim of this initiative is to provide professors from the Humanities and Social Sciences, who have proved themselves through outstanding work, with the freedom to focus all their attention on challenging scientific work. The work of the Frankfurt sociologist was first recognised by the Volkswagen Foundation in 2008. Lemke's book "The Genetic Police. Forms and Fields of Genetic Discrimination" received translation funding from the Foundation and is now also available in an extended English version.
Thomas Lemke studied Political Science, Sociology and Law in Frankfurt, Southampton and Paris and in 1996 earned his doctorate at the Goethe University with a thesis on Michel Foucault's concept of power. Following his doctorate, Lemke worked as an Assistant Professor at the Faculty of Economic and Social Sciences at the University of Wuppertal, where he habilitated in 2006. For many years he worked at the Institute for Social Research in Frankfurt, and as a visiting researcher at Goldsmiths College in London and at New York University. Lemke also held visiting professorships at the Copenhagen Business School and the University of New South Wales in Sydney. In 2007 he was awarded a Heisenberg scholarship from DFG, which was converted into a Heisenberg professorship one year later. Since September 2008, Thomas Lemke has been Professor of Sociology with a focus on "Biotechnology, Nature and Society" at the Faculty of Social Sciences and since last year is also Honorary Professor at the University of New South Wales in Sydney.
In his research and his teaching, Lemke has primarily focussed on the conditions, context and consequences of bioscientific knowledge and biotechnical innovation. A major focus of his work was the analysis of genetic discourses and practices. He has published several books on the effects of genetic knowledge on self-image, health concepts and prevention policies, and together with his colleague, Katharina Liebsch, he produced the first systematic study of the practice of genetic discrimination in Germany.
Information: Prof. Dr. Thomas Lemke, Institute for Sociology, Faculty of Social Sciences, Westend Campus, Tel. (069) 798 36664, firstname.lastname@example.org, www.fb03.uni-frankfurt.de/45646661/tlemke?legacy_request=1
Photo available to download at: www.uni-frankfurt.de/53929509
Large structures for the rural extended family, small structures for the urban couple
FRANKFURT. European wild rabbits (Oryctolagus cuniculus) not only achieve high population densities in the city, their burrows are also built more densely and on a smaller external scale. That is something researchers in theGoetheUniversity's Task Force on Ecology and Evolution have discovered in their study on wild rabbit populations in and aroundFrankfurt. As they report in the advance version of the Journal of Zoology, small burrow structures with fewer entrances and exits predominate inFrankfurt's inner city. These structures are inhabited by few animals - often only pairs or single wild rabbits. In contrast to this, the structural systems in the rural environs ofFrankfurt are substantially larger and are also inhabited by larger social rabbit groups.
"The optimal habitat for a wild rabbit offers both, access to sufficient nourishment and the opportunity to establish rabbit burrows in very close proximity, or to seek out protective vegetation" explains doctoral candidate Madlen Ziege, a member of Prof. Bruno Streit's team. In rural, often agricultural used areas, with their cleared and open landscapes, these conditions are getting harder to find. Apparently, urban and suburban habitats satisfy the needs of wild rabbits far better.
In view of the fact that in some cities there is already talk of a "rabbit infestation", while in recent years the rabbit population in many rural areas of Germany has declined significantly, the scientists currently want to determine whether in the future urban populations could play a significant role as the source populations for the preservation of this wild animal species in Germany. They are therefore examining the population genetics or dynamics, their use of habitat and the state of health of rural, urban and suburban wild rabbit populations.
Link to the publication: http://onlinelibrary.wiley.com
You can find an image for the download at: www.uni-frankfurt.de/53984081
Caption: European wild rabbits Oryctolagus cuniculus in the inner city of Frankfurt.
Information: Madlen Ziege, Institute for Ecology, Evolution and Diversity, Campus Riedberg, tel.: 015773883101, email@example.com
A new DFG Research Unit looks at the behaviour of the mineral under high pressures and temperatures
FRANKFURT. Carbonates are the most important carbon reservoirs on the planet. But what role do they play in the Earth's interior? How do they react to conditions in the Earth's mantle? These are the questions being asked by a group of scientific researchers from Frankfurt, Bayreuth, Berlin/Potsdam, Freiberg and Hamburg, in a project funded by the DFG. The Research Unit brings together experts from various geoscience disciplines and cutting edge technology.
The Earth has an average radius of around 6,400 kilometers. However, the deepest borehole thus far drilled has only reached a depth of twelve kilometers. And even with huge technical advances, it is unthinkable that we will ever be able to carry out empirical research on the deepest layers, according to Björn Winkler, Professor of Crystallography at the Goethe University Frankfurt and coordinator of the new Research Unit. "We can only get an idea of the conditions in the Earth's interior by combining experiments and model calculations", he explains. While we already have detailed knowledge of silicates, which are a key component of the earth's mantle, very little research on carbonates has been done to date. "The composition of the earth can be explained without carbonates - but the question is, how well?", continues Winkler.
"Structures, Properties and Reactions of Carbonates at High Temperatures and Pressures" is the title of the project being funded by the DFG as of mid-February. "We want to understand how the Earth works", is the way Winkler describes the primary research goal of the approximately 30 scientists and their teams. What possibilities our planet has for storing carbon, how much carbon there actually is on the earth – the entire carbon cycle is still a complete mystery.
The research group, which combines seven individual projects, is focusing its attention on the Earth's mantle: the 2,850 kilometer thick middle layer in the internal structure of the earth. The aim is to come to a better understanding of the phase relationships, crystal chemistry and physical properties of carbonates. To that end, the plan is to simulate the conditions of the mantle transition zone and the lower earth mantle below it – namely very high temperatures and very high pressure. Each of the seven projects examines a different aspect; for example the carbonate calcite, or the combination of carbonates with iron or silicates, or the behavior of carbonates under shock.
Winkler and his team have been dealing with this issue for six years already. His colleague, Dr. Lkhamsuren Bayarjargal has already been awarded the Max-von-Laue Prize from the German Association of Crystallography for his work with high-power lasers, and has received funding from the Focus Program of the Goethe University. The nationwide collaboration among the researchers is not an entirely new phenomenon either. The DFG funding will enable them to build special equipment to simulate the conditions in the Earth's mantle. This research apparatus includes diamond anvil cells, capable of producing pressures a million times greater than atmospheric pressure, and high-power lasers that can generate temperatures of up to 5,000 degrees Celsius. Calculations have shown that these are the conditions that prevail in the Earth's mantle.
The tiniest amounts of a carbonate are enough for an experiment. During the experiment, the substance is exposed to the respective conditions while the researchers examine it for any changes. A variety of techniques are used for this, such as Raman spectroscopy in Frankfurt, and infrared spectroscopy in Potsdam. "If we come to the same conclusions using different methods, we will know that we have got it right", says Prof. Winkler.
Information: Prof. Dr. Björn Winkler, Faculty of Mineralogy, Institute for Geosciences, Riedberg Campus, Phone: (069) 798-40107, b.winkler@ kristall.uni-frankfurt.de.
Communication by bacteria as a therapeutic target for medicines.
FRANKFURT. Bacteria communicate by means of chemical signals and can develop common characteristics through this "agreement" and also develop their potential pathogenic effects in this way. Scientists working with Dr. Helge B. Bode, an Merck-endowed professor for molecular biotechnology at the Goethe University in Frankfurt, and Dr. Ralf Heermann from the department of microbiology at the Ludwig Maximilian University in Munich, have now described a hitherto unknown communication pathway that appears to be widely distributed. They report on this in the journal Proceedings of the National Academy of Science.
The investigation of bacterial communication is also of medical interest. This is because the bacterial communication pathways are a possible therapeutic target for new medicines. If the relevant communication options are prevented, the bacteria cannot develop their pathogenic properties. "When pathogens are no longer destroyed by antibiotics as we have seen to date, but rather be impaired beforehand the formation of the pathogenic properties, the danger of resistance development would be substantially reduced", says Bode.
Different types of bacteria also have different methods of communication. The team lead by Heerman and Bode had already discovered a new bacterial communication pathway in 2013. Now they have succeeded in decoding a further new and widely distributed chemical type of bacterial communication.
To date, the best known communication between bacteria occurs via the N-acyl homoserine lactone (AHL): The enzyme Luxl produces signals that are recognised by the LuxR receptor, at which point the bacteria develop certain properties and modulate their behaviour towards one another. Since a certain number of bacteria must be available for this to occur, this process is known as "quorum sensing".
However, Heermann's and Bode's working groups investigate bacteria that possess a LuxR receptor, but not the enzyme Luxl. In the current study, the microbiologists have investigated the bacteria Photorhabdus asymbiotica, which is a deadly pathogen in insects, which also infects humans and can cause skin infections. These bacteria communicate via the signal molecule dialkylresorcinol, which recognised the associated LuxR receptor. "The influence on the pathogenic properties of the bacteria is at its strongest in this 'quorum sensing' system. P. asymbiotica requires dialkylresorcinol and in this way coordinates the communication with the conspecifics for the successful infection of the larvae", says Helge Bode, whose group in 2013 also described the biosynthesis of this new signal molecule.
The researchers have not only investigated P. asymbiotica, but also a series of other bacterial genomes. The newly discovered signal pathway appears to be widely distributed. "We were able to identify several other bacteria that are pathogenic to humans that also do not express Luxl and also possess this ability for forming these signals", says Heerman.
Sophie Brameyer, Darko Kresovic, Helge B. Bode and Ralf Heermann:
Dialkylresorcinols as bacterial signaling molecules
In: PNAS 112 (2), 572-577.
Prof. Helge Bode, Merck endowed Professor for Molecular Biotechnology, Biosciences Department & Buchmann Institute for Molecular Life Sciences, Campus Riedberg, Tel.: (069) 798-29557, H.Bode@bio.uni-frankfurt.de.
Image can be downloaded at: www.uni-frankfurt.de/53683200
The insect larvae were infected with P. asymbiotica. Since the bacteria are bioluminescent, the larvae glow in the dark. The pathogenicity of organisms pathogenic to humans is frequently investigated in insect models. (Figure: Ralf Heermann, LMU).