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Scientists from the Goethe University (GU) Frankfurt, the European Molecular Biology Laboratory (EMBL) Heidelberg and the University of Zurich explain skin fusion at a molecular level and pinpoint the specific molecules that do the job in their latest publication in the journal Nature Cell Biology.

In order to prevent death by bleeding or infection, every wound (skin opening) must close at some point. The events leading to skin closure had been unclear for many years. Mikhail Eltsov (GU) and colleagues used fruit fly embryos as a model system to understand this process. Similarly to humans, fruit fly embryos at some point in their development have a large opening in the skin on their back that must fuse. This process is called zipping, because two sides of the skin are fastened in a way that resembles a zipper that joins two sides of a jacket.

The scientists have used a top-of-the-range electron microscope to study exactly how this zipping of the skin works. “Our electron microscope allows us to distinguish the molecular components in the cell that act like small machines to fuse the skin. When we look at it from a distance, it appears as if skin cells simply fuse to each other, but if we zoom in, it becomes clear that membranes, molecular machines, and other cellular components are involved", explains Eltsov.

“In order to visualize this orchestra of healing, a very high-resolution picture of the process is needed. For this purpose we have recorded an enormous amount of data that surpasses all previous studies of this kind”, says Mikhail Eltsov.

As a first step, as the scientists discovered, cells find their opposing partner by “sniffing” each other out. As a next step, they develop adherens junctions which act like a molecular Velcro. This way they become strongly attached to their opposing partner cell. The biggest revelation of this study was that small tubes in the cell, called microtubules, attach to this molecular Velcro and then deploy a self-catastrophe, which results in the skin being pulled towards the opening, as if one pulls a blanket over.

Damian Brunner who led the team at the University of Zurich has performed many genetic manipulations to identify the correct components. The scientists were astonished to find that microtubules involved in cell-division are the primary scaffold used for zipping, indicating a mechanism conserved during evolution.

“What was also amazing was the tremendous plasticity of the membranes in this process which managed to close the skin opening in a very short space of time. When five to ten cells have found their respective neighbors, the skin already appears normal”, says Achilleas Frangakis from the Goethe University Frankfurt, who led the study.

The scientists hope that their results will open new avenues into the understanding of epithelial plasticity and wound healing. They are also investigating the detailed structural organization of the adherens junctions, work for which they were awarded a starting grant from European Research Council (ERC).

The original publication

Nature Cell Biology: Quantitative analysis of cytoskeletal reorganisation during epithelial tissue sealing by large-volume electron tomography, Eltsov, Dubé, Yu, Pasakarnis, Haselmann-Weiss, Brunner and Frangakis, 2015, AOP 21 April 2015, DOI 10.1038/ncb3159

http://www.uni-frankfurt.de/55227362

Figure legend: Perspective view of the zipping area with 17 skin cells "zipping". Membranes are colored in shades of brown and green to discriminate individual skin cells coming from the left or the right. The cells expand various types of protrusions in all directions to find their respective neighbor.

If the skin cells are computationally removed the shaping of the cells underneath is visualized, with the sealing of the skin visible in the back.

Information: Prof. Achilleas Frangakis, Institute for Biophysics, Cluster of Excellence Macromelecular Complexes, Goethe University, Phone +49(0)69 798-46462, achilleas.frangakis@biophysik.org.

FRANKFURT.Optogenetics is a new field of research that introduces light-sensitive proteins into cells in a genetically targeted manner, for example, to obtain information on signalling pathways and the function of neurons in a living organism. A new priority program supported by the German Research Foundation (DFG) under the auspices of Goethe University has now set itself the goal of developing the next generation of optogenetic tools and expanding their application both in basic research and also for medical purposes. DFG will provide six million Euros in funding for the programme over the next three years.

"We see our role as a pathfinder, to build a scientific network for optogenetics in Germany," says Prof. Alexander Gottschalk, spokesperson for the priority programme "Next generation optogenetics: Tool development and applications". After an application phase in the autumn of 2015, between 30 and 40 scientists from different universities will become involved; primarily biophysicists, cell biologists, chemists, medical scientists, and "photo-biologists." These are the types of specialists who will search for new, light-sensitive proteins, which will be introduced into cells and act like light switches to turn cellular processes on and off.

"Optogenetics already has many applications in basic research, but as a technology it is still in its infancy," explains Gottschalk. In order to achieve more widespread use of optogenetics in cell biology and neurobiology, the researchers want to develop new optogenetic tools. These will have higher light sensitivity, clarify the processes within individual cells and between different cells, and ultimately also be tested in animal models. This is necessary, especially with regard to medical applications; for example, for the enabling treatment of certain vision and hearing impairments or aspects of previously incurable diseases, such as Parkinson’s disease, seizure disorders, or cardiac diseases.

The scientists are placing special importance on informing the public about the opportunities and risks of optogenetics. This will be done through intelligible presentations for the lay public, and through articles on websites such as www.OpenOptogenetics.org, http://dasgehirn.info, and the future website of the research programme.

Information: Prof. Alexander Gottschalk, Institute for Biochemistry, Campus Riedberg, Tel.: (069) 798-42518, a.gottschalk@em.uni-frankfurt.de.

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FRANKFURT/DARMSTADT. It has long been proven that people who follow a Mediterranean diet and keep physically and mentally active are less likely to suffer from dementia. Olives in particular appear to play a key role in this regard. But just what are the substances contained in these small, oval fruit that are so valuable? This is what a Hessen-based group of researchers from the Goethe University Frankfurt, the Technical University (TU) of Darmstadt and Darmstadt company N-Zyme BioTec GmbH intends to find out. The three-year project “NeurOliv” has a project volume of 1.3 million Euros and is funded by the Federal Ministry of Education and Research as part of the high-tech initiative "KMU-innovativ Biochance".

This collaboration combines a number of approaches, the initiative of which came from N-Zyme BioTec GmbH. The aim is to use substances contained in olives to develop new functional food for the ageing society, which will protect against Alzheimer’s disease. “We want to test whether olive polyphenols can even help to cure the disease. This is why we believe our products also relate to the pharmaceutical sector”, says Dr. Joachim Tretzel, Managing Director of N-Zyme BioTec GmbH. The high-tech initiative of the German government was set up to fund small and medium-sized enterprises.

The team, led by Prof. Heribert Warzecha of the Department of Biology of TU Darmstadt, is examining the development of new biotechnological processes designed to extract specific plant substances. With the relevant genetic information, bacterial cultures are said to help bring out substances in a pure and defined form. “Our new techniques make it easier to extract substances from olive leaves and significantly improve low yields“, explains Warzecha. “When it comes to production, this means we aren’t dependent on the seasonal harvesting of olives in growing areas”, adds Dr. Stefan Marx, also Managing Director of N-Zyme BioTec.

The “nutritional-neuroscience” working group of Dr. Gunter Eckert, food chemist and private lecturer at the Goethe University Frankfurt (GU), will test the effectiveness of these biotechnologically produced olive substances. Firstly, olive substances will be tested in cell culture models, which may protect against Alzheimer’s disease. “We focus on changes to the power houses of nerve cells (mitochondria), which change early on in Alzheimer’s disease”, says Eckert. The most active compounds should then demonstrate in a mouse model of the disease that they can improve brain function.
“We are testing the hypothesis that certain polyphenols from olives slow down disease processes in the brain, improve mitochondrial dysfunction and, as a result, provide evidence to suggest they protect against Alzheimer’s disease”, explains pharmacological expert Eckert, summarizing the objective of his research. GU researchers have been awarded funding of 288,000 Euros for the project. In another research project, Eckert is examining the relationship between diet and exercise with regard to the development of Alzheimer’s disease.

Download images from: www.uni-frankfurt.de/54645204

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FRANKFURT. The discovery of the soccer ball-shaped C₆₀ molecule in 1985 was a milestone for the development of nanotechnology. In parallel with the fast-blooming field of research into carbon fullerenes, researchers have spent a long time trying in vain to create structurally similar silicon cages. Goethe University chemists have now managed to synthesise a compound featuring an Si₂₀ dodecahedron. The Platonic solid, which was published in the "Angewandte Chemie" journal, is not just aesthetically pleasing, it also opens up new perspectives for the semiconductor industry. 

The Si₂₀ dodecahedron is roughly as large as the C₆₀ molecule. However, there are some crucial differences between the types of bonding: All of the carbon atoms in C₆₀ have a coordination number of three and form double bonds. In the silicon dodecahedron, in contrast, all atoms have a coordination number of four and are connected through single bonds, so that the molecule is also related to dodecahedrane (C₂₀H₂₀). "In its day, dodecahedrane was viewed as the 'Mount Everest' of organic chemistry, because it initially could only be synthesized through a 23- step sequence. In contrast, our Si₂₀ cage can be created in one step starting from Si₂ building blocks," explains Prof. Matthias Wagner of the Goethe University Institute of Inorganic and Analytical Chemistry.

The Si₂₀ hollow bodies, which have been isolated by his PhD student, Jan Tillmann, are always filled with a chloride ion. The Frankfurt chemists therefore suppose that the cage forms itself around the anion, which thus has a structure-determining effect. On its surface, the cluster carries eight chlorine atoms and twelve Cl₃Si groups. These have highly symmetric arrangements in space, which is why the molecule is particularly beautiful. Quantum chemical calculations carried out by Professor Max C. Holthausen's research group at Goethe University show that the substitution pattern that was observed experimentally indeed produces a pronounced stabilisation of the Si₂₀ structure. 

In future, Tillmann and Wagner are planning to use the surface-bound Cl₃Si anchor groups to produce three dimensional nanonetworks out of Si₂₀ units. The researchers are particularly interested in the application potential of this new compound: "Spatially strictly limited silicon nanoparticles display fundamentally different properties to conventional silicon wafers," explains Matthias Wagner. The long strived-for access to siladodecahedrane thus opens up the possibility of studying the fundamental electronic properties of cage-like Si nanoparticles compared to crystalline semiconductor silicon.

Publication:
J. Tillmann et al: One-Step Synthesis of a [20]Silafullerane with an Endohedral Chloride
Ion, in: Angew. Chem. Int. Ed. 2015, DOI: 10.1002/anie.201412050

Download an image from: http://www.muk.uni-frankfurt.de/54612947?

Information: Prof. Matthias Wagner, Institute for Anorganic and Analytic Chemistry, Campus Riedberg, phone: +49(069)798-29156, email: Matthias.Wagner@chemie.uni-frankfurt.de

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FRANKFURT.Are leaves and buds developing earlier in the spring? And do leaves stay on the trees longer in autumn? Do steppe ecosystems remaining green longer and are the savannas becoming drier and drier?  In fact, over recent decades, the growing seasons have changed everywhere around the world. This was determined by a doctoral candidate at the Goethe University as part of an international collaboration based on satellite data. The results are expected to have consequences for agriculture, interactions between species, the functioning of ecosystems, and the exchange of carbon dioxide and energy between the land surface and the atmosphere.  

"There is almost no part of the Earth that is not affected by these changes", explains Robert Buitenwerf, doctoral candidate at the Institute for Physical Geography at the Goethe University. He has evaluated satellite data from 1981 to 2012 with regard to 21 parameters on vegetation activity, in order to determine the point in time, the duration, and the intensity of growth from the northernmost conifer forests to tropical rain forests. His conclusion: On 54 percent of the land surface, at least one parameter of vegetation activity has moved away from the mean value by more than two standard deviations.

As reported by researchers from Frankfurt, Freiburg and New Zealand in the current edition of the professional journal "Nature Climate Change", leaves are now sprouting earlier in most of the climate zones of the far north. Although they are also dropped somewhat earlier in autumn, the overall vegetation period has grown longer. On the other hand, in our latitudes, trees and shrubs are losing their leaves later than they have up to now.

To date, not much research has been conducted on the regions of the southern hemisphere.  In those areas, the researchers found that in several savannas of South America, southern Africa and Australia, the vegetation activity has decreased during dry seasons. "Although these savannas have similar vegetation and comparable climates, the changes in vegetation activity differ. That may be attributable to the differences in the functioning of the respective ecosystems", says Buitenwerf.

In this respect, the seasonal distribution of leaf growth constitutes a sensitive indicator: it indicates how various ecosystems react to changes in the environment. "Although vegetation changes in the northern hemisphere have conclusively been attributed to climate change by other studies, attributing all the changes found in our study would require a more complex analysis," Buitenwerf emphasizes. In the northern hemisphere it has already been shown that species whose life cycles depend on the vegetation period are endangered by these severe changes.  Consequences for species in the southern hemisphere are as yet unclear.

Publication:
Robert Buitenwerf, Laura Rose and Steven I. Higgins: Three decades of multi-dimensional change in global leaf phenology, in: Nature Climate Change, March 2 2015,
DOI: 10.1038/NCLIMATE2533.

Information:
Robert Buitenwerf, Landcare Research, Lincoln, New Zealand. Tel: +6433219706, buitenwerfrobert@hotmail.com

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