Switching Brain Cells with Less Light

from

Bioengineer.org http://ift.tt/1dO6PPa

Networked nerve cells are the control center of organisms. In a nematode, 300 nerve cells are sufficient to initiate complex behavior. To understand the properties of the networks, re-searchers switch cells on and off with light and observe the resulting behavior of the organism. In the Science journal, sci-entists now present a protein that facilitates the control of nerve cells by light. It might be used as a basis of studies of diseases of the nervous system.

Nerve cells form networks that can process signals (Photo: J. Wietek/HU Berlin).

To switch a nerve cell with light, certain proteins forming ion chan-nels in the cell membrane are used. These proteins are called chan-nelrhodopsins. If light strikes the channels, they open and ions enter and render the cell specifically active or inactive. In this way, a very fine tool is obtained to study functions in the network of nerve cells. So far, however, large amounts of light have been required and only closely limited areas in the network could be switched. The ChlocC channelrhodopsin presented now reacts about 10,000 times more sensitively to light than other proteins used so far for switching off nerve cells.

“For the modification of the protein, we analyzed its structure on the computer,” Marcus Elstner, KIT, explains. The theoretical chemist and his team modeled the proteins that consist of about 5000 atoms. For this purpose, they used the highest-performance computers of KIT’s computing center, the Steinbuch Centre for Computing, SCC. Together with the protein environment, i.e. the cell membrane and cell water, about 100,000 atoms had to be considered for the computations that took several weeks. “It was found that ion conductivity of the channel is essentially based on three amino acids in the central region, i.e. on about 50 atoms in the channel only.” By exchanging the amino acids, scientists have now succeeded in increasing the sensitivity of the ion channel.

Light-activated ion channels, the so-called channelrhodopsins, from microalgae have been used since 2005. In neural sections or living transgenic model organisms, such as flies, zebrafish, or mice, they allow for the specific activation of selected cells with light. Thus, understanding of their role in the cell structure can be improved. This technology is known as optogenetics and applied widely. In the past years, it contributed to the better understanding of the biology of signal processing. So far inaccessible neural pathways were mapped and many relationships were discovered among proteins, cells, tissues, and functions of the nervous system.

Within the framework of the study reported in the latest Science issue, researchers from Karlsruhe, Hamburg, and Berlin developed the ion channels further. Jonas Wietek and Nona Adeishvili working in the team of Peter Hegemann at the Humboldt-Universität Berlin have succeeded in identifying the selectivity filter of the channelrho-dopsins and in modifying it such that negatively charged chloride ions are conducted. These chloride-conducting channels have been called ChlocC by the scientists. Hiroshi Watanabe from the team of Marcus Elstner, Karlsruhe Institute of Technology (KIT), computed ion distribution in the protein and visualized the increased chloride distribution. Simon Wiegert from the team of Thomas Oertner of the Center for Molecular Neurobiology, Hamburg, demonstrated that ChlocC can be introduced into selected neurons for the inactivation of the latter with very small light intensities similar to the processes taking place in the living organism. With ChloC a novel optogenetic tool is now available that can be used in neurosciences to study the switching of neural networks together with the already known light-activated cation channels that mainly conduct sodium ions and pro-tons. This fundamental knowledge might help better understand the mechanisms of diseases like epilepsy and Parkinson’s. In some years from now, this may give rise to therapy concepts, which might be much more specific than the medical drugs used today.

Story Source:

The above story is based on materials provided by Karlsruhe Institute of Technology, Monika Landgraf.

The post Switching Brain Cells with Less Light appeared first on Bioengineer.org.

Light-Based Chip Inspired by Our Brain

from

Bioengineer.org http://ift.tt/1jUzbtJ

In a recent paper in Nature Communications, researchers from Ghent University report on a novel paradigm to do optical information processing on a chip, using techniques inspired by the way our brain works.

Photo Credits: Photonics Research Group of the Department of Information Technology

- Prof. Dr. Peter Bienstman

Neural networks have been employed in the past to solve pattern recognition problems like speech recognition or image recognition, but so far, these bio-inspired techniques have been implemented mostly in software on a traditional computer. What UGent researchers have done is implemented a small (16 nodes) neural network directly in hardware, using a silicon photonics chip. Such a chip is fabricated using the same technology as traditional computer chips, but uses light rather than electricity as the information carrier. This approach has many benefits including the potential for extremely high speeds and low power consumption.

The UGent researchers have experimentally shown that the same chip can be used for a large variety of tasks, like arbitrary calculations with memory on a bit stream or header recognition (an operation relevant in telecom networks: the header is an address indicating where the data needs to be sent). Additionally, simulations have shown that the same chip can perform a limited form of speech recognition, by recognising individual spoken digits (“one”, “two”, …).

This research is a collaboration between members of the Photonics Research Group of the Department of Information Technology (P. Bienstman) and the Reservoir Lab of the Department of Electronics and Information Systems (J. Dambre, B. Schrauwen). It was funded by the European Research Council (ERC) through the Starting Grant NaResCo and by the Belgian IAP programme through the Photonics@BE network.

Story Source:

The above story is based on materials provided by Ghent University.

The post Light-Based Chip Inspired by Our Brain appeared first on Bioengineer.org.

Synthesizing textiles from sugar

from

Bioengineer.org http://ift.tt/1gYpDfc

In the future, the clothes you wear could be made from sugar. Researchers at the Institute of Bioengineering and Nanotechnology (IBN) have discovered a new chemical process that can convert adipic acid directly from sugar.

The IBN research team, who invented the new green chemistry method to turn sugar into adipic acid (from left) Dr Ting Lu, Dr Yugen Zhang, Dr Xiukai Li and Dr Guangshun Yi.

Adipic acid is an important chemical used to produce nylon for apparel and other everyday products like carpets, ropes and toothbrush bristles. Commercially, adipic acid is produced from petroleum-based chemicals through the nitric acid oxidation process, which emits large amounts of nitrous oxides, a major greenhouse gas that causes global warming.

IBN Executive Director Professor Jackie Y. Ying said, “In the face of growing environmental concerns over the use of fossil fuels and diminishing natural resources, there is an increasing need for a renewable source for energy and chemicals. We have designed a sustainable and environmentally friendly solution to convert sugar into adipic acid via our patented catalytic process technology.”

Bio-based adipic acid can be synthesized from mucic acid, which is oxidized from sugar; and the mucic acid can be obtained from fruit peels. Current processes are either performed using multiple steps with low product efficiency and yield, or under harsh reaction conditions using high-pressure hydrogen gas and strong acids, which are costly and unsafe.

The new chemical catalytic protocol designed by IBN is simple, efficient and green. To convert mucic acid to adipid acid, the target reaction is deoxydehydration, that is, oxygen and water will be removed simultaneously by reduction and dehydration. The researchers found that by combining deoxydehydration and the transfer hydrogenation reaction – adding an alcohol solvent – in one reactor, they could obtain a high yield of adipic acid at 99% of the starting material. Existing protocols can only achieve a yield of around 60%.

This method is ideal for industrial development because the process can be performed in one or two steps, the end product is pure, and the reaction conditions are mild and safe.

Dr Yugen Zhang, IBN Group Leader in green chemistry and energy said, “This work shows the tremendous potential of developing bio-based adipic acid. We are excited that our new protocol can efficiently convert adipic acid from sugar, bringing us one step closer toward industrialization. To complete this green technology, we are now working on using raw biomass as the feedstock.”

This finding was published recently in the leading Chemistry journal Angewandte Chemie International Edition. The work was funded by a grant from the A*STAR Science and Engineering Council to develop chemicals from biomass.

Dr Yugen Zhang’s group also holds patented technologies for converting other valuable chemical intermediates such as 5-hydroxymethylfurfural (HMF) and furfuraldicarboxylic acid (FDCA) from sugar. HMF is a key platform chemical that can be converted to biofuels and biochemicals, and FDCA can be used to make plastics and polyester. IBN seeks industrial collaborations to commercialize its portfolio of green technologies.

Story Source:

The above story is based on materials provided by Agency for Science, Technology and Research (A*STAR), Singapore, Elena Tan and Nidyah Sani.

The post Synthesizing textiles from sugar appeared first on Bioengineer.org.

New discovery gives hope that nerves could be repaired after spinal cord injury

from

Bioengineer.org http://ift.tt/1ol2lnU

A new discovery suggests it could one day be possible to chemically reprogram and repair damaged nerves after spinal cord injury or brain trauma.

Lead study author Professor Simone Di Giovanni, from Imperial College London’s Department of Medicine

Researchers from Imperial College London and the Hertie Institute, University of Tuebingen have identified a possible mechanism for re-growing damaged nerve fibres in the central nervous system (CNS). This damage is currently irreparable, often leaving those who suffer spinal cord injury, stroke or brain trauma with serious impairments like loss of sensation and permanent paralysis.

Published in Nature Communications today, the research highlights the role of a protein called P300/CBP-associated factor (PCAF), which appears to be essential for the series of chemical and genetic events that allow nerves to regenerate. Regenerating nerve fibres is one of the best hopes for those suffering from CNS damage to recover.

When researchers injected PCAF into mice with damage to their central nervous system, this significantly increased the number of nerve fibres that grew back, indicating that it may be possible to chemically control the regeneration of nerves in the CNS.

“The results suggest that we may be able to target specific chemical changes to enhance the growth of nerves after injury to the central nervous system,” said lead study author Professor Simone Di Giovanni, from Imperial College London’s Department of Medicine. “The ultimate goal could be to develop a pharmaceutical method to trigger the nerves to grow and repair and to see some level of recovery in patients. We are excited about the potential of this work but the findings are preliminary.

“The next step is to see whether we can bring about some form of recovery of movement and function in mice after we have stimulated nerve growth through the mechanism we have identified. If this is successful, then there could be a move towards developing a drug and running clinical trials with people. We hope that our new work could one day help people to recover feeling and movement, but there are many hurdles to overcome first,” he added.

The researchers were interested in understanding how axons in the peripheral nervous system (PNS) make a vigorous effort to grow back when they are damaged, whereas CNS axons mount little or no effort. If damage occurs in the peripheral nervous system, which controls areas outside of the brain and spinal cord, about 30% of the nerves grow back and there is often recovery of movement and function. The researchers wanted to explore whether it was possible to generate a similar response in the CNS.

Co-author Dr Radhika Puttagunta from the University of Tuebingen said: “With this work we add another level of understanding into the specific mechanisms of how the body is able to regenerate in the PNS and have used this knowledge to drive regeneration where it is lacking in the CNS. We believe this will help further our understanding of mechanisms that could enhance regeneration and physical recovery after CNS injury.”

To investigate the differences between how the two systems respond to damage, the researchers looked at mouse models and cells in culture. They compared the responses to PNS damage and CNS damage in a type of neuron called a dorsal root ganglion, which connects to both the CNS and the PNS.

They found that epigenetic mechanisms were at the core of this capacity to regenerate. Epigenetic mechanisms are processes that, without altering our DNA, manage to activate or deactivate genes in response to the environment. They normally take the form of chemical reactions and have been shown to control how genes influence diseases such as cancer and diabetes. However this is the first demonstration of a specific epigenetic mechanism responsible for nerve regeneration.

When nerves are damaged in the PNS, the damaged nerves send ‘retrograde’ signals back to the cell body to switch on an epigenetic program to initiate nerve growth. Very little was previously known about the mechanism which allows this ‘switching on’ to occur.

The researchers identified the sequence of chemical events that lead to the ‘switching on’ of the program to initiate nerve regrowth and pinpointed the protein PCAF as being central to the process. Furthermore when they injected PCAF into mice with damage to their central nervous system, there was a significant increase in the number of nerve fibres that grew back.

Story Source:

The above story is based on materials provided by Imperial College London, Franca Davenport.

The post New discovery gives hope that nerves could be repaired after spinal cord injury appeared first on Bioengineer.org.

Japan lab says stem cell research falsified

from

Bioengineer.org http://ift.tt/1pE0o38

A Japanese government-funded laboratory says it has found data in a widely heralded stem-cell research paper was falsified, holding one researcher responsible for the fabrication.

Haruko Obokata, the lead author of a widely heralded stem-cell research paper, speaks about her research results on stimulus-triggered acquisition of pluripotency (STAP) cells during a press conference in Kobe, western Japan. (AP Photo/Kyodo News)

The research results were seen as a possible groundbreaking method for growing tissue to treat illnesses such as diabetes and Parkinson’s disease using a simple lab procedure

Scientists at the RIKEN research institute said Tuesday that discrepancies in research published in January in scientific journal Nature stemmed from image manipulation and data fabrication.

They said researcher Haruko Obokata, the lead author of the paper in Nature, had manipulated or falsified images of DNA fragments used in the research.

The scientists said three other co-authors of the papers had not falsified the data but were still “gravely responsible” for failing to fully verify the research findings.

Story Source:

The above story is based on materials provided by AP, Elaine KURTENBACH.

The post Japan lab says stem cell research falsified appeared first on Bioengineer.org.

Can antibiotics cause autoimmunity?

from

Bioengineer.org http://ift.tt/1fj6SRA

The code for every gene includes a message at the end of it that signals the translation machinery to stop. Some diseases, such as cystic fibrosis and Duchenne muscular dystrophy, can result from mutations that insert this stop signal into the middle of an essential gene, causing the resulting protein to be truncated. Some antibiotics cause the cell’s translation machinery to ignore the stop codons and are therefore being explored as a potential therapy for these diseases. But new research reported online in Proceedings of the National Academy of Sciences (the week of March 31st) shows that this approach could come with the price of triggering autoimmune disease.

Photo Credits: oceanservice.noaa.gov

“It’s worth thinking about this as a potential mechanism for autoimmunity,” says co-lead investigator, Laurence Eisenlohr, Ph.D., a professor in the department of Microbiology and Immunology at Thomas Jefferson University.

Autoimmune diseases such as Crohn’s disease, eczema, or lupus are caused by an immune system that attacks normal components of various tissues of the body. The immune system attacks these normal tissues just as it would attack tissue infected by a bacteria or virus. What causes the immune system to malfunction in some people but not others, however, has been a puzzle. “Often, the trigger happens years before the disease has been diagnosed,” says Dr. Eisenlohr.

The researchers looked at a class of antibiotics that includes gentamicin because these antibiotics have the unique property of inducing cells to read through stop codons in the genetic code – producing a longer protein product. This mechanism can help save the translation of mutated genes whose processing is interrupted by aberrant stop codons, such as in cystic fibrosis. However, when cellular machinery reads through normal stop codons, it could create abnormally elongated proteins in the cell. Pieces of these abnormal proteins may be presented to the immune system as a part of normal protein processing, where they could be detected by the immune system. At least, that’s the theory.

To test this theory, Eisenlohr’s team, in collaboration with a translation biology group at the University of Utah led by Michael Howard, Ph.D., used a gene that they knew would get presented to the immune system and added a stop codon in the middle of it. They then inserted this gene into a mammalian cell line. Because the stop codon truncates the gene, normal cells did not produce the protein. However, when the researchers treated the cells with gentamicin, they began to detect the protein on the surface of cells.

While a very low number of these proteins were produced – too little to detect by normal biochemical tests – the T cells of the immune system are sensitive enough to pick up these miniscule amounts. Indeed, the group showed that the immune cells could detect the protein produced by gentamicin-treated cells, even at low quantities.

To test whether this process was active even in normal cells that weren’t expressing an experimental gene, first author Elliot Goodenough exposed the HeLa human cell line to gentamicin and then searched for novel peptides presented on the surface of the cells. He identified 17 peptides that hadn’t been characterized before in cells treated with gentamicin and showed that the peptides were presentable to the immune system. “The results suggest that gentamicin can cause cells to display novel protein fragments to the immune system,” says Goodenough. In other words, “what may be garbage biologically may be important immunologically,” says Eisenlohr.

However, presenting an antigen to the immune system does not guarantee that it will activate the kind of immune response that initiates autoimmunity. But because gentamicin is usually used to treat infections, “all of the right conditions are in place to potentially initiate autoimmunity,” says Eisenlohr. The inflammation associated with bacterial diseases gives a signal to immune cells that the peptides they encounter are dangerous. So even as gentamicin fights the bacteria causing the infection, it also causes normal cells to produce abnormal proteins that are presented to the immune system and have a potential of initiating an autoimmune reaction.

“A number of autoimmune diseases are thought to be triggered by infections,” says Eisenlohr. “The results of this study suggest that certain antibiotics used to treat those infections may also contribute to that trigger.”

The next steps, says Eisenlohr, could be to look at population data to see whether use of gentamicin correlates with higher rates of autoimmune diseases, as well as testing whether the peptides generated during gentamicin treatment actually do cause autoimmunity in a mouse model of the disease.

Story Source:

The above story is based on materials provided by Thomas Jefferson University, Edyta Zielinska.

The post Can antibiotics cause autoimmunity? appeared first on Bioengineer.org.

Scientists discover a protein in nerves that determines which brain connections stay and which go

from

Bioengineer.org http://ift.tt/1pDtuQ7

A newborn baby, for all its cooing cuddliness, is a data acquisition machine, absorbing information to finish honing the job of brain wiring that started before birth. This is true nowhere more so than the eyes, which start life peering at a blurry world and within months can make out a crisp, three-dimensional image of a mobile dangling overhead.

Research by Carla Shatz, the David Starr Jordan Director of Stanford Bio-X, helps explain how the brain prunes back unused connections early in life. – Photo Credits: Norbert von der Groeben

This process of refining the brain’s wiring involves cutting off some of the excess nerve connections we have at birth while strengthening connections we use all the time. Some estimates show that as many as half of the brain’s connections formed during development are clipped back as the final wiring takes shape.

Carla Shatz, the David Starr Jordan Director of Stanford Bio-X, and her team, including postdoctoral researcher Hanmi Lee and Bio-X Graduate Fellow Jaimie Adelson, recently found a protein that is essential for the brain to remove those excess connections. The team specifically showed a role for the protein in the developing visual system in mice, but the work appears to apply broadly across the developing brain. They published their findings online March 30 in the journal Nature.

Shatz said the discovery helps clear up something that has been a mystery to those who study brain development: How does the decision get made to eliminate some connections? It also settles a decade-long debate over whether the nervous system or the immune system is making those decisions. (Spoiler alert: It’s the nervous system.)

A single vision

“Vision is a challenging problem because you have two eyes and only one view of the world,” said Shatz, who is the Sapp Family Provostial Professor and professor of biology and of neurobiology. “There’s a very beautiful set of wiring steps that makes sure the eyes are pointed at the same place and the two images get aligned.”

Shatz said the rule of which connections the brain cuts back to create that single vision follows a simple mantra: “Fire together, wire together. Out of sync, lose your link.” Or rather, if early in life the left sides of both eyes see the same duck motif wallpaper, those neurons fire together and stay linked up. When the top of one eye and bottom of the other eye form a connection, the nerves fire out of sync, and the connection weakens and is eventually pruned back. Over time, the only connections that remain are between parts of the two eyes that are seeing the same thing.

The ability to detect which nerves fire out of sync and should therefore lose their link requires the protein Shatz’s team reported, which goes by the name of MHC Class I D, or D for short. This protein is one that is famous for its role in the immune system, but only in the past decade has Shatz’s team started building a case for D’s independent role in the brain.

Two camps, one protein

In 2000 Shatz first published work suggesting that a group of immune proteins called MHC in mice and HLA in people played a role in the developing nervous system. At the time, this caused a stir among immunologists, who were surprised to find their proteins showing up in the brain.

Lawrence Steinman, professor of neurology and neurological sciences and of pediatrics at Stanford School of Medicine, has followed Shatz’s work from the perspective of both a neurologist and immunologist. “One of the reasons that I think the research is so interesting is that it shows us that molecules thought to be the province of one group can be in another,” he said, adding, “It slowed the prevailing idea that people believed that some molecules were the domain of one camp.”

Shatz is in the privileged position of directing Stanford Bio-X, which includes faculty members and students from both immunology and the neurological sciences. She said being able to talk about her work and collaborate with this mix of colleagues has helped break down barriers in thinking about her unexpected findings.

After the initial discovery, Shatz went on to show that two of those MHC proteins – D and its sister protein K – seemed to be important in eliminating connections in the brain. Mice genetically engineered to lack both K and D had poorly functioning immune systems and also ended up with the visual system in a jumble, with unrelated parts of the two eyes forming connections. Without D and K the mice weren’t detecting which connections fired out of sync, so those connections didn’t lose their link.

After Shatz published that work, some immunologists argued that perhaps D and K were necessary for brain remodeling only because of their key function in the immune system. “They were saying that the immune system was telling the nervous system what to prune,” Shatz said.

It was a theory, but not one Shatz agreed with. Her feeling was that just because D and K were first found in the immune system didn’t mean they couldn’t have a unique role in the brain. “The nervous system has just as much right to these immune proteins as the immune system,” Shatz said. Her most recent work makes that point clear.

D on the brain

Shatz and her group worked with the mice that were lacking D and K everywhere, then used genetic engineering tricks to add D back, but only in the neurons. These mice still had poorly functioning immune systems, but had perfectly normal eye connections. In these mice, the nerves were able to determine which connections to cut and which to keep, even without the immune system.

Steinman said the work settles the issue of whether D is acting in the brain separate from its role in the immune system. “If Carla had studied MHC proteins before the immunologists, then we would consider them to be part of the nervous system. They clearly have major roles in both the nervous system and the immune system,” he said.

The group went on to show that the presence of D alters the composition of other proteins on the nerve cell surface that are in charge of receiving signals from other nerves. Her team thinks that it is this difference in how the nerve receives signals with or without D that makes the pruning process go awry.

Essentially, without D all nerve connections appear to be firing together and therefore they stay wired together.

Shatz says that in addition to explaining an important part of brain development, the work could also provide a new avenue for studying schizophrenia. Some studies have shown that people with mutations in the human genes related to D (called HLA genes) are more prone to the disease. Other studies have associated schizophrenia with improperly formed connections in the brain. Shatz suggests that this new role for D in the brain could mean that the pruning process has gone awry in schizophrenia. The group plans to explore this idea further, as well as to tease apart what D is doing to alter the composition of neurotransmitter receptors on the nerve cell surface.

Story Source:

The above story is based on materials provided by University of Stanford Report, Amy Adams.

The post Scientists discover a protein in nerves that determines which brain connections stay and which go appeared first on Bioengineer.org.