Tag Archives: University of Zurich

Connecting biological and artificial neurons (in UK, Switzerland, & Italy) over the web

Caption: The virtual lab connecting Southampton, Zurich and Padova. Credit: University of Southampton

A February 26, 2020 University of Southampton press release (also on EurekAlert) describes this work,

Research on novel nanoelectronics devices led by the University of Southampton enabled brain neurons and artificial neurons to communicate with each other. This study has for the first time shown how three key emerging technologies can work together: brain-computer interfaces, artificial neural networks and advanced memory technologies (also known as memristors). The discovery opens the door to further significant developments in neural and artificial intelligence research.

Brain functions are made possible by circuits of spiking neurons, connected together by microscopic, but highly complex links called ‘synapses’. In this new study, published in the scientific journal Nature Scientific Reports, the scientists created a hybrid neural network where biological and artificial neurons in different parts of the world were able to communicate with each other over the internet through a hub of artificial synapses made using cutting-edge nanotechnology. This is the first time the three components have come together in a unified network.

During the study, researchers based at the University of Padova in Italy cultivated rat neurons in their laboratory, whilst partners from the University of Zurich and ETH Zurich created artificial neurons on Silicon microchips. The virtual laboratory was brought together via an elaborate setup controlling nanoelectronic synapses developed at the University of Southampton. These synaptic devices are known as memristors.

The Southampton based researchers captured spiking events being sent over the internet from the biological neurons in Italy and then distributed them to the memristive synapses. Responses were then sent onward to the artificial neurons in Zurich also in the form of spiking activity. The process simultaneously works in reverse too; from Zurich to Padova. Thus, artificial and biological neurons were able to communicate bidirectionally and in real time.

Themis Prodromakis, Professor of Nanotechnology and Director of the Centre for Electronics Frontiers at the University of Southampton said “One of the biggest challenges in conducting research of this kind and at this level has been integrating such distinct cutting edge technologies and specialist expertise that are not typically found under one roof. By creating a virtual lab we have been able to achieve this.”

The researchers now anticipate that their approach will ignite interest from a range of scientific disciplines and accelerate the pace of innovation and scientific advancement in the field of neural interfaces research. In particular, the ability to seamlessly connect disparate technologies across the globe is a step towards the democratisation of these technologies, removing a significant barrier to collaboration.

Professor Prodromakis added “We are very excited with this new development. On one side it sets the basis for a novel scenario that was never encountered during natural evolution, where biological and artificial neurons are linked together and communicate across global networks; laying the foundations for the Internet of Neuro-electronics. On the other hand, it brings new prospects to neuroprosthetic technologies, paving the way towards research into replacing dysfunctional parts of the brain with AI [artificial intelligence] chips.”

I’m fascinated by this work and after taking a look at the paper, I have to say, the paper is surprisingly accessible. In other words, I think I get the general picture. For example (from the Introduction to the paper; citation and link follow further down),

… To emulate plasticity, the memristor MR1 is operated as a two-terminal device through a control system that receives pre- and post-synaptic depolarisations from one silicon neuron (ANpre) and one biological neuron (BN), respectively. …

If I understand this properly, they’ve integrated a biological neuron and an artificial neuron in a single system across three countries.

For those who care to venture forth, here’s a link and a citation for the paper,

Memristive synapses connect brain and silicon spiking neurons by Alexantrou Serb, Andrea Corna, Richard George, Ali Khiat, Federico Rocchi, Marco Reato, Marta Maschietto, Christian Mayr, Giacomo Indiveri, Stefano Vassanelli & Themistoklis Prodromakis. Scientific Reports volume 10, Article number: 2590 (2020) DOI: https://doi.org/10.1038/s41598-020-58831-9 Published 25 February 2020

The paper is open access.

Hallucinogenic molecules and the brain

Psychedelic drugs seems to be enjoying a ‘moment’. After decades of being vilified and  declared illegal (in many jurisdictions), psychedelic (or hallucinogenic) drugs are once again being tested for use in therapy. A Sept. 1, 2017 article by Diana Kwon for The Scientist describes some of the latest research (I’ve excerpted the section on molecules; Note: Links have been removed),

Mind-bending molecules

© SEAN MCCABE

All the classic psychedelic drugs—psilocybin, LSD, and N,N-dimethyltryptamine (DMT), the active component in ayahuasca—activate serotonin 2A (5-HT2A) receptors, which are distributed throughout the brain. In all likelihood, this receptor plays a key role in the drugs’ effects. Krähenmann [Rainer Krähenmann, a psychiatrist and researcher at the University of Zurich]] and his colleagues in Zurich have discovered that ketanserin, a 5-HT2A receptor antagonist, blocks LSD’s hallucinogenic properties and prevents individuals from entering a dreamlike state or attributing personal relevance to the experience.12,13

Other research groups have found that, in rodent brains, 2,5-dimethoxy-4-iodoamphetamine (DOI), a highly potent and selective 5-HT2A receptor agonist, can modify the expression of brain-derived neurotrophic factor (BDNF)—a protein that, among other things, regulates neuronal survival, differentiation, and synaptic plasticity. This has led some scientists to hypothesize that, through this pathway, psychedelics may enhance neuroplasticity, the ability to form new neuronal connections in the brain.14 “We’re still working on that and trying to figure out what is so special about the receptor and where it is involved,” says Katrin Preller, a postdoc studying psychedelics at the University of Zurich. “But it seems like this combination of serotonin 2A receptors and BDNF leads to a kind of different organizational state in the brain that leads to what people experience under the influence of psychedelics.”

This serotonin receptor isn’t limited to the central nervous system. Work by Charles Nichols, a pharmacology professor at Louisiana State University, has revealed that 5-HT2A receptor agonists can reduce inflammation throughout the body. Nichols and his former postdoc Bangning Yu stumbled upon this discovery by accident, while testing the effects of DOI on smooth muscle cells from rat aortas. When they added this drug to the rodent cells in culture, it blocked the effects of tumor necrosis factor-alpha (TNF-α), a key inflammatory cytokine.

“It was completely unexpected,” Nichols recalls. The effects were so bewildering, he says, that they repeated the experiment twice to convince themselves that the results were correct. Before publishing the findings in 2008,15 they tested a few other 5-HT2A receptor agonists, including LSD, and found consistent anti-inflammatory effects, though none of the drugs’ effects were as strong as DOI’s. “Most of the psychedelics I have tested are about as potent as a corticosteroid at their target, but there’s something very unique about DOI that makes it much more potent,” Nichols says. “That’s one of the mysteries I’m trying to solve.”

After seeing the effect these drugs could have in cells, Nichols and his team moved on to whole animals. When they treated mouse models of system-wide inflammation with DOI, they found potent anti-inflammatory effects throughout the rodents’ bodies, with the strongest effects in the small intestine and a section of the main cardiac artery known as the aortic arch.16 “I think that’s really when it felt that we were onto something big, when we saw it in the whole animal,” Nichols says.

The group is now focused on testing DOI as a potential therapeutic for inflammatory diseases. In a 2015 study, they reported that DOI could block the development of asthma in a mouse model of the condition,17 and last December, the team received a patent to use DOI for four indications: asthma, Crohn’s disease, rheumatoid arthritis, and irritable bowel syndrome. They are now working to move the treatment into clinical trials. The benefit of using DOI for these conditions, Nichols says, is that because of its potency, only small amounts will be required—far below the amounts required to produce hallucinogenic effects.

In addition to opening the door to a new class of diseases that could benefit from psychedelics-inspired therapy, Nichols’s work suggests “that there may be some enduring changes that are mediated through anti-inflammatory effects,” Griffiths [Roland Griffiths, a psychiatry professor at Johns Hopkins University] says. Recent studies suggest that inflammation may play a role in a number of psychological disorders, including depression18 and addiction.19

“If somebody has neuroinflammation and that’s causing depression, and something like psilocybin makes it better through the subjective experience but the brain is still inflamed, it’s going to fall back into the depressed rut,” Nichols says. But if psilocybin is also treating the inflammation, he adds, “it won’t have that rut to fall back into.”

If it turns out that psychedelics do have anti-inflammatory effects in the brain, the drugs’ therapeutic uses could be even broader than scientists now envision. “In terms of neurodegenerative disease, every one of these disorders is mediated by inflammatory cytokines,” says Juan Sanchez-Ramos, a neuroscientist at the University of South Florida who in 2013 reported that small doses of psilocybin could promote neurogenesis in the mouse hippocampus.20 “That’s why I think, with Alzheimer’s, for example, if you attenuate the inflammation, it could help slow the progression of the disease.”

For anyone who was never exposed to the anti-hallucinogenic drug campaigns, this turn of events is mindboggling. There was a great deal of concern especially with LSD in the 1960s and it was not entirely unfounded. In my own family, a distant cousin, while under the influence of the drug, jumped off a building believing he could fly.  So, Kwon’s story opening with a story about someone being treated successfully for depression with a psychedelic drug was surprising to me . Why these drugs are being used successfully for psychiatric conditions when so much damage was apparently done under the influence in decades past may have something to do with taking the drugs in a controlled environment and, possibly, smaller dosages.

A nano fabrication technique used to create next generation heart valve

I am going to have take the researchers’ word that these somehow lead to healthy heart valve tissue,

In rotary jet spinning technology, a rotating nozzle extrudes a solution of extracellular matrix (ECM) into nanofibers that wrap themselves around heart valve-shaped mandrels. By using a series of mandrels with different sizes, the manufacturing process becomes fully scalable and is able to provide JetValves for all age groups and heart sizes. Credit: Wyss Institute at Harvard University

From a May 18, 2017 news item on ScienceDaily,

The human heart beats approximately 35 million times every year, effectively pumping blood into the circulation via four different heart valves. Unfortunately, in over four million people each year, these delicate tissues malfunction due to birth defects, age-related deteriorations, and infections, causing cardiac valve disease.

Today, clinicians use either artificial prostheses or fixed animal and cadaver-sourced tissues to replace defective valves. While these prostheses can restore the function of the heart for a while, they are associated with adverse comorbidity and wear down and need to be replaced during invasive and expensive surgeries. Moreover, in children, implanted heart valve prostheses need to be replaced even more often as they cannot grow with the child.

A team lead by Kevin Kit Parker, Ph.D. at Harvard University’s Wyss Institute for Biologically Inspired Engineering recently developed a nanofiber fabrication technique to rapidly manufacture heart valves with regenerative and growth potential. In a paper published in Biomaterials, Andrew Capulli, Ph.D. and colleagues fabricated a valve-shaped nanofiber network that mimics the mechanical and chemical properties of the native valve extracellular matrix (ECM). To achieve this, the team used the Parker lab’s proprietary rotary jet spinning technology — in which a rotating nozzle extrudes an ECM solution into nanofibers that wrap themselves around heart valve-shaped mandrels. “Our setup is like a very fast cotton candy machine that can spin a range of synthetic and natural occurring materials. In this study, we used a combination of synthetic polymers and ECM proteins to fabricate biocompatible JetValves that are hemodynamically competent upon implantation and support cell migration and re-population in vitro. Importantly, we can make human-sized JetValves in minutes — much faster than possible for other regenerative prostheses,” said Parker.

A May 18,2017 Wyss Institute for Biologically Inspired Engineering news release (also on EurekAlert), which originated the news item, expands on the theme of Jetvalves,

To further develop and test the clinical potential of JetValves, Parker’s team collaborated with the translational team of Simon P. Hoerstrup, M.D., Ph.D., at the University of Zurich in Switzerland, which is a partner institution with the Wyss Institute. As a leader in regenerative heart prostheses, Hoerstrup and his team in Zurich have previously developed regenerative, tissue-engineered heart valves to replace mechanical and fixed-tissue heart valves. In Hoerstrup’s approach, human cells directly deposit a regenerative layer of complex ECM on biodegradable scaffolds shaped as heart valves and vessels. The living cells are then eliminated from the scaffolds resulting in an “off-the-shelf” human matrix-based prostheses ready for implantation.

In the paper, the cross-disciplinary team successfully implanted JetValves in sheep using a minimally invasive technique and demonstrated that the valves functioned properly in the circulation and regenerated new tissue. “In our previous studies, the cell-derived ECM-coated scaffolds could recruit cells from the receiving animal’s heart and support cell proliferation, matrix remodeling, tissue regeneration, and even animal growth. While these valves are safe and effective, their manufacturing remains complex and expensive as human cells must be cultured for a long time under heavily regulated conditions. The JetValve’s much faster manufacturing process can be a game-changer in this respect. If we can replicate these results in humans, this technology could have invaluable benefits in minimizing the number of pediatric re-operations,” said Hoerstrup.

In support of these translational efforts, the Wyss Institute for Biologically Inspired Engineering and the University of Zurich announced today a cross-institutional team effort to generate a functional heart valve replacement with the capacity for repair, regeneration, and growth. The team is also working towards a GMP-grade version of their customizable, scalable, and cost-effective manufacturing process that would enable deployment to a large patient population. In addition, the new heart valve would be compatible with minimally invasive procedures to serve both pediatric and adult patients.

The project will be led jointly by Parker and Hoerstrup. Parker is a Core Faculty member of the Wyss Institute and the Tarr Family Professor of Bioengineering and Applied Physics at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS). Hoerstrup is Chair and Director of the University of Zurich’s Institute for Regenerative Medicine (IREM), Co-Director of the recently founded Wyss Translational Center Zurich and a Wyss Institute Associate Faculty member.

Since JetValves can be manufactured in all desired shapes and sizes, and take seconds to minutes to produce, the team’s goal is to provide customized, ready-to-use, regenerative heart valves much faster and at much lower cost than currently possible.

“Achieving the goal of minimally invasive, low-cost regenerating heart valves could have tremendous impact on patients’ lives across age-, social- and geographical boundaries. Once again, our collaborative team structure that combines unique and leading expertise in bioengineering, regenerative medicine, surgical innovation and business development across the Wyss Institute and our partner institutions, makes it possible for us to advance technology development in ways not possible in a conventional academic laboratory,” said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at HMS and the Vascular Biology Program at Boston Children’s Hospital, as well as Professor of Bioengineering at SEAS.

This scanning electron microscopy image shows how extracellular matrix (ECM) nanofibers generated with JetValve technology are arranged in parallel networks with physical properties comparable to those found in native heart tissue. Credit: Wyss Institute at Harvard University

Here’s a link to and a citation for the paper,

JetValve: Rapid manufacturing of biohybrid scaffolds for biomimetic heart valve replacement by Andrew K. Capulli, Maximillian Y. Emmert, Francesco S. Pasqualini, b, Debora Kehl, Etem Caliskan, Johan U. Lind, Sean P. Sheehy, Sung Jin Park, Seungkuk Ahn, Benedikt Webe, Josue A. Goss. Biomaterials Volume 133, July 2017, Pages 229–241  https://doi.org/10.1016/j.biomaterials.2017.04.033

This paper is behind a paywall.

New model to track flow of nanomaterials through our air, earth, and water

Just how many tons of nanoparticles are making their way through the environment? Scientists at the Swiss Federal Laboratories for Materials Science and Technology (Empa) have devised a new model which could help answer that question. From a May 12, 2016 news item on phys.org,

Carbon nanotubes remain attached to materials for years while titanium dioxide and nanozinc are rapidly washed out of cosmetics and accumulate in the ground. Within the National Research Program “Opportunities and Risks of Nanomaterials” (NRP 64) a team led by Empa scientist Bernd Nowack has developed a new model to track the flow of the most important nanomaterials in the environment.

A May 12, 2016 Empa press release by Michael Hagmann, which also originated the news item, provides more detail such as an estimated tonnage for titanium dioxide nanoparticles produced annually in Europe,

How many man-made nanoparticles make their way into the air, earth or water? In order to assess these amounts, a group of researchers led by Bernd Nowack from Empa, the Swiss Federal Laboratories for Materials Science and Technology, has developed a computer model as part of the National Research Program “Opportunities and Risks of Nanomaterials” (NRP 64). “Our estimates offer the best available data at present about the environmental accumulation of nanosilver, nanozinc, nano-tinanium dioxide and carbon nanotubes”, says Nowack.

In contrast to the static calculations hitherto in use, their new, dynamic model does not just take into account the significant growth in the production and use of nanomaterials, but also makes provision for the fact that different nanomaterials are used in different applications. For example, nanozinc and nano-titanium dioxide are found primarily in cosmetics. Roughly half of these nanoparticles find their way into our waste water within the space of a year, and from there they enter into sewage sludge. Carbon nanotubes, however, are integrated into composite materials and are bound in products such as which are immobilized and are thus found for example in tennis racquets and bicycle frames. It can take over ten years before they are released, when these products end up in waste incineration or are recycled.

39,000 metric tons of nanoparticles

The researchers involved in this study come from Empa, ETH Zurich and the University of Zurich. They use an estimated annual production of nano-titanium dioxide across Europe of 39,000 metric tons – considerably more than the total for all other nanomaterials. Their model calculates how much of this enters the atmosphere, surface waters, sediments and the earth, and accumulates there. In the EU, the use of sewage sludge as fertilizer (a practice forbidden in Switzerland) means that nano-titanium dioxide today reaches an average concentration of 61 micrograms per kilo in affected soils.

Knowing the degree of accumulation in the environment is only the first step in the risk assessment of nanomaterials, however. Now this data has to be compared with results of eco-toxicological tests and the statutory thresholds, says Nowack. A risk assessment has not been carried out with his new model so far. Earlier work with data from a static model showed, however, that the concentrations determined for all four nanomaterials investigated are not expected to have any impact on the environment.

But in the case of nanozinc at least, its concentration in the environment is approaching the critical level. This is why this particular nanomaterial has to be given priority in future eco-toxicological studies – even though nanozinc is produced in smaller quantities than nano-titanium dioxide. Furthermore, eco-toxicological tests have until now been carried out primarily with freshwater organisms. The researchers conclude that additional investigations using soil-dwelling organisms are a priority.

Here are links to and citations for papers featuring the work,

Dynamic Probabilistic Modeling of Environmental Emissions of Engineered Nanomaterials by Tian Yin Sun†, Nikolaus A. Bornhöft, Konrad Hungerbühler, and Bernd Nowack. Environ. Sci. Technol., 2016, 50 (9), pp 4701–4711 DOI: 10.1021/acs.est.5b05828 Publication Date (Web): April 04, 2016

Copyright © 2016 American Chemical Society

Probabilistic environmental risk assessment of five nanomaterials (nano-TiO2, nano-Ag, nano-ZnO, CNT, and fullerenes) by Claudia Coll, Dominic Notter, Fadri Gottschalk, Tianyin Sun, Claudia Som, & Bernd Nowack. Nanotoxicology Volume 10, Issue 4, 2016 pages 436-444 DOI: 10.3109/17435390.2015.1073812 Published online: 10 Nov 2015

The first paper, which is listed in Environmental Science & Technology, appears to be open access while the second paper is behind a paywall.

Saharan silver ants: the nano of it all (science and technology)

Researchers at Columbia University (US) are on quite a publishing binge lately. The latest is a biomimicry story where researchers (from Columbia amongst other universities and including Brookhaven National Laboratory, which has issued its own news release) have taken a very close look at Saharan silver ants to determine how they stay cool in one of the hottest climates in the world. From a June 18, 2015 Columbia University news release (also on EurekAlert), Note: Links have been removed,

Nanfang Yu, assistant professor of applied physics at Columbia Engineering, and colleagues from the University of Zürich and the University of Washington, have discovered two key strategies that enable Saharan silver ants to stay cool in one of the hottest terrestrial environments on Earth. Yu’s team is the first to demonstrate that the ants use a coat of uniquely shaped hairs to control electromagnetic waves over an extremely broad range from the solar spectrum (visible and near-infrared) to the thermal radiation spectrum (mid-infrared), and that different physical mechanisms are used in different spectral bands to realize the same biological function of reducing body temperature. Their research, “Saharan silver ants keep cool by combining enhanced optical reflection and radiative heat dissipation,” is published June 18 [2015] in Science magazine.

The Columbia University news release expands on the theme,

“This is a telling example of how evolution has triggered the adaptation of physical attributes to accomplish a physiological task and ensure survival, in this case to prevent Saharan silver ants from getting overheated,” Yu says. “While there have been many studies of the physical optics of living systems in the ultraviolet and visible range of the spectrum, our understanding of the role of infrared light in their lives is much less advanced. Our study shows that light invisible to the human eye does not necessarily mean that it does not play a crucial role for living organisms.”

The project was initially triggered by wondering whether the ants’ conspicuous silvery coats were important in keeping them cool in blistering heat. Yu’s team found that the answer to this question was much broader once they realized the important role of infrared light. Their discovery that there is a biological solution to a thermoregulatory problem could lead to the development of novel flat optical components that exhibit optimal cooling properties.

“Such biologically inspired cooling surfaces will have high reflectivity in the solar spectrum and high radiative efficiency in the thermal radiation spectrum,” Yu explains. “So this may generate useful applications such as a cooling surface for vehicles, buildings, instruments, and even clothing.”

Saharan silver ants (Cataglyphis bombycina) forage in the Saharan Desert in the full midday sun when surface temperatures reach up to 70°C (158°F), and they must keep their body temperature below their critical thermal maximum of 53.6°C (128.48°F) most of the time. In their wide-ranging foraging journeys, the ants search for corpses of insects and other arthropods that have succumbed to the thermally harsh desert conditions, which they are able to endure more successfully. Being most active during the hottest moment of the day also allows these ants to avoid predatory desert lizards. Researchers have long wondered how these tiny insects (about 10 mm, or 3/8” long) can survive under such thermally extreme and stressful conditions.

Using electron microscopy and ion beam milling, Yu’s group discovered that the ants are covered on the top and sides of their bodies with a coating of uniquely shaped hairs with triangular cross-sections that keep them cool in two ways. These hairs are highly reflective under the visible and near-infrared light, i.e., in the region of maximal solar radiation (the ants run at a speed of up to 0.7 meters per second and look like droplets of mercury on the desert surface). The hairs are also highly emissive in the mid-infrared portion of the electromagnetic spectrum, where they serve as an antireflection layer that enhances the ants’ ability to offload excess heat via thermal radiation, which is emitted from the hot body of the ants to the cold sky. This passive cooling effect works under the full sun whenever the insects are exposed to the clear sky.

“To appreciate the effect of thermal radiation, think of the chilly feeling when you get out of bed in the morning,” says Yu. “Half of the energy loss at that moment is due to thermal radiation since your skin temperature is temporarily much higher than that of the surrounding environment.”

The researchers found that the enhanced reflectivity in the solar spectrum and enhanced thermal radiative efficiency have comparable contributions to reducing the body temperature of silver ants by 5 to 10 degrees compared to if the ants were without the hair cover. “The fact that these silver ants can manipulate electromagnetic waves over such a broad range of spectrum shows us just how complex the function of these seemingly simple biological organs of an insect can be,” observes Norman Nan Shi, lead author of the study and PhD student who works with Yu at Columbia Engineering.

Yu and Shi collaborated on the project with Rüdiger Wehner, professor at the Brain Research Institute, University of Zürich, Switzerland, and Gary Bernard, electrical engineering professor at the University of Washington, Seattle, who are renowned experts in the study of insect physiology and ecology. The Columbia Engineering team designed and conducted all experimental work, including optical and infrared microscopy and spectroscopy experiments, thermodynamic experiments, and computer simulation and modeling. They are currently working on adapting the engineering lessons learned from the study of Saharan silver ants to create flat optical components, or “metasurfaces,” that consist of a planar array of nanophotonic elements and provide designer optical and thermal radiative properties.

Yu and his team plan next to extend their research to other animals and organisms living in extreme environments, trying to learn the strategies these creatures have developed to cope with harsh environmental conditions.

“Animals have evolved diverse strategies to perceive and utilize electromagnetic waves: deep sea fish have eyes that enable them to maneuver and prey in dark waters, butterflies create colors from nanostructures in their wings, honey bees can see and respond to ultraviolet signals, and fireflies use flash communication systems,” Yu adds. “Organs evolved for perceiving or controlling electromagnetic waves often surpass analogous man-made devices in both sophistication and efficiency. Understanding and harnessing natural design concepts deepens our knowledge of complex biological systems and inspires ideas for creating novel technologies.”

Next, there’s the perspective provided by Brookhaven National Laboratory in a June 18, 2015 news item on Nanowerk (Note: It is very similar to the Columbia University news release but it takes a turn towards the technical challenges as you’ll see if you keep reading),

The paper, published by Columbia Engineering researchers and collaborators—including researchers from the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory—describes how the nanoscale structure of the hairs helps increase the reflectivity of the ant’s body in both visible and near-infrared wavelengths, allowing the insects to deflect solar radiation their bodies would otherwise absorb. The hairs also enhance emissivity in the mid-infrared spectrum, allowing heat to dissipate efficiently from the hot body of the ants to the cool, clear sky.

A June 18, 2015 BNL news release by Alasdair Wilkins, which originated the Nanowerk news item, describes the collaboration between the researchers and the special adjustments made to the equipment in service of this project (Note: A link has been removed),

In a typical experiment involving biological material such as nanoscale hairs, it would usually be sufficient to use an electron microscope to create an image of the surface of the specimen. This research, however, required Yu’s group to look inside the ant hairs and produce a cross-section of the structure’s interior. The relatively weak beam of electrons from a standard electron microscope would not be able to penetrate the surface of the sample.

The CFN’s dual beam system solves the problem by combining the imaging of an electron microscope with a much more powerful beam of gallium ions.  With 31 protons and 38 neutrons, each gallium ion is about 125,000 times more massive than an electron, and massive enough to create dents in the nanoscale structure – like throwing a stone against a wall. The researchers used these powerful beams to drill precise cuts into the hairs, revealing the crucial information hidden beneath the surface. Indeed, this particular application, in which the system was used to investigate a biological problem, was new for the team at CFN.

“Conventionally, this tool is used to produce cross-sections of microelectronic circuits,” said Camino. “The focused ion beam is like an etching tool. You can think of it like a milling tool in a machine shop, but at the nanoscale. It can remove material at specific places because you can see these locations with the SEM. So locally you remove material and you look at the under layers, because the cuts give you access to the cross section of whatever you want to look at.”

The ant hair research challenged the CFN team to come up with novel solutions to investigate the internal structures without damaging the more delicate biological samples.

“These hairs are very soft compared to, say, semiconductors or crystalline materials. And there’s a lot of local heat that can damage biological samples. So the parameters have to be carefully tuned not to do much damage to it,” he said. “We had to adapt our technique to find the right conditions.”

Another challenge lay in dealing with the so-called charging effect. When the dual beam system is trained on a non-conducting material, electrons can build up at the point where the beams hit the specimen, distorting the resulting image. The team at CFN was able to solve this problem by placing thin layers of gold over the biological material, making the sample just conductive enough to avoid the charging effect.

Revealing Reflectivity

While Camino’s team focused on helping Yu’s group investigate the structure of the ant hairs, Matthew Sfeir’s work with high-brightness Fourier transform optical spectroscopy helped to reveal how the reflectivity of the hairs helped Saharan silver ants regulate temperature. Sfeir’s spectrometer revealed precisely how much those biological structures reflect light across multiple wavelengths, including both visible and near-infrared light.

“It’s a multiplexed measurement,” Sfeir said, explaining his team’s spectrometer. “Instead of tuning through this wavelength and this wavelength, that wavelength, you do them all in one swoop to get all the spectral information in one shot. It gives you very fast measurements and very good resolution spectrally. Then we optimize it for very small samples. It’s a rather unique capability of CFN.”

Sfeir’s spectroscopy work draws on knowledge gained from his work at another key Brookhaven facility: the original National Synchrotron Light Source, where he did much of his postdoc work. His experience was particularly useful in analyzing the reflectivity of the biological structures across many different wavelengths of the electromagnetic spectrum.

“This technique was developed from my experience working with the infrared synchrotron beamlines,” said Sfeir. “Synchrotron beamlines are optimized for exactly this kind of thing. I thought, ‘Hey, wouldn’t it be great if we could develop a similar measurement for the type of solar devices we make at CFN?’ So we built a bench-top version to use here.”

Fascinating, non? At last, here’s a link to and a citation for the paper,

Keeping cool: Enhanced optical reflection and heat dissipation in silver ants by Norman Nan Shi, Cheng-Chia Tsai, Fernando Camino, Gary D. Bernard, Nanfang Yu, and Rüdiger Wehner. Science DOI: 10.1126/science.aab3564 Published online June 18, 2015

This paper is behind a paywall.

Wound healing is nature’s way of zipping up your skin

Scientists have been able to observe the healing process at the molecular scale—in fruit flies. From an April 21, 2015 news item on ScienceDaily,

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.

An April 21, 2015 Goethe University Frankfurt press release on EurekAlert, which originated the news item, describes similarities between humans and fruit flies allowing scientists to infer the wound healing process for human skin,

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).

Here’s a link to and a citation for the paper,

Quantitative analysis of cytoskeletal reorganization during epithelial tissue sealing by large-volume electron tomography by Mikhail Eltsov, Nadia Dubé, Zhou Yu, Laurynas Pasakarnis, Uta Haselmann-Weiss, Damian Brunner, & Achilleas S. Frangakis. Nature Cell Biology (2015) doi:10.1038/ncb3159 Published online 20 April 2015

This paper is behind a paywall but there is a free preview available via ReadCube Access.

The researchers have provided an image illustrating ‘wound zipping’.

Caption: This is a perspective view of the zipping area with 17 skin cells. Credit: GU

Caption: This is a perspective view of the zipping area with 17 skin cells.
Credit: GU