Tech

Discovery of quantum behavior in insulators suggests possible new particle

image: A team led by Princeton physicists discovered a surprising quantum phenomenon in an atomically thin insulator made of tungsten ditelluride. The results suggest the formation of completely new types of quantum phases previously hidden in insulators.

Image: 
Image designed by Kai Fu for the Wu Lab, Princeton University

In a surprising discovery, Princeton physicists have observed an unexpected quantum behavior in an insulator made from a material called tungsten ditelluride. This phenomenon, known as quantum oscillation, is typically observed in metals rather than insulators, and its discovery offers new insights into our understanding of the quantum world. The findings also hint at the existence of an entirely new type of quantum particle.

The discovery challenges a long-held distinction between metals and insulators, because in the established quantum theory of materials, insulators were not thought to be able to experience quantum oscillations.

"If our interpretations are correct, we are seeing a fundamentally new form of quantum matter," said Sanfeng Wu, assistant professor of physics at Princeton University and the senior author of a recent paper in Nature detailing this new discovery. "We are now imagining a wholly new quantum world hidden in insulators. It's possible that we simply missed identifying them over the last several decades."

The observation of quantum oscillations has long been considered a hallmark of the difference between metals and insulators. In metals, electrons are highly mobile, and resistivity -- the resistance to electrical conduction -- is weak. Nearly a century ago, researchers observed that a magnetic field, coupled with very low temperatures, can cause electrons to shift from a "classical" state to a quantum state, causing oscillations in the metal's resistivity. In insulators, by contrast, electrons cannot move and the materials have very high resistivity, so quantum oscillations of this sort are not expected to occur, no matter the strength of magnetic field applied.

The discovery was made when the researchers were studying a material called tungsten ditelluride, which they made into a two-dimensional material. They prepared the material by using standard scotch tape to increasingly exfoliate, or "shave," the layers down to what is called a monolayer -- a single atom-thin layer. Thick tungsten ditelluride behaves like a metal. But once it is converted to a monolayer, it becomes a very strong insulator.

"This material has a lot of special quantum properties," Wu said.

The researchers then set about measuring the resistivity of the monolayer tungsten ditelluride under magnetic fields. To their surprise, the resistivity of the insulator, despite being quite large, began to oscillate as the magnetic field was increased, indicating the shift into a quantum state. In effect, the material -- a very strong insulator -- was exhibiting the most remarkable quantum property of a metal.

"This came as a complete surprise," Wu said. "We asked ourselves, 'What's going on here?' We don't fully understand it yet."

Wu noted that there are no current theories to explain this phenomenon.

Nonetheless, Wu and his colleagues have put forward a provocative hypothesis -- a form of quantum matter that is neutrally charged. "Because of very strong interactions, the electrons are organizing themselves to produce this new kind of quantum matter," Wu said.

But it is ultimately no longer the electrons that are oscillating, said Wu. Instead, the researchers believe that new particles, which they have dubbed "neutral fermions," are born out of these strongly interacting electrons and are responsible for creating this highly remarkable quantum effect.

Fermions are a category of quantum particles that include electrons. In quantum materials, charged fermions can be negatively charged electrons or positively charged "holes" that are responsible for the electrical conduction. Namely, if the material is an electrical insulator, these charged fermions can't move freely. However, particles that are neutral -- that is, neither negatively nor positively charged -- are theoretically possible to be present and mobile in an insulator.

"Our experimental results conflict with all existing theories based on charged fermions," said Pengjie Wang, co-first author on the paper and postdoctoral research associate, "but could be explained in the presence of charge-neutral fermions."

The Princeton team plans further investigation into the quantum properties of tungsten ditelluride. They are particularly interested in discovering whether their hypothesis -- about the existence of a new quantum particle -- is valid.

"This is only the starting point," Wu said. "If we're correct, future researchers will find other insulators with this surprising quantum property."

Despite the newness of the research and the tentative interpretation of the results, Wu speculated about how this phenomenon could be put to practical use.

"It's possible that neutral fermions could be used in the future for encoding information that would be useful in quantum computing," he said. "In the meantime, though, we're still in the very early stages of understanding quantum phenomena like this, so fundamental discoveries have to be made."

Credit: 
Princeton University

Canada must dismantle anti-Black racism in medicine

Canada must dismantle anti-Black racism in health care to address its harmful effects on people's health, argue authors of a commentary in CMAJ (Canadian Medical Association Journal)
http://www.cmaj.ca/lookup/doi/10.1503/cmaj.201579

Racism has significant negative effects on the physical and mental health of Black people and people of nondominant racial groups. For example, there have been significantly higher death rates from COVID-19 among Black people in North America and the United Kingdom. Anti-Black racism also exists in the medical system, with stereotyping and bias by health care providers and an underrepresentation of Black physicians.

"First, we who work in health care must acknowledge the existence of anti-Black racism in our systems and commit to meaningful, sustained change. We can do this by listening to the voices of Black Canadians, patients and health care professionals who have been grappling with anti-Black racism for generations, and by engaging with the many communities that have made recommendations for meaningful change to address the problem," write Drs. OmiSoore Dryden, Dalhousie University, Halifax, Nova Scotia, and Onye Nnorom, University of Toronto, Toronto, Ontario, co-leads of Canada's Black Health Education Collaborative.

They recommend anti-racism training for health care providers, collecting race-based data in partnership with specific communities, addressing anti-Black racism in medical schools and the health system, and increasing accessibility and admission for Black students.

"The field of medicine can no longer deny or overlook the existence of systemic anti-Black racism in Canada and how it affects the health of Black people and communities. It is time to acknowledge and commit to dismantling systemic racism within our institutions of care and education," they argue.

Credit: 
Canadian Medical Association Journal

Transition metal 'cocktail' helps make brand new superconductors

image: Schematic of the CuAl2-type crystal structure of the newly created superconducting Co0.2Ni0.1Cu0.1Rh0.3Ir0.3Zr2 compound, with an HEA-type Tr site.

Image: 
Tokyo Metropolitan University

Tokyo, Japan - Researchers from Tokyo Metropolitan University mixed and designed a new, high entropy alloy (HEA) superconductor, using extensive data on simple superconducting substances with a specific crystal structure. HEAs are known to preserve superconducting characteristics up to extremely high pressures. The new superconductor, Co0.2Ni0.1Cu0.1Rh0.3Ir0.3Zr2, has a superconducting transition at 8K, a relatively high temperature for an HEA. The team's approach may be applied to discovering new superconducting materials with specific desirable properties.

It's been over a hundred years since the discovery of superconductivity, where certain materials were found to suddenly show minimal resistance to electrical currents below a transition temperature. As we explore ways to eliminate power waste, a way to dramatically reduce losses in power transmission is a fascinating prospect. But the widespread use of superconductivity is held back by the demands of existing superconductors, particularly the low temperatures required. Scientists need a way to discover new superconducting materials without brute-force trial and error, and tune key properties.

A team led by Associate Professor Yoshikazu Mizuguchi at Tokyo Metropolitan University have been pioneering a "discovery platform" that has already led to the design of many new superconducting substances. Their method is based on high entropy alloys (HEAs), where certain sites in simple crystal structures can be occupied by five or more elements. After being applied to heat resistant materials and medical devices, certain HEAs were found to have superconducting properties with some exceptional characteristics, particularly a retention of zero resistivity under extreme pressures. The team surveys material databases and cutting-edge research and finds a range of superconducting materials with a common crystal structure but different elements on specific sites. They then mix and engineer a structure that contains many of those elements; throughout the crystal, those "HEA sites" are occupied by one of the elements mixed (see Figure 1). They have already succeeded in creating high entropy variants of layered bismuth-sulfide superconductors and telluride compounds with a sodium chloride crystal structure.

In their latest work, they focused on the copper aluminide (CuAl2) structure. Compounds combining a transition metal element (Tr) and zirconium (Zr) into TrZr2 with this structure are known to be superconducting, where Tr could be Sc, Fe, Co, Ni, Cu, Ga, Rh, Pd, Ta, or Ir. The team combined a "cocktail" of these elements using arc melting to create a new HEA-type compound, Co0.2Ni0.1Cu0.1Rh0.3Ir0.3Zr2, which showed superconducting properties. They looked at both resistivity and electronic specific heat, the amount of energy used by the electrons in the material to raise the temperature, and identified a transition temperature of 8.0K. Not only is this relatively high for an HEA-type superconductor, they confirmed that the material had the hallmarks of "bulk" superconductivity.

The most exciting aspect of this is the vast range of other transition metals and ratios that can be tried and tuned to aim for higher transition temperatures and other desirable properties, all without changing the underlying crystal structure. The team hopes their success will lead to more discoveries of new HEA-type superconductors in the near future.

Credit: 
Tokyo Metropolitan University

NIST publishes a beginner's guide to DNA origami

image: Collage shows some of the techniques and designs employed in DNA origami.

Image: 
K. Dill/NIST

In a technique known as DNA origami, researchers fold long strands of DNA over and over again to construct a variety of tiny 3D structures, including miniature biosensors and drug-delivery containers. Pioneered at the California Institute of Technology in 2006, DNA origami has attracted hundreds of new researchers over the past decade, eager to build receptacles and sensors that could detect and treat disease in the human body, assess the environmental impact of pollutants, and assist in a host of other biological applications.

Although the principles of DNA origami are straightforward, the technique's tools and methods for designing new structures are not always easy to grasp and have not been well documented. In addition, scientists new to the method have had no single reference they could turn to for the most efficient way of building DNA structures and how to avoid pitfalls that could waste months or even years of research.

That's why Jacob Majikes and Alex Liddle, researchers at the National Institute of Standards and Technology (NIST) who have studied DNA origami for years, have compiled the first detailed tutorial on the technique. Their comprehensive report provides a step-by-step guide to designing DNA origami nanostructures, using state-of-the-art tools. Majikes and Liddle described their work in the Jan .8 issue of the Journal of Research of the National Institute of Standards and Technology.

"We wanted to take all the tools that people have developed and put them all in one place, and to explain things that you can't say in a traditional journal article," said Majikes. "Review papers might tell you everything that everyone's done, but they don't tell you how the people did it. "

DNA origami relies on the ability of complementary base pairs of the DNA molecule to bind to each other. Among DNA's four bases -- adenine (A), cytosine (C), guanine (G) and thymine (T) -- A binds with T and G with C. This means that a specific sequence of As, Ts, Cs and Gs will find and bind to its complement.

The binding enables short strands of DNA to act as "staples," keeping sections of long strands folded or joining separate strands. A typical origami design may require 250 staples. In this way, the DNA can self-assemble into a variety of shapes, forming a nanoscale framework to which an assortment of nanoparticles -- many useful in medical treatment, biological research and environmental monitoring -- can attach.

The challenges in using DNA origami are twofold, said Majikes. First, researchers are fabricating 3D structures using a foreign language -- the base pairs A, G, T and C. In addition, they're using those base-pair staples to twist and untwist the familiar double helix of DNA molecules so that the strands bend into specific shapes. That can be difficult to design and visualize. Majikes and Liddle urge researchers to strengthen their design intuition by building 3D mock-ups, such as sculptures made with bar magnets, before they start fabrication. These models, which can reveal which aspects of the folding process are critical and which ones are less important, should then be "flattened" into 2D to be compatible with computer-aided design tools for DNA origami, which typically use two-dimensional representations.

DNA folding can be accomplished in a variety of ways, some less efficient than others, noted Majikes. Some strategies, in fact, may be doomed to failure.

"Pointing out things like 'You could do this, but it's not a good idea' -- that type of perspective isn't in a traditional journal article, but because NIST is focused on driving the state of technology in the nation, we're able to publish this work in the NIST journal," Majikes said. "I don't think there's anywhere else that would have given us the leeway and the time and the person hours to put all this together."

Liddle and Majikes plan to follow up their work with several additional manuscripts detailing how to successfully fabricate nanoscale devices with DNA.

Credit: 
National Institute of Standards and Technology (NIST)

'Invisible' stem cells evade natural killer cells using immune 'off-switch'

UC San Francisco scientists have discovered a new way to control the immune system's "natural killer" (NK) cells, a finding with implications for novel cell therapies and tissue implants that can evade immune rejection. The findings could also be used to enhance the ability of cancer immunotherapies to detect and destroy lurking tumors.

The study, published January 8, 2021 in the Journal of Experimental Medicine, addresses a major challenge for the field of regenerative medicine, said lead author Tobias Deuse, MD, the Julien I.E. Hoffman, MD, Endowed Chair in Cardiac Surgery in the UCSF Department of Surgery.

"As a cardiac surgeon, I would love to put myself out of business by being able to implant healthy cardiac cells to repair heart disease," said Deuse, who is interim chair and director of minimally invasive cardiac surgery in the Division of Adult Cardiothoracic Surgery. "And there are tremendous hopes to one day have the ability to implant insulin-producing cells in patients with diabetes or to inject cancer patients with immune cells engineered to seek and destroy tumors. The major obstacle is how to do this in a way that avoids immediate rejection by the immune system."

Deuse and Sonja Schrepfer, MD, PhD, also a professor in the Department of Surgery's Transplant and Stem Cell Immunobiology Laboratory, study the immunobiology of stem cells. They are world leaders in a growing scientific subfield working to produce "hypoimmune" lab-grown cells and tissues -- capable of evading detection and rejection by the immune system. One of the key methods for doing this is to engineer cells with molecular passcodes that activate immune cell "off switches" called immune checkpoints, which normally help prevent the immune system from attacking the body's own cells and modulate the intensity of immune responses to avoid excess collateral damage.

Schrepfer and Deuse recently used gene modification tools to engineer hypoimmune stem cells in the lab that are effectively invisible to the immune system. Notably, as well as avoiding the body's learned or "adaptive" immune responses, these cells could also evade the body's automatic "innate" immune response against potential pathogens. To achieve this, the researchers adapted a strategy used by cancer cells to keep innate immune cells at bay: They engineered their cells to express significant levels of a protein called CD47, which shuts down certain innate immune cells by avtivating a molecular switch found on these cells, called SIRPα. Their success became part of the founding technology of Sana Biotechnology, Inc, a company co-founded by Schrepfer, who now directs a team developing a platform based on these hypoimmune cells for clinical use.

But the researchers were left with a mystery on their hands -- the technique was more successful than predicted. In particular, the field was puzzled that such engineered hypoimmune cells were able to deftly evade detection by NK cells, a type of innate immune cell that isn't supposed to express a SIRPα checkpoint at all.

NK cells are a type of white blood cell that acts as an immunological first responder, quickly detecting and destroying any cells without proper molecular ID proving they are "self" -- native body cells or at least permanent residents -- which takes the form of highly individualized molecules called MHC class I (MHC-I). When MHC-I is artificially knocked out to prevent transplant rejection, the cells become susceptible to accelerated NK cell killing, an immunological rejection that no one in the field had yet succeeded in inhibiting fully. Deuse and Schrepfer's 2019 data, published in Nature Biotechnology, suggested they might have stumbled upon an off switch that could be used for that purpose.

"All the literature said that NK cells don't have this checkpoint, but when we looked at cells from human patients in the lab we found SIRPα there, clear as day," Schrepfer recalled. "We can clearly demonstrate that stem cells we engineer to overexpress CD47 are able to shut down NK cells through this pathway."

To explore their data, Deuse and Schrepfer approached Lewis Lanier, PhD, a world expert in NK cell biology. At first Lanier was sure there must be some mistake, because several groups had looked for SIRPα in NK cells already and it wasn't there. But Schrepfer was confident in her team's data.

"Finally it hit me," Schrepfer said. "Most studies looking for checkpoints in NK cells were done in immortalized lab-grown cell lines, but we were studying primary cells directly from human patients. I knew that must be the difference."

Further examination revealed that NK cells only begin to express SIRPα after they are activated by certain immune signaling molecules called cytokines. As a result, the researchers realized, this inducible immune checkpoint comes into effect only in already inflammatory environments and likely functions to modulate the intensity of NK cells' attack on cells without proper MHC class I identification.

"NK cells have been a major barrier to the field's growing interest in developing universal cell therapy products that can be transplanted "off the shelf" without rejection, so these results are extremely promising," said Lanier, chair and J. Michael Bishop Distinguished Professor in the Department of Microbiology and Immunology.

In collaboration with Lanier, Deuse and Schrepfer comprehensively documented how CD47-expressing cells can silence NK cells via SIRPα. While other approaches can silence some NK cells, this was the first time anyone has been able to inhibit them completely. Notably, the team found that NK cells' sensitivity to inhibition by CD47 is highly species-specific, in line with its function in distinguishing "self" from potentially dangerous "other".

As a demonstration of this principle, the team engineered adult human stem cells with the rhesus macaque version of CD47, then implanted them into rhesus monkeys, where they successfully activated SIRPα in the monkeys' NK cells, and avoided killing the transplanted human cells. In the future the same procedure could be performed in reverse, expressing human CD47 in pig cardiac cells, for instance, to prevent them from activating NK cells when transplanted into human patients.

"Currently engineered CAR T cell therapies for cancer and fledgling forms of regenerative medicine all rely on being able to extract cells from the patient, modify them in the lab, and then put them back in the patient. This avoids rejection of foreign cells, but is extremely laborious and expensive," Schrepfer said. "Our goal in establishing a hypoimmune cell platform is to create off-the shelf products that can be used to treat disease in all patients everywhere."

The findings could also have implications for cancer immunotherapy, as a way of boosting existing therapies that attempt to overcoming the immune checkpoints cancers use to evade immune detection. "Many tumors have low levels of self-identifying MHC-I protein and some compensate by overexpressing CD47 to keep immune cells at bay," said Lanier, who is director of the Parker Institute for Cancer Immunotherapy at the UCSF Helen Diller Family Comprehensive Cancer Center. "This might be the sweet spot for antibody therapies that target CD47."

Credit: 
University of California - San Francisco

Bats with white-nose syndrome prefer suboptimal habitats despite the consequences

image: Four little brown bats. Photo courtesy of Joseph Hoyt of Virginia Tech

Image: 
Joseph Hoyt of Virginia Tech

Since 2006, a fungal disease called white-nose syndrome has caused sharp declines in bat populations across the eastern United States. The fungus that causes the disease, Pseudogymnoascus destructans, thrives in subterranean habitats where bats hibernate over the winter months.

Bats roosting in the warmest sites have been hit particularly hard, since more fungus grows on their skin, and they are more likely to die from white-nose syndrome, according to a new study by researchers at Virginia Tech.

But instead of avoiding these warm and deadly sites, bats continue to use them year after year. The reason? Bats are mistakenly preferring sites where fungal growth is high and therefore their survival is low. This is one of the first clear examples of an infectious disease creating an "ecological trap" for wildlife.

Kate Langwig and Joseph Hoyt, both assistant professors from the Department of Biological Sciences in the College of Science, have been studying little brown bat (Myotis lucifugus) populations in Michigan and Wisconsin since 2012, before the fungus first reached those states. This long-term study was the perfect opportunity to see if bats alter their preferences across hibernacula, or hibernation sites, in response to the invasion of white-nose syndrome.

"We see that there is a shift across the regional bat population over time," said Skylar Hopkins, a previous postdoctoral scholar at Virginia Tech and now assistant professor at North Carolina State University.

"When we look at the population post-invasion, we see that more than 50 percent of the bats are still choosing to roost in warmer sites, even though colder sites are available. But on average, bat roosting temperatures have declined, because the colder-roosting bats have had higher survival rates."

Their findings were posted in Nature Communications.

To understand how temperatures are playing a role in bat population declines, the researchers used a mark-recapture method, which involves banding bats and then trying to find them later.

The team visited bat hibernacula for sampling twice per year: once in early hibernation, after all of the bats had arrived and settled down for the winter, and once again in late hibernation, before the bats emerged from their hibernation habitat.

If bats were missing in late hibernation that had been present earlier in the winter, those bats had left the hibernacula early and likely died in the cold, insect-free Midwest winter.

The research team also used a swab to measure the fungal loads that were on each individual bat and used a laser thermometer to measure the roosting temperature of the rocks next to each bat.

Now that they know that bats are preferring high mortality sites, Hopkins hopes that their data can be used to think about which sites researchers and conservationists need to prioritize for conservation and how to conserve them.

"Because we know that bats are doing better in the cold sites, the cold sites may be good ones for us to conserve," said Hopkins. "We can also think more about the warm sites that are acting as ecological traps and whether we should be trying to manage those sites in a different way. Maybe there are interventions that should be done at those sites to prevent most of the population from going there each year and having these big mortality events."

One's first instinct upon hearing about these interventions would be to close off these deadly hibernacula entirely. But according to Langwig, it's just not that simple.

"The thing that is hard is that there are multiple bat species in these habitats. And I worry that there would be cascading impacts on some of the other bat species if we attempted to alter the sites. It depends a lot on the physiology of the bat," said Langwig, who is an affiliated faculty member of the Fralin Life Sciences Institute and the Global Change Center. "But there may be some creative solutions. There are researchers in Michigan and Pennsylvania who have been working to cool down the warmer sites by modifying the entrances or using solar power to pump air into the sites."

Of course, temperature is just one aspect of the microclimate that bats experience while they are hibernating. Hopkins and Langwig expect that humidity could also play a role in the spread of white-nose syndrome. But, measuring humidity is easier said than done. Since underground hibernacula have a high relative humidity, it can be difficult to make accurate measurements.

"We've designed new humidity loggers to collect better humidity data than has been possible before. These loggers are already deployed in caves and mines across the eastern United States, so we hope to soon understand how humidity has played a role in bat population declines, if at all," said Hopkins.

Credit: 
Virginia Tech

Entangling electrons with heat

image: False-colour electron microscope image of the sample, the green layers are graphene on top of the grey superconductor. The blue metal electrodes are used to extract the entangled electrons

Image: 
Aalto University

A joint group of scientists from Finland, Russia, China and the USA have demonstrated that temperature difference can be used to entangle pairs of electrons in superconducting structures. The experimental discovery, published in Nature Communications, promises powerful applications in quantum devices, bringing us one step closer towards applications of the second quantum revolution.

The team, led by Professor Pertti Hakonen from Aalto University, has shown that the thermoelectric effect provides a new method for producing entangled electrons in a new device. "Quantum entanglement is the cornerstone of the novel quantum technologies. This concept, however, has puzzled many physicists over the years, including Albert Einstein who worried a lot about the spooky interaction at a distance that it causes", says Prof. Hakonen.

In quantum computing, entanglement is used to fuse individual quantum systems into one, which exponentially increases their total computational capacity. "Entanglement can also be used in quantum cryptography, enabling the secure exchange of information over long distances", explains Prof. Gordey Lesovik, from the Moscow Institute of Physics and Technology, who has acted several times as a visiting professor at Aalto University School of Science. Given the significance of entanglement to quantum technology, the ability to create entanglement easily and controllably is an important goal for researchers.

The researchers designed a device where a superconductor was layered withed graphene and metal electrodes. "Superconductivity is caused by entangled pairs of electrons called "cooper pairs". Using a temperature difference, we cause them to split, with each electron then moving to different normal metal electrode," explains doctoral candidate Nikita Kirsanov, from Aalto University. "The resulting electrons remain entangled despite being separated for quite long distances."

Along with the practical implications, the work has significant fundamental importance. The experiment has shown that the process of Cooper pair splitting works as a mechanism for turning temperature difference into correlated electrical signals in superconducting structures. The developed experimental scheme may also become a platform for original quantum thermodynamical experiments.

Credit: 
Aalto University

Engineers find antioxidants improve nanoscale visualization of polymers

image: Adding antioxidants can push the resolution limit of polymer electron microscopy to reveal a structure smaller in scale (blue) compared to the structure previously observed (pink) in this false-color image.

Image: 
Brooke Kuei, Penn State

Reactive molecules, such as free radicals, can be produced in the body after exposure to certain environments or substances and go on to cause cell damage. Antioxidants can minimize this damage by interacting with the radicals before they affect cells.

Led by Enrique Gomez, professor of chemical engineering and materials science and engineering, Penn State researchers have applied this concept to prevent imaging damage to conducting polymers that comprise soft electronic devices, such as organic solar cells, organic transistors, bioelectronic devices and flexible electronics. The researchers published their findings in Nature Communications today (Jan. 8).

According to Gomez, visualizing the structures of conducting polymers is crucial to further develop these materials and enable commercialization of soft electronic devices -- but the actual imaging can cause damage that limits what researchers can see and understand.

"It turns out antioxidants, like those you'd find in berries, aren't just good for you but are also good for polymer microscopy," Gomez said.

Polymers can only be imaged to a certain point with high-resolution transmission electron microscopy (HRTEM) because the bombardment of electrons used to form images breaks the sample apart.

The researchers examined this damage with the goal of identifying its fundamental cause. They found the HRTEM electron beam generated free radicals that degraded the sample's molecular structure. Introducing butylated hydroxytoluene, an antioxidant often used as a food additive, to the polymer sample prevented this damage and removed another restriction on imaging conditions -- temperature.

"Until now, the main strategy for minimizing polymer damage has been imaging at very low temperatures," said paper co-author Brooke Kuei, who earned her doctorate in materials science and engineering in the Penn State College of Earth and Mineral Sciences in August. "Our work demonstrates that the beam damage can be minimized with the addition of antioxidants at room temperature."

Although the researchers did not quantitatively test the resolution limits that resulted from this method, they were able to image the polymer at a resolution of 3.6 angstroms, an improvement from their previous resolution of 16 angstroms. For comparison, an angstrom is about one-millionth the breadth of a human hair.

Polymers are made up of molecular chains lying on top of each other. The previously imaged distance of 16 angstroms was the distance between chains, but imaging at 3.6 angstroms allowed researchers to visualize patterns of close contacts along the chains. For the electrically conductive polymer examined in this study, researchers could follow the direction along which electrons travel. According to Gomez, this allows them to better understand the conductive structures in polymers.

"The key to this advancement in polymer microscopy was understanding the fundamentals of how the damage occurs in these polymers," Gomez said. "This technological advance will hopefully help lead to the next generation of organic polymers."

Credit: 
Penn State

Which came first, sleep or the brain?

image: Hydra vulgaris is a tiny cnidarian with a simple anatomy. Collaborative research led by Kyushu University found that, despite lacking a central nervous system, hydras exhibit characteristics at a molecular and genetic level associated with sleep in more evolved animals, indicating that sleep-related mechanisms may have been acquired before the evolution of the brain.

Image: 
Taichi Q. Itoh, Kyushu University

Stay awake too long, and thinking straight can become extremely difficult. Thankfully, a few winks of sleep is often enough to get our brains functioning up to speed again. But just when and why did animals start to require sleep? And is having a brain even a prerequisite?

In a study that could help to understand the evolutional origin of sleep in animals, an international team of researchers has shown that tiny, water-dwelling hydras not only show signs of a sleep-like state despite lacking central nervous systems but also respond to molecules associated with sleep in more evolved animals.

"We now have strong evidence that animals must have acquired the need to sleep before acquiring a brain," says Taichi Q. Itoh, assistant professor at Kyushu University's Faculty of Arts and Science and leader of the research reported in Science Advances.

While sleeping behavior was also recently found in jellyfish, a relative of hydras and fellow member of the phylum Cnidaria, the new study from researchers at Kyushu University in Japan and Ulsan National Institute of Science and Technology in Korea found that several chemicals eliciting drowsiness and sleep even in humans had similar effects on the species Hydra vulgaris.

"Based on our findings and previous reports regarding jellyfish, we can say that sleep evolution is independent of brain evolution," states Itoh.

"Many questions still remain regarding how sleep emerged in animals, but hydras provide an easy-to-handle creature for further investigating the detailed mechanisms producing sleep in brainless animals to help possibly one day answer these questions."

Only a couple of centimeters long, hydras have a diffuse network of nerves but lack the centralization associated with a brain.

While sleep is often monitored based on the measurement of brain waves, this is not an option for tiny, brainless animals.

As an alternative, the researchers used a video system to track movement to determine when hydras were in a sleep-like state characterized by reduced movement--which could be disrupted with a flash of light.

Instead of repeating every 24 hours like a circadian rhythm, the researchers found that the hydras exhibit a four-hour cycle of active and sleep-like states.

More importantly, the researchers uncovered many similarities related to sleep regulation on a molecular and genetic level regardless of the possession of a brain.

Exposing the hydras to melatonin, a commonly used sleep aid, moderately increased the sleep amount and frequency, while the inhibitory neurotransmitter GABA, another chemical linked to sleep activity in many animals, greatly increased sleep activity.

On the other hand, dopamine, which causes arousal in many animals, actually promoted sleep in the hydras.

"While some sleep mechanisms appear to have been conserved, others may have switched function during evolution of the brain," suggests Itoh.

Furthermore, the researchers could use vibrations and temperature changes to disturb the hydras' sleep and induce signs of sleep deprivation, causing the hydras to sleep longer during the following day and even suppressing cell proliferation.

Investigating more closely, the researchers found that sleep deprivation led to changes in the expression of 212 genes, including one related to PRKG, a protein involved in sleep regulation in the wide range of animals, including mice, fruit flies, and nematodes.

Disrupting other fruit fly genes appearing to share a common evolutional origin with the sleep-related ones in hydras altered sleep duration in fruit flies, and further investigation of such genes may help to identify currently unknown sleep-related genes in animals with brains.

"Taken all together, these experiments provide strong evidence that animals acquired sleep-related mechanisms before the evolutional development of the central nervous system and that many of these mechanisms were conserved as brains evolved," says Itoh.

Credit: 
Kyushu University

Scientists paint multicolor atlas of the brain

image: A NeuroPAL worm coiled into an O-shape with the head and tail touching each other at the top of the ring. Every neuron (the colored dots) can be identified by its color. The colors are added with fluorescent proteins using a newly developed genetic engineering technique.

Image: 
Eviatar Yemini

The human brain contains approximately 86 billion neurons, or nerve cells, woven together by an estimated 100 trillion connections, or synapses. Each cell has a role that helps us to move muscles, process our environment, form memories, and much more.

Given the huge number of neurons and connections, there is still much we don't know about how neurons work together to give rise to thought or behavior.

Now Columbia scientists have engineered a coloring technique, known as NeuroPAL (a Neuronal Polychromatic Atlas of Landmarks), which makes it possible--at least in experiments with Caenorhabditis elegans (C. elegans), a worm species commonly used in biological research--to identify every single neuron in the mind of a worm.

Their research appears in the Jan. 7 issue of the journal Cell.

NeuroPAL, which uses genetic methods to "paint" neurons with fluorescent colors, permits, for the first time ever, scientists to identify each neuron in an animal's nervous system, all while recording a whole nervous system in action.

"It's amazing to 'watch' a nervous system in its entirety and see what it does," said Oliver Hobert, professor in the Department of Biological Sciences at Columbia and a principal investigator with the Howard Hughes Medical Institute. "The images created are stunning-- brilliant spots of color appear in the worm's body like Christmas lights on a dark night."

To conduct their research, the scientists created two software programs: one that identifies all the neurons in colorful NeuroPAL worm images and a second that takes the NeuroPAL method beyond the worm by designing optimal coloring for potential methods of identification of any cell type or tissue in any organism that permits genetic manipulations.

"We used NeuroPAL to record brainwide activity patterns in the worm and decode the nervous system at work," said Eviatar Yemini, a postdoctoral researcher in the Department of Biological Sciences at Columbia and lead author of the study.

Because the colors are painted into the neuron's DNA and linked to specific genes, the colors can also be used to reveal whether these specific genes are present or absent from a cell.

The researchers said that the novelty of the technique may soon be overshadowed by the discoveries it makes possible. In advance of their Cell publication, Hobert and Yemini released NeuroPAL to the scientific community, and several studies already have been published showing the utility of the tool.

"Being able to identify neurons, or other types of cells, using color can help scientists visually understand the role of each part of a biological system,” Yemini said. “That means when something goes wrong with the system, it may help pinpoint where the breakdown occurred.”

Collaborators on the study include Liam Paninski, Columbia University; Vivek Venkatachalam, Northeastern University; and Aravinthan Samuel, Harvard University.

Credit: 
Columbia University

Scientists develop a cheaper method that might help create fuels from plants

COLUMBUS, Ohio - Scientists have figured out a cheaper, more efficient way to conduct a chemical reaction at the heart of many biological processes, which may lead to better ways to create biofuels from plants.

Scientists around the world have been trying for years to create biofuels and other bioproducts more cheaply; this study, published today in the journal Scientific Reports, suggests that it is possible to do so.

"The process of converting sugar to alcohol has to be very efficient if you want to have the end product be competitive with fossil fuels," said Venkat Gopalan, a senior author on the paper and professor of chemistry and biochemistry at The Ohio State University. "The process of how to do that is well-established, but the cost makes it not competitive, even with significant government subsidies. This new development is likely to help lower the cost."

At the heart of their discovery: A less expensive and simpler method to create the "helper molecules" that allow carbon in cells to be turned into energy. Those helper molecules (which chemists call cofactors) are nicotinamide adenine dinucleotide (NADH) and its derivative (NADPH). These cofactors in their reduced forms have long been known to be a key part of turning sugar from plants into butanol or ethanol for fuels. Both cofactors also play an important role in slowing the metabolism of cancer cells and have been a target of treatment for some cancers.

But NADH and NADPH are expensive.

"If you can cut the production cost in half, that would make biofuels a very attractive additive to make flex fuels with gasoline," said Vish Subramaniam, a senior author on the paper and recently retired professor of engineering at Ohio State. "Butanol is often not used as an additive because it's not cheap. But if you could make it cheaply, suddenly the calculus would change. You could cut the cost of butanol in half, because the cost is tied up in the use of this cofactor."

To create these reduced cofactors in the lab, the researchers built an electrode by layering nickel and copper, two inexpensive elements. That electrode allowed them to recreate NADH and NADPH from their corresponding oxidized forms. In the lab, the researchers were able to use NADPH as a cofactor in producing an alcohol from another molecule, a test they did intentionally to show that ¬the electrode they built could help convert biomass - plant cells - to biofuels. This work was performed by Jonathan Kadowaki and Travis Jones, two mechanical and aerospace engineering graduate students in the Subramaniam lab, and Anindita Sengupta, a postdoctoral researcher in the Gopalan lab.

But because NADH and NADPH are at the heart of so many energy conversion processes inside cells, this discovery could aid other synthetic applications.

Subramaniam's previous work showed that electromagnetic fields can slow the spread of some breast cancers. He retired from Ohio State on Dec. 31.

This finding is connected, he said: It might be possible for scientists to more easily and affordably control the flow of electrons in some cancer cells, potentially slowing their growth and ability to metastasize.

Subramaniam also has spent much of his later scientific career exploring if scientists could create a synthetic plant, something that would use the energy of the sun to convert carbon dioxide into oxygen. On a large enough scale, he thought, such a creation could potentially reduce the amount of carbon dioxide in the atmosphere and help address climate change.

"I've always been interested in that question of, 'Can we make a synthetic plant? Can we make something that can solve this global warming problem with carbon dioxide?'" Subramaniam said. "If it's impractical to do it with plants because we keep destroying them via deforestation, are there other inorganic ways of doing this?"

This discovery could be a step toward that goal: Plants use NADPH to turn carbon dioxide into sugars, which eventually become oxygen through photosynthesis. Making NADPH more accessible and more affordable could make it possible to produce an artificial photosynthesis reaction.

But its most likely and most immediate application is for biofuels.

That the researchers came together for this scientific inquiry was rare: Biochemists and engineers don't often conduct joint laboratory research.

Gopalan and Subramaniam met at a brainstorming session hosted by Ohio State's Center for Applied Plant Sciences (CAPS), where they were told to think about "big sky ideas" that might help solve some of society's biggest problems. Subramaniam told Gopalan about his work with electrodes and cells, "and the next thing we knew, we were discussing this project," Gopalan said. "We certainly would not have talked to each other if it were not for the CAPS workshop."

Credit: 
Ohio State University

Bioenergetics: New features of ATP synthase

video: ATP synthase hexamer assemblies shape cristae of Toxoplasma mitochondria

Image: 
Falconieri Visuals

The mitochondrial ATP synthase is energy-converting macromolecular machine that uses the electrochemical potential across the bioenergetic membrane called cristae. This potential is maintained via a membrane curvature that is induced by ATP synthase assembled in dimers. The dimers shaping the bioenergetic membrane were thought to be universal across the eukaryotic organisms. Two newly published cryo-EM studies by Kock-Flygaard et al and Mühleip et al from Alexey Amunts lab, identify different types of ATP synthase organization.

The structure of the ATP synthase from ciliates revealed a dimer, which unlike in all the previously investigated complexes, the two membrane-embedded parts are not identical to each other. The commonly observed symmetry is broken by the accommodation of a single subunit at the dimer interface that anchors an inhibitor. In addition, the ATP synthase has an unusual U-shape arrangement, and thus the generation of the membrane curvature is achieved through tetramerization. Therefore, this work defines ATP synthase tetramer as the intact structural unit propagating cristae formation in ciliates.

The investigation of the infectious apicomplexan parasites Toxoplasma, revealed that their ATP synthase is arranged in cyclic hexamers. However, within the hexamer, the lipid bilayer turns out to be near-planar, which is not sufficient to shape the bioenergetic membrane. Therefore, the cryo-electron tomography approach was applied to the native membranes isolated from the parasites' mitochondria, which revealed that the hexamers are further arranged in a higher order of organization. Particularly, 20 units of ATP synthase are linked together in large arrays with icosahedral symmetry. They form pentagonal pyramids at the size of 20 mega-Dalton. In the center of each pyramid, hexamer ATP synthase planes are oriented by 40°. Therefore, the mechanism of pentagonal pyramids generates cristae morphology in a way that differs from the canonical dimers thought to be universal.

Finally, the structural studies identified a key subunit ATPTG11 holding the hexamers together. A removal of the subunit showed loss of pentagonal pyramids, aberrantly shaped cristae, and defective growth of the parasites. This demonstrates that the unique macromolecular arrangement is critical for the maintenance of bioenergetics in Apicomplexa.

Together, these studies illustrate the structural basis for the diversity of the membrane-shaping properties of mitochondrial ATP synthases. This suggests that the fundamental mechanism of the ATP synthase association varies between eukaryotic lineages.

Credit: 
Science For Life Laboratory

USTC develops ultrahigh-performance plasmonic metal-oxide materials

In a study published in Advanced Materials, the researchers from Hefei National Laboratory for Physical Sciences at the Microscale, the University of Science and Technology of China of the Chinese Academy of Sciences, using an electron-proton co-doping strategy, invented a new metal-like semiconductor material with excellent plasmonic resonance performance. This material achieves a metal-like ultrahigh free-carrier concentration that leads to strong and tunable plasmonic field.

Plasmonic materials are widely used in the fields including microscopy, sensing, optical computing and photovoltaics. Most common plasmonic materials are gold and silver. Some other materials also show metal-like optical properties but just perform poor in limited wavelength ranges.

In recent years, much effort has been made in finding high-performance plasmonic materials excluding noble metals. Metal-oxide semiconductor materials have rich and tunable properties such as light, electricity, heat, and magnetism. Hydrogenation treatment can effectively modify their electronic structure to reach rich and tunable plasmon effects. It is a challenge to significantly increase the intrinsically low concentration of free carriers in metal-oxide materials.

The researchers in this study developed a electron-proton co-doping strategy with theoretical calculations. They hydrogenated the semiconductor material MoO3 via a simplified metal-acid treatment at mild conditions, realizing the controllable insulator-to-metal phase transition, which significantly increase the concentration of free carriers in the metal-oxide material.

The free electron concentration in the hydrogenated MoO3 material is equivalent to that of the precious metal. This property makes the plasmon resonance response of the material moving from the near infrared area to the visible light area. The plasmon resonance response of the material has both strong gain and adjustability.

Using ultrafast spectroscopy characterizations and first-principle simulations, the researchers unraveled the quasi-metallic energy band structure in the hydrogen-doped HxMoO3 with its dynamical features of plasmonic responses.

To verify their modification, they performed the surface-enhanced Raman spectra (SERS) of rhodamine 6G molecules on the material. The result showed that the SERS enhancement factor reached as high as 1.1 × 107 with a detection limit at concentration as low as 1 × 10-9 mol/L.

This study developed a general strategy to increase the concentration of free carriers in a non-metal semiconductor material system, which not only realized a quasi-metallic phase material with strong and tunable plasmon effect at low cost, but also significantly broadened the variable range of the physical and chemical properties of semiconductor materials. It provides a unique idea and guidance for designing novel metal oxide functional materials.

Credit: 
University of Science and Technology of China

Tiny wireless device sheds light on combating obesity

image: Dr. Sung II Park's paddle-shaped device consists of a harvestor that contains microchips for wireless communication. The harvestor also produces currents to power LEDs inserted near the end of the shaft.

Image: 
Texas A&M University College of Engineering

Gastric bypass surgery is sometimes the last resort for those who struggle with obesity or have serious health-related issues due to their weight. Since this procedure involves making a small stomach pouch and rerouting the digestive tract, it is very invasive and prolongs the recovery period for patients. In a new study, researchers at Texas A&M University have described a medical device that might help with weight loss and requires a simpler operative procedure for implantation.

Researchers said their centimeter-sized device provides the feeling of fullness by stimulating the endings of the vagus nerve with light. Unlike other devices that require a power cord, their device is wireless and can be controlled externally from a remote radio frequency source.

"We wanted to create a device that not only requires minimal surgery for implantation but also allows us to stimulate specific nerve endings in the stomach," said Dr. Sung II Park, assistant professor in the Department of Electrical and Computer Engineering. "Our device has the potential to do both of these things in the harsh gastric conditions, which, in the future, can be hugely beneficial to people needing dramatic weight-loss surgeries."

Further details about their device are published in the January issue of Nature Communications.

Obesity is a global epidemic. Furthermore, its associated health problems have a significant economic impact on the U.S. health care system, costing $147 billion a year. Additionally, obesity puts people at risk for chronic diseases such as diabetes, heart disease and even some cancers. For those with a body mass index greater than 35 or who have at least two obesity-related conditions, surgery offers a path for patients to not only lose the excess weight but maintain their weight over the long term.

In recent years, the vagus nerve has received much attention as a target for treating obesity since it provides sensory information about fullness from the stomach lining to the brain. Although there are medical devices that can stimulate the vagus nerve endings and consequently help in curbing hunger, these devices are similar in design to a pacemaker, that is, wires connected to a current source provide electrical jolts to activate the tips of the nerve.

However, Park said wireless technology, as well as the application of advanced genetic and optical tools, have the potential to make nerve stimulation devices less cumbersome and more comfortable for the patient.

"Despite the clinical benefit of having a wireless system, no device, as of yet, has the capability to do chronic and durable cell-type specific manipulation of neuron activity inside of any other organ other than the brain," he said.

To address this gap, Park and his team first used genetic tools to express genes that respond to light into specific vagus nerve endings in vivo. Then, they designed a tiny, paddle-shaped device and inserted micro LEDs near the tip of its flexible shaft, which was fastened to the stomach. In the head of the device, called the harvester, they housed microchips needed for the device to wirelessly communicate with an external radio frequency source. The harvester was also equipped to produce tiny currents to power the LEDs. When the radio frequency source was switched on, the researchers showed that the light from the LEDs was effective at suppressing hunger.

The researchers said they were surprised to uncover that the biological machinery coordinating hunger suppression in their experiments was different from conventional wisdom. In other words, it is widely accepted that when the stomach is full, it expands and the information about stretch is conveyed to the brain by mechanoreceptors on the vagus nerve.

"Our findings suggest that stimulating the non-stretch receptors, the ones that respond to chemicals in the food, could also give the feeling of satiety even when the stomach was not distended," said Park.

Looking ahead, he said that the current device could also be used to manipulate nerve endings throughout the gastrointestinal tract and other organs, like the intestine, with little or no modifications.

"Wireless optogenetics and identifying peripheral neural pathways that control appetite and other behaviors are all of great interest to researchers in both the applied and basic fields of study in electronics, material science and neuroscience," said Park. "Our novel tool now enables interrogation of neuronal function in the peripheral nervous systems in a way that was impossible with existing approaches."

Credit: 
Texas A&M University

Study reveals jellyfish create a 'virtual wall' to enhance performance

video: High-speed camera captures jellyfish swimming through a laser sheet with tracer particles.

Image: 
University of South Florida

TAMPA, Fla. (Jan. 8, 2021)- New research led by the University of South Florida has uncovered one of the reasons jellyfish have come to be known as the "world's most efficient swimmer." Brad Gemmell, associate professor of integrative biology, found jellyfish produce two vortex rings, which are donut-shaped bodies of fluid underneath their translucent bodies, that spin in opposite directions. They appear as jellyfish squeeze and reopen throughout each swim cycle, providing a "ground effect" force as if they were to be pushing off the seafloor.

The "ground effect" is most widely understood on airport runways. During take-off, air squeezes between the airplane and ground, which builds pressure and a force that boosts performance. Gemmell's experiments have shown that jellyfish can use their two vortex rings in place of the ground. The vortex rings resist each other, creating a "virtual wall" that provides a similar boost in performance compared to animals that swim near the bottom. Never before has it been proven that an animal can create this phenomenon away from a solid boundary.

"The fact that these simple animals have figured out how to achieve a 'ground effect' type boost in open water, away from any solid surfaces, has the potential to open up a range of new possibilities for engineered vehicles to take advantage of this phenomenon," Gemmell said.

In the study published in "Proceedings of the Royal Society B," Gemmell captured the motion by recording the movements of eight jellyfish swimming in a glass filming vessel using a high-speed digital camera at 1,000 frames per second. He and his colleagues witnessed jellyfish that were in motion had a 41% increase in maximum swimming speed and a 61% increase in cumulative distance traveled per swimming cycle compared to those starting from rest.

Unlike locomotion by propellers, jellyfish do not produce cavitation bubbles and are silent, allowing them to move quietly through the water. The high efficiency of swimming also helps them store energy for growth and reproduction. Several research groups use jellyfish as a model for developing underwater vehicles that can be equipped with sensors that monitor the ocean without disruption. These new findings may enhance development of these technologies and further understanding of the ocean.

Credit: 
University of South Florida