Culture

Coronavirus testing kits to be developed using SFU-invented RNA imaging technology

image: SFU researcher Lena Dolgosheina holds up tubes to demonstrate the Mango imaging technology.

Image: 
Simon Fraser University

Simon Fraser University researchers will use their pioneering imaging technology--called Mango, for its bright colour-- to develop coronavirus testing kits. They're among a small set of Canadian researchers who responded to the rapid funding opportunity recently announced by the Canadian Institutes of Health Research (CIHR) to help address COVID-19.

SFU researchers Lena Dolgosheina, a post-doctoral fellow and Peter Unrau, a professor of molecular biology and biochemistry, developed Mango to sensitively detect RNA molecules, helping to improve viral screening for viruses such as the coronavirus while enabling basic discoveries into the functioning of cells.

The latest research, led by Unrau, involves using Mango to detect individual molecules of RNA within a living cell.

"We are made of molecules so when something goes wrong within a cell it happens at the molecular level, says Unrau. "We are using the Mango system as a catalyst, to allow us to not only extend fundamental research questions but also to detect pathogens like the coronavirus, faster and more efficiently."

The Mango system consists of an RNA Mango aptamer that binds tightly and specifically to a fluorescent dye. The aptamer acts like a magnet - targeting and binding those dye molecules. The dye becomes excitable when bound and glows brightly. RNA molecules modified to contain the aptamer 'magnet' now stand out from the other parts of the cell, which makes it much easier for researchers to see and study RNA molecules under a microscope.

"Cell regulation takes place at the level of RNA," he says. "For a long time, the focus has been on protein but it is RNA and not protein that regulates the vast majority of processes within a cell."

RNA Mango dyes are currently available from Applied Biological Materials (ABM) in Richmond, B.C. The coronavirus research made possible by CIHR funding will allow the team to develop an isothermal testing methodology, known as Mango NABSA (nucleic acid sequence-based amplification).

The Mango NABSA kits can be used to test for the coronavirus, which is a positive strand RNA virus. ABM is actively involved with this project as a partner and will supply the enzymes and buffers needed, which the SFU team originally developed.

"Mango technology is state of the art and the development of effective cures for cancer and other diseases demand better imaging methodologies to rapidly learn how cells work in detail," Unrau adds.

The team's research is published in Nature Communications.

Credit: 
Simon Fraser University

Army scientists create quantum sensor that covers entire radio frequency spectrum

image: Atoms in a glass vapor cell are excited with laser beams to Rydberg states. They detect the electric fields (coming from the gold antenna in the background) and imprint the information back onto the laser beams.

Image: 
U.S. Army photo

ADELPHI, Md. (March 19, 2020) - A quantum sensor could give Soldiers a way to detect communication signals over the entire radio frequency spectrum, from 0 to 100 GHz, said researchers from the Army.

Such wide spectral coverage by a single antenna is impossible with a traditional receiver system, and would require multiple systems of individual antennas, amplifiers and other components.

In 2018, Army scientists were the first in the world to create a quantum receiver that uses highly excited, super-sensitive atoms--known as Rydberg atoms--to detect communications signals, said David Meyer, a scientist at the U.S. Army Combat Capabilities Development Command's Army Research Laboratory. The researchers calculated the receiver's channel capacity, or rate of data transmission, based on fundamental principles, and then achieved that performance experimentally in their lab--improving on other groups' results by orders of magnitude, Meyer said.

"These new sensors can be very small and virtually undetectable, giving Soldiers a disruptive advantage," Meyer said. "Rydberg-atom based sensors have only recently been considered for general electric field sensing applications, including as a communications receiver. While Rydberg atoms are known to be broadly sensitive, a quantitative description of the sensitivity over the entire operational range has never been done."

To assess potential applications, Army scientists conducted an analysis of the Rydberg sensor's sensitivity to oscillating electric fields over an enormous range of frequencies--from 0 to 1012 Hertz. The results show that the Rydberg sensor can reliably detect signals over the entire spectrum and compare favorably with other established electric field sensor technologies, such as electro-optic crystals and dipole antenna-coupled passive electronics.

"Quantum mechanics allows us to know the sensor calibration and ultimate performance to a very high degree, and it's identical for every sensor," Meyer said. "This result is an important step in determining how this system could be used in the field."

This work supports the Army's modernization priorities in next-generation computer networks and assured position, navigation and timing, as it could potentially influence novel communications concepts or approaches to detection of RF signals for geolocation.

In the future, Army scientists will investigate methods to continue to improve the sensitivity to detect even weaker signals and expand detection protocols for more complicated waveforms.

Credit: 
U.S. Army Research Laboratory

Composite metal foams take the heat, move closer to widespread applications

image: This image shows steel-steel composite metal foam samples before testing (right) and after 100 minutes exposure to 825C (left).

Image: 
Afsaneh Rabiei, NC State University

North Carolina State University researchers have demonstrated that composite metal foams (CMFs) can pass so-called "simulated pool fire testing" with flying colors, moving the material closer to use in applications such as packaging and transportation of hazardous materials. In addition, researchers used this experimental data to develop a model for predicting how variations in the CMF would affect its performance.

Simulated pool fire testing is not a computational simulation. It's an experimental test that materials must pass in order to be considered for use in manufacturing rail tank cars that transport hazardous materials. In simulated pool fire testing, a panel of material is exposed to a temperature of at least 816 degrees Celsius on one side for 100 minutes. A suite of thermal sensors rests on the other side of the panel. If those protected sensors register a temperature of 427 degrees Celsius or higher at any point during the 100 minutes, the material fails the test.

For their tests, the NC State researchers used panels made of steel-steel CMF. CMF is a foam that consists of hollow, metallic spheres - made of materials such as carbon steel, stainless steel or titanium - embedded in a metallic matrix made of steel, aluminum or other metallic alloys. "Steel-steel" CMF indicates that the spheres and the matrix were both made of steel.

"A solid steel plate with the same thickness hits 427 degrees Celsius in about 12 minutes," says Afsaneh Rabiei, first author of a paper on the work and a professor of mechanical and aerospace engineering at NC State. "In three rounds of testing, our steel-steel CMF was exposed to the same temperatures of 825 degrees Celsius for the full 100 minutes - and the highest temperatures recorded on the back of the panel using protected sensors were between 351 and 379 degrees Celsius. It is worth noting that the steel-steel CMF panel is only one-third of the weight of the solid steel plate that failed the test in about 12 minutes.

"In other words, the CMF passed the test by a wide margin," Rabiei says. "Based on the experimental and modeling results, as well as the uncertainty studies - all of which were reported in this paper - a 15.9 mm thick steel-steel CMF met the acceptance criteria for the simulated pool fire test by a large margin. We were testing the CMF for use as novel insulation system for transportation of HAZMAT, but it's also relevant to applications from military vehicles to architectural structures."

The new research builds on previous work that found CMFs are significantly more effective at insulating against high heat than the conventional metals and alloys that they're made of, such as steel. Taken together, the findings highlight CMF's potential for use in storing and transporting nuclear material, hazardous materials, explosives and other heat-sensitive materials, as well as space exploration.

But the new research also gave researchers a lot of data they could use to help fine-tune the desirable characteristics of CMFs, depending on the intended application.

"Because we can control the features of the CMF, such as the size of the hollow spheres in the foam, we wanted to create a model that could be used to predict how different types of CMF would perform in simulated pool fire testing," Rabiei says. "This would allow us to design future foams in order to find the best balance of physical, mechanical and thermal properties."

The researchers built the model by drawing on data from their simulated pool fire test experiments. And based on rigorous evaluations of the model, they found that the model's predictions are accurate to within 10 degrees Celsius.

"Our next steps include expanding the model to allow us to simulate so-called torch-fire testing," Rabiei says. "Torch-fire testing is also required for materials to be used in tank cars that transport hazardous materials, but it requires larger samples - panels that measure 4 feet by 4 feet."

Credit: 
North Carolina State University

Vampire bats form deep social bonds by grooming before sharing blood

For vampire bats, sharing blood with a roostmate is the mark of a true bond. Though these relationships are uncommon, they demonstrate behavior akin to what some might call friendship. In a paper appearing March 19 in the journal Current Biology, researchers show how social grooming and food sharing can build up trust among unrelated vampire bats to form life-saving bonds that can last a lifetime.

"We go from bats starting as strangers from different colonies to groupmates that act to save each other's life," says Gerald Carter (@gerrygcarter), a behavioral ecologist and assistant professor at Ohio State University. "This is the first animal study to look carefully at how a new cooperative relationship forms and can be maintained between complete strangers of the same species."

Vampire bats sustain themselves on only blood, and if a bat is unable to feed for 3 days, it runs the risk of starving. "They have this 'boom and bust' foraging experience, so they either hit it big and get a large blood meal or they're starved for that night. If they starve three nights in a row there is a high chance they'll die," says Carter. Because of this, vampire bats with close social ties can rescue their weakened partners from the brink.

To test how these bonds emerge, Carter and his colleagues collected bats from Las Pavas and Tolé, Panamá, two geographically distant sites. Bats were then placed either in pairs--one from each location--or in small mixed cohorts. For each group, the research team withheld food from one of the bats and observed how it interacted with its cagemates. Several bats, particularly those in the pairs, began grooming one another more over time, and in some cases, this eventually led to sharing blood with underfed companions.

"Even if you remove all ectoparasites from their fur, they still groom each other more than necessary for just hygiene," says Carter. "We think of social grooming as a kind of a currency--a way to gain tolerance and bond with another individual."

Furthermore, Carter suggests the increased grooming over time demonstrates "raising the stakes" of friendship. The idea of "testing the waters" or "raising the stakes" to build cooperative relationships was first proposed in a theory paper in Nature in 1998, but it has been difficult to demonstrate in animals. "When you make a cooperative investment in another individual, there is a kind of risk, because if you have a bad partner, you can be even worse off than if you had just avoided them altogether," he says. "So, what you could do is invest a little bit to test the waters. Then, if they invest back in you, that's a signal to ramp up your investment, and so on."

If pairs raise the stakes enough, one might provide food by regurgitating blood into the mouth of a hungry partner. Visually resembling a sort of French kiss, "food sharing in vampire bats is like how a lot of birds regurgitate food for their offspring. But what's special with vampire bats is they do this for other adults, eventually even with some previous strangers," says Carter. These social interactions could be a fundamental step in creating bonds that last years in vampire bats--some unrelated pairs have been found to travel together for more than a decade.

"The idea of using low-cost behaviors to build up to higher-cost investments can be something of much more general importance outside just food sharing in vampire bats," says Carter. This idea could be applied to other social animals such as primates and could provide insight into how humans build relationships.

For next steps, Carter wants to better understand how bats assess and choose their partners. "When two bats are unfamiliar, we have the opportunity to make a good partner or a bad partner and really see how that affects how the relationships form," he says. "So what we're trying to do now is use a variety of methods to really manipulate the relationships."

Credit: 
Cell Press

Scientists learn how vampire bat strangers make friends

COLUMBUS, Ohio - We humans can explain how our relationships with college roommates and co-workers have formed over the years, but scientists haven't had a good grip on how friendly connections among strangers are made between animals - until now.

A new study of vampire bats living in captivity with strangers supports the "raising-the-stakes" model of the development of cooperative relationships, which suggests that trust builds over time through the gradual acceleration of smaller mutual investments in each other's well-being.

Researchers studied vampire bats in captivity over 15 months that were brought together from two geographically separate roosts. They considered a cooperative relationship to be formed when the previously unfamiliar bats shared food with each other, and found that any relationships that reached that point began with increases in grooming, a lower-cost behavior.

After researchers created thousands of opportunities for the animals to interact over the course of the study, almost 15 percent of the possible food-sharing relationships between previously unfamiliar female adult bats materialized.

That might seem like a small percentage, but that the relationships formed at all shows that even unfamiliar adult bats can gradually develop strong bonds, said Gerald Carter, lead author of the study and assistant professor of evolution, ecology and organismal biology at The Ohio State University. When they do develop, they follow a pattern that looks like a series of conditional and increasing investments.

And though previous research has shown that people don't like to think of their friendships as strategic, Carter said this finding suggests that human relationships might be more conditional than we want to admit.

"I don't think you can understand human relationships that well by just asking people to reflect on them," Carter said. "It may often be subconscious, but I think both human and nonhuman relationships have a lot of little conflicts that are negotiated and navigated in a subtle way."

The study is published today (March 19) in the journal Current Biology.

Efforts to test the raising-the-stakes idea to date have focused on the duration of stretches of grooming behavior among familiar primates - which tells scientists nothing about what happened when they first met.

Carter and his colleagues at the Smithsonian Tropical Research Institute (STRI) collected vampire bats, a very social species, from two roosts hundreds of miles apart in Panama. After initially setting up introductions of strangers in isolated groups of two or four for several months, the researchers put all 39 adult and juvenile bats together in a single roost for a year.

Over all of that time, the researchers measured different kinds of behavior, including grooming and food sharing. Vampire bats commonly regurgitate their blood meals to feed roostmates that have been unsuccessful at getting their own meal of live animal blood. The scientists repeatedly fasted the unfamiliar bats after introducing them to each other to test whether bats would make the food-sharing sacrifice for an individual they don't know - a big, costly investment.

After the bats spent 15 months together, the researchers found that a lot of grooming connections were made between strangers, but relatively few food-sharing relationships formed - however, seeing one bat feed an unfamiliar bat and then receive food from that same bat in return happened much more frequently than would be expected by chance, Carter said.

Several of the scientists' predictions were on target: Grooming preceded food sharing among strangers, the frequency of grooming ramped up before food sharing and then leveled off, and relationships between strangers were more likely to form when familiar bats weren't around.

"We predicted that when we introduced them as isolated pairs, like in a college dorm room, they would form relationships faster and more frequently, and that was true," Carter said. "When we put the two large groups together, there's this strong in-group and out-group bias that prevents relationships from forming within unfamiliar pairs."

The raise-the-stakes model of relationships was published in 1998, and it was based on mathematical game theory: The idea is that because cooperation among strangers can be risky, individuals can avoid that risk by making incrementally increasing investments in each other with the expectation of reciprocity. If those conditions aren't met, no relationship forms - and individuals haven't threatened their own survival by spending too much time and energy on a connection that doesn't work out.

"The theory hasn't garnered much support over time, probably because we're not testing for it in the right way," Carter said. "I think it is generally true that this is how relationships build up."

A good next step, he said, would be studying the transitions between behaviors that come at a higher cost.

"It could be that first you tolerate each other, then cluster together, then groom each other and then share food. Maybe then you do something even more risky, like defending each other from harm," he said.

Credit: 
Ohio State University

Chip-based devices improve practicality of quantum-secured communication

image: New chip-based devices contain all the optical components necessary for quantum key distribution. The cost-effective platform is designed to facilitate citywide networks.

Image: 
Henry Semenenko, University of Bristol

monstrated new chip-based devices that contain all
the optical components necessary for quantum key distribution while increasing real-world security. The fast and cost-effective platform is poised to facilitate implementation of extremely secure data communication that can be used to protect everything from emails to online banking information.

Advances in computing technology will soon leave today's methods for encrypting online data vulnerable to eavesdropping. Quantum key distribution offers impenetrable encryption by using the quantum properties of light to generate secure random keys between users for encrypting and decrypting their online data. Although quantum key distribution is compatible with most fiber-optic networks, more robust and less expensive devices are needed to carry out this encryption method outside the lab.

In Optica, The Optical Society's (OSA) journal for high-impact research, the researchers report that secure quantum key exchange can be accomplished between two chip-based devices -- measuring just 6 x 2 millimeters -- potentially over a fiber network with links up to 200 kilometers long.

"Chip-based devices significantly reduce the barrier for widespread uptake of quantum-secured communication by providing a robust, mass-manufacturable platform," said research team leader Henry Semenenko from the University of Bristol, UK. "In the future, these devices will form part of a standard household connection to the internet that keeps our data secure regardless of advances in computing technology."

Reducing size and power needs

The new quantum key distribution devices are based on the same semiconductor technology found in every smartphone and computer. Instead of wires to guide electricity, they contain highly complex circuits that control the weak photonic signals of light necessary for quantum key distribution. Nanoscale components in the chips make it possible to drastically reduce the size and power consumption of quantum communication systems while maintaining high-speed performance vital for modern networks.

"With its densely packed optical components, our chip-based platform offers a level of precise control and complexity not achievable with alternatives," said Semenenko. "It will allow users to access a secure network with a cost-effective device the same size as the routers we use today to access the internet."

The researchers designed the new platform to facilitate citywide networks and drastically reduce the number of connections required between users.

"Our platform allows single users to connect to a centralized node that enables secure communication with every other user," said Semenenko. "As quantum networks develop, the centralized node will offer crucial infrastructure that will eventually support more complex communication protocols."

Demonstrating the devices

The researchers demonstrated their new chip-based devices with a proof of principle experiment in which they emulated a 200-kilometer fiber network at the University of Bristol Quantum Engineering Technology Labs. Using two independent chip devices, they showed that error rates and speed were comparable to state-of-the-art, commercial components.

"We showed that these chip-based devices can be used to produce quantum effects even when photons were generated by different devices," said Semenenko. "This is vital for quantum networks where each user will control their own devices that are distributed around a city."

The researchers plan to make the system more practical by developing application-specific hardware. They will then use the fiber-optic network in place around the city of Bristol to create a demonstration metropolitan network with many users.

Credit: 
Optica

Building a better color vision test for animals

image: University of Cincinnati biologist John Layne modified an LCD screen and used LEDs to test color vision in animals.

Image: 
Andrew Higley/UC Creative Services

Fiddler crabs have a simple solution to life's daily perils: run.

University of Cincinnati biologists are using this compulsion to test the crabs' color vision using simple modified electronics.

Most people can detect a huge variety of colors - more than 1 million. We can even tell when one shade is slightly different from another. UC biologist John Layne wants to know if crabs can do likewise.

Layne and his students created a miniature movie theater that uses a stripped-down liquid crystal display like the kind found in many computer monitors. A crab is placed in a little glass arena under a tilted screen projecting a video illuminated in color by blue and green light-emitting diodes.

?The video shows a looming stimulus -- a round ball that appears to approach the crabs quickly on screen -- like the famous boulder scene in "Raiders of the Lost Ark."

And like Indiana Jones, the crabs react in kind.

"They run like a bat out of hell. Their reaction is not subtle. They will sprint really fast and bang into the wall," Layne said.

The consistent reaction to the approaching virtual ball helps UC biologists measure the spectrum of visible light the crabs can see.

"We're using it to test color discrimination. For an animal to have color vision, what that really means is the ability to discriminate different wavelengths of light," Layne said. "They can see green light. They can see blue light. But can they tell the difference? That's the test."

Layne and student co-authors Jeremiah Didion and Karleigh Smith described their vision-testing device in the journal Methods in Ecology and Evolution.

Researchers have only begun to explore the complex visual abilities of animals. While we can see about 1 million colors, some spiders are believed to see 100 times that. And the reigning record holder? Scientists believe it's the mantis shrimp, which has four times as many color receptors as we do.

"Just having these color cells doesn't mean they use them for color vision like we do. They might just have these cells that cover more of the spectrum to capture more light," Layne said. "That would be advantageous for animals that live in dim or dark conditions."

Fiddler crabs usually have the opposite problem: too much light, Layne said. Their eyes sit on tall eyestalks that serve as periscopes to peer across the mudflats. Their eyes wrap around the tips of these eyestalks.

"Part of their eye is staring at the sun at all times. That is a problem for them," Layne said.

They compensate with screening pigments that prevent their vision cells from getting fried by excessive solar radiation, he said.

Layne keeps his fiddler crabs in ingenious tanks that mimic the changing tides, draining from one tank to the other and back in slightly more than six-hour intervals. At "low tide," the tank's algae-covered rocks are exposed for the crabs. A second tank is full of deep sand so the crabs can dig burrows that periodically flood with rising tide.

The male crabs skitter sideways, holding their larger "fiddle" claw in front of them like a gladiator's shield. Some are right-clawed; some left-clawed. It's random. Females have two equally small front claws.

Didion is continuing his biology studies at Case Western Reserve University. He said insights we gain from animals can lead in surprising directions.

"The value of studying the animal kingdom is exploration. You feel like a modern-day explorer," Didion said. "You never know where the next big contribution to science will come from."

Credit: 
University of Cincinnati

Synergy emergence in deep reinforcement motor learning

video: Human motor learning encompasses motor synergy. The central nervous system produces movement through the combination of synergies that specify movement across a set of muscles, simplifying the control of movement. The question is, can this synergy development process be observed in deep learning for robotics?

Image: 
Jiazheng Chai & M. Hayashibe

Human motor control has always been efficient at executing complex movements naturally, efficiently, and without much thought involved. This is because of the existence of motor synergy in the central nervous system (CNS). Motor synergy allows the CNS to use a smaller set of variables to control a large group of muscles; thereby simplifying the control over coordinated and complex movements.

Now, researchers at Tohoku University have observed a similar concept in robotic agents using deep reinforcement learning (DRL) algorithms.

DRL allows robotic agents to learn the best action possible in their virtual environment. It allows complex robotic tasks to be solved whilst minimalising manual operations and achieving peak performance. Classical algorithms, on the other hand, require manual intervention to find specific solutions for every new task that appears.

However, applying motor synergy from the human world to the robotic world is no small task. Even though many studies support the employment of motor synergy in human and animal motor control, the background process is still largely unknown.

In the current study, researchers from Tohoku University utilised two DRL algorithms on walking robotic agents known as HalfCheetah and FullCheetah. The two algorithms were TD3, a classical DRL, and SAC, a high-performing DRL.

The two robotic agents were tasked with running forward as far as possible within a given time. In total, the robotic agents completed 3 million steps. Synergy information was not used vis-à-vis the DRLs but the robotic agents demonstrated the emergence of motor synergy throughout their movements.

Mitsuhiro Hayashibe, Tohoku University professor and co-author of the study, notes, "We first confirmed in a quantitative way that motor synergy can emerge even in deep learning as humans do." Professor Hayashibe adds, "After employing deep learning, the robotic agents improved their motor performances while limiting energy consumption by employing motor synergy."

Going forward, the researchers aim to explore more task with different body models to further confirm their findings.

Credit: 
Tohoku University

New technology helps in hunt for new cancer drug combinations

image: A collaborative team of researchers at the Walter and Eliza Hall Institute and Stanford University researchers has used a new technology to discover potential new drug combinations for myeloma.
(L-R) Ms Tania Tan, Associate Professor Daniel Gray and Dr Charis Teh

Image: 
Walter and Eliza Hall Institute, Australia

A revolutionary new technology has been applied to reveal the inner workings of individual cancer cells - potentially identifying more effective treatment combinations for people with cancer.

A joint Walter and Eliza Hall Institute and Stanford University team used a technique called mass cytometry (also called CyTOF) to simultaneously analyse the levels of more than 20 different proteins in millions of individual blood cancer cells. This revealed how these cells responded to different anti-cancer medicines, even suggesting potential new treatment combinations.

The research team hope that the new technique could be integrated into clinical trials both to understand why some patients are resistant to anti-cancer therapies, and to predict suitable 'biomarkers' for matching patients with the most effective therapies for their disease.

The study was led by Walter and Eliza Hall Institute researchers Dr Charis Teh and Associate Professor Daniel Gray, in collaboration with Professor Garry Nolan and Dr Melissa Ko from Stanford University, US.

At a glance

- A new technique called mass cytometry, or CyTOF, is providing new insights into a range of key proteins in blood cancer cells.

- By studying the blood cancer myeloma, researchers were able to understand why some cells were not killed by standard anti-cancer drugs, and to devise a more effective therapy.

- The team hope to apply their mass cytometry protocol to current clinical trials to better understand why some cancers are resistant to anti-cancer therapies, and to match these patients to other, potentially more effective, treatments.

Discovering vulnerabilities in myeloma

Cancers are made up of millions of individual cells which are all similar, but not exactly the same. Until recently almost all studies of cancers looked at the cells grouped together, missing any potential differences between individual cells, said Dr Teh.

"We wanted to better understand the molecular differences between individual cancer cells so we could discover how these differences impact the cancer's response to therapies - for example, whether some cells are more resistant than others to an anti-cancer drug," Dr Teh said. "We decided that a new technology, called mass cytometry, would be an ideal approach to address this question."

Mass cytometry can simultaneously measure the quantity of different proteins in a single cell. With funding support from the Australian-American Fulbright Commission, Dr Teh was able to visit Stanford University to learn the technology and develop a test that measures a range of proteins known to regulate cancer cell survival, division, signalling and growth.

"The system we developed simultaneously and precisely measures 26 separate proteins in a blood cancer cell line derived from myeloma - an incurable cancer of immune B cells," Dr Teh said. "We focussed on understanding why some cells are sensitive to anti-cancer agents, while others are resistant.

"We used machine learning to analyse the mass cytometry results of thousands of cells, and were able to distinguish which cells survived treatment with standard medicines used to treat myeloma - and see how they differed from cells that were sensitive to these medicines," she said.

The team pinpointed the protein MCL-1 as a key factor determining whether cells lived or died when exposed to the myeloma medicines dexamethasone or bortezomib. MCL-1 is a type of protein that can prevent cell death when overproduced in cancer cells.

"Excitingly, there are already drugs in clinical trials that inhibit MCL-1 - and when we tested these against myeloma cells, we found the MCL-1 inhibitor made the cells more sensitive to dexamethasone. This was even the case in myeloma samples taken from a patient - our system had identified a potential new therapeutic approach for myeloma," Dr Teh said.

A new approach

Mass cytometry may even have a role in providing real-time detailed analysis of patient samples from clinical trials, Associate Professor Gray said.

"The panel of markers developed in this study gives researchers considerable scope to understand how cancer cells are responding to anti-cancer therapies - and as we found, it can even help to identify better drug combinations," he said.

"Adding mass cytometry to the analysis of clinical studies could reveal why some patients respond to therapies differently from others, and how resistance to anti-cancer medicines can develop in a small fraction of cancer cells.

"Mass cytometry could also identify a small number of proteins that can be used as specific 'biomarkers' that can predict a patient's response to therapy, and be used to match that patient with the most effective treatments. We've already started collaborations with our clinical colleagues to investigate this possibility further," Associate Professor Gray said.

The research was published in the journal Cell Death & Differentiation.

The research was supported by the Australian National Health and Medical Research Council, a Fulbright Australia-America Postdoctoral Fellowship, Royal Australasian College of Physicians, Leukaemia Foundation of Australia, Cancer Council Victoria, US Leukemia and Lymphoma Society, US National Institutes of Health and the Victorian Government.

Credit: 
Walter and Eliza Hall Institute

NTU scientists transform ultra-tough pollen into flexible material

image: This pollen-derived material has the potential to serve as a “building block” for the design of new categories of eco-friendly materials. Pictured in the foreground: sponges and paper derived from pollen.

Image: 
NTU Singapore

Scientists at Nanyang Technological University, Singapore (NTU Singapore) have found a way to turn pollen, one of the hardest materials in the plant kingdom, into a soft and flexible material, with the potential to serve as 'building blocks' for the design of new categories of eco-friendly materials.

The findings, published in Nature Communications today, show how they used a simple chemical process akin to conventional soap-making to turn pollen grains from sunflowers and other types of plants into soft microgel particles that respond to various stimuli.

They suggest that, coupled with advances in 3D and 4D printing, the resulting pollen-based particles might one day be turned into a range of different forms including polymer gels, sheets of 'paper' and sponges.

The corresponding authors of this paper are Assistant Professor Song Juha of the School of Chemical and Biomedical Engineering, and Professor Cho Nam-Joon and Professor Subra Suresh of the School of Materials Science and Engineering at NTU Singapore.

NTU Distinguished University Professor Subra Suresh, who is also the NTU President, said: "Our NTU research team has transformed hard pollen grains beyond their natural performance limits, and converted them into soft microgel particles that alter their properties in response to external stimuli. This holds promise for a wide range of applications that are environmentally sustainable, economically affordable, and practically scalable."

The results to date also suggest that the pollen-based microgel particles' biocompatibility - meaning it does not cause an immunological, allergic or toxic reaction when exposed to body tissues - also makes it potentially suitable for applications such as wound dressing, prosthetics, and implantable electronics.

Professor Cho Nam-Joon, who holds the Materials Research Society of Singapore Chair in Materials Science and Engineering, said: "Both our experimental and computational results give insight into the pollen's basic biological mechanisms, and demonstrate how altering the pollen wall structure can cause the pollen particles to swell - much like the shape transformations that occur during biological processes such as harmomegathy (the folding of the pollen grain to prevent water loss) and germination. The results also show that we can go beyond the performance limits of what nature can accomplish by itself."

Pollen, described by scientists as the diamond of the plant world for its indestructible traits, encapsulates and transports a plant's male genetic material within a wall structure composed of two mechanically distinct layers - a tough outer layer (exine), and a soft and elastic cellulose inner layer (intine).

When released from a flower's male reproductive part, pollen grains become dehydrated and individual grains fold onto themselves. Conversely, when these grains arrive on the plant's female reproductive structure, they become hydrated and germinate, with a pollen tube growing out of the grain and towards the female part.

The pollen tube growth process is controlled by enzymes within the pollen wall structure that alter the wall's elasticity and lead to structural changes. These processes, leading to structural changes in the pollen wall, inspired the NTU team to attempt to remodel the pollen's entire wall structure and alter its material properties, using a process similar to conventional soap-making.

Pollen grains from the sunflower plant, with their sticky oil-based 'pollen cement' layer removed, were incubated under alkaline conditions for up to 12 hours. This softened the two parts of the pollen wall, and the pollen grain particles swelled and became more gel-like. The longer the grains were incubated, the more gel-like the resulting material became.

In computer simulations, the team also found that the elastic properties of the outer and inner wall layers need to fall within a precise range for the pollen-derived material to exhibit this gel-like behavior, suggesting that for an individual pollen particle, there is a chemical and physical pathway that determines whether hydration leads to its successful germination.

NTU Assistant Professor Song Juha said: "Our study inspires future investigation into understanding how the materials science of pollen might influence plant reproductive success."

Credit: 
Nanyang Technological University

The strange orbits of 'Tatooine' planetary disks

video: Ian Czekala of the University of California at Berkeley explains his research on 'Tatooine' protoplanetary disks.

Image: 
NRAO/AUI/NSF

Astronomers using the Atacama Large Millimeter/submillimeter Array (ALMA) have found striking orbital geometries in protoplanetary disks around binary stars. While disks orbiting the most compact binary star systems share very nearly the same plane, disks encircling wide binaries have orbital planes that are severely tilted. These systems can teach us about planet formation in complex environments.

In the last two decades, thousands of planets have been found orbiting stars other than our Sun. Some of these planets orbit two stars, just like Luke Skywalker's home Tatooine. Planets are born in protoplanetary disks - we now have wonderful observations of these thanks to ALMA - but most of the disks studied so far orbit single stars. 'Tatooine' exoplanets form in disks around binary stars, so-called circumbinary disks.

Studying the birthplaces of 'Tatooine' planets provides a unique opportunity to learn about how planets form in different environments. Astronomers already know that the orbits of binary stars can warp and tilt the disk around them, resulting in a circumbinary disk misaligned relative to the orbital plane of its host stars. For example, in a 2019 study led by Grant Kennedy of the University of Warwick, UK, ALMA found a striking circumbinary disk in a polar configuration.

"With our study, we wanted to learn more about the typical geometries of circumbinary disks," said astronomer Ian Czekala of the University of California at Berkeley. Czekala and his team used ALMA data to determine the degree of alignment of nineteen protoplanetary disks around binary stars. "The high resolution ALMA data was critical for studying some of the smallest and faintest circumbinary disks yet," said Czekala.

The astronomers compared the ALMA data of the circumbinary disks with the dozen 'Tatooine' planets that have been found with the Kepler space telescope. To their surprise, the team found that the degree to which binary stars and their circumbinary disks are misaligned is strongly dependent on the orbital period of the host stars. The shorter the orbital period of the binary star, the more likely it is to host a disk in line with its orbit. However, binaries with periods longer than a month typically host misaligned disks.

"We see a clear overlap between the small disks, orbiting compact binaries, and the circumbinary planets found with the Kepler mission," Czekala said. Because the primary Kepler mission lasted 4 years, astronomers were only able to discover planets around binary stars that orbit each other in fewer than 40 days. And all of these planets were aligned with their host star orbits. A lingering mystery was whether there might be many misaligned planets that Kepler would have a hard time finding. "With our study, we now know that there likely isn't a large population of misaligned planets that Kepler missed, since circumbinary disks around tight binary stars are also typically aligned with their stellar hosts," added Czekala.

Still, based on this finding, the astronomers conclude that misaligned planets around wide binary stars should be out there and that it would be an exciting population to search for with other exoplanet-finding methods like direct imaging and microlensing. (NASA's Kepler mission used the transit method, which is one of the ways to find a planet.)

Czekala now wants to find out why there is such a strong correlation between disk (mis)alignment and the binary star orbital period. "We want to use existing and coming facilities like ALMA and the next generation Very Large Array to study disk structures at exquisite levels of precision," he said, "and try to understand how warped or tilted disks affect the planet formation environment and how this might influence the population of planets that form within these disks."

"This research is a great example of how new discoveries build on previous observations," said Joe Pesce, National Science Foundation Program Officer for NRAO and ALMA. "Discerning trends in the circumbinary disk population was only made possible by building on the foundation of archival observational programs undertaken by the ALMA community in previous cycles."

Credit: 
National Radio Astronomy Observatory

Unraveling the optical parameters: New method to optimize plasmon enhanced spectroscopy

image: On the left side a schematic view of a tip-enhanced Raman scattering (TERS) experiment is shown. A metallized AFM probe is brought in close proximity to a specimen surface, a laser is focused on the tip-sample interface. Such a setup allows to obtain vibrational spectra (Raman spectra) of an extremely small region, as small as a single molecule or even a single bond. An example of so-called Stokes and Anti-Stokes regions of spectra that are obtained by such an experiment is shown on the upper right column. A thorough assessment of the spectra, as shown by the authors, allows to obtain the structure sensitive Raman spectra and synchronously the specific plasmon resonance properties of the particular tip and the respective temperature. This way tip-induced changes during a measurement are revealed consequently improving the comprehension of the experiment significantly.

Image: 
by Marie Richard-Lacroix and Volker Deckert

For exploring the nanoscale far beyond the optical resolution limit, tip-enhanced Raman spectroscopy (TERS) is widely recognized as an essential yet still emergent technique. Using this marker-free spectroscopic method scientists gain insights into the structural and chemical composition of surfaces with nanoscale resolution, which are not accessible with other methods. Examples where such nanoscale resolution spectroscopies are crucial are structure investigations, of novel materials (e.g. diamond layers, 2D materials etc.), of protein aggregates, discussed as triggers for diseases like diabetes type II or Alzheimer's, or even of catalytical reactions at work. However, scientists' lack of comprehension of crucial parameters of the actual probe still limits the potential of TERS as a user-friendly analytical tool. Until now scientists have not been able to unravel the most fundamentally relevant experimental parameters as the tip's surface plasmon resonance, heating due to near-field temperature rise, and the link towards spatial resolution.

In a new paper in "Light: Science & Application", a research team from Jena, Germany now presents the first accessible method to gain unprecedented insights into the plasmonic activity of a single nanoparticle during a typical TERS experiment. Prof. Volker Deckert from the Leibniz Institute of Photonic Technology, Jena, and Dr. Marie Richard-Lacroix from the Friedrich Schiller University Jena propose a straightforward and purely experimental method to assess the plasmon resonance and near-field temperature experienced exclusively by the molecules directly contributing to the TERS signal. Using standard TERS experimental equipment, the scientists evaluate the detailed near-field optical response, both at the molecular level and as a function of time by probing simultaneously the Stokes and anti-Stokes spectral intensities. This enables them to characterize the optical properties of each individual TERS tip during the measurement.

"The proposed method could be a major step to improve the usability of TERS in day-to-day operation", Prof. Deckert explains. "The actual conditions to which the molecules are submitted from one experiment to the next can now be investigated and optimized directly, in real-time, and at the sample scale." This is especially relevant when it comes to examining biological samples like e.g. proteins which cannot tolerate high temperatures.

"To the best of our knowledge, no other accessible methodology opens up access to such a wealth of information on the plasmonic activity during a typical TERS experiment", Dr. Richard-Lacroix says.

"We believe that this methodology will contribute to improve the accuracy of theoretical models and facilitate any experimental plasmonic investigation and the application of TERS in the field of nanoscale thermometry", the scientists foresee.

Credit: 
Light Publishing Center, Changchun Institute of Optics, Fine Mechanics And Physics, CAS

Understanding how COVID-19 affects children vital to slowing pandemic, doctors say

image: Steven L. Zeichner, MD, PhD, is the head of UVA Health's Division of Pediatric Infectious Diseases.

Image: 
Sanjay Suchak | UVA Communications

Though COVID-19 so far appears to be largely sparing children, researchers are cautioning that it is critical to understand how the virus affects kids to model the pandemic accurately, limit the disease's spread and ensure the youngest patients get the care they need.

The warning comes from Steven L. Zeichner, MD, PhD, the head of UVA Health's Division of Pediatric Infectious Diseases, and Andrea T. Cruz, MD, MPH, a pediatric emergency medicine physician at Houston's Baylor College of Medicine. They have authored a commentary in the journal Pediatrics accompanying a new article that reveals a small percentage of infected children become seriously ill. Those at greatest risk include babies and preschoolers.

"Many infectious diseases affect children differently than adults and understanding those differences can yield important insights," the commentary authors write. "This will likely be true for COVID-19, just as it was for older infectious diseases."

Assessing COVID-19 Risks

Zeichner and Cruz note that there are subgroups of children who appear to be at greater risk of COVID-19 complications, particularly those who are younger, immunocompromised or have other pulmonary health problems.

However, the presence of other viral infections in up to two-thirds of childhood coronavirus cases makes it very difficult to assess the true effect of COVID-19 on children, they state. (This figure is based on prior studies of children with coronaviruses detectable in the respiratory tract.)

While much remains unknown, Cruz and Zeichner caution that children, even asymptomatic children, could play a "major role" in disease transmission. For example, they cite a study that found the virus remained in children's stool for several weeks after diagnosis. That, combined with other routes of transmission such as nasal secretions, could pose a major challenge for schools, day care centers and the children's families, they note.

"Since many children infected with COVID-19 appear to have have mild symptoms, or even no symptoms at all, it is important to practice all the social distancing, hygiene and other precautions being recommended by public health authorities to minimize transmission from children to others, including family members who may be at greater risk from the infection, such as grandparents or family members with chronic medical conditions," said Zeichner, who is working on innovative potential COVID-19 vaccines in his lab. "In addition, studies of the reasons why children are affected differently than adults by the infection may yield insights that can be helpful in understanding the disease and ways to treat or prevent it."

Credit: 
University of Virginia Health System

Social policies might not only improve economic well-being, but also health

March 19, 2020 -- A comprehensive review of U.S. social policies evaluated for their health outcomes found suggestive evidence that early life, income, and health insurance interventions have the potential to improve health. Scientists have long known that "social" risk factors, like poverty, are correlated with health. However, until this study, there was little research carried out to understand whether it was actually possible to improve population health by addressing these risk factors with social policies. The findings are published in The Milbank Quarterly, a multidisciplinary journal of population health and health policy published by the Milbank Memorial Fund.

"Since the 1960s, a large number of social policies that have been experimentally evaluated include health outcomes, but these were mostly overlooked. By tracking down these studies, we found a unique opportunity to inform evidence-based policymaking. It was sitting right there in front of us this whole time," said Peter Muennig, MD, a professor of Health Policy and Management at the Mailman School of Public Health at Columbia University. "Our goal was to conduct a comprehensive review of experimental studies of social and economic interventions that were not explicitly designed for the purpose of improving the health of participants. Health outcomes were often added as an afterthought and were overlooked." He added, "This is remarkable given the magnitude of expenditures in the nonmedical determinants of health in the United States and the weak evidence base supporting these investments."

The systematic review of all known randomized social experiments in the United States that involved health outcomes included 5,876 papers, reports, and data sources, ultimately encompassing 60 papers, reports, or datasets from 38 randomized social experiments. These experiments spanned the period 1962-2018 and featured a range of policies, analytic approaches, and target groups and measured a wide variety of health outcomes.

The final analysis was based on a sample of 450 unique health estimates across the 38 interventions. Of these, 77% were not able to reliably detect health outcomes because the sample was too small. Among those from which reliable estimates could be obtained, 49% demonstrated a significant health improvement, 44% had no effect on health, and 7% were associated with significant worsening of health. The most commonly reported outcome was mental health.

Eleven of the studies included tested interventions in the domain of early life and education. Nine of the included studies examined the social and health impacts of income maintenance and supplementation programs. Twelve of the included studies focused on employment and welfare-to-work: team-based supported employment, job training programs, employment support services.

The researchers found that early life and education interventions were associated with an 8% reduction in smoking. "Although this is a fairly small percentage, it could have wide implications and may be a proxy for other forms of risk-taking behaviors, such as condom or seatbelt use" noted Emilie Courtin, PhD, a fellow at Harvard University.

Income support and health insurance programs showed the most promise in improving population health. For a very small number of studies, harmful effects of social policies on health were indicated. These were mainly concentrated among time-limited welfare-to-work interventions.

The researchers point out that interventions in the domains of early life and education, income, and health insurance are particularly promising as population health policies. While many experiments were at high risk of bias, the research--all based on the "gold standard" randomized, controlled trial, gives us confidence that income support programs save lives.

Still, some studies that should have been able to measure health outcomes showed no health impact. This may indicate that they were true negative findings--and that health care providers and insurers should not randomly invest in social policies and expect health benefits, noted Muennig.

"Our study is exciting because it shows for the first time that it is possible for the government to improve health by making investments outside of the health system. The strong investments made by peer nations in welfare may explain why they have left the United States in the dust with respect to health and longevity. Still, policymakers need to be careful about how they make these investments, because they also have the potential to do harm."

Credit: 
Columbia University's Mailman School of Public Health

Improving success of giraffe translocations

image: According to a new study, giraffes should be translocated in groups of at least 30 females and 3 males to ensure long-term population success.

Image: 
Wild Nature Institute

Giraffes that are being translocated for conservation purposes should be moved in groups that contain at least 30 females and 3 males to ensure long-term population success. In two new studies, an international team of researchers identifies the ideal composition of a group to be moved and provides guidelines for all aspects of the translocation process, including decision-making and planning, transportation and monitoring of animals, and evaluation of success.

Giraffe populations declined by 40% between 1985 and 2015, according to the International Union for Conservation of Nature (IUCN) Red List of Threatened Species. This led the IUCN to classify the species as vulnerable -- likely to become endangered unless circumstances change -- and some subspecies as endangered -- likely to become extinct in the immediate future.

"Translocations have been used as a conservation strategy to establish new populations, augment small or declining populations, or re-introduce the species to previously occupied areas," said Derek E. Lee, associate research professor of biology at Penn State and leader of the research team. "Translocations could be an important conservation tool for giraffes, but until now, there has been little guidance about how best to plan, implement, or report them."

The researchers used a modeling technique called a population viability analysis to determine the ideal size and sex distribution of a newly established population. They simulated a variety of scenarios to project long-term viability and genetic diversity -- which can buffer a population against disease and environmental change -- of founding populations. The researchers deemed a translocation scenario a success if there was a 95% probability that the population continued for 100 years while maintaining most of the original genetic diversity. They report their results in a paper published Feb. 27 in the journal Endangered Species Research.

A founding population of 30 females and 3 males resulted in long-term population viability, but to maintain more than 95% of the genetic diversity of the source population, groups of 50 females and 5 males are recommended. More females are required than males, because females, unlike males, provide care to young and are an important element of giraffe social structure.

"Small numbers of founders with fewer than ten females can appear to be successful in the first decades due to short-term population growth, but are not successful in the long-term," said Lee. "Small groups can suffer from inbreeding depression, and they are more likely to lose genetic diversity due to random events in the first years after translocation."

Because giraffes are physically difficult to move, they are often translocated as juveniles, which have higher rates of mortality than adults. A larger founding population can also buffer against the loss of young individuals.

"Most giraffe translocations in the past have moved too few animals to ensure the successful establishment of new population," said Lee. "Our recommendation of 30 to 50 females should greatly increase the success rate of future translocations that adhere to these rules."

The researchers provide additional guidelines about the translocation process in a paper published March 2 in the African Journal of Ecology. They reviewed documented cases of giraffe translocation and considered published accounts of giraffe biology and ecology as well as their personal experience.

The researchers describe how to set translocation goals and assess risk, including to the giraffes being moved, to the source population whose numbers are being reduced, and to other species--including humans--in the area of introduction. They explore how to select individuals and assess suitability of the new site and discuss how to transport animals, which the researchers stress should be performed by experts.

"Ongoing monitoring of the translocated population, adaptive management of the population, and documentation of the entire translocation process are also crucial, both for long-term success of the population and to improve future efforts," said Lee.

Credit: 
Penn State