Engineers put tens of thousands of artificial brain synapses on a single chip

Brain on chip abstract concept

MIT engineers have designed a "brain-on-a-chip," smaller than a piece of confetti, that is made from tens of thousands of artificial brain synapses known as memristors -- silicon-based components that mimic the information-transmitting synapses in the human brain.

The researchers borrowed from principles of metallurgy to fabricate each memristor from alloys of silver and copper, along with silicon. When they ran the chip through several visual tasks, the chip was able to "remember" stored images and reproduce them many times over, in versions that were crisper and cleaner compared with existing memristor designs made with unalloyed elements.

Their results, published today in the journal Nature Nanotechnology, demonstrate a promising new memristor design for neuromorphic devices -- electronics that are based on a new type of circuit that processes information in a way that mimics the brain's neural architecture. Such brain-inspired circuits could be built into small, portable devices, and would carry out complex computational tasks that only today's supercomputers can handle.

"So far, artificial synapse networks exist as software. We're trying to build real neural network hardware for portable artificial intelligence systems," says Jeehwan Kim, associate professor of mechanical engineering at MIT. "Imagine connecting a neuromorphic device to a camera on your car, and having it recognize lights and objects and make a decision immediately, without having to connect to the internet. We hope to use energy-efficient memristors to do those tasks on-site, in real-time."

Wandering ions

Memristors, or memory transistors, are an essential element in neuromorphic computing. In a neuromorphic device, a memristor would serve as the transistor in a circuit, though its workings would more closely resemble a brain synapse -- the junction between two neurons. The synapse receives signals from one neuron, in the form of ions, and sends a corresponding signal to the next neuron.

A transistor in a conventional circuit transmits information by switching between one of only two values, 0 and 1, and doing so only when the signal it receives, in the form of an electric current, is of a particular strength. In contrast, a memristor would work along a gradient, much like a synapse in the brain. The signal it produces would vary depending on the strength of the signal that it receives. This would enable a single memristor to have many values, and therefore carry out a far wider range of operations than binary transistors.

Like a brain synapse, a memristor would also be able to "remember" the value associated with a given current strength, and produce the exact same signal the next time it receives a similar current. This could ensure that the answer to a complex equation, or the visual classification of an object, is reliable -- a feat that normally involves multiple transistors and capacitors.

Ultimately, scientists envision that memristors would require far less chip real estate than conventional transistors, enabling powerful, portable computing devices that do not rely on supercomputers, or even connections to the Internet.

Existing memristor designs, however, are limited in their performance. A single memristor is made of a positive and negative electrode, separated by a "switching medium," or space between the electrodes. When a voltage is applied to one electrode, ions from that electrode flow through the medium, forming a "conduction channel" to the other electrode. The received ions make up the electrical signal that the memristor transmits through the circuit. The size of the ion channel (and the signal that the memristor ultimately produces) should be proportional to the strength of the stimulating voltage.

Kim says that existing memristor designs work pretty well in cases where voltage stimulates a large conduction channel, or a heavy flow of ions from one electrode to the other. But these designs are less reliable when memristors need to generate subtler signals, via thinner conduction channels.

The thinner a conduction channel, and the lighter the flow of ions from one electrode to the other, the harder it is for individual ions to stay together. Instead, they tend to wander from the group, disbanding within the medium. As a result, it's difficult for the receiving electrode to reliably capture the same number of ions, and therefore transmit the same signal, when stimulated with a certain low range of current.

Borrowing from metallurgy

Kim and his colleagues found a way around this limitation by borrowing a technique from metallurgy, the science of melding metals into alloys and studying their combined properties.

"Traditionally, metallurgists try to add different atoms into a bulk matrix to strengthen materials, and we thought, why not tweak the atomic interactions in our memristor, and add some alloying element to control the movement of ions in our medium," Kim says.

Engineers typically use silver as the material for a memristor's positive electrode. Kim's team looked through the literature to find an element that they could combine with silver to effectively hold silver ions together, while allowing them to flow quickly through to the other electrode.

The team landed on copper as the ideal alloying element, as it is able to bind both with silver, and with silicon.

"It acts as a sort of bridge, and stabilizes the silver-silicon interface," Kim says.

To make memristors using their new alloy, the group first fabricated a negative electrode out of silicon, then made a positive electrode by depositing a slight amount of copper, followed by a layer of silver. They sandwiched the two electrodes around an amorphous silicon medium. In this way, they patterned a millimeter-square silicon chip with tens of thousands of memristors.

As a first test of the chip, they recreated a gray-scale image of the Captain America shield. They equated each pixel in the image to a corresponding memristor in the chip. They then modulated the conductance of each memristor that was relative in strength to the color in the corresponding pixel.

The chip produced the same crisp image of the shield, and was able to "remember" the image and reproduce it many times, compared with chips made of other materials.

The team also ran the chip through an image processing task, programming the memristors to alter an image, in this case of MIT's Killian Court, in several specific ways, including sharpening and blurring the original image. Again, their design produced the reprogrammed images more reliably than existing memristor designs.

"We're using artificial synapses to do real inference tests," Kim says. "We would like to develop this technology further to have larger-scale arrays to do image recognition tasks. And some day, you might be able to carry around artificial brains to do these kinds of tasks, without connecting to supercomputers, the internet, or the cloud."

New light shed on intelligent life existing across the galaxy

Illustration of alien world, starry background

One of the biggest and longest-standing questions in the history of human thought is whether there are other intelligent life forms within our Universe. Obtaining good estimates of the number of possible extraterrestrial civilizations has however been very challenging.

A new study led by the University of Nottingham and published today in The Astrophysical Journal has taken a new approach to this problem. Using the assumption that intelligent life forms on other planets in a similar way as it does on Earth, researchers have obtained an estimate for the number of intelligent communicating civilizations within our own galaxy -- the Milky Way. They calculate that there could be over 30 active communicating intelligent civilizations in our home Galaxy.

Professor of Astrophysics at the University of Nottingham, Christopher Conselice who led the research, explains: "There should be at least a few dozen active civilizations in our Galaxy under the assumption that it takes 5 billion years for intelligent life to form on other planets, as on Earth." Conselice also explains that, "The idea is looking at evolution, but on a cosmic scale. We call this calculation the Astrobiological Copernican Limit."

First author Tom Westby explains: "The classic method for estimating the number of intelligent civilizations relies on making guesses of values relating to life, whereby opinions about such matters vary quite substantially. Our new study simplifies these assumptions using new data, giving us a solid estimate of the number of civilizations in our Galaxy.

The two Astrobiological Copernican limits are that intelligent life forms in less than 5 billion years, or after about 5 billion years -- similar to on Earth where a communicating civilization formed after 4.5 billion years. In the strong criteria, whereby a metal content equal to that of the Sun is needed (the Sun is relatively speaking quite metal rich), we calculate that there should be around 36 active civilizations in our Galaxy."

The research shows that the number of civilizations depends strongly on how long they are actively sending out signals of their existence into space, such as radio transmissions from satellites, television, etc. If other technological civilizations last as long as ours which is currently 100 years old, then there will be about 36 ongoing intelligent technical civilizations throughout our Galaxy.

However, the average distance to these civilizations would be 17,000 light-years away, making detection and communication very difficult with our present technology. It is also possible that we are the only civilization within our Galaxy unless the survival times of civilizations like our own are long.

Professor Conselice continues: "Our new research suggests that searches for extraterrestrial intelligent civilizations not only reveals the existence of how life forms, but also gives us clues for how long our own civilization will last. If we find that intelligent life is common then this would reveal that our civilization could exist for much longer than a few hundred years, alternatively if we find that there are no active civilizations in our Galaxy it is a bad sign for our own long-term existence. By searching for extraterrestrial intelligent life -- even if we find nothing -- we are discovering our own future and fate."

As many as six billion Earth-like planets in our galaxy, according to new estimates

Exoplanet illustration

There may be as many as one Earth-like planet for every five Sun-like stars in the Milky way Galaxy, according to new estimates by University of British Columbia astronomers using data from NASA's Kepler mission.

To be considered Earth-like, a planet must be rocky, roughly Earth-sized and orbiting Sun-like (G-type) stars. It also has to orbit in the habitable zones of its star -- the range of distances from a star in which a rocky planet could host liquid water, and potentially life, on its surface.

"My calculations place an upper limit of 0.18 Earth-like planets per G-type star," says UBC researcher Michelle Kunimoto, co-author of the new study in The Astronomical Journal. "Estimating how common different kinds of planets are around different stars can provide important constraints on planet formation and evolution theories, and help optimize future missions dedicated to finding exoplanets."

According to UBC astronomer Jaymie Matthews: "Our Milky Way has as many as 400 billion stars, with seven per cent of them being G-type. That means less than six billion stars may have Earth-like planets in our Galaxy."

Previous estimates of the frequency of Earth-like planets range from roughly 0.02 potentially habitable planets per Sun-like star, to more than one per Sun-like star.

Typically, planets like Earth are more likely to be missed by a planet search than other types, as they are so small and orbit so far from their stars. That means that a planet catalogue represents only a small subset of the planets that are actually in orbit around the stars searched. Kunimoto used a technique known as 'forward modelling' to overcome these challenges.

"I started by simulating the full population of exoplanets around the stars Kepler searched," she explained. "I marked each planet as 'detected' or 'missed' depending on how likely it was my planet search algorithm would have found them. Then, I compared the detected planets to my actual catalogue of planets. If the simulation produced a close match, then the initial population was likely a good representation of the actual population of planets orbiting those stars."

Kunimoto's research also shed more light on one of the most outstanding questions in exoplanet science today: the 'radius gap' of planets. The radius gap demonstrates that it is uncommon for planets with orbital periods less than 100 days to have a size between 1.5 and two times that of Earth. She found that the radius gap exists over a much narrower range of orbital periods than previously thought. Her observational results can provide constraints on planet evolution models that explain the radius gap's characteristics.

Up to 45 percent of SARS-CoV-2 infections may be asymptomatic

Coronavirus in crowd,

An extraordinary percentage of people infected by the virus behind the ongoing deadly COVID-19 pandemic never show symptoms of the disease, according to the results of a Scripps Research analysis of public datasets on asymptomatic infections.

The findings, published in Annals of Internal Medicine, suggest that asymptomatic infections may account for as much as 45 percent of all COVID-19 cases, playing a significant role in the early and ongoing spread of COVID-19. The report highlights the need for expansive testing and contact tracing to mitigate the pandemic.

"The silent spread of the virus makes it all the more challenging to control," says Eric Topol, MD, founder and director of the Scripps Research Translational Institute and professor of Molecular Medicine at Scripps Research. "Our review really highlights the importance of testing. It's clear that with such a high asymptomatic rate, we need to cast a very wide net, otherwise the virus will continue to evade us."

Together with behavioral scientist Daniel Oran, Topol collected information from testing studies on 16 diverse cohorts from around the world. These datasets -- gathered via keyword searches of PubMed, bioRxiv and medRxiv, as well as Google searches of relevant news reports -- included data on nursing home residents, cruise ship passengers, prison inmates and various other groups.

"What virtually all of them had in common was that a very large proportion of infected individuals had no symptoms," says Oran. "Among more than 3,000 prison inmates in four states who tested positive for the coronavirus, the figure was astronomical: 96 percent asymptomatic."

The review further suggests that asymptomatic individuals are able to transmit the virus for an extended period of time, perhaps longer than 14 days. The viral loads are very similar in people with or without symptoms, but it remains unclear whether their infectiousness is of the same magnitude. To resolve that issue, we'll need large-scale studies that include sufficient numbers of asymptomatic people.

The authors also conclude that the absence of symptoms may not imply an absence of harm. CT scans conducted on 54 percent of 76 asymptomatic individuals on the Diamond Princess cruise ship, appear to show significant subclinical lung abnormalities raising the possibility of SARS-CoV-2 infection impacting lung function that might not be immediately apparent. The scientists say further research is needed to confirm the potential significance of this finding.

The authors also acknowledge that the lack of longitudinal data makes distinguishing between asymptomatic and presymptomatic individuals difficult. An asymptomatic individual is someone who is infected with SARS-CoV-2, but never develops symptoms of COVID-19, while a presymptomatic person is similarly infected, but will eventually develop symptoms. Longitudinal testing, which refers to repeated testing of individuals over time, would help differentiate between the two.

"Our estimate of 40 to 45 percent asymptomatic means that, if you're unlucky enough to get infected, the probability is almost a flip of a coin on whether you're going to have symptoms. So to protect others, we think that wearing a mask makes a lot of sense," Oran concludes.

Face masks critical in preventing spread of COVID-19

Crowd of people wearing medical masks

A study by a team of researchers led by a Texas A&M University professor has found that not wearing a face mask dramatically increases a person's chances of being infected by the COVID-19 virus.

Renyi Zhang, Texas A&M Distinguished Professor of Atmospheric Sciences and the Harold J. Haynes Chair in the College of Geosciences, and colleagues from the University of Texas, the University of California-San Diego and the California Institute of Technology have had their work published in the current issue of PNAS (Proceedings of the National Academy of Sciences).

The team examined the chances of COVID-19 infection and how the virus is easily passed from person to person. From trends and mitigation procedures in China, Italy and New York City, the researchers found that using a face mask reduced the number of infections by more than 78,000 in Italy from April 6-May 9 and by over 66,000 in New York City from April 17-May 9.

"Our results clearly show that airborne transmission via respiratory aerosols represents the dominant route for the spread of COVID-19," Zhang said. "By analyzing the pandemic trends without face-covering using the statistical method and by projecting the trend, we calculated that over 66,000 infections were prevented by using a face mask in little over a month in New York City. We conclude that wearing a face mask in public corresponds to the most effective means to prevent inter-human transmission.

"This inexpensive practice, in conjunction with social distancing and other procedures, is the most likely opportunity to stop the COVID-19 pandemic. Our work also highlights that sound science is essential in decision-making for the current and future public health pandemics."

One of the paper's co-authors, Mario Molina, is a professor at the University of California-San Diego and a co-recipient of the 1995 Nobel Prize in Chemistry for his role in understanding the threat to the Earth's ozone layer of human-made halocarbon gases.

"Our study establishes very clearly that using a face mask is not only useful to prevent infected coughing droplets from reaching uninfected persons, but is also crucial for these uninfected persons to avoid breathing the minute atmospheric particles (aerosols) that infected people emit when talking and that can remain in the atmosphere tens of minutes and can travel tens of feet," Molina said.

Zhang said that many people in China have worn face masks for years, mainly because of the bad air quality of the country.

"So people there are sort of used to this," he said. "Mandated face-covering helped China in containing the COVID-19 outbreak."

Zhang said the results should send a clear message to people worldwide -- wearing a face mask is essential in fighting the virus.

"Our work suggests that the failure in containing the propagation of COVID-19 pandemic worldwide is largely attributed to the unrecognized importance of airborne virus transmission," he said. "Social-distancing and washing our hands must continue, but that's not sufficient enough protection. Wearing a face mask as well as practicing good hand hygiene and social distancing will greatly reduce the chances of anyone contracting the COVID-19 virus."

Diluting blood plasma rejuvenates tissue, reverses aging in mice

Red blood cells in artery illustration

In 2005, University of California, Berkeley, researchers made the surprising discovery that making conjoined twins out of young and old mice -- such that they share blood and organs -- can rejuvenate tissues and reverse the signs of aging in the old mice. The finding sparked a flurry of research into whether a youngster's blood might contain special proteins or molecules that could serve as a "fountain of youth" for mice and humans alike.

But a new study by the same team shows that similar age-reversing effects can be achieved by simply diluting the blood plasma of old mice -- no young blood needed.

In the study, the team found that replacing half of the blood plasma of old mice with a mixture of saline and albumin -- where the albumin simply replaces protein that was lost when the original blood plasma was removed -- has the same or stronger rejuvenation effects on the brain, liver and muscle than pairing with young mice or young blood exchange. Performing the same procedure on young mice had no detrimental effects on their health.

This discovery shifts the dominant model of rejuvenation away from young blood and toward the benefits of removing age-elevated, and potentially harmful, factors in old blood.

"There are two main interpretations of our original experiments: The first is that, in the mouse joining experiments, rejuvenation was due to young blood and young proteins or factors that become diminished with aging, but an equally possible alternative is that, with age, you have an elevation of certain proteins in the blood that become detrimental, and these were removed or neutralized by the young partners," said Irina Conboy, a professor of bioengineering at UC Berkeley who is the first author of the 2005 mouse-joining paper and senior author of the new study. "As our science shows, the second interpretation turns out to be correct. Young blood or factors are not needed for the rejuvenating effect; dilution of old blood is sufficient."

In humans, the composition of blood plasma can be altered in a clinical procedure called therapeutic plasma exchange, or plasmapheresis, which is currently FDA-approved in the U.S. for treating a variety of autoimmune diseases. The research team is currently finalizing clinical trials to determine if a modified plasma exchange in humans could be used to improve the overall health of older people and to treat age-associated diseases that include muscle wasting, neuro-degeneration, Type 2 diabetes and immune deregulation.

"I think it will take some time for people to really give up the idea that that young plasma contains rejuvenation molecules, or silver bullets, for aging," said Dobri Kiprov, a medical director of Apheresis Care Group and a co-author of the paper. "I hope our results open the door for further research into using plasma exchange -- not just for aging, but also for immunomodulation."

The study appears online in the journal Aging.

A molecular 'reset' button

In the early 2000s, Conboy and her husband and research partner Michael Conboy, a senior researcher and lecturer in the Department of Bioengineering at UC Berkeley and co-author of the new study, had a hunch that our body's ability to regenerate damaged tissue remains with us into old age in the form of stem cells, but that somehow these cells get turned off through changes in our biochemistry as we age.

"We had the idea that aging might be really more dynamic than people think," Conboy said. "We thought that it could be caused by transient and very reversible declines in regeneration, such that, even if somebody is very old, the capacity to build new tissues in organs could be restored to young levels by basically replacing the broken cells and tissues with healthy ones, and that this capacity is regulated through specific chemicals which change with age in ways that become counterproductive."

After the Conboys published their groundbreaking 2005 work, showing that making conjoined twins from the old mouse and a young mouse reversed many signs of aging in the older mouse, many researchers seized on the idea that specific proteins in young blood could be the key to unlocking the body's latent regeneration abilities.

However, in the original report, and in a more recent study, when blood was exchanged between young and old animals without physically joining them, young animals showed signs of aging. These results indicated that that young blood circulating through young veins could not compete with old blood.

As a result, the Conboys pursued the idea that a buildup of certain proteins with age is the main inhibitor of tissue maintenance and repair, and that diluting these proteins with blood exchange could also be the mechanism behind the original results. If true, this would suggest an alternative, safer path to successful clinical intervention: Instead of adding proteins from young blood, which could do harm to a patient, the dilution of age-elevated proteins could be therapeutic, while also allowing for the increase of young proteins by removing factors that could suppress them.

To test this hypothesis, the Conboys and their colleagues came up with the idea of performing "neutral" blood exchange. Instead of exchanging the blood of a mouse with that of a younger or an older animal, they would simply dilute the blood plasma by swapping out part of the animal's blood plasma with a solution containing plasma's most basic ingredients: saline and a protein called albumin. The albumin included in the solution simply replenished this abundant protein, which is needed for overall biophysical and biochemical blood health and was lost when half the plasma was removed.

"We thought, 'What if we had some neutral age blood, some blood that was not young or not old?'" said Michael Conboy. "We'll do the exchange with that, and see if it still improves the old animal. That would mean that by diluting the bad stuff in the old blood, it made the animal better. And if the young animal got worse, then that would mean that that diluting the good stuff in the young animal made the young animal worse."

After finding that the neutral blood exchange significantly improved the health of old mice, the team conducted a proteomic analysis of the blood plasma of the animals to find out how the proteins in their blood changed following the procedure. The researchers performed a similar analysis on blood plasma from humans who had undergone therapeutic plasma exchange.

They found that the plasma exchange process acts almost like a molecular reset button, lowering the concentrations of a number of pro-inflammatory proteins that become elevated with age, while allowing more beneficial proteins, like those that promote vascularization, to rebound in large numbers.

"A few of these proteins are of particular interest, and in the future, we may look at them as additional therapeutic and drug candidates," Conboy said. "But I would warn against silver bullets. It is very unlikely that aging could be reversed by changes in any one protein. In our experiment, we found that we can do one procedure that is relatively simple and FDA-approved, yet it simultaneously changed levels of numerous proteins in the right direction."

Therapeutic plasma exchange in humans lasts about two to three hours and comes with no or mild side effects, said Kiprov, who uses the procedure in his clinical practice. The research team is about to conduct clinical trials to better understand how therapeutic blood exchange might best be applied to treating human ailments of aging.

Super-potent human antibodies protect against COVID-19 in animal tests

Coronavirus illustration 

A team led by Scripps Research has discovered antibodies in the blood of recovered COVID-19 patients that provide powerful protection against SARS-CoV-2, the coronavirus that causes the disease, when tested in animals and human cell cultures.

The research, published today in Science, offers a paradigm of swift reaction to an emergent and deadly viral pandemic, and sets the stage for clinical trials and additional tests of the antibodies, which are now being produced as potential treatments and preventives for COVID-19.

"The discovery of these very potent antibodies represents an extremely rapid response to a totally new pathogen," says study co-senior author Dennis Burton, PhD, the James and Jessie Minor Chair in Immunology in the Department of Immunology & Microbiology at Scripps Research.

In principle, injections of such antibodies could be given to patients in the early stage of COVID-19 to reduce the level of virus and protect against severe disease. The antibodies also may be used to provide temporary, vaccine-like protection against SARS-CoV-2 infection for healthcare workers, elderly people and others who respond poorly to traditional vaccines or are suspected of a recent exposure to the coronavirus.

The project was led by groups at Scripps Research; IAVI, a nonprofit scientific research organization dedicated to addressing urgent, unmet global health challenges; and University of California San Diego School of Medicine.

"It has been a tremendous collaborative effort, and we're now focused on making large quantities of these promising antibodies for clinical trials," says co-lead author Thomas Rogers, MD, PhD, an adjunct assistant professor in the Department of Immunology & Microbiology at Scripps Research, and assistant professor of Medicine at UC San Diego.

An approach that's worked for other deadly viruses

Developing a treatment or vaccine for severe COVID-19 is currently the world's top public health priority. Globally, almost 8 million people have tested positive for SARS-CoV-2 infection, and more than 400,000 have died of severe COVID-19. The daily toll of new infections is still rising.

One approach to new viral threats is to identify, in the blood of recovering patients, antibodies that neutralize the virus's ability to infect cells.

These antibodies can then be mass-produced, using biotech methods, as a treatment that blocks severe disease and as a vaccine-like preventive that circulates in the blood for several weeks to protect against infection. This approach already has been demonstrated successfully against Ebola virus and the pneumonia-causing respiratory syncytial virus, commonly known as RSV.

Potent patient antibodies block the virus

For the new project, Rogers and his UC San Diego colleagues took blood samples from patients who had recovered from mild-to-severe COVID-19. In parallel, scientists at Scripps Research and IAVI developed test cells that express ACE2, the receptor that SARS-CoV-2 uses to get into human cells. In a set of initial experiments, the team tested whether antibody-containing blood from the patients could bind to the virus and strongly block it from infecting the test cells.

The scientists were able to isolate more than 1,000 distinct antibody-producing immune cells, called B cells, each of which produced a distinct anti-SARS-CoV-2 antibody. The team obtained the antibody gene sequences from these B cells so that they could produce the antibodies in the laboratory. By screening these antibodies individually, the team identified several that, even in tiny quantities, could block the virus in test cells, and one that could also protect hamsters against heavy viral exposure.

All of this work -- including the development of the cell and animal infection models, and studies to discover where the antibodies of interest bind the virus -- was completed in less than seven weeks.

"We leveraged our institution's decades of expertise in antibody isolation and quickly pivoted our focus to SARS-CoV-2 to identify these highly potent antibodies," says study co-author Elise Landais, PhD, an IAVI principal scientist.

If further safety tests in animals and clinical trials in people go well, then conceivably the antibodies could be used in clinical settings as early as next January, the researchers say.

"We intend to make them available to those who need them most, including people in low- and middle-income countries," Landais says.

In the course of their attempts to isolate anti-SARS-CoV-2 antibodies from the COVID-19 patients, the researchers found one that can also neutralize SARS-CoV, the related coronavirus that caused the 2002-2004 outbreak of severe acute respiratory syndrome (SARS) in Asia.

"That discovery gives us hope that we will eventually find broadly neutralizing antibodies that provide at least partial protection against all or most SARS coronaviruses, which should be useful if another one jumps to humans," Burton says.

"Rapid isolation of potent SARS-CoV-2 neutralizing antibodies and protection in a small animal model" was co-authored by 30 scientists including lead authors Thomas Rogers, Fangzhu Zhao, Deli Huang, and Nathan Beutler, all of Scripps Research. The corresponding authors were Devin Sok and Joseph Jardine of IAVI, and Dennis Burton of Scripps Research.

Scientists engineer human cells with squid-like transparency

Swimming squid

Octopuses, squids and other sea creatures can perform a disappearing act by using specialized tissues in their bodies to manipulate the transmission and reflection of light, and now researchers at the University of California, Irvine have engineered human cells to have similar transparent abilities.

In a paper published today in Nature Communications, the scientists described how they drew inspiration from cephalopod skin to endow mammalian cells with tunable transparency and light-scattering characteristics.

"For millennia, people have been fascinated by transparency and invisibility, which have inspired philosophical speculation, works of science fiction, and much academic research," said lead author Atrouli Chatterjee, a UCI doctoral student in chemical & biomolecular engineering. "Our project -- which is decidedly in the realm of science -- centers on designing and engineering cellular systems and tissues with controllable properties for transmitting, reflecting and absorbing light."

Chatterjee works in the laboratory of Alon Gorodetsky, UCI associate professor of chemical & biomolecular engineering, who has a long history of exploring how cephalopods' color-changing capabilities can be mimicked to develop unique technologies to benefit people. His team's bioinspired research has led to breakthrough developments in infrared camouflage and other advanced materials.

For this study, the group drew inspiration from the way female Doryteuthis opalescens squids can evade predators by dynamically switching a stripe on their mantle from nearly transparent to opaque white. The researchers then borrowed some of the intercellular protein-based particles involved in this biological cloaking technique and found a way to introduce them into human cells to test whether the light-scattering powers are transferable to other animals.

This species of squid has specialized reflective cells called leucophores which can alter the how they scatter light. Within these cells are leucosomes, membrane-bound particles which are composed of proteins known as reflectins, which can produce iridescent camouflage.

In their experiments, the researchers cultured human embryonic kidney cells and genetically engineered them to express reflectin. They found that the protein would assemble into particles in the cells' cytoplasm in a disordered arrangement. They also saw through optical microscopy and spectroscopy that the introduced reflectin-based structures caused the cells to change their scattering of light.

"We were amazed to find that the cells not only expressed reflectin but also packaged the protein in spheroidal nanostructures and distributed them throughout the cells' bodies," said Gorodetsky, a co-author on this study. "Through quantitative phase microscopy, we were able to determine that the protein structures had different optical characteristics when compared to the cytoplasm inside the cells; in other words, they optically behaved almost as they do in their native cephalopod leucophores."

In another important part of the study, the team tested whether the reflectance could potentially be toggled on and off through external stimuli. They sandwiched cells in between coated glass plates and applied different concentrations of sodium chloride. Measuring the amount of light that was transmitted by the cells, they found that the ones exposed to higher sodium levels scattered more light and stood out more from the surroundings.

"Our experiments showed that these effects appeared in the engineered cells but not in cells that lacked the reflectin particles, demonstrating a potential valuable method for tuning light-scattering properties in human cells," Chatterjee said.

While invisible humans are still firmly in the realm of science fiction, Gorodetsky said his group's research can offer some tangible benefits in the near term.

"This project showed that it's possible to develop human cells with stimuli-responsive optical properties inspired by leucophores in celphalopods, and it shows that these amazing reflectin proteins can maintain their properties in foreign cellular environments," he said.

He said the new knowledge also could open the possibility of using reflectins as a new type of biomolecular marker for medical and biological microscopy applications.

Study in twins finds our sensitivity is partly in our genes

DNA illustration

Some people are more sensitive than others -- and around half of these differences can be attributed to our genes, new research has found.

The study, led by Queen Mary University of London, compared pairs of identical and non-identical 17-year-old twins to see how strongly they were affected by positive or negative experiences -- their 'sensitivity' level. The aim was to tease out how much of the differences in sensitivity could be explained by either genetic or environmental factors during development: nature or nurture.

Twins who are brought up together will mostly experience the same environment. But only identical twins share the same genes: non-identical twins are like any other sibling. If identical twins show no more similarity in their levels of sensitivity than non-identical twins, then genes are unlikely to play a role.

Using this type of analysis, the team found that 47 percent of the differences in sensitivity between individuals were down to genetics, leaving 53 percent accounted for by environmental factors. The research, from Queen Mary University of London and Kings College London, is the first to show this link conclusively in such a large study. The findings are published in Molecular Psychiatry.

Michael Pluess, Professor of Developmental Psychology at Queen Mary University of London and study lead, said: "We are all affected by what we experience -- sensitivity is something we all share as a basic human trait. But we also differ in how much of an impact our experiences have on us. Scientists have always thought there was a genetic basis for sensitivity, but this is the first time we've been able to actually quantify how much of these differences in sensitivity are explained by genetic factors."

Over 2800 twins were involved in the study, split between around 1000 identical twins and 1800 non-identical twins, roughly half of whom were same sex. The twins were asked to fill out a questionnaire, developed by Professor Pluess, which has been widely used to test an individual's levels of sensitivity to their environment This test will be made available online later this month so anyone can assess their own sensitivity.

The questionnaire is also able to tease out different types of sensitivity -- whether someone is more sensitive to negative experiences or positive experiences -- as well as general sensitivity. The analysis by the team suggested that these different sensitivities also have a genetic basis.

Co-researcher Dr Elham Assary said: "If a child is more sensitive to negative experiences, it may be that they become more easily stressed and anxious in challenging situations. On the other hand, if a child has a higher sensitivity to positive experiences, it may be that they are more responsive to good parenting or benefit more from psychological interventions at school. What our study shows is that these different aspects of sensitivity all have a genetic basis."

Finally, the team explored how sensitivity to other common and established personality traits, known as the 'Big Five': openness, conscientiousness, agreeableness, extraversion and neuroticism. They found that there was a shared genetic component between sensitivity, neuroticism and extraversion, but not with any of the other personality traits.

Professor Pluess believes the findings could help us in how we understand and handle sensitivity, in ourselves and others.

"We know from previous research that around a third of people are at the higher end of the sensitivity spectrum. They are generally more strongly affected by their experiences," he said. "This can have both advantages and disadvantages. Because we now know that this sensitivity is as much due to biology as environment, it is important for people to accept their sensitivity as an important part of who they are and consider it as a strength not just as a weakness."

Synthetic red blood cells mimic natural ones, and have new abilities

                                                             Illustration of red blood cells 

Scientists have tried to develop synthetic red blood cells that mimic the favorable properties of natural ones, such as flexibility, oxygen transport and long circulation times. But so far, most artificial red blood cells have had one or a few, but not all, key features of the natural versions. Now, researchers reporting in ACS Nano have made synthetic red blood cells that have all of the cells' natural abilities, plus a few new ones.

Red blood cells (RBCs) take up oxygen from the lungs and deliver it to the body's tissues. These disk-shaped cells contain millions of molecules of hemoglobin -- an iron-containing protein that binds oxygen. RBCs are highly flexible, which allows them to squeeze through tiny capillaries and then bounce back to their former shape. The cells also contain proteins on their surface that allow them to circulate through blood vessels for a long time without being gobbled up by immune cells. Wei Zhu, C. Jeffrey Brinker and colleagues wanted to make artificial RBCs that had similar properties to natural ones, but that could also perform new jobs such as therapeutic drug delivery, magnetic targeting and toxin detection.

The researchers made the synthetic cells by first coating donated human RBCs with a thin layer of silica. They layered positively and negatively charged polymers over the silica-RBCs, and then etched away the silica, producing flexible replicas. Finally, the team coated the surface of the replicas with natural RBC membranes. The artificial cells were similar in size, shape, charge and surface proteins to natural cells, and they could squeeze through model capillaries without losing their shape. In mice, the synthetic RBCs lasted for more than 48 hours, with no observable toxicity. The researchers loaded the artificial cells with either hemoglobin, an anticancer drug, a toxin sensor or magnetic nanoparticles to demonstrate that they could carry cargoes. The team also showed that the new RBCs could act as decoys for a bacterial toxin. Future studies will explore the potential of the artificial cells in medical applications, such as cancer therapy and toxin biosensing, the researchers say.