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New AI tool predicts viral outbreaks, using generative model

A radical new AI tool called EVEscape predicts viral mutations and new variants, using evolutionary biological information.

In tests, it successfully predicted the most concerning new SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) variants that occurred during the COVID-19 pandemic, according to its developers at Harvard Medical School and the University of Oxford. EVEscape can also help inform the development of vaccines and therapies for SARS-CoV-2 and other rapidly mutating viruses.

Model predicts changes about likely variants every two weeks

EVEscape has a generative model of evolutionary sequences that predicts changes that can occur to a virus, along with detailed biological and structural information about the virus. Together, they allow EVEscape to make predictions about the variants most likely to occur as the virus evolves.

In a study published Oct. 11 in Nature, the researchers show that if it had been deployed at the start of the COVID-19 pandemic, EVEscape would have predicted the most frequent mutations and identified the most concerning variants for SARS-CoV-2. The tool also made accurate predictions about other viruses, including HIV and influenza.

“We want to know if we can anticipate the variation in viruses and forecast new variants—because if we can, that’s going to be extremely important for designing vaccines and therapies,” said senior author Debora Marks, associate professor of systems biology in the Blavatnik Institute at Harvard Medical School.

From EVE to EVEscape

The researchers first developed EVE, short for evolutionary model of variant effect, in a different context: gene mutations that cause human diseases. In a previous study, EVE allowed researchers to discern disease-causing from benign mutations in genes linked to various conditions, including cancers and heart rhythm disorders.

Designing mutation-proof vaccines and therapies 

The team is now applying EVEscape to SARS-CoV-2 in real time, using all of the information available to make predictions about how it might evolve next. 

The researchers publish a biweekly ranking of new SARS-CoV-2 variants on their website and share this information with entities such as the World Health Organization. The complete code for EVEscape is also freely available online.

They are also testing EVEscape on understudied viruses such as Lassa and Nipah, two pathogens of pandemic potential for which relatively little information exists.al.

Funding for the research was provided by the National Institutes of Health (GM141007-01A1), the Coalition for Epidemic Preparedness Innovations, the Chan Zuckerberg Initiative, GSK, the UK Engineering and Physical Sciences Research Council, and the Alan Turing Institute.

Citation: Thadani, N. N., Gurev, S., Notin, P., Youssef, N., Rollins, N. J., Ritter, D., Sander, C., Gal, Y., & Marks, D. S. (11-Oct-2023). Learning from prepandemic data to forecast viral escape. Nature, 1-8. https://doi.org/10.1038/s41586-023-06617-0 (open-access)

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Wound-healing research produces full-thickness human bioprinted skin

Researchers at the Wake Forest Institute for Regenerative Medicine (WFIRM) have developed bioprinted skin that accelerates wound healing, supports healthy extracellular matrix remodeling, and may lead to complete wound recovery, according to a research paper in Science Translational Medicine.

This study involved bioprinting all six major primary human cell types present in skin. When transplanted onto mice and pigs in pre-clinical settings, the bioprinted skin formed blood vessels, skin patterns, and normal tissue formation. The study demonstrated improved wound closure, reduced skin contraction, and more collagen production to reduce scarring.

Important for burn victims, wounded warriors, and those with skin disorders

Skin regeneration has long been studied with hopes of providing complete healing for burn victims, wounded warriors, and those with skin disorders. Available grafts are often temporary, or if permanent, have only some of the elements of normal skin, which often have a scarred appearance. The creation of full-thickness skin has not been possible to date.

Anthony Atala, M.D., director of WFIRM and Adam Jorgensen, M.D., Ph.D., post-doctorate researcher at WFIRM, co-led the study.

Citation: Jorgensen, A. M., Gorkun, A., Mahajan, N., Willson, K., Clouse, C., Jeong, C. G., Varkey, M., Wu, M., Walker, S. J., Molnar, J. A., Murphttps://doi.org/adf7547hy, S. V., Lee, S. J., Yoo, J. J., Soker, S., & Atala, A. (2023). Multicellular bioprinted skin facilitates human-like skin architecture in vivo. Science Translational Medicine. https://doi.org/adf7547. https://www.science.org/doi/10.1126/scitranslmed.adf7547

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Researchers find evidence of largest-ever solar storm in ancient 14,300-year-old tree rings

Evidence of a largest-ever solar storm —a huge spike in radiocarbon levels—has been found by a team of scientists in ancient 14,300-year-old tree rings in the French Alps.

A similar solar storm today would be catastrophic for modern technological society, potentially wiping out telecommunications and satellite systems, causing massive electricity grid blackouts lasting months and costing us billions of pounds, the scientists say.

Miyake Events

Extreme solar storms could have huge impacts on Earth,” said Tim Heaton, Professor of Applied Statistics in the School of Mathematics at the University of Leeds. Nine such extreme solar storms—known as Miyake Events—have now been identified as having occurred over the last 15,000 years. 

The collaborative research is published today (Oct. 9) in the Royal Society’s Philosophical Transactions A: Mathematical, Physical and Engineering Sciences.

The largest, directly-observed solar storm occurred in 1859, known as the Carringon Event. It caused massive disruption on Earth, destroying telegraph machines and creating a night-time aurora so bright that birds began to sing, believing the Sun had begun to rise. 

Citation: Bard E, Miramont C, Capano M, Guibal F, Marschal C, Rostek F, Tuna T, Fagault Y, Heaton TJ (9-Oct-2023). A radiocarbon spike at 14,300 cal yr BP in subfossil trees provides the impulse response function of the global carbon cycle during the Late Glacial. Philosophical Transactions of the Royal Society A Mathematical Physical and Engineering Sciences. DOI 10.1098/rsta.2022.0206 (pending publication)

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First map of neural connections of a mouse brain at the synapse level

The brain is incredibly complex, with nearly 100 billion neurons that communicate across trillions of junctions called synapses.

To understand how it all works, Harvard neuroscientist Jeff Lichtman has spent several decades generating maps of this complexity, pioneering a field known as “connectomics.”

Jeff Lichtman on connectomics

To further explore connectomics, Lichtman and partners, including Princeton University, MIT, Cambridge University and Johns Hopkins, have just received $30 million from the National Institutes of Health (NIH) and an additional $3 million from Harvard and Princeton.

Starting with mouse hippocampus

For this initial funding, the researchers will image just a 10-cubic-millimeter region in the hippocampus. “This region is of clinical interest because it is an essential part of the circuit underlying spatial navigation and memory, and of the earliest impairments and degeneration related to Alzheimer’s disease,” Lichtman said.

“The mouse brain is much smaller than a human’s. But when looking at individual neurons, synaptic vesicles and glial cells, you can’t tell the difference, At the level of cells and synapses, all mammalian brains are basically the same.”

The 33 million funding is “a grant for a proof-of-concept prequel to doing a whole mouse brain and the funds support the entire team,” Lichtman explained in an interview.

Wiring diagram to use machine learning

To explore the brain, the researchers will apply biological imaging techniques that Lichtman and colleagues have invented over several decades. For the NIH project, they will use two 91-beam scanning electron microscopes at Harvard and Princeton to capture images of thin sections of the mouse hippocampal formation.

Next, to explore further, the surface of each studied section will be etched away with an ion beam a few nanometers at a time. This imaging process will be repeated until the entire volume is viewed.

A team at Google Research will then computationally extract the resulting wiring diagram, using machine learning.

The team expects to generate about 10,000 terabytes of data for this initial 10-square-millimeter mouse brain section (50 times that amount of data would be generated, in future research, for a whole mouse brain).

The researchers also plan to develop a rapid-imaging strategy for connectomics, working with other awardees.

Related papers

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Artificial-life nanostructures: medicine of the future?

Two researchers have proposed that we use a type of “artificial life” called “hybrid peptide-DNA nanostructures” (based on viral vaccines and artificial life forms) to develop new methods of diagnosing and treating diseases.

Associate professor Chenguang Lou from the Department of Physics, Chemistry, and Pharmacy, University of Southern Denmark and Professor Hanbin Mao from Kent State University have just written a research review of such nanostructures, published today in the open-access journal Cell Reports Physical Science.

Lou’s vision is to create viral vaccines (modified and weakened versions of a virus) and artificial life forms to diagnose and treat diseases.

“In nature, most organisms have natural enemies, but some do not,” Lou says. “For example, some disease-causing viruses have no natural enemy. It would be a logical step to create an artificial life form that could become an enemy to them.”

Artificial cellular organisms

Lou also envisions that such artificial life forms can act as vaccines against viral infection—using nanorobots or nanomachines loaded with medication or diagnostic elements, and sent and delivered to a patient’s body.

“An artificial viral vaccine may be about 10 years away,” says Lou. “An artificial cell, on the other hand, is on the horizon, because it consists of many elements that need to be controlled before we can start building with them. But with the knowledge we have, there is, in principle, no hindrance to produce artificial cellular organisms in the future.”

Building blocks: DNA and peptides

“DNA and peptides are some of the most important biomolecules in nature, making DNA technology and peptide technology the two most powerful molecular tools in the nanotechnological toolkit today,” according to Lou. “DNA technology provides precise control over programming, from the atomic level to the macro level; but it can only provide limited chemical functions since it only has four bases: A, C, G, and T.

“Peptide technology, on the other hand, can provide sufficient chemical functions on a large scale, as there are 20 amino acids to work with. Nature uses both DNA and peptides to build various protein factories found in cells, allowing them to evolve into organisms.”

Mao and Lou have recently succeeded in linking three-stranded DNA structures with three-stranded peptide structures, creating an artificial hybrid molecule that combines the strengths of both (see “Chirality transmission in macromolecular domains” by Lou et al., 2022).

Other Approaches

Other researchers are also working on connecting DNA and peptides, because this connection forms a strong foundation for the development of more advanced biological entities and life forms. These include:

Oxford University: A nanomachine made of DNA and peptides that can drill through a cell membrane, creating an artificial membrane channel through which small molecules can pass (Spruijt et al., Nat. Nanotechnol. 2018, 13, 739-745).

Arizona State University: Nicholas Stephanopoulos and colleagues have enabled DNA and peptides to self-assemble into 2D and 3D structures. (Buchberger et al., J. Am. Chem. Soc. 2020, 142, 1406-1416)

Northwest University: researchers have shown that microfibers can form in conjunction with DNA and peptides self-assembling. DNA and peptides operate at the nano level, so when considering the size differences, microfibers are huge. (Freeman et al., Science, 2018, 362, 808-813)

Ben-Gurion University of the Negev: scientists have used hybrid molecules to create an onion-like spherical struture containing cancer medication, which holds promise to be used in the body to target cancerous tumors. ()

“In my view, the overall value of all these efforts is that they can be used to improve society’s ability to diagnose and treat sick people. Looking forward, I will not be surprised that one day we can arbitrarily create hybrid nanomachines, viral vaccines and even artificial life forms from these building blocks to help the society to combat those difficult-to-cure diseases. It would be a revolution in healthcare,” says Lou.

Citation: Mathias Bogetoft Danielsen, Hanbin Mao, Chenguang Lou. (Oct. 5, 2023) Peptide-DNA conjugates as building blocks for de novo design of hybrid nanostructures. Cell Reports Physical Science (Open Access) DOI: https://doi.org/10.1016/j.xcrp.2023.101620 (open access)

Citation: Pandey, S., Mandal, S., Danielsen, M. B., Brown, A., Hu, C., Christensen, N. J., Kulakova, A. V., Song, S., Brown, T., Jensen, K. J., Wengel, J., Lou, C., & Mao, H. (2022). Chirality transmission in macromolecular domains. Nature Communications, 13(1), 1-11. https://doi.org/10.1038/s41467-021-27708-4 (open-access)

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Microdosing psilocybin mushrooms as a therapeutic tool

New research supports the use of psilocybin—the active compound in mushrooms with psychedelic properties—as a therapeutic tool. It examines the effects of microdosing (small daily doses) of psilocybin on rats, avoiding bias in humans from suggestion and other factors.

Understanding the effects and side effects of lower doses

Psilocybin is being widely investigated for its potential to assist in the treatment of various psychiatric disorders, primarily depression and addiction, through therapy supplemented with a high dose of psilocybin.

Now, research by Associate Professor Mikael Palner and PhD student Kat Kiilerich at the University of Southern Denmark has focused on repeated microdoses of psilocybin, which are significantly lower than the doses typically used in therapeutic settings.

Published in the journal Nature Molecular Psychiatry, the paper focuses on a study of how rats tolerated the repeated low doses of psilocybin (well) and didn’t exhibit signs of reduced pleasure, anxiety, or altered locomotor activity.

New research method

“The increased anxiety and stress in society currently have placed a strong focus on microdosing, leading to a surge in the trade of mushrooms,” said Palner. “Countries such as the Netherlands, Australia, the USA, and Canada have either legalized or are in the process of legalizing psilocybin for therapeutic treatment.”

The researchers say they have established a valid new method that can be used for further research into the effects of repeated low doses of psilocybin. The study also supports the numerous anecdotal reports of the benefits of microdosing as a therapeutic intervention, and suggests new approaches to treating various mental disorders.

Enhanced Understanding

Mikael Palne, an associate professor affiliated with the Research Unit for Clinical Physiology and Nuclear Medicine at SDU and OUH, conducts research on the biological understanding of mental illness and treatment with psychedelic substances.

Palner developed an interest in researching psychedelic substances and psilocybin when he lived in Silicon Valley, California, eleven years ago, where he witnessed the surge of self-improvement practices that garnered significant media attention and prompted more people to experiment with microdosing.

“This motivated me to launch the project I’ve been devoted to for the past six years,” he says.

Psilocybin’s ubiquitous uses

Palner notes that Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is a naturally occurring psychoactive compound found in over 200 different species of mushrooms. It has been used in religious and ceremonial contexts by various cultures for centuries, particularly among Native American tribes.

In the body, psilocybin is converted into psilocin, which is responsible for its psychoactive effects. Psilocin affects serotonin receptors in the brain that can alter mood, perception, and cognition.

Citation: Kiilerich, K.F., Lorenz, J., Scharff, M.B. et al. Repeated low doses of psilocybin increase resilience to stress, lower compulsive actions, and strengthen cortical connections to the paraventricular thalamic nucleus in rats. Mol Psychiatry (2023). https://doi.org/10.1038/s41380-023-02280-z

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Simple modified-earbud biosensors can record and diagnose brain activity and exercise levels

Close up of the device and sensors
Screen-printed flexible sensors attached to earbuds on a flexible, stamp-like surface can be used for health monitoring and diagnosis of neuro-degenerative conditions (credit: Erik Jepsen/University of California San Diego)

A multidisciplinary research team of engineers at the University of California San Diego has developed biosensors that can be used for health monitoring and diagnosis of neurodegenerative conditions during exercise.

Data from an electroencephalogram (EEG), which measures electrical activity in the brain, and sweat lactate, an organic acid the body produces during exercise and normal metabolic activity, can now be combined for a variety of purposes. For example, they can be used to diagnose epileptic and other seizures or to monitor effort during physical exercise and levels of stress and focus. 

“Being able to measure the dynamics of both brain cognitive activity and body metabolic state in one in-ear integrated device that doesn’t intrude on the comfort and mobility of the user opens up tremendous opportunities for advancing health and wellness of people of all ages, anytime and anywhere,” said Gert Cauwenberghs, a professor in the Shu Chien Gene Lay Department of Bioengineering at UC San Diego.

Building the sensors

The first step in building the in-ear sensors was confirming that EEG and lactate data could be gathered in the ear. Researchers had to design smaller, more compact instruments to gather electrophysiological signals, such as EEG data, that would fit on an earbud.

They also had to find a suitable material to collect sweat and sense lactate.  After preliminary experiments on human subjects, researchers determined that the best location to collect and record lactate data was the tragus, where sweat accumulates at the entrance of the ear. The team also knew from previous experience that to collect EEG data, high-performance physiological electrodes pointed  toward the temporal lobe were required. 

“The primary technical challenge was fitting two sensors in the ear, which is a small space that varies from an individual to another, but also reliably acquiring signals from both EEG and lactate,” said Yuchen Xu, co-first author of the paper, and a postdoctoral researcher in Cauwenberghs’s lab. “It’s a natural entry point–people are used to wearing earbuds.”

“We also had to accommodate for earbuds integration and reduce crosstalk. That’s when we landed on the idea of a stamp-like stretchable sensor, which is a simple addition to the earbud itself, but has all the necessary functions we needed and gave us enough freedom for our designs.”

To make sure that the electrophysiological sensors had firm contact with the ear, researchers designed 3D spring-loaded sensors that hold contact but can adjust as earbuds move. To improve sweat collection, researchers covered the electrochemical sensors with a see-through hydrogel film. “It’s sponge-like and hydrophilic,” Xu said. “It acts as a mechanical cushion between skin and sensors and also helps collect sweat.” 

“This new and powerful in-ear multimodal wearable bioelectronic platform offers a rich source of real-time information on the health of the users by recording physical and biochemical information simultaneously and dynamically,” said Joseph Wang, a professor in the Department of NanoEngineering and director of the Center for Wearable Sensors at the Jacobs School.

The researchers foresee a future in which neuroimaging and health monitoring systems work with wearable sensors and mobile devices, such as phones, earbuds, watches, and more to track brain activity and levels of many health-related metabolites throughout the day. This would allow users to enhance brain and body capabilities.

Citation: UC San Diego Department of Bioengineering: Shu Chien-Gene Lay, Yuchen Xu, Akshay Paul, Min Lee, Abhinav Uppal, William Chen, Stephen Deiss, Gert Cauwenberghs; UC San Diego Department of NanoEngineering and Chemical Engineering: Ernesto De la Paz, Kuldeep Mahato, Juliane R. Sempionatto, Nicholas Tostado, Muyang Lin, Srishty Dua, Lu Yin, Sheng Xu, Joseph Wang. UC San Diego Department of Electrical and Computer Engineering: Gopabandhu Hota, Brian L. Wuerstle, Patrick Mercier. (28-Sep-2023). Unobtrusive in-ear integrated physiological and metabolic sensors for continuous brain-body activity monitoring. Nature Biomedical Engineering. https://www.nature.com/articles/s41551-023-01095-1 (open-access)

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You can learn to control a robotic arm in one hour

One-hour training is enough for people to carry out a task with one or more robotic arms, according to a new study by researchers at Queen Mary University of London, Imperial College London and The University of Melbourne.

The study, published in the journal IEEE Open Journal of Engineering in Medicine and Biology, investigated the potential of multiple robotic arms to help people perform tasks that require more than two hands.

“Many tasks in daily life, such as opening a door while carrying a big package, require more than two hands,” said Dr. Ekaterina Ivanova, lead author of the study, from Queen Mary University of London. “Supernumerary robotic arms have been proposed as a way to allow people to do these tasks more easily, but until now, it was not clear how easy they would be to use.” 

Perhaps like Doctor Octopus in Spider-Man 2 (1963)?

Dr. Octopus, with four long tentacles as extra hands. After a failed fusion experiment, eccentric and obsessive scientist Dr. Otto Octavius is transformed into super-villain Doctor Octopus (credit: Sony Pictures)

The study involved 24 participants who were asked to perform a variety of tasks with more than two robotic arms. The participants were either given one hour of training in how to use the arm, or they were asked to work with a partner. 

The results showed that the participants who had received training on the supernumerary arm performed the tasks just as well as the participants who were working with a partner.

“Our findings are promising for the development of supernumerary robotic arms,” said Ivanova. “They suggest that these arms could be used to help people with a variety of tasks, such as surgery, industrial work, or rehabilitation.” 

Citation: Yanpei Huang, Jonathan Eden, Ekaterina Ivanova, Etienne Burdet (16-Aug-2023). Can Training Make Three Arms Better Than Two Heads for Trimanual Coordination? IEEE Open Journal of Engineering in Medicine and Biology. Vol. 4. 10.1109/OJEMB.2023.3305808 (open-access)

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The Tong test for AGI

Researchers in China have developed an AGI test platform for evaluating and benchmarking AGI models.

Funded by the National Key Research and Development Program of China, the Tong* test architecture consists of infrastructure, “dynamic embodied physical and social interactions” (DEPSI), and evaluation tools, the researchers report in the journal Engineering.

Reasonable, but not AGI in general

“The Tong test looks fairly reasonable,” says AGI pioneer Dr. Ben Goertzel, CEO of SingularityNet, “but it’s plainly a test of what I’d call ‘human-capable AGI,’ not AGI in general.

“This sort of test can be valuable, but I don’t think it’s really meaningful to have a single litmus test for ‘general AGI’ nor for ‘human-capable AGI.’ These are multidimensional things that can be measured in a lot of different ways. And different in-progress AGI systems are going to perform differently on different dimensions.   

Useful evaluation tools

“However, it’s useful to have some standardized environments and tests for evaluating in-progress AGI systems, as long as one interprets these as useful tools to play with, rather than as definitive measurement devices,” says Goertzel. 

“General intelligence is not something highly precisely defined, like temperature or pressure, which can be accurately measured if one just builds the right instrument (and I say this being very aware of how hard it is to build an accurate calorimeter…!).”

* “Tong” corresponds to the pronunciation of the Chinese character of “general,” as in “artificial general intelligence”

Citation: Peng, Y., Han, J., Zhang, Z., Fan, L., Liu, T., Qi, S., Feng, X., Ma, Y., Wang, Y., & Zhu, S. (2023). The Tong Test: Evaluating Artificial General Intelligence Through Dynamic Embodied Physical and Social Interactions. Engineering. https://www.sciencedirect.com/science/article/pii/S209580992300293X (open access)

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Finger-worn device can ‘translate’ text messages to braille on-the-fly

Engineers and chemists at Lawrence Livermore National Laboratory (LLNL) and Meta have developed a new kind of 3D-printed material that can replicate some characteristics of biological tissue.

The researchers say the advancement could impact the future of “augmented humanity,” where technology enhances human performance by closely interfacing engineered devices with our anatomy. 

Emulating the range of bio materials

As described In a paper in the journal Matter, the method patterns smooth gradients in stiffness to approximate gradients found in biology, such as where bone meets muscle. This overcomes “mechanical mismatch” (natural tissues are soft; electronic devices are usually made of rigid materials).

“For engineers, it’s very hard to get a softer material combined with a stiffer material such as is common in nature,” explained lead author and LLNL engineer Sijia Huang. “Engineers make a part that is stiff and another part that is soft, and then manually assemble them together, so we have a very sharp interface that compromises the mechanical property.

The new technique works by manipulating the intensity of light applied to a photopolymer resin, using a layer-by-layer technique that can rapidly produce parts by projecting light into a liquid resin. Lower light intensity results in a softer material; higher light a stiffer material.

Wearable braille display

To demonstrate the potential, engineers at Meta used the material to 3D-print an inexpensive braille display that could be worn on a single finger and connected to a smartphone and an air pump.

When text is transmitted via the phone, sections of the wearable fill with air, causing it to deform and create braille letters, enabling a sightless person to “read” the text through the device.

The material is stretchable to around 200 times its original properties, and as its gradient transitions from soft to stiffer material, its toughness increases by 10 times. Huang said the material could be tailored for energy-absorbing materials, soft robotics and wearable electronic devices.

Citation: Sijia Huang et al. (June 20, 2023) One-pot ternary sequential reactions for photopatterned gradient multimaterials. Matter. DOI: https://doi.org/10.1016/j.matt.2023.05.040 (open-access)

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