Memory Problems Common in Old Age Can Be Reversed

While immortality might forever be out of reach, a long, healthy retirement is the stuff dreams are made of. To that end, a recent study suggests that the kinds of memory problems common in old age can be reversed, and all it takes is some cerebrospinal fluid (CSF) harvested from the young. In mice, at least.

If this is sounding a little familiar, you might be thinking of a similar series of studies done back in the mid-2010s, which found that older mice could be generally ‘rejuvenated‘ with the blood of younger animals – both from humans and from mice. The FDA even had to warn people to stop doing it. This new study instead examined the links between memory and cerebrospinal fluid  (CSF), and the results show considerable promise, even providing a mechanism for how it works, and highlighting a potential growth factor that could mimic the results.

“We know that CSF composition changes with age, and, in fact, these changes are used routinely in the clinic to assess brain health and disease biomarkers,” Stanford University neurologist Tal Iram said. “However, we don’t know well how these changes affect the function of the cells in the aging brain.

To investigate, the researchers, led by Iram, took older mice (between 18–22 months old) and gave them light shocks on the foot, at the same time as a tone and flashing light were activated. The mice were then split into groups, and either given young mouse CSF (from animals 10 weeks old) or artificial CSF. In experiments like this, if the mice ‘freeze’ when they see the tone and light, it means they’re remembering the foot shock, and are preparing for it to happen again. In this study, three weeks after the foot shocks were conducted (which the team called “memory acquisition“), the researchers tested the mice, finding that the animals that had been given the CSF from young mice showed higher-than-average freezing rates, suggesting they had better memory. This was followed up by a battery of other experiments to test the theory, which revealed that certain genes (that are different in young-versus-old CSF) could be used to get the same response. In other words, without needing to extract someone’s brain fluid.

When we took a deeper look into gene changes that occurred in the hippocampus (a region associated with memory and aging-related cognitive decline), we found, to our surprise, a strong signature of genes that belong to oligodendrocytes,” Iram explained. “Oligodendrocytes are unique because their progenitors are still present in vast numbers in the aged brain, but they are very slow in responding to cues that promote their differentiation. We found that when they are re-exposed to young CSF, they proliferate and produce more myelin in the hippocampus.” Oligodendrocytes are particularly helpful because they produce myelin, a material that covers and insulates neuron fibers.

Super-Speedy Diagnosis of Rare Genetic Diseases

About a year ago, Matthew Kunzman’s heart was failing, despite doctors’ best attempts to bolster it with every pump and gadget they could think of. But the 14-year-old has bounced back in large part due to super-speedy genetic sequencing that pinpointed the cause of his disease and helped doctors decide how to treat it — in just 11 and a half hours. That speedy diagnosis — faster than any other medical team has previously reported — resulted from a new approach to DNA sequencing to help patients with deadly and rare diseases. On Wednesday, a team of Stanford researchers and collaborators published a letter in the New England Journal of Medicine reporting that they had sequenced 12 seriously ill patients and successfully diagnosed five of them (including Matthew). In all five cases, the information led to tangible changes in how patients were treated.

Typical turnaround time for diagnosis was around eight hours and as short as seven hours and eighteen minutes – less than half the current record. And the scientists are convinced they can cut that in half yet again. Such speed could be life-saving for critically ill patients, according to Euan Ashley, a Stanford cardiologist and the study’s senior author.

You can not only make care better, and help patients more, but do it cheaper, save money, save the system money,” Ashley said. “It seems like a win, win, win all around.”

There’s a lot to be learned by exploring your genetic code, which influences everything from your height and eye color to your likelihood of developing certain diseases. For doctors, knowing whether a patient’s symptoms are linked to specific DNA mutations — and, if so, which ones — can help them determine what treatments and surgical procedures to try and which ones to avoid. But it typically takes weeks to run, process, and interpret sequencing results. That’s time some patients don’t have. And hospital stays spent chasing down the cause of an unknown disease can cost tens of thousands of dollars.

Ashley wanted to see how quickly he could speed things up. He and his team enrolled a dozen seriously ill patients admitted at Stanford, taking about half a teaspoon of blood from each of them for genetic sequencing. The participants, who ranged in age from 3 months to 57 years old, suffered from everything from seizures to cardiac arrest. Throughout the six-month study, which kicked off in December 2020, researchers tweaked nearly every step of the sequencing process, from having someone run samples from the hospital to the lab to shortening the time needed to prep DNA for sequencing. It was round-the-clock work.

Source: https://www.statnews.com/

Ultrathin, Lightweight Solar Panels

A race is on in solar engineering to create almost impossibly-thin, flexible solar panels. Engineers imagine them used in mobile applications, from self-powered wearable devices and sensors to lightweight aircraft and electric vehicles. Against that backdrop, researchers at Stanford University have achieved record efficiencies in a promising group of photovoltaic materials. Chief among the benefits of these transition metal dichalcogenides – or TMDs – is that they absorb ultrahigh levels of the sunlight that strikes their surface compared to other solar materials.

Transition metal dichalcogenide solar cells on a flexible polyimide substrate

Imagine an autonomous drone that powers itself with a solar array atop its wing that is 15 times thinner than a piece of paper,” said Koosha Nassiri Nazif, a doctoral scholar in electrical engineering at Stanford and co-lead author of a study published in the Dec. 9 edition of Nature Communications. “That is the promise of TMDs.”

The search for new materials is necessary because the reigning king of solar materials, silicon, is much too heavy, bulky and rigid for applications where flexibility, lightweight and high power are preeminent, such as wearable devices and sensors or aerospace and electric vehicles.

Silicon makes up 95 percent of the solar market today, but it’s far from perfect. We need new materials that are light, bendable and, frankly, more eco-friendly,” said Krishna Saraswat, a professor of electrical engineering and senior author of the paper. While TMDs hold great promise, research experiments to date have struggled to turn more than 2 percent of the sunlight they absorb into electricity. For silicon solar panels, that number is closing in on 30 percent. To be used widely, TMDs will have to close that gap.

The new Stanford prototype achieves 5.1 percent power conversion efficiency, but the authors project they could practically reach 27 percent efficiency upon optical and electrical optimizations. That figure would be on par with the best solar panels on the market today, silicon included.

Moreover, the prototype realized a 100-times greater power-to-weight ratio of any TMDs yet developed. That ratio is important for mobile applications, like drones, electric vehicles and the ability to charge expeditionary equipment on the move. When looking at the specific power – a measure of electrical power output per unit weight of the solar cell – the prototype produced 4.4 watts per gram, a figure competitive with other current-day thin-film solar cells, including other experimental prototypes. “We think we can increase this crucial ratio another ten times through optimization,” Saraswat said, adding that they estimate the practical limit of their TMD cells to be a remarkable 46 watts per gram.”

Source: https://news.stanford.edu/

Brain Surgery Without a Scalpel

The School of Medicine from the University of Virginia (UVA) researchers have developed a noninvasive way to remove faulty brain circuits that could allow doctors to treat debilitating neurological diseases without the need for conventional brain surgery. The UVA team, together with colleagues at Stanford University, indicate that the approach, if successfully translated to the operating room, could revolutionize the treatment of some of the most challenging and complex neurological diseases, including epilepsy, movement disorders and more. The approach uses low-intensity focused ultrasound waves combined with microbubbles to briefly penetrate the brain’s natural defenses and allow the targeted delivery of a neurotoxin. This neurotoxin kills the culprit brain cells while sparing other healthy cells and preserving the surrounding brain architecture.

A new alternative to brain surgery developed at UVA can wipe out out problematic neurons, a type of brain cell, without causing collateral damage.

This novel surgical strategy has the potential to supplant existing neurosurgical procedures used for the treatment of neurological disorders that don’t respond to medication,” said researcher Kevin S. Lee, PhD, of UVA’s Departments of Neuroscience and Neurosurgery and the Center for Brain Immunology and Glia (BIG). “This unique approach eliminates the diseased brain cells, spares adjacent healthy cells and achieves these outcomes without even having to cut into the scalp.”

The new approach is called PING, and it has already demonstrated exciting potential in laboratory studies. For instance, one of the promising applications for PING could be for the surgical treatment of epilepsies that do not respond to medication. Approximately a third of patients with epilepsy do not respond to anti-seizure drugs, and surgery can reduce or eliminate seizures for some of them. Lee and his team, along with their collaborators at Stanford, have shown that PING can reduce or eliminate seizures in two research models of epilepsy. The findings raise the possibility of treating epilepsy in a carefully-targeted and noninvasive manner without the need for traditional brain surgery.

Another important potential advantage of PING is that it could encourage the surgical treatment of appropriate patients with epilepsy who are reluctant to undergo conventional invasive or ablative surgery. In a scientific paper newly published in the Journal of Neurosurgery, Lee and his collaborators detail the ability of PING to focally eliminate neurons in a brain region, while sparing non-target cells in the same area. In contrast, currently available surgical approaches damage all cells in a treated brain region.

A key advantage of the approach is its incredible precision. PING harnesses the power of magnetic-resonance imaging (MRI) to let scientists peer inside the skull so that they can precisely guide sound waves to open the body’s natural blood-brain barrier exactly where needed. This barrier is designed to keep harmful cells and molecules out of the brain, but it also prevents the delivery of potentially beneficial treatments.

The UVA group’s new paper concludes that PING allows the delivery of a highly targeted neurotoxin, cleanly wiping out problematic neurons, a type of brain cell, without causing collateral damage.

Source: https://newsroom.uvahealth.com/

Type Words Just by Thinking Them

Scientists at Stanford have developed a brain implant that allowed a man with paralyzed hands to “type” words just by thinking them. According to the findings, the man was able to type up to 90 characters per minute. This is a big improvement over past implants. Previous options have relied on the patients using their thoughts to move cursors to specific characters on a digital keyboard. With this new implant, people would be able to freely type and communicate via text by simply thinking about the words that they want to use.

One of the main focuses of brain-computer interfaces (BCIs) is to restore motor skills such as talking and moving to people who have lost those abilities. With this new implant, scientists trying to build off of that idea by using an intracortical BCI that decodes the handwriting movements and neural activity in the motor cortex. The implant then takes that information and translates it to text in real-time. Essentially, it allows the person with the implant to think about writing a letter or word. That letter or word is then translated into text, allowing for quick communication from the user.

When tested, the implant was able to achieve a 94.1 percent raw accuracy when online. It was also able to deliver 99 percent accuracy when offline. This number is comparable to the typical smartphone typing speeds of individuals in the age group of the test’s participant.

When we really understand the brain through neuroscience in the coming decades, we should be able to do much better in a wider variety of tasks,” Krishna Shenoy, a neuroscientist and engineer, said during the WE Summit (via the South China Morning Post).

We’ve already seen brain implants allowing blind users to see shapes. Shenoy believes that these findings are just the “tip of the iceberg”. With more testing and engineering, the implants they use could provide even stronger results.

The group originally published its work in Nature in May, with a full presentation released at a recent science teleconference called the WE Summit.

Source: https://bgr.com/

The Drugmaker Merck Says Its Antiviral Pill Is Effective Against Coronavirus

The drug maker says its pill was shown in a clinical trial to cut the risk of hospitalization or death from the virus in half. Australia is accelerating plans to ease international travel restrictions for its citizens and permanent residents.

The drug maker Merck said on Friday that it would seek authorization for the first antiviral pill for Covid after its drug, known as molnupiravir, was shown in a clinical trial to cut the risk of hospitalization or death in half when given to high-risk people early in their infections.

The treatment could become the first in a wave of antiviral pill products, which experts say could offer a powerful new tool in efforts to tame the pandemic, as they could reach more people than the antibody treatments that are being widely used in the United States for similar patients.

I think it will translate into many thousands of lives being saved worldwide, where there’s less access to monoclonal antibodies, and in this country, too,” said Dr. Robert Shafer, an infectious disease specialist and expert on antiviral therapy at Stanford University.

Late-stage study results of two other antiviral pills, one developed by Pfizer and the other by Atea Pharmaceuticals and Roche, are expected within the next few months.

The Merck drug, which is designed to stop the coronavirus from replicating, is to be taken as four capsules twice a day for five days.

Merck said an independent board of experts monitoring its study data had recommended that its trial be stopped early because the drug’s benefit to patients had proved so convincing. The company said that the Food and Drug Administration had agreed with that decision.

For the research, the monitors looked at data through early August, when the study had enrolled 775 volunteers in the United States and overseas. For volunteers who received the drug, their risk of being hospitalized or dying fell 50 percent, without any concerning side effects, compared with those who received placebo pills, Merck said in a news release announcing the findings.

Seven percent of volunteers in the group that received the drug were hospitalized, and none of them died, compared with a 14 percent rate of hospitalization and death — including eight deaths — in the group that received the placebo.

The Merck pill’s efficacy was lower than that of monoclonal antibody treatments, which mimic antibodies that the immune system generates naturally when fighting the virus. Those drugs have been in high demand recently, but they are expensive, are typically given intravenously, and have proved cumbersome and labor-intensive for hospitals and clinics to administer. Studies have shown that they reduce hospitalizations and deaths 70 to 85 percent in similar high-risk Covid patients.

Source: https://www.nytimes.com/

High Speed Typing Brain-Computer Interface

The ancient art of handwriting has just pushed the field of brain-computer interface (BCI) to the next level. Researchers have devised a system that allows a person to communicate directly with a computer from his brain by imagining creating handwritten messages. The approach enables communication at a rate more than twice as fast as previous typing-by-brain experiments.

Researchers at Stanford University performed the study on a 65-year-old man with a spinal cord injury who had had an electrode array implanted in his brain. The scientists described the experiment recently in the journal Nature.

The big news from this paper is the very high speed,” says Cynthia Chestek, a biomedical engineer at the University of Michigan, who was not involved in the study. “It’s at least half way to able-bodied typing speed, and that’s why this paper is in Nature.”

For years, researchers have been experimenting with ways to enable people to directly communicate with computers using only their thoughts, without verbal commands, hand movement, or eye movement. This kind of technology offers a life-giving communication method for people who are “locked in” from brainstem stroke or disease, and unable to speak.

Successful BCI typing-by-brain approaches so far typically involve a person imagining moving a cursor around a digital keyboard to select letters. Meanwhile, electrodes record brain activity, and machine learning algorithms decipher the patterns associated with those thoughts, translating them into the typed words. The fastest of these previous typing-by-brain experiments allowed people to type about 40 characters, or 8 words, per minute.

That we can do this at all is impressive, but in real life that speed of communication is quite slow. The Stanford researchers were able to more than double that speed with a system that decodes brain activity associated with handwriting. In the new system, the participant, who had been paralyzed for about a decade, imagines the hand movements he would make to write sentences.

We ask him to actually try to write—to try to make his hand move again, and he reports this somatosensory illusion of actually feeling like his hand is moving,” says Frank Willett, a researcher at Stanford who collaborated on the experiment.

A microelectrode array implanted in the motor cortex of the participant’s brain records the electrical activity of individual neurons as he tries to write. “He hasn’t moved his hand or tried to write in more than ten years and we still got these beautiful patterns of neural activity,” says Willett.

The new findings, published online in Nature, could spur further advances benefiting hundreds of thousands of Americans, and millions globally, who’ve lost the use of their upper limbs or their ability to speak due to spinal-cord injuries, strokes or amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease, said Jaimie Henderson, MD, professor of neurosurgery.

This approach allowed a person with paralysis to compose sentences at speeds nearly comparable to those of able-bodied adults of the same age typing on a smartphone,” said Henderson, the John and Jene Blume — Robert and Ruth Halperin Professor.” The goal is to restore the ability to communicate by text.”

The participant in the study produced text at a rate of about 18 words per minute. By comparison, able-bodied people of the same age can punch out about 23 words per minute on a smartphone.

Surce: https://med.stanford.edu/
AND
https://spectrum.ieee.org/

Breakthrough Against COVID-19

A team of scientists from Stanford University is working with researchers at the Molecular Foundry, a nanoscience user facility located at the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab), to develop a gene-targeting, antiviral agent against COVID-19. Last year, Stanley Qi, an assistant professor in the departments of bioengineering, and chemical and systems biology at Stanford University and his team had begun working on a technique called PAC-MAN – or Prophylactic Antiviral CRISPR in human cells – that uses the gene-editing tool CRISPR to fight influenza.

But that all changed in January, when news of the COVID-19 pandemic emerged. Qi and his team were suddenly confronted with a mysterious new virus for which no one had a clear solution.

Lipitoids, which self-assemble with DNA and RNA, can serve as cellular delivery systems for antiviral therapies that could prevent COVID-19 and other coronavirus infections.

So we thought, ‘Why don’t we try using our PAC-MAN technology to fight it?’” said Qi.

Since late March, Qi and his team have been collaborating with a group led by Michael Connolly, a principal scientific engineering associate in the Biological Nanostructures Facility at Berkeley Lab’s Molecular Foundry, to develop a system that delivers PAC-MAN into the cells of a patient.

Like all CRISPR systems, PAC-MAN is composed of an enzyme – in this case, the virus-killing enzyme Cas13 – and a strand of guide RNA, which commands Cas13 to destroy specific nucleotide sequences in the coronavirus’s genome. By scrambling the virus’s genetic code, PAC-MAN could neutralize the coronavirus and stop it from replicating inside cells.

Qi said that the key challenge to translating PAC-MAN from a molecular tool into an anti-COVID-19 therapy is finding an effective way to deliver it into lung cells. When SARS-CoV-2, the coronavirus that causes COVID-19, invades the lungs, the air sacs in an infected person can become inflamed and fill with fluid, hijacking a patient’s ability to breathe.

But my lab doesn’t work on delivery methods,” he said. So on March 14, they published a preprint of their paper, and even tweeted, in the hopes of catching the eye of a potential collaborator with expertise in cellular delivery techniques. Soon after, they learned of Connolly’s work on synthetic molecules called lipitoids at the Molecular Foundry. Lipitoids are a type of synthetic peptide mimic known as a “peptoid” first discovered 20 years ago by Connolly’s mentor Ron Zuckermann. In the decades since, Connolly and Zuckermann have worked to develop peptoid delivery molecules such as lipitoids. And in collaboration with Molecular Foundry users, they have demonstrated lipitoids’ effectiveness in the delivery of DNA and RNA to a wide variety of cell lines.

Today, researchers studying lipitoids for potential therapeutic applications have shown that these materials are nontoxic to the body and can deliver nucleotides by encapsulating them in tiny nanoparticles just one billionth of a meter wide – the size of a virus. Now Qi hopes to add his CRISPR-based COVID-19 therapy to the Molecular Foundry’s growing body of lipitoid delivery systems.

Source: https://newscenter.lbl.gov/

Bionic Jellyfish

It may sound more like science fiction than science fact, but researchers have created bionic jellyfish by embedding microelectronics into these ubiquitous marine invertebrates with hopes to deploy them to monitor and explore the world’s oceans.

A small prosthetic enabled the jellyfish to swim three times faster and more efficiently without causing any apparent stress to the animals, which have no brain, central nervous system or pain receptors, the researchers said.

The next steps will be to test ways to control where the jellyfish go and develop tiny sensors that could perform long-term measurements of ocean conditions such as temperature, salinity, acidity, oxygen levels, nutrients and microbial communities. They even envision installing miniscule cameras.

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It’s very sci-fi futuristic,” said Stanford University bioengineer Nicole Xu, co-author of the research published this week in the journal Science Advances. “We could send these bionic jellyfish to different areas of the ocean to monitor signs of climate change or observe natural phenomena.

An initial goal will be deep dives because measurements at great depths are a major gap in our understanding of the oceans, added California Institute of Technology mechanical engineering professor John Dabiri, the study’s other co-author.

Basically, we’d release the bionic jellyfish at the surface, have it swim down to increasing depths, and see just how far we can get it to go down into the ocean and still make it back to the surface with data,” Dabiri added.

Source: https://www.caltech.edu/
AND
https://www.reuters.com/

How To Trap CO2 Molecules

Scientists from the Department of Energy’s SLAC National Accelerator Laboratory and Stanford University have taken the first images of carbon dioxide molecules within a molecular cage ­­– part of a highly porous nanoparticle known as a MOF, or metal-organic framework, with great potential for separating and storing gases and liquids.

The images, made at the Stanford-SLAC Cryo-EM Facilities, show two configurations of the COmolecule in its cage, in what scientists call a guest-host relationship; reveal that the cage expands slightly as the CO2 enters; and zoom in on jagged edges where MOF particles may grow by adding more cages.

This is a groundbreaking achievement that is sure to bring unprecedented insights into how these highly porous structures carry out their exceptional functions, and it demonstrates the power of cryo-EM for solving a particularly difficult problem in MOF chemistry,” said Omar Yaghi, a professor at the University of California, Berkeley and a pioneer in this area of chemistry, who was not involved in the study.

The team, led by SLAC/Stanford professors Yi Cui and Wah Chiu, described the study  in the journal Matter.

Source: https://www6.slac.stanford.edu/