Autism-related conditions converge on same loss of DNA tags

BY GIORGIA GUGLIELMI  /  20 JANUARY 2021

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GENES, SIGNS & SYMPTOMS, THE BRAIN

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 Weekly  DailyDirect deposit: DNMT3A protein attaches a methyl group tag onto the DNA base cytosine.

Christoph Bock / Max Planck Institute for Informatics

Mutations in the gene DNMT3A disrupt how other genes are turned on and off, and can lead to a range of neurodevelopmental conditions, a study in mice has found.

The results hint at how mutations in DNMT3A, seen in people with autism and a related condition called Tatton-Brown Rahman syndrome, interfere with brain function, says lead investigator Harrison Gabel, assistant professor of neuroscience at Washington University in St. Louis, Missouri.

DNMT3A codes for a protein that deposits a chemical tag called a methyl group onto the DNA base cytosine. The protein targets only those cytosine molecules that are followed by another base, called adenine, in a DNA sequence. This type of chemical modification, called ‘CA methylation,’ occurs primarily after birth in neurons and accumulates during the first 18 months of life, when neurons are forming connections with other cells, Gabel says.

The protein missing in Rett syndrome — a rare condition characterized by language deficits and repetitive behavior — typically binds to CA methylation sites. So Gabel and his team hypothesized that disrupting the activity of DNMT3A would affect the same cellular mechanisms as those involved in Rett syndrome.

Mice with mutations in DNMT3A show changes in gene expression that mirror those observed in mouse models of Rett syndrome, they found.

“Looking for shared underlying pathology is really important, so that we can start to think about therapeutic approaches that can ameliorate the effects of more than one neurodevelopmental condition,” Gabel says.

Methylation changes:

The researchers assessed the effects of nine DNMT3A mutations on DNA methylation in cultured neurons. All nine blocked methylation at CA sites. Mutations associated with intellectual disability had stronger effects than those associated with autism, they found.

The team then deleted one copy of DNMT3A from mice and found that the rodents were heavier and had longer bones, on average, than control mice. These physical features are similar to the overgrowth seen in people with Tatton-Brown Rahman syndrome.

The mice lacking DNMT3A also showed social deficits and other behaviors that resemble core autism traits: The mice spent less time than controls inspecting a new mouse or a new object, and as pups they squeaked less for their mothers than control mice did.

The mice’s neurons have nearly half the usual amount of CA methylation, the researchers found, especially at enhancers, portions of the genome that can regulate gene expression. As a result, several genes showed altered expression.

Many of these genes are also altered in mouse models of Rett syndrome, which suggests that some traits in people with DNMT3A mutations arise from cellular changes like those in people with Rett syndrome, Gabel says. The study was published in November in Cell Reports.

Convergent pathways:

The findings also suggest that CA methylation at enhancers is critical for brain development, and that mutations in DNMT3A contribute to neurodevelopmental conditions, says Magdalena Janecka, assistant professor of psychiatry at the Icahn School of Medicine at Mount Sinai in New York City, who was not involved in the work.

“But this is a study in mice, so it’s a very big leap to say that those mutations are definitely causative of the disease in humans,” Janecka says.

The convergence between mice with one working copy of DNMT3A and mouse models of Rett syndrome is “surprising,” says Annie Vogel Ciernia, assistant professor of biochemistry and molecular biology at the University of British Columbia in Vancouver, Canada, who was not involved in the study. Ciernia notes that mice with one working copy of DNMT3A don’t seem to have the severe motor deficits observed in Rett syndrome mice, perhaps because different types of neurons are affected. But, she adds, “it’s interesting how you can have overlap in the molecular mechanism that leads to very different phenotypic outputs.”

The challenge for researchers is to understand why different mutations can lead to similar features, says Zhaolan Zhou, professor of genetics at the University of Pennsylvania in Philadelphia, who was not involved with the study. Therapeutic applications are years away, Zhou adds, but finding shared features across different conditions could help scientists identify core mechanisms to target.

Next, Gabel and his team plan to assess whether other genes associated with autism affect the methylation at CA sites. They also intend to investigate how CA methylation regulates gene expression in the brain.

When Is the Best Time to Meditate for Better Sleep?

A sleep expert explains why meditating yourself to sleep doesn’t work.

Posted Jan 19, 2021

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If you struggle with insomnia, you’ve probably tried just about everything to fall asleep—including meditation. It seems like a reasonable solution, since meditation is known to lower stress, quiet the mind, and calm the nervous system. You might have even struggled to stay awake when practicing meditation during the day, so why not use this soporific at bedtime?  

Maybe you tried meditating in bed, but for some reason it didn’t work. Or maybe it seemed to help the first night, and you hoped against hope that you’d cured your sleep troubles. But it didn’t help the next night, and now it’s helpful only occasionally, like everything else you’ve tried.

Trying Too Hard

The problem with using meditation as a sleep aid comes down to one word: effort. “One of the biggest issues with insomnia is that people are trying really hard to sleep,” clinical psychologist Dr. Jason Ong told me recently on the Think Act Be podcast. Ong is an expert in treating sleep problems, and the creator of Mindfulness-Based Therapy for Insomnia.

In most areas of our lives, “we try harder to solve problems,” said Ong, which is usually a good thing. But that approach backfires when we’re struggling with insomnia. “Sleep is one thing that the harder you try, the worse it gets,” he told me. I know from personal experience that he’s right, having been through years of consistently poor sleep.

A big part of the problem, according to Ong, is that using more effort to fall asleep can lead to performance anxiety, as we see sleep as our final “task” for the day. If we’re trying to use meditation to knock ourselves out, we make it just another thing to do to ensure good sleep. But effort and doing are incompatible with sleep.

Setting Your Intention

So why do we often get sleepy when meditating during the day, but it doesn’t help us fall asleep at night? Ong points out that “the important thing isn’t what you do, but the intention. There may be times when you’re trying to practice a mindful meditation and you fall asleep,” he said, “but the intention should not be to use it for sleep.”

The same goes for activities we might do before bed, or if we get out of bed in the middle of the night because we can’t fall asleep. “You can read, you can watch TV, you can crochet,” said Ong. “But the idea is that you shouldn’t be doing something to try to fall asleep, or lull yourself to sleep. You’re just doing something for the sake of doing it.”

Rather than treating meditation as a self-administered sedative, we can use it as a way to practice mindful presence and acceptance, as we let go and do less. “We’re trained to want things on demand,” said Ong. “Mindfulness is different, and in some ways the opposite of that. It challenges us to step back from this need for something immediate.”article continues after advertisement

How Meditation Can Help

So how can meditation help with sleep? Ong described the mindful awareness that we practice through meditation as a “tool to help people let go of the grip” of trying harder to fall asleep. In his treatment approach, the focus is on “cultivating a sense of how to be mindful. That’s what the meditation practice is really about—it’s an opportunity to practice being mindful.”

Ong recommends starting with a quiet sitting meditation as the easiest place to start. A common practice is to close the eyes and focus the attention on the sensations of breathing. Each time the mind wanders, as you can be sure it will, gently bring the attention back to the breath. Subsequent practices can include things like walking meditation, yoga, and tai chi.

Daytime is also the best place to start practicing meditation, according to Ong, “not when you’re trying to sleep. Because the idea here is not that you’re trying to ‘meditate yourself to sleep’”—a misconception that he said is quite common. “After someone gets a sense of how to do this during their daytime meditation practices, then they can bring it into the nighttime.”

How to Practice

So when you get in bed tonight, let go of trying to sleep, and simply do… nothing. Sleep will come on its own, not because we willed it. When you notice you’re using effort to try to sleep, deliberately let go of any sense of responsibility for how long you’re awake, and just be in the moment. “When you get yourself into a calm and relaxed space,” Ong said, “then sleepiness is much more likely to emerge. And that’s what’s actually going to help you fall asleep.”article continues after advertisement

One final word: Meditation probably won’t be very effective for improving sleep if we’re doing other things that contribute to insomnia. Meditation and mindfulness are most helpful in the context of good sleep habits. Important ones include:

• Get up at a consistent time each day.
• Have a relaxing wind-down period for 30-60 minutes before bedtime.
• Don’t stay in bed for a lot longer than you’re able to sleep.
• Be careful not to nap too long or too late in the day.
• Avoid caffeine later in the day.
• Don’t use alcohol to fall asleep.
• Keep your bedroom cool, quiet, and dark.

A practice in mindful presence, along with these other practices, was one of the things that helped restore my own sleep. I hope you find it helpful as well.

The full interview with Dr. Jason Ong is available here: “The Most Important Principles for Good Sleep.”

References

Ong, J. (2016). Mindfulness-based therapy for insomnia. Washington, DC: American Psychological Association. 

Entangled electron pairs created using heat

19 Jan 2021

A new device that produces entangled pairs of electrons by the application of heat has been unveiled by international team of researchers led by Pertti Hakonen at Aalto University in Finland. The device works by splitting up Cooper pairs of electrons in a superconductor — and then collecting the entangled electrons. This ability to produce entangled, tuneable electrical signals could be an important step towards creating new electron-based quantum technologies and research applications.

Entanglement is a purely quantum-mechanical phenomenon that allows two or more particles, such as electrons, to have a much closer relationship than is predicted by classical physics. Once considered an exotic consequence of quantum physics, entanglement now has very practical applications in quantum computing and quantum sensing. As a result, physicists are very keen on developing new and better ways of creating entangled particles.

Temperature gradient

When a temperature gradient is applied across a conducting material, its electrons will diffuse from the hot side to the cold side, generating a voltage. Known as the Seebeck effect, this phenomenon is widely exploited in modern technologies, including thermoelectric power generators and temperature sensors.

A Cooper pair comprises two entangled electrons that are bound together within a superconductor. Because Cooper pairs are bosons, they can condense at very low temperatures and flow with zero electrical resistance. The interaction that binds the electrons is long range and therefore the electrons in Cooper pairs do not necessarily have to be very close together.

In their study, Hakonen’s team created a tiny section of aluminium superconductor that is sandwiched between two tiny graphene electrodes that functioned as quantum dots – these are semiconductors that behave like artificial atoms with electron energy levels that can be tuned separately.

Nonlocal Seebeck effect

When the researchers applied a temperature gradient across their device, Cooper pairs within the superconductor split up. Thanks to the nonlocal Seebeck effect, electrons could then leave the superconductor by tunnelling through different quantum dots – which is encouraged by setting different energy levels on the two quantum dots. These electrons can then be extracted from the device by separate metal electrodes, one connected to each quantum dot. Because the two electrons were quantum-mechanically entangled in a Cooper pair, they maintain this special relationship when separated.READ MOREGraphene quantum dots split Cooper pairs

By tuning the quantum dots, the team could vary relative contributions to the currents of electrons from Cooper pair splitting and another process called elastic co-tunnelling. This gave the team control over the two output signals of their device.

The new device could have a wealth of potential applications in electron-based quantum technologies. Furthermore, the tuneability of the device could soon facilitate fundamental tests of theoretical concepts in entanglement and thermodynamics.

The device is described in Nature Communications.

Superintelligent AI May Be Impossible to Control; That’s the Good News

Postcard from the 23rd century: Not even possible to know if an AI is superintelligent, much less stop it

By Charles Q. Choi

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It may be theoretically impossible for humans to control a superintelligent AI, a new study finds. Worse still, the research also quashes any hope for detecting such an unstoppable AI when it’s on the verge of being created. 

Slightly less grim is the timetable. By at least one estimate, many decades lie ahead before any such existential computational reckoning could be in the cards for humanity. 

Alongside news of AI besting humans at games such as chess, Go and Jeopardy have come fears that superintelligent machines smarter than the best human minds might one day run amok. “The question about whether superintelligence could be controlled if created is quite old,” says study lead author Manuel Alfonseca, a computer scientist at the Autonomous University of Madrid. “It goes back at least to Asimov’s First Law of Robotics, in the 1940s.”

The Three Laws of Robotics, first introduced in Isaac Asimov’s 1942 short story “Runaround,” are as follows:

1. A robot may not injure a human being or, through inaction, allow a human being to come to harm.
2. A robot must obey the orders given it by human beings except where such orders would conflict with the First Law.
3. A robot must protect its own existence as long as such protection does not conflict with the First or Second Laws.

In 2014, philosopher Nick Bostrom, director of the Future of Humanity Institute at the University of Oxford, not only explored ways in which a superintelligent AI could destroy us but also investigated potential control strategies for such a machine—and the reasons they might not work.

Bostrom outlined two possible types of solutions of this “control problem.” One is to control what the AI can do, such as keeping it from connecting to the Internet, and the other is to control what it wants to do, such as teaching it rules and values so it would act in the best interests of humanity. The problem with the former is that Bostrom thought a supersmart machine could probably break free from any bonds we could make. With the latter, he essentially feared that humans might not be smart enough to train a superintelligent AI.

Now Alfonseca and his colleagues suggest it may be impossible to control a superintelligent AI, due to fundamental limits inherent to computing itself. They detailed their findings this month in the Journal of Artificial Intelligence Research.

The researchers suggested that any algorithm that sought to ensure a superintelligent AI cannot harm people had to first simulate the machine’s behavior to predict the potential consequences of its actions. This containment algorithm then would need to halt the supersmart machine if it might indeed do harm.

However, the scientists said it was impossible for any containment algorithm to simulate the AI’s behavior and predict with absolute certainty whether its actions might lead to harm. The algorithm could fail to correctly simulate the AI’s behavior or accurately predict the consequences of the AI’s actions and not recognize such failures.

“Asimov’s first law of robotics has been proved to be incomputable,” Alfonseca says, “and therefore unfeasible.” 

We may not even know if we have created a superintelligent machine, the researchers say. This is a consequence of Rice’s theorem, which essentially states that one cannot in general figure anything out about what a computer program might output just by looking at the program, Alfonseca explains.

On the other hand, there’s no need to spruce up the guest room for our future robot overlords quite yet. Three important caveats to the research still leave plenty of uncertainty to the group’s predictions. 

First, Alfonseca estimates AI’s moment of truth remains, he says, “At least two centuries in the future.” 

Second, he says researchers do not know if so-called artificial general intelligence, also known as strong AI, is theoretically even feasible. “That is, a machine as intelligent as we are in an ample variety of fields,” Alfonseca explains.

Last, Alfonseca says, “We have not proved that superintelligences can never be controlled—only that they can’t always be controlled.”

Although it may not be possible to control a superintelligent artificial general intelligence, it should be possible to control a superintelligent narrow AI—one specialized for certain functions instead of being capable of a broad range of tasks like humans. “We already have superintelligences of this type,” Alfonseca says. “For instance, we have machines that can compute mathematics much faster than we can. This is [narrow] superintelligence, isn’t it?”

HOW RIVIAN IS OFFERING SOMETHING TESLA CYBERTRUCK CANNOT

The all-electric Tesla Cybertruck is not for everyone, and Rivian may be able to capitalize.MIKE BROWN12 HOURS AGO

THE TESLA CYBERTRUCK IS PERHAPS the firm’s most striking design — for better or for worse.

“It just screams ‘obnoxious guy truck,’” Rebecca Puck Stair, an Alberquerque-based movie location scout, told the New York Times in a story this week. The Cybertruck was first revealed in November 2019 with a late 2021 release date. Around a year ago, Stair heard about the electric automaker Rivian, and instead put a deposit down for its upcoming R1S SUV.

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Stair represents a segment of the market that is taking a chance on the relative newcomer. While Tesla’s angular Cybertruck has attracted widespread media attention, Rivian, led by CEO RJ Scaringe, is opting for a more approach that’s more reserved in comparison. The R1S and R1T truck will roll out of its Normal, Illinois factory this summer with an equally normal design.

The two cars represent Rivian’s big jump into the consumer electric car market:

• The R1S starts at $70,000 and uses a quad-motor arrangement, offers a towing capacity of up to 7,700 pounds, can go from 0 to 60 mph in three seconds, and has a wading depth of three feet. It can travel over 300 miles per charge with the premium battery option, over 250 miles on the entry-level pack. The Tesla Model X SUV, by comparison, starts at $78,490 with 371 miles of range.
• The R1T starts at $67,500 with similar specs to the R1S. The main differences are a towing capacity of up to 11,000 pounds, and an option for a battery pack with over 400 miles of range.

Tesla’s closest competitor, the Cybertruck, starts at $39,900 for a single-motor truck. A tri-motor Cybertruck starts at $69,900. The entry-level model has a battery range of over 250 miles, a towing capacity of over 7,500 pounds, and acceleration times of under 6.5 seconds. For the tri-motor model, it has a range of over 500 miles, a towing capacity of over 14,000 pounds, and acceleration times of under 2.9 seconds.

RIVIAN IS FOCUSING ITS MARKETING EFFORTS on fans of the outdoors. The firm is placing electric car chargers in less traditional locations, like near hiking trails. Scaringe told TechCrunch in December 2020 that the strategy means drivers can decide “if you want to stop midway through the trip for a one-mile, two-mile or five-mile hike.”

MORE MONEY — Investors are taking note. On Tuesday, the firm announced it had raised $2.65 billion from its latest fundraising round, valuing the company at $27 billion and bringing total investments to $8 billion.

For comparison, Tesla was worth $27 billion as recently as December 2016. At the time of writing it’s worth $800 billion.

BACK TO CYBERTRUCK — Musk has claimed before that the Cybertruck is angular for a reason. Its body is made from cold-rolled 30X steel, which essentially acts as the car’s exoskeleton. The material can’t be stamped with regular tools, Musk said days after the reveal, “because it breaks the stamping press.”

It’s possible that Tesla could respond if the Cybertruck’s design proves too divisive. In August 2020, Musk said in an interview that “our fallback strategy” is that “we could just do some copycat truck.” He also said that “if it turns out nobody wants to buy a weird-looking truck, we’ll build a normal truck, no problem.”

THE INVERSE ANALYSIS — Rivian could find a receptive audience of electric car buyers turned off by the divisive Cybertruck.

Scaringe has been keen to avoid comparisons with Tesla before, telling Inverse in March 2019 that “Tesla’s not who we’re taking volume from…we’re taking volume from all the non-electric vehicles.”

Make no mistake, though: both companies want to convert more gas car drivers to EVs. Musk’s goal at Tesla is to produce 20 million cars per year by 2030. Factories in Shanghai and Berlin will produce entry-level Model 3 and Y cars to reach more consumers than ever.

Beyond Rivian’s first two electric cars, the firm also plans electric delivery trucks for Amazon. Scaringe then plans to reach markets like Europe and China with smaller vehicles that use their predecessors’ components — a plan that bears striking similarities to Tesla.

In this emerging race to attract more buyers, the main beneficiary could end out being the consumer.

Synthetic cornea helped a legally blind man regain his sight

CorNeat’s artificial cornea integrates with the eye wall with no donor tissue needed.

S. Dent|01.19.21@stevetdent

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A legally blind 78-year old man has regained his sight after being the inaugural patient to receive a promising new type of corneal implant, Israel Hayom has reported. Developed by a company called CorNeat, the KPro is the first implant that can be integrated directly into the eye wall to replace scarred or deformed corneas with no donor tissue. Immediately after the surgery, the patient was able to recognize family members and read numbers on an eye chart.

The corona is the clear layer that covers and protects the front portion of the eye. It can degenerate or scar for various reasons, including diseases like pseudophakic bullous keratopathy, kerotoconus and trauma.

Artificial cornea implants already exist for patients with corneal degeneration, but because the surgeries are complex, they’re usually a last resort when transplants or cornea ring implants don’t work. By contrast, inserting the CorNeat transplant is a relatively simple procedure that requires minimal stitches and cutting. On top of that, it uses a biomimetic material that “stimulates cellular proliferation, leading to progressive tissue integration,” according to CorNeat.https://www.youtube.com/embed/-sNW3F933v8

A very cool animation (above) shows exactly how this works, with the end result that the device is fully transplanted inside the eye wall. “Fibroblasts and collagen gradually colonize the integrating skirt and full integration is achieved within weeks, permanently embedding the device within the patient’s eye,” according to CorNeat. That allows for improved visual acuity and “exceptionally fast healing times,” and it looks fairly natural, to boot.

The company said that ten more patients are approved for trials in Israel. It plans to open two more this month in Canada, with six others in the approval process in France, the US and the Netherlands. While the implant doesn’t contain any electronics, it could help more people than any robotic eye. “After years of hard work, seeing a colleague implant the CorNeat KPro with ease and witnessing a fellow human being regain his sight the following day was electrifying and emotionally moving, there were a lot of tears in the room,” said CorNeat Vision co-founder Dr. Gilad Litvin.

Should you wake a sleepwalker? And other sleepwalking FAQs answered

Experts explain sleepwalking and the strange behaviors of nocturnal wanderers

Amanda CaprittoJan. 20, 2021 5:00 a.m. PT

LISTEN- 07:10

Maybe you’ve seen someone do it. Maybe you’ve done it yourself. Maybe you’ve only seen videos of people doing it and you don’t really understand what’s going on. “It” is sleepwalking and, boy, is it a strange thing to find someone doing. 

If you’ve ever encountered a sleepwalker in person, you likely felt spooked or weirded out. Sleepwalkers often exhibit glassy, glazed eyes staring into nothing (although it feels like they are staring into your soul). 

Read more: Best mattress for 2021: Casper, Nectar, Purple and more

They do strange things, like brush their teeth or make a sandwich at 3 a.m. Sometimes, they do dangerous things, like attempt to drive a car or walk outside alone in the dark. Sleepwalkers can exhibit funny, silly behaviors or scary, aggressive behaviors. 

It’s a phenomenon so well-known, and yet, so mysterious. Everyone knows that sleepwalking happens, but not everyone knows why — or how. With the help of several sleep experts and doctors, we answer your burning questions about sleepwalking.

What is sleepwalking?

Medically termed somnambulism, sleepwalking is literally the act of walking or performing other physical activities while asleep. Sleepwalking usually occurs when a person in a deep stage of sleep is woken up partially or in a manner that triggers physical activity, says Wayne Leslie Ross, senior sleep researcher at InsideBedroom.

Dr. Abhinav Singh, facility director of the Indiana Sleep Center and medical review expert for SleepFoundation.org, explains that a “switch” flips in response to a stimulus. “Any stimulus that wakes you in the middle of the night, such as a dog barking or your spouse snoring, causes your brain to keep trying to flip the switch from wake to sleep,” he says. 

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“This switch is a little sloppier for certain folks,” which can result in the limbo of half-awakeness, Dr. Singh explains. Essentially, some of your brain wakes up and some of it doesn’t.

Why do people sleepwalk? 

“There is still much we do not know when it comes to why it happens and what goes on in the brain when it occurs,” says Frida Rångtel, PHD, sleep educator and science advisor at Sleep Cycle. 

Because sleepwalking is related to a defect in the switch from sleep to wakefulness, “this means that deep sleep, combined with the risk of arousal, such as during sleep apnea, [creates a]  higher risk of sleepwalking,” Rångtel explains.

People sleepwalk for a number of reasons, genetics being a primary cause. It’s also more common in children, but most children grow out of it. Although the exact causes of sleepwalking are unknown, Rångtel says medical professionals have concluded that the following can trigger sleepwalking or make an existing problem worse:

• Sleep deprivation
• Medical conditions that cause nighttime wake-ups, such as sleep apnea and gastroesophageal reflux disease (GERD)
• Alcohol use 
• Recreational drugs
• Prescription medications 
• Fever
• Stress or anxiety 
• Brain injuries
• Sleeping in new or unfamiliar environments (for example, hotels or overnight camps)

Is sleepwalking a problem?

According to the Mayo Clinic, isolated incidents of sleepwalking don’t usually indicate a problem. Children may exhibit recurrent sleepwalking, but they typically grow out of it by their teen years, the Mayo Clinic reports. Recurrent sleepwalking in adults may signal an underlying sleep, medical or psychological disorder, though. 

Is it really dangerous to wake a sleepwalker?

Because no one can anticipate how a sleepwalker will react when roused, it’s best to avoid waking a sleepwalker if possible, Ross says. “Experts continue to discourage attempts to wake a sleepwalking person, as it would be at most times unsuccessful and leave the person shocked, disoriented and confused,” he says.

Getting too close, touching or interrupting a sleepwalker may result in an exaggerated reaction which, in some sleepwalkers, may include aggression. Ross says the best course of action is to gently lead the sleepwalker back to bed without waking them, if possible. 

In the case that the sleepwalker is doing something dangerous (such as attempting to drive a car), waking the sleepwalker might be necessary. 

Can people see when they sleepwalk?

Yes and no. “Often, a sleepwalker will have a blank gaze with open glassy eyes,” says Dr. Dave Rabin, neuroscientist and board-certified psychiatrist. “While their eyes may be open, they’re not necessarily seeing what they would see if they were awake. They may think they’re in a different room or part of the house.”

This is why sleepwalkers often bump into things, trip or fall, Dr. Singh says — and also why it’s important to keep sleepwalkers away from cars, stairs, bodies of water and other potentially dangerous areas.

Why do sleepwalkers do such weird things?

Dr. Alex Dimitriu, psychiatrist and sleep medicine doctor at Menlo Park Psychiatry and Sleep Medicine, says sleepwalking is an example of a “disorder of confusional arousal.” 

“People do weird things at night when they are half awake and half asleep,” he says. “You are confused, because you are half asleep. I compare it to your bed partner poking you in the side every two minutes — you might eventually wake up and say something thoughtless, half asleep. Sleepwalking is not much different.” 

Online, amusing videos of sleepwalkers circulate, showing them engaging in odd behaviors. Common sleepwalking behaviors include: 

• Cooking and eating, especially strange food combinations that one wouldn’t necessarily eat while fully awake
• Starting one’s usual morning routine, including getting dressed and brushing their teeth
• Bolting from bed or the house 
• Talking, shouting or singing at other people, pets, inanimate objects or nothing at all
• Moving furniture around

Dr. Dawn Dore-Stites, sleep advisor to Reverie and sleep disorders specialist at Michigan Medicine Pediatric Sleep Medicine Clinic, explains that sleepwalkers probably do these things because they’re in a body-first state. 

“The body is on but the brain is not, leading to a body moving around and engaging in easy behaviors like urinating and eating,” she says, “but that a fully awake brain would not do, like urinating in non-bathroom spaces and eating non-food items.”

How long does sleepwalking last? 

Sleepwalkers only amble for a very short time, from just a few seconds up to a half hour, Dr. Singh says. According to the US National Library of Medicine, most sleepwalking episodes last less than 10 minutes.

Do people remember sleepwalking?

Sleepwalking typically occurs during deep, non-REM sleep, so it’s thought that most sleepwalkers don’t recall their nighttime saunters. 

However, a study published in 2013 found that some sleepwalkers do remember what they did — and, more interestingly, why they did it. The authors of the study believe some people remember their actions and motivation because different parts of the brain fall asleep while others remain awake. 

Is it possible to stop sleepwalking?

Yes, it is possible to treat sleepwalking, experts agree. Much of treatment involves interventions, such as “anticipated awakening,” Dr. Dore-Stites says. Anticipated awakening involves waking up a sleepwalker just before they’re about to start sleepwalking — clearly, this will only work for people who recurrently sleepwalk around the same time each night. 

To do it, gently wake the person and have them sit up, take a sip of water or do something else to achieve full awakeness. This can reset the sleep cycle and prevent sleepwalking, Dr. Dore-Stites says.

In many cases, sleepwalking is a symptom of an underlying condition, so treatment involves pinpointing and treating the cause. Improving sleep hygiene and habits can help, too. Sleepwalking is less likely to happen when fewer triggers exist — make sure the room is cool, dark, quiet and comfortable to reduce the chances of partially waking up. 

Lastly, practicing relaxation techniques before bed (or at any regular interval) can help. Try deep breathing, meditation, journaling or another calming activity to reduce stress and anxiety before going to sleep. 

The information contained in this article is for educational and informational purposes only and is not intended as health or medical advice. Always consult a physician or other qualified health provider regarding any questions you may have about a medical condition or health objectives.

Chinese scientists develop gene therapy which could delay aging

Author of the article:ReutersMartin Quin PollardPublishing date:Jan 20, 2021  •  19 hours ago  •  2 minute read

BEIJING — Scientists in Beijing have developed a new gene therapy which can reverse some of the effects of aging in mice and extend their lifespans, findings which may one day contribute to similar treatment for humans.

The method, detailed in a paper in the Science Translational Medicine journal earlier this month, involves inactivating a gene called kat7 which the scientists found to be a key contributor to cellular aging.https

The specific therapy they used and the results were a world first, said co-supervisor of the project Professor Qu Jing, 40, a specialist in aging and regenerative medicine from the Institute of Zoology at the Chinese Academy of Sciences (CAS).

“These mice show after 6-8 months overall improved appearance and grip strength and most importantly they have extended lifespan for about 25%,” Qu said.

The team of biologists from different CAS departments used the CRISPR/Cas9 method to screen thousands of genes for those which were particularly strong drivers of cellular senescence, the term used to describe cellular aging.

They identified 100 genes out of around 10,000, and kat7 was the most efficient at contributing to senescence in cells, Qu said.

Kat7 is one of tens of thousands of genes found in the cells of mammals. The researchers inactivated it in the livers of the mice using a method called a lentiviral vector.

“We just tested the function of the gene in different kinds of cell types, in the human stem cell, the mesenchymal progenitor cells, in the human liver cell and the mouse liver cell and for all of these cells we didn’t see any detectable cellular toxicity. And for the mice, we also didn’t see any side effect yet.”

Despite this, the method is a long way from being ready for human trials, Qu said.

“It’s still definitely necessary to test the function of kat7 in other cell types of humans and other organs of mice and in the other pre-clinical animals before we use the strategy for human aging or other health conditions,” she said.

Qu said she hopes to be able to test the method on primates next, but it would require a lot of funding and much more research first.

“In the end, we hope that we can find a way to delay aging even by a very minor percentage…in the future.”

Natural CRISPR’s Safety Feature Could Become Genetic Dimmer Switch

January 19, 20210

Source: Juan Gaertner/Science Photo Library/Getty Images Share

The CRISPR systems inside bacteria serve as adaptive immune systems, but they also threaten to unleash autoimmune reactions. Fortunately, for bacteria such as Streptococcus pyogenes, these systems have a built-in safety feature: a long-form transactivating CRISPR RNA (tracrRNA). Unlike the short-form tracrRNA, which together with CRISPR RNA (crRNA) complexes with the CRISPR-Cas9 enzyme and guides it to DNA sites where it executes cuts, the long-form tracrRNA guides the enzyme to the enzyme’s own genetic promoter.

The short-form tracrRNA that complexes CRISPR-Cas9 enzyme doesn’t need to bind to crRNA, and it doesn’t cut. Instead, it merely lingers in place, preventing gene expression.

Essentially, long-form tracrRNA acts as a safety feature, dialing down a bacterium’s immune system to prevent it from attacking the bacterium itself rather than foreign DNA. This self-protection function for long-form tracrRNA was uncovered by researchers at Johns Hopkins University. The researchers, led by Joshua W. Modell, PhD, also explored whether long-form tracrRNA could be reprogrammed to guide CRISPR-Cas9 to DNA sites other than the CRISPR-Cas9 promoter.

The researchers’ findings appeared in the journal Cell, in an article titled, “A natural single-guide RNA repurposes Cas9 to autoregulate CRISPR-Cas expression.” According to the researchers, long-form tracrRNA could serve as a programmable genetic dimmer switch, one that could be used to inhibit the expression of designated genes in research applications.

“We show that in the S. pyogenes CRISPR-Cas system, a long-form transactivating CRISPR RNA folds into a natural single guide that directs Cas9 to transcriptionally repress its own promoter (P_cas),” the article’s authors wrote. “Further, we demonstrate that P_cas serves as a critical regulatory node.”

Scientists have long worked to unravel the precise steps of CRISPR-Cas9’s mechanism and how its activity in bacteria is dialed up or down. Looking for genes that ignite or inhibit the CRISPR-Cas9 gene-cutting system for the common, strep-throat causing bacterium S. pyogenes, the Johns Hopkins scientists found a clue regarding how that aspect of the system works.

Specifically, the scientists found a gene in the CRISPR-Cas9 system that, when deactivated, led to a dramatic increase in the activity of the system in bacteria. The product of this gene appeared to re-program Cas9 to act as a brake, rather than as a “scissor,” to dial down the CRISPR system.

“From an immunity perspective, bacteria need to ramp up CRISPR-Cas9 activity to identify and rid the cell of threats, but they also need to dial it down to avoid autoimmunity—when the immune system mistakenly attacks components of the bacteria themselves,” said graduate student Rachael Workman, a bacteriologist working in Modell’s laboratory.

To further nail down the particulars of the “brake,” the team’s next step was to better understand the product of the deactivated gene, a tracrRNA. tracrRNAs belong to a unique family of RNAs that do not make proteins. Instead, they act as a kind of scaffold that allows the Cas9 enzyme to carry the guide RNA that contains a “mug shot” of previously encountered phage DNA. The mug shot allows Cas9 to cut matching DNA sequences in newly invading viruses.

tracrRNA comes in two sizes: long and short. Most of the modern gene-cutting CRISPR-Cas9 tools use the short form. However, the research team found that the deactivated gene product was the long-form of tracrRNA, the function of which has been entirely unknown.

The long and short forms of tracrRNA are similar in structure and have in common the ability to bind to Cas9. The short-form tracrRNA also binds to the guide RNA. However, the long-form tracrRNA doesn’t need to bind to the crRNA, because it contains a segment that mimics the crRNA. Essentially, long-form tracrRNAs have combined the function of the short-form tracrRNA and crRNA, explained Modell, assistant professor of molecular biology and genetics at the Johns Hopkins University School of Medicine.

The researchers used genetic engineering to alter the length of a certain region in long-form tracrRNA to make the tracrRNA appear more like a guide RNA. They found that with the altered long-form tracrRNA, Cas9 once again behaved more like a scissor.

Other experiments showed that in lab-grown bacteria with a plentiful amount of long-form tracrRNA, levels of all CRISPR-related genes were very low. When the long-form tracrRNA was removed from bacteria, however, expression of CRISPR-Cas9 genes increased a hundredfold.

Bacterial cells lacking the long-form tracrRNA were cultured in the laboratory for three days and compared with similarly cultured cells containing the long-form tracrRNA. By the end of the experiment, bacteria without the long-form tracrRNA had completely died off. “De-repression causes a dramatic 3,000-fold increase in immunization rates against viruses,” the article’s authors noted. “However, heightened immunity comes at the cost of increased autoimmune toxicity.”

These findings suggest that long-form tracrRNA normally protects cells from the sickness and death that happen when CRISPR-Cas9 activity is very high. “We started to get the idea that the long form was repressing but not eliminating its own CRISPR-related activity,” recalled Workman.

To see if the long-form tracrRNA could be re-programmed to repress other bacterial genes, the research team altered the long-form tracrRNA’s spacer region to let it sit on a gene that produces green fluorescence. Bacteria with this mutated version of long-form tracrRNA glowed less green than bacteria containing the normal long-form tracrRNA, suggesting that the long-form tracrRNA can be genetically engineered to dial down other bacterial genes.

Another research team, from Emory University, found that in the parasitic bacteria Francisella novicida, Cas9 behaves as a dimmer switch for a gene outside the CRISPR-Cas9 region. The CRISPR-Cas9 system in the Johns Hopkins study is more widely used by scientists as a gene-cutting tool, and the Johns Hopkins team’s findings provide evidence that the dimmer action controls the CRISPR-Cas9 system in addition to other genes.

“Using bioinformatic analyses, we provide evidence that tracrRNA-mediated autoregulation is widespread in type II-A CRISPR-Cas systems,” the Johns Hopkins scientists added. “Collectively, we unveil a new paradigm for the intrinsic regulation of CRISPR-Cas systems by natural single guides, which may facilitate the frequent horizontal transfer of these systems into new hosts that have not yet evolved their own regulatory strategies.”

The researchers also found the genetic components of long-form tracrRNA in about 40% of the Streptococcus group of bacteria. Further study of bacterial strains that don’t have the long-form tracrRNA, said Workman, will potentially reveal whether their CRISPR-Cas9 systems are intact, and other ways that bacteria may dial back the CRISPR-Cas9 system.

The dimmer capability that the experiments uncovered offers opportunities to design new or better CRISPR-Cas9 tools aimed at regulating gene activity for research purposes. “In a gene editing scenario,” Modell suggested, “a researcher may want to cut a specific gene, in addition to using the long-form tracrRNA to inhibit gene activity.”