DECEMBER 30, 2021

New neural network for more accurate DNA editing

by Skolkovo Institute of Science and Technology

New neural network for more accurate DNA editing
The UML (Unified Modeling Language) sequence diagram of a single input use case for the GuideHOM architecture. First, the user supplies the model with an input through the Dataset object. The Dataset object supplies the preselected preprocessing module with one-hot encoded sequence or pair. Either of the preprocessing modules supplies the HOM capsule layer with the preprocessing output. The HOM capsule layer computes coordinates of gRNA/gRNA pairs in the guide space, then, sends the coordinates to the Gaussian Process. The Gaussian Process samples activities from the approximate distribution it has learnt, computes the mean and variance, then, sends the outputs back to the user. Credit: DOI: 10.1093/nar/gkab1065

Russian bioinformaticians have proposed a new neural network architecture capable of evaluating how well a guide RNA has been chosen for a gene editing experiment. Their approach will facilitate more efficient DNA modification with the popular CRISPR/Cas method and therefore will help develop new strategies for creating genetically modified organisms and find ways of treating grave hereditary disorders. The study, supported by a Russian Science Foundation grant, was published in the Nucleic Acids Research journal.

Genomic editing, and the CRISPR/Cas method in particular, is widely used in various areas of experimental biology, as well as in agriculture and biotechnology.

CRISPR/Cas is one of the many weapons bacteria use to combat viruses. As infection occurs, the pathogen’s DNA penetrates the cell, and since its sequences differ from those of the bacterium, Cas proteins recognize it as foreign hereditary material and cleave it. For the bacterium to respond to the virus faster, the cell stores fragments of the pathogen’s DNA—much like a computer antivirus keeps a collection of viral signatures—and passes them on to next generations so that its Cas could thwart further attacks.

In 2011–2013, teams from different laboratories (Jennifer Doudna, Emmanuelle Charpentier, and Feng Zhang in the United States, and Virginijus Šikšnys in Lithuania) independently of one another adapted the CRISPR/Cas system to the task of introducing arbitrary changes into DNA sequences in human and animal cells, making genomic editing much easier and more efficient. The system’s core elements are guide RNA, which “marks the spot,” and the Cas9 protein, which cleaves DNA at that position. The cell then “mends the wound” but the changes to the genetic code have already been made.

The problem is that guide RNA targeting is not always precise and may mislead Cas9. Transforming the CRISPR/Cas technology into a practical high-precision tool is highly important, especially when it comes to medical interventions.

Skoltech researchers led by Konstantin Severinov have used deep learning, Gaussian processes, and other methods to make the selection of optimal guide RNAs more accurate. The team produced a set of neural networks, that is, trainable mathematical models implemented as sequential multiplication of matrices—large arrays of numbers with complex internal structure. A neural network is able to learn because it has “memory” in the form of numbers that are altered in a particular way every time the system completes a calculation in the training mode. The team trained the models on different datasets containing tens of thousands of experimentally validated guide RNAs that had displayed high-accuracy performance in human and animal cells.

The researchers proposed an algorithm that estimates the probability of DNA cleavage for a given guide RNA. The resulting scores can direct experimental design for any CRISPR/Cas-based application. The team used its neural networks to come up with a set of guide RNAs for making precise changes to the genes of the 22nd human chromosome. This has been possible thanks to the high accuracy of cleavage frequency prediction and a prediction uncertainty estimation feature, which none of the previously existing methods provided.

“Our findings can be used for a variety of CRISPR/Cas-based technology applications, such as genetic disorder treatment, farming technologies, and basic research experiments,” commented Skoltech Ph.D. student Bogdan Kirillov, one of the creators of the new method and the first author of the study.

Explore furtherNew findings on the link between CRISPR gene-editing and mutated cancer cells

More information: Bogdan Kirillov et al, Uncertainty-aware and interpretable evaluation of Cas9–gRNA and Cas12a–gRNA specificity for fully matched and partially mismatched targets with Deep Kernel Learning, Nucleic Acids Research (2021). DOI: 10.1093/nar/gkab1065Journal information:Nucleic Acids ResearchProvided by Skolkovo Institute of Science and Technology

Can Elon Musk and Tesla really build a humanoid robot in 2022?

The car company’s expertise in AI could help it design a working prototype, but delivering a reliable product on schedule will be challengingTECHNOLOGY 30 December 2021

By Matthew Sparkes

New Scientist Default Image
An image of the Optimus robot released by TeslaTesla

In August 2021, Elon Musk announced that Tesla would build a humanoid robot designed to “eliminate dangerous, repetitive, boring tasks” and respond to voice commands, promising to show off a prototype in 2022. Can the company deliver on Musk’s goal?

Tesla has achieved a great deal since Musk founded the electric car firm in 2003: building a valuation of $1 trillion, selling in excess of half a million cars and installing a global network of more than 2000 charging stations for them. But there have also been failures and delays.

Musk promised to have a million self-driving taxis on the road by 2020. He has long touted the imminent arrival of full autonomy for his cars; scheduled a Tesla lorry for production in 2020 and a Cybertruck soon after in 2021. All of those deadlines have been or are due to be missed. Musk himself has admitted that he lacks punctuality but insists that most of his predictions come to pass eventually.

The robot, referred to as Optimus inside the company, will be 173 centimetres tall and weigh 57 kilograms, and it will be able to carry a cargo of up to 20 kilograms, according to Musk’s presentation in August.

He said much of the technology in Tesla’s self-driving cars is applicable to humanoid robots and should give them a head start. “Tesla is arguably the world’s biggest robotics company because our cars are like semi-sentient robots on wheels,” he said. “It kind of makes sense to put that onto a humanoid form.”

Read more: What’s next now Tesla is worth a trillion dollars?

Tetsuya Ogata at Waseda University in Tokyo, Japan, believes that engineering of the robot must be progressing well, or the company wouldn’t make such bold claims. But he expects that it will not only run into AI problems, where Tesla certainly has a lot of experience, but hardware problems, where it doesn’t, because humanoid robots are much more complex than cars.

“It’s very difficult to develop robot hands that can perform the same tasks as a human,” he says. “How to reproduce senses that allow tactile feedback is also a big problem.”

Zhongyu Li at the University of California, Berkeley, says he admires the vision, but thinks the deadline is “very ambitious”. He expects Tesla to hit its target of demonstrating a prototype of some kind, but perhaps encounter problems bringing it to market.

“Getting a prototype to walk for some short demos is not that challenging for their clever engineers, but getting humanoid robots to reliably operate in daily life is another story. It needs reliable hardware, a robust control algorithm that can prevent the robot falling, recover from a fall, and detect and avoid obstacles, and these may take years,” he says.

Others believe that the technology is possible, but not in the slender form that Musk promises. Florian Richter at the University of California, San Diego, points to the Atlas robot from Boston Dynamics which can run, jump and perform a range of tasks, but which also has a bulky body and a large backpack-style battery pack.

“They have a lot of work to do. I think their goal of a hardware prototype within a year is totally feasible, but with probably half of their desired power and some sort of weight compromise,” says Richter. “They also should be able to get it walking around on flat surfaces pretty quickly, but other human-level tasks like grasping will take a few years of research and a lot of innovation.”

Neither Tesla nor Elon Musk responded to a request for interview.

Read more:

Keeping the Aging Brain Connected With Words and Music

FeaturedNeuroscience·December 29, 2021

Summary: Learning a new language or playing a musical instrument has a positive impact on cognitive function in the aging brain, researchers report.

Source: Duke University

In an era of seemingly endless panaceas for age-based mental decline, navigating through the clutter can be a considerable challenge.

However, a team of Duke researchers, led by cognitive neuroscientist Edna Andrews, PhD, think they may have found a robust and long-term solution to countering this decline and preventing pathologies in an aging brain.

Their approach does not require an invasive procedure or some pharmacological intervention, just a good ear, some sheet music, and maybe an instrument or two.

In early 2021, Andrews and her team published one of the first studies to look at musicianship’s impact in building cognitive brain reserve. Cognitive brain reserve, simply put, is a way to qualify the resilience of the brain in the face of various pathologies. High levels of cognitive reserve can help stave off dementia, Parkinson’s disease or multiple sclerosis for years on end.

These levels are quantified through structural measurements of gray matter and white matter in the brain. The white matter may be thought of as the insulated wiring that helps different areas of the brain communicate.

In this particular study, Andrews’ team focused on measurements of white matter integrity through an advanced MRI technique known as diffusion tensor imaging, to see what shape it is in.

Previous neuroimaging studies have revealed that normal aging leads to a decrease in white matter integrity across the brain. Over the past fifteen years, however, researchers have found that complex sensory-motor activities may be able to slow down and even reverse the loss of white matter integrity. The two most robust examples of complex sensory-motor activities are multilingualism and musicianship.

Andrews has long been fascinated by the brain and languages. In 2014, she published one of the seminal texts in the field of cognitive neurolinguistics where she laid the groundwork for a new neuroscience model of language. Around the same time, she published the first and to-date only longitudinal fMRI study of second language acquisition. Her findings, built upon decades of research in cognitive neuroscience and linguistics, served as the foundation for her popular FOCUS course: Neuroscience/Human Language.

In more recent years, she has shifted her research focus to understanding the impact of musicianship on cognitive brain reserve. Invigorated by her lived experience as a professional musician and composer, she wanted to see whether lifelong musicianship could increase white matter integrity as one ages. She and her team hypothesized that musicianship would increase white matter integrity in certain fiber tracts related to the act of music-making

To accomplish this goal, she and her team scanned the brains of eight different musicians ranging in age from 20 years to 67 years old. These musicians dedicated an average of three hours per day to practice and had gained years’ worth of performance experience. After participants were placed into the MRI machine, the researchers used diffusion tensor imaging to calculate fractional antisotropy (FA) values for certain white matter fiber tracts.

This shows the white matter fiber tracts in the subcortical area of the brain
Relative location of subcortical white matter fiber tracts (lateral view). Image adapted from Duke University.

A higher FA value meant higher integrity and, consequently, higher cognitive brain reserve. Andrews and her team chose to observe FA values in two fiber tracts, the superior longitudinal fasciculus (SLF) and the uncinate fasciculus (UF), based on their relevance to musicianship in previous studies.

Previous studies of the two fiber tracts in non-musicians found that their integrity decreased with age. In other words, the older the participants, the lower their white matter integrity in these regions. After analyzing the anisotropy values via linear regression, they observed a clear positive correlation between age and fractional anisotropy in both fiber tracts. These trends were visible in both tracts of both the left and right hemispheres of the brain. Such an observation substantiated their hypothesis, suggesting that highly proficient musicianship can increase cognitive brain reserve as one ages.

These findings expand the existing literature of lifestyle changes that can improve brain health beyond diet and exercise. Though more demanding, neurological changes resulting from the acquisition and maintenance of language and music capabilities have the potential to endure longer into the life cycle.

Andrews is one of the strongest advocates of lifelong learning, not solely for the satisfaction it brings about, but also for the tangible impact it can have on cognitive brain reserve. Picking up a new language or a new instrument should not be pursuits confined to the young child.

It appears, then, that the kindest way to treat the brain is to throw something new at it. A little bit of practice couldn’t hurt either.

About this brain aging research news

Author: Vibhav Nandagiri
Source: Duke University
Contact: Vibhav Nandagiri – Duke University
Image: The image is adapted from Duke University

Original Research: Open access.
Effects of Lifelong Musicianship on White Matter Integrity and Cognitive Brain Reserve” by Edna Andrews et al. Brain Sciences

AbstractSee also

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Effects of Lifelong Musicianship on White Matter Integrity and Cognitive Brain Reserve

There is a significant body of research that has identified specific, high-end cognitive demand activities and lifestyles that may play a role in building cognitive brain reserve, including volume changes in gray matter and white matter, increased structural connectivity, and enhanced categorical perception.

While normal aging produces trends of decreasing white matter (WM) integrity, research on cognitive brain reserve suggests that complex sensory–motor activities across the life span may slow down or reverse these trends.

Previous research has focused on structural and functional changes to the human brain caused by training and experience in both linguistic (especially bilingualism) and musical domains. The current research uses diffusion tensor imaging to examine the integrity of subcortical white matter fiber tracts in lifelong musicians.

Our analysis, using Tortoise and ICBM-81, reveals higher fractional anisotropy, an indicator of greater WM integrity, in aging musicians in bilateral superior longitudinal fasciculi and bilateral uncinate fasciculi. Statistical methods used include Fisher’s method and linear regression analysis. Another unique aspect of this study is the accompanying behavioral performance data for each participant.

This is one of the first studies to look specifically at musicianship across the life span and its impact on bilateral WM integrity in aging.

The science on sleep: Three things we learned from research, from fatigue to mental agility


Compiled by Tauhira DeanSHARE



Find a 10 Minute Run for Your Mood and Mind

A new study shows you can cure your mood and cognitive function with a quick 10 minute run! Buzz60’s Chloe Hurst has the story!

A good night’s rest is essential for your health; unfortunately, though, not everyone gets enough sleep.  

People are sleeping less than in the past, and many factors contribute to the disruption of natural sleeping patterns.

We put together some findings from researchers:

1. Researchers say taking a nap can increase mental agility in elderly people

Large group of people dancing at Zumba class

Several studies have provided opposing results regarding afternoon napping – some indicate that it promotes cognitive function, whereas others produced contradicting results.

This led a group of medical researchers to further examine the impact napping has on cognition. Their study, published in BMJ’s General Psychiatry Division, shows that a brief afternoon nap can benefit cognitive function in the elderly.

2. Having trouble sleeping? Here’s the science on 3 traditional bedtime remedies

green tea

Sleep is essential for good health. Poor sleep quality, or not enough sleep, can negatively affect our mood, cognitive function, and immune system.

Stress can impact our sleep, and stress and anxiety associated with the Covid pandemic are causing many of us not to sleep as well as we used to.

3. Feeling tired? Here’s how the brain’s ‘hourglass’ controls your need for sleep – new research

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brain scan

No one can stay awake forever. While we’re awake, our need for sleep gradually increases. If we deprive ourselves of sleep, our brain functions – such as attention and judgement – are impaired, and sleep becomes unavoidable.

No matter whether we are on a couch or at work – if we ignore our need for sleep, we ultimately crash. Video43s

Website seeking nap reviewers to get paid for sleeping are seeking ‘nap reviewers’ who will be paid to document their naps over a period of 30 days.

Running Out of Ideas? Dozing off Could Be the Secret to Unlocking Your Creativity

FeaturedNeuroscience·December 29, 2021

Summary: Researchers report taking a small nap can significantly boost creativity.

Source: The Conversation

At the fringe between wakefulness and sleep, there is a grey zone where our consciousness fluctuates, our responsiveness decreases and our awareness of the real world starts to dissolve, giving way to spontaneous sensations close to dreaming.

Brief and fleeting, this sleep onset phase remains a mystery that has long intrigued artists, scientists and inventors, who considered the period fertile ground for insights and discoveries.

Among those, German chemist August Kékulé reported how a daydream of a snake biting its own tail revealed to him the circular structure of benzene.

Thomas Edison and Salvador Dali were both so convinced of the creative virtues of sleep onset that they developed a method to catch these brief insights. Their secret was simple: they took naps while holding an object in their hand. The said object would fall and make noise as their muscles relaxed at the transition to sleep, waking them up in time to write down the illuminations occurring during this pre-sleep period.

But is catching creative ideas at sleep onset the mark of geniuses or is it accessible to everyone?

Dozing off to solve problems

To find out if a muse hides at the gates of sleep, we compared the ability of volunteers to solve a problem after a cat nap compared to volunteers staying awake.

Our hypothesis was that individuals who had dozed off would have a higher chance of having a Eureka! moment. But how to measure this in the lab? We decided to use the Number Reduction Task (NRT), in which participants must solve a series of arithmetic problems as quickly as possible following two simple rules.

Finding the solution is easy but tedious: you just need to proceed step by step. The beauty of the NRT lies in a hidden trick, a shortcut that allows the participant to skip most of the steps and find the solution rapidly and effortlessly.

Participants were not aware of the existence of this trick when starting the task. However, if they spontaneously uncover it, we immediately observed a sudden reduction in their solving time, allowing us to precisely track when these Eureka! moments occurred.

We tested 103 volunteers at the Sleep Disorders Department of the Pitié-Salpêtrière Hospital in Paris. These volunteers were first given 60 trials in advance, to get used to the task. A small proportion of them (16%) found the shortcut during this phase and were not included in further analyses. Then, participants were allowed to have a 20-minute break, in a dark room, on a comfortable chair with their eyes closed.

These conditions were chosen to facilitate sleep onset. However, we did not just want people to fall asleep, but we also wanted them to stay in the grey zone between wake and sleep to test the specific effect of this phase on creativity. This transition phase is unstable and usually rapidly turns into deeper sleep, making it very hard to anticipate when to wake people up before they fall into deeper sleep.

To help participants stay at the gates of sleep, we took inspiration from Edison and Dali. We asked participants to hold a plastic bottle in their hand, so they would wake themselves up by dropping it before falling too deeply asleep. At the end of this break, participants were asked to work on 330 new trials of the same NRT task and we monitored the occurrence of Eureka! moments.

Throughout the experiment, participants wore sensors, placed on their head, chin and around their eyes to monitor their cerebral, ocular and muscular activity. From these signals, we could monitor the sleep state of participants in real time and divide the sample into three groups: those who stayed awake during the whole break, those who dozed off (and entered only the first stage of sleep called N1), and those reached the second stage, N2.

So, were Edison and Dali right in thinking that remaining on the brink of sleep provides direct access to our creative self? We found that 83% of participants who dozed off (N1 group) found the hidden rule, compared to only 31% of volunteers in the group who stayed awake.

This three-fold increase in the proportion of Eureka! is all the more surprising given that the difference between the N1 group and the awake group amounted on average to spending just one minute in the first stage of sleep. The creativity boost disappeared in volunteers who reached N2 – only 14% found the hidden rule. It thus seems that there is a fertile ground for creativity during sleep onset: to reach it, one must fall asleep easily but not too deeply.

Edison and Dali were right

Is Edison’s technique efficient to capture this creative sweet spot? We observed a slowing down of brain activity (a marker of sleep onset) just before the drops. Because the sound provoked by the falling bottle woke up participants each time, Edison’s technique could prevent participants from transitioning deeper into N2, which does not seem to benefit creativity.

This shows a person writing on a board
Can’t find the answer? You might want to take a nap. Credit: The Conversation

However, we also observed that participants would sometimes drop the bottle even before reaching N1. These premature drops suggest that this technique is sensitive to early signs of sleepiness and could thus sometimes prevent participants from reaching the creative zone.

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In a nutshell, cat napping with an object in hand is efficient to stay in the creative sweet spot, but only if you could reach it in the first place.

If you want to try this method at home, you need to find a light, slippery object. The object must make enough noise when falling to wake you up before you get into a deep slumber.

Once you have found the perfect object, take a short nap with your arm sticking out of the chair or bed. When dropping your object makes you wake up from this creative nap, you might have to wait to hear your muse whisper the solution to the problem you are trying to solve.

Indeed, contrary to the many anecdotes of Eureka! moments occurring right upon awakening, our participants found the secret trick with a delay of about 94 new trials on average. The neural mechanisms by which sleep onset fosters creative insights thus remain mysterious. But one thing is sure – you now have a perfect excuse to doze off during meetings.


Delphine Oudiette has received funding from the Agence Nationale de la Recherche.

Célia Lacaux has received funding from the ED3C doctoral school and the Société Française de Recherche et Médecine du Sommeil.

Thomas Andrillon is a neuroscientist at the Paris Brain Insitute (Paris, France) and an adjunct research fellow at the Centre for Consciousness and Contemplative Studies at Monash University (Melbourne, Australia). He has received research fundings from the Human Frontier Science Program (HFSP, France) and the National Health and Medical Research Council (NHMRC, Australia).

About this creativity and sleep research news

Authors: Delphine OudietteCélia LacauxThomas Andrillon
Source: The Conversation
Contact: Delphine Oudiette, Célia Lacaux, Thomas Andrillon – The Conversation
Image: The image is credited to The Conversation

How to sleep: The tea shown to improve sleep quality in two weeks

THE HERBAL tea chamomile has been identified as improving sleep quality, however it has no effect on insomnia.

By MASON QUAH22:50, Tue, Dec 28, 2021 | UPDATED: 22:50, Tue, Dec 28, 20210Copy link

Jim Donovan details trick to help with falling asleep

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Poor sleep quality is a common issue that disproportionately impacts elderly people. It can be made worse by fatigue and depression, which can also worsen waking quality of life. Teas with sedative effects, such as chamomile, have been found to improve sleep quality, including one study published in the Journal of Advanced Nursing. The research is conflicted on whether the effects persist when taking it for a long time, and whether it can help other sleep related conditions such as insomnia.


Multiple studies have examined the effects of chamomile on sleep quality.

Many of these have small sample groups and run for short periods of time.—&gdpr_consent=CPSAkT1PSAkT1AKAlAENB7CsAP_AAH_AAAwIIfNf_X__bX9j-_5_f_t0eY1P9_r3v-QzjhfNt-8F2L_W_L0X42E7NF36pq4KuR4Eu3LBIQFlHMHUTUmwaokVrzHsak2cpyNKJ7LEmnMZO2dYGHtPn9lTuYKY7_7___fz3j-v_t_-39T378X_3_d5_2—vC_V_99zLv9____39nP___9v-_9_3_wQpAJMNS8AC7MscGSaNKoUQIQrCQqAUAFFAMLRFYAMDAp2VgEeoIGACE1ARgRAgxBRgwCAAASAJCIgJACwQCIAiAQAAgBQgIQAETAILACwMAgAFANCxAigAECQgyOCo5TAgKkWiglsrAEoK9jTCAMo8CKBRHRUICNZogWBkJCwcAAAAAAgAAEAAAA.f_gAAAAAAAAA&addtl_consent=1~×280&!a&btvi=1&fsb=1&xpc=l0S0q13gRJ&p=https%3A// systematic review of these smaller trials found a significant impact on sleep quality.

This same review also failed to find a positive effect of the tea on anxiety and insomnia, two areas where it has been looked to as a potential treatment.

READ MORE: Vitamin B12 deficiency: Two ‘problems’ that arise in the mouth following very low levels 


Chamomile tea could improve sleep quality (Image: Getty)

The method used for taking chamomile differs, but the medicinal effects seem to occur however it is taken.

One study focused on twice daily capsules containing chamomile extract.

The active ingredients in chamomile are a group of plant chemicals called terpenoids, which also have use in perfumes and cosmetic products.