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Comment by Dr. Krishna Kumari Challa on July 10, 2022 at 10:02am

Researchers discover how sound reduces pain in mice

An international team of scientists has identified the neural mechanisms through which sound blunts pain in mice. The findings, which could inform development of safer methods to treat pain, were published in Science.

By uncovering the circuitry that mediates the pain-reducing effects of sound in mice, this study adds critical knowledge that could ultimately inform new approaches for pain therapy.

Dating back to 1960, studies in humans have shown that music and other kinds of sound can help alleviate acute and chronic pain, including pain from dental and medical surgery, labor and delivery, and cancer. However, how the brain produces this pain reduction, or analgesia, was less clear.

Human brain imaging studies have implicated certain areas of the brain in music-induced analgesia, but these are only associations. Now  researchers first exposed mice with inflamed paws to three types of sound: a pleasant piece of classical music, an unpleasant rearrangement of the same piece, and white noise. Surprisingly, all three types of sound, when played at a low intensity relative to background noise (about the level of a whisper) reduced pain sensitivity in the mice. Higher intensities of the same sounds had no effect on animals' pain responses.

So the intensity of sound, and not the category or perceived pleasantness of sound would matter.

To explore the brain circuitry underlying this effect, the researchers used non-infectious viruses coupled with fluorescent proteins to trace connections between brain regions. They identified a route from the auditory cortex, which receives and processes information about sound, to the thalamus, which acts as a relay station for sensory signals, including pain, from the body. In freely moving mice, low-intensity white noise reduced the activity of neurons at the receiving end of the pathway in the thalamus.

In the absence of sound, suppressing the pathway with light- and small molecule-based techniques mimicked the pain-blunting effects of low-intensity noise, while turning on the pathway restored animals' sensitivity to pain.

 It is unclear if similar brain processes are involved in humans, or whether other aspects of sound, such as its perceived harmony or pleasantness, are important for human pain relief.
We don't know if human music means anything to rodents, but it has many different meanings to humans—you have a lot of emotional components.

The results could give scientists a starting point for studies to determine whether the animal findings apply to humans, and ultimately could inform development of safer alternatives to opioids for treating pain.

Zhou W, et al. Sound induces analgesia via corticothalamic circuits. Science. July 7, 2022. DOI: science.org/doi/10.1126/science.abn4663

Comment by Dr. Krishna Kumari Challa on July 9, 2022 at 9:05am

Building blocks for RNA-based life abound at center of our galaxy

Nitriles, a class of organic molecules with a cyano group—that is, a carbon atom bound with a triple unsaturated bond to a nitrogen atom—are typically toxic. But paradoxically, they are also a key precursor for molecules essential for life, such as ribonucleotides, composed of the nucleobases or "letters" A, U, C, and G joined to a ribose and phosphate group, which together make up RNA. Now, an international team of researchers  show that a wide range of nitriles occurs in interstellar space within the molecular cloud G+0.693-0.027, near the center of the Milky Way.

The researchers show that the chemistry that takes place in the interstellar medium is able to efficiently form multiple nitriles, which are key molecular precursors of the 'RNA World' scenario.

According to this scenario, life on Earth was originally based on RNA only, and DNA and protein enzymes evolved later. RNA can fulfill both their functions: storing and copying information like DNA, and catalyzing reactions like enzymes. According to the "RNA World" theory, nitriles and other building blocks for life needn't necessarily all have arisen on Earth itself: They might also have originated in space and "hitchhiked" to the young Earth inside meteorites and comets during the "Late Heavy Bombardment" period, between 4.1 and 3.8 billion years ago. In support, nitriles and other precursor molecules for nucleotides, lipids, and amino acids have been found inside contemporary comets and meteors.

But from where in space could these molecules have come? Prime candidates are molecular clouds, which are dense and cold regions of the interstellar medium, and are suitable for the formation of complex molecules. For example, the molecular cloud G+0.693-0.027 has a temperature of around 100 K and is approximately three light years across, with a mass approximately one thousand times that of our sun. There's no evidence that stars are currently forming inside G+0.693-0.027, although scientists suspect that it might evolve to become a stellar nursery in the future.

The chemical content of G+0.693-0.027 is similar to those of other star-forming regions in our galaxy, and also to that of solar system objects like comets. This means that its study can give us important insights about the chemical ingredients that were available in the nebula that give rise to our planetary system.

Thanks to the observations over the past few years, including the present results, we now know that nitriles are among the most abundant chemical families in the universe. We have found them in molecular clouds in the center of our galaxy, protostars of different masses, meteorites and comets, and also in the atmosphere of Titan, the largest moon of Saturn.

Molecular precursors of the RNA-world in space: new nitriles in the G+0.693-0.027 molecular cloud, Frontiers in Astronomy and Space Sciences (2022). DOI: 10.3389/fspas.2022.876870, www.frontiersin.org/articles/1 … pas.2022.876870/full

Comment by Dr. Krishna Kumari Challa on July 8, 2022 at 11:58am

Scientists see life-saving potential in spider venom

Comment by Dr. Krishna Kumari Challa on July 8, 2022 at 11:41am

Researchers discover brain pathway that helps to explain light's effect on mood

From changes in daylight across seasons to the artificial lighting choices in workplaces, it's clear that the quantity and quality of light that a person encounters can significantly impact mood. Now scientists know why.

In a new study published in the Proceedings of the National Academy of Science, a  research team used functional MRI to reveal how light-intensity signals reach the brain, and how brain structures involved in mood process those signals. The study demonstrated that some regions of the cerebral cortex involved in cognitive processing and mood show sensitivity for light intensity.

The discovery has implications for understanding mood problems like seasonal affective disorder and major depressive disorders, as well as how to treat them.

Identifying this pathway and understanding its function might directly promote development of approaches to treat depression, either by pharmacological manipulations or non-invasive brain stimulation in selected nodes of the pathway or with targeted bright-light therapy.

Shai Sabbah et al, Luxotonic signals in human prefrontal cortex as a possible substrate for effects of light on mood and cognition, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2118192119

Comment by Dr. Krishna Kumari Challa on July 8, 2022 at 11:34am

Chemists find a contrary effect: How diluting with water makes a solution firm

In Science, researchers have published a study on new phase transitions of solutions and gels in water, which seem to go against the basic principles of chemistry.

In chemistry, a hydrogel changes to a liquid by diluting it with water. For the reverse transition, you increase the hydrogel concentration. However,  researchers accidentally discovered that their liquid solution turned into a hydrogel when diluted. This phenomenon hadn't been researched or described before and could have consequences in many areas in chemistry and biology.

The research focuses on the formation of certain hydrogels. This means that it starts with an aqueous solution of, in this case, two substances (a surfactant and a monomer). The research shows that a gel is formed at a specific ratio of these two substances in water. This gel is formed by long, supramolecular networks composed of both substances. The amounts of these substances in water (the concentrations) also determine where the phase transition of the gel formation is located. When decreasing the concentration without changing the ratio between the two components, the gel dissolves and becomes liquid. So far, this is familiar territory.

What is extraordinary, however, is that if the solution is diluted even further, a gel once again forms. Other supramolecular structures now form and it becomes a hydrogel again. And if it is then diluted even further, it becomes a liquid again. The paper carefully examined what the correct proportions of the active substances should be and at which concentrations the phase transitions take place. These transitions are also fully reversible. If concentrations are increased, the transitions from liquid to gel to liquid to gel occur at the same points. This phenomenon should be present in other fields, such as biology, but has never been researched and documented before.

Lu Su et al, Dilution-induced gel-sol-gel-sol transitions by competitive supramolecular pathways in water, Science (2022). DOI: 10.1126/science.abn3438. www.science.org/doi/10.1126/science.abn3438

Matthew J. Webber, Less is more when forming gels by dilution, Science (2022). DOI: 10.1126/science.abo7656 , www.science.org/doi/10.1126/science.abo7656

Comment by Dr. Krishna Kumari Challa on July 7, 2022 at 11:56am

New study appears to answer one of Formula 1's oldest questions: Which is more important—car and team, or driver?

Which is more important to driving success in Formula 1, driver, or team and machine? A new eight-season-long study out recently, following this weekend's exciting British Grand Prix, finds surprisingly the answer is not as much to do with the car as you might expect.

There is a long-held belief, the so-called '80-20 rule' in F1 that the car/team are responsible for 80% of race success, while the skill of the driver only accounts for 20%.

What the researchers found, however, is that the car and team's input has been greatly overestimated. Rather than 80%, it is closer to 20%. The driver's input accounts for roughly 15%.

The biggest factor is more nuanced and it's the interaction between the driver and team which accounts for 30-40%. Random factors that occur during the race make up the rest.

These findings are particularly validating for drivers, as it shows they do not just drive the cars but also provide valuable input and feedback on the development of the cars. More skilled drivers improve the return to team technology and vice-versa. After all, F1 cars do not drive themselves and drivers cannot ply their trade without an F1 car. The 80-20 rule vastly underestimates the role of the driver, given the critical complementarity between driver and team.

 Race to the Podium: Separating and Conjoining the Car and Driver in F1 Racing, Applied Economics (2022). DOI: 10.1080/00036846.2022.2083068

Comment by Dr. Krishna Kumari Challa on July 7, 2022 at 11:17am

Scientists set out to try to learn more about those lesser-known structures. They embedded the proteins in a special type of self-assembling membrane called a nanodisc, which mimics the cell membrane. Then, they used single molecule FRET (fluorescence resonance energy transfer) to study how the conformation of the receptor changes when it binds to EGF.

FRET is commonly used to measure tiny distances between two fluorescent molecules. The researchers labeled the nanodisc membrane and the end of the intracellular tail of the protein with two different fluorophores, which allowed them to measure the distance between the protein tail and the cell membrane, under a variety of circumstances.

To their surprise, the researchers found that EGF binding led to a major change in the conformation of the receptor. Most models of receptor signaling involve interaction of multiple transmembrane helices to bring about large-scale conformational changes, but the EGF receptor, which has only a single helical segment within the membrane, appears to undergo such a change without interacting with other receptor molecules.

To learn more about how this shape change would affect the receptor's function,  they did computer simulations of molecular interactions. This kind of modeling, known as molecular dynamics, can model how a molecular system changes over time.

The modeling showed that when the receptor binds to EGF, the extracellular segment of the receptor stands up vertically, and when the receptor is not bound, it lies flat against the cell membrane. Similar to a hinge closing, when the receptor falls flat, it tilts the transmembrane segment and pulls the intracellular segment closer to the membrane. This blocks the intracellular region of the protein from being able to interact with the machinery needed to launch cell growth. EGF binding makes those regions more available, helping to activate growth signaling pathways.

The researchers also used their model to discover that positively charged amino acids in the intracellular segment, near the cell membrane, are key to these interactions. When the researchers mutated those amino acids, switching them from charged to neutral, ligand binding no longer activated the receptor.

The researchers also found that cetuximab, a drug that binds to the EGF receptor, prevents this conformational change from occurring. 

 Nature Communications (2022). DOI: 10.5281/zenodo.6564353

Part 2

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Comment by Dr. Krishna Kumari Challa on July 7, 2022 at 11:14am

How a shape-shifting receptor influences cell growth

Receptors found on cell surfaces bind to hormones, proteins, and other molecules, helping cells respond to their environment. MIT chemists have now discovered how one of these receptors changes its shape when it binds to its target, and how those changes trigger cells to grow and proliferate.

This receptor, known as epidermal growth factor receptor (EGFR), is overexpressed in many types of cancer and is the target of several cancer drugs. These drugs often work well at first, but tumors can become resistant to them. Understanding the mechanism of these receptors better may help researchers design drugs that can evade that resistance.

Thinking about more general mechanisms to target EGFR is an exciting new direction, and gives you a new avenue to think about possible therapies that may not evolve resistance as easily.

The EGF receptor is one of many receptors that help control cell growth. Found on most types of mammalian epithelial cells, which line body surfaces and organs, it can respond to several types of growth factors in addition to EGF. Some types of cancer, especially lung cancer and glioblastoma, overexpress the EGF receptor, which can lead to uncontrolled growth.

Like most cell receptors, the EGFR spans the cell membrane. An extracellular region of the receptor interacts with its target molecule (also called a ligand); a transmembrane section is embedded within the membrane; and an intracellular section interacts with cellular machinery that controls growth pathways.

The extracellular portion of the receptor has been analyzed in detail, but the transmembrane and intracellular sections have been difficult to study because they are more disordered and can't be crystallized.

Part 1

Comment by Dr. Krishna Kumari Challa on July 7, 2022 at 10:07am

Scientists discover how first quasars in universe formed

The mystery of how the first quasars in the universe formed—something that has baffled scientists for nearly 20 years—has now been solved by a team of astrophysicists whose findings are published in Nature.

The existence of more than 200 quasars powered by supermassive balckholes less than a billion years after the Big Bang had remained one of the outstanding problems in astrophysics because it was never fully understood how they formed so early.

 Daniel Whalen, Turbulent cold flows gave birth to the first quasars, Nature (2022). DOI: 10.1038/s41586-022-04813-y. www.nature.com/articles/s41586-022-04813-y

Daniel Whalen et al, Revealing the origin of the first supermassive black holes, Nature (2022). DOI: 10.1038/d41586-022-01560-y , www.nature.com/articles/d41586-022-01560-y

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Comment by Dr. Krishna Kumari Challa on July 7, 2022 at 10:02am

Mathematical calculations show that quantum communication across interstellar space should be possible

A team of physicists  has used mathematical calculations to show that quantum communications across interstellar space should be possible. In their paper published in the journal Physical Review D, the group describes their calculations and also the possibility of extraterrestrial beings attempting to communicate with us using such signaling.

Over the past several years, scientists have been investigating the possibility of using quantum communications as a highly secure form of message transmission. Prior research has shown that it would be nearly impossible to intercept such messages without detection. In this new effort, the researchers wondered if similar types of communications might be possible across interstellar space. To find out, they used math that describes that movement of X-rays across a medium, such as those that travel between the stars. More specifically, they looked to see if their calculations could show the degree of decoherence that might occur during such a journey.

With quantum communications, engineers are faced with quantum particles that lose some or all of their unique characteristics as they interact with obstructions in their path—they have been found to be quite delicate, in fact. Such events are known as decoherence, and engineers working to build quantum networks have been devising ways to overcome the problem. Prior research has shown that the space between the stars is pretty clean. But is it clean enough for quantum communications? The math shows that it is. Space is so clean, in fact, that X-ray photons could travel hundreds of thousands of light years without becoming subject to decoherence—and that includes gravitational interference from astrophysical bodies. They noted in their work that optical and microwave bands would work equally well.

The researchers noted that because quantum communication is possible across the galaxy, if other intelligent beings exist in the Milky Way, they could already be trying to communicate with us using such technology and we could begin looking for them. They also suggest that quantum teleportation across interstellar space should be possible.

Arjun Berera et al, Viability of quantum communication across interstellar distances, Physical Review D (2022). DOI: 10.1103/PhysRevD.105.123033

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