“From worms to flies to humans, neurons are the starting block for generalized intelligence,” says first author Brett Kagan (@ANeuroExplorer), chief scientific officer at Cortical Labs in Melbourne, Australia. “So, the question was, can we interact with neurons in a way to harness that inherent intelligence?”

To start, the researchers connected the neurons to a computer in such a way where the neurons received feedback on whether their in-game paddle was hitting the ball. They monitored the neuron’s activity and responses to this feedback using electric probes that recorded “spikes” on a grid.

The spikes got stronger the more a neuron moved its paddle and hit the ball. When neurons missed, their playstyle was critiqued by a software program created by Cortical Labs. This demonstrated that the neurons could adapt activity to a changing environment, in a goal-oriented way, in real time.

“We chose Pong due to its simplicity and familiarity, but, also, it was one of the first games used in machine learning, so we wanted to recognize that,” says Kagan, who worked with collaborators from 10 other institutions on the project.

“An unpredictable stimulus was applied to the cells, and the system as a whole would reorganize its activity to better play the game and to minimize having a random response,” he says. “You can also think that just playing the game, hitting the ball and getting predictable stimulation, is inherently creating more predictable environments.”

The theory behind this learning is rooted in the free-energy principle. Simply put, the brain adapts to its environment by changing either its world view or its actions to better fit the world around it.

Pong wasn’t the only game the research team tested. “You know when the Google Chrome browser crashes and you get that dinosaur that you can make jump over obstacles (Project Bolan). We’ve done that and we’ve seen some nice preliminary results, but we still have more work to do building new environments for custom purposes,” says Kagan.

Future directions of this work have potential in disease modeling, drug discoveries, and expanding the current understanding of how the brain works and how intelligence arises.

“This is the start of a new frontier in understanding intelligence,” Kagan says. “It touches on the fundamental aspects of not only what it means to be human but what it means to be alive and intelligent at all, to process information and be sentient in an ever changing, dynamic world.”

Story Source:

Materials provided by Cell Press. Note: Content may be edited for style and length.

In a complementary study of WR140, published in Nature Astronomy, NASA’s James Webb Space Telescope (JWST) was able to see much deeper to snap an image of not just a single accelerating dust plume, but almost 20 of them, nested inside each other like a giant set of onion skins.

WR140 is comprised of a huge Wolf-Rayet star and an even bigger blue supergiant star, gravitationally bound in an eight-year orbit. This binary star, in the Cygnus constellation, has been monitored for two decades with one of the world’s largest optical telescopes at the Keck Observatory in Hawaii.

WR140 episodically puffs out plumes of dust stretching thousands of times the distance from the Earth to the Sun. These dust plumes, produced every eight years, give astronomers a unique opportunity to observe how starlight can affect matter.

It’s known that light carries momentum, exerting a push on matter known as radiation pressure. Astronomers often witness the outcome of this phenomenon in the form of matter coasting at high speed around the cosmos, but it’s been a difficult process to catch in the act. Direct recording of acceleration due to forces other than gravity is rarely witnessed, and never in a stellar environment like this.

“It’s hard to see starlight causing acceleration because the force fades with distance, and other forces quickly take over,” said Yinuo Han from Cambridge’s Institute of Astronomy, first author of the Nature paper. “To witness acceleration at the level that it becomes measurable, the material needs to be reasonably close to the star or the source of the radiation pressure needs to be extra strong. WR140 is a binary star whose ferocious radiation field supercharges these effects, placing them within reach of our high-precision data.”

All stars generate stellar winds, but those from Wolf-Rayet stars can be more like a stellar hurricane. Elements such as carbon in the wind condense out as soot, which remains hot enough to glow bright in the infrared. Like smoke in the wind, this gives telescopes something that can be observed.

The team used an imaging technology known as interferometry which was able to act like a zoom lens for the 10-metre Keck telescope mirror, enabling the researchers to recover sufficiently sharp images of WR140 for the study.

Han and his team found that the dust does not stream out from the star with the wind in a hazy ball. Instead, the dust forms where the winds from the two stars collide, on the surface of a cone-shaped shock front between them.

Because the orbiting binary star is in constant motion, the shock front also rotates. The sooty plume gets wrapped into a spiral, in the same way that droplets form a spiral in a garden sprinkler.

The researchers found that WR140 has other tricks up its sleeve. The two stars are not on circular but rather elliptical orbits, and dust production turns on and off as the binary nears and departs the point of closest approach. By modelling these effects into the three-dimensional geometry of the dust plume, the astronomers were able to measure to location of dust features in three-dimensional space.

“Like clockwork, this star puffs out sculpted smoke rings every eight years, with all this wonderful physics written then inflated in the wind like a banner for us to read,” said co-author Professor Peter Tuthill from the University of Sydney. “Eight years later as the binary returns in its orbit, another appears the same as the one before, streaming out into space inside the bubble of the previous one, like a set of giant nested Russian dolls.”

Because the dust produced by this Wolf-Rayet is so predictable and expands to such large distances, it offered the astronomers a unique laboratory to examine the acceleration zone.

“In the absence of external forces, each dust spiral should expand at a constant speed,” said Han, who is also a co-author on the JWST paper. “We were puzzled at first because we could not get our model to fit the observations, until we finally realised that we were seeing something new. The data did not fit because the expansion speed wasn’t constant, but rather that it was accelerating. We’d caught that for the first time on camera.”

“In one sense, we always knew this must be the reason for the outflow, but I never dreamed we’d be able to see the physics at work like this,” said Tuthill. “When I look at the data now, I see WR140’s plume unfurling a like giant sail made of dust. When it catches the photon wind streaming from the star, like a yacht catching a gust, it makes a sudden leap forward.”

With JWST now in operation, researchers can learn much more about WR140 and similar systems. “The Webb telescope offers new extremes of stability and sensitivity,” said Ryan Lau who led the JWST study. “We’ll now be able to make observations like this much more easily than from the ground, opening a new window into the world of Wolf-Rayet physics.”

The research was funded in part by the Gates Cambridge Trust.

The quantum material in question is known by the chemical formula Mn₃Si₂Te₆. But you could also call it “honeycomb” because its manganese and tellurium atoms form a network of interlocking octahedra that look like the cells in a beehive.

Physicist Gang Cao and his colleagues at CU Boulder synthesized this molecular beehive in their lab in 2020, and they were in for a surprise: Under most circumstances, the material behaved a lot like an insulator. In other words, it didn’t allow electric currents to pass through it easily. When they exposed the honeycomb to magnetic fields in a certain way, however, it suddenly became millions of times less resistant to currents. It was almost as if the material had morphed from rubber into metal.

“It was both astonishing and puzzling,” said Cao, professor in the Department of Physics and corresponding author of the new study. “Our follow-up effort in pursuing a better understanding of the phenomena led us to even more surprising discoveries.”

Now, he and his colleagues think they can explain that astonishing behavior. The group, including several graduate students at CU Boulder, published its most recent results on Nov. 17 in the journal Nature.

Drawing on experiments in Cao’s lab, the group reports that, under certain conditions, the honeycomb is abuzz with tiny, internal currents known as chiral orbital currents, or loop currents. Electrons zip around in loops within each of the octahedra in this quantum material. Since the 1990s, physicists have theorized that loop currents could exist in a handful of known materials, such as high-temperature superconductors, but they have yet to directly observe them.

Cao said they could be capable of driving startling transformations in quantum materials like the one he and his team stumbled on.

“We’ve discovered a new quantum state of matter,” Cao said. “Its quantum transition is almost like ice melting into water.”

Colossal changes

The study homes in on a strange property in physics called colossal magnetoresistance (CMR).

In the 1950s, physicists realized that if they exposed certain types of materials to magnets that generate a magnetic polarization, they could make those materials undergo a shift — causing them to switch from insulators to more wire-like conductors. Today, this technology shows up in computer disk drives and many other electronic devices where it helps to control and shuttle electric currents along distinct paths.

The honeycomb in question, however, is vastly different from those materials — the CMR occurs only when conditions avoid that same kind of magnetic polalrization. The shift in electrical properties is also much more extreme than what you can see in any other known CMR material, Cao added.

“You have to violate all the conventional conditions to achieve this change,” Cao said.

Melting ice

He and his colleagues, including CU Boulder graduate students Yu Zhang, Yifei Ni and Hengdi Zhao, wanted to find out why.

They, along with co-author Itamar Kimchi of Georgia Institute of Technology, hit on the idea of loop currents. According to the team’s theory, countless electrons circulate around inside their honeycombs at all times, tracing the edges of each octahedron. In the absence of a magnetic field, those loop currents tend to stay disorderly, or flow in both clockwise and counterclockwise patterns. It’s a bit like cars driving through a roundabout in both directions at once.

That disorder can cause “traffic jams” for electrons traveling in the material, Cao said, increasing the resistance and making the honeycomb an insulator.

As Cao put it: “Electrons like order.”

The physicist added, however, that if you pass an electric current into the quantum material in the presence of a specific kind of magnetic field, the loop currents will begin to circulate only in one direction. Put differently, the traffic jams disappear. Once that happens, electrons can speed through the quantum material, almost as if it was a metal wire.

“The internal loop currents circulating along the edges of the octahedra are extraordinarily susceptible to external currents,” Cao said. “When an external electric current exceeds a critical threshold, it disrupts and eventually ‘melts’ the loop currents, leading to a different electronic state.”

He noted that in most materials, the switch from one electronic state to another happens almost instantaneously, or in the span of trillionths of a second. But in his honeycomb, that transformation can take seconds or even longer to occur.

Cao suspects the entire structure of the honeycomb begins to morph, with the bonds between atoms breaking and reforming in new patterns. That kind of reordering takes an unusually long time, he noted — a bit like what happens when ice melts into water.

Cao said the work provides a new paradigm for quantum technologies. For now, you probably won’t see this honeycomb in any new electronic devices. That’s because the switching behavior only takes place at cold temperatures. He and his colleagues, however, are searching for similar materials that will do the same thing under much more hospitable conditions.

“If we want to use this in future devices, we need to have materials that show the same type of behavior at room temperature,” Cao said.

Now, that sort of invention could be buzz-worthy.

The novel compound — a polyamine — seems to destroy Staphylococcus aureus, the bacterium that causes (among other things) deadly Methicillin-resistant Staphylococcus aureus (MRSA) infections, by disrupting the pathogen’s cell membrane.

The compound was tested in-vitro against 10 different antibiotic-resistant strains of S. aureus, including some that are known to be resistant to vancomycin — the final drug of choice given to patients fighting an MRSA infection. The compound was completely successful against all strains, resulting in no further bacterial growth.

The study shows that as well as destroying S. aureus directly, the compound is able to restore the sensitivity of multidrug resistant strains of the bacteria to three important antibiotics (daptomycin, oxacillin and vancomycin). This could mean that antibiotics that have become ineffective through decades of overuse may, in time, reclaim their ability to bring serious infections under control.

“We’re not entirely sure why these synergies occur between the compound and antibiotics, but we’re keen to explore this further,” said Dr Laabei, researcher from the Department of Live Sciences at Bath.

The pathogen’s vulnerability

Polyamines are naturally occurring compounds found in most living organisms. Until a decade ago, they were thought to be essential to all life, but scientists now know they are both absent in, and toxic to, S. aureus. Since making this discovery, researchers have been attempting to exploit the pathogen’s unusual vulnerability to polyamines to inhibit bacterial growth.

Now Dr Laabei and his colleagues have found that a modified polyamine (named AHA-1394) is far more effective at destroying antibiotic-resistant strains of S. aureus than even the most active natural polyamine.

Explaining, Dr Laabei said: “Using our novel compound, the pathogen is destroyed — meaning growth is inhibited — when it’s used at a concentration that’s over 128 times lower than that required to destroy the pathogen when we use a natural polyamine.

“This is important, as drugs that have the lowest minimum inhibitory concentration are likely to be more effective antimicrobial agents, and to be safer to the patient.”

Though further research is needed, Dr Laabei believes the new compound “could have important implications in a clinical setting as a new treatment option.”

He said: “Preliminary research suggests the compound is non-toxic to humans, which of course is essential. In our next study, for which we’re seeking funding, we hope to focus on the precise mechanisms used by the compound to inhibit S. aureus. We believe the compound attacks the membrane of S. aureus, resulting in the membrane becoming permeable, resulting in bacterial death.”

The compound was also tested against biofilm — the thin, hard-to-treat layer of microorganisms that grows on hard surfaces (seen, for instance, as plaque on teeth or a stubborn film on urinary catheters) and can result in serious infection. The results were promising here too, with the compound preventing the formation of new biofilm, though not disrupting established biofilm.

Antibiotic resistance

Antibiotic resistance (or antimicrobial resistance — AMR) poses a major threat to human health around the world, and S. aureus has become one of the most notorious multidrug-resistant pathogens.

A recent study looking back at the health effects of AMR in 2019 finds the pathogen was associated with one-million deaths worldwide, as a result of infections not responding to antibiotics.

S. aureus is found in 30% of the population, living in people’s nasal passages and on the skin, and mostly it does not cause infection. Until quite recently, an MRSA infection was regarded as a hospital problem, and those affected were mostly people with an already compromised immune system. Over the past 20 years, however, for complex and only partially understood reasons, there has been an upswing in community-wide infections even among otherwise healthy individuals, bringing a sense of urgency to the quest to find fresh ways to tackle the problem.

“New treatments are urgently needed to treat infections,” said Dr Laabei.

The study, published in Cell Reports Medicine, built on ongoing collaborative Cleveland Clinic research to support further investigation into metformin as a drug repurposing candidate. Researchers used advanced computation and genetic sequencing to determine that metformin’s targets overlap significantly with genes dysregulated in atrial fibrillation.

“Finding drugs or procedures to treat atrial fibrillation is difficult because of potential serious side effects,” said Mina Chung, M.D., senior author of the study who is in Cleveland Clinic’s Department of Cardiovascular Medicine in the Heart, Vascular and Thoracic Institute. “There is a significant need for new treatments for atrial fibrillation as there have been no new drugs approved in more than a decade.”

“It’s not that we’ve found a new drug target where it takes 20 years to test this in individuals,” said Jessica Castrillon Lal, the study’s first author and a fifth-year graduate student in the Cleveland Clinic Molecular Medicine program.

“We can cut off 10+ years in the drug development pipeline. We already have the information there. We just have to test it in a very computationally efficient way, such as artificial intelligence technology,” said Feixiong Cheng, Ph.D., co-senior author of the study who is Associate Staff at the Genomic Medicine Institute in Cleveland Clinic’s Lerner Research Institute.

The analysis found metformin targeted 30 genes associated with atrial fibrillation, with direct effects on gene expression for eight. Eight other candidate drugs surfaced in the analysis, but researchers were able to identify metformin as the most promising candidate through testing and reviewing outcomes in large stores of patient data.

Castrillon Lal conducts research in Dr. Cheng’s lab, which uses network medicine approaches to find candidate drugs for repurposing, creating vast networks of molecular interactions. For this study, researchers winnowed down a list of 2,800 FDA-approved treatments by analyzing three data sources: a map of interactions between proteins called an “interactome”; a network of genes associated with atrial fibrillation; and each medicine’s molecular or genetic targets.

Atrial fibrillation is the most common type of heart arrhythmia in the world and can lead to complications, including stroke and heart failure. Treatments have been primarily directed toward trying to prevent the arrhythmia using drugs targeting the electrical system, including ion channels in the heart, or using catheter ablation to isolate the pulmonary veins where initiating beats of atrial fibrillation occur.

However, side effects, limited success and potential complications can limit these approaches.

The research was conducted in collaboration with labs led by Dr. Chung, Dr. Cheng, David Van Wagoner, Ph.D.; Jonathan Smith, Ph.D., Department of Cardiovascular and Metabolic Sciences; and John Barnard, Ph.D., Department of Quantitative Health Sciences in the Lerner Research Institute.

Prior work from Drs. Chung, Smith, Van Wagoner, and Barnard had also identified the enzyme AMPK as a potential key regulator for metabolic stress. Metabolic stress has been associated with atrial fibrillation.

Story Source:

Materials provided by Cleveland Clinic. Note: Content may be edited for style and length.