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Human behavior guided by fast changes in dopamine levels

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Human behavior guided by fast changes in dopamine levels


What happens in the human brain when we learn from positive and negative experiences? To help answer that question and better understand decision-making and human behavior, scientists are studying dopamine.

Dopamine is a neurotransmitter produced in the brain that serves as a chemical messenger, facilitating communication between nerve cells in the brain and the body. It is involved in functions such as movement, cognition and learning. While dopamine is most known for its association with positive emotions, scientists are also exploring its role in negative experiences.

Now, a new study from researchers at Wake Forest University School of Medicine shows that dopamine release in the human brain plays a crucial role in encoding both reward and punishment prediction errors. This means that dopamine is involved in the process of learning from both positive and negative experiences, allowing the brain to adjust and adapt its behavior based on the outcomes of these experiences.

The study was published today in Science Advances.

“Previously, research has shown that dopamine plays an important role in how animals learn from ‘rewarding’ (and possibly ‘punishing’) experiences. But, little work has been done to directly assess what dopamine does on fast timescales in the human brain,” said Kenneth T. Kishida, Ph.D., associate professor of physiology and pharmacology and neurosurgery at Wake Forest University School of Medicine. “This is the first study in humans to examine how dopamine encodes rewards and punishments and whether dopamine reflects an ‘optimal’ teaching signal that is used in today’s most advanced artificial intelligence research.”

For the study, researchers on Kishida’s team utilized fast-scan cyclic voltammetry, an electrochemical technique, paired with machine learning, to detect and measure dopamine levels in real-time (i.e., 10 measurements per second). However, this method is challenging and can only be performed during invasive procedures such as deep-brain stimulation (DBS) brain surgery. DBS is commonly employed to treat conditions such as Parkinson’s disease, essential tremor, obsessive-compulsive disorder and epilepsy.

Kishida’s team collaborated with Atrium Health Wake Forest Baptist neurosurgeons Stephen B. Tatter, M.D., and Adrian W. Laxton, M.D., who are also both faculty members in the Department of Neurosurgery at Wake Forest University School of Medicine, to insert a carbon fiber microelectrode deep into the brain of three participants at Atrium Health Wake Forest Baptist Medical Center who were scheduled to receive DBS to treat essential tremor.

While the participants were awake in the operating room, they played a simple computer game. As they played the game, dopamine measurements were taken in the striatum, a part of the brain that is important for cognition, decision-making, and coordinated movements.

During the game, participants’ choices were either rewarded or punished with real monetary gains or losses. The game was divided into three stages in which participants learned from positive or negative feedback to make choices that maximized rewards and minimized penalties. Dopamine levels were measured continuously, once every 100 milliseconds, throughout each of the three stages of the game.

“We found that dopamine not only plays a role in signaling both positive and negative experiences in the brain, but it seems to do so in a way that is optimal when trying to learn from those outcomes. What was also interesting, is that it seems like there may be independent pathways in the brain that separately engage the dopamine system for rewarding versus punishing experiences. Our results reveal a surprising result that these two pathways may encode rewarding and punishing experiences on slightly shifted timescales separated by only 200 to 400 milliseconds in time,” Kishida said.

Kishida believes that this level of understanding may lead to a better understanding of how the dopamine system is affected in humans with psychiatric and neurological disorders. Kishida said additional research is needed to understand how dopamine signaling is altered in psychiatric and neurological disorders.

“Traditionally, dopamine is often referred to as ‘the pleasure neurotransmitter,”‘ Kishida said. “However, our work provides evidence that this is not the way to think about dopamine. Instead, dopamine is a crucial part of a sophisticated system that teaches our brain and guides our behavior. That dopamine is also involved in teaching our brain about punishing experiences is an important discovery and may provide new directions in research to help us better understand the mechanisms underlying depression, addiction, and related psychiatric and neurological disorders.”

This study was supported by grants from the National Institutes of Health: R01MH121099, R01DA048096, R01MH124115, P50DA006634, 5KL2TR001420, F31DA053174, T32DA041349 and F30DA053176.



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Researchers create artificial cells that act like living cells

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Researchers create artificial cells that act like living cells


In a new study published in Nature Chemistry, UNC-Chapel Hill researcher Ronit Freeman and her colleagues describe the steps they took to manipulate DNA and proteins — essential building blocks of life — to create cells that look and act like cells from the body. This accomplishment, a first in the field, has implications for efforts in regenerative medicine, drug delivery systems, and diagnostic tools.

“With this discovery, we can think of engineering fabrics or tissues that can be sensitive to changes in their environment and behave in dynamic ways,” says Freeman, whose lab is in the Applied Physical Sciences Department of the UNC College of Arts and Sciences.

Cells and tissues are made of proteins that come together to perform tasks and make structures. Proteins are essential for forming the framework of a cell, called the cytoskeleton. Without it, cells wouldn’t be able to function. The cytoskeleton allows cells to be flexible, both in shape and in response to their environment.

Without using natural proteins, the Freeman Lab built cells with functional cytoskeletons that can change shape and react to their surroundings. To do this, they used a new programmable peptide-DNA technology that directs peptides, the building blocks of proteins, and repurposed genetic material to work together to form a cytoskeleton.

“DNA does not normally appear in a cytoskeleton,” Freeman says. “We reprogrammed sequences of DNA so that it acts as an architectural material, binding the peptides together. Once this programmed material was placed in a droplet of water, the structures took shape.”

The ability to program DNA in this way means scientists can create cells to serve specific functions and even fine-tune a cell’s response to external stressors. While living cells are more complex than the synthetic ones created by the Freeman Lab, they are also more unpredictable and more susceptible to hostile environments, like severe temperatures.

“The synthetic cells were stable even at 122 degrees Fahrenheit, opening up the possibility of manufacturing cells with extraordinary capabilities in environments normally unsuitable to human life,” Freeman says.

Instead of creating materials that are made to last, Freeman says their materials are made to task — perform a specific function and then modify themselves to serve a new function. Their application can be customized by adding different peptide or DNA designs to program cells in materials like fabrics or tissues. These new materials can integrate with other synthetic cell technologies, all with potential applications that could revolutionize fields like biotechnology and medicine.

“This research helps us understand what makes life,” Freeman says. “This synthetic cell technology will not just enable us to reproduce what nature does, but also make materials that surpass biology.”



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This alloy is kinky

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This alloy is kinky


Researchers have uncovered a remarkable metal alloy that won’t crack at extreme temperatures due to kinking, or bending, of crystals in the alloy at the atomic level.  A metal alloy composed of niobium, tantalum, titanium, and hafnium has shocked materials scientists with its impressive strength and toughness at both extremely hot and cold temperatures, a combination of properties that seemed so far to be nearly impossible to achieve. In this context, strength is defined as how much force a material can withstand before it is permanently deformed from its original shape, and toughness is its resistance to fracturing (cracking). The alloy’s resilience to bending and fracture across an enormous range of conditions could open the door for a novel class of materials for next-generation engines that can operate at higher efficiencies.

The team, led by Robert Ritchie at Lawrence Berkeley National Laboratory (Berkeley Lab) and UC Berkeley, in collaboration with the groups led by professors Diran Apelian at UC Irvine and Enrique Lavernia at Texas A&M University, discovered the alloy’s surprising properties and then figured out how they arise from interactions in the atomic structure. Their work is described in a study that was published April 11, 2024 in Science.

“The efficiency of converting heat to electricity or thrust is determined by the temperature at which fuel is burned — the hotter, the better. However, the operating temperature is limited by the structural materials which must withstand it,” said first author David Cook, a Ph.D. student in Ritchie’s lab. “We have exhausted the ability to further optimize the materials we currently use at high temperatures, and there’s a big need for novel metallic materials. That’s what this alloy shows promise in.”

The alloy in this study is from a new class of metals known as refractory high or medium entropy alloys (RHEAs/RMEAs). Most of the metals we see in commercial or industrial applications are alloys made of one main metal mixed with small quantities of other elements, but RHEAs and RMEAs are made by mixing near-equal quantities of metallic elements with very high melting temperatures, which gives them unique properties that scientists are still unraveling. Ritchie’s group has been investigating these alloys for several years because of their potential for high-temperature applications.

“Our team has done previous work on RHEAs and RMEAs and we have found that these materials are very strong, but generally possess extremely low fracture toughness, which is why we were shocked when this alloy displayed exceptionally high toughness,” said co-corresponding author Punit Kumar, a postdoctoral researcher in the group.

According to Cook, most RMEAs have a fracture toughness less than 10 MPa√m, which makes them some of the most brittle metals on record. The best cryogenic steels, specially engineered to resist fracture, are about 20 times tougher than these materials. Yet the niobium, tantalum, titanium, and hafnium (Nb45Ta25Ti15Hf15) RMEA alloy was able to beat even the cryogenic steel, clocking in at over 25 times tougher than typical RMEAs at room temperature.

But engines don’t operate at room temperature. The scientists evaluated strength and toughness at five temperatures total: -196°C (the temperature of liquid nitrogen), 25°C (room temperature), 800°C, 950°C, and 1200°C. The last temperature is about 1/5 the surface temperature of the sun.

The team found that the alloy had the highest strength in the cold and became slightly weaker as the temperature rose, but still boasted impressive figures throughout the wide range. The fracture toughness, which is calculated from how much force it takes to propagate an existing crack in a material, was high at all temperatures.

Unraveling the atomic arrangements

Almost all metallic alloys are crystalline, meaning that the atoms inside the material are arranged in repeating units. However, no crystal is perfect, they all contain defects. The most prominent defect that moves is called the dislocation, which is an unfinished plane of atoms in the crystal. When force is applied to a metal it causes many dislocations to move to accommodate the shape change. For example, when you bend a paper clip which is made of aluminum, the movement of dislocations inside the paper clip accommodates the shape change. However, the movement of dislocations becomes more difficult at lower temperatures and as a result many materials become brittle at low temperatures because dislocations cannot move. This is why the steel hull of the Titanic fractured when it hit an iceberg. Elements with high melting temperatures and their alloys take this to the extreme, with many remaining brittle up to even 800°C. However, this RMEA bucks the trend, withstanding snapping even at temperatures as low as liquid nitrogen (-196°C).

To understand what was happening inside the remarkable metal, co-investigator Andrew Minor and his team analyzed the stressed samples, alongside unbent and uncracked control samples, using four-dimensional scanning transmission electron microscopy (4D-STEM) and scanning transmission electron microscopy (STEM) at the National Center for Electron Microscopy, part of Berkeley Lab’s Molecular Foundry.

The electron microscopy data revealed that the alloy’s unusual toughness comes from an unexpected side effect of a rare defect called a kink band. Kink bands form in a crystal when an applied force causes strips of the crystal to collapse on themselves and abruptly bend. The direction in which the crystal bends in these strips increases the force that dislocations feel, causing them to move more easily. On the bulk level, this phenomenon causes the material to soften (meaning that less force has to be applied to the material as it is deformed). The team knew from past research that kink bands formed easily in RMEAs, but assumed that the softening effect would make the material less tough by making it easier for a crack to spread through the lattice. But in reality, this is not the case.

“We show, for the first time, that in the presence of a sharp crack between atoms, kink bands actually resist the propagation of a crack by distributing damage away from it, preventing fracture and leading to extraordinarily high fracture toughness,” said Cook.

The Nb45Ta25Ti15Hf15 alloy will need to undergo a lot more fundamental research and engineering testing before anything like a jet plane turbine or SpaceX rocket nozzle is made from it, said Ritchie, because mechanical engineers rightfully require a deep understanding of how their materials perform before they use them in the real world. However, this study indicates that the metal has potential to build the engines of the future.

This research was conducted by David H. Cook, Punit Kumar, Madelyn I. Payne, Calvin H. Belcher, Pedro Borges, Wenqing Wang, Flynn Walsh, Zehao Li, Arun Devaraj, Mingwei Zhang, Mark Asta, Andrew M. Minor, Enrique J. Lavernia, Diran Apelian, and Robert O. Ritchie, scientists at Berkeley Lab, UC Berkeley, Pacific Northwest National Laboratory, and UC Irvine, with funding from the Department of Energy (DOE) Office of Science. Experimental and computational analysis was conducted at the Molecular Foundry and the National Energy Research Scientific Computing Center — both are DOE Office of Science user facilities.



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Giant galactic explosion exposes galaxy pollution in action

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Giant galactic explosion exposes galaxy pollution in action


A team of international researchers studied galaxy NGC 4383, in the nearby Virgo cluster, revealing a gas outflow so large that it would take 20,000 years for light to travel from one side to the other.

The discovery was published today in the journal Monthly Notices of the Royal Astronomical Society.

Lead author Dr Adam Watts, from The University of Western Australia node at the International Centre for Radio Astronomy Research (ICRAR), said the outflow was the result of powerful stellar explosions in the central regions of the galaxy that could eject enormous amounts of hydrogen and heavier elements.

The mass of gas ejected is equivalent to more than 50 million Suns.

“Very little is known about the physics of outflows and their properties because outflows are very hard to detect,” Dr Watts said.

“The ejected gas is quite rich in heavy elements giving us a unique view of the complex process of mixing between hydrogen and metals in the outflowing gas.

“In this particular case, we detected oxygen, nitrogen, sulphur and many other chemical elements.”

Gas outflows are crucial to regulate how fast and for how long galaxies can keep forming stars. The gas ejected by these explosions pollutes the space between stars within a galaxy, and even between galaxies, and can float in the intergalactic medium forever.

The high-resolution map was produced with data from the MAUVE survey, co-led by ICRAR researchers Professors Barbara Catinella and Luca Cortese, who were also co-authors of the study.

The survey used the MUSE Integral Field Spectrograph on the European Southern Observatory’s Very Large Telescope, located in northern Chile.

“We designed MAUVE to investigate how physical processes such as gas outflows help stop star formation in galaxies,” Professor Catinella said.

“NGC 4383 was our first target, as we suspected something very interesting was happening, but the data exceeded all our expectations.

“We hope that in the future, MAUVE observations reveal the importance of gas outflows in the local Universe with exquisite detail.”



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