Researchers at Indiana University and Wuhan University in China have unveiled a groundbreaking chemical process that could streamline the development of pharmaceutical compounds, chemical building blocks that influence how drugs interact with the body. Their study, published in Chem, describes a novel light-driven reaction that efficiently produces tetrahydroisoquinolines, a group of chemicals that play a crucial role in medicinal chemistry.

Tetrahydroisoquinolines serve as the foundation for treatments targeting Parkinson’s disease, cancer, and cardiovascular disorders. These compounds are commonly found in medications such as painkillers and drugs for high blood pressure, as well as in natural sources like certain plants and marine organisms.

Traditionally, chemists have relied on well-established but limiting methods to synthesize these molecules. The new research, co-authored by Kevin Brown, the James F. Jackson Professor of Chemistry in the College of Arts and Sciences at Indiana University Bloomington, and Professors Xiaotian Qi, Wang Wang, and Bodi Zhao of Wuhan University, presents a fundamentally different approach.

How It Works: Light as a Chemical Tool

Instead of using traditional chemical reactions, scientists harness light to trigger a process called photoinduced energy transfer, wherein light initiates a controlled reaction between sulfonylimines (a type of chemical compound) and alkenes (another type of compound), leading to the creation of tetrahydroisoquinolines — a type of complex molecule. This method allows for the development of new structural patterns in the molecules, which were previously difficult or impossible to create using other methods, offering a more efficient way to make complex molecules.

“The key innovation in this study is the use of a light-activated catalyst, a special molecule that speeds up the reaction without being used up itself,” said Professor Brown. “Traditional methods require high temperatures or strong acids — like trying to cook food with a blowtorch instead of a stove. These harsh conditions can sometimes create unwanted side reactions, or make the process less useful for certain chemicals. The new process, however, uses molecules that respond to light, and can bypass heating by access new energy states. This makes the reaction cleaner, more efficient, and less likely to create unwanted byproducts.”

Brown and colleagues also found that tiny changes in the location of electrons within the starting materials had a huge impact on how the reaction played out — akin to if these electrons were puzzle pieces that needed to fit together just right. By tweaking the shapes of these pieces, the scientists made sure that only the desired product was formed, making the process highly selective. This is crucial for making medicines, where even a small mistake in a molecule’s structure can turn a helpful drug into something useless or even harmful.

Implications for Medicine and Other Industries

“The ability to create a wider range of tetrahydroisoquinoline-based molecules means that medicinal chemists can now explore new drug candidates for treating diseases like Parkinson’s, certain types of cancer, and heart conditions,” noted Professor Qi. “Right now, some diseases have very few effective treatment options, and this method could help scientists discover new and better drugs more quickly.”

Beyond pharmaceuticals, this research could also impact other industries that rely on fine chemicals. In agriculture, for example, similar chemical reactions could be used to develop more effective pesticides or fertilizers. In materials science, it could help create new synthetic materials with specific properties, such as better durability and longevity and greater resistance to heat for the aerospace, automotive, electronics, and medical industries.

The researchers plan to fine-tune the reaction conditions, meaning, they will experiment with different ingredients and settings to make the improve the process further. They also aim to find out if this method can work on even more types of molecules, expanding its usefulness. In addition, they hope to partner with pharmaceutical companies to test whether this technique can be used to produce medicines, potentially leading to new drug discoveries that could make a difference in people’s lives.

“This approach gives chemists a powerful new tool,” said Professor Brown. “We hope especially it will open the door to the development of new and improved therapies for patients around the world.”

As the field of photochemistry continues to expand, innovations like this may redefine how medicines and essential chemicals are made, paving the way for faster, cleaner, and more efficient production methods.

With computer assistance, the researchers assembled these fragments like puzzle pieces to compile the entire genome. It was only then that they realised they were dealing with a previously unknown group of archaea.

Like bacteria, archaea are single-celled organisms. Genetically, however, there are significant differences between the two domains, especially regarding their cell envelopes and metabolic processes.

After a further search, microbiologists identified the corresponding organisms, described them and classified them as a separate archaeal sub-group: Asgard archaea. Their name, taken from the heavenly realm in Norse mythology, references their initial discovery close to Loki’s Castle — a black smoker on the mid-Atlantic ridge between Norway and Svalbard.

In fact, Asgard archaea appeared almost heaven-sent for research: they turned out to be a missing link between archaea and eukaryotes — that is, between archaea and organisms whose cells contain a nucleus, such as plants and animals.

Tree of life with one branch fewer

In recent years, researchers have found growing indications of close links between Asgard archaea and eukaryotes, and that the latter may have evolved from the former. The division of all living organisms into the three domains of bacteria, archaea and eukaryotes did not hold up to this surprising discovery.

Some researchers have since proposed regarding eukaryotes as a group within Asgard archaea. This would reduce the number of domains of life from three to two: archaea, including eukaryotes, and bacteria.

At ETH Zurich, Professor Martin Pilhofer and his team are fascinated by Asgard archaea and have examined the mysterious microbes for several years.

In an article published in Nature two years ago, the ETH researchers explored details of the cellular structure and architecture of Lokiarchaeum ossiferum. Originating in the sediments of a brackish water channel in Slovenia, this Asgard archaeon was isolated by researchers in Christa Schleper’s laboratory at the University of Vienna.

In that study, Pilhofer and his postdoctoral researchers Jingwei Xu and Florian Wollweber demonstrated that Lokiarchaeum ossiferum possesses certain structures also typical of eukaryotes. “We found an actin protein in that species that appears very similar to the protein found in eukaryotes — and occurs in almost all Asgard archaea discovered to date,” says Pilhofer.

In the first study, the researchers combined different microscopy techniques to demonstrate that this protein — called Lokiactin — forms filamentous structures, especially in the microbes’ numerous tentacle-like protrusions. “They appear to form the skeleton for the complex cell architecture of Asgard archaea,” adds Florian Wollweber.

In addition to actin filaments, eukaryotes also possess microtubules. These tube-shaped structures are the second key component of the cytoskeleton and are comprised of numerous tubulin proteins. These tiny tubes are important for transport processes within a cell and the segregation of chromosomes during cell division

The origin of these microtubules has been unclear — until now. In a newly published article in Cell , the ETH researchers discovered related structures in Asgard archaea and describe their structure. These experiments show that Asgard tubulins form very similar microtubules, albeit smaller than those in their eukaryotic relatives.

However, only a few Lokiarchaeum cells form these microtubules. And, unlike actin, these tubulin proteins only appear in very few species of Asgard archaea.

Scientists do not yet understand why tubulins appear so rarely in Lokiarchaea, or why they are needed by cells. In eukaryotes, microtubuless are responsible for transport processes within the cell. In some cases, motor proteins “walk along” these tubes. The ETH researchers have not yet observed such motor proteins in Asgard archaea.

“We have shown, however, that the tubes formed from these tubulins grow at one end. We therefore suspect that they perform similar transport functions as the microtubules in eukaryotes,” says Jingwei Xu, the co-first author of the Cell study. He produced the tubulins in a cell culture with insect cells and examined their structure.

Researchers from the fields of microbiology, biochemistry, cell biology and structural biology collaborated closely on the study. “We would never have progressed so far without this interdisciplinary approach,” emphasises Pilhofer with a degree of pride.

Was the cytoskeleton essential for the development of complex life? While some questions remain unanswered, the researchers are confident that the cytoskeleton was an important step in the evolution of eukaryotes.

This step could have occurred aeons ago, when an Asgard archaeon entwined a bacterium with its appendages. In the course of evolution, this bacterium developed into a mitochondrion, which serves as the powerhouse of modern cells. Over time, the nucleus and other compartments evolved — and the eukaryotic cell was born.

“This remarkable cytoskeleton was probably at the beginning of this development. It could have enabled Asgard archaea to form appendages, thereby allowing them to interact with, and then seize and engulf a bacterium,” says Pilhofer.

Fishing for Asgard archaea

Pilhofer and his colleagues now plan to turn their attention to the function of actin filaments and archaeal tubulin along with the resulting microtubules.

They also aim to identify the proteins that researchers have discovered on the surface of these microbes. Pilhofer hopes his team will be able to develop antibodies precisely tailored to these proteins. This would enable researchers to “fish” specifically for Asgard archaea in mixed microbe cultures.

“We still have a lot of unanswered questions about Asgard archaea, especially regarding their relation to eukaryotes and their unusual cell biology,” says Pilhofer. “Tracking down the secrets of these microbes is fascinating.”

In a new paper, published in the journal of Additive Manufacturing, the team introduces a new framework they’ve dubbed the Accurate Inverse process optimization framework in laser Directed Energy Deposition (AIDED).

The new AIDED framework optimizes laser 3D printing to enhance the accuracy and robustness of the finished product. This advancement aims to produce higher quality metal parts for industries, such as aerospace, automotive, nuclear and health care, by predicting how the metal will melt and solidify to find optimal printing conditions.

“The wider adoption of directed energy deposition — ?a major metal 3D printing technology — is currently hindered by the high cost of finding optimal process parameters through trial and error,” says Xiao Shang, PhD candidate and first author of the new study.

“Our framework quickly identifies the optimal process parameters for various applications based on industry needs.”

Metal additive manufacturing uses a high-powered laser to selectively fuse fine metallic powder, building parts layer by layer from a precise 3D digital model.

Unlike traditional methods, which involve cutting, casting or machining materials, metal additive manufacturing directly creates complex, highly customized components with minimal material waste.

“One major challenge of 3D metal printing is the speed and precision of the manufacturing process,” says Zou. “Variations in printing conditions can lead to inconsistencies in the quality of the final product, making it difficult to meet industry standards for reliability and safety.

“Another major challenge is determining the optimal settings for printing different materials and parts. Each material — whether it’s titanium for aerospace and medical applications or stainless steel for the nuclear reactors — has unique properties that require specific laser power, scanning speed and temperature conditions. Finding the right combination of these parameters across a vast range of process parameters is a complex and time-consuming task.”

These challenges inspired Zou and his lab group to develop their new framework. AIDED operates in a closed-loop system where a genetic algorithm — a method that mimics natural selection to find optimal solutions — first suggests process parameters combinations, which machine learning models then evaluate for printing quality.

The genetic algorithm checks these predictions for optimality, repeating the process until the best parameters are found.

“We have demonstrated that our framework can identify optimal process parameters from customizable objectives in as little as one hour, and it accurately predicts geometries from process parameters,” says Shang. “It is also versatile and can be used with various materials.”

To develop the framework, the researchers conducted numerous experiments to collect their vast datasets. This essential but time-consuming challenge ensured that the datasets covered a wide range of process parameters.

Looking ahead, the team is working to develop an enhanced autonomous, or self-driving, additive manufacturing system that operates with minimal human intervention, similar to how autonomous vehicles drive themselves, says Zou.

“By combining cutting-edge additive manufacturing methods with artificial intelligence, we aim to create a novel closed loop controlled self-driving laser system,” he says.

“This system will be capable of sensing potential defects in real-time, predicting issues before they occur, and automatically adjusting processing parameters to ensure high-quality production. It will be versatile enough to work with different materials and part geometries, making it a game-changer for manufacturing industries.”

In the meantime, the researchers hope AIDED will transform process optimization in industries that use metal 3D printing.

“Industries such as aerospace, biomedical, automotive, nuclear and more would welcome such a low-cost yet accurate solution to facilitate their transition from traditional manufacturing to 3D printing,” says Shang.

“By the year 2030, additive manufacturing is expected to reshape manufacturing across multiple high-precision industries,” adds Zou. “The ability to adaptively correct defects and optimize parameters will accelerate its adoption.”

This discovery stems from studies in mice, in which researchers observed memory formation using advanced imaging techniques, including miniature microscopes that captured single-cell resolution in live animals.

The study shows that memories are stored in dendritic compartments: When one memory forms, the affected dendrites are primed to capture new information arriving within the next few hours, linking memories formed close in time.

“If you think of a neuron as a computer, dendrites are like tiny computers inside it, each performing its own calculations,” said lead author Megha Sehgal, assistant professor of psychology at The Ohio State University. “This discovery shows that our brains can link information arriving close in time to the same dendritic location, expanding our understanding of how memories are organized.”

The research was published recently in the journal Nature Neuroscience.

Though most learning and memory studies have focused on how a single memory is formed in the brain, Sehgal’s lab aims to determine how we organize multiple memories.

“The idea is that we don’t form memories in isolation. You don’t form a single memory. You use that memory, make a framework of memories, and then pull from that framework when you need to make adaptive decisions,” she said.

Neurons, the principal brain cells, are known to encode and relay information. Dendrites — the branch-like projections extending from neurons — serve a critical role in how information is processed, receiving incoming information and passing it to the neuronal cell body.

But dendrites are not just passive conduits — each dendritic branch can act as an independent computational unit. While dendrites have been thought to play an important role in the brain’s function, how they shape learning and memory has been unclear until now, Sehgal said.

When mice were exposed in experiments to two different environments within a short period of time, the team found that memories of these spaces became linked. If mice received a mild shock in one of these spaces, the animals ended up freezing out of fear in both environments, associating the shock from one room with the other.

The study focused on the retrosplenial cortex (RSC), a brain region crucial for spatial and contextual memory. The researchers observed that linked memories consistently engaged the same groups of RSC neurons and their dendritic branches.

The team tracked these changes at the dendritic level by visualizing dendritic spines, tiny protrusions on dendrites where neurons communicate. The formation of new memories triggered the addition of clustered dendritic spines, a process critical for strengthening communication between neurons and facilitating learning.

Dendritic spine clusters formed after the first memory were more likely to attract new spines during a second closely timed memory, physically linking those experiences in the brain.

To confirm the role of dendrites in linking memories, the team used optogenetics, a technique that allows researchers to control neurons with light. By reactivating specific dendritic segments that had been active during memory formation, they were able to link otherwise unrelated memories, further demonstrating the importance of dendritic changes in shaping memory networks.

In addition to illuminating a previously unknown role for dendrites in linking memories, the findings open new avenues for understanding memory-related disorders, Sehgal said.

“Our work not only expands our understanding of how memories are formed but also suggests exciting new possibilities for manipulating higher order memory processes,” she said. “This could have implications for developing therapies for memory-related conditions such as Alzheimer’s disease.”

Sehgal co-led the study with Alcino Silva, director of the Integrative Center for Learning and Memory at UCLA, and Panayiota Poirazi, research director of the Foundation for Research and Technology-Hellas in Greece.

This work was supported by the National Institute of Mental Health, the National Institute on Aging, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the European Commission, the National Institutes of Health and the Einstein Foundation Berlin.