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.

Now, Johns Hopkins Medicine scientists say they have shed new light on how bacteria protect themselves from certain phage invaders — by seizing genetic material from weakened, dormant phages and using it to “vaccinate” themselves to elicit an immune response.

In their experiments, the scientists say Streptococcus pyogenes bacteria (which cause strep throat) take advantage of a class of phages known as temperate phages, which can either kill cells or become dormant. The bacteria steal genetic material from temperate phages during this dormant period and form a biological “memory” of the invader that their offspring inherit as the bacteria multiply. Equipped with these memories, the new population can recognize these viruses and fight them off.

A report on the experiments, supported in part by the National Institutes of Health, was published March 12 in the journal Cell Host & Microbe. The findings help scientists better understand how bacterial cells that cause serious diseases, including Staph and E. coli infections and cholera, become toxic to humans — a process that involves toxic genes expressed by otherwise dormant phages that reside within the bacterial cell, says corresponding author Joshua Modell, Ph.D., associate professor of molecular biology and genetics at the Johns Hopkins University School of Medicine.

“We essentially wanted to answer the question: If bacterial cells don’t have any memory, or survival skills, to combat a new temperate phage that shows up, how do they buy themselves enough time to establish a new memory, before they succumb to that initial infection?” says Modell.

The Johns Hopkins investigators say bacteria have long been known to use CRISPR-Cas systems to chop up phage DNA, break it down and get rid of it. Crucially, CRISPR systems can only destroy DNA that matches a “memory” captured from a prior infection and stored within the bacteria’s own genome, say the researchers. In this way, the CRISPR system acts as a recording device that documents the long list of foreign invaders encountered by a particular bacterial strain.

To conduct their research, the scientists say they infected populations of bacteria with naturally occurring phages that go dormant or genetically engineered non-dormant phages in separate flasks that contained millions of bacterial cells.

“Our results indicate that the bacteria’s CRISPR system was more effective at using the naturally dormant phage to pull parts of the viral genetic code into their genome,” says Modell. “When we tested phages that could not go dormant, the CRISPR system did not work nearly as well.”

After isolating the bacteria that survived, and letting the survivors repopulate the flask, the scientists used genome sequencing to catalog hundreds of thousands of new DNA memories that the CRISPR Cas9 system had created from the test phages, honing in on those that contribute to cell immunity. The scientists also determined that bacteria created those memories during the temperate phage’s dormancy period, when it did not pose a threat to the population.

“This is conceptually similar to a vaccine with an attenuated virus,” says Nicholas Keith, a graduate student and first author of the paper. “We believe this is the reason why the CRISPR Cas9 system has a unique relationship with this specific class of temperate phage.”

“We can use these types of experiments to find what elements of the phage, the bacterial host and its CRISPR system are important for all stages of bacterial immunity,” Keith says.

In future experiments, the scientists aim to learn more about how CRISPR systems protect bacteria cells from viruses that don’t go dormant, Modell says.

“We know CRISPR systems are one of the first lines of defense against the transfer of hazardous genes from phages that turn bacterial cells toxic,” says Modell. “Furthermore, our studies will inform the design of ‘phage therapies’ which could be used in clinical cases where a bacterial infection is resistant to all available antibiotics.”

In addition to Keith and Modell, study contributors are Rhett Snyder from Johns Hopkins and Chad Euler from Hunter College.

The research was funded by the Johns Hopkins University School of Medicine, the National Institutes of Health National Institute of General Medical Sciences (R35GM142731), the Rita Allen Foundation and the National Science Foundation.

New research from the University of Chicago shows how a specially trained population of immune cells keeps the peace by preventing other immune cells from attacking their own. The study, published in Science, provides a better understanding of immune regulation during infection and could provide a foundation for interventions to prevent or reverse autoimmune diseases.

Several groups of white blood cells help coordinate immune responses. Dendritic cells take up proteins from foreign pathogens, chop them up into peptides called antigens, and display them on their surface. CD4+ conventional T (Tconv) cells, or helper T cells, inspect the peptides presented by dendritic cells. If the peptides are foreign antigens, the T cells expand in numbers and transform into an activated state, specialized to eradicate the pathogen. If the dendritic cell is carrying a “self-peptide,” or peptides from the body’s own tissue, the T cells are supposed to lay off.

During an autoimmune response, the helper T cells don’t distinguish between foreign peptide antigens and self-peptides properly and go on the attack no matter what. To prevent this from happening, another group of T cells called CD4+ regulatory T (Treg) cells, are supposed to intervene and prevent friendly fire from the Tconv cells.

“You can think of them [Treg cells] as peacekeeper cells,” said Pete Savage, PhD, Professor of Pathology at UChicago and senior author of the new study. Tregs obviously do their job well most of the time, but Savage said that it has never been clear how they know when to intervene and prevent helper T cells from starting an autoimmune response, and when to hold back and let them fight an infection.

So, Savage and his team, led by David Klawon, PhD, a former graduate student in his lab who is now a postdoctoral fellow at MIT, wanted to explore this property of the immune system, known in the field as self-nonself discrimination. T cells are produced in the thymus, a specialized organ of the immune system. During development, Treg cells are trained to recognize specific peptides, including self-peptides from the body. When dendritic cells present a self-peptide, the Treg cells trained to spot them intervene to stop helper T cells from getting triggered.

This specificity is what Savage’s team found makes a crucial difference in self-nonself discrimination. The researchers experimentally depleted Treg cells in mice that were specific to a single self-peptide from the prostate. In healthy mice in the absence of infection, this change did not trigger autoimmunity to the prostate. When the researchers infected mice with a bacterium that expressed the prostate self-peptide, however, the absence of matched, prostate-specific Treg cells triggered prostate-reactive T helper cells and introduced autoimmunity to the prostate.

Interestingly though, this alteration did not impair the ability of helper T cells to control the bacterial infection by responding to foreign peptides.

“It’s like a doppelganger population of T cells. The CD4 helper cells that could induce disease by attacking the self share an equivalent, matched population of these peacekeeper Treg cells,” Savage said. “When we removed Treg cells reactive to a single self-peptide, the T helper cells reactive to that self-peptide were no longer controlled, and they induced autoimmunity.”

The root causes of autoimmune disease are a complex interaction of genetics, the environment, lifestyle, and the immune system. Classic, conventional thinking in the immunology field promoted the idea that the immune system establishes self-nonself discrimination by purging the body of helper T cells that are reactive to self-peptides, thereby preventing autoimmunity. Savage said this study shows that purging is inefficient though, and that specificity matching by Treg cells may be equally as important.

“The idea is that specificity matters, and for a fully healthy immune system, you need to have a good collection of these doppelganger Treg cells,” he said. As long as the immune system generates enough matched Treg cells, they can prevent autoimmune responses without impacting responses to infections.

“It’s like flipping the idea of self-nonself discrimination upside down. Instead of having to delete all helper T cells reactive to self-antigens, you simply generate enough of these Treg peacekeeper cells instead,” Savage said.

Analysis built on national studies from Germany, Australia, the United Kingdom, and the Netherlands

It is a common fact that satisfaction in a romantic relationship declines over time. This reduction in satisfaction is particularly marked in the first years of a relationship, and a distinctive low point is often reached after a period of ten years. Instead of considering the processes that occur in the time-since-beginning of a romantic relationship, Janina Bühler and Ulrich Orth decided to look at the time-to-separation of relationships for the purposes of their research.

With this in view, they used data from four representative studies conducted in Germany, Australia, the United Kingdom, and the Netherlands. All these countries are WEIRD, i.e., Western, Educated, Industrialized, Educated, Rich, Democratic, and their individuals are free — by law — to decide about their relationship status. For each of the four data sets covering a total of 11,295 individuals there was a control group roughly the same size consisting of couples that had not separated. The surveys in the four countries were conducted over different periods of time, ranging from 12 to 21 years. In the case of Germany, the researchers employed the data of the Panel Analysis of Intimate Relationships and Family Dynamics (pairfam), a multidisciplinary longitudinal study. In all countries, the subjects were asked to specify how satisfied they were right then with their existing romantic relationship.

Using the available data, Bühler and Orth assessed the extent to which the satisfaction with the relationship developed in the light of their subsequent separation. “In order to better understand dissolving relationships, we examined them from the point of view of time-to-separation. To do this, we applied a concept that is in general use in other fields of psychology,” said Janina Bühler. Based on the data of the four national representative studies, the researchers were able to determine that relationships can be subjected to what is known as terminal decline. This decline in relationship satisfaction occurs in two phases. The initial preterminal phase, which can have a duration of several years, is characterized by a minor decline in satisfaction. However, this is followed by a transition or tipping point from which there is an accelerated decline in satisfaction. The terminal phase of a relationship after this transition point lasts 7 to 28 months, one to two years on average. “Once this terminal phase is reached, the relationship is doomed to come to an end. This is apparent from the fact that only the individuals in the separation group go through this terminal phase, not the control group,” explained Bühler.

Partners assess the terminal phase of a relationship differently

At the same time, the two partners do not experience the transition phase in the same way. The partner who initiates the separation has already become dissatisfied with the relationship at an earlier point in time. For the recipient of the separation, the transition point arrives relatively shortly before the actual separation. They experience a very rapid decline in relationship satisfaction.

“Partners pass through various phases. They do not normally separate from one day to the next, and the way these phases impact on the two partners differs,” added Bühler. In many cases, couples seek help too late, i.e., when the transition point has already been reached. “It is thus important to be aware of these relationship patterns. Initiating measures in the preterminal phase of a relationship, i.e., before it begins to go rapidly downhill, may thus be more effective and even contribute to preserving the relationship,” concluded Bühler, who also works as a couples therapist.