University of Arizona neuroscientists have come up with a new treatment approach for PPA that combines traditional speech therapy with noninvasive electrical stimulation of the brain. The technique — called transcranial direct current stimulation — uses a low electrical current applied through electrodes on the scalp.

A new study published in the Journal of Speech, Language, and Hearing Research describes the treatment approach, which the researchers found to be more effective at managing PPA compared to speech therapy alone.

“Primary progressive aphasia is a condition that causes worsening of communication skills over time. It was identified in the literature only in the last three to four decades, so it is considered pretty new in the health care world — it’s still an understudied area,” said Katlyn Nickels, the study’s lead researcher and a postdoctoral researcher in the U of A Department of Speech, Language and Hearing Sciences.

While writing and speaking words, people don’t just retrieve their meaning. They also retrieve the sound of a word while it is being spoken or written, said Aneta Kielar, the study’s senior author and an associate professor in the Department of Speech, Language and Hearing Sciences.

If there is a problem with associating words with the way they sound, it is difficult to put letters together and speak or write a word, Kielar said. This affects people’s communication in their day-to-day life and their ability to work. For their study, the researchers focused on a type of PPA called the logopenic PPA, in which people have trouble finding the right words and repeating phrases or sentences.

The researchers did neuroimaging analysis of the brain to determine the area of the brain that needs to be stimulated, as people with PPA have brain atrophy or a loss of brain cells.

“We wanted to stimulate the area that is most responsive to language and were careful not to stimulate an area that would have been atrophied already,” Kielar said.

Twelve individuals with written language deficits each received two phases of treatment: in one phase, they got speech therapy paired with active transcranial direct current stimulation. In another phase, they received the same speech therapy with placebo transcranial direct current stimulation. The order of the phases was randomized and separated by a two-month break in between.

Although all participants improved after both treatments, they showed greater and more lasting improvement following the phase with active transcranial direct current stimulation compared to placebo transcranial direct current stimulation.

“People who made numerous spelling errors and struggled to frame complete sentences before the treatment were able to form sentences that were grammatically correct, had fewer spelling errors and were more meaningful after treatment,” Kielar said.

The researchers say brain stimulation helped induce neuroplasticity, the brain’s capacity to continue to reorganize and learn. And it boosted the effects of speech therapy.

“What that means is that brain stimulation can induce the formation of synapses, the connections between neurons. These connections are important for people’s ability to learn and maintain new skills,” Kielar said.

In the future, the research group is planning to look at the genetic, cognitive and neural markers that influence the recovery from PPA. The researchers’ long-term goal is to translate their research findings to a clinical setting.

Because transcranial direct current stimulation is inexpensive, safe and easy to perform, the barriers to implementing it in clinical practice are less significant, Nickels said.

“There’s a misconception sometimes with neurodegenerative diseases, that once you get a diagnosis, there is nothing that can be done,” Nickels said. “But we have learned through our research that even when there’s a progressive brain disease, we can help restore lost function and even slow down the progression.”

This work was supported by the following grants to the senior author, Aneta Kielar: Arizona Alzheimer’s Consortium Grant, Arizona Department of Health Services (018676-00001); Innovations in Healthy Aging: Grand Challenges of Aging Seed Grant, The University of Arizona Health Sciences (2259304); and Data Science Academy-Transdisciplinary Research in Principles of Data Science at The University of Arizona (2259910). Research reported in the publication was supported by the Arizona Department of Health Services and the state of Arizona (ADHS Grant No. CTR057001) to Aneta Kielar.

Proteins and protein coding genes increase in length

The article in PNAS demonstrates that the distributions of protein lengths and their corresponding genes follow log-normal distributions across the whole tree of life. To do this, 9,913 different proteomes and 33,627 genomes were analyzed. Log-normal distributions typically arise as a result of multiplicative processes. Following Ockham’s razor principle, the researchers modeled the evolution of gene length distributions as multiplicative stochastic processes. In fact, they modeled the action of all genetic operators combined in relation to sequence length. Starting from LUCA, i.e., the hypothesized last universal common ancestor from which the three domains of life — the Bacteria, the Archaea, and the Eukarya — originated, the researchers found both theoretically and observationally that the average gene lengths have evolved exponentially over evolutionary time across different species. Furthermore, they discovered a scaling-invariant mechanism of gene growth across the entire tree of life, where the variance directly depends on the mean protein length. By representing all the species captured in the 33,627 genomes, the team was able to observationally verify the predictions and, moreover, show that the average gene length is a very good surrogate for organismal complexity. In a pure exercise of quantitative biology, Dr. Bartolo Luque from the Polytechnic University of Madrid added: “From knowing the average length of protein-coding genes in a species, we can calculate the whole distribution of gene length within that species.”

When representing the evolution of the average protein lengths versus their corresponding gene lengths across different species, it is observed that they evolve simultaneously in prokaryotes, because there are almost no non-coding sequences in their genes. However, once the average gene length reaches 1,500 nucleotides, the proteins decouple from the multiplicative process of gene growth, and the average protein length stabilizes after the onset of the eukaryotic cell at about 500 amino acids in a clear threshold, marking the appearance of the eukaryotic cell. From that point onward, and unlike what happens with proteins, the average gene length continues to increase as it did in prokaryotes, due to the presence of non-coding sequences.

Algorithmic phase transition

A critical phenomena analysis then concluded that a phase transition, well studied in the physics of magnetic materials, occurred at a critical gene length of 1,500 nucleotides. This marked eukaryogenesis and divides the evolution of life into two distinct phases: a coding phase (Prokarya) and a non-coding phase (Eukarya). Additionally, characteristic phenomena of these transitions are observed, such as critical slowing down, where the system’s dynamics become trapped in many metastable states around the critical point. “This is corroborated in early protists and fungi,” said Dr. Fernando Ballesteros from the University of Valencia.

Moreover, “the phase transition was algorithmic,” added Professor Jordi Bascompte from the University of Zurich. In the coding phase, in a scenario close to LUCA, with short proteins, increasing the length of proteins and their corresponding genes was computationally simple. However, as the protein lengths grew, the search for longer proteins became unfeasible. This tension caused by genes that grew at the same rate as before while proteins could not was resolved continuously but abruptly with the incorporation of non-coding sequences into the genes. With this innovation, the algorithm for searching for new proteins rapidly reduced its computational complexity, becoming non-linear through the spliceosome and the nucleus, which separated transcription and splicing from translation. This happened at the critical point of phase transition, which this study dates to 2.6 billion years ago.

The study recently published in PNAS not only answers essential questions, but is interdisciplinary, combining computational biology, evolutionary biology, and physics. “It has the potential to interest a wide audience across many disciplines and serve as a foundation for other groups to explore different research avenues, such as energy or information theory,” emphasized Dr. Enrique Muro of the Institute of Organismic and Molecular Evolution at Mainz University. The eukaryotic cell, the most significant increase in complexity in the history of life’s evolution on Earth, emerged as a phase transition and unlocked the path toward other major transitions — such as multicellularity, sexuality, and sociability — that shaped life on our planet as we know it today.

Published on Friday in the International Journal of Obesity, the research is the first to test in humans the relationship between HFHS diets, particularly those high in refined sugar and saturated fat, and first-person spatial navigation. Spatial navigation is the ability to learn and remember a path from one location to another, a process that can approximate the health of the brain’s hippocampus.

Dr Dominic Tran from the Faculty of Science’s School of Psychology led the research, which found HFHS diets have a detrimental effect on some aspects of cognitive function. It is likely those effects centre on the hippocampus, the brain structure important for spatial navigation and memory formation, rather than acting across the entire brain.

“The good news is we think this is an easily reversible situation,” Dr Tran said. “Dietary changes can improve the health of the hippocampus, and therefore our ability to navigate our environment, such as when we’re exploring a new city or learning a new route home.”

The research team recruited 55 university students aged between 18 and 38. Each participant completed questionnaires capturing their intake of sugary and fatty foods. They also had their working memory tested in a number recall exercise, and their body mass index (BMI) recorded.

The experiment itself required participants to navigate a virtual reality maze and locate a treasure chest six times. The maze was surrounded by landmarks that participants could use to remember their route. Their starting point and the location of the treasure chest remained constant in each trial.

If participants found the treasure in less than four minutes, they continued to the next trial. If they failed to find the treasure in this time, they were teleported to its location and given 10 seconds to familiarise themselves with that location before the next trial.

A seventh trial removed the treasure chest from the virtual maze but asked participants to find and mark its former location based purely on memory. Those with lower levels of fat and sugar in their diets were able to pinpoint the location with a higher degree of accuracy than those who consumed these foods multiple times a week.

“After controlling for working memory and BMI, measured separately to the experiment, participants’ sugar and fat intake was a reliable predictor of performance in that final, seventh, test,” Dr Tran said.

Dr Tran said the results highlight the importance of making good dietary choices to maintain healthy brain function.

“We’ve long known eating too much refined sugar and saturated fat brings the risk of obesity, metabolic and cardiovascular disease, and certain cancers. We also know these unhealthy eating habits hasten the onset of age-related cognitive decline in middle age and older adults.

“This research gives us evidence that diet is important for brain health in early adulthood, a period when cognitive function is usually intact,” Dr Tran said.

Dr Tran said the sample group used in this research was not representative of the wider population, but the findings still apply more broadly.

“It’s likely our participants were a little healthier than the general population and we think, if our sample better represented the public, the impact of diet on spatial navigation would likely be even more pronounced.”

Dr Tran is a recipient of an Australian Research Council Discovery Early Career Research Award (DECRA).

“Earth-like planets in the habitable zone — the region around a star where temperatures could allow liquid water to exist — can easily be up to a billion times dimmer than their host star,” said research team leader Nico Deshler from the University of Arizona. “This makes them difficult to detect because their faint light is overwhelmed by the star’s brightness. Our new coronagraph design siphons away starlight that might obscure exoplanet light before capturing an image.”

In Optica, the researchers show that the new coronagraph can theoretically achieve the fundamental limits of exoplanet detection and localization set by quantum optics. They also used it to capture images that allowed them to estimate the position of artificial exoplanets with distances from their host star up to 50 times smaller than what the telescope’s resolution limit would normally allow.

“Compared to other coronagraph designs, ours promises to supply more information about so-called sub-diffraction exoplanets — those which lie below the resolution limits of the telescope,” said Deshler. “This could allow us to potentially detect biosignatures and discover the presence of life among the stars.”

Blinded by the light

Optically analyzing exoplanets poses a formidable challenge because, at astronomical scales, they are often too close to their parent star for current telescopes to resolve. Exoplanets can also be orders of magnitude dimmer than their host star. Although astronomers have developed various ways to indirectly infer the presence of a planet around a prospective star, directly observing exoplanets in images would be ideal.

With NASA’s next-generation space telescope, the Habitable Worlds Observatory (HWO), being dedicated to exoplanet science, many coronagraph designs have emerged, each with different practical and theoretical performance trade-offs. At the same time, recent work has shown that traditional notions of resolution for telescopes do not reflect fundamental limits and can be circumvented with careful optical pre-processing.

Inspired by these developments, the researchers decided to use a spatial mode sorter available in their lab to develop an improved coronagraph that theoretically rejects all the light from an on-axis star while achieving maximal throughput of an off-axis exoplanet.

Much like piano notes emit different acoustic frequencies, light sources in space excite different spatial modes — unique shapes and patterns of oscillation — depending on their position. The researchers separated these different modes using a mode sorter to isolate and eliminate light from a star and an inverse mode sorter to recompose the optical field after the starlight is rejected. This made it possible to capture an image of the exoplanet without the star.

“Our coronagraph directly captures an image of the exoplanet, as opposed to measuring only the quantity of light from the exoplanet without any spatial orientation,” said Deshler. “Images can provide context and composition information that can be used to determine exoplanet orbits and identify other objects that scatter light from a star such as exozodiacal dust clouds.”

Imaging faint exoplanets

After configuring their coronagraph in the lab, the researchers constructed an artificial star-exoplanet scene in which the exoplanet was positioned close enough to the star to be unresolvable with a traditional telescope. The contrast ratio between the star and the planet was set to 1000:1.

The researchers scanned the position of the exoplanet to simulate an orbit where the planet traverses in front of the star and then tried to determine its position in each frame. The images captured with their experimental setup incorporating the new coronagraph allowed them to estimate the position of the exoplanet at sub-diffraction planet-star separations.

The researchers are working to improve the mode sorter to reduce crosstalk, a type of interference in which light leaks across different optical modes. For scenes with moderate contrast levels, crosstalk is not very problematic. However, the extreme contrasts found in exoplanet science would require a very high-fidelity spatial mode sorter to sufficiently isolate light from the star.

The researchers say that this proof-of-principle experiment could inspire further exploration of optical pre-processing with spatial mode sorters in future astronomical instrumentation. For example, the spatial mode filtering methods they used could address more complex scenarios, such as treating stars as extended objects, and may also lead to new imaging methods for quantum sensing, medical imaging and communications.

Scientists at the Medical Research Council (MRC) Mitochondrial Biology Unit, University of Cambridge, have worked out the structure of this machine and shown how it operates like the lock on a canal to transport pyruvate — a molecule generated in the body from the breakdown of sugars — into our mitochondria.

Known as the mitochondrial pyruvate carrier, this molecular machine was first proposed to exist in 1971, but it has taken until now for scientists to visualise its structure at the atomic scale using cryo-electron microscopy, a technique used to magnify an image of an object to around 165,000 times its real size. Details are published today in Science Advances.

Dr Sotiria Tavoulari, a Senior Research Associate from the University of Cambridge, who first determined the composition of this molecular machine, said: “Sugars in our diet provide energy for our bodies to function. When they are broken down inside our cells they produce pyruvate, but to get the most out of this molecule it needs to be transferred inside the cell’s powerhouses, the mitochondria. There, it helps increase 15-fold the energy produced in the form of the cellular fuel ATP.”

Maximilian Sichrovsky, a PhD student at Hughes Hall and joint first author of the study, said: “Getting pyruvate into our mitochondria sounds straightforward, but until now we haven’t been able to understand the mechanism of how this process occurs. Using state-of-the-art cryo-electron microscopy, we’ve been able to show not only what this transporter looks like, but exactly how it works. It’s an extremely important process, and understanding it could lead to new treatments for a range of different conditions.”

Mitochondria are surrounded by two membranes. The outer one is porous, and pyruvate can easily pass through, but the inner membrane is impermeable to pyruvate. To transport pyruvate into the mitochondrion, first an outer ‘gate’ of the carrier opens, allowing pyruvate to enter the carrier. This gate then closes, and the inner gate opens, allowing the molecule to pass through into the mitochondrion.

“It works like the locks on a canal but on the molecular scale,” said Professor Edmund Kunji from the MRC Mitochondrial Biology Unit, and a Fellow at Trinity Hall, Cambridge. “There, a gate opens at one end, allowing the boat to enter. It then closes and the gate at the opposite end opens to allow the boat smooth transit through.”

Because of its central role in controlling the way mitochondria operate to produce energy, this carrier is now recognised as a promising drug target for a range of conditions, including diabetes, fatty liver disease, Parkinson’s disease, specific cancers, and even hair loss.

Pyruvate is not the only energy source available to us. Our cells can also take their energy from fats stored in the body or from amino acids in proteins. Blocking the pyruvate carrier would force the body to look elsewhere for its fuel — creating opportunities to treat a number of diseases. In fatty liver disease, for example, blocking access to pyruvate entry into mitochondria could encourage the body to use potentially dangerous fat that has been stored in liver cells.

Likewise, there are certain tumour cells that rely on pyruvate metabolism, such as in some types of prostate cancer. These cancers tend to be very ‘hungry’, producing excess pyruvate transport carriers to ensure they can feed more. Blocking the carrier could then starve these cancer cells of the energy they need to survive, killing them.

Previous studies have also suggested that inhibiting the mitochondrial pyruvate carrier may reverse hair loss. Activation of human follicle cells, which are responsible for hair growth, relies on metabolism and, in particular, the generation of lactate. When the mitochondrial pyruvate carrier is blocked from entering the mitochondria in these cells, it is instead converted to lactate.

Professor Kunji said: “Drugs inhibiting the function of the carrier can remodel how mitochondria work, which can be beneficial in certain conditions. Electron microscopy allows us to visualise exactly how these drugs bind inside the carrier to jam it — a spanner in the works, you could say. This creates new opportunities for structure-based drug design in order to develop better, more targeted drugs. This will be a real game changer.”

The research was supported by the Medical Research Council and was a collaboration with the groups of Professors Vanessa Leone at the Medical College of Wisconsin, Lucy Forrest at the National Institutes of Health, and Jan Steyaert at the Free University of Brussels.

It depends, of course, on whether you’re making a hearty winter stew or getting ready to watch the Super Bowl.

Most scientists agree that categorizing an object — like thinking of a carrot as either a root vegetable or a party snack — is the job of the prefrontal cortex, the brain region responsible for reasoning and other high-level functions that make us smart and social. In that account, the eyes and visual regions of the brain are kind of like a security camera collecting data and processing it in a standardized way before passing it off for analysis.

However, a new study led by biomedical engineer and neuroscientist Nuttida Rungratsameetaweemana, an assistant professor at Columbia Engineering, shows that the brain’s visual regions play an active role in making sense of information. Crucially, the way it interprets the information depends on what the rest of the brain is working on.

If it’s Super Bowl Sunday, the visual system sees those carrots on a veggie tray before the prefrontal cortex knows they exist.

Published April 11 in Nature Communications, the study provides some of the clearest evidence yet that early sensory systems play a role in decision-making — and that they adapt in real-time. It also points to new approaches for designing AI systems that can adapt to new or unexpected situations.

Chromosomal rearrangements where large chunks of chromosomes are inverted, moved, deleted or duplicated, provide a possible source for such large-scale “macromutations.” However, characterizing chromosomal rearrangements with commonly tried DNA sequencing methods has been difficult.

Many organisms, including humans, are diploid, meaning they have two sets of chromosomes — one from each parent. The same is true for stick insects. This makes identifying chromosomal rearrangements with species challenging when assembling genomes.

“In the past, we’ve averaged data from each chromosome set, but the limited accuracy of this method doesn’t tell the whole story,” says Utah State University evolutionary biologist Zachariah Gompert. “Using newer, molecular and computational approaches that generate phased genome assemblies, where the two copies of each chromosome are assembled separately, has enabled us to directly show how complex chromosomal rearrangements have allowed stick insects to adapt by being cryptic on different host plants and thereby avoid predation.”

In the April 18, 2025 online issue of the American Association for the Advancement of Science journal Science, Gompert and colleagues report adaptive divergence in cryptic color pattern is underlain by two distinct, complex chromosomal rearrangements, where millions of bases of DNA were flipped backwards and moved from one part of a chromosome to another, independently in populations of stick insects on different mountains. Contributing authors on the paper include Gompert’s long-time collaborator Patrik Nosil and other researchers from the French National Center for Scientific Research (CNRS), along with scientists from the University of Notre Dame, the University of Nevada, Reno, and The Institute of Cancer Research in the United Kingdom. The research is supported by the National Science Foundation and the European Research Council.

The scientists studied Timema cristinae insects with varied color patterns, collected from two mountains near Santa Barbara, California. The wingless, plant-feeding insects are divergently adapted to two different plant species in the coastal chaparral habitats. One stick insect pattern is green, allowing it to blend in with the California lilac, while the other sports a thin, white stripe on its back making it nearly undetectable among the needle-like leaves of the chamise shrub.

Gompert and colleagues showed this adaptive difference in color pattern is almost completely explained by the presence versus absence of these individual complex, chromosomal rearrangements.

“The new phased genomic assembly technology used in this study was a critical piece in helping us examine how color pattern evolved in these insects,” says Gompert, professor in USU’s Department of Biology and the USU Ecology Center. “Our findings suggest chromosomal rearrangements might be more widespread and more complex than we previously thought.”

He says these mutations, despite being large, are easy to miss using traditional DNA sequencing approaches.

“Chromosomal rearrangements can be difficult to detect and characterize using standard approaches,” Gompert says. “We’re essentially exploring the ‘dark matter’ of the genome.”

Structural variation, he says, rather than being rare, may be regularly available to prompt evolution.

“We’re just scratching the surface,” Gompert says. “We’ve lacked the tools to detect structural variation, but with improved technology we hypothesize it plays a more important role in evolution than previously recognized.”