There has been mounting interest in the value of psychedelic-inspired compounds as treatments for brain disorders including depression, post-traumatic stress disorder and substance use disorder. Psychedelic compounds like LSD, DMT and psilocybin promote the growth and strengthening of neurons and their connections in the brain’s prefrontal cortex. The new tool could help scientists unlock the benefits of psychedelic treatments for patients with brain disorders.

“It’s important to think about the cellular mechanisms that these psychedelics act upon,” said Christina Kim, an assistant professor of neurology at the UC Davis Center for Neuroscience and School of Medicine, and an affiliate of the UC Davis Institute for Psychedelics and Neurotherapeutics. “What are they? Once we know that, we can design different variants that target the same mechanism but with fewer side effects.”

This research provides scientists with a new technique that could be used to track step by step the molecular signaling processes that are responsible for these compounds’ beneficial neuroplastic effects. What’s more, CaST accomplishes the task of cellular tagging in rapid time, taking 10 to 30 minutes rather than the hours typical of other tagging methods.

“We designed these proteins in the lab that can be packaged into DNA and then put into harmless adeno-associated viruses,” Kim said. “Once we deliver the CaST tool and these proteins into neurons, then they incubate inside the cells and start expressing.”

The research was conducted in collaboration with David Olson, founding director of the Institute for Psychedelics and Neurotherapeutics and a professor in the departments of Chemistry and Biochemistry and Molecular Medicine.

A snapshot of the brain

The CaST tool takes advantage of changes in intracellular calcium concentrations, a nearly universal marker to track activity in a neuron. When neurons exhibit high activity, they exhibit high calcium levels. CaST uses this cue to tag the cell with a small biomolecule called biotin.

In the study, Kim and her colleagues dosed mice with the psychedelic psilocybin. They then used CaST in tandem with biotin to identify neurons with increased calcium in the prefrontal cortex. The prefrontal cortex is an area affected by many brain disorders and also an area where psychedelics promote neuronal growth and strengthening.

The researchers also monitoring the head-twitch responses in the mice. Head-twitch responses are the primary behavioral correlate for hallucinations caused by psychedelics.

“What’s nice about CaST is that it can be used in a freely behaving animal,” said Kim, noting that other cellular tagging technologies require stabilizing a mouse’s head to accomplish imaging. “Biotin is also a great tagging substrate because there are many pre-existing commercial tools that can report whether biotin is present or not just by a simple staining and imaging method.”

The proof-of-concept experiment gave what Kim called “a camera snapshot” of the areas in the prefrontal cortex activated by psilocybin.

Next steps

Kim and her colleagues are now working on methods to enable brain-wide cellular labeling with the CaST tool. Additionally, they’re exploring ways to enrich the signature of individual proteins produced by neurons affected by psychedelics.

“We can send those samples to the UC Davis Proteomics Core Facility and they can give us an unbiased picture of all the proteins we identified,” Kim said. “We want to examine their entire contents in terms of what proteins they express, what genes they express, and try to see what’s different in psilocybin-treated animals versus control animals or animal models of diseases.”

The goal is to identify how psychedelics benefit the cellular profiles of those with brain disorders, elucidating the step-by-step cellular process of their therapeutic effects.

Kim expressed interest in conducting future experiments in collaboration with Olson’s lab that use the CaST tool to compare the neuronal activity induced by psychedelics to the activity induced by non-hallucinogenic neurotherapeutics.

“CaST will be an important tool for studying the mechanisms of action of these neurotherapeutic drugs,” Kim said.

Additional UC Davis authors on the study include lead authors Run Zhang and Maribel Anguiano, and Isak K. Aarrestad, Sophia Lin, Joshua Chandra and Sruti S. Vadde.

The work was supported by grants from the Brain and Behavior Research Foundation, Kinship Foundation, Arnold and Mabel Beckman Foundation, NIH, NSF and the Boone Family Foundation.

“Few stars have been thought to generate enough UV radiation through flares to impact planet habitability. Our findings show that many more stars may have this capability,” said astronomer Vera Berger, who undertook the study while in the Research Experiences for Undergraduates program at IfA, an initiative supported by the National Science Foundation.

Berger and her team used archival data from the GALEX space telescope to search for flares among 300,000 nearby stars. GALEX is a now-decommissioned NASA mission that simultaneously observed most of the sky at near-and far-UV wavelengths from 2003 to 2013. Using new computational techniques, the team mined novel insights from the data.

“Combining modern computer power with gigabytes of decades-old observations allowed us to search for flares on thousands and thousands of nearby stars,” said Michael Tucker, a PhD graduate of IfA and now a postdoctoral fellow at Ohio State University.

UV’s double edge

According to researchers, UV radiation from stellar flares can either erode planetary atmospheres, threatening their potential to support life, or contribute to the formation of RNA building blocks, which are essential for the creation of life.

This study challenges existing models of stellar flares and exoplanet habitability, showing that far-UV emission from flares is on average three times more energetic than typically assumed, and can reach up to twelve times the expected energy levels.

“A change of three is the same as the difference in UV in the summer from Anchorage, Alaska to Honolulu, where unprotected skin can get a sunburn in less than 10 minutes,” said Benjamin J. Shappee, an Associate Astronomer at IfA who mentored Berger.

Hidden causes

The exact cause of this stronger far-UV emission remains unclear. The team believes it might be that flare radiation is concentrated at specific wavelengths, indicating the presence of atoms like carbon and nitrogen.

“This study has changed the picture of the environments around stars less massive than our Sun, which emit very little UV light outside of flares,” said Jason Hinkle, a PhD candidate at IfA who co-authored the study.

According to Berger, now a Churchill Scholar at the University of Cambridge, more data from space telescopes is needed to study the UV light from stars, which is crucial for understanding the source of this emission.

Schizophrenia is a neuropsychiatric disorder featuring recurrent episodes of psychosis — such as hallucinations, delusions, and disorganized thinking — with many patients developing apathy, social withdrawal, and poor emotional control as a result.

Because schizophrenia has been known to run in families for centuries, researchers have turned to genetic testing and analyses to identify risk factors for the condition. Recent genomic research on schizophrenia has identified nearly 300 common genetic variants and over 20 rare variants as significant risk factors for the disorder.

These discoveries have emerged from extensive genome-wide association studies, whole-exome sequencing, and other analyses. Simultaneously, studies of the functional organization of the brain have shed light on the intricate cellular composition and interconnections of the brain in both neurotypical individuals and those with schizophrenia.

These findings reveal a surprising complexity in the mechanisms underlying schizophrenia, emphasizing the role of multiple genes rather than single-gene causation. This “polygenicity” highlights a mechanism that remains challenging to fully understand due to the lack of robust theoretical frameworks and experimental tools. Sullivan and colleagues reviewed these issues and provided ideas for a path forward in the Nature Reviews Neuroscience article.

However, Sullivan and colleagues stress that environmental factors (including lifestyle, drug use, poverty, stress, and complications at birth) are also relevant in addition to genomic risk. Although these factors are more difficult to study compared to the genome, this genetic information is important for researchers to consider because some environmental factors are modifiable.

“The findings to date resoundingly indicate complexity,” wrote Sullivan, who is also director of the UNC Center for Psychiatric Genomics and the UNC Suicide Prevention Institute. “Rather than being a deterrent to future research, this knowledge underscores the importance of accepting schizophrenia as a genetic and environmental enigma and scaling our research accordingly in our efforts improve the lives of those impacted by schizophrenia.”

Long COVID, also known as Post-COVID-19 condition, is generally defined as symptoms persisting for three months or more after acute COVID-19. The condition can affect and damage many organ systems, leading to severe and long-term impaired function and a broad range of symptoms, including fatigue, cognitive impairment — often referred to as ‘brain fog’ — breathlessness and pain.

Long COVID can affect almost anyone, including all age groups and children. It is more prevalent in females and those of lower socioeconomic status, and the reasons for such differences are under study. The researchers found that while some people gradually get better from long COVID, in others the condition can persist for years. Many people who developed long COVID before the advent of vaccines are still unwell.

“Long COVID is a devastating disease with a profound human toll and socioeconomic impact,” said Janko Nikolich, MD, PhD, senior author of the paper, director of the Aegis Consortium at the U of A Health Sciences, professor and head of the Department of Immunobiology at the U of A College of Medicine — Tucson, and BIO5 Institute member. “By studying it in detail, we hope to both understand the mechanisms and to find targets for therapy against this, but potentially also other infection-associated complex chronic conditions such as myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia.”

If a person has been fully vaccinated and is up to date with their boosters, their risk of long COVID is much lower. However, 3%-5% of people worldwide still develop long COVID after an acute COVID-19 infection. According to the Centers for Disease Control and Prevention, long COVID affects an estimated 4%-10% of the U.S. adult population and 1 in 10 adults who had COVID develop long COVID.

The review study also found that a wide range of biological mechanisms are involved, including persistence of the original virus in the body, disruption of the normal immune response, and microscopic blood clotting, even in some people who had only mild initial infections.

There are no proven treatments for long COVID yet, and current management of the condition focuses on ways to relieve symptoms or provide rehabilitation. Researchers say there is a dire need to develop and test biomarkers such as blood tests to diagnose and monitor long COVID and to find therapies that address root causes of the disease.

People can lower their risk of developing long COVID by avoiding infection — wearing a close-fitting mask in crowded indoor spaces, for example — taking antivirals promptly if they do catch COVID-19, avoiding strenuous exercise during such infections, and ensuring they are up to date with COVID vaccines and boosters.

“Long COVID is a dismal condition but there are grounds for cautious optimism,” said Trisha Greenhalgh, lead author of the study and professor at Oxford’s Nuffield Department of Primary Care Health Sciences. “Various mechanism-based treatments are being tested in research trials. If proven effective, these would allow us to target particular subgroups of people with precision therapies. Treatments aside, it is becoming increasingly clear that long COVID places an enormous social and economic burden on individuals, families and society. In particular, we need to find better ways to treat and support the ‘long-haulers’ — people who have been unwell for two years or more and whose lives have often been turned upside down.”

The full paper, “Long COVID: a clinical update,” is published in The Lancet.

Despite feeling like a stationary mass, most solid ground is undergoing a process of deformation, sinking and rising in response to many environmental factors. In Antarctica, melting glacial ice means less weight on the bedrock below, allowing it to rise. How the rising earth interacts with the overlying ice sheet to affect sea level rise is not well-studied, said Terry Wilson, co-author of the study and a senior research scientist at the Byrd Polar and Climate Research Center at The Ohio State University.

In the new study, Wilson’s colleagues at McGill University developed a model to predict how these interactions could impact global sea level, finding that if humans can lower greenhouse gas emissions and global warming is slowed, upward shifts in the solid earth could reduce Antarctica’s contribution to sea level rise by about 40%, significantly bolstering the best case scenarios for global sea level rise. In this low-emissions scenario, land uplift slows the flow of ice from land to ocean, allowing for more of the ice sheet to be preserved.

Conversely, if humans are unable to lower carbon emissions in time, ice retreat will outpace uplift, pushing ocean water away from Antarctica and amplifying sea level rise. These events could significantly worsen the most dire models of projected sea level rise along populated coastlines, said Wilson.

“Our measurements show that the solid earth that forms the base of the Antarctic ice sheet is changing shape surprisingly quickly,” said Wilson. “The land uplift from reduced ice on the surface is happening in decades, rather than over thousands of years.”

The study was published today in Science Advances.

To arrive at these conclusions, the team developed a 3D model of the Earth’s interior using geophysical field measurements from the Antarctic Network (ANET) of the Polar Earth Observing Network (POLENET) project. The mission is focused on studying the changing polar regions by collecting GPS and seismic data from an array of autonomous systems across Antarctica.

Researchers then performed a number of simulations to capture many possible evolutions of Antarctica’s ice sheet and the extent of global sea level rise Earth may experience until the year 2500, according to those parameters.

“We can project what difference it actually will make if we all contribute to a low-emission scenario now, versus what’s come to be called ‘business as usual’ emissions,” said Wilson, who is also the lead investigator of the ANET-POLENET project.

She attributes the model’s unprecedented level of detail to how deftly it incorporates data from Antarctica. GPS stations monitor how the land is moving and seismometers measure how fast seismic waves from earthquakes travel through the earth, yielding important insight into where the land uplift will be fast or slow.

Surprisingly, according to some of the team’s GPS observations processed by researchers at Ohio State, Wilson said, the Antarctic Ice Sheet is currently experiencing a solid earth uplift of about 5 centimeters per year, about 5 times the rate that North America experiences.

Another significant aspect of the study is how the changes in Antarctica under different carbon emissions scenarios will impact coastlines around the world. Because sea level change will not be uniform, the study notes that nearly 700 million people around the world living in coastal regions will be most impacted by rising seas due to Antarctic ice loss.

Since some regions, such as small island nations, will be more vulnerable than others, mitigating environmental conditions like atmospheric and ocean warming is a vital issue for society, said Wilson.

“Many people are now more aware they’re experiencing the effects of climate change,” she said. “This work reinforces that our actions as individuals, nations and globally can make a difference in what kind of Earth our offspring will experience in their lifetimes.”

The study results highlight how complex the relationship between the solid earth and the processes that happen atop it is, as well as the importance of continuing to gather enough data to make prompt and accurate predictions about what the next few centuries of our planet will look like.

“There’s a lot of uncertainty in every model and every prediction that you make,” said Wilson. “But to document how fast our world is changing, it’s very important to continue advancing our ability to make predictions that are more certain, which is the only path that will allow us to tend to our future in a meaningful way.”

Wilson completed the study with colleagues from McGill University, Pennsylvania State University, the University of Massachusetts Amherst, Columbia University, Washington University, Colorado State University and the Union of Concerned Scientists. This study was supported by the U.S National Science Foundation and the Natural Sciences and Engineering Research Council of Canada.