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L.A. could better target homeless prevention services with predictive analytics

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Photograph of homeless tent encampment.

Photo credit: California Policy Lab

Each year, 2 million single adults receive housing, health, and emergency services from Los Angeles County. About 2% of them — around 76,000 people — will become homeless. Predictive modeling could help address the homelessness crisis in Los Angeles County, according to a report by researchers from the California Policy Lab at UCLA, and the Poverty Lab at the University of Chicago Harris School of Public Policy.

Using data from seven Los Angeles County agencies about services they provided to county residents between 2012 and 2016 — the residents’ names and personally identifiable information were omitted and each person was assigned an ID number for the study — researchers developed a model to predict which 3,000 residents were most likely to become homeless in 2017.

The researchers then checked the accuracy of their predictions against county records, and found that 46% of the people predicted by the model to be at risk for first-time homelessness or a repeat spell of homelessness did in fact become homeless at some point during 2017.

“Bringing together data from multiple county agencies gave us a more nuanced understanding about what’s happening to people right before they slip into homeless and how services can be better targeted to prevent that from happening,” said Till von Wachter, a UCLA economics professor and co-author of the report.  Von Wachter is also faculty director at the California Policy Lab.

The California Policy Lab pairs UCLA and other UC researchers with policymakers to solve urgent social problems, including homelessness, poverty, crime and education inequality.

The research informed an action plan that was developed by the county-led Mainstream Systems Homelessness Prevention Workgroup. That plan, which was submitted to the Los Angeles County Board of Supervisors on Dec. 16, recommends that the county use predictive models to intervene with adults who are identified as having a high risk for homelessness before they reach a crisis.

It also suggests that the county launch a multidisciplinary homelessness prevention unit that includes representatives of the county’s departments of mental health, health services and social services, and the sheriff and probation offices. The unit would accept referrals from the risks lists generated by the predictive models, identify which programs or services would be most helpful for each individual, and then reach out to people to connect them to those services.

The plan is expected to receive $3 million in funding during 2020 from Measure H, a sales tax approved by Los Angeles County voters in 2017 to help address the homeless crisis, in addition to drawing some existing resources from Los Angeles County departments.

“Last year, despite providing housing to tens of thousands of people, we saw more and more individuals and families becoming homeless,” said Phil Ansell, the director of the Los Angeles County Homeless Initiative. “The county is focused on using strategic approaches to preventing homelessness, and these groundbreaking models will make it possible to reach those who need us the most before they reach the crisis point and fall into homelessness.”

The models allowed researches to identify warning signs that could help local governments intervene early, especially for residents living in deep poverty, said Harold Pollack, the Helen Ross Professor at the University of Chicago School of Social Service Administration and a co-author of the study. The research that led to the new recommendations was begun at Chicago.

“The models suggest that sharp spikes in service use, increasingly frequent service use and the receipt of multiple services from a single agency are all warning signs that someone is at high risk for homelessness,” Pollack said. “We’re now diving deeper into the models with our Los Angeles County partners to learn more and to see how these results can help focus public health and social services to this vulnerable population.”

Janey Rountree, executive director of the California Policy Lab at UCLA, said using the predictive models could go a long way toward making sure homeless prevention services reach the right people at the right time.

“Predictive modeling can help ensure that happens, before they’re in a full-blown crisis,” she said. “We look forward to seeing its impact in connecting people to the help they need.”

The study also found:

  • Effectively serving the 1% of county clients who have the greatest risk for a new homeless spell would prevent nearly 6,900 homeless spells in one year.
  • County residents who have the highest risk for homelessness are interacting with multiple agencies.
  • Falling into homelessness happens very quickly, typically within six months of a precipitating event, meaning that Los Angeles County and service providers must react quickly.

The research was provided at no cost to the county. Financial support was provided by Arnold Ventures and the Max Factor Family Foundation.

This article originally appeared in the UCLA Newsroom.

Chronic opioid treatment may raise risk of post-traumatic stress disorder, study finds

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Senior author Michael Fanselow said the research suggests that chronic opioid use increases susceptibility to developing anxiety disorders. Photo credit: Reed Hutchinson/UCLA

While opioids are often prescribed to treat people with trauma-related pain, a new UCLA-led study suggests doctors should use caution before prescribing the drug to those they believe may experience severe stress in the future, in order to reduce the risk the patient will develop PTSD.

In the study, researchers administered doses of the opioid morphine to a group of 22 mice for one week, then gave the mice relatively strong foot shocks. After the morphine wore off, the mice were given mild electric foot shocks. These mice showed a substantially longer “freezing response” than a second, control group of 24 mice that had not been given morphine. When mice recall a frightening memory, they freeze. Their heart rates and blood pressure go up, and the more frightening the memory, the more they freeze.

“While we are generally aware that drug use, such as that in the current opioid crisis, has many deleterious effects, our results suggest yet another effect — increased susceptibility to developing anxiety disorders,” said senior author Michael Fanselow, UCLA distinguished Staglin family professor of psychology and director of UCLA’s Staglin Family Music Festival Center for Brain and Behavioral Health. “As opioids are often prescribed to treat symptoms such as pain that may accompany trauma, caution may be needed because this may lead to a greater risk of developing PTSD, if exposed to further traumatic events, such as an accident, later on.”

“The foot shocks produced lasting fear and anxiety-like behaviors, such as freezing,” Fanselow said.

“Our data are the first to show a possible effect of opioids on future fear learning, suggesting that a person with a history of opioid use may become more susceptible to the negative effects of stress,” Fanselow said. “The ability of opioids to increase PTSD-like symptoms far outlasted the direct effects of the drug or withdrawal from the drug, suggesting the effect may continue even after opioid treatment has stopped.”

Fanselow’s view is if there is reason to believe a patient is likely to experience severe emotional stress after opioid treatment, then doctors should use caution about prescribing an opioid. If opioid use is medically called for, then the patient should be kept away from potentially stressful situations. So, for example, a soldier treated with opioids for pain should not be sent back into combat for a period of time, he said. The development of post-traumatic stress disorder requires some stressful experience after opioid use, he said.

The researchers also gave some of the mice morphine after the initial trauma had occurred but before exposing them to the second, mild stressor. They found that mice treated with morphine after the initial trauma did not show enhanced fear learning following exposure to the mild stressor. This finding suggests that chronic use of opioids before — but not after — a traumatic event occurs affects fear learning during subsequent stressful events.

The researchers concluded the mice given morphine were more susceptible to post-traumatic stress disorder than the control group of mice not given any opioids, and inferred that people with a history of using opioids are more susceptible to PTSD than the general population.

The study is published in Neuropsychopharmacology, an international scientific journal focusing on clinical and basic science research that advances understanding of the brain and behavior.

The research was funded by the National Institute on Drug Abuse and National Institute of Mental Health.

An opiate is a drug naturally derived from the opium poppy plant, such as heroin, morphine and codeine. Opioid is a broader term that includes opiates and any substance, natural or synthetic, that binds to the brain’s opioid receptors — which play a key role in controlling pain, rewards and addictive behaviors. Synthetic opioids include the prescription painkillers Vicodin and OxyContin, as well as fentanyl and methadone.

Substance abuse and PTSD often go hand-in-hand, Fanselow said, and people with PTSD often take drugs to self-medicate. Nearly 40% of people with PTSD also have a drug disorder.

Fanselow and colleagues reported last month that a traumatic brain injury causes changes in a brain region called the amygdala; and the brain processes fear differently after such an injury.

This article originally appeared in the UCLA Newsroom.

New NASA image provides more details about first observed interstellar comet

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Image of interstellar comet.

The interstellar comet Comet 2I/Borisov (blueish image at right) near a spiral galaxy (left), in an image taken Nov. 16. Photo credit: NASA, ESA and David Jewitt/UCLA

A new image from NASA’s Hubble Space Telescope provides important new details about the first interstellar comet astronomers have seen in our solar system.

The comet, called Comet 2I/Borisov (the “I” stands for interstellar), was spotted near a spiral galaxy known as 2MASX J10500165-0152029. It was approximately 203 million miles from Earth when the image was taken on Nov. 16.

“Data from the Hubble Space Telescope give us the best measure of the size of comet 2I/Borisov’s nucleus, which is the really important part of the comet,” said David Jewitt, a UCLA professor of planetary science and astronomy who analyzed and interpreted the data from the new image.

Jewitt collaborated on the new analysis with colleagues from the University of Hawaii, Germany’s Max Planck Institute for Solar System Research, the Space Telescope Science Institute in Baltimore and Johns Hopkins University’s Applied Physics Laboratory. The scientists were surprised to learn that the nucleus has a radius measuring only about half of a kilometer — or less than one-fifteenth the size that earlier investigations suggested it might be.

“That is important because knowing its size helps us to determine the total number, and mass, of other similar objects in the solar system and the Milky Way,” Jewitt said. “2I/Borisov is the first known interstellar comet, and we would like to learn how many others there are.”

The comet is traveling at a breathtaking speed of 110,000 miles per hour — one of the fastest comets ever seen, Jewitt said. More commonly, comets travel at about half that speed.

Crimean astronomer Gennady Borisov discovered the comet on Aug. 30, using a telescope he built. Based on precise measurements of its changing position, the International Astronomical Union’s Minor Planet Center calculated a likely orbit for the comet, which shows that it came from elsewhere in the galaxy. Jewitt said its precise point of origin is unknown.

A second Hubble Space Telescope image of the comet, taken on Dec. 9, shows the comet even closer to Earth, approximately 185 million miles from Earth, he said.

Comets are icy bodies thought to be fragments left behind when planets form in the outer parts of planetary systems.

Observations by numerous telescopes show that the comet’s chemical composition is similar to that of comets previously observed in our solar system, which provides evidence that comets also form around other stars, Jewitt said. By mid-2020, the comet will have zoomed past Jupiter on its way back into interstellar space, where it will drift for billions of years, Jewitt said.

This article originally appeared in the UCLA Newsroom.

Student Spotlight – Julia Nakamura

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Photo of student smiling.

Fourth-year UCLA student researcher Julia Nakamura

Meet fourth-year UCLA student researcher Julia Nakamura!

Julia majors in Psychobiology with a minor in Gerontology and is in our Undergraduate Research Scholars Program. The title of her research project is “The Role of Social Support in the Association between Early Life Stress, Depression, and Inflammation in Older Adults.”

 

How did you first get interested in your research project?

UCLA’s Cluster course “Frontiers in Human Aging” initially sparked my interest in aging populations. Through a service learning project at ONEgeneration Adult Day Care Center, I directly witnessed the burden of chronic disease in later-life adults and realized the pressing need to understand the mechanisms underlying these adverse health outcomes. Through my coursework in psychology, I became interested in the psychological factors that influence biological mechanisms and have the potential to positively impact the trajectory of chronic disease outcomes.

I began research in psychology in Dr. Julienne Bower’s Mind-Body Lab under the direction of Dr. Kate Kuhlman. We study the effects of childhood adversity on biological and behavioral responses to psychological stress. My experiences in this lab led me to wonder what factors could mitigate adverse physical and mental health outcomes from stressful experiences, specifically in older adults. My honors research projects examines if social support moderates the relationship between early-life stress, depressive symptoms, and inflammation in older adults using data from the Health and Retirement Study.

What has been the most exciting aspect of your research so far?

Getting to test my own research questions has been the best part of this project. Specifically, it has been really exciting for me to run my own data analyses for the first time with Dr. Kuhlman’s guidance. Experiencing the “behind-the-scenes” of research and systematically moving through the steps of conducting an independent project has been really informative. This project has helped me to feel that I am truly developing the skill set of an independent researcher, which is very exciting!

What has surprised you about your research or the research process?

The immensely collaborative nature of research in academia was quite surprising to me when I first started on this project. Through my research, I’ve had the privilege of working with several scientists and professors who are experts in their respective areas of study. They have all welcomed me and helped to make my project as scientifically sound and comprehensive as possible. Research really builds on itself. Learning from other people’s projects and ideas, even if they are outside of your immediate area of study, can result in high levels of collaboration and really interesting research!

What is one piece of advice you have for other UCLA students thinking about doing research?

I would advise students interested in research to actively pursue research opportunities. There are plenty of amazing opportunities to be involved in research at UCLA, but you have to seek them out. It can be intimidating to take the initial steps to reach out to professors and discuss their research interests, but it is so worthwhile to find a lab and professor that are a good fit! I would recommend that students find an area of study that they are really passionate about. I think that your passion for your area of study and your continued curiosity will drive your research questions and help you get the most out of each research experience.

What effect do you hope your research has in your field, at UCLA, in your community, or in the world?

I hope to spend my life contributing to our understanding of the biobehavioral processes that promote mental and physical health across the lifespan. As the number of older adults (a majority of whom have at least one chronic disease) increase in our society, it is now more important than ever to identify potential intervention targets that can improve the trajectory of chronic disease outcomes.

This article originally appeared on the Undergraduate Research Center website.

One of California’s iconic tree species offers lessons for conservation

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Picture of a valley oak tree.

The valley oak, the largest oak in California, grows to over 100 feet tall and provides habitat and food for a variety of animals. Photo credit: Victoria Sork/UCLA

 

With increasing regularity, Californians are witnessing firsthand the destructive power of wildfires. But not everyone sees what happens after the flames die down, when debris is cleared, homes and lives rebuilt — and trees replanted to help nature recover.

New research led by UCLA evolutionary biologist Victoria Sork examines whether the trees being replanted in the wake of California’s fires will be able to survive a climate that is continuing to warm.

The study, which is published in the Proceedings of the Natural Academy of Sciences, focuses on California’s iconic valley oak. The research is among the first to demonstrate the potential of using genomics to inform conservation strategies — essentially giving species an evolutionary boost. The study showed that planting trees that are genetically better suited to higher temperatures makes them more likely to survive and grow to maturity.

“When we think about managing ecosystems under rapidly changing climates, we have to realize trees need to be able to survive past 50 years,” Sork said.

The paper also discovered something surprising: The valley oak, an essential component of many ecosystems in California, is already poorly adapted to its environment — even considering climate conditions in 2019.

“They actually seem to grow better in cooler climates than they’re in right now,” said Luke Browne, a postdoctoral scholar at the UCLA La Kretz Center for California Conservation Science and the study’s lead author. “They might grow better if climates were more like they were 21,000 years ago, during the last ice age.”

During the peak of the last ice age, summer temperatures were about 4 to 5 degrees Celsius colder, and ice covered most of Canada and mountainous areas of the U.S.

In the fields of conservation and land management, it is a common assumption that plants and animals are adapted to their environments — that’s how evolution and natural selection are supposed to work. The new research casts doubt on that assumption.

The study is part of an ongoing project initiated by Sork and Jessica Wright, an expert in conservation genetics at the USDA Forest Service, more than 10 years ago.

Researchers gathered 11,000 seeds from 94 locations throughout the trees’ range, which stretches from the Santa Monica Mountains to the Cascade foothills in the northern part of the state. They grew them to saplings in a greenhouse and planted them in two large experimental gardens, in Chico and Placerville, California. They tracked how well trees from different locations grew, and sequenced the genomes of their mother trees to link genetic information and growth rates.

The researchers then identified which genetic variants would be more likely to thrive as climate change continues to warm California. They predicted that, under predicted future warmer temperatures, trees containing beneficial genetic variations would have 11% higher growth rates than the average for all of the trees in the experiment, and 25% higher growth rates than the trees without the beneficial variations.

Information like that could help the U.S. Forest Service, for example, in its efforts to restore forests with species that have the best chance for long-term survival.

“Studies like this one provide valuable insights that help land managers make informed decisions on reforestation projects,” Wright said. “When planting trees in a particular location, managers have to decide where to collect the acorns.”

By 2070, average temperatures in the state are projected to be up to 4.8 degrees warmer than they were during the mid- to late 20th century.

“That’s going to have consequences for how fast these trees grow,” Browne said. “We’re at a challenging time to figure out the best way to do conservation science. This paper shows one approach we could use that takes advantage of modern genomics.”

The study did not determine why valley oaks are not well adapted to their environment. It might be because the climate has already warmed up so much, the trees’ long lifespans — up to 500 years — or some other, unknown factor.

The valley oak is the largest oak in California; it grows to over 100 feet tall, and has dark green leaves and a deeply grooved trunk. It is considered a foundational species because it provides habitat and food for a variety of animals, including squirrels, birds, deer and insects. In parts of the state, it is one of the only species of tree that exists. Valley oaks provide benefits to humans, too: filtering water and providing shady places to escape the heat.

Although it focuses on the oak, the paper has broader implications for conservation science in a changing climate — especially for species that evolve and adapt slowly. That’s what Sork and Wright were thinking when they initiated the project.

At the time, they hoped to find conservation strategies that could eventually be implemented using genetic information alone — without extensive field experiments.

“Not everyone in the world is going to be able to collect 11,000 seeds and plant them in a common garden,” Sork said.

This article originally appeared in the UCLA Newsroom.

Black hole at the center of our galaxy appears to be getting hungrier

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Rendering of a star called S0-2 orbiting the supermassive black hole at the center of the Milky Way. It did not fall in, but its close approach could be one reason for the black hole’s growing appetite. Photo credit: Nicolle Fuller/National Science Foundation

The enormous black hole at the center of our galaxy is having an unusually large meal of interstellar gas and dust, and researchers don’t yet understand why.

“We have never seen anything like this in the 24 years we have studied the supermassive black hole,” said Andrea Ghez, UCLA professor of physics and astronomy and a co-senior author of the research. “It’s usually a pretty quiet, wimpy black hole on a diet. We don’t know what is driving this big feast.”

A paper about the study, led by the UCLA Galactic Center Group, which Ghez heads, is published today in Astrophysical Journal Letters.

The researchers analyzed more than 13,000 observations of the black hole from 133 nights since 2003. The images were gathered by the W.M. Keck Observatory in Hawaii and the European Southern Observatory’s Very Large Telescope in Chile. The team found that on May 13, the area just outside the black hole’s “point of no return” (so called because once matter enters, it can never escape) was twice as bright as the next-brightest observation.

They also observed large changes on two other nights this year; all three of those changes were “unprecedented,” Ghez said.

The brightness the scientists observed is caused by radiation from gas and dust falling into the black hole; the findings prompted them to ask whether this was an extraordinary singular event or a precursor to significantly increased activity.

“The big question is whether the black hole is entering a new phase — for example if the spigot has been turned up and the rate of gas falling down the black hole ‘drain’ has increased for an extended period — or whether we have just seen the fireworks from a few unusual blobs of gas falling in,” said Mark Morris, UCLA professor of physics and astronomy and the paper’s co-senior author.

The team has continued to observe the area and will try to settle that question based on what they see from new images.

“We want to know how black holes grow and affect the evolution of galaxies and the universe,” said Ghez, UCLA’s Lauren B. Leichtman and Arthur E. Levine Professor of Astrophysics. “We want to know why the supermassive hole gets brighter and how it gets brighter.”

► UCLA astronomers discussed the project in a Keck Observatory video

The new findings are based on observations of the black hole — which is called Sagittarius A*, or Sgr A* — during four nights in April and May at the Keck Observatory. The brightness surrounding the black hole always varies somewhat, but the scientists were stunned by the extreme variations in brightness during that timeframe, including their observations on May 13.

“The first image I saw that night, the black hole was so bright I initially mistook it for the star S0-2, because I had never seen Sagittarius A* that bright,” said UCLA research scientist Tuan Do, the study’s lead author. “But it quickly became clear the source had to be the black hole, which was really exciting.”

One hypothesis about the increased activity is that when a star called S0-2 made its closest approach to the black hole during the summer 2018, it launched a large quantity of gas that reached the black hole this year.

Another possibility involves a bizarre object known as G2, which is most likely a pair of binary stars, which made its closest approach to the black hole in 2014. It’s possible the black hole could have stripped off the outer layer of G2, Ghez said, which could help explain the increased brightness just outside the black hole.

Morris said another possibility is that the brightening corresponds to the demise of large asteroids that have been drawn in to the black hole.

No danger to Earth

The black hole is some 26,000 light-years away and poses no danger to our planet. Do said the radiation would have to be 10 billion times as bright as what the astronomers detected to affect life on Earth.

Astrophysical Journal Letters also published a second article by the researchers, describing speckle holography, the technique that enabled them to extract and use very faint information from 24 years of data they recorded from near the black hole.

Ghez’s research team reported July 25 in the journal Science the most comprehensive test of Einstein’s iconic general theory of relativity near the black hole. Their conclusion that Einstein’s theory passed the test and is correct, at least for now, was based on their study of S0-2 as it made a complete orbit around the black hole.

► Watch a four-minute film about Ghez’s research

Ghez’s team studies more than 3,000 stars that orbit the supermassive black hole. Since 2004, the scientists have used a powerful technology that Ghez helped pioneer, called adaptive optics, which corrects the distorting effects of the Earth’s atmosphere in real time. But speckle holography enabled the researchers to improve the data from the decade before adaptive optics came into play. Reanalyzing data from those years helped the team conclude that they had not seen that level of brightness near the black hole in 24 years.

“It was like doing LASIK surgery on our early images,” Ghez said. “We collected the data to answer one question and serendipitously unveiled other exciting scientific discoveries that we didn’t anticipate.”

Co-authors include Gunther Witzel, a former UCLA research scientist currently at Germany’s Max Planck Institute for Radio Astronomy; Mark Morris, UCLA professor of physics and astronomy; Eric Becklin, UCLA professor emeritus of physics and astronomy; Rainer Schoedel, a researcher at Spain’s Instituto de Astrofısica de Andalucıa; and UCLA graduate students Zhuo Chen and Abhimat Gautam.

The research is funded by the National Science Foundation, W.M. Keck Foundation, the Gordon and Betty Moore Foundation, the Heising-Simons Foundation, Lauren Leichtman and Arthur Levine, and Howard and Astrid Preston.

This article originally appeared in the UCLA Newsroom.

UCLA receives $20 million to establish UCLA Bedari Kindness Institute

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Jennifer and Matthew C. Harris ‘84.

The Bedari Foundation, established by philanthropists Jennifer and Matthew C. Harris, has given $20 million to the UCLA College to establish the UCLA Bedari Kindness Institute.

The institute, which is housed in the division of social sciences, will support world-class research on kindness, create opportunities to translate that research into real-world practices, and serve as a global platform to educate and communicate its findings. Among its principal goals are to empower citizens and inspire leaders to build more humane societies.

“Universities should always be places where we teach students to reach across lines of difference and treat one another with empathy and respect — even when we deeply disagree,” UCLA Chancellor Gene Block said. “The UCLA Bedari Kindness Institute will bring the best thinking to this vital issue and, I think, will allow us to have a real social impact on future generations.”

The institute, which will begin operating immediately, will take an interdisciplinary approach to understanding kindness — through evolutionary, biological, psychological, economic, cultural and sociological perspectives. It will focus on research about the actions, thoughts, feelings and social institutions associated with kindness and will bring together researchers from across numerous disciplines at UCLA and at external organizations.

The inaugural director of the institute is Daniel Fessler, a UCLA anthropology professor whose research interests include exploring how witnessing acts of remarkable kindness can cause an uplifting emotional experience that in turn motivates the observer to be kind. Studies by Fessler and his colleagues have shed light on why some people are open to that type of “contagious kindness” experience.

The Bedari Foundation is a private family foundation whose aim is to enable significant cultural shifts in the fields of health and wellness, community displacement and environmental conservation.

“Our vision is that we will all live in a world where humanity discovers and practices the kindness that exists in all of us,” said Matthew Harris, the foundation’s co-founder and a 1984 UCLA graduate. “Much research is needed to understand why kindness can be so scarce in the modern world. As we seek at Bedari to bridge the divide between science and spirituality, through the establishment of the UCLA Bedari Kindness Institute we hope to educate and empower more and more people in the practice of kindness.”

Already, a range of researchers at UCLA are studying the types of questions that will be the basis of the institute’s work. For example, UCLA anthropologists are examining how kindness spreads from person to person and group to group. UCLA sociologists are analyzing how people who regularly act unkind might be encouraged to engage in kind acts instead, and UCLA psychologists are researching how kindness can improve people’s moods and reduce symptoms of depression. Others are pursuing research on changes in neurobiology and behaviors resulting from mindfulness, and how those changes can influence kindness and people’s mental, physical and social well-being.

“In the midst of current world politics, violence and strife, the UCLA Bedari Kindness Institute seeks to be an antidote,” said Darnell Hunt, dean of the UCLA division of social sciences. “Rooted in serious academic work, the institute will partner and share its research on kindness broadly in accessible formats. The Bedari Foundation’s extraordinary gift is truly visionary and we are grateful for its support and leadership.”

The Kindness Institute will provide seed funding for research projects that examine the social and physical mechanics of kindness and how kindness might be harnessed to create more humane societies. It also will provide mindfulness awareness training to students, faculty and staff and in underserved Los Angeles communities, and host an annual conference at which presenters will examine new discoveries in kindness research, among other activities.

“The mission of the Kindness Institute perfectly aligns with that of the division of social sciences, where engaging the amazing diversity and social challenges shaping Los Angeles routinely inspires research that has the potential to change the world,” Hunt said.

The gift is part of the Centennial Campaign for UCLA, which is scheduled to conclude in December.

Study shows how serotonin and a popular anti-depressant affect the gut’s microbiota

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Senior author Elaine Hsiao says researchers hope to build on their current study to learn whether microbial interactions with antidepressants have consequences for health and disease. Photo: Reed Hutchinson/UCLA

A new study in mice led by UCLA biologists strongly suggests that serotonin and drugs that target serotonin, such as anti-depressants, can have a major effect on the gut’s microbiota — the 100 trillion or so bacteria and other microbes that live in the human body’s intestines.

Serotonin — a neurotransmitter, or chemical messenger that sends messages among cells — serves many functions in the human body, including playing a role in emotions and happiness. An estimated 90% of the body’s serotonin is produced in the gut, where it influences gut immunity.

The team — led by senior author Elaine Hsiao and lead author Thomas Fung, a postdoctoral fellow — identified a specific gut bacterium that can detect and transport serotonin into bacterial cells. When mice were given the antidepressant fluoxetine, or Prozac, the biologists found this reduced the transport of serotonin into their cells. This bacterium, about which little is known, is called Turicibacter sanguinis. The study is published this week in the journal Nature Microbiology.

“Our previous work showed that particular gut bacteria help the gut produce serotonin. In this study, we were interested in finding out why they might do so,” said Hsiao, UCLA assistant professor of integrative biology and physiology, and of microbiology, immunology and molecular genetics in the UCLA College; and of digestive diseases in the David Geffen School of Medicine at UCLA.

Hsiao and her research group reported in the journal Cell in 2015 that in mice, a specific mixture of bacteria, consisting mainly of Turicibacter sanguinis and Clostridia, produces molecules that signal to gut cells to increase production of serotonin. When Hsiao’s team raised mice without the bacteria, more than 50% of their gut serotonin was missing. The researchers then added the bacteria mixture of mainly Turicibacter and Clostridia, and their serotonin increased to a normal level.

That study got the team wondering why bacteria signal to our gut cells to make serotonin. Do microbes use serotonin, and if so, for what?

In this new study, the researchers added serotonin to the drinking water of some mice and raised others with a mutation (created by altering a specific serotonin transporter gene) that increased the levels of serotonin in their guts. After studying the microbiota of the mice, the researchers discovered that the bacteria Turicibacter and Clostridia increased significantly when there was more serotonin in the gut.

If these bacteria increase in the presence of serotonin, perhaps they have some cellular machinery to detect serotonin, the researchers speculated. Together with study co-author Lucy Forrest and her team at the National Institutes of Health’s National Institute of Neurological Disorders and Stroke, the researchers found a protein in multiple species of Turicibacter that has some structural similarity to a protein that transports serotonin in mammals. When they grew Turicibacter sanguinis in the lab, they found that the bacterium imports serotonin into the cell.

In another experiment, the researchers added the antidepressant fluoxetine, which normally blocks the mammalian serotonin transporter, to a tube containing Turicibacter sanguinis. They found the bacterium transported significantly less serotonin.

The team found that exposing Turicibacter sanguinis to serotonin or fluoxetine influenced how well the bacterium could thrive in the gastrointestinal tract. In the presence of serotonin, the bacterium grew to high levels in mice, but when exposed to fluoxetine, the bacterium grew to only low levels in mice.

“Previous studies from our lab and others showed that specific bacteria promote serotonin levels in the gut,” Fung said. “Our new study tells us that certain gut bacteria can respond to serotonin and drugs that influence serotonin, like anti-depressants. This is a unique form of communication between bacteria and our own cells through molecules traditionally recognized as neurotransmitters.”

The team’s research on Turicibacter aligns with a growing number of studies reporting that anti-depressants can alter the gut microbiota. “For the future,” Hsiao said, “we want to learn whether microbial interactions with antidepressants have consequences for health and disease.” Hsiao wrote a blog post for the journal about the new research.

Other study co-authors are Helen Vuong, Geoffrey Pronovost, Cristopher Luna, Anastasia Vavilina, Julianne McGinn and Tomiko Rendon, all of UCLA; and Antoniya Aleksandrova and Noah Riley, members of Forrest’s team.

The research was supported by funding from the National Institutes of Health’s Director’s Early Independence Award, Klingenstein-Simons Fellowship Award, and David & Lucile Packard Foundation’s Packard Fellowship for Science and Engineering.

This article originally appeared in the UCLA Newsroom.

Biochemists discover new insights into what may go awry in brains of people with Alzheimer’s

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Photo of two researchers in lab.

Research by UCLA professor Steven Clarke and former graduate student Rebeccah Warmack, as well as UCLA colleagues, reveals new information about the brain’s biochemistry.

More than three decades of research on Alzheimer’s disease have not produced any major treatment advances for those with the disorder, according to a UCLA expert who has studied the biochemistry of the brain and Alzheimer’s for nearly 30 years. “Nothing has worked,” said Steven Clarke, a distinguished professor of chemistry and biochemistry. “We’re ready for new ideas.” Now, Clarke and UCLA colleagues have reported new insights that may lead to progress in fighting the devastating disease.

Scientists have known for years that amyloid fibrils — harmful, elongated, water-tight rope-like structures — form in the brains of people with Alzheimer’s, and likely hold important clues to the disease. UCLA Professor David Eisenberg and an international team of chemists and molecular biologists reported in the journal Nature in 2005 that amyloid fibrils contain proteins that interlock like the teeth of a zipper. The researchers also reported their hypothesis that this dry molecular zipper is in the fibrils that form in Alzheimer’s disease, as well as in Parkinson’s disease and two dozen other degenerative diseases. Their hypothesis has been supported by recent studies.

Alzheimer’s disease, the most common cause of dementia among older adults, is an irreversible, progressive brain disorder that kills brain cells, gradually destroys memory and eventually affects thinking, behavior and the ability to carry out the daily tasks of life. More than 5.5 million Americans, most of whom are over 65, are thought to have dementia caused by Alzheimer’s.

The UCLA team reports in the journal Nature Communications that the small protein beta amyloid, also known as a peptide, that plays an important role in Alzheimer’s has a normal version that may be less harmful than previously thought and an age-damaged version that is more harmful.

Rebeccah Warmack, who was a UCLA graduate student at the time of the study and is its lead author, discovered that a specific version of age-modified beta amyloid contains a second molecular zipper not previously known to exist. Proteins live in water, but all the water gets pushed out as the fibril is sealed and zipped up. Warmack worked closely with UCLA graduate students David Boyer, Chih-Te Zee and Logan Richards; as well as senior research scientists Michael Sawaya and Duilio Cascio.

What goes wrong with beta amyloid, whose most common forms have 40 or 42 amino acids that are connected like a string of beads on a necklace?

The researchers report that with age, the 23rd amino acid can spontaneously form a kink, similar to one in a garden hose. This kinked form is known as isoAsp23. The normal version does not create the stronger second molecular zipper, but the kinked form does.

“Now we know a second water-free zipper can form, and is extremely difficult to pry apart,” Warmack said. “We don’t know how to break the zipper.”

The normal form of beta amyloid has six water molecules that prevent the formation of a tight zipper, but the kink ejects these water molecules, allowing the zipper to form.

When one of its amino acids forms a kink, beta amyloid creates a harmful molecular zipper, shown here in green. Photo credit: Rebeccah Warmack/UCLA

When one of its amino acids forms a kink, beta amyloid creates a harmful molecular zipper, shown here in green.
“Rebeccah has shown this kink leads to faster growth of the fibrils that have been linked to Alzheimer’s disease,” said Clarke, who has conducted research on biochemistry of the brain and Alzheimer’s disease since 1990. “This second molecular zipper is double trouble. Once it’s zipped, it’s zipped, and once the formation of fibrils starts, it looks like you can’t stop it. The kinked form initiates a dangerous cascade of events that we believe can result in Alzheimer’s disease.”

Why does beta amyloid’s 23rd amino acid sometimes form this dangerous kink?

Clarke thinks the kinks in this amino acid form throughout our lives, but we have a protein repair enzyme that fixes them.

“As we get older, maybe the repair enzyme misses the repair once or twice,” he said. “The repair enzyme might be 99.9% effective, but over 60 years or more, the kinks eventually build up. If not repaired or if degraded in time, the kink can spread to virtually every neuron and can do tremendous damage.”

“The good news is that knowing what the problem is, we can think about ways to solve it,” he added. “This kinked amino acid is where we want to look.”

The research offers clues to pharmaceutical companies, which could develop ways to prevent formation of the kink or get the repair enzyme to work better; or by designing a cap that would prevent fibrils from growing.

Clarke said beta amyloid and a much larger protein tau — with more than 750 amino acids — make a devastating one-two punch that forms fibrils and spreads them to many neurons throughout the brain. All humans have both beta amyloid and tau. Researchers say it appears that beta amyloid produces fibrils that can lead to tau aggregates, which can spread the toxicity to other brain cells. However, exactly how beta amyloid and tau work together to kill neurons is not yet known.

In this study, Warmack produced crystals, both the normal and kinked types, in 15 of beta amyloid’s amino acids. She used a modified type of cryo-electron microscopy to analyze the crystals. Cryo-electron microscopy, whose development won its creators the 2017 Nobel Prize in chemistry, enables scientists to see large biomolecules in extraordinary detail. Professor Tamir Gonen pioneered the modified microscopy, called microcrystal electron diffraction, which enables scientists to study biomolecules of any size.

Eisenberg is UCLA’s Paul D. Boyer Professor of Molecular Biology and a Howard Hughes Medical Institute investigator. Other researchers are co-author Gonen, a professor of biological chemistry and physiology at the UCLA David Geffen School of Medicine and a Howard Hughes Medical Institute investigator; and Jose Rodriguez, assistant professor of chemistry and biochemistry who holds the Howard Reiss Career Development Chair.

The research was funded by the National Science Foundation, National Institutes of Health, Howard Hughes Medical Institute, and the UCLA Longevity Center’s Elizabeth and Thomas Plott Chair in Gerontology, which Clarke held for five years.

This article originally appeared in the UCLA Newsroom.

Einstein’s general relativity theory is questioned but still stands ‘for now,’ team reports

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Photo of artist rendering of SO-2 star.

A star known as S0-2 (the blue and green object in this artist’s rendering) made its closest approach to the supermassive black hole at the center of the Milky Way in 2018. Artist’s rendering by Nicolle Fuller/National Science Foundation.

More than 100 years after Albert Einstein published his iconic theory of general relativity, it is beginning to fray at the edges, said Andrea Ghez, UCLA professor of physics and astronomy. Now, in the most comprehensive test of general relativity near the monstrous black hole at the center of our galaxy, Ghez and her research team report July 25 in the journal Science that Einstein’s theory of general relativity holds up.

“Einstein’s right, at least for now,” said Ghez, a co-lead author of the research. “We can absolutely rule out Newton’s law of gravity. Our observations are consistent with Einstein’s theory of general relativity. However, his theory is definitely showing vulnerability. It cannot fully explain gravity inside a black hole, and at some point we will need to move beyond Einstein’s theory to a more comprehensive theory of gravity that explains what a black hole is.”

Einstein’s 1915 theory of general relativity holds that what we perceive as the force of gravity arises from the curvature of space and time. The scientist proposed that objects such as the sun and the Earth change this geometry. Einstein’s theory is the best description of how gravity works, said Ghez, whose UCLA-led team of astronomers has made direct measurements of the phenomenon near a supermassive black hole — research Ghez describes as “extreme astrophysics.”

The laws of physics, including gravity, should be valid everywhere in the universe, said Ghez, who added that her research team is one of only two groups in the world to watch a star known as S0-2 make a complete orbit in three dimensions around the supermassive black hole at the center of the Milky Way. The full orbit takes 16 years, and the black hole’s mass is about 4 million times that of the sun.

The researchers say their work is the most detailed study ever conducted into the supermassive black hole and Einstein’s theory of general relativity.

The key data in the research were spectra that Ghez’s team analyzed last April, May and September as her “favorite star” made its closest approach to the enormous black hole. Spectra, which Ghez described as the “rainbow of light” from stars, show the intensity of light and offer important information about the star from which the light travels. Spectra also show the composition of the star. These data were combined with measurements Ghez and her team have made over the last 24 years.

Spectra — collected at the W.M. Keck Observatory in Hawaii using a spectrograph built at UCLA by a team led by colleague James Larkin — provide the third dimension, revealing the star’s motion at a level of precision not previously attained. (Images of the star the researchers took at the Keck Observatory provide the two other dimensions.) Larkin’s instrument takes light from a star and disperses it, similar to the way raindrops disperse light from the sun to create a rainbow, Ghez said.

“What’s so special about S0-2 is we have its complete orbit in three dimensions,” said Ghez, who holds the Lauren B. Leichtman and Arthur E. Levine Chair in Astrophysics. “That’s what gives us the entry ticket into the tests of general relativity. We asked how gravity behaves near a supermassive black hole and whether Einstein’s theory is telling us the full story. Seeing stars go through their complete orbit provides the first opportunity to test fundamental physics using the motions of these stars.”

Ghez’s research team was able to see the co-mingling of space and time near the supermassive black hole. “In Newton’s version of gravity, space and time are separate, and do not co-mingle; under Einstein, they get completely co-mingled near a black hole,” she said.

“Making a measurement of such fundamental importance has required years of patient observing, enabled by state-of-the-art technology,” said Richard Green, director of the National Science Foundation’s division of astronomical sciences. For more than two decades, the division has supported Ghez, along with several of the technical elements critical to the research team’s discovery. “Through their rigorous efforts, Ghez and her collaborators have produced a high-significance validation of Einstein’s idea about strong gravity.”

Keck Observatory Director Hilton Lewis called Ghez “one of our most passionate and tenacious Keck users.” “Her latest groundbreaking research,” he said, “is the culmination of unwavering commitment over the past two decades to unlock the mysteries of the supermassive black hole at the center of our Milky Way galaxy.”

The researchers studied photons — particles of light — as they traveled from S0-2 to Earth. S0-2 moves around the black hole at blistering speeds of more than 16 million miles per hour at its closest approach. Einstein had reported that in this region close to the black hole, photons have to do extra work. Their wavelength as they leave the star depends not only on how fast the star is moving, but also on how much energy the photons expend to escape the black hole’s powerful gravitational field. Near a black hole, gravity is much stronger than on Earth.

Ghez was given the opportunity to present partial data last summer, but chose not to so that her team could thoroughly analyze the data first. “We’re learning how gravity works. It’s one of four fundamental forces and the one we have tested the least,” she said. “There are many regions where we just haven’t asked, how does gravity work here? It’s easy to be overconfident and there are many ways to misinterpret the data, many ways that small errors can accumulate into significant mistakes, which is why we did not rush our analysis.”

Ghez, a 2008 recipient of the MacArthur “Genius” Fellowship, studies more than 3,000 stars that orbit the supermassive black hole. Hundreds of them are young, she said, in a region where astronomers did not expect to see them.

It takes 26,000 years for the photons from S0-2 to reach Earth. “We’re so excited, and have been preparing for years to make these measurements,” said Ghez, who directs the UCLA Galactic Center Group. “For us, it’s visceral, it’s now — but it actually happened 26,000 years ago!”

This is the first of many tests of general relativity Ghez’s research team will conduct on stars near the supermassive black hole. Among the stars that most interest her is S0-102, which has the shortest orbit, taking 11 1/2 years to complete a full orbit around the black hole. Most of the stars Ghez studies have orbits of much longer than a human lifespan.

Ghez’s team took measurements about every four nights during crucial periods in 2018 using the Keck Observatory — which sits atop Hawaii’s dormant Mauna Kea volcano and houses one of the world’s largest and premier optical and infrared telescopes. Measurements are also taken with an optical-infrared telescope at Gemini Observatory and Subaru Telescope, also in Hawaii. She and her team have used these telescopes both on site in Hawaii and remotely from an observation room in UCLA’s department of physics and astronomy.

Black holes have such high density that nothing can escape their gravitational pull, not even light. (They cannot be seen directly, but their influence on nearby stars is visible and provides a signature. Once something crosses the “event horizon” of a black hole, it will not be able to escape. However, the star S0-2 is still rather far from the event horizon, even at its closest approach, so its photons do not get pulled in.)

Photo of telescope pointing to the sky.

Lasers from the two Keck telescopes point in the direction of the center of our galaxy. Each laser creates an “artificial star” that astronomers can use to correct for the blurring caused by the Earth’s atmosphere. Photo: Ethan Tweedie

Ghez’s co-authors include Tuan Do, lead author of the Science paper, a UCLA research scientist and deputy director of the UCLA Galactic Center Group; Aurelien Hees, a former UCLA postdoctoral scholar, now a researcher at the Paris Observatory; Mark Morris, UCLA professor of physics and astronomy; Eric Becklin, UCLA professor emeritus of physics and astronomy; Smadar Naoz, UCLA assistant professor of physics and astronomy; Jessica Lu, a former UCLA graduate student who is now a UC Berkeley assistant professor of astronomy; UCLA graduate student Devin Chu; Greg Martinez, UCLA project scientist; Shoko Sakai, a UCLA research scientist; Shogo Nishiyama, associate professor with Japan’s Miyagi University of Education; and Rainer Schoedel, a researcher with Spain’s Instituto de Astrofısica de Andalucıa.

The National Science Foundation has funded Ghez’s research for the last 25 years. More recently, her research has also been supported by the W.M. Keck Foundation, the Gordon and Betty Moore Foundation and the Heising-Simons Foundation; as well as Lauren Leichtman and Arthur Levine, and Howard and Astrid Preston.

In 1998, Ghez answered one of astronomy’s most important questions, helping to show that a supermassive black hole resides at the center of our Milky Way galaxy. The question had been a subject of much debate among astronomers for more than a quarter of a century.

A powerful technology that Ghez helped to pioneer, called adaptive optics, corrects the distorting effects of the Earth’s atmosphere in real time. With adaptive optics at Keck Observatory, Ghez and her colleagues have revealed many surprises about the environments surrounding supermassive black holes. For example, they discovered young stars where none was expected to be seen and a lack of old stars where many were anticipated. It’s unclear whether S0-2 is young or just masquerading as a young star, Ghez said.

In 2000, she and colleagues reported that for the first time, astronomers had seen stars accelerate around the supermassive black hole. In 2003, Ghez reported that the case for the Milky Way’s black hole had been strengthened substantially and that all of the proposed alternatives could be excluded.

In 2005, Ghez and her colleagues took the first clear picture of the center of the Milky Way, including the area surrounding the black hole, at Keck Observatory. And in 2017, Ghez’s research team reported that S0-2 does not have a companion star, solving another mystery.

This article originally appeared in the UCLA Newsroom.