A photo of Dr. Steven Jonas, Jason Belling and Paul Weiss of UCLA .

A step toward a more efficient way to make gene therapies to attack cancer, genetic disorders

A photo of Dr. Steven Jonas, Jason Belling and Paul Weiss of UCLA .

(From left) Dr. Steven Jonas, Jason Belling and Paul Weiss of UCLA (Photo Credit: Reed Hutchinson)

A UCLA-led research team today reports that it has developed a new method for delivering DNA into stem cells and immune cells safely, rapidly and economically. The method, described in the journal Proceedings of the National Academy of Sciences, could give scientists a new tool for manufacturing gene therapies for people with cancer, genetic disorders and blood diseases.

The study’s co-senior author is Paul Weiss, a UCLA distinguished professor of chemistry and biochemistry, of bioengineering and of materials science and engineering. “We are figuring out how to get gene-editing tools into cells efficiently, safely and economically,” he said. “We want to get them into enormous numbers of cells without using viruses, electroshock treatments or chemicals that will rip open the membrane and kill many of the cells, and our results so far are promising.”

In current practice, cells used for genetic therapies are sent to specialized labs, which can take up to two months to produce an individualized treatment. And those treatments are expensive: A single regimen for one patient can cost hundreds of thousands of dollars.

“We hope our method could be used in the future to prepare treatments that can be performed at the patient’s bedside,” Weiss said.

The method could be used with CRISPR, the genetic engineering technique that enables DNA to be edited with remarkable precision. However, using CRISPR efficiently, safely and economically in medical therapies has proven to be a challenge — one this new method may be able to solve.

The technique uses high-frequency acoustic waves coupled with millions of cells that flow through an “acoustofluidic device” in a cell culture liquid. The device was invented by the research team as part of the study; inside of it are tiny speakers that convert electrical signals to mechanical vibrations that are used to manipulate the cells.

That procedure opens up pores along the cells’ membranes that allow DNA and other biological cargo to enter the cells, and it enables the researchers to insert the cargo without the risk of damaging the cells by contacting them directly.

Dr. Steven Jonas, the study’s co-senior author and a UCLA clinical instructor in pediatrics, likened the soundwaves’ ability to move cells to the experience when audience members actually feel the sound at a concert.

“At a concert hall, you can feel the bass — and if you can feel the sound, the cell can feel the acoustic wave,” said Jonas, a member of the California NanoSystems Institute at UCLA, the UCLA Jonsson Comprehensive Cancer Center and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. “We can engineer the acoustic waves to direct the cells as needed.”

The researchers delivered short strands of DNA called plasmids into human blood cells and blood-forming stem cells that were intended specifically for laboratory research, and pumped millions of such cells through the acoustofluidic device. Once inside a cell, a plasmid can be made into a protein that may be missing or damaged, or it can give the cell new capabilities.

“When combined with new gene-editing approaches, the method enables us to correct a DNA sequence that is miscoded in a disease,” said Weiss, who also is a member of CNSI.

Plasmids used as templates for gene editing can make the correction because they have the right coded sequence for the desired protein, he explained.

Lead author Jason Belling, a UCLA graduate student in chemistry and biochemistry, was able to insert plasmids into the model cells used for testing about 60% of the time, without using any chemical and physical treatments.

“The viability is very high compared with other techniques,” Weiss said, “but we still want higher efficiencies and are working toward that.”

Jonas — whose expertise is in treating childhood cancer and blood disorders — said the research has the potential to benefit adults and children with cancer, immune system disorders and genetic diseases.

“If the delivery works, and it seems to, this research is an important step toward bringing new therapies more broadly to the patients who need them,” Jonas said. “Traditionally, we have treated cancers with chemotherapy, surgery, radiation and bone marrow transplantations. Now, we’re at an amazing era of medicine, where we can use different types of gene therapies that can train the immune system to fight cancer.”

A photo of a prototype of the acoustofluidic device developed by UCLA researchers.

A prototype of the acoustofluidic device developed by UCLA researchers. (Photo Credit: Reed Hutchinson)

Jonas said some existing treatments can take a patient’s T cells and adapt them with a gene that encodes for a receptor that allows it to target the cancer.

“We want to be the delivery service that gets these therapeutic packages to the cells,” he said. “I want to treat my patients with cells that are engineered in this way.”

For the technique to lead to viable treatments for disease, it would need to allow doctors  to process at least a couple hundred million cells — and in some cases, billions of cells — safely, rapidly and cost-effectively for each patient.

The new approach is still the subject of research and is not available to treat human patients.

The study’s other co-authors include Duke University professor Tony Huang, a pioneer of acoustofluidics and a UCLA alumnus; Dr. Stephen Young, distinguished professor of medicine and human genetics at the David Geffen School of Medicine at UCLA; and Dr. Satiro De Oliveira, a UCLA assistant professor of pediatrics.

The study was funded in part through a National Institutes of Health Director’s Early Independence Award for Jonas; the University of California Center for Accelerated Innovation; and Belling’s predoctoral fellowship through the National Heart, Lung, and Blood Institute. Jonas also has received young investigator awards from the Alex’s Lemonade Stand Foundation for Childhood Cancer Research, Hyundai Hope on Wheels Foundation for Pediatric Cancer Research, and the Tower Cancer Research Foundation. UCLA’s Technology Development Group Innovation Fund also provided funding.

Weiss’ research group has applied for patents on the acoustofluidic device and related devices, working with the Technology Development Group.

This article originally appeared in the UCLA Newsroom.

Keeping Our First Responders in LA County Hospitals Safe

A photo of a first responder receives safety glasses and goggles.

A first responder receives safety glasses and goggles. (Photo Courtesy of UCLA Department of Chemistry and Biochemistry)

The Department of Chemistry and Biochemistry, spurred on by Professor Neil Garg, donated hundreds of safety glasses and goggles to help keep first responders in Los Angeles County hospitals safe. The distribution, orchestrated in a single weekend, was a way to express thanks to the selfless medical personnel in Los Angeles.

This post originally appeared on the Department of Chemistry and Biochemistry’s Facebook.

A photo of a student meditating during a break.

UCLA Students Find COVID-19 Silver Linings

Commentary on mindful awareness training by Sara Melzer, Professor Emerita of French & Francophone Studies:

Surprising as it may sound, some of my UCLA students are finding meaning during the pandemic. One student reports: “I’m excited at the inner changes this quarantine is bringing out in me.” Almost all the students are discovering that their lives are fuller than they had realized – when they re-direct their attention. This training is the work of a mindful awareness.

Mindfulness is not necessarily spiritual or mystical, although it can be. Mainly, it trains our most fundamental faculty: our attention. If skillfully cultivated, our attention can dramatically transform our experience and promote well-being, even during a crisis. This claim may seem astonishing because we are not taught to value our attention, even though it is the ever-present background to all thought and experience.

Mindfulness highlights the vast potential of this resource. Our attention is a muscle — a mental muscle that needs to be trained, just as athletes train their bodies, insists Shinzen Young, founder of Unified Mindfulness and my teacher for 20 years.

My students experienced the power of their attention to transform their relationship to pain in a class experiment where I had them hold ice-cubes in one hand, for two rounds. In round one, I offered no guidance and they relied on their standard coping strategy. After five minutes, they were in agony. In round two, I guided them to hold the ice mindfully. One student reported, “I felt blissfully calm. I could have held the ice forever.”

What made the difference? Their attention – what they focused on and how. In the first round, they tightened their bodies and narrowed their lens to block the pain. This mental image, a cortical homunculus, simulates the brain mapping the body from the inside: hands swell up like balloons and dwarf the body.

A photo of a student meditating during a break.

A student meditating during a break. (Photo Credit: Christian Ibarra)

Their hand defined their whole body. When we are in pain, physical or emotional, we often identify with the ailing part and let it become the whole.

Alternatively, we can re-frame our attention. I invited my students to expand their focus beyond their hands to include their feet, where they noticed pockets of calm.  I activated their attention’s telescopic lens when I had them zoom their awareness out, first to sounds inside the room, then outside, before extending to the silence beyond. While they felt their hands throb, they simply included it within a wider attentional field. The impact of the ice was diffused. Just as a few drops of red dye can define the water’s color in a fish-bowl, but not in a lake, my students could dilute and transform their experience of pain by enlarging their attentional frame.

The momentary shift of attention is actually not the hard part. Keeping it there is. To achieve this, Unified Mindfulness emphasizes sensory clarity as a key attentional skill. It can open up our awareness to a fascinating “something” within the seeming “nothing” of our ordinary experience. Take the breath, for example. Using a microscopic lens, we zero in on the outbreath to notice a subtle release of air. Other forms of release – in the jaws, shoulders, rib cage – ripple out. This inter-connectedness is a source of wonder.

Sensory clarity helps anchor our attention because our sensory world becomes more richly layered and attention-grabbing.  One student wrote, “I invited my family to join me in my mindful eating exercise. For desert, we had grapes — just ordinary grapes. They exploded with extraordinary taste sensations. Waves of sweetness, then sourness rippled out towards my ears, then throughout my whole body. It was so satisfying I almost felt full.” When we tune into the nuanced layers of something as ordinary as an exhale or a grape, any experience can anchor our attention and nourish us.

Managing our attention in this way contrasts with our standard notion of concentration. The term “concentration” in English mainly signifies a forcible narrowing of focus to bear down on an object. But our bodies tighten and we slip back into a version of the ice-cube scenario. What we resist, persists! Mindfulness, however, emphasizes that the truest concentration comes from an ease that unifies our energies. Coupled with sensory clarity, concentration holds our attention not through coercion, but fascination and wonder.

Of course, the COVID crisis is much more serious than ice-cubes. But the underlying principle still pertains: include the ailing part within a larger whole so that fear does not occupy all our attentional space or define our whole life. One student described how a shift in her attention helped ease her panic after learning that the “shelter-in-place” would continue longer than expected. Initially, she was glued to social media which convinced her “all of life was closing up shop.” Finally, she remembered she had a choice. She could re-frame her attention to include her anxiety within a wider container that diluted its power. She did not deny her fear but included it within a larger lens. As poet Maya Angelou wrote: “You may not control all the events that happen to you, but you can choose not to be reduced by them.”

When all their attention was not colonized by fear, my students freed up energy to explore what was available to them. I had asked them to notice their COVID-19 Silver Linings. Since they were on the look-out for them, they found them. They used their mindfulness muscle to soak their awareness into them and anchor their attention there. Many experienced a surprising inner freedom when they discovered creative resources they didn’t know they had.

Creativity thrives when we are confronted with constraints. Let us seize this opportunity to turn our focus towards what remains possible and open up their hidden depths. In this way lies freedom and well-being.

Sara E. Melzer is a Humanities Professor of French and Francophone Studies at the University of California, Los Angeles. Her latest book is Colonizer or Colonized: The Hidden Stories of Early Modern French Culture. Currently, she is working to integrate mindfulness into Higher Education through UCLA’s EPIC program

A photo of Lynn Vavreck and Miguel García-Garibay.

Two elected to American Academy of Arts and Sciences

A photo of Lynn Vavreck and Miguel García-Garibay.

From left: Lynn Vavreck, Miguel García-Garibay

Six exceptional UCLA professors and leaders — including the UCLA College’s Physical Sciences Dean Miguel García-Garibay and Political Science Professor Lynn Vavreck — were elected April 23 to the American Academy of Arts and Sciences, one of the nation’s most prestigious honorary societies. The other honorees include School of Law Dean Jennifer Mnookin, Education Professor Pedro Noguera, environmental champion Mary Nichols and Hammer Museum Director Ann Philbin.

“I am delighted to congratulate each of this year’s UCLA inductees, who are all deserving of this wonderful honor,” UCLA Chancellor Gene Block said. “Election to the American Academy of Arts and Sciences is a testament to the exceptional work of our scholars and leaders. The entire campus community can take pride in this news and their many accomplishments.”

A total of 276 artists, scholars, scientists and leaders in the public, nonprofit and private sectors who were elected to the Academy today. More about UCLA’s honorees:

Miguel García-Garibay, dean of the UCLA Division of Physical Sciences and professor of chemistry and biochemistry, has earned worldwide recognition in the fields of artificial molecular machines, organic photochemistry, solid-state organic chemistry and physical organic chemistry. He studies the interaction of light and molecules in crystals. Light can have enough energy to break and make bonds in molecules, and García-Garibay’s research team has shown that crystals offer an opportunity to control the outcome of these chemical reactions.

His research has applications for green chemistry — the design of chemical products and processes that reduce or eliminate the generation of hazardous substances — and it could lead to the production of specialty chemicals that would be very difficult to produce using traditional methods. Among his many honors, he was elected a fellow of the American Chemical Society in 2019.

Lynn Vavreck is UCLA’s Marvin Hoffenberg Professor of American Politics and Public Policy, a contributing columnist to the Upshot at the New York Times, and a recipient of many awards and honors, including the Andrew F. Carnegie Prize in the Humanities and Social Sciences. She is the author of five books, including “Identity Crisis: The 2016 Presidential Campaign and the Battle for the Meaning of America” and “The Gamble: Choice and Chance in the 2012 Presidential Election,” which has been described as the “definitive account” of that election.

Consultants in both political parties refer to her work on political messaging in “The Message Matters” as required reading for presidential candidates. “Identity Crisis” was awarded the 2019 Richard E. Neustadt Prize for the Best Book on Executive Politics by the Presidents and Executive Politics Section of the American Political Science Association.

Vavreck’s 2020 election project, Nationscape, is the largest study of presidential elections ever conducted in the United States. Interviewing more than 6,000 people a week, Nationscape will complete 500,000 interviews before next January’s inauguration.

► Read more about the Nationscape election project.

“The members of the class of 2020 have excelled in laboratories and lecture halls, they have amazed on concert stages and in surgical suites, and they have led in board rooms and courtrooms,” said David Oxtoby, president of the Academy. “With [the] election announcement, these new members are united by a place in history and by an opportunity to shape the future through the Academy’s work to advance the public good.”

The American Academy of Arts and Sciences was founded in 1780 by John Adams, John Hancock and others who believed the new republic should honor exceptionally accomplished individuals. Previous fellows have included George Washington, Benjamin Franklin, Alexander Hamilton, Ralph Waldo Emerson, Albert Einstein, Charles Darwin, Winston Churchill, Martin Luther King Jr. and Nelson Mandela.

It also is an independent policy research center that undertakes studies of complex and emerging problems. Current academy members represent today’s innovative thinkers in many fields and professions, including more than 250 Nobel and Pulitzer Prize winners.

This article originally appeared in the UCLA Newsroom.

An image of dust over the Sahara Desert.

Earth’s atmosphere far dustier than previously believed

An image of dust over the Sahara Desert.

Dust over the Sahara Desert (Photo Credit: NASA GSFC)

Dust is a key component of Earth’s climate system. When it interacts with clouds, oceans and the sun’s radiation, it has an overall impact on our planet’s living systems, affecting everything from weather and rainfall to global warming.

There are two types of dust in the atmosphere, both kicked up by high-velocity winds in dry areas. Fine dust tends to cool because it scatters sunlight, much like clouds do. Coarse dust, which is larger in size and originates in places like the Sahara Desert, tends to warm the atmosphere, much like greenhouse gases.

Knowing precisely how much coarse dust is in the atmosphere is essential for understanding not only the atmospheric phenomena that dust influences but also the degree to which dust may be warming the planet.

Now, UCLA scientists report that there is four times the amount of coarse dust in Earth’s atmosphere than is currently simulated by climate models. Their findings appear in the journal Science Advances.

The researchers found that Earth’s atmosphere contains 17 million metric tons of coarse dust — equivalent to 17 million elephants or the mass of every person in America put together.

“To properly represent the impact of dust as a whole on the Earth system, climate models must include an accurate treatment of coarse dust in the atmosphere,” said the study’s first author, Adeyemi Adebiyi, a postdoctoral researcher in UCLA’s Department of Atmospheric and Oceanic Sciences and a recipient of the University of California President’s Postdoctoral Fellowship.

By plugging this amount of missing coarse dust into models, Adebiyi said, it increases the likelihood that the net amount of dust overall — both fine and coarse — is warming rather than cooling the Earth’s climate system, from air to oceans.

Coarse dust particles warm the Earth’s entire climate system by absorbing both incoming radiation from the sun and outgoing radiation from the Earth’s surface. These particles can impact stability and circulation within our atmosphere, which may affect atmospheric phenomena like hurricanes.

Adebiyi worked with Jasper Kok, a UCLA associate professor of atmospheric and oceanic sciences, to determine the actual amount of coarse dust in the atmosphere by analyzing dozens of published aircraft-based observations, including recent measurements taken over the Sahara Desert, and comparing those with half a dozen widely used global atmospheric model simulations.

“When we compared our results with what is predicted by current climate models, we found a drastic difference,” Kok said. “State-of-the-art climate models account for only 4 million metric tons, but our results showed more than four times that amount.”

In addition, Adebiyi and Kok found that coarse dust leaves the atmosphere less quickly than current climate models predict. Air has a tendency to mix more turbulently when dust is present. In the case of the Sahara, air and dust mix in ways that push the dust upward, which can work against gravity and keep the dust in the air much longer, they said.

The scientists’ findings also show that because dust particles stay in the atmosphere longer, they are ultimately deposited further from their source than has been predicted by these models or explained by current theory. Dust particles blown from the Sahara, for example, can travel thousands of miles in the atmosphere, reaching as far as the Caribbean and the United States.

When desert dust ends up in oceans, it may stimulate the productivity of ocean ecosystems and increase the amount of carbon dioxide absorbed by the oceans.

Due to the way coarse dust interacts with the sun’s energy and clouds, it can also have a major impact on the timing of precipitation, as well as how much, or how little, rain falls.

“Models have been an invaluable tool for scientists,” said Adebiyi, “but when they miss most of the coarse dust in the atmosphere, it underestimates the impact that this type of dust has on critical aspects of life on Earth, from precipitation to cloud cover to ocean ecosystems to global temperature.”

This article originally appeared in the UCLA Newsroom.

A photo of Matie Zubiaurre, professor of Spanish and Portuguese in the UCLA College.

Spanish professor wins award for book on the cultural uses of garbage

A photo of Matie Zubiaurre, professor of Spanish and Portuguese in the UCLA College.

Matie Zubiaurre, professor of Spanish and Portuguese in the UCLA College. (Photo Courtesy of Matie Zubiaurre)

Maite Zubiaurre, professor of Spanish and Portuguese in the UCLA College, has been awarded the 2020 Norman L. and Roselea J. Goldberg Prize from Vanderbilt University Press for her book “Talking Trash. Cultural Uses of Waste.” The award recognizes the best book in the area of art and medicine.

In “Talking Trash,” Zubiaurre looks at refuse in its early stages, when it is still litter that can be found on city streets. She also focuses on a significant non-urban scene: the desert landscape and the clothing and other items that immigrants discard as they make their journey across the border.

Zubiaurre’s other books include “El espacio en la novela realista. Paisajes, miniaturas, perspectivas,” a book-length study of the dialectics of space and gender in European and Latin American realist fiction, and of “Cultures of the Erotic. Spain 1898-1939”, the first scholarly monograph that analyzes the diverse visual and textual representations of the erotic in Spanish popular culture during the so-called Silver Age between 1898 and 1936.

Some of Zubiaurre’s areas of expertise include comparative literature, gender studies, urban studies, cultural studies, European and Latin American Realism and Latina and Chicana fiction. She is also the author of numerous articles and critical editions and co-editor of an anthology of Spanish feminist thought, “Antología del pensamiento feminista español: 1726-2008.”

This article originally appeared in the UCLA Newsroom.

A photo of a valley oak tree.

UCLA College Celebrates Earth Day

A photo of a Griffith Park vista; the view of the Los Angeles skyline from Griffith Park.

Los Angeles County is home to more than 4,000 distinct species of plants and animals, and the sustainability plan aims for “no loss of native biodiversity.” (Photo Credit: Jake Dobkin)

Not only does this mark its 50th anniversary, this Earth Day is unlike any other we have seen as the global pandemic continues to impact the way we live our lives. Yes, it has disrupted our daily routines but it has also benefited the environment in myriad ways. For example, freeways once clogged with traffic have opened up, clearing the air and making way for bright blue skies and views for miles. Even before COVID-19, UCLA College faculty members and teams were out in the field and in their labs, working on groundbreaking research and advising on county and statewide plans. In honor of Earth Day, we are highlighting stories about conservation, sustainability, global warming, solar geoengineering and protecting our precious ecosystems.

 

A photo of vegetation and mountains in California's Anza-Borrego State Park.

Vegetation and mountains in California’s Anza-Borrego State Park. (Photo Credit: Sean Brenner/UCLA)

UCLA to lead $10 million California conservation project

UCLA scientists are leading a $10 million project to help California officials make ecologically wise decisions as the state continues to confront the effects of climate change. The initiative will give California officials scientific data they can use to make decisions about conserving the state’s ecosystems.

A photo 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)

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

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.

A photo of a Griffith Park vista; the view of the Los Angeles skyline from Griffith Park.

Los Angeles County is home to more than 4,000 distinct species of plants and animals, and the sustainability plan aims for “no loss of native biodiversity.” (Photo Credit: Jake Dobkin)

L.A. County taps UCLA to help create first-ever sustainability plan

The Los Angeles County Board of Supervisors unanimously approved an ambitious sustainability plan that calls for phasing out fossil fuels to address climate change and improve quality of life in the region. Sixteen UCLA researchers contributed to the OurCounty plan, which was created by the county’s Chief Sustainability Office.

A photo of the Santa Monica Pier at night.

The Santa Monica Pier at night. Artificial light can cause problems for a range of species that live and breed in coastal environments. (Photo Credit: William Chen/Pexels)

Study draws Southern California coastal light pollution into focus

Artificial light is known to disrupt mating cycles in species along the Southern California coast. A team of UCLA and University of Southern California researchers led by Travis Longcore, UCLA adjunct professor of urban conservation biology, has mapped light pollution conditions that will be used to inform decisions about future infrastructure and construction plans.

A photo of members of the UCLA Center for Diverse Leadership in Science, which was founded by Aradhna Tripati, associate professor in the UCLA Institute of the Environment and Sustainability.

Members of the Center for Diverse Leadership in Science, which was founded by Professor Aradhna Tripati, third row, far right, and their colleagues. (Photo: Courtesy of Aradhna Tripati)

Professor pays it forward by promoting diversity and environmental justice

When she was appointed in 2009, Aradhna Tripati was the first woman of color out of 50 faculty in UCLA’s Institute of the Environment and Sustainability. Along with colleagues in UCLA’s Anthropology department and American Indian Studies Center, she conducts community engaged research on water in the context of global warming in the southwestern United States. She also formed the first university-based center for diversity in environmental science, with the goal of inspiring a generation of leaders that matches the demographics of the U.S. population.

A photo of Stephanie Correa and Edward van Veen in Correa's UCLA laboratory

Research provides new insights into menopause and weight gain

A photo of Stephanie Correa and Edward van Veen in Correa's UCLA laboratory

Stephanie Correa and Edward van Veen in Correa’s UCLA laboratory (Photo Credit: Reed Hutchinson)

Can women in menopause get the benefits of hormone replacement therapy without the risks? A new UCLA study conducted with mice points in that direction, but additional research is necessary.

Women commonly experience hot flashes and weight gain, among other changes, during and after menopause. Hormone therapy, which gives women additional estrogen, can help alleviate some of these symptoms, but it has been linked to a higher risk of heart disease and breast cancer.

UCLA life scientists now report that a gene called reprimo, which is expressed by certain neurons in the brain, may play a role in menopause-related weight gain, a phenomenon not linked to increased eating. Their findings are published today in the journal Nature Metabolism.

“We want to figure out which neurons are mediating the beneficial portions of hormone therapy and mimic them without hormones,” said senior author Stephanie Correa, a UCLA assistant professor of integrative biology and physiology and a member of UCLA’s Brain Research Institute. “Hormone therapy can be beneficial, but it treats the entire brain and body with hormones. We may be able to bypass the hormone. That’s our goal, and it’s a big one. We haven’t achieved it yet, but we’re learning.”

Correa and her research team show that the reprimo gene is important for regulating temperature. Changes in temperature are known to affect body weight and may contribute to the weight gain often seen in menopause.

“It’s possible that reprimo is involved in the weight gain that accompanies menopause,” said co-lead author Edward van Veen, a project scientist in Correa’s laboratory. “If equivalent neurons exist in humans and we can find some way to tweak them, it might relieve much of the weight gain without the side effects of hormone therapy.”

A brain region called the hypothalamus is essential for survival in many species, from mice to humans; it controls eating, drinking, reproduction and body-temperature regulation, among other vital functions. Correa and her research team studied dozens of genes in the hypothalami of more than 50 mice, both female and male, starting at about eight weeks of age, shortly after they reach reproductive age.

The team used a technique known as single-cell RNA-seq, which allows biologists to study individual cells one at a time, to investigate which neurons in an area of the hypothalamus known as the ventromedial hypothalamus might mediate these different functions.

“We had hints there were different types of neurons in the ventromedial hypothalamus, and this region is very different in males and females, so we studied hundreds of cells in males and females to identify the different types of neurons and determine whether there are sex differences,” Correa said.

The biologists were most interested in neurons that have estrogen receptors. These receptors bind to the hormone and are subsequently able regulate to the activity of specific genes in the neuron, a process known as gene expression. The team’s most significant findings centered on the reprimo gene, which is expressed in one group, or population, of these estrogen-responsive neurons, restricted almost entirely to females.

“We were excited to find not only populations of estrogen-responsive neurons but also differences in these populations between males and females,” said co-lead author Laura Kammel, a former UCLA doctoral student in Correa’s laboratory.

“The difference between females and males in reprimo in the ventromedial hypothalamus is like night and day,” Correa said. “The females express a ton of it, and males express little, if any, reprimo in this brain region. Of the dozens of genes I have studied in this region, this is easily the strongest sex difference I have ever seen.”

In a series of experiments, the biologists interfered with the function of reprimo in the ventromedial hypothalamus in about two dozen mice. In one experiment, they shut off reprimo in female mice by using an RNA molecular compound that interferes with how the gene works in neurons. In another, they increased reprimo expression in male mice by removing an estrogen receptor from the neurons. In both cases, body temperature changed substantially, demonstrating a link between reprimo’s role in temperature and the effects of estrogen.

“We know that reprimo is important in regulating body temperature, but we don’t know what it is actually doing in neurons,” van Veen said. “We want to find out.”

Correa and her team also report that estrogen acts on another gene, Tac1, that is significantly increased in the ventromedial hypothalamus of female mice, although the difference is not nearly as dramatic as with reprimo. Tac1 has been shown to promote physical activity in female mice.

Estrogen receptor alpha, one of three estrogen receptors, is found in neurons in the same region of the ventromedial hypothalamus as Tac1 and reprimo. When the researchers removed that estrogen receptor, they found it led to obesity and reduced movement in female mice.

The results, the researchers said, not only aid in their understanding of the interplay between genes and estrogen but may also have implications for understanding obesity.

Summarizing the research, van Veen said: “The ventromedial hypothalamus is involved in movement and temperature regulation. We know estrogen affects movement and temperature. From Stephanie Correa’s previous research, we learned the estrogen response of neurons that affect movement, and now we think we know the estrogen response of neurons that affect temperature. It’s interesting that they are in the same location but distinct.”

“Our findings suggest reprimo is controlling some of the effects of estrogen on temperature,” Correa said. “If it is controlling the beneficial effects, then maybe we can manipulate it — with a drug that targets reprimo or the neurons that express reprimo — as an alternative to hormone therapy and get around the requirement for estrogen. We are studying the brain in a nuanced way and trying to learn which cells or which genes are important to target for potential therapies.”

Co-authors are co-lead author Laura Kammel, a former UCLA doctoral student in Correa’s laboratory; Xia Yang, a UCLA associate professor of integrative biology and physiology; Arthur Arnold, a UCLA distinguished professor of integrative biology and physiology; and Marc Liesa-Roig, a UCLA assistant professor-in-residence at the David Geffen School of Medicine at UCLA.

This article originally appeared in the UCLA Newsroom.

A photo of the sidewalk with chalk that says "Play your part, stay apart"

Play your part, stay apart: Advice and insight on physical distancing

A photo of the sidewalk with chalk that says "Play your part, stay apart"

Play your part, stay apart (Photo Credit: Jessica Wolf)

It has been a month since the wide-ranging safer-at-home directive went into effect in Los Angeles on March 17, following, and followed by, similar policies in other states and countries around the world.

It’s been hard. It’s wreaked havoc on our economy, our communities and our sense of emotional well-being. People understandably want to connect, go outside, share physical spaces, make a living, enjoy friends and family.

We asked Daniel Fessler, professor of anthropology and director of the UCLA Bedari Kindness Institute to help unpack why physical distancing feels so counterintuitive even while it represents one of the greatest mass acts of kindness — what scientists call “prosocial” behavior — we have witnessed as a species.

Why is it so hard to stay away from the people we are closest to socially? 

Our evolved mental mechanisms prioritize close social relationships over disease avoidance because those relationships were so important to the survival of our ancestors. One of the results of this is that we underestimate the risk of contagion that is posed by those to whom we are emotionally close. And as a consequence, people visit their relatives and close friends, and by so doing, they put at risk those whom they love the most.

The truth is, you’re probably even more dangerous to your loved ones than you are to strangers. After all, when’s the last time that you hugged a stranger on the street? If you care about the welfare of people you care about, then stay away from them.

Why is it so hard for us to fully accept that we might be dangerous to others, even if we don’t feel sick?  

Our evolved mental mechanisms are only attuned to overt cues of illness, so it’s difficult for us to grasp that we can be symptom-free and still infectious.

We can sort of understand that in an abstract way, but it’s hard for us to understand it in an emotional way. Likewise, our evolved mechanisms are attuned to harm that is tangible and immediate. The harm that we can do others is transmitted invisibly in this current situation and occurs after a delay of days or weeks. I’m quite confident that none of those college students who were partying on the beach in Florida during spring break would ever intentionally run over an elderly person in a crosswalk, but they’re potentially doing exactly that by contracting and spreading the virus.

How do we remind ourselves that staying away from one another physically is actually a huge act of kindness right now? 

As individuals, we all have a role to play in mitigating the impact of this disease. But problematically, social distancing doesn’t feel like prosocial behavior. And the reason it doesn’t feel like prosocial behavior is because in the world of our ancestors, helping other people and working together meant working face-to-face and side-by-side. You can think, for example, about how good it feels to help a stranger on the street or to work as a team to clean up trash on a beach or repaint an elementary school.

These things feel really good, right? And this is because our evolved psychological mechanisms are sensitive to cues that we are part of a prosocial cooperative group.

You may also think about how great it feels to do the wave with a huge crowd at a sporting event or to sing the national anthem together with thousands of people. These things are emotionally moving. They feel great because we are sensitive to the situation in which we’re coordinating our actions with those of many people around us towards a common goal.

Yet in the current crisis, for most of us, the first prosocial action that we must engage in is to stay away from other people. And ordinarily, staying away from other people can feel selfish. So staying away from other people doesn’t feel like we’re helping anyone.

I encourage everyone to think creatively. How can you help? For example, millions of kids are out of school right now. Can you tutor children via video link? Maybe just read a child a story. Many small businesses are in danger of going bankrupt. Can you purchase products or services at a distance that will help them to stay afloat?

Or maybe you can help deliver meals or medication to the elderly or to children who normally rely on school lunches and school nurses for their needs — of course, conducting yourself appropriately with regard to the safeguards of hygiene and social distancing when you are making those deliveries. Think outside the box. Get some ideas online. Find a way to help other people while still playing your part and staying apart.

What can we do to encourage others to continue to practice safe distancing until city and state leaders relax guidelines?

If you see someone ignoring social distancing guidelines, you need to acknowledge in discussion with them that you understand that it may seem safe because neither you nor they feel sick right now. But despite this, it doesn’t mean that either of you can’t transmit the virus to the other or to someone else. How we feel physically is simply not an accurate index of whether we might harm other people by being near them. Those kinds of conversations, of course, you need to hold at a safe distance, six feet or so.

In having those conversations, it’s helpful to think about language. Language can reflect the priorities and needs at the moment. People coin new words all the time. Just think, for example: Phrases like “gig economy,” “screen time” or “trending” weren’t things a few years back. I find acronyms particularly useful in this regard. You can Google the origins of two of my favorites — snafu (situation normal, all fouled up) and fubar (fouled up beyond all recognition) — two terms that were coined during other desperate emergency times.

We can coin a new acronym, a new word: PYPSA. It stands for “Play Your Part, Stay Apart.” You can use the word as praise for people who are doing a great job of social distancing: “Hey, man, way to go! You’re really PYPSA-ing,” and remind people who might forget or who might underestimate the importance of social distancing.

This article originally appeared in the UCLA Newsroom.