Fructose and head injuries adversely affect hundreds of brain genes linked to human diseases

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By Stuart Wolpert

Consuming fructose, a sugar that’s common in the Western diet, alters hundreds of brain genes that may be linked to many diseases, UCLA life scientists report. However, they discovered good news as well: an important omega-3 fatty acid known as DHA (docosahexaenoic acid) seems to reverse the harmful changes produced by fructose.

“DHA changed not just one or two genes, but seems to push the entire gene pattern back to normal, which is remarkable, and we can see why it has such a powerful effect,” said Xia Yang, a senior author of the study and a UCLA associate professor of integrative biology and physiology.

DHA is found in brain cell membranes, but “the brain and the body are deficient in the machinery to make DHA; it has to come through our diet,” said co-senior author Fernando Gomez-Pinilla, a UCLA professor of neurosurgery and of integrative biology and physiology.

DHA, which strengthens synapses in the brain and enhances learning and memory, is abundant in wild salmon and, to a lesser extent, in fish oil and other fish, while its biochemical precursors are high in walnuts, flaxseed, and to a less extent, fruits and vegetables, Gomez-Pinilla said.

Americans consume most of their fructose from processed foods sweetened with high-fructose corn syrup, an inexpensive liquid sweetener made from cornstarch, as well as from sweet drinks, syrups, honey, ice cream and other desserts, he said. It’s also in baby food. Fruit contains fructose, but has high levels of fiber, which substantially slows the absorption of fructose and increases the feeling of fullness, Yang said. Fruits also contain many other healthy components that protect the brain and body, they noted.

Lab-tested

The researchers trained laboratory rats to escape from a maze, then randomly divided the rats into three groups. They gave one group of rats water with fructose added for six weeks that would be roughly equivalent to a person drinking about a liter of soda a day. A second group of rats was given the water with fructose and a diet rich in DHA for six weeks, and a control group was given water without fructose and not given the DHA supplement.

The rats that had been given the fructose had significantly higher blood glucose, triglycerides and insulin levels than the control group, and had impaired memory when navigating the maze; they were about 30 percent slower than the control group in escaping from the maze. The rats given the

DHA supplement, however, showed very similar results to the control group.

Yang and Gomez-Pinilla’s research team sequenced more than 20,000 genes in the rats, and discovered that fructose adversely affected more than 700 genes in the hypothalamus and more than 200 genes in the hippocampus – genes that interact to regulate metabolism, cell communication and inflammation.

Xia Yang and Fernando Gomez-Pinilla

Humans have genes that are counterparts to the genes affected by fructose in rats, and the human genes are associated with obesity, diabetes, cardiovascular disease, Alzheimer’s disease, Parkinson’s disease, depression, bipolar disorder, attention-deficit hyperactivity disorder (ADHD) and other brain diseases, said Yang, a member of UCLA’s Institute for Quantitative and Computational Biosciences.

The researchers identified two genes, called Bgn and Fmod, that are important for cell communication, and are potential targets for new pharmaceuticals. Fructose seems to act first on these genes, which then affect many other genes, in a cascade effect, Yang said. After the researchers removed these genes in mice, the mice had substantially higher levels of cholesterol and triglycerides.

The research, which used state-of-the-science genomic technology, was published last year in the journal EBioMedicine.

This research is the first comprehensive genomics study of all the genes, pathways and gene networks affected by high fructose consumption in brain regions controlling metabolism and brain function.

How food affects the brain

Fructose damages communication between brain cells, and increases toxic molecules in

the brain, Gomez-Pinilla’s research team reported in 2015. Earlier research has demonstrated how fructose contributes to cancer, diabetes, obesity and fatty liver.

Gomez-Pinilla recommends reducing the sugar and saturated fat we consume, including reducing drinking soda and eating dessert. “Food is like a pharmaceutical compound that affects the brain,” said Gomez-Pinilla, also a member of UCLA’s Brain Injury Research Center.

Co-authors include lead author Qingying Meng, a postdoctoral scholar in Yang’s laboratory; Zhe Ying, a staff research associate in

Gomez-Pinilla’s laboratory; and colleagues from UCLA, the National Institutes of Health and Icahn School of Medicine at Mount Sinai in New York.

Ties to head trauma

In February 2017, Yang, Gomez-Pinilla and colleagues reported in EBioMedicine that head injuries can adversely affect hundreds of genes in the brain that put people at high risk for diseases including Alzheimer’s, Parkinson’s,

Examples of gene networks in the hippocampus affected by brain trauma. UCLA researchers report that the “master regulator” genes (in red) influence many other genes responsible for the effects of brain trauma.

post-traumatic stress disorder, stroke, ADHD, autism, depression and schizophrenia.

“Very little is known about how people exposed to brain trauma, such as football players and soldiers, develop symptoms for other neurological disorders later in life. We hope to learn much more,” Gomez-Pinilla said.

The researchers have identified for the first time potential master genes, which they believe control hundreds of other genes that they linked to many neurological and psychiatric disorders. These master genes are likely targets for new pharmaceuticals to potentially treat many diseases of the brain.

“We believe these master genes are a kind of hub responsible for traumatic brain injury adversely triggering changes in many other genes,” Yang said.

Traumatic brain injury can do damage first to the master genes and then to other “downstream genes” in a couple of ways, she said. One way is to produce different forms of a protein. Another is to reduce, or increase, the number of expressed copies of a gene in each cell. Both can prevent a gene from properly performing its cellular function.

“If a gene turns into the wrong form of protein, it could lead to Alzheimer’s disease, for example,” Gomez-Pinilla said.

Implications for treating a range of diseases

More than 100 of the genes that changed following the brain injury have human counterparts that have been linked to Alzheimer’s disease, Parkinson’s disease, ADHD and other neurological and psychiatric disorders, the researchers report.Targeting these genes to treat disease seems promising. “We now know which genes are affected by traumatic brain injury and linked to serious disease, and have predicted which genes are the likely master regulators that may have strong therapeutic potential,” Yang said.

The research team is further studying whether modifying some of the master genes also modifies large numbers of other genes. If so, then targeting the master genes will be even more promising.

One of the genes, Fmod, is also a master regulator in the brain that becomes altered by fructose.

The research may lead to new treatments for traumatic brain injury to get the genes to return to their normal state. In addition the researchers potentially could target and modify the master genes so they won’t lead to disease. They may also be able to identify chemical compounds and foods that can fight disease.

Yang’s research is funded by the National Institutes of Health and the UCLA Clinical and Translational Science Institute. Gomez-Pinilla’s research is funded by the National Institutes of Health and the UCLA Brain Injury Research Center.

LGBTQ Studies Program Celebrates 20 Years

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By Jessica Wolf

For two decades, the field of queer studies has been thriving and evolving within the Humanities Division of the UCLA College. Now Alicia Gaspar de Alba, chair of what is currently known as LGBTQ studies, is ready to take the program to the next level by introducing a Ph.D. It would the first in the nation.

A mural depicting the 1967 LGBTQ rights protests outside the Black Cat Tavern in Silver Lake was installed in the LGBTQ Studies offices in Haines Hall in 2014.

“It’s great that we are still here, that we have survived, but now I’m ready to move forward,” said Gaspar de Alba, a professor of Chicana and Chicano studies. Her Ph.D. proposal is in the works and she is confident it will succeed – particularly because she was the architect of UCLA’s Ph.D. program in Chicana and Chicano studies. A concurrent proposal for changing the program from a freestanding minor to an interdepartmental program with 50 percent full-time faculty is also in progress.

Fall 2017 marks the 20th anniversary of the interdisciplinary program. The program was originally called Lesbian, Gay and Bisexual Studies in 1997, but soon after expanded to add the word Transgender.

Recently, faculty and students decided it was important also to add Queer to that title, catching up to the vernacular of the community. It is now formally known as Lesbian, Gay, Bisexual, Transgender & Queer Studies.

“It’s the most inclusive word, and absolutely about reclaiming the word ‘queer’ from a pejorative use,” said Gaspar de Alba, who began teaching at UCLA in 1994 and was among the first to participate in the Faculty Advisory Committee that launched the minor.

Pioneering efforts

The formation of UCLA’s LGBTQ studies was championed by former UCLA professor of anthropology Peter Hammond and initially chaired by Jim Schultz, emeritus professor of Germanic languages. At the time it was one of a few but growing number of academic units in the country to examine the history, culture and challenges of queer individuals.

Other comparable programs exist, though at other universities many are housed within a women’s studies or gender studies department.

UCLA’s program has remained autonomous and unique. It was among the first in the country to host an annual graduate student conference, called QGrad. That conference changed in 2005 to a broader Queer Studies Conference. Since becoming chair in 2013, Gaspar de Alba has revived QGrad and added an undergraduate conference called QScholars, both of which are programmed, curated and produced by students under her mentorship. In 2015, the program launched an e-journal called Queer Cats Journal of LGBTQ Studies.

Learning across disciplines

Alicia Gaspar de Alba

More than 120 students have graduated from UCLA with the LGBTQ minor. Exponentially more students have taken cross-listed LGBTQ courses as part of other majors.

Students pursuing the minor choose from relevant courses in a variety of humanities and social sciences departments – English, gender studies, Chicana/Chicano studies, history, sociology – as well as education, law, public policy, musicology and courses from within the Department of World Arts and Cultures and the School of Theater, Film and Television. The program annually hires several UCLA Ph.D. candidates to design new courses, which keeps the curriculum reflective of the issues of the moment.

The minor also requires students to participate in a service-learning course where they intern at local LGBTQ-focused nonprofits.

According to Gaspar de Alba, many former students have gone on to work at those nonprofits or have become journalists, filmmakers and artists. Some go on to pursue graduate degrees, while others aspire to law school and policymaking careers.

 

Many students join LGBTQ studies out of a desire to know more about the community with which they personally identify. In recent years more students who don’t identify as queer, but want to be allies, also elect to take courses or even commit to the minor, said Tomarian Brown, administrative manager for the program.

Schultz, who returns once a year to teach a section of the introductory course he originally created, said he hopes students take away from queer studies courses a more complex understanding of gender and sexual minorities, and the way those identities intersect with race and social status.

“I think it’s eye-opening,” he said. “Many students will talk about how these courses have opened up their thinking.”

First-year student Meredith Yates specifically chose to attend UCLA because of the LGBTQ studies program. She is the first in her family to leave her home of Virginia to study, and had never traveled outside of the South or East Coast before.

Yates, who volunteers as part of Project One, a team of UCLA students who mentor, befriend and advise queer high schoolers in Los Angeles, hopes to major in communication studies. She plans to return to the South and use her minor in LGBTQ studies to help spread awareness of existing and emerging resources for queer youth who might find themselves feeling isolated. She’s already learning a lot about queer history, she said.

“In the case of the queer rights movement of today, a lot of times we forget that the LGBT rights movement in the U.S., the people who brought it to light, were black and transgender and Latina, people who at the time had been pushed to the very bottom of society,” she said.

Honoring LA’s role in the movement

In the LGBTQ common spaces in Haines Hall there is a remembrance of Los Angeles’ role in fighting for those hard-won rights – and a reminder that the fight is ongoing – by way of a mural depicting the 1967 protests outside the Black Cat Tavern on Sunset Boulevard. It was created in 2014 by UCLA lecturer Alma Lopez and students from her “Queer Art in LA” course.

The mural depicts a scene from 50 years ago this year when members of the queer community and their allies gathered to formally protest the violent New Year’s Eve arrests of patrons of the Black Cat Tavern. These protests predate the well-documented Stonewall riots in Greenwich Village.

UCLA lecturer Alma Lopez led students in creating the mural through her “Queer Art in LA” course.

“Stonewall is seen as the birthplace of the movement,” Gaspar de Alba said. “But we’re here in LA and I wanted to commemorate that the movement for gay rights was actually happening here even earlier.”

Queer studies students are keenly aware

of the challenges this community continues to face, Gaspar de Alba said. Nevertheless, they forge ahead with conviction as they

learn to think and write critically; to inquire, debate and attempt to understand opposing points of view; and to understand themselves.

“These spaces become sacred,” she said, especially for young students who are just coming out. “These classes become places where they can talk about their own lives and issues, but also truly learn to understand others.”

 

Learn more: http://lgbtqstudies.ucla.edu

Mapping the costs of incarceration in Los Angeles

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Million dollar hoods website provides unprecedented access to jail data

By Jessica Wolf

 

Image: The Million Dollar Hoods website lets users examine incarceration data for dozens of areas in Los Angeles County. In this screen grab from the site, the red sections of Los Angeles County show where the most money is spent locking up people from that area.

 

As the realities of mass incarceration face increased scrutiny across the nation, UCLA researchers have launched Million Dollar Hoods, a website and digital mapping project that shows the disparate impact of the Los Angeles jail system — the largest in the United States.

Million Dollar Hoods maps how much money the Los Angeles County Sheriff’s Department and the Los Angeles Police Department spend per neighborhood to incarcerate residents in county and city jails.

The project’s goal is to provide unprecedented public access to jail data in Los Angeles and identify patterns of incarceration throughout the county. The maps also let users examine the data by race, gender, type of crime and leading cause of arrest for every neighborhood.

“What we have uncovered is that L.A.’s nearly billion-dollar jail budget is largely committed to incarcerating residents of just a few neighborhoods,” said Kelly Lytle-Hernandez, UCLA professor of history and African American Studies. “In some neighborhoods, such as Lancaster, Palmdale and Compton, tens of millions of dollars have been spent since 2010.”

Breaking down a billion-dollar jail budget

Since 2010 Los Angeles County spent more than $82 million incarcerating residents from Lancaster and more than $61 million incarcerating people from Palmdale, with DUI and possession of a controlled substance the top two causes of arrest. In that time, nearly $40 million was spent incarcerating residents from Compton, where the top cause of arrest was possession of a controlled substance.

Lytle-Hernandez, who led the project, secured the required data via requests to the sheriff’s department and LAPD through the California Public Records Act. The sheriff’s department repeatedly denied her requests but granted access in January 2016. Since then, she has worked with a team of UCLA geographic information systems experts to bring to Los Angeles a robust mapping database that has been successfully used in New York, Chicago, New Orleans and elsewhere.

“Much like the Million Dollar Blocks projects in New York and Chicago, we are looking at the costs of incarceration by identifying the communities where the most has been spent to incarcerate residents,” Lytle-Hernandez said. Million Dollar Hoods differs from those projects in that it uses local jail data versus state prison data.

 

Image: Los Angeles County Men’s Central Jail in downtown. Los Angeles operates the largest jail system in the United States. PHOTO: Mike Fricano/UCLA

 

“We made this choice because Los Angeles operates the largest jail system in the United States and we wanted to betterunderstand the impact of L.A.’s jails and lockups,” Lytle-Hernandez said.

Lytle-Hernandez pointed out that the dollar amounts posted on the Million Dollar Hoods map are conservative estimates owing to gaps in how the departments track this information. For example, the sheriff’s department does not record the number of days spent incarcerated by people who may have posted bail but then returned to custody after trial. The data also do not capture information on prisoners transferred into the L.A. County jail system from city police departments or the California state prison system.

For many of the communities mapped in this project, the total cost of incarceration to the L.A. County jail system is actually much higher, Lytle-Hernandez said.

Connecting data to personal stories

“But the costs of incarceration are more than fiscal,” Lytle-Hernandez added. “So we are committed to also sharing the personal experiences that residents of L.A.’s Million Dollar Hoods have had with arrest and incarceration, allowing for a fuller accounting of the social costs of incarceration, to families, communities and society at large.”

The Million Dollar Hoods research team has partnered with the Los Angeles County Commission on Human Relations, which is currently holding a series of public hearings on policing in Los Angeles. At these hearings, the commission is inviting community members to share their experiences with law enforcement officers and agencies. The Million Dollar Hoods website hosts video footage of testimony from these hearings.

Geographic information systems technologists Yoh Kawano and Albert Kochaphum from UCLA’s Institute for Digital Research and Education coded and mapped the data and built the website. Robert Habans, a fellow at the UCLA Institute for Research on Labor and Employment, identified data trends and developed the formulas that revealed the rate of daily incarceration costs per prison bed.

 

Image: Incarceration data for Lancaster, California. PHOTO: milliondollarhoods.org

 

Collaborating with law enforcement, advocacy groups and media

The team plans to work with LAPD and the sheriff’s department to regularly add information to the maps. Million Dollar Hoods research partners also include several community-based organizations that are working to reform systems of incarceration in Los Angeles. Representatives from Critical Resistance-Los Angeles, Californians United for a Responsible Budget, Dignity and Power Now, and Youth Justice Coalition are collaborators in the Million Dollar Hoods project.

Million Dollar Hoods also has partnered with Los Angeles public radio station KCRW for a six-episode series that launched Sept. 13. Off the Block will examine how a trip to jail, even for just a few hours or days, can upend many lives, tracing the path from city block to jail block and back.

Lytle-Hernandez will also release her new book City of Inmates: Conquest, Rebellion, and the Rise of Human Caging in Los Angeles this spring. It is a history of incarceration in the city from the days of Spanish conquest to the outbreak of the 1965 Watts Rebellion.

In City of Inmates she marshals two centuries of evidence to show that incarceration has historically and consistently operated to remove, banish, and otherwise eliminate unwanted communities from the city. Across time, some of the communities most targeted for incarceration have been indigenous peoples, sexual minorities, non-white immigrants and African Americans.

UCLA’s Million Dollar Hoods project is supported by the John Randolph and Dora Haynes Foundation, the UCLA Institute for Research on Labor and Employment, and the Institute on Inequality and Democracy at the UCLA Luskin School of Public Affairs.

LEARN MORE:

Visit Million Dollar Hoods at http://milliondollarhoods.org

Listen to episodes of KCRW’s Off the Block at http://kcrw.co/2ejmN5t

Bridging the Gap in Human Aging

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YEARLONG COURSE HELPS FRESHMEN BETTER UNDERSTAND THE AGING PROCESS AND OLDER ADULTS

By Dan Gordon

A participant in the nonprofit Wise Adult Day Service Center in Santa Monica, California, talks to UCLA student Emma Skeie, who took the yearlong cluster course “Frontiers in Human Aging.”

 

 

One of the first tasks freshman Suzannah Henderson was assigned in the course “Frontiers in Human Aging” called for her to reflect on ageism in America and the negative stereotypes about older adults that are everywhere, from the grumpy old man portrayed on TV to birthday cards that poke fun at dotty old folks.

For Henderson, who had not thought about ageism before, reflection turned into revelation. “I didn’t even know ageism was a thing, but I learned that it is,” said Henderson, who completed the yearlong course in June. “It was eye-opening, and that was just the beginning.”

“Frontiers in Human Aging” is one of 10 cluster courses offered to freshmen that are interdisciplinary, explore major issues of timely importance and are taught by teams of three or four distinguished faculty members.

Each year approximately 120 UCLA freshmen journey through “Frontiers in Human Aging,” learning about growing old from multiple vantage points – biology, psychology, sociology, ethics, policy and public health — through lessons delivered by a wide-ranging group of faculty experts and from older adults themselves, via hands-on community service experiences.

Faculty from across campus

While many instructors are brought in as guest lecturers to cover the vast scope of disciplinary approaches to the study of aging, the course’s three core UCLA faculty members have connections to the UCLA Fielding School of Public Health, the UCLA Luskin School of Public Affairs and the UCLA David Geffen School of Medicine: Paul Hsu, adjunct assistant professor in epidemiology; Lené Levy-Storms, associate professor of social welfare and geriatrics; and Rita Effros, a professor of pathology and laboratory medicine who specializes in immunology.

“Our goal is to convey to students the concept of aging as a lifelong phenomenon, and to show students that there are multiple dimensions to the aging process, which is inherently interdisciplinary,” Levy-Storms said.

Students learn that there are positive aspects of aging, for example, the wisdom that comes with experience and the increased time older age affords to giving back to society, she said. The first-year students also gain a fuller appreciation of their elders through an assignment in which they are required to interview someone about his or her life.

“The students tend to forget that older adults were once young,” Levy-Storms said, “or that they will one day be old too.”

Students also learn about aging at the cellular level, including what is known and being investigated about the biological aging processes and the potential to manipulate them for better health. Issues are raised about how gender, race, ethnicity and social environment interact with aging. Ethical questions, economic concerns and intergenerational dynamics are explored. Students delve into aging-relevant policy, from Medicare to the implications of the Affordable Care Act for older adults. Psychological and social elements of aging are discussed, as are the differences among chronological, social and functional age. They find out about successful approaches to remaining mentally, socially and physically engaged later in life.

Hsu noted that nearly all of these discussions are guided by public health concepts, including the importance of prevention and health promotion and the role public health has had in the last century in increasing life expectancy in the U.S. by more than 30 years. “Many students haven’t really heard about public health before,” Hsu said. “I try to introduce them to what it means to treat populations as opposed to individuals, including promoting immunizations and other strategies, as opposed to waiting for people to get sick.”

Beyond the classroom

Students also spend meaningful time interacting with older adults in the winter quarter through a five-week service-learning experience in which they are placed in agencies that serve elders, such as senior centers, assisted-living facilities and adult day care centers. The students keep journals where they reflect on their experiences and link them with classroom and book concepts.

The lessons can be poignant. Henderson spent her service-learning time at a senior living community, interacting with residents who have dementia. She found herself bonding with one older man who reminded her of her grandfather.

“He was a kind, soft-spoken person who would be reading his Bible when I came in,” Henderson said. “He was always eager to participate in conversation. He would talk about how he had done track and field when he was younger and how much he loved physical activity.”

But Henderson learned that people with dementia commonly experience ups and downs in their cognitive and physical functioning. “One day I came in, and he wasn’t doing well at all,” she recalled. “He tried to stand up after lunch, and his knees buckled and he almost fell. It broke my heart to see someone I had really connected with struggling like that.”

 

“They are more than just grandparents; they are individuals with a wealth of knowledge, wisdom and life experiences to share.” – Freshman Suzannah Henderson

 

Inspiring action

Nonetheless, Henderson came away from her year in the “Frontiers in Human Aging” cluster energized, to the point that she is now contemplating enrolling in UCLA’s gerontology interdisciplinary minor and ultimately pursuing a career working with older adults.

“When I was younger I really didn’t think about these things, but in college your perspective broadens, and you begin to become more analytical about the world,” she said. “Now I see older people and realize they are more than just grandparents; they are individuals with a wealth of knowledge, wisdom and life experiences to share.”

Levy-Storms said one of the unstated goals of the yearlong cluster course is that it will lead more students like Henderson to become interested in careers working with older adults or on elder-related issues. “There is such a need and so many opportunities, whether it’s in public health, medicine, law, policy or any other field you can think of,” she said.

The students aren’t the only ones who come away from “Frontiers in Human Aging” feeling energized. “You don’t typically encounter 18-year-olds who are interested in gerontology,” Hsu observed. “To see it in these students is inspiring.”

UCLA freshmen are learning about aging and older adults in the classroom and from the elders themselves.

UCLA researchers determine the structure of a toxin that kills malaria-carrying mosquitoes

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Results pave the way for genetically engineering the toxin to be lethal to other mosquito species transmitting Zika virus and dengue fever

By Katherine Kornei

Figure showing BinA and BinB folds and carbohydrate-binding modules. BinA and BinB are structurally similar to each other. The most noticeable differences correspond to insertions in surface loops on the trefoil domains (purple). UCLA researchers used an X-ray laser to determine the arrangement of atoms.

An international team of scientists, including five UCLA researchers, has used X-rays to reveal the structure of a molecule toxic to disease-carrying mosquitoes.

Nearly half of the world’s population is at risk of contracting malaria, a life-threatening disease transmitted by mosquitoes. Chemical insecticides are often a first line of defense against mosquitoes, but their application can result in both environmental pollution and resistance to the pesticide. The research was published in the journal Nature.

Countries around the globe have recently begun killing mosquito larvae using a natural toxin derived from bacteria. Now UCLA scientists and their collaborators have used X-rays to determine the atomic structure of this larvicide, which is lethal to mosquitoes transmitting malaria and West Nile virus. These results reveal how the toxin functions, knowledge that will inform future efforts to genetically engineer it to also kill mosquitoes carrying Zika virus and dengue fever.

“This is a chance to have a positive effect on a lot of the world’s population,” said senior author David Eisenberg, UCLA’s Paul D. Boyer Professor of Molecular Biology and a Howard Hughes Medical Institute investigator.

Eisenberg and his colleagues studied the larvicide known as BinAB, which is produced by soil-dwelling bacteria. The bacteria pack BinAB into tiny crystals, thousands of which could be stacked across the head of a pin. When these crystals are scattered into the watery environments in which mosquitoes thrive, hungry mosquito larvae eat the crystals. But the meal turns out to be a deadly one.

As the crystals pass through the larvae’s digestive tract, the gut juices of the larvae trigger the crystals to dissolve. The BinAB toxin is released, and its component molecules — called BinA and BinB — play distinct roles in entering the cells of the larvae’s guts and killing the young mosquitoes within 48 hours.

BinAB is toxic to the Culex and Anopheles species of mosquitoes — carriers of West Nile virus and malaria, respectively — but at this point is harmless to the Aedes species, the carriers of Zika virus and dengue fever.

“The toxin is this complex shape, and it has to fit with another shape on the intestine of the larvae. If the shapes don’t match up precisely, the toxin cannot get in the cell. It’s like a lock and key,” said Michael Sawaya, a staff scientist at UCLA involved in the study, to explain BinAB’s specificity.

Genetically engineering an effective toxin

Researchers are interested in genetically engineering BinAB to also kill the larvae of Aedes mosquitoes, work that requires a detailed understanding of BinAB’s atomic structure. However, the small size of the crystals containing BinAB has made it difficult for scientists to hold them securely in laboratory instruments for analysis.

The UCLA researchers and their colleagues, including Dr. Jacques-Philippe Colletier, a former UCLA researcher now working in France, overcame this size limitation by harvesting crystals from a particular strain of soil-dwelling bacteria engineered to produce larger crystals. The scientists then studied the precise shape of the BinAB toxin within the crystals using an X-ray laser. Eisenberg and his colleagues bombarded the crystals with an X-ray laser invented by a UCLA physicist.

“When we shine X-rays on the crystals, the X-rays are scattered into thousands of X-ray beams,” said Eisenberg, who is also a professor of chemistry, biochemistry and biological chemistry and a member of UCLA’s California NanoSystems Institute. “These beams contain information about the arrangement of the atoms that make up BinA and BinB.”

 

“It would be hard to find a problem that could potentially affect the health of more people.” –  Senior author David Eisenberg

 

Novel use of X-ray laser

This type of X-ray laser has never before been used to study a sample with an unknown structure. “We can do entirely new types of experiments using these X-ray lasers,” said co-author Jose Rodriguez, a UCLA assistant professor of chemistry and biochemistry.

The researchers found that the BinA and BinB molecules making up BinAB were crossed in an “X” shape. “They’re hugging each other,” Eisenberg said of the BinA and BinB molecules. This geometry helps ensure that the BinA and BinB molecules exist in equal numbers, which contributes to BinAB’s toxicity.

The scientists also isolated four special sites on the BinAB toxin that were most likely to be involved in the larvicide splitting into BinA and BinB, a transformation critical to the lethal nature of the toxin.

“You can think of the molecule as…having four latches,” Rodriguez said. “When these latches open, the molecule can change its shape. These crystals have to go through a lot of transformations before they actually reach the target location.”

The scientific world is now one step closer to genetically engineering BinAB to be lethal to the mosquitoes that carry Zika virus and dengue fever.

Eisenberg is optimistic. “It would be hard to find a problem that could potentially affect the health of more people,” he said.

Funding sources for the research include the Howard Hughes Medical Institute, W.M. Keck Foundation, National Science Foundation, National Institutes of Health, and the U.S. Department of Energy Office of Science and Office of Basic Energy Sciences.

David Eisenberg, UCLA’s Paul D. Boyer Professor of Molecular Biology

‘Jump-starting’ the brain of a patient recovering from a coma

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Image: Representation of ultrasonic stimulation of the brain’s thalamus in a post-comatose patient.

New noninvasive technique could result in low-cost therapy for patients with severe brain injury

By Stuart Wolpert

A 25-year-old man recovering from a coma has made remarkable progress following a treatment to “restart” his brain using ultrasounds, a team of UCLA scientists reported in a letter published in the journal Brain Stimulation. This is the first time such an approach to severe brain injury has been tried.

“Our technique uses sonic stimulation to excite the neurons in the thalamus – almost as if we were jump-starting them back into function,” said lead author Martin Monti, associate professor of psychology and neurosurgery. “Until now, the only way of achieving this was for a patient to undergo brain surgery and have electrodes implanted directly inside the thalamus – an egg-shaped structure which serves as the bustling central hub for information flow within the brain – a risky procedure known as deep brain stimulation. Our approach directly targets the thalamus, but is noninvasive.”

This new technique, called low intensity focused ultrasound pulsation (LIFUP), has been pioneered by co-author Alexander Bystritsky, professor of psychiatry and biobehavioral sciences in the Semel Institute for Neuroscience and Human Behavior and founder of Brainsonix, which provided the experimental device for this research. In this approach, a small device, about the size of a coffee cup saucer, is placed by the side of a patient’s head. The device creates a small sphere of acoustic energy that can be aimed at different regions of the brain to excite or inhibit brain tissue. Monti said the technique is quite safe, partly because the amount of energy from each stimulation is small. The researchers repeated it 10 times over 10 minutes.

The changes in the patient’s brain were remarkable, Monti said. Before sonic stimulation, the patient could show only minimal signs of being conscious and of understanding speech. By the day after the sonic stimulation, he was able to show greater responses and started vocalizing responses. Three days later, the patient was fully conscious, had regained full language comprehension, could reliably communicate by gesturing “yes” or “no” with his head, and even gave a fist-bump.

“This result is exactly what we expected,” Monti said.

However, he cautioned that this is only one patient. “It is possible that we were just very lucky and happened to have stimulated the patient just as he

was spontaneously recovering,” Monti said. “This is why it is so crucial, before we get too excited, that we repeat this procedure in more patients.”

Joining with Ronald Reagan UCLA Medical Center

Monti and his colleagues, under the direction of UCLA professor Paul Vespa, are planning to perform this procedure in several more patients at the Ronald Reagan UCLA Medical Center, working with UCLA’s Brain Injury Research Center, and with funding from the Dana Foundation and the Tiny Blue Dot Foundation.

If the researchers are able to demonstrate that the recovery in this patient was linked to the ultrasound stimulation, the potential for this technique could be very large. There are currently few effective treatment options for patients in a coma, Monti said.

Monti’s long-term goal is to one day be able to build a small portable device, perhaps a helmet, that could be brought to the bedside of a patient who is in a coma and, with no surgery, help the brain return to normal levels of function, leading to the return of cognitive functions and consciousness.

Hope for an entirely new treatment

Monti said he hopes his technique could be the beginning of a new noninvasive, low-cost therapy to help wake up patients in a coma — perhaps even patients in a vegetative state and in a minimally conscious state, for whom there is almost no effective treatment.

The idea behind this new approach is that when patients fail to fully recover from a coma, and awaken to a state of deeply impaired mental function, this is due partly to an impairment in the functioning of the thalamus. Pharmacological treatment targets the thalamus only indirectly.

Co-authors are Vespa, who holds UCLA’s Gary L. Brinderson Family Chair in Neurocritical Care, and is a professor of neurology and neurosurgery at the UCLA David Geffen School of Medicine, and director of neurocritical care at the Ronald Reagan UCLA Medical Center; Caroline Schnakers, a UCLA researcher in neurosurgery; Bystritsky; and Alexander Korb, a researcher in the Semel Institute.

 

Meet the Professor- In his own words

By Martin Monti

In my laboratory we focus on two of the most fundamental aspects of being human:
1. What is the relationship between language and thought?
Does language make us special? One of the most striking features of human cognition is the ability to generate an infinite number of ideas by combining a finite set of elements according to structure-dependent principles. This ability is most clearly displayed in language, but also characterizes other aspects of our cognition such as drawing inferences, performing mental arithmetic or music cognition. Does language enable other types of structure-dependent cognition? Does the structure of natural language provide a scaffolding on which to build other forms of high-level cognition? In my research I employ behavioral and fMRI tools in healthy volunteers and patients to address these questions.
2. How is consciousness lost and recovered after severe brain injury?
How do we ever know that someone, other than ourselves, is conscious? Philosophical considerations aside, this issue is at the heart of one of the most challenging and least understood conditions of the human brain: the Vegetative State. This is a condition in which, after severe brain injury, patients are awake but not aware. In my research I focus on brain processing and consciousness in these patients, to try to ameliorate diagnostic procedures and to develop new interventions that may help recovery.

 

Watch it here Professor Monti on “The Mystery of Consciousness and the Vegetative State” at TEDx Claremont Colleges

 

 

Digital humanities students shine a light on the history of African American filmmakers

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By Jessica Wolf

While the #OscarsSoWhite controversy raged over the dearth of people of color nominated for Academy Awards this past year, a group of digital humanities students at UCLA channeled their frustration into meticulously building the little-known history of silent films made for and by African Americans in the early 20th century.

 

Photo from Within Our Gates (1919), the oldest known surviving film made by an African American director.

What they found, and sought to highlight, is that African American artists are deeply entwined in the history of filmmaking,  and can be traced back to the medium’s beginnings.

The result of their efforts is “Early African American Film: Reconstructing the History of Silent Race Films, 1909-1930,” an informational website and searchable database that tracks the African American actors, crew members, writers, producers and other artists who were making films during the silent era.

“We were venturing into pretty unknown territory and I really wanted to be a part of telling the stories of this generation of African American people and their contributions,” said Shayna Norman, who graduated last spring. “The fact that the #OscarsSoWhite controversy blew up at the same time we worked on it made this project feel even more relevant and important.”

Hands-on research

Students worked closely with UCLA Library Special Collections, combing through old journals, production notes, posters and fliers to reconstruct what was once a thriving and collaborative network of African American writers, directors, actors and producers who were making what were known as “race films.”

Relying partially on the work of historians who have unearthed documentation of these forgotten filmmakers, the UCLA student team set its parameters to include films from 1909 to 1930 that featured African American cast members, were produced by an independent production company and discussed or advertised as a race film in the African American press.

While the community was vibrant, it struggled to gain mainstream traction. In the silent-film era, productions that fit the “race films”description, like those produced by the Hampton and Tuskegee Institutes, A Trip to Tuskegee (1909), John Henry at Hampton (1913) and A Day at Tuskegee (1913), could be shown only in certain theaters, or often in African American churches, and were played to segregated audiences. Most of these films, therefore, received scant mainstream media attention. The actual film reels were not preserved in any systematic way or protected in hermetically sealed vaults, which has led to physical degradation.

Motion picture director Oscar Micheaux (center) with an actor and a possible crew member appearing in an advertisement for the Micheaux Film Corporation.

Finding forgotten films

Few films survive, though Miriam Posner, core faculty and program coordinator for the digital humanities at UCLA, was partially inspired to ignite the project thanks to the recent release of a compilation of films from Kino Lorber called Pioneers of African-American Cinema.

The scarcity drove the students.

Coming up empty on internet searches caught students particularly off guard, Norman said.

“We’re not used to that kind of obscurity, but so much of the data has been lost or damaged, is not in any history textbooks in our educational system, and is not easily searchable,” she said.

A centering figure in the students’ archival exploration was Oscar Micheaux, author, filmmaker and founder of the Micheaux Film Corporation, one of the most prominent producers of the era’s race films. He kept copious notes and records on the actors and crew members he worked with, providing much-needed fodder for the database. Micheaux’s Within Our Gates (1919) is one of the few examples of a race film that garnered some attention — and an audience — from the white press.

Making data accessible worldwide

The project exists as a perusable database on the code-sharing site GitHub that others may use, build upon and correct. The site maintains a trail of attribution to the UCLA project.

“Not everyone knows how to work with data like ours, so we also spent a lot of time building tutorials that show people exactly how to create their own network graphs, maps and other kinds of analysis using our data,” Posner said.

Capstone activities like this are extremely important in the digital humanities field because students have the best, most meaningful experiences while apprenticing on an active project, she said.

“We love the way that students and faculty come to rely on each other, developing mutual respect for each other’s skills and abilities,” Posner said. “In a lot of cases, the capstone projects like this are specifically designed to live on after the q

Poster for Black Gold, Richard E. Norman’s lost final feature. Norman was a pioneer in the development of films for African American audiences.

uarter has ended. In all cases, we ensure that we preserve a ‘snapshot’ of the work from the time the quarter ended, and that all students are credited for their work.”

Working on a project like this has made lasting impact on the students.

“We get to work on a project that leaves an important footprint,” Girma said. “That’s the amazing part of the digital humanities.” A World Arts and Cultures major, Girma said she added a digital humanities minor in her fourth year after she heard from a friend that the coursework was “life-changing.”

Norman said that she hopes to pursue a career that allows her to continue working at the intersection of entertainment and digital technology.

“I’m a media junkie and by being involved in digital humanities projects like this one, I can see how such digital research methods and skills are relevant and needed in this growing age of mass consumer media.”

LEARN MORE:
Explore the students’ research,
“Early African American Film: Reconstructing the History of Silent Race Films, 1909-1930,”on their website at http://ucla.in/2fhm3BQ

 

 

 

Watch race film Within Our Gates at https://youtu.be/h1E0NrcnwAE

 

The Brain: Our Next Frontier

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Cover Story

UCLA faculty and students are at the brink of historic breakthroughs in the most complex and least understood organ in the body. Through the use of the latest technology, the top-rated UCLA Department of Psychology is studying all aspects of brain health.