The 287-member team included urban landscape entomologist Emily Meineke of the UC Davis Department of Entomology and Nematology and marine evolutionary ecologist Joanna Griffiths of the UC Davis Department of Environmental Toxicology.
The research, “Global Urbanization Drives Adaptation in the Plant White Clover,” published March 17 in the journal Science, reveals that “urbanization leads to similar environmental changes across 160 cities throughout the world, which leads to repeated adaptive evolution in the cosmopolitan invasive plant white clover,” said Johnson, the principal investigator (PI) of the 160-city, 26-country project and director of the Centre for Urban Environments at the University of Toronto.
“It is the largest scale study of parallel evolution and urban adaptation ever performed, involving 287 collaborators across 26 countries,” said Johnson, adding “This project would have been impossible without the hard work and dedication of an amazing network of collaborators around the world, people like Emily Meineke and Joanna Griffiths at UC Davis.”
Of the main forces behind evolution--natural selection, genetic drift, and gene flow—the white clover's dominant evolutionary force is natural selection, Johnson pointed out.
Team members performed cyanogenesis assays to determine the plant's defense production of a toxin called hydrogen cyanide (HCN). White clover is less likely to produce HCN in colder environments but more likely in rural areas, the research shows. Half of the world's population lives in urban environments, but by 2050, that figure is expected to jump to 70 percent.
“Urbanization transforms environments in ways that alter biological evolution,” the scientists explained in the abstract. “We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.”
Meineke, who holds a doctorate in entomology (2016) from NCSU, designed the sampling effort in Raleigh, collected clover from there, and did cyanogenesis assays.
“Increasingly, it is clear that we are living in a time when humans are the dominant drivers of biotic change globally,” commented Meineke, who joined the UC Davis Department of Entomology in Nematology in 2020 as an assistant professor. “Somehow, we still don't understand how we are affecting the species we see every day, in part because biologists have only recently become aware of our complex effects on species that live in our own habitats.”
“This project sparked my interest because it focuses on the evolution of clover, a plant that I've had under my feet my entire life,” Meineke said. “I remember stepping in clover as a kid and watching bumble bees bob across it during PE class in elementary school. It turns out that kids worldwide have had this experience because white clover is a cosmopolitan plant. Being part of this study gave me the opportunity to be part of a large group studying effects of humans on clover all over the world.”
Griffiths, a postdoctoral researcher in the UC Davis labs of Professors Andrew Whitehead and Nann Fangue, received her doctorate in ecology and evolution (2020) from LSU. She said her LSU team, including Luis Santiago-Rosario and Katherine Hovanes, "collected clovers from Baton Rouge, and my contribution was performing the lab work, that is, I quantified the amount of hydrogen cyanide present in each clover sample from rural Baton Rouge all the way to the city center. Each sample was digested and incubated for a couple hours. (See image of data sheet.) “The cyanide in the sample chemically reacts with the special paper, turning it blue. Thus, a blue spot on the paper indicates that the clover sample had cyanide present.”
Urbanization is a global phenomenon, in which thousands of cities cover up to three percent of Earth's land surface, according to the GLUE Project website. “For an evolutionary biologist, these cities represent an amazing opportunity to study evolution in action.”
The website describes the GLUE project as “an initiative that will provide the largest scale, best replicated test of parallel evolution ever attempted. To do this, we will study the evolution of the production of hydrogen cyanide (HCN) in white clover (Trifolium repens). We previously showed that white clover evolves parallel clines in HCN (a potent chemical defense) along urban-rural gradients in eastern North America.”
In addition to lead PI Marc Johnson, the 12-member leadership team included two University of Toronto scientists: co-PI and assistant professor Rob Ness, the second author of the paper; and doctoral student James Santangelo, first author.
The project drew financial support from a Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant; Canada Research Chair; and NSERC E.W.R. Steacie Fellowship.
A natural product from the dried root of a pea-family plant, potentially combined with an enzyme inhibitor discovered in the Bruce Hammock laboratory at the University of California, Davis, may provide hope in alleviating neuroinflammation in Parkinson's disease, an eight-member team of researchers from Dalian Medical University, China, and UC Davis announced today.
Their novel research, published in the current edition of the Proceedings of the National Academy of Sciences (PNAS), shows that a soluble epoxide hydrolase (sEH) inhibitor and kurarinone, a compound from the dried root of Sophora flavescens, reduced neuroinflammation in an animal model with Parkinson's disease (PD). The dried root, also known as kushen in Chinese, has been used for hundreds of years in traditional Chinese medicines.
“Traditional Chinese medicines play an immeasurable role in the treatment of all kinds of diseases,” said thelead researcher Cheng-Peng Sun, a Dalian Medical University associate professor who is partnering with the Hammock lab on the PD research. For the past 35 years, Hammock, a distinguished professor who holds a joint appointment with the Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center, has researched enzyme inhibitors that dramatically reduce inflammation, inflammatory pain and neuropathic pain.
“We investigated the neuroprotective effects of S. flavescens in Parkinson's disease based on the neuroinflammation,” Sun explained. “Our extensive studies indicated that kurarinone possesses several pharmacological effects, including anti-inflammatory and antioxidative activities.”
The research, titled “Kurarinone Alleviated Parkinson's Disease via Stabilization of Epoxyeicosatrienoic Acids in Animal Model (Mice),” may lead to an effective therapy for PD, a progressive neurogenerative or brain disorder which affects more than 10 million people worldwide, including a million in the United States, according to the Mayo Clinic. Most PD patients are 65 or over and most are men. There is no cure.
“Basically, kurarinone targets the soluble epoxide hydrolase (sEH), which is a key regulatory enzyme involved in the metabolism of fatty acids, and inhibitors of the sEH enzyme resolve neuroinflammation,” said Professor Hammock, corresponding author. “The enzyme regulates a newly studied class of natural chemical mediators, which in turn regulates inflammation, blood pressure and pain.”
“We have known for a number of years that the soluble epoxide hydrolase inhibitors, now in human safety trials, are active in reducing the development of Parkinson's disease in several rodent models,” Hammock said. “The evidence for this is quite strong, particular based on work of our longterm collaborator Kenji Hashimoto at Chiba University in Japan. Certainly, Parkinson's disease is one of our targets for the sEH inhibitors, but the regulatory path is slow and expensive. This path becomes much faster for a natural product, so the discovery of this natural product from Cheng-Peng's laboratory potentially offers relief to patients far faster than a classical pharmaceutical.”
“In addition to its use as a natural product for treating Parkinson's disease, kurarinone provides a new model for the design of still more active compounds to block the neuroinflammation associated with multiple neurodegenerative diseases where sEH inhibitors have shown efficacy in rodent models including Alzheimer's, autism, and other disorders,” Hammock said. “The fact that kurarinone binds in the sEH enzyme in an adjacent but non-identical site opens the door to new synthetic drugs for these diseases.”
Co-author Christophe Morisseau, a biochemist in the Hammock lab, performed the enzyme kinetics, demonstrating the potency of the compound and how it interacts with the enzyme. “This research is important in two ways,” he said. “In lay terms, it demonstrates the use of a natural compound to treat Parkinson's disease. Right now, there is no effective treatment for this disease, so this is pretty cool. And we show that the compound used has a novel mechanism of inhibiting sEH compared to the previous inhibitors published.”
UC Davis Health System neurologist and School of Medicine Professor Lin Zhang, who is known for his PD expertise (he was not involved in the study), praised the research as novel and “Although we now have multiple medications to manage the debilitating symptoms of Parkinson's disease, we still don't have a way to stop the progression of the disease, not to mention having a cure,” said Zhang, who treats PD patients. “The conventional wisdom believes the reason for that is that we have been only treating the symptoms, not the cause of the disease. One of the contributing causes, as evidenced recently, has been neuroinflammation.”
A common Parkinson model comes from mice treated with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). Tragically this deadly drug was discovered as an impurity in a recreational “This paper shows that when parkinsonian mice were treated with the natural product kurarinone, their Parkinson-like behaviors were significantly alleviated by attenuation of neurotoxicity,” Zhang said. “The same natural product was able to suppress sEH activities selectively so much so that neuroinflammation was markedly ameliorated. Furthermore, when the same models had their sEH gene knocked out, kurarinone did not provide additional protection against Parkinsonism.”
“This paper shows that kurarinone, a natural product, is able to alleviate Parkinson symptoms,” Zhang pointed out. “The mechanism for that has something to do with the fact that kurarinone targets soluble epoxide hydrolase (sEH) which mediates neuroinflammation. Products capable of inhibiting sEH like kurarinone can provide a novel, yet promising, mechanism to reduce neuroinflammation, subsequently treating neurodegenerative disorders including PD at its core.”
Added Zhang: “These findings presented in this paper help to solidify the candidacy of sEH as a key player of PD pathogenesis via neuroinflammation, underscoring the role of sEH inhibitors as a new class of anti-neuroinflammatory pharmaceuticals treating neurodegenerative disorders including PD.”
What's the next step?
“We hope that the natural herbal medicine will offer some relief from Parkinson's disease,” said Sun.
Added Morisseau: “We also hope to increase kurarinone levels in the plant and ensure that the extracts are nontoxic and effective. Possibly we can even find a food plant that is effective.”
Hammock lab researcher Sung Hee Hwang, an organic chemist, has been making small molecule inhibitors for Parkinson's disease, “and the crystal structure of sEH bound to kurarinone will be a great help to him,” Hammock said. “He has been working with Jogen Atone who is just finishing his doctorate in the UC Davis Pharmacology Toxicology program working on basic aspects of Parkinson's disease and environmental chemicals that may cause it.”
Sophora (the Arabic name for a pea-flowered tree) is a genus of about 45 species of evergreen trees and shrubs in the pea family, Fabaceae. The species are native to southern Asia, Australasia, various Pacific islands, western South America, the western United States, Florida and Puerto Rico. About fifteen of these species have a long history of use in traditional Chinese
“Now that we have a lead structure, we hope to screen related species for related compounds and efficacy,” Morisseau said.
“Parkinson's disease occurs when nerve cells in the basal ganglia, an area of the brain that controls movement, become impaired and/or die,” according to the National Institute on Aging (NIA). “Normally, these nerve cells, or neurons, produce an important brain chemical known as dopamine. When the neurons die or become impaired, they produce less dopamine, which causes the movement problems of Parkinson's. Scientists still do not know what causes cells that produce dopamine to die.”
“One clear risk factor for Parkinson's disease is age,” NIA says. “Although most people with Parkinson's first develop the disease at about age 60, about 5 to 10 percent of people with Parkinson's have ‘early-onset' disease, which begins before the age of 50. Early-onset forms of Parkinson's are often, but not always, inherited, and some forms have been linked to specific gene mutations.”
Hammock expressed hope that a variety of research pathways, such as the one resulting in kurarinone, “can lead to therapies, preventions and cures of Parkinson's disease and other neuroinflammatory problems associated with aging.”
Bruce Hammock, firstname.lastname@example.org
His seminar, to be both in-person and virtual, begins at 4:10 p.m., Pacific Time in 122 Briggs Hall. The Zoom link is https://ucdavis.zoom.us/j/99515291076.
"From the moment of initial encounter with an insect herbivore, a suite of inducible plant defenses are triggered; however, the molecular mechanisms for recognition and response are not highly studied," Steinbrenner writes in his abstract. "Specific molecular patterns from insects can serve as elicitors of defense responses on host plants, but precise receptors mediating such responses have remained elusive. We recently identified a cell surface receptor, Inceptin Receptor (INR), which detects a set of ubiquitous peptide fragments found in the oral secretions of Lepidopteran larval herbivores. INR is specific to select legume species and may structure insect host range across this plant family. We hypothesize that INR serves as a recently evolved and highly potent mechanism to perceive a specific danger signal, above and beyond cues associated with generic tissue damage. I will discuss our recent transcriptiomic characterization of inceptin responses in bean and cowpea, highlighting strong anti-herbivore defense outputs which occur after inceptin treatment but not wounding alone. I will also compare plant responses to herbivory with well-characterized pathways mediating recognition of microbial pathogens."
Steinbrenner focuses his research on cell and molecular biology, genetics and genomics, and plant biology. He holds a bachelor of science degree in biology from Tufts University (2010) and a doctorate from UC Berkeley in plant biology (2015). He was awarded a Howard Hughes Medical Institute Postdoctoral Fellowship of $180,000 in 2016 and studied with Eric Schmelz at UC San Diego.
The Steinbrenner lab studies the molecular bases of plant immunity to pathogens and pests. "We are specifically interested in recognition and signaling functions of cell surface receptors and evolutionary processes driving novel immune specificity," he says on his website.
Steinbrenner served as the lead author of a paper published Nov. 23, 2021 in the Proceedings of the National Academy of Sciences on how cowpea plants detect that they're being eaten by caterpillars. In the article, A Receptor-Like Protein Mediates Plant Immune Responses to Herbivore-Associated Molecular Patterns, scientists from the University of Washington and UC San Diego reported that the cowpea plants harbor receptors on the surface of their cells that can detect a compound in caterpillar saliva and initiate anti-herbivore defenses.
"Despite chemical controls, crop yield losses to pests and disease generally range from 20-30 percent worldwide," Steinbrenner related in a University of Washington news release. "Yet many varieties are naturally resistant or immune to specific pests. Our findings are the first to identify an immune recognition mechanism that sounds the alarm against chewing insects.”
Wrote UW science writer James Urton: "The team showed that, in response to both leaf wounds and the presence of a protein fragment specific to caterpillar saliva, the cowpea's INR protein boosts the production of ethylene, a hormone that plants often produce in response to munching by herbivores and other types of environmental stress. The protein fragment in caterpillar spit that elicited this response, Vu-IN, is actually a fragment of a cowpea protein, which gets broken down by the caterpillar as it dines on cowpea leaves." (See full article.)
Nematologist Shahid Siddique, assistant professor, UC Davis Department of Entomology and Nematology, coordinates the Wednesday seminars. For any Zoom technical issues, contact him at email@example.com.
"We are working with scientists and public health authorities in STP to establish the conditions that would facilitate an informed societal and government decision about a proposed release of Anopheles mosquitoes engineered to prevent transmission of the malaria parasite Plasmodium falciparum on the islands,” said principal investigator Gregory Lanzaro, director of the Vector Genetics Laboratory and a PMI professor.
This award will be used to extend their ongoing entomological, engagement and capacity building work through 2025.
“We are working in collaboration with the UC Irvine Malaria Initiative (UCIMI), a research consortium including scientists from UC Irvine, San Diego and Berkeley as well as Johns Hopkins University,” Lanzaro said. “We are working toward the application of advanced genetic tools aimed at the mosquito vector. It is our belief that this approach, used in conjunction with early malaria treatment and detection, can provide a cost effective, sustainable, and environmentally responsible program to ultimately eliminate malaria from Africa.”
Said Ana Kormos, engagement program manager and lead author of the proposal: “These funds provide the UCIMI program with support to strengthen our existing relationship-based approach to the co-development of this technology and ensures that our partners in STP lead the decision-making processes involved in all aspects of the research. This is a huge step forward in advancing a truly collaborative approach to translational research.”
The Vector Genetics Laboratory is engaged in research and training in the areas of population and molecular genetics, genomics and bioinformatics of insect vectors of human and animal disease. The website: “We have developed a program aimed at expanding knowledge that may be applied to improving control of disease vectors and that also addresses problems of interest in the field of evolutionary genetics. We are currently engaged in a range of projects, but our major research focus is on vectors of malaria in Africa."
Directors of the Vector Genetics Laboratory research programs are Lanzaro and Anthony "Anton" Cornel, a research entomologist with the UC Davis Department of Entomology and Nematology and director of the Mosquito Control Research Laboratory, Parlier.
New Tools. "The fight to reduce and possibly eliminate malaria continues and becomes especially challenging as efforts to reduce malaria morbidity have plateaued since 2015,” said Cornel. “Therefore, we must seriously consider new tools. One such tool is genetically modifying the major mosquito vector in the Afrotropics so that it cannot transmit malaria."
"The project aims to use genetically modified (GM) mosquito strategy to reduce and eliminate malaria from the Islands of São Tomé and Príncipe, as proof of concept, before using this technology on larger scales on mainland Africa,” Cornel said, adding that his role, as a field team co-investigator for UCIMI and VGL, is to work with Lanzaro and Pinto “to understand as much as we can about the behavior, population structure and population sizes of Anopheles coluzzi (the malaria vector) on these islands to design the most efficient strategy of releasing the genetically modified mosquitoes to have maximum effect.”
Malaria is an acute illness caused by Plasmodium parasites, which spread to humans through the bites of infected female Anopheles mosquitoes, according to the World Health Organization (WHO). In 2020, nearly half of the world's population was at risk of malaria. An estimated 241 million cases of malaria occurred worldwide in 2020, with 627,000 dying.
Tremendous Burden. Medical entomologist and geneticist Geoffrey Attardo of the UC Davis Department of Entomology and Nematology (who is not involved in this project), noted that “Malaria is a disease which creates a tremendous burden on people living in affected areas. In particular its impacts on the mortality in young children and pregnant women are devastating. Attempts to control this disease using traditional methods have been effective in recent years.”
The island nation of São Tomé and Príncipe, population of 178,700 in 2016, is located about 200 miles west of Gabon on Africa's mainland. It shares maritime borders with Equatorial Guinea, Gabon, and Nigeria. The combined area of the archipelago is about five times the size of Washington, DC. The United States established diplomatic relations with São Tomé and Príncipe in 1976, following its independence from Portugal.
Open Philanthropy's mission, as noted on its website, is to “give as effectively as we can and share our findings openly so that anyone can build on our work. Through research and grant-making, we hope to learn how to make philanthropy go especially far in terms of improving lives. We're passionate about maximizing the impact of our giving, and we're excited to connect with other donors who share our passion.”
São Tomé and Príncipe (nationsonline.org)
No. Make that “Have insect specimens in portable glass-topped display boxes and will travel throughout Northern California to school classrooms, youth group meetings, festivals, events, museums, hospitals--and more--to help people learn about the exciting world of entomology."
“When COVID halted our in-person outreach programs, we were still able to safely loan these educational materials to teachers,” said Tabatha Yang, the Bohart Museum's education and outreach coordinator.
“Now that UC Davis is open again to students we have all these bright, students on campus with fresh and diverse perspectives,” she said. “We want to support their talent, so the funds we are raising will go to students for the creation of new traveling displays. This fleet of new educational drawers will expand and update what we can offer. Some of our current displays were created 15 years ago! One can only imagine all the places these drawers have been and all the people who have been inspired."
Donate in Someone's Memory. The minimum donation is $5, Yang said. "You can donate in honor or in memory of someone, a place, or an organism, too! There is a map (states and countries) that lights up donor locations. Those of you with a fondness in your hearts for insects, college student experiences, science education, and/or museums, please donate to light up our map!" Access the donation page and map at https://bit.ly/3v4MoaJ
The Bohart Museum of Entomology, a research collection and public museum dedicated to understanding, documenting and communicating terrestrial arthropod diversity, is now celebrating its 75th year. It maintains a robust outreach program that typically connects with more than 10,000 people annually, according to Lynn Kimsey, director of the museum and a UC Davis distinguished professor of entomology.
Portable educational boxes are considered a great way to share the museum experience with others. They are housed in the same specimen boxes that the Bohart scientists use for their research collections. UC Davis students, staff, teachers and scout leaders routinely borrow these materials to enrich their programs.
"Our current educational boxes were created 15 to 20 years ago by staff and students at UC Davis," the scientists related on the CrowdFund page. "After years of wear and tear and new developments in biology, we need to update and create a new suite of display boxes. These displays will not only be scientifically accurate, but they will be intriguing to view by all ages. With every $500 in donations, a student will be able to create a fresh new box, complete with an informational sheet and a short video. The goal of this fundraiser is to provide 10 students the opportunity to create 10 portable educational displays that will enhance the outreach mission of the Bohart Museum and the University of California."
Virtual Tour. The public is invited to access the Bohart's Facebook Live virtual tour for Aggie Spirit Week on Wednesday, Oct. 13. The "Bugology" link is: https://fb.me/e/XKtXPrsB. Plans are to spotlight Professor Kimsey; senior museum scientist Steve Heydon; Lepidoptera collection curator Jeff Smith; and graduate student Socrates Letana (who researches bot flies) and others.
The Bohart Museum, temporarily closed to the public due to the COVID-19 pandemic, is located in Room 1124 of the Academic Surge Building, Crocker Lane. It houses nearly eight million insect specimens, collected from around the world. It is also home to a live "petting zoo" comprised of Madagascar hissing cockroaches, walking sticks and tarantulas, as well as an online gift shop stocked with insect-themed jewelry, clothing, books, posters and other items.