The monoclonal antibody 19A11, developed by Professor Barry Gumbiner at the University of Washington and Seattle Children’s Research Institute, binds E-cadherin, a protein that helps cells stick together, especially in epithelial layers that line the skin, the gut and other organs. Cadherins and other adhesion molecules are important for maintaining the structure of vessels and preventing cancer metastasis, as well as playing a role in inflammation and related conditions such as Crohn’s disease and inflammatory bowel disease.

Researchers have previously found that treatment with 19A11 can prevent spread of lung cancer cells in mice.

Bin Xie, graduate student in biophysics, Professor Sanjeevi Sivasankar, Department of Biomedical Engineering, and colleagues at UC Davis and in Seattle, carried out detailed studies of how 19A11 binds to E-cadherin. Using X-ray crystallography, they found that the antibody binds E-cadherin near the site where it attaches to another E-cadherin molecule. With a combination of simulations and atomic force microscopy, they showed that 19A11 has two binding modes, one of which increases the adhesive strength of E-cadherin. That increased adhesion comes from the formation of a type of chemical link called a salt bridge between the molecules.

By better understanding how this antibody can increase stickiness between cells, the researchers hope to find ways to design even more effective treatments along the same lines.

Additional authors on the paper are: Andrew Priest at UC Davis; Allison Maker, Seattle Children’s Research Institute and University of Washington; David Dranow, Jenny Phan and Thomas Edwards, Seattle Structural Genomics Center for Infectious Disease and UCB Pharma; Bart Staker and Peter Myler, Seattle Structural Genomics Center for Infectious Disease and Seattle Children’s Research Institute. The work was partly supported by grants from the NIH and used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated by Argonne National Laboratory.

Story Source:

Materials provided by University of California – Davis. Original written by Andy Fell. Note: Content may be edited for style and length.

Blood samples show that children have elevated markers of inflammation, such as interleukin 6, if they were exposed to higher air pollution. Further, higher air pollution was linked to lower cardiac autonomic regulation in children, which impacts how fast the heart beats and how hard it pumps, according to the study.

In the study, published Aug. 3 date in the journal New Directions for Child and Adolescent Research, researchers looked at blood samples from more than 100 healthy children ages 9-11 in the Sacramento area where pollutants near their homes were recorded by the Environmental Protection Agency. The study was authored by Anna M. Parenteau, a doctoral student, and Camelia E. Hostinar, associate professor, both from the UC Davis Department of Psychology. The work took place at UC Davis.

These findings are important because exposure to pollutants released during wildfires has been related to numerous negative health outcomes in children, who have smaller bodies and organ systems than adults, including asthma and decreased lung function, as well as neurodevelopmental outcomes like attention deficit hyperactivity disorder, autism, and deficits in school performance and memory, researchers said.

Looked at particulates

Researchers looked at fine particulate matter data from the EPA (PM2.5) — or the fine particles that can penetrate lungs and pass into the bloodstream — finding the children’s blood contained markers of systemic inflammation. Additionally, PM2.5, which refers to particulate matter measuring 2.5 micrometers or smaller by the EPA, was linked to lower cardiac autonomic regulation assessed using an electrocardiogram. Specifically, researchers used data files maintained by the EPA, which have daily air quality summary information from each outdoor monitor in the country.

In total, 27 of the children studied had inflammation markers in their blood recorded during significant fires when their neighborhoods recorded significant levels of PM2.5 in the air. These times when fires were burning included during the Mendocino Complex Fire in 2018, which was active about 100 miles from the lab where blood was drawn. The findings were similar to those found in an earlier study, in which the blood of young primates was collected by UC Davis researchers after significant wildfires.

“By examining daily and monthly levels of particulate matter in relation to children’s inflammation and autonomic physiology, this study further demonstrates the immediate consequences of exposure to air pollution, which may increase risk of future disease,” Parenteau said. Furthermore, Parenteau added: “As climate change continues to impact children and families, it is paramount to understand the impact of environmental contaminants such as air pollution on children’s physiology.”

Previous studies with children have shown significant associations between ambient air pollution and allergic sensitization, respiratory symptoms, and ultra-structural and cellular changes to their lungs and airways, researchers said.

Researchers have found children may be especially susceptible to the effects of air pollution, given that, compared to adults, they have a higher intake of contaminants and greater lung surface area relative to their body weight.

Continued developmental research on environmental contaminants can sound the alarm about the effects of air pollution and inform policy changes that could promote long-term population health, researchers concluded.

Co-authors, all who had graduated and completed research at UC Davis during the study, include researchers from University of Trier, Germany; UC San Francisco; Whitman College; and University of Denver.

Story Source:

Materials provided by University of California – Davis. Original written by Karen Michele Nikos-Rose. Note: Content may be edited for style and length.

Publishing in the journal Science on Aug. 5, 2022, as part of a special issue on grasslands, the study contradicts years of assumptions that grasslands’ ecological development is quick and their recovery is rapid, posing new challenges to their successful restoration.

“Old growth grasslands have a unique suite of characteristics that develop over a really long time. Recovering grasslands do not have the same species or the same characteristics as they did prior to soil tilling or tree planting, and they take centuries to redevelop,” said Katharine Suding, senior author of the paper and Distinguished Professor in the Department of Ecology and Evolutionary Biology and Institute of Arctic and Alpine Research (INSTAAR) at CU Boulder. “It’s an important reminder that we need to conserve the ancient grasslands that are still intact.”

An expert in the field of North American grasslands, Suding partnered with other experts from around the world to evaluate the current state of global grassland science, conservation and restoration — from arid, prairie and coastal grasslands, to those in the tropics and savannahs.

Grasslands, which account for nearly 40% of land-based ecosystems, provide habitat for a wide diversity of animals and plants, and contribute to the livelihoods of over 1 billion people worldwide. They also provide significant carbon sequestration and biodiversity benefits, and can be more resilient than forests in the face of a quickly changing climate.

Yet over the past couple of centuries, ancient grasslands around the world have largely been converted into farmland, used to grow trees or been developed as cities expand.

The researchers found that while the destruction of these pristine grasslands can occur very quickly, complete recovery of grassland biodiversity and essential ecosystem functions occurs slowly or not at all. The findings further emphasize the importance of conserving the world’s remaining untouched grasslands.

“If you plant trees in an older grassland or till it for agriculture, you will probably never get many of the unique diversity and belowground characteristics back. It is irreversible,” said Suding.

Restoration takes time

Grasslands store the bulk of their material underground, in roots that can reach as far as 20 feet deep. This unseen physical presence is how they can store a lot of carbon — about a third of all carbon stored on land — and remain resilient to fire and other ecological disturbances. It’s also why grasslands are often underappreciated in comparison to forests. If it’s out of sight, it’s out of mind.

Grassland restoration, however, can take a page out of forests’ playbook.

“‘Old growth’ is not only a term for forests, but one that applies to grasslands as well,” said co-author Elise Buisson, who co-authored that finding in a 2015 publication.

Old growth grasslands are unique in their underground structures and biodiversity compared to newer, younger grasslands. And while these old growth ecosystems may never be fully replicated in modern-day landscapes, they provide a model for restoration efforts, said Suding.

Even a decade ago, grassland restoration focused on distributing species’ seed onto a landscape, adding grazing or fire, and stepping aside. The new analysis finds that it takes more than a hands-off approach to be successful. Instead of tossing all the ingredients into a crockpot and turning it on high, grasslands may need more of a step-by-step recipe approach to restoration.

“We should think of restoration as more of guiding a trajectory. Some species don’t come in right at the start, and the disturbance that maintains the grassland needs time to grow and be tweaked as these species get established and the soil develops,” said Suding. “These processes take time.”

For example, some plants do well reproducing from seed in, say, the upper Midwest but not in Colorado due to the drier climate. Many tropical grasses don’t spread by seed at all, instead by rhizomes and tubers underground, and are much more difficult to reestablish.

Implications for policy

The report comes a year after the start of the United Nations Decade on Ecosystem Restoration, which aims to restore degraded ecosystems around the world to increase biodiversity, help achieve the Sustainable Development Goals and the Paris Climate Agreement. At the same time, planting trees has become a popular “natural solution” around the world to remove large quantities of carbon from the atmosphere.

Yet while the UN initiative explicitly states, “planting trees on natural grassland may destroy more than it creates,” as countries make ambitious goals and commitments to ecosystem restoration this decade, Suding worries that for many, this only means planting trees.

“We would lose a huge element of the biodiversity on Earth if we planted trees in old growth grasslands,” said Suding. “I think we need to be a little bit more careful about what’s best for the globe, in terms of where to restore what.”

As climate change threatens the American West through drought, heat and wildfire, grasslands are also a resilient choice to use less water, reduce soil erosion and keep carbon in the ground over time. It’s the older, veteran grasslands that are most beneficial in this regard.

“They’re very resilient to a lot of these threats that we’re increasingly experiencing. Grasslands are resilient and can deliver well in terms of our priorities of carbon storage, water infiltration and soil health,” said Suding.