The findings are published in the January 6, 2023 issue of the journal Science of the Total Environment.

“This was a pilot study to test the feasibility of using archived samples of plankton from the Continuous Plankton Recorder (CPR) Survey to reconstruct historical trends in marine pollution over space and time,” said senior author Robert K. Naviaux, MD, PhD, professor in the Department of Medicine, Pediatrics and Pathology at UC San Diego School of Medicine. “We were motivated to explore these new methods by the alarming increase in childhood and adult chronic disease that has occurred around the world since the 1980s.

“Recent studies have underscored the tight linkage between ocean pollution and human health. In this study, we asked the question: Do changes in the plankton exposome (the measure of all exposures in a lifetime) correlate with ecosystem and fisheries health?

“We also wanted to lay the groundwork for asking a second question: Can humanmade chemicals in plankton be used as a barometer to measure changes in the global chemosphere that might contribute to childhood and adult illness? Stated another way, we wanted to test the hypothesis that the rapid turnover and sensitivity to contamination of plankton might make them a marine version of the canary in the coal mine.”

Based in the United Kingdom, the CPR Survey is the longest running, most geographically extensive marine ecology survey in the world. Since 1931, almost 300 ships have traveled more than 7.2 million miles towing sampling devices that capture plankton and environmental measurements in all of the world’s oceans, the Mediterranean, Baltic and North seas and in freshwater lakes.

The effort, along with complementary programs elsewhere, is intended to document and monitor the general health of oceans, based upon the well-being of marine plankton — a diverse collection of usually tiny organisms that provide sustenance for many other aquatic creatures, from mollusks to fish to whales.

“Marine plankton exist in all ocean ecosystems,” said study co-author Sonia Batten, PhD, former coordinator of the Pacific CPR and currently executive secretary of the North Pacific Marine Science Organization. “They create complex communities that form the base of the food web, and they play essential roles in maintaining the health and balance of the oceans. Plankton are generally short-lived and very sensitive to environmental changes.”

Naviaux, co-corresponding author Kefeng Li, PhD, a project scientist in Naviaux’s lab, and colleagues evaluated plankton specimens taken from three different locations in the North Pacific at different times between 2002 and 2020, then used a variety of technologies to assess their exposure to different humanmade chemicals, including pharmaceuticals; persistent organic pollutants (POPs) such as industrial chemicals; pesticide; phthalates and plasticizers (chemicals derived from plastics); and personal care products.

Many of these pollutants have decreased in amount over the past two decades, the researchers said, but not universally, and often in complex ways. For example, analyses suggest levels of legacy POPs and the common antibiotic amoxicillin have broadly declined in the North Pacific Ocean over the past 20 years, perhaps in part from increased federal regulation and a decrease in overall antibiotic use in the United States and Canada, but the findings are confounded by coinciding increases in use in Russia and China.

The most polluted samples were taken from nearshore areas closest to human activity and subject to phenomena like terrestrial runoff and aquaculture. In these places, there were higher levels and greater numbers of different chemicals found in plankton taxa living in those nearshore environments.

The authors said their pilot project points the way toward follow-up research designed to examine correlations between the plankton exposome, predator-prey relationships and impacted fisheries.

“Follow-up studies by epidemiologists and marine ecologists are needed to test if and how the plankton exposome correlates with important medical trends in nearby human populations like infant mortality, autism, asthma, diabetes, and dementia,” Naviaux said.

Naviaux noted the findings present new clues to explaining the nature of many chronic diseases in which phases of the cell danger response (CDR) persist, leading to chronic symptoms.

For more than a decade, Naviaux and colleagues have posited that accumulating data suggests numerous diseases and chronic illnesses, from neurodevelopmental disorders like autism spectrum disorder and neurodegenerative disorders like ALS to cancer and major depression are at least partly the consequence of metabolic dysfunction that results in incomplete healing, characterized as CDR.

Naviaux has published extensively on the topic, including how CDR can be affected by environmental factors that result in metabolic dysfunction and chronic disease.

“The purpose of CDR is to help protect the cell and jump-start the healing process after injury, by causing the cell to harden its membranes, decrease and change its interaction with neighbors, and redirect energy and resources for defense until the danger has passed,” said Naviaux.

“But sometimes the CDR gets stuck. This prevents completion of the natural healing cycle, altering the way the cell responds to the world. When this happens, cells behave as if they are still injured or in imminent danger, even though the original cause of the injury or threat has passed. We have learned that many kinds of environmental chemicals, trauma, infection, or other kinds of stress can delay or block the completion of the healing cycle. When this happens, it leads to the symptoms of chronic disease.”

“The CDR is a whole-body process that begins with mitochondria and the cell. Mitochondria are organelles in the cell that act as bio-sentinels that are constantly monitoring the chemistry of the cell and its surroundings. Mitochondria regulate metabolic activity needed for energy and movement, innate immunity, for regulating the health of the microbiome, and for making the building blocks needed for tissue repair after injury.”

In the marine plankton study, Naviaux and co-authors found that perfluoroalkyl substances (chemicals commonly used to enhance water-resistance in various everyday products, from packaging to clothing to cookware) were prominent in the plankton exposome.

Such substances are known to inhibit some mitochondrial proteins, including an important enzyme used to regulate cortisol metabolism and organisms’ responses to stress. Other chemicals found included phthalates from plastics and personal care products, such as lotions and shampoos. Phthalates are endocrine-disrupting chemicals that have been increasing in the plankton exposome for more than 20 years, and have both direct and indirect effects on mitochondria.

“Plankton are responding to the chemicals in their exposome, in part by changes in their own mitochondria that change their biology,” said Naviaux, “and so too, I would argue, are humans. It is my hope that the use of our methods by research groups around the world will reinforce the connection between ecosystem health and human health, and provide new tools to monitor how the human chemical footprint has changed over the past century.

“If the linkages are found to be close enough, plankton exposomics from observatory sites around the world might be used in the future to track and curb pollution that leads to human disease.”

Co-authors include: Jane C. Naviaux, Sai Sachin Lingampelly, Lin Wang and Jonathan M. Monk, all at UC San Diego; and Claire M. Taylor and Clare Ostle, both at the Marine Biological Association.

Funding for this research came, in part, from a consortium of funders through the North Pacific Marine Science Organization, comprised of the North Pacific Research Board, Exxon Valdez Oil Spill Trustee Council through Gulf Watch Alaska, Canadian Department of Fisheries and Oceans and the Marine Biological Association; the UC San Diego Christini Fund and the Lennox Foundation.

Using an approach that simultaneously modifies multiple sites in fungal genomes, Rice University chemical and biomolecular engineer Xue Sherry Gao and collaborators coax fungi into revealing their best-kept secrets, ramping up the pace of new drug discovery.

It is the first time that the technique, multiplex base-editing (MBE), has been deployed as a tool for mining fungal genomes for medically useful compounds. Compared to single-gene editing, the MBE platform reduces the research timeline by over 80% in equivalent experimental settings, from an estimated three months to roughly two weeks.

Fungi and other organisms produce bioactive small molecules such as penicillin to protect themselves from disease agents. These bioactive natural products (NPs) can be used as drugs or as molecular blueprints for designing new drugs.

Using the MBE technology, the Gao lab at Rice’s Brown School of Engineering induced fungi to produce significantly more natural compounds, including some previously unknown to the scientific community.

The study is published in the Journal of the American Chemical Society.

Base-editing refers to the use of CRISPR-based tools in order to modify a rung in the spiral ladder of DNA known as a base pair. Previously, gene modifications using base-editing had to be carried out one at a time, making the research process more time-consuming. “We created a new machinery that enables base-editing to work on multiple genomic sites, hence the ‘multiplex,'” Gao said.

Gao and her team first tested the efficacy of their new base-editing platform by targeting genes encoding for pigment in a fungal strain known as Aspergillus nidulans. The effectiveness and precision of MBE-enabled genome edits was readily visible in the changed color displayed by A. nidulans colonies.

“To me, the fungal genome is a treasure,” Gao said, referring to the significant medical potential of fungi-derived compounds. “However, under most circumstances, fungi ‘keep to themselves’ in the laboratory and don’t produce the bioactive small molecules we are looking for. In other words, the majority of genes or biosynthetic gene clusters of interest to us are ‘cryptic,’ meaning they do not express their full biosynthetic potential.

“The genetic, epigenetic and environmental factors that instruct organisms to produce these medically useful compounds are extremely complicated in fungi,” Gao said. Enabled by the MBE platform, her team can easily delete several of the regulatory genes that restrict the production of bioactive small molecules. “We can observe the synergistic effects of eliminating those factors that make the biosynthetic machinery silent,” she said.

Disinhibited, the engineered fungal strains produce more bioactive molecules, each with their own distinct chemical profiles. Five of the 30 NPs generated in one assay were new, never-before-reported compounds.

“These compounds could be useful antibiotics or anticancer drugs,” Gao said. “We are in the process of figuring out what the biological functions of these compounds are and we are collaborating with groups in the Baylor College of Medicine on pharmacological small-molecule drug discovery.”

Funded by a five-year National Institutes of Health grant, Gao’s research plumbs fungal genomes in search of gene clusters that synthesize NPs. “Approximately 50% of clinical drugs approved by the U.S. Food and Drug Administration are NPs or NP-derivatives,” and fungi-derived NPs “are an essential pharmaceutical source,” she said. Penicillin, lovastatin and cyclosporine are some examples of drugs derived from fungal NPs.

Gao, the T.N. Law Assistant Professor of Chemical and Biomolecular Engineering and an assistant professor of bioengineering and chemistry, is a 2022 recipient of the prestigious CAREER Award from the National Science Foundation. Her lab’s previous discoveries include a fungal biocatalyst that drugmakers can use to control a molecule’s 3D structure and a tool to detect RNA from SARS-CoV-2, the virus that causes COVID-19.

The National Institutes of Health (GM138207) and the Robert A. Welch Foundation (C-1952) supported the research.

Story Source:

Materials provided by Rice University. Original written by Silvia Cernea Clark. Note: Content may be edited for style and length.

The new study comes from the labs of Maiken Nedergaard, co-director of the Center for Translational Neuromedicine at University of Rochester and the University of Copenhagen and Kjeld Møllgård, M.D., a professor of neuroanatomy at the University of Copenhagen. Nedergaard and her colleagues have transformed our understanding of the fundamental mechanics of the human brain and made significant findings to the field of neuroscience, including detailing the many critical functions of previously overlooked cells in the brain called glia and the brain’s unique process of waste removal, which the lab named the glymphatic system.

“The discovery of a new anatomic structure that segregates and helps control the flow of cerebrospinal fluid (CSF) in and around the brain now provides us much greater appreciation of the sophisticated role that CSF plays not only in transporting and removing waste from the brain, but also in supporting its immune defenses,” said Nedergaard.

The study focuses on the membranes that encase the brain, which create a barrier from the rest of the body, and keep it bathed in CSF. The traditional understanding of what is collectively called the meningeal layer, a barrier comprised of individual layers known as the dura, arachnoid, and pia matter.

The new layer discovered by the U.S. and Denmark-based research team further divides the space below the arachnoid layer, the subarachnoid space, into two compartments, separated by the newly described layer, which the researchers name the SLYM, an abbreviation of Subarachnoidal LYmphatic-like Membrane. While much of the research in the paper describes the function of SLYM in mice, they also report its actual presence in the adult human brain as well.

The SLYM is a type of membrane called mesothelium, which is known to line other organs in the body, including the lungs and heart. Mesothelia typically surround and protect organs, and harbor immune cells. The idea that a similar membrane might exist in the central nervous system was a question first posed by Møllgård, the first author of the study. His research focuses on developmental neurobiology, and on the systems of barriers that protect the brain.

The new membrane is very thin and delicate, and consists of only one or a few cells in thickness. Yet the SLYM is a tight barrier, and allows only very small molecules to transit; it seems to separate “clean” and “dirty” CSF. This last observation hints at the likely role played by SLYM in the glymphatic system, which requires a controlled flow and exchange of CSF, allowing the influx of fresh CSF while flushing the toxic proteins associated with Alzheimer’s and other neurological diseases from the central nervous system. This discovery will help researchers more precisely understand the mechanics of the glymphatic system, which was the subject of a recent $13 million grant from the National Institutes of Health’s BRAIN Initiative to the Center for Translational Neuromedicine at the University of Rochester.

The SLYM also appears important to the brain’s defenses. The central nervous system maintains its own native population of immune cells, and the membrane’s integrity prevents outside immune cells from entering. In addition, the SLYM appears to host its own population of central nervous system immune cells that use the SLYM for surveillance at the surface of brain, allowing them to scan passing CSF for signs of infection.

Discovery of the SLYM opens the door for further study of its role in brain disease. For example, the researchers note that larger and more diverse concentrations of immune cells congregate on the membrane during inflammation and aging. When the membrane was ruptured during traumatic brain injury, the resulting disruption in the flow of CSF impaired the glymphatic system and allowed non-central nervous system immune cells to enter the brain.

These and similar observations suggest that diseases as diverse as multiple sclerosis, central nervous system infections, and Alzheimer’s might be triggered or worsened by abnormalities in SLYM function. They also suggest that the delivery of drugs and gene therapeutics to the brain may be impacted by SLYM function, which will need to be considered as new generations of biologic therapies are being developed.

Additional co-authors include Felix Beinlich, Peter Kusk, Leo Miyakoshi, Christine Delle, Virginia Pla, Natalie Hauglund, Tina Esmail, Martin Rasmussen, Ryszard Gomolka, and Yuki Mori with Center for Translational Neuromedicine at the University of Copenhagen. The study was supported with funding from the Lundbeck Foundation, Novo Nordisk Foundation, the National Institute of Neurological Disorders and Stroke, the U.S. Army Research Office, the Human Frontier Science Program, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation and the Simons Foundation.

Now, 230 years later, a plant biology team led by Northwestern University, the Chicago Botanic Garden and the St. Vincent Botanical Gardens has, for the first time, traced five major lineages of Caribbean breadfruit back to that single introduction from Bligh’s voyage.

Not only have the original breadfruit tree cultivars (or varieties produced by selective breeding) survived for centuries, they also are thriving, the researchers found.

The study will be published on Jan. 5, 2023 — the 230th anniversary of Bligh’s arrival in the Caribbean — in the journal Current Biology.

“Breadfruit is an underutilized crop, and it doesn’t get nearly as much attention as the major crops,” said Nyree Zerega, the study’s senior author. “However, interest in breadfruit is increasing globally, and we thought this would be a fascinating puzzle to solve.”

“Outside of Oceania, the Caribbean is one of the largest producers of breadfruit worldwide,” added Lauren Audi, the study’s first author. “And we really don’t know much about the genetic diversity of the fruit in the Caribbean. Because this is an important crop for food security — especially for island nations that are highly susceptible to climate change — we wanted to characterize the genetic diversity of breadfruit crops in order to conserve them. The first step for that is to characterize the diversity of what we already have.”

A breadfruit expert, Zerega is director of the Program in Plant Biology and Conservation, a partnership between Northwestern’s Weinberg College of Arts and Sciences and the Chicago Botanic Garden, and a conservation scientist with the Negaunee Institute for Plant Conservation Science and Action at the Chicago Botanic Garden. Audi was a graduate student in Zerega’s laboratory at the time of the research. Now, she is a lab manager at the Sackler Institute for Comparative Genomics at the American Museum of Natural History in New York City and a Ph.D. candidate at New York University.

Breadfruit on the ‘Bounty’

Many people might be familiar with Capt. Bligh from “Mutiny on the Bounty,” a classic book series and film starring Clark Gable that fictionalized the arduous journey and mission’s ultimate failure. (The film was later remade twice — with Marlon Brando in 1962 and Anthony Hopkins in 1984.)

Aboard a British Royal Navy vessel called the HMS Bounty, Capt. Bligh and his crew stopped in Tahiti, where they worked with locals to collect breadfruit. The goal was to introduce breadfruit as a cheap food for slave populations forced to work on British plantations in the Caribbean islands. But these plans were abruptly abandoned in April 1789 when the Bounty’s crew seized control of the ship, throwing Bligh and his 18 loyalists overboard.

Yet Bligh survived — and remained dedicated to the original goal of collecting and transporting breadfruit. Just two years later, he set sail again — this time on the HMS Providence with an accompanying vessel, the HMS Assistant. Although Bligh recorded names of eight types of breadfruit in his log for the Bounty, the Providence’s logs are curiously missing these crucial details.

“When you look at the logs from the Bounty, Bligh carefully documented what was collected,” Zerega said. “But on his second voyage, the time spent in Tahiti was shorter, and there weren’t any notes about the names of the breadfruit cultivars they actually collected. He did indicate that five kinds of seedless breadfruit were collected, but subsequent historical texts have suggested different numbers. Wanting to know this is partly curiosity, but it’s also useful because it links cross-cultural knowledge about the plants.”

Genetic challenges

The lack of historical records from the Providence is not the only reason why characterizing breadfruit genetic diversity in the Caribbean has been challenging. There are several genetic challenges. First, seedless breadfruit trees are triploid. In other words, they have three copies of chromosomes, instead of two (diploid), which is more common. There are not as many genetic tools designed to analyze triploids, compared to diploids.

Triploid breadfruit trees also are unable to reproduce sexually and can only survive if humans clonally propagate them. This is done with many cultivated fruit trees — even those that can sexually reproduce — to ensure quality control.

“When you bite into a Honey Crisp apple, you expect a different taste and texture than a McIntosh,” Zerega explained. “Clonal propagation ensures that you get what you expect. When plants develop seeds through sexual reproduction, they give rise to variation in offspring — just like the variation among human siblings.”

Over thousands of years of clonal propagation, however, variation can still arise due to somatic mutations, which are mutations in the tree’s non-reproductive cells. Somatic mutations can occur spontaneously, due to stress or errors in DNA repair. In search of the best fruits, humans sometimes select the part of the plant where the somatic mutation occurred and propagate it. So, if the mutation gives rise to a desirable new leaf or fruit type, people can cut the branch where the mutation occurred, propagate it and essentially clone that new mutation to grow a tree with the desirable fruit again.

Whatever mutation gave rise to the change can be extremely tiny and difficult to pinpoint genetically. Detecting DNA differences across different clonal lines (that is, lineages that arose from different historical “mother” trees) is much easier than detecting differences due to mutations within the same clonal line. Nonetheless, all seedless breadfruit cultivars are quite similar, making it challenging to genetically characterize different cultivars.

Finally, both within and across island groups in the Pacific and the Caribbean, people use many different names for what sometimes appear to be the same cultivars. This adds to the confusion when characterizing diversity.

Connecting the pieces

To overcome these challenges, the researchers employed a variety of tools. They integrated local knowledge with historical documents and specimens, morphological data (observations about the fruits’ size, shape and texture) and targeted genome sequencing.

Partnering with the St. Vincent Botanical Gardens, the St. Vincent Ministry of Tourism and the St. Vincent National Parks, Rivers and Beaches Authority, members of the research team traveled throughout St. Vincent. They collected leaves and took measurements, such as leaf size, fruit size and shape. Then, they supplemented these samples with historical dried, pressed specimens stored in herbaria in museums and botanic gardens around the world — including a specimen collected in 1769 from the HMS Endeavor Voyage led by Captain James Cook.

Back in the lab at the Chicago Botanic Garden, the researchers analyzed more than 200 individual breadfruit specimens, focusing predominantly on seedless breadfruit from St. Vincent and Tahiti as well as samples from around the world. The process involved extracting and sequencing DNA from leaf samples. Among these samples, the researchers ultimately identified eight major global breadfruit lineages — five of which are found in the Caribbean and likely represent the original 1793 introduction by the HMS Providence.

“This is an exciting project,” said Diane Ragone, director emeritus of the Breadfruit Institute at the National Tropical Botanical Garden in Hawaii, study co-author and Zerega’s former adviser. “Through laboratory, herbarium and library research and fieldwork in Tahiti and the Caribbean and by studying breadfruit trees conserved at the National Tropical Botanical Garden in Hawaii, three generations of women scientists were able to provide answers to a centuries-old mystery: ‘Which varieties of breadfruit did Captain Bligh introduce into the Caribbean?'”

Based on previous work by Zerega and others, there are many more global breadfruit lineages when the great diversity of seeded cultivars from Oceania are included. The current study focused mostly on seedless breadfruit.

“We identified five genetic lineages in the Caribbean, which matches what we found in some historical texts,” Audi said. “It was exciting to tease apart this history and characterize breadfruit’s diversity in the Caribbean genomically for the first time.”

“Still, there may be more types of breadfruit in St. Vincent than our genetic methods could identify because they are so closely related,” Zerega said. “Even if we don’t find genetic differences among plants that people assign different names to, those names still have significance and value.”

Breadfruit’s importance

Although breadfruit began with a dark history in the Caribbean as slave food, the nutritious fruit eventually became an important part of island diet and culture. Despite having “fruit” in its name, breadfruit is starchy and seedless, playing a culinary role more like a potato. Closely related to jackfruit, the nutrient-rich food is high in fiber, vitamins and minerals. In its native Oceania where breadfruit was domesticated, people have been eating breadfruit for thousands of years — whether steamed, roasted, fried or fermented. Breadfruit also can be turned into flour, in order to lengthen its shelf life.

Once established, a single breadfruit tree can live for decades, producing a large number of fruits each year. And, because it’s a perennial crop, it also requires less energy input (water and fertilizer) than annual crops that must be replanted each year. Like other trees, it also sequesters carbon dioxide from the atmosphere.

“Food security and food sovereignty for the next millennium lies in the endless untapped possibility of breadfruit,” said Gordon J.P. Shallow, study co-author, who was curator of the St. Vincent Botanical Garden at the time of the research.

Earlier this year, Zerega and Northwestern climate scientists authored another study (published in PLOS Climate), which found that breadfruit is particularly resilient in the face of human-caused climate change. Although other staple crops struggle in hot conditions, the researchers predict that changing conditions will have less effect on breadfruit. That means it could play an important role in fighting climate-driven hunger.

The study, “Linking breadfruit cultivar names across the globe connects histories after 230 years of separation,” was supported by the Garden Club of America, Botanical Society of America, the Institute for Sustainability and Energy at Northwestern Resnick Social Impact Fund and the Northwestern University Alumnae Research Award.