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.

An international study coordinated from Stockholm and Reykjavik investigates the development of the Scandinavian gene pool over the latest 2000 years. In this effort the scientists relied on historic and prehistoric genomes, and from material excavated in Scandinavia. These ancient genomes were compared with genomic data from 16,638 contemporary Scandinavians. As the geographical origin and the datings were known for all these individuals, it was possible to resolve the development of the gene pool to a level never realised previously.

Dr Ricardo Rodríguez Varela at the Centre for Palaeogenetics*, who analysed all the data and extracted some of the ancient DNA used in the study, explains: “With this level of resolution we not only confirm the Viking Age migration. We are also able to trace it to the east Baltic region, the British-Irish Isles and southern Europe. But not all parts of Scandinavia received the same amounts of gene flow from these areas. For example, while British-Irish ancestry became widespread in Scandinavia the eastern-Baltic ancestry mainly reached Gotland and central Sweden.”

The gene pool bounced back after the Viking period

Another new discovery in this study was what happened to the gene pool after the Viking period. The scientists were surprised to find that it bounced back in the direction of what it looked like before the Viking period migration.

Professor Anders Götherström at the Centre for Palaeogenetics, who is a senior scientist on the study, is intrigued: “Interestingly, the non-local ancestry peaks during the Viking period while being lower before and after. The drop in current levels of external ancestry suggests that the Viking-period migrants got less children, or somehow contributed proportionally less to the gene pool than the people who were already in Scandinavia.”

Yet a new discovery was the history of the northern Scandinavian gene pool. There is a genetic component in northern Scandinavia that is rare in central and western Europe, and the scientists were able to track this component in northern Scandinavia through the latest 1000 years.

Dr Ricardo Rodríguez Varela comments, “We suspected that there was a chronology to the northern Scandinavian gene pool, and it did indeed prove that a more recent influx of Uralic ancestry into Scandinavia define much of the northern gene pool. But if it is recent, it is comparatively so. For example, we know that this Uralic ancestry was present in northern Scandinavia as early as during the late Viking period.”

Based on well-known Swedish archaeological sites

The study is based on a number of well-known Swedish archaeological sites. For example, there are genomes from the 17^th century warship Kronan, from the Viking and Vendel period boat burials in the lake Mälaren Valley, and from the migration period ring fortress Sandby borg on Öland.

Anders Götherström conclude: “We were working on a number of smaller studies on different archaeological sites. And at some point it just made sense to combine them into a larger study on the development of the Scandinavian gene pool.

The study, published today in Cell, is an international effort with several collaborators, but it was led by Dr Ricardo Rodríguez Varela and Professor Anders Götherstörm at Stockholm University, and Professor Agnar Helgason, and Kristján Moore at deCODE in Reykavijk.

*The Centre for Palaeogenetics (CPG) is a joint venture between Stockholm University and the Swedish Museum of Natural History.

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