The first followed a northern route out of what is today the Philippines and the second followed a southern route from Taiwan and New Guinea. People arrived on the islands between these routes — now making up the Federated States of Micronesia — about 1,000 years later.

But a new finding by a Tufts sea-level researcher and his colleagues suggests that the islands in Micronesia were possibly settled much earlier than supposed and that voyagers on the two routes may have interacted with one another. They reported their research in the journal PNAS.

Andrew Kemp, an associate professor in the Department of Earth and Climate Sciences, was drawn to Micronesia to improve understanding of how climate change impacts global sea level change by collecting new data from the tropical Pacific Ocean, which is not nearly as well documented as the north Atlantic Ocean.

With support from the National Science Foundation, the research team collected cores of mangrove sediment on the islands of Kosrae and Pohnpei in the Federated States of Micronesia.

Although relative sea level — the height of the land relative to the height of the ocean next to it — fell during the past 5,000 years across much of the tropical Pacific, in Micronesia radiocarbon dating showed that relative sea level rose significantly, by about 4.3 meters (14 feet) because the islands are sinking.

Although the researchers can’t yet fully explain why the two islands are subsiding so much faster than others in the Pacific, they could clearly see the results and their meaning for understanding how people came to populate remote Oceania.

The team — including Juliet Sefton, then a postdoctoral researcher at Tufts and now an assistant lecturer at Monash University in Australia, and Mark McCoy, an associate professor of anthropology at Southern Methodist University — was struck by the implications of relative sea level for interpreting the monumental ruins of Nan Madol, a large series of stone buildings constructed on islets separated by canals filled with ocean water just offshore from the island of Pohnpei.

The ruins, now a U.N. World Heritage site, are long presumed to have been administrative or religious buildings constructed about 1,000 years ago for the island’s elite to live apart from the main population in the island.

But Kemp and his colleagues realized that long-term relative sea-level rise meant that this presumption was incorrect. When the structures were built, they were on the island itself, not separated by water. According to McCoy, the prevailing description of Nan Madol as the “Venice of the Pacific” may not have been accurate when it was constructed.

It got the researchers thinking about when these islands were in fact first settled. Kemp notes that the seafaring people who first came to the islands would probably have lived at the coastline — that’s why researchers look for archaeological evidence there, but haven’t seen it for older inhabitation.

“We propose that Pohnpei and Kosrae perhaps weren’t settled anomalously late, but rather they were settled around the same time as the other islands in the Pacific,” Sefton says. “People arrived and lived at the coast, but subsidence of the islands caused relative sea level rise, which submerged the oldest archeological evidence. It’s probably underwater, yet to be found — if it will ever be found.”

If that is the case, people on the northern and southern migrations may have interacted with one another around the volcanic islands of Micronesia — Kosrae, Pohnpei, Chuuk, and Yap.

There’s been no evidence of this before because researchers were building on the wrong assumptions about when the islands were first inhabited based on sea levels. McCoy points out that archaeologists “have been looking in the wrong place for years, because we assumed that relative sea level was falling.”

“Although we can’t prove that there was interaction between these two pathways, we can present an argument that says the data that exists now about migration in the Pacific is probably a lot more incomplete than it is thought to be,” says Kemp.

Story Source:

Materials provided by Tufts University. Original written by Taylor McNeil. Note: Content may be edited for style and length.

Why polar bears?

The project team included Ali Dhinojwala, the H.A. Morton Professor of Polymer Science in the School of Polymer Science and Polymer Engineering, Nathaniel Orndorf, a 2022 Ph.D. graduate who is now employed as a senior material scientist at Bridgestone Americas, and Austin Garner, a 2021 Ph.D. graduate who is now an assistant professor of biology at Syracuse University. The project began during the height of the pandemic when things were on lockdown.

“We had an ongoing project for many years focused on ice; we were looking at the friction of materials and we were interested in this topic because we are in Akron and our national partners need to develop tires with a strong grip on the road in ice and snow conditions,” said Dhinojwala. “Nate had an interest in how nature has adapted to this solution for snow. The example that came to his mind was polar bears — and the research began from there.”

The project was very interdisciplinary, combining approaches and techniques from both biological and materials research. Orndorf and Dhinojwala are polymer scientists who integrate biology into their research, while Garner is an animal biologist who integrates materials science into his research.

The idea was to look at the paw pads of polar bears. Reviewing older literature, the team discovered that previous work studied the microstructures (papillae, the little bumps on the pad of the foot) of polar bear paws and asserted that the papillae were adaptations for improved traction on snow. The previous studies did not include other species of bear so Garner helped identify two species closely related to the polar bear (the brown bear and American black bear) and one distantly related (the sun bear) to include in the study.

“The quietness of the lab during COVID gave me the opportunity to connect with a variety of scientists and environmentalists across the country,” said Orndorf. “I reached out to museums, taxidermists and many others to collect and view actual samples and replicas of bear paw pads.”

Orndorf and Garner then prepared the paw pad samples from the bears and imaged them using a scanning electron microscope. The team also created 3D printouts of the structures to vary diameter and height of features. They were then tested in snow in the lab to see how they reacted to the conditions.

What the team discovered was that all bears (except sun bears) have papillae on their paw pads, but that the papillae on polar bears were taller — up to 1.5 times. And, that the taller papillae of polar bears help to increase traction on snow relative to shorter ones. Even though polar bears have smaller paw pads compared to the other species (likely because of greater fur coverage for heat conservation), the taller papillae of polar bears compensate for their smaller paw pads, giving them a 30-50% increase in frictional shear stress.

“Papillae are not unique to polar bears. Previous work [in that area] made the implicit assumption that papillae themselves are adaptations for enhanced traction on snow without studying the paw pads of other bears. It was fascinating for us to discover that the other North American bears have them as well and that the physical characteristics of the papillae are what matters for traction on snow,” said Garner.

Impact on traction

Now that the research has been published, other scientists and manufacturers can look at its application to their specific projects.

“If you look at snow tires you will see that they do have some deeper treads, but this research could also show various ways to design them that could have a larger impact,” said Dhinojwala.

But the interest isn’t just for tire manufacturers. “Individuals who do high altitude climbing are interested in this research, companies that specialize in the delivery of goods in bad weather would love to have better grip, etc.” he added.

The same experiments could also be performed on animals such as dogs, wolves, foxes and mountain goats to determine if specific snow/ice induced surface roughness profiles are present in different animals, [TE1] or if nature has evolved different surface roughness profiles in order to increase traction on ice and snow, and which profile has the best performance.

Building on past research

This isn’t the first research conducted in the area of traction or grip at UA. As part of the Biomimicry Research Center (BRIC) at The University of Akron, and in collaboration with faculty members in the BRIC program, Dhinojwala and his team have examined gecko adhesion, spider silk, mussel adhesion, and structural colors inspired by birds and other organisms. His research is supported by National Science Foundation, Air Force Office of Scientific Research and Industries.

His team is continuing to look at ice — how ice formation takes place, ice adhesion, etc. Research that is very helpful for the automotive and aircraft industries. His students have just begun working with NASA on a grant funded project in this area.

“It’s exciting to give our students such interesting research projects to be part of,” said Dhinojwala. “They are an asset to our team, and many go on to continue to be excellent research partners after they leave UA.”

“The Integrated Bioscience Ph.D. Program at UA provided exceptional interdisciplinary research experiences that were formative in my development as a researcher — this collaboration was certainly one of them,” said Garner. “It was a particularly unique experience for me because most of my work before this had focused on how small lizards, like geckos, attach to surfaces. So, it was an exciting and rewarding opportunity to apply my existing skills and expertise to large mammals like bears.”

“Serotonin is a chemical produced in the brain that acts as a neurotransmitter, that is, it relays messages from one part of the brain to another. Serotonin communicates the message by binding to brain cells carrying serotonin receptors. These brain cells are involved in a variety of functions, including mood, appetite and some social behaviors, among others,” said co-corresponding author Dr. Yong Xu, professor of pediatrics- nutrition and molecular and cellular biology at Baylor.

In the current study, the Xu lab and the lab of Dr. I. Sadaf Farooqi at the University of Cambridge, collaborated to investigate the role of one of the serotonin receptors, namely serotonin 2C receptor, in weight regulation and behavior. By combining the individual expertise of each lab — basic and genetic animal studies in the Xu lab and human genetics in the Farooqi lab — the team was able to make the case that serotonin 2C receptor is an important regulator of body weight and certain behaviors.

The project started with the finding that some children diagnosed with severe obesity carried rare mutations or variants of the serotonin 2C receptor gene. The researchers identified 13 different variants associated with obesity in 19 unrelated people. Further characterization of the variants revealed that 11 of them cause loss-of-function of the receptor.

“People who carried loss-of-function variants had hyperphagia, or an extreme appetite, some degree of maladaptive behavior and emotional lability, which refers to rapid, often exaggerated changes in mood including strong emotions such as uncontrollable laughing or crying or heightened irritability or temper,” Xu said.

The researchers found that animal models carrying one of the human loss-of-function mutations also became obese, which confirmed the team’s suspicion that loss-of-function mutations of the serotonin 2C receptor gene were involved in obesity.

“This is an important discovery from the diagnostic point of view,” Xu said. “We suggest that the serotonin 2C receptor gene should be included in diagnostic gene panels for severe childhood-onset obesity.”

In addition, the team identified a mechanism by which such mutations can lead to obesity. “We found that the serotonin 2C receptor is required to maintain normal firing activity of POMC neurons in the hypothalamus,” Xu said. “When the receptor has a loss-of-function mutation, the firing activity of POMC neurons is impaired and as a result the animals overeat and become obese. A normal firing activity of these neurons is required to suppress overeating.”

The researchers also worked with a mouse model to explore the connection between the loss-of-function mutations and behavior.

“We confirmed that having the mutation led to decreased sociability and increased aggression in mice,” Xu said. “Before these findings, there was little evidence that the serotonin 2C receptor was required to maintain normal behavior and to prevent aggression. We are interested in investigating the mechanism.”

At the translational level, the findings suggest that patients who develop obesity because of a loss-of-function mutation of this gene, might benefit from compounds that can bypass the deficit in the mutated receptor, such as setmelanotide, by acting directly on downstream pathways. Further studies need to be implemented to test this approach.

Other contributors to this work include Yang He, Bas Brouwers, Hesong Liu, Hailan Liu, Katherine Lawler, Edson Mendes de Oliveira, Dong-Kee Lee, Yongjie Yang, Aaron R. Cox, Julia M. Keogh, Elana Henning, Rebecca Bounds, Aliki Perdikari, Vikram Ayinampudi, Chunmei Wang, Meng Yu, Longlong Tu, Nan Zhang, Na Yin, Junying Han, Nikolas A. Scarcelli, Zili Yan, Kristine M. Conde, Camille Potts, Jonathan C. Bean, Mengjie Wang, Sean M. Hartig, Lan Liao, Jianming Xu, Inês Barroso and Jacek Mokrosinski. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, the University of Cambridge and the University of Exeter Medical School.

This study was supported by funding from Wellcome (207462/Z/17/Z and 208363/Z/17/Z), the NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, the Botnar Foundation and the Bernard Wolfe Health Neuroscience Endowment. Further support was provided by an EMBO Longterm Fellowship, NIH grants (P01DK113954, R01DK115761, R01DK117281, R01DK120858, K01DK119471, R01CA193455, R01DK126042, R01DK114356), the USDA/CRIS (51000-064-01S), Nancy Chang Award for Research Excellence at Baylor College of Medicine, the American Diabetes Association (1-18-IBS-105), Baylor College of Medicine Bridge to Independence Award, the American Heart Association, a USDA/ARS fellowship and Research England.

Bacteriophages or “phages” is the terms used for viruses that infect bacteria. The UAB researchers, led by Terje Dokland, Ph.D., in collaboration with Asma Hatoum-Aslan, Ph.D., at the University of Illinois Urbana-Champaign, have described atomic models for all or part of 11 different structural proteins in phage Andhra. The study is published in Science Advances.

Andhra is a member of the picovirus group. Its host range is limited to S. epidermidis. This skin bacterium is mostly benign but also is a leading cause of infections of indwelling medical devices. “Picoviruses are rarely found in phage collections and remain understudied and underused for therapeutic applications,” said Hatoum-Aslan, a phage biologist at the University of Illinois.

With emergence of antibiotic resistance in S. epidermidis and the related pathogen Staphylococcus aureus, researchers have renewed interest in potentially using bacteriophages to treat bacterial infections. Picoviruses always kill the cells they infect, after binding to the bacterial cell wall, enzymatically breaking through that wall, penetrating the cell membrane and injecting viral DNA into the cell. They also have other traits that make them attractive candidates for therapeutic use, including a small genome and an inability to transfer bacterial genes between bacteria.

Knowledge of protein structure in Andhra and understanding of how those structures allow the virus to infect a bacterium will make it possible to produce custom-made phages tailored to a specific purpose, using genetic manipulation.

“The structural basis for host specificity between phages that infect S. aureus and S. epidermidis is still poorly understood,” said Dokland, a professor of microbiology at UAB and director of the UAB Cryo-Electron Microscopy Core. “With the present study, we have gained a better understanding of the structures and functions of the Andhra gene products and the determinants of host specificity, paving the way for a more rational design of custom phages for therapeutic applications. Our findings elucidate critical features for virion assembly, host recognition and penetration.”

Staphylococcal phages typically have a narrow range of bacteria they can infect, depending on the variable polymers of wall teichoic acid on the surface of different bacterial strains. “This narrow host range is a double-edged sword: On one hand, it allows the phages to target only the specific pathogen causing the disease; on the other hand, it means that the phage may need to be tailored to the patient in each specific case,” Dokland said.

The general structure of Andhra is a 20-faced, roundish icosahedral capsid head that contains the viral genome. The capsid is attached to a short tail. The tail is largely responsible for binding to S. epidermidis and enzymatically breaking the cell wall. The viral DNA is injected into the bacterium through the tail. Segments of the tail include the portal from the capsid to the tail, and the stem, appendages, knob and tail tip.

The 11 different proteins that make up each virus particle are found in multiple copies that assemble together. For instance, the capsid is made of 235 copies each of two proteins, and the other nine virion proteins have copy numbers from two to 72. In total, the virion is made up of 645 protein pieces that include two copies of a 12th protein, whose structure was predicted using the protein structure prediction program AlphaFold.

The atomic models described by Dokland, Hatoum-Aslan, and co-first authors N’Toia C. Hawkins, Ph.D., and James L. Kizziah, Ph.D., UAB Department of Microbiology, show the structures for each protein — as described in molecular language like alpha-helix, beta-helix, beta-strand, beta-barrel or beta-prism. The researchers have described how each protein binds to other copies of that same protein type, such as to make up the hexameric and pentameric faces of the capsid, as well as how each protein interacts with adjacent different protein types.

Electron microscopes use a beam of accelerated electrons to illuminate an object, providing much higher resolution than a light microscope. Cryo-electron microscopy adds the element of super-cold temperatures, making it particularly useful for near-atomic structure resolution of larger proteins, membrane proteins or lipid-containing samples like membrane-bound receptors, and complexes of several biomolecules together.

In the past eight years, new electron detectors have created a tremendous jump in resolution for cryo-electron microscopy over normal electron microscopy. Key elements of this so-called “resolution revolution” for cryo-electron microscopy are:

• Flash-freezing aqueous samples in liquid ethane cooled to below -256 degrees F. Instead of ice crystals that disrupt samples and scatter the electron beam, the water freezes to a window-like “vitreous ice.”
• The sample is kept at super-cold temperatures in the microscope, and a low dose of electrons is used to avoid damage to the proteins.
• Extremely fast direct electron detectors are able to count individual atoms at hundreds of frames per second, allowing sample movement to be corrected on the fly.
• Advanced computing merges thousands of images to generate three-dimensional structures at high resolution. Graphics processing units are used to churn through terabytes of data.
• The microscope stage that holds the sample can also be tilted as images are taken, allowing construction of a three-dimensional tomographic image, similar to a CT scan at the hospital.

The analysis of Andhra virion structure by the UAB researchers started with 230,714 particle images. Molecular reconstruction of the capsid, tail, distal tail and tail tip started with 186,542, 159,489, 159,489 and 159,489 images, respectively. Resolution ranged from 3.50 to 4.90 angstroms.