Brain discovery holds key to boosting body's ability to fight Alzheimer's, MS

UVA Health researchers have discovered a molecule in the brain responsible for orchestrating the immune system's responses to Alzheimer's disease and multiple sclerosis (MS), potentially allowing doctors to supercharge the body's ability to fight those and other devastating neurological diseases.

The molecule the researchers identified, called a kinase, is crucial to both removing plaque buildup associated with Alzheimer's and preventing the debris buildup that causes MS, the researchers found. It does this, the researchers showed, by directing the activity of brain cleaners called microglia. These immune cells were once largely ignored by scientists but have, in recent years, proved vital players in brain health.

UVA's important new findings could one day let doctors augment the activity of microglia to treat or protect patients from Alzheimer's, MS and other neurodegenerative diseases, the researchers report.

"Unfortunately, medical doctors do not currently possess effective treatments to target the root causes of most neurodegenerative diseases, such as Alzheimer's, Parkinson's or ALS [amyotrophic lateral sclerosis, commonly called Lou Gehrig's disease]. In our studies, we have discovered a master controller of the cell type and processes that are required to protect the brain from these disorders," said senior researcher John Lukens, PhD, of the University of Virginia School of Medicine and its Center for Brain Immunology and Glia (BIG), as well as the Carter Immunology Center and the UVA Brain Institute. "Our work further shows that targeting this novel pathway provides a potent strategy to eliminate the toxic culprits that cause memory loss and impaired motor control in neurodegenerative disease."

Toxic Brain Buildup

Many neurodegenerative diseases, including Alzheimer's and MS, are thought to be caused by the brain's inability to cleanse itself of toxic buildup. Recent advances in neuroscience research have shed light on the importance of microglia in removing harmful debris from the brain, but UVA's new discovery offers practical insights into how this cleaning process occurs -- and the dire consequences when it doesn't.

Using a mouse model of Alzheimer's disease, the UVA researchers found that a lack of the molecule they identified, spleen tyrosine kinase, triggered plaque buildup in the brain and caused the mice to suffer memory loss -- like the symptoms seen in humans with Alzheimer's. Further, the neuroscientists were able to reduce the plaque buildup by activating this molecule and microglia in the brain, suggesting a potential treatment approach for human patients, though that would require significantly more research and testing.

"Our work has described a critical element of microglial function during Alzheimer's disease and MS," said researcher Hannah Ennerfelt, the first author of a new scientific paper outlining the findings. "Understanding the underlying biology of these cells during neurodegeneration may allow for scientists and doctors to develop increasingly informed and effective therapeutic interventions."

A lack of the molecule in a mouse model of MS, meanwhile, led to the buildup of damaged myelin, a protective coating on nerve cells. When myelin is damaged, the cells cannot transmit messages properly, causing MS symptoms such as mobility problems and muscle spasms. The UVA researchers conclude in a new scientific paper that the molecule they identified, abbreviated as SYK, is "critically involved" in the crucial removal of myelin debris. "If boosting SYK activity in microglia can decrease the amount of myelin debris in MS lesions, developing new drugs to target SYK could stop the progression of MS and help to reverse the damage," said Elizabeth L. Frost, PhD, a critical researcher on the project. "This is an especially promising option given that most of the currently available drugs for MS treatment dampen adaptive immunity. These immunosuppressive drugs lead to susceptibility to infection and higher risk of potentially fatal side effects like progressive multifocal leukoencephalopathy. Additionally, some forms of MS do not have a strong involvement of the immune system, and therefore there are currently very limited treatment options for those patients."

"Targeting SYK in microglia," she noted, "would circumvent multiple limitations of present-day therapeutics for MS."

Based on their promising results, the researchers report that targeting the molecule to stimulate the brain's immune activity could offer a way to treat not just Alzheimer's and MS but a "spectrum" of neurodegenerative diseases.

"These findings are especially exciting because they point to a treatment avenue in which we could alter the behavior of these native brain cells, microglia, to behave in a more neuroprotective way," said researcher Coco Holliday, a UVA undergraduate working in the Lukens lab. "It could potentially be applied to a variety of different neurological diseases that all share the problem of a buildup of toxic waste in the brain. It's been a very exciting project to be a part of."

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New analysis of obsidian blades reveals dynamic Neolithic social networks

An analysis of obsidian artifacts excavated during the 1960s at two prominent archaeological sites in southwestern Iran suggests that the networks Neolithic people formed in the region as they developed agriculture are larger and more complex than previously believed, according to a new study by Yale researchers.

The study, published Oct. 17 in the journal Proceedings of the National Academy of Sciences, is the first to apply state-of-the-art analytical tools to a collection of 2,100 obsidian artifacts housed at the Yale Peabody Museum. The artifacts were unearthed more than 50 years ago at Ali Kosh and Chagha Sefid, sites on Iran's Deh Luran Plain that yielded important archaeological discoveries from the Neolithic Era -- the period beginning about 12,000 years ago when people began farming, domesticating animals, and establishing permanent settlements.

Original analyses performed shortly after the artifacts were discovered had suggested people first acquired the obsidian -- volcanic glass -- from Nemrut Dağ, a now dormant volcano in Eastern Turkey, and then relied on an unknown second source for the material. This new elemental analysis showed the obsidian came from seven distinct sources, including Nemrut Dağ, in present-day Turkey and Armenia, which is as far as about 1,000 miles on foot from the excavation sites.

"It wasn't a simple pattern of people obtaining obsidian from one source and then shifting to the next," said Ellery Frahm, an archaeological scientist in the Department of Anthropology in Yale's Faculty of Arts and Sciences, and the study's lead author. "Rather, our analysis shows that they were acquiring obsidian from an increasingly diverse number of geological sources over time -- a trend that was impossible to detect with the technology and methods available 50 years ago."

The new analysis, combined with computer modeling, indicates that there were intensifying connections among Neolithic people, suggesting the presence of a greater number of settlements between the source volcanoes and the two sites where the artifacts were unearthed thousands of years later, Frahm said.

The artifacts were collected in the 1960s during multiple excavations of the two sites led by Frank Hole, the C.J. MacCurdy Professor Emeritus of Anthropology at Yale. The initial analyses were based largely on the artifacts' appearance, specifically their color when held up to sunlight. A subset of 28 artifacts were then subjected to an elemental analysis method common at the time that involved grinding them into powder.

Frahm and coauthor Christina M. Carolus, a doctoral student in the Department of Anthropology, are the first researchers to study the elemental composition of the obsidian artifacts since these early analyses. They used state-of-the-art portable X-ray fluorescence instruments, which allowed them to examine the entire collection without damaging the artifacts.

"Every aspect of the discoveries made at these sites had been revisited since the 1960s except the elemental composition and sourcing of the obsidian artifacts," Carolus said. "A lot more is known about the source volcanoes today than 50 years ago, and we know that sorting obsidian by color will miss a lot of nuances. Fortunately, we have instruments the size of cordless drills that, in a matter of seconds and without destroying material, give us a more accurate elemental signature than anything that was possible in the past."

Scientists widely believed that humanity's transition from the hunter-gatherer lifestyle to agriculture produced a period of rapid population growth due to the increased birth rates made possible by enhanced food supplies and permanent settlements. Finding evidence of this demographic shift often requires excavating locations that include burial sites, which can indicate a given settlement's population and provide a clearer picture of how agriculture allowed people to disperse across a landscape, Frahm said.

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Metabolism, not genes, may offer more insight into risk of some diseases

Our ancestry can be detected not only in our genes, but also in our metabolism, a new Yale-led study has found.

In an analysis of the metabolic profiles of healthy American babies, researchers found surprising differences among ethnic groups which may help make screening for inherited metabolic disorders, cystic fibrosis, or hypothyroidism much more accurate than traditional genetic disease screens.

"We don't want to miss a baby who is potentially sick, and we don't want to put families through the burdens and concerns that can stem from a false-positive test," said Curt Scharfe, associate professor of genetics at Yale School of Medicine and senior author of the study published in the journal Molecular Genetics and Metabolism.

For the study, Scharfe and colleagues analyzed data collected from more than 400,000 babies, representing 17 self-reported ethnic groups, who were part of California's newborn screening program. Specifically, they wanted to know if these ethnic differences could be detected in metabolites, molecules that provide energy by breaking down food or body tissue such as fat, found in the blood of the infants.

The question was not only of academic interest but of concern to pediatricians. For instance, it is known that babies of African heritage are more likely to have elevated blood biomarkers indicating cystic fibrosis than babies born to white parents, even though babies born to white parents are far more likely to eventually develop the disease. Researchers hope that using ancestry to interpret these differences in marker levels might offer more accurate ways to assess risks than traditional genetic tests.

People of African heritage are also known to have greater genetic diversity than those from ethnic groups because they are descendants of the world's oldest ancestral population. Modern humans emigrated from Africa to regions across the planet; other ethnic groups are descendants of these original migrants, and have enough variation in their DNA to make them genetically identifiable.

But metabolic lineages can tell a different story, the researchers found. For instance, while there is a clear delineation between genetic variants among African-Americans and Americans of European descent, researchers found that metabolically these two groups are more closely related. Conversely, while people of Japanese and Chinese descent, for instance, are closely related genetically, the researchers found larger differences in their metabolic profiles.

"This attests to the role of environment in forming our metabolism," Scharfe said. "Where people share the same culture and food, metabolic profiles are more similar. Where people are separated by circumstances, such as language or lifestyles, then differences in metabolism are greater than genetic variations."

Scharfe cautions that more work needs to be done before findings can be applied clinically. Researchers only analyzed 41 out of many hundreds of metabolites and relied on parents own reports of their ethnic heritage, which might not always correspond to reality.

"This is just a first snap shot, but understanding our metabolic ancestry has a promising future," Scharfe said.

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Isotope data strengthens suspicions of ivory stockpile theft

In January 2019, a seizure of 3.3 tons of ivory in Uganda turned up something surprising: markings on some of the tusks suggested that they may have been taken from a stockpile of ivory kept, it was thought, strictly under lock and key by the government of Burundi.

A new study from University of Utah distinguished professor Thure Cerling and colleagues, published in Proceedings of the National Academy of Sciences, uses carbon isotope science to show that the marked tusks were more than 30 years old and somehow had found their way from the guarded government stockpile into the hands of illegal ivory traders. The results suggest that governments that maintain ivory stockpiles may want to take a closer look at their inventory.

Ivory's isotope signatures

Cerling is a pioneer in the use of isotopes to answer questions about physical and biological processes. "Isotopes" of a given element refer to atoms of the element that vary in their number of neutrons, and thus vary oh-so-slightly in mass. A carbon-14 isotope has one more neutron than carbon-13, for example.

Some isotopes are stable and some are unstable. Unstable isotopes decay into other isotopes or elements through radioactive decay. Since the rate of decay is known for unstable isotopes, we can use the amounts present in a sample to determine ages. That's how carbon dating works -- it uses the rate of decay of unstable carbon-14 to determine the age of organic matter.

Around a decade ago, Cerling attended a presentation at the U by Sam Wasser of the University of Washington, who was studying the genetics of wildlife and using those tools to investigate the date and place of wildlife poaching. Cerling, recognizing that his expertise in isotope science might be able to add useful information, began an ongoing collaboration with Wasser.

In 2016, Cerling, Wasser and colleagues published a study that addressed a key question in the ivory trade: how old is the ivory seized by governments? Some traders have claimed their ivory is old, taken before 1976, and thus exempt from sales bans. And with the average size of ivory seizures more than 2.5 tons, researchers, governments and conservationists wonder how much of the ivory is recent and how much is coming from criminal stockpiles -- or is stolen from one of several ivory stockpiles held by the governments of some countries in Africa.

"Governments keep their stockpiles for multiple reasons," Wasser says. "They hope to sell the ivory for revenue, sometimes to support conservation efforts. However, they can only sell ivory from elephants that died of natural causes or were culled because they were problem animals. They can't sell seized ivory because they don't know it came from the country."

With the combination of Cerling's isotope data and Wasser's genetic data, the 2016 study found that more than 90% of seized ivory was from elephants that had been killed less than three years before. It was a sobering result, showing active and well-developed poaching and export networks. The study seemed to show that little ivory from government stockpiles had ended up on the black market.

Marked tusks

But the 2019 seizure of ivory in Uganda showed something concerning. Some of the tusks sported markings that looked suspiciously like the markings that CITES, the Convention on International Trade in Endangered Species of Wild Fauna and Flora, uses to inventory stockpiled ivory.

Due to the markings seen on some samples of the ivory," Cerling says, "it was thought that quite a few samples in this shipment could be related to material held in a government stockpile in Burundi. We were asked to date samples from this, and three other recent ivory seizures, to see if some samples could possibly be from older stockpiles."

To determine the ivory's age, the researchers collected small samples from the tusks and analyzed them for the amount of carbon-14 isotopes in each sample. They were looking specifically for the amount of "bomb carbon" in the tusks. Between 1945 and 1963, nuclear weapons testing doubled the amount of carbon-14 in the atmosphere, so anything living that's consumed carbon since then -- including you -- has a measurable carbon-14 signature. The amount of carbon-14 in a sample of ivory that hasn't yet radioactively decayed can tell scientists when the ivory stopped growing, or when the elephant died.

The method takes some calibration, using samples from organisms living in the same area. Some of the samples came from schoolchildren in Kenya, through a program called "Kids and Goats for Elephants." Because most families in rural Kenya keep goats the program, run by Cerling and Paula Kahumbu of WildlifeDirect engages children in collecting hair samples from goats for isotopic analysis. The isotope data is useful for many applications, including fighting elephant poaching and, in this case, calibrating the bomb carbon decay rate for more accurate dating of ivory.

A consequential result

The researchers analyzed ivory from four seizures in Angola, Hong Kong, Singapore and Uganda. Genetic data ensured that they weren't sampling two tusks from the same individual. The results of analysis from the Angola, Hong Kong and Singapore seizures were as expected -- the samples were mostly around three years after the death of the elephant, with no tusks having been taken more than 10 years previous.

But the Uganda seizure, with the inventory markings on the tusks, showed something very different. Nine of the 11 tusks tested had been taken more than 30 years before, with the dates of death ranging between 1985 and 1988. Those dates are consistent with the age of ivory in the stockpile of the government of Burundi, which was inventoried and stored in sealed containers in 1989.

"My suspicions were affirmed," Wasser says. "The bigger surprise was how near to 1989 the elephants were killed." At the time Burundi assembled its stockpile, a condition of joining CITES, which assists governments in managing ivory reserves, was that the ivory to be stockpiled was old. The results suggest that that wasn't the case, Wasser says, which would have violated conditions for Burundi to join CITES.

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Revealing the mysteries of the universe under the skin of an atomic nucleus

Massive neutron stars colliding in space are thought to be able to create precious metals such as gold and platinum. The properties of these stars are still an enigma, but the answer may lie beneath the skin of one of the smallest building blocks on Earth -- an atomic nucleus of lead. Getting the nucleus of the atom to reveal the secrets of the strong force that governs the interior of neutron stars has proven difficult. Now a new computer model from Chalmers University of Technology, Sweden, can provide answers.

In a recently published article in the scientific journal Nature Physics, Chalmers researchers present a breakthrough in the calculation of the atomic nucleus of the heavy and stable element lead.

The strong force plays the main role

Despite the huge size difference between a microscopic atomic nucleus and a neutron star several kilometers in size, it is largely the same physics that governs their properties. The common denominator is the strong force that holds the particles -- the protons and neutrons -- together in an atomic nucleus. The same force also prevents a neutron star from collapsing. The strong force is fundamental in the universe, but it is difficult to include in computational models, not least when it comes to heavy neutron-rich atomic nuclei such as lead. Therefore, the researchers have wrestled with many unanswered questions in their challenging calculations.

A reliable way to make calculations

"To understand how the strong force works in neutron-rich matter, we need meaningful comparisons between theory and experiment. In addition to the observations made in laboratories and with telescopes, reliable theoretical simulations are therefore also needed. Our breakthrough means that we have been able to carry out such calculations for the heaviest stable element -- lead," says Andreas Ekström, Associate Professor at the Department of Physics at Chalmers and one of the main authors of the article.

The new computer model from Chalmers, developed together with colleagues in North America and England, now shows the way forward. It enables high precision predictions of properties for the isotope* lead-208 and its so-called 'neutron skin'.

The thickness of the skin matters

It is the 126 neutrons in the atomic nucleus that form an outer envelope, which can be described as a skin. How thick the skin is, is linked to the properties of the strong force. By predicting the thickness of the neutron skin, knowledge can increase about how the strong force works -- both in atomic nuclei and in neutron stars.

"We predict that the neutron skin is surprisingly thin, which can provide new insights into the force between the neutrons. A groundbreaking aspect of our model is that it not only provides predictions, but also has the ability to assess theoretical margins of error. This is crucial for being able to make scientific progress," says research leader Christian Forssén, Professor at the Department of Physics at Chalmers.

Model used for the spread of the coronavirus

To develop the new computational model, the researchers have combined theories with existing data from experimental studies. The complex calculations have then been combined with a statistical method previously used to simulate the possible spread of the coronavirus.

With the new model for lead, it is now possible to evaluate different assumptions about the strong force. The model also makes it possible to make predictions for other atomic nuclei, from the lightest to the heaviest.

The breakthrough could lead to much more precise models of, for example, neutron stars and increased knowledge of how these are formed.

"The goal for us is to gain a greater understanding of how the strong force behaves in both neutron stars and atomic nuclei. It takes the research one step closer to understanding how, for example, gold and other elements could be created in neutron stars- and at the end of the day it is about understanding the universe," says Christian Forssén.

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Properties of 'baby talk' similar across many languages

A study by the University of York and Aarhus University has revealed that baby talk displays similar properties across 36 languages.

'Baby talk' or infant directed speech (IDS) refers to the way caregivers talk to young infants, and generally includes a high-pitched, slow-paced, animated speech.

This spontaneous, automatic and intuitive way of speaking has been studied for decades to understand why human beings communicate in this way with infants and what it might suggest about child development.

The York and Aarhus team addressed the question of whether IDS had a universal quality -- does it, for example, have the same properties in English as it does in other languages? They also addressed whether this changes as the child's grasp on language and speech increases.

Using a meta-analytic method, they examined all previous studies that investigated sound properties of IDS and asked what these revealed about its function in child language development. They found that certain features of IDS, such as pitch, melody, and articulation rates have the same properties across most of the world's languages.

How much caregivers exaggerate the differences between vowel sounds, however, was markedly different across the languages.

Christopher Cox, who led the study and is a joint PhD student at the University of York's Department of Language & Linguistic Science and Aarhus University's Department of Linguistics & Cognitive Science, said: "We use a higher pitch, more melodious phrases, and a slower articulation rate when talking to infants compared to how we talk to adults, and this appears to be the same across most languages.

"In the English language, caregivers typically exaggerate the difference in vowel sounds in infant directed speech, but this seemed to vary across other languages. More work is needed to understand why that is, but we might expect, for example, that speakers of languages with lots of vowels would be more inclined to clarify this speech signal for their children."

Languages that have been studied so far have focused on English and European languages, but to understand more about the instinctive use of IDS and how it helps in child development, the researchers argue more work is needed in understudied, non-Western languages.

The study also showed that IDS changes over time, as infants get a better grasp on language and speech. Most features of IDS gradually become more similar to adult speech style -- such as pitch and speed of delivery -- but other features, such as the high pitch melodic sounds and exaggerated vowels continue into early life.

Associate Professor Riccardo Fusaroli, co-author of the study from Aarhus University, said: "These results really highlight the interactive nature of this speech style, with caregivers providing dynamic and tailored feedback to their children's vocalisations and reacting to infants' changing developmental needs."

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Back to the future of photosynthesis

The central biocatalyst in photosynthesis, Rubisco, is the most abundant enzyme on earth. By reconstructing billion-year-old enzymes, a team of Max Planck researchers has deciphered one of the key adaptations of early photosynthesis. Their results not only provide insights into the evolution of modern photosynthesis but also offer new impulses for improving it.

Present day life fully depends on photosynthetic organisms like plants and algae that capture and convert CO2. At the heart of these processes lies an enzyme called Rubisco that captures more than 400 billion tons CO2 annually. Organisms alive today make staggering amounts of it: the mass of Rubisco on our planet outweighs that of all humans. In order to assume such a dominant role in the global carbon cycle, Rubisco had to adapt constantly to changing environmental conditions.

Using a combination of computational and synthetic approaches, a team from the Max Planck Institute for Terrestrial Microbiology in Marburg, Germany, in collaboration with the University of Singapore has now successfully resurrected and studied billion-year-old enzymes in the lab. In this process, which they describe as "molecular paleontology," the researchers found that instead of direct mutations in the active center, an entirely new component prepared photosynthesis to adapt to rising oxygen levels.

Rubisco's early confusion

Rubisco is ancient: it emerged approximately four billion years ago in primordial metabolism prior to the presence of oxygen on earth. However, with the invention of oxygen-producing photosynthesis and rise of oxygen in the atmosphere, the enzyme started catalyzing an undesired reaction, in which it mistakes O2 for CO2 and produces metabolites that are toxic to the cell. This confused substrate scope still scars Rubiscos to date and limits photosynthetic efficiency. Even though Rubiscos that evolved in oxygen-containing environments became more specific for CO2 over time, none of them could get completely rid of the oxygen capturing reaction.

The molecular determinants of increased CO2 specificity in Rubisco remain largely unknown. However, they are of great interest to researchers aiming to improve photosynthesis. Interestingly, those Rubiscos that show increased CO2 specificity recruited a novel protein component of unknown function. This component was suspected to be involved in increasing CO2 specificity, however, the true reason for its emergence remained difficult to determine because it already evolved billions of years ago.

Studying evolution by resurrecting ancient proteins in the lab

To understand this key event in the evolution of more specific Rubiscos, collaborators at the Max Planck Institute for Terrestrial Microbiology in Marburg and Nanyang Technological University in Singapore used a statistical algorithm to recreate forms of Rubiscos that existed billions of years ago, before oxygen levels began to rise. The team led by Max Planck researchers Tobias Erb and Georg Hochberg resurrected these ancient proteins in the lab to study their properties. In particular, the scientists wondered whether Rubisco's new component had anything to do with the evolution of higher specificity.

The answer was surprising, as doctoral researcher Luca Schulz explains: "We expected the new component to somehow directly exclude oxygen from Rubisco catalytic center. That is not what happened. Instead, this new subunit seems to act as a modulator for evolution: recruitment of the subunit changed the effect that subsequent mutations had on Rubisco's catalytic subunit. Previously inconsequential mutations suddenly had a huge effect on specificity when this new component was present. It seems that having this new subunit completely changed Rubisco's evolutionary potential."

An enzyme's addiction to its new subunit

This function as an "evolutionary modulator" also explains another mysterious aspect of the new protein component: Rubiscos that incorporated it are completely dependent on it, even though other forms of Rubisco can function perfectly well without. The same modulating effect explains why: When bound to this small protein component, Rubisco become tolerant to mutations that would otherwise be catastrophically detrimental. With the accumulation of such mutations, Rubisco effectively became addicted to its new subunit.

Altogether, the findings finally explain the reason why Rubisco kept this new protein component around ever since it encountered it. Max Planck Research Group Leader Georg Hochberg explains: "The fact that this connection was not understood until now highlights the importance of evolutionary analysis for understanding the biochemistry that drives life around us. The history of biomolecules like Rubisco can teach us so much about why they are the way they are today. And there are still so many biochemical phenomena whose evolutionary history we really have no idea about. So it's a very exciting time to be an evolutionary biochemist: almost the entire molecular history of the cell is still waiting to be discovered."

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Impact of coral chemical compounds on reef composition and health

Stumbling upon a new source of underwater caffeine was just an added bonus of a new study examining the impact of chemical compounds that corals release into the seawater.

The study found that the organic chemical compounds produced through metabolism -- known as metabolites or exudates -- vary significantly by coral species and that the compounds impact the abundances and compositions of reef microorganisms differently.

This differential release of metabolites from benthic reef organisms is particularly significant in the Caribbean where coral dominance is shifting from hard stony corals to soft octocorals in response to human-caused stressors such as eutrophication, overfishing, and global climate change.

The study "demonstrates the importance of benthic exudates for structuring microbial communities on oligotrophic reefs by focusing on the exudates released from abundant stony corals, octocorals, and an invasive alga," according to the paper led by authors from the Woods Hole Oceanographic Institution (WHOI), "Benthic exometabolites and their ecological significance on threatened Caribbean coral reefs," published in ISME Communications.

"We wanted to know what are the molecules that coral organisms release into the environment, and how do those molecules impact the reef microbes in the seawater surrounding the corals," said lead author Laura Weber, a former postdoc and current information systems associate in WHOI's Marine Chemistry & Geochemistry Department.

"As the species composition of these reefs shifts, it is likely changing the chemicals that are released on the reef that then will have impacts on the microbial community," Weber said. "We need to pay more attention to how changes in reef structure and species composition might influence the microbes that live on the reef, leading to more feedbacks in terms of reef health." She said that understanding microbes on reefs, how they are functioning, and how they might be contributing to the health of corals and of reefs themselves is "pretty much an untapped area to explore."

Here's the caffeine connection.

For the study, researchers collected exudates from six species of Caribbean benthic organisms in a lab setting, using organisms obtained from within the Virgin Islands National Park, including stony corals, octocorals, and an invasive encrusting alga called Ramicrusta textilis. The researchers surprisingly found that R. textilis released caffeine in high quantities.

Their results further "demonstrate that exudates from benthic organisms contribute to the complex pool of extracellular metabolites in reef seawater and that exudate composition varies significantly by species," according to the study

As to why R. textilis produces caffeine, the study notes that caffeine production has not been widely investigated for marine organisms, but that it is a common metabolite produced by land plants generally to deter herbivores and pathogenic microbes. These characteristics "could contribute to the ability of R. textilis to invade and flourish on Caribbean reefs," according to the report. "Given the growing prevalence of Ramicrusta on diverse Caribbean reefs, follow-up research examining the ecological significance of its metabolites on microbes and other reef organisms is needed."

This study "is an important step forward in identifying chemical signals that can help scientists assess reef health," said Elizabeth Kujawinski, co-author of the paper. "Similar to human health diagnostics, the chemical signals within a reef ecosystem are intimately linked to the functions of the symbiotic relationships within reefs." Kujawinski is a senior scientist in WHOI's Marine Chemistry & Geochemistry Department and director of the Center for Chemical Currencies of a Microbial Planet (C-CoMP), a National Science Foundation Science and Technology Center that is based at WHOI.

Co-author Amy Apprill, associate scientist in WHOI's Marine Chemistry & Geochemistry Department, said an important implication of the research is that a diverse benthic community helps to contribute to a more varied metabolite pool and likely supports a more diverse microbial community.

"We are trying to build kind of a library of what microbes and metabolites are present on reefs. My dream is to be able to go out to a reef, take a bucket of reef water, screen it for microbes and metabolites, and be able to tell something about the health of that ecosystem," Apprill said. "This is so important to do because the current methods to monitor reefs are highly visual-based, and it can take months or years to determine if coral is sick or growing. Metabolites and microbes have the potential to be really sensitive sensors for reef health."

This research was conducted with support from the National Oceanic and Atmospheric Administration and the National Science Foundation.

Key Takeaways

Chemical compounds produced through metabolism and then released -- known as metabolites or exudates -- vary significantly by coral species and impact the abundances and compositions of reef microorganisms differently.

The differential release of metabolites from benthic reef organisms is particularly significant in the Caribbean where coral dominance is shifting from hard stony corals to soft octocorals in response to human-caused stressors such as eutrophication, overfishing, and global climate change.

"As the species composition of these reefs shifts, it is likely changing the chemicals that are released on the reef that then will have impacts on the microbial community. We need to pay more attention to how changes in reef structure and species composition might influence the microbes that live on the reef, leading to more feedbacks in terms of reef health."

Stumbling on a new source of underwater caffeine was just an added bonus of a new study examining the impact of chemical compounds that corals release into the seawater.

This study "is an important step forward in identifying chemical signals that can help scientists assess reef health. Similar to human health diagnostics, the chemical signals within a reef ecosystem are intimately linked to the functions of the symbiotic relationships within reefs."

Read more at Science Daily

'Wobbling black hole' most extreme example ever detected

Researchers at Cardiff University have identified a peculiar twisting motion in the orbits of two colliding black holes, an exotic phenomenon predicted by Einstein's theory of gravity.

Their study, which is published in Nature and led by Professor Mark Hannam, Dr Charlie Hoy and Dr Jonathan Thompson, reports that this is the first time this effect, known as precession, has been seen in black holes, where the twisting is 10 billion times faster than in previous observations.

The binary black hole system was found through gravitational waves in early 2020 in the Advanced LIGO and Virgo detectors. One of the black holes, 40 times bigger than our Sun, is likely the fastest spinning black hole to be found through gravitational waves. And unlike all previous observations, the rapidly revolving black hole distorted space and time so much that the binary's entire orbit wobbled back and forth.

This form of precession is specific to Einstein's theory of general relativity. These results confirm its existence in the most extreme physical event we can observe, the collision of two black holes.

"We've always thought that binary black holes can do this," said Professor Mark Hannam of Cardiff University's Gravity Exploration Institute. "We have been hoping to spot an example ever since the first gravitational wave detections. We had to wait for five years and over 80 separate detections, but finally we have one!"

A more down-to-earth example of precession is the wobbling of a spinning top, which may wobble -- or precess -- once every few seconds. By contrast, precession in general relativity is usually such a weak effect that it is imperceptible. In the fastest example previously measured from orbiting neutron stars called binary pulsars, it took over 75 years for the orbit to precess. The black-hole binary in this study, colloquially known as GW200129 (named after the date it was observed, January 29, 2020), precesses several times every second -- an effect 10 billion times stronger than measured previously.

Dr Jonathan Thompson, also of Cardiff University, explained: "It's a very tricky effect to identify. Gravitational waves are extremely weak and to detect them requires the most sensitive measurement apparatus in history. The precession is an even weaker effect buried inside the already weak signal, so we had to do a careful analysis to uncover it."

Gravitational waves were predicted by Einstein in 1916. They were first directly detected from the merger of two black holes by the Advanced LIGO instruments in 2015, a breakthrough discovery that led to the 2017 Nobel Prize. Gravitational wave astronomy is now one of the most vibrant fields of science, with a network of the Advanced LIGO, Virgo and KAGRA detectors operating in the US, Europe and Japan. To date there have been over 80 detections, all of merging black holes or neutron stars.

"So far most black holes we've found with gravitational waves have been spinning fairly slowly," said Dr Charlie Hoy, a researcher at Cardiff University during this study, and now at the University of Portsmouth. "The larger black hole in this binary, which was about 40 times more massive than the Sun, was spinning almost as fast as physically possible. Our current models of how binaries form suggest this one was extremely rare, maybe a one in a thousand event. Or it could be a sign that our models need to change."

The international network of gravitational-wave detectors is currently being upgraded and will start its next search of the universe in 2023. They are likely to find hundreds more black holes colliding, and will tell scientists whether GW200129 was a rare exception, or a sign that our universe is even stranger than they thought.

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Clusters of genes help mice live longer

Researchers from the National Institute on Aging (NIA)-funded Interventions Testing Program recently reported the discovery of multiple candidate genes that influence longevity. The three Interventions Testing Program sites -- The University of Texas Health Science Center at San Antonio, The University of Michigan at Ann Arbor and The Jackson Laboratory at Bar Harbor, Maine -- collaborated on the study with the labs of Robert W. Williams, PhD, of the University of Tennessee Health Science Center at Memphis and Johan Auwerx, MD, PhD, of the École Polytechnique Fédérale de Lausanne in Lausanne, Switzerland.

"Some candidate genes impacted female life span while others affected the male life span," said Randy Strong, PhD, of the Sam and Ann Barshop Institute for Longevity and Aging Studies at UT Health San Antonio. "One cluster of genes increased longevity of both sexes. In a rarity for these types of studies, the findings were made in a population of mice with genetic diversity comparable to human populations."

The high-impact journal Science published the findings Sept. 30. Strong directs the Interventions Testing Program site at the Barshop Institute, which first attracted National Institute on Aging (NIA) grant funding for the Interventions Testing Program in 2003 and is in its 19th year of the NIA funding.

Genetic smorgasbord

"The study models what happens in people," said research coauthor James Nelson, PhD, of the Barshop Institute. "Unlike mice in many other studies, mice in this newly reported research are not all the same. Each has different genetic variants, resulting in slightly different proteins that do slightly different things, which together can impact aging."

Even subtle differences can lead to different health outcomes as we age. Slight variations in the hemoglobin gene, for example, can cause the hemoglobin protein in red blood cells to be less effective at binding to oxygen and transferring it from the lungs to the body's tissues, Nelson noted. Anemia is one effect.

Female longevity

The discovery of genetic loci that influence longevity only in females is interesting and important, Strong said. Genetic loci are clusters of between 10 and 100 genes.

"Females and males differ in almost every aspect of aging you can explore," Strong said. "They each must be studied, both to understand aging in the two sexes and to develop effective treatments. If we offer the same drug therapies to females that we offer to males, and females' aging is caused by different genes, we are not going to be as effective in our treatments."

Confirmation in roundworms

The next steps are scrutinizing these candidate genes to find ones that are responsible for increased longevity. In the final part of the Science article, the team reported doing this. The researchers tested candidate genes in roundworms, which are often used in aging research because of their short life span. "A number of the candidate genes did affect longevity in the worms," Nelson said.

That doesn't prove that those same genes in humans are going to affect human life span, the researchers said. But it's another part of the case for continuing to study the genetic basis of longevity.

Powerful study design

As envisioned when the Interventions Testing Program began, having three sites where studies are conducted ensures statistical power and rigor and reproducibility of findings, Strong said.

The study is unique in that it is based on a large sample size of animals numbering several thousand, the authors said. "It is among the largest number of mice of any study that has attempted to identify genes that influence life span," Nelson said.

Barshop Institute excellence

The Interventions Testing Program is one of several NIA-funded centers at the Sam and Ann Barshop Institute. Among them, the Nathan Shock Center of Excellence in the Basic Biology of Aging provides core services to enhance research of the fundamental biological questions of aging. The Claude D. Pepper Older Americans Independence Center, named for the late U.S. representative, is a center of excellence aimed at increasing scientific knowledge to develop better ways of maintaining or restoring independence in senior adults. The Barshop Institute is the only institute or university in the nation to have these three centers.

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