“This work expands the way we can look at brain activity during sleep,” said Prerau. “By moving beyond traditional notions that break up the complex continuum of sleep into specific categories and waveform classes, we can reveal new types of signals and dynamics that may be important for understanding brain health and disease.”

Scientists typically study brain activity during sleep using the electroencephalogram, or EEG, which measures brainwaves at the scalp. Starting in the mid 1930s, the sleep EEG was first studied by looking at the traces of brainwaves drawn on a paper tape by a machine. Many important features of sleep are still based on what people almost a century ago could most easily observe in the complex waveform traces. Even the latest machine learning and signal processing algorithms for detecting sleep waveforms are judged against their ability to recreate human observation. In this study, the researchers asked: What can we learn if we expand our notion of sleep brainwaves beyond what was historically easy to identify by eye?

One particularly important set of sleep brainwave events are called sleep spindles. These spindles are short oscillation waveforms, usually lasting less than 1-2 seconds, that are linked to our ability to convert short-term memories to long-term memories. Changes in spindle activity have been linked with numerous disorders such as schizophrenia, autism, and Alzheimer’s disease, as well as with natural aging. In this study, rather than looking for spindle activity according to the historical definition, the team developed a new approach to automatically extract tens of thousands of short spindle-like waveform events from the EEG data throughout the entire night. Next, instead of looking at the waveforms in terms of fixed sleep stages (i.e., Wake, REM, and non-REM stages 1-3) as standard sleep studies do, they characterized the full continuum of gradual changes that occur in the brain during sleep. Using all these data, the team created graphical representations called slow oscillation power and phase histograms, which provide a powerful visualization of the activity of all the waveforms as a function of continuous sleep depth and synchronized activity in the cortex. “This further demonstrates the richness of the information that traditional, manual scoring leaves on the table,” said co-author Shaun Purcell, PhD, of the Department of Psychiatry at the Brigham.

When the team looked at a group of healthy participants, each with two nights of sleep recordings, the patterns observed appeared to be almost like fingerprints — highly specific to each person with strong consistency across nights. These results suggest new ways in which brain activity differs from person to person, even within groups of healthy people selected as control groups. The researchers then compared the activity between the healthy subjects and a population of people with schizophrenia, a disorder that reduces spindle activity. Using their approach, the team not only saw the known differences in participants with schizophrenia, but also found differences in other spindle-like waveforms occurring at other frequencies in the brain. This suggests new potential EEG biomarkers of schizophrenia that could be useful in better understanding the mechanisms of the disorder and in the development of targeted treatments.

“This approach is really exciting,” said co-author Dara Manoach, PhD, of the Department of Psychiatry at Massachusetts General Hospital. “We look forward to seeing how we can enhance our understanding, not only of schizophrenia, but also of other neurodevelopmental disorders characterized by differences in sleep, such as autism and pediatric epilepsy.”

“We are just starting to understand the scope of neurodiversity that exists within the general population,” said Prerau. “If we can more accurately characterize the individual differences observed in both neurological health and disease, we can work towards improved diagnostics and treatments.”

Co-authors were Preetish Rath, Tom Possidente, Mingjian He, Shaun Purcell, Dara Manoach, and Robert Stickgold. Michael Prerau was the senior author.

This work was supported by the National Institute of Neurological Disorders and Stroke (R01NS096177) and the National Institute of Aging (R01AG054081 (MJP).

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Materials provided by Brigham and Women’s Hospital. Note: Content may be edited for style and length.

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.

“The hope is that CITES will request the stockpile to be re-inventoried,” Wasser says, “including aging randomly selected tusks and secure the remaining stocks.”

A study led by Yi-Ping Li, PhD, professor in the Department of Integrative Biology and Pharmacology with McGovern Medical School at UTHealth Houston, found that an enzyme known as UBR2 plays a critical role in cancer-induced muscle wasting, also called cancer cachexia.

The results were published today in the scientific journal PNAS.

“The findings will fill a key gap in understanding how cancer causes muscle mass and function loss,” said Li, senior author of the study and a faculty member with The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences.

Cancer cachexia is a complication developed in the late stages of cancer in roughly 60% of all cancer patients. Cachexia patients waste away by losing body weight, primarily due to progressive loss of muscle mass, causing respiratory and heart failure. Approximately 30% of all cancer patients die of cachexia, making the complication a major determinant of cancer survival.

Historically, there has been no treatment of cancer cachexia due to poor understanding of its origins. Therefore, a key focus of Li’s lab over the past two decades has been to decipher the molecular mechanisms through which cancer causes cachexia.

Building upon a series of discoveries in mice, his lab recently identified the role of the enzyme UBR2. This is the key enzyme in muscle that seeks out subtypes of the contractile protein myosin heavy chain, a critical component for sustaining muscle contraction, for destruction in response to cancer.

Cancer causes an increase of UBR2 in muscle, and blocking the increase of or removing UBR2 spares mice from tumor-caused muscle mass and function loss. By examining the muscle of cancer patients, researchers obtained evidence that UBR2 is increased, which is associated with loss of the specific subtype of myosin heavy chain preferentially lost in cachexia.

Li said this discovery is significant for the future of cancer cachexia therapy.

“We have learned in animal studies that muscle wasting in cancer hosts can be ameliorated by blocking UBR2 increase through repurposing some existing drugs,” he said. “Based on the findings, we plan to conduct clinical trials for the therapy of cancer cachexia.”

Song Gao, PhD, former postdoctoral research fellow with McGovern Medical School, was the first author of the study. Co-authors with the Department of Integrative Biology and Pharmacology at McGovern Medical School included Yong Zhou, PhD, assistant professor, as well as former faculty members Guohua Zhang, PhD; Zicheng Zhang, MD, PhD; James Z. Zhu; and Li Li, PhD.

Other co-authors were George G. Rodney Jr., PhD, and Reem S. Abo-Zahrah, PhD, both with Baylor College of Medicine in Houston; Lindsey Anderson, PhD, and Jose M. Garcia, MD, PhD, both with VA Puget Sound Health Care System in Seattle; and Yong Tae Kwon, PhD, with Seoul National University in South Korea.

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.

Gang Peng, an associate research scientist of biostatistics and bioinformatics in Yale’s departments of Biostatistics and Genetics, is the first author of the study.

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Materials provided by Yale University. Original written by Bill Hathaway. Note: Content may be edited for style and length.