Culture

CAMBRIDGE, MD (December 16, 2019)--In recent years, scientists have projected increasingly large summer dead zones in the Chesapeake Bay, areas where there is little or no oxygen for living things like crabs and fish to thrive, even as long-term efforts to reduce nutrient pollution continue. Researchers warn that climate may also have significant impact that could change the equation for nutrient reduction goals.

Researchers including Ming Li and Wenfei Ni from University of Maryland Center for Environmental Science factored in local impacts of climate change to make projections of what the oxygen content of the Chesapeake Bay will look like in the future.

"We projected that the hypoxic and anoxic volumes in Chesapeake Bay would increase by 10-30% between the late 20th and mid?21st century," said study author Ming Li of the University of Maryland Center for Environmental Science.

The bay's hypoxic (low oxygen) and anoxic (no oxygen) zones, also called "dead zones," are caused by excess nutrient pollution, primarily from agriculture and wastewater. The excess nutrients stimulate an overgrowth of algae, which then sinks and decomposes in the water, consuming oxygen. The resulting low oxygen levels are insufficient to support most marine life and habitats in near-bottom waters, threatening the bay's crabs, oysters and other fisheries.

The Chesapeake Bay has been experiencing rapid warming and accelerating relative sea level rise. In coastal waters, the depletion of oxygen in bottom water has occurred at faster rates than the open ocean and has been traditionally attributed to nutrient pollution and organic matter from the surrounding watershed and rivers.

"Previous studies have suggested that the climate change impact on hypoxia in Chesapeake Bay would be modest," said Ming Li. "We are saying there might actually be a bigger increase in hypoxia, and we need to factor climate change in to nutrient management strategies. Maybe we'll have to make a bigger reduction of nutrient loading to offset the impact of climate change."

The researchers used several climate models to make hypoxia projections for 2050 and got similar results.

"This has really raised some questions," he said. "Chesapeake is vulnerable to climate change."

A major study led by researchers at La Trobe University in Australia has identified key themes that will be used to inform strategies to support Australian Aboriginal and Torres Strait Islander parents in the first years of their children's lives.

The Healing the Past by Nurturing the Future project aims to break the cycle of intergenerational and complex trauma experienced by Aboriginal and Torres Strait islander people, by co-designing strategies for new parents.

The international research team, led by Associate Professor Catherine Chamberlain of La Trobe's Judith Lumley Centre and published today in the journal PLOS ONE, reviewed more than 20,000 scholarly articles to build a comprehensive understanding of pregnancy and birth for parents who have experienced trauma in their own childhood.

The study identified seven themes, derived from studying interviews with more than 350 parents who experienced trauma as children, relate to parents' experiences during pregnancy, birth and the first few weeks after birth.

Associate Professor Catherine Chamberlain said the research is critical for informing discussions with Aboriginal parents and communities to create a strong foundation for work to heal complex trauma.

"This gives us a thorough and deep understanding needed to help co-design support strategies with communities to improve the lives of Aboriginal and Torres Strait Islander people and their babies," Associate Professor Chamberlain said.

"We have shared these themes in discussions with Aboriginal and Torres Strait Islander parents and community members to see if any are relevant. Doing so also helps parents to understand these experiences are shared, even in other countries.

"The next stage of our Healing the Past by Nurturing the Future project will use these themes to examine what support strategies have been evaluated in research. We will look at whether this research reflects what support parents say they want and what they feel works."

The seven themes are:

New beginnings: Becoming a parent is an opportunity for 'a fresh start', to put the past behind them and move forward with hope for the future to create a new life for themselves and their

child.

Changing roles and identities: Becoming a parent is a major life transition, influenced by perceptions of the parenting role.

Feeling connected: The quality of relationships with self, baby and others has major impacts on the experiences of becoming a parent.

Compassionate care: Kindness, empathy and sensitivity enables parents to build trust and feel valued and cared for.

Empowerment: Control, choice and 'having a voice' are critical to fostering safety.

Creating safety: Parents perceive the 'world as unsafe' and use conscious strategies to build safe places and relationships to protect themselves and their baby.

'Reweaving' a future: Managing distress and healing while becoming a parent is a personal ongoing and complex process requiring strength, hope and support.

Associate Professor Chamberlain said the seven themes also resonated strongly with Aboriginal and Torres Strait Islander parents and she was grateful to the research team for all their hard work and expertise, and to Lowitja Institute and the NHMRC for funding this phase of her work.

A new approach to trapping light in artificial photonic materials by a City College of New York-led team could lead to a tremendous boost in the transfer speed of data online.

Research into topological photonic metamaterials headed by City College physicist Alexander B. Khanikaev reveals that long-range interactions in the metamaterial changes the common behavior of light waves forcing them to localize in space. Further, the study shows that by controlling the degree of such interactions one can switch between trapped and extended (propagating) character of optical waves.

"The new approach to trap light allows the design of new types of optical resonators, which may have a significant impact on devices used on a daily basis, said Khanikaev. "These range from antennas in smartphones and Wi-Fi routers, to optical chips in optoelectronics used for transferring data over the Internet with unprecedented speeds."

Entitled "Higher-order topological states in photonic kagome crystals with long-range interactions," the research appears in the journal Nature Photonics published today.

It is a collaboration between CCNY, the Photonics Initiative at the Graduate Center, CUNY; and ITMO University in St. Petersburg, Russia. As the lead organization, CCNY initiated the research and designed the structures, which were then tested both at CCNY and at ITMO University.

Khanikaev's research partners included: Andrea Alù, Mengyao Li, Xiang Ni (CCNY/CUNY); Dmitry Zhirihin (CCNY/ ITMO); Maxim Gorlach, Alexey Slobozhanyuk (both ITMO), and Dmitry Filonov (Center for Photonics and 2D Materials, Moscow Institute of Physics and Technology.

Research continues to extend the new approach to trap visible and infra-red light. This would further expand the range of possible applications of the discovery.

In the world of squirrels, moving away from your home turf has better outcomes for males than for females, according to a new study by University of Alberta ecologists.

The study uses 30 years of data on a population of North American red squirrels in Yukon, Canada, examining how the number of offspring and total lifespan differed between squirrels who lived in the same area in which they were born and those who were newcomers to the area. And the results show that sex plays a major role.

"The benefits to living in a different population than you were born are sex-dependent," explained April Martinig, PhD student in the Department of Biological Sciences and lead author on the study. "Males benefit from moving away, whereas females do not. We also found that the decision to move away or stay at home has an impact on offspring."

New research shows that male squirrels who move outside of the population they were born to live longer and have more offspring.

For male squirrels, moving away is beneficial because they no longer need to compete with their siblings for limited resources, such as mates or food. Males also benefit, because female squirrels prefer to mate with newcomer males. Female squirrels, on the other hand, do not reap the same benefits, and instead lose out on the support of nearby family--something that male squirrels don't receive.

"Squirrels live in a world where there are only so many 'empty apartments' to live in," said Martinig, who is conducting her PhD studies under the supervision of Professor Stan Boutin. "Sometimes one sibling is allowed to stay at home--so everyone else must go. If there are no vacancies nearby, squirrels then have no choice but to move further away. This is what females face: losing the benefits of having family nearby."

"Movement is a crucial component of species persistence," added Martinig. "Understanding how and why certain individuals move is key to protecting populations as climate change impacts their distribution on the landscape."

Research shows that white blood cells in the human brain are regulated by a protein called CD33--a finding with important implications in the fight against Alzheimer's disease, according to a new study by University of Alberta chemists.

"Immune cells in the brain, called microglia, play a critical role in Alzheimer's disease," explained Matthew Macauley, assistant professor in theDepartment of Chemistry and co-author on the paper. "They can be harmful or protective. Swaying microglia from a harmful to protective state could be the key to treating the disease."

Scientists have identified the CD33 protein as a factor that may decrease a person's likelihood of Alzheimer's disease. Less than 10 percent of the population have a version of CD33 that makes them less likely to get Alzheimer's disease. "The fact that CD33 is found on microglia suggests that immune cells can protect the brain from Alzheimer's disease under the right circumstances," said Abhishek Bhattacherjee, first author and postdoctoral fellow in the Macauley lab.

Now, Macauley's research shows that the most common type of CD33 protein plays a crucial role in modulating the function of microglia.

"These findings set the stage for future testing of a causal relationship between CD33 and Alzheimer's Disease, as well as testing therapeutic strategies to sway microglia from harmful to protecting against the disease--by targeting CD33," said Macauley. "Microglia have the potential to 'clean up' the neurodegenerative plaques, through a process called phagocytosis--so a therapy to harness this ability to slow down or reverse Alzheimer's disease can be envisioned."

Macauley is an investigator with GlycoNet, a Canada-wide network of researchers based at the University of Alberta that is working to further our understanding of biological roles for sugars. GlycoNet provided key funding to get this project off the ground in the Macauley lab and continues to support the ongoing applications of the project.

According to the Alzheimer's Association, 747,000 Canadians are currently living with Alzheimer's or another form of dementia. The disease affects more than 44 million people around the world.

Opioid use among psychiatric hospital patients needs to be addressed through an integrated approach to managing mental illness, pain and substance use, a study by researchers at the University of Waterloo has found.

The study found that 7.5 per cent of 165,434 patients admitted to psychiatric hospitals in Ontario between 2006 and 2017 had used opioids in the year prior to admission, which compares to estimates that 2 per cent of the general population used opioids in 2015. Among patients who said they experience daily pain, the percentage who reported opiate use jumped to 22 per cent.

"The patterns of use we saw are problematic," said Christopher Perlman, a public health researcher. "Opiate use is strongly linked to pain, mental health conditions and use of other drugs. While we don't know how many patients were initially prescribed an opioid for pain, we do know that a large number of patients reporting pain in psychiatry also have an addiction concern."

The study highlights the challenging circumstances faced by those who use opioids. For instance, opiate use was almost twice as common among those whose employment or education was at risk (10.5 per cent) compared to those not at risk (5.8 per cent). Many patients who had used opiates did not have a partner or spouse, and individuals living in rural and northern communities were more likely to use opiates, as were young people, and males rather than females.

"If we are serious about supporting people with mental and physical health concerns, we need an integrated approach to service delivery, which includes assessing and addressing the risk of addiction," said Perlman, who is a professor in the School of Public Health and Health Systems at the University of Waterloo. "Right now, the way our health system is structured and funded, it's not easy to integrate physical, mental and substance use services."

"This study was able to shed some light on the needs of persons who use opioids, but this is really the tip of the iceberg. Because we lack integrated health information systems across various health providers, we really don't know the extent of the physical and health needs of individuals who use opioids across the population. That means they are either getting help elsewhere, which would be good - or more likely, that they are not getting care they need."

The paper, "Factors Associated With Opiate Use Among Psychiatric Inpatients: A Population-Based Study of Hospital Admissions in Ontario, Canada" was co-authored by Oluwakemi Aderibigbe (Waterloo), Anthony Renda (independent), and Christopher Perlman (Waterloo), and published in Health Services Insights.

DURHAM, N.C. -- Born pink, blind, and helpless, giant pandas typically weigh about 100 grams at birth -- the equivalent of a stick of butter. Their mothers are 900 times more massive than that.

This unusual size difference has left researchers puzzled for years. With a few exceptions among animals such as echidnas and kangaroos, no other mammal newborns are so tiny relative to their mothers. No one knows why, but a Duke University study of bones across 10 species of bears and other animals finds that some of the current theories don't hold up.

Duke biology professor Kathleen Smith and her former student Peishu Li published their findings this month in the Journal of Anatomy.

Baby panda skeletons are hard to come by, but the researchers were able to study the preserved remains of baby pandas born at the Smithsonian's National Zoo in Washington, D.C.

The National Zoo's first panda couple, Ling-Ling and Hsing-Hsing, had five full-term cubs in the 1980s, but none of them survived long after birth.

The researchers took micro-CT scans of two of those cubs, along with newborn grizzlies, sloth bears, polar bears, dogs, a fox, and other closely related animals from the Smithsonian National Museum of Natural History and the North Carolina State College of Veterinary Medicine.

They used the scans to create 3-D digital models of each baby's bony interior at birth.

As a baby animal grows and develops inside the womb, its bones and teeth do, too. The researchers examined the degree of ossification, or how much the skeleton has formed by the time of birth. They looked at whether the teeth had started to calcify or erupt, and the degree of fusion between the bony plates that make up the skull.

The panda may be an extreme example, but all bears have disproportionately small babies, Li said. A newborn polar bear's birthweight as a fraction of mom's is less than 1:400, or less than one-half of one percent of her body mass. For the vast majority of baby mammals, including humans, the average is closer to 1:26.

One decades-old idea links low birthweights in bears to the fact that, for some species, pregnancy overlaps with winter hibernation. Pregnant females don't eat or drink during this time, relying mostly on their fat reserves to survive, but also breaking down muscle to supply protein to the fetus.

The thinking is that, energetically, females can only afford to nourish their babies this way for so long before this tissue breakdown threatens their health. By cutting pregnancy short and giving birth to small, immature babies, bears would shift more of their growth to outside the womb, where babies can live off their mother's fat-rich milk instead of depleting her muscles.

Proponents of the theory concede that not all bears -- including pandas -- hibernate during the winter. But the idea is that small birthweight is 'locked in' to the bear family tree, preventing non-hibernating relatives from evolving bigger babies too.

"It's certainly an appealing hypothesis," Smith said.

But the Duke team's research shows this scenario is unlikely. The researchers didn't find any significant differences in bone growth between hibernating bears and their counterparts that stay active year-round and don't fast during pregnancy.

In fact, despite being small, the researchers found that most bear skeletons are just as mature at birth as their close animal cousins.

The panda bear is the one exception to this rule, results show. Even in a full-term baby panda, the bones look a lot like those of a beagle puppy delivered several weeks premature.

"That would be like a 28-week human fetus" at the beginning of the third trimester, Smith said.

Other factors might have pushed panda babies toward smaller sizes over time -- some researchers blame their bamboo-only diet -- but data are scarce, Li said. The researchers say the panda bear's embryonic appearance likely has to do with a quirk of panda pregnancy.

All bears experience what's called "delayed implantation." After the egg is fertilized, the future fetus enters a state of suspended animation, floating in the womb for several months before implanting in the uterine wall to resume its development and get ready for birth.

But while other bears gestate for two months after implantation, giant pandas are done in a month.

"They're basically undercooked," said Li, now a Ph.D. student at the University of Chicago.

The researchers say they only looked at skeletons in this study, and it could be that other organs like the brain tell a different story. But the new study suggests that baby pandas follow the same trajectory as other mammal relatives -- their bones mature in the same sequence and at similar rates -- but on a truncated timetable.

"Development is just cut short," Smith said.

Scientists are still searching for a complete explanation of why the panda's peculiar size differential evolved over geological time, and how.

"We really need more information about their ecology and reproduction in the wild," Smith said, and we may not have much time given their risk of extinction. But this study brings them one step closer to an answer.

Rapa Nui (or Easter Island, as it is commonly known) is home to the enigmatic Moai, stone monoliths that have stood watch over the island landscape for hundreds of years. Their existence is a marvel of human ingenuity -- and their meaning a source of some mystery.

Ancient Rapanui carvers worked at the behest of the elite ruling class to carve nearly 1,000 Moai because they, and the community at large, believed the statues capable of producing agricultural fertility and thereby critical food supplies, according to a new study from Jo Anne Van Tilburg, director of the Easter Island Statue Project, recently published in Journal of Archaeological Science.

Van Tilburg and her team, working with geoarchaeologist and soils specialist Sarah Sherwood, believe they have found scientific evidence of that long-hypothesized meaning thanks to careful study of two particular Moai excavated over five years in the Rano Raraku quarry on the eastern side of the Polynesian island.

Van Tilburg's most recent analysis focused on two of the monoliths that stand within the inner region of the Rano Raraku quarry, which is the origin of 95 percent of the island's more than 1,000 Moai. Extensive laboratory testing of soil samples from the same area shows evidence of foods such as banana, taro and sweet potato.

Van Tilburg said the analysis showed that in addition to serving as a quarry and a place for carving statues, Rano Raraku also was the site of a productive agricultural area.

"Our excavation broadens our perspective of the Moai and encourages us to realize that nothing, no matter how obvious, is ever exactly as it seems. I think our new analysis humanizes the production process of the Moai," Van Tilburg said.

Van Tilburg has been working on Rapa Nui for more than three decades. Her Easter Island Statue Project is supported in part by UCLA's Cotsen Institute of Archaeology. Tom Wake, a Cotsen Institute colleague, analyzes small-animal remains from the excavation site. Van Tilburg also serves as director of UCLA's Rock Art Archive.

Van Tilburg, in partnership with members of the local community, heads the first legally permitted excavations of Moai in Rano Raraku since 1955. Cristián Arévalo Pakarati, a noted Rapanui artist, is project co-director.

The soils in Rano Raraku are probably the richest on the island, certainly over the long term, Sherwood said. Coupled with a fresh-water source in the quarry, it appears the practice of quarrying itself helped boost soil fertility and food production in the immediate surroundings, she said. The soils in the quarry are rich in clay created by the weathering of lapilli tuff (the local bedrock) as the workers quarried into deeper rock and sculpted the Moai.

A professor of earth and environmental systems at the University of the South in Sewanee, Tenn., Sherwood joined the Easter Island Project after meeting another member of Van Tilburg's team at a geology conference.

She wasn't originally looking for soil fertility, but out of curiosity and research habit, she did some fine-scale testing of samples brought back from the quarry.

"When we got the chemistry results back, I did a double take," Sherwood said. "There were really high levels of things that I never would have thought would be there, such as calcium and phosphorous. The soil chemistry showed high levels of elements that are key to plant growth and essential for high yields. Everywhere else on the island the soil was being quickly worn out, eroding, being leeched of elements that feed plants, but in the quarry, with its constant new influx of small fragments of the bedrock generated by the quarrying process, there is a perfect feedback system of water, natural fertilizer and nutrients."

She said it also looks like the ancient indigenous people of Rapanui were very intuitive about what to grow -- planting multiple crops in the same area, which can help maintain soil fertility.

The Moai that Van Tilburg's team excavated were discovered upright in place, one on a pedestal and the other in a deep hole, indicating they were meant to remain there.

"This study radically alters the idea that all standing statues in Rano Raraku were simply awaiting transport out of the quarry," Van Tilburg said. "That is, these and probably other upright Moai in Rano Raraku were retained in place to ensure the sacred nature of the quarry itself. The Moai were central to the idea of fertility, and in Rapanui belief their presence here stimulated agricultural food production."

Van Tilburg and her team estimate the statues from the inner quarry were raised by or before A.D. 1510 to A.D.1645. Activity in this part of the quarry most likely began in A.D.1455. Most production of Moai had ceased in the early 1700s due to western contact.

The two statues Van Tilburg's team excavated had been almost completely buried by soils and rubble.

"We chose the statues for excavation based on careful scrutiny of historical photographs and mapped the entire Rano Raraku inner region before initiating excavations," she said.

Van Tilburg has worked hard to establish connections with the local community on Rapa Nui. The project's field and lab teams are made up of local workers, mentored by professional archeologists and geologists.

The result of their collective efforts is a massive detailed archive and comparative database that documents more than 1,000 sculptural objects on Rapa Nui, including the Moai, as well as similar records on more than 200 objects scattered in museums throughout the world. In 1995, UNESCO named Easter Island a World Heritage Site, with most of the island's sacred sites protected within Rapa Nui National Park.

This is the first definitive study to reveal the quarry as a complex landscape and to make a definitive statement that links soil fertility, agriculture, quarrying and the sacred nature of the Moai.

Take a deep breath in. Slowly let it out.

You have just participated in one of the most profound evolutionary revolutions on Earth--breathing air on land. It's unclear how the first vertebrates thrived after crawling out of the sea nearly 400 million years ago, but the lungs hold an important clue.

Birds, reptiles, mammals and birds have evolved diverse lung structures through which air flows in complicated ways. Birds and mammals are on extreme ends of the airflow spectrum. Mammals inhale oxygen-rich air that funnels into smaller branches, ending in tiny sacs where oxygen enters and carbon dioxide leaves the bloodstream. When mammals exhale, the depleted air follows the same route out of the body, exhibiting a so-called tidal flow pattern.

In contrast, bird breath travels tidally through part of the respiratory system, but in a one-way loop throughout most of the lung. Thanks to a unique design with aerodynamic valves, air always moves toward the head through many tiny tubes in birds--during both inhalation and exhalation. Scientists thought this pattern of flow is hyper efficient and evolved to support flight until University of Utah biologist Colleen Farmer's research group discovered that alligators and iguanas also have a unidirectional air flow pattern.

In their latest study, U biologists have discovered that Savannah monitor lizards have lung structures that are a kind of a hybrid system of bird and mammal lungs. The researchers took CT scans of the entire lung labyrinth and used two different supercomputers to simulate airflow patterns at the highest resolution. The software used computational fluid dynamics similar to those used to forecast weather, calculating millions of equations every tenth of a second. The findings show that vertebrate lung evolution is complicated and we have yet to understand the full picture.

"We don't know why animals have different types of lung air flow," said lead author Robert Cieri, a postdoc at the University of the Sunshine Coast who did the research while a graduate student in Farmer's lab. "Why do humans have the lungs we have verses the lungs of a bird? That's not a simple question. By answering that, maybe we can find out more about our own history."

The paper published on Dec. 13 in The Anatomical Record.

A unique airflow pattern

The Savannah monitor lizard has long fascinated scientists because they have one of the most complicated lung systems of any reptile. In 2014, Cieri and colleagues analyzed one section of the lung that had primarily one-way airflow. This new study uses more powerful techniques to paint a completer and more complicated picture. Savannah monitor lizard lungs are structured around a long branchial tube that runs through to the back of the lung and opens into a big sac. Many smaller tubes branch off from the main one and distribute air into tiny chambers. These chambers have holes in their walls, allowing air to flow also from chamber to chamber. This complicated layout results in an airflow pattern that changes over the course of a breath cycle. It's a unique pattern that is part bird, part mammal.

When the animal exhales, nearly all of the air flows towards the front of the lung and out of the trachea in a net unidirectional flow. At the beginning of inhalation, air enters through the trachea and flows towards the back of the lung. As the inhale continues, the air begins to distribute throughout the different side chambers and starts to loop back around towards the front of the lung. As these loops become more dominant, the late stages of inhalation look similar to exhalation because most of the air is flowing unilaterally back from the central chamber. The complicated structure has no flaps or valves that determine airflow, like the heart pumps blood. Pure aerodynamics guide the complicated physics.

"This study is important in demonstrating it is possible to numerically analyze patterns of airflow in these extremely complicated lungs. This quantitative ability opens up new avenues to study the basic mechanisms of how aerodynamic valve work, and gives us better tools to piece together the evolutionary history of these patterns of flow and the structures that underpin them," said senior author Farmer.

Supercomputers tell a complicated story

The physics is so complicated that Cieri needed two supercomputers from the Center for High Performance Computing at the U and the National Science Foundation Blue Waters to run the computer fluid dynamics simulation. After creating the CT scans, he modified existing software to predict the velocity and pressure based on the lung structure. He divided the structures into millions of tiny "boxes." Each box has the physical parameters of that section of the lung. The simulation uses equations to predict what the pressure and velocity will be in the next box, and so on.

"There are millions of these elements. Each one is influencing another one every ten-thousandth of a second in every direction. That's why we needed the computer power--the simulation is brute force balancing two equations at each step to figure out the next piece," said Cieri.

The evolution of lungs is one crucial clue to understanding the pressures that led to where we are now. Along with learning more about lung evolution, Cieri believes we can learn something from the physics of the structure.

"We have this amazing wealth of really cool fluid dynamics out there in the animal world that we want to know more about. Maybe we can apply that knowledge to engineering or for human health," he said.

LA JOLLA--(December 13, 2019) Mitochondria, tiny structures present in most cells, are known for their energy-generating machinery. Now, Salk researchers have discovered a new function of mitochondria: they set off molecular alarms when cells are exposed to stress or chemicals that can damage DNA, such as chemotherapy. The results, published online in Nature Metabolism on December 9, 2019, could lead to new cancer treatments that prevent tumors from becoming resistant to chemotherapy.

"Mitochondria are acting as a first line of defense in sensing DNA stress. The mitochondria tell the rest of the cell, 'Hey, I'm under attack, you better protect yourself,'" says Gerald Shadel, a professor in Salk's Molecular and Cell Biology Laboratory and the Audrey Geisel Chair in Biomedical Science.

Most of the DNA that a cell needs to function is found inside the cell's nucleus, packaged in chromosomes and inherited from both parents. But mitochondria each contain their own small circles of DNA (called mitochondrial DNA or mtDNA), passed only from a mother to her offspring. And most cells contain hundreds--or even thousands--of mitochondria.

Shadel's lab group previously showed that cells respond to improperly packaged mtDNA similarly to how they would react to an invading virus--by releasing it from mitochondria and launching an immune response that beefs up the cell's defenses.

In the new study, Shadel and his colleagues set out to look in more detail at what molecular pathways are activated by the release of damaged mtDNA into the cell's interior. They homed in on a subset of genes known as interferon-stimulated genes, or ISGs, that are typically activated by the presence of viruses. But in this case, the team realized, the genes were a particular subset of ISGs turned on by viruses. And this same subset of ISGs is often found to be activated in cancer cells that have developed resistance to chemotherapy with DNA-damaging agents like doxorubicin.

To destroy cancer, doxorubicin targets the nuclear DNA. But the new study found that the drug also causes the damage and release of mtDNA, which in turn activates ISGs. This subset of ISGs, the group discovered, helps protect nuclear DNA from damage--and, thus, causes increased resistance to the chemotherapy drug. When Shadel and his colleagues induced mitochondrial stress in melanoma cancer cells, the cells became more resistant to doxorubicin when grown in culture dishes and even in mice, as higher levels of the ISGs were protecting the cell's DNA.

"Perhaps the fact that mitochondrial DNA is present in so many copies in each cell, and has fewer of its own DNA repair pathways, makes it a very effective sensor of DNA stress," says Shadel.

Most of the time, he points out, it's probably a good thing that the mtDNA is more prone to damage--it acts like a canary in a coal mine to protect healthy cells. But in cancer cells, it means that doxorubicin--by damaging mtDNA first and setting off molecular alarm bells--can be less effective at damaging the nuclear DNA of cancer cells.

"It says to me that if you can prevent damage to mitochondrial DNA or its release during cancer treatment, you might prevent this form of chemotherapy resistance," Shadel says.

His group is planning future studies on exactly how mtDNA is damaged and released and which DNA repair pathways are activated by the ISGs in the cell's nucleus to ward off damage.

What The Study Did: Nearly 200 years of military records from 1819 to 2017 were used to examine suicide rates among active-duty personnel in the U.S. Army in this observational study.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

Authors: Jeffrey Allen Smith, Ph.D.,of the University of Hawaii in Hilo, is the corresponding author.

(doi:10.1001/jamanetworkopen.2019.17448)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Problem drinkers are more likely than teetotalers and moderate drinkers to take benzodiazepines, a class of sedatives that are among the most commonly prescribed drugs -- and the most abused. When taken by heavier drinkers, benzodiazepines may heighten the risk for overdoses and accidents as well as exacerbate psychiatric conditions.

In a study by UC San Francisco and Kaiser Permanente Northern California, researchers found that primary care patients with "unhealthy alcohol use" had a 15 percent higher likelihood of using benzodiazepines than moderate drinkers and nondrinkers. Benzodiazepines -- colloquially known as "benzos" -- are usually prescribed for anxiety and insomnia, and include Valium (diazepam), Xanax (alprazolam), Klonopin (clonazepam), Ativan (lorazepam), Restoril (temazepam) and others.

In the study, which appears in the American Journal of Managed Care on Dec. 13, 2019, researchers reviewed the health records of more than two million primary care patients, who were Kaiser Permanente enrollees. The patients were screened for unhealthy alcohol use, defined as at least 15 drinks per week for men under 65, and at least eight drinks a week for women and males aged 65 and older. They found that 4 percent of the patient pool had unhealthy alcohol use and 7.5 percent of the patient pool had filled a prescription for a benzodiazepine within the last 12 months. The researchers excluded patients who had been prescribed benzodiazepines for alcohol withdrawal.

However, the authors also found that when problem drinkers were prescribed benzodiazepines, their average dose was 40 percent lower and the duration of use was 16 percent shorter than moderate drinkers and abstainers. It is unknown whether the impetus for this regimen came from the prescribing physician or the patients themselves, who "voluntarily limited their use of benzodiazepines to avoid functional impairment," the authors noted.

Patients May Believe Daily Benzos 'Harmless'

"Some physicians may be refilling prescriptions, unaware that their patients have unhealthy alcohol use. In many cases, patients have been taking benzodiazepines for years and believe them to be harmless," said first author Matthew Hirschtritt, MD, clinical professor in the UCSF Department of Psychiatry.

"When benzodiazepines are consumed with alcohol, overdose can result from the impact of two central nervous system depressants. Their effects can reduce motor coordination, impact judgment and decision-making, and result in falls and accidents. Long-term use can lead to cardiovascular, gastrointestinal, liver, kidney and neurological injury, as well as psychosis or suicidal ideation for those with pre-existing psychiatric conditions," he said.

Numerous studies have already demonstrated that long-term benzodiazepine use has been linked to an increased risk for dementia. "It's possible that unhealthy alcohol use may amplify this dementia risk," said Hirschtritt, who is also an associate physician in the Department of Psychiatry of The Permanente Medical Group and an adjunct investigator in the Kaiser Permanente Division of Research.

Alcohol Implicated in 1 in 5 Benzo-Related Deaths

Between 1996 and 2013, the percentage of U.S. adults who filled a benzodiazepine prescription increased from 4.1 percent to 5.6 percent, and the number of overdose deaths involving the drugs spiraled from 0.58 to 3.07 per 100,000 adults. Alcohol was a factor in one-in-four benzodiazepine-related visits and one-in-five benzodiazepine-related deaths in U.S. emergency departments, according to the Centers for Disease Control and Prevention.

The finding that patients with unhealthy alcohol use were 15 percent more likely to be prescribed a benzodiazepine runs counter to the researchers' hypothesis they would have a lower likelihood of obtaining the drugs. "In prescribing drugs, physicians weigh the risks and benefits," said Hirschtritt. "While the risks of benzodiazepines for all patients, and especially those with problem alcohol use, are becoming clearer, their benefits may appear to be negligible given that safer prescription drugs are effective for treating anxiety."

"As we learn more about drinking habits of primary care patients, especially among vulnerable populations such as benzodiazepine users, providers and health systems can better tailor practices and focus identification and prevention efforts," said senior author Stacy Sterling, DrPH, MSW, research scientist at the Division of Research, Kaiser Permanente Northern California.

Pullman, Wash. - When people learn that a charitable contribution they earmarked for a specific project was used for another cause, they feel betrayed - and often punish the charity, new research from Washington State University indicates.

Those donors were less likely to give money to the charity in the future or do volunteer work for the organization. They also were more likely to say negative things about the charity, according to the research published in the January 2020 issue of the Journal of the Association for Consumer Research and available online.

The findings held true even when their contribution was directed to another worthwhile cause, said Jeff Joireman, a professor in the Department of Marketing and International Business at WSU's Carson College of Business.

"The whole idea that a charity could activate a sense of betrayal is quite novel," said Joireman, who worked with research collaborators from Pacific Lutheran University, HEC Montreal, University of Wyoming and WSU Ph.D. student Pavan Munaganti.

"This wasn't fraud or embezzlement--the donor's money was still being used for good," Joireman said. "But because the expectations were so high, they were upset when their donation was redirected."

The study comes amid the increasing popularity of donor-directed charities.

Instead of giving to a traditional charity that supports multiple causes, many people prefer to specify that their contributions will support a new well in a Tanzanian village, or help a Costa Rican entrepreneur open a coffee business. As a result, contributions to donor-directed charities such as Donors Choose and Kiva have risen by 700 percent over the past decade.

Charities held to high standards

The research involved three studies conducted at WSU's Center for Behavioral Business Research. Participants made $1 donations to specific projects in rural areas of India or Peru, then they were told the charity used their money for a different purpose.

Respondents were most upset when their money was directed away from projects considered essential for survival, Joireman said. If they wanted their donation to finance a drinking water project, for instance, and it was used for a library instead, they had higher feelings of betrayal than if the library donation was used for the drinking water project.

In both instances, however, the respondents chose not to support the charity with their next donation.

Charities are viewed as "moral actors" by the public and held to high standards, the research indicates. That magnifies people's sense of betrayal when a charity re-directs funds, Joireman said.

"It's almost like finding out that a police officer has committed a crime," he said.

The value of transparency

In the information age, stories about charities re-directing funds can easily go viral, said Mark Mulder, a coauthor of the research and associate professor at Pacific Lutheran University.

He gave the example of country singer Garth Brooks, who sued an Oklahoma hospital when it wouldn't return a $500,000 donation that Brooks thought was going to fund a women's health center named after his mother, but was used by the hospital for other purposes. When Brooks prevailed in his lawsuit, the New York Times came out with an article.

"When it happens, the cases often become high profile," Mulder said. "The stories are publicized on national news outlets and are shared on social media by individual users."

For charities, the research highlights the importance of transparency about how donations will be used, Joireman said.

"Donor-directed contributions are popular because they foster a sense of connection and impact," Joireman said. "But people feel betrayed if their money doesn't go to where they thought it would. The main takeaway is: Do what you say you're going to do."

At a prehistoric archaeological site in Turkey, researchers have discovered two 8,500-year-old human teeth, which had been used as pendants in a necklace or bracelet. Researchers have never documented this practice before in the prehistoric Near East, and the rarity of the find suggests that the human teeth were imbued with profound symbolic meaning for the people who wore them.

During excavations at the Neolithic site of Çatalhöyük in Turkey between 2013 and 2015, researchers found three 8,500-year-old-teeth that appeared to have been intentionally drilled to be worn as beads in a necklace or bracelet. Subsequent macroscopic, microscopic and radiographic analyses confirmed that two of the teeth had indeed been used as beads or pendants, researchers conclude in a newly published article in Journal of Archaeological Science: Reports.

"Not only had the two teeth been drilled with a conically shaped microdrill similar to those used for creating the vast amounts of beads from animal bone and stone that we have found at the site, but they also showed signs of wear corresponding to extensive use as ornaments in a necklace or bracelet," University of Copenhagen archaeologist and first author of the article Scott Haddow said. He added:

"The evidence suggests that the two teeth pendants were probably extracted from two mature individuals post-mortem. The wear on the teeth's chewing surfaces indicates that the individuals would have been between 30-50 years old. And since neither tooth seems to have been diseased-which would likely have caused the tooth to fall out during life, the most likely scenario is that both teeth were taken from skulls at the site."

Deep symbolic value

Researchers have previously found human teeth used for ornamental purposes at European sites from the Upper Palaeolithic and the Neolithic, but this practice has never been documented before in the Near East during these or subsequent timeframes. This makes these finds extremely rare and surprising.

"Given the amount of fragmentary skeletal material often circulating within Neolithic sites, not least at Çatalhöyük where secondary burial practices associated with the display of human skulls were frequent, what is most interesting is the fact that human teeth and bone were not selected and modified more often. Thus, because of the rarity of the find, we find it very unlikely that these modified human teeth were used solely for aesthetic purposes but rather carried profound symbolic meaning for the people who wore them," Scott Haddow explained.

He concluded:

"The fact that the teeth were recovered from non-burial contexts is also highly interesting in that burials at the site often contain beads and pendants made from animal bone/teeth and other materials, indicating that it seems to have been a deliberate choice not to include items made from human bone and teeth with burials. So perhaps these human teeth pendants were related to specific - and rare - ritual taboos? Or perhaps we should look to the identity of the two individuals from whom the teeth were extracted for an explanation? However, given the small sample size, the ultimate meaning of the human teeth pendants will remain elusive until new findings at Çatalhöyük or elsewhere in the Near East can help us better contextualise the meaning these human teeth artefacts."

When proteins in the brain form deposits consisting of insoluble aggregates, diseases such as Alzheimer's or Parkinson's can occur. Now a research team has come a step closer to understanding this process.

In Parkinson's disease the alpha-synuclein (α-synuclein) protein forms aggregates leading to impaired brain function and the development of the disease.

Now researchers at the University of Gothenburg and universities in Basel and Zurich have published a new study in Nature that demonstrates how a certain class of proteins can regulate and prevent α-synuclein from forming protein deposits and insoluble aggregates within healthy cells.

"In each cell there are auxiliary proteins called molecular chaperones. They take care of newly made proteins to help them in the process of protein folding and prevent misfolding or unfolding," says Björn Burmann, assistant professor at the Department of Chemistry and Molecular Biology at the University of Gothenburg.

A breakthrough in research

Protein folding describes the process by which a protein takes on its specific three-dimensional shape, enabling the protein to fulfil its function.

Countless proteins in mammalian cells do not have a stable protein fold, despite the important functions they serve in the cells. One of these proteins is α-synuclein. In the new study, the research team could now reveal the basic process that affects how the α-synuclein protein is folded and aggregated as well as how molecular chaperones in living mammalian cells can prevent the misfolding of α-synuclein.

"A large pool of various chaperones prevents α-synuclein from forming protein aggregates in healthy cells. By studying the protein directly in mammalian cells, we have found that inhibition of chaperones leads to aggregation of α-synuclein at the amino acid level."

Disruption of the α-synuclein-chaperone interaction may be the long-sought first step that initiates the development of a-synuclein-related diseases, according to Björn Burmann and his research colleagues.