Some cancers, however, can hijack these pathways for their own benefit. Susanna Stroik, PhD, and Dale Ramsden, PhD, both researchers in the Department of Biochemistry and Biophysics in the UNC School of Medicine and the UNC Lineberger Comprehensive Cancer Center, have pieced together the lesser-known DNA repair pathway, called polymerase theta-mediated end joining (TMEJ).

The pathway — which has been found to be upregulated in many patients with hereditary breast cancer, ovarian cancer, and prostate cancer, specifically those involving BRCA1 and BRCA2 mutations — has been laid out step by step in a published article in Nature, and the new knowledge could lead to new therapies for cancer.

“People with these breast cancer mutations, their cancers rely on polymerase theta’s repair pathway to keep the tumors alive and repair DNA damage in the cancerous tissue,” said Stroik, a postdoctoral researcher in Ramsden’s lab. “Now that we know more about this pathway, scientists could, in theory, produce a drug that could disrupt key pieces of the pathway in cancer cells, as opposed to using conventional chemotherapies that destroy healthy cells along with the cancer.”

Polymerase Theta’s Discovery

Out of all DNA repair pathways, TMEJ has been the most elusive. Richard Wood, PhD, a distinguished professor at University of Texas MD Anderson Cancer Center played a key role in the first characterization of polymerase theta in 2003.

Over the next 15 years, multiple labs, including the Wood, Ramsden, and Gupta labs (also at Lineberger Comprehensive Cancer Center), were able to link polymerase theta to DNA repair (TMEJ) and cancer. Sylvie Doublié, PhD, an alumnus of UNC-Chapel Hill and professor of microbiology and molecular genetics at the University of Vermont, then solved the first structure of polymerase theta.

Together, and with other scientists from Penn State and New York University, these researchers were dedicated to understanding precisely what steps are involved in TMEJ, and which of those steps polymerase theta does and does not perform.

With the help of these collaborators, Stroik was able to use a wide variety of cutting-edge experimental approaches to fill in the gaps in our understanding of the TMEJ pathway. Critically, she discovered that another polymerase, called polymerase delta, uses a buddy system with polymerase theta to assist it in this repair pathway.

A Unique Buddy System

Stroik’s research showed that polymerase theta is good at some things, but not others.

“It makes a lot of errors and it’s not capable of creating large swaths of DNA at once,” said Stroik. “What was so beautiful and kind of elegant about the whole discovery is that there are two different enzymes alternating between pathway steps and helping each other out.”

When a double stranded break occurs, both strands of DNA are cut at the same spot, much like scissors severing a braid of hair. Polymerase theta acts quickly, grabbing the two single strands of DNA, matching up the closest base pairs to the break, and holding them together.

However, this often leaves some residual flaps of single stranded DNA at the ends. Polymerase delta jumps in to cut the extraneous flaps, giving polymerase theta enough room to start synthesizing new DNA to fill in gaps in the DNA strands. Finally, polymerase delta jumps in one last time to help polymerase theta complete synthesis.

Stroik had another breakthrough finding: polymerases theta and delta are physically attached to one another. This new information could prove to be especially useful to drug developers hoping to create a new cancer treatment by drugging this interaction.

Cancer Treatment Potential

Since many cancers make use of the TMEJ pathway to keep tumors alive, many researchers have investigated creating drugs that can interfere with the pathway, essentially preventing cancer from repairing itself, leading to its eventual demise.

“Anytime you find new pieces of the pathway, you can ‘drug’ it,” said Ramsden.

Stroik and Ramsden’s new research will contribute to ongoing basic studies in polymerases theta and delta, while also aiding new cancer drugs called polymerase theta inhibitors, which are currently in clinical trials.

An Oregon Health & Science University study published in the journal Obesity found people who have a healthy weight use more energy during the day, when most people are active and eat, while those who have obesity spend more energy during the night, when most people sleep. The study also found that during the day, those with obesity have higher levels of the hormone insulin — a sign that the body is working harder to use glucose, an energy-packed sugar.

“It was surprising to learn how dramatically the timing of when our bodies burn energy differed in those with obesity,” said the study’s first author, Andrew McHill, Ph.D., an assistant professor in the OHSU School of Nursing and the Oregon Institute of Occupational Health Sciences at OHSU. “However, we’re not sure why. Burning less energy during the day could contribute to being obese, or it could be the result of obesity.”

Obesity is defined as having a Body Mass Index, or BMI, of 30 or more. Being overweight or obese increases the risk for health conditions such as high blood pressure and Type 2 diabetes.

Schedules and when people sleep, eat and exercise can also affect health, by either complementing or going against the body’s natural, daily rhythms. Every 24 hours, people experience numerous changes that are triggered by the human body’s internal clock. These changes normally occur at certain times of the day in order to best serve the body’s needs at any given hour.

McHill and the study’s senior author, Steven A. Shea, Ph.D., director of the Oregon Institute of Occupational Health Sciences at OHSU, focus their research on how circadian rhythms and sleep impact the human body. McHill leads theOHSU Sleep, Chronobiology and Health Laboratory.

While previous research has suggested circadian rhythm misalignment affects energy metabolism and glucose regulation, those studies have largely involved participants who have a healthy weight. To explore this further, McHill, Shea and colleagues organized a study that included people of different body sizes.

A total of 30 people volunteered to participate in the study, which involved participants staying at a specially designed circadian research lab for six days. The study followed a rigorous circadian research protocol involving a schedule designed to have participants be awake and sleep at different times throughout each day.

After each period of sleep, volunteers were awakened to eat and participate in a variety of tests for the remaining time of each day. One test had participants exercise while wearing a mask that was connected to a machine called an indirect calorimeter, which measures exhaled carbon dioxide and helps estimate energy usage. Blood samples were also collected to measure glucose levels in response to an identical meal provided during each day.

Next, the research team plans to explore eating habits and hunger in people who are obese, as well as those who have a healthy weight. That new study will also follow up on a 2013 study, led by Shea, that found circadian clocks naturally increase food cravings at night.

In a study of air pollution data in relation to markers of reproductive development in infancy, Rutgers researchers found certain pollutants may negatively alter anogenital distance, a measure of prenatal exposure to hormones.

“These findings suggest air pollution may interfere with normal hormone activity during critical periods of prenatal and early infant development, and we suspect that disruption may have long-term consequences for reproductive health,” said Emily Barrett, a professor in the Department of Biostatistics and Epidemiology at the Rutgers School of Public Health and lead author of the study published in the journal Environmental Health Perspectives.

Cross-sectional studies in adult men and women have shown that alterations in anogenital distance — the length between genitals and the anus — may be related to hormone levels as well as semen quality, fertility and reproductive disorders.

In animal studies, anogenital distance is used to determine developmental toxicity of pollutants. One measurable impact is on the reproductive system. When anogenital distance is reduced in male offspring, it’s a sign that a toxic exposure is interfering with fetal testosterone production, Barrett said.

Researchers have speculated that a similar relationship may exist in humans. To test their hypothesis, Barrett and colleagues used data from The Infant Development and Environment Study (TIDES), an ongoing longitudinal study of pregnant women and their children launched in 2010 in four U.S. cities: Minneapolis; Rochester, N.Y.; San Francisco; and Seattle. Anogenital distance at birth in children, and at one year for boys, was measured as part of the TIDES program.

These data were then compared with levels of nitrogen dioxide and fine particulate matter (PM2.5) — particle pollution 2.5 micrometers or smaller released during the burning of gasoline, oil, diesel and wood. An air pollution monitoring system administered by the University of Washington tracked pollution levels in the residential areas of TIDES participants during pregnancy.

By comparing these two measures, the researchers identified a link between exposure to air pollution during key developmental windows and anogenital distance.

For instance, higher PM2.5 exposure during the so-called male programming window at the end of the first trimester, when the male fetus typically receives a surge of hormones, was associated with shorter anogenital length at birth.

The researchers also observed that higher PM2.5 during mini puberty (a period in early infancy when hormone production is high) was associated with shorter anogenital distance in males at age one. These findings suggest there may be multiple points during early development that the reproductive system may be vulnerable to the impacts of air pollutants.

“PM2.5 is like a trojan horse,” said Barrett, adding that particulate matter can carry metals such as cadmium and lead, known endocrine disruptors. “When these disruptors interfere with the body’s hormones, the result could be lifelong impacts on our health, from cancer risks to impaired ability to conceive a child.”

Kenneth S. Campbell, Ph.D., the director of translational research in the Division of Cardiovascular Medicine in the UK College of Medicine, helped map out an important part of the heart on a molecular level. The study titled “Cryo-EM structure of the human cardiac myosin filament” was published online in the journal Nature earlier this month.

The heart is made up of billions of cells. Each cell contains thousands of smaller structures, called sarcomeres. These are the building blocks of muscle. Within each block, are hundreds of myosin filaments. To put this microscopic level into perspective, if the heart is a continent, Campbell and fellow researchers are looking at single strands of hair.

“Each filament has roughly 2,000 molecules arranged in a really complicated structure that scientists have been trying to understand for decades,” said Campbell. “We knew quite a lot about the individual molecules and people thought the myosins could be arranged in groups of six that were called crowns, but not much beyond that.”

Campbell explained the most interesting discovery in the paper is that there are three different types of crowns. The interactions between them are shown in the second photo below.

“We think this means that heart muscle can be controlled more precisely than we had realized. We were also excited to see how myosin binding protein-C, another protein that is linked to genetic heart disease, sits within the structure. It gives us a new level of information about how the molecules are arranged in the heart,” said Campbell.

Working with researchers at the University of Massachusetts Chan Medical School, the group produced single-particle 3D reconstructions of the cardiac thick filaments. The pictures provide a new framework for interpreting structural, physiological and clinical observations.

“This study is important for discovering new drug therapies for heart disease which Kentucky desperately needs,” said Campbell. “It gives us a much better understanding of how the molecules in our hearts interact.”

Heart disease is the leading cause of death in Kentucky and puts the Commonwealth among the top 10 states with the highest death rate from the disease, according to the Centers for Disease Control and Prevention (CDC).

“We’re interested in therapies for different kinds of heart failure and myopathies, where the heart muscles don’t work very well,” said Campbell. “Our research is one of many projects underway at the university to help come up with better therapies for heart disease.”

The research team collected heart samples from the Gill Cardiovascular Biorepository, of which Campbell is the director. Samples are donated for research purposes from patients who receive cardiovascular care at UK.

“We started the Gill Cardiovascular Biorepository in 2008. With the help of a surgeon at UK HealthCare, we started collecting samples of myocardium from organ donors and from patients who were getting cardiac transplants,” said Campbell. “Now we’ve built a huge resource with roughly 15,000 samples from nearly 500 people.

“We also share these samples with research groups around the world. This study in Nature comes from one of those collaborations.”

The researchers analyzed the impacts of decreased sea ice in the Amundsen Sea in West Antarctica and found the ice-free ocean surface leads to more moisture in the atmosphere and heavier snowfalls on the ice sheet, the team reported in the journal Geophysical Research Letters.

While the additional snowfall is not enough to offset the impacts of melting ice, including it in climate models may improve predictions of things like sea level rise, said Luke Trusel, assistant professor of geography at Penn State and co-author of the study.

The Antarctic ice sheet plays a significant role in global sea level dynamics. As one of the world’s largest reservoirs of freshwater, any change in its volume directly impacts sea levels. Trusel noted that while popular attention is often on visible processes like chunks of ice breaking away, or calving, and floating away as icebergs, more subtle interactions — like snowfall on the ice sheet — can be equally significant.

“For a place like Antarctica, which is just massive, the amount of snow falling on top of the ice sheet is as important or even more important than other processes like meltwater or ice breaking off,” Trusel said. “We’re tracking both snowfall and melt to understand both ends of the equation — what takes from sea level and what gets returned to the ocean. We want to know how those factors are impacting the ice sheets.”

The primary source of snowfall in Antarctica is evaporation from the surrounding oceans, with sea ice playing a pivotal role in modulating this process, according to researchers.

“Sea ice is significant,” said Jessica Kromer, a doctoral candidate at Penn State and lead author. “It reflects sunlight, aids in cooling the planet and influences interactions between the atmosphere and ocean, including oceanic evaporation. We found that precipitation varies so much year to year. In some years, precipitation can take away from sea level or lessen the impact of the ice discharged from the sheets.”

Using satellite observations and climate data, the researchers analyzed the relationship between the ocean surface, atmosphere and Antarctic ice sheet’s mass. Their findings highlighted that during periods of reduced sea ice, the atmosphere retained more moisture. This moisture, when reaching the colder ice sheet boundaries, condenses, leading to increased snowfall.

The findings, researchers said, suggest that as global temperatures inch upwards and Antarctica warms, shrinking sea ice levels will amplify oceanic evaporation and consequent precipitation over Antarctica. This increased snowfall can momentarily stave off rising sea levels. However, sea levels will still rise overall.

“With global warming, there’s an expectation of reduced sea ice,” Trusel said. “As sea ice diminishes, there could be increased evaporation from the ocean leading to more precipitation over Antarctica. While this might appear to offset the loss of sea ice, the implications are multifaceted. Increased snowfall in Antarctica might slow the sea level rise, but it’s essential to recognize that the ice sheet will continue to contribute to rising sea levels.”

The scientists identified a feedback loop between sea ice and atmospheric water vapor. A more ice-free ocean surface intensifies evaporation, contributing to increased atmospheric water vapor. This enhanced moisture causes a locally amplified greenhouse effect, resulting in heightened downward longwave radiation, which subsequently reduces sea ice the next month.

Kromer highlighted recent satellite data, which indicates notable changes in the patterns of sea ice.

“While Arctic sea ice has been rapidly declining over the satellite record, the Antarctic experienced a slight increase until 2015, followed by a sharp decline in 2016,” Kromer said. “In 2022, we witnessed a new record low, and this year’s levels are even lower, significantly below previous observations. These recent rapid changes in Antarctic sea ice highlight the urgency of understanding their causes and their potential impact on the Antarctic ice sheet.”

The team’s findings emphasize the need for refining current climate models to enhance their predictive accuracy, the scientists said.

“If we aim to project future sea level changes with precision, it’s essential to enhance our models, particularly in representing sea ice dynamics,” Trusel said.

The NASA Cryospheric Sciences Program supported this work.

In April, the Super Pressure Balloon Imaging Telescope (SuperBIT) was launched from Wānaka Airport, New Zealand, suspended under a helium-filled balloon the size of a sports stadium on top of the Earth’s atmosphere, and floated around the world 5.5 times. Unfortunately, it was damaged on landing in southern Argentina the following month.

Separately, two Data Recovery System packages storing more than 200 gigabytes of SuperBIT’s information descended by parachute and landed safely, including a map of dark matter around galaxies and stunning photos of space. Dark matter is an invisible substance that has a mass six times greater than regular matter in the universe.

A study led by Dr Ellen Sirks from the University of Sydney’s School of Physics, published today in the journal Aerospace, provides instructions to build the Data Recovery System she designed, and recounts the mission that demonstrated, for a relatively small cost, scientists can ensure the information they gather can be salvaged in the worst-case scenario.

The authors of the study, comprised of a team of international scientists from Australia, the United Kingdom, the United States, Canada, Europe and Taiwan, said that the first use of the Data Recovery System capsules during a live science mission proved a huge success.

“Our telescope got to the point where it was completely destroyed, and we lost high bandwidth communications, so not only did the Data Recovery System work; it was really quite essential to the mission’s success,” Dr Sirks said.

“When you’re dropping something from the sky, in our case from 33 kilometres, there’s always a chance that something goes wrong, so recovery packages are quite essential to keep your data safe.

“This drop package is something we’ve been developing for about five years, but only now have we been able to test it in its final configuration. It’s got to the point where NASA wants to start producing these packages for other science missions as well, so this was really our final test to show that this system works.”

Dr Sirks said Data Recovery Systems are comprised of small computers with SD cards to store the data, a home-made “find my phone” satellite link, and parachutes — housed in foam enclosures using everyday objects such as chicken roasting bags to keep them waterproof.

The story of recovering the packages itself was a mission. Dr Sirks said the local police in the Argentinian countryside helped retrieve the packages, given the rough terrain where they landed.

“We couldn’t find one at first and when we did, there were cougar tracks in the snow near it, so we thought maybe the chicken roast bag was not the best idea. It was quite funny. But we did retrieve them quite easily,” Dr Sirks said.

In a typical balloon-based mission like NASA’s, data is downloaded by satellite, but Dr Sirks said scientists often need line-of-sight communication to download the data quickly, which isn’t always efficient or possible.

Balloon-based observations also provide the quality of space telescopes at a fraction of the budget — millions of dollars compared to billions.

“In our case, we were getting so much data per night that it would just be incredibly slow and expensive to retrieve this data mid-flight,” Dr Sirks said.

“At the moment, the most efficient way for us to download data is to copy it onto an SD drive and just drop it to Earth which is kind of crazy, but it works well.”