. Scientific Frontline

Thursday, September 1, 2022

Scientists discover surprise anticancer properties of common lab molecule

Nobel laureate Dr. Aziz Sancar at an event in 2016.
Photo credit: Jon Gardiner/UNC-Chapel Hill

Scientists at the UNC School of Medicine have made the surprising discovery that a molecule called EdU, which is commonly used in laboratory experiments to label DNA, is in fact recognized by human cells as DNA damage, triggering a runaway process of DNA repair that is eventually fatal to affected cells, including cancer cells.

The discovery, published in the Proceedings of the National Academy of Sciences, points to the possibility of using EdU as the basis for a cancer treatment, given its toxicity and its selectivity for cells that divide fast.

“The unexpected properties of EdU suggest it would be worthwhile to conduct further studies of its potential, particularly against brain cancers,” said study senior author Dr. Aziz Sancar, the Sarah Graham Kenan Professor of Biochemistry and Biophysics at the UNC School of Medicine and member of the UNC Lineberger Comprehensive Cancer Center. “We want to stress that this is a basic but important scientific discovery. The scientific community has much work ahead to figure out if EdU could actually become a weapon against cancer.”

EdU (5-ethynyl-2′-deoxyuridine) is essentially a popular scientific tool first synthesized in 2008 as an analog, or chemical mimic, of the DNA building block thymidine – which represents the letter “T” in the DNA code of adenine (A), cytosine (C), guanine (G) and thymine (T). Scientists add EdU to cells in lab experiments to replace the thymidine in DNA. Unlike other thymidine analogs, it has a convenient chemical “handle” to which fluorescent probe molecules will bond tightly. It thus can be used relatively easily and efficiently to label and track DNA, for example in studies of the DNA replication process during cell division.

Soaking up the sun with artificial intelligence

Machine learning methods are being developed at Argonne to advance solar energy research with perovskites.
Credit: Maria Chan/ Argonne National Laboratory

The sun continuously transmits trillions of watts of energy to the Earth. It will be doing so for billions more years. Yet, we have only just begun tapping into that abundant, renewable source of energy at affordable cost.

Solar absorbers are a material used to convert this energy into heat or electricity. Maria Chan, a scientist in the U.S. Department of Energy’s (DOE) Argonne National Laboratory, has developed a machine learning method for screening many thousands of compounds as solar absorbers. Her co-author on this project was Arun Mannodi-Kanakkithodi, a former Argonne postdoc who is now an assistant professor at Purdue University.

“We are truly in a new era of applying AI and high-performance computing to materials discovery.” — Maria Chan, scientist, Center for Nanoscale Materials

“According to a recent DOE study, by 2035, solar energy could power 40% of the nation’s electricity,” said Chan. ​“And it could help with decarbonizing the grid and provide many new jobs.”

Corals pass mutations acquired during their lifetimes to offspring

The Elkhorn coral, Acropora palmata, grows into large stands via polyp budding and fragmentation so that many colonies belong to the same clone or genet. During growth, mutations can accumulate in its cells and new research shows that the Ekhorn coral is able to pass these mutations onto to their sexual offspring. This is unlike most animals that prevent such a transfer from the body to reproductive cells.
 Credit: Ilian Baums / Penn State. Creative Commons

In a discovery that challenges over a century of evolutionary conventional wisdom, corals have been shown to pass somatic mutations — changes to the DNA sequence that occur in non-reproductive cells — to their offspring. The finding, by an international team of scientists led by Penn State biologists, demonstrates a potential new route for the generation of genetic diversity, which is the raw material for evolutionary adaptation, and could be vital for allowing endangered corals to adapt to rapidly changing environmental conditions.

“For a trait, such as growth rate, to evolve, the genetic basis of that trait must be passed from generation to generation,” said Iliana Baums, professor of biology at Penn State and leader of the research team. “For most animals, a new genetic mutation can only contribute to evolutionary change if it occurs in a germline or reproductive cell, for example in an egg or sperm cell. Mutations that occur in the rest of the body, in the somatic cells, were thought to be evolutionarily irrelevant because they do not get passed on to offspring. However, corals appear to have a way around this barrier that seems to allow them to break this evolutionary rule.”

Since the time of Darwin, our understanding of evolution has become ever more detailed. We now know that an organism’s traits are heavily determined by the sequence of their DNA. Individuals in a population vary in their DNA sequence, and this genetic variation can lead to the variation in traits, such as body size, that could give an individual a reproductive advantage. Only rarely does a new genetic mutation occur that gives an individual such a reproductive advantage and evolution can only proceed further if — and this is the key — the individual can pass the change to its offspring.

Cannabis users no less likely to be motivated or able to enjoy life’s pleasure

Credit: RODNAE Productions

Cannabis users also show no difference in motivation for rewards, pleasure taken from rewards, or the brain’s response when seeking rewards, compared to non-users.

Cannabis is the third most commonly used controlled substance worldwide, after alcohol and nicotine. A 2018 report from the NHS Digital Lifestyles Team stated that almost one in five (19%) of 15-year-olds in England had used cannabis in the previous 12 months, while in 2020 the National Institute on Drug Abuse reported the proportion in the United States to be 28% of 15-16-year-olds.

A common stereotype of cannabis users is the ‘stoner’ – think Jesse Pinkman in Breaking Bad, The Dude in The Big Lebowski, or, more recently, Argyle in Stranger Things. These are individuals who are generally depicted as lazy and apathetic.

At the same time, there has been considerable concern of the potential impact of cannabis use on the developing brain and that using cannabis during adolescence might have a damaging effect at an important time in an individual’s life.

A team led by scientists at UCL, the University of Cambridge and the Institute of Psychiatry, Psychology & Neuroscience at King’s College London carried out a study examining whether cannabis users show higher levels of apathy (loss of motivation) and anhedonia (loss of interest in or pleasure from rewards) when compared to controls and whether they were less willing to exert physical effort to receive a reward. The research was part of the CannTEEN study.

Global fish stocks can’t rebuild if nothing is done to halt climate change and overfishing

Photo by Hiroko Yoshii on Unsplash

Global fish stocks will not be able to recover to sustainable levels without strong actions to mitigate climate change, a new study has projected.

Researchers at UBC, the Stanford Center for Ocean Solutions and University of Bern projected the impact that different global temperature increases and ranges of fishing activity would have on biomass, or the amount of fish by weight in a given area, from 1950 to 2100. Their simulations suggest that climate change has reduced fish stocks in 103 of 226 marine regions studied, including Canada, from their historical levels. These stocks will struggle to rebuild their numbers under projected global warming levels in the 21st century.

“More conservation-oriented fisheries management is essential to rebuild over-exploited fish stocks under climate change. However, that alone is not enough,” says lead author Dr. William Cheung, professor in the Institute for the Oceans and Fisheries (IOF). “Climate mitigation is important for our fish stock rebuilding plans to be effective”

The research team, including co- author Dr. Colette Wabnitz of Stanford Centre for Ocean Solutions, used computer models to find out the climate change levels at which over-exploited fish stocks cannot rebuild. Currently, the world is on track to exceed 1.5 degrees of warming relative to preindustrial levels and approach two degrees in the next few decades, says Dr. Cheung.

Wednesday, August 31, 2022

Study finds tiny brain area controls work for rewards

The lateral habenula in the mouse brain, with axons streaming down to dopaminergic and serotonergic centers. Credit: Warden Lab

A tiny but important area in the middle of the brain acts as a switch that determines when an animal is willing to work for a reward and when it stops working, according to a study published Aug. 31 in the journal Current Biology.

“The study changes how we think about this particular brain region,” said senior author Melissa Warden, assistant professor and Miriam M. Salpeter Fellow in the Department of Neurobiology and Behavior, which is shared between the College of Arts and Sciences and the College of Agriculture and Life Sciences.

“It has implications for psychiatric disorders, particularly depression and anxiety,” Warden said.

The paper, “Tonic Activity in Lateral Habenula Neurons Acts as a Neutral Valence Brake on Reward-Seeking Behavior,” illuminates the role of the lateral habenula, a small structure on top of the thalamus, which funnels higher-level information from the front and center of the brain to areas that produce neurotransmitters such as serotonin and dopamine.

The lateral habenula’s exact role has been unclear until now. The new study shows that when neurons in this brain area turn off, an animal will work for rewards; when those neurons fire, the animal becomes disengaged and stops working. Experiments revealed that the lateral habenula turns on specifically when an animal has had enough of a reward and is satisfied, or when it finds its work no longer yields a reward.

Signs of Saturation Emerge from Particle Collisions at RHIC

Brookhaven Lab physicists Xiaoxuan Chu and Elke-Caroline Aschenauer at the STAR detector of the Relativistic Heavy Ion Collider (RHIC).
Source/Credit: Brookhaven National Laboratory

Nuclear physicists studying particle collisions at the Relativistic Heavy Ion Collider (RHIC)—a U.S. Department of Energy Office of Science user facility at DOE’s Brookhaven National Laboratory—have new evidence that particles called gluons reach a steady “saturated” state inside the speeding ions. The evidence is suppression of back-to-back pairs of particles emerging from collisions between protons and heavier ions (the nuclei of atoms), as tracked by RHIC’s STAR detector. In a paper just published in Physical Review Letters, the STAR collaboration shows that the bigger the nucleus the proton collides with, the larger the suppression in this key signature, as predicted by theoretical models of gluon saturation.

“We varied the species of the colliding ion beam because theorists predicted that this sign of saturation would be easier to observe in heavier nuclei,” explained Brookhaven Lab physicist Xiaoxuan Chu, a member of the STAR collaboration who led the analysis. “The good thing is RHIC, the world’s most flexible collider, can accelerate different species of ion beams. In our analysis, we used collisions of protons with other protons, aluminum, and gold.”

Peering Into Mirror Nuclei

Diagram showing a high-energy electron scattering from a correlated nucleon in the mirror nuclei tritium (left) and helium-3 (right). The electron exchanges a virtual photon with one of the two correlated nucleons, knocking it out of the nucleus and allowing its energetic partner to escape. Both nuclei have neutron-proton pairs, while tritium has an additional neutron pair and helium-3 has an additional proton pair.
Credit: Jenny Nuss/Berkeley Lab

The atomic nucleus is a busy place. Its constituent protons and neutrons occasionally collide, and briefly fly apart with high momentum before snapping back together like the two ends of a stretched rubber band. Using a new technique, physicists studying these energetic collisions in light nuclei found something surprising: protons collide with their fellow protons and neutrons with their fellow neutrons more often than expected.

The discovery was made by an international team of scientists that includes researchers from the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab), using the Continuous Electron Beam Accelerator Facility at DOE’s Thomas Jefferson National Accelerator Facility (Jefferson Lab) in Virginia. It was reported in a paper published today in the journal Nature.

Understanding these collisions is important for interpreting data in a wide range of physics experiments studying elementary particles. It will also help physicists better understand the structure of neutron stars – collapsed cores of giant stars that are among the densest forms of matter in the universe.

John Arrington, a Berkeley Lab scientist, is one of four spokespersons for the collaboration, and Shujie Li, the lead author on the paper, is a Berkeley Lab postdoc. Both are in Berkeley Lab’s Nuclear Science Division.

"Greener" Fertilizer and Carbon-free Fuels Come Closer to Reality

Photo by Richard Bell on Unsplash

A little over 100 years ago, humankind learned how to take nitrogen from the atmosphere (where it is plentiful) and turn it into ammonia that can be used as source of fertilizer for growing food. That chemical process, known as nitrogen fixation, has allowed huge increases in crop production and a subsequent boom in human populations fed by those crops.

Nearly all artificial nitrogen fixation is done with what is known as the Haber–Bosch process, which uses a metal catalyst to combine gaseous nitrogen and hydrogen into ammonia, at high pressures and temperatures. Ammonia fixed through this process is estimated to be responsible for growing crops that feed half the world's population.

But there is another large source of nitrogen fixation: bacteria that live in soil, which fix nitrogen at normal atmospheric temperatures and pressures. In recent decades, researchers searching for sustainable agriculture practices have looked to these microbes as inspiration for developing nitrogen-fixation processes that are easier to conduct and more environmentally friendly than the energy-intensive Haber-Bosch process. Now, a team at Caltech led by Jonas Peters, Bren Professor of Chemistry and director of the Resnick Sustainability Institute, has made a breakthrough that increases the efficiency of one of these low-temperature and low-pressure processes, further opening the door to greener fertilizer, and even the production of zero-carbon fuels.

Climate change and ocean oxygen

Oxygen-deficient zones (in red) shrank during long warm periods in the past, contrary to widespread expectations.   
Image Credit: Alexandra Auderset, Princeton and MPIC

In the last 50 years, oxygen-deficient zones in the open ocean have increased. Scientists have attributed this development to rising global temperatures: Less oxygen dissolves in warmer water, and the tropical ocean’s layers can become more stratified.

But now, contrary to widespread expectations, an international team of scientists led by researchers from the Max Planck Institute for Chemistry and Princeton University has discovered that oxygen-deficient zones shrank during long warm periods in the past.

“We had not expected such a clear effect,” said Alexandra Auderset, first author of the new paper in the journal Nature and currently a visiting postdoctoral research fellow at Princeton University. She led the study with Alfredo Martínez-García at the Max Planck Institute for Chemistry in Mainz, as part of a long-term collaboration with Daniel Sigman’s group at Princeton University.

Understanding these changes is important because “when oxygen becomes scarce, life has a harder time,” said Sigman, Dusenbury Professor of Geological and Geophysical Sciences. For example, in low-oxygen regions of the eastern Pacific and northern Indian Ocean, only specialized microbes and organisms with a slow metabolism — such as jellyfish — can survive.

Featured Article

Discovery of unexpected collagen structure could ‘reshape biomedical research’

Jeffrey Hartgerink is a professor of chemistry and bioengineering at Rice. Photo Credit: Courtesy of Jeffrey Hartgerink / Rice University Co...

Top Viewed Articles