The findings, published in Nature, show that cancer cells can adapt when they don’t have access to glucose. Researchers have previously identified other nutrients that serve as fuel sources for pancreatic cancer; this study adds uridine to the catalog.

Pancreatic tumors have few functioning blood vessels and can’t easily access nutrients that come from the bloodstream, like glucose. Costas Lyssiotis, Ph.D., Maisel Research Professor of Oncology and lead investigator of the study, explained that without the right nutrients, the cancer cells get hungry. “We know they still grow, obviously, but what are they using to grow?” he said. “These findings show that, under certain circumstances, uridine is one of those fuels.”

Asked about impact, Zeribe Nwosu, Ph.D., one of the co-first authors in the study, says “the ability of cancer to switch to alternative nutrients has fascinated me for a long time. Blocking such compensatory switches could lead us to new treatments and that’s the door we hope this study will open.”

Uridine is present in the tumor microenvironment, but its exact source, and how cancer cells access it, remains a mystery. “Part of the picture is it’s in the bloodstream, but we don’t know where it’s coming from specifically,” said Lyssiotis. “Likely, it’s coming from multiple places, and so far we haven’t been able to pin it to a single source.”

Events that Lyssiotis refers to as “times of crisis” — when cells don’t have enough nutrients, because of limited blood access and/or intense competition between cells — could be a clue as to why, and where, cells turn to uridine. “The cancer cells seem to be sensing the concentrations of glucose and uridine in the local environment to inform their adaptation,” says Matt Ward, another co-first author. Lyssiotis’ team recognize this unknown regulatory process, as well as a cancer-promoting mutation in the KRAS gene, which is common in pancreatic cancer, as two ways that cancer cells control their usage of uridine.

Lyssiotis and his team have been working on this research for nearly a decade alongside their collaborators in the Sadanandam lab at the Institute for Cancer Research in London. They used a technology that screens hundreds of different nutrients to see which ones support pancreatic cancer growth. Typically, researchers look at standard nutrients like sugar, protein and fat, but Lyssiotis’s team took an unbiased approach. “We used a large panel with over 20 pancreatic cell lines and around 200 different nutrients to assess different ways pancreatic cancer cells grow,” he explained. “What do they actually metabolize? This method led us to discover uridine.”

This method offers therapeutic insight, too. The findings showed that uridine is metabolized by the enzyme uridine phoshorylase-1, or UPP1. Blocking UPP1 had a major impact on the growth of pancreatic tumors in mice, findings that suggest the importance of testing drugs that block uridine as possible new treatment options.

“There’s potential to better understand and treat pancreatic cancer with new drug targets and new therapeutic approaches,” said Sadanandam, co-author on the study.

More research is needed to determine the best way to move this discovery to the clinic.

In current lithium-ion batteries, the main problem lies in the liquid electrolyte. This key battery component transfers charge-carrying particles called ions between the battery’s two electrodes, causing the battery to charge and discharge. But the liquid begins to freeze at sub-zero temperatures. This condition severely limits the effectiveness of charging electric vehicles in cold regions and seasons.

To address that problem, a team of scientists from the U.S. Department of Energy’s (DOE) Argonne and Lawrence Berkeley national laboratories developed a fluorine-containing electrolyte that performs well even in sub-zero temperatures.

“Our team not only found an antifreeze electrolyte whose charging performance does not decline at minus 4 degrees Fahrenheit, but we also discovered, at the atomic level, what makes it so effective,” said Zhengcheng “John” Zhang, a senior chemist and group leader in Argonne’s Chemical Sciences and Engineering division.

This low-temperature electrolyte shows promise of working for batteries in electric vehicles, as well as in energy storage for electric grids and consumer electronics like computers and phones.

In today’s lithium-ion batteries, the electrolyte is a mixture of a widely available salt (lithium hexafluorophosphate) and carbonate solvents such as ethylene carbonate. The solvents dissolve the salt to form a liquid.

When a battery is charged, the liquid electrolyte shuttles lithium ions from the cathode (a lithium-containing oxide) to the anode (graphite). These ions migrate out of the cathode, then pass through the electrolyte on the way into the anode. While being transported through the electrolyte, they sit at the center of clusters of four or five solvent molecules.

During the initial few charges, these clusters strike the anode surface and form a protective layer called the solid-electrolyte interphase. Once formed, this layer acts like a filter. It allows only the lithium ions to pass through the layer while blocking the solvent molecules. In this way, the anode is able to store lithium atoms in the structure of the graphite on charge. Upon discharge, electrochemical reactions release electrons from the lithium that generate electricity that can power vehicles.

The problem is that in cold temperatures, the electrolyte with carbonate solvents begins to freeze. As a result, it loses the ability to transport lithium ions into the anode on charge. This is because the lithium ions are so tightly bound within the solvent clusters. Hence, these ions require much higher energy to evacuate their clusters and penetrate the interface layer than at room temperature. For that reason, scientists have been searching for a better solvent.

The team investigated several fluorine-containing solvents. They were able to identify the composition that had the lowest energy barrier for releasing lithium ions from the clusters at sub-zero temperature. They also determined at the atomic scale why that particular composition worked so well. It depended on the position of the fluorine atoms within each solvent molecule and their number.

In testing with laboratory cells, the team’s fluorinated electrolyte retained stable energy storage capacity for 400 charge-discharge cycles at minus 4 F. Even at that sub-zero temperature, the capacity was equivalent to that of a cell with a conventional carbonate-based electrolyte at room temperature.

“Our research thus demonstrated how to tailor the atomic structure of electrolyte solvents to design new electrolytes for sub-zero temperatures,” Zhang said.

The antifreeze electrolyte has a bonus property. It is much safer than the carbonate-based electrolytes that are currently used, since it will not catch fire.

“We are patenting our low-temperature and safer electrolyte and are now searching for an industrial partner to adapt it to one of their designs for lithium-ion batteries,” Zhang said.

This research appears in Advanced Energy Materials. In addition to John Zhang, Argonne authors are Dong-Joo Yoo, Qian Liu and Minkyu Kim. Berkeley Lab authors are Orion Cohen and Kristin Persson.

This work was funded by the DOE Office of Energy Efficiency and Renewable Energy, Vehicle Technologies Office.

While environmental factors such as pesticide exposure have long been linked to Parkinson’s, it has been harder to pinpoint which pesticides may raise risk for the neurodegenerative disorder. Just in California, the nation’s largest agricultural producer and exporter, there are nearly 14,000 pesticide products with over 1,000 active ingredients registered for use.

Through a novel pairing of epidemiology and toxicity screening that leveraged California’s extensive pesticide use database, UCLA and Harvard researchers were able to identify 10 pesticides that were directly toxic to dopaminergic neurons. The neurons play a key role in voluntary movement, and the death of these neurons is a hallmark of Parkinson’s.

Further, the researchers found that co-exposure of pesticides that are typically used in combinations in cotton farming were more toxic than any single pesticide in that group.

For this study, published May 16 in Nature Communications, UCLA researchers examined exposure history going back decades for 288 pesticides among Central Valley patients with Parkinson’s disease who had participated in previous studies. The researchers were able to determine long-term exposure for each person and then, using what they labeled a pesticide-wide association analysis, tested each pesticide individually for association with Parkinson’s. From this untargeted screen, researchers identified 53 pesticides that appeared to be implicated in Parkinson’s — most of which had not been previously studied for a potential link and are still in use.

Those results were shared for lab analysis led by Richard Krolewski, MD, PhD, an instructor of neurology at Harvard and neurologist at Brigham and Women’s Hospital. He tested the toxicity for most of those pesticides in dopaminergic neurons that had been derived from Parkinson’s patients through what’s known as induced pluripotent stem cells, which are a type of “blank slate” cell that can be reprogrammed into neurons that closely resemble those lost in Parkinson’s disease.

The 10 pesticides identified as directly toxic to these neurons included: four insecticides (dicofol, endosulfan, naled, propargite), three herbicides (diquat, endothall, trifluralin), and three fungicides (copper sulfate [basic and pentahydrate] and folpet). Most of the pesticides are still in use today in the United States.

Aside from their toxicity in dopaminergic neurons, there is little that unifies these pesticides. They have a range of use types, are structurally distinct, and do not share a prior toxicity classification.

Researchers also tested the toxicity of multiple pesticides that are commonly applied in cotton fields around the same time, according to California’s pesticide database. Combinations involving trifluralin, one of the most commonly used herbicides in California, produced the most toxicity. Previous research in the Agricultural Health Study, a large research project involving pesticide applicators,had also implicated trifluralin in Parkinson’s.

Kimberly Paul, PhD, a lead author and assistant professor of neurology at UCLA, said the study demonstrated their approach could broadly screen for pesticides implicated in Parkinson’s and better understand the strength of these associations.

“We were able to implicate individual agents more than any other study has before, and it was done in a completely agnostic manner,” Paul said. “When you bring together this type of agnostic screening with a field-to-bench paradigm, you can pinpoint pesticides that look like they’re quite important in the disease.”

The researchers are next planning to study epigenetic and metabolomic features related to exposure using integrative omics to help describe which biologic pathways are disrupted among Parkinson’s patients who experienced pesticide exposure. More detailed mechanistic studies of the specific neuronal processes impacted by pesticides such as trifluralin and copper are also underway at the Harvard/Brigham and Women’s labs. The lab work is focused on distinct effects on dopamine neurons and cortical neurons, which are important for the movement and cognitive symptoms in Parkinson’s patients, respectively. The basic science is also expanding to studies of pesticides on non-neuronal cells in the brain — the glia — to better understand how pesticides influence the function of these critical cells.

Other authors include Edinson Lucumi Moreno, Jack Blank, Kristina M. Holton, Tim Ahfeldt, Melissa Furlong, Yu Yu, Myles Cockburn, Laura K. Thompson, Alexander Kreymerman, Elisabeth M. Ricci-Blair, Yu Jun Li, Heer B. Patel, Richard T Lee, Jeff Bronstein, Lee L. Rubin, Vikram Khurana, and Beate Ritz.

Melanin, the pigment that gives humans their skin, eye, and hair colour, is the body’s first and best natural defense against the sun’s harmful rays. Cosmetics companies have long tried to harness the protective powers of natural and synthetic melanin for use in chemical sunscreens and other personal care products. For example, melanin could, in theory, be used to produce a radiation barrier that augments skin care products by matching a more diverse range of natural skin tones. But melanin is so notoriously unstable and difficult to study that, thus far, scientists have not been able to see what it looks like at the molecular level, resulting in a slow, trial-and-error approach to its potential use in personal care products.

“As we gain a better understanding of the structure of melanin, we should be able to predictably make alternatives that perform better than what is currently available,” said Jean-Philip Lumb, one of the lead authors of the paper. The study found that the melanin component converted light into heat from all wavelengths, spanning the ultraviolet to the infrared, offering a broad spectrum of protection. The molecule was also remarkably small, which the researchers say has practical benefits because the number of atoms needed to provide this level of sun protection is fewer than anything reported up to now. “We’ve taken a major step forward in understanding a new mechanism for how melanin can serve as a sunscreen,” Lumb said.

The significance of the study lies in its potential to revolutionise conservation efforts. Instead of focusing solely on population numbers and reproductive success, the research explores the quality of life experienced by wild animals.

This shift in perspective could provide crucial early warning signals about species challenges and population declines, leading to more effective conservation strategies.

“While research on the welfare of domestic and farm animals has been considerable, including indicators of emotional states such as stress, pain and fear, my aim is to bridge the gap by examining the individual lives, feelings and mental experiences of wild animals,” Dr Harvey said.

“A deeper understanding of the wellbeing of wild animal populations can not only enhance conservation efforts, but also provide an indication of the state of the natural environment and its recognised links to human health and wellbeing.”

The study, which was part of Andrea’s PhD research at the UTS Centre for Compassionate Conservation, focuses on brumbies — free-roaming wild horses — from Australia’s alpine regions, however the framework is widely applicable for evaluating many wildlife species.

Dr Harvey chose brumbies as horse welfare has been studied in domestic environments, providing a bridge to wild animals. The paper, Mental Experiences in Wild Animals: Scientifically Validating Measurable Welfare Indicators in Free-Roaming Horses, was recently published in Animals.

Her comprehensive conceptual framework, called the ’10 Stage Protocol’, includes physical and behavioural indicators for both negative and positive mental experiences in wild animals.

“If you have a dog, you know their usual routine, what they like, and how they behave in certain circumstances. You know if they’re happy, sad, or distressed, so this research is shifting that understanding to wild animals.

“We can never be certain what’s going through an animal’s mind and exactly what they’re feeling. It’s also an area that scientists have traditionally shied away from. However, we know mental experiences arise from physical states, and we can directly measure these states.

“Nutrition, the physical environment, health, and behavioural interactions all provide clues to the mental experience of animals. This includes negative states such as thirst, hunger, heat and cold discomfort, pain, fatigue, anxiety and fear and positive ones such as satiety, exercising agency, physical vitality and positive social interactions.”

This holistic approach brings together different areas of scientific knowledge, including neuroscience, behaviour, and neuroethology — the study of the neural basis of an animal’s natural behaviour — to interpret the data collected and gain insights into wellbeing.

Dr Harvey is currently collaborating with researchers studying Australian water birds, such as the straw-necked ibis and pelicans. These birds serve as indicators of water quality and wetland health, which could inform management decisions in the Murray Darling Basin.

The welfare of koalas, which have been declared endangered in NSW, is also under scrutiny. Previous koala research has focused primarily on survival and disease. Dr Harvey’s research aims to evaluate overall koala wellbeing to inform policy decisions around conservation and habitat protection.

Dr Harvey is also working with other researchers studying the welfare of kangaroos and dingoes at a field station in southern Queensland, focusing on the predator-prey relationship, and the impact of climate change and drought recovery.

Each species presents unique challenges, such as identifying individuals, evaluating mental experiences in large populations, and considering different environments and habitats.

Dr Harvey acknowledges the challenges of studying the mental experiences of wild animals compared to domesticated ones. The absence of close human relationships with individual animals and the difficulty in observing them for extended periods pose significant hurdles.

However, innovative methods like remote camera traps have proven valuable in collecting fine-detail data on wild animal behaviour, including body posture and facial expressions.

Dr Harvey’s ground-breaking research holds immense potential in transforming the field of conservation biology, by shedding light on the mental experiences of wild and endangered animals.

“Welfare assessments need to be part of all wildlife monitoring, and ultimately all environmental policy decision making, which needs to take into account not just individual species, but also interactions between different species, and their ecosystems.”

This is partly because the mathematics in this field is highly complicated. At the same time, it is tough to perform suitable experiments: One would have to create situations in which phenomena of both the relativity theory play an important role, for example, a spacetime curved by heavy masses, and at the same time, quantum effects become visible, for example the dual particle and wave nature of light.

At the TU Wien in Vienna, Austria, a new approach has now been developed for this purpose: A so-called “quantum simulator” is used to get to the bottom of such questions: Instead of directly investigating the system of interest (namely quantum particles in curved spacetime), one creates a “model system” from which one can then learn something about the system of actual interest by analogy. The researchers have now shown that this quantum simulator works excellently. The findings of this international collaboration involving physicists from the University of Crete, Nanyang Technological University, and FU Berlin are now published in the scientific journal Proceedings of the National Academy of Sciences of the USA (PNAS).

Learning from one system about another

The basic idea behind the quantum simulator is simple: Many physical systems are similar. Even if they are entirely different kinds of particles or physical systems on different scales that, at first glance, have little to do with each other, these systems may obey the same laws and equations at a deeper level. This means one can learn something about a particular system by studying another.

“We take a quantum system that we know we can control and adjust very well in experiments,” says Prof. Jörg Schmiedmayer of the Atomic Institute at TU Wien. “In our case, these are ultracold atomic clouds held and manipulated by an atom chip with electromagnetic fields.” Suppose you properly adjust these atomic clouds so that their properties can be translated into another quantum system. In that case, you can learn something about the other system from the measurement of the atomic cloud model system — much like you can learn something about the oscillation of a pendulum from the oscillation of a mass attached to a metal spring: They are two different physical systems, but one can be translated into the other.

The gravitational lensing effect

“We have now been able to show that we can produce effects in this way that can be used to resemble the curvature of spacetime,” says Mohammadamin Tajik of the Vienna Center for Quantum Science and Technology (VCQ) — TU Wien, first author of the current paper. In the vacuum, light propagates along a so-called “light cone.” The speed of light is constant; at equal times, the light travels the same distance in each direction. However, if the light is influenced by heavy masses, such as the sun’s gravitation, these light cones are bent. The light’s paths are no longer perfectly straight in curved spacetimes. This is called “gravitational lens effect.”

The same can now be shown in atomic clouds. Instead of the speed of light, one examines the speed of sound. “Now we have a system in which there is an effect that corresponds to spacetime curvature or gravitational lensing, but at the same time, it is a quantum system that you can describe with quantum field theories,” says Mohammadamin Tajik. “With this, we have a completely new tool to study the connection between relativity and quantum theory.”

A model system for quantum gravity

The experiments show that the shape of light cones, lensing effects, reflections, and other phenomena can be demonstrated in these atomic clouds precisely as expected in relativistic cosmic systems. This is not only interesting for generating new data for basic theoretical research — solid-state physics and the search for new materials also encounter questions that have a similar structure and can therefore be answered by such experiments.

“We now want to control these atomic clouds better to determine even more far-reaching data. For example, interactions between the particles can still be changed in a very targeted way,” explains Jörg Schmiedmayer. In this way, the quantum simulator can recreate physical situations that are so complicated that they cannot be calculated even with supercomputers.

The quantum simulator thus becomes a new, additional source of information for quantum research — in addition to theoretical calculations, computer simulations, and direct experiments. When studying the atomic clouds, the research team hopes to come across new phenomena that may have been entirely unknown up to now, which also take place on a cosmic, relativistic scale — but without a look at tiny particles, they might never have been discovered.