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.