“We have only a good record of the deep ocean for the last ~180 million years,” said David Fike, the Glassberg/Greensfelder Distinguished University Professor of Earth, Environmental, and Planetary Sciences in Arts & Sciences at Washington University in St. Louis. “Everything else is just shallow-water deposits. So it’s really important to understand the bias that might be present when we look at shallow-water deposits.”

One of the ways that scientists like Fike use deposits from the seafloor is to reconstruct timelines of past ecological and environmental change. Researchers are keenly interested in how and when oxygen began to build up in the oceans and atmosphere, making Earth more hospitable to life as we know it.

For decades they have relied on pyrite, the iron-sulfide mineral known as “fool’s gold,” as a sensitive recorder of conditions in the marine environment where it is formed. By measuring the bulk isotopic composition of sulfur in pyrite samples — the relative abundance of sulfur atoms with slightly different mass — scientists have tried to better understand ancient microbial activity and interpret global chemical cycles.

But the outlook for pyrite is not so shiny anymore. In a pair of companion papers published Nov. 24 in the journal Science, Fike and his collaborators show that variations in pyrite sulfur isotopes may not represent the global processes that have made them such popular targets of analysis.

Instead, Fike’s research demonstrates that pyrite responds predominantly to local processes that should not be taken as representative of the whole ocean. A new microanalysis approach developed at Washington University helped the researchers to separate out signals in pyrite that reveal the relative influence of microbes and that of local climate.

For the first study, Fike worked with Roger Bryant, who completed his graduate studies at Washington University, to examine the grain-level distribution of pyrite sulfur isotope compositions in a sample of recent glacial-interglacial sediments. They developed and used a cutting-edge analytical technique with the secondary-ion mass spectrometer (SIMS) in Fike’s laboratory.

“We analyzed every individual pyrite crystal that we could find and got isotopic values for each one,” Fike said. By considering the distribution of results from individual grains, rather than the average (or bulk) results, the scientists showed that it is possible to tease apart the role of the physical properties of the depositional environment, like the sedimentation rate and the porosity of the sediments, from the microbial activity in the seabed.

“We found that even when bulk pyrite sulfur isotopes changed a lot between glacials and interglacials, the minima of our single grain pyrite distributions remained broadly constant,” Bryant said. “This told us that microbial activity did not drive the changes in bulk pyrite sulfur isotopes and refuted one of our major hypotheses.”

“Using this framework, we’re able to go in and look at the separate roles of microbes and sediments in driving the signals,” Fike said. “That to me represents a huge step forward in being able to interpret what is recorded in these signals.”

In the second paper, led by Itay Halevy of the Weizmann Institute of Science and co-authored by Fike and Bryant, the scientists developed and explored a computer model of marine sediments, complete with mathematical representations of the microorganisms that degrade organic matter and turn sulfate into sulfide and the processes that trap that sulfide in pyrite.

“We found that variations in the isotopic composition of pyrite are mostly a function of the depositional environment in which the pyrite formed,” Halevy said. The new model shows that a range of parameters of the sedimentary environment affect the balance between sulfate and sulfide consumption and resupply, and that this balance is the major determinant of the sulfur isotope composition of pyrite.

“The rate of sediment deposition on the seafloor, the proportion of organic matter in that sediment, the proportion of reactive iron particles, the density of packing of the sediment as it settles to the seafloor — all of these properties affect the isotopic composition of pyrite in ways that we can now understand,” he said.

Importantly, none of these properties of the sedimentary environment are strongly linked to the global sulfur cycle, to the oxidation state of the global ocean, or essentially any other property that researchers have traditionally used pyrite sulfur isotopes to reconstruct, the scientists said.

“The really exciting aspect of this new work is that it gives us a predictive model for how we think other pyrite records should behave,” Fike said. “For example, if we can interpret other records — and better understand that they are driven by things like local changes in sedimentation, rather than global parameters about ocean oxygen state or microbial activity — then we can try to use this data to refine our understanding of sea level change in the past.”

“The noise is greatly suppressed compared to ordinary wires,” said Rice’s Douglas Natelson, the study’s corresponding author. “Maybe this is evidence that quasiparticles are not well-defined things or that they’re just not there and charge moves in more complicated ways. We have to find the right vocabulary to talk about how charge can move collectively.”

The experiments were performed on nanoscale wires of a quantum critical material with a precise 1-2-2 ratio of ytterbium, rhodium and silicon (YbRh2Si2), which has been studied in great depth during the past two decades by Silke Paschen, a solid-state physicist at the Vienna University of Technology (TU Wien). The material contains a high degree of quantum entanglement that produces a very unusual (“strange”) temperature-dependent behavior that is very different from the one in normal metals such as silver or gold.

In such normal metals, each quasiparticle, or discrete unit, of charge is the product of incalculable tiny interactions between countless electrons. First put forward 67 years ago, the quasiparticle is a concept physicists use to represent the combined effect of those interactions as a single quantum object for the purposes of quantum mechanical calculations.

Some prior theoretical studies have suggested that the charge in a strange metal might not be carried by such quasiparticles, and shot noise experiments allowed Natelson, study lead author Liyang Chen, a former student in Natelson’s lab, and other Rice and TU Wien co-authors to gather the first direct empirical evidence to test the idea.

“The shot noise measurement is basically a way of seeing how granular the charge is as it goes through something,” Natelson said. “The idea is that if I’m driving a current, it consists of a bunch of discrete charge carriers. Those arrive at an average rate, but sometimes they happen to be closer together in time, and sometimes they’re farther apart.”

Applying the technique in YbRh2Si2 crystals presented significant technical challenges. Shot noise experiments cannot be performed on single macroscopic crystals but, rather, require samples of nanoscopic dimensions. Thus, the growth of extremely thin but nevertheless perfectly crystalline films had to be achieved, something that Paschen, Maxwell Andrews and their collaborators at TU Wien managed after almost a decade of hard work. Next, Chen had to find a way to maintain that level of perfection while fashioning wires from these thin films that were about 5,000 times narrower than a human hair.

Rice co-author Qimiao Si, the lead theorist on the study and the Harry C. and Olga K. Wiess Professor of Physics and Astronomy, said he, Natelson and Paschen first discussed the idea for the experiments while Paschen was a visiting scholar at Rice in 2016. Si said the results are consistent with a theory of quantum criticality he published in 2001 that he has continued to explore in a nearly two-decade collaboration with Paschen.

“The low shot noise brought about fresh new insights into how the charge-current carriers entwine with the other agents of the quantum criticality that underlies the strange metallicity,” said Si, whose group performed calculations that ruled out the quasiparticle picture. “In this theory of quantum criticality, the electrons are pushed to the verge of localization, and the quasiparticles are lost everywhere on the Fermi surface.”

Natelson said the larger question is whether similar behavior might arise in any or all of the dozens of other compounds that exhibit strange metal behavior.

“Sometimes you kind of feel like nature is telling you something,” Natelson said. “This ‘strange metallicity’ shows up in many different physical systems, despite the fact that the microscopic, underlying physics is very different. In copper-oxide superconductors, for example, the microscopic physics is very, very different than in the heavy-fermion system we’re looking at. They all seem to have this linear-in-temperature resistivity that’s characteristic of strange metals, and you have to wonder is there something generic going on that is independent of whatever the microscopic building blocks are inside them.”

The research was supported by the Department of Energy’s Basic Energy Sciences program (DE-FG02-06ER46337), the National Science Foundation (1704264, 2220603), the European Research Council (101055088), the Austrian Science Fund (FWF I4047, FWF SFB F 86), the Austrian Research Promotion Agency (FFG 2156529, FFG 883941), the European Union’s Horizon 2020 program (824109-EMP), the Air Force Office of Scientific Research (FA8665-22-1-7170), the Welch Foundation (C-1411) and the Vannevar Bush Faculty Fellowship (ONR-VB-N00014-23-1-2870).

The Telescope Array has since observed more than 30 ultra-high-energy cosmic rays, though none approaching the Oh-My-God-level energy. No observations have yet revealed their origin or how they are able to travel to the Earth.

On May 27, 2021, the Telescope Array experiment detected the second-highest extreme-energy cosmic ray. At 2.4 x 10²⁰eV, the energy of this single subatomic particle is equivalent to dropping a brick on your toe from waist height. Led by the University of Utah (the U) and the University of Tokyo, the Telescope Array consists of 507 surface detector stations arranged in a square grid that covers 700 km² (~270 miles²) outside of Delta, Utah in the state’s West Desert. The event triggered 23 detectors at the north-west region of the Telescope Array, splashing across 48 km² (18.5 mi²). Its arrival direction appeared to be from the Local Void, an empty area of space bordering the Milky Way galaxy.

“The particles are so high energy, they shouldn’t be affected by galactic and extra-galactic magnetic fields. You should be able to point to where they come from in the sky,” said John Matthews, Telescope Array co-spokesperson at the U and co-author of the study. “But in the case of the Oh-My-God particle and this new particle, you trace its trajectory to its source and there’s nothing high energy enough to have produced it. That’s the mystery of this — what the heck is going on?”

In their observation that published on Nov. 24, 2023, in the journal Science, an international collaboration of researchers describe the ultra-high-energy cosmic ray, evaluate its characteristics, and conclude that the rare phenomena might follow particle physics unknown to science. The researchers named it the Amaterasu particle after the sun goddess in Japanese mythology. The Oh-My-God and the Amaterasu particles were detected using different observation techniques, confirming that while rare, these ultra-high energy events are real.

“These events seem like they’re coming from completely different places in the sky. It’s not like there’s one mysterious source,” said John Belz, professor at the U and co-author of the study. “It could be defects in the structure of spacetime, colliding cosmic strings. I mean, I’m just spit-balling crazy ideas that people are coming up with because there’s not a conventional explanation.”

Natural particle accelerators

Cosmic rays are echoes of violent celestial events that have stripped matter to its subatomic structures and hurled it through universe at nearly the speed of light. Essentially cosmic rays are charged particles with a wide range of energies consisting of positive protons, negative electrons, or entire atomic nuclei that travel through space and rain down onto Earth nearly constantly.

Cosmic rays hit Earth’s upper atmosphere and blasts apart the nucleus of oxygen and nitrogen gas, generating many secondary particles. These travel a short distance in the atmosphere and repeat the process, building a shower of billions of secondary particles that scatter to the surface. The footprint of this secondary shower is massive and requires that detectors cover an area as large as the Telescope Array. The surface detectors utilize a suite of instrumentation that gives researchers information about each cosmic ray; the timing of the signal shows its trajectory and the amount of charged particles hitting each detector reveals the primary particle’s energy.

Because particles have a charge, their flight path resembles a ball in a pinball machine as they zigzag against the electromagnetic fields through the cosmic microwave background. It’s nearly impossible to trace the trajectory of most cosmic rays, which lie on the low- to middle-end of the energy spectrum. Even high-energy cosmic rays are distorted by the microwave background. Particles with Oh-My-God and Amaterasuenergy blast through intergalactic space relatively unbent. Only the most powerful of celestial events can produce them.

“Things that people think of as energetic, like supernova, are nowhere near energetic enough for this. You need huge amounts of energy, really high magnetic fields to confine the particle while it gets accelerated,” said Matthews.

Ultra-high-energy cosmic rays must exceed 5 x 10¹⁹ eV. This means that a single subatomic particle carries the same kinetic energy as a major league pitcher’s fast ball and has tens of millions of times more energy than any human-made particle accelerator can achieve. Astrophysicists calculated this theoretical limit, known as the Greisen-Zatsepin-Kuzmin (GZK) cutoff, as the maximum energy a proton can hold traveling over long distances before the effect of interactions of the microwave background radiation take their energy. Known source candidates, such as active galactic nuclei or black holes with accretion disks emitting particle jets, tend to be more than 160 million light years away from Earth. The new particle’s 2.4 x 10²⁰ eV and the Oh-My-God particle’s 3.2 x 10²⁰ eV easily surpass the cutoff.

Researchers also analyze cosmic ray composition for clues of its origins. A heavier particle, like iron nuclei, are heavier, have more charge and are more susceptible to bending in a magnetic field than a lighter particle made of protons from a hydrogen atom. The new particle is likely a proton. Particle physics dictates that a cosmic ray with energy beyond the GZK cutoff is too powerful for the microwave background to distort its path, but back tracing its trajectory points towards empty space.

“Maybe magnetic fields are stronger than we thought, but that disagrees with other observations that show they’re not strong enough to produce significant curvature at these ten-to-the-twentieth electron volt energies,” said Belz. “It’s a real mystery.”

Expanding the footprint

The Telescope Array is uniquely positioned to detect ultra-high-energy cosmic rays. It sits at about 1,200 m (4,000 ft), the elevation sweet-spot that allows secondary particles maximum development, but before they start to decay. Its location in Utah’s West Desert provides ideal atmospheric conditions in two ways: the dry air is crucial because humidity will absorb the ultraviolet light necessary for detection; and the region’s dark skies are essential, as light pollution will create too much noise and obscure the cosmic rays.

Astrophysicists are still baffled by the mysterious phenomena. The Telescope Array is in the middle of an expansion that that they hope will help crack the case. Once completed, 500 new scintillator detectors will expand the Telescope Array will sample cosmic ray-induced particle showers across 2,900 km² (1,100 mi² ), an area nearly the size of Rhode Island. The larger footprint will hopefully capture more events that will shed light on what’s going on.

The findings, based on research in mice and in human cells, are reported Nov. 22 in Cell. The research adds an important piece to the long-standing puzzle of itch and helps explain why common skin conditions like eczema and atopic dermatitis are often accompanied by persistent itch.

In such conditions, the equilibrium of microorganisms that keep our skin healthy is often thrown off balance, allowing S. aureus to flourish, the researchers said. Up until now, the itch that occurs with eczema and atopic dermatitis was believed to arise from the accompanying inflammation of the skin. But the new findings show that S. aureus single-handedly causes itch by instigating a molecular chain reaction that culminates in the urge to scratch.

“We’ve identified an entirely novel mechanism behind itch — the bacterium Staph aureus, which is found on almost every patient with the chronic condition atopic dermatitis. We show that itch can be caused by the microbe itself,” said senior author Isaac Chiu, associate professor of immunology in the Blavatnik Institute at HMS.

The study experiments showed that S. aureus releases a chemical that activates a protein on the nerve fibers that transmit signals from the skin to the brain. Treating animals with an FDA-approved anti-clotting medicine successfully blocked the activation of the protein to interrupt this key step in the itch-scratch cycle. The treatment relieved symptoms and minimized skin damage.

The findings can inform the design of oral medicines and topical creams to treat persistent itch that occurs with various conditions linked to an imbalance in the skin microbiome, such as atopic dermatitis, prurigo nodularis, and psoriasis.

The repeated scratching that is a hallmark of these conditions can cause skin damage and amplify inflammation.

“Itch can be quite debilitating in patients who suffer from chronic skin conditions. Many of these patients carry on their skin the very microbe we’ve now shown for the first time can induce itch,” said study first author Liwen Deng, a postdoctoral research fellow in the Chiu Lab.

Identifying the molecular spark plug that ignites itch

Researchers exposed the skin of mice to S. aureus. The animals developed intensifying itch over several days, and the repeated scratching caused worsening skin damage that spread beyond the original site of exposure.

Moreover, mice exposed to S. aureus became hypersensitive to innocuous stimuli that would not typically cause itch. The exposed mice were more likely than unexposed mice to develop abnormal itching in response to a light touch.

This hyperactive response, a condition called alloknesis, is common in patients with chronic conditions of the skin characterized by persistent itch. But it can also happen in people without any underlying conditions — think of that scratchy feeling you might get from a wool sweater.

To determine how the bacterium triggered itch, the researchers tested multiple modified versions of the S. aureus microbe that were engineered to lack specific pieces of the bug’s molecular makeup. The team focused on 10 enzymes known to be released by this microbe upon skin contact. One after another, the researchers eliminated nine suspects — showing that a bacterial enzyme called protease V8 was single-handedly responsible for initiating itch in mice. Human skin samples from patients with atopic dermatitis also had more S. aureus and higher V8 levels than healthy skin samples.

The analyses showed that V8 triggers itch by activating a protein called PAR1, which is found on skin neurons that originate in the spinal cord and carry various signals — touch, heat, pain, itch — from the skin to the brain. Normally, PAR1 lies dormant but upon contact with certain enzymes, including V8, it gets activated. The research showed that V8 snips one end of the PAR1 protein and awakens it. Experiments in mice showed that once activated, PAR1 initiates a signal that the brain eventually perceives as itch. When researchers repeated the experiments in lab dishes containing human neurons, they also responded to V8.

Interestingly, various immune cells implicated in skin allergies and classically known to cause itch — mast cells and basophils — did not drive itch after bacterial exposure, the experiments showed. Nor did inflammatory chemicals called interleukins, or white cells, which are activated during allergic reactions and are also known to be elevated in skin diseases and even in certain neurologic disorders.

“When we started the study, it was unclear whether the itch was a result of inflammation or not,” Deng said. “We show that these things can be decoupled, that you don’t necessarily have to have inflammation for the microbe to cause itch, but that the itch exacerbates inflammation on the skin.”

Interrupting the itch-scratch cycle

Because PAR1 — the protein activated by S. aureus — is involved in blood-clotting, researchers wanted to see whether an already approved anticlotting drug that blocks PAR1 would stop itch. It did.

The itchy mice whose skin was exposed to S. aureus experienced rapid improvement when treated with the drug. Their desire to scratch diminished dramatically, as did the skin damage caused by scratching.

Moreover, once treated with PAR1 blockers, the mice no longer experienced abnormal itch in response to innocuous stimuli.

The PAR1 blocker is already used in humans to prevent blood clots and could be repurposed as anti-itch medication. For example, the researchers noted, the active ingredient in the medicine could become the basis for anti-itch topical creams.

One immediate question that the researchers plan to explore in future work is whether other microbes besides S. aureus can trigger itch.

“We know that many microbes, including fungi, viruses, and bacteria, are accompanied by itch but how they cause itch is not clear,” Chiu said.

Beyond that, the findings raise a broader question: Why would a microbe cause itch? Evolutionarily speaking, what’s in it for the bacterium?

One possibility, the researchers said, is that pathogens may hijack itch and other neural reflexes to their advantage. For example, previous research has shown that the TB bacterium directly activates vagal neurons to cause cough, which might enable it to spread more easily from one host to another.

“It’s a speculation at this point, but the itch-scratch cycle could benefit the microbes and enable their spread to distant body sites and to uninfected hosts,” Deng said. “Why do we itch and scratch? Does it help us, or does it help the microbe? That’s something that we could follow up on in the future.”

The work was funded by the National Institutes of Health (grants R01AI168005, R01AI153185, R01NS065926, R01NS102161, R01NS111929, R37AI052453, R01AR076082, U01AI152038, UM1AI151958, R01AI153185, R01JL160582, F32AI172080, T32AI049928, 1R21AG075419), Food Allergy Science Initiative (FASI), Burroughs Wellcome Fund, Drako Family Fund, Jackson-Wijaya Research Fund, Canadian Institutes of Health Research (CIHR) (grants 376560 and 469411), and ANR-PARCURE (PRCE-CE18, 2020).

Chiu serves on the scientific advisory board of GSK Pharmaceuticals. Provisional patent application Serial No. 63/438,668, in which some coauthors are listed as inventors, was filed based on these findings.

The cells, with a size twice the thickness of a strand of hair, have significant advantages over conventional solar technologies, reducing electrode-induced shadowing by 95% and potentially lowering energy production costs by up to three times.

The technological breakthrough — led by Mathieu de Lafontaine, a postdoctoral researcher at the University of Ottawa and a part-time physics professor; and Karin Hinzer, vice-dean, research, and University Research Chair in Photonic Devices for Energy at the Faculty of Engineering — paves the way for a new era of miniaturization in the field of electronic devices.

The micrometric photovoltaic cell manufacturing process involved a partnership between the University of Ottawa, the Université de Sherbrooke in Quebec and the Laboratoire des Technologies de la Microélectronique in Grenoble, France.

“These micrometric photovoltaic cells have remarkable characteristics, including an extremely small size and significantly reduced shadowing. Those properties lend themselves to various applications, from densification of electronic devices to areas such as solar cells, lightweight nuclear batteries for space exploration and miniaturization of devices for telecommunications and the internet of things,” Hinzer says.

A breakthrough with huge potential

“This technological breakthrough promises significant benefits for society. Less expensive, more powerful solar cells will help accelerate the energy shift. Lightweight nuclear batteries will facilitate space exploration, and miniaturization of devices will contribute to the growth of the internet of things and lead to more powerful computers and smartphones,” de Lafontaine says.

“The development of these first back-contact micrometric photovoltaic cells is a crucial step in the miniaturization of electronic devices,” he adds.

“Semiconductors are vital in the shift to a carbon-neutral economy. This project is one of many research initiatives that we’re undertaking at the Faculty of Engineering to achieve our societal goals,” says Hinzer. Semiconductors are included in three of the five research areas at the Faculty of Engineering, namely, information technologies, photonics and emerging materials, and two of the four strategic areas of research at the University of Ottawa, namely, creating a sustainable environment and shaping the digital world.

This international partnership between Canada and France illustrates the importance of innovation and research in micromanufacturing, leading the way to a future in which technology will become more powerful and accessible than ever. It also marks an historic step in the evolution of the global scientific and technology scene.

This initiative was funded by the Natural Sciences and Engineering Research Council of Canada, the Fonds de recherche du Québec Nature et technologies, the Horizon Europe Framework program, Prompt Québec and STACE Inc.

One chemical used in some anti-cancer drugs, for example, costs pharmaceutical companies $3,200 per gram — 50 times more than a gram of gold. The UCLA researchers devised an inexpensive way to produce this drug molecule from a chemical costing just $3 per gram. They were also able to apply the process to produce many other chemicals used in medicine and agriculture for a fraction of the usual cost.

This feat, published in the journal Science, involves a process known as “aminodealkenylation.” Using oxygen as a reagent and copper as a catalyst to break the carbon-carbon bonds of many different organic molecules, the researchers replaced these bonds with carbon-nitrogen bonds, converting the molecules into derivatives of ammonia called amines.

Because amines interact strongly with molecules in living plants and animals, they are widely used in pharmaceuticals, as well as in agricultural chemicals. Familiar amines include nicotine, cocaine, morphine and amphetamine, and neurotransmitters like dopamine. Fertilizers, herbicides and pesticides also contain amines.

Industrial production of amines is therefore of great interest, but the raw materials and reagents are often expensive, and the processes can require many complicated steps to complete. Using fewer steps and no expensive ingredients, the process developed at UCLA can produce valuable chemicals at a much lower cost than current methods.

“This has never been done before,” Kwon said. “Traditional metal catalysis uses expensive metals such as platinum, silver, gold and palladium, and other precious metals such as rhodium, ruthenium and iridium. But we are using oxygen and copper, one of the world’s most abundant base metals.”

The new method uses a form of oxygen called ozone, a potent oxidant, to break the carbon-carbon bond in hydrocarbons called alkenes, and a copper catalyst to couple the broken bond with nitrogen, turning the molecule into an amine. In one example, the researchers produced a c-Jun N-terminal kinase inhibitor — an anti-cancer drug — in just three chemical steps, instead of the 12 or 13 steps previously needed. The cost per gram can thus be reduced from thousands of dollars to just a few dollars.

In another example, the protocol took just one step to convert adenosine — a neurotransmitter and DNA building block that costs less than 10 cents per gram — into the amine N6-methyladenosine. The amine plays crucial roles in controlling gene expression in cellular, developmental and disease processes, and its production cost has previously been $103 per gram.

Kwon’s research group was able to modify hormones, pharmaceutical reagents, peptides and nucleosides into other useful amines, showing the new method’s potential to become a standard production technique in drug manufacturing and many other industries.

The research was funded by the National Institutes of Health.