In their study, which initially published in an unedited version on March 28, 2024, in Nature, the chemists showed that their new methods can be used to perform two modifications — called dehydrogenations and lactonizations — on a broad class of inexpensive starting compounds. The reactions require only a simple copper-based catalyst, whereas related reactions typically require much more cumbersome and expensive methods — though this specific type of reaction was previously inaccessible by any organic synthesis method.

“This new two-mode approach could be particularly useful for late-stage modifications and diversifications of natural products and drug molecules,” says study senior author Jin-Quan Yu, PhD, Frank and Bertha Hupp Professor of Chemistry and Bristol Myers Squibb Endowed Chair in Chemistry at Scripps Research.

The study’s first authors were postdoctoral research associate Shupeng Zhou, PhD, and doctoral student Annabel Zhang, PhD, both of the Yu lab during the study.

The initial goal of the research was to find a new and better method for what chemists call carbon-hydrogen (CH) activation, in which a hydrogen atom on the carbon backbone of an organic compound is detached and replaced with something else — a valuable tool for drug synthesis.

In this case, the Yu lab — which has a history of innovations in CH activation chemistry — sought a better way to do CH activations that replace the hydrogen with an oxygen atom. This is a common transformation in the construction or modification of biologically active molecules, though chemists haven’t had laboratory methods for doing it that are as simple, direct and broadly useful as they would like.

Yu and his team looked to nature for inspiration, in particular to cytochrome P450 enzymes, which are found in most living organisms, and help clear potentially toxic molecules in the human liver. Cytochrome P450 enzymes perform oxygen-for-hydrogen reactions very efficiently. Some of these enzymes have the additional ability to catalyze a different hydrogen-removal process called dehydrogenation, which can be used to strip hydrogens from two carbons simultaneously, allowing other atoms — or clusters of atoms — to replace them. The chemists set themselves the ambitious goal of finding a general organic synthesis method for doing either the oxygenation or dehydrogenation reaction, as these versatile “bimodal” enzymes do in living cells.

After months of experimentation, Yu’s team found that, through chemical transformations similar to those done by the bimodal cytochrome P450 enzymes, they could efficiently make compounds called unsaturated primary amides — a class that includes many drug molecules — by dehydrogenating inexpensive starting compounds called methoxyamides. For the catalyst, they needed only copper fluoride — also inexpensive and easy to use.

As the chemists explored the breadth of their new dehydrogenation method using different specific starting compounds, they observed trace amounts of a type of molecule called a lactone, indicating that an oxygenation reaction had occurred. Ultimately, they were able to determine the reaction conditions that favored this oxygenation or “lactonization” over the dehydrogenation. In other words, like the bimodal enzymes that had inspired them, they were able to control whether their approach led down one reaction path or the other.

The team demonstrated the remarkable versatility of this set of reactions by using it to modify — via dehydrogenation or lactonization, or both — a wide variety of starting compounds, including the neurological drug valproic acid and the cholesterol-lowering drug gemfibrozil. (Modifications of existing complex molecules to create potentially better variants are a common drug discovery and optimization technique.)

Yu and his group are currently developing a similar approach for making and modifying lactone- and amide-related compounds called lactams, which include some antibiotics.

“We’ve already had a lot of interest in this new approach from pharma industry chemists,” Yu says.

“Copper-catalyzed dehydrogenation or lactonization of C(sp3)−H bonds” was co-authored by Shupeng Zhou, Zi-Jun Zhang and Jin-Quan Yu.

Support for the research was provided by the National Institutes of Health (2R01GM084019).

Scientists have performed a new, more sensitive measurement of beta decay properties to hunt for a theorized feature of the weak nuclear force not currently included in the Standard Model. The weak nuclear force drives the process of nuclear beta decay. In beta decay, a proton or neutron in a nucleus emits a beta particle (an electron or its anti-particle, a positron) and a neutrino. The properties of the beta decays of the radioactive mirror nuclei lithium-8 and boron-8 are in perfect agreement with the predictions of the Standard Model. This effort combines state-of-the-art experimental and theoretical methods and paves the way for future advances in the study of the weak nuclear force.

A team of nuclear scientists from Lawrence Livermore National Laboratory, Argonne National Laboratory, and Louisiana State University precisely measured the beta-decay properties of the “mirror” nuclei lithium-8 and boron-8 to better understand the weak nuclear force. Mirror nuclei have the same total number of protons and neutrons, but the numbers of each particle are reversed. Mirror nuclei provide an opportunity to study the weak nuclear force with increased sensitivity. The predicted signature of many of the sought-after new effects would give rise to opposite contributions in the two different nuclei. This would allow scientists to compare the lithium-8 and boron-8 results to isolate the contributions to the decay from each nucleus.

By studying both these nuclei with the Beta-decay Paul Trap, a device that holds clouds of ions in vacuum, the researchers determined the energies and directions of the emitted beta particle and two alpha particles with high precision. This approach allowed the researchers to reconstruct the full decay properties, including the contribution from the unseen neutrino. The Standard Model (SM) predicts the distribution of emission angles for the beta particle and neutrino, and any observed difference would reveal new aspects of the weak nuclear force. The team was looking for differences smaller than 1%, which required a thorough understanding of the apparatus and detection system, paired with a newly developed first-principle approach using “Symmetry-Adapted No-Core Shell Model theory” to account for a number of small effects that arise from the complicated environment of the nucleus. The results were the highest precision of their kind and confirmed the SM prediction with increased confidence.

“The goal of this innovative insole technology is to mitigate the risk of diabetic foot ulcers by addressing one of their most significant causes: skin and soft tissue breakdown due to repetitive stress on the foot during walking,” said Muthu B.J. Wijesundara, principal research scientist at The University of Texas at Arlington Research Institute (UTARI).

Affecting about 39 million people in the U.S., diabetes can damage the small blood vessels that supply blood to the nerves, leading to poor circulation and foot sores, also called ulcers. About one-third of people with diabetes develop foot ulcers during their lifetime. In the U.S., more than 160,000 lower extremity amputations are performed annually due to complications from diabetic foot ulcers, costing the American health system about $30 billion a year. Those who have foot ulcers often die at younger ages than those without ulcers.

“Although many shoe insoles have been created over the years to try to alleviate the problem of foot ulcers, studies have shown that their success in preventing them is marginal,” Wijesundara said. “We took the research a step further by creating a pressure-alternating shoe insole that works by cyclically relieving pressure from different areas of the foot, thereby providing periods of rest to the soft tissues and improving blood flow. This approach aims to maintain the health of the skin and tissues, thereby reducing the risk of diabetic foot ulcers.”

In an article in the peer-reviewed International Journal of Lower Extremity Wounds, Wijesundara and UTA colleagues Veysel Erel, Aida Nasirian and Yixin Gu, along with Larry Lavery of UT Southwestern Medical Center, described their innovative insole technology. After this successful pilot project, the next step for the research team will be refining the technology to make it more accessible for users with varying weights and shoe sizes.

“Considering the impact of foot ulcers, it’s exciting that we may be able to make a real difference in the lives of so many people,” Wijesundara said.

This work was supported by a $229,480 grant from the National Institute of Aging of the National Institutes of Health, grant number 7R21AG061471.

But a study by University of Rhode Island researchers has found direct evidence of a species — the American woodcock, a migratory shorebird from eastern and central North America — that overlaps periods of migration and reproduction, a rare breeding strategy known as “itinerant breeding.” Their work, backed by collaborators across the East Coast, was published today in the biological sciences journal Proceedings of the Royal Society B.

“I think this is a very exciting moment for bird researchers,” said Colby Slezak, a URI Ph.D. student in biological and environmental sciences who led the study. “It’s interesting to see that these distinct periods in a bird’s annual cycle are not so cut and dried. We often think of migration, breeding, fall migration and wintering as separate events. But woodcock are combining two of these into one period, which is interesting because both are so energetically expensive.”

“Each year the period of migration is distinct from the period of breeding in the vast majority of migratory birds, presumably because doing so at the same time is simply too costly,” said Scott McWilliams, URI professor in natural resources science and principal investigator on the study. “This paper provides the best documented case of a migratory bird that is an itinerant breeder. Such itinerant breeding is exceptionally rare, and documenting exceptions often proves the rules of nature.”

The American woodcock — also called a timberdoodle, bogsucker, night partridge, and Labrador twister, among many more — is a migratory shorebird that occurs throughout eastern and central North America but its populations have been declining over the past half century. The species is known for its long, needlelike bill that can extract earthworms from deep in the ground and the males’ elaborate mating dance and “peent” call to attract females, Slezak said.

While there are about a dozen bird species in the world believed to be itinerant breeders, the study is the first to show direct evidence of the rare strategy. “They’ve suspected other species of being itinerant breeders, but this is the first time we’ve had detailed GPS-tracking data and on-the-ground verification of nests to confirm that this was happening.” said Slezak, of Broadalbin, New York.

To do that, the study benefitted from the work of scores of biologists from federal, state and non-governmental agencies along the American woodcock’s flyway, from the southern U.S. into Canada, who tagged more than 350 females with GPS transmitters between 2019 and 2022. That initiative was part of the University of Maine’s Eastern Woodcock Migration Research Cooperative.

Slezak, whose work on the study was part of his dissertation research, organized and analyzed the tracking data and alerted collaborators along the bird’s range to verify possible nesting locations. URI graduate students Liam Corcoran, Megan Gray and Shannon Wesson also worked on other aspects of the woodcock project, all part of a collaborative research program with biologists from the Rhode Island Department of Environmental Management Division of Fish & Wildlife.

“I was looking for really short movement patterns during the breeding season to find suspected nests,” Slezak said. “Relying on all of these collaborators from across the East Coast, I would reach out to them to tell them there was a suspected nest. They would travel out to the sites, sometimes quite far. It was amazing that we got the buy-in that we did.”

Based on GPS tracking of more than 200 females, the URI study found that more than 80% of the tagged females nested more than once during migration — some up to six times. During northward migration, females traveled an average of 800 kilometers between first and second nests, and shorter distances between subsequent nests, the study said. During 2021-22, URI researchers oversaw onsite verification of 26 nests from 22 females. Four females nested more than once, three of which migrated a substantial distance northward after their first nest attempt, the study said.

“There are many records of woodcock males singing along their migration routes, which has always been a mystery because it’s energetically expensive,” said Slezak. “With this new data on females, we’re seeing that females are also nesting in the south early, moving north and nesting as they go. So, these males are probably getting breeding opportunities along the way.”

While migration and reproduction take a lot of energy, American woodcock reduce the cost in other ways, Slezak said. They have shorter migration distances than other species and have the flexibility of using various young-forest habitats. Also, females are larger than males and their eggs are small relative to the size of the females.

“A lot of birds probably can’t do it because they don’t have these lower reproductive costs that woodcock have evolved to do,” he said.

Another evolutionary driver of itinerant breeding in woodcock could be predation. While they use a variety of habitats — wetlands, young forests with different tree types — they often nest near edges of open fields, leaving them prone to numerous predators.

“We think most of these post-nesting migratory movements are in response to predation events,” he said. “They’re sitting on the nest and something comes and eats the eggs. The female takes off and keeps migrating north before trying to nest again. What we don’t know is: if the female has a successful nest, does she stop nesting the rest of the year?”

Despite steady declines in woodcock populations and their preferred young forest habitat over the last half century, the study offers a glimmer of hope for woodcock, and other itinerant breeders facing the challenges of ongoing human development and climate change.

“Itinerant breeders may be more flexible in their response to environmental change because they are willing to breed in a wide variety of places,” said Slezak. “So as long as some suitable habitat remains, the consequences may be less.”

Interference among photons, a fundamental phenomenon in quantum optics, serves as a cornerstone of optical quantum computing. It involves harnessing the properties of light, such as its wave-particle duality, to induce interference patterns, enabling the encoding and processing of quantum information.

In traditional multi-photon experiments, spatial encoding is commonly employed, wherein photons are manipulated in different spatial paths to induce interference. These experiments require intricate setups with numerous components, making them resource-intensive and challenging to scale. In contrast, the international team, comprising scientists from University of Vienna, Politecnico di Milano, and Université libre de Bruxells, opted for an approach based on temporal encoding. This technique manipulates the time domain of photons rather than their spatial statistics. To realize this approach, they developed an innovative architecture at the Christian Doppler Laboratory at the University of Vienna, utilizing an optical fiber loop. This design enables repeated use of the same optical components, facilitating efficient multi-photon interference with minimal physical resources.

First author Lorenzo Carosini explains: “In our experiment, we observed quantum interference among up to eight photons, surpassing the scale of most of existing experiments. Thanks to the versatility of our approach, the interference pattern can be reconfigured and the size of the experiment can be scaled, without changing the optical setup.” The results demonstrate the significant resource efficiency of the implemented architecture compared to traditional spatial-encoding approaches, paving the way for more accessible and scalable quantum technologies.

Anqa is located just across the Syrian border from Dura-Europos, in the present-day Al-Qaim district of the Anbar Governorate in Iraq. Its remains include an identifying tell mound, at the northern end of the site, a polygonal inner wall circuit, and a large outer defensive wall, or enceinte. Situated at a point where the Euphrates floodplain drastically narrows, the city would have controlled movement between the populous section of the valley upstream and the trade route downstream linking Syria, Northern Mesopotamia, and Babylonia, giving it great strategic and economic significance. However, the site was ignored entirely by archaeologists until the 1850 publication of a British Middle Euphrates expedition survey. A more thorough study of the site was performed in the late 1930s by Aurel Stein, including aerial photographs of the standing structures, but even after these forays, there was little desire to learn more than the geographical location of this twin city to Dura-Europos.

One reason for the disparity in interest between Anqa and Dura-Europos, posits article author Simon James, is the history of British and French colonial intervention in the region. In 1920, as a result of the San Remo conference, Iraq was seized for British control, and Syria for French. As James writes, the “new political, military, and administrative boundary created a barrier to research and understanding of the earlier history of the region as a whole.” Yet while Dura-Europos and some other sites in Iraq and Syria have suffered from looting, destruction, and civilian death as a consequence of conflict in the region, Anqa has remained relatively untouched. As further archaeological inquiry is performed, Anqa may continue to provide valuable insight into the history of the Middle Euphrates. And furthermore, as methods of digital scholarship bring thinkers together “despite political borders,” the practice of studying sites like it may even, in the words of Simon James, help “address the consequences of colonialism in archaeology.”

The study offers the first experimental evidence that chemicals present as additives in microplastics can leach into human sweat, and then be absorbed through the skin, into the bloodstream.

Many chemicals used as flame retardants and plasticisers have already been banned, due to evidence of adverse health effects including damage to the liver or nervous system, cancer, and risks to reproductive health. However, these chemicals are still present in the environment in older electronics, furniture, carpets, and building materials.

While the harm caused by microplastics is not fully understood, there is increasing concern over their role as conduits of human exposure to toxic chemicals.

The research team demonstrated in a study published last year, that chemicals were leached from microplastics into human sweat. The current study now shows that those chemicals can also be absorbed from sweat across the skin barrier into the body.

In their experiments, the team used innovative 3D human skin models as alternatives to laboratory animals and excised human tissues. The models were exposed over a 24-hour period to two common forms of microplastics containing polybrominated diphenyl ethers (PBDEs), a chemical group commonly used to flame retard plastics.

The results, published in Environment International, showed that as much as 8% of the chemical exposed could be taken up by the skin, with more hydrated — or ‘sweatier’ — skin absorbing higher levels of chemical. The study provides the first experimental evidence into how this process contributes to levels of toxic chemicals found in the body.

Dr Ovokeroye Abafe, now at Brunel University, carried out the research while at the University of Birmingham. He said: “Microplastics are everywhere in the environment and yet we still know relatively little about the health problems that they can cause. Our research shows that they play a role as ‘carriers’ of harmful chemicals, which can get into our bloodstream through the skin. These chemicals are persistent, so with continuous or regular exposure to them, there will be a gradual accumulation to the point where they start to cause harm.”

Dr Mohamed Abdallah, Associate Professor of Environmental Sciences at the University of Birmingham, and principal investigator for the project, said: “These findings provide important evidence for regulators and policymakers to improve legislation around microplastics and safeguard public health against harmful exposure.”

Professor Stuart Harrad, co-author of the paper, added “the study provides an important step forward in understanding the risks of exposure to microplastics on our health. Building on our results, more research is required to fully understand the different pathways of human exposure to microplastics and how to mitigate the risk from such exposure.”

In future research, the team plan to investigate other routes through which microplastics could be responsible for toxic chemicals entering the body, including inhalation and ingestion. The work is funded by a Marie Curie Research Fellowship, within the European Union’s Horizon 2020 Research and Innovation Programme.

A new study published in the journal Nature Geoscience led by scientists at University of Miami Rosenstiel School of Marine, Atmospheric, and Earth Science, and the National Oceanic and Atmospheric Administration’s Atlantic Oceanographic and Meteorological Laboratory, found that human-induced environmental changes around Antarctica are contributing to sea level rise in the North Atlantic.

The research team analyzed two decades of deep sea oceanographic data collected by observational mooring programs to show that a critical piece of Earth’s global system of ocean currents in the North Atlantic has weakened by about 12 percent over the past two decades.

“Although these regions are tens of thousands of miles away from each other and abyssal areas are a few miles below the ocean surface, our results reinforce the notion that even the most remote areas of the world’s oceans are not untouched by human activity,” said the study’s lead author Tiago Biló, an assistant scientist at the Rosenstiel School’s NOAA Cooperative Institute for Marine and Atmospheric Studies.

As part of the NOAA-funded project DeepT (Innovative analysis of deep and abyssal temperatures from bottom-moored instrument), the scientists analyzed data from several observational programs to study changes over time in a cold, dense, and deep water mass located at depths greater than 4,000 meters (2.5 miles) below the ocean surface that flow from the Southern Ocean northward and eventually upwells to shallower depths in other parts of the global ocean such as the North Atlantic.

This shrinking deep-ocean branch — that scientists call the abyssal limb — is part of the Atlantic Meridional Overturning Circulation (AMOC), a three-dimensional system of ocean currents that act as a “conveyer belt” to distribute heat, nutrients, and carbon dioxide across the world’s oceans.

This near-bottom branch is comprised of Antarctic bottom water, which forms from the cooling of seawater in the Southern Ocean around Antarctica during winter months. Among the different formation mechanisms of this bottom water, perhaps the most important is the so-called brine rejection, a process that occurs when salty water freezes. As sea ice forms, it releases salt into the surrounding water, increasing its density. This dense water sinks to the ocean floor, creating a cold, dense water layer that spreads northward to fill all three ocean basins — the Indian, Pacific, and Atlantic oceans. During the 21^st century, the researchers observed that the flow of this Antarctic layer across 16°N latitude in the Atlantic had slowed down, reducing the inflow of cold waters to higher latitudes, and leading to warming of waters in the deep ocean.

“The areas affected by this warming spans thousands of miles in the north-south and east-west directions between 4,000- and 6,000-meters of depth,” said William Johns, a co-author and professor of ocean sciences at the Rosenstiel School. “As a result, there is a significant increase in the abyssal ocean heat content, contributing to local sea level rise due to the thermal expansion of the water.”

“Our observational analysis matches what the numerical models have predicted — human activity could potentially impose circulation changes on the entire ocean,” said Biló. “This analysis was only possible because of the decades of collective planning and efforts by multiple oceanographic institutions worldwide.”