Scientists serendipitously discover rare cluster compound

Scientists at Kyoto University’s Institute for Cell-Material Sciences have discovered a novel cluster compound that could prove useful as a catalyst. Compounds, called polyoxometalates, contain a large metal-oxide cluster carry a negative charge. They are found everywhere, from anti-viral medicines to rechargeable batteries and flash memory devices.

The new cluster compound is a hydroxy-iodide (HSbOI) and is unusual, as it has large, positively charged clusters. Only a handful of such positively charged cluster compounds have been found and studied.

“In science, the discovery of new material or molecule can create a new science,” says Kyoto University chemist Hiroshi Kageyama. “I believe that these new positively charged clusters have great potential.”

The first metal oxide cluster was discovered in 1826. Chemists have since synthesised hundreds of compounds with negatively charged clusters, which have properties useful in magnetism, catalysis, ionic conduction, biological applications and quantum information. Their properties make them useful in diverse fields from catalysis to medicine and chemical synthesis.

In more recent years, scientists have focused their attention on synthesising compounds with positively charged clusters and learning their properties.

Kageyama and his colleague Ryu Abe found their positive cluster by accident. Since 2016, the two scientists — Kageyama, a solid-state chemist and Abe, a catalytic chemist — have been on a quest to develop new compounds that can absorb visible light for photocatalysis. They were studying a chlorine-containing (Sb4O5Cl2) compound and trying to replace the chlorine atom with iodine.

“However, a new material that was completely different from what we expected was obtained accidentally,” says Kageyama.

What the scientists expected was a material that contains 22 atoms in the unit cell. What they got instead was a compound that contains 800 atoms in its unit cell.

At the beginning, the scientists could not unravel the chemical’s structure. A traditional technique called powder X-ray diffraction failed when faced with the material’s complexity. After a year, Kageyama thought he could use three-dimensional electron tomography, a cutting-edge electron microscopy technique that has attracted recent attention as a tool to image the structure of proteins. The scientists approached Artem Abakumov and Joke Hadermann at University of Antwerp, Belgium, to work on the structure. And when their collaborators sent the data back, the scientists were thrilled to see large clusters.

Further lab work showed the hydroxyiodide molecule contained acidic protons, which is important in catalysis.

“This finding may open up new possibilities in the design of solid-state catalysts,” says Kageyama.

Their work will be published in Science Advances.

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Materials provided by Kyoto University. Note: Content may be edited for style and length.

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Rethinking the rabies vaccine

Rabies virus kills a shocking 59,000 people each year, many of them children. Some victims, especially kids, don’t realize they’ve been exposed until it is too late. For others, the intense rabies treatment regimen is out of the question: treatment is not widely available and the average $3,800 expense poses unthinkable economic burden for most people around the world.

Rabies vaccines, rather than treatments, are much more affordable and easier to administer. But those vaccines also come with a massive downside:

“Rabies vaccines don’t provide lifelong protection. You have to get your pets boosted every year to three years,” says LJI Professor Erica Ollmann Saphire, Ph.D. “Right now, rabies vaccines for humans and domestic animals are made from killed virus. But this inactivation process can cause the molecules to become misshapen — so these vaccines aren’t showing the right form to the immune system. If we made a better shaped, better structured vaccine, would immunity last longer?”

Saphire and her team, in collaboration with a team led by Hervé Bourhy, Ph.D., at the Institut Pasteur, may have discovered the path to better vaccine design. In a new study, published in Science Advances, the researchers share one of the first high-resolution looks at the rabies virus glycoprotein in its vulnerable “trimeric” form.

“The rabies glycoprotein is the only protein that rabies expresses on its surface, which means it is going to be the major target of neutralizing antibodies during an infection,” says LJI Postdoctoral Fellow Heather Callaway, Ph.D., who serves as the study’s first author.

“Rabies is the most lethal virus we know. It is so much a part of our history — we’ve lived with its specter for hundreds of years,” adds Saphire, who also serves as LJI’s President and CEO. “Yet scientists have never observed the organization of its surface molecule. It is important to understand that structure to make more effective vaccines and treatments — and to understand how rabies and other viruses like it enter cells.”

Rabies the shapeshifter

Scientists don’t know exactly why rabies vaccines don’t provide long-term protection, but they do know that its shape-shifting proteins are a problem.

Like a Swiss Army knife, the rabies glycoprotein has sequences that unfold and flip upward when needed. The glycoprotein can shift back and forth between pre-fusion (before fusing with a host cell) and post-fusion forms. It can also fall apart, changing from a trimer structure (where three copies come together in a bundle) to a monomer (one copy by itself).

This shapeshifting gives rabies a kind of invisibility cloak. Human antibodies are built to recognize a single site on a protein. They can’t follow along when a protein transforms to hide or move those sites.

The new study gives scientists a critical picture of the correct glycoprotein form to target for antibody protection.

Capturing the glycoprotein at last

Over the course of three years, Callaway worked to stabilize and freeze the rabies glycoprotein in its trimeric form. This “pre-fusion” form is the shape the glycoprotein takes before it infects human cells.

Callaway paired the glycoprotein with a human antibody, which helped her pinpoint one site where the viral structure is vulnerable to antibody attacks. The researchers then captured a 3D image of the glycoprotein using cutting-edge cryo-electron microscope equipment at LJI.

The new 3D structure highlights several key features researchers hadn’t seen before. Importantly, the structure shows two key pieces of the virus structure, called the fusion peptides, the way they appear in real life. These two sequences link the bottom of the glycoprotein to the viral membrane, but project into the target cell during infection. It is very hard to get a stable image of these sequences. In fact, other rabies researchers have had to cut them off to try to get images of the glycoprotein.

Callaway solved this problem by capturing the rabies glycoprotein in detergent molecules. “That let us see how the fusion sequences are attached before they snap upward during infection,” says Saphire.

Now that scientists have a clear view of this viral structure, they can better design vaccines that tell the body how to make antibodies to target the virus.

“Instead of being exposed to four-plus different protein shapes, your immune system should really just see one — the right one,” says Callaway. “This could lead to a better vaccine.”

Preventing a family of viruses

Saphire hopes stronger, broader immunity could help people in regular contact with animals, such as veterinarians and wildlife workers, as well as the billions of people who may accidentally come in contact with a rabid animal. Rabies is endemic across every continent except Antarctica and infects numerous species including dogs, racoons, bats, and skunks.

This new work may also open the door to a vaccine to protect against the whole lyssavirus genus, which includes rabies and similar viruses that can spread between humans and other mammals.

The next step in this work is to capture more images of rabies virus and its relatives together with neutralizing antibodies. Callaway says scientists are working on solving several of these structures, which could reveal antibody targets that lyssaviruses have in common.

“Because we didn’t have these structures of the rabies virus in this conformational state before, it’s been hard to design a broad-spectrum vaccine,” says Callaway.

Additional authors of the study, “Structure of the rabies virus glycoprotein trimer bound to a pre-fusion specific 4 neutralizing antibody,” include Dawid Zyla, Florence Larrous, Guilherme Dias de Melo, Kathryn M. Hastie, Ruben Diaz Avalos, Alyssa Agarwal and Davide Corti.

This study was supported by the National Institutes of Health (grants 5T32AI07244-36 and 5F32AI147531-03) and a Swiss National Science Foundation Early Postdoc Mobility Fellowship (P2EZP3_195680). A portion of this research was supported by NIH grant U24GM129547 and performed at the 742 PNCC at OHSU and accessed through EMSL (grid.436923.9), a DOE Office of Science User Facility sponsored by the Office of Biological and Environmental Research. Confocal microscopy on the Zeiss LSM 880 was supported by equipment grant NIH 745 S10OD021831.

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Mangrove and reef restoration yield positive returns on investment for flood protection, study shows

A new analysis demonstrates that restoration of mangroves and coral reefs can be a cost-effective solution for coastal flood reduction in more than 20 countries across the Caribbean.

The study, published May 28 in the journal Ecosystem Services, used methods from the risk and insurance industry to provide rigorous valuations of these natural defenses and show that they can deliver a positive return on investment, with the benefits from reduced flood damage exceeding the costs of restoration.

The results point toward new opportunities to support restoration efforts with funds from sources that support hazard mitigation, climate adaptation, and disaster recovery, including the U.S. Federal Emergency Management Agency (FEMA).

“We identify a number of funding sources that have traditionally supported artificial ‘gray infrastructure,’ such as concrete sea walls, and that could be applied to nature-based solutions,” said lead author Michael Beck, a research professor in the Institute of Marine Sciences at UC Santa Cruz who holds the AXA Chair in Coastal Resilience.

Coastal ecosystems such as coral reefs and mangroves act as natural barriers to waves and storm surges and reduce flood damages to people and property. In many places, however, degradation of reefs and coastal wetlands has reduced their natural ability to protect coastlines from flooding and erosion. Effective strategies exist for restoring these critical ecosystems, but funding for restoration projects can be hard to find.

Beck noted that the global spending on disaster recovery is more than 100 times larger than the spending on conservation. “Recovery funding will grow as climate change increases the impacts from storms, and environmental funding will likely shrink as national budgets are strained by natural disasters,” he said.

The study highlights opportunities to align conservation, flood risk reduction, and climate adaptation to reduce storm risks. “Funding for artificial infrastructure such as seawalls can be redirected to natural defenses, which provide multiple benefits beyond coastal protection,” Beck said.

The study’s results for return on investment are robust to changes in discount rates and the timing of flood protection benefits, he added. “This may sound esoteric, but it can be critical to getting funding for restoration projects from sources such as FEMA,” he said.

The researchers identified specific sites where there could be significant returns on investment for coral reef and mangrove restoration across the Caribbean.

In addition to Beck, the coauthors of the paper include Nadine Heck, Siddharth Narayan, Pelayo Menéndez, Borja G. Reguero, and Stephan Bitterwolf at UC Santa Cruz; Saul Torres-Ortega and Iñigo J. Losada at the University of Cantabria, Spain; Glenn-Marie Lange at the World Bank; Kerstin Pfliegner at ERM, Germany; and Valerie Pietsch McNulty at the Nature Conservancy.

This work was supported in part by the Kingfisher Foundation, the World Bank, AXA XL, AXA Research Fund, the Nature Conservancy, and Germany’s Federal Ministry for the Environment, Nature Conservation and Nuclear Safety.

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Materials provided by University of California – Santa Cruz. Original written by Tim Stephens. Note: Content may be edited for style and length.

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Math model predicts efficacy of drug treatments for heart attacks

Researchers used mice to develop a mathematical model of a myocardial infarction, popularly known as a heart attack.

The new model predicts several useful new drug combinations that may one day help treat heart attacks, according to researchers at The Ohio State University.

Typically caused by blockages in the coronary arteries — or the vessels that supply blood to the heart — these cardiovascular events are experienced by more than 800,000 Americans every year, and about 30% end up dying. But even for those who survive, the damage these attacks inflict on the muscles of the heart is permanent and can lead to dangerous inflammation in the affected areas of the heart.

Treatment to restore blood flow to these blocked passages of the heart often includes surgery and drugs, or what’s known as reperfusion therapy. Nicolae Moise, lead author of the study and a postdoctoral researcher in biomedical engineering at Ohio State, said the study uses mathematical algorithms to assess the efficacy of the drugs used to combat the potentially lethal inflammation many patients experience in the aftermath of an attack.

“Biology and medicine are starting to become more mathematical,” Moise said. “There’s so much data that you need to start integrating it into some kind of framework.” While Moise has worked on other mathematical models of animal hearts, he said that the framework detailed in the current paper is the most detailed schematic of myocardial infarctions in mice ever made.

The research is published in the Journal of Theoretical Biology.

Represented by a series of differential equations, the model Moise’s team created was made using data from previous animal studies. In medicine, differential equations are often used to monitor the growth of diseases in graph form.

But this study chose to model how certain immune cells like myocytes, neutrophils and macrophages — cells imperative to fighting infection and combating necrosis (toxic injury to the heart) — react to four different immunomodulatory drugs over a period of one month. These drugs are designed to suppress the immune system so that it doesn’t cause as much damaging inflammation in parts of the heart that were damaged.

This research focused on the drugs’ efficacy an hour after the mice were treated.

Their findings showed that certain combinations of these drug inhibitors were more efficient at reducing inflammation than others. “In medicine, math and equations can be used to describe these systems,” Moise said. “You just need to observe, and you’ll find rules and a coherent story between them.

“With the therapies that we’re investigating in our model, we can make the patient outcome better, even with the best available medical care,” he said.

Depending on their health beforehand, it can take a person anywhere from six to eight months to heal from a heart attack. The quality of care patients receive in those first few weeks could set the tone for how long their road to recovery will be.

Because Moise’s simulation is purely theoretical, it won’t lead to improved therapies anytime soon. More precise mouse data is needed before their work can become an asset to other scientists, but Moise said he does envision the model as a potential tool in the fight against the ravages of heart disease.

“Its going to be some years before we can actually integrate this kind of approach into actual clinical work,” Moise said. “But what we’re doing is the first step towards that.”

The co-author of the study was Avner Friedman, professor of mathematics at Ohio State. This research was supported by Ohio State’s Mathematical Biosciences Institute and the National Science Foundation.

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Materials provided by Ohio State University. Original written by Tatyana Woodall. Note: Content may be edited for style and length.

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Biogas and biomethane supply chains leak twice as much methane as first thought

A new Imperial analysis has found that biogas and biomethane, while more climate friendly, leak more than twice as much methane as previously thought.

Although biogas and biomethane remain climate-friendlier than non-renewable alternatives, the researchers call for better monitoring and fixing of leaks to ensure biogas and biomethane continue to live up to their green credentials.

Biomethane and biogas are produced from the breakdown of organic matter including food, animal waste, energy crops, grass, or sewage sludge, making them renewable alternatives to natural gas, coal and oil. However, researchers at Imperial College London have identified potential pitfalls in energy supply chains for these climate-friendlier gases, concluding that more efforts should be made to reduce methane leakage.

Methane traps around 27 times the amount of heat in the atmosphere as carbon dioxide (CO2) and is responsible for at least a quarter of global warming, according to the Intergovernmental Panel on Climate Change’s AR6 report.

The new Imperial study, published today in One Earth journal, found that supply chains for biomethane and biogas release more than twice as much methane as the International Energy Agency (IEA)’s previous estimation. It also reveals that 62 per cent of these leaks were concentrated in a small number of facilities and pieces of equipment within the chain, which they call ‘super-emitters’, though methane was found to be released at every stage.

The researchers say urgent attention is needed to fix the methane leaks, and knowing precisely where the majority of them are happening will help production plants to do so.

Lead author of the study Dr Semra Bakkaloglu, of Imperial’s Department of Chemical Engineering and Sustainable Gas Institute, said: “Biomethane and biogas are great candidates for renewable and clean energy sources, but they can also emit methane. For them to really help mitigate the warming effects of energy use, we must act urgently to reduce their emissions.

“We want to encourage the continued use of biogas and biomethane as a renewable resource by taking the necessary actions to tackle methane emissions.”

The researchers note that compared to the oil and gas industry, the biomethane industry suffers from poorly designed and managed production facilities as well as a lack of investment for modernisation, operation, and monitoring. Because oil and natural gas supply chains have been primarily operated by large companies with huge resources for decades, they have been able to invest more in leak detection and repair.

What is biomethane and biogas?

In response to the climate crisis, many countries are replacing heavily carbon-emitting sources of energy, like natural gas, coal and oil, with biomethane and biogas.

Although they are made from a mixture of CO2 and methane, biomethane and biogas release less of both gases, making them greener energy alternatives.

However, these replacement fuels still release methane along their supply chains, such as at processing facilities and from long pipelines. This new analysis gives us a more thorough understanding of where, when, and how much methane is released from biomethane and biogas supply.

Analysing emissions

The researchers analysed 51 previously published studies on mobile methane measurements and site data taken from emission sources along the biomethane and biogas supply chain. They analysed the data and calculated the total methane emissions using a statistical model called Monte Carlo. This allowed them to consider all measurements of total supply chain emissions at each stage of the chain, which they then compared with the off-site emissions reported from whole-site measurements in previously published studies.

They found that the supply chains release up to 343 g of CO2-equivalent methane per megajoule higher heating value, which may account for 18.5 megatonnes of methane per year. IEA estimates had reported emissions as just 9.1 megatonnes in 2021.

While overall methane emissions from biogas and biomethane are lower than those from oil and natural gas, the amount of methane released from their supply chains relative to total gas production is much higher than for oil and gas.

The data is reported in ‘CO2 equivalents’ — a unit of measurement used to compare emissions across the oil and natural gas supply chain without interfering with downstream operations. This unit also allows us to compare the global-warming potential of various greenhouse gas emissions from different studies.

The researchers identified the reasons behind the leakiness of supply chains as intermittent emissions patterns, which make them harder to track; insufficient usage of process equipment; and inadequate operations and maintenance strategies. Since super-emitters are unlikely to remain constant over time, the researchers say that continual monitoring is required to detect intermittent emission patterns or unpredictable leaks from supply chains.

Dr Bakkaloglu said: “To prevent biogas methane emissions negating the overall benefits of biogas use, urgent attention is needed including continuous monitoring of biogas supply chains. We believe that with the proper detection, measurement, and repair techniques, all emissions can be avoided.We need better regulations, continuous emission measurements, and close collaboration with biogas plant operators in order to address methane emissions and meet Paris Agreement targets.”

“Given the growth in biomethane due to national decarbonisation strategies, urgent efforts are needed for the biomethane supply chain to address not only methane emissions but also the sustainability of biomethane.”

Co-author Dr Jasmin Cooper, also of the Department of Chemical Engineering, said: “Addressing the fundamental design issues and investment problems within the biofuel and methane industry would be a good starting point for stopping these leaks and preventing more from arising.”

The researchers are now focusing on the super-emitters within supply chains to better understand how to reduce them using the best available technologies.

This study was funded by Imperial’s Sustainable Gas Institute.

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Ed Sheeran tickets cancelled for NHS and emergency staff

Organiser AEG Presents said the Glasgow ticket allocation for NHS and emergency staff was oversold.

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Coeliac patient died days after being fed Weetabix, inquest hears

An 80-year-old coeliac patient was given the cereal in hospital and died four days later.

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Covid infections up after Platinum Jubilee celebrations

The latest UK figures cover the long weekend of partying and suggest one in 45 has Covid.

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England appoints ambassador to shake up women’s health

The aim of the role for England is to help tackle decades of health inequalities.

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‘Long Covid’ risk lower with Omicron, study finds

Last winter’s Omicron variant was less likely to cause lingering symptoms, researchers say.

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