Researcher helps solve 60-year mystery inside heart

One University of Kentucky researcher has helped solve a 60-year-old mystery about one of the body’s most vital organs: The heart.

Kenneth S. Campbell, Ph.D., the director of translational research in the Division of Cardiovascular Medicine in the UK College of Medicine, helped map out an important part of the heart on a molecular level. The study titled “Cryo-EM structure of the human cardiac myosin filament” was published online in the journal Nature earlier this month.

The heart is made up of billions of cells. Each cell contains thousands of smaller structures, called sarcomeres. These are the building blocks of muscle. Within each block, are hundreds of myosin filaments. To put this microscopic level into perspective, if the heart is a continent, Campbell and fellow researchers are looking at single strands of hair.

“Each filament has roughly 2,000 molecules arranged in a really complicated structure that scientists have been trying to understand for decades,” said Campbell. “We knew quite a lot about the individual molecules and people thought the myosins could be arranged in groups of six that were called crowns, but not much beyond that.”

Campbell explained the most interesting discovery in the paper is that there are three different types of crowns. The interactions between them are shown in the second photo below.

“We think this means that heart muscle can be controlled more precisely than we had realized. We were also excited to see how myosin binding protein-C, another protein that is linked to genetic heart disease, sits within the structure. It gives us a new level of information about how the molecules are arranged in the heart,” said Campbell.

Working with researchers at the University of Massachusetts Chan Medical School, the group produced single-particle 3D reconstructions of the cardiac thick filaments. The pictures provide a new framework for interpreting structural, physiological and clinical observations.

“This study is important for discovering new drug therapies for heart disease which Kentucky desperately needs,” said Campbell. “It gives us a much better understanding of how the molecules in our hearts interact.”

Heart disease is the leading cause of death in Kentucky and puts the Commonwealth among the top 10 states with the highest death rate from the disease, according to the Centers for Disease Control and Prevention (CDC).

“We’re interested in therapies for different kinds of heart failure and myopathies, where the heart muscles don’t work very well,” said Campbell. “Our research is one of many projects underway at the university to help come up with better therapies for heart disease.”

The research team collected heart samples from the Gill Cardiovascular Biorepository, of which Campbell is the director. Samples are donated for research purposes from patients who receive cardiovascular care at UK.

“We started the Gill Cardiovascular Biorepository in 2008. With the help of a surgeon at UK HealthCare, we started collecting samples of myocardium from organ donors and from patients who were getting cardiac transplants,” said Campbell. “Now we’ve built a huge resource with roughly 15,000 samples from nearly 500 people.

“We also share these samples with research groups around the world. This study in Nature comes from one of those collaborations.”

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Melting ice falling snow: Sea ice declines enhance snowfall over West Antarctica

As the world continues to warm, Antarctica is losing ice at an increasing pace, but the loss of sea ice may lead to more snowfall over the ice sheets, partially offsetting contributions to sea level rise, according to Penn State scientists.

The researchers analyzed the impacts of decreased sea ice in the Amundsen Sea in West Antarctica and found the ice-free ocean surface leads to more moisture in the atmosphere and heavier snowfalls on the ice sheet, the team reported in the journal Geophysical Research Letters.

While the additional snowfall is not enough to offset the impacts of melting ice, including it in climate models may improve predictions of things like sea level rise, said Luke Trusel, assistant professor of geography at Penn State and co-author of the study.

The Antarctic ice sheet plays a significant role in global sea level dynamics. As one of the world’s largest reservoirs of freshwater, any change in its volume directly impacts sea levels. Trusel noted that while popular attention is often on visible processes like chunks of ice breaking away, or calving, and floating away as icebergs, more subtle interactions — like snowfall on the ice sheet — can be equally significant.

“For a place like Antarctica, which is just massive, the amount of snow falling on top of the ice sheet is as important or even more important than other processes like meltwater or ice breaking off,” Trusel said. “We’re tracking both snowfall and melt to understand both ends of the equation — what takes from sea level and what gets returned to the ocean. We want to know how those factors are impacting the ice sheets.”

The primary source of snowfall in Antarctica is evaporation from the surrounding oceans, with sea ice playing a pivotal role in modulating this process, according to researchers.

“Sea ice is significant,” said Jessica Kromer, a doctoral candidate at Penn State and lead author. “It reflects sunlight, aids in cooling the planet and influences interactions between the atmosphere and ocean, including oceanic evaporation. We found that precipitation varies so much year to year. In some years, precipitation can take away from sea level or lessen the impact of the ice discharged from the sheets.”

Using satellite observations and climate data, the researchers analyzed the relationship between the ocean surface, atmosphere and Antarctic ice sheet’s mass. Their findings highlighted that during periods of reduced sea ice, the atmosphere retained more moisture. This moisture, when reaching the colder ice sheet boundaries, condenses, leading to increased snowfall.

The findings, researchers said, suggest that as global temperatures inch upwards and Antarctica warms, shrinking sea ice levels will amplify oceanic evaporation and consequent precipitation over Antarctica. This increased snowfall can momentarily stave off rising sea levels. However, sea levels will still rise overall.

“With global warming, there’s an expectation of reduced sea ice,” Trusel said. “As sea ice diminishes, there could be increased evaporation from the ocean leading to more precipitation over Antarctica. While this might appear to offset the loss of sea ice, the implications are multifaceted. Increased snowfall in Antarctica might slow the sea level rise, but it’s essential to recognize that the ice sheet will continue to contribute to rising sea levels.”

The scientists identified a feedback loop between sea ice and atmospheric water vapor. A more ice-free ocean surface intensifies evaporation, contributing to increased atmospheric water vapor. This enhanced moisture causes a locally amplified greenhouse effect, resulting in heightened downward longwave radiation, which subsequently reduces sea ice the next month.

Kromer highlighted recent satellite data, which indicates notable changes in the patterns of sea ice.

“While Arctic sea ice has been rapidly declining over the satellite record, the Antarctic experienced a slight increase until 2015, followed by a sharp decline in 2016,” Kromer said. “In 2022, we witnessed a new record low, and this year’s levels are even lower, significantly below previous observations. These recent rapid changes in Antarctic sea ice highlight the urgency of understanding their causes and their potential impact on the Antarctic ice sheet.”

The team’s findings emphasize the need for refining current climate models to enhance their predictive accuracy, the scientists said.

“If we aim to project future sea level changes with precision, it’s essential to enhance our models, particularly in representing sea ice dynamics,” Trusel said.

The NASA Cryospheric Sciences Program supported this work.

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Downloading NASA’s dark matter data from above the clouds

Data from a NASA mission to map dark matter around galaxy clusters has been saved by a new recovery system designed by scientists at the University of Sydney. The system allowed the retrieval of gigabytes of information, even after communication failed and the balloon-based telescope was damaged in the landing process.

In April, the Super Pressure Balloon Imaging Telescope (SuperBIT) was launched from Wānaka Airport, New Zealand, suspended under a helium-filled balloon the size of a sports stadium on top of the Earth’s atmosphere, and floated around the world 5.5 times. Unfortunately, it was damaged on landing in southern Argentina the following month.

Separately, two Data Recovery System packages storing more than 200 gigabytes of SuperBIT’s information descended by parachute and landed safely, including a map of dark matter around galaxies and stunning photos of space. Dark matter is an invisible substance that has a mass six times greater than regular matter in the universe.

A study led by Dr Ellen Sirks from the University of Sydney’s School of Physics, published today in the journal Aerospace, provides instructions to build the Data Recovery System she designed, and recounts the mission that demonstrated, for a relatively small cost, scientists can ensure the information they gather can be salvaged in the worst-case scenario.

The authors of the study, comprised of a team of international scientists from Australia, the United Kingdom, the United States, Canada, Europe and Taiwan, said that the first use of the Data Recovery System capsules during a live science mission proved a huge success.

“Our telescope got to the point where it was completely destroyed, and we lost high bandwidth communications, so not only did the Data Recovery System work; it was really quite essential to the mission’s success,” Dr Sirks said.

“When you’re dropping something from the sky, in our case from 33 kilometres, there’s always a chance that something goes wrong, so recovery packages are quite essential to keep your data safe.

“This drop package is something we’ve been developing for about five years, but only now have we been able to test it in its final configuration. It’s got to the point where NASA wants to start producing these packages for other science missions as well, so this was really our final test to show that this system works.”

Dr Sirks said Data Recovery Systems are comprised of small computers with SD cards to store the data, a home-made “find my phone” satellite link, and parachutes — housed in foam enclosures using everyday objects such as chicken roasting bags to keep them waterproof.

The story of recovering the packages itself was a mission. Dr Sirks said the local police in the Argentinian countryside helped retrieve the packages, given the rough terrain where they landed.

“We couldn’t find one at first and when we did, there were cougar tracks in the snow near it, so we thought maybe the chicken roast bag was not the best idea. It was quite funny. But we did retrieve them quite easily,” Dr Sirks said.

In a typical balloon-based mission like NASA’s, data is downloaded by satellite, but Dr Sirks said scientists often need line-of-sight communication to download the data quickly, which isn’t always efficient or possible.

Balloon-based observations also provide the quality of space telescopes at a fraction of the budget — millions of dollars compared to billions.

“In our case, we were getting so much data per night that it would just be incredibly slow and expensive to retrieve this data mid-flight,” Dr Sirks said.

“At the moment, the most efficient way for us to download data is to copy it onto an SD drive and just drop it to Earth which is kind of crazy, but it works well.”

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NHS England promises to eliminate cervical cancer by 2040

Jabs are to be offered in libraries and sports venues to improve access, the boss of NHS England will say.

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Give toddlers chickenpox jab, advisers tell NHS

All UK children should be protected against the virus at 12 and 18 months of age, advisers tell NHS.

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NHS struggling to open extra winter beds and fill staffing gaps

Hospitals in England warn a lack of funds means they must scale back on extra beds and recruitment.

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Ammonia for fertilizers without the giant carbon footprint

The production of ammonia for fertilisers — which has one of the largest carbon footprints among industrial processes — will soon be possible on farms using low-cost, low-energy and environmentally friendly technology.

This is thanks to researchers at UNSW Sydney and their collaborators who have developed an innovative technique for sustainable ammonia production at scale.

Up until now, the production of ammonia has relied on high-energy processes that leave a massive global carbon footprint — temperatures of more than 400 oC and pressures exceeding 200 atmospheres that account for 2 per cent of the world’s energy and 1.8 per cent of its CO2.

But the researchers have come up with a method that significantly enhances energy efficiency while making environmentally friendly ammonia economically feasible. The new technique eliminates the requirement for high temperatures, high pressure, and extensive infrastructure in ammonia production.

In a paper published recently in the journal Applied Catalysis B: Environmental, the authors show that the process they developed has enabled the large-scale synthesis of green ammonia by increasing its energy efficiency and production rate.

The foundation of this research, previously published by the same research group, has already been licensed to an Australian industry partner, PlasmaLeap Technologies, through the UNSW Knowledge Exchange program. It is set to be translated into the Australian agriculture industry, with a prototype already scaled up and ready for deployment.

The latest study follows on from the proof-of-concept research performed by the same UNSW research group three years ago with significant advances in energy efficiency and production rate in the process, thus improving commercial profitability.

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The research also represents an opportunity to use green ammonia in the hydrogen transport market, as liquid ammonia (NH3) can store more hydrogen in a smaller space than liquefied hydrogen (H2), making the transportation of hydrogen energy more economical.

Net zero objectives

While the conventional process used for ammonia production is notably energy-intensive — relying heavily on fossil fuels as its primary energy and hydrogen sources — it has been instrumental in increasing crop yields and sustaining a growing global population.

Dr. Ali Jalili, the study’s leader and a former Australian Research Council DECRA Fellow at UNSW, says adopting a sustainable approach to ammonia production is crucial for global net zero objectives.

“Currently, the traditional method of producing ammonia — known as the Haber-Bosch process — accounts for 2.4 tonnes of CO2 per tonne of ammonia, equivalent to approximately 2 per cent of global carbon emissions. Additionally, Haber-Bosch is economically viable only in large-scale and centralised facilities. Consequently, the transportation from these facilities to farms will increase the CO2 emission by 50 per cent,” he says.

“Ammonia-based fertilisers are in critically short supply due to international supply chain disruptions and geopolitical issues, which impact our food security and production costs.

“This, together with its potential for hydrogen energy storage and transportation, makes ammonia key to Australia’s renewable energy initiatives, positioning the country among the leaders in renewable energy exports and utilisation.”

As well as addressing economic and logistical challenges associated with intermittent energy sources for cities or farms, Dr Jalili says to fully unlock its potential, it is “essential to establish a decentralised and energy-efficient production method that can effectively use surplus renewable electricity.”

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Some of today’s earthquakes may be aftershocks from quakes in the 1800s

In the 1800s, some of the strongest earthquakes in recorded U.S. history struck North America’s continental interior. Almost two centuries later, the central and eastern United States may still be experiencing aftershocks from those events, a new study finds.

When an earthquake strikes, smaller quakes known as aftershocks can continue to shake the area for days to years after the original earthquake occurred. These smaller quakes decrease over time and are part of the fault’s readjustment process following the original quake. While aftershocks are smaller in magnitude than the main shock, they can still damage infrastructure and impede recovery from the original earthquake.

“Some scientists suppose that contemporary seismicity in parts of stable North America are aftershocks, and other scientists think it’s mostly background seismicity,” said Yuxuan Chen, a geoscientist at Wuhan University and lead author of the study. “We wanted to view this from another angle using a statistical method.”

The study was published in the Journal of Geophysical Research: Solid Earth, AGU’s journal dedicated to research on the structure, evolution and deformation of the interior of our planet.

Regions near these historic earthquakes’ epicenters are still seismically active today, so it’s possible that some modern earthquakes could be long-lived aftershocks of past quakes. However, they could also be foreshocks that precede larger earthquakes or background seismicity, which is the normal amount of seismic activity for a given region.

According to the U.S. Geological Survey (USGS), there’s no way to distinguish foreshocks from background seismicity until a larger earthquake strikes, but scientists can still discern aftershocks. Thus, identifying the cause of modern earthquakes is important for understanding these regions’ future disaster risk, even if current seismic activity is causing little to no damage.

The team focused on three historic earthquake events estimated to range from magnitude 6.5-8.0: an earthquake near southeastern Quebec, Canada, in 1663; a trio of quakes near the Missouri-Kentucky border from 1811 to 1812; and an earthquake from Charleston, South Carolina, in 1886. These three events are the largest earthquakes in stable North America’s recent history — and larger quakes trigger more aftershocks.

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The stable continental interior of North America is located far from plate boundaries and has less tectonic activity than regions close to plate boundaries, such as North America’s west coast. As a result, the three study areas don’t encounter earthquakes often, raising even more questions about the origins of their modern seismicity.

To figure out if some of today’s earthquakes are long-lived aftershocks, the team first needed to determine which modern quakes to focus their efforts on. Aftershocks cluster around the original earthquake’s epicenter, so they included earthquakes within a 250-kilometer (155-mile) radius of the historic epicenters. They focused on earthquakes that were greater than or equal to a magnitude of 2.5 because anything smaller than that is difficult to reliably record.

The team applied a statistical approach called the nearest neighbor method to USGS earthquake data to determine whether recent earthquakes were likely to be aftershocks or unrelated background seismic activity. Aftershocks occur close to the original quake’s epicenter and before the level of background seismicity has resumed, according to the USGS. Thus, scientists can use a region’s background seismicity and an earthquake’s location to link a quake back to a mainshock.

“You use the time, distance and the magnitude of event pairs, and try to find the link between two events — that’s the idea,” Chen said. “If the distance between a pair of earthquakes is closer than expected from background events, then one earthquake is likely the aftershock of the other.”

Susan Hough, a geophysicist with the USGS who was not involved in the study, mentions that the distance between epicenters is only one piece of the puzzle.

“In some respects, the earthquakes look like aftershocks if you look at the spatial distribution, but earthquakes could be tightly clustered for a couple of reasons,” Hough said. “One is that they’re aftershocks, but also you could have a process of creep going on that’s not part of an aftershock process. Exactly what their results mean is still open to question.”

Looking at the spatial distribution, the study found that the 1663 aftershock sequence near southeastern Quebec, Canada, has ended and modern seismicity in the area is unrelated to the old quake. However, the other two historic events may still be triggering aftershocks centuries later.

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Near the Missouri-Kentucky border, the researchers found that around 30% of all earthquakes from 1980 to 2016 were likely aftershocks from the major earthquakes that struck the area between 1811 and 1812. And in Charleston, South Carolina, the team found around 16% of modern-day quakes were likely aftershocks from the earthquake of 1886. Thus, modern seismicity in these regions is likely attributable to both aftershocks and background seismicity.

“It’s kind of a mixture,” Chen said.

For assessing a region’s modern seismic risk, scientists monitor creep and background seismicity in addition to any aftershocks. The study found background seismicity to be the dominant cause of earthquakes in all three of the study regions, which could be a sign of continued strain accrual. Aftershock sequences weaken over time, but strain accrual can lead to larger earthquakes in the future. However, some faults can creep along without building up strain.

“To come up with a hazard assessment for the future, we really need to understand what happened 150 or 200 years ago,” Hough said. “So bringing modern methods to bear on the problem is important.”

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Scientists discover key to a potential natural cancer treatment’s potency

Slumbering among thousands of bacterial strains in a collection of natural specimens at The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, several fragile vials held something unexpected, and possibly very useful.

Writing in the journal Nature Chemical Biology, a team led by chemist Ben Shen, Ph.D., described discovery of two new enzymes, ones with uniquely useful properties that could help in the fight against human diseases including cancer. The discovery, published last week, offers potentially easier ways to study and manufacture complex natural chemicals, including those that could become medicines.

The contribution of bacterial chemicals to the history of drug discovery is remarkable, said Shen, who directs the Natural Products Discovery Center at the institute, one of the world’s largest microbial natural product collections.

“Few people realize that nearly half of the FDA-approved antibiotics and anticancer drugs on the market are natural products or are inspired by them,” Shen said. “Nature is the best chemist to make these complex natural products. We are applying modern genomic technologies and computational tools to understand their fascinating chemistry and enzymology, and this is leading to progress at unprecedented speed. These enzymes are the latest exciting example.”

The enzymes the team discovered have a descriptive, if unwieldy, name. They are called “cofactorless oxygenases.” This means the bacterial enzymes pull oxygen from the air and incorporate it into new compounds, without requiring the typical metals or other cofactors to initiate the necessary chemical reaction.

This new way of synthesizing defensive substances would confer a survival advantage, enabling the organism to fend off infections or invaders. And because enzymes are to chemists what drill bits or saw blades are to a carpenter, they offer scientists new ways to create useful things, said the paper’s first authors, postdoctoral researchers Chun Gui, Ph.D., and Edward Kalkreuter, Ph.D.

Most immediately, the discovery of the enzymes, TnmJ and TnmK2, solves a lingering mystery of how a potential antibiotic and anticancer compound the Shen lab had first discovered in 2016, tiancimycin A, achieved such potency, Gui and Kalkreuter said.

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The enzymes enable the bacteria to produce compounds for targeting and breaking up DNA, Gui said. This would be immensely useful in fighting off a virus or other germ — or killing cancer.

Tiancimycin A is being developed as part of a cancer-targeting antibody therapy. These types of combined antibody-drug therapeutics represent a rapidly growing new approach to fighting cancer. But a critical step to using tiancimycin A as an antibody’s payload is making enough to study it at a larger scale. That proved challenging.

“Even after we identified genes responsible for encoding tiancimycin A, several of the steps required to synthesize it could not be predicted,” Gui said. “The two enzymes described in the current study are highly unusual.”

Tiancimycin A was first found in a soil-dwelling bacteria, a type of Streptomyces from the strain collection at the Natural Products Discovery Center. To make its powerful chemical weapon, the organism had to solve a problem. It somehow had to break three highly stable carbon-carbon bonds and replace them with more reactive carbon-oxygen bonds. For a long time, the scientists couldn’t understand how the bacteria managed that feat.

Cracking the mystery involved finding other tiancimycin A-like natural product-producing bacteria among the institute’s Natural Products Discovery Center collection of 125,000 bacterial strains, and analyzing their genomes to search for the evolutionary hints.

The historic collection had long been housed in a pharmaceutical company’s basement, collected over decades following the discovery of penicillin in the scientific community’s hopeful rush to find the next great antibiotic. The collection did generate several historically important drugs through the years, including the tuberculosis antibiotic streptomycin and the organ transplant drug sirolimus. But the majority of the collection’s freeze-dried bacterial strains had rested in their glass vials, unexplored.

In 2018, Shen won a competition for the collection, so that it could be fully investigated in an academic setting, where it would be open to science. His team is now developing ways to study the strains, read their genomes and deposit the information into a searchable database for the scientific community to access. Modern genome sequencing and bioinformatics techniques are proving that there may be as many as 30 interesting gene clusters in each strain of bacteria they study, and many of them code for natural products never before documented by scientists, said Shen, who is a member of the UF Health Cancer Center.

The discovery of the new cofactorless enzymes is but the latest example of the chemical riches that lie within The Wertheim UF Scripps Institute’s collection, Shen said. Their discovery has sparked new excitement about further investigating the reasons the unique chemistry evolved, and the ways it may prove useful.

“This publication underscores how many surprises nature still has for us,” Shen said, “It can teach us much about fundamental chemistry and biology and provide us with the tools and inspiration we need to translate laboratory findings into medicines that impact society and address many problems faced by humanity.”

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Indi Gregory: Critically ill baby dies after life support turned off

Indi Gregory’s parents say they feel heartbroken and angry following the legal battle over her care.

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