Rare diseases point to connections between metabolism and immunity

Inherited diseases of metabolism and immunity have more in common than previously recognized, according to a new study published in the journal Science Immunology. The findings point to a new set of metabolic genes that are important for the function of immune system T cells, and they offer insights that could improve care for patients with these disorders.

The study examined genes that cause inborn errors of metabolism (disorders of the processes that cells use to convert food to energy) and inborn errors of immunity (disorders that affect immune system function). These rare and complex diseases are not fully understood.

“There had previously been only a small number of genes that were on both lists of diseases, but we found that many more have overlap,” said Andrew Patterson, PhD, who led the study as a postdoctoral fellow working with Jeffrey Rathmell, PhD, at Vanderbilt University Medical Center. “Our study showed that a large number of genes associated with inborn errors of metabolism can also potentially affect T cell function when they are mutated.”

The findings suggest that patients with an inborn error of metabolism may also have immune defects that could impact their care, and conversely that metabolic defects may contribute to symptoms in patients with inborn errors of immunity.

“There’s a lot more that will have to be learned, but these connections might point to different therapies,” said Rathmell, Cornelius Vanderbilt Professor of Immunobiology and director of the Vanderbilt Center for Immunobiology. “Rather than different categories, these diseases are part of a continuum; there’s a gray zone between them and a potential new class of inborn errors of immunometabolism that intersects the two.”

Patterson and the research team used a gene-editing CRISPR approach to screen the inborn errors of metabolism genes for immune defects and the inborn errors of immunity genes for metabolic defects. They further analyzed one example from each set — one metabolic gene that had an immune defect; one immunity gene that had a metabolic defect — to more carefully examine the mechanistic impact.

Overall, Rathmell’s team is interested in discovering how metabolic pathways regulate T cell function, with the goal of developing targeted therapies for immune-mediated disorders.

“What we’ve done is lay the foundation for further investigation,” Patterson said. “The two examples we studied in detail point to new biology and new mechanisms, and there are hundreds of other genes we identified to analyze for their roles in T cell function.”

The findings are available on the Functional ImmunoGenomices reSource (FIGS) website for other researchers to use.

“If you’re trying to understand the connections between metabolism and immunity, this is a great place to start,” Rathmell said.

Patterson recently joined the faculty of the University of Louisville as an assistant professor of Biochemistry and Molecular Genetics. Vanderbilt collaborators Vivian Gama, PhD, associate professor of Cell and Developmental Biology, and Janet Markle, PhD, assistant professor of Pathology, Microbiology and Immunology, were important contributors to the study.

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Scientists discover phenomenon impacting Earth’s radiation belts

Two University of Alaska Fairbanks scientists have discovered a new type of “whistler,” an electromagnetic wave that carries a substantial amount of lightning energy to the Earth’s magnetosphere.

The research is published in Science Advances.

Vikas Sonwalkar, a professor emeritus, and Amani Reddy, an assistant professor, discovered the new type of wave. The wave carries lightning energy, which enters the ionosphere at low latitudes, to the magnetosphere. The energy is reflected upward by the ionosphere’s lower boundary, at about 55 miles altitude, in the opposite hemisphere.

It was previously believed, the authors write, that lightning energy entering the ionosphere at low latitudes remained trapped in the ionosphere and therefore was not reaching the radiation belts. The belts are two layers of charged particles surrounding the planet and held in place by Earth’s magnetic field.

“We as a society are dependent on space technology,” Sonwalkar said. “Modern communication and navigation systems, satellites, and spacecraft with astronauts aboard encounter harmful energetic particles of the radiation belts, which can damage electronics and cause cancer.

“Having a better understanding of radiation belts and the variety of electromagnetic waves, including those originating in terrestrial lightning, that impact them is vital for human operations in space,” he said.

Sonwalkar and Reddy’s discovery is a type of whistler wave they call a “specularly reflected whistler.” Whistlers produce a whistling sound when played through a speaker.

Lightning energy entering the ionosphere at higher latitudes reaches the magnetosphere as a different type of whistler called a magnetospherically reflected whistler, which undergoes one or more reflections within the magnetosphere.

The ionosphere is a layer of Earth’s upper atmosphere characterized by a high concentration of ions and free electrons. It is ionized by solar radiation and cosmic rays, making it conductive and crucial for radio communication because it reflects and modifies radio waves.

Earth’s magnetosphere is a region of space surrounding the planet and created by Earth’s magnetic field. It provides a protective barrier that prevents most of the solar wind’s particles from reaching the atmosphere and harming life and technology.

Sonwalkar and Reddy’s research shows that both types of whistlers — specularly reflected whistlers and magnetospherically reflected whistlers — coexist in the magnetosphere.

In their research, the authors used plasma wave data from NASA’s Van Allen Probes, which launched in 2012 and operated until 2019, and lightning data from the World Wide Lightning Detection Network.

They developed a wave propagation model that, when considering specularly reflected whistlers, showed the doubling of lightning energy reaching the magnetosphere.

Review of plasma wave data from the Van Allen Probes showed that specularly reflected whistlers are a common magnetospheric phenomenon.

A majority of lightning occurs at the low latitudes, which are tropical and subtropical regions prone to thunderstorm development.

“This implies that specularly reflected whistlers probably carry a greater part of lightning energy to the magnetosphere relative to that carried by magnetospherically reflected whistlers,” Sonwalkar said.

The impact of lightning-generated whistler waves on radiation belt physics and their use in remote sensing of magnetospheric plasma have been researched since the 1950s.

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Failures led to girl’s Costa drink death – coroner

The girl’s mother accuses the food industry of treating allergy training as a “tick box exercise”.

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Researchers develop new chemical method to enhance drug discovery

Moffitt Cancer Center researchers have developed a novel reagent that enhances the precision of drug synthesis. This innovative method, published in Nature Communications, introduces a new sulfur fluoride exchange (SuFEx) reagent that allows for highly controlled production of crucial sulfur-based molecules, including sulfinamides, sulfonimidamides and sulfoximines.

These compounds are essential in the pharmaceutical industry but have been challenging to synthesize with the required stereochemical accuracy. The innovative reagent t-BuSF uses strain-release reactivity to achieve a level of efficiency and selectivity previously unattainable, paving the way for more effective drug development and broader applications in medical research.

“Sulfur-based compounds, including those developed using the new methods, are known to have favorable physiochemical properties that make them ideal candidates for drug development,” said Justin M. Lopchuk, Ph.D., lead author and associate member of the Drug Discovery Department at Moffitt. “The ability to synthesize these compounds rapidly and stereochemical control open new possibilities for designing targeted therapies that combat cancer cells more effectively while minimizing side effects.”

By leveraging the unique properties of the t-BuSF reagent, researchers were able to explore previously inaccessible chemical space within the sulfur family, particularly in the S(IV) and S(VI) oxidation states. This advancement has resulted in the creation of over 70 new chemical compounds, many of which have immediate applications in medicinal chemistry and the development of new pharmaceutical agents.

Lopchuk adds that this research has already been used to significantly improve the scalable synthesis of DFV890, an investigational compound from Novartis currently in clinical trials at Moffitt and other locations for myeloid diseases.

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Tracking down the asteroid that sealed the fate of the dinosaurs

Geoscientists from the University of Cologne have led an international study to determine the origin of the huge piece of rock that hit the Earth around 66 million years ago and permanently changed the climate. The scientists analysed samples of the rock layer that marks the boundary between the Cretaceous and Paleogene periods. This period also saw the last major mass extinction event on Earth, in which around 70 percent of all animal species became extinct. The results of the study published in Science indicate that the asteroid formed outside Jupiter’s orbit during the early development of our solar system.

According to a widely accepted theory, the mass extinction at the Cretaceous-Paleogene boundary was triggered by the impact of an asteroid at least 10 kilometres in diameter near Chicxulub on the Yucatán Peninsula in Mexico. On impact, the asteroid and large quantities of earth rock vaporized. Fine dust particles spread into the stratosphere and obscured the sun. This led to dramatic changes in the living conditions on the planet and brought photosynthetic activity to a halt for several years.

The dust particles released by the impact formed a layer of sediment around the entire globe. This is why the Cretaceous-Paleogene boundary can be identified and sampled in many places on Earth. It contains high concentrations of platinum-group metals, which come from the asteroid and are otherwise extremely rare in the rock that forms the Earth’s crust.

By analysing the isotopic composition of the platinum metal ruthenium in the cleanroom laboratory of the University of Cologne’s Institute of Geology and Mineralogy, the scientists discovered that the asteroid originally came from the outer solar system. “The asteroid’s composition is consistent with that of carbonaceous asteroids that formed outside of Jupiter’s orbit during the formation of the solar system,” said Dr Mario Fischer-Gödde, first author of the study.

The ruthenium isotope compositions were also determined for other craters and impact structures of different ages on Earth for comparison. This data shows that within the last 500 million years, almost exclusively fragments of S-type asteroids have hit the Earth. In contrast to the impact at the Cretaceous-Paleogene boundary, these asteroids originate from the inner solar system. Well over 80 percent of all asteroid fragments that hit the Earth in the form of meteorites come from the inner solar system. Professor Dr Carsten Münker, co-author of the study, added: “We found that the impact of an asteroid like the one at Chicxulub is a very rare and unique event in geological time. The fate of the dinosaurs and many other species was sealed by this projectile from the outer reaches of the solar system.”

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It’s a rave: Underground acoustics amplify soil health

Barely audible to human ears, healthy soils produce a cacophony of sounds in many forms — a bit like an underground rave concert of bubble pops and clicks.

Special recordings made by Flinders University ecologists in Australia show this chaotic mixture of soundscapes can be a measure of the diversity of tiny living animals in the soil, which create sounds as they move and interact with their environment.

With 75% of the world’s soils degraded, the future of the teeming community of living species that live underground face a dire future without restoration, says microbial ecologist Dr Jake Robinson, from the Frontiers of Restoration Ecology Lab in the College of Science and Engineering at Flinders University.

This new field of research aims to investigate the vast, teeming hidden ecosystems where almost 60% of the Earth’s species live, he says.

“Restoring and monitoring soil biodiversity has never been more important.

“Although still in its early stages, ‘eco-acoustics’ is emerging as a promising tool to detect and monitor soil biodiversity and has now been used in Australian bushland and other ecosystems in the UK.

“The acoustic complexity and diversity are significantly higher in revegetated and remnant plots than in cleared plots, both in-situ and in sound attenuation chambers.

“The acoustic complexity and diversity are also significantly associated with soil invertebrate abundance and richness.”

The latest study, including Flinders University expert Associate Professor Martin Breed and Professor Xin Sun from the Chinese Academy of Sciences, compared results from acoustic monitoring of remnant vegetation to degraded plots and land that was revegetated 15 years ago.

The passive acoustic monitoring used various tools and indices to measure soil biodiversity over five days in the Mount Bold region in the Adelaide Hills in South Australia. A below-ground sampling device and sound attenuation chamber were used to record soil invertebrate communities, which were also manually counted.

“It’s clear acoustic complexity and diversity of our samples are associated with soil invertebrate abundance — from earthworms, beetles to ants and spiders — and it seems to be a clear reflection of soil health,” says Dr Robinson.

“All living organisms produce sounds, and our preliminary results suggest different soil organisms make different sound profiles depending on their activity, shape, appendages and size.

“This technology holds promise in addressing the global need for more effective soil biodiversity monitoring methods to protect our planet’s most diverse ecosystems.”

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Hailstone library to improve extreme weather forecasting

A University of Queensland library — full of hailstones instead of books — is helping researchers to better understand and predict damaging storms.

Dr Joshua Soderholm, an Honorary Senior Research Fellow from UQ’s School of the Environment, and lead researcher PhD candidate Yuzhu Lin from Penn State in the US, have found storm modelling outcomes change significantly when using real hailstones.

Key points:

  • Researchers are measuring and scanning samples for a global ‘hailstone library’
  • Storm simulations using 3-D modelling of real hailstones show it behaves differently than spherical hail shapes
  • Data from the hail library could lead to more accurate storm forecasts

“People tend to think of a hailstone as a perfect sphere, like a golf ball or cricket ball,” Dr Soderholm said.

“But hail can be all sorts of weird shapes, from oblong to a flat disc or have spikes coming out — no two pieces of hail are the same.

“Conventional scientific modelling of hail assumes spherical hailstones, and we wanted to know if that changed when non-spherical, natural hail shapes are used.”

Ms Lin said they found the differences were dramatic.

“Modelling of the more naturally shaped hail showed it took different pathways through the storm, experienced different growth and landed in different places,” Ms Lin said.

“It also affected the speed and impact the hail had on the ground.

“This way of modelling had never been done before, so it’s exciting science.”

Dr Soderholm said building a ‘hailstone library’ was critical to further fine-tuning hailstorm simulations.

“This is effectively a dataset to represent the many and varied shapes of hailstones, to make weather modelling more accurate,” he said.

“Our study used data from 217 hail samples, which were 3-D scanned and the sliced in half, to tell us more about how the hailstone formed.

“This data is now part of a global library, as we try and get a really clear picture of hailstone shape and structure.”

Dr Soderholm said the research has significant potential.

“At the moment, the modelling is specifically for scientists studying storms, but the end game is to be able to predict in real-time how big hail will be, and where it will fall,” he said.

“More accurate forecasts would of course warn the public so they can stay safe during hailstorms and mitigate damage.

“But it could also significantly benefit industries such as insurance, agriculture and solar farming which are all sensitive to hail.”

The research paper was published in the Journal of the Atmospheric Sciences.

Dr Soderholm is also a Research Scientist at the Australian Bureau of Meteorology.

Some hail samples for the UQ data set were provided by Higgins Storm Chasing.

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Travellers advised to consider mpox vaccine

There is concern about a new strain of the disease that has been spreading in parts of Africa.

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Infected blood compensation payouts on the way

Ministers promise first payments by the end of the year with some victims entitled to more than £2m.

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Blind cavefish have extraordinary taste buds

Over thousands of years, cavefish evolved and lost their vision, earning the moniker “the blind cavefish,” but some cavefish also developed an inordinate number of taste buds on the head and chin.

In a new study, now published in the Nature journal Communications Biology, scientists at the University of Cincinnati have determined when the taste buds start to appear in areas beyond the oral cavity. The study was supported by the National Science Foundation.

To begin, blind cavefish evolved in cave ponds in northeastern Mexico. They are pale pink and nearly translucent compared to their silvery counterparts that live in surface rivers and streams. While cavefish have the faintest outline of eye sockets, the surface fish have enormous round eyes that give them a perpetually surprised expression.

Despite the many obvious physical differences, the two fish are considered the same species.

“Regression, such as the loss of eyesight and pigmentation, is a well-studied phenomenon, but the biological bases of constructive features are less well understood,” says the article’s senior author UC professor and biologist Joshua Gross, whose laboratory is dedicated to the study of evolution and development of cave-dwelling vertebrates.

Although scientists in the 1960s discovered that certain populations of blind cavefish had extra taste buds — on the head and chin — there was no further study of the developmental or genetic processes that explain this unusual trait, says Gross.

To determine when the extra taste buds appear, Gross and his research team looked at the species Astyanax mexicanus, including two separate cavefish populations that dwell in the Pachón and Tinaja caves in northwestern Mexico, known to have the additional taste buds.

The research team found that the number of taste buds is similar to the surface fish from birth through 5 months of age. The taste buds then start to increase in number and appear on the head and chin in smatterings, well into adulthood, at approximately 18 months.

Cavefish can live much longer than 18 months in nature and captivity, and the authors suspect even more taste buds continually accumulate as the fish get older.

While timing of taste bud appearance was comparable for the Pachón and Tinaja cavefish populations, some differences were evident with respect to density and timing of expansion, says Gross. The other surprising discovery from this study, says Gross, is the genetic architecture of this trait: “Despite the complexity of this feature, it appears that more taste buds on the head are controlled mainly by only two regions of the genome.”

The increase correlates with the time that the cavefish stop eating other live foods for sustenance and start to pursue other food sources, Gross says, such as bat guano. Equally fascinating, he says, is that the expansion may occur in other cave locations where there are no bat populations.

With more taste buds, he says, the cavefish have a keener sense of taste, “which is likely an adaptive trait.”

“It remains unclear what is the precise functional and adaptive relevance of this augmented taste system,” says Gross, which has led the team to begin new studies that focus on taste, by exposing the fish to different flavors such as sour, sweet and bitter.

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