. Scientific Frontline

Tuesday, March 21, 2023

New method to identify and explore functional proteoforms and their associations with drug response in childhood acute lymphoblastic leukemia

Rozbeh Jafari, senior researcher at the Department of Oncology-Pathology.
Photo Credit: Courtesy of Rozbeh Jafari

Researchers at the Department of Oncology-Pathology have together with researchers from The European Molecular Biology Laboratory published a paper in Nature Chemical Biology where they developed a method that can identify important differences between proteins in an unbiased way.

The paper examines melting behavior of proteins to define cases where portions of the protein melt differently. In these cases, the method can identify that the protein is likely to exist in multiple physical forms, called proteoforms. Therefore, a new perspective on variations between proteins can be interpreted. The method is applied in the context of childhood acute lymphoblastic leukemia cell lines, and is used to identify specific proteoforms associated with disease biology and drug response. This disease was selected as a proof of principle due to the need for improved precision therapies for patients.

First results from ESO telescopes on the aftermath of DART’s asteroid impact

This series of images, taken with the MUSE instrument on ESO’s Very Large Telescope, shows the evolution of the cloud of debris that was ejected when NASA’s DART spacecraft collided with the asteroid Dimorphos.  The first image was taken on 26 September 2022, just before the impact, and the last one was taken almost one month later on 25 October. Over this period several structures developed: clumps, spirals, and a long tail of dust pushed away by the Sun’s radiation. The white arrow in each panel marks the direction of the Sun.  Dimorphos orbits a larger asteroid called Didymos. The white horizontal bar corresponds to 500 kilometers, but the asteroids are only 1 kilometer apart, so they can’t be discerned in these images.  The background streaks seen here are due to the apparent movement of the background stars during the observations while the telescope was tracking the asteroid pair. 
Full Size Image
Image Credit: ESO/Opitom et al.

Using ESO’s Very Large Telescope (VLT), two teams of astronomers have observed the aftermath of the collision between NASA’s Double Asteroid Redirection Test (DART) spacecraft and the asteroid Dimorphos. The controlled impact was a test of planetary defense, but also gave astronomers a unique opportunity to learn more about the asteroid’s composition from the expelled material.

On 26 September 2022 the DART spacecraft collided with the asteroid Dimorphos in a controlled test of our asteroid deflection capabilities. The impact took place 11 million kilometers away from Earth, close enough to be observed in detail with many telescopes. All four 8.2-metre telescopes of ESO’s VLT in Chile observed the aftermath of the impact, and the first results of these VLT observations have now been published in two papers.

”Asteroids are some of the most basic relics of what all the planets and moons in our Solar System were created from,” says Brian Murphy, a PhD student at the University of Edinburgh in the UK and co-author of one of the studies. Studying the cloud of material ejected after DART’s impact can therefore tell us about how our Solar System formed. “Impacts between asteroids happen naturally, but you never know it in advance,” continues Cyrielle Opitom, an astronomer also at the University of Edinburgh and lead author of one of the articles. “DART is a really great opportunity to study a controlled impact, almost as in a laboratory.”

Surprise from the quantum world

The ferromagnetism of the topological isolator manganese-bismuth-telluride only arises when the atomic structure fails. To do this, some manganese atoms (green) must be moved out of their original position (second green atomic plane from above). Only when there are manganese atoms in all levels with bismuth atoms (gray) is the magnetic orientation of the manganese atoms so contagious that ferromagnetism arises.
Illustration Credit: Jörg Bandmann / ct.qmat

The Würzburg-Dresden Cluster of Excellence ct.qmat has designed a ferromagnetic topological isolator - a milestone on the way to energy-efficient quantum technologies.

As early as 2019, an international research team around the material chemist Anna Isaeva - then junior professor at the Würzburg-Dresden Cluster of Excellence ct.qmat - complexity and topology in quantum materials - succeeded in producing the first antiferromagnetic topological isolator manganese-bismuth-tilluride. (Mn2Te4) a little sensation.

This miracle material no longer needs a strong external magnetic field - it brings its own inner magnetic field with it. This offers the opportunity for new types of electronic components that magnetically encode information and transport it on the surface without resistance. This could make information technology more sustainable and energy-saving in the future, for example. Since then, researchers worldwide have been analyzing different facets of this promising quantum material.

Researchers create exotic quantum light states

The graphic symbolizes how photons are coupled after they have been scattered on an artificial atom - a so-called quantum dot - in a cavity resonator.
Illustration Credit: © University of Basel

Coupled light particles could advance both medical imaging and quantum computing.

Light particles, also called photons, do not normally interact with each other. An international research team has now been able to show for the first time that a few photons can be manipulated in a controlled manner and brought into interaction. This opens up new opportunities in the development of quantum technologies. The results are described by a team from the University of Basel, the University of Sydney and the Ruhr University Bochum in the journal Nature Physics, published online on the 20th. March 2023.

Measure distances and transmit information using light

Photons do not interact with each other in a vacuum; they can fly through each other undisturbed. This makes them valuable for data transfer because information can be transported almost trouble-free at the speed of light. Light is helpful not only for data transmission, but also in certain measuring instruments, because it can be used to determine tiny distances, for example in medical imaging. The sensitivity of such measuring instruments depends on the average number of photons in the system.

Iron Nanoparticles Neurotoxic Even at Low Doses

Scientists discovered this by studying the brains of rats
Photo Credit: Aleksandr Gusev

Iron oxide nanoparticles, which pollute the air, are toxic to the central nervous system even in low doses. To find out, Ural scientists injected rats intranasally with suspensions containing iron oxide particles and studied functional and structural changes in their brains. The data may help to develop measures to prevent neurodegenerative diseases. The study was conducted at the Ekaterinburg Medical Research Centre of Rospotrebnadzor, and the analysis and synthesis of the data was carried out as part of the Priority 2030 program. The results have been published in the International Journal of Molecular Sciences.

"Many technological processes can produce nanoparticles in the metallurgical industry. Inhalation of nanoparticles is harmful to human health, because even at low concentrations they can penetrate directly into the brain: through the nasal cavity, through the olfactory tract, directly into various brain structures", - says Ilzira Minigalieva, Doctor of Biological Sciences and Head of the UrFU Laboratory "Stochastic transport of nanoparticles in a living organism".

To understand exactly how low doses of iron oxide affect the central nervous system, scientists conducted an experiment on rats and injected each rat intranasally with a suspension containing 0.45 mg of nanoparticles. This amount was not chosen at random because the main purpose of the study was to see if such low doses could have a neurotoxic effect.

UCLA-led study uses base editing to correct mutation that causes rare immune deficiency

Image Credit: Sangharsh Lohakare

A new UCLA-led study suggests that advanced genome editing technology could be used as a one-time treatment for the rare and deadly genetic disease CD3 delta severe combined immunodeficiency.

The condition, also known as CD3 delta SCID, is caused by a mutation in the CD3D gene, which prevents the production of the CD3 delta protein that is needed for the normal development of T cells from blood stem cells.

Without T cells, babies born with CD3 delta SCID are unable to fight off infections and, if untreated, often die within the first two years of life. Currently, bone marrow transplant is the only available treatment, but the procedure carries significant risks.

In a study published in Cell, the researchers showed that a new genome editing technique called base editing can correct the mutation that causes CD3 delta SCID in blood stem cells and restore their ability to produce T cells.

The potential therapy is the result of a collaboration between the laboratories of Dr. Donald Kohn and Dr. Gay Crooks, both members of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA and senior authors of the study.

Monday, March 20, 2023

Humans are Leading Source of Death for California Mountain Lions, Despite Hunting Protections

A female mountain lion (P-19) near Malibu Creek State Park in March 2014.
Photo Credit: National Park Service

Mountain lions are protected from hunting in California by a law passed by popular vote in 1990. However, a team of researchers working across the state found that human-caused mortality—primarily involving conflict with humans over livestock and collisions with vehicles—was more common than natural death for this protected large carnivore.

The study, published today in the Proceedings of the National Academy of Sciences, was led by the University of Nebraska-Lincoln, along with a broad team of coauthoring California researchers, including from the University of California, Davis.

Most research on mountain lions is conducted at relatively small scales, which limits understanding of mortality caused by humans across the large areas they roam. To address this, scientists from multiple universities, government agencies, and private organizations teamed up to better understand human-caused mortality for mountain lions across the entire state of California.

The team tracked almost 600 mountain lions in 23 different study areas, including the Sierra Nevada mountains, the northern redwoods, wine country north of San Francisco, the city of Los Angeles, and many other areas of the state.

Artificial light at night aids caterpillar predators

Under moderate levels of artificial light, predators have more opportunity to attack caterpillars.
Photo Credit: John Deitsch/Cornell University  

To save caterpillars, turn off your porch light.

Moderate levels of artificial light at night – like the fixture illuminating your backyard – bring more caterpillar predators and reduce the chance that these lepidoptera larvae grow up to become moths and serve as food for larger prey.

This new Cornell research was published March 8 in the Proceedings of the Royal Society B: Biological Sciences.

Scientists can place clay models that look like caterpillars in the woods. Due to the soft clay, the researchers can examine the marks and get a sense of how often larvae are attacked by predators.

The Cornell scientists placed more than 550 soft clay caterpillar models – lifelike replicas – in a forest setting to ascertain how the mockups were attacked and hunted by predators, compared to a control group.

Lack of canine COVID-19 data fuels persisting concerns over dog-human interactions

A research literature review by Purdue University researchers published in the journal Animals highlights unanswered questions about the COVID-19 virus dynamics between dogs and humans.
 Photo Credit: Purdue Agricultural Communications photo/Tom Campbell

Early COVID-19 pandemic suspicions about dogs’ resistance to the disease have given way to a long-haul clinical data gap as new variants of the virus have emerged.

“It is not confirmed that the virus can be transmitted from one dog to another dog or from dogs to humans,” said veterinarian Mohamed Kamel, a postdoctoral fellow at Purdue University.

During the pandemic’s early days, dogs seemed resistant to the coronavirus, showing little evidence of infection or transmission, said Mohit Verma, assistant professor of agricultural and biological engineering and Purdue’s Weldon School of Biomedical Engineering. “As the virus evolved, or maybe the surveillance technology advanced, there seem to be more instances of potentially asymptomatic dogs.”

These are among the findings that Kamel, Verma and two co-authors summarized in a research literature review “Interactions Between Humans and Dogs in the COVID-19 Pandemic.” The summary, with recent updates and future perspectives, recently appeared in a special issue of the journal Animals on Susceptibility of Animals to SARS-CoV-2.

Can synthetic polymers replace the body’s natural proteins?

Biological fluids are made up of hundreds or thousands of different proteins (represented by space filling models above) that evolved to work together efficiently but flexibly. UC Berkeley polymer scientists are trying to create artificial fluids composed of random heteropolymers (threads inside spheres) with much less complexity, but which mimic many of the properties of the natural proteins (right), such as stabilizing fragile molecular markers.
Illustration Credit: Zhiyuan Ruan, Ting Xu lab

Most life on Earth is based on polymers of 20 amino acids that have evolved into hundreds of thousands of different, highly specialized proteins. They catalyze reactions, form backbone and muscle and even generate movement.

But is all that variety necessary? Could biology work just as well with fewer building blocks and simpler polymers?

Ting Xu, a University of California, Berkeley, polymer scientist, thinks so. She has developed a way to mimic specific functions of natural proteins using only two, four or six different building blocks — ones currently used in plastics — and found that these alternative polymers work as well as the real protein and are a lot easier to synthesize than trying to replicate nature’s design.

As proof of concept, she used her design method, which is based on machine learning or artificial intelligence, to synthesize polymers that mimic blood plasma. The artificial biological fluid kept natural protein biomarkers intact without refrigeration and even made the natural proteins more resistant to high temperatures — an improvement over real blood plasma.

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