. Scientific Frontline

Tuesday, March 21, 2023

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.

Ultrafast beam-steering breakthrough at Sandia Labs

As a red beam of light is reflected in an arch, Prasad Iyer, right, and Igal Brener demonstrate optical hardware used for beam steering experiments at Sandia National Laboratories’ Center for Integrated Nanotechnologies.
Photo Credit: Craig Fritz

In a major breakthrough in the fields of nanophotonics and ultrafast optics, a Sandia National Laboratories research team has demonstrated the ability to dynamically steer light pulses from conventional, so-called incoherent light sources.

This ability to control light using a semiconductor device could allow low-power, relatively inexpensive sources like LEDs or flashlight bulbs to replace more powerful laser beams in new technologies such as holograms, remote sensing, self-driving cars and high-speed communication.

“What we’ve done is show that steering a beam of incoherent light can be done,” said Prasad Iyer, Sandia scientist and lead author of the research, which was reported in the current issue of the journal Nature Photonics

Incoherent light is emitted by many common sources, such as an old-fashioned incandescent light bulb or an LED bulb. This light is called incoherent since the photons are emitted with different wavelengths and in a random fashion. A beam of light from a laser, however, does not spread and diffuse because the photons have the same frequency and phase and is thus called coherent light.

Researchers Separate Cotton from Polyester in Blended Fabric

A cotton knit fabric dyed blue and washed 10 times to simulate worn garments is enzymatically degraded to a slurry of fine fibers and "blue glucose" syrup that are separated by filtration - both of these separated fractions have potential recycle value.
Photo Credit: Sonja Salmon.

In a new study, North Carolina State University researchers found they could separate blended cotton and polyester fabric using enzymes – nature’s tools for speeding chemical reactions. Ultimately, they hope their findings will lead to a more efficient way to recycle the fabric’s component materials, thereby reducing textile waste.

However, they also found the process needs more steps if the blended fabric was dyed or treated with chemicals that increase wrinkle resistance.

“We can separate all of the cotton out of a cotton-polyester blend, meaning now we have clean polyester that can be recycled,” said the study’s corresponding author Sonja Salmon, associate professor of textile engineering, chemistry and science at NC State. “In a landfill, the polyester is not going to degrade, and the cotton might take several months or more to break down. Using our method, we can separate the cotton from polyester in less than 48 hours.”

Researchers create breakthrough spintronics manufacturing process that could revolutionize the electronics industry


University of Minnesota researchers, along with a team at the National Institute of Standards and Technology (NIST), developed a breakthrough process for making spintronic devices that has the potential to become the new industry standard for semiconductors chips that are essential to computers, smartphones and many other electronics. The new process will allow for faster, more efficient spintronics devices that can be scaled down smaller than ever before. ​​

The paper is published in Advanced Functional Materials.

“We believe we’ve found a material and a device that will allow the semiconducting industry to move forward with more opportunities in spintronics that weren’t there before for memory and computing applications,” said Jian-Ping Wang, senior author of the paper and professor in the College of Science and Engineering. 

The semiconductor industry is constantly trying to develop smaller and smaller chips that can maximize energy efficiency, computing speed and data storage capacity in electronic devices. Spintronic devices, which leverage the spin of electrons rather than the electrical charge to store data, provide a promising and more efficient alternative to traditional transistor-based chips. These materials also have the potential to be non-volatile, meaning they require less power and can store memory and perform computing even after you remove their power source.

Underactive immune response may explain obesity link to COVID-19 severity

Intensive care unit at Addenbrooke's Hospital 
Photo Credit: Cambridge University Hospitals NHS Foundation Trust

Scientists at the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID) and Wellcome Sanger Institute showed that following SARS-CoV-2 infection, cells in the lining of the lungs, nasal cells, and immune cells in the blood show a blunted inflammatory response in obese patients, producing suboptimal levels of molecules needed to fight the infection.

Since the start of the pandemic, there have been almost 760 million confirmed cases of SARS-CoV-2 infection, with almost 6.9 million deaths. While some people have very mild – or even no – symptoms, others have much more severe symptoms, including acute respiratory distress syndrome requiring ventilator support.

One of the major risk factors for severe COVID-19 is obesity, which is defined as a body mass index (BMI) of over 30. More than 40% of US adults and 28% of adults in England are classed as obese.

While this link has been shown in numerous epidemiological studies, until now, it has not been clear why obesity should increase an individual’s risk of severe COVID-19. One possible explanation was thought to be that obesity is linked to inflammation: studies have shown that people who are obese already have higher levels of key molecules associated with inflammation in their blood. Could an overactive inflammatory response explain the connection?

Upgraded tumor model optimizes search for cancer therapies

Study co-authors (from left) Caleb Bashor, Antonios Mikos and Letitia Chim.
Photo Credit: Gustavo Raskosky/Rice University

Tumor cells won’t show their true selves in a petri dish, isolated from other cells.

To find out how they really behave, Rice University researchers developed an upgraded tumor model that houses osteosarcoma cells beside immune cells known as macrophages inside a three-dimensional structure engineered to mimic bone. Using the model, bioengineer Antonios Mikos and collaborators found that the body’s immune response can make tumor cells more resistant to chemotherapy.

The study, which is published in Biomaterials, sheds light on why some cancer drugs that appear to be good candidates in the lab do not perform as well as expected in actual patients. It underscores weaknesses in traditional tumor modeling and points the way toward more effective cancer therapies.

“Existing tumor models used to test drug performance do not mimic the actual environment in the human body closely enough,” Mikos said. “We are trying to create an environment for the experiment that is closer to what is happening in the organism of actual patients. Having such an environment will allow us to test multiple drugs in a time- and cost-effective way.”

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