. Scientific Frontline

Thursday, March 2, 2023

Lipid nanoparticles highly effective in gene therapy

The RNP-ssODN is designed to ensure the CRISPR-Cas9 molecule is encapsulated by the LNP. Once inside the cells, the ssODN dissociates and CRISPR-Cas9 can carry out its effect.
Illustration Credits: Haruno Onuma, Yusuke Sato, Hideyoshi Harashima. Journal of Controlled Release. February 10, 2023.

Lipid nanoparticles have been used to encapsulate CRISPR-Cas9 and deliver it to cells in mice, where it was highly effective at knocking down expression of a target protein.

Gene therapy is a potential mode of treatment for a wide variety of diseases caused by genetic mutations. While it has been an area of diverse and intense research, historically, only a very few patients have been treated using gene therapy—and fewer still cured. The advent of the genetic modification technique called CRISPR-Cas9 in 2012 has revolutionized gene therapy—as well as biology as a whole—and it has recently entered clinical trials for the treatment of some diseases in humans.

Haruno Onuma, Yusuke Sato and Hideyoshi Harashima at Hokkaido University have developed a new delivery system for CRISPR-Cas9, based on lipid nanoparticles (LNPs), that could greatly increase the efficiency of in vivo gene therapy. Their findings were published in the Journal of Controlled Release.

Wednesday, March 1, 2023

Social bird species may be less competitive

Northern mockingbird
Photo Credit: Brian E. Kushner/Cornell Lab of Ornithology 

Using Cornell Lab of Ornithology data, a new study finds that birds that have evolved to be more social are less likely to kick other birds off a bird feeder or a perch.

Spend any time watching backyard bird feeders and it becomes clear that some species are more “dominant” than others. They evict other birds from a feeder or perch, usually based on their body size. Scientists wanted to learn if birds that have evolved to be more social have also evolved to be less aggressive.

Their findings published March 1 in the Proceedings of the Royal Society B, “The Effect of Sociality on Competitive Interactions Among Birds.”

“We found that species’ sociality was inversely related to dominance,” said lead author Ilias Berberi from Carleton University in Ottawa, Canada. “Using data collected from thousands of birdwatching volunteers, we measured the sociality of different species based on their typical group size when seen at bird feeders. Though some species are often found in groups, other tend to be loners. When we examined their dominance interactions, we found that more social species are weaker competitors. Overall, the more social bird species are less likely to evict competing species from the feeders.”

Chemical imaging could help predict efficacy of radiation therapy for an individual cancer patient

Concept illustration of body chemistry.
Image Credit: Nicole Smith, made with Midjourney. Courtesy of University of Michigan

Decisions on cancer treatment could become better tailored to individual patients with the adoption of a new imaging method being developed by University of Michigan researchers that maps the chemical makeup of a patient’s tumor.

Today, treatment methods for cancer—whether surgery, radiation therapy or immunotherapy—are recommended based mainly on the tumor’s location, size and aggressiveness. This information is usually obtained by anatomical imaging—MRI or CT scans or ultrasound and by biological assays performed in tissues obtained by tumor biopsies.

Yet, the chemical environment of a tumor has a significant effect on how effective a particular treatment may be. For example, a low oxygen level in tumor tissue impairs the effectiveness of radiation therapy.

Now, a team of scientists from the University of Michigan and two universities in Italy has demonstrated that an imaging system that uses special nanoparticles can provide a real-time, high-resolution chemical map that shows the distribution of chemicals of interest in a tumor.

It could lead to a way to help clinicians make better recommendations on cancer therapy tailored to a particular patient—precision medicine.

Climate change raises the threat of multiple hurricanes

Princeton researchers explored the increasing risk of multiple destructive storms hitting locations on the Atlantic and Gulf coasts. In this image, three storms formed in the Atlantic basin in 2017. 
Photo Credit: NASA

Getting hit with one hurricane is bad enough, but new research from Princeton Engineering shows that back-to-back versions may become common for many areas in coming decades.

Driven by a combination of rising sea levels and climate change, destructive hurricanes and tropical storms could become far more likely to hit coastal areas in quick succession, researchers found. In an article published Feb. 27 in the journal Nature Climate Change, the researchers said that in some areas, like the Gulf Coast, such double hits could occur as frequently as once every three years.

“Rising sea levels and climate change make sequential damaging hurricanes more likely as the century progresses,” said Dazhi Xi, a postdoctoral researcher and a former graduate student in civil and environmental engineering and the paper’s lead author. “Today’s extremely rare events will become far more frequent.”

Supernova From the Year 185: A Rare View of the Entirety of This Supernova Remnant

Dark Energy Camera captures the glowing remains of the first-ever documented supernova
Full Size Hi-Res Image
Image Credit: CTIO/NOIRLab/DOE/NSF/AURA T.A. Rector (University of Alaska Anchorage/NSF’s NOIRLab), J. Miller (Gemini Observatory/NSF’s NOIRLab), M. Zamani & D. de Martin (NSF’s NOIRLab)

The tattered shell of the first-ever historically recorded supernova was captured by the US Department of Energy-fabricated Dark Energy Camera, which is mounted on the National Science Foundation’s (NSF) Víctor M. Blanco 4-meter Telescope at Cerro Tololo Inter-American Observatory in Chile, a Program of NSF’s NOIRLab. RCW 86’s ring of debris is all that remains of a white-dwarf star that exploded more than 1800 years ago, when it was recorded by Chinese stargazers as a ‘guest star’.

Draped around the outer edges of this star-filled image are wispy tendrils that appear to be flying away from a central point, like the tattered remains of a burst balloon. These cloud-like features are thought to be the glowing remains of a supernova that was witnessed by Chinese astronomers in the year 185 C.E. When it appeared, this baffling addition to the night sky was referred to as a ‘guest star’ by ancient astronomers. It remained visible to the naked eye for about eight months before fading from view. 

How to generate new neurons in the brain

Mitochondria (green) in proliferating (A) and dormant (B) cells. Newly produced neurons (C) (red) in the dentate gyrus with cell nuclei (blue) and a marker for immature neurons (green).
Image Credit: © Knobloch Lab – UNIL

A team of biologists led by UNIGE and UNIL has discovered how to awaken neural stem cells and reactivate them in adult mice.

Some areas of the adult brain contain quiescent, or dormant, neural stem cells that can potentially be reactivated to form new neurons. However, the transition from quiescence to proliferation is still poorly understood. A team led by scientists from the Universities of Geneva (UNIGE) and Lausanne (UNIL) has discovered the importance of cell metabolism in this process and identified how to wake up these neural stem cells and reactivate them. Biologists succeeded in increasing the number of new neurons in the brain of adults and even elderly mice. These results, promising for the treatment of neurodegenerative diseases, are to be discovered in the journal Science Advances.

Stem cells have the unique ability to continuously produce copies of themselves and give rise to differentiated cells with more specialized functions. Neural stem cells (NSCs) are responsible for building the brain during embryonic development, generating all the cells of the central nervous system, including neurons.

Glacier National Park could provide climate haven for Canada lynx

An image of a Canada lynx taken by a motion sensitive camera as part of a study conducted in Glacier National Park
Photo Credit: Alissa Anderson

Glacier National Park is home to around 50 Canada lynx, more than expected, surprising scientists who recently conducted the first parkwide occupancy survey for the North American cat. 

The Washington State University-led survey reveals the iconic predator resides across most of Glacier’s 1,600 square-mile landscape, although at lower densities than in the core of its range further north. 

“The population in the park is still substantial and exceeded our expectations,” said Dan Thornton, WSU wildlife ecologist and senior author of the study published in the Journal of Wildlife Management. “Our results suggest the park could provide a much-needed climate refuge for the cats in the future.” 

Canada lynx are known for their long, black ear tufts and ability to hunt almost ghost-like across the surface of deep snow. Historically, the predator’s habitat extended from Alaska and Canada south down into much of the Northern United States. In the lower 48 today, the Canada lynx exists only in several disjunct populations in Maine, Minnesota, Montana, Colorado, Idaho and Washington.  

AI offers ‘paradigm shift’ in Stanford study of brain injury

Models discovered by the Constitutive Artificial Neural Network outperform existing models for brain tissue.
Image Credit: Ellen Kuhl

By helping researchers choose among thousands of available computational models of mechanical stress on the brain, AI is yielding powerful new insight on traumatic brain injury.

From the gridiron to the battlefield, the study of traumatic brain injury has exploded in recent years. Crucial to understanding brain injury is the ability to model the mechanical forces that compress, stretch, and twist the brain tissue and cause damage that ranges from fleeting to fatal.

Researchers at Stanford University now say they have tapped artificial intelligence to produce a profoundly more accurate model of how deformations translate into stresses in the brain and believe that their approach could reveal a more definitive understanding of when and why concussion sometimes leads to lasting brain damage, and other times not.

“The problem in brain modeling to date is that the brain is not a homogeneous tissue – it’s not the same in every part of the brain. Yet, trauma is often pervasive,” said Ellen Kuhl, professor of mechanical engineering, director of the Living Matter Lab, and senior author of a new study appearing in the journal, Acta Biomaterialia. “The brain is also ultrasoft, much like Jell-O, which makes both testing and modeling physical effects on the brain very challenging.”

Pseudomonas aeruginosa Bacteria produce a molecule that paralyzes immune system cells

Human endothelial cells use the molecules cadherin (green) and actin (purple) to form a flexible barrier around blood vessels. After adding the isolated LecB, their localization in the cell changes significantly: in the right half of the image, cadherin is no longer on the outside of the cell, but near the nucleus (blue).
Image Credit: Yubing Guo / Universities of Freiburg and Strasbourg

Bacteria of the species Pseudomonas aeruginosa are antibiotic-resistant hospital germs that can enter blood, lungs and other tissues through wounds and cause life-threatening infections. In a joint project, researchers from the Universities of Freiburg and Strasbourg in France have discovered a mechanism that likely contributes to the severity of P. aeruginosa infections. At the same time, it could be a target for future treatments. The results recently appeared in the journal EMBO Reports.

Many bacterial species use sugar-binding molecules called lectins to attach to and invade host cells. Lectins can also influence the immune response to bacterial infections. However, these functions have hardly been researched so far. A research consortium led by Prof. Dr. Winfried Römer from the Cluster of Excellence CIBSS - Centre for Integrative Biological Signaling Studies at the University of Freiburg and Prof. Dr. Christopher G. Mueller from the IBMC - Institute of Molecular and Cell Biology at the CNRS/University of Strasbourg has investigated the effect of the lectin LecB from P. aeruginosa on the immune system. It found that isolated LecB can render immune cells ineffective: The cells are then no longer able to migrate through the body and trigger an immune response. The administration of a substance directed against LecB prevented this effect and led to the immune cells being able to move unhindered again.

Flamingos form cliques with like-minded pals

The partner of one Caribbean flamingo helps it out in an argument with another pair.
Photo Credit Paul Rose

Flamingos form cliques of like-minded individuals within their flocks, new research shows.

Scientists analyzed the personalities and social behavior of Caribbean and Chilean flamingos.

Birds of both species tended to spend time with others whose personality was similar to their own.  

The study, by the University of Exeter and the Wildfowl & Wetlands Trust (WWT), reveals the complex nature of flamingo societies and could help in the management of captive flocks.

“Our previous research has shown that individual flamingos have particular ‘friends’ within the flock,” said Dr Paul Rose, from WWT and Exeter’s Centre for Research in Animal Behavior.

“In this study, we wanted to find out whether individual character traits explain why these friendships form.

“The answer is yes – birds of a feather flock together.

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