. Scientific Frontline

Tuesday, January 14, 2025

Tracking delivery: new technology for nanocarriers

Lipid nanoparticles visualized using SCP-Nano technology at the cellular level in lung tissue.
Image Credit: © Ali Ertürk / Helmholtz Munich

How can we ensure that life-saving drugs or genetic therapies reach their intended target cells without causing harmful side effects? Researchers at Helmholtz Munich, LMU and Technical University Munich (TUM) have taken an important step to answer this question. They have developed a method that, for the first time, enables the precise detection of nanocarriers – tiny transport vehicles – throughout the entire mouse body at a single-cell level. This innovation, called “Single-Cell Profiling of Nanocarriers” or short “SCP-Nano”, combines advanced imaging with artificial intelligence to provide unparalleled insights into the functionality of nanotechnology-based therapies. The results, published in Nature Biotechnology, pave the way for safer and more effective treatments, including mRNA vaccines and gene therapies.

Nanocarriers will play a central role in the next wave of life-saving medicines. They enable the targeted delivery of drugs, genes, or proteins to cells within patients. With SCP-Nano, researchers can analyze the distribution of extremely low doses of nanocarriers throughout the entire mouse body, visualizing each cell that has taken them up. SCP-Nano combines optical tissue clearing, light-sheet microscopy imaging, and deep-learning algorithms. First, whole mouse bodies are made transparent. After the three-dimensional imaging of whole mouse bodies, nanocarriers within the transparent tissues can then be identified down to the single-cell level. By integrating AI-based analysis, researchers can quantify which cells and tissues are interacting with the nanocarriers and precisely where this occurs.

Researchers create lab model that could lead to new, non-hormonal birth control methods

Oregon Health & Science University researchers have developed a new lab model to study how changes in cervical mucus during the menstrual cycle help regulate fertility. This model could help develop new, non-hormonal birth control methods for women.
Photo Credit: OHSU/Christine Torres Hicks

Oregon Health & Science University researchers have developed a new lab model to study how changes in cervical mucus during the menstrual cycle help regulate fertility. This model could help develop new, non-hormonal birth control methods for women.

The study, published in the journal Biology of Reproduction, is part of ongoing work by senior author Leo Han, M.D., M.P.H., associate professor of obstetrics and gynecology in the OHSU School of Medicine and the OHSU Oregon National Primate Research Center. Han is a complex family planning specialist whose research focuses on developing new, non-hormonal contraceptives. 

In this study, his research team analyzed the genetic activity in lab-cultured cervical cells, identifying hundreds of different genes that could be drug targets for birth control that uses innovative new methods to block sperm. 

Gene editing extends lifespan in mouse model of prion disease

Broad Communications Eric Minikel and Sonia Vallabh run a lab with a singular focus: preventing and treating prion disease within their lifetime.
Photo Credit: Maria Nemchuk

Researchers at the Broad Institute of MIT and Harvard have developed a gene-editing treatment for prion disease that extends lifespan by about 50 percent in a mouse model of the fatal neurodegenerative condition. The treatment, which uses base editing to make a single-letter change in DNA, reduced levels of the disease-causing prion protein in the brain by as much as 60 percent. 

There is currently no cure for prion disease, and the new approach could be an important step towards treatments that prevent the disease or slow its progression in patients who have already developed symptoms. A base-editing approach could also likely be a one-time treatment for all prion disease patients regardless of the genetic mutation causing their disease. 

The work, led by Broad senior group leaders Sonia Vallabh and Eric Minikel, as well as Broad core institute member David Liu, is the first demonstration that lowering levels of the prion protein improves lifespan in animals that have been infected with a human version of the protein. The findings appear in Nature Medicine.

NIH-funded study finds cases of ME/CFS increase following SARS-CoV-2

Photo Credit: Bruno Aguirre

New findings from the National Institutes of Health’s (NIH) Researching COVID to Enhance Recovery (RECOVER) Initiative suggest that infection with SARS-CoV-2, the virus that causes COVID-19, may be associated with an increase in the number of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) cases. According to the results, 4.5% post-COVID-19 participants met ME/CFS diagnostic criteria, compared to 0.6% participants that had not been infected by SARS-CoV-2 virus.  RECOVER is NIH’s national program to understand, diagnose, prevent, and treat Long COVID.

The research team, led by Suzanne D. Vernon, Ph.D., from the Bateman Horne Center in Salt Lake City, examined adults participating in the RECOVER adult cohort study to see how many met the IOM clinical diagnostic criteria for ME/CFS at least six months after their infection. Included in the analysis were 11,785 participants who had been infected by SARS-CoV-2 and 1,439 participants who had not been infected by the virus. Findings appear in the Journal of General Internal Medicine.

Monday, January 13, 2025

Inorganic and biocatalysts work together to reduce CO2

First author Panpan Wang tested the catalysis cascade in the laboratory.
Photo Credit: Ruhr-Universität Bochum / Marquard

In a hybrid cascade, climate-damaging CO2 is turned back into valuable methanol. An international research team has shown how this works. 

In order to recover valuable substances from CO2, it must be reduced in many individual steps. If electrocatalysis is used for this, many potentially different potential molecules are formed, which cannot necessarily be used. Biocatalysts, on the other hand, are selective and only produce one product – but they are also very sensitive. An international research team led by Professor Wolfgang Schuhmann from the Center for Electrochemistry at Ruhr-Universität Bochum, Germany, and Dr. Felipe Conzuelo from the Universidade Nova de Lisboa, Portugal, has developed a hybrid catalysis cascade that makes use of the advantages of both processes. The researchers report in the journal “Angewandte Chemie Interational Edition” from December 23, 2024.

Polygamy is (not) for the birds

Rafael S. Marcondes, a faculty fellow in ecology and evolutionary biology at Rice
Photo Credit: Alex Becker/Rice University

Researchers at Rice University have uncovered new insights into the evolution of bird behavior, revealing why certain mating systems persist while others disappear over time. In a recent paper published in the journal Evolution, Rafael S. Marcondes and Nicolette Douvas reveal that lekking — a mating system where males display for females without forming lasting bonds — is an evolutionarily stable strategy. In contrast, resource-defense polygamy, where one sex — usually but not always the male — guards territories to attract mates, is highly unstable and often reverts to monogamy.

“This research not only examines how mating behaviors influence species survival but also sheds light on larger evolutionary questions,” said Marcondes, the corresponding author and a faculty fellow in ecology and evolutionary biology at Rice. “By studying birds, we’re uncovering principles that may resonate across other species too.”

The study analyzed data from more than 60% of the world’s bird species — approximately 6,620 species — making it one of the most comprehensive analyses of its kind.

Oxford researchers develop blood test to enable early detection of multiple cancers

Photo Credit: Fernando Zhiminaicela

Oxford University researchers have unveiled a new blood test, powered by machine learning, which shows real promise in detecting multiple types of cancer in their earliest stages, when the disease is hardest to detect.

Named TriOx, this innovative test analyses multiple features of DNA in the blood to identify subtle signs of cancer, which could offer a fast, sensitive and minimally invasive alternative to current detection methods.

The study, published in Nature Communications, showed that TriOx accurately detected cancer (including in its early stages) across six cancer types and reliably distinguished those people who had cancer from those that did not.

Cancers are more likely to be cured if they’re caught early, and early treatment is also much cheaper for healthcare systems. While the test is still in the development phase, it demonstrates the promise of blood-based early cancer detection, a technology that could revolutionize screening and diagnostic practices.

A team of researchers at the University of Oxford have developed a new liquid biopsy test capable of detecting six cancers at an early stage. The cancer types evaluated in this study were colorectal, esophageal, pancreatic, renal, ovarian and breast.

Apex predators in prehistoric Colombian oceans would have snacked on killer whales today

. Illustration of some of the apex predators in the Paja Formation biota with a human for scale.
Illustration Credit: Guillermo Torres, Hace Tiempo, Instituto von Humboldt.

Predators at the top of a marine food chain 130 million years ago ruled with more power than any modern species, McGill research into a marine ecosystem from the Cretaceous period revealed. 

The study, published in the Zoological Journal of the Linnean Society, reconstructs the ecosystem of Colombia’s Paja Formation, and finds it was teeming with marine reptiles reaching over 10 meters in length that inhabited a seventh trophic level.  

Trophic levels are the layers or ranks within a food chain that describe the roles organisms play in an ecosystem based on their source of energy and nutrients. Essentially, they help define who eats whom in an ecosystem. Today’s marine trophic levels cap at six, with creatures like killer whales and great white sharks. 

The discovery of giant marine reptile apex predators occupying a seventh trophic level underscores the Paja ecosystem’s unmatched diversity and complexity, offering a rare view into an evolutionary arms race among predators and prey. 

Unraveling the Mysteries of DNA Damage in the Brain

Immunofluorescent staining of mouse brain, showing neurons and glial cells in the hippocampus. Blue are cell nuclei, while green are microfilaments of the cell extensions. Red is a marker of DNA damage and is predominantly in the neurons.
Image Credit: Aris Polyzos/Berkeley Lab

Brain cells receive sensory inputs from the outside world and send signals throughout the body telling organs and muscles what to do. Although neurons comprise only 10% of brain cells, their functional and genomic integrity must be maintained over a lifetime. Most dividing cells in the body have well-defined checkpoint mechanisms to sense and correct DNA damage during DNA replication.

Neurons, however, do not divide. For this reason, they are at greater risk of accumulating damage and must develop alternative repair pathways to avoid dysfunction. Scientists do not understand how neuronal DNA damage is controlled in the absence of replication checkpoints.

A recent study led by Cynthia McMurray and Aris Polyzos in Lawrence Berkeley National Laboratory’s (Berkeley Lab’s) Molecular Biophysics and Integrated Bioimaging Division addressed this knowledge gap, shedding light on how DNA damage and repair occur in the brain. Their results suggest that DNA damage itself serves as the checkpoint, limiting the accumulation of genomic errors in cells during natural aging. The paper, published in Nature Communications, offers clues to understanding the potential role of unrepaired DNA damage in the progression of neurodegenerative diseases and could help inform the development of therapies.

Team makes sustainable aviation fuel additive from recycled polystyrene

Illinois Sustainable Technology Center research scientist Hong Lu and his colleagues developed a method for converting waste polystyrene into a sustainable jet fuel additive, ethylbenzene. Their work overcomes a key obstacle to the wider use of sustainable aviation fuels.
Photo Credit: Fred Zwicky

A new study overcomes a key challenge to switching commercial aircraft in the U.S. from their near-total reliance on fossil fuels to more sustainable aviation fuels. The study details a cost-effective method for producing ethylbenzene — an additive that improves the functional characteristics of sustainable aviation fuels — from polystyrene, a hard plastic used in many consumer goods. 

The findings are reported in the journal ACS Sustainable Chemistry and Engineering.  

Fuels derived from waste fat, oil, grease, plant biomass or other nonpetroleum sources lack sufficient levels of aromatic hydrocarbons, which help keep fuel systems operational by lubricating mechanical parts and swelling the seals that protect from leaks during normal operations, said Hong Lu, a research scientist at the Illinois Sustainable Technology Center who led the new research. ISTC is a division of the Prairie Research Institute at the University of Illinois Urbana-Champaign. 

While ethylbenzene is an aromatic hydrocarbon and can be derived from fossil fuels, finding a sustainable way to produce it would aid the aviation industry’s conversion to sustainable jet fuels. 

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