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Unlocking the Secrets of mRNA Vaccines: A Breakthrough in Cellular Regulation Revealed

A team of researchers has uncovered a key cellular mechanism that affects the function of mRNA vaccines and therapeutics. Their study provides the first comprehensive understanding of how mRNA vaccines are delivered, processed, and degraded within cells — a breakthrough that could pave the way for more effective vaccines and RNA-based treatments.

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A team of researchers led by Dr. KIM V. Narry has made a groundbreaking discovery in understanding how mRNA vaccines are delivered, processed, and degraded within cells. Their study, published in Science, sheds light on the cellular mechanisms that affect the function of mRNA vaccines and therapeutics, paving the way for more effective treatments.

Messenger RNA (mRNA) plays a crucial role in mRNA vaccines, such as those used for COVID-19, and is also a promising tool for treating diseases like cancer and genetic disorders. When foreign mRNA enters cells, it must evade the body’s natural defense mechanisms to be effective. However, the detailed mechanisms by which mRNA is regulated inside cells have remained largely unknown.

The research team employed CRISPR-based knockout screening to identify the cellular factors involved in the delivery of mRNA into cells. This approach revealed three key factors that facilitate the cellular uptake or surveillance of exogenous mRNAs:

1. Heparan sulfate (HSPG), a sulfated glycoprotein on the cell surface, plays a crucial role in attracting LNPs and facilitating mRNA entry into the cell.
2. V-ATPase, a proton pump at the endosome, acidifies the vesicle and causes LNPs to become positively charged, enabling them to temporarily disrupt the endosomal membrane and release the mRNA into the cytoplasm.
3. TRIM25, a protein involved in the cellular defense mechanism, binds to and induces the rapid degradation of exogenous mRNAs, preventing their function.

The study highlights that mRNA molecules containing a special modification called N1-methylpseudouridine (m1Ψ) can evade TRIM25 detection, enhancing the stability and effectiveness of mRNA vaccines. This discovery emphasizes the importance of this modification in enhancing the therapeutic potential of mRNA-based treatments.

Additionally, the research demonstrates that proton ions serve as immune signaling molecules, providing new insights into how cells protect themselves from foreign RNA.

Dr. KIM V. Narry emphasized the importance of understanding these processes, stating, “Understanding how cells respond to mRNA vaccines is key to improving mRNA therapeutics. To develop effective RNA treatments, we need to find ways to bypass the cellular defense mechanisms and harness the endosomal system effectively.”

This research paves the way for more efficient mRNA vaccine delivery and offers a framework for future development of RNA-based therapies. The findings underscore the critical importance of early intervention and provide new directions for developing more effective treatments for a variety of diseases.

Biodiversity

Unveiling Hidden Gems: Two New Crocodile Species Discovered in Mexico

Biologists have discovered two previously unknown species of crocodiles, one living on the island of Cozumel and the other on the atoll of Banco Chinchorro, both off the Yucat n Peninsula. The findings challenge long-held assumptions about the American crocodile (Crocodylus acutus) and highlight the urgent need for conservation efforts, the researchers say.

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The American crocodile, a species once thought to be widespread across the Caribbean, Central America, and Mexico’s Pacific coast, has been hiding secrets. Researchers from McGill University, in collaboration with Mexican scientists, have made a groundbreaking discovery that challenges long-held assumptions about this iconic creature. Two previously unknown species of crocodiles have been found on the island of Cozumel and the atoll of Banco Chinchorro, both located off the Yucatán Peninsula.

“Biodiversity is disappearing faster than we can discover what we’re losing,” said Biology Professor Hans Larsson, the principal investigator. “Most species of crocodiles are already endangered, and rapid shoreline development threatens nearly every population. Our research aimed to uncover the true diversity of crocodiles on these isolated islands.”

Larsson and his team analyzed the genetic sequences of crocodile populations from Cozumel and Banco Chinchorro. By comparing these sequences to those of crocodiles across the Caribbean, Central America, and Mexico’s Pacific coast, they found striking levels of genetic differentiation, leading them to conclude that these populations were not simply variants of Crocodylus acutus.

“These results were totally unexpected,” former Larsson graduate student and lead author José Avila-Cervantes said. “We assumed Crocodylus acutus was a single species ranging from Baja California to Venezuela and across the Caribbean. Our study is the first to extensively explore genomic and anatomical variation in these animals.”

This discovery has significant conservation implications, as the newly identified species live in small, isolated populations, each numbering fewer than 1,000 breeding individuals. While both populations appear stable, their limited numbers and habitat restrictions make them vulnerable.

“The rapid loss of biodiversity can only be slowed if we know what species are most at risk,” said Larsson. “Now that we recognize these crocodiles as distinct species, it’s crucial to protect their habitats. Limiting land development and implementing careful conservation strategies on Cozumel and Banco Chinchorro will be key to ensuring their survival.”

The research was conducted with the help of local colleagues, including Pierre Charruau at El Colegio de la Frontera Sur in Mexico. The team captured and released crocodiles, collecting blood and scale samples for analysis. Genetic sequencing was carried out at McGill by José Avila-Cervantes during his graduate studies, with additional research on skull morphology by fellow McGill graduate student Hoai-Nam Bui.

This research was funded by the Canadian Foundation for Innovation, the Digital Research Alliance of Canada), the Comisión Nacional para el Conocimiento y Uso de la Biodiversidad, and the Natural Sciences and Engineering Research Council of Canada.

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Biochemistry

Unraveling Nature’s Secret: How Velvet Worm Slime Could Revolutionize Sustainable Materials Design

A new discovery about the slime ejected by velvet worms could revolutionize sustainable material design. The findings outline how a naturally occurring protein structure, conserved across species from Australia, Singapore and Barbados over nearly 400 million years of evolution, enables the slime’s transformation from liquid to fiber and back again. It’s a discovery that could inspire next-generation recyclable bioplastics.

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The discovery of the remarkable properties of velvet worm slime has sent shockwaves through the scientific community, offering new hope for sustainable material design. Researchers from McGill University have made a groundbreaking find that could lead to the development of next-generation recyclable bioplastics.

Velvet worms, small caterpillar-like creatures found in humid forests of the southern hemisphere, possess an extraordinary ability – their slime can transform from liquid to fibre and back again. This remarkable property has puzzled scientists for centuries, but a team led by Matthew Harrington, a chemistry professor and Canada Research Chair in green chemistry, has finally decoded the molecular structure behind this phenomenon.

Using protein sequencing and AI-driven structure prediction (AlphaFold), the researchers identified previously unknown proteins in the slime that function similarly to cell receptors in the immune system. These receptor proteins appear to link large structural proteins during fibre formation, enabling the slime’s remarkable reversibility.

The implications of this discovery are profound. Traditional plastics and synthetic fibres require energy-intensive processes to manufacture and recycle, often involving heat or chemical treatments. In contrast, the velvet worm uses simple mechanical forces – pulling and stretching – to generate strong, durable fibres from biorenewable precursors, which can later be dissolved and reused without harmful byproducts.

While a plastic bottle that dissolves in water may seem like an impractical solution, Harrington believes that adjusting the chemistry of this binding mechanism could overcome this limitation. The team’s next challenge will be to experimentally verify the binding interactions and explore whether the principle can be adapted for engineered materials.

The study was co-authored by researchers from McGill University and Nanyang Technological University (NTU) in Singapore, highlighting the importance of international collaboration in addressing pressing global challenges.

As Harrington aptly puts it, “Nature has already figured out a way to make materials that are both strong and recyclable. By decoding the molecular structure of velvet worm slime, we’re now one step closer to replicating that efficiency for the materials we use every day.”

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Agriculture and Food

The Dark Side of Cannabis Use in Pregnancy

A systematic evidence review finds that consuming cannabis while pregnant appears to increase the odds of preterm birth, low birth weight and infant death.

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The Dark Side of Cannabis Use in Pregnancy

A recent systematic review has raised significant concerns about the risks associated with consuming cannabis while pregnant. The study, conducted by researchers at Oregon Health & Science University, analyzed 51 observational studies involving over 21 million people to examine the potential adverse effects of cannabis use during pregnancy.

The findings are alarming: consuming cannabis appears to increase the odds of preterm birth, low birth weight, and infant death. These results are consistent with definitive evidence in nonhuman primate models exposed to THC, the main psychoactive compound in cannabis.

The placenta, a vital organ responsible for supplying oxygen and nutrients to the fetus, is particularly affected by cannabis use during pregnancy. Research has shown that cannabis can lead to decreased blood flow and reduced availability of oxygen in the placenta, ultimately affecting fetal development and growth.

While many pregnant women may view cannabis as a harmless substance due to its increasingly widespread legalization, the reality is far more concerning. Cannabis remains a Schedule 1 substance under federal law, and its use during pregnancy is not recommended by medical professionals.

The lead author of the study, Dr. Jamie Lo, emphasizes the importance of prioritizing fetal health over any perceived benefits of cannabis use during pregnancy. “Abstinence is ideal,” she notes, “but it’s not realistic for many patients.” In such cases, a harm-reduction approach can be recommended, advising pregnant women to reduce their cannabis consumption and frequency to minimize potential risks.

The research, part of the Systematically Testing the Evidence on Marijuana (STEM) project, highlights the need for more comprehensive studies on the effects of cannabis use during pregnancy. By understanding these risks, healthcare providers can better counsel expectant mothers and promote healthier outcomes for both mother and child.

Sources:

* The study was published in JAMA Pediatrics.
* Funding for this research was provided by the Office of Rural Health in the Veterans Health Administration of the U.S. Department of Veterans Affairs and the National Institute on Drug Abuse of the National Institutes of Health.

Key Takeaways:

* Consuming cannabis during pregnancy appears to increase the odds of preterm birth, low birth weight, and infant death.
* The placenta is particularly affected by cannabis use during pregnancy, leading to decreased blood flow and reduced availability of oxygen.
* A harm-reduction approach can be recommended for pregnant women who cannot abstain from cannabis use.
* More comprehensive studies are needed to fully understand the effects of cannabis use during pregnancy.

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