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Environmental Policies

A Flawed Model Threatens COVID-19 Research Progress

A promising path to fighting COVID and other coronaviruses may have been based on a serious mistake. Scientists had zeroed in on a part of the virus called the NiRAN domain, believed to be a powerful target for new antiviral drugs. But when a Rockefeller team revisited a highly cited 2022 study, they found the evidence didn’t hold up. Key molecules shown in the original virus model were actually missing. Their discovery could help prevent wasted time and resources in the race to develop better treatments—and highlights how even one bad blueprint can throw off years of research.

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The COVID-19 pandemic has brought attention to the urgent need for antiviral medications capable of treating coronavirus infections. In their quest to develop such treatments, researchers have focused on targeting the NiRAN domain, an enzyme region essential to viral replication that is common to many coronaviruses. A drug targeting this domain could potentially treat known diseases like COVID-19 and help prevent future pandemics caused by related viruses.

In 2022, scientists in China published a structural model describing how the NiRAN domain works. However, their work contains critical errors, according to Gabriel Small, a graduate fellow at Rockefeller University. The data does not support their conclusions, and the original paper’s findings could have sweeping implications for drug developers already working on antivirals based on flawed assumptions.

The Campbell and Darst labs were familiar with the NiRAN domain and its importance as a therapeutic target. They had previously characterized the molecular interactions that coordinate viral replication in SARS-CoV-2. The NiRAN domain is essential for helping viruses cap their RNA, a step that allows them to replicate and survive.

In one version of this process, the NiRAN domain uses GDP to attach a protective cap to the beginning of the virus’s RNA. Small had previously described this process in detail, and its structure was considered solved. However, the NiRAN domain can also use GTP to form a protective cap, and researchers were keen to discover the particulars of this mechanism.

The 2022 paper described a chain of chemical steps involving the breakdown of a water molecule, the attachment of the RNA’s 5′ phosphate end to the beta-phosphate end of GTP, and the subsequent transfer of the remaining portion of GTP to the RNA. The team’s evidence included a cryo-electron microscopy image showing the process caught in action, using a GTP mimic called GMPPNP.

However, Small was unable to access the data after downloading it, which raised red flags. Months later, when he finally accessed the data, he began to uncover significant flaws in the original paper’s conclusions. The placement of key molecules in the NiRAN domain’s active site violated basic rules of chemistry, causing severe atomic clashes and unrealistic charge interactions.

Small led an effort with Campbell and Darst to reprocess all of their data themselves. They found that there was no supporting image data for the claimed structures, and advanced methods designed to pick out rare particles turned up empty. The team’s findings were submitted to Cell, where they were published alongside the original paper, highlighting the importance of rigorous validation in biomedical research.

The corrections to high-profile papers are often overlooked when published in lower-tier journals. This confusion in the field could cause problems that reach far beyond the lab bench, Campbell adds, including costly reminders that basic biomedical research is not just academic but essential to real-world progress.

Companies keep their cards close to their chests, but we know that several industry groups are studying this, she says. Efforts based on a flawed structural model could result in years of wasted time and resources.

Educational Policy

700,000 Years Ahead of Their Teeth: The Carbs That Made Us Human

Long before evolution equipped them with the right teeth, early humans began eating tough grasses and starchy underground plants—foods rich in energy but hard to chew. A new study reveals that this bold dietary shift happened 700,000 years before the ideal dental traits evolved to handle it.

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The article reveals that early human ancestors began consuming carbohydrate-rich foods such as grains and underground plant organs before they had the ideal teeth to do so. This behavior drove evolution, leading to longer molars in modern humans that allow for efficient chewing of tough plant fibers.

A Dartmouth-led study analyzed fossilized hominin teeth for carbon and oxygen isotopes left behind from eating plants known as graminoids, which includes grasses and sedges. The researchers found that ancient humans gravitated toward consuming these plants far earlier than their teeth evolved to chew them efficiently. This shift in diet was a significant factor in the success of early humans.

The study’s findings suggest that the ability to adapt to new environments despite physical limitations was a key advantage for hominins. As anthropologists, they often assume behaviors on the basis of morphological traits, but these traits can take a long time to appear in the fossil record.

However, the researchers used isotope analysis to overcome this challenge and show that behavior can be a force of evolution in its own right. They analyzed the teeth of various hominin species, including Australopithecus afarensis, and found that they began consuming graminoids before their teeth evolved to chew them efficiently.

The study also explored how the consumption of different parts of graminoids progressed over millennia. The researchers found that all three species (hominins and two primates) veered away from fruits, flowers, and insects toward grasses and sedges between 3.4 million to 4.8 million years ago.

The team’s analysis revealed a significant lag between the emergence of novel feeding behaviors and the physical adaptations necessary to support them. This suggests that behavior can drive evolution, leading to changes in morphology and diet.

One possible explanation for this spike is that later hominins gained regular access to underground plant organs like tubers, bulbs, and corms, which provided a reliable source of carbohydrates. This shift would have made sense for a species growing in population and physical size.

The transition from grasses to these high-energy plant tissues may have created a glut of carbs that were perennial, allowing early humans to access them at any time of year to feed themselves and other people.

Measurements of hominin teeth showed that while they became consistently smaller, molars grew longer. The study found that the ratio flipped about 2 million years ago with Homo habilis and Homo ergaster, whose teeth exhibited a spurt of change in shape and size more suited to eating cooked tissues, such as roasted tubers.

Overall, this groundbreaking study sheds light on how early humans adapted to their environments and developed behaviors that drove evolution. By analyzing fossilized hominin teeth for carbon and oxygen isotopes, researchers were able to identify the key role that carbohydrates played in shaping human history.

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Cancer

Safer Non-Stick Coatings: Scientists Develop Alternative to Teflon

Scientists at the University of Toronto have developed a new non-stick material that rivals the performance of traditional PFAS-based coatings while using only minimal amounts of these controversial “forever chemicals.” Through an inventive process called “nanoscale fletching,” they modified silicone-based polymers to repel both water and oil effectively. This breakthrough could pave the way for safer cookware, fabrics, and other products without the environmental and health risks linked to long-chain PFAS.

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The scientific community has been working towards developing safer alternatives to per- and polyfluoroalkyl substances (PFAS), a family of chemicals commonly used in non-stick coatings. Researchers at the University of Toronto Engineering have made significant progress in this area by creating a new material that repels both water and grease about as well as standard PFAS-based coatings, but with much lower amounts of these chemicals.

Professor Kevin Golovin and his team have been working on developing alternative materials to replace Teflon, which has been used for decades due to its non-stick properties. However, the chemical inertness that makes Teflon so effective also causes it to persist in the environment and accumulate in biological tissues, leading to health concerns.

The researchers’ solution is a material called polydimethylsiloxane (PDMS), often sold as silicone. They have developed a new chemistry technique called nanoscale fletching, which bonds short chains of PDMS to a base material, resembling bristles on a brush. To improve the oil-repelling ability, they added the shortest possible PFAS molecule, consisting of a single carbon with three fluorines on it.

When coated on a piece of fabric and tested with various oils, the new coating achieved a grade of 6, placing it on par with many standard PFAS-based coatings. While this may seem like a small improvement, it’s a crucial step towards creating safer alternatives to Teflon and other PFAS-based materials.

The team is now working on further improving their material, aiming to create a substance that outperforms Teflon without using any PFAS at all. This would be a significant breakthrough in the field, paving the way for the development of even safer non-stick coatings for consumer products.

In conclusion, scientists have made significant progress in developing a safer alternative to Teflon and other PFAS-based materials. The new material has shown promising results, and further research is needed to improve its performance and scalability. As we move forward, it’s essential to prioritize the development of safe and sustainable technologies that minimize harm to both humans and the environment.

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Depression

The Unseen Toll of the Pandemic: How Stress and Isolation May Be Aging Your Brain

Even people who never caught Covid-19 may have aged mentally faster during the pandemic, according to new brain scan research. This large UK study shows how the stress, isolation, and upheaval of lockdowns may have aged our brains, especially in older adults, men, and disadvantaged individuals. While infection itself impacted some thinking skills, even those who stayed virus-free showed signs of accelerated brain aging—possibly reversible. The study highlights how major life disruptions, not just illness, can reshape our mental health.

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The COVID-19 pandemic has left an indelible mark on humanity, but its impact may go beyond the physical toll of the virus itself. A recent study suggests that even those who never contracted COVID-19 may have experienced accelerated brain aging due to the stresses and disruptions caused by the pandemic.

Led by experts at the University of Nottingham, the research team analyzed longitudinal brain scans from nearly 1,000 healthy adults, taken as part of the UK Biobank study. Some participants had scans before and after the pandemic, while others only had pre-pandemic scans. Using advanced imaging and machine learning, the researchers estimated each person’s “brain age” – how old their brain appeared to be compared to their actual age.

The findings were striking: people who lived through the pandemic showed signs of faster brain aging over time than those scanned entirely before it. The changes were most noticeable in older individuals, men, and those from more disadvantaged backgrounds. Notably, only participants who were infected with COVID-19 between their scans showed a drop in certain cognitive abilities, such as mental flexibility and processing speed.

“This study reminds us that brain health is shaped not only by illness but by our everyday environment,” said Dorothee Auer, Professor of Neuroimaging and senior author on the study. “The pandemic put a strain on people’s lives, especially those already facing disadvantage. We can’t yet test whether the changes we saw will reverse, but it’s certainly possible, and that’s an encouraging thought.”

Stress, isolation, and global disruption may have left their mark on people’s minds, leading to accelerated brain aging. However, the study highlights the possibility of reversibility, offering a glimmer of hope for those affected. The pandemic has taught us that even in the face of adversity, our brains can adapt and potentially recover – a testament to the resilience of the human spirit.

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