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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.

Earth & Climate

“Native Hubs: How Preserved Vegetation Supports Brunch and Global Food Security”

Preserving strips of native vegetation beside avocado orchards gives insects a buffet of wild pollen when blossoms are scarce, doubling their plant menu and boosting their resilience. Using cutting-edge eDNA metabarcoding, Curtin scientists revealed how this botanical diversity underpins pollination, a service vital to 75% of crops and our brunch-worthy avocados. Their findings urge farmers to weave natural habitat back into farmland to secure food supplies for a swelling global population.

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The future of brunch, as we know it, might depend on patches of native vegetation preserved alongside farmland. New research from Curtin University reveals the hidden role of these habitats in supporting the insects that keep crops – and our breakfast menus – thriving.

The study, published this week, found that insect communities in avocado orchards adjacent to native remnant vegetation foraged on more than twice as many plant species during times when crop flowering was limited. This is a significant finding, as it suggests that preserving natural habitats can enhance the resilience of insect communities and contribute to greater food security.

Lead author Dr Joshua Kestel explained that their research used a novel method – environmental DNA (eDNA) metabarcoding – to quantify the diversity of pollen collected by entire insect communities. This approach allowed them to demonstrate that natural vegetation adjacent to orchards may enhance the resilience of insect communities, potentially contributing to greater food security.

Co-author Associate Professor Paul Nevill highlighted the importance of this research, noting that insects pollinate 75% of all agricultural crops, yet many face extinction. In order to meet the food needs of the planet, diverse and healthy insect communities play a critical role in supporting essential ecosystem services such as pollination and biological control of pests.

The researchers collected over 2,000 insect specimens and identified more than 250 plant taxa from eDNA, including crops, weeds, and native Australian flora. Their findings have significant implications for global food security, particularly given the projected increase in population by 2050, requiring a 25-75% boost in agricultural productivity.

The team recommended incorporating standardized biodiversity surveys into regular farm monitoring, protecting agroecosystems by recognizing the value of natural vegetation, and revegetating uncultivated land within orchards. By preserving native habitats, we can safeguard not only our brunch menus but also global food security for generations to come.

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Energy Issues

A Revolutionary Sponge: Harnessing Sunlight for Efficient Desalination

In a leap toward sustainable desalination, researchers have created a solar-powered sponge-like aerogel that turns seawater into drinkable water using just sunlight and a plastic cover. Unlike previous materials, this new 3D-printed aerogel maintains its efficiency at larger sizes, solving a key scalability issue. In outdoor tests, it produced clean water directly from the ocean without any electricity, pointing to a future of low-cost, energy-free freshwater production.

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The sun-powered sponge, created by researchers in ACS Energy Letters, has the potential to revolutionize desalination methods. Most of Earth’s water is found in oceans, which are too salty for human consumption. Traditional desalination plants require large amounts of energy, but this innovative sponge-like material uses sunlight and a simple plastic cover to produce freshwater.

Previous attempts at creating spongy materials have been made using hydrogels inspired by loofahs. However, these hydrogels are limited in their ability to transport liquid water or water vapor due to their squishy and liquid-filled nature. In contrast, the researchers behind this new sponge-like material used a more rigid aerogel containing solid pores that can efficiently release water through evaporation.

The team developed a paste of carbon nanotubes and cellulose nanofibers, which they 3D-printed onto a frozen surface to create a sponge-like material. Each layer solidified before the next was added, resulting in evenly distributed tiny vertical holes. The researchers tested square pieces of the material at different sizes and found that the larger pieces released water through evaporation at rates as efficient as the smaller ones.

In an outdoor test, the sponge-like material was placed in a cup containing seawater and covered by a curved plastic cover. Sunlight heated the top of the spongy material, evaporating just the water into water vapor. The vapor collected on the plastic cover and dripped into a funnel and container below. After 6 hours in natural sunlight, the system generated about 3 tablespoons of potable water.

This revolutionary sponge has the potential to provide a simple, scalable solution for energy-free desalination. With funding from various organizations, including the National Natural Science Foundation of China, the researchers continue to explore the possibilities of this innovative material.

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Disaster Plan

“Unraveling Ancient Secrets: Indian DNA Holds Clues to Neanderthal Genome”

India’s complex ancestry—intertwined with Iranian farmers, Steppe herders, and local hunter-gatherers—has now been decoded through genomic data from 2,762 people. The study uncovers surprising levels of Neanderthal and Denisovan DNA, and how ancient migrations and community traditions have shaped today’s genetic diversity and disease risks.

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The study of genetics has long been shaped by the availability of data from various regions around the world. However, despite its vast population diversity, India remains underrepresented in global genetic datasets. A recent study published in Cell Press’s journal Cell aimed to fill this critical gap and reshape our understanding of how ancient migrations, archaic admixture, and social structures have influenced Indian genetic variation.

The researchers analyzed genomic data from over 2,700 people across India, capturing genetic variation from most geographic regions, linguistic groups, and communities. Their findings revealed that the majority of modern-day Indians’ ancestry can be traced back to Neolithic Iranian farmers, Eurasian Steppe pastoralists, and South Asian hunter-gatherers.

“This study fills a critical gap and reshapes our understanding of how ancient migrations, archaic admixture, and social structures have shaped Indian genetic variation,” says senior author Priya Moorjani of the University of California, Berkeley. “Studying these subpopulations allows us to explore how ancient ancestry, geography, language, and social practices interacted to shape genetic variation.

The researchers used data from the Longitudinal Aging Study in India (LASI) and generated whole-genome sequences from 2,762 individuals in India, including people who spoke a range of different languages. They used these data to reconstruct the evolutionary history of India over the past 50,000 years at fine scale, showing how history impacts adaptation and disease in present-day Indians.

Their study showed that most Indians derive ancestry from populations related to three ancestral groups: Neolithic Iranian farmers, Eurasian Steppe pastoralists, and South Asian hunter-gatherers. This is a significant finding, as it highlights the complex population history of India and its impact on genetic variation related to disease.

The researchers also focused on the impact of archaic hominin ancestry – specifically, Neanderthal and Denisovan – on disease susceptibility. They found that some genes inherited from these archaic groups have an impact on immune functions.

One of the most striking findings was that India harbors the highest variation in Neanderthal ancestry among non-Africans. This allowed the researchers to reconstruct around 50% of the Neanderthal genome and 20% of the Denisovan genome from Indian individuals, more than any other previous archaic ancestry study.

The limitations of this work were acknowledged by the researchers, who noted that the limited availability of ancient DNA from South and Central Asia will require refinement as more data becomes available. They plan to continue studying the LASI cohort to enable a closer look at the source of genetic adaptations and disease variants across India.

Overall, this study provides a deeper understanding of the origin of functional variation and informs precision health strategies in India. It also highlights the importance of including diverse populations in genetic studies to prevent biased interpretations of genetic patterns and uncover functional variation related to all major communities.

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