Efficient mRNA delivery by branched lipids

A cross-section of an LNP-RNA. The mRNA (red) is encapsulated by lipids (blue spheres with tails.
 Image Credit: Yusuke Sato

Scientific Frontline: "At a Glance" Summary

• Main Discovery: A novel branched ionizable lipid, CL4F 8-6, significantly improves the storage stability and intracellular delivery efficiency of mRNA encapsulated in lipid nanoparticles (LNPs).
• Methodology: Researchers synthesized a systematic library of 32 branched ionizable lipids defined by symmetry and carbon number, then screened them to identify correlations between lipid structure, microviscosity, and in vivo performance.
• Key Data: The optimized lipid formulation achieved a 77% suppression of a target gene in mice following a single dose.
• Significance: This research establishes a positive correlation between lipid symmetry/microviscosity and LNP stability, overcoming previous barriers in systematic lipid analysis and enhancing gene editing potential.
• Future Application: Development of more stable and effective mRNA vaccines and gene-editing therapies with targeted organ selectivity.
• Branch of Science: Pharmaceutical Sciences and Nanotechnology
• Additional Detail: The study identified that the length of the branched lipid chains directly influences which organs, specifically the liver or spleen, express the delivered proteins.

Searching for traces of dark matter with neutron spin clocks

Part of the experimental apparatus in the laboratory in Bern with PhD student Ivo Schulthess.
Credit: zvg/mad/Courtesy of F. Piegsa

With the use of a precision experiment developed at the University of Bern, an international research team has succeeded in significantly narrowing the scope for the existence of dark matter. The experiment was carried out at the European Research Neutron Source at the Institute Laue-Langevin in France, and makes an important contribution to the search for these particles, of which little remains known.

Cosmological observations of the orbits of stars and galaxies enable clear conclusions to be drawn about the attractive gravitational forces that act between the celestial bodies. The astonishing finding: visible matter is far from sufficient for being able to explain the development or movements of galaxies. This suggests that there exists another, so far unknown, type of matter. Accordingly, in the year 1933, the Swiss physicist and astronomer Fritz Zwicky inferred the existence of what is known now as dark matter. Dark matter is a postulated form of matter which isn’t directly visible but interacts via gravity, and consists of approximately five times more mass than the matter with which we are familiar.

Recently, following a precision experiment developed at the Albert Einstein Center for Fundamental Physics (AEC) at the University of Bern, an international research team succeeded in significantly narrowing the scope for the existence of dark matter. With more than 100 members, the AEC is one of the leading international research organizations in the field of particle physics. The findings of the team, led by Bern, have now been published in the highly-regarded journal Physical Review Letters.

Evolution of tree roots may have driven mass extinctions

Scientists collect rock samples on Ymer Island in eastern Greenland, one of several sites whose analysis provided insight into the chemical makeup of lake beds in the Devonian Period.
Photo Credit: John Marshall, University of Southampton

The evolution of tree roots may have triggered a series of mass extinctions that rocked the Earth’s oceans during the Devonian Period over 300 million years ago, according to a study led by scientists at IUPUI, along with colleagues in the United Kingdom.

Evidence for this new view of a remarkably volatile period in Earth’s pre-history is reported in the Geological Society of America Bulletin, one of the oldest and most respected publications in the field of geology. The study was led by Gabriel Filippelli, Chancellor’s Professor of Earth Sciences in the School of Science at IUPUI, and Matthew Smart, a Ph.D. student in his lab at the time of the study.

“Our analysis shows that the evolution of tree roots likely flooded past oceans with excess nutrients, causing massive algae growth,” Filippelli said. “These rapid and destructive algae blooms would have depleted most of the oceans’ oxygen, triggering catastrophic mass extinction events.”

Previously unseen processes reveal path to better rechargeable battery performance

Materials science and engineering postdoctoral researcher Wenxiang Chen is the first author of a new study that applies imaging techniques common in ceramics and metallurgy to rechargeable ion battery research. 
Photo by Fred Zwicky

To design better rechargeable ion batteries, engineers and chemists from the University of Illinois Urbana-Champaign collaborated to combine a powerful new electron microscopy technique and data mining to visually pinpoint areas of chemical and physical alteration within ion batteries.

A study led by materials science and engineering professors Qian Chen and Jian-Min Zuo is the first to map out altered domains inside rechargeable ion batteries at the nanoscale – a 10-fold or more increase in resolution over current X-ray and optical methods.

The findings are published in the journal Nature Materials.

The team said previous efforts to understand the working and failure mechanisms of battery materials have primarily focused on the chemical effect of recharging cycles, namely the changes in the chemical composition of the battery electrodes.

A new electron microscopy technique, called four-dimensional scanning transmission electron microscopy, allows the team to use a highly focused probe to collect images of the inner workings of batteries.

A mysterious outbreak of bone-eating tb resembled an ancestral form

Scientific Frontline: "At a Glance" Summary: Tuberculosis Mutation and Mobility

• Main Discovery: Researchers identified that a highly mobile strain of tuberculosis capable of infecting bone tissue possesses an active secretion factor called EsxM, which closely resembles an ancestral bacterial lineage rather than modern lung-restricted strains.
• Methodology: Scientists conducted genetic sequencing on the infectious strain and compared its genetic variants against 225 tuberculosis strains, focusing on secreted factors. They further validated their findings by analyzing 3,236 strains and manipulating the EsxM factor in laboratory macrophage cultures to directly observe cellular mobility.
• Key Data: While tuberculosis spreads beyond the lungs in only 2 percent of typical United States cases, this specific outbreak resulted in severe bone infections in four out of six initially identified individuals, representing a highly anomalous transmission rate.
• Significance: The study reveals that modern tuberculosis strains have evolutionarily silenced the EsxM secretion factor to remain isolated in the lungs for optimal airborne transmission, whereas the ancestral active version promotes aggressive bacterial migration throughout the host's body.
• Future Application: Uncovering the genetic drivers of bacterial mobility provides a foundational understanding that could inform future targeted therapeutics designed to prevent tuberculosis and similar pathogens from disseminating into vulnerable extrapulmonary regions.
• Branch of Science: Molecular Genetics, Microbiology, Epidemiology, and Evolutionary Biology.
• Additional Detail: The ancestral lineage 1 of tuberculosis, which retains the active migratory EsxM secretion factor, is still actively circulating and is predominantly found in South and Southeast Asia.

Workplace cafeteria study finds no evidence that physical activity calorie-equivalent labeling changes food purchasing

PACE labels alongside menus 
Credit: University of Cambridge

More than three in five UK adults are overweight or obese, increasing their risk of diseases such as type 2 diabetes and cancer. A major factor that contributes to this is excess energy intake – in other words, eating too many calories. Measures that can help reduce energy intake could help tackle the obesity problem.

In the UK, adults eat as many as a third of their meals out of home, including in workplace cafeterias, and these meals are often much higher in calories than meals eaten at home. Since April 2022 calorie labelling is now required on food and drink served out of the home in businesses employing 250 or more people. While many people welcome this information, evidence for its effectiveness in reducing calories purchased or consumed is limited in quantity and quality. For example, two previous studies conducted by the authors in nine worksite cafeterias found no evidence for an effect of simple calorie labelling (kcal) on calories purchased.

Another option is to show the amount of exercise required to burn off these calories – so-called PACE (physical activity calorie-equivalent) labels – for example, a 1014kcal ‘large battered haddock’ portion would take upwards of five hours walking (278 minutes) to burn off. A recent systematic review – a type of study that brings together existing evidence – concluded that PACE labels may reduce energy selected from menus and decrease the energy consumed when compared with simple calorie labels or no labels, but only one of the 15 studies reviewed was in a ‘real world’ setting.

How Pathogens Hijack Immune System to Cause Vaccine-Enhanced Disease

Associate Professor Steven Szczepanek (standing, left) with graduate students Tyler Gavitt (seated) and Arlind Mara (standing, right).
Photo Credit: Jason Sheldon/UConn

Researchers in the College of Agriculture, Health and Natural Resources are working to unlock a decades-long mystery that has hampered development of a walking pneumonia vaccine.

Associate Professor Steven Szczepanek and Professor Steven Geary from the Department of Pathobiology and Veterinary Science, along with former graduate students Tyler Gavitt and Arland Mara, published findings that help explain how Mycoplasma pneumoniae (Mp) hijacks our immune system following vaccination.

They shared their findings in two recent publications in Nature journal npj Vaccines.

Mp is a common pathogen that causes walking pneumonia. While this respiratory infection is not typically severe, it is a common co-pathogen with illnesses that spread in the same way, like the flu or COVID-19, which can cause more severe illnesses, especially in older or immunocompromised adults.

In the 1960s, scientists began working to develop an Mp vaccine. They killed the bacteria and injected it into human subjects, thinking it would provide protection from actual infection. But that’s not what happened.

Screening for stroke risk can save lives and money

Emma Svennberg, specialist in cardiology. Screening involves placing the thumbs onto a hand-held ECG machine.
Photo Credit: Johan Adelgren

Atrial fibrillation is the greatest risk factor for stroke. Screening to detect atrial fibrillation in older people would not only increase the chance of preventing stroke, it would also save money for the healthcare system and society. This is the conclusion from research conducted at Linköping University and Karolinska Institutet.

“The greatest benefit from screening is that you receive information that could be used to reduce an individual’s risk of stroke and thus may help them live longer with a good quality of life,” says Emma Svennberg, specialist in cardiology at Karolinska University Hospital, and affiliated researcher at Karolinska Institutet.

A systematic screening program for atrial fibrillation is not in use anywhere in the world. The researchers who conducted the present study, published in European Journal of Heart, have calculated the cost effectiveness of screening for atrial fibrillation in people aged 75-76 years, and conclude that there are strong reasons for introducing such a program.

Fertilizers limit pollination by changing how bumblebees sense flowers

Photo Credit: Myriams-Fotos

Pollinators are less likely to land on flowers sprayed with fertilizers or pesticides as they can detect electric field changes around the flower, researchers at the University of Bristol have found.

The study, published in PNAS Nexus today, shows that chemical sprays alter the electric field around flowers for up to 25 minutes after exposure. This impact lasts substantially longer than natural fluctuations, such as those caused by wind, and causes a reduction in bee feeding effort in nature.

Dr Ellard Hunting of Bristol’s School of Biological Sciences and his team noted that fertilizers did not affect vision and smell, and set out to mimic the electrical changes caused by fertilizers and pesticides in the field by electrically manipulating flowers. This showed that bumblebees were able to detect and discriminate against the small and dynamic electric field alterations that are caused by the chemicals.

Dr. Ellard Hunting said: “We know that chemicals are toxic, but we know little about how they affect the immediate interaction between plants and pollinators.

“Flowers have a range of cues that attract bees to promote feeding and pollination. For instance, bees use cues like flower odor and color, but they also use electric fields to identify plants.

Natural carbon dioxide reduction implemented faster and with less risk than high-tech approaches

Researchers have investigated the potential of various carbon dioxide removal processes. 
Photo Credit: Shameer Pk

Carbon dioxide can be removed from the atmosphere by natural or technical means. Natural sinks such as peatlands can be restored, and innovative technologies already exist to extract carbon from the air. Researchers from the Helmholtz Climate Initiative's Net Zero 2050 Cluster have identified the approaches with the highest potential for carbon removal in Germany. They show that natural sinks can be expanded in the short term, while high-tech approaches can reduce greenhouse gases only in the medium term and carry potential risks.

To reach the targets of the Paris agreement and limit global warming to 1.5 to 2 degrees Celsius, simply reducing our carbon dioxide (CO2) emissions will probably not be enough, and it will likely be necessary to additionally remove CO2 from the atmosphere. Such CO2 removal could be realized naturally through natural sink enhancement (NSE) such as forest reforestation, or through new technologies which use chemical processes for carbon capture. However, the potential and feasibility of these so-called carbon dioxide removal (CDR) measures depend on many variables, like the availability of infrastructure and resources such as land and energy, to name a few.