Reading out RNA structures in real time

The fluorescent blinking of cyanine dye (Alexa Fluor 647, pink star) bound to RNA changes depending on the structure of the RNA. When the RNA is folded like a hairpin, the fluorescent blinking is fast, and when the RNA switches to a G-quadruplex, the blinking is slow
Illustration Credit: Akira Kitamura

A new microscopic technique allows for the real-time study of RNA G-quadruplexes in living cells, with implications for the fight against amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig’s disease and Stephen Hawking’s disease, is a neurodegenerative disease that results in the gradual loss of control over the muscles in the body. It is currently incurable and the cause of the disease is unknown in over 90% of all cases — although both genetic and environmental factors are believed to be involved.

The research groups of Dr. Akira Kitamura at the Faculty of Advanced Life Science, Hokkaido University, and Prof. Jerker Widengren at the KTH Royal Institute of Technology, Sweden, have developed a novel technique that is able to detect a characteristic structure of RNA in real time in live cells. The technique, which is based on fluorescence-microscopic spectroscopy, was published in the journal Nucleic Acids Research.

New, safe, and biodegradable compound blocks radiation

Hesham Zakali: The material developed by an international group of scientists could become an alternative to toxic lead, for example.
Photo Credit: Anastasia Kurshpel

Polylactic acid combined with tungsten trioxide effectively blocks gamma radiation, an international group of scientists including specialists from Russia (Ural Federal University), Saudi Arabia and Egypt has found. In the future, it will be possible to create safe and biodegradable screens for protection against low-energy radiation on the basis of the new material, the researchers believe. Such screens are used in medicine, agriculture and the food industry. A description of the material has been published in the journal Radiation Physics and Chemistry.

"Polylactic acid is a non-toxic polymer of natural origin. It is inexpensive and, importantly, can be broken down by microbes when placed in an industrial plant at high temperatures. Since lactic acid is regularly produced as a byproduct of metabolism in both plants and animals, polylactic acid and its degradation products are non-toxic and safe for the environment," explains Hesham Zakali, co-author of the development and Researcher at the Department of Experimental Physics at UrFU.

Cyborg Cells Could Be Tools for Health and Environment

UC Davis biomedical engineers have created semi-living “cyborg cells” that have many of the capabilities of living cells but are unable to divide and grow. The cells could have applications in medicine and environmental cleanup.
Illustration Credit: Cheemeng Tan, UC Davis.

Biomedical engineers at the University of California, Davis, have created semi-living “cyborg cells.” Retaining the capabilities of living cells, but unable to replicate, the cyborg cells could have a wide range of applications, from producing therapeutic drugs to cleaning up pollution. The work was published in Advanced Science.

Synthetic biology aims to engineer cells that can carry out novel functions. There are essentially two approaches in use, said Cheemeng Tan, associate professor of biomedical engineering at UC Davis and senior author on the paper. One is to take a living bacterial cell and remodel its DNA with new genes that give it new functions. The other is to create an artificial cell from scratch, with a synthetic membrane and biomolecules.

The first approach, an engineered living cell, has great flexibility but is also able to reproduce itself, which may not be desirable. A completely artificial cell cannot reproduce but is less complex and only capable of a limited range of tasks.

Tens of thousands of possible catalysts on the diameter of a hair

The results of the sputtering process can be seen under the light microscope.
Image Credit: © Lars Banko

New methods make it possible to produce countless new materials in one step and to examine them quickly.

When looking for catalysts for the energy transition, materials made from at least five elements are particularly promising. Only there are theoretically millions of them - how do you find the most powerful? A Bochum research team led by Prof. Dr. Alfred Ludwig, head of the Materials Discovery and Interfaces chair, MDI, managed to accommodate all possible combinations of five elements on one carrier in a single step. In addition, the researchers developed a method to analyze the electrocatalytic potential of each of the combinations in this micromaterial library in high throughput. In this way, they want to speed up the search for potential catalysts many times over. The team at the Ruhr University Bochum reports in the journal Advanced Materials.

New approach successfully traces genomic variants back to genetic disorders

Doctors researching DNA and genetics.
Illustration Credit: Julia Fekecs, NHGRI

National Institutes of Health researchers have published an assessment of 13 studies that took a genotype-first approach to patient care. This approach contrasts with the typical phenotype-first approach to clinical research, which starts with clinical findings. A genotype-first approach to patient care involves selecting patients with specific genomic variants and then studying their traits and symptoms; this finding uncovered new relationships between genes and clinical conditions, broadened the traits and symptoms associated with known disorders, and offered insights into newly described disorders. The study was published in the American Journal of Human Genetics.

“We demonstrated that genotype-first research can work, especially for identifying people with rare disorders who otherwise might not have been brought to clinical attention,” says Caralynn Wilczewski, Ph.D., a genetic counselor at the National Human Genome Research Institute’s (NHGRI) Reverse Phenotyping Core and first author of the paper.

Typically, to treat genetic conditions, researchers first identify patients who are experiencing symptoms, then they look for variants in the patients’ genomes that might explain those findings. However, this can lead to bias because the researchers are studying clinical findings based on their understanding of the disorder. The phenotype-first approach limits researchers from understanding the full spectrum of symptoms of the disorders and the associated genomic variants.

Developing antibiotics that target multiple-drug-resistant bacteria

The sphaerimicin analogs (SPMs) inhibit the activity of MraY, and hence the replication of bacteria, with different degrees of effectiveness. The potency of the analog increases as the IC50 decrease Illustration Credit: Takeshi Nakaya, et al. Nature Communications. December 20, 2022

Researchers have designed and synthesized analogs of a new antibiotic that is effective against multidrug-resistant bacteria, opening a new front in the fight against these infections.

Antibiotics are vital drugs in the treatment of a number of bacterial diseases. However, due to continuing overuse and misuse, the number of bacteria strains that are resistant to multiple antibiotics is increasing, affecting millions of people worldwide. The development of new antibacterial compounds that target multiple drug resistant bacteria is also an active field of research so that this growing issue can be controlled.

A team led by Professor Satoshi Ichikawa at Hokkaido University has been working on the development of new antibacterial. Their most recent research, published in the journal Nature Communications, details the development of a highly effective antibacterial compound that is effective against the most common multidrug-resistant bacteria.

The clever glue keeping the cell’s moving parts connected

This liquid droplet is actually made from protein molecules. It acts as a glue that keeps the microtubule attached, via moving motor proteins, to an actin cable – a process essential for cell division to proceed.
 Illustration Credit: Ella Maru Studios, Courtesy of Paul Scherrer Institute

Researchers from Paul Scherrer Institute PSI and ETH Zurich have discovered how proteins in the cell can form tiny liquid droplets that act as a smart molecular glue. Clinging to the ends of filaments called microtubules, the glue they discovered ensures the nucleus is correctly positioned for cell division. The findings, published in Nature Cell Biology, explain the long-standing mystery of how moving protein structures of the cell’s machinery are coupled together.

Couplings are critical to machines with moving parts. Rigid or flexible, whether the connection between the shafts in a motor or the joints in our body, the material properties ensure that mechanical forces are transduced as desired. Nowhere is this better optimized than in the cell, where the interactions between moving subcellular structures underpin many biological processes. Yet how nature makes this coupling has long baffled scientists.

Now researchers, investigating a coupling crucial for yeast cell division, have revealed that to do this, proteins collaborate such that they condense into a liquid droplet. The study was a collaboration between the teams of Michel Steinmetz at Paul Scherrer Institute PSI and Yves Barral at ETH Zurich, with the help of the groups of Eric Dufresne and Jörg Stelling, both at ETH Zurich.

Scientists use machine learning to gain unprecedented view of small molecules

Metabolites are extremely small – the diameter of a human hair is 100,000 nanometers, while that of a glucose molecule is approximately one nanometer.
Illustration Credit: Matti Ahlgren/Aalto University.

A new tool to identify small molecules offers benefits for diagnostics, drug discovery and fundamental research.

A new machine learning model will help scientists identify small molecules, with applications in medicine, drug discovery and environmental chemistry. Developed by researchers at Aalto University and the University of Luxembourg, the model was trained with data from dozens of laboratories to become one of the most accurate tools for identifying small molecules.

Thousands of different small molecules, known as metabolites, transport energy and transmit cellular information throughout the human body. Because they are so small, metabolites are difficult to distinguish from each other in a blood sample analysis – but identifying these molecules is important to understand how exercise, nutrition, alcohol use and metabolic disorders affect wellbeing.

The Donnan Potential, Revealed at Last

Staff scientist Ethan Crumlin at Berkeley Lab's Advanced Light Source.
Photo Credit: Marilyn Sargent/Berkeley Lab

The Donnan electric potential arises from an imbalance of charges at the interface of a charged membrane and a liquid, and for more than a century it has stubbornly eluded direct measurement. Many researchers have even written off such a measurement as impossible.

But that era, at last, has ended. With a tool that’s conventionally used to probe the chemical composition of materials, scientists at the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) recently led the first direct measurement of the Donnan potential.

“We were naïve enough to believe we could do the impossible.”

Ethan Crumlin, Berkeley Lab staff scientist, Advanced Light Source (ALS)

Crumlin and his collaborators recently reported the measurement in Nature Communications.

Such a measurement could yield new insights in many areas that focus on membranes. The Donnan potential plays a critical role in transporting ions through a cellular membrane, for example, which ties it to biological functions ranging from muscle contractions to neural signaling. Ion exchange membranes are also important in energy storage strategies and water purification technologies.

Scientists use materials to make stem cells behave like human embryos

Stem cells confined in a circular shape on a soft gel display characteristic of embryonic development.
Photo Credit: University of New South Wales

A serendipitous discovery in the lab has the potential to revolutionize embryo models and targeted drug therapies.

Materials scientists at UNSW Sydney have shown that human pluripotent stem cells in a lab can initiate a process resembling the gastrulation phase – where cells begin differentiating into new cell types – much earlier than occurs in mother nature.

For an embryo developing in the womb, gastrulation occurs at day 14. But in a lab at UNSW’s Kensington campus, Scientia Associate Professor Kris Kilian oversaw an experiment where a gastrulation-like event was triggered within two days of culturing human stem cells in a unique biomaterial that, as it turned out, set the conditions to mimic this stage of embryo development.

“Gastrulation is the key step that leads to the human body plan,” says A/Prof. Kilian.

“It is the start of the process where a simple sheet of cells transforms to make up all the tissues of the body – nerves, cardiovascular and blood tissue and structural tissue like muscle and bone. But we haven’t really been able to study the process in humans because you can’t study this in the lab without taking developing embryonic tissue.

Researchers kick goals with soccer findings

Photo Credit: Joshua Hoehne

University of Queensland scientists have developed a model that gives soccer players their best chance of kicking a penalty goal.

After analyzing strategies used by penalty shot kickers and goalkeepers, researchers developed a model that coaches can use to identify the best shooting strategy against a particular goalkeeper.

Professor Robbie Wilson, head of the UQ Football Research Group at UQ’s School of Biological Sciences, said the outcome of a penalty shot was determined by a complex interaction between the shooter and the goalkeeper.

“Usually, a player’s performance is constrained by biomechanical trade-offs but each player has a range of strategies to overcome these,” Professor Wilson said.

“For example, if a shooter kicks at a high speed, accuracy is decreased, and if a goalkeeper moves early, the probability they’ll move in the correct direction is reduced.”

He said every player, including international stars like Cristiano Ronaldo and Lionel Messi, had a range of kicking speeds and areas of the goal in which they were naturally better or worse.

Neural Network Learned to Create a Molecular Dynamics Model of Liquid Gallium

The melt viscosity determines the choice of casting mode, ingot formation conditions and other parameters.
Photo Credit: Ilya Safarov

Scientists at the Institute of Metallurgy, Ural Branch of the Russian Academy of Sciences, and Ural Federal University have developed a method for theoretically high-precision determination of the viscosity of liquid metals using a trained artificial neural network. The method was successfully tested in the process of building the deep learning potential of the neural network on the example of liquid gallium. Scientists were able to significantly increase the spatiotemporal scale of the simulation. The results of molecular dynamics modeling of liquid gallium are particularly accurate. Previous calculations were notoriously inaccurate, especially in the low temperature range. An article describing the research was published in the journal Computational Materials Science.

"First, liquids are in principle difficult to be described theoretically. The reason, in our opinion, lies in the absence of a simple initial approximation for this class of systems (for example, the initial approximation for gases is the ideal gas model). Secondly, the atomistic calculation of viscosity requires processing of a large volume of statistical data and, at the same time, a large accuracy of description of the potential energy surface and forces acting on atoms. Direct calculations cannot achieve such an effect. Thirdly, gallium in the liquid state is difficult to describe theoretically, because, due to certain features, its structure differs from that of most other metals," explains Vladimir Filippov, Senior Researcher at the Department of Rare Metals and Nanomaterials at UrFU, research participant and co-author of the article.

FAU study finds low salinity can work to culture Florida pompano fish

Florida Pompano larvae (juvenile fish) pictured under a microscope.
Photo Credit: Victoria Uribe, FAU Harbor Branch

The Florida pompano, Trachinotus carolinus, a fish species that can live in waters of a wide range of salinity, is a prime candidate for aquaculture commercial fish production in the United States. Identified by its compressed silvery body with yellow dorsal and ventral surfaces, this species is found in warm water habitats along the eastern Atlantic Ocean. Florida pompano also is a popular target for recreational anglers along the U.S. Atlantic Coast from Massachusetts to Florida.

There are less than 10 aquaculture farms across the U.S. that have been successful in commercially raising and distributing Florida pompano. Many farms import their broodstock from countries such as Mexico, the Dominican Republic and Brazil. When attempting to rear Florida pompano from hatch to market, farms face a variety of challenges including access to seawater. On inland farms, seawater must be mixed on-site using artificial sea salt products, which can contribute to high production costs and lower profit returns.

While several studies have investigated using juvenile Florida pompano in low salinity, no low salinity experiments have been conducted on Florida pompano larvae (early stages of a fish). To address the knowledge gaps of the impact of low salinity on Florida pompano larval health, researchers from Florida Atlantic University’s Harbor Branch Oceanographic Institute, in collaboration with two local fish farms, Live Advantage Baits and Proaquatix, conducted a novel experiment that serves as a model study for future on-farm collaborations and helps build a bridge between scientists and farmers in aquaculture.

Business Professors Solve Century-old Math Problem

Illustration Credit: Yesenia Carrero /UConn

These professors made a ridiculously hard logistics problem easy to solve. In the process, they smashed a basic tenet of computer theory. And now they’re offering a $10,000 prize to anyone who can show they’re wrong.

“You have many choices to make. What’s your best choice, given limited resources, to maximize your profit?” asks Moustapha Diaby, an associate professor of operations management in UConn’s School of Business.

It may be the basic question of life in a capitalist society. It’s also the basic question behind operations research, a field of study that blossomed in the 1940s. One of operations research’s basic insights is that linear programming, which is part of a broader technique called “constrained optimization,” can answer these common business questions, says Diaby.

Imagine, for example, that you run an oil refinery. You need to decide how much gasoline (g) and diesel fuel (d) to make from each barrel of oil in order to maximize your profit. If you make a $3 profit per gallon of gas, and $5 per gallon of diesel, the objective of the optimization problem would be to maximize 3g + 5d.

Male orb-weaving spiders fight less in female-dominated colonies

 Orb-weaving spiders spin webs connected to each other in vast networks; within their colonies, individual spiders guard their own webs from intruders and often fight each other over food and mates.
Photo Credit: Gregory Grether/UCLA

Birds do it. Bees do it. Even spiders in their webs do it: cooperate for more peaceful colonies.

That’s one of the surprising findings of a new study by UCLA undergraduates of orb-weaving spiders in Peru.

The study also revealed that when there are more females than males in colonies of orb-weaving spiders, males fight less with each other — and that females fight less in female-dominated colonies than in male-dominated ones, leading to colonies that are somewhat more peaceful. The spiders also showed little hostility to individuals from different colonies, a discovery that has not been previously documented for colonial spiders.

The research was published in the Journal of Arachnology.

“We’re used to thinking of animals like honeybees and elephants living cooperatively,” said the paper’s senior author, Gregory Grether, a UCLA professor of ecology and evolutionary biology. “But spiders usually live solitarily, so we were excited to study these colonial spiders and find out how they interact with colony mates as well as with individuals from other colonies.”

NIST Finds a Sweet New Way to Print Microchip Patterns on Curvy Surfaces

Using sugar and corn syrup (i.e., candy), researcher Gary Zabow transferred the word "NIST" onto a human hair in gold letters, shown in false color in this grayscale microscope image. 
Image Credit: G. Zabow/NIST

NIST scientist Gary Zabow had never intended to use candy in his lab. It was only as a last resort that he had even tried burying microscopic magnetic dots in hardened chunks of sugar — hard candy, basically — and sending these sweet packages to colleagues in a biomedical lab. The sugar dissolves easily in water, freeing the magnetic dots for their studies without leaving any harmful plastics or chemicals behind.

By chance, Zabow had left one of these sugar pieces, embedded with arrays of micromagnetic dots, in a beaker, and it did what sugar does with time and heat — it melted, coating the bottom of the beaker in a gooey mess.

“No problem,” he thought. He would just dissolve away the sugar, as normal. Except this time when he rinsed out the beaker, the microdots were gone. But they weren’t really missing; instead of releasing into the water, they had been transferred onto the bottom of the glass where they were casting a rainbow reflection.

“It was those rainbow colors that really surprised me,” Zabow recalls. The colors indicated that the arrays of microdots had retained their unique pattern.

New CRISPR-based tool inserts large DNA sequences at desired sites in cells

Building on the CRISPR gene-editing system, MIT researchers designed a new tool that can snip out faulty genes and replace them with new ones.
Image Credit: Sangharsh Lohakare

Building on the CRISPR gene-editing system, MIT researchers have designed a new tool that can snip out faulty genes and replace them with new ones, in a safer and more efficient way.

Using this system, the researchers showed that they could deliver genes as long as 36,000 DNA base pairs to several types of human cells, as well as to liver cells in mice. The new technique, known as PASTE, could hold promise for treating diseases that are caused by defective genes with a large number of mutations, such as cystic fibrosis.

“It’s a new genetic way of potentially targeting these really hard to treat diseases,” says Omar Abudayyeh, a McGovern Fellow at MIT’s McGovern Institute for Brain Research. “We wanted to work toward what gene therapy was supposed to do at its original inception, which is to replace genes, not just correct individual mutations.”

The new tool combines the precise targeting of CRISPR-Cas9, a set of molecules originally derived from bacterial defense systems, with enzymes called integrases, which viruses use to insert their own genetic material into a bacterial genome.

Key cause of type 2 diabetes uncovered

Oxford Research reveals high blood glucose reprograms the metabolism of pancreatic beta-cells in diabetes.
Photo Credit: Steve Buissinne

Glucose metabolites (chemicals produced when glucose is broken down by cells), rather than glucose itself, have been discovered to be key to the progression of type 2 diabetes. In diabetes, the pancreatic beta-cells do not release enough of the hormone insulin, which lowers blood glucose levels. This is because a glucose metabolite damages pancreatic beta-cell function.

An estimated 415 million people globally are living with diabetes. With nearly 5 million people diagnosed with the condition in the UK, it costs the NHS some £10 billion each year. Around 90% of cases are type 2 diabetes (T2D), which is characterized by the failure of pancreatic beta-cells to produce insulin, resulting in chronically elevated blood glucose. T2D normally presents in later adult life, and by the time of diagnosis, as much as 50% of beta cell function has been lost. While researchers have known for some time that chronically elevated blood sugar (hyperglycemia) leads to a progressive decline in beta-cell function, what exactly causes beta-cell failure in T2D has remained unclear.

Now a new study led by Dr Elizabeth Haythorne and Professor Frances Ashcroft of the Department of Physiology, Anatomy and Genetics at the University of Oxford has revealed how chronic hyperglycemia causes beta-cell failure. Using both an animal model of diabetes and beta-cells cultured at high glucose, they showed, for the first time, that glucose metabolism, rather than glucose itself, is what drives the failure of beta-cells to release insulin in T2D. Importantly, they also demonstrated that beta-cell failure caused by chronic hyperglycemia can be prevented by slowing the rate of glucose metabolism.

New Technique Helps ID Genes Related to Aging

The head of a C. elegans showing fluorescently labeled protein aggregates.
Source: North Carolina State University

Researchers from North Carolina State University have developed a new method for determining which genes are relevant to the aging process. The work was done in an animal species widely used as a model for genetic and biological research, but the finding has broader applications for research into the genetics of aging.

“There are a lot of genes out there that we still don’t know what they do, particularly in regard to aging,” says Adriana San Miguel, corresponding author of a paper on the work and an assistant professor of chemical and biomolecular engineering at NC State. “That’s because this field faces a very specific technical challenge: by the time you know whether an organism is going to live for a long time, it’s old and no longer able to reproduce. But the techniques we use to study genes require us to work with animals that are capable of reproducing, so we can study the role of specific genes in subsequent generations.

“To expedite research in this field, we wanted to find a way of identifying genes that may be relevant to aging while the organisms are still young enough to work with.”

For this work, the researchers focused on a species of roundworm called C. elegans, which is one of the most important model species for research into genetics and aging. Specifically, the researchers focused on protein aggregation in cells, which is well established as being related to aging.

Physicists Proposed Theory of Solidification of Nickel and Iron Alloys

Nickel-iron alloy is used when high dimensional stability of finished parts is required.
Photo: unsplash.com / Laura Ockel

Physicists at Ural Federal University have created a theory for the solidification of a nickel-iron alloy (invar). They determined that an important role in the technology of creating products from invar, namely in the solidification process, is played by the oncoming flow: when the alloy cools, the liquid layer flows on top of the solidified layer. If you regulate this process, you can control the characteristics of the alloys, obtain a more homogeneous structure, thereby improving the properties of the final product.

The work of scientists is extremely important because nickel and iron alloys are used in creating high-precision devices: clocks, seismic sensors, substrates for chips, valves and engines in aircraft structures, and instruments for telescopes. The calculations will help to create an alloy with the desired structure, which will affect the quality of the finished products. Description of the model and behavior of melts, as well as analytical calculations, scientists have published in the journal Scientific Reports. The research was supported by the Russian Science Foundation (Project No. 21-79-10012).

"Let me explain the work with an analogy. When water freezes, it pushes out all the dirt. So, you can put a piece of ice in your mouth, it will be clean. This is roughly what happens to melts when they cool. The only difference is that they do not push out all the impurities, but some of them. Some of the impurities leak out, and some of the impurities stay in the melt. What remains in the melt fills the gaps between the crystals, which solidify, and the voids, which remain. As a result, the alloys are heterogeneous: one tiny piece is enriched and the neighboring piece is not. This affects the properties of the finished product," says Dmitry Aleksandrov, Head of the Ural Federal University's Laboratory of Multi-Scale Mathematical Modeling.