Scientists uncover new information about cellular death process, previously thought to be irreversible

A study published by researchers at the University of Illinois Chicago describes a new method for analyzing pyroptosis—the process of cell death that is usually caused by infections and results in excess inflammation in the body—and shows that process, long thought to be irreversible once initiated, can in fact be halted and controlled.

The discovery, which is reported in Nature Communications, means that scientists have a new way to study diseases that are related to malfunctioning cell death processes, like some cancers, and infections that can be complicated by out-of-control inflammation caused by the process. These infections include sepsis, for example, and acute respiratory distress syndrome, which is among the major complications of COVID-19 illness.

Pyroptosis is a series of biochemical reactions that uses gasdermin, a protein, to open large pores in the cell membrane and destabilize the cell. To understand more about this process, the researchers designed an "optogenetic" gasdermin by genetically engineering the protein to respond to light.

The researchers applied the optogenetic gasdermin tool and used florescent imaging technology to precisely activate gasdermin in cell experiments and observe the pores under various circumstances. They discovered that certain conditions, like specific concentrations of calcium ions, for example, triggered the pores to close within only tens of seconds.

This automatic response to external circumstances provides evidence that pyroptosis dynamically self-regulates.

"This showed us that this form of cell death is not a one-way ticket. The process is actually programmed with a cancel button, an off-switch.

Understanding how to control this process unlocks new avenues for drug discovery, and now we can find drugs that work for both sides—it allows us to think about tuning, either boosting or limiting, this type of cell death in diseases, where we could previously only remove this important process.

Ana Beatriz Santa Cruz Garcia et al, Gasdermin D pores are dynamically regulated by local phosphoinositide circuitry, Nature Communications (2022). DOI: 10.1038/s41467-021-27692-9

https://phys.org/news/2022-01-scientists-uncover-cellular-death-pre...

First person receives gene-edited pig heart

A person in the United States is the first to receive a transplant of a genetically modified pig heart. Yesterday, the University of Maryland Medical Center announced that the 57-year-old patient was still doing well 3 days after the surgery. The heart came from a pig raised by Revivicor, a US firm that spun off from the UK company that helped to clone Dolly the sheep. It’s not clear exactly how the pig was gene-edited, but the company has developed pigs whose cell surfaces do not have a sugar molecule called α-1,3-galactose, or α-gal, which triggers the human immune system. The man also received an experimental drug made by Kiniksa Pharmaceuticals designed to stave off rejection.

‘If it’s not on arXiv, it doesn’t exist’

On January 3, the arXiv server hit a milestone when it published its two milliont.... Since it was created in 1991 by physicist Paul Ginsparg, the repository has become indispensable for sharing research in fields such as astronomy, particle physics and mathematics. Such explosive growth is not painless: a handful of staff and volunteer moderators work to ensure that the 1,200 daily submissions meet basic quality standards. Critics worry that the full diversity of scientific thought — and of scientists themselves — is not represented among those gatekeepers. And the site has struggled with stability. “We’re an old classic car, and the rust has finally come through, and the pistons are wearing out,” says astrophysicist Steinn Sigurdsson, arXiv’s scientific director. “We are understaffed and underfunded — and have been for years.”

Study challenges evolutionary theory that DNA mutations are random

A simple roadside weed may hold the key to understanding and predicting DNA mutation, according to new research.

The findings, published January 12 in the journal Nature, radically change our understanding of evolution and could one day help researchers breed better crops or even help humans fight cancer.

Mutations occur when DNA is damaged and left unrepaired, creating a new variation. The scientists wanted to know if mutation was purely random or something deeper. What they found was unexpected.

Scientists thought of mutation as basically random across the genome till now. It turns out that mutation is very non-random and it's non-random in a way that benefits the plant. It's a totally new way of thinking about mutation.

Researchers spent three years sequencing the DNA of hundreds of Arabidopsis thaliana, or thale cress, a small, flowering weed considered the "lab rat among plants" because of its relatively small genome comprising around 120 million base pairs. Humans, by comparison, have roughly 3 billion base pairs. It's a model organism for genetics. 

Researchers grew specimens in a protected lab environment, which allowed plants with defects that may not have survived in nature be able to survive in a controlled space.

Sequencing of those hundreds of Arabidopsis thaliana plants revealed more than 1 million mutations. Within those mutations a nonrandom pattern was revealed, counter to what was expected.

Instead of randomness scientists found patches of the genome with low mutation rates. In those patches, they were surprised to discover an over-representation of essential genes, such as those involved in cell growth and gene expression. 

These are the really important regions of the genome. The areas that are the most biologically important are the ones being protected from mutation.

The areas are also sensitive to the harmful effects of new mutations. DNA damage repair seems therefore to be particularly effective in these regions.

Part 1

The scientists found that the way DNA was wrapped around different types of proteins was a good predictor of whether a gene would mutate or not. It means we can predict which genes are more likely to mutate than others and it gives us a good idea of what's going on.

The findings add a surprising twist to Charles Darwin's theory of evolution by natural selection because it reveals that the plant has evolved to protect its genes from mutation to ensure survival.

The plant has evolved a way to protect its most important places from mutation. This is exciting because we could even use these discoveries to think about how to protect human genes from mutation.

Knowing why some regions of the genome mutate more than others could help breeders who rely on genetic variation to develop better crops. Scientists could also use the information to better predict or develop new treatments for diseases like cancer that are caused by mutation.

Detlef Weigel, Mutation bias reflects natural selection in Arabidopsis thaliana, Nature (2022). DOI: 10.1038/s41586-021-04269-6. www.nature.com/articles/s41586-021-04269-6

https://phys.org/news/2022-01-evolutionary-theory-dna-mutations-ran...

Antibody Cocktail Therapy Explained

Researchers propose new explanation for Moon's half-century magnetic mystery

Rocks returned to Earth during NASA's Apollo program from 1968 to 1972 have provided volumes of information about the Moon's history, but they've also been the source of an enduring mystery. Analysis of the rocks revealed that some seemed to have formed in the presence of a strong magnetic field—one that rivaled Earth's in strength. But it wasn't clear how a Moon-sized body could have generated a magnetic field that strong.

Now, new research proposes a new explanation for the Moon's magnetic mystery. The study, published in Nature Astronomy, shows that giant rock formations sinking through the Moon's mantle could have produced the kind of interior convection that generates strong magnetic fields. The processes could have produced intermittently strong magnetic fields for the first billion years of the Moon's history, the researchers say.

The Moon lacks a magnetic field today, and models of its core suggest that it was probably too small and lacked the convective force to have ever produced a continuously strong magnetic field. In order for a core to have a strong convective churn, it needs to dissipate a lot of heat. In the case of the early Moon, researchers say, the mantle surrounding the core wasn't much cooler than the core itself. Because the core's heat didn't have anywhere to go, there wasn't much convection in the core. But this new study shows how sinking rocks could have provided intermittent convective boosts.

The story of these sinking stones starts a few million years after the Moon's formation. Very early in its history, the Moon is thought to have been covered by an ocean of molten rock. As the vast magma ocean began to cool and solidify, minerals like olivine and pyroxene that were denser than the liquid magma sank to the bottom, while less dense minerals like anorthosite floated to form the crust. The remaining liquid magma was rich in titanium as well as heat-producing elements like thorium, uranium and potassium, so it took a bit longer to solidify. When this titanium layer finally crystallized just beneath the crust, it was denser than the earlier-solidifying minerals below it. Over time, the titanium formations sank through the less-dense mantle rock underneath, a process known as gravitational overturn.

There could have been as many as 100 of these downwelling events over the Moon's first billion years of existence, the researchers say, and each one could have produced a strong magnetic field lasting a century or so.

Alexander Evans, An episodic high-intensity lunar core dynamo, Nature Astronomy (2022). DOI: 10.1038/s41550-021-01574-y. www.nature.com/articles/s41550-021-01574-y

https://phys.org/news/2022-01-explanation-moon-half-century-magneti...

Lost birds and mammals spell doom for some plants

In one of the first studies of its kind, researchers have gauged how biodiversity loss of birds and mammals will impact plants' chances of adapting to human-induced climate warming.

More than half of plant species rely on animals to disperse their seeds. In a study  researchers showed the ability of animal-dispersed plants to keep pace with climate change has been reduced by 60% due to the loss of mammals and birds that help such plants adapt to environmental change.

As climate changes, many plant species must move to a more suitable environment. Plants that rely on seed dispersers can face extinction if there are too few animals to move their seeds far enough to keep pace with changing conditions.

If there are no animals available to eat their fruits or carry away their nuts, animal-dispersed plants aren't moving very far. And many plants people rely on, both economically and ecologically, are reliant on seed-dispersing birds and mammals.

The study showed seed-dispersal losses were especially severe in temperate regions across North America, Europe, South America and Australia. If endangered species go extinct, tropical regions in South America, Africa and Southeast Asia would be most affected.

Evan C. Fricke, The effects of defaunation on plants' capacity to track climate change, Science (2022). DOI: 10.1126/science.abk3510. www.science.org/doi/10.1126/science.abk3510

https://phys.org/news/2022-01-lost-birds-mammals-doom.html?utm_sour...

Some birds sing the same song for hundreds of thousands of years

Many of the birds that awaken us each morning learn their melodious songs the same way that humans learn a dialect—from parents and neighbours.

But to most biologists, learning songs through mimicry is an uncertain and error-prone process, resulting in slow but inevitable change in song over the years.

A new study by biologists , however, documents songs in East African sunbirds that have remained nearly unchanged for more than 500,000 years, and perhaps for as long as 1 million years, making the songs nearly indistinguishable from those of relatives from which they've long been separated.

The amazingly static nature of their songs may be due to a lack of change in these birds' environments, which are stable mountain forests—so-called sky islands—isolated from other sky island populations of the same or similar species for tens of thousands to millions of years. The coloration of the birds' feathers has changed little, as well, making their plumage nearly indistinguishable from each other, even though some are separate, but closely related, species.

Jay P. McEntee et al, Punctuated evolution in the learned songs of African sunbirds, Proceedings of the Royal Society B: Biological Sciences (2021). DOI: 10.1098/rspb.2021.2062

https://phys.org/news/2022-01-birds-song-hundreds-thousands-years.h...

How to image atoms

A mysterious new way of producing oxygen
Researchers have discovered that some microbes that live in the deep sea produce oxygen in a way never seen before. The surprising species, Nitrosopumilus maritimus, uses a common method to generate energy: the oxidation of ammonia to nitrite. But when researchers sealed the microbes in airtight containers, without light or oxygen, they were still somehow able to produce O2. The findings could have implications for everything from detecting the signs of life to determining how bacteria might adapt to a drop in ocean oxygen caused by climate change.

This has only been found previously in NC10 bacteria, which break up nitric oxide into nitrogen and oxygen and use the oxygen to oxidise methane. However, the NC10 bacteria are not known to release oxygen. https://www.chemistryworld.com/news/single-celled-marine-organism-f...

Strong evidence shows Sixth Mass Extinction of global biodiversity in progress

The history of life on Earth has been marked five times by events of mass biodiversity extinction caused by extreme natural phenomena. Today, many experts warn that a Sixth Mass Extinction crisis is underway, this time entirely caused by human activities.

A comprehensive assessment of evidence of this ongoing extinction event was published recently in the journal Biological Reviews by biologists .

Drastically increased rates of species extinctions and declining abundances of many animal and plant populations are well documented, yet some deny that these phenomena amount to mass extinction. This denial is based on a biased view of the crisis which focuses on mammals and birds and ignores invertebrates, which of course constitute the great majority of biodiversity.

By extrapolating from estimates obtained for land snails and slugs, biologists estimated that since the year 1500, Earth could already have lost between 7.5 and 13% of the two million known species on Earth—a staggering 150,000 to 260,000 species.

Including invertebrates was key to confirming that we are indeed witnessing the onset of the Sixth Mass Extinction in Earth's history.

The situation is not the same everywhere, however. Although marine species face significant threats, there is no evidence that the crisis is affecting the oceans to the same extent as the land. On land, island species, such as those of the Hawaiian Islands, are much more affected than continental species. And the rate of extinction of plants seems lower than that of terrestrial animals.

To fight the crisis, various conservation initiatives have been successful for certain charismatic animals. But these initiatives cannot target all species, and they cannot reverse the overall trend of species extinction. Nonetheless, it is essential to continue such efforts, to continue to cultivate a wonder for nature, and to document biodiversity before it disappears.

Robert H. Cowie et al, The Sixth Mass Extinction: fact, fiction or speculation?, Biological Reviews (2022). DOI: 10.1111/brv.12816

https://phys.org/news/2022-01-strong-evidence-sixth-mass-extinction...

Copper-based chemicals may be contributing to ozone depletion

Copper released into the environment from fungicides, brake pads, antifouling paints on boats and other sources may be contributing significantly to stratospheric ozone depletion, according to a new study .

In a paper appearing this week in the journal Nature Communications, UC Berkeley geochemists show that copper in soil and seawater acts as a catalyst to turn organic matter into both methyl bromide and methyl chloride, two potent halocarbon compounds that destroy ozone. Sunlight worsens the situation, producing about 10 times the amount of these methyl halides.

The findings answer, at least in part, a long-standing mystery about the origin of much of the methyl bromide and methyl chloride in the stratosphere. Since the worldwide ban on chlorofluorocarbon (CFC) refrigerants and brominated halons used in fire extinguishers starting in 1989, these methyl halides have become the new dominant sources of ozone-depleting bromine and chlorine in the stratosphere. As the long-lived CFCs and halons slowly disappear from the atmosphere, the role of methyl halides increases.

Yi Jiao et al, Application of copper(II)-based chemicals induces CH3Br and CH3Cl emissions from soil and seawater, Nature Communications (2022). DOI: 10.1038/s41467-021-27779-3

https://phys.org/news/2022-01-copper-based-chemicals-contributing-o...

Being in space destroys more red blood cells

A world-first study has revealed how space travel can cause lower red blood cell counts, known as space anemia. Analysis of 14 astronauts showed their bodies destroyed 54 percent more red blood cells in space than they normally would on Earth, according to a study published in Nature Medicine.

Space anemia has consistently been reported when astronauts returned to Earth since the first space missions, but we didn't know why. This study shows that upon arriving in space, more red blood cells are destroyed, and this continues for the entire duration of the astronaut's mission.

Before this study, space anemia was thought to be a quick adaptation to fluids shifting into the astronaut's upper body when they first arrived in space. Astronauts lose 10 percent of the liquid in their blood vessels this way. It was thought astronauts rapidly destroyed 10 percent of their red blood cells to restore the balance, and that red blood cell control was back to normal after 10 days in space.

Now it was found that  the red blood cell destruction was a primary effect of being in space, not just caused by fluid shifts. They demonstrated this by directly measuring red blood cell destruction in 14 astronauts during their six-month space missions.

On Earth, our bodies create and destroy 2 million red blood cells every second. The researchers found that astronauts were destroying 54 percent more red blood cells during the six months they were in space, or 3 million every second. These results were the same for both female and male astronauts.

This discovery was made thanks to techniques and methods researchers developed to accurately measure red blood cell destruction. These methods were then adapted to collect samples aboard the International Space Station. They were able to precisely measure the tiny amounts of carbon monoxide in the breath samples from astronauts. One molecule of carbon monoxide is produced every time one molecule of heme, the deep-red pigment in red blood cells, is destroyed.

Trudel, G et al, Hemolysis contributes to anemia during long-duration space flight. Nat Med (2022). doi.org/10.1038/s41591-021-01637-7

https://phys.org/news/2022-01-space-red-blood-cells.html?utm_source...

Your gut senses the difference between real sugar and artificial sweetener

 Your taste buds may or may not be able to tell real sugar from a sugar substitute like Splenda, but there are cells in your intestines that can and do distinguish between the two sweet solutions. And they can communicate the difference to your brain in milliseconds.

Not long after the sweet taste receptor was identified in the mouths of mice 20 years ago, scientists attempted to knock those taste buds out. But they were surprised to find that mice could still somehow discern and prefer natural sugar to artificial sweetener, even without a sense of taste.

The answer to this riddle lies much further down in the digestive tract, at the upper end of the gut just after the stomach, according to research.

The researchers have  identified the cells that make us eat sugar, and they are in the gut. The sensing cells are in the upper reaches of the gut. 

Having discovered a gut cell called the neuropod cell, researchers have been pursuing this cell’s critical role as a connection between what’s inside the gut and its influence in the brain. The gut talks directly to the brain, changing our eating behaviour. And in the long run, these findings may lead to entirely new ways to treat diseases.

Originally termed enteroendrocrine cells because of their ability to secrete hormones, specialized neuropod cells can communicate with neurons via rapid synaptic connections and are distributed throughout the lining of the upper gut. In addition to producing relatively slow-acting hormone signals, the  researchers have shown that these cells also produce fast-acting neurotransmitter signals that reach the vagus nerve and then the brain within milliseconds.

 These latest findings further show that neuropods are sensory cells of the nervous system just like taste buds in the tongue or the retinal cone cells in the eye that help us see colors. They sense traces of sugar versus sweetener and then they release different neurotransmitters that go into different cells in the vagus nerve, and ultimately, the animal knows ‘this is sugar’ or ‘this is sweetener.’”

Using lab-grown organoids from mouse and human cells to represent the small intestine and duodenum (upper gut), the researchers showed in a small experiment that real sugar stimulated individual neuropod cells to release glutamate as a neurotransmitter. Artificial sugar triggered the release of a different neurotransmitter, ATP.

Using a technique called optogenetics, the scientists were then able to turn the neuropod cells on and off in the gut of a living mouse to show whether the animal’s preference for real sugar was being driven by signals from the gut.

Sugar has both taste and nutritive value and the gut is able to identify both.
Many people struggle with sugar cravings, and now we have a better understanding of how the gut senses sugars (and why artificial sweeteners don’t curb those cravings).

1. Kelly L. Buchanan, Laura E. Rupprecht, M. Maya Kaelberer, Atharva Sahasrabudhe, Marguerita E. Klein, Jorge A. Villalobos, Winston W. Liu, Annabelle Yang, Justin Gelman, Seongjun Park, Polina Anikeeva, Diego V. Bohórquez. The preference for sugar over sweetener depends on a gut sensor cell. Nature Neuroscience, 2022; DOI: 10.1038/s41593-021-00982-7

https://researchnews.cc/news/11088/Your-gut-senses-the-difference-b...

Tiger Shark Migrations Altered by Climate Change

How Salmonella overcomes host resistance

 The microbial species living in our gastrointestinal tract — the gut microbiota — help protect us against invading pathogens. One way they exert this “colonization resistance” is by producing antimicrobial products, such as the fatty acid propionate. The gut microbiota benefits the host by limiting enteric pathogen expansion (colonization resistance), partially via the production of inhibitory metabolites. Propionate, a short-chain fatty acid produced by microbiota members, is proposed to mediate colonization resistance against Salmonella enterica serovar Typhimurium (S. Tm).

Propionate is used in agricultural animals to limit infection by varieties of Salmonella bacteria, which cause food poisoning in humans.

Now, however, researchers have demonstrated that Salmonella can turn the tables and use propionate for its own purposes. The researchers showed in animal models that in the presence of inflammation, Salmonella changes its metabolism and uses propionate as a source of energy. They demonstrated that propionate metabolism supports expansion of Salmonella in the inflamed gut.

The findings, published in Cell Reports, show that in addition to promoting colonization resistance, propionate can fuel Salmonella growth, changing the understanding of propionate’s role and complicating its use as an antimicrobial treatment.

https://pubmed.ncbi.nlm.nih.gov/34986344/

https://researchnews.cc/news/11098/Salmonella-overcomes-host-resist...

The circadian clock in heart failure

Disrupting circadian rhythms, which change naturally on a 24-hour cycle, has been implicated in heart disease, but it is unclear how it leads to the condition. A research team investigated the function of the protein Rev-erbα/β, a key component of the circadian clock, on heart disease development in animal models and human patients.

The team reports in the journal Circulation that Rev-erbα/β in cardiomyocytes mediates a normal metabolic rhythm that enables the cells to prefer lipids as a source of energy during the animal's resting time, daytime for mice. Removing Rev-erbα/β disrupts this rhythm, reduces the cardiomyocytes' ability to use lipids in the resting time and leads to progressive dilated cardiomyopathy and lethal heart failure.

They found that the Rev-erbα/β gene is highly expressed only during the sleep hours, and its activity is associated with fat and sugar metabolisms.

The heart responds differently to different sources of energy, depending on the time of the day. In the resting phase, which for humans is at night and for mice in the day, the heart uses fatty acids that are released from fats as the main source of energy. In the active phase, which is during the day for people and at night for mice, the heart has some resistance to dietary carbohydrates. The researchers found that without Rev-erbα/β, hearts have metabolic defects that limit the use of fatty acids when resting, and there is overuse of sugar in the active phase.

Scientists also found that when Rev-erbα/β knockout hearts cannot burn fatty acids efficiently in the resting phase, then they don't have enough energy to beat. That energy deficiency would probably lead to changes in the heart that resulted in progressive dilated cardiomyopathy.

To test this hypothesis, the researchers determined whether restoring the defect in fatty acid use would improve the condition.

Part 1

The researchers fed Rev-erbα/β knockout mice one of two high-fat diets. One diet was mostly high-fat. The other was a high-fat/high-sucrose diet, resembling human diets that promote obesity and insulin resistance. The high-fat/high-sucrose diet partially alleviated the cardiac defects, but the high-fat diet did not.

These findings support that the metabolic defect that prevents the heart cells from using fatty acids as fuel is causing the majority of the cardiac dysfunction we see in the Rev-erbα/β knockout mice. Importantly, we also show that correcting the metabolic defect can help improve the condition.

Chronotype Myocardial Rev-erb-mediated diurnal metabolic rhythm and obesity paradox, Circulation (2022). DOI: 10.1161/CIRCULATIONAHA.121.056076

https://medicalxpress.com/news/2022-01-circadian-clock-heart-failur...

Part2

Nanotherapy offers new hope for the treatment of Type 1 diabetes

Individuals living with Type 1 diabetes must carefully follow prescribed insulin regimens every day, receiving injections of the hormone via syringe, insulin pump or some other device. And without viable long-term treatments, this course of treatment is a lifelong process.

Pancreatic islets control insulin production when blood sugar levels change, and in Type 1 diabetes, the body's immune system attacks and destroys such insulin-producing cells. Islet transplantation has emerged over the past few decades as a potential cure for Type 1 diabetes. With healthy transplanted islets, Type 1 diabetes patients may no longer need insulin injections, but transplantation efforts have faced setbacks as the immune system continues to eventually reject new islets. Current immunosuppressive drugs offer inadequate protection for transplanted cells and tissues and are plagued by undesirable side effects.

Now a team of researchers at Northwestern University has discovered a technique to help make immunomodulation more effective. The method uses nanocarriers to re-engineer the commonly used immunosuppressant rapamycin. Using these rapamycin-loaded nanocarriers, the researchers generated a new form of immunosuppression capable of targeting specific cells related to the transplant without suppressing wider immune responses.

The concept of enhancing and controlling side effects of drugs via nanodelivery is not a new one. But  in this study researchers are not enhancing an effect, they are changing it—by repurposing the biochemical pathway of a drug, in this case mTOR inhibition by rapamycin, they are generating a totally different cellular response.

The team's discovery could have far-reaching implications. This approach can be applied to other transplanted tissues and organs, opening up new research areas and options for patients.

Guillermo Ameer, Subcutaneous nanotherapy repurposes the immunosuppressive mechanism of rapamycin to enhance allogeneic islet graft viability, Nature Nanotechnology (2022). DOI: 10.1038/s41565-021-01048-2. www.nature.com/articles/s41565-021-01048-2

https://phys.org/news/2022-01-nanotherapy-treatment-diabetes.html?u...

Are There Rainbows on Mars? 

Chal­lenging the the­ory of the nar­row host range of phages

Viruses that infect bacteria could one day replace antibiotics because they precisely attack only specific pathogens. Researchers  are now showing that this is not always the case. This new finding is important because bacterial viruses can transfer antibiotic resistance genes.

Bacteriophages—phages for short—are viruses that infect only bacteria. To capture a bacterial host, they first attach to specific molecules on its cell surface. Then they inject their genetic material into the bacterial cell. In order to reprogram the bacteria's cellular machinery to produce new virus particles, phages also have to outsmart the target bacteria's immune system.

The molecular entry points and the immune system differ from one bacterium to another, so it was commonly believed that most phages have a narrow host range—that is, that they infect only a single bacterial species or even subspecies. This is also what prompted the idea of using natural bacteria killers to treat infections—particularly when the disease-causing bacteria have acquired antibiotic resistances.

However, a new study challenges the theory of the narrow host range of phages. Phages within the Staphylococcus group of bacteria often infect multiple species simultaneously. The researchers recently published their results in the journal Nature Communications.

The findings could have direct consequences for phage therapy, which is not yet approved for use in Switzerland, but has long been in use in eastern Europe. Phages not only kill bacteria, they can also transfer antibiotic resistance genes from one bacterium to another. Accordingly, their unexpectedly broad range of prey means that phages could spread their resistance genes much further in the environment than was previously thought.

The mechanism through which phages can transfer antibiotic resistance among bacteria is already known. In short, when these viruses multiply in the bacterial cells, they not only inject their own genetic material into new virus particles; in some cases, they smuggle genetic material from the infected bacterium—a resistance gene, for instance—into the virus particles. If one of these virus particles then infects a new bacterium, the resistance may be transferred.

Therefore, if we want to assess the role of phages as vectors of antibiotic resistance, we have to look at the whole picture—not just the situation in human medicine. When using phages in medicine, one must be careful that they don't additionally act as vectors of antibiotic resistance genes. It is thus important to ensure that phages used in medicine have a propagation mechanism that functions as flawlessly as possible.

 Pauline C. Göller et al, Multi-species host range of staphylococcal phages isolated from wastewater, Nature Communications (2021). DOI: 10.1038/s41467-021-27037-6

https://phys.org/news/2022-01-theory-narrow-host-range-phages.html?...

This  Terrifying NEW Discovery on Neptune Changes Everything!

Research team identifies new mechanism for protecting DNA

Researchers  have identified a new mechanism by which a protein known for repairing damaged DNA also protects the integrity of DNA by preserving its structural shape.

The discovery, involving the protein 53BP1, offers insight into understanding how cells maintain the integrity of DNA in the nucleus, which is critical for preventing diseases like premature aging and cancer.

DNA, or deoxyribonucleic acid, is the chemical name for the molecule that carries genetic instructions in all living things.

The large protein 53BP1 is known for determining how cells will repair a particular type of DNA damage—DNA double-strand break (DSB), in which the two strands of DNA are both broken, leaving a free DNA end floating around in the cell's nucleus.

When DSB occurs, if it is not repaired, the DNA ends could fuse to what they should not under normal conditions, which could lead to the disruption of genetic information. In the short term, cells with unrepaired DNA may kill themselves off, but if a cell loses this self-surveillance, it may start the journey toward cancer.

In this study, the team discovered that 53BP1 has a biological function in mediating the structure of DNA, specifically at a highly compacted region called heterochromatin.

The researchers found that this new function involves a new form of activity of 53BP1, in which the protein accumulates at the condensed DNA regions and forms small liquid droplets—a process called liquid-liquid phase separation, similar to mixing oil with water for salad dressing.

The team determined how 53BP1 can form liquid droplets: They found that this process requires the participation of other proteins known to support the structure of the highly condensed DNA. But, in turn, they discovered that 53BP1 actually stabilized the gathering of these proteins at these DNA regions, which is important for keeping the overall function of the DNA.

They then carried out detailed molecular analysis to break the large protein into small pieces and determined which pieces are important for the liquid droplet formation of 53BP1. They further changed amino acid of a specific position of the 53BP1 protein and determined the contribution of several amino acids that are critical for this new function.

With this new information, Zhang and his team hope to better understand how diseases like cancer can be prevented, and even design therapies that use this new feature of 53BP1 to treat cancers in the future.

Lei Zhang et al, 53BP1 regulates heterochromatin through liquid phase separation, Nature Communications (2022). DOI: 10.1038/s41467-022-28019-y

https://phys.org/news/2022-01-team-mechanism-dna.html?utm_source=nw...

Scientists find previously unknown jumping behavior in insects

Using a bacteriophage to successfully treat a patient infected with a drug-resistant bacteria

A team of doctors and researchers working at Erasmus Hospital in Belgium has successfully treated an adult woman infected with a drug-resistant bacteria using a combination of bacteriophage therapy and antibiotics. In their paper published in the journal Nature Communications, the group describes the reasons for the use of the treatment and the ways it might be used in other cases.

Bacteriophages are viruses that infect and kill bacteria. Research involving their use in human patients has been ongoing for several decades, but they are still not used to treat patients. In this new effort, the researchers were presented with a unique opportunity not only to treat a patient in need of help, but to learn more about the possible use of viruses to treat patients infected with bacteria that have become resistant to conventional antibiotics.

In this case, the patient had been severely injured by a terrorist's bomb—she suffered multiple injuries, including damage to her leg. Doctors treating her had to remove some of the bone, which led to a bacterial infection. Unfortunately for the patient, the bacteria was Klebsiella pneumoniae, which is known to be resistant to antibiotics, and it also creates films that make it difficult for antibiotics to reach infected areas. Over the course of several years, the researchers tried multiple ways to rid the patient of the infection, to no avail. Her medical team, finding no other options, chose to pursue bacteriophage therapy.

To use a bacteriophage, a virus must be found that attacks the exact strain of bacteria behind an infection. The researchers conducted an exhaustive search and test regimen until finally coming across a virus they found in a sample of sewer water. The virus was cultured and then mixed into a liquid solution that was applied directly to the infected site on the patient's leg. They also administered a host of antibacterial agents. The patient finally began recovering from her infection, and over a period of three years, she recovered to the point that she was not only free of the bacterial infection, but able to walk again.

Anaïs Eskenazi et al, Combination of pre-adapted bacteriophage therapy and antibiotics for treatment of fracture-related infection due to pandrug-resistant Klebsiella pneumoniae, Nature Communications (2022). DOI: 10.1038/s41467-021-27656-z

https://medicalxpress.com/news/2022-01-bacteriophage-successfully-p...

Air pollution significantly reduces pollination by confusing butterflies and bees

Common air pollutants from both urban and rural environments may be reducing the pollinating abilities of insects by preventing them from sniffing out the crops and wildflowers that depend on them, new research has shown.

Scientists found that there were up to 70% fewer pollinators, up to 90% fewer flower visits and an overall pollination reduction of up to 31% in test plants when common ground-level air pollutants, including diesel exhaust pollutants and ozone, were present.

The study, published in the journal Environmental Pollution, is the first to observe a negative impact of common air pollutants on pollination in the natural environment. The theory is that the pollutants react with and change the scents of flowers, making them harder to find.

Researchers knew from their previous lab studies that diesel exhaust can have negative effects on insect pollinators, but the impacts they found in the field were much more dramatic than they had expected.

The findings are worrying because these pollutants are commonly found in the air many of us breathe every day. These pollutants are bad for our health, and the significant reductions researchers saw in pollinator numbers and activity shows that there are also clear implications for the natural ecosystems we depend on.

James M.W. Ryalls et al, Anthropogenic air pollutants reduce insect-mediated pollination services, Environmental Pollution (2022). DOI: 10.1016/j.envpol.2022.118847

https://phys.org/news/2022-01-air-pollution-significantly-pollinati...

Scientists develop new coating to protect kidney failure patients on dialysis

We Have Breached The Safe Planetary Limit For Synthetic Chemicals, Scientists Warn

From sea to land to sky, Earth's systems are contaminated with synthetic substances, and scientists warn it has already pushed the integrity of our planet over the brink.

Today, there are about 350,000 human-made chemicals on the market, including plastics, pesticides, industrial chemicals, cosmetic chemicals, antibiotics, and other drugs.

The fact this number continues to rise at an extraordinary rate makes it virtually impossible for any authority to keep track of their potential impacts on the environment.

At this point, there's no keeping up. Now, a new analysis of the situation suggests we have firmly crossed a planetary boundary into an unsafe space.

Since the 1950s, chemical production has increased by 50-fold. By 2050, it's on track to triple again.

"The rate at which these pollutants are appearing in the environment far exceeds the capacity of governments to assess global and regional risks, let alone control any potential problems.

Even if we can slow chemical production in the future, novel entities of our own making have already infiltrated the atmosphere, the hydrosphere, the cryosphere, the geosphere, and the biosphere.

Given that many of these chemicals can live 'forever' in the environment, any potential threat they pose could be the foundation for ongoing problems far into the future.

Ignoring the problem is foolish, but that is largely what humanity has done.

Part1

In 2009, an international team of researchers put together a list of nine boundaries that kept our planet stable for human existence, including greenhouse gas emissions, the ozone layer, forests, and freshwater.

In 2015, they concluded humanity had breached four of these boundaries: climate change, greenhouse gas emissions, land-system change, and the extinction rate.

Until now, chemical pollution, or 'novel entities', had never been quantified.

Like a cap on greenhouse gases, researchers say nations also need to limit the rapid production of synthetic chemicals, while assessing the ones they've already got.

Today, tens of thousands of chemicals on the market are untested, and even the ones that have been assessed for health and safety still hold many unknown risks.

While some chemicals might be safe on their own, for instance, studies have shown they can grow toxic when breaking down or in the presence of other chemicals. If enough of these byproducts accumulate in the environment, it could potentially have long-lasting and detrimental impacts.

The chemicals in some sunscreens, for instance, have turned out to be toxic to coral. In recent years, antidepressants have also been found accumulating in water sources, where they appear to impact how some fish hunt for food.

Avoiding similar mistakes in the future will be all but impossible if we do not dramatically slow the global production of novel entities, and soon.

"Shifting to a circular economy is really important. That means changing materials and products so they can be reused not wasted, designing chemicals and products for recycling, and much better screening of chemicals for their safety and sustainability along their whole impact pathway in the Earth system."

https://pubs.acs.org/doi/10.1021/acs.est.1c04158

https://www.sciencealert.com/synthetic-chemicals-aren-t-just-pushin...

Part2

We're Facing a Myopia 'Epidemic', Scientists Say. Here's Why

Scientists are warning of an emerging 'epidemic' of myopia or near-sightedness, having observed sharp increases in the adult onset of myopia among late baby boomers.

Based on data collected from 107,442 participants in the extensive Biobank program in the UK, people born in the late 1960s are 10 percent more likely to be near-sighted than people born three decades earlier.

The biggest leap was in individuals who experienced their vision changes later in life, although among those with child-onset myopia, the number of severe cases doubled over the same period.

The condition is thought to be caused by a combination of genetic and environmental factors, including increased screen time – though the study also finds evidence that these are trends that can be changed with the right public health initiatives.

Digging further into the data, the researchers suggest several reasons for the jump: changes in the nutrition of diets in childhood, rises in the use of digital screens, and shifts in teaching methods (more homework and less time spent outdoors, for example).

An increase in the number of people staying in education past the age of 18 could also be a factor, according to the research. This association between higher education (more years spent reading, revising, and taking exams) and a higher risk of myopia has previously been noted in several previous studies.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0...

https://www.sciencealert.com/we-re-facing-a-myopia-epidemic-scienti...

Are the northern lights caused by 'particles from the Sun'? Not exactly

What a spectacle a big aurora is, its shimmering curtains and colorful rays of light illuminating a dark sky. Many people refer to aurora as the northern lights (the aurora borealis), but there are southern lights too (the aurora australis). Either way, if you're lucky enough to catch a glimpse of this phenomenon, it's something you won't soon forget.

The aurora is often explained simply as "particles from the Sun" hitting our atmosphere. But that's not technically accurate except in a few limited cases. So what does happen to create this natural marvel?

We see the aurora when energetic charged particles—electrons and sometimes ions—collide with atoms in the upper atmosphere. While the aurora often follows explosive events on the Sun, it's not quite true to say these energetic particles that cause the aurora come from the Sun.

Earth's magnetism, the force that directs the compass needle, dominates the motions of electrically charged particles in space around Earth. The magnetic field near the surface of Earth is normally steady, but its strength and direction fluctuate when there are displays of the aurora. These fluctuations are caused by what's called a magnetic substorm—a rapid disturbance in the magnetic field in near-Earth space.

To understand what happens to trigger a substorm, we first need to learn about plasma. Plasma is a gas in which a significant number of the atoms have been broken into ions and electrons. The gas of the uppermost regions of Earth's atmosphere is in the plasma state, as is the gas that makes up the Sun and other stars. A gas of plasma flows away continuously from the Sun: this is called the solar wind.

Plasma behaves differently from those gases we meet in everyday life. Wave a magnet around in your kitchen and nothing much happens. The air of the kitchen consists overwhelmingly of electrically neutral atoms, so it's quite undisturbed by the moving magnet. In a plasma, however, with its electrically charged particles, things are different. So if your house was filled with plasma, waving a magnet around would make the air move.

Part 1

When solar wind plasma arrives at the earth it interacts with the planet's magnetic field (as illustrated below—the magnetic field is represented by the lines that look a bit like a spider). Most of the time, plasma travels easily along the lines of the magnetic field, but not across them. This means that solar wind arriving at Earth is diverted around the planet and kept away from the Earth's atmosphere. In turn, the solar wind drags the field lines out into the elongated form seen on the night side, called the magnetotail.

Sometimes moving plasma brings magnetic fields from different regions together, causing a local breakdown in the pattern of magnetic field lines. This phenomenon, called magnetic reconnection, heralds a new magnetic configuration, and, importantly, unleashes a huge amount of energy.

These events happen fairly often in the Sun's outer atmosphere, causing an explosive energy release and pushing clouds of magnetized gas, called coronal mass ejections, away from the Sun (as seen in the image above).

If a coronal mass ejection arrives at Earth it can in turn trigger reconnection in the magnetotail, releasing energy that drives electrical currents in near-Earth space: the substorm. Strong electric fields that develop in this process accelerate electrons to high energies. Some of these electrons may have come from the solar wind, allowed into near-Earth space by reconnection, but their acceleration in the substorm is essential to their role in the aurora.

These particles are then funneled by the magnetic field towards the atmosphere high above the polar regions. There they collide with the oxygen and nitrogen atoms, exciting them to glow as the aurora.

Part 2

Now you know exactly what causes the northern lights, how do you optimize your chances of seeing it? Seek out dark skies far from cities and towns. The further north you can go the better but you don't need to be in the Arctic Circle. We see them from time to time in Scotland, and they've even been spotted in the north of England—although they're still better seen at higher latitudes.

Websites such as AuroraWatch UK can tell you when it's worth heading outside. And remember that while events on the Sun can give us a few days warning, these are indicative, not foolproof. Perhaps part of the magic lies in the fact that you need a little bit of luck to see the aurora in all its glory.

This article is republished from The Conversation under a Creative Commons license. Read the original article.

https://phys.org/news/2022-01-northern-particles-sun.html?utm_sourc...

Part 3 

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These scientists are racing to beat Omicron

They  have been racing to piece together a picture of Omicron, a variant that differs drastically from its predecessors. What they’re learning could guide the development of new vaccines that offer protection against future pandemics. In the near-term, such vaccines could provide a fresh supply of shots for those still awaiting their first dose – roughly 40 percent of people on the planet.

https://www.eurekalert.org/news-releases/940888

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This Cheap, Effective, Patent-Free COVID Vaccine Could Be a Global ...

Using ice to boil water: Researcher makes heat transfer discovery that expands on 18th century principle

have made a discovery about the properties of water that could provide an exciting addendum to a phenomenon established over two centuries ago. The discovery also holds interesting possibilities for cooling devices and processes in industrial applications using only the basic properties of water. Their work was published on Jan. 21 in the journal Physical Review Fluids.

Water can exist in three phases: a frozen solid, a liquid, and a gas. When heat is applied to a frozen solid, it becomes a liquid. When applied to the liquid, it becomes vapour. This elementary principle is familiar to anyone who has observed a glass of iced tea on a hot day, or boiled a pot of  water.

When the heat source  is hot enough, the water's behaviour changes dramatically.

Awater droplet deposited onto an aluminum plate heated to 150 degrees Celsius (302 degrees Fahrenheit) or above will no longer boil. Instead, the vapor that forms when the droplet approaches the surface will become trapped beneath the droplet, creating a cushion that prevents the liquid from making direct contact with the surface. The trapped vapor causes the liquid to levitate, sliding around the heated surface like an air hockey puck. This phenomenon is known as the Leidenfrost effect, named for the German doctor and theologian who first described it in a 1751 publication.

This commonly accepted scientific principle applies to water as a liquid, floating on a bed of vapour. Could ice perform in the same way?

While trying to answer this Q, what the researchers observed was fascinating. Even when the aluminum was heated above 150 C, the ice did not levitate on vapor as liquid does. Researchers continued raising the temperature, observing the behaviour of the ice as the heat increased. What he found was that the threshold for levitation was dramatically higher: 550 C (1022 F) rather than 150 C. Up until that threshold, the meltwater beneath the ice continued to boil in direct contact with the surface, rather than exhibit the Leidenfrost effect.

What was going on underneath the ice that prolonged the boiling?

The answer turned out to be the temperature differential in the meltwater layer beneath the ice. The meltwater layer has two different extremes: Its bottom is boiling, which fixes the temperature at about 100 C, but its top is adhered to the remaining ice, which fixes it at about 0 C. Edalatpour's model revealed that the maintenance of this extreme temperature differential consumes most of the surface's heat, explaining why levitation was more difficult for ice.

Part 1

The temperature differential the ice is uniquely creating across the water layer has changed what happens in the water itself, because now most of the heat from the hot plate has to go across the water to maintain that extreme differential. So only a tiny fraction of the energy can be used to produce vapor anymore.

The elevated temperature of 550 degrees Celsius for the icy Leidenfrost effect is practically important. Boiling water is optimally transporting heat away from the substrate, which is why you feel ample heat rising from a pot of water that is boiling, but not from a pot of water that is merely hot. This means that the difficulty in levitating ice is actually a good thing, as the larger temperature window for boiling will result in better heat transfer compared to using a liquid alone.

It is much harder to levitate the ice than it was to levitate the water droplet. Heat transfer plummets as soon as levitation begins, because when liquid levitates, it doesn't boil anymore. It's floating over the surface rather than touching, and touching is what causes it to boil the heat away. So, for heat transfer, levitation is terrible. Boiling is incredible.

Practical applications: 

Heat transfer comes most into play for cooling off things like computer servers or car engines. It requires a substance or mechanism that can move energy away from a hot surface, redistributing heat quickly to reduce the wear and tear on metal parts. In nuclear power plants, the application of ice to induce rapid cooling could become an easily-deployed emergency measure if power fails, or a regular practice for servicing power plant parts.

There are also potential applications for metallurgy. To produce alloys, it is necessary to quench the heat from metals that have been shaped in a narrow window of time, making the metal stronger and less brittle. If ice were applied, it would allow heat to be offloaded rapidly through the three water phases, quickly cooling the metal.

A  potential for applications in firefighting: You could imagine having a specially made hose that is spraying ice chips as opposed to a jet of water.

Physical Review Fluids, DOI: 10.1103/PhysRevFluids.00.004000

https://phys.org/news/2022-01-ice-discovery-18th-century-principle....

Part 2

**

A Black Hole Igniting Star Formation in a Dwarf Galaxy

Sars-CoV-2 spike protein activates human endogenous retroviruses in blood cells

Transposable elements, or jumping genes, are now known to be responsible for many human diseases. Keeping them repressed by methylation, RNA binding, or the attentions of the innate immune system is a full-time jump for cells.

Earlier researchers reviewed the activation of one particular kind of transposable element, the Line-1 retrotransposons, in an ever-expanding host of neurodegenerative conditions. Retrotransposons derive from human endogenous retrovirus (HERVs) but typically have lost their signature long terminal repeat sequences at the beginning and ends of their genes.

Recently a real zinger was dropped onto the medRxiv preprint server that could potentially explain many of the commonly observed pathogenic features of SARS-CoV-2. The authors provide solid evidence that the SARS-CoV-2 spike protein activates the envelope (ENV) protein encoded by HERV-W in blood cells, which is in turn directly responsible for many pathological features of the disease. HERV-W is named for the fact that many retroviruses in the group use a tryptophan tRNA in the primer binding site. Apparently, the shape of the letter W somehow reminded the naming committee of the shape of the ring structure of atoms in the side chain of tryptophan.

Part 1

Researchers had previously observed a correlation in the expression of HERV-W ENV protein in T lymphocytes with severe respiratory distress in SARS-CoV-2 patients. However, the exact mechanisms involved were not clear. Now, the real culprit in HERV-W activation has been discovered. Researchers added a recombinant trimeric spike protein without stabilizing mutations to cultured peripheral blood mononuclear cells (PBMCs) from SARS-CoV-2 patients. They found immediate and significant upregulation of the RNAs for the ENV protein from both HERV-W and HERV-K. Curiously, only the RNAs for HERV-W resulted in subsequent ENV protein expression.

Native spike proteins tend to prematurely refold into a post-fusion conformation, which compromises immunogenic properties and prefusion trimer yields. mRNA vaccines therefore have slight modifications that simultaneously make the mRNA less immunogenic, and the spike protein it encodes more immunogenic. One way this has been done is to stabilize specific conformers through the addition of two strategic prolines to the code. However, more research is needed to fully characterize the fusogenic potential of stabilized spike proteins. Some vaccine manufacturers have eliminated the furin cleavage site from their mRNA construct in order to reduce potential residual fusion of a 2-PP stabilized construct. A few of these observations were initially pointed out by some researchers. 

A key finding in these studies is that not all COVID patients had significant HERV-W ENV activation; only 20 or 30 percent of them did. This finding likely reflects an underlying genetic susceptibility among the infected that absolutely needs to be defined and taken into account, particularly if HERV-W is going to be used as a general marker for disease severity, or as a therapeutic target for a humanized monoclonal antibody therapy, as is now envisioned. For example, activation of a soluble hexameric form of HERV-W was found in multiple sclerosis, and is earmarked as potentially druggable option.

Part 2

But which HERV-W, exactly? Over 1 percent of our genomes are HERV-W remnants, more than all our protein-coding regions put together. In fact, there are at least 13 HERV-W loci with full-length ENV genes in the human genome. One of these, which hails from chromosome region 7q21.2, has an uninterrupted open reading frame for a complete HERV-W ENV protein. This protein, Syncytin-1, figures famously and essentially in normal placental development. To complicate things, MS now seems to have many eclectic potential origins. Researchers revealed this week, to considerable acclaim, that infection with Epstein-Barr virus is an important upstream, or downstream, or perhaps altogether independent trigger for MS.

HERV-W is not the only retroviral game in town. Researchers recently discovered that a retrovirus-like protein known as PEG10 directly binds to and secretes its own mRNA in extracellular virus-like capsids. This behavior is eerily similar to that of the ARC1 retroviral protein now understood to be critical in the formation of memory at synaptic sites. Incredibly, researchers are already well on their way to pseudotyping these virus-like particles with fusogens to create an endogenous vector for delivering functional mRNA cargos as a gene therapy. Clearly, some caution in these affairs is warranted.

In heart tissue samples from COVID-19 patients, HERV-W ENV was mainly found in endothelial cells from numerous small blood vessels and in the pericardial fatty tissue. The endothelial nature of HERV-W ENV positive cells was confirmed in this case with CD31 staining. Ominously, significant HERV-W ENV in patients was found in blood clots, nasal mucosa and also in the central nervous system, particularly in microglial cells, even when SARS-CoV-2 could not be detected in those tissues. The authors note that SARS-CoV-2 induced HERV-W ENV expression in human lymphoid cells, cells that neither express the canonical ACE2 receptor, nor the TMPRSS2 protease. This suggests other routes for the virus into these cells. One recent clue to other candidate mechanisms might come from alternative receptors like ASGR1, which is highly expressed in liver cells.

It is now of the utmost importance to find out how SARS-CoV-2 activates HERVs. In light of the known penchant for transposable elements to both be activated by, and further integrate into sites of active DNA repair, it may be worth revisiting earlier studies that purported to show that reverse transcribed SARS-CoV-2 RNA could integrate into the genome of cultured human cells and subsequently express in patient-derived tissues. These authors found target site duplications flanking the viral sequences and consensus LINE1 endonuclease recognition sequences at the integration sites—features consistent with a LINE1 retrotransposon-mediated, target-primed reverse transcription and retroposition mechanism.

Part 3

Benjamin Charvet et al, SARS-CoV-2 induces human endogenous retrovirus type W envelope protein expression in blood lymphocytes and in tissues of COVID-19 patients, medRxiv (2022). DOI: 10.1101/2022.01.18.21266111

https://phys.org/news/2022-01-sars-cov-spike-protein-human-endogeno...

Part 4

**

New antimicrobial therapeutics to fight superbugs

Researchers  have discovered a potential new way to prevent antibiotic resistance and reduce antibiotic intake.

Antimicrobial resistance occurs when pathogens (bacteria, viruses, fungi and parasites) change over time and no longer respond to medicines, consequently infections become increasingly difficult or impossible to treat.

The study, "A Polytherapy based approach to combat antimicrobial resistance using cubosomes," published in Nature Communications, has found that the use of nanoparticles in combination with other antibiotics, is an effective strategy to improve bacterial killing.

The paper makes an important new contribution to the field of antimicrobial resistance, finding a new way forward to fight multidrug-resistant bacteria.

Researchers now have demonstrated that nanoparticle-based polytherapy treatments disrupt the outer membrane of superbug bacteria, and offer an improved alternative to the conventional use of loading the antibiotic within lipid nanoparticles.

When bacteria becomes resistant, the original antibiotics can no longer kill them. Instead of looking for new antibiotics to counteract superbugs, we can use the nanotechnology approach to reduce the dose of antibiotic intake, effectively killing multidrug-resistant organisms.

 Xiangfeng Lai et al, A polytherapy based approach to combat antimicrobial resistance using cubosomes, Nature Communications (2022). DOI: 10.1038/s41467-022-28012-5

https://phys.org/news/2022-01-antimicrobial-therapeutics-superbugs....

How proteins pair up inside cells

A  single cell contains billions of molecules that bustle around and bind to one another, carrying out vital functions. The human genome encodes about 20,000 proteins, most of which interact with partner proteins to mediate upwards of 400,000 distinct interactions. These partners don't just latch onto one another haphazardly; they only bind to very specific companions that they must recognize inside the crowded cell. If they create the wrong pairings—or even the right pairings at the wrong place or wrong time—cancer or other diseases can ensue. Scientists are hard at work investigating these protein-protein relationships, in order to understand how they work, and potentially create drugs that disrupt or mimic them to treat disease.

The average human protein is composed of approximately 400 building blocks called amino acids, which are strung together and folded into a complex 3D structure. Within this long string of building blocks, some proteins contain stretches of 4-6 amino acids called short linear motifs (SLiMs), which mediate protein-protein interactions. Despite their simplicity and small size, SLiMs and their binding partners facilitate key cellular processes. However, it's been historically difficult to devise experiments to probe how SLiMs recognize their specific binding partners.

To address this problem, a group of researchers designed a screening method to understand how SLiMs selectively bind to certain proteins, and even distinguish between those with similar structures. Using the detailed information they gleaned from studying these interactions, the researchers created their own synthetic molecule capable of binding extremely tightly to a protein called ENAH, which is implicated in cancer metastasis. The team shared their findings in a pair of eLife studies, one published on January 25, 2022 and the other on December 2, 2021.

Part 1

The ability to test hundreds of thousands of potential SLiMs for binding provides a powerful tool to explore why proteins prefer specific SLiM partners over others.

As we gain an understanding of the tricks that a protein uses to select its partners, we can apply these in protein design to make our own binders to modulate protein function for research or therapeutic purposes.

The researchers also suspected that the amino acids on either side of the SLiM's core 4-6 amino acid sequence might play an underappreciated role in binding. To test their theory, they used MassTitr to screen the human proteome in longer chunks comprised of 36 amino acids, in order to see which "extended" SLiMs would associate with the protein ENAH.

ENAH, sometimes referred to as Mena, helps cells to move. This ability to migrate is critical for healthy cells, but cancer cells can coopt it to spread. Scientists have found that reducing the amount of ENAH decreases the cancer cells's ability to invade other tissues—suggesting that formulating drugs to disrupt this protein and its interactions could treat cancer.

Part 2

Next, the researchers combined a computer program called dTERMen with X-ray crystallography in order understand how and why PCARE binds to ENAH over ENAH's two nearly identical sister proteins (VASP and EVL). Researchers saw that the amino acids flanking PCARE's core SliM caused ENAH to change shape slightly when the two made contact, allowing the binding sites to latch onto one another. VASP and EVL, by contrast, could not undergo this structural change, so the PCARE SliM did not bind to either of them as tightly.

Inspired by this unique interaction, researchers designed their own protein that bound to ENAH with unprecedented affinity and specificity. "It was exciting that we were able to come up with such a specific binder," she says. "This work lays the foundation for designing synthetic molecules with the potential to disrupt protein-protein interactions that cause disease—or to help scientists learn more about ENAH and other SLiM-binding proteins.

Native proline-rich motifs exploit sequence context to target actin-remodeling Ena/VASP protein ENAH, eLife, DOI: 10.7554/eLife.70680 , elifesciences.org/articles/70680

A distributed residue network permits conformational binding specificity in a conserved family of actin remodelers, eLife, DOI: 10.7554/eLife.70601 , elifesciences.org/articles/70601

https://phys.org/news/2022-01-probing-proteins-pair-cells.html?utm_...

Part 3

**

 Exercise, age effects on plaque formation in arteries

Plaque formation in the arteries carrying blood to the head and neck is a serious medical problem, potentially leading to strokes and heart attacks. In Physics of Fluids, engineers from China use fluid dynamics simulations to study the effect of exercise at various ages on plaque formation.

It has been known for years that exercise and age affect the formation of plaques through a process known as atherosclerosis. What has not been fully understood, however, is how the geometrical features of the arteries affect plaque formation, although a dilated region in the inner carotid branch, the sinus, appears to be a vulnerable site.

"It is commonly accepted that the disturbed flow induces atherosclerosis.

To study this, the authors considered two arterial geometries, one with a bulging outer artery and the other without, and modeled the effect of exercise and age on blood flow through the two model arteries.

Two main arteries carrying blood to the head and neck, known as the carotid arteries, branch off from a single large artery at a position near the thyroid gland. One branch, the internal carotid artery, or ICA, carries blood inside the cranium to the brain, while the external carotid artery remains outside the cranium and brings blood to the neck, face, and scalp.

Just above the bifurcation, the ICA bulges outward, forming a region known as a sinus that is sensitive to blood pressure changes and helps regulate blood flow and heart rate.

Part 1