They have created a novel nanocrystal made from cellulose that sparkles in light and is biodegradable. Cellulose is made from glucose and is the component that gives tree wood its strength.

They wanted to compare the potential toxicity of conventional glitter with the new cellulose glitter as part of testing how sustainable the new glitter is.

They used a little soil critter called a springtail (Folsomia candida). Springtails are small, white, eyeless invertebrates that are closely related to insects. They are widespread in soils around the world where they feed on leaf litter and compost.

These critters are used as an indicator of soil quality and, because they are sensitive to toxic compounds, are often used to test for potential pollutants.

Using soil from the University of Melbourne's Dookie campus, the researchers exposed the springtails to different concentrations of conventional and cellulose glitter and studied the impact on their reproduction, survival and growth.

They found that neither glitter impacted springtail survival or size. However, once the concentrations of conventional glitter in the soil reached 1,000 mg of glitter per kg of soil, the reproduction of the springtails was reduced by 61%.
Part 3

The level of contamination they studied is on par with a soil contaminated with microplastics. Contaminated soils have been found to have up to approximately 100,000 mg per kg of microplastics with most soils below 10,000 mg per kg.

In comparison to conventional glitter, there were no toxic effects on springtail reproduction at any concentration of the cellulose glitter.

So, although it's promising that neither type of glitter was directly harmful to the springtails, it's worrying that the conventional glitter affected their ability to reproduce.

Fewer springtails being born can weaken their population, which might lead to bigger problems for soil health like less organic matter breaking down and fewer nutrients being released for plants.

The researchers suggest you think twice before using conventional glitter in make-up, clothing or for arts and crafts, but are hopeful that peope will soon be able to buy a safer, more sustainable and just as sparkly alternative.

Po-Hao Chen et al, Assessing the ecotoxicological effects of novel cellulose nanocrystalline glitter compared to conventional polyethylene terephthalate glitter: Toxicity to springtails (Folsomia candida), Chemosphere (2024). DOI: 10.1016/j.chemosphere.2024.143315

Part 4

**

Scientists discover how innate immunity envelops bacteria and destroy them

The protein GBP1 is a vital component of our body's natural defense against pathogens. This substance fights against bacteria and parasites by enveloping them in a protein coat, but how the substance manages to do this has remained unknown until now.

Researchers  have now unraveled how this protein operates. This new knowledge, published in Nature Structural & Molecular Biology, could aid in the development of medications and therapies for individuals with weakened immune systems.

Guanylate Binding Proteins (GBPs) play a crucial role in our innate immune system. GBPs form the first line of defense against various infectious diseases caused by bacteria and parasites. Examples of such diseases include dysentery, typhoid fever caused by Salmonella bacteria, and tuberculosis. The protein also plays a significant role in the sexually transmitted infection chlamydia as well as in toxoplasmosis, which is particularly dangerous during pregnancy and for unborn children. 

In their publication,  researchers describe for the first time how the innate immune system fights against bacteria using GBP1 proteins.

The protein surrounds bacteria by forming a sort of coat around them. By pulling this coat tighter, it breaks the membrane of the bacteria—the protective layer surrounding the intruder—after which immune cells can clear the infection.

To decode the defense strategy of GBPs, the researchers examined how GBP1 proteins bind to bacterial membranes using a cryogenic electron microscope. This allowed them to see the process in great detail down to the scale of molecules.

 Tanja Kuhm et al, Structural basis of antimicrobial membrane coat assembly by human GBP1, Nature Structural & Molecular Biology (2024). DOI: 10.1038/s41594-024-01400-9

Targeting 'undruggable' diseases: Researchers reveal new levels of detail in targeted protein degradation

Researchers  have revealed in the greatest detail yet the workings of molecules called protein degraders which can be deployed to combat what have previously been regarded as "undruggable" diseases, including cancers and neurodegenerative diseases.

Protein degrader molecules are heralding a revolution in drug discovery, with more than 50 drugs of this type currently being tested in clinical trials for patients with diseases for which no other options exist.

Now researchers have revealed previously invisible levels of detail and understanding of how the protein degraders work, which in turn is allowing for even more targeted use of them at the molecular level.

They used a technique called cryo-electron microscopy (cryo-EM), which enables scientists to see how biomolecules move and interact with each other.

This works by flash-freezing proteins and using a focused electron beam and a high-resolution camera to generate millions of 2D images of the protein. They then used sophisticated software and artificial intelligence (AI) models which allowed them to generate 3D snapshots of the degrader drugs working in action.

Their latest research is published in the journal Science Advances and is expected to constitute a landmark contribution to research in the field of TPD and ubiquitin mechanisms.

They  have reached a level of detail where they can see how these protein degraders work and can be deployed to recruit the disease-causing protein  and target the 'bull's eye,' in molecular terms.

Part 1

Protein degrader molecules work in a way that is fundamentally different from the way conventional drugs work. However, until recently the exact details of how this process works at the molecular level had remained elusive.

Proteins are typically a few nanometers large, which is 1 billionth of a meter, or 1 millionth of the width of a hair. So being able to 'see' them in action has not been possible, up until now.
Scientists have now been able to build a moving image of how it all happens, which means they can more specifically control the process with an incredible level of detail.
Proteins are essential for our cells to function properly, but when these do not work correctly they can cause disease.

Targeted protein degradation involves redirecting protein recycling systems in our cells to destroy the disease-causing proteins. Protein degraders work by capturing the disease-causing protein and making it stick like a glue to the cellular protein-recycling machinery, which then tags the protein as expired in order to destroy it.

The tag is a small protein called ubiquitin, which effectively gets fired at the disease-causing protein like a bullet. In order for the process to work effectively, ubiquitin must hit the right spots on the target protein so that it gets tagged effectively. The new work by the researchers enables them to see how the bullet hits the proverbial bull's eye.
Working with a protein degrader molecule called MZ1, which was developed in the Ciulli laboratory at Dundee, and using high-end mass spectrometry, they were able to identify exactly where on the target protein the vital "tags" are added.

The work shows how degrader drugs hold onto and position disease-causing proteins, making them good targets for receiving ubiquitin molecules (i.e., "ubiquitin-atable") which then leads to their destruction inside the cell.

Protein degradation efficiency and productivity is dependent on the degrader molecule's ability to hold tight onto the disease-causing protein, and in a position where it can most effectively act. This latest research paints a bull's eye and holds it steady enough for the molecule to be accurately targeted.

Charlotte Crowe et al, Mechanism of degrader-targeted protein ubiquitinability, Science Advances (2024). DOI: 10.1126/sciadv.ado6492. www.science.org/doi/10.1126/sciadv.ado6492

Part 2

'Killer electrons' of Lightning storms 

When lightning strikes, the electrons come pouring down. In a new study, researchers have discovered a novel connection between weather on Earth and space weather. The team utilized satellite data to reveal that lightning storms on our planet can dislodge particularly high-energy, or "extra-hot," electrons from the inner radiation belt—a region of space enveloped by charged particles that surround Earth like an inner tube.

The team's results could help satellites and even astronauts avoid dangerous radiation in space. This is one kind of downpour you don't want to get caught in.

These particles are the scary ones or what some people call 'killer electrons. They can penetrate metal on satellites, hit circuit boards and can be carcinogenic if they hit a person in space.

The findings cast an eye toward the radiation belts, which are generated by Earth's magnetic field.

 Two of these regions encircle our planet: While they move a lot over time, the inner belt tends to begin more than 600 miles above the surface. The outer belt starts roughly around 12,000 miles from Earth. These pool floaties in space trap charged particles streaming toward our planet from the sun, forming a sort of barrier between Earth's atmosphere and the rest of the solar system.

But they're not exactly airtight. Scientists, for example, have long known that high-energy electrons can fall toward Earth from the outer radiation belt.

Researchers also spotted a similar rain coming from the inner belt.

Earth and space, in other words, may not be as separate as they look. Space weather is really driven both from above and below.

Part 1

When a lightning bolt flashes in the sky on Earth, that burst of energy may also send radio waves spiraling deep into space. If those waves smack into electrons in the radiation belts, they can jostle them free—a bit like shaking your umbrella to knock the water off. In some cases, such "lightning-induced electron precipitation" can even influence the chemistry of Earth's atmosphere.
Here's what the team thinks is happening: Following a lightning strike, radio waves from Earth kick off a kind of manic pinball game in space. They knock into electrons in the inner belt, which then begin to bounce between Earth's northern and southern hemispheres—going back and forth in just 0.2 seconds.

And each time the electrons bounce, some of them fall out of the belt and into our atmosphere.

You have a big blob of electrons that bounces, and then returns and bounces again. You'll see this initial signal, and it will decay away.

Researchers aren't sure how often such events happen. They may occur mostly during periods of high solar activity when the sun spits out a lot of high-energy electrons, stocking the inner belt with these particles.

The researchers want to understand these events better so that they can predict when they may be likely to occur, potentially helping to keep people and electronics in orbit safe.

Max Feinland et al, Lightning-induced relativistic electron precipitation from the inner radiation belt, Nature Communications (2024). DOI: 10.1038/s41467-024-53036-4

Part 2

Study links children's bedtimes to gut health, finds early sleepers have greater microbial diversity in gut flora

Researchers  have found significant differences in the gut microbiota of children who go to bed early compared to those who stay up late. The study revealed that children with earlier bedtimes had greater microbial diversity in their gut flora.

Beneficial bacteria like Akkermansia muciniphila were more abundant in the early sleepers. These bacteria are associated with maintaining gut health and have been linked to healthy cognitive functions.

Previous studies have shown that adequate sleep improves academic performance, physical growth and is associated with healthier BMI levels. The current study investigated the relationship between children's sleep patterns and their gut microbiota.

In a paper, "Characteristics of gut flora in children who go to bed early versus...," published in Scientific Reports, researchers analyzed the genomics of fecal samples from 88 healthy children aged 2 to 14 years.

The children were split into two groups based on their bedtimes: those who slept before 9:30 p.m. and those who slept after. Over two weeks, sleep diaries recorded factors such as time at falling asleep, night awakenings, sleep efficiency, and sleep quality.

Genomic analysis found that children who went to bed early had a higher abundance of certain beneficial gut bacteria. Specifically, Akkermansia muciniphila was significantly more prevalent in the early bedtime group.

Other elevated bacteria among early sleepers included Holdemania filiformis, Firmicutes bacterium CAG-95, Streptococcus sp. A12, Weissella confusa, Clostridium sp. CAG-253, Alistipes finegoldii, and Eubacterium siraeum. Additionally, levels of CAG-83 fungi were higher in the early bedtime group.

At the phylum and genus levels, Verrucomicrobia, Akkermansia, Holdemania and unclassified Firmicutes showed greater abundance in the early sleep group.

Correlation analysis between sleep metrics and microbial species revealed that Akkermansia muciniphila and Alistipes finegoldii were positively correlated with the time it took to fall asleep. Clostridium sp. CAG-253 was negatively correlated with sleep onset latency.

The finding could be correlating sleep patterns to microbiome outcomes or the inverse, where the microbiome influences sleep patterns. While the study focused on the first scenario, the children's sleep schedules were their own regular, habitual bedtimes without any intervention from the researchers.

These correlations have great potential to be followed up in multiple directions to determine the causal mechanisms behind the sleep-gut-cognitive connection.

Vagus nerve stimulation enhances perceptual learning in mice, study suggests

Recent neuroscience studies have been investigating how the stimulation of some nerves, particularly the vagus nerve, using electrical pulses affects neural activity in the mammalian brain. The vagus nerve, the longest cranial nerve in the human body, is known to play a key role in the regulation of heart rate, digestion, stress and other physiological processes.

Some findings suggest that stimulating the vagus nerve can enhance the plasticity of the brain, which is its ability to reorganize itself following experiences. This could in turn facilitate perceptual learning, the process by which humans and other animals become better at distinguishing and interpreting different sensory inputs.

Researchers at New York University School of Medicine set out to further examine the effects of vagus nerve stimulation (VNS) on neural activity and perceptual learning in mice. Their findings, published in Nature Neuroscience, suggest that stimulating the vagus nerve enhances the performance of mice on a perceptual learning task by activating the central cholinergic system.

Part 1

As the mice gradually learned to complete the perceptual learning task, the researchers stimulated their vagus nerve using the electrode they developed. Concurrently, they also recorded activity in the animals' auditory cortex (involved in processing sounds), as well as in the locus coeruleus of the brainstem and the basal forebrain, two regions implicated in attention.

They found that indeed, VNS could augment training and improve perceptual discrimination beyond the limit achieved by training and effort alone. However, it takes a while, a few weeks of daily training and stimulation to see enduring gains at the most challenging difficulty levels. They also identified neural changes supporting this perceptual improvement..
The evidence gathered by the team at New York University suggests that in mice VNS activates the central cholinergic system, a neural network that utilizes the neurotransmitter acetylcholine to communicate with other neurons and supports various brain functions. The activation of this neural network was found to in turn enhance the performance of mice in the perceptual learning task they developed.

 Kathleen A. Martin et al, Vagus nerve stimulation recruits the central cholinergic system to enhance perceptual learning, Nature Neuroscience (2024). DOI: 10.1038/s41593-024-01767-4.

Part 2

Amazing Moment as SpaceX Catches Giant Starship Booster

For the first time ever, SpaceX has followed through on a Starship test launch by bringing back the Super Heavy booster for an on-target catch in the arms of its "Mechazilla" launch-tower cradle .

Today's successful catch marks a giant step toward using — and reusing — Starship for missions ranging from satellite deployments to NASA's moon missions to migrations to Mars.

This is really Funny! 

Male mice use female mice to distract aggressors and avoid conflict, study shows

A research group tracked the behaviour of mice using machine learning to understand how they handle aggressive behaviour from other mice. The researchers' findings, published on October 15 in the open-access journal PLOS Biology, show that male mice deescalate aggressive encounters by running over to a female mouse to distract the aggressive male mouse.

The researchers recorded groups of two male and two female mice interacting over five hours. Like many other animals, mice have social hierarchies, and in almost each group recorded, one male was always significantly more aggressive towards the other.

Social interactions can be challenging to study objectively, so the researchers used a machine learning approach to analyze aggressive interactions and how the mice respond. In total, they observed over 3,000 altercations between the male mice, and the machine learning algorithm helped researchers determine the most likely responses to aggression and whether these actions resolved or furthered the conflict.

The researchers found that the male mouse who was aggressively encountered often ran over to one of the female mice and that this deescalated the aggression. This may be a "bait-and-switch" tactic, as the aggressive male mouse typically followed the other male but then interacted with the female mouse instead of continuing the aggressive encounter.

Some other tactics, even if they avoided aggression for a moment, would then escalate to full fights. However, the researchers found this was not the case after the bait-and-switch. After this tactic was used, fights rarely occurred, the male mice often remaining further apart from each other with the aggressive mouse continuing to interact with the female mouse.

While the bait-and-switch may be an effective way to deescalate conflicts, there may be costs to the victim, such as sacrificing time with the female mice, and further research may look into whether these tactics are effective in larger groups of mice.

Clein RS, Warren MR, Neunuebel JP, Mice employ a bait-and-switch escape mechanism to de-escalate social conflict, PLoS Biology (2024). DOI: 10.1371/journal.pbio.3002496

The physics of red blood cells in bats could be a key to 'artificial hibernation' for humans

The mechanical properties of red blood cells (erythrocytes) at various temperatures could play an important role in mammals' ability to hibernate. This is the outcome of a study that compared the thermomechanical properties of erythrocytes in two species of bats and humans.

The study was published in October 2024 in the Proceedings of the National Academy of Sciences. The new findings could contribute towards the development of new medical treatments.

Hibernation is common for mammals, especially bats, and even some primates hibernate. In this current study, the interdisciplinary team of researchers compared the mechanical properties of hundreds of thousands of individual erythrocytes from a hibernating native bat species, the common noctule (Nyctalus noctula), a non-hibernating bat species, the Egyptian fruit bat (Rousettus aegyptiacus), and healthy human donors. Data was collected for temperatures between 10°C and 37°C.

In all three species, the individual erythrocytes became more viscous when the temperature of the blood samples was lowered from a normal body temperature of 37°C to a temperature of 10°C, which is typical for temperatures in hibernating mammals.

The observed behaviour is a result of the properties of the cell membrane and is much more evident in both bat species than in humans. Interestingly, this special adaptation in bats is not only due to seasonal fluctuations such as changing diets and surrounding temperatures.

Humans are unable to significantly lower their core body temperature in order to save energy. Based on the collected data, it could be possible in the future to develop pharmaceutical methods that change the mechanical properties of human erythrocytes in order to optimize the blood circulation in artificially induced states similar to hibernation. If this is successful, the dream of hibernation for extended space missions could also come a step closer to reality.

Bob Fregin et al, Thermomechanical properties of bat and human red blood cells—Implications for hibernation, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2405169121

‘Neural tourniquet’ could stem bleeding

Electrical stimulation near the ear that targets the vagus nerves might help to reduce bleeding during surgery or childbirth. The ‘neural tourniquet’ seems to stimulate the spleen, which stores about one-third of the body’s clot-forming platelets, according to preliminary results presented at the 2024 Society for Neuroscience conference. Tests in injured pigs and mice with the blood-clotting condition haemophilia showed that the animals bled less, and for less time, than untreated ones. The time scale could be a real-world limitation for emergency treatment: platelets were most highly activated 2 hours after stimulation.

https://www.nature.com/articles/d41586-024-03330-4?utm_source=Live+...

Study finds PFAS in fish far from contamination sources

Fish can accumulate high levels of per- and polyfluoroalkyl substances (PFAS), even far from sources of contamination, according to a new study by researchers .

This study underscores the urgent need for more comprehensive monitoring of PFAS in aquatic ecosystems, particularly in regions where freshwater fishing is an important food source .

PFAS, also called forever chemicals because of their persistence in the environment, are a family of thousands of synthetic chemicals widely used for their stain-resistant, water-resistant, non-stick properties. They have seeped into our water, soil, and food, and can be found in more than 98-99% of people in some countries. 

 Freshwater fish and shellfish, a staple in many diets, often contain high levels of these forever chemicals.

The researchers found that a substantial portion of PFAS contamination remains undetected by conventional monitoring techniques, which typically target only a limited number of PFAS compounds. To fully grasp the scale of PFAS contamination and its risks, environmental monitoring programs and fish consumption advisories must include a wider range of PFAS compounds, the researchers recommend.

Heidi M. Pickard et al, Characterizing the Areal Extent of PFAS Contamination in Fish Species Downgradient of AFFF Source Zones, Environmental Science & Technology (2024). DOI: 10.1021/acs.est.4c07016

https://www.sciencedirect.com/science/article/abs/pii/S004565352302...

Researchers call for PFAS ban after alarming findings in marine environments

Washing your pots and pans—among many other day-to-day activities—could have a significant impact on marine environments for hundreds of years, according to a new study.

Scientists have partnered with the  leading marine membership charities to investigate the presence of harmful chemicals in a protected area. They found that sewage discharges are contributing significantly to per- and polyfluoroalkyl substances (PFAS) in marine environments.

PFAS are a complex group of nearly 15,000 synthetic substances used in consumer products around the world since the 1950s. They keep food from sticking to packaging or cookware, make clothes and carpets resistant to stains, and are found in firefighting foam.

The "forever chemicals" don't break down easily in the environment. They have been linked to adverse effects on human health and wildlife.

Wastewater treatment plants (WWTPs) are not effective at removing PFAS, and therefore they are often released into the environment through combined sewer overflows (CSOs).

The findings of the study, published in Chemosphere, revealed PFAS concentrations increased significantly after sewage discharges. Eight different PFAS compounds were detected post-discharge, compared to just one detectable compound before the discharge.

Banned substances Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were also found at levels exceeding annual average environmental quality standards.

The paper raises concerns about the health of marine ecosystems and the potential impacts of industries using seafood products.

Samples also showed the amount of one particular PFAS called Perfluorobutanoic acid (PFBA) in the seaweed was more than 6,000 times higher than the amount found in the surrounding water.

These seaweeds could potentially be acting as a reservoir for these forever chemicals around our coasts. High concentrations of PFAS compounds in macroalgae might be harmful for marine life that graze on seaweed and as a result provide a trophic link up the food chain.

Toxicity studies in the laboratory and human epidemiological studies of those drinking PFAS contaminated water have highlighted these chemical compounds can impact the immune, nervous and reproductive systems as well as being carcinogenic and cause birth defects.

"It is important that we get these chemicals banned as we are still seeing the impacts of persistent chemical contaminants—like PCBs—impacting wildlife that were banned decades ago, which is why it is so important we act faster, the researchers say.

 Alex T. Ford et al, Insights into PFAS contaminants before and after sewage discharges into a marine protected harbour, Chemosphere (2024). DOI: 10.1016/j.chemosphere.2024.143526

Plastic pollution harms bees and their pollinator functions, research team finds

Nano- and microplastic particles (NMP) are increasingly polluting urban and rural landscapes, where bees and other beneficial insects come into contact with them. If insects ingest plastic particles from food or the air, it can damage their organs and cause changes in their behavior, preventing them from properly performing ecosystem services such as pollination and pest control.

Plastic pollution thus poses considerable risks to biodiversity, agricultural production, and global food security. These are the main findings of a new review in the journal Nature Communications, which was conducted by an international team of researchers .

Microplastic particles are between one micrometer and five millimeters in size; still smaller particles are referred to as nanoplastics. Whereas the harmful effects of NMP in water and for individual species are well documented, there have as yet been no systematic reviews on how the particles affect agricultural ecosystems.

To fill this gap, the authors of the review summarized 21 already published individual studies for the first time. They were interested particularly in the question of how pollinator insects and other beneficial insects come into contact with NMP and what consequences the ingestion of the particles has for them, as well as for the ecosystems that are dependent on them and for agricultural production. 

In this way, the researchers first succeeded in identifying different sources from which NMP end up on agricultural land, including plastic films, fertilizers, polluted water, and atmospheric depositions. The plastic particles accumulate in the soil, and pollinators and beneficial insects that are important for pest control ingest them from the air and food or use them to build nests.

The authors of the study establish that the bees' ingestion of NMP leads, for example, to damage to their digestive system, to a weakening of their immune system, and to changes in their behavior. This makes the bees more susceptible to diseases, possibly causing them to pollinate plants less effectively. This leads to decline in agriculture production.

A decline in pollination services has a negative effect on crop yield. Thus, plastic pollution could further aggravate existing uncertainties in the global food supply, the researchers warn.

In addition, NMP also exacerbates the threats posed by other environmental stressors, such as pesticides, chemical pollution, fungi, and pathogens. For example, some areas become "hotspots," where plastic particles interact with harmful viruses. As a result of such interactions, NMP could have serious effects on pollinators and thus on the stability of the food system.

It is already clear today, however, that there is a pressing need for political control of plastic pollution, the researchers stress.

 Dong Sheng et al, Plastic pollution in agricultural landscapes: an overlooked threat to pollination, biocontrol and food security, Nature Communications (2024). DOI: 10.1038/s41467-024-52734-3

Men and women use different biological systems to process pain, study discovers

In a new study evaluating meditation for chronic lower back pain, researchers have discovered that men and women utilize different biological systems to relieve pain. While men relieve pain by releasing endogenous opioids, the body's natural painkillers, women rely instead on other, non-opioid based pathways.

Synthetic opioid drugs, such as morphine and fentanyl, are the most powerful class of painkilling drugs available. Women are known to respond poorly to opioid therapies, which use synthetic opioid molecules to bind to the same receptors as naturally-occurring endogenous opioids. This aspect of opioid drugs helps explain why they are so powerful as painkillers, but also why they carry a significant risk of dependence and addiction.

Dependence develops because people start taking more opioids when their original dosage stops working.

These findings, although speculative,  suggest that maybe one reason that females are more likely to become addicted to opioids is that they're biologically less responsive to them and need to take more to experience any pain relief.

The study combined data from two clinical trials involving a total of 98 participants, including both healthy individuals and those diagnosed with chronic lower back pain. Participants underwent a meditation training program, then practiced meditation while receiving either placebo or a high-dose of naloxone, a drug that stops both synthetic and endogenous opioids from working.

At the same time, they experienced a very painful but harmless heat stimulus to the back of the leg. The researchers measured and compared how much pain relief was experienced from meditation when the opioid system was blocked versus when it was intact.

Part 1

The study found:

Blocking the opioid system with naloxone inhibited meditation-based pain relief in men, suggesting that men rely on endogenous opioids to reduce pain.
Naloxone increased meditation-based pain relief in women, suggesting that women rely on non-opioid mechanisms to reduce pain.
In both men and women, people with chronic pain experienced more pain relief from meditation than healthy participants.
These results underscore the need for more sex-specific pain therapies, because many of the treatments we use don't work nearly as well for women as they do for men.
The researchers conclude that by tailoring pain treatment to an individual's sex, it may be possible to improve patient outcomes and reduce the reliance on and misuse of opioids.

 Jon G Dean et al, Self-regulated analgesia in males but not females is mediated by endogenous opioids, PNAS Nexus (2024). DOI: 10.1093/pnasnexus/pgae453

Part 2

New type of insulin that switches on and off could help diabetics avoid sudden drops in blood sugar levels

A modified insulin that can prevent sudden drops in blood sugar has been demonstrated in laboratory experiments and animal models, reports a paper in Nature. This could provide a more flexible way to supplement insulin for individuals with diabetes and reduce sudden drops in blood glucose.

For some people with diabetes, supplementary insulin injections are needed to control blood glucose levels. Fluctuations in blood glucose levels are difficult to predict, making it hard to select the appropriate insulin doses. Even a slightly high dose can lead to hypoglycemia (blood glucose levels decreasing too much), which can be life-threatening.

This has happened to my mother twice. As I used to give her the injections, this bothered me a lot then.
Researchers now present a modified form of insulin with activity that varies according to the levels of glucose in the blood. The molecule, named NNC2215, is equipped with a switch that can open and close in response to glucose. Under high glucose concentrations, the switch opens, and the insulin becomes more active, removing glucose from the blood. When glucose levels decrease, the switch moves to a closed state, which prevents glucose uptake.
Laboratory experiments showed that upon an increase in glucose concentration from 3 to 20 mM (approximately the fluctuation range experienced by individuals with diabetes), the NNC2215 insulin receptor affinity increased by 3.2-fold, validating its potential to respond to changes in blood glucose levels. In rat and pig models of diabetes, NNC2215 proved to be as effective as human insulin in lowering blood glucose. Its increased glucose sensitivity was shown to provide protection against hypoglycemia in these animal subjects.

This modified insulin shows promise in preventing the sharp drops in glucose that can severely affect individuals with diabetes, especially during sleep. This could improve both long- and short-term complications associated with diabetes, the authors note.

Oh, what a relief from the concerns people like me face?!

Rita Slaaby, Glucose-sensitive insulin with attenuation of hypoglycaemia, Nature (2024). DOI: 10.1038/s41586-024-08042-3

Cats associate human words with images, experiment suggests

A small team of animal scientists  has found via experimentation that common house cats are capable of associating human words with images without prompting or reward. In their study, published in the journal Scientific Reports, the group tested volunteer cats looking at images on a computer screen to see if they form associations between the images and spoken words.

Prior research has shown that cats know when a human is speaking their name—they respond in ways that are different than when hearing other words.

Other experiments have shown that they are able to match photos of people they know to their names. In this new effort, the researchers found that cats may be able to understand many of the words spoken to them.

To find out if cats have the ability to match a word to an object, the research team enlisted the assistance of 31 volunteer adult house cats. Each was given a word test originally designed to learn more about word association in growing human infants. It involves being shown short animations.

While the image is displayed, a nonsensical word is broadcast. Each cat saw two such animations—one was accompanied by the word "keraru," the other "parumo." The videos were played on a loop until the cats looked away.

After giving each cat a break, each was once again placed in front of the computer screen and the same two animations were shown on a loop. But this time, the spoken words were reversed.

As the cats watched the videos, the researchers watched the cats.

They found that they stared longer when hearing the word than during the original broadcast—some even showed pupil dilation. Both were signs that the cats were confused by the switch-up and were looking intently to find an explanation, evidence that they had associated the words with the images on the computer screen, even in the absence of a reward.

This finding, the team suggests, indicates that it is likely that cats commonly associate words they hear from humans with objects in their environment.

Saho Takagi et al, Rapid formation of picture-word association in cats, Scientific Reports (2024). DOI: 10.1038/s41598-024-74006-2

**

I am not very convinced with this work, though!

COVID-19 linked to type 2 diabetes onset in children

Pediatric patients aged 10 to 19 years old diagnosed with COVID-19 have a higher risk of new-onset type 2 diabetes within six months compared to those diagnosed with other respiratory infections, according to researchers.

 The research is a follow-up of meta-data analysis showing an increased risk of type 2 diabetes in adults. The meta-analysis revealed a 66% higher average risk of new-onset diabetes after SARS-CoV-2 infection in adults. In the current retrospective study, "SARS-CoV-2 Infection and New-Onset Type 2 Diabetes Among Pediatric Patients, 2020 to 2022," published in JAMA Network Open, researchers looked to see if a similar pattern existed in children.

The study analyzed a cohort of 613,602 pediatric patients aged 10 to 19 years. After propensity score matching, this cohort was divided equally into two groups: 306,801 patients diagnosed with COVID-19 and 306,801 patients diagnosed with other respiratory infections (ORI).

A subset of the cohort with obesity and COVID or ORI was also analyzed, with two groupings of 16,469 patients.

The research compared the incidence of new type 2 diabetes diagnoses at one, three, and six months after the initial respiratory infection. The risk ratios (RR) for developing type 2 diabetes after COVID-19 were found to be significantly higher than for those with ORI.

Specifically, the RR was 1.55 (95% CI, 1.28–1.89) at one month, 1.48 (95% CI, 1.24–1.76) at three months, and 1.58 (95% CI, 1.35–1.85) at six months post-infection.

The smaller subgroup analyses revealed even greater elevated risks among children classified as overweight, with RRs of 2.07 at one month, 2.00 at three months, and 2.27 at six months. Hospitalized patients also showed increased risks, with RRs of 3.10 at one month, 2.74 at three months, and 2.62 at six months after COVID-19 diagnosis.

The study concluded that SARS-CoV-2 infection is associated with a higher incidence of type 2 diabetes diagnoses in children than those with other respiratory infections. Further research is necessary to determine whether the diabetes persists or is a recoverable condition that reverses later in life.

Margaret G. Miller et al, SARS-CoV-2 Infection and New-Onset Type 2 Diabetes Among Pediatric Patients, 2020 to 2022, JAMA Network Open (2024). DOI: 10.1001/jamanetworkopen.2024.39444

City microbes surviving on disinfectants, research reveals

New research shows microbes in our cities are evolving to resist the very cleaners we use to eliminate them. 

After the recent pandemic, the use of disinfectants has increased, but are efforts to create sterile urban environments backfiring?

A study published in the journal Microbiome has identified novel strains of microbes that have adapted to use the limited resources available in cities and shown that our everyday behavior is changing the makeup of microorganisms in indoor environments.

Built environments offer distinct conditions that set them apart from natural and engineered habitats.

Areas with many buildings are low in the traditional nutrients and essential resources microbes need for survival, so these built environments have a unique microbiome.

Our use of cleaning and other manufactured products creates a unique setting that puts selective pressures on microbes, which they must adapt to or be eliminated.

The researchers collected 738 samples from a variety of built environments, including subways, residences, public facilities, piers and human skin in Hong Kong. They then used shotgun metagenomic sequencing to analyze the microbes' genomic content and understand how they have adapted to the challenging urban conditions.

The team identified 363 microbial strains that have not been previously identified that live on the skin and the surrounding environment. Some of these strains' genomes contained genes for metabolizing manufactured products found in cities and using them as carbon and energy sources. This includes the discovery of a strain of Candidatus phylum Eremiobacterota, previously only reported in Antarctic desert soil.

The genome of this novel strain of Eremiobacterota enables it to metabolize ammonium ions found in cleaning products. The strain also has genes for alcohol and aldehyde dehydrogenases to break down residual alcohol found in common disinfectants.

"Microbes possessing enhanced capabilities to utilize limited resources and tolerate manufactured products, such as disinfectants and metals, out-compete non-resistant strains, enhancing their survival and even evolution within built environments. They could, therefore, pose health risks if they are pathogenic.

Part 1

The team identified 11 unique, previously uncharacterized strains of Micrococcus luteus, typically non-pathogenic but capable of causing opportunistic infections in immunocompromised individuals.

"The issue of their adaptation to our behavior becomes particularly critical in clinical settings where hospitals serve as hotspots for diverse pathogens that cause hospital-acquired infections (HAIs). HAIs pose a significant threat, particularly in intensive care units where mortality rates can reach up to 30%.
The researchers also characterized two novel strains of Patescibacteria, known as "nanobacteria", as they have tiny genomes that do not contain many genes for producing their own resources.
Some strains of Patescibacteria are considered parasitic as they rely on bacterial hosts to supply their nutrients. However, in this study, the researchers found that one of the nanobacteria strains, recovered from human skin, contains genes for the biosynthesis of carotenoids and ubiquinone.
These antioxidant compounds are vital to humans, and we typically acquire them, especially carotenoids, through our diets, suggesting a possible mutualistic relationship between bacteria and us as their hosts.
This enhanced understanding of microbial metabolic functions within built environments helps develop strategies to create a healthy indoor ecosystem of microbes for us to live alongside.
--
The team is now investigating the transmission and evolution of resistance in pathogenic microbes in intensive care units that are exposed to stringent and extensive disinfectant practices. They hope to improve infection control practices and increase the safety of clinical environments for health care workers and patients.

 Xinzhao Tong, et al. Diverse and specialized metabolic capabilities of microbes in oligotrophic built environments. Microbiome (2024) DOI: 10.1186/s40168-024-01926-6

Part 2

mRNA vaccines for disease outbreaks can be synthesized in less time with new technique

In an era where viral outbreaks can escalate into global pandemics with alarming speed, the ability to quickly develop new vaccines has become crucial. However, the speed of vaccine production is limited because the mRNA used in it is partly chemically synthesized and partly synthesized using enzymes, a relatively slow process.

A team of researchers has successfully developed an innovative synthesis technology capable of producing high purity, fully chemically-synthesized mRNA, cutting out the slower enzyme reactions.

This advancement establishes a foundation for more rapid reactions to viral outbreaks and emerging diseases, which will hopefully lead to mitigation of future infections at a preliminary stage. Their results were published in the journal Nucleic Acids Research.

Given its significant role in combating the COVID-19 pandemic, mRNA is now widely recognized for its potential to help prevent infectious diseases. Experts anticipate that in the future mRNA technology will be used to treat genetic disorders and emerging illnesses. However, producing mRNA remains challenging because of concerns about purity and production speed.

These problems can be addressed using fully chemically-synthesized mRNA.

One of the most significant advantages of fully chemically-synthesized mRNA is its ability to bypass the complex and time-consuming enzymatic reactions typically required in mRNA production. A method that relies purely on chemical reactions would significantly shorten the production process.

It also offers benefits to people that have strong immune responses to vaccines. mRNA that is derived from 5'-monophosphorylated RNA is susceptible to contamination by incomplete RNA fragments, causing a strong immune reaction. This immune response increases the risk of side effects, particularly inflammation. However, existing purification technologies have struggled to remove these impurities, limiting its potential.

So researchers now devised a novel phosphorylation reagent with a nitrobenzyl group that serves as a hydrophobic purification tag.

"Nitrobenzyl groups have high hydrophobicity; therefore, when the nitrobenzyl group is introduced into the RNA molecule, the mRNA becomes more hydrophobic. As impure RNA lacks nitrobenzyl groups, it can be easily separated from the target RNA containing nitrobenzyl groups using reverse-phase high-performance liquid chromatography.

"This approach yields pure RNA, free from length inconsistencies and impurities typically associated with transcription-based synthesis methods."

Besides fully synthesizing mRNA chemically, the team also created pure circular mRNA using the same method. Circular mRNAs are unique because they lack terminal structures, making them resistant to degradation by nucleic acid-degrading enzymes in the body, resulting in a longer-lasting medicinal effect.

The breakthrough in mRNA production has significant implications for the future of medical treatments.

Mami Ototake et al, Development of hydrophobic tag purifying monophosphorylated RNA for chemical synthesis of capped mRNA and enzymatic synthesis of circular mRNA, Nucleic Acids Research (2024). DOI: 10.1093/nar/gkae847

Forever chemicals found in bottled and tap water from around the world

Researchers found 10 'target' PFAS (perfluoroalkyl substances)—chemicals which do not break down in nature—in tap and bottled water available for consumption in major cities.

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) were detected in over 99% of samples of bottled water sourced from 15 countries around the world.

However, the study demonstrates that measures such as boiling and/or activated carbon filtration—typically using a 'jug' water filter—can substantially reduce PFAS concentrations in drinking water, with removal rates ranging from 50% to 90% depending on the PFAS and treatment type.

Publishing their findings in ACS ES&T Water, researchers reveal a wide range of PFAS contamination for target PFAS, starting at 63% of bottled waters tested.

These findings highlight the widespread presence of PFAS in drinking water and the effectiveness of simple treatment methods to reduce their levels. Either using a simple water filtration jug or boiling the water removes a substantial proportion of these substances.

Chuanzi Gao et al, Factors Influencing Concentrations of PFAS in Drinking Water: Implications for Human Exposure, ACS ES&T Water (2024). DOI: 10.1021/acsestwater.4c00533

Water crisis threatening world food production: report
Inaction on the water crisis could put more than half of the world's food production at risk by 2050, experts warned in a major report published this week.

Nearly 3 billion people and more than half of the world's food production are now in areas where total water storage is projected to decline," said the report by the Global Commission on the Economics of Water (GCEW).

The report also warned the water crisis could lead to an eight percent drop in GDP on average for high-income countries by 2050 and as much as 15 percent for lower-income countries.

Disruptions of the water cycle "have major global economic impacts," said the report.

The economic declines would be a consequence of "the combined effects of changing precipitation patterns and rising temperatures due to climate change, together with declining total water storage and lack of access to clean water and sanitation".

Facing this crisis, the report called for the water cycle to be viewed as a "global common good" and for a transformation of water governance at all levels.

"The costs entailed in these actions are very small in comparison to the harm that continued inaction will inflict on economies and humanity," it said.

While water is often perceived as "an abundant gift of nature", the report stressed it was scarce and costly to transport.

It called for the elimination of "harmful subsidies in water-intensive sectors or redirecting them towards water-saving solutions and providing targeted support for the poor and vulnerable".

Source: News agencies

Dancer Develops a "Cone-Shaped" Head from Breakdancing Too Much 

According to a 2024 medical case report, a breakdancer who'd been performing for 19 years was treated for "headspin hole", a condition also known as "breakdancer bulge" that's unique to breakdancers. It entails a cone shaped mass developing on top of the scalp after repetitive head-spinning. Additional symptoms can include hair loss and sometimes pain around the lump.

Approximately 30% of breakdancers report hair loss and inflammation of their scalp from head-spinning. A headspin hole is caused by the body trying to protect itself. The repeated trauma from head-spinning causes the epicranial aponeurosis—a layer of connective tissue similar to a tendon, running from the back of your head to the front—to thicken along with the layer of fat under the skin on top of the head in an attempt to protect the bones of skull from injury. The body causes a similar protective reaction to friction on the hands and feet, where callouses form to spread the pressure and protect the underlying tissues from damage. Everyday repetitive activities from holding smartphones or heavy weights through to poorly fitting shoes can result in callouses.

But a cone-shaped head isn't the only injury to which breakdancers are prone, however. Common issues can include wrist, knee, hip, ankle, foot and elbow injuries, and moves such as the "windmill" and the "backspin" can cause bursitis—inflammation of the fluid filled sacs that protect the vertebrae of the spine. A headspin hole isn't the worst injury you could sustain from breakdancing either. One dancer broke their neck but thankfully they were lucky enough not to have any major complications.

https://casereports.bmj.com/content/17/9/e261854

Different types of fears activate different parts of the brain. 

For a long time, people assumed that the responses to all fearful scenarios occurred similarly within the brain.

There's this story that we've had in the literature that the brain regions that predict fear are things like the amygdala, or the orbital frontal cortex area, or the brainstem. Those are thought to be part of a so-called 'fear circuit' that's been a very dominant model in neuroscience for decades.

In early October 2024,  researchers released new research that undermines that persistent model. In a study published in The Journal of Neuroscience the researchers used MRI scans to observe brain activity when confronted with three distinctive scenarios meant to evoke different types of fear: fear of heights, fear of spiders, and fear of "social threats" (public speaking, confrontations with police).

And contrary to the prevailing scientific wisdom, the neural response to each type of scenario activated different areas of the brain—rather than following a single pattern.

Although based on a small sample size, the study revealed two things: fear responses happened across a wider range of brain regions than expected. But not all brain regions responded across all three situations.

The amygdala, for instance, seemed to carry information that predicted fear during the heights context, but not some of the other contexts. The so-called 'classic threat areas' involved in being predictive of fear across situations are not seen here.

When scientists look at the brain and the neural correlates of fear, part of the reason they want to understand is so they can intervene on it. Their new findings suggest the interventions might also need to be tailored to the person and situation.

This could now affect behaviour-based therapies, but also, much further down the line, pharmacological ones.

Yiyu Wang et al, Neural predictors of fear depend on the situation, The Journal of Neuroscience (2024). DOI: 10.1523/JNEUROSCI.0142-23.2024

Bumblebee queens choose to hibernate in pesticide-contaminated soil, scientists discover

An alarming discovery by researchers raises concerns for bumblebee health, survival and reproduction. U of G environmental sciences researchers have found that bumblebee queens are more likely to hibernate in soil contaminated with pesticides than in clean soil—for reasons they still don't quite understand.

The team conducted field experiments in which newly emerged queens of the common eastern bumblebee (Bombus impatiens) were left to fly freely in outdoor enclosures, mate and then choose a site in which to hibernate for the winter.

The choice was between clean soil or soil contaminated with one of five common pesticides, including insecticides and fungicides, across different concentrations.

The School of Environmental Sciences researchers then carefully searched through the soils for hibernating bumblebee queens. They found queens avoided the pesticide-free soil and, in fact, were about twice as likely to be drawn to the pesticide-contaminated soil.

Most bees in the study survived, but other consequences for the colony are highlighted in the study, published in Science of the Total Environment.

"This raises serious concerns for bumblebee health," say the researchers, "especially as this group of important insect pollinators already face many challenges.

Bumblebee queens typically hibernate underground during winter before emerging in spring to start new colonies. Researchers wanted to investigate how bees respond to contaminants at this key but vulnerable life stage.

Previous studies showed that pesticides on crops can either attract or repel bees, depending on the type, the environmental situation and the concentration used.

One possible explanation is that pesticides altered the soil properties and made it more appealing to the queens.

For example, the fungicides used in the study could have killed soil fungi and nematodes, and queens might avoid soils with fungi because they can be harmful during hibernation.

Another possibility is that the queens could have developed an "acquired taste" for pesticides, as researchers put it, due to prior exposure in their environment.

They might also be looking for something new, as novelty-seeking behavior is common for bees and often leads the colony to discover new resources.

More research is needed to fully understand the mechanisms behind this unexpected queen behaviour. But the findings suggest the need to reconsider how pesticides are used and managed in agricultural settings as exposure to pesticides is contributing to a worldwide decline of insects.

 Sabrina Rondeau et al, Bumblebee (Bombus impatiens) queens prefer pesticide-contaminated soils when selecting underground hibernation sites, Science of The Total Environment (2024). DOI: 10.1016/j.scitotenv.2024.176534

Climate justice broadly encompasses recognition that (1) climate change impacts are unequally felt across society; (2) the worst affected groups often have the least say in the selection and implementation of societal responses to climate change, and (3) climate change-related policymaking processes often fail to recognize the legitimate interests of politically voiceless communities, consequently contributing to further disenfranchisement of marginalized groups. It is a framework that enables those involved in policymaking to identify and tackle the multiple different ways in which the climate crisis intersects with longstanding patterns of social injustice.

How scientists are trying to tackle drug resistance in cancer therapies

One of the major challenges in cancer treatment is drug resistance. Mutations in cancer cells mean that over time they become less responsive to therapies. After cancer has become resistant to the initial treatment, the following therapies are known as second-line therapies and options for these can be limited. Understanding what molecular changes are causing the resistance, and what can be done to tackle this, can help uncover new options and inform clinical pathways for specific mutations.

All cancer mutations that cause drug resistance fall into one of four categories. New research has detailed each type, helping to uncover targets for drug development and identify potential effective second-line therapies.

In a new large-scale study, researchers  used CRISPR gene editing to map the genetic landscape of drug resistance in cancers, focusing on colon, lung, and Ewing sarcoma. The team explains how known mutations impact drug resistance and highlights new DNA changes that could be explored further.

The research,  published in Nature Genetics, investigated the effect of mutations on the sensitivity to 10 cancer drugs, also identifying possible effective second-line treatments based on a person's genetic makeup.

By understanding the mechanisms of how cancers become resistant to treatment, researchers can identify new targets for personalized therapies, help treat patients based on their cancer's genetic makeup, give second-line treatment options to those who currently have none, and help further research to develop next-generation cancer drugs that could avoid drug resistance emerging.

Part 1

Researchers were able to create a map showing drug resistance across different cancers, focusing on colon, lung, and Ewing sarcoma. The map uncovers more about the mechanisms of drug resistance, highlights DNA changes that may be potential treatment biomarkers, and identifies promising combinations or second-line therapies.

The team found that cancer mutations fall into four different categories depending on the impact of the DNA change. Drug resistance mutations, otherwise known as canonical drug resistance mutations, are genetic changes in the cancer cell that lead to the drug being less effective. For example, changes that mean the drug can no longer bind to its target in the cancer cell.

Drug addiction mutations lead to some of the cancer cells using the drug to help them grow, instead of destroying them. This research supports the use of drug holidays in the case of drug addiction mutations, which are periods without treatment. This could help destroy the cancer cells with this type of mutation, as the cells are now dependent on treatment.

Driver mutations are gain-of-function genetic changes that allow cancer cells to use a different signaling pathway to grow, avoiding the pathway that the drug may have blocked.

Lastly, drug sensitizing variants are genetic mutations that make the cancer more sensitive to certain treatments and could mean that patients with these genetic changes in their tumor would benefit from particular drugs.

The research focused on colon, lung, and Ewing sarcoma cancer cell lines, as these are all prone to developing resistance and have limited second-line treatments available. The team used 10 cancer drugs that are either currently prescribed or going through clinical trials to help highlight if any of these could be repurposed or used in combination to address resistance, decreasing the time it would take to get any potential treatments to the clinic.

Understanding more about the four different types of DNA changes can help support clinical decisions, explain why treatments are not working, support the idea of drug holidays in certain patients, and help develop new treatments. This knowledge also helps accelerate drug companies' research into next-generation cancer inhibitors that could better prevent drug resistance.

Base editing screens define the genetic landscape of cancer drug resistance mechanisms, Nature Genetics (2024). DOI: 10.1038/s41588-024-01948-8

Part 2

Scientists show how sperm and egg come together like a key in a lock

How a sperm and an egg fuse together?

New research by scientists  provides tantalizing clues, showing fertilization works like a lock and key across the animal kingdom, from fish to people. This mechanism is really fundamental across all vertebrates.

 The team found that three proteins on the sperm join to form a sort of key that unlocks the egg, allowing the sperm to attach. Their findings, drawn from studies in zebrafish, mice, and human cells, show how this process has persisted over millions of years of evolution. Results were published this week in the journal Cell.

Scientists had previously known about two proteins, one on the surface of the sperm and another on the egg's membrane. Working with international collaborators, researchers used Google DeepMind's artificial intelligence tool AlphaFold—whose developers were awarded a Nobel Prize earlier this month—to help them identify a new protein that allows the first molecular connection between sperm and egg. They also demonstrated how it functions in living things.

It wasn't previously known how the proteins "worked together as a team in order to allow sperm and egg to recognize each other".

The work provides targets for the development of male contraceptives in particular.

Victoria E. Deneke et al, A conserved fertilization complex bridges sperm and egg in vertebrates, Cell (2024). DOI: 10.1016/j.cell.2024.09.035

Sound of Earth’s magnetic flip 41 000 years ago

How Some Fish Regrow Their Fins

Animals like the African killifish can regrow entire body parts after amputation, but how cells know where and how much to grow after injury remains a mystery. A recent iScience publication from Augusto Ortega Granillo, Alejandro Sànchez Alvarado, and their research team at the Stowers Institute for Medical Research sheds light on the mechanisms of positional memory.

1. Otsuki L, Tanaka EM. Positional memory in vertebrate regeneration: A century’s insights .... Cold Spring Harb Perspect Biol. 2021;14(6):a040899.
2. Ortega Granillo A, et al. Positional information modulates transient regeneration-activated c.... iScience. 2024;27(9):110737.

Chemical trick activates antibiotic directly at the pathogen

Due to increasing resistance, it is becoming more and more frequent that common and well-tolerated antibiotics no longer work against dangerous bacterial pathogens.

Colistin was developed in the 1950s. Due to its highly nephrotoxic effect, it was no longer used in humans for many decades after its development. The lack of effective antibiotics, however, has made its revival necessary: for example, in the treatment of dangerous hospital germs such as carbapenem-resistant enterobacteriaceae or Acinetobacter baumannii. Colistin is also on the list of essential medicines of the World Health Organization (WHO).

Colistin is a last-resort antibiotic that is usually only used for severe infections with resistant bacteria. This is due to its severe kidney-damaging side effects, which occur in about 30% of treated patients.

The last-resort antibiotic colistin is an important helper in this emergency. However, its administration is associated with risks of severe side effects: It has a strong nephrotoxic effect, and long-term consequences cannot be ruled out.

It would be advantageous if colistin could be chemically modified so that it is no longer as damaging to the kidneys while maintaining its high antibiotic efficacy.

A research team has now been able to produce an inactivated, harmless form of colistin that is only activated in the body with the help of chemical switches.

In this so-called click-to-release technique, the chemical switches are specifically bound to the disease-causing bacteria. The administered masked colistin is therefore activated specifically at the site of action. The researchers hope that this could reduce side effects. The study is published in the journal Angewandte Chemie International Edition.

The researchers hope that this approach can help minimize the side effects of antibiotics and other medical agents in the future and make them more tolerable for patients.

Jiraborrirak Charoenpattarapreeda et al, A Targeted Click‐to‐Release Activation of the Last‐Resort Antibiotic Colistin Reduces its Renal Cell Toxicity, Angewandte Chemie International Edition (2024). DOI: 10.1002/anie.202408360

Evolution in action: How ethnic Tibetan women thrive in thin oxygen at high altitudes

Breathing thin air at extreme altitudes presents a significant challenge—there's simply less oxygen with every lungful. Yet, for more than 10,000 years, Tibetan women living on the high Tibetan Plateau have not only survived but thrived in that environment.

A new study  answers some of those questions. The research, published in the journal Proceedings of the National Academy of Sciences of the United States of America, reveals how the Tibetan women's physiological traits enhance their ability to reproduce in such an oxygen-scarce environment.

The findings not only underscore the remarkable resilience of Tibetan women but also provide valuable insights into the ways humans can adapt in extreme environments. Such research also offers clues about human development, how we might respond to future environmental challenges, and the pathobiology of people with illnesses associated with hypoxia at all altitudes.

Researchers  studied 417 Tibetan women aged 46 to 86 who live between 12,000 and 14,000 feet above sea level in a location in Upper Mustang, Nepal on the southern edge of the Tibetan Plateau.

They collected data on the women's reproductive histories, physiological measurements, DNA samples and social factors. They wanted to understand how oxygen delivery traits in the face of high-altitude hypoxia (low levels of oxygen in the air and the blood) influence the number of live births—a key measure of evolutionary fitness.

They discovered that the women who had the most children had a unique set of blood and heart traits that helped their bodies deliver oxygen. Women reporting the most live births had levels of hemoglobin, the molecule that carries oxygen, near the sample's average, but their oxygen saturation was higher, allowing more efficient oxygen delivery to cells without increasing blood viscosity; the thicker the blood, the more strain on the heart.

This is a case of ongoing natural selection. Tibetan women have evolved in a way that balances the body's oxygen needs without overworking the heart.

One  genetic trait they studied likely originated from the Denisovans who lived in Siberia about 50,000 years ago; their descendants later migrated onto the Tibetan Plateau.

The trait is a variant of the EPAS1 gene that is unique to populations indigenous to the Tibetan Plateau and regulates hemoglobin concentration. Other traits, such as increased blood-flow to the lungs and wider heart ventricles, further enhanced oxygen delivery.

These traits contributed to greater reproductive success, offering insight into how humans adapt to lifelong levels of low oxygen in the air and their bodies.

Beall, Cynthia M., Higher oxygen content and transport characterize high-altitude ethnic Tibetan women with the highest lifetime reproductive success, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2403309121. doi.org/10.1073/pnas.2403309121

'Nano-weapon' discovery boosts fight against antibiotic-resistant hospital superbugs

Researchers have discovered how a bacteria found in hospitals uses "nano-weapons" to enable their spread, unlocking new clues in the fight against antibiotic-resistant superbugs.

Published in Nature Communications, the Monash Biomedicine Discovery Institute (BDI)–led study investigated the common hospital bacterium, Acinetobacter baumannii.

A. baumannii is particularly dangerous as it is often resistant to common antibiotics, making infections hard to treat. Due to this, the World Health Organization has listed it as a top-priority critical bacterium, where new treatments are urgently needed.

Bacteria rarely exist alone; like plants and animals, different types compete for space and resources. In many environments, A. baumannii must engage in bacterial 'warfare' to survive in the presence of other species.

To outcompete surrounding bacteria, A. baumannii (and many other bacteria) use a nano-weapon called the Type VI Secretion System (T6SS). This is a tiny needle-like machine that injects toxins directly into nearby bacteria, killing them so that A. baumannii can dominate.

Using advanced microscopy on a highly purified bacterial protein, researchers discovered the molecular structure of a key toxin from a hospital strain of A. baumannii.

They learned how this toxin, called Tse15, is attached to the needle and then delivered into other bacteria to kill them. They showed that the toxin is stored in a protective cage-like structure inside A. baumannii, preventing it from harming the bacterium itself. When ready to attack other bacteria, the toxin must be released from the cage.

This happens through a series of interactions between the toxin, the exterior of the cage, and the T6SS needle. Once the needle injects the toxin into a competitor, the toxin activates and kills the other bacterium, allowing A. baumannii to take over that surface.

The find is a significant step in the fight against antibiotic-resistant superbugs.

Understanding how such toxins are delivered may allow us to engineer new protein toxins for delivery into bacteria. By learning how this system works, scientists can explore new ways to fight against antibiotic resistant bacteria like A. baumannii.

Brooke K. Hayes et al, Structure of a Rhs effector clade domain provides mechanistic insights into type VI secretion system toxin delivery, Nature Communications (2024). DOI: 10.1038/s41467-024-52950-x

How plants compete for light: Researchers discover new mechanism in shade avoidance

Plants that are close together do everything they can to intercept light. This "shade avoidance" response has been extensively researched. It is therefore even more remarkable that researchers  have discovered another entirely new mechanism: the important role of the hormone cytokinin.

Their research has been published in Nature Communications.

Plants in nature, in the field or in the greenhouse compete with each other for light, moisture and nutrients. The more densely planted they are, the tougher the competition. But how do they know they are getting a bit crowded?

In densely planted crops, red light is absorbed faster than far-red light, which is instead reflected. The red-to-far-red ratio therefore decreases with greater density. Plants 'see' this through the light-sensitive pigment phytochrome.

The pigment is like a switch: it can be active or inactive. The red-to-far-red ratio operates the button, so to speak. That sets off a whole series of responses.

With relatively high levels of far-red light, as is the case in densely planted crops, the stems grow longer, as do the petioles. The leaves themselves move from a horizontal to a more vertical position. Anything to rise above their neighbors and intercept more light.

The leaves of bean plants are constantly in motion, helping them to optimally position themselves for light capture. Leaf movements also help the model plant Arabidopsis to outgrow its competitors. Video credit: Ronald Pierik and Christa Testerink

Part 1

However, plants not only compete for light but also for nutrients, for example.
You should therefore consider shade avoidance in conjunction with other responses to competition. You would then get much closer to the situation in the field.
The researchers started examining aboveground and belowground competition in conjunction. One of the research questions was whether the plant, if it does not receive much nutrition in the form of nitrogen, can still respond well to far-red light.
For this, the growing tissues need to know how much nitrogen is available in the soil. They know that because a message passes from the roots to the growth points. In this case, the messenger is the plant hormone cytokinin. This hormone is formed in the roots and passes through the veins to the part of the plant that is above ground. If there is a large amount of nitrogen present, there will also be lots of cytokinin.
In fact, the shade avoidance response appears to be inhibited when nitrogen is low. However, the researchers have demonstrated that you can actually trick the plant. If you give it extra cytokinin, when nitrogen is low, you still get substantial length growth with extra far-red light. This is the first time that anyone has shown that cytokinin plays a role in shade avoidance. The researchers have therefore discovered a new mechanism.
And it gets even more remarkable: Until now, cytokinin was known to be the very hormone that inhibits length growth. Looking back, all the trials on which that conclusion was based involved seedlings raised in the dark. You only get that response when you grow them in the light. And not with ordinary white light, but only with an excess of far-red light.
The researchers also investigated how this mechanism works at the genetic level.

There are specific proteins that inhibit plant sensitivity to cytokinin. The genes encoding these proteins are themselves inhibited when exposed to far-red light. In other words, the inhibitor is inhibited. And that is precisely what stimulates sensitivity. These are also very new insights.

Now re-write the text books!

Pierre Gautrat et al, Phytochrome-dependent responsiveness to root-derived cytokinins enables coordinated elongation responses to combined light and nitrate cues, Nature Communications (2024). DOI: 10.1038/s41467-024-52828-y

How fear memories transform over time, offering new insights into PTSD

An innovative study, published in Nature Communications, reveals the mechanism behind two seemingly contradictory effects of fear memories: the inability to forget yet the difficulty to recall.

The study shows how fear experiences are initially remembered as broad, associative memories, but over time become integrated into episodic memories with a more specific timeline.

The researchers conducted experiments using functional Magnetic Resonance Imaging (fMRI) and machine learning algorithms to track brain activity as participants experienced simulated threatening events, such as a car accident.

They found that immediately after a fear-inducing event, the brain relies on associative memories, generalizing the fear regardless of event sequences. However, the following day, the dorsolateral prefrontal cortex takes over a role initially led by the hippocampus to integrate the event's sequence into fear memory, reducing the scope of fear.

The study also highlights that individuals with high anxiety, who are at greater risk for PTSD, may struggle with this memory integration. Their brains show weaker integration of time-based episodic memories through the dorsolateral prefrontal cortex, which may lead to persistent, overwhelming fear linked to associative cues. This insight opens new avenues for PTSD interventions by targeting the brain's ability to integrate episodic memories after trauma.

This time-dependent rebalancing between brain regions may explain why some individuals develop PTSD while others don't.

The study's findings have the potential to reshape our understanding of PTSD and fear memory processing, offering novel perspectives for developing more effective interventions.

Time-dependent neural arbitration between cue associative and episodic fear memories, Nature Communications (2024). DOI: 10.1038/s41467-024-52733-4

How cancer cells may be using ribosomes to hide from the immune system

The protein factories of our cells are much more diverse than we thought they were. Scientists  have now shown that cancer cells can use these ribosomes to boost their invisibility cloak, helping them hide from the immune system.

Our immune system is constantly monitoring our body. In order to survive, cancer cells need to evade this inspection. Making cells more visible to the immune system has revolutionized treatment procedures.

However, many patients don't respond to these immunotherapies or become resistant. How cancer cells manage to circumvent elimination by the immune system is still intriguing. 

Turns out cancer cells might use our very own protein factories to hide. Each of our cells contains a million of these minuscule factories, called ribosomes.

They make all the protein we need. This job is so essential: all life depends on it! This is why people have always thought that every ribosome is the same, and that they just passively churn out protein as dictated by the cell's nucleus. Scientists have  now shown that this is not necessarily the case.

Cells change their ribosomes when they receive a danger signal from the immune system, the new study showed.

They change the balance towards a type of ribosome that has a flexible arm sticking out, called a P-stalk. In doing so, they become better at showing themselves to the immune system.

Cells coat themselves with little chunks of protein, which is how our immune system can recognize them and tell when there is something wrong. This is an essential part of our immune response. If a cancer cell can block this, it can become invisible to the immune system.

 Scientists now uncovered a new way in which cancer cells could pull such a poker face: by affecting their ribosomes. Less flexible-arm-ribosomes, means less clues on their surface.

They are now trying to figure out exactly how they go about this, so they can maybe block this ability. This would make cancer cells more visible, enabling the immune system to detect and destroy them.

P-stalk ribosomes act as master regulators of cytokine-mediated processes, Cell (2024). DOI: 10.1016/j.cell.2024.09.039. www.cell.com/cell/fulltext/S0092-8674(24)01139-5

How fast is quantum entanglement? Scientists investigate it at the attosecond scale

 An attosecond is a billionth of a billionth of a second.

Quantum theory describes events that take place on extremely short time scales. In the past, such events were regarded as 'momentary' or 'instantaneous': An electron orbits the nucleus of an atom—in the next moment it is suddenly ripped out by a flash of light. Two particles collide—in the next moment they are suddenly 'quantum entangled.'

Today the temporal development of such almost 'instantaneous' effects can be investigated.

Researchers developed computer simulations that can be used to simulate ultrafast processes. This makes it possible to find out how quantum entanglement arises on a time scale of attoseconds. 

If two particles are quantum entangled, it makes no sense to describe them separately. Even if you know the state of this two-particle system perfectly well, you cannot make a clear statement about the state of a single particle.

You could say that the particles have no individual properties, they only have common properties. From a mathematical point of view, they belong firmly together, even if they are in two completely different places.

Scientists are now interested in knowing how this entanglement develops in the first place and which physical effects play a role on extremely short time scales.

The researchers looked at atoms that were hit by an extremely intense and high-frequency laser pulse. An electron is torn out of the atom and flies away. If the radiation is strong enough, it is possible that a second electron of the atom is also affected: It can be shifted into a state with higher energy and then orbit the atomic nucleus on a different path.

So, after the laser pulse, one electron flies away and one remains with the atom with unknown energy. Physicists can show that these two electrons are now quantum entangled. You can only analyze them together—and you can perform a measurement on one of the electrons and learn something about the other electron at the same time.

The research team has now been able to show, using a suitable measurement protocol that combines two different laser beams, that it is possible to achieve a situation in which the 'birth time' of the electron flying away, i.e., the moment it left the atom, is related to the state of the electron that remains behind. These two properties are quantum entangled.

This means that the birth time of the electron that flies away is not known in principle. You could say that the electron itself doesn't know when it left the atom. It is in a quantum-physical superposition of different states. It has left the atom at both an earlier and a later point in time.

Part 1

Which point in time it 'really' was cannot be answered—the 'actual' answer to this question simply does not exist in quantum physics. But the answer is quantum-physically linked to the—also undetermined—state of the electron remaining with the atom. If the remaining electron is in a state of higher energy, then the electron that flew away was more likely to have been torn out at an early point in time; if the remaining electron is in a state of lower energy, then the 'birth time' of the free electron that flew away was likely later—on average around 232 attoseconds.

This is an almost unimaginably short period of time. However, these differences can not only be calculated, but also measured in experiments.
The work shows that it is not enough to regard quantum effects as 'instantaneous'. Important correlations only become visible when one manages to resolve the ultra-short time scales of these effects.

The electron doesn't just jump out of the atom. It is a wave that spills out of the atom, so to speak—and that takes a certain amount of time. It is precisely during this phase that the entanglement occurs, the effect of which can then be precisely measured later by observing the two electrons.

 Jiang, Wei-Chao et al, Time Delays as Attosecond Probe of Interelectronic Coherence and Entanglement. Physical Review Letters (2024). DOI: 10.1103/PhysRevLett.133.163201

Part 2

Bioengineered antibodies target mutant HER2 proteins

For some proteins, a single mutation, or change in its DNA instructions, is all it takes to tip the balance between functioning normally and causing cancer. But despite causing major disease, these slightly mutated proteins can resemble their normal versions so closely that treatments designed to target mutants could also harm healthy cells.

A new study describes the development of a biologic, a drug derived from natural biological systems, that targets a mutant cancer protein called HER2 (human epidermal growth factor receptor 2) without attacking its nearly identical normal counterpart on healthy cells.

The study was published in the journal Nature Chemical Biology on Oct. 22.

While still in the early stages, this technique could lead to new therapies to treat cancer patients with HER2 mutations with minimal side effects, the researchers say.

And this is an antibody that can recognize a single change in the 600 amino acid building blocks that make up the exposed part of the HER2 protein.

The new findings revolve around HER2, a protein that occurs on the surfaces of many cell types and that turns on signaling pathways that control cell growth. It can cause cancer when a single amino acid swap locks the protein into "always-active" mode, which in turn causes cells to divide and multiply uncontrollably.

Cancer can also result when cells accidentally make extra copies of the DNA instructions that code for the normal version of HER2 and express higher levels of the protein on their surfaces.

 Selective targeting of oncogenic hotspot mutations of the 1 HER2 extracellular 2 region, Nature Chemical Biology (2024). DOI: 10.1038/s41589-024-01751-w

Microplastics and PFAS: new study finds combined impact results in greater environmental harm

The combined impact of so-called "forever chemicals" is more harmful to the environment than single chemicals in isolation, a new study shows. 

Researchers  investigated the environmental effects of microplastics and PFAS and showed that, combined, they can be very harmful to aquatic life.

Microplastics are tiny plastic particles that come from plastic bottles, packaging, and clothing fibers. PFAS (Per- and Polyfluoroalkyl Substances) are a group of chemicals used in everyday items like non-stick cookware, water-resistant clothing, firefighting foams, and numerous industrial products. PFAS and microplastic are known as "forever chemicals" because they don't break down easily and can build up in the environment, leading to potential risks for both wildlife and humans.

Both PFAS and microplastics can be transported through water systems for long distances, all the way to the Arctic. They are often released together from consumer products. Yet, their combined effects, and also the ways in which they interact with other polluting compounds in the environment is a cause for concern. 

To better understand the combined impact of these pollutants, researchers used Daphnia, commonly known as water fleas. These tiny creatures are often used to monitor pollution levels because they are highly sensitive to chemicals, making them ideal for determining safe chemical limits in the environment.

In this study, published in Environmental Pollution, the team compared two groups of water fleas: one that had never been exposed to chemicals and another that had experienced chemical pollution in the past. This unique approach was possible thanks to Daphnia's ability to remain dormant for long periods, allowing researchers to "resurrect" older populations with different pollution histories.

Both groups of Daphnia were exposed for their entire life cycle to a mixture of microplastics of irregular shapes—reflecting natural conditions- together with two PFAS chemicals at levels typically found in lakes.

The team showed that PFAS and microplastics together caused more severe toxic effects than each chemical alone. The most worrying result was developmental failures, observed together with delayed sexual maturity and stunted growth. When combined, the chemicals caused Daphnia to abort their eggs and to produce fewer offspring. These effects were more severe in Daphnia historically exposed to pollutants, making them less tolerant to the tested forever chemicals.

Importantly, the study found that the two chemicals lead to greater harm when combined—59% additive and 41% synergistic interactions were observed across critical fitness traits, such as survival, reproduction and growth.

 Tayebeh Soltanighias et al, Combined toxicity of perfluoroalkyl substances and microplastics on the sentinel species Daphnia magna: Implications for freshwater ecosystems, Environmental Pollution (2024). DOI: 10.1016/j.envpol.2024.125133

Oriental hornets do not get sick or die when consuming very large amounts of alcohol

A team of behavioral ecologists, zoologists and crop protection specialists report that Oriental hornets have the highest-known tolerance to alcohol in the animal kingdom. In their study published in Proceedings of the National Academy of Sciences, the group fed ethanol solutions to hornets.

Prior research has shown that many plants produce fruits or nectar that ferment naturally as they rot, which results in the production of ethanol. Fermented foods are a source of both nutrients and energy for many animals due to their high caloric content, and most animals that consume ethanol in concentrations higher than 4% suffer adverse effects, such as difficulties moving or flying normally.

In this new study, the research team  noticed the Oriental hornets did not seem to be troubled by their diet heavy in rotten fruit. To find out more about the tolerance of ethanol consumption by Oriental hornets, the group collected multiple samples and brought them back to their lab for testing.

The team gave the hornets solutions of sucrose with added ethanol. They began by giving them low doses and found that even at levels of 20%, the hornets showed no adverse effects. They kept upping the dose to 80%. At that level, the hornets behaved as if slightly tipsy for just a few moments, then sobered up and resumed their normal behaviour. The research team notes that any other creature would have been killed by such high amounts of alcohol.

Taking a closer look, the researchers found that the hornets have multiple copies of the alcohol dehydrogenase gene, which is involved in breaking down alcohol. This most likely explains the hornet's high tolerance for alcohol.

They suggest extra copies of the gene likely evolved due to the mutualistic relationship the hornets have with fermenting brewer's yeast—prior research has shown they reside and even reproduce inside the hornets' intestines, a relationship that also helps the yeast move between hornets.

Sofia Bouchebti et al, Tolerance and efficient metabolization of extremely high ethanol concentrations by a social wasp, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2410874121