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

Discovery of new bacterial toxins could be key to fighting infections

Researchers have discovered a new group of bacterial toxins that can kill harmful bacteria and fungi, opening the door to potential new treatments for infections. These toxins, found in over 100,000 microbial genomes, can destroy the cells of bacteria and fungi without harming other organisms.

The study, published in Nature Microbiology, has uncovered how some bacteria use these toxins to compete with other microbes, and the findings could lead to new ways to fight infections, especially as antibiotic resistance becomes a growing concern.

These toxins, which are encoded in the genomes of certain bacteria, exhibit potent antibacterial and antifungal properties, offering exciting new possibilities for clinical and biotechnological applications.

Microbial competition is a natural phenomenon, and bacteria have evolved sophisticated methods, including toxins, to eliminate competitors. The most famous examples of natural compounds used in competition in nature are antibiotics produced by bacteria and fungi.

These toxins, which are encoded in the genomes of certain bacteria, exhibit potent antibacterial and antifungal properties, offering exciting new possibilities for clinical and biotechnological applications. Microbial competition is a natural phenomenon, and bacteria have evolved sophisticated methods, including toxins, to eliminate competitors. The most famous examples of natural compounds used in competition in nature are antibiotics produced by bacteria and fungi.

The research team successfully validated nine newly-discovered toxins, each representing a large evolutionary conserved family, demonstrating their ability to cause cell death in both Escherichia coli and Saccharomyces cerevisiae when expressed in these model organisms. Of particular note, five antitoxin genes--also known as immunity genes--were identified, which protect the bacteria producing the toxins from self-destruction.

It is interesting to note that the toxins exhibit powerful antifungal activity against a range of pathogenic fungi, while leaving certain invertebrate species and macrophages unaffected. 

Systematic Discovery of Antibacterial and Antifungal Bacterial Toxins, Nature Microbiology (2024). DOI: 10.1038/s41564-024-01820-9

Worst agricultural practices: plastic mulch is contaminating agricultural fields

Using plastic sheets for weed control, even under current best management practices, pollutes soil with macro- and micro-plastics and negatively affects critical soil functions, according to a study. The United Nations considers soil plastic contamination an environmental health and food security threat.

Around the world, over 25 million acres of farmland is seasonally covered with opaque plastic films used as "mulch" to prevent weeds, retain moisture, and warm soil—a practice known as "plasticulture." Most studies have assessed plastic mulch soil contamination impacts using lab-based models or in experimental plots.

Researchers surveyed fields after plastic mulch had been carefully removed for the season—a "best practice" to reduce plastic contamination in fields. However, all the fields surveyed had plastic contamination and the authors found up to 25 kg of macroplastic debris per hectare, covering up to 3.4% of field surface area. Microplastics were also found in all fields and microplastic concentrations positively correlated with macroplastic concentrations.

Key soil heath traits were negatively correlated with macroplastic accumulation even at relatively low contamination levels. 

Thus, current "best practices" are causing subtle but deleterious effects to soil.

Because the use of plastic film mulch is rapidly expanding globally, the authors suggest exploring a non-plastic, biodegradable alternative to limit the threat to soil function and agricultural productivity caused by unabated plastic accumulation.

Agricultural plastic pollution reduces soil function even under best management practices, PNAS Nexus (2024). DOI: 10.1093/pnasnexus/pgae433. academic.oup.com/pnasnexus/art … 3/10/pgae433/7828925

Psychopaths could be suffering from alexithymia or emotional blindness, study finds

Psychopathic people have great difficulty or are even unable to show empathy and regulate their emotions. According to a new study this could be because these people suffer from alexithymia, also known as emotional blindness. The work is published in the journal PLOS ONE.

The term alexithymia is an amalgam of the Greek prefix a- (without) and the words lexis (reading) and thymos (emotion). It refers to the inability of a person to recognize and describe their own emotions. People with alexithymia tend to perceive their feelings as purely physical sensations. For example, emotional tension is registered as mere physical discomfort or pain.

Previous research has linked alexithymia to mental health issues such as depression and anxiety. However, research in clinical psychology shows that the ability to properly identify and understand one's own emotions is essential for the healthy functioning of other emotional abilities such as empathy and emotion regulation.

The result of the study: the "forensic sample" ( comprising people who committed crimes) was found to exhibit significantly higher levels of boldness, meanness, and disinhibition compared to the general population cohort. These characteristics are considered typical psychopathic traits.

This result corresponds to earlier studies and indicates that there is a higher proportion of people with psychopathic symptoms in groups of offenders from forensic clinics than in the general population.

What is new, however, is the scientific finding that individuals with strong psychopathic traits tend to have greater difficulty recognizing and describing their own emotions (i.e., to be suffering from alexithymia), which in turn contributes to a lack of empathy and poor emotion regulation. Conversely, this means that therapeutic measures to improve emotional awareness could be helpful for people with psychopathic personalities.

If these people manage to recognize and describe their own emotions, their empathy and ability to regulate their emotions may also improve. Ideally, this therapeutic approach could reduce the risk of recidivism in offenders.

Matthias Burghart et al, Understanding empathy deficits and emotion dysregulation in psychopathy: The mediating role of alexithymia, PLOS ONE (2024). DOI: 10.1371/journal.pone.0301085

Man Declared Brain Dead Wakes Up as Organs About to Be Removed

This story brought back traumatic memories to me.
I decided to donate my mother's corneas when the doctors treating her declared her brain dead. But my sister was very scared. "What if she isn't actually dead?", she asked me, "What if she gets up again from her deep sleep? She won't have eyes to see!"

In a chaotic and emotionally charged response to the situation, surgeons declined to continue the procedure .

"It was very chaotic. Everyone was just very upset."

That's everybody's worst nightmare, right? Being alive during surgery and knowing that someone is going to cut you open and take your body parts out?

Deep concerns have been raised about the potential for errors such as these. 

But these are rare cases. You don't have to worry.

Please donate your organs and those of your loved ones without any hesitation. 

Physicists observed a "black hole triple" for the first time: sheds new light on blackhole formation

The new system holds a central black hole in the act of consuming a small star that's spiraling in very close to the black hole, every 6.5 days—a configuration similar to most binary systems. But surprisingly, a second star appears to also be circling the black hole, though at a much greater distance. The physicists estimate this far-off companion is orbiting the black hole every 70,000 years.

That the black hole seems to have a gravitational hold on an object so far away is raising questions about the origins of the black hole itself. Black holes are thought to form from the violent explosion of a dying star—a process known as a supernova, by which a star releases a huge amount of energy and light in a final burst before collapsing into an invisible black hole.

The team's discovery, however, suggests that if the newly-observed black hole resulted from a typical supernova, the energy it would have released before it collapsed would have kicked away any loosely bound objects in its outskirts. The second, outer star, then, shouldn't still be hanging around.

Instead, the team suspects the black hole formed through a more gentle process of "direct collapse," in which a star simply caves in on itself, forming a black hole without a last dramatic flash. Such a gentle origin would hardly disturb any loosely bound, faraway objects.

Because the new triple system includes a very far-off star, this suggests the system's black hole was born through a gentler, direct collapse. And while astronomers have observed more violent supernovae for centuries, the team says the new triple system could be the first evidence of a black hole that formed from this more gentle process.

 Kevin Burdge, The black hole low-mass X-ray binary V404 Cygni is part of a wide triple, Nature (2024). DOI: 10.1038/s41586-024-08120-6. www.nature.com/articles/s41586-024-08120-6

People with no sense of smell found to have abnormal breathing patterns

A team of neuroscientists  has found that people who have lost the ability to smell have slightly different breathing patterns than those with a normal sense of smell. 

Anosmia is the inability to smell. Unfortunately, the condition was found to be a common symptom for people with COVID-19. The condition has been studied for hundreds of years and has a variety of causes, from depression to drug use, and negatively impacts quality of life. In this new effort, the research team has found yet another feature of the condition.

The researchers sought to address anecdotal accounts of people who could not smell and began "breathing funny" after contracting COVID-19. To find out if such accounts were true and to quantify the differences, the research team recruited 52 volunteers, 21 of whom were suffering from anosmia.

Each of the volunteers was fitted with a device that monitors breathing and each wore it for 24 hours. The research team found that those volunteers with anosmia did have slightly different than normal breathing patterns.

People without the condition, they note, have small inhalation peaks, which prior research suggests coincides with a suspected change in smell. People without the ability to smell had no such peaks.

The research team also found that they could identify with 83% accuracy which members of the group had anosmia simply by evaluating the breathing patterns. They suggest more research is required to determine if changes inbreathing patterns have later impacts, such as an increase in risk of developing depression.

Study shows birth is a tight squeeze for chimpanzees, too

According to a new study, chimpanzees, like humans, must contend with a confined bony birth canal when giving birth. In humans, the problem is exacerbated by our unique form of upright walking, since this led to a twisting of the bony birth canal, while the fetal head grew larger. The obstetrical dilemma therefore evolved gradually over the course of primate evolution rather than suddenly in humans as originally argued.

The birth process in chimpanzees and other great apes is generally considered to be easy. This is usually attributed to a relatively large pelvis and the small head of their newborn. In contrast, human childbirth is both more complex and riskier when compared to other mammals.

According to the original obstetrical dilemma hypothesis, our birth difficulty stems from a conflict that arose during human evolution between adaptations in the pelvis for upright walking and an increase in our infants' brain size.

On the one hand, the pelvis shortened to improve balance while moving bipedally, while the baby's larger head still had to fit through the birth canal. As a solution to this dilemma, the shape of the pelvic bones differs between the sexes (with females having larger dimensions despite smaller body sizes), and human babies are born more neurologically immature than other primates, so that brain growth is delayed to the postnatal period.

An international team of researchers simulated birth in chimpanzees and humans and quantified the space between the bony birth canal and the fetal head. The work is published in the journal Nature Ecology & Evolution.

The study shows that narrow birth canals in relation to the infant head size are not unique to humans. Accordingly, the obstetrical dilemma hypothesis, which had previously been explained solely by the development of bipedalism and the size of the human brain, did not suddenly appear during the development of modern humans, but rather developed gradually over the course of primate evolution—and then intensified in humans, thus explaining the high rates of birth complications observed today.

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To test the obstetrical dilemma hypothesis, the research team first compared the available space in the birth canal of chimpanzees and humans, using the average distance between the fetal head and the pelvic bones while accounting for soft tissue contributions.

Using a three-dimensional virtual simulation of the birth process, they were able to show that the space in the chimpanzee pelvis is actually just as tight as it is in humans. Interestingly, after a detailed shape analysis, they also found that female chimpanzees have a more spacious pelvis than males, especially the smaller females, providing evidence of adaptations to deal with these space limitations.

The researchers also show that the great apes appear to trend towards humans in how neurologically immature, or how secondarily altricial their infants are compared to monkeys—again surprisingly similar to humans, although to a lesser magnitude.
Based on these intriguing parallels, the researchers propose a new hypothesis that the obstetrical dilemma developed gradually and became increasingly exacerbated over the course of evolution. This contradicts the previous theory that our long and difficult births emerged abruptly with the enlargement of the brain in Homo erectus.
The increase in body size in the ancestors of the great apes made their pelvis stiffer, which limited the ability of their ligaments to stretch during birth. In early hominins, the upright gait also led to a twisted bony birth canal, which required complex movements of the fetal head. This mechanism, rather than the narrowness of the birth canal, is likely the main cause of the difficult birth process in humans, the researchers argue.
The study shows that the remarkably complex human birth process is the result of gradual compromises during hominoid evolution. The difficult birth and the neurological immaturity of our newborns, with the long learning phase that follows, are a prerequisite for the evolution of our intelligence. At the same time, we humans are only at one extreme—we are not unique among primates, say the researchers.

Nicole M. Webb et al, Gradual exacerbation of obstetric constraints during hominoid evolution implied by re-evaluation of cephalopelvic fit in chimpanzees, Nature Ecology & Evolution (2024). DOI: 10.1038/s41559-024-02558-7

Part 2

Scientists glue two proteins together, driving cancer cells to self-destruct

Our bodies divest themselves of 60 billion cells every day through a natural process of cell culling and turnover called apoptosis. These cells—mainly blood and gut cells—are all replaced with new ones, but the way our bodies rid themselves of material could have profound implications for cancer therapies in a new approach developed by  researchers.

They aim to use this natural method of cell death to trick cancer cells into disposing of themselves. Their method accomplishes this by artificially bringing together two proteins in such a way that the new compound switches on a set of cell death genes, ultimately driving tumor cells to turn on themselves.

The researchers describe their latest such compound in a paper published Oct. 4 in Science.

Apoptosis turns out to be critical for many biological processes, including proper development of all organs and the fine-tuning of our immune systems. That system retains pathogen-recognizing cells but kills off self-recognizing ones, thus preventing autoimmune disease.

Traditional treatments for cancer—namely chemotherapy and radiation—often kill large numbers of healthy cells alongside the cancerous ones. To harness cells' natural and highly specific self-destruction abilities, researchers developed a kind of molecular glue that sticks together two proteins that normally would have nothing to do with one another.

One of these proteins, BCL6, when mutated, drives the blood cancer known as diffuse large cell B-cell lymphoma. This kind of cancer-driving protein is also referred to as an oncogene. In lymphoma, the mutated BCL6 sits on DNA near apoptosis-promoting genes and keeps them switched off, helping the cancer cells retain their signature immortality.

The researchers developed a molecule that tethers BCL6 to a protein known as CDK9, which acts as an enzyme that catalyzes gene activation, in this case, switching on the set of apoptosis genes that BCL6 normally keeps off.

When the team tested the molecule in diffuse large cell B-cell lymphoma cells in the lab, they found that it indeed killed the cancer cells with high potency. They also tested the molecule in healthy mice and found no obvious toxic side effects, even though the molecule killed off a specific category of the animals' healthy B cells, a kind of immune cell, which also depends on BCL6.

They're now testing the compound in mice with diffuse large B-cell lymphoma to gauge its ability to kill cancer in a living animal.

The research team hopes that by blasting the cells with multiple different cell death signals at once, the cancer will not be able to survive long enough to evolve resistance, although this idea remains to be tested.

Roman C. Sarott et al, Relocalizing transcriptional kinases to activate apoptosis, Science (2024). DOI: 10.1126/science.adl5361

'Inflexible thinking style' behind why some people won't accept vaccines, says new research

An "inflexible thinking style" could explain why some people are hesitant about taking a vaccine, new research  has revealed. It is a finding that could have implications for public health policy, especially during pandemics.

Researchers  conducted the first study evaluating the relationship between COVID-19 "vaccine hesitancy and cognitive flexibility."

Cognitive flexibility is how good people are at responding to changing situations and changing feedback, and especially when rules change. Inflexibility is generally described as the incapacity to adjust one's behavior in response to changing circumstances, update one's knowledge, and maintain optimum decision-making.

This explorative study found that those with greater vaccine hesitancy persisted with the same erroneous responses during a computerized test of flexible thinking, even when they received direct feedback telling them that their responses were no longer correct. This response pattern is the hallmark of a cognitively inflexible thinking style.

Vaccine hesitancy is quite common, occurring in approximately 12% of the population and may occur for multiple underlying reasons. In this study, researchers found the relationship between it and cognitive inflexibility can be predicted through an online test. This may be of value for public health policy in identifying this specific group.

The research, conducted between June 2021 and July 2022 after lockdown from COVID-19 was eased, has just been published in the Journal of Psychiatric Research.

L. Pellegrini et al, The inflexible mind: A critical factor in understanding and addressing COVID-19 vaccine hesitancy, Journal of Psychiatric Research (2024). DOI: 10.1016/j.jpsychires.2024.09.028

Experiments find people assume unidentified bystanders in a war zone are combatants, acceptable collateral damage

People's bias toward sacrificing unknown bystanders appears to stem from assuming the unidentified person is an enemy, according to a study published October 23, 2024, in the open-access journal PLOS ONE.

About as many civilians as soldiers die in war each year, some during strikes targeted at enemy combatants. There have been many reported cases of mistaking innocent civilians for enemy combatants, with the possibility of many more being unreported.

Researchers conducted five experiments to test when people assume unknown bystanders in a combat zone are enemies rather than civilians, reducing their concerns about collateral damage. A total of 2,204 participants were presented with a realistic moral dilemma: A military pilot must decide whether to bomb a dangerous enemy target, also killing a bystander. 

In the study, few people endorsed bombing when the bystander was known to be an innocent civilian. However, when the bystander's identity was unknown, more than twice as many people endorsed the bombing despite no evidence they were enemies.

Bombing endorsement was predicted by attitudes toward total war: the theory that there should be no distinction between military and civilian targets in wartime conflict. 

According to the authors, these findings have implications for military strategists who must decide whether to attack areas with enemy militants and unidentified bystanders. The results support a common tendency in people to assume the bystanders are enemies, with important consequences if they turn out to be innocent civilians.

The real-world cases of civilians struck by bombs could result from the same error in judgment reported in this study.

What I don't know can hurt you: Collateral combat damage seems more acceptable when bystander victims are unidentified, PLoS ONE (2024). DOI: 10.1371/journal.pone.0298842

Scientists Revived a Pig's Brain Nearly a Whole Hour After It Died

Scientists have revived activity in the brains of pigs up to nearly an hour after circulation had ceased. In some cases, functionality was sustained for hours through a surprising discovery by researchers.

 This achievement represents a huge step forward in working out how to restore brain function after a patient has suffered a sudden cardiac arrest. It suggests that doctors may be able to widen the brief window for successful resuscitation of patients following cardiac arrest.

Sudden cardiac arrest causes a lot of problems in the body due to the rapid cessation of blood flow. The subsequent drop in circulation to parts of the body is called ischemia, and when it occurs in the brain, it can cause serious, irreparable damage within minutes. This is why the resuscitation window for cardiac arrest is so short.

It's known that multi-organ ischemia plays a role in the brain's ability to recover after a cardiac arrest, but the individual organs have not been fully investigated.

In recent years, scientists have been using pig models to test methods for limiting brain injury. Supervised by physician Xiaoshun He of Sun Yat-Sen University in China, a team of scientists has turned to the animal to try and understand the role of the liver in brain recovery after ischemia due to cardiac arrest.

Using 17 lab-raised Tibetan minipigs, the team compared the inclusion of a liver in a loss of circulation. In one set of experiments, two groups of pigs were subjected to brain ischemia for 30 minutes; one of the groups was also subjected to liver ischemia, and the other was not. Meanwhile a control group underwent no ischemia.

Part 1

When the pigs were euthanized and their brains examined, the control group obviously had the least brain damage; but the group that had not been subjected to liver ischemia showed significantly less brain damage than the group that had.

The next stage of the research involved attempting to incorporate an undamaged liver into the life support system reviving a brain that had been removed from a euthanized pig entirely. This is unlikely to be a scenario used to treat humans, but it helps scientists understand the windows in which resuscitation may be viable.

The basic life support system involved an artificial heart and lungs to help pump fluid through the brain. For one group, a pig's liver was integrated into the system, known as liver-assisted brain normothermic machine perfusion.

First, brains were connected to the life support systems 10 minutes after commencement of the life support procedure. For the system without a liver, electrical activity in the brain emerged within half an hour before declining over time.
Part 2

The team also experimented with different delays, connecting brains to the liver-assisted system at intervals of 30 minutes, 50 minutes, 60 minutes, and 240 minutes. The longest interval that showed the most promise was 50 minutes after being deprived of blood: the brain restarted electrical activity, and was maintained in that state for six hours until the experiment was shut off.
Remarkably, in brains that had been starved of oxygen for 60 minutes, activity only returned for three hours before fading, suggesting a critical interval in which resuscitation can be successful with the addition of a functioning liver.

These results, the researchers say, suggest the liver plays an important role in the development of brain injury following cardiac arrest. The findings suggest new avenues for research into brain injury, and may, hopefully, improve survival rates and recovery outcomes for human patients in the future.

https://www.embopress.org/doi/full/10.1038/s44321-024-00140-z

Part 3

The Human Mind Isn't Meant to Be Awake After Midnight, Scientists Warn

In the middle of the night, the world can sometimes feel like a dark place. Under the cover of darkness, negative thoughts have a way of drifting through your mind, and as you lie awake, staring at the ceiling, you might start craving guilty pleasures

Plenty of evidence suggests the human mind functions differently if it is awake at nighttime. Past midnight, negative emotions tend to draw our attention more than positive ones, dangerous ideas grow in appeal and inhibitions fall away. Some researchers think the human circadian rhythm is heavily involved in these critical changes in function, as they outline in a 2022 paper(1) summarizing the evidence of how brain systems function differently after dark.

Their hypothesis, called 'Mind After Midnight', suggests the human body and the human mind follow a natural 24-hour cycle of activity that influences our emotions and behavior.

In short, at certain hours, our species is inclined to feel and act in certain ways. In the daytime, for instance, molecular levels and brain activity are tuned to wakefulness. But at night, our usual behavior is to sleep.

From an evolutionary standpoint this, of course, makes sense. Humans are much more effective at hunting and gathering in the daylight, and while nighttime is great for rest, humans were once at greater risk of becoming the hunted.

According to the researchers, to cope with this increased risk our attention to negative stimuli is unusually heightened at night. Where it might once have helped us jump at invisible threats, this hyper-focus on the negative can then feed into an altered reward/motivation system, making a person particularly prone to risky behaviours.

Add sleep loss to the equation, and this state of consciousness only becomes more problematic.

The authors of the hypothesis use two examples to illustrate their point. The first example is of a heroin user who successfully manages their cravings in the day but succumbs to their desires at night.

Part 1

The second is of a college student struggling with insomnia, who begins to feel a sense of hopelessness, loneliness and despair as the sleepless nights stack up.

Both scenarios can ultimately prove fatal. Suicide and self-harm are very common at nighttime. In fact, some research reports a three-fold higher risk of suicide between midnight and 6:00 am compared to any other time of day.

A study in 2020 concluded that nocturnal wakefulness is a suicide risk factor, "possibly through misalignment of circadian rhythms."

Illicit or dangerous substances are also taken more by people at night.

Some of these behaviors could be explained by sleep debt or the cover that darkness offers, but there are probably nighttime neurological changes at play, too.

https://www.frontiersin.org/journals/network-physiology/articles/10...

Footnotes:

1. https://www.frontiersin.org/journals/network-physiology/articles/10...

Part 2

Throat Cancer Is Becoming an Epidemic, And Oral Sex May Be Why

Over the past two decades, there has been a rapid increase in throat cancer in the west, to the extent that some have called it an epidemic. This has been due to a large rise in a specific type of throat cancer called oropharyngeal cancer (the area of the tonsils and back of the throat).

The main cause of this cancer is the human papillomavirus (HPV), which are also the main cause of cancer of the cervix. Oropharyngeal cancer has now become more common than cervical cancer in the US and the UK.

HPV is sexually transmitted. For oropharyngeal cancer, the main risk factor is the number of lifetime sexual partners, especially oral sex. Those with six or more lifetime oral-sex partners are 8.5 times more likely to develop oropharyngeal cancer than those who do not practice oral sex.

https://theconversation.com/oral-sex-is-now-the-leading-risk-factor...

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New AI tool predicts protein-protein interaction mutations in hundreds of diseases

Scientists have designed a publicly-available software and web database to break down barriers to identifying key protein-protein interactions to treat with medication.

The computational tool is called PIONEER (Protein-protein InteractiOn iNtErfacE pRediction). Researchers demonstrated PIONEER's utility by identifying potential drug targets for dozens of cancers and other complex diseases in a recently published Nature Biotechnology article.

Genomic research is key in drug discovery, but it is not always enough on its own. When it comes to making medications based on genomic data, the average time between discovering a disease-causing gene and entering clinical trials is 10–15 years.

In theory, making new medicines based on genetic data is straightforward: mutated genes make mutated proteins. Scientists try to create molecules that stop these proteins from disrupting critical biological processes by blocking them from interacting with healthy proteins, but in reality, that is much easier said than done.

One protein in our body can interact with hundreds of other proteins in many different ways. Those proteins can then interact with hundreds more, forming a complex network of protein-protein interactions called the interactome.

This becomes even more complicated when disease-causing DNA mutations are introduced into the mix. Some genes can be mutated in many ways to cause the same disease, meaning one condition can be associated with many interactomes arising from just one differently mutated protein.

Drug developers are left with tens of thousands of potential disease-causing interactions to pick from—and that's only after they generate the list based on the affected protein's physical structures.

Some scientists,  especially the drug developers, are taking the help of  artificial intelligence (AI) tools  to  identify the most promising protein-protein interactions more easily and speedily.

Their resulting database allows researchers to navigate the interactome for more than 10,500 diseases, from alopecia to von Willebrand Disease.

Researchers who identified a disease-associated mutation can input it into PIONEER to receive a ranked list of protein-protein interactions that contribute to the disease and can potentially be treated with a drug. Scientists can search for a disease by name to receive a list of potential disease-causing protein interactions that they can then go on to research. PIONEER is designed to help biomedical researchers who specialize in almost any disease across categories including autoimmune, cancer, cardiovascular, metabolic, neurological and pulmonary.

Part 1

The team validated their database's predictions in the lab, where they made almost 3,000 mutations on over 1,000 proteins and tested their impact on almost 7,000 protein-protein interaction pairs. Preliminary research based on these findings is already underway to develop and test treatments for lung and endometrial cancers. The team also demonstrated that their model's protein-protein interaction mutations can predict:

Survival rates and prognoses for various cancer types, including sarcoma, a rare but potentially deadly cancer.
Anti-cancer drug responses in large pharmacogenomics databases.
The researchers also experimentally validated that protein-protein interaction mutations between the proteins NRF2 and KEAP1 can predict tumor growth in lung cancer, offering a novel target for targeted cancer therapeutic development.

A structurally informed human protein–protein interactome reveals proteome-wide perturbations caused by disease mutations, Nature Biotechnology (2024). DOI: 10.1038/s41587-024-02428-4

Part 2

Unique mRNA delivery method could fix faulty genes before birth

A new study shows that a biomedical tool can successfully deliver genetic material to edit faulty genes in developing fetal brain cells. The technology, tested in mice, might have the potential to stop the progression of genetic-based neurodevelopmental conditions, such as Angelman syndrome and Rett syndrome, before birth.

The implications of this tool for treating neurodevelopmental conditions are profound. We can now potentially correct genetic anomalies at a foundational level during critical periods of brain development, say the researchers associated with the study.

 The research team hopes to develop this technology into treatments for genetic conditions that can be diagnosed during prenatal testing. The treatments can be given in the womb to avoid more damage as cells develop and mature.

Proteins have a crucial role in the way our bodies function. They are assembled in cells based on instructions from messenger RNA (mRNA). In certain genetic conditions, the genes express (produce) more or fewer proteins than the body needs. In such cases, the body might get dysregulated and need to silence an overactive gene or supplement the low protein levels.

Proteins have large and complex structures, which makes them hard to deliver. Their delivery remains a huge challenge and a dream for treating diseases.

Instead of delivering proteins, scientists found a way to deliver mRNA to cells that will be translated to functional proteins within the cells. This delivery method uses a unique lipid nanoparticle (LNP) formulation to carry mRNA. The objective is to introduce (transfect) mRNA genetic material into the cells. The mRNA would then translate instructions to build proteins.
Delivery of mRNA using LNP is already transforming disease treatments. It has applications in vaccine development, gene editing and protein replacement therapy. Recently, mRNA delivery has become more popular with its use in Pfizer and Moderna COVID-19 vaccines.

 Kewa Gao et al, Widespread Gene Editing in the Brain via In Utero Delivery of mRNA Using Acid-Degradable Lipid Nanoparticles, ACS Nano (2024). DOI: 10.1021/acsnano.4c05169 Sheng Zhao et al, Acid-degradable lipid nanoparticles enhance the delivery of mRNA, Nature Nanotechnology (2024). DOI: 10.1038/s41565-024-01765-4

The smart 3D printer that can upgrade your home instantly

If someone wants to add 3D-printed elements to a room—a footrest beneath a desk, for instance—the project gets more difficult. A space must be measured. The objects must then get scaled, printed elsewhere and fixed in the right spot. Handheld 3D printers exist, but they lack accuracy and come with a learning curve.

Researchers now created Mobiprint, a mobile 3D printer that can automatically measure a room and print objects onto its floor. The team's graphic interface lets users design objects for a space that the robot has mapped out. The prototype, which the team built on a modified consumer vacuum robot, can add accessibility features, home customizations or artistic flourishes to a space.

The team presented its work Tuesday, Oct. 15, at the ACM Symposium on User Interface Software and Technology

https://programs.sigchi.org/uist/2024/program/content/170934

How microbes feed on iron

Pipelines, sprinklers, and other infrastructure in oxygen-free environments are vulnerable to microbially induced corrosion (MIC)—a process where microorganisms degrade iron-based structures, potentially leading to costly damages or even collapses.

Unlike rust, which is caused by a chemical reaction with oxygen, MIC occurs in oxygen-free environments. The microbes responsible thrive on the iron itself, producing a destructive reaction that damages the material. This kind of corrosion costs industries billions of dollars annually, particularly in sectors such as oil and gas. Identifying and preventing the microbial activity behind the corrosion is therefore of importance.

Now microbiologists have uncovered new details about how one microbial strain of the species Methanococcus maripaludis corrodes iron in an extremely efficient way. The study is  published in npj Biofilms and Microbiomes.

The study refutes the long-standing belief that these microbes release enzymes into the environment to corrode iron and have them produce nutrients for the microbe's growth. Instead, the researchers show that the microbes cling directly to the iron surface, using sticky enzymes on their cell walls to extract what they need without wasting energy on releasing enzymes that may not reach the iron surface.

Once attached to the iron surface, the microbe initiates corrosion, quickly developing a black film on the material's surface.

The microbes will quickly create pits under this black film, and within a few months, significant damage will occur. 

According to the researchers, microbial adaptation like this is an example of how microbes can learn to thrive in human-made environments. In this case, Methanococcus maripaludis, has learned to survive on and efficiently get energy from iron structures.

Such microbial adaptation poses not only a financial burden but also an environmental one. These microbes are methanogenic, meaning they produce methane. Methane is a potent greenhouse gas, so it does cause some concern that microbes adapting to human-made, built environments produce methane more effectively. These new adaptations may spur increases in methane emissions.

Satoshi Kawaichi et al, Adaptation of a methanogen to Fe⁰ corrosion via direct contact, npj Biofilms and Microbiomes (2024). DOI: 10.1038/s41522-024-00574-w

Methane-producing microbes also thrive on a variety of mineral particles that are being released to the natural environment by climate change and other anthropogenic activities. Such particles come from industry, agriculture, forest fires, river runoffs, melting glaciers, etc., and they may promote the activity of certain methane-producing microbes.

Plastic chemical phthalate causes DNA breakage and chromosome defects in sex cells, new study finds

A new study conducted on roundworms finds that a common plastic ingredient causes breaks in DNA strands, resulting in egg cells with the wrong number of chromosomes.

Benzyl butyl phthalate (BBP) is a chemical that makes plastic more flexible and durable, and is found in many consumer products, including food packaging, personal care products and children's toys. Previous studies have shown that BBP interferes with the body's hormones and affects human reproduction and development. In the new study, researchers tested a range of doses of BBP on the nematode Caenorhabditis elegans and looked for abnormal changes in egg cells. They saw that at levels similar to those detected in humans, BBP interferes with how newly copied chromosomes are distributed into the sex cells. Specifically, BBP causes oxidative stress and breaks in the DNA strands, which lead to cell death and egg cells with the wrong number of chromosomes.
Based on these findings, the researchers propose that BBP exposure alters gene expression in ways that cause significant damage to the DNA, ultimately leading to lower quality egg cells with abnormal chromosomes. The study also showed that C. elegans metabolizes BBP in the same way as mammals, and is impacted at similar BBP levels that occur in humans, suggesting that C. elegans is an effective model for studying the impacts on people. Overall, the study underscores the toxic nature of this very common plastic ingredient and the damage it causes to animal reproduction.

 Henderson AL, Karthikraj R, Berdan EL, Sui SH, Kannan K, Colaiácovo MP (2024) Exposure to benzyl butyl phthalate (BBP) leads to increased double-strand break formation and germline dysfunction in Caenorhabditis elegans, PLoS Genetics (2024). DOI: 10.1371/journal.pgen.1011434

Study shows that LLMs could maliciously be used to poison biomedical knowledge graphs

In recent years, medical researchers have devised various new techniques that can help them to organize and analyze large amounts of research data, uncovering links between different variables (e.g., diseases, drugs, proteins, etc.). One of these methods entails building so-called biomedical knowledge graphs (KGs), which are structured representations of biomedical datasets.

Researchers  recently showed that large language models (LLMs), machine learning techniques which are now widely used to generate and alter written texts, could be used by malicious users to poison biomedical KGs. Their paper, published in Nature Machine Intelligence, shows that LLMs could be used to generate fabricated scientific papers that could in turn produce unreliable KGs and adversely impact medical research.

Junwei Yang et al, Poisoning medical knowledge using large language models, Nature Machine Intelligence (2024). DOI: 10.1038/s42256-024-00899-3.

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The preparation makes the poison: How muscarine in mushrooms becomes toxic

Mushrooms exist in a breathtaking variety of shapes, colors and sizes. Especially in autumn, mushroom hunters go into the forests to find the tastiest of them, prepare them in multiple ways and eat them with relish. However, it is well known that there are also poisonous mushrooms among them and it is life-saving to distinguish between them. But are these mushrooms really poisonous?

Researchers have investigated this question and recently published the results of a study about muscarine in Angewandte Chemie International Edition.

This toxin is found in various mushrooms, the best known of which is the fly agaric mushroom (Amanita muscaria), which also gave the toxin its name. However, considerably higher concentrations of muscarine are found in fiber cap mushrooms and fool's funnel mushrooms.

Researchers have now been able to show that muscarine is not only present in mushrooms as such, but it can also be stored as a harmless precursor and only be released when mushrooms got injured.

Muscarine was discovered 150 years ago as the first fungal toxin. The current study was able to prove that it is stored, for example, in the fool's funnel mushroom Clitocybe rivulosa as 4phosphomuscarin, which is less toxic.

There are indications that other substances are also present because pure muscarine apparently has a different effect than a mushroom containing muscarine.

The fool's funnel mushroom is also known as the false champignon and can easily be confused with the real champignon. Only when the mushroom is damaged by cutting, cooking or digestion, an enzyme releases the poisonous muscarine from this precursor molecule.

In other mushrooms however, muscarine is already present in its active form. It is not uncommon for organisms to show defense and protective reactions when they are damaged, for example by being eaten by animals.

The mixture of free active and "hidden" inactive muscarine, which only becomes active poison when eaten, increases the danger of certain types of mushrooms such as the funnel mushrooms. These results could help doctors and toxicologists to better assess the actual danger of certain types of fungi and treat poisoning more efficiently.

Muscarine interferes with the transmission of signals by the neurotransmitter acetylcholine and leads to permanent excitation. The consequences are increased salivation and lacrimation, sweating, vomiting, diarrhea, circulatory collapse and even fatal cardiac paralysis.

It is irrelevant whether the poison has already been ingested in free form or as a precursor that is only activated in the body. The correct identification of edible mushrooms is therefore still an important prerequisite for an enjoyable and carefree mushroom meal.

Sebastian Dörner et al, The Fatal Mushroom Neurotoxin Muscarine is Released from a Harmless Phosphorylated Precursor upon Cellular Injury, Angewandte Chemie International Edition (2024). DOI: 10.1002/anie.202417220

Ancient viral DNA activates blood cell production during pregnancy and after significant bleeding, researchers discover

Ancient viral remnants in the human genome are activated during pregnancy and after significant bleeding in order to increase blood cell production, an important step toward defining the purpose of "junk DNA" in humans, according to research published in Science.

These scientists set out to discover how hematopoietic, or blood-forming, stem cells—which typically divide infrequently—are activated during pregnancy and after blood loss. 

When they compared activated genes in stem cells from pregnant versus nonpregnant mice, they found retrotransposons had switched on in stem cells from pregnant mice.
Retrotransposons are ancient viral gene sequences now permanently part of our genome and sometimes called "junk DNA" because they don't encode proteins that contribute to cellular function. They use an enzyme called reverse transcriptase, just like the human immunodeficiency virus (HIV), to replicate themselves.

Humans have evolved mechanisms to keep retrotransposons turned off most of the time, because retrotransposons have the ability to damage DNA when they replicate and reinsert into other parts of the genome.

There are hundreds of these retrotransposon sequences in our genome. Why not permanently inactivate them, like some species have done? They must have some adaptive value for us, the scientists thought.
They used reverse transcriptase inhibiting drugs, commonly used to suppress HIV replication in patients, to inhibit the replication of retrotransposons in mice. These drugs did not alter blood cell production in normal mice but blocked the increase in blood-forming stem cells and red blood cell production during pregnancy, leading to anemia.
As researchers further explored mechanisms activating blood cell production, they found retrotransposons were being detected by the immune sensors, cGAS and STING. These sensors induce interferon production after viral infection or replication of retrotransposons.

They found the retrotransposons turned on just enough interferon to activate blood cell production.
What these scientists discovered in mice is also true in humans, they found.
Earlier they also found that estrogen contributes to blood-forming stem cell activation during pregnancy.

Julia Phan et al, Retrotransposons are co-opted to activate hematopoietic stem cells and erythropoiesis, Science (2024). DOI: 10.1126/science.ado6836

Part2

Dysfunction of neurons in the amygdala may be behind negative perceptions of the environment

Between 15% and 20% of people experience a depressive episode—"a state of deep, lasting distress"—at some point in their lives. But 30% of patients with depression are resistant to conventional medical treatment with antidepressants. To develop novel therapies, we need to improve our understanding of the mechanisms underlying depression, especially those that induce a "negativity bias.

One of the characteristics of depression is a tendency to perceive sensory stimuli and everyday situations in an excessively negative way. Depression causes patients to perceive the world and all sensory stimuli in an excessively negative way—pleasant stimuli become less attractive and unpleasant stimuli become more undesirable—and this contributes to the development and maintenance of depressive symptoms.

But the mechanisms underpinning this "negativity bias," which can fuel the development of depressive symptoms, had previously remained largely unknown until now.

To shed light on the question, scientists explored the amygdala and observed how it functions during depressive episodes.

Their findings suggest that a depressive state alters certain specific neural circuits, leading to a reduction in the activity of neurons involved in pleasant perceptions of positive stimuli and an overactivation of those responsible for the perception of negative stimuli.

We now know that the amygdala is not only involved in our emotional response to environmental stimuli, fostering attraction or repulsion, but that it also plays a role in depression.

These results, which could pave the way for the development of new drugs for people resistant to conventional therapy, were published in the journal Translational Psychiatry in September 2024.

The scientists revealed that in a depressive state, the neurons preferentially involved in encoding positive stimuli are less active than normal, while the neurons preferentially involved in encoding negative stimuli are much more recruited. In other words, depression seems to induce a dysfunction of the amygdala circuits involved in encoding environmental stimuli, and this in turn further encourages the negative valence bias typical of depression.

These data are extremely valuable for the development of novel treatments for people with depression and also for those with bipolar disorder, who experience disproportionately lengthy and severe mood swings.

Mathilde Bigot et al, Disrupted basolateral amygdala circuits supports negative valence bias in depressive states, Translational Psychiatry (2024). DOI: 10.1038/s41398-024-03085-6

What animal societies can teach us about aging

Red deer may become less sociable as they grow old to reduce the risk of picking up diseases, while older house sparrows seem to have fewer social interactions as their peers die off, according to new research showing that humans are not the only animals to change their social behaviour as they age.

A collection of 16 studies, including six from the University of Leeds, have been published recently as part of a special issue of the Philosophical Transactions of the Royal Society B, investigating aging and society across the natural world.

One study into red deer shows that as older female deer become less and less social with age, they are cutting down on competition and reducing their risk of parasite infection. The study used data from a long-running project tracking a wild herd on the Scottish island of Rum.

 Like people who firmly believe in social contacts, while previous research has often considered the process of becoming less social with age, known as "social aging," as potentially negative, these new meta studies show changing habits could in fact bring benefits.

These kinds of effects might be expected across societies, where individuals might avoid social interactions as they become more vulnerable to the costs of infection. Animal populations are a great way of considering the fundamental rules of how aging may shape societies in Nature.

Like older humans who cut down their social interactions to avoid infections like COVID-19—"shielding" during the pandemic in 2020 and 2021—the less sociable older does are less likely to pick up certain parasite infections. "Wild animals provide a good model system for considering the costs and benefits of changing social behavior with age, and in this case may provide an example of aging individuals reducing their social connections to avoid disease and other forms of suffering. 

The special edition is an international collaboration and looks at how individuals of different species age, how this shapes their social interactions, and what this means for their societies.

Even the common garden bird, the house sparrow, changes its social behaviour as it ages, according to another paper in the collection.

This study is one of the first to suggest that birds, like mammals, also reduce the size of their social network as they age. Specifically, the number of friendships, and how central a bird is to the wider social network, declined with age.

The results may be driven by existing friends of the same cohort groups dying as they age, and because it takes more effort for older birds to make friendships with fewer same-age individuals available to bond with. Conversely, the benefits of social connections may be lower than they are for younger individuals, who may come to rely on those connections for things like reproduction or information later in life.

The research collection shows that the social effects of aging are a very general biological phenomenon, extending even to fruit flies.

So nature tells us "cut social interactions" for your own good after a certain age. 

Josh A. Firth et al, Understanding age and society using natural populations, Philosophical Transactions of the Royal Society B: Biological Sciences (2024). DOI: 10.1098/rstb.2022.0469

Scientists discover a promising way to create new superheavy elements

What is the heaviest element in the universe? Are there infinitely many elements? Where and how could superheavy elements be created naturally?

The heaviest abundant element known to exist is uranium, with 92 protons (the atomic number "Z"). But scientists have succeeded in synthesizing super heavy elements  up to oganesson, with a Z of 118. Immediately before it are livermorium, with 116 protons and tennessine, which has 117.

All have short half-lives—the amount of time for half of an assembly of the element's atoms to decay—usually less than a second and some as short as a microsecond. Creating and detecting such elements is not easy and requires powerful particle accelerators and elaborate measurements.

But the typical way of producing high-Z elements is reaching its limit. In response, a group of scientists from the United States and Europe have come up with a new method to produce superheavy elements beyond the dominant existing technique. Their work, done at the Lawrence Berkeley National Laboratory in California, was published in Physical Review Letters.

Part 1

The island of stability is a region where superheavy elements and their isotopes—nuclei with the same number of protons but different numbers of neutrons—may have much longer half-lives than the elements near it. It's been expected to occur for isotopes near Z=112.

While there have been several techniques to discover superheavy elements and create their isotopes, one of the most fruitful has been to bombard targets from the actinide series of elements with a beam of calcium atoms, specifically an isotope of calcium, 48-calcium (48Ca), that has 20 protons and 28 (48 minus 20) neutrons. The actinide elements have proton numbers from 89 to 103, and 48Ca is special because it has a "magic number" of both protons and neutrons, meaning their numbers completely fill the available energy shells in the nucleus.
Proton and/or neutron numbers being magic means the nucleus is extremely stable; for example, 48Ca has a half-life of about 60 billion billion (6 x 1019) years, far larger than the age of the universe. (By contrast, 49Ca, with just one more neutron, decays by half in about nine minutes.)

These reactions are called "hot-fusion" reactions. Another technique saw beams of isotopes from 50-titanium to 70-zinc accelerated onto targets of lead or bismuth, called "cold-fusion" reactions. Superheavy elements up to oganesson (Z=118) were discovered with these reactions.

But the time needed to produce new superheavy elements, quantified via the cross section of the reaction which measures the probability they occur, was taking longer and longer, sometimes weeks of running time. Being so close to the predicted island of stability, scientists need techniques to go further than oganesson. Targets of einsteinium or fermium, themselves superheavy, cannot be sufficiently produced to make a suitable target.
Part 2

Theoretical models of the nucleus have successfully predicted the production rates of superheavy elements below oganesson using actinide targets and beams of isotopes heavier than 48-calcium. These models also agree that to produce elements with Z=119 and Z=120, beams of 50-titanium would work best, having the highest cross sections.

But not all necessary parameters have been pinned down by theorists, such as the necessary energy of the beams, and some of the masses needed for the models haven't been measured by experimentalists. The exact numbers are important because the production rates of the superheavy elements could otherwise vary enormously.

Several experimental efforts to produce atoms with proton numbers from 119 to 122 have already been attempted. All have been unsatisfactory, and the limits they determined for the cross sections have not allowed different theoretical nuclear models to be constrained. Gates and his team investigated the production of isotopes of livermorium (Z=116) by beaming 50-titanium onto targets of 244-Pu (plutonium).
Part 3

Using the 88-Inch Cyclotron accelerator at Lawrence Berkeley National Laboratory, the team produced a beam that averaged 6 trillion titanium ions per second that exited the cyclotron. These impacted the plutonium target, which had a circular area of 12.2 cm, over a 22-day period. Making a slew of measurements, they determined that 290-livermorium had been produced via two different nuclear decay chains.

"This is the first reported production of a SHE [superheavy element] near the predicted island of stability with a beam other than 48-calcium," they concluded. The reaction cross section, or probability of interaction, did decrease, as was expected with heavier beam isotopes, but "success of this measurement validates that discoveries of new SHE are indeed within experimental reach."
The discovery represents the first time a collision of non-magic nuclei has shown the potential to create other superheavy atoms and isotopes (both), hopefully paving the way for future discoveries. About 110 isotopes of superheavy elements are known to exist, but another 50 are expected to be out there, waiting to be uncovered by new techniques such as this.

J. M. Gates et al, Toward the Discovery of New Elements: Production of Livermorium ( Z=116 ) with Ti50, Physical Review Letters (2024). DOI: 10.1103/PhysRevLett.133.172502

Part 4

Scientists transport protons in truck, paving way for antimatter delivery

Antimatter might sound like something out of science fiction, but at the CERN Antiproton Decelerator (AD), scientists produce and trap antiprotons every day. The BASE experiment can even contain them for more than a year—an impressive feat considering that antimatter and matter annihilate upon contact.

The CERN AD hall is the only place in the world where scientists are able to store and study antiprotons. But this is something that scientists working on the BASE experiment hope to change one day with their subproject BASE-STEP: an apparatus designed to store and transport antimatter.

Most recently, the team of scientists and engineers took an important step towards this goal by transporting a cloud of 70 protons in a truck across CERN's main site.

If you can do it with protons, it will also work with antiprotons. The only difference is that you need a much better vacuum chamber for the antiprotons.

This is the first time that loose particles have been transported in a reusable trap that scientists can then open in a new location and then transfer the contents into another experiment. The end goal is to create an antiproton-delivery service from CERN to experiments located at other laboratories.

Part 1

Antimatter is a naturally occurring class of particles that is almost identical to ordinary matter except that the charges and magnetic properties are reversed.
According to the laws of physics, the Big Bang should have produced equal amounts of matter and antimatter. These equal-but-opposite particles would have quickly annihilated each other, leaving a simmering but empty universe. Physicists suspect that there are hidden differences that can explain why matter survived and antimatter all but disappeared.
The BASE experiment aims to answer this question by precisely measuring the properties of antiprotons, such as their intrinsic magnetic moment, and then comparing these measurements with those taken with protons. However, the precision the experiment can achieve is limited by its location.

The accelerator equipment in the AD hall generates magnetic field fluctuations that limit how far we can push our precision measurements.
If scientists want to get an even deeper understanding of the fundamental properties of antiprotons, they need to move out.
This is where BASE-STEP comes in. The goal is to trap antiprotons and then transfer them to a facility where scientists can study them with a greater precision. To be able to do this, they need a device that is small enough to be loaded onto a truck and can resist the bumps and vibrations that are inevitable during ground transport.
The current apparatus—which includes a superconducting magnet, cryogenic cooling, power reserves, and a vacuum chamber that traps the particles using magnetic and electric fields—weighs 1,000 kilograms and needs two cranes to be lifted out of the experimental hall and onto the truck. Even though it weighs a ton, BASE-STEP is much more compact than any existing system used to study antimatter. For example, it has a footprint that is five times smaller than the original BASE experiment, as it must be narrow enough to fit through ordinary laboratory doors.
Part 2

During the rehearsal, the scientists used trapped protons as a stand-in for antiprotons. Protons are a key ingredient of every atom, the simplest of which is hydrogen (one proton and one electron.) But storing protons as loose particles and then moving them onto a truck is a challenge because any tiny disturbance will draw the unbonded protons back into an atomic nucleus.

When it's transported by road, our trap system is exposed to acceleration and vibrations, and laboratory experiments are usually not designed for this. Scientists needed to build a trap system that is robust enough to withstand these forces, and they have now put this to a real test for the first time.
the biggest potential hurdle isn't currently the bumpiness of the road but traffic jams.

If the transport takes too long, they will run out of helium at some point.
Liquid helium keeps the trap's superconducting magnet at a temperature below 8.2 Kelvin: its maximum operating temperature. If the drive takes too long, the magnetic field will be lost and the trapped particles will be released and vanish as soon as they touch ordinary matter.
Eventually, they want to be able to transport antimatter to our dedicated precision laboratories at the Heinrich Heine University in Düsseldorf, which will allow us to study antimatter with at least 100-fold improved precision
In the longer term, they want to transport it to any laboratory in Europe. This means that they need to have a power generator on the truck. They are currently investigating this possibility.
After this successful test, which included ample monitoring and data-taking, the team plans to refine its procedure with the goal of transporting antimatter next year.

"This is a totally new technology that will open the door for new possibilities of study, not only with antiprotons but also with other exotic particles, such as ultra-highly-charged ions.
Another experiment, PUMA, is preparing a transportable trap. Next year, it plans to transport antiprotons 600 meters from the ADH hall to CERN's ISOLDE facility in order to use them to study the properties and structure of exotic atomic nuclei.
Source: CERN
Part 3