Navigating the future: Brain cells that plan where to go

Researchers  have discovered a region of the brain that encodes where an animal is planning to be in the near future. Linked to internal maps of spatial locations and past movements, activity in the newly discovered grid cells accurately predicts future locations as an animal travels around its environment.

Published in Science on August 15, the study helps explain how planned spatial navigation is possible.

It might seem effortless, but navigating the world requires quite a bit of under-the-hood brain activity. For example, simply walking around a supermarket picking up groceries requires internalized maps of the outside world, information about one's own changing position and speed, and memories about where one has been and what one is trying to buy.

Much of this kind of information is contained in cells within two connected parts of the brain—the hippocampus and the medial entorhinal cortex, or MEC for short—which are extremely similar in all mammals, from rats to humans. In particular, the MEC contains maps of an animal's current location in space, a discovery that won the Nobel Prize for Physiology or Medicine in 2014.

Prediction grid cells in the medial entorhinal cortex became active before rats entered the region of space that they encode. In this video, activity of two neurons is represented by the flashing of red and blue squares. for convenience, the squares are placed in the location of the grid that the neurons encode. Credit: RIKEN

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The new study focuses on the MEC, but not on the stored information needed for spatial navigation or an animal's current location. Instead, the experiments performed now concentrate on how this brain region creates maps of future positions, which are continuously updated as animals move.

While rats traversed an open square field in search of freely available water that was moved around to different locations, the researchers recorded all movements, which included hundreds of trajectories. At the same time, they recorded the activity of individual brain cells in the MEC.

Afterward, they checked how well the  brain activity over time matched the rats' changing positions.

They found that the activity of some brain cells in the MEC created an internal grid that mapped future positions within the field. For example, an MEC cell might encode a certain location in the field, but only when a rat reached a spot 30 cm to 40 cm earlier in a route that eventually crossed that location—regardless of which direction the rat was coming from.

This is very different from the grid cells that helped win the Nobel Prize, which become active only when an animal is currently in a particular location. The authors call the newly discovered neurons "predictive grid cells," and conducted several follow-up experiments to get a better idea of what exactly they encode.

First, they tested whether the newly discovered grid cells predicted the future location in terms of distance or time from the present. They found that both were encoded, although the "gridness" of the cells was higher when considering distance.

They also found that future positions were faithfully encoded in different situations, whether the rats were trying to go to specific targets or if they were randomly foraging for food. This means that the function of the predictive grid cells is not limited to goal-directed behavior.

This study provides important insights into the mechanisms of spatial navigation and episodic memory formation in hippocampal and entorhinal cortical circuits.

Ayako Ouchi et al, Predictive grid coding in the medial entorhinal cortex, Science (2024). DOI: 10.1126/science.ado4166. www.science.org/doi/10.1126/science.ado4166

Sleep resets neurons for new memories the next day, study finds

While everyone knows that a good night's sleep restores energy, a new  study finds it resets another vital function: memory.

Learning or experiencing new things activates neurons in the hippocampus, a region of the brain vital for memory. Later, while we sleep, those same neurons repeat the same pattern of activity, which is how the brain consolidates those memories that are then stored in a large area called the cortex. But how is it that we can keep learning new things for a lifetime without using up all of our neurons?

A study, "A Hippocampal Circuit Mechanism to Balance Memory Reactivation During Sleep,"  published in Science, finds at certain times during deep sleep, certain parts of the hippocampus go silent, allowing those neurons to reset.

This mechanism could allow the brain to reuse the same resources, the same neurons, for new learning the next day.

The hippocampus is divided into three regions: CA1, CA2 and CA3. CA1 and CA3 are involved in encoding memories related to time and space and are well-studied; less is known about CA2, which the current study found generates this silencing and resetting of the hippocampus during sleep.

The researchers now realized that there are other hippocampal states that happen during sleep where everything is silenced. The CA1 and CA3 regions that had been very active were suddenly quiet. It's a reset of memory, and this state is generated by the middle region, CA2.

Cells called pyramidal neurons are thought to be the active neurons that matter for functional purposes, such as learning. Another type of cell, called interneurons, has different subtypes. The researchers discovered that the brain has parallel circuits regulated by these two types of interneurons—one that regulates memory, the other that allows for resetting of memories.

The researchers think they now have the tools to boost memory, by tinkering with the mechanisms of memory consolidation, which could be applied when memory function falters, such as in Alzheimer's disease. Importantly, they also have evidence for exploring ways to erase negative or traumatic memories, which may then help treat conditions such as post-traumatic stress disorder.

The result helps explain why all animals require sleep, not only to fix memories, but also to reset the brain and keep it working during waking hours. 

 Lindsay A. Karaba et al, A hippocampal circuit mechanism to balance memory reactivation during sleep, Science (2024). DOI: 10.1126/science.ado5708. www.science.org/doi/10.1126/science.ado5708

Why do plants wiggle?

Sunflower plants wiggling ( known as  "circumnutations")

Plants don't usually shift around like animals but, instead, move by growing in different directions over time.

Plants naturally and consistently arranged themselves into a zig-zag pattern, almost like the teeth of a zipper. The arrangement likely helps the plants maximize their access to sunlight as a group.

In greenhouse experiments and computer simulations, researchers showed that sunflowers take advantage of circumnutations to search the environment around them for patches of sunlight.

For climbing plants, it's obvious that it's about searching for supports to twine on.

 If they moved with just the right amount of randomness, however, the sunflowers formed that tell-tale zig-zag, which, in real life plants, provides a lot of access to sunlight.

 Chantal Nguyen et al, Noisy Circumnutations Facilitate Self-Organized Shade Avoidance in Sunflowers, Physical Review X (2024). DOI: 10.1103/PhysRevX.14.031027

Newly discovered protein stops DNA damage

Researchers have discovered a protein that has the never-before-seen ability to stop DNA damage in its tracks. The finding could provide the foundation for developing everything from vaccines against cancer, to crops that can withstand the increasingly harsh growing conditions brought on by climate change.

The researchers found the protein—called DdrC (for DNA Damage Repair Protein C)—in a fairly common bacterium called Deinococcus radiodurans (D. radiodurans), which has the decidedly uncommon ability to survive conditions that damage DNA—for example, 5,000 to 10,000 times the radiation that would kill a regular human cell.  Deinococcus also excels in repairing DNA that has already been damaged.

Newly discovered protein stops DNA damage: Could lead to cancer vaccines and drought-resistant crops

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Turns out that DdrC scans for breaks along the DNA and when it detects one it snaps shut—like a mousetrap. This trapping action has two key functions.

It neutralizes it (the DNA damage), and prevents the break from getting damaged further. And it acts like a little molecular beacon. It tells the cell 'Hey, over here. There's damage. Come fix it.

Typically proteins form complicated networks that enable them to carry out a function. DdrC appears to be something of an outlier, in that it performs its function all on its own, without the need for other proteins. The team was curious whether the protein might function as a "plug-in" for other DNA repair systems.

They tested this by adding it to a different bacterium: E. coli. It actually made the bacterium over 40 times more resistant to UV radiation damage. This seems to be a rare example where you have one protein and it really is like a standalone machine.

In theory, this gene could be introduced into any organism—plants, animals, humans—and it should increase the DNA repair efficiency of that organism's cells.

DdrC is just one out of hundreds of potentially useful proteins in this bacterium. The next step is to prod further, look at what else this cell uses to fix its own genome—because  scientists are sure to find many more tools where they have no idea how they work or how they're going to be useful until they look. And they are looking for them now.

Robert Szabla et al, DdrC, a unique DNA repair factor from D. radiodurans, senses and stabilizes DNA breaks through a novel lesion-recognition mechanism, Nucleic Acids Research (2024). DOI: 10.1093/nar/gkae635

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Photon entanglement could explain the rapid brain signals behind consciousness

Understanding the nature of consciousness is one of the hardest problems in science. Some scientists have suggested that quantum mechanics, and in particular quantum entanglement, is the key to unraveling the phenomenon.

Now, a research group in China has shown that many entangled photons can be generated inside the myelin sheath that covers nerve fibers. It could explain the rapid communication between neurons, which so far has been thought to be below the speed of sound, too slow to explain how the neural synchronization occurs.

The paper is published in the journal Physical Review E.

The brain communicates within itself by firing electrical signals called synapses between neurons, which are the main components of nervous tissue. It is the synchronized activity of millions of neurons that consciousness (among other brain business) relies on. But the way this precise synchronization takes place is unknown.

Connections between neurons are called axons—long structures akin to electrical wires—and covering them is a coating ("sheath") made of myelin, a white tissue made of lipids.

Comprised of up to hundreds of layers, myelin insulates the axons, as well as shaping them and delivering energy to the axons. (In actuality, a series of such sheaths stretches across the length of the axon. The myelin sheath is typically about 100 microns long, with 1 to 2 micron gaps between them.) Recent evidence suggests myelin also plays an important role in promoting synchronization between neurons.

But the speed at which signals propagate along the axons is below the speed of sound, sometimes much below—too slow to create the millions of neuron synchronizations that are the basis for all the amazing things the brain can do.

Part 1

To remedy this problem, researchers investigated if there could be entangled photons within this axon-myelin system that could, though the magic of quantum entanglement, communicate instantly across the involved distances.
A tricarboxylic acid cycle releases energy stored in nutrients, with a cascade of infrared photons released during the cycling process. These photons couple to vibrations from carbon-hydrogen (C-H) bonds in lipid molecules and excite them to a higher vibrational energy state. As the bond then transitions to a lower vibrational energy state, it releases a cascade of photons.

The researchers applied cavity quantum electrohydrodynamics to a perfect cylinder surrounded by the myelin, making the reasonable assumption that the outer wall of the myelin sheath is a perfectly cylindrical conducting wall.
Using quantum mechanical techniques, they quantized the electromagnetic fields and the electric field inside the cavity, as well as the photons—that is, treated them all as quantum objects—and then, with some simplifying assumptions, solved the resulting equations.

Doing so gave the wavefunction for the system of the two photons interacting with the matter inside the cavity. They then calculated the photons' degree of entanglement by determining its quantum entropy, a measure of disorder, using an extension of classical entropy developed by the science polymath John von Neumann.
The researchers showed that the two photons can indeed have higher rate of being entangled under occasions.
The conducting wall limits the electromagnetic wave modes that can exist inside the cylinder, making the cylinder an electromagnetic cavity that keeps most of its energy within it. These modes are different from the continuous electromagnetic waves ("light") that exist in free space.

It is these discrete modes that result in the frequent production of highly entangled photons within the myelin cavity, whose rate of production can be significantly enhanced compared to two untangled photons.
Part 2

Entanglement means the two-photon state is not a classical combination of two photon states. Instead, measuring or interacting with one of the photons instantly affects the same property of the second photon, no matter how far away it is.
Entanglement has been demonstrated for a system whose members are over 1,000 km apart. Nothing like it exists in classical physics; it is purely a quantum phenomenon. Here entanglement would raise the possibility of much faster signaling along the sections of myelin that encase segments of the axon's length.

One possibility, the authors write, is that the entanglement of photons could transform into entanglement along potassium ion channels in the neuron. If so, the opening and closing of one channel may affect the performance of another somewhere else.
These results are a combination of two phenomena that exist but are still largely mysterious: consciousness (let alone quantum consciousness) and quantum entanglement.
the researchers didn't say there is a direct connection. At this early stage, their primary goal is to identify possible mechanisms of neural synchronization, which affects numerous neurobiological processes. Through this work, they hope to gain a better understanding.

Zefei Liu et al, Entangled biphoton generation in the myelin sheath, Physical Review E (2024). DOI: 10.1103/PhysRevE.110.024402. On arXiv: DOI: 10.48550/arxiv.2401.11682

Part 3

The banana apocalypse is near, but biologists  have found a key to their survival

The bananas in your supermarket and that you eat for breakfast are facing functional extinction due to the disease Fusarium wilt of banana (FWB), caused by a fungal pathogen called Fusarium oxysporum f.sp. cubense (Foc) tropical race 4 (TR4).

However, thanks to recent research by an international team of scientists  we now know that Foc TR4 did not evolve from the strain that wiped out commercial banana crops in the 1950s, and that the virulence of this new strain seems to be caused by some accessory genes that are associated the production of nitric oxide.

The research, published in Nature Microbiology, opens the door to treatments and strategies that can slow—if not control—the as-of-yet unchecked spread of Foc TR4.

The kind of banana we eat today is not the same as the one your grandparents ate. Those old ones, the Gros Michel bananas, are functionally extinct, victims of the first Fusarium outbreak in the 1950s.

Today, the most popular type of commercially available banana is the Cavendish variety, which was bred as a disease-resistant response to the Gros Michel extinction. For about 40 years, the Cavendish banana thrived across the globe in the vast monocultured plantations that supply the majority of the world's commercial banana crop.

But by the 1990s, the good times for the Cavendish banana had begun to come to a close. There was another outbreak of banana wilt. It spread like wildfire from southeast Asia to Africa and Central America.

Scientists have spent the last 10 years studying this new outbreak of banana wilt.

As a result of their hard work, we now know that the Cavendish banana-destroying pathogen TR4 did not evolve from the race that decimated the Gros Michel bananas. TR4's genome contains some accessory genes that are linked to the production of nitric oxide, which seems to be the key factor in TR4's virulence.

While the research team working on the problem  doesn't yet know exactly how these activities contribute to disease infestation in Cavendish banana, they were able to determine that the virulence of Foc TR4 was greatly reduced when two genes that control nitric oxide production were eliminated.

Identifying these accessory genetic sequences opens up many strategic avenues to mitigate—or even control—the spread of Foc TR4.

The researchers are quick to point out that the ultimate problem facing one of our favorite fruits is the practice of monocropping.

When there's no diversity in a huge commercial crop, it becomes an easy target for pathogens.

Virulence of the banana wilt-causing fungal pathogen Fusarium oxysporum tropical race 4 is mediated by nitric oxide biosynthesis and accessory genes, Nature Microbiology (2024). DOI: 10.1038/s41564-024-01779-7

Sounds of soil heartbeat: How underground acoustics can amplify soil health

Barely audible to human ears, healthy soils produce a cacophony of sounds in many forms—a bit like an underground rave concert of bubble pops and clicks.

Special recordings made by Flinders University ecologists in Australia show that this chaotic mixture of soundscapes can be a measure of the diversity of tiny living animals in the soil, which create sounds as they move and interact with their environment.

 Acoustic complexity and diversity of  samples are associated with soil invertebrate abundance—from earthworms, beetles to ants and spiders—and it seems to be a clear reflection of soil health.

All living organisms produce sounds, and these preliminary results suggest different soil organisms make different sound profiles depending on their activity, shape, appendages and size. Understanding it makes a better prediction of soil health.

This technology holds promise in addressing the global need for more effective soil biodiversity monitoring methods to protect our planet's most diverse ecosystems.

Sounds of the underground reflect soil biodiversity dynamics across a grassy woodland restoration chronosequence, Journal of Applied Ecology (2024). DOI: 10.1111/1365-2664.14738

During a heat wave temperatures are not the only threat!

Isn't heat what kills during a heat wave?

Experts say, more things can kill you during a heat wave!

The impact of heat on health is far more than just temperature... its effect can be felt across income levels, age groups, socio-economic conditions, health care, and different cultural approaches to heat.

If you divide a country into several regions, 40 degrees Celsius (104 Fahrenheit) is not even classed as a heat wave in some areas, whereas in others, the temperature which defines a heat wave can be just 26 degrees.

When there is a heat wave, only 3.0 percent of mortality is due to heat stroke. Heat kills by aggravating other illnesses.

In the first heat wave (of the year) much more people are likely to be susceptible (to death) than the second because it claims the frailest, leaving fewer susceptible people in the second and fewer still in the third... That's why the first heat wave always has a greater impact on mortality. This is what epidemiology experts call the 'harvest effect'.

It's clear that the impact of heat is much greater in poorer neighborhoods.

It is not the same thing to experience a heat wave in a room with three people and one window and no air conditioning or fan, than going through the same thing in a villa with a swimming pool.

It's not even a question of having air conditioning or not, but about being able to turn it on. During a heat wave, the price of electricity in some countries can  skyrocket making it unaffordable for many!

Part 1

Heatstroke happens when a person is exposed to high temperatures... and their body is not able to regulate that temperature. If you go out in the sun at 42C or exercise at those temperatures, your body is unable -- no matter how much it sweats, which is the main mechanism for regulating heat -- to lower and maintain its temperature at 37C.

When your body is no longer at 37C... your organs stop working properly, including your brain. Then hyperthermia sets in and the person can die.

How heat waves affects culture: (heat culture)

In 2003, Europe suffered a brutal heat wave and 70,000 people died in 15 days. People were not prepared, and there were no prevention plans, which meant it had a brutal impact on mortality. Now nobody doubts that heat kills.
But people adapt. Between 1983 to 2003, for every degree above the temperature classed as a heat wave, the mortality in Spain increased by 14 percent. But after 2003, it barely increased by three percent.

In a city like Madrid, you never used to see older people wearing shorts but nowadays they all wear them -- you see them going out for a walk wearing a hat and with a bottle of water.

In places where they are used to having heat waves, there are now much more air conditioning units and secondly, homes are much more adapted to cope with this heat.

People don't go out from 3:00 pm, that's why the siesta exists in Spain. And in the southern Andalusia region, the villages are painted white and the streets are wide so the wind can freely circulate.

Source: AFP and other news agencies

Part 2

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Uterus transplants are leading to healthy pregnancies

till now, that is.

Uterine transplants are relatively rare and recent—the first was performed in 2011, and to date a little more than 100 transplants have been conducted worldwide.

However, a new study finds that these procedures are often successful, leading to pregnancies and live births in 14 out of the 20 patients assessed.

"A successfully transplanted uterus is capable of functioning at least on par with a native, in situ uterus," concluded a research team who assessed the outcomes.

As the researchers explained, uterus transplants are typically needed by women with what's known as "absolute uterine infertility," a condition affecting about 1 in every 500 women where the organ is either dysfunctional or absent.

In the past, these women would have had to resort to adoption or surrogacy, but 13 years ago doctors first transplanted a donated uterus into a woman with uterine infertility.

Since then, the procedure has gained acceptance.

Just how successful are these transplants?

The Dallas team tracked outcomes for 20 women averaging 30 years of age who opted for uterus transplant at their facility between 2016 and 2019.

Organs came from 18 living donors and 2 deceased donors.

In 14 of the women who underwent uterus transplant, the operation was successful, the study found, and "all 14 recipients gave birth to at least 1 live-born infant."

Complications were common and occurred in 50% of these pregnancies, with gestational high blood pressure and preterm labor being two of the most common. However, "congenital abnormalities and developmental delays have not occurred to date in [any of] the live-born children," the researchers noted. Overall, uterus transplant was "technically feasible and was associated with a high live birth rate," the team concluded.

Giuliano Testa et al, Uterus Transplant in Women With Absolute Uterine-Factor Infertility, JAMA (2024). DOI: 10.1001/jama.2024.11679

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Weight gain appears to have greater metabolic consequences in South Asian men

Gaining even a small amount of weight may lead to adverse metabolic responses in young South Asian men according to new research.

The study— published in Nature Metabolism—may shed light on why South Asians are at greater risk of developing type 2 diabetes compared with other ethnic groups, and why their risk of diabetes increases more steeply with increasing BMI.

The research—which is part of the GlasVegas (Glasgow visceral and ectopic fat with weight gain in South Asians) study—investigated 14 young normal weight men of South Asian ethnic origin and 21 men of white European ethnicity before and after an overfeeding protocol to gain approximately 5 kg in weight ( please note the small sample size).

The main finding was that this modest weight gain resulted in substantial adverse metabolic responses in the South Asian men. In contrast, the white European men appeared to exhibit a degree of "metabolic buffering capacity," such that the same weight gain led to much smaller metabolic changes. Insulin sensitivity—or how well body tissues respond to insulin—decreased by 38% in the South Asian men, but only by 7% in the white Europeans.

South Asians comprise about a quarter of the world's population and have 3–5 times the prevalence of type 2 diabetes compared to white Europeans. South Asians also develop type 2 diabetes at much lower BMIs (Body Mass Indexes) than white Europeans.

A South Asian person with a BMI of around 22 kg/m²—well within the "normal" weight range—has an equivalent risk of type 2 diabetes as a white European person with a BMI of 30 kg/m² (the conventional threshold for obesity).

The adverse metabolic consequences of weight gain in the South Asian men appeared to be related to the size of fat cells at baseline, and the change in the amount of fat in small fat cells.

The South Asians had larger fat cells before weight gain and appeared to be unable to recruit small fat cells to grow into larger fat cells with weight gain. This suggests that, unlike white Europeans, the fat was more likely to go into other areas such as the liver, which can have adverse metabolic consequences.

 found that when young, lean white European men gained a little weight—about 5 kg—they did not experience any substantial adverse metabolic consequences; but when young, lean South Asian men gained the same amount of weight, they started to exhibit metabolic dysfunction.

"Insulin sensitivity decreased by 38% in South Asians, but only by 7% in white Europeans, indicating that South Asians were not able to buffer against the adverse effects of weight gain in the way that their white European counterparts were able to.

This appears to be related, at least in part, to differences in the size of fat cells between South Asian and white European men, and how they respond to the effects of weight gain.

The South Asian men had more large fat cells, and the very small fat cells that they had were less able to grow in size as they put on weight. Both these factors were related to the adverse metabolic changes with weight gain.

Another interesting observation was that when the European men put on weight, they put on some lean tissue as well as fat tissue, but the South Asian men essentially just put on fat tissue.

This may be important, as increasing lean tissue may help protect against some of the adverse effects of weight gain, as sugar is cleared from the blood in lean tissue, or muscle.

The study's findings reinforce the need for the prevention of weight gain in South Asian men, in order to prevent further risk of type 2 diabetes.

James McLaren et al, Weight gain leads to greater adverse metabolic responses in South Asian compared with white European men: the GlasVEGAS study, Nature Metabolism (2024). DOI: 10.1038/s42255-024-01101-z

Part 2

Risk for developing type 1 diabetes doubled with paternal link

Individuals are less likely to have type 1 diabetes if their mother has the condition than if their father is affected, according to a study scheduled to be presented at the annual meeting of the European Association for the Study of Diabetes, being held from Sept. 9 to 13 in Madrid.

Researchers conducted a meta-analysis across five cohorts of individuals with type 1 diabetes (total, 11,475 individuals) to compare the proportion of individuals with affected fathers versus mothers.

The researchers found that almost twice as many individuals had an affected father versus mother (overall odds ratio [OR], 1.79). The proportion of individuals with an affected father was higher both among individuals diagnosed with type 1 diabetes older than 18 years (OR, 1.64) and those 18 years or younger (OR, 1.80). There was an excess of individuals with affected fathers only if parental diagnosis was before offspring birth compared with diagnosis after birth. Age at diagnosis and type 1 diabetes-free survival curves were similar among offspring of affected fathers and mothers.

Cell death types and their relations to host immune pathways

A new review was published as the cover paper of Aging, titled "Types of cell death and their relations to host immunological pathways."

Various immune pathways in the host, such as TH1, TH2, TH3, TH9, TH17, TH22, TH1-like, and THαβ, have been identified. While TH2 and TH9 responses primarily target multicellular parasites, host immune pathways against viruses, intracellular microorganisms (like bacteria, protozoa, and fungi), and extracellular microorganisms utilize programmed cell death mechanisms to initiate immune responses and effectively eliminate pathogens.

These relationships can help us understand the host defense mechanisms against invading pathogens and provide new insights for developing better therapeutic strategies against infections or autoimmune disorders.

Types of Cell Death and Relations to Host Immunological Pathways | Aging-US

Kuo-Cheng Lu et al, Types of cell death and their relations to host immunological pathways, Aging (2024). DOI: 10.18632/aging.206035

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Bacteria Put on an Invisibility Cloak to Cause Asymptomatic Infections 

Biofilms prevent Pseudomonas aeruginosa toxins from being detected by sensory neurons, tricking the body into not looking sick.

When someone catches a lung infection, be it viral or bacterial, they usually show tell-tale symptoms, such as weakness, breathing difficulties, or brain fog. These indicators signal others to keep a safe distance from the contagious individual. But Pseudomonas aeruginosa can cause a range of lung infections, from mild bronchitis to life-threatening pneumonia, that are acutely asymptomatic yet cause inflammation and destruction of tissue.

In chronic infections, these bacteria form a biofilm of extracellular polymer matrix around themselves that shields them from antimicrobials, enzymes, and neutrophils.² Now, in a paper published in Cell, a group of scientists investigated the underlying mechanism and reported that the biofilm hides Pseudomonas bacteria from sensory neurons in mice, preventing signals from reaching the brain and reducing sickness symptoms. These findings provide a deeper understanding of how biofilm-forming bacteria evade the lung-to-brain communication channel, a potentially crucial tactic in persistent infections. 

https://www.cell.com/cell/abstract/S0092-8674(24)00249-6#%20

Study of fasting and ketogenic diet reveals a new vulnerability of pancreatic tumors

Scientists  have discovered a way to get rid of pancreatic cancer in mice by putting them on a high fat, or ketogenic, diet and giving them cancer therapy.

The cancer therapy blocks fat metabolism, which is the cancer's only source of fuel for as long as the mice remain on the ketogenic diet, and the tumors stop growing.

A scientific team made the discovery, which appears August 14 in Nature, while they were trying to figure out how the body manages to subsist on fat while fasting.

The research team first uncovered how a protein known as eukaryotic translation initiation factor (eIF4E) changes the body's metabolism to switch to fat consumption during fasting. The same switch also occurs, thanks to eIF4E, when an animal is on a ketogenic diet.

They found that a new cancer drug called eFT508, currently in clinical trials, blocks eIF4E and the ketogenic pathway, preventing the body from metabolizing fat. When the scientists combined the drug with a ketogenic diet in an animal model of pancreatic cancer, the cancer cells starved.

The scientists first treated pancreatic cancer with a cancer drug called eFT508 that disables eIF4E, intending to block tumor growth. Yet, the pancreatic tumors continued to grow, sustained by other sources of fuel like glucose and carbohydrates. Knowing that pancreatic cancer can thrive on fat, and that eIF4E is more active during fat burning, the scientists first placed the animals on a ketogenic diet, forcing the tumors to consume fats alone, and then put them on the cancer drug. In this context, the drug cut off the cancer cells' only sustenance—and the tumors shrank.

This method is to treat cancer after knowing its vulnerability and attaining success.

Davide Ruggero, Remodeling of the translatome controls diet and its impact on tumorigenesis, Nature (2024). DOI: 10.1038/s41586-024-07781-7. www.nature.com/articles/s41586-024-07781-7

Spinal cerebrospinal fluid (CSF) leak and  an upright headache

First Major Study Links Cannabis Use Disorder to Deadly Cancers

A new investigation from the American Head and Neck Society finds that excessive cannabis use disorder may increase the risk of developing any head or neck cancer, including oral, oropharyngeal, nasopharyngeal, salivary gland, and laryngeal cancer.

However, the  results should be "interpreted cautiously", as there is a chance they did not fully control for alcohol and tobacco use, as well as HPV status – all of which can contribute to the risk of developing head or neck cancers.

What's more, the study did not measure the amount or the potency of the cannabis participants consumed, how often it was consumed, or how the cannabis was consumed (whether it be vaped, smoked, or ingested).

But this is one of the first studies – and the largest that we know of to date – to associate head and neck cancer with cannabis use. The detection of this risk factor is important because head and neck cancer may be preventable once people know which behaviors increase their risk.

The research relied on 20 years of clinical records belonging to 116,076 individuals diagnosed with a cannabis-related disorder that was "substantial enough to cause physical or emotional symptoms with the inability to cease cannabis use."

The two peaks of aging in humans
The progress of a human being through life might be thought of as a mostly gradual succession of changes from the ovum to the grave.
But according to new research into the molecular changes associated with aging, humans experience two drastic lurches forward, one at the average age of 44 and the other at the average age of 60.
We're not just changing gradually over time; there are some really dramatic changes at these peaks. 
It turns out the mid-40s is a time of dramatic change, as is the early 60s. And that's true no matter what class of molecules you look at.
Researchers noticed that in some conditions, such as Alzheimer's and cardiovascular disease, risk doesn't rise gradually with time, it escalates sharply after a certain age.
 Using the samples from their cohort, the researchers have been tracking different kinds of biomolecules. The different molecules studied include RNA, proteins, lipids, and gut, skin, nasal, and oral microbiome taxa, for a total of 135,239 biological features.
Scientists now noticed that there's a very clear change in the abundances of many different kinds of molecules in the human body at two distinct stages.
Around 81 percent of all the molecules they studied showed changes during one or both of these stages. Changes peaked in the mid-40s, and again in the early 60s, with slightly different profiles.

The mid-40s peak showed changes in molecules related to the metabolism of lipids, caffeine, and alcohol, as well as cardiovascular disease, and dysfunctions in skin and muscle. The early 60s peak was associated with carbohydrate and caffeine metabolism, cardiovascular disease, skin and muscle, immune regulation, and kidney function.

The first peak, the mid-40s, is typically when women start undergoing menopause or perimenopause, but the researchers ruled this out as a main factor: men, too, also underwent significant molecular changes at the same age.

This suggests that while menopause or perimenopause may contribute to the changes observed in women in their mid-40s, there are likely other, more significant factors influencing these changes in both men and women

https://www.nature.com/articles/s43587-024-00692-2

Part 1

Fatherhood at Fifty Impacts your Child Health

We all know that motherhood is constrained by a biological clock. 

And there is a "diminished concerns of the male 'biological clock' !

But mature fatherhood comes with its own risks, and a new study finds the proportion of US fathers aged 50 or older at the time of their child's birth is on the rise, meaning more children are likely to be impacted.

A 2018 study identified many of the risks of mature fatherhood, using data from 2007 to 2016 for more than 40 million live births in the US.

The data revealed that babies born to fathers over the age of 35 were at higher risk for adverse outcomes like low birth weight, seizures, and breathing problems immediately after birth.

And the older a father was, the greater the risk – for a man aged 45 years or older, his baby was 14 percent more likely to be born prematurely, and for a man aged 50 or older, his child was 28 percent more at risk of being admitted to neonatal intensive care.

Even after controlling for maternal age and other factors, every 10-year increase in the father's age increased the proportion of births that relied on assisted reproductive technology (ART). It was also associated with a higher likelihood of being the mother's first birth, and an increased risk of preterm birth and low birth weight compared to fathers aged 30 to 39.

Age-related conditions, such as erectile dysfunction and hypogonadism, impair paternal fecundity, while older age is associated with decreased semen volume, motility, and morphology.

Research has also linked older paternal age to declines in sperm quality, meaning the squiggly little gene packets that contribute half of a baby's DNA are more likely to be affected by DNA fragmentation, abnormal chromosome numbers, new mutations, and epigenetic alterations.

Overall, the accumulation of alterations in older men may increase the risk of conditions like autism, pediatric cancers, achondroplasia, and schizophrenia; decrease likelihood of ART success; and heighten risk of perinatal complications.

There were no significant differences found in infant sex ratio based on a father's age, except among fathers aged 70 years or older, who were more likely to have a female baby.

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/282181...

Poisonous books containing toxic dyes!

If you come across brightly colored, cloth-bound books from the Victorian era, you might want to handle them gently, or even steer clear altogether. Some of their attractive hues come from dyes that could pose a health risk to readers, collectors or librarians.

The latest research on these poisonous books used three techniques—including one that hasn't previously been applied to books—to assess dangerous dyes in a university collection and found some volumes may be unsafe to handle.

The researchers present their results at the fall meeting of the American Chemical Society.

These old books with toxic dyes may be in universities, public libraries and private collections. Users can be put at risk if pigments from the cloth covers rub onto their hands or become airborne and are inhaled.

Emerald-green pigment was used in Victorian-era wallpaper, garments and—as researchers found out—in cloth book covers. This discovery led to the launch of the Poison Book Project, a crowdsourced research effort that uses X-ray fluorescence (XRF), Raman spectroscopy and other techniques to reveal toxic pigments in books around the world.

Weinstein-Webb and the Lipscomb students he recruited launched their own investigation in 2022. For the Lipscomb book project, the team used three spectroscopic techniques:

XRF to qualitatively check whether arsenic or other heavy metals were present in any of the book covers.

Inductively coupled plasma optical emission spectroscopy (ICP-OES) to determine the concentration of those metals.

X-ray diffraction (XRD) to identify the pigment molecules that contain those metals.

Researchers used XRF data to show that lead and chromium were present in some of the Lipscomb books. To quantify the amounts, they snipped samples roughly the size of a small paperclip from the cloth covers and then dissolved them in nitric acid.

Their analysis by ICP-OES showed that lead and chromium were both present at high levels in some samples. Subsequent XRD testing indicated that in some instances these heavy metals were in the form of lead(II) chromate, one of the compounds that contributes to the chrome yellow pigment favoured by Vincent van Gogh in his sunflower paintings.

Source: Multimodal detection of toxic metals in Victorian era book cloths as part of the Beaman library collection, ACS Fall 2024.

Researchers develop an instant version of trendy, golden turmeric milk

"Golden" turmeric milk is the new trend in the USA. Though recently advertised as a caffeine-free, healthy coffee alternative, the drink is a fancified version of haldi doodh—a traditional Indian beverage often used as an at-home cold remedy.

Now, researchers have developed an efficient method to make a plant-based, instant version that maintains the beneficial properties of the ingredients while also extending its shelf life.

The researchers present their results at the fall meeting of the American Chemical Society.

They first added turmeric powder to an alkaline solution, where the high pH made the curcumin more soluble and easier to extract than in plain water. This deep red solution was then added to a sample of soy milk, turning it a dark yellow colour. They brought it down to a neutral pH around 7.

Just like low-pH acids, high-pH bases are not the most pleasant things to consume. The neutralized pseudo-golden milk could be enjoyed as-is, but to further preserve it, the team removed the water from the solution through freeze-drying, producing an instant golden milk powder.

Not only does the method extract curcumin from turmeric more efficiently than existing methods, but it also encapsulates the curcumin in oil droplets within the soy milk. This means that when consumed, our bodies recognize the curcumin as fat and digest it as such, theoretically making the curcumin more bioavailable, or likely to be absorbed and able to have an effect in the body.

Encapsulating the curcumin also protects it from air and water, preserving it and keeping it shelf-stable for longer.

Utilizing a green pH-driven approach for developing curcumin-infuse..., ACS Fall 2024.

New statistical mechanics formula suggests urban street networks and building density shape severity of floods

Cities around the globe are experiencing increased flooding due to the compounding effects of stronger storms in a warming climate and urban growth. New research  suggests that urban form, specifically the building density and street network of a neighborhood, is also affecting the intensity of flooding.

For a paper published recently in Nature Communications, researchers  turned to statistical mechanics to generate a new formula allowing urban planners to more easily assess flood risks presented by land development changes.

 Sarah K. Balaian et al, How urban form impacts flooding, Nature Communications (2024). DOI: 10.1038/s41467-024-50347-4 www.nature.com/articles/s41467-024-50347-4

Spider exploits firefly's flashing signals to lure more prey

Fireflies rely on flashing signals to communicate to other fireflies using light-emitting lanterns on their abdomens. In fireflies of the species Abscondita terminalis, males make multi-pulse flashes with two lanterns to attract females, while females make single-pulse flashes with their one lantern to attract males.

Now researchers reporting in the journal Current Biology on August 19 have evidence that an orb-weaving spider (Araneus ventricosus) manipulates the flashing signals of male fireflies ensnared in its web such that they mimic the typical flashes of a female firefly, thereby luring other males to serve as their next meal.

Araneus ventricosus practices deceptive interspecific communication by first ensnaring firefly males in its web and then predisposing the entrapped male fireflies to broadcast bioluminescent signals that deviate from female-attracting signals typically made by A. terminalis males and instead mimic the male-attracting signals typically made by females," the researchers wrote.

The outcome is that the entrapped male fireflies broadcast false signals that lure more male fireflies into the web.

The findings show that animals can use indirect yet dynamic signaling to target an exceptionally specific category of prey in nature.

Spiders manipulate and exploit bioluminescent signals of male fireflies, Current Biology (2024). DOI: 10.1016/j.cub.2024.07.011. www.cell.com/current-biology/f … 0960-9822(24)00914-X

Animals with higher body temperatures are more likely to evolve into herbivores, study finds

A new study has uncovered a surprising relationship between an animal's body temperature and its likelihood of evolving into an herbivore. The study, published in the journal Global Ecology and Biogeography, offers fresh insights into the evolution of plant-based diets across tetrapods, which include the land vertebrates—amphibians, birds, reptiles and mammals. The findings could reshape scientists' understanding of the evolution of animal diets.

The study, which analyzed data from 1,712 species, found a consistent pattern: Animals with higher body temperatures are more likely to evolve into herbivores. This relationship holds true across the major land vertebrate groups.

The relationship between body temperature and herbivory is linked to the unique digestive challenges posed by a plant-based diet.

Higher body temperatures may be necessary to support the gut bacteria that break down cellulose, the primary component of plant cell walls. The relationship between an animal's body temperature and its gut microbiome could be key to understanding why certain species are better equipped to adopt and maintain herbivorous diets.

The research team conducted extensive analyses, examining various other factors that might influence the evolution of diet, including body size and day or night activity patterns. Body temperature ultimately emerged as the most crucial factor in predicting the evolution of an herbivorous diet.

The researchers really didn't see any herbivores that don't have a high body temperature. Typically, the body temperature was more than 86 degrees Fahrenheit.

 Kristen E. Saban et al, Diet Evolution and Body Temperature in Tetrapods: Cool Old Carnivores and Hot Young Herbivores, Global Ecology and Biogeography (2024). DOI: 10.1111/geb.13900

Researchers discover new way to control the sense of touch

Researchers have found a new way to manage the receptors that control the sense of touch, which could lead to treating chronic pain more effectively.

Identifying a natural molecule that specifically reduces pain sensitivity offers hope for new therapeutic strategies in the management of pain.

A natural molecule called phosphatidic acid can reduce the activity of certain touch-sensing ion channels in the body, according to the study published in Nature Communications.

Researchers found that increasing the levels of phosphatidic acid in cells makes them less sensitive to touch. This finding was confirmed through experiments on sensory neurons and tests in mice, where the animals became more sensitive to touch when the formation of phosphatidic acid was inhibited.

This finding adds to a growing body of evidence suggesting that lipids are key regulators of somatosensation (the body's ability to perceive sensations such as touch, temperature and pain).

By targeting the natural pathways that regulate these channels, we can develop more targeted and effective pain treatments that could be especially useful for conditions involving inflammatory pain, where current pain relief options are often inadequate.

Matthew Gabrielle et al, Phosphatidic acid is an endogenous negative regulator of PIEZO2 channels and mechanical sensitivity, Nature Communications (2024). DOI: 10.1038/s41467-024-51181-4

Study finds constipation is a significant risk factor for major cardiac events

An international study led by Monash University researchers has found a surprising connection between constipation and an increased risk of major adverse cardiac events (MACE), including heart attacks, strokes and heart failure.

The study, led by Professor Francine Marques from the School of Biological Sciences and published in the American Journal of Physiology-Heart and Circulatory Physiology analyzed data from over 400,000 participants in the UK Biobank.

The study suggests that constipation, a common yet often overlooked health issue, may be a significant contributor to cardiovascular disease .

 Traditional cardiovascular risk factors such as high blood pressure, obesity and smoking have long been recognized as key drivers of heart disease.

However, these factors alone do not fully explain the occurrence of major cardiac events. This study explored the potential role of constipation as an additional risk factor, revealing concerning results.

The research team analyzed data from 408,354 individuals, identifying 23,814 cases of constipation.

The findings showed that individuals suffering from constipation were more than twice as likely to suffer from a major cardiac event as those without constipation.

Moreover, the study highlighted a particularly concerning link between constipation and hypertension.

Hypertensive individuals who also suffered from constipation were found to have a 34% increased risk of subsequent cardiac events compared to those with hypertension alone.

Part 1

In addition to these epidemiological findings, the study also explored the genetic links between constipation and cardiovascular disease.

Positive genetic correlations were identified between constipation and various forms of MACE, indicating that shared genetic factors may underlie both conditions. This discovery opens new avenues for research into the underlying mechanisms that connect gut health and heart health.

 Tenghao Zheng et al, Constipation is associated with an increased risk of major adverse cardiac events in a UK population, American Journal of Physiology-Heart and Circulatory Physiology (2024). DOI: 10.1152/ajpheart.00519.2024

Part 2 

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Why laws are written in an incomprehensible style

Legal documents are notoriously difficult to understand, even for lawyers. This raises the question: Why are these documents written in a style that makes them so impenetrable?

MIT cognitive scientists think they have uncovered the answer to that question. Just as "magic spells" use special rhymes and archaic terms to signal their power, the convoluted language of legalese acts to convey a sense of authority, they conclude.

In a study appearing in the Proceedings of the National Academy of Sciences, the researchers found that even non-lawyers use this type of language when asked to write laws.

People seem to understand that there's an implicit rule that this is how laws should sound, and they write them that way.

The analysis revealed that legal documents frequently have long definitions inserted in the middle of sentences—a feature known as "center-embedding." Linguists have previously found that this kind of structure can make text much more difficult to understand.

Legalese somehow has developed this tendency to put structures inside other structures, in a way which is not typical of human languages.

 Lawyers don't like it, laypeople don't like it, so the point of this current paper was to try and figure out why they write documents this way.

The researchers had a couple of hypotheses for why legalese is so prevalent. One was the "copy and edit hypothesis," which suggests that legal documents begin with a simple premise, and then additional information and definitions are inserted into already existing sentences, creating complex center-embedded clauses.

Researchers  thought it was plausible that what happens is you start with an initial draft that's simple, and then later you think of all these other conditions that you want to include. And the idea is that once you've started, it's much easier to center-embed that into the existing provision.

Martínez, Eric, Even laypeople use legalese, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2405564121. doi.org/10.1073/pnas.2405564121

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Blood platelet score detects previously unmeasured risk of heart attack and stroke

Platelets are circulating cell fragments known to clump up and form blood clots that stop bleeding in injured vessels. Researchers and cardiologists have long known that platelets can become "hyperreactive" to cause abnormal clotting that blocks arteries and contributes to heart attack, stroke, and poor blood flow (peripheral artery disease) in the legs.

Despite this major contribution to cardiovascular risk, routine measurement of whether each patient's platelets clump (aggregate) too much has been infeasible to date. This is because results delivered by the method typically used to determine platelet activity, called platelet aggregometry, vary too much from lab to lab.

To address this challenge, a new study  by researchers has precisely identified a group of patients with platelet hyperreactivity, and then surveyed them to reveal 451 genes, the activity of which differed significantly in those with hyperreactive platelets versus those without. Publishing in Nature Communications, the research team then used bioinformatics to assign a weight to each genetic difference and generate each patient's Platelet Reactivity ExpresSion Score (PRESS).

The researchers found that their new score can detect platelet hyperreactivity, both in patients at imminent risk of heart attack, and in healthy patients whose future risk may otherwise remain unknown.

Physicians currently prescribe aspirin, a medication that counters platelet activity, to patients based on available risk factors, including high cholesterol or high blood pressure, which are not directly related to platelet function.

PRESS promises to help physicians confine anti-platelet treatment to the people most likely to benefit: those with platelet hyperreactivity.

By acting on platelets, aspirin is known to protect against abnormal clotting, but in doing so, increases risk of bleeding, said the study authors. The field needs a reliable way to identify patients for whom protection against heart attack outweighs bleeding risk. This work helps with that.

A Platelet Reactivity ExpreSsion Score Predicts 1 Cardiovascular Risk, Nature Communications (2024). DOI: 10.1038/s41467-024-50994-7

When a foe turns a friend: Deadly sea snail toxin could be key to making better medicines

Scientists are finding clues on how to treat diabetes and hormone disorders in an unexpected place: a toxin from one of the most venomous animals on the planet.

A multinational research team led by University of Utah scientists has identified a component within the venom of a deadly marine cone snail, the geography cone, that mimics a human hormone called somatostatin, which regulates the levels of blood sugar and various hormones in the body. The hormone-like toxin's specific, long-lasting effects, which help the snail hunt its prey, could also help scientists design better drugs for people with diabetes or hormone disorders, conditions that can be serious and sometimes fatal.

The somatostatin-like toxin the researchers characterized could hold the key to improving medications for people with diabetes and hormone disorders. Somatostatin acts like a brake pedal for many processes in the human body, preventing the levels of blood sugar, various hormones, and many other important molecules from rising dangerously high.

The cone snail toxin, called consomatin, works similarly, the researchers found—but consomatin is more stable and specific than the human hormone, which makes it a promising blueprint for drug design.

By measuring how consomatin interacts with somatostatin's targets in human cells in a dish, the researchers found that consomatin interacts with one of the same proteins that somatostatin does. But while somatostatin directly interacts with several proteins, consomatin only interacts with one. This fine-tuned targeting means that the cone snail toxin affects hormone levels and blood sugar levels but not the levels of many other molecules.

In fact, the cone snail toxin is more precisely targeted than the most specific synthetic drugs designed to regulate hormone levels, such as drugs that regulate growth hormone. Such drugs are an important therapy for people whose bodies overproduce growth hormone. Consomatin's effects on blood sugar could make it dangerous to use as a therapeutic, but by studying its structure, researchers could start to design drugs for endocrine disorders that have fewer side effects.

Consomatin is more specific than top-of-the-line synthetic drugs—and it also lasts far longer in the body than the human hormone, thanks to the inclusion of an unusual amino acid that makes it difficult to break down. This is a useful feature for pharmaceutical researchers looking for ways to make drugs that will have long-lasting benefits.

 Disruption of Glucose Homeostasis in Prey: Combinatorial Use of Weaponized Mimetics of Somatostatin and Insulin by a Fish-Hunting Cone Snail, Nature Communications (2024). DOI: 10.1038/s41467-024-50470-2. www.nature.com/articles/s41467-024-50470-2

Extraterrestrial chemistry with earthbound possibilities

Who are we? Why are we here? We are stardust, the result of chemistry occurring throughout vast clouds of interstellar gas and dust. To better understand how that chemistry could create prebiotic molecules—the seeds of life on Earth and possibly elsewhere—researchers have investigated the role of low-energy electrons created as cosmic radiation traverses through ice particles. Their findings may also inform medical and environmental applications on our home planet.

The first detection of molecules in space was made by Wellesley College alum Annie Jump Cannon more than a hundred years ago. Since Cannon's discovery, scientists have been interested in finding out how extraterrestrial molecules form.

A new work's   goal is to explore the relative importance of low-energy electrons versus photons in instigating the chemical reactions responsible for the extraterrestrial synthesis of these prebiotic molecules. 

The few studies that previously probed this question suggested that both electrons and photons can catalyze the same reactions. Recent Studies , however, hint that the prebiotic molecule yield from low-energy electrons and photons could be significantly different in space.

Their calculations suggest that the number of cosmic-ray-induced electrons within cosmic ice could be much greater than the number of photons striking the ice. Therefore, electrons likely play a more significant role than photons in the extraterrestrial synthesis of prebiotic molecules

Part 1

Aside from cosmic ice, the present research into low-energy electrons and radiation chemistry also has potential applications on Earth. The researchers studied the radiolysis of water, finding evidence of electron-stimulated release of hydrogen peroxide and hydroperoxyl radicals, which destroy stratospheric ozone and act as damaging reactive oxygen species in cells.

A lot of their water radiolysis research findings could be used in medical applications and medical simulations.
Humans are basically bags of water. So scientists are investigating how low-energy electrons produced in water affect our DNA molecules.
In attempting to better understand prebiotic molecule synthesis, the researchers didn't limit their efforts to mathematical modeling; they also tested their hypothesis by mimicking the conditions of space in the lab. They use an ultrahigh-vacuum chamber containing an ultrapure copper substrate that they can cool to ultralow temperatures, along with an electron gun that produces low-energy electrons and a laser-driven plasma lamp that produces low-energy photons. The scientists then bombard nanoscale ice films with electrons or photons to see what molecules are produced.
Although researchers have previously focused on how this research is applicable to interstellar submicron ice particles, it is also relevant to cosmic ice on a much larger scale, like that of Jupiter's moon Europa, which has a 20-mile-thick ice shell.
The research team's results will be presented at the fall meeting of the American Chemical Society (ACS). ACS Fall 2024
Source: American Chemical Society
https://www.acs.org/meetings/acs-meetings/fall.html
Part 2
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How air pollution increases thunderstorm danger

Air pollution is increasing the severity of summertime thunderstorms, according to a recent study conducted by researchers at James Madison University and published in the journal Atmospheric Research.

Pollution acts as cloud nuclei. It gets brought into the cloud through the updraft; the updraft and downdraft then separate the pollution particles, which divides the electrical charges in the cloud and leads to more lightning production.

The three-year study examined nearly 200,000 thunderstorms.

Using 12 years of lightning data from the National Lightning Detection Network, US, and data from hundreds of air pollution stations, the researchers were able to determine that in environments with high instability, adding more pollution increases cloud-to-ground lightning strikes.

Similar research on Bangkok, a megacity with more pollution than most US cities and located in a hot, tropical climate, show similar results, albeit with lightning rates even higher in those storms.

It looks like no matter where you go in the world, urban pollution is capable of enhancing thunderstorms and lightening, the researchers conclude.

Mace Bentley et al, Toward untangling thunderstorm-aerosol relationships: An observational study of regions centered on Washington, DC and Kansas City, MO, Atmospheric Research (2024). DOI: 10.1016/j.atmosres.2024.107402

Genomic surveillance method tracks multiple superbugs in hospitals

Researchers have developed a new genomic technique that can track the spread of multiple superbugs in a hospital simultaneously, which could help prevent and manage common hospital infections quicker and more effectively than ever before.

The proof-of-concept study details a new deep sequencing approach that captures all the common infectious bacteria in a hospital at once. Current methods culture and sequence all pathogens separately, which takes longer and requires more work.

Published 20 August in the Lancet Microbe, the study captured the whole population of pathogenic bacteria found in multiple hospital intensive care units (ICUs) and ordinary wards during the first wave of the 2020 COVID-19 pandemic. Researchers could see the type of bacteria patients had, including any well-known antibiotic-resistant pathogens found in hospitals.

They discovered that each ICU patient tested in the study was colonized by at least one such treatment-resistant bacteria, while the majority were colonized by several of them simultaneously.

Researchers think their approach could be integrated with existing hospital clinical surveillance systems. As drug resistance is a widespread issue in hospitals and other clinical settings, this system could identify, track and limit the spread of common multiple treatment-resistant bacteria at the same time.

Bacteria are commonly found in or on the body without causing harm, known as colonization. However, if certain strains get into the bloodstream due to a weakened immune system, they can cause severe and life-threatening infections, unless they can be effectively treated with antibiotics.

As an added challenge for health care providers, some of these bacteria are antibiotic-resistant (AMR). Infections caused by AMR bacteria are a major issue in hospitals, with these treatment-resistant bacteria predicted to cause more deaths than cancer by 2050. While some hospitals test for AMR bacteria on arrival, no system effectively tracks all multi-drug resistant bacteria throughout a hospital.

Part 1

Over the last 15 years, genomic surveillance has become a powerful tool for tracking pathogen evolution and transmission, giving critical insights to help manage the spread of disease.

However, current methods involve culturing a single strain of bacteria in a sample at a time and then conducting whole genome sequencing for all of them separately. This is a labor-intensive process, which can easily take several days and only provides a partial snapshot of all the clinically relevant bacteria found in a sample.

In this new study the research team developed a new approach that captured whole genome sequencing data across multiple pathogens at once. This is known as a 'pan-pathogen' deep sequencing approach and can provide genomic data as rapidly as hospitals can process the samples.

Pan-pathogen deep sequencing of nosocomial bacterial pathogens during the early COVID-19 pandemic, spring 2020: A prospective cohort study, The Lancet Microbe (2024). DOI: 10.1016/S2666-5247(24)00113-7

Part 2

A galactic theory disproven: Dark matter and stars not interacting as previously thought

A longstanding theory in astronomy—that stars and dark matter are interacting in inexplicable ways—has been overturned by an international team of astronomers, in a paper in Monthly Notices of the Royal Astronomical Society.

The  theory emerged to explain a phenomenon that had puzzled astronomers for a quarter of a century. The density of matter in different galaxies appeared to be decreasing at the same rate from their center to outer edges. This was perplexing because galaxies are diverse, with many different ages, shapes, sizes, and numbers of stars. So why would they have the same density structure?

This homogeneity suggested that dark matter and stars must somehow compensate for each other in order to produce such regular mass structures.

Part 1

Like many conspiracies, no researcher could come up with a mechanism. If dark matter and stars could interact in this way, then we would need to change our understanding of how galaxies form and evolve. But they also couldn't find an alternate reason to explain what they were seeing, until now.

Present research work found that the similarity in density might not be due to the galaxies themselves but in how astronomers were measuring and modeling them.

The team which made this observation observed 22 middle-aged galaxies (looking back some four billion years in the past due to their great distance) in extraordinary detail, using the European Southern Observatory's Very Large Telescope in Chile. It enabled them to create more complex models that better captured the diversity of galaxies in the universe.
In the past, people built simple models that had too many simplifications and assumptions. Galaxies are complicated, and researchers have to model them with freedom or they're going to measure the wrong things. The new models ran on the OzStar supercomputer at Swinburne University, using the equivalent of about 8,000 hours of desktop computing time.

C Derkenne et al, The MAGPI Survey: Evidence against the bulge-halo conspiracy, Monthly Notices of the Royal Astronomical Society (2024). DOI: 10.1093/mnras/stae1836

Part 2

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Gut microbial pathway identified as target for improved heart disease treatment

 Researchers have made a significant discovery about how the gut microbiome interacts with cells to cause cardiovascular disease. The study published in Nature Communications found that phenylacetylglutamine (PAG), produced by gut bacteria as a waste product, then absorbed and formed in the liver, interacts with previously undiscovered locations on beta-2 adrenergic receptors on heart cells once it enters the circulation.

PAG was shown to interact with beta-2 adrenergic receptors to influence how forcefully the heart muscle cells contract—a process that investigators think contributes to heart failure. Researchers showed mutating parts of the beta-2 adrenergic receptor that were previously thought to be unrelated to signaling activity in preclinical models prevented PAG from depressing the function of the receptor.

The same researchers earlier demonstrated that elevated circulating levels of PAG in subjects are associated with heightened risk for developing heart failure, and lead to worse outcomes for patients with heart failure.

They also showed that the gut microbial PAG signaling pathway was mechanistically linked to numerous heart failure-related features and cardiovascular disease risks. The new findings bring us one step closer to therapeutically targeting this pathway to develop an improved treatment for the prevention of heart failure.

 Prasenjit Prasad Saha et al, Gut microbe-generated phenylacetylglutamine is an endogenous allosteric modulator of β2-adrenergic receptors, Nature Communications (2024). DOI: 10.1038/s41467-024-50855-3

Research pinpoints how early-life antibiotics turn immunity into allergy

Researchers  have shown for the first time how and why the depletion of microbes in a newborn's gut by antibiotics can lead to lifelong respiratory allergies.

In a study published recently in the Journal of Allergy and Clinical Immunology, a research team from the school of biomedical engineering (SBME) has identified a specific cascade of events that lead to allergies and asthma. In doing so, they have opened many new avenues for exploring potential preventions and treatments.

This new research  finally shows how the gut bacteria and antibiotics shape a newborn's immune system to make them more prone to allergies.

Allergies are a result of the immune system reacting too strongly to harmless substances like pollen or pet dander, and a leading cause for emergency room visits in kids. Normally, the immune system protects us from harmful invaders like bacteria, viruses and parasites. In the case of allergies, it mistakes something harmless for a threat—in this case, parasites—and triggers a response that causes symptoms like sneezing, itching or swelling.

The stage for our immune system's development is set very early in life. Research over the past two decades has pointed toward microbes in the infant gut playing a key role. Babies often receive antibiotics shortly after birth to combat infections, and these can reduce certain bacteria. Some of those bacteria produce a compound called butyrate, which is key to halting the processes uncovered in this research.

The same researchers had previously shown that infants with fewer butyrate-producing bacteria become particularly susceptible to allergies. They had also shown that this could be mitigated or even reversed by providing butyrate as a supplement in early life.

Now, by studying the process in mice, they have discovered how this works.
Mice with depleted gut bacteria who received no butyrate supplement developed twice as many of a certain type of immune cell called ILC2s. These cells, discovered less than 15 years ago, have quickly become prime suspects in allergy development.

The researchers showed that ILC2s produce molecules that 'flip a switch' on white blood cells to make them produce an abundance of certain kinds of antibodies. These antibodies then coat cells as a defense against foreign invaders, giving the allergic person an immune system that is ready to attack at the slightest provocation.

Ahmed Kabil et al, Microbial intestinal dysbiosis drives long-term allergic susceptibility by sculpting an ILC2-B1 cell–innate IgE axis., Journal of Allergy and Clinical Immunology (2024). DOI: 10.1016/j.jaci.2024.07.023

A legend in one's own mind: The link between ambition and leadership evaluations

Ambitious people aren't born leaders, research suggests

Do ambitious people make good leaders? Ambition can lead people to strive for leadership roles. But could there be a mismatch between qualities that motivate people to strive for leadership and qualities that make people good leaders?

asked 472 executives enrolled in a leadership development program offered by a West Coast business school in the United States to rate their ambition. The authors then compared these ambition scores with 360-degree leadership assessments obtained from the executives themselves, as well as their current managers, peers, and subordinates.

Thepaper is published in the journal PNAS Nexus.

The authors found, as expected, that leadership ambition increases self-ratings of effectiveness in a leadership role. That is, leaders with high self-reported ambition also rated themselves as highly-effective leaders. However, the authors found no relationship between leadership ambition and third-party ratings of leadership effectiveness; highly ambitious executives, compared to less ambitious executives, were rated as no more effective in their leadership roles by their managers, peers, or direct reports.

These results suggest that the pool of people striving for leadership roles may be filled with ambitious people who seek extrinsic rewards, such as high salaries and social status, and regard themselves more positively than others do. According to the authors, society may want to develop alternative approaches to choosing and training leaders.

Researchers develop world's fastest microscope that can see electrons in motion

Imagine owning a camera so powerful it can take freeze-frame photographs of a moving electron—an object traveling so fast it could circle the Earth many times in a matter of a second. Researchers have developed the world's fastest electron microscope that can do just that.

And they think their work will lead to groundbreaking advancements in physics, chemistry, bioengineering, materials sciences and more.

This transmission electron microscope is like a very powerful camera in the latest version of smart phones; it allows us to take pictures of things we were not able to see before—like electrons. With this microscope, the researchers hope the scientific community can understand the quantum physics behind how an electron behaves and how an electron moves.

A transmission electron microscope is a tool used by scientists and researchers to magnify objects up to millions of times their actual size in order to see details too small for a traditional light microscope to detect.

Instead of using visible light, a transmission electron microscope directs beams of electrons through whatever sample is being studied. The interaction between the electrons and the sample is captured by lenses and detected by a camera sensor in order to generate detailed images of the sample.

Ultrafast electron microscopes using these principles were first developed in the 2000's and use a laser to generate pulsed beams of electrons. This technique greatly increases a microscope's temporal resolution—its ability to measure and observe changes in a sample over time.

In these ultrafast microscopes, instead of relying on the speed of a camera's shutter to dictate image quality, the resolution of a transmission electron microscope is determined by the duration of electron pulses.

The faster the pulse, the better the image.

Ultrafast electron microscopes previously operated by emitting a train of electron pulses at speeds of a few attoseconds. An attosecond is one quintillionth of a second. Pulses at these speeds create a series of images, like frames in a movie—but scientists were still missing the reactions and changes in an electron that takes place in between those frames as it evolves in real time.

In order to see an electron frozen in place,  researchers, for the first time, generated a single attosecond electron pulse, which is as fast as electrons move, thereby enhancing the microscope's temporal resolution, like a high-speed camera capturing movements that would otherwise be invisible.

Part 1

The researchers who developed this microscope based their work on the Nobel Prize-winning accomplishments of Pierre Agostini, Ferenc Krausz and Anne L'Huilliere, who won the Novel Prize in Physics in 2023 after generating the first extreme ultraviolet radiation pulse so short it could be measured in attoseconds.

Using that work as a steppingstone, the researchers developed a microscope in which a powerful laser is split and converted into two parts—a very fast electron pulse and two ultra-short light pulses. The first light pulse, known as the pump pulse, feeds energy into a sample and causes electrons to move or undergo other rapid changes.

The second light pulse, also called the "optical gating pulse" acts like a gate by creating a brief window of time in which the gated, single attosecond electron pulse is generated. The speed of the gating pulse therefore dictates the resolution of the image. By carefully synchronizing the two pulses, researchers control when the electron pulses probe the sample to observe ultrafast processes at the atomic level.
The electron movements happen in attoseconds. But now, for the first time, researchers are able to attain attosecond temporal resolution with their electron transmission microscope—and they coined it 'attomicroscopy.' For the first time, they could see pieces of the electron in motion.

Dandan Hui et al, Attosecond electron microscopy and diffraction, Science Advances (2024). DOI: 10.1126/sciadv.adp5805. www.science.org/doi/10.1126/sciadv.adp5805

Part 2

New research suggests rainwater helped form the first protocell walls

In the paper, published in Science Advances researchers show how rainwater could have helped create a meshy wall around protocells 3.8 billion years ago, a critical step in the transition from tiny beads of RNA to every bacterium, plant, animal, and human that ever lived.

The research looks at "coacervate droplets"—naturally occurring compartments of complex molecules like proteins, lipids, and RNA. The droplets, which behave like drops of cooking oil in water, have long been eyed as a candidate for the first protocells. But there was a problem. It wasn't that these droplets couldn't exchange molecules between each other, a key step in evolution, the problem was that they did it too well, and too fast.

Any droplet containing a new, potentially useful pre-life mutation of RNA would exchange this RNA with the other RNA droplets within minutes, meaning they would quickly all be the same. There would be no differentiation and no competition—meaning no evolution.

And that means no life. If molecules continually exchange between droplets or between cells, then all the cells after a short while will look alike, and there will be no evolution because you are ending up with identical clones.

DNA is the molecule which encodes information, but it cannot do any function. Proteins are the molecules which perform functions, but they don't encode any heritable information.

RNA is a molecule which, like DNA, can encode information, but it also folds like proteins so that it can perform functions such as catalysis as well.

RNA was a likely candidate for the first biological material. Coacervate droplets were likely candidates for the first protocells. Coacervate droplets containing early forms of RNA seemed a natural next step.

What the researchers now showed in this new paper is that you can overcome at least part of that problem by transferring these coacervate droplets into distilled water—for example, rainwater or freshwater of any type—and they get a sort of tough skin around the droplets that restricts them from exchanging RNA content.

Where do you think distilled water could come from in a prebiotic world? Rain!

Working with RNA samples the researchers found that transferring coacervate droplets into distilled water increased the time scale of RNA exchange—from mere minutes to several days. This was long enough for mutation, competition, and evolution.

Part 1

If you have protocell populations that are unstable, they will exchange their genetic material with each other and become clones. There is no possibility of Darwinian evolution. But if they stabilize against exchange so that they store their genetic information well enough, at least for several days, so that the mutations can happen in their genetic sequences, then a population can evolve.
In their experiments with the actual rainwater and with lab water modified to mimic the acidity of rainwater, the researchers found the same results. The meshy walls formed, creating the conditions that could have led to life.
The new paper proves that this approach of building a meshy wall around protocells is possible and can work together to compartmentalize the molecules of life, putting researchers closer than ever to finding the right set of chemical and environmental conditions that allow protocells to evolve.

Aman Agrawal et al, Did the exposure of coacervate droplets to rain make them the first stable protocells?, Science Advances (2024). DOI: 10.1126/sciadv.adn9657. www.science.org/doi/10.1126/sciadv.adn9657

Part 2

A free-living eukaryote is the first known to have lost its mitochondria

An international team of geneticists and molecular biologists has discovered the first-known, free-living eukaryote to have lost its mitochondria. In their study, published in Nature Communications, the group found the eukaryote while investigating the patterns and processes of genome and mitochondrion-related organelles' evolution in metamonads in water samples collected from saltwater lakes and shallow marine environments.

Mitochondria are organelles in almost every living eukaryotic cell on Earth. They are responsible for generating the energy that allows creatures to grow and to move around. Mitochondria have a double membrane and use aerobic respiration to generate adenosine triphosphate (ATP)—the fuel that provides the energy for the cell. Eukaryotes belong to one of four types: plants, animals, fungi and protists.

Prior research has shown that there are eukaryotes that have devolved mitochondria to the point that they have none—generally because they get their energy elsewhere. Such creatures are able to gather energy by absorbing nutrients directly from another creature that does have functioning mitochondria—several have been found in the human gut, for example.

For this new research, the team studied eukaryote evolution in metamonads, a type of microscopic eukaryote. They collected specimens from various locations and studied them in their lab. They found five that caught their eye: three found in salty soda lake sediment beds and two in shallow ocean sediments.

One stood out clearly from the other four due to its complete lack of mitochondria. They named it Skoliomonas litria and noted that it was the first-ever finding of a free-living eukaryote to have lost its mitochondria. They also note that more work is required to determine how the creature makes its ATP without using oxygen.

Shelby K. Williams et al, Extreme mitochondrial reduction in a novel group of free-living metamonads, Nature Communications (2024). DOI: 10.1038/s41467-024-50991-w