Bright Light at Night May Raise Type 2 Diabetes Risk, Study Suggests

The glow of a lightbulb or smartphone at night can mess with the body's circadian rhythm. Now, a new study suggests that exposure to artificial light after midnight may raise the risk of developing type 2 diabetes. The research was conducted among nearly 85,000 people, between the ages of 40 and 69, who wore devices on their wrists, day and night for one week, to track their exposure to different levels of light.

As part of the UK Biobank experiment, the health of the cohort was tracked for as long as nine years. Those volunteers who later went on to develop type 2 diabetes were more likely to have been exposed to light between 12:30 am and 6:00 am, during the week-long study period.

The results do not prove cause and effect, but they do reveal a dose-dependent relationship between brighter light in the middle of the night and the risk of a metabolic disorder, which bolsters the association.

Those participants in the top 10 percent for light exposure at night had as much as a 67 percent higher risk of developing type 2 diabetes than those in the bottom 50th percentile.

Research suggests that exposure to artificial light at night, whether it be yellow light from your reading lamp or blue light from your smartphone or TV, can make it harder to fall asleep. But even when researchers accounted for sleep patterns and duration in the current study, the results held, which suggests another mechanism is at play.
Other possible contributing factors, like a person's sex, their genetic risk for diabetes, their diet, physical activity, daylight exposure, smoking, or alcohol use, also had no impact on the results.

Advising people to avoid night light is a simple and cost-effective recommendation that may ease the global health burden of type 2 diabetes," conclude the authors of the study.
Part 1

In the past, some other observational studies have also linked artificial light at night to insulin resistance, but these experiments did not measure indoor, artificial light sources nearly as closely or for as long.

Emerging evidence in animals and humans suggests exposure to artificial light can disrupt circadian rhythms, leading to reduced glucose tolerance, altered insulin secretion, and weight gain – all of which are tied to an increased risk of metabolic disorders like type 2 diabetes.

One major limitation of the study is that researchers were not able to take into account meal times, which can have an impact on both circadian rhythms and glucose tolerance. Furthermore, some socioeconomic factors, like a person's housing situation, were accounted for at a regional, not an individual level, and only older adults were considered.

There's also the fact that individual bodies respond very differently to light, with some studies suggesting the intensity of light needed to suppress the production of melatonin, which helps regulate our circadian rhythm, can range from 6 to 350 lux.
Nevertheless, previous experiments suggest that when melatonin is disrupted and the circadian rhythm is thrown out of whack, it can lead to the pancreas secreting less insulin. This could be a contributing factor to the development of diabetes.

Far more rigorous studies are needed before scientists can truly understand how light at night impacts the circadian rhythm and what that may do, in turn, to the health of the body's metabolism.

Some studies suggest that even a weekend of camping without artificial light can help reset a person's circadian rhythm. Perhaps that's just what the doctor should order.

https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(24)00110-8/fulltext

Part 2

**

Strategies that could stop cats from scratching your furniture, according to science

Many cat owners are familiar with torn cushions, carpets, and couches. The feline instinct to scratch is innate, but is often perceived as a behavioral problem by cat owners, and sometimes leads to interventions that are not cat-friendly.

Now, an international team of researchers has investigated which factors influence undesired scratching behavior in domestic cats. The team has published its findings in Frontiers in Veterinary Science.

Scientists found that  certain factors—such as the presence of children at home, personality traits of cats, and their activity levels—significantly impact the extent of scratching behaviour.

The researchers' results showed that there are several factors that influence cats' scratching behaviour. They saw a clear link between certain environmental and behavioural factors and increased scratching behaviour in cats.

Specifically, the presence of children in the home as well as high levels of play and nocturnal activity significantly contribute to increased scratching. Cats described as aggressive or disruptive also exhibited higher levels of scratching.

Stress, the researchers said, was found to be a leading reason for unwanted scratching. For example, the presence of children, particularly while they are small, might amplify stress and be one of several causes that can make felines stress-scratch. The link between increased scratching and children in the home, however, is not fully understood and further study is needed. Another factor that could also be connected to stress is playfulness. When cats play for a long time, their stress levels can rise because of the uninterrupted stimulation.

Part 1

While some factors that favor scratching—such as the cat's personality or the presence of children—cannot be changed, others can, the researchers said. Placing scratch posts in areas the cat frequently passes or near to their preferred resting spot, or the use of pheromones, for example, can lessen cats' scratching on furniture.

Providing safe hiding places, elevated observation spots, and ample play opportunities can also help alleviate stress and engage the cat in more constructive activities.

The key is to establish multiple short play sessions that mimic successful hunting scenarios. These play sessions are more likely to sustain cats' interest and reduce stress, which ultimately can reduce excessive scratching on furniture. They can also foster the bond between cats and their caretakers, the researchers say.

Understanding the underlying emotional motivations of scratching behavior, such as frustration, which seem to be linked to personality traits and environmental factors, allows caregivers to address these issues directly.

Evaluating Undesired Scratching in Domestic Cats: A Multifactorial Approach to Understand Risk Factors, Frontiers in Veterinary Science (2024). DOI: 10.3389/fvets.2024.1403068

Part 2

Scientists discover PVP-037, a potent vaccine adjuvant

Many vaccines are only partially effective, have waning efficacy, or do not work well in the very young or the very old. For several years researchers have tried improving vaccines by adding compounds known as adjuvants to boost vaccine recipients' immune responses.

Now they've identified a new and promising adjuvant of their own, dubbed PVP-037. The finding is published in Science Advances.

In principle, this compound can be added to any vaccine to enhance its action.

 Adjuvants are like rocket fuel for the immune system. PVP-037 is one of the most active adjuvants scientists 've discovered, and they think it induces a greater, more durable, and broader immune response to vaccines.

The researchers began by screening more than 200,000 small molecules from a Harvard Medical School library in human immune cells—specifically, in primary peripheral blood mononuclear cells, obtained from donors and cultured in their own plasma using a method developed within the Precision Vaccines Program. This yielded about 25 confirmed hits, with PVP-037 being the most active.

PVP-037 belongs to a family of molecules called imidazopyrimidines, which the study found to be active immunomodulators. PVP-037 and its analogs target the innate immune system, stimulating the pattern-recognition receptors TLR7 and TLR8 on antigen-presenting cells such as monocytes and dendritic cells.

An optimized version of PVP-037 demonstrated broad innate immune activation in the donor immune cells, inducing NF-κB and production of TNF and other cytokines, signaling molecules that rally a wider immune response. Notably, PVP-037 did not provoke such a response in cultured cell lines. In live mice, it enhanced antibody responses against influenza and SARS-CoV-2 vaccine proteins.

In addition to inducing robust immune activity, the compound is stable, easy to work with, and lends itself to chemical optimization for medical use. It can be formulated in most standardly-used drug delivery systems, such as oil-in-water emulsions.

 Dheeraj Soni et al, From Hit to Vial: Precision discovery and development of an imidazopyrimidine TLR7/8 agonist adjuvant formulation, Science Advances (2024). DOI: 10.1126/sciadv.adg3747. www.science.org/doi/10.1126/sciadv.adg3747

Fighting COVID-19 with a cancer drug: A new approach to preventing irreversible organ damage in infectious diseases

Twelve years ago, cancer researchers identified a molecule that helps cancer cells survive by shuttling damaging inflammatory cells into tumor tissue. In new research, they show that the same molecule does the same thing in lung tissue infected with COVID-19—and that the molecule can be suppressed with a repurposed cancer drug.

The work, published in Science Translational Medicine, represents a new approach to preventing irreversible organ damage in infectious diseases like COVID-19 and methicillin-resistant Staphylococcus aureus (MRSA).

The two key players in this scenario are inflammatory cells called myeloid cells, and an enzyme called PI3K gamma (phosphatidylinositol 3,4,5-kinase gamma). Myeloid cells belong to our innate immune system—the immunity we're born with before we're exposed to pathogens in the environment—and work very quickly to kill deadly agents like SARS-CoV-2, the virus that causes COVID-19.

This work shows that drugs that can prevent the recruitment of damaging myeloid cells into tissues that are infected with severe agents like COVID-19 or MRSA have a significant benefit in preserving tissue function if given early enough in an infection.

Most other COVID-19 drugs target the virus, either preventing infection in the first place or preventing the virus from making more of itself after infection. The current approach targets the host, keeping the immune system from overreacting or fibers building up in the lungs.

Myeloid cells protect us, but they can also do a lot of damage. 

If you have a little infection, myeloid cells come in, kill bacteria, release alerts that recruit even more potent killer immune cells, and produce substances that can heal the damage. But if you get an infection that's too strong, you get overproduction of these alert signals, and the substances they release to kill these infective agents can also kill yourself. That's what happens in COVID-19.

Part 1

PI3K gamma promotes the movement of myeloid cells into cancerous tissues, as found in the team's work with cancer twelve years ago. In the current work, they show that PI3K gamma also helps move myeloid cells into tissues infected with SARS-CoV-2.

That led them to reason that a cancer drug that inhibits PI3K gamma, called eganelisib, might be effective in suppressing inflammation in COVID-19 by suppressing PI3K gamma's ability to move myeloid cells into infected tissue.

Using a combination of bulk RNA sequencing and bioinformatics, the scientists analyzed tissues from humans and mice to see how SARS-CoV-2 changed the cellular and molecular makeup of infected tissues. They then treated the tissue with eganelisib to see if suppressing PI3K gamma made a difference.
The researchers sequenced COVID-19 patient lung tissue and showed that when patients have COVID-19, a lot of their lung cells are killed and there's a huge increase in myeloid cells. They also found the same thing in infected mice.

When they treated with the drug, they showed that eganelisib prevents entry of myeloid cells into tissue so they can't do all that damage. Further studies will determine if it can actually reverse damage. The team also had the same results in mice infected with MRSA.

Ryan Shepard et al, PI3Kγ inhibition circumvents inflammation and vascular leak in SARS-CoV-2 and other infections, Science Translational Medicine (2024). DOI: 10.1126/scitranslmed.adi6887. www.science.org/doi/10.1126/scitranslmed.adi6887

Part 2

Human crying stresses out dogs more than pigs

Some animals can have babies without a sexual partner

Science explains how

A boa constrictor in the U.K. gave birth to 14 babies—without a mate.

 The result of a secret rendezvous? Probably not. Females of species have the ability to reproduce asexually, without sperm from a male. The process is called parthenogenesis, from the Greek words for "virgin" and "birth."

Some plants and insects can do it, as well as some amphibians, reptiles, birds and fish. A stingray named Charlotte that was thought to have become pregnant by this method died this week at an aquarium in North Carolina, though she never delivered and it is unclear if she was ever pregnant.

Some wasps, crustaceans and lizards reproduce only through parthenogenesis. But in other species it's rare and usually only observed in captivity. Scientists have a good idea how it happens, though they aren't clear why it happens.

A female's egg fuses with another cell, often a cell leftover from a process that allows the female to create the egg. That cell, known as a polar body, gives the egg the genetic information it would normally get from sperm. The cell starts dividing and that leads to the creation of an embryo.

The snake, a 6-foot, 13-year-old Brazilian Rainbow Boa named Ronaldo, gave birth last week after having no contact with any other snakes for at least nine years, according to the City of Portsmouth College, which kept the snake.

AP

Re-engineering cancerous tumors to self-destruct and kill drug-resistant cells

Treating cancer can sometimes feel like a game of Whac-A-Mole. The disease can become resistant to treatment, and clinicians never know when, where and what resistance might emerge, leaving them one step behind. But a team of researchers has found a way to reprogram disease evolution and design tumors that are easier to treat.

They created a modular genetic circuit that turns cancer cells into a "Trojan horse," causing them to self-destruct and kill nearby drug-resistant cancer cells. Tested in human cell lines and in mice as proof of concept, the circuit outsmarted a wide range of resistance.

The findings were published today, July 4, in the journal Nature Biotechnology. The researchers also filed a provisional application to patent the technology described in the paper.

Selection gene drives are a powerful new paradigm for evolution-guided anticancer therapy.The idea that we can use a tumor's inevitability of evolution against it is an excellent strategy.

Newer personalized cancer medicines often fail, not because the therapeutics aren't good, but because of cancer's inherent diversity and heterogeneity. Even if a frontline therapy is effective, resistance eventually develops and the medication stops working, allowing the cancer to return.

Clinicians then find themselves back at square one, repeating the process with a new drug until resistance emerges again. The cycle escalates with each new treatment until no further options are available.

You are dealing with an unpredictable opponent. You don't know what is going to be the best drug to treat the tumor. You're always on your back foot, unprepared.

The researchers wondered if, instead, they could get one step ahead. Could they potentially eliminate resistance mechanisms before the cancer cells have a chance to evolve and pop up unexpectedly? Could they force a specific "mole" to pop out on the board, one that they prefer and are prepared to fight?
What started as a thought experiment is proving to work. The team created a modular circuit, or dual-switch selection gene drive, to introduce into non-small lung cancer cells with an EGFR gene mutation. This mutation is a biomarker that existing drugs on the market can target.
Part1

The circuit has two genes, or switches. Switch one acts like a selection gene, allowing the researchers to turn drug resistance on and off, like a light switch. With switch one turned on, the genetically modified cells become temporarily resistant to a specific drug, in this case, to a non-small lung cancer drug.

When the tumor is treated with the drug, the native drug-sensitive cancer cells are killed off, leaving behind the cells modified to resist and a small population of native cancer cells that are drug-resistant. The modified cells eventually grow and crowd out the native resistant cells, preventing them from amplifying and evolving new resistance.
The resulting tumor predominantly contains genetically modified cells. When switch one is turned off, the cells become drug-sensitive again. Switch two is the therapeutic payload. It contains a suicide gene that enables the modified cells to manufacture a diffusible toxin that's capable of killing both modified and neighboring unmodified cells.

It not only kills the engineered cells, but it also kills the surrounding cells, namely the native resistant population.
That's critical. That's the population you want to get rid of so that the tumor doesn't grow back.
The team first simulated the tumor cell populations and used mathematical models to test the concept. Next, they cloned each switch, packaging them separately into viral vectors and testing their functionality individually in human cancer cell lines. They then coupled the two switches together into a single circuit and tested it again. When the circuit proved to work in vitro, the team repeated the experiments in mice.

However, the team didn't just want to know that the circuit worked; they wanted to know it could work in every way. They stress tested the system using complex genetic libraries of resistance variants to see if the gene drive could function robustly enough to counter all the genetic ways that resistance could occur in the cancer cell populations.
And it worked: Just a handful of engineered cells can take over the cancer cell population and eradicate high levels of genetic heterogeneity. It's one of the biggest strengths of the paper, conceptually and experimentally.
The beauty is that they're able to target the cancer cells without knowing what they are, without waiting for them to grow out or resistance to develop because at that point it's too late.
The researchers are currently working on how to translate this genetic circuit so that it can be delivered safely and selectively into growing tumors and eventually metastatic disease.

 Programming tumor evolution with selection gene drives to proactively combat drug resistance, Nature Biotechnology (2024). DOI: 10.1038/s41587-024-02271-7. www.nature.com/articles/s41587-024-02271-7

Part 2

Reversing chemotherapy resistance in pancreatic cancer

Pancreatic cancer is a particularly aggressive and difficult-to-treat cancer, in part because it is often resistant to chemotherapy. Now, researchers  have revealed that this resistance is related to both the physical stiffness of the tissue around the cancerous cells and the chemical makeup of that tissue. Their work, published on July 4 in Nature Materials, shows that this resistance can be reversed and reveals potential targets for new pancreatic cancer treatments.

They found that stiffer tissue can cause pancreatic cancer cells to become resistant to chemotherapy, while softer tissue made the cancer cells more responsive to chemotherapy.

The researchers focused their efforts on pancreatic ductal adenocarcinoma, a cancer that starts in the cells lining the ducts of the pancreas and accounts for 90% of pancreatic cancer cases. In these cancers, the network of materials between the cells, known as the extracellular matrix, becomes notably stiffer. Scientists have theorized that this stiff material acts as a physical block, stopping chemotherapy drugs from reaching cancerous cells, but treatments based on this idea have not been effective in humans.

The researchers worked to develop a new system to study these changes to the extracellular matrix and better understand their impact on pancreatic cancer cells. They designed three-dimensional materials that mimicked the biochemical and mechanical properties of both pancreatic tumors and healthy pancreas tissues, and used them to culture cells from pancreatic cancer patients.

They  created a designer matrix that would allow us to test the idea that these cancerous cells might be responding to the chemical signals and mechanical properties in the matrix around them.

Part 1

Using their new system, the researchers selectively activated certain types of receptors in the cancerous cells and adjusted the chemical and physical properties of their designer matrix. They found that pancreatic cancer needed two things to become resistant to chemotherapy: a physically stiff extracellular matrix and high amounts of hyaluronic acid—a polymer that helps stiffen the extracellular matrix and interacts with cells through a receptor called CD44.
Initially, the pancreatic cancer cells in a stiff matrix full of hyaluronic acid responded to chemotherapy. But after some time in these conditions, the cancerous cells became resistant to chemotherapy—they made proteins in the cell membrane that could quickly pump out chemotherapy drugs before they could take effect. The researchers found that they could reverse this development by moving the cells to a softer matrix (even if it was still high in hyaluronic acid) or blocking the CD44 receptor (even if the matrix was still stiff).

They could revert the cells back to a state where they are sensitive to chemotherapy. This suggests that if they can disrupt the stiffness signaling that's happening through the CD44 receptor, we could make patients' pancreatic cancer treatable by normal chemotherapy.

Other cancers can be affected by mechanical properties of the extracellular matrix, but these interactions typically work through a different class of receptors called integrins.

The researchers showed that pancreatic cancer cells weren't really using integrin receptors at all in our materials. That's important, because if you want to design a drug to resensitize patient cells to chemotherapy, you need to know which biological pathway to interfere with.

Engineered matrices reveal stiffness-mediated chemoresistance in patient-derived pancreatic cancer organoids, Nature Materials (2024). DOI: 10.1038/s41563-024-01908-x

Researchers identify unknown signaling pathway in the brain responsible for migraine with aura

A previously unknown mechanism by which proteins from the brain are carried to a particular group of sensory nerves causes migraine attacks, a new study shows. This may pave the way for new treatments for migraine and other types of headaches.

In around a fourth of all migraine patients, headache attacks are preceded by aura—symptoms from the brain such as temporary visual or sensory disturbances preceding the migraine attack by 5–60 minutes.

While we know with some certainty why patients experience aura, it has been a bit of a mystery why they get headaches, and why migraines are one-sided, until now.

A new study in mice conducted by researchers  is the first to demonstrate that proteins released from the brain during migraine with aura are carried with cerebrospinal fluid to the pain-signaling nerves responsible for headaches.

The researchers have discovered that these proteins activate a group of sensory nerve cell bodies at the base of the skull, the so-called trigeminal ganglion, which can be described as a gateway to the peripheral sensory nervous system of the skull.

At the root of the trigeminal ganglion, the barrier that usually prevents substances from entering the peripheral nerves is missing, and this enables substances in the cerebrospinal fluid to enter and activate pain-signaling sensory nerves, resulting in headaches.

The research results  results suggest that they have identified the primary channel of communication between the brain and the peripheral sensory nervous system. It is a previously unknown signaling pathway important for the development of migraine headache, and it might be associated with other headache diseases too.

The peripheral nervous system consists of all the nerve fibers responsible for communication between the central nervous system—the brain and spinal cord—and the skin, organs and muscles. The sensory nervous system, which is part of the peripheral nervous system, is responsible for communicating information about e.g. touch, itching and pain to the brain.

The study results offer insight into why migraine is usually one-sided. 

Most patients experience one-sided headaches, and this signaling pathway can help explain why. This study of how proteins from the brain are transported shows that the substances are not carried to the entire intracranial space, but primarily to the sensory system in the same side, which is what causes one-sided headaches.

The study was conducted on mice, but also included MR scans of the human trigeminal ganglion, and according to the scientists, there is every indication that the function of the signaling pathway is the same in mice and humans, and that in humans too, the proteins are carried by cerebrospinal fluid.

Martin Kaag Rasmussen et al, Trigeminal ganglion neurons are directly activated by influx of CSF solutes in a migraine model, Science (2024). DOI: 10.1126/science.adl0544

Phage viruses, used to treat antibiotic resistance, gain advantage by cutting off competitors' reproduction ability

Curious bits of DNA tucked inside genomes across all kingdoms of life historically have been disregarded since they don't seem to have a role to play in the competition for survival, or so researchers thought.

These DNA pieces came to be known as "selfish genetic elements" because they exist, as far as scientists could tell, to simply reproduce and propagate themselves, without any benefit to their host organisms. They were seen as genetic hitchhikers that have been inconsequentially passed from one generation to the next.

Research conducted by scientists at the University of California San Diego has provided fresh evidence that such DNA elements might not be so selfish after all. Instead, they now appear to factor considerably into the dynamics between competing organisms.

Publishing in the journal Science, researchers in the School of Biological Sciences studied selfish genetic elements in bacteriophages (phages), viruses that are considered the most abundant organisms on Earth. To their surprise, researchers found that selfish genetic elements known as "mobile introns" provide their virus hosts with a clear advantage when competing with other viruses: Phages have weaponized mobile introns to disrupt the ability of competing phage viruses to reproduce.

This is the first time a selfish genetic element has been demonstrated to confer a competitive advantage to the host organism it has invaded.

Understanding that selfish genetic elements are not always purely 'selfish' has wide implications for better understanding the evolution of genomes in all kingdoms of life.

Erica A. Birkholz et al, An intron endonuclease facilitates interference competition between coinfecting viruses, Science (2024). DOI: 10.1126/science.adl1356. www.science.org/doi/10.1126/science.adl1356

Cool roofs outperform green roofs in urban climate modeling study

Painting roofs white or covering them with a reflective coating would be more effective at cooling cities than vegetation-covered "green roofs," street-level vegetation or solar panels, finds a new study  by  researchers.

Conversely, extensive use of air conditioning would warm the outside environment by as much as 1 degree C in a dense city center, the researchers found.

The research, published in Geophysical Research Letters, used a three-dimensional urban climate model of Greater London to test the thermal effects of different passive and active urban heat management systems, including painted "cool roofs," rooftop solar panels, green roofs, ground level tree vegetation and air conditioning during the two hottest days of the summer of 2018.

It found that if adopted widely throughout London, cool roofs could reduce outdoor temperatures across the city, on average, about 1.2 degrees C, and up to 2 degrees C in some locations. Other systems, such as extensive street-level vegetation or solar panels would provide a smaller net cooling effect, only about 0.3 degrees C on average across London, though they offer other environmental benefits. Similarly, while green roofs offer benefits like water drainage and wildlife habitats, their net cooling effect on the city was found to be negligible on average.

Air conditioning, which transfers heat from within buildings to the outside, would warm the outdoor urban environment by about 0.15 degrees C for the city overall, but by as much as 1 degree C in dense central London. The researchers also found that the increase in the distribution of air conditioning units in their model could be entirely powered by photovoltaic solar panels if they were similarly installed to their fullest extent.

To gauge the potential full effect of each method, the team modeled each one as though they had been as widely adopted as theoretically feasible across housing, commercial and industrial buildings throughout Greater London.

The researchers  comprehensively tested multiple methods that cities like London could use to adapt to and mitigate warming temperatures, and found that cool roofs were the best way to keep temperatures down during extremely hot summer days. Other methods had various important side benefits, but none were able to reduce outdoor urban heat to nearly the same level.

 Cool roofs could be most effective at reducing outdoor urban temperatures in London compared with other roof top and vegetation interventions: a mesoscale urban climate modelling study, Geophysical Research Letters (2024). DOI: 10.1029/2024GL109634

Air pollution drives 7% of deaths in big Indian cities: Study

More than seven percent of all deaths in 10 of India's biggest cities are linked to air pollution, a large study said recently, leading researchers to call for action to save tens of thousands of lives a year.

Smog-filled Indian cities including the capital Delhi suffer from some of the world's worst air pollution, choking the lungs of residents and posing a rising threat to health still being revealed by researchers.

For the new study, an Indian-led team looked at the levels of cancer-causing microparticles known as PM2.5 pollutants in the cities of Ahmedabad, Bengaluru, Chennai, Delhi, Hyderabad, Kolkata, Mumbai, Pune, Shimla and Varanasi.

From 2008 to 2019, more than 33,000 deaths a year could be attributed to PM2.5 exposure above the World Health Organization's recommendation of 15 micrograms per cubic meter, the study said.

That represents 7.2 percent of the recorded deaths in those cities during that period, according to the study in The Lancet Planetary Health journal.

India's capital Delhi was the worst offender, with 12,000 annual deaths linked to air pollution -- or 11.5 percent of the total.

But even cities where air pollution is not thought to be as bad -- such as Mumbai, Kolkata and Chennai -- had high death rates, the researchers emphasized.

They called for India's air quality standards to be toughened.

The country's current recommendation is 60 micrograms of PM2.5 per cubic meter, which is four times higher than the WHO's guidelines.

Lowering and enforcing the limit "will save tens of thousands of lives per year", say the researchers. 

"Methods for controlling pollution exist and are used elsewhere. They urgently need to be applied in India," they said in a statement.

The WHO says that almost everyone on Earth breathes in more than the recommended amount of air pollution, which can trigger strokes, heart disease, lung cancer and other respiratory diseases.

Jeroen de Bont et al, Ambient air pollution and daily mortality in ten cities of India: a causal modelling study, The Lancet Planetary Health (2024). DOI: 10.1016/S2542-5196(24)00114-1

Health study illustrates the interconnectedness of humans and wildlife

According to a growing body of evidence, including a recent study, the seemingly separate fields of health sciences and conservation are inextricably linked.

The study, published in the journal Environmental Science & Technology, measured lead levels in the blood of house sparrows (Passer domesticus) in Australian mining towns to accurately predict lead levels in the blood of children living in the same areas.

It shows that wildlife and human health are so intimately linked that when something like lead, which we know is a toxin, gets out into the environment and affects wildlife, it's also affecting people.

The study illustrates the growing relevance of the One Health concept, coalescing aspects of public health, veterinary health and conservation.

Max M. Gillings et al, House Sparrows as Sentinels of Childhood Lead Exposure, Environmental Science & Technology (2024). DOI: 10.1021/acs.est.4c00946

These oldest inhabited termite mounds have been active for 34,000 years

Scientists in South Africa have been stunned to discover that termite mounds that are still inhabited in an arid region of the country are more than 30,000 years old, meaning they are the oldest known active termite hills.

Some of the mounds near the Buffels River in Namaqualand were estimated by radiocarbon dating to be 34,000 years old, according to the researchers from Stellenbosch University.

Some fossilized termite mounds have been discovered dating back millions of years. The oldest inhabited mounds before this study were found in Brazil and are around 4,000 years old. They are visible from space.

 M.L. Francis et al, Calcareous termite mounds in South Africa are ancient carbon reservoirs, Science of The Total Environment (2024). DOI: 10.1016/j.scitotenv.2024.171760

Caterpillars pass down food preferences to offspring through blood

Many caterpillars are known for their specific food preferences, which they bring with them when they morph into butterflies. For instance, the monarch butterfly only feeds on milkweed plants, while the Lime butterfly feeds on lime leaves. Despite deriving from a common ancestral species, these unique diet preferences are a point of interest for researchers.

In an earlier study by researchers, they demonstrated that when caterpillars fed on leaves outside of their usual diet, they would prefer the smell of that type of plant after a few days. Remarkably, these caterpillars also passed on the acquired smell preference to their offspring.

Such a phenomenon is also seen in nature when caterpillars find themselves on a new food plant when the female butterfly lays eggs on the wrong plant by mistake. The new plant is edible but has a new smell, the caterpillars will learn to prefer this new smell and pass this preference on to their offspring.

This type of inheritance may facilitate host switching and ultimately the formation of new species, each with their own food preferences.

 V. Gowri et al, Haemolymph transfusions transfer heritable learned novel odour preferences to naive larvae of Bicyclus anynana butterflies, Biology Letters (2024). DOI: 10.1098/rsbl.2023.0595

Researchers identify 'first responder' cells in pancreas crucial for blood sugar control

How does our body control blood sugar so precisely?

Researchers found a special group of "first responder" cells in the pancreas that are crucial for triggering blood sugar response.

Their findings were published in the journal Science Advances.

Our bodies need to keep blood sugar levels just right. Too high or too low can be dangerous. This balance is disturbed in diabetes, leading to serious health issues. Beta cells in the pancreas manage this balance by releasing insulin when blood sugar levels rise.

Understanding how beta cells work and coordinate the response to rising blood sugar can ultimately help develop better treatments for diabetes.

To understand the work of the pancreas, the research team turned to zebrafish. This small tropical fish has a pancreas that works similarly to a human one. At the same time, it offers a huge advantage. Researchers can use transparent fish that have no pigment whatsoever and observe the pancreas at work in real-time in the living fish.

The group discovered that a small group of beta cells are more sensitive to sugar levels than the others. These cells respond to glucose quicker than the rest of the cells, so the research  team referred to them as "first responder" cells. They initiate the glucose response, which is followed by the remaining "follower cells."

The team wanted to test if first responders are necessary for the follower cells to respond to glucose.

Using transparent fish, the  group took advantage of optogenetics, a modern light-based technology that allows to turn single cells on or off with a beam of light.

Turning off the first responder cells lowered the response to the blood sugar of the follower cells. At the same time, when the first responders were selectively activated, the response of the follower cells was enhanced.

The first responders lie at the top of the beta cell hierarchy when it comes to control of the sugar response. Interestingly, only about 10% of the beta-cells act as first responders. It suggests that this small population of cells serves as a control centre for regulating the activity of the rest of the beta cells.

To find out what makes the first responder cells unique, the researchers compared the gene expression of highly glucose-sensitive beta cells to those that are less sensitive. They found that first responders are involved in vitamin B6 production. The first responder cells express a key enzyme involved in transforming the inactive form of dietary vitamin B6 into the form that is active in the cells.

Part1

The researchers turned off the vitamin B6 production in both zebrafish and mouse pancreas. The ability of the beta cells to respond to high blood sugar was dramatically reduced in both species.

This indicates that vitamin B6 plays an evolutionarily conserved role in the response to glucose. It is possible that the first responders produce and supply Vitamin B6 to the rest of the beta cells to regulate their activity.
We now know there are specific cells that start the glucose response and that Vitamin B6 is essential for this process.
Vitamin B6 serves as a cofactor for more than a hundred essential enzymes that play critical roles in the cells, ranging from the control of cellular respiration to neurotransmitter production.

There is actually a body of research that shows a correlation between low levels of vitamin B6 and incidence of metabolic disease and type 2 diabetes.
Understanding how Vitamin B6 regulates the beta cells in the pancreas could lead to new insights into the pathology of diabetes and ultimately to new treatments.

Luis Fernando Delgadillo-Silva et al, Optogenetic β cell interrogation in vivo reveals a functional hierarchy directing the Ca 2+ response to glucose supported by vitamin B6, Science Advances (2024). DOI: 10.1126/sciadv.ado4513

Part 2

**

Key mechanisms identified for regeneration of neurons

Neurological disorders, such as trauma, stroke, epilepsy, and various neurodegenerative diseases, often lead to the permanent loss of neurons, causing significant impairments in brain function. Current treatment options are limited, primarily due to the challenge of replacing lost neurons.

Direct neuronal reprogramming, a complex procedure that involves changing the function of one type of cell into another, offers a promising strategy.

In cell culture and in living organisms, glial cells—the non-neuronal cells in the central nervous system—have been successfully transformed into functional neurons. However, the processes involved in this reprogramming are complex and require further understanding. This complexity presents a challenge, but also a motivation, for researchers in the field of neuroscience and regenerative medicine.

Two research teams now explored the molecular mechanisms at play when glial cells are converted to neurons by a single transcription factor.

The findings are published in the journal Nature Neuroscience.

Specifically, the researchers focused on small chemical modifications in the epigenome. The epigenome helps control which genes are active in different cells at different times. For the first time, the teams have now shown how coordinated the epigenome rewiring is, elicited by a single transcription factor.

Using novel methods in epigenome profiling, the researchers identified that a posttranslational modification of the reprogramming neurogenic transcription factor Neurogenin2 profoundly impacts the epigenetic rewiring and neuronal reprogramming. However, the transcription factor alone is not enough to reprogram the glial cells.

In an important discovery, the researchers identified a novel protein, the transcriptional regulator YingYang1, as a key player in this process. YingYang1 is necessary to open up the chromatin for reprogramming, to which end it interacts with the transcription factor.

The protein YingYang1 is crucial for achieving the conversion from astrocytes to neurons. 

These findings are important to understand and improve reprogramming of glial cells to neurons, and thus bring us closer to therapeutic solutions.

Allwyn Pereira et al, Direct neuronal reprogramming of mouse astrocytes is associated with multiscale epigenome remodeling and requires Yy1, Nature Neuroscience (2024). DOI: 10.1038/s41593-024-01677-5

High ambient temperature in pregnancy associated with childhood leukemia

As climate change warms the planet, high ambient temperatures are expected to be more common and intense over the coming decades  worldwide.

Researchers  have studied how rising temperatures adversely affect human health. A study appearing in  journal finds that exposure to high ambient temperatures during pregnancy can have detrimental impact on the health of the offspring.

This is the first study that directly evaluates the association between hot temperatures during pregnancy and the risk of cancer in children.

This study is adding to a growing body of literature that underscores that high ambient temperature not only has immediate health effects, but also may be a cause of future chronic diseases.

Tormod Rogne et al, High ambient temperature in pregnancy and risk of childhood acute lymphoblastic leukaemia: an observational study, The Lancet Planetary Health (2024). DOI: 10.1016/S2542-5196(24)00121-9

**

Study explores the link between stock market fluctuations and emergency room visits

The advent of computerized trading and fintech platforms has made investing in stocks easier and more accessible to individuals worldwide. This has led to an increase in stock market participation in many countries.

As a result of this spike in investments, fluctuations in the stock market can have a significant effect on the finances of numerous individuals and their families.

Drastic changes in wealth or financial difficulties resulting from these stock market fluctuations could potentially also affect the mental and physical health of investors. In fact, some recent reports have found a correlation between stock market fluctuations and specific physical and psychological issues.

Researchers at the National University of Singapore, Jinan University, Peking University and Sun Yat-sen University recently explored this potential link further, focusing on the relationship between stock market fluctuations and stress-related emergency room visits in China. Their findings, published in Nature Mental Health, unveiled a trend marked by greater visits to emergency rooms by individuals experiencing stress-related mental health issues during periods of stock market volatility.

To study the relationship between stock market fluctuations and emergency room visits in China, this team of researchers statistically analyzed data collected at the largest hospitals in Beijing over the course of three years, spanning from 2009 to 2012. This data, which was specific to emergency room visits for reasons potentially related to stress, was analyzed in conjunction with stock market trends in China during the same period.

Overall, the results of the analyses run by the researchers suggest that stock market shocks had immediate effects on cardiovascular diseases and mental health disorders in the period ranging between 2009 and 2012, as volatility in stock markets was linked to more visits to the emergency room for these stress-related physical and mental issues. As the data used by the researchers was over a decade old, they highlighted the need for additional studies using newer medical and financial data.
The health effects are highly nonlinear, instantaneous and more salient for older people and males.

Sumit Agarwal et al, Associations between stock market fluctuations and stress-related emergency room visits in China, Nature Mental Health (2024). DOI: 10.1038/s44220-024-00267-5

 Fungi and lichens pose deadly threat to 5,000-year-old rock art

The Negev desert of southern Israel is renowned for its unique rock art. Since at least the third millennium BCE, the hunters, shepherds, and merchants who roamed the Negev have left thousands of carvings (petroglyphs) on the rocks. These figures are mostly cut into desert varnish: a thin black coating on limestone rock, which forms naturally. Many represent animals such as ibexes, goats, horses, donkeys, and domestic camels, but abstract forms also occur.

Researchers find a way to protect microbes from extreme conditions

Microbes that are used for health, agricultural, or other applications need to be able to withstand extreme conditions, and ideally the manufacturing processes used to make tablets for long-term storage. Researchers have now developed a new way to make microbes hardy enough to withstand these extreme conditions.

Their method involves mixing bacteria with food and drug additives from a list of compounds that the FDA classifies as "generally regarded as safe." The researchers identified formulations that help to stabilize several different types of microbes, including yeast and bacteria, and they showed that these formulations could withstand high temperatures, radiation, and industrial processing that can damage unprotected microbes.

In an even more extreme test, some of the microbes recently returned from a trip to the International Space Station, coordinated by Space Center Houston, the researchers are now analyzing how well the microbes were able to withstand those conditions.

What this project was about is stabilizing organisms for extreme conditions. Scientists are really thinking about a broad set of applications, whether it's missions to space, human applications, or agricultural uses.

Synthetic extremophiles via species-specific formulations improve microbial therapeutics, Nature Materials (2024). DOI: 10.1038/s41563-024-01937-6

Scientists visualize magnetic fields at atomic scale with holography electron microscope

A research team  has achieved a major breakthrough in the observation of magnetic fields at unimaginably small scales.

The team used Hitachi's atomic-resolution holography electron microscope—with a newly developed image acquisition technology and defocus correction algorithms—to visualize the magnetic fields of individual atomic layers within a crystalline solid.

Many advances in electronic devices, catalysis, transportation, and energy generation have been made possible by the development and adoption of high-performance materials with tailored characteristics. Atom arrangement and electron behavior are among the most critical factors that dictate a crystalline material's properties.

Notably, the orientation and strength of magnetic fields right at the interface between different materials or atomic layers are particularly important, and often help explain many peculiar physical phenomena.

Toshiaki Tanigaki et al, Electron holography observation of individual ferrimagnetic lattice planes, Nature (2024). DOI: 10.1038/s41586-024-07673-w

Scientists identify thousands of high-risk cancer gene variants

More than 5,000 genetic variants that enable certain cancers to thrive have been identified by scientists, along with a potential therapeutic target to treat or even prevent these cancers from developing.

Researchers from the Wellcome Sanger Institute, and their collaborators at The Institute of Cancer Research, London, and the University of Cambridge assessed the health impact of all possible genetic changes in the "tumor protection" gene, BAP1. They found around a fifth of these possible changes were pathogenic, significantly increasing the risk of developing cancers of the eye, lung lining, brain, skin, and kidney.

The findings, published recently (5 July) in Nature Genetics, are freely available so that they can be immediately used by doctors to help diagnose patients and choose the most effective therapies for them. Importantly, as all possible variants were assessed, the findings benefit individuals from diverse ethnic backgrounds, who have historically been underrepresented in genetics research.

The team also uncovered a link between certain disruptive BAP1 variants and higher levels of IGF-1, a hormone and growth factor. This discovery opens the door to developing new drugs that could inhibit these harmful effects, potentially slowing down or preventing the progression of certain cancers.

The BAP1 protein acts as a powerful tumor suppressor in the body, protecting against cancers of the eye, lung lining, brain, skin, and kidney. Inherited variants that disrupt the protein can increase a person's lifetime risk of developing these cancers by up to 50%, typically occurring around middle age.

Andrew J. Waters et al, Saturation genome editing of BAP1 functionally classifies somatic and germline variants, Nature Genetics (2024). DOI: 10.1038/s41588-024-01799-3

WHO agency says talc is 'probably' cancer-causing

The World Health Organization's cancer agency on Friday classified talc as "probably carcinogenic" for humans, however an outside expert warned against misinterpreting the announcement as a "smoking gun".

The decision was based on "limited evidence" that talc could cause ovarian cancer in humans, "sufficient evidence" it was linked to cancer in rats and "strong mechanistic evidence" that it shows carcinogenic signs in human cells, the WHO's International Agency for Research on Cancer (IARC) said.

Talc is a naturally occurring mineral which is mined in many parts of the world and is often used to make talcum baby powder.

Most people are exposed to talc in the form of baby powder or cosmetics, according to the Lyon-based IARC.

But the most significant exposure to talc occurs when talc is being mined, processed or used to make products, it added.

The agency said there were numerous studies which consistently showed an increase in the rate of ovarian cancer in women who use talc on their genitals.

But it could not rule out that the talc in some studies was contaminated with cancer-causing asbestos.

"A causal role for talc could not be fully established," according the agency's findings published in The Lancet Oncology.

 Leslie T Stayner et al, Carcinogenicity of talc and acrylonitrile, The Lancet Oncology (2024). DOI: 10.1016/S1470-2045(24)00384-X

**

True scale of carbon impact from long-distance travel revealed

The reality of the climate impact of long-distance passenger travel has been revealed in new research.

Despite only accounting for less than 3% of all trips by UK residents, journeys of more than 50 miles (one way) are responsible for 70% of all passenger travel-related carbon emissions.

The disparity is even greater when international travel is singled out: International journeys are only 0.4% of total trips, but are responsible for 55% of emissions.

The new research, published recently in the journal Nature Energy, also shows that targeting long-distance travel may be a more effective way of tackling emissions than current efforts focusing on local and commuter journeys.

While the number of long and short distance domestic journeys by car has fallen slightly over the last 25 years, international air travel has increased significantly, driven by an increase in trips for leisure and visiting friends and family.

The scale of the impact of long-distance travel is very large indeed. That just less than 3% of our trips are responsible for around 60% of miles and 70% of emissions shows how important long-distance travel is in the fight to combat climate change. Worryingly, long-distance trips, especially flights, have been growing; however, they offer opportunities too.

Using a new metric they have created, called emission reduction sensitivity, the research team has calculated which types of travel could be changed to maximize a reduction in carbon emissions from passenger travel while affecting as few people or trips as possible.

Part 1

The research found that if all car journeys under eight miles were shifted to walking or cycling, there would be a 9.3% reduction in carbon emissions. However, around 55% of all journeys would need to be shifted to achieve this, as most travel is done locally and in cars.

Calculated by dividing the carbon reduction percentage by the percentage of journeys altered, the emission reduction sensitivity for this change would be just 0.17—the lowest recorded in the study.

By contrast, if all flights of less than 1,000 miles were moved to rail, there would be a 5.6% reduction in emissions but only 0.17% of journeys would be affected—resulting in a sensitivity value of 33.2.

At the top end, theoretically limiting everyone who flies now to one return flight abroad per year would have a value of 158.3, as so few journeys would be affected.

The researchers stress that the potential changes are only suggestions meant to make us realize and reassess the impact of our long-distance travel, rather than concrete policy proposals.

While efforts to move local journeys to more sustainable modes of transport are really positive, by omitting aviation emissions from national statistics—as is the case at the moment in nearly all countries—we are not getting a holistic picture and ignoring a large part of the problem.

A call to rethink our travel's carbon impact

The researchers also hope that their findings can act as a driver for policymakers to look at changes in how effort is assigned when dealing with the impact of travel on the environment.

The research also offers the public an insight into the impact that changing their behavior could have.

The important thing both at the policy and personal level is that we prioritize the relatively fewer longer distance trips—especially flights—in order to realize the largest reductions.

Casting a long shadow: the role of long distance travel in carbon emissions from and decarbonisation of passenger travel, Nature Energy (2024). DOI: 10.1038/s41560-024-01561-3 , www.nature.com/articles/s41560-024-01561-3

Part 2

The evidence is mounting: Humans were responsible for the extinction of large mammals

The debate has raged for decades: Was it humans or climate change that led to the extinction of many species of large mammals, birds, and reptiles that have disappeared from Earth over the past 50,000 years?

By "large," we mean animals that weighed at least 45 kilograms—known as megafauna. At least 161 species of mammals were driven to extinction during this period. This number is based on the remains found so far.

The largest of them were hit the hardest—land-dwelling herbivores weighing over a ton, the megaherbivores. Fifty thousand years ago, there were 57 species of megaherbivores. Today, only 11 remain. These remaining 11 species have also seen drastic declines in their populations, but not to the point of complete extinction.

A research group  now concludes that many of these vanished species were hunted to extinction by humans.

They present this conclusion in a review article invited by and published in the journal Cambridge Prisms: Extinction. A review article synthesizes and analyses existing research within a particular field.

The researchers incorporated several research fields, including studies directly related to the extinction of large animals, such as:

• The timing of species extinctions
• The animals' dietary preferences
• Climate and habitat requirements
• Genetic estimates of past population sizes
• Evidence of human hunting

Additionally, they included a wide range of studies from other fields necessary to understand the phenomenon, such as:

• Climate history over the past 1–3 million years
• Vegetation history over the past 1–3 million years
• Evolution and dynamics of fauna over the past 66 million years
• Archaeological data on human expansion and lifestyle, including dietary preferences

Part 1

The dramatic climate changes during the last interglacial and glacial periods (known as the late Pleistocene, from 130,000 to 11,000 years ago) certainly affected populations and distributions of both large and small animals and plants worldwide. However, significant extinctions were observed only among the large animals, particularly the largest ones.

An important observation is that the previous, equally dramatic ice ages and interglacials over the past couple of million years did not cause a selective loss of megafauna. Especially at the beginning of the glacial periods, the new cold and dry conditions caused large-scale extinctions in some regions, such as trees in Europe. However, there were no selective extinctions of large animals.

The large and very selective loss of megafauna over the last 50,000 years is unique over the past 66 million years. Previous periods of climate change did not lead to large, selective extinctions, which argues against a major role for climate in the megafauna extinctions.
Another significant pattern that argues against a role for climate is that the recent megafauna extinctions hit just as hard in climatically stable areas as in unstable areas.
Archaeologists have found traps designed for very large animals, and isotope analyses of ancient human bones and protein residues from spear points show that they hunted and ate the largest mammals.
Early modern humans were effective hunters of even the largest animal species and clearly had the ability to reduce the populations of large animals. These large animals were and are particularly vulnerable to overexploitation because they have long gestation periods, produce very few offspring at a time, and take many years to reach sexual maturity.
The analysis shows that human hunting of large animals such as mammoths, mastodons, and giant sloths was widespread and consistent across the world.

It also shows that the species went extinct at very different times and at different rates around the world. In some local areas, it happened quite quickly, while in other places it took over 10,000 years. But everywhere, it occurred after modern humans arrived, or in Africa's case, after cultural advancements among humans.
Part 2

Species went extinct on all continents except Antarctica and in all types of ecosystems, from tropical forests and savannas to Mediterranean and temperate forests and steppes to arctic ecosystems.
Many of the extinct species could thrive in various types of environments. Therefore, their extinction cannot be explained by climate changes causing the disappearance of a specific ecosystem type, such as the mammoth steppe—which also housed only a few megafauna species.
Most of the species existed under temperate to tropical conditions and should actually have benefited from the warming at the end of the last ice age.
The researchers point out that the loss of megafauna has had profound ecological consequences. Large animals play a central role in ecosystems by influencing vegetation structure (e.g., the balance between dense forests and open areas), seed dispersal, and nutrient cycling. Their disappearance has resulted in significant changes in ecosystem structures and functions.

Jens-Christian Svenning et al, The late-Quaternary megafauna extinctions: Patterns, causes, ecological consequences and implications for ecosystem management in the Anthropocene, Cambridge Prisms: Extinction (2024). DOI: 10.1017/ext.2024.4

The numbers of extinct and surviving species come from the freely accessible database PHYLACINE 1.2.1, which lists all known mammals that have lived in the past 129,000 years, including those that have gone extinct recently or are only found in captivity.

Part 3

**

Incredible New Tech Lets Scientists Watch Fetuses Develop in Real Time

Bacterial glitter: New findings open up possibilities for sustainable color technologies

An international team of researchers  has investigated the mechanism that makes some types of bacteria reflect light without using pigments. The researchers were interested in the genes responsible and discovered important ecological connections. Their findings appear in the Proceedings of the National Academy of Sciences.

The iridescent colors known from peacock feathers or butterfly wings are created by tiny structures that reflect light in a special way. Some bacterial colonies form similar glittering structures.

The scientists sequenced the DNA of 87 structurally colored bacteria and 30 colorless strains and identified genes that are responsible for these fascinating colonies. These findings could lead to the development of environmentally-friendly dyes and materials.

Scientists  discovered that the genes responsible for structural color are mainly found in oceans, freshwater, and special habitats such as intertidal zones and deep-sea areas. In contrast, microbes in host-associated habitats such as the human microbiome displayed very limited structural colour. 

The study results indicate that the colorful bacterial colony structures are not only used to reflect light. Surprisingly, these genes are also found in bacteria that live in deep oceans without sunlight. This could imply that the colors could reflect deeper processes of cell organization with important functions, such as protecting the bacteria from viruses, or efficiently colonizing floating food particles. These findings could inspire new, sustainable technologies based on these natural structures.

Colin J. Ingham et al, Structural color in the bacterial domain: The ecogenomics of a 2-dimensional optical phenotype, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2309757121

Researchers reveal a master controller of development and aging

Researchers have unlocked crucial molecular secrets of aging in cells, potentially paving the way to improve quality of life as people age.

The study, published in Cell Metabolism, decoded the process by which genes regulate how people mature as they grow and age.

By analyzing molecular datasets from both people and mice and then comparing different age groups over time, the researchers investigated the activity of genes involved in both developmental and aging processes.

Master controller genes regulate which genes are turned on or off in each of our cells, making sure that each cell does its specific job.

The scientists followed the activity of the master regulator Activator Protein 1 or AP-1 and found that it progressively activated adult genes, while the activity of 'early-life' genes involved in development were dialed down, and this process was shared across cell types.

The study found this process in our cells was predictable across the different life stages, as people mature.

It was ongoing in adulthood, likely because AP-1 is also activated by a number of stress and inflammatory processes as well as by a protein in our blood that increases with age. This further dampens genes most active early in life, which may drive many of the predictable changes of aging.

To address the diseases associated with aging, like Alzheimer's disease, metabolic liver disorders and stroke, researchers must first understand the process causing bodies to age.

By pinpointing AP-1 as a master controller linked to aging across cell types, scientists can now study the effects of drugs that reduce its activity to extend quality of life. The goal is to prevent diseases of aging from escalating or occurring in the first place by targeting the underlying aging process to allow people to grow older in better health.

 Ralph Patrick et al, The activity of early-life gene regulatory elements is hijacked in aging through pervasive AP-1-linked chromatin opening, Cell Metabolism (2024). DOI: 10.1016/j.cmet.2024.06.006

Boys born with higher natural resistance to HIV, study finds

Baby girls are more likely to acquire HIV from their mothers during pregnancy or childbirth than infant boys, who are conversely more likely to achieve cure or remission, researchers say in a new study that sheds light on the gender differences in immune systems.

An estimated 1.3 million women and girls living with HIV become pregnant each year and the rate of transmission to the child during pregnancy, labor, delivery or breastfeeding—in the absence of any intervention—ranges from 15 to 45%, according to the World Health Organization.

This new study identified some of the key mechanisms by which sustained HIV remission can be achieved—mechanisms that are relevant to children and adults alike.

Researchers  evaluated 284 infants in KwaZulu-Natal, South Africa, one of the world's highest HIV-prevalent areas, who were started at birth on a mix of HIV medicines known as combination anti-retroviral therapy (cART), after being exposed to HIV during pregnancy.

They found that HIV transmission to male fetuses was 50% less common than to females.

Affected males had lower levels of the virus in the blood and to date, in this study, four male infants have been identified who have achieved HIV cure/remission—i.e. maintained undetectable levels of HIV in the blood even without therapy.

HIV cure is categorized as "true cure" in which the virus has been eradicated totally from the body and "functional cure" or "cure/remission," in which the virus is no longer detectable in the blood even after treatment has been discontinued.

The researchers say the disparity found between male and female infants is likely due to the lower levels of activated CD4 T cells in male fetuses than in females, making it harder for the virus to establish a reservoir and providing a barrier against infection.

If by chance a virus gets transmitted to a male, it struggles to persist because there are not enough activated CD4 T cells available to sustain the infection.

CD4 T cells are a type of white blood cell that help the body fight infections such as HIV. They are an important part of the immune system and are targeted by HIV during infection. HIV spreads more slowly with lower CD4 T cell counts.

Nomonde Bengu et al, Sustained aviremia despite anti-retroviral therapy non-adherence in male children after in utero HIV transmission, Nature Medicine (2024). DOI: 10.1038/s41591-024-03105-4

Air pollution linked to a decrease in IVF birth rate success, new study shows

A pioneering study, presented at the ESHRE 40th Annual Meeting in Amsterdam, has revealed that exposure to fine particulate matter (PM) prior to the retrieval of oocytes (eggs) during in vitro fertilization (IVF) can reduce the odds of achieving a live birth by almost 40%.

The study analyzed PM10 exposure in the two weeks leading up to oocyte collection, finding that the odds of a live birth decreased by 38% (OR 0.62, 95% CI 0.43–0.89, p=0.010) when comparing the highest quartile of exposure (18.63 to 35.42 µg/m3) to the lowest quartile (7.08 to 12.92 µg/m3). The study abstract was published in Human Reproduction.

Conducted over an eight-year period in Perth, Australia, the research analyzed 3,659 frozen embryo transfers from 1,836 patients. The median female age was 34.5 years at the time of oocyte retrieval and 36.1 years at the time of frozen embryo transfer.

The study examined air pollutant concentrations over four exposure periods prior to oocyte retrieval (24 hours, two weeks, four weeks, and three months), with models created to account for co-exposures.

Increasing PM_2.5 exposure in the three months prior to oocyte retrieval was also associated with decreased odds of live birth, falling from 0.90 (95% CI 0.70–1.15) in the second quartile to 0.66 (95% CI 0.47–0.92) in the fourth quartile.

Importantly, the negative impact of air pollution was observed despite excellent overall air quality during the study period, with PM₁₀ and PM_2.5 levels exceeding WHO guidelines on just 0.4% and 4.5% of the study days, respectively.

 Leathersich S.J, et al, Particulate matter (PM2.5 and PM10) exposure prior to oocyte collection is associated with decreased live birth rates in subsequent frozen embryo transfers. Human Reproduction (2024).

Scientists create a cell that precludes malignant growth

Cell therapies could help in the treatment of hereditary diseases, myocardial infarction and hundreds of other diseases. For many blood diseases, new cells can already be transplanted into human patients, and diabetes has also been treated by transplanting cells obtained through organ donation or, more recently, β-cells modified from the patient's own stem cells.

A risk associated with gene-edited cells is unintentional DNA mutations, including those that predispose patients to cancer. Moreover, the difference in tissue types makes it impossible to transfer cells simply from one person to another.

Cells that suit anyone, or immunologically invisible cells, as it were, have been created, but they too are associated with an increased risk of cancer. Over a decade ago,  a research group set out to develop cells where these problems could be avoided. Now, the group has succeeded in producing cells which cannot proliferate unaided and which cannot therefore turn into malignant cells.

The study was published in Molecular Therapy.

Almost all of our diseases are fundamentally caused by cellular dysfunction. One medical dream is to fight tissue damage, diseases or even aging with new healthy cells. This new study takes us a step closer to safe and novel cell therapies.

The researchers modified stem cells to divide only if they are supplemented with thymidine, one of the building blocks of DNA. The cells that have been subjected to this safety treatment cannot replicate their genome without the supplementary component vital for DNA synthesis. This precludes their proliferation. When the cells are differentiated for their various tasks, they cease to divide and no longer require the supplement. The innovation has been protected by the University's Helsinki Innovation services (HIS).

Part 1

Initially, the researchers investigated whether cell growth can be regulated with an externally administered substance. Once successful, they examined whether the cells functioned normally.

They used stem cells to create insulin-producing β-cells that they then transplanted into laboratory animals. The cells regulated the blood glucose levels of the animals throughout the almost six-month experiment.
The cells are also able to differentiate into other tissue types as usual, and the researchers have not observed any differences in them other than their inability to proliferate without their say-so.
Stem cells are very primitive cells, as they have to be able to divide in abundance and develop in many different directions. They have potential for a range of purposes, but their primitive nature also poses a problem: What if some cells are not differentiated, but continue to grow in a primitive form? According to the scientists of the study, the research group's solution enables the efficient proliferation of cells during production, which can be halted at the desired time, such as following transplantation.
The solution also makes it possible to edit cells without fear of adverse effects of the editing itself. For example, cells can be made into something that the recipient's immune system does not recognize.
Previously, such cells would have been highly risky, as the immune system also monitors the onset of cancer. Now, that risk is very small or non-existent. Ideally, these cells could be turned into products suited to everyone and, when necessary, quickly deployed.

Rocio Sartori-Maldonado et al, Thymidylate synthase disruption to limit cell proliferation in cell therapies, Molecular Therapy (2024). DOI: 10.1016/j.ymthe.2024.06.014

Scientists successfully create a time crystal made of giant atoms

A crystal is an arrangement of atoms that repeats itself in space, in regular intervals: At every point, the crystal looks exactly the same. In 2012, Nobel Prize winner Frank Wilczek raised the question: Could there also be a time crystal—an object that repeats itself not in space but in time? And could it be possible that a periodic rhythm emerges, even though no specific rhythm is imposed on the system and the interaction between the particles is completely independent of time?

For years, Frank Wilczek's idea has caused much controversy. Some considered time crystals to be impossible in principle, while others tried to find loopholes and realize time crystals under certain special conditions.

Now, a particularly spectacular kind of time crystal has successfully been created at Tsinghua University in China, with the support from TU Wien in Austria. The team used laser light and special types of atoms, namely Rydberg atoms, with a diameter that is several hundred times larger than normal.  The results have been published in the journal Nature Physics.

The ticking of a clock is also an example of a temporally periodic movement. However, it does not happen by itself: Someone must have wound the clock and started it at a certain time. This starting time then determined the timing of the ticks. It is different with a time crystal:

According to Wilczek's idea, a periodicity should arise spontaneously, although there is actually no physical difference between different points in time.

The tick frequency is predetermined by the physical properties of the system, but the times at which the tick occurs are completely random; this is known as spontaneous symmetry breaking.

How this new work was done: 

Laser light was shone into a glass container filled with a gas of rubidium atoms. The strength of the light signal that arrived at the other end of the container was measured.

This is actually a static experiment in which no specific rhythm is imposed on the system. 

The interactions between light and atoms are always the same, the laser beam has a constant intensity. But surprisingly, it turned out that the intensity that arrives at the other end of the glass cell begins to oscillate in highly regular patterns.

The key to the experiment was to prepare the atoms in a special way: The electrons of an atom can orbit the nucleus on different paths, depending on how much energy they have. If energy is added to the outermost electron of an atom, its distance from the atomic nucleus can become very large.

Part1

In extreme cases, it can be several hundred times further away from the nucleus than usual. In this way, atoms with a giant electron shell are created—so-called Rydberg atoms.

If the atoms in their glass container are prepared in such Rydberg states and their diameter becomes huge, then the forces between these atoms also become very large.

And that in turn changes the way they interact with the laser. If you choose laser light in such a way that it can excite two different Rydberg states in each atom at the same time, then a feedback loop is generated that causes spontaneous oscillations between the two atomic states. This in turn also leads to oscillating light absorption. All by themselves, the giant atoms stumble into a regular beat, and this beat is translated into the rhythm of the light intensity that arrives at the end of the glass container.

So the researchers have created a new system here that provides a powerful platform for deepening their understanding of the time crystal phenomenon in a way that comes very close to Frank Wilczek's original idea.
Precise, self-sustained oscillations could be used for sensors.

Xiaoling Wu et al, Dissipative time crystal in a strongly interacting Rydberg gas, Nature Physics (2024). DOI: 10.1038/s41567-024-02542-9. On arXiv: arxiv.org/html/2305.20070v3

Part 2

New study sheds light on brain responses to emotionally-charged scenes

The ability to recognize and respond to emotionally-charged situations is essential to a species' evolutionary success. A new study published in Nature Communications advances our understanding of how the brain responds to emotionally charged objects and scenes.

This new  research reveals that the occipital temporal cortex is tuned not only to different categories of stimuli but it also breaks down these categories based on their emotional characteristics in a way that is well suited to guide selection between alternate behaviours.

The researchers analyzed the brain activity of a small group of volunteers viewing over 1,500 images depicting natural emotional scenes such as a couple hugging, an injured person in a hospital bed, a luxurious home, and an aggressive dog. Participants were asked to categorize the images as positive, negative or neutral and to also rate the emotional intensity of the images.

A second group of participants picked the behavioural responses that best matched each scene.

Using cutting-edge modeling of brain activity divided into tiny cubes (of under 3mm3), the study discovered that the occipital temporal cortex (OTC), a region at the back of the brain, is tuned to represent both the type of stimulus (single human, couple, crowd, reptile, mammal, food, object, building, landscape etc.) and the emotional characteristics of the stimulus—whether it's negative, positive or neutral and also whether it's high or low in emotional intensity. 

Machine learning showed that these stable tuning patterns were more efficient in predicting the behaviors matched to the images by the second group of participants than could be achieved by applying machine learning directly to image features—suggesting that the OTC efficiently extracts and represents the information needed to guide behaviour.

These findings expand our knowledge of how the human brain represents emotional natural stimuli.

Occipital-temporal cortical tuning to semantic and affective features of natural images predicts associated behavioral responses, Nature Communications (2024). DOI: 10.1038/s41467-024-49073-8

First local extinction due to sea level rise identified in the US

The United States has lost its only stand of the massive Key Largo tree cactus in what researchers think is the first local extinction of a species caused by sea level rise in the country.

The Key Largo tree cactus (Pilosocereus millspaughii) still grows on a few scattered islands in the Caribbean, including northern Cuba and parts of the Bahamas. In the United States, it was restricted to a single population in the Florida Keys, first discovered in 1992 and monitored intermittently since.

Salt water intrusion from rising seas, soil depletion from hurricanes and high tides, and herbivory by mammals had put significant pressure on the population. By 2021, what had been a thriving stand of about 150 stems was reduced to six ailing fragments, which researchers salvaged for off-site cultivation to ensure their survival.

"Unfortunately, the Key Largo tree cactus may be a bellwether for how other low-lying coastal plants will respond to climate change," say scientists. 

But don't worry, the researchers are studying and trying to rescue the remnants of a dwindling stock of this cactus. 

 First U.S. vascular plant extirpation linked to sea level rise? Pilosocereus millspaughii (Cactaceae) in the Florida Keys, U.S.A., Journal of the Botanical Research Institute of Texas (2024). DOI: 10.17348/jbrit.v18.i1.1350

'Unhealthy' gut microbiome patterns linked to heightened risk of death after organ transplant

'Unhealthy' gut microbiome patterns are linked to a heightened risk of death after a solid organ transplant, finds research published online in the journal Gut.

While these particular microbial patterns are associated with deaths from any cause, they are specifically associated with deaths from cancer and infection, regardless of the organ—kidney, liver, heart, or lung—transplanted, the findings show.

The make-up of the gut microbiome is associated with various diseases, including inflammatory bowel disease and diabetes. But few studies have had the data to analyze the association between the gut microbiome and long term survival, explain the researchers.

And while a shift away from a normal pattern of microbes to an 'unhealthy' pattern, known as gut dysbiosis, has been linked to a heightened risk of death generally, it's not clear whether this might also be associated with overall survival in specific diseases, they add.

To find out, they looked at the relationship between gut dysbiosis and death from all and specific causes in solid organ transplant recipients among whom the prevalence of gut dysbiosis is much higher than that of the general population. This makes them an ideal group to study the associations between gut dysbiosis and long term survival, say the researchers.

Part1

To find out, they looked at the relationship between gut dysbiosis and death from all and specific causes in solid organ transplant recipients among whom the prevalence of gut dysbiosis is much higher than that of the general population. This makes them an ideal group to study the associations between gut dysbiosis and long term survival, say the researchers.

They analyzed the microbiome profiles from 1,337 fecal samples provided by 766 kidney, 334 liver, 170 lung, and 67 heart transplant recipients and compared those with the gut microbiome profiles of 8,208 people living in the same geographical area of northern Netherlands.

The average age of the transplant recipients was 57, and over half were men (784; 59%). On average, they had received their transplant 7.5 years previously.

Part2

During a follow-up period of up to 6.5 years, 162 recipients died: 88 kidney, 33 liver, 35 lung and six heart recipients. Forty eight (28%) died from an infection, 38 (23%) from cardiovascular disease, 38 (23%) from cancer, and 40 (25%) from other causes.

The researchers looked at several indicators of gut dysbiosis in these samples: microbial diversity; how much their gut microbiomes differed from the average microbiome of the general population; the prevalence of antibiotic resistance genes; and virulence factors which help bacteria to invade cells and evade immune defenses.
The analysis revealed that the more the gut microbiome patterns of the transplant recipients diverged from those of the general population, the more likely they were to die sooner after their procedure, irrespective of the organ transplanted.

Similar associations emerged for the abundance of antibiotic resistance genes and virulence factors.

The researchers identified 23 bacterial species among all the transplant recipients that were associated with either a heightened or lower risk of death from all causes.
Part3

The researchers further analyzed all bacterial species simultaneously using AI. This revealed a second pattern of 19 different species that were also associated with an increased risk of death.

This is an observational study, and as such, no definitive conclusions can be drawn about the causal roles of particular bacteria.

But, conclude the researchers, "Our results support emerging evidence showing that gut dysbiosis is associated with long-term survival, indicating that gut microbiome targeting therapies might improve patient outcomes, although causal links should be identified first."

 Casper Swarte et al, Multiple indicators of gut dysbiosis predict all-cause and cause-specific mortality in solid organ transplant recipients, Gut (2024). DOI: 10.1136/gutjnl-2023-331441

Part4