Novel biomarker catches aging cells in the act

Researchers have identified interleukin-23 receptor (IL-23R) as a significant biomarker of cellular senescence and aging in both mice and humans. Experiments show that IL-23R levels in the bloodstream increase with age and can decrease, reflecting senescent cell clearing, with senolytic therapies.

Cellular senescence occurs when cells stop dividing but do not trigger apoptosis mechanisms that would allow them to die naturally. Instead, they are stuck in a zombie-like state, where they still have the urge to feed and carry out metabolic activities, but with increasingly incoherent cell signaling and increased pro-inflammatory cytokine secretions.

Senescent cell activity has been linked to several age-related diseases, including those of the immune, cardiovascular, metabolic, pulmonary, musculoskeletal and neurological systems.
Scientists have been searching for a biomarker that reliably estimates the levels of active senescent cells in the body. If found, this biomarker could inform clinical interventions, potentially intervening before disease conditions present themselves.

In the study "IL-23R is a senescence-linked circulating and tissue biomarker of aging," published in Nature Aging, researchers sought to identify senescence-related biomarkers and measure their responsiveness to different therapeutics in mice of various ages.

The team tested 92 plasma proteins through the Olink Target 96 Mouse Exploratory panel and ultimately analyzed 67 (25 were excluded due to low or no detection).

Tissues, including kidney, liver, spleen, cerebral cortex, adipose and lung, were examined with real-time PCR for 21 gene expressions related to senescence secretions and inflammation markers.
Part 1

Applying short-term interventions with drugs that clear senescent cells, including venetoclax, navitoclax, fisetin and luteolin, as well as transgenic clearance methods targeting p16-positive senescent cells, mice were examined for changes in plasma proteins and tissue transcripts.

Analyses showed that three of the tested plasma proteins, IL-23R, CCL5 and CA13, displayed age-related alterations in circulation and tissues, indicating potential biomarker marker viability.

Age-dependent increases in IL-23R and CCL5 were reversed by senolytic treatment, and CA13 levels, which normally decline with age, were restored to more youthful levels.

Researchers identified IL-23R as the most promising plasma protein biomarker due to its obvious and consistent association with aging across multiple tissue parameters. IL-23R increased with age in both mice and humans and had a robust change response to senolytic interventions.

The strong correlation between IL-23R and other well-defined senescence tissue markers makes it a potential reliable biomarker of systemic senescent cell burden, offering an important new tool for probing and possibly preventing age-related diseases.

Chase M. Carver et al, IL-23R is a senescence-linked circulating and tissue biomarker of aging, Nature Aging (2024). DOI: 10.1038/s43587-024-00752-7

Part 2

**

New genetic mutation found to suppress cancer growth

 Researchers have identified a genetic mutation that slows the growth of melanoma and potentially other cancers by harnessing the power of the immune system. Their findings, published in the Journal of Experimental Medicine, could lead to new treatments that improve outcomes from existing cancer immunotherapies.

Researchers have identified many genes, known as oncogenes, that initiate and drive cancer when mutated. Although scientists have long speculated that mutations protecting against cancer also exist in the human genome but finding them by studying human subjects has been difficult because people carrying these genetic variants don't show any obvious differences compared to others.

To search for genes that confer tumor resistance, researchers created mouse models with various genetic mutations and then searched for mice that didn't develop tumors or had limited cancer growth. Next, they used a method recently developed  called automated meiotic mapping (AMM), which traces unusual features of interest in mutant mice to the causative mutations.

Part 1

The researchers quickly homed in on a gene called H2-Aa. Mice carrying two mutated copies of this gene, causing them to completely lack the H2-Aa protein, often showed no tumor growth after exposure to melanoma cells. Those carrying one mutant copy had significantly reduced growth compared with mice carrying strictly the "wild type" form of the gene. H2-Aa is responsible for producing part of an immune protein called MHC class II, which helps the immune system distinguish self-proteins from non-self-proteins, readying it to attack potential invaders.
Using genetic engineering, the researchers narrowed H2-Aa's cancer-supporting function to its presence on the surface of a subclass of immune cells called dendritic cells. Eliminating H2-Aa in only these cells was enough to mimic having the absence of H2-Aa throughout the body. When the researchers compared tumors that developed in wild-type mice and those in mice lacking H2-Aa, the tumors in mutant mice were infiltrated with more dendritic cells as well as more tumor-fighting CD8 T cells, and far fewer regulatory T cells that suppress anticancer immune activity.

Seeking a pharmaceutical that could produce the same effects as mutant H2-Aa, the researchers developed a monoclonal antibody—a protein that blocks the effects of other proteins—against H2-Aa. Although the antibody had a considerable anticancer effect when delivered to mice with melanoma tumors, its effect was greatly enhanced when the researchers also treated the same mice with a checkpoint inhibitor drug, a type of immunotherapy. On the other hand, without monoclonal antibodies against H2-Aa, checkpoint inhibitors had no effect on cancer growth.
Monoclonal antibodies targeting the human form of this and other closely related proteins could have a similar effect, serving as a viable cancer treatment on its own or as a boost to immunotherapy treatments. This idea might eventually be tested in clinical trials.

Hexin Shi et al, Suppression of melanoma by mice lacking MHC-II: Mechanisms and implications for cancer immunotherapy, Journal of Experimental Medicine (2024). DOI: 10.1084/jem.20240797

Part 2

 Bacteria in human gut rarely update their CRISPR defense systems

Within the human digestive tract are trillions of bacteria from thousands of different species. These bacteria form communities that help digest food, fend off harmful microbes, and play many other roles in maintaining human health.

These bacteria can be vulnerable to infection from viruses called bacteriophages. One of bacterial cells' most well-known defenses against these viruses is the CRISPR system, which evolved in bacteria to help them recognize and chop up viral DNA.

A new study  has yielded new insight into how bacteria in the gut microbiome adapt their CRISPR defenses as they encounter new threats. The researchers found that while bacteria grown in the lab can incorporate new viral recognition sequences as quickly as once a day, bacteria living in human gut add new sequences at a much slower rate—on average, one every three years.

The findings suggest that the environment within the digestive tract offers many fewer opportunities for bacteria and bacteriophages to interact than in the lab, so bacteria don't need to update their CRISPR defenses very often. It also raises the question of whether bacteria have more important defense systems than CRISPR.

This finding is significant because we use microbiome-based therapies like fecal microbiota transplant to help treat some diseases, but efficacy is inconsistent because new microbes do not always survive in patients. Learning about microbial defenses against viruses helps us to understand what makes a strong, healthy microbial community.

In bacteria, CRISPR serves as a memory immune response. When bacteria encounter viral DNA, they can incorporate part of the sequence into their own DNA. Then, if the virus is encountered again, that sequence produces a guide RNA that directs an enzyme called Cas9 to snip the viral DNA, preventing infection.

These virus-specific sequences are called spacers, and a single bacterial cell may carry more than 200 spacers. These sequences can be passed onto offspring, and they can also be shared with other bacterial cells through a process called horizontal gene transfer.

Previous studies have found that spacer acquisition occurs very rapidly in the lab, but the process appears to be slower in natural environments.

Part 1

The researchers looked at how CRISPR sequences changed over time in two different datasets obtained by sequencing microbes from the human digestive tract. One of these datasets contained 6,275 genomic sequences representing 52 bacterial species, and the other contained 388 longitudinal "metagenomes," that is, sequences from many microbes found in a sample, taken from four healthy people.
By analyzing those two datasets, the researchers found out that spacer acquisition is really slow in human gut microbiome: On average, it would take 2.7 to 2.9 years for a bacterial species to acquire a single spacer in our gut, which is super surprising because our gut is challenged with viruses almost every day from the microbiome itself and in our food.
--
The researchers then built a computational model to help them figure out why the acquisition rate was so slow. This analysis showed that spacers are acquired more rapidly when bacteria live in high-density populations. However, the human digestive tract is diluted several times a day, whenever a meal is consumed. This flushes out some bacteria and viruses and keeps the overall density low, making it less likely that the microbes will encounter a virus that can infect them.
Another factor may be the spatial distribution of microbes, which the researchers think prevents some bacteria from encountering viruses very frequently.

Sometimes one population of bacteria may never or rarely encounter a phage because the bacteria are closer to the epithelium in the mucus layer and farther away from a potential exposure to viruses.
--
Among the populations of bacteria that they studied, the researchers identified one species—Bifidobacteria longum—that had gained spacers much more recently than others. The researchers found that in samples from unrelated people, living on different continents, B. longum had recently acquired up to six different spacers targeting two different Bifidobacteria bacteriophages.
This acquisition was driven by horizontal gene transfer—a process that allows bacteria to gain new genetic material from their neighbors. The findings suggest that there may be evolutionary pressure on B. longum from those two viruses.
Analyzing microbes' immune defenses may offer a way for scientists to develop targeted treatments that will be most effective in a particular patient, the researchers say. For example, they could design therapeutic microbes that are able to fend off the types of bacteriophages that are most prevalent in that person's microbiome, which would increase the chances that the treatment would succeed.

An-Ni Zhang et al. CRISPR-Cas spacer acquisition is a rare event in human gut microbiome, Cell Genomics (2024). DOI: 10.1016/j.xgen.2024.100725. www.cell.com/cell-genomics/ful … 2666-979X(24)00354-9

Part 2

Microplastics found in multiple human organ tissues correlated with lesions

Researchers have recently performed a metadata investigation into the presence of microplastics in humans. They report a concerning relationship between micro and nanoplastic (MNP) concentrations in damaged tissues and links with multiple health conditions.

With the increased use in consumer products came elevated microscopic plastic pollution circulating in soil and waterways, eventually accumulating in the environment, food webs and human tissues.

In the study, "Mapping micro(nano)plastics in various organ systems: Their emerging links to human diseases?" published in TrAC Trends in Analytical Chemistry, investigators collected 61 available research articles for MNP detection in human tissues, plus 840 articles on MNP toxicological mechanisms.

Data came from spectroscopy, microscopy, and pyrolysis-gas chromatography/mass spectrometry investigations to identify polymer types in different tissues. Toxicological studies employed cell models and animal experiments to examine oxidative stress, inflammatory responses, and related signaling pathways.

The studies documented particles detected in skin, arteries, veins, thrombi, bone marrow, testes, semen, uterus, and placenta. MNPs were found in the digestive system, from saliva to feces, liver, and gallstones.

Within the respiratory system, MNPs were everywhere, including lung tissue, with microscopic fibers common in bronchoalveolar lavage fluid and sputum. Positive correlations emerged between particle abundance and specific disorders, such as inflammatory bowel disease, thrombosis, cervical cancer, and uterine fibroids.

Toxicological tests showed possible MNP-triggered oxidative stress, mitochondrial dysfunction, inflammatory responses, and apoptosis in various cell types, along with organ-level concerns like neurodegenerative disease onset when crossing the blood-brain barrier.

A critically important signal in the metadata discovered by the researchers was that measured levels of MNPs tended to be higher in tissues with lesions than in non-lesioned tissues. These included inflamed intestines, fibrotic lungs, or cancerous growths, suggesting a potential link between MNP buildup and local pathology.

Part 1

what came first, the lesion or the microplastic," it is possible that MNPs contribute to inflammation, oxidative stress, and cellular damage, which can cause or worsen tissue lesions. But it is also possible that these lesions accumulate more MNPs in already damaged tissue areas. While the current findings do not provide a direct cause-and-effect relationship, they offer good targets for further study.
There are no conventional methods for removing microplastics from the environment or human tissues. While efforts are underway to discover methods of environmental mitigation, developing such strategies to handle diverse particle sizes and chemistries of the particles embedded in living tissues presents an immense and potentially unattainable challenge.

Yating Luo et al, Mapping micro(nano)plastics in various organ systems: Their emerging links to human diseases?, TrAC Trends in Analytical Chemistry (2024). DOI: 10.1016/j.trac.2024.118114

Part 2

Analysis of 160,000 films shows rise in 'murderous verbs' since 1970

The amount of murdering and killing in movies has increased overall over the past 50 years, according to a study that analyzed a massive database of film dialogue.

Researchers used machine learning to search a database of subtitles from more than 160,000 English-language movies produced from 1970 to 2000. They calculated the amount of dialogue from characters using variations of the words "murder" or "kill" in each of the films.

While the total use of these "murderous verbs" varied widely from year to year, there was a clear increasing trend over the five-decade period.

And not just in crime movies, where violence might be expected. Characters in noncrime movies are also talking more about killing and murdering today than they did 50 years ago.

It is still happening. Researchers found increases in violence cross all genres.

These findings suggest that references to killing and murder in movie dialogue not only occur far more frequently than in real life but are also increasing over time.

Movies are trying to compete for the audience's attention and research shows that violence is one of the elements that most effectively hooks audiences."

That means we need to promote "mindful consumption and media literacy to protect vulnerable populations, especially children," the researchers wrote in the study.

Why only in English movies, we find this trend in all Indian language movies too!

Trends of Violence in Movies During the Past Half Century, JAMA Pediatrics (2024). DOI: 10.1001/jamapediatrics.2024.5741

Preclinical study finds surges in estrogen promote binge drinking in females

The hormone estrogen regulates binge drinking in females, causing them to "pregame," or consume large quantities of alcohol in the first 30 minutes after it's offered, according to a preclinical study led by scientists at Weill Cornell Medicine. The study establishes—for what is thought to be the first time—that circulating estrogen increases binge alcohol consumption in females and contributes to known sex differences in this behaviour.

The findings, published Dec. 30 in the journal Nature Communications, could lead to novel approaches for treating alcohol use disorder.

In a 2021 study, researchers showed that a specific subpopulation of neurons in a brain region called the bed nucleus of the stria terminalis (BNST) were more excitable in female mice than in males. This enhanced activity correlated with their binge-drinking behaviour.

But what makes this neural circuit more excitable in females? Estrogen has such powerful effects on so many behaviors, particularly in females. So, it makes sense that it would also modulate drinking.

To assess estrogen's potential involvement, the researchers began by monitoring the hormone levels throughout the estrous cycle of female mice. Then, they served up the alcohol. They found that when a female has a high level of circulating estrogen, she drinks much more than on days when her estrogen is low.

That enhanced binging behaviour was reflected in heightened activity in those same neurons in the BNST. When a female takes her first sip from the bottle containing alcohol, those neurons go crazy. And if she's in a high-estrogen state, they go even crazier. That extra boost of neural activity means the mice hit the bottle even harder, particularly within the first 30 minutes after the alcohol was made available, a behavior researchers refer to as "front-loading."
part2

Although the researchers suspected estrogen would have an effect on drinking, they were surprised by its mechanism of action. This steroid hormone typically regulates behaviours by binding to receptors that then travel to the nucleus, where they alter the activity of specific genes—a process that could take hours.

However, researchers now realized that something else must be happening when estrogen infused directly into the BNST excited the neurons and triggered binge drinking within minutes.

So, the researchers tested estrogen that had been doctored so it could not enter cells and bind to nuclear receptors—a feat of chemical engineering performed by Dr. Jacob Geri, assistant professor of pharmacology at Weill Cornell Medicine. They determined that when estrogen promotes binging, the hormone is binding to receptors on the neurons' surface, where it directly modulates cell-cell communication.
This is the first time that anybody has shown that during a normal estrous cycle, endogenous estrogen made by the ovaries can use such a rapid mechanism to control behaviour.
The team identified the estrogen receptor that mediates this effect and determined that it is expressed in the excited BNST neurons and in neurons from other brain regions that excite them. The researchers are now investigating the signaling mechanisms for this effect, and they will also examine whether the same system regulates drinking in males.

 Lia J. Zallar et al, Rapid nongenomic estrogen signaling controls alcohol drinking behavior in mice, Nature Communications (2024). DOI: 10.1038/s41467-024-54737-6

Part 3

Common Plastic Additives May Have Affected The Health of Millions

Exposure to a trio of chemicals found in many everyday household and industrial items may have contributed to millions of cases of heart disease, stroke, and deaths over the years according to estimations of the health and economic impacts of common plastic additives.

An international team of researchers pooled findings from over 1,700 existing studies from 38 different countries investigating links between people's exposure to the chemicals and certain health impacts.

The researchers argue the results are concerning enough to warrant global action, but critics say we still need conclusive proof that these chemicals are the true cause.

The suspects in question – BPA (bisphenol A), DEHP (di(2-ethylhexyl) phthalate) and PBDEs (polybrominated diphenyl ethers) – have been previously associated with serious health issues.

The safety of BPA has been questioned for a while: widespread in our food packaging, especially in the form of the epoxy that lines some food and drink cans and bottles, exposure to this compound has been linked to higher rates of ischemic heart disease and stroke.

This latest study found 5.4 million cases of ischemic heart disease and 346,000 cases of stroke in 2015 could be associated with BPA exposure. That suggests BPA exposure could be associated with 431,000 deaths. An estimate on the total economic impact suggests the resulting loss in health could have cost nations an equivalent of US$1 trillion in purchasing power.

DEHP is present in the flexible plastics of garden hoses, shower curtains, medical tubing, and synthetic leathers.

Part 1

Animal studies have shown its potential as an endocrine disruptor, affecting pregnancy in mice and puberty in rats. A study published back in 2022 found a significant link between increased DEHP metabolites in the urine samples of 5303 US adults and an increase in mortality rate. This recent study calculates 164,000 deaths worldwide could be related to DEHP exposure, with an estimated US$398 billion in equivalent economic losses.

PBDEs are a class of brominated flame retardants controversially behind advice to throw out your black plastic spatula. Common in materials that are exposed to high levels of heat, they're also present in electronics, car parts, aircraft, and certain textiles.

They can enter your body by inhalation, dermal absorption, or via your food – a seemingly unlikely route, but they've turned up in utensils, food packaging, and children's toys made from recycled black plastic.
A correlation between PBDE exposure and measures of intelligence suggests almost 12 million collective IQ points may have been lost due to maternal PBDE exposure.
The cumulative impact, it seems, is damning. BPA and DEHP may be eliminated from the body relatively quickly over a course of days, but the continuous stream of plastics in our lives means we have little relief from their exposure. The 'stickiness' of PBDE in our bodies is less clear, and depends on the specific chemical makeup.
All of the study's estimates lean heavily on the data from existing observational studies, making causation difficult to confirm. Some unrelated factor might increase people's exposure to the chemicals as well as their health problems – a diet high in fast food, for instance, would increase a person's exposure to plastics and is also known to increase the risk of cardiovascular disease.

https://www.pnas.org/doi/epub/10.1073/pnas.2412714121

Part 2

**

Needle-Free Shock Syringes for painless medical treatments

Medical practitioners have been using needles to inject medicines into human bodies for decades. But no one likes getting pricked, be it children or adults. In some cases, the fear is so strong, especially in children, that many miss out on vaccinations and other medical treatments. For patients who have diabetes, the stress is even greater as they may require frequent insulin injections. 

As a relief to patients, a team of researchers led by Prof. Viren Menezes from the Department of Aerospace Engineering at the Indian Institute of Technology Bombay (IIT Bombay) has now worked a way around to deliver drugs without needles by developing a shock syringe. In their study published in the Journal of Biomedical Materials & Devices, the IIT Bombay researchers compared the effectiveness of drug delivery by a shock syringe versus a regular needle on laboratory rats. 

Unlike syringes with needles, the shock syringe doesn’t rely on piercing the skin with a sharp tip. Instead, it uses high-energy pressure waves (shock waves) that can travel faster than the speed of sound to pierce the skin. These waves, when generated, compress the surrounding medium (such as air or liquid) through which they travel. A similar effect happens during a sonic boom; when an aircraft flies faster than the speed of sound, it creates shock waves that push and disturb the air.

The shock syringe, developed earlier in 2021 in Prof. Menezes’ lab, is slightly longer than a regular ballpoint pen. The device has a micro shock tube consisting of three sections: the driver, driven, and drug holder, which work together to create the shockwave-driven microjet for drug delivery. Pressurised nitrogen gas is applied to the shock syringe (driver section of micro shock tube part) filled with liquid drugs to create a microjet of the drug. The microjet travels at a speed nearly twice as fast as a commercial aeroplane at takeoff. This jet stream of liquid drug passes through the nozzle of the syringe before penetrating the skin. The entire process of delivering drugs using a shock syringe is rapid and gentle; most patients wouldn’t feel a thing.

To minimise tissue damage and ensure consistent and precise drug delivery, the pressure in the shock syringe is continuously monitored. Additionally, the researchers have optimised the nozzle design to have an opening of just 125 μm (roughly the width of a human hair).

The development of a shock syringe promises more than pain-free injections. It could make immunization drives quicker and more efficient for both children and adults. It could prevent the occurrence of bloodborne diseases caused by needle-stick injuries due to mishandling or improper disposal.

https://link.springer.com/article/10.1007/s44174-024-00239-4

How does a hula hoop master gravity? Mathematicians prove that body shape matters

Hula hooping is so commonplace that we may overlook some interesting questions it raises: "What keeps a hula hoop up against gravity?" and "Are some body types better for hula hooping than others?" A team of mathematicians explored and answered these questions with findings that also point to new ways to better harness energy and improve robotic positioners.

The results are the first to explain the physics and mathematics of hula hooping.

A paper based on the results appears in the Proceedings of the National Academy of Sciences.

The researchers tested different shapes and motions in a series of experiments on robotic hula hoopers using 3D-printed bodies of different shapes (e.g., cylinders, cones, hourglass shapes) to represent human forms at one-tenth the size.

These shapes were driven to gyrate by a motor, replicating the motions we take when hula hooping. Hoops approximately 6 inches in diameter were launched on these bodies, with high-speed video capturing the movements.

The results showed that the exact form of the gyration motion or the cross-section shape of the body (circle versus ellipse) wasn't a factor in hula hooping.

In all cases, good twirling motions of the hoop around the body could be set up without any special effort.

However, keeping a hoop elevated against gravity for a significant period of time was more difficult, requiring a special "body type"—one with a sloping surface as "hips" to provide the proper angle for pushing up the hoop and a curvy form as a "waist" to hold the hoop in place.

The  results explain why some people are natural hoopers and others seem to have to work extra hard.

The paper's authors conducted mathematical modeling of these dynamics to derive formulas that explained the results—calculations that could be used for other purposes.

 The math and physics involved are very subtle, and the knowledge gained could be useful in inspiring engineering innovations, harvesting energy from vibrations, and improving robotic positioners and movers used in industrial processing and manufacturing.

Xintong Zhu et al, Geometrically modulated contact forces enable hula hoop levitation, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2411588121

Abnormal blood vessel growth in the brain may be an early diagnostic sign of cognitive impairment

Gender differences define how the human brain ages, and telltale biomarkers in the blood may be strongly suggestive of cognitive impairment and dementia, according to a comprehensive new study involving more than 500 people.

Just as skin wrinkles and muscles sag, the human body's massive network of vasculature can be waylaid by the vagaries of age. Indeed, growing older can impact the very process by which healthy new blood vessels are made, resulting in aberrant angiogenesis—an abnormal and disordered formation of new vasculature.

A team of neuroscientists  was able to uncover differences in brain aging between men and women by pinpointing biomarkers—fragments of blood vessel growth factors—the remains of aberrant angiogenesis in their blood. These scientists suggest that an ailing angiogenesis system offers a new target for early intervention against neurodegenerative disorders.

Aberrant angiogenesis can contribute to the development of cognitive impairment the  new analysis published in Science Translational Medicine says.

Many forms of dementia and cognitive impairment are linked to abnormalities in small vessels and capillaries in the brain. Vascular dementia is a prime example of a brain disorder that develops as a direct consequence of blood vessel impairment. But Alzheimer's disease is among a host of others that are also marked by damaged vasculature in the brain.

As people age, vessels can lose their tensile strength as well as undergo a decline in density, and this can be accompanied by an overall slowdown in angiogenesis. While these problems do not become pervasive for many people, for some they contribute to irreversible brain disorders.

With aging, numerous pathologies result in abnormal blood vessels across calibers of vessels, from capillaries to large vessels. The pathologies present in small blood vessels are among the most insidious and yet most prevalent and detrimental consequences of aging.

 The task now, they say, is to conduct additional studies to tease out how to exploit aberrant angiogenesis as a druggable target.

Part 1

In the new study, the team studied brain imaging, clinical data, and blood markers of angiogenesis, including the family of VEGF growth factors and their receptors. VEGF stands for vascular endothelial growth factor. VEGF is critically necessary for angiogenesis and plays a central role in stimulating the growth and development of new blood vessels.

There are multiple types of VEGF that contribute to angiogenesis, with the most prominent being VEGF-A, but also VEGF-B, VEGF-C and placental growth factor, PlGF. Each has a slightly different role and binding affinity to VEGF receptors.
The research identified two main pathways to brain abnormalities—aberrant angiogenesis and sex-specific patterns in the trajectories of VEGF growth factors in the brain.

"The trajectories of some markers of angiogenesis are associated with better executive function and less brain atrophy in younger women, but not in men. However, these trajectories reversed at the age of 75, suggesting that both sex and age are critical variables for future study.
The study revealed that angiogenesis markers weren't the only ones that showed differences across a gender divide. For example, about 30% of participants were carriers of the APOE4 genotype with significant differences between men and women.

APOE4 is strongly associated with an increased risk of developing Alzheimer's disease. In the study, men represented a higher proportion of APOE4 carriers—34.2%—compared with 25.6% among women. APOE4 is also linked with elevated cholesterol levels, particularly low-density lipoprotein, or LDL, the so-called bad form of the compound, which is additionally associated with obstructed arteries.

At the beginning of the research project, the Clinical Dementia Rating scale showed that 73% of participants were considered to be functionally normal with no evidence of cognitive impairment or dementia at first visit. However, by the end of the study, only 66% were considered functionally normal. The average age was 71 at the beginning of the analysis, and 77 by the end of the study.

There were statistically significant differences between men and women for Clinical Dementia Rating scores at both first and last visit. A higher proportion of men presented with signs of cognitive impairment at both visits.

Abel Torres-Espin et al, Sexually dimorphic differences in angiogenesis markers are associated with brain aging trajectories in humans, Science Translational Medicine (2024). DOI: 10.1126/scitranslmed.adk3118

Part 2

Researchers reveal why the lung is a frequent site of cancer metastasis

More than half of cancer patients in whom the cancer spreads beyond the primary site have lung metastases. What makes the lungs such a tempting place for cancer cells?

To find out, researchers investigated the gene expression in cells from aggressive lung metastases. They found evidence for an alternative translation program. Translation is the process that uses our genetic code as a blueprint to make proteins in cells. A change in the translational program results in a set of different proteins that allow cancer cells to grow easier in the lung environment

They  found high levels of aspartate in the lungs of mice and patients with breast cancer compared to mice and patients without cancer, which suggests that aspartate may be important for lung metastasis.

Aspartate is an amino acid (a protein building block) that has very low concentrations in blood plasma but, surprisingly, very high concentrations in the lungs of mice with metastatic breast cancer.

Many proteins in our bodies can affect the translation process, among them the so-called initiation factors. One such initiation factor is eIF5A, which kickstarts translation. In the cells of cancer cells within lung metastases, the researchers found an activating modification to eIF5A called "hypusination," which was associated with higher cancer aggressiveness of lung metastases.

Aspartate has something to do with this. The researchers discovered that aspartate triggered this modification on eIF5A through an unexpected mechanism. Surprisingly, aspartate was not taken up by the cancer cells. Instead, it activated a cell surface protein called an NMDA receptor in cancer cells, leading to a signaling cascade that eventually triggered eIF5A hypusination.

This subsequently drives a translational program that enhances the ability of cancer cells to change their environment and make it more suitable for aggressive growth.

Looking at human lung tumor samples from patients with metastatic breast cancer, the scientists noted a similar translational program as in mice and an elevated expression of the NMDA receptor subunit that binds aspartate compared to metastases from other organs.

 Ginevra Doglioni et al, Aspartate signalling drives lung metastasis via alternative translation, Nature (2025). DOI: 10.1038/s41586-024-08335-7

Plastic crystals could replace greenhouse gases used in refrigerators

A team of chemical engineers  has found that a type of plastic crystal can be used as a refrigerant, possibly replacing the greenhouse gas currently used in most refrigerators. Their study is published in the journal Science.

The most commonly used gas in modern refrigerators is R-134a, a hydrofluorocarbon that has largely replaced freon. And while it does not contribute to the breakdown of the Earth's ozone layer, it is a greenhouse gas and thus, as it leaks from refrigerators, contributes to global warming. In this new effort, the researchers have found a possible replacement—one that is not even a gas.

The idea involves the use of "plastic crystals"—so named because once they are grown, their molecules can move under certain conditions. Prior research had shown that when pressurized, the molecules in organic ionic crystals move from a disorganized state to a neat grid configuration. When pressure is released, the molecules return to their disorganized state. More importantly, when they are pressed into an organized state, the crystals absorb heat, which chills the air around them.

In their work, the researchers tested several types of such crystals to find one that viably chills the air around it when compressed at ambient temperatures. They found several that were capable of pulling heat from the air at temperatures ranging from -37°C to 10°C.

To use the crystals as a refrigerant, the researchers built a compression chamber to squeeze the crystals and added a fan to blow the chilled air into the area around the device. By repeatedly squeezing and un-squeezing the crystals, the researchers found they functioned as a clean refrigerant. They acknowledge that more work is required due to the extreme amount of pressure needed to squeeze the crystals, making it an expensive way to cool a home.

 Samantha L. Piper et al, Organic ionic plastic crystals having colossal barocaloric effects for sustainable refrigeration, Science (2025). DOI: 10.1126/science.adq8396

Josep-Lluís Tamarit et al, Compressed ionic plastic crystals are cool, Science (2025). DOI: 10.1126/science.adu3670

Carbon in our bodies likely left galaxy and came back!

Life on Earth could not exist without carbon. But carbon itself could not exist without stars. Nearly all elements except hydrogen and helium—including carbon, oxygen and iron—only exist because they were forged in stellar furnaces and later flung into the cosmos when their stars died. In an ultimate act of galactic recycling, planets like ours are formed by incorporating these star-built atoms into their makeup, be it the iron in Earth's core, the oxygen in its atmosphere or the carbon in the bodies of Earthlings.

A team of scientists  recently confirmed that carbon and other star-formed atoms don't just drift idly through space until they are dragooned for new uses. For galaxies like ours, which are still actively forming new stars, these atoms take a circuitous journey. They circle their galaxy of origin on giant currents that extend into intergalactic space.

These currents—known as the circumgalactic medium—resemble giant conveyer belts that push material out and draw it back into the galactic interior, where gravity and other forces can assemble these raw materials into planets, moons, asteroids, comets and even new stars.

The heavy elements that stars make get pushed out of their host galaxy and into the circumgalactic medium through their explosive supernovae deaths, where they can eventually get pulled back in and continue the cycle of star and planet formation.

So the same carbon in our bodies most likely spent a significant amount of time outside of the galaxy.

 Samantha L. Garza et al, The CIViL* Survey: The Discovery of a C iv Dichotomy in the Circumgalactic Medium of L* Galaxies, The Astrophysical Journal Letters (2024). DOI: 10.3847/2041-8213/ad9c69

Scientists Identify New Blood Group After 50 Year Mystery

When a pregnant woman had her blood sampled back in 1972, doctors discovered it was mysteriously missing a surface molecule found on all other known red blood cells at the time.

After 50 years, this strange molecular absence finally led to researchers from the UK and Israel describing a new blood group system in humans. In September, the team published their paper on the discovery.

It represents a huge achievement, and the culmination of a long team effort, to finally establish this new blood group system and be able to offer the best care to rare, but important, patients.

While we're all more familiar with the ABO blood group system and the rhesus factor (that's the plus or minus part), humans actually have many different blood group systems based on the wide variety of cell-surface proteins and sugars that coat our blood cells.

Our bodies use these antigen molecules, amongst their other purposes, as identification markers to separate 'self' from potentially harmful not-selves.

Part 1

Blood type (or blood group) is determined, in part, by the ABO blood group antigens present on red blood cells. Antibodies in our blood plasma detect when a foreign antigen marker is present. (InvictaHOG/Public Domain/Wikimedia Commons)

Part 2

If these markers do not match up when receiving a blood transfusion, this life-saving tactic can cause reactions or even end up being fatal.

Most major blood groups were identified early in the 20th century. Many discovered since, like the Er blood system first described by researchers in 2022, only impact a small number of people. This is also the case for the new blood group.
Previous research found more than 99.9 percent of people have the AnWj antigen that was missing from the 1972 patient's blood. This antigen lives on a myelin and lymphocyte protein, leading the researchers to call the newly described system the MAL blood group.
When someone has a mutated version of both copies of their MAL genes, they end up with an AnWj-negative blood type, like the pregnant patient. Researchers identified three patients with the rare blood type that didn't have this mutation, suggesting that sometimes blood disorders can also cause the antigen to be suppressed.
MAL is a very small protein with some interesting properties which made it difficult to identify and meant we needed to pursue multiple lines of investigation to accumulate the proof we needed to establish this blood group system.
Part 3

To determine they had the correct gene, after decades of research, the team inserted the normal MAL gene into blood cells that were AnWj-negative. This effectively delivered the AnWj antigen to those cells.

The MAL protein is known to play a vital role in keeping cell membranes stable and aiding in cell transport. What's more, previous research found that the AnWj isn't actually present in newborn babies but appears soon after birth.

Interestingly, all the AnWj-negative patients included in the study shared the same mutation. However, no other cell abnormalities or diseases were found to be associated with this mutation.

Now that the researchers have identified the genetic markers behind the MAL mutation, patients can be tested to see if their negative MAL blood type is inherited or due to suppression, which could be a sign of another underlying medical problem.
These rare blood quirks can have devastating impacts on patients, so the more of them we can understand, the more lives can be saved.

Deletions in the MAL gene result in loss of Mal protein, defining the rare inherited AnWj-negative blood group phenotype

https://ashpublications.org/blood/article-abstract/144/26/2735/5174...

To understand the complex relationships between face perception, mental state judgment, trait judgment, and situational effect, they used computational models to quantitatively select a large number of faces, mental state terms, trait terms, and situation descriptions that are representative of those people encounter in everyday life.

They asked participants to view faces and infer how much those individuals would feel certain mental states in given situations. The researchers also asked a separate group of participants to look at the same images of faces and infer the traits of the people they belonged to. Using the information they gathered, they then digitally manipulated the traits of faces.

The researchers  quantified to which degree changing the perceived traits of a face would change people's expectations of how this individual may feel and think in different situations. 

To make sure that their results can be applied to a wide range of populations,  their data and models were based on participants from five continents: Africa, Asia, Europe, North America, and South America.

The researchers  closely examined how their study participants thought specific people in images would feel 60 different mental states in 60 real-world scenarios.

The researchers found that 47 of these 60 mental state inferences were shaped by how the individual looks.

This means that in most circumstances, when other people are trying to understand how you feel and think, their understanding will be biased by their first impressions of your personality (which is not necessarily your true personality but just others' judgments).

Interestingly, the researchers found that first impressions shaped mental state inferences across participants living in all five continents on Earth. This suggests that their findings are robust and the effect they observed is relevant to all people, irrespective of their nationality or cultural background.

Chujun Lin et al, How trait impressions of faces shape subsequent mental state inferences, Nature Human Behaviour (2024). DOI: 10.1038/s41562-024-02059-4.

Part 2

Global study links millions of diabetes and heart disease cases to sugary drinks

A new study from researchers  published in Nature Medicine, estimates that 2.2 million new cases of type 2 diabetes and 1.2 million new cases of cardiovascular disease occur each year globally due to consumption of sugar-sweetened beverages.

In developing countries, the case count is particularly sobering. In Sub-Saharan Africa, the study found that sugar-sweetened beverages contributed to more than 21% of all new diabetes cases. In Latin America and the Caribbean, they contributed to nearly 24% of new diabetes cases and more than 11% of new cases of cardiovascular disease.

Colombia, Mexico, and South Africa are countries that have been particularly hard hit. More than 48% of all new diabetes cases in Colombia were attributable to consumption of sugary drinks. Nearly one-third of all new diabetes cases in Mexico were linked to sugary drink consumption. In South Africa, 27.6% of new diabetes cases and 14.6% of cardiovascular disease cases were attributable to sugary drink consumption.

Sugary beverages are rapidly digested, causing a spike in blood sugar levels with little nutritional value. Regular consumption over time leads to weight gain, insulin resistance, and a host of metabolic issues tied to type 2 diabetes and heart disease, two of the world's leading causes of death.

Sugar-sweetened beverages are heavily marketed and sold in low- and middle-income nations. Not only are these communities consuming harmful products, but they are also often less well equipped to deal with the long-term health consequences.

As countries develop and incomes rise, sugary drinks become more accessible and desirable, the authors say. Men are more likely than women to suffer the consequences of sugary drink consumption, as are younger adults compared to their older counterparts, the researchers say.

"We need urgent, evidence-based interventions to curb consumption of sugar-sweetened beverages globally, before even more lives are shortened by their effects on diabetes and heart disease", the researchers emphasize.

The study's authors call for a multi-pronged approach, including public health campaigns, regulation of sugary drink advertising, and taxes on sugar-sweetened beverages.

Laura Lara-Castor, Burdens of type 2 diabetes and cardiovascular disease attributable to sugar-sweetened beverages in 184 countries, Nature Medicine (2025). DOI: 10.1038/s41591-024-03345-4

Sugary drinks, also known as sugar-sweetened beverages or "soft" drinks, include:

• Soda: Includes cola, pop, tonic, and other sodas
• Fruit drinks: Includes fruit juice, fruit punch, and lemonade
• Sports and energy drinks: Includes drinks with added sugar or other sweeteners
• Sweetened milks: Includes chocolate milk
• Sweetened teas and coffees: Includes iced tea, sweetened hot or cold tea, and sweetened coffee
• Almost all branded soft drinks

Dietary choices create distinct gut microbiomes, influencing health outcomes

A varied diet rich in vegetables is known to be healthy for one's well-being. Excessive consumption of meat, especially red meat, can lead to chronic and cardiovascular diseases. That is also because what we eat shapes the gut microbiome. At the same time, excluding certain foods, such as dairy or animal products, is not necessarily a general solution to achieve microbial balance. But can we find out which food products determine differences in the gut microbiome?

Starting from this question, a group of researchers has analyzed biological samples from 21,561 individuals (vegans, vegetarians and omnivores) living in the United States, the United Kingdom and Italy, and found that the dietary pattern has a strong influence on the gut microbiome and on specific gut microbes that are associated with better health. The data is published in Nature Microbiology.

The gut microbiome, the set of microorganisms that inhabit our intestine, plays a crucial role in determining a person's health, as it influences many aspects, from digestion to the immune response. So far, only a few large-scale studies have examined how different diets impact the composition of gut bacteria.

This study focused in particular on the differences and consequences of different diets on the microbiome. The results show that diet patterns shape the gut microbiome, as they not only determine the microbes necessary for digestion, but also the acquisition of microbes directly from the food itself.

Based on the results of the analyses,  on average vegans have the healthiest diets, followed by vegetarians and omnivores. However, the most interesting data emerged from the study of the diversity of the gut microbiome; that is, by measuring the variety of bacteria that inhabit our intestines.

Overall, there was less diversity in vegetarians and vegans than in omnivores, but scientists point out that diversity alone is not a reliable means to determine the health of the microbiome, as it does not take into account the quality and functionality of bacteria.

Part 1

The microbial signatures of vegan, vegetarian and omnivorous diets:
A key aspect of the study was to examine the differences between gut microbiomes. The researchers were able to see how each dietary pattern leads to a unique microbial signature. The microbiomes of omnivores have an increased presence of bacteria associated with meat digestion, such as Alistipes putredinis, involved in protein fermentation. Omnivores also have more bacteria associated with inflammatory bowel disease and an increased risk of colon cancer, such as Ruminococcus torques and Bilophila wadsworthia.
The microbiomes of vegans differ in the number of bacteria involved in fiber fermentation, such as several species in the Bacteroides and Firmicutes phyla, which help produce short-chain fatty acids, such as butyrate. These compounds have beneficial effects on gut health, as they reduce inflammation and maintain a better homeostatic balance with our metabolism and immune system.

Finally, the main single difference between vegetarians and vegans is the presence of Streptococcus thermophilus in the microbiome of vegetarians, a bacterium found mainly in dairy products and used in the production of yogurt.
Healthy diet and healthy microbiome
The study highlighted that it is the quality of the diet—rather than the dietary pattern itself—that influences the composition of the microbiome. People with healthier dietary patterns, whether vegan, vegetarian or omnivorous, showed a more favorable microbiome composition. This suggests that regardless of the type of diet, eating more plant-based foods and fewer animal-based foods, especially if highly processed, can be good for gut health.
Another innovative aspect of the research was the study of how bacteria transfer from food to the microbiome. The scientists found that vegans had the fewest food-associated bacteria in the microbiome, except for those derived from fruits and vegetables, which were most present. Vegetarians and omnivores, on the other hand, showed a greater number of bacteria linked to dairy products, especially fermented ones.
The researchers observed that the quantity and diversity of plant-based foods have a very positive impact on the microbiome. Avoiding meat or dairy products does not necessarily have a positive effect if it does not come with a variety of quality plant-based products. From the point of view of the microbiome, what we can generally recommend is that it is important to eat many plant-based foods, especially those rich in fiber. And that food diversity is important.

Nicola Segata, Gut microbiome signatures of vegan, vegetarian and omnivore diets and associated health outcomes across 21,561 individuals, Nature Microbiology (2025). DOI: 10.1038/s41564-024-01870-z

Part 2

Three years of solar fireworks

This video combines ultraviolet images of the sun's outer atmosphere (the corona, yellow) taken by Solar Orbiter's Extreme Ultraviolet Imager (EUI) instrument, with the size and locations of solar flares (blue circles) as recorded by the Spectrometer/Telescope for Imaging X-rays (STIX) instrument. The accompanying audio is a sonification based on the detected flares and the spacecraft's distance to the sun.

Scientists identify 11 genes affected by PFAS, shedding light on neurotoxicity

Per- and polyfluorinated alkyl substances (PFAS) earn their "forever chemical" moniker by persisting in water, soil and even the human brain. This unique ability to cross the blood-brain barrier and accumulate in brain tissue makes PFAS particularly concerning, but the underlying mechanism of their neurotoxicity must be studied further.

To that end, a new study by  researchers has identified 11 genes that may hold the key to understanding the brain's response to these pervasive chemicals commonly found in everyday items. The paper is published in the journal ACS Chemical Neuroscience.

These genes, some involved in processes vital for neuronal health, were found to be consistently affected by PFAS exposure, either expressing more or less, regardless of the type of PFAS compounds tested. For example, all compounds caused a gene key for neuronal cell survival to express less, and another gene linked to neuronal cell death to express more.

Still, the study found that hundreds more genes whose expression changed in different directions based on the compound tested. Plus, there was no correlation between the level at which PFAS accumulates in a cell and the extent to which it causes differential gene expression.

Taken together, this suggests that distinct molecular structures within each type of PFAS drive changes in gene expression.

PFAS aren't immediately toxic. We're exposed to them practically every day, including through drinking water and food packaging, and don't notice.

Therefore, researchers need to find points of assessment further upstream in the cellular process than just whether a cell lives or dies.

Part 1

The research team decided to focus on how PFAS affects the gene expression of neuronal-like cells, as well as how PFAS affects lipids, which are molecules that help make up the cell membrane, among other important functions. Exposure to different PFAS for 24 hours resulted in modest but distinct changes in lipids, and over 700 genes expressing differently.

Of the six types of PFAS tested, perfluorooctanoic acid (PFOA)—once commonly used in nonstick pans and recently deemed hazardous by the EPA—was by far the most impactful. Despite its small uptake, PFOA altered the expression of almost 600 genes—no other compound altered more than 147. Specifically, PFOA decreased the expression of genes involved in synaptic growth and neural function.

Altogether, the six compounds caused changes in biological pathways involved in hypoxia signaling, oxidative stress, protein synthesis and amino acid metabolism, all of which are crucial for neuronal function and development.

 Logan Running et al, Investigating the Mechanism of Neurotoxic Effects of PFAS in Differentiated Neuronal Cells through Transcriptomics and Lipidomics Analysis, ACS Chemical Neuroscience (2024). DOI: 10.1021/acschemneuro.4c00652

Part 2

Researchers Explore Touchless Fingerprints: The Next Step in Biometric Technology

Fingerprints have always been one of the most reliable ways to identify a person. 

Traditionally, fingerprints are captured by pressing your finger against a surface, like when you unlock your phone or when using biometric scanners at work. However, new research is exploring a touch-free way to capture fingerprints aiming to make this process cleaner, easier, and more accurate. A collaboration between researchers is looking to use a photograph of your finger to capture fingerprints.

A fingerprint is composed of unique patterns of ridges and valleys on the skin of your fingers. Features called "minutiae," where ridges end, or split, are unique to an individual and play a crucial role in distinguishing one fingerprint from another. In this study, the scientists devised a method that begins with capturing a picture of your finger instead of pressing it against a scanner. They then use a range of image processing techniques to highlight and enhance the intricate details of your fingerprint in the photo.

A method called Adaptive Thresholding helps adjust the brightness levels to make the fingerprint patterns more distinct. Next, a "Gabor Filter," which sharpens the textures, emphasizing those all-important ridges and valleys, is applied. Once the minutiae are clearly visible, they use something called a K-means clustering algorithm to remove the background from the image, much like focusing a camera lens to blur out everything except the main subject – your fingerprint. Once the image is processed, it undergoes a thinning process to make the fingerprint one pixel wide. This skeletonized version of the fingerprint is then used to extract minutiae.

Additionally, the researchers used an innovative combination of machine learning, specifically a kind of artificial intelligence called a "Siamese network," with traditional techniques. The Siamese network aids in learning patterns by comparing more than one fingerprint image and recognizing similar features, making the system very accurate. Using this combination method, the system achieves impressive accuracy, with the error rate dropping as low as 2.5% or 3.76% depending on the datasets used for testing.

While the current research is promising, there are still areas that need further exploration. Researchers are interested in testing different types of wavelets (a mathematical function used to analyze the details at different frequencies) that could potentially enhance the process and results. Additionally, they aim to develop even more advanced techniques for fusing all the gathered information, making the fingerprint identification process even more robust.

This touchless method has some immediate perks. For one, it’s more hygienic since you don’t have to physically touch a scanner. Imagine not having to worry about transferring germs and viruses, as experienced during the COVID-19 pandemic. Moreover, it overcomes problems like sensor wear and tear, which can happen very quickly when a device gets pressed repeatedly. In the future, these advancements could even allow for systems that recognize other biometric data like palm prints or face characteristics, integrating them into a singular system for even more secure identification.

https://ieeexplore.ieee.org/document/10759693

Basking too long in a sauna without adequate hydration may risk heat stroke, doctors warn

Basking too long in a sauna may put bathers at risk of heat stroke, particularly if they haven't drunk enough water beforehand, warn doctors in the journal BMJ Case Reports, after treating a woman whose condition required admission to hospital.

Although relatively rare, heat stroke can be life-threatening, even in the absence of various underlying risk factors, such as heart, lung, or neurological disease, and heavy drinking or taking a cocktail of prescription meds, they point out.

Heat stroke is defined as a sharp increase in core body temperature above 40°C that is associated with acutely impaired brain function, and 'non-exertional' heat stroke results from prolonged exposure to high environmental temperatures, explain the authors.

They treated a woman in her early 70s who had been found unconscious in her local gym's sauna, where she had been doing stretching exercises for around 45 minutes. Her core body temperature was 42°C—normal temperature is 36.4°C—her blood pressure was extremely low, and her heart rate was extremely high. She had a seizure after her arrival in emergency care.

She had previously been diagnosed with type 1 diabetes and an underactive thyroid, but she wasn't a smoker or heavy drinker, and was a regular gym goer, so had few risk factors, point out the authors.

She was rapidly cooled with wet towels and a fan and given intravenous fluids and blood products to stabilize her.

Blood tests revealed malfunctioning kidneys and liver, evidence of a minor heart attack, and muscle tissue breakdown (rhabdomyolysis).

She regained consciousness within two hours of reaching normal core temperature but was confused and drowsy for two days. By day three, this had resolved and she had no further seizures during her inpatient stay, which lasted 12 days.

After 26 days, she had more or less fully recovered, except for some mild fatigue and mild liver function disturbance.

This is just one case report after prolonged sauna use, and as far as the authors are aware, only nine other similar cases have been reported. But three of those people died as a result.

Part 1

The prognosis of heat stroke varies according to patient factors, particularly extremes of age," explain the authors. "Classical heat stroke in elderly people carries a mortality rate of [more than] 50%, and this increases further with each additional organ dysfunction.

"Heat-related deaths spike during heat waves, as has been observed in multiple large international datasets. Deaths from heat stroke are expected to rise as global temperatures continue to increase," they add.

"Once heat stroke has occurred, the key determinate of outcome is how rapidly a patient is cooled, as the time spent with elevated core body temperature is correlated to the degree of cellular damage," they emphasize.

Severe heat stroke with multiorgan failure following collapse in a sauna, BMJ Case Reports (2025). DOI: 10.1136/bcr-2024-262069

Part 2

Mathematical methods point to possibility of particles long thought impossible

From the early days of quantum mechanics, scientists have thought that all particles can be categorized into one of two groups—bosons or fermions—based on their behaviour.

However, new research shows the possibility of particles that are neither bosons nor fermions. The study, published in Nature, mathematically demonstrates the potential existence of paraparticles that have long been thought impossible.

Quantum mechanics has long held that all observable particles are either fermions or bosons. These two types of particles are distinguished by how they behave when near other particles in a given quantum state. Bosons are able to congregate in unlimited numbers, whereas only one fermion can exist in a given state. This behaviour of fermions is referred to as the Pauli exclusion principle, which states that no more than two electrons, each with opposite spins, can occupy the same orbital in an atom.

In the 1930s and 1940s, researchers began trying to understand whether other types of particles could exist. A concrete quantum theory of such particles, known as paraparticles, was formulated in 1953 and extensively studied by the high energy physics community. However, by the 1970s, mathematical studies seemed to show that so-called paraparticles were actually just bosons or fermions in disguise. The one exception was the existence of anyons, an exotic type of particle that exists only in two dimensions.

However, the mathematical theories of the 1970s and beyond were based on assumptions that are not always true in physical systems. Using a solution to the Yang-Baxter equation, an equation useful for describing the interchange of particles, along with group theory and other mathematical tools,  researchers set to work to show that paraparticles could theoretically exist and be fully compatible with the known constraints of physics.

The researchers focused on excitations—which can be thought of as particles—in condensed matter systems such as magnets to provide a concrete example of how paraparticles can emerge in nature.

Part 1

Particles aren't just these fundamental things, they're also important in describing materials.
This is cross-disciplinary research that involves several areas of theoretical physics and mathematics.
Using advanced mathematics, such as Lie algebra, Hopf algebra and representation theory, as well as a pictorial method based on something known as tensor network diagrams to better handle equations, the researchers were able to perform abstract algebraic calculations to develop models of condensed matter systems where paraparticles emerge.

They showed that, unlike fermions or bosons, paraparticles behave in strange ways when they exchange their positions with the internal states of the particles transmuting during the process.
While they are groundbreaking on their own, these models are the first step toward a better understanding of many new physical phenomena that could occur in paraparticle systems. Further development of this theory could guide experiments that could detect paraparticles in the excitations of condensed matter systems.

Zhiyuan Wang et al, Particle exchange statistics beyond fermions and bosons, Nature (2025). DOI: 10.1038/s41586-024-08262-7

Part 2

Discovery of new class of particles could take quantum mechanics one step further

Amid the many mysteries of quantum physics, subatomic particles don't always follow the rules of the physical world. They can exist in two places at once, pass through solid barriers and even communicate across vast distances instantaneously. These behaviors may seem impossible, but in the quantum realm, scientists are exploring an array of properties once thought impossible.

In a new study, physicists  have now observed a novel class of quantum particles called fractional excitons, which behave in unexpected ways and could significantly expand scientists' understanding of the quantum realm.

The findings point toward an entirely new class of quantum particles that carry no overall charge but follow unique quantum statistics.

The most exciting part is that this discovery unlocks a range of novel quantum phases of matter, presenting a new frontier for future research, deepening our understanding of fundamental physics, and even opening up new possibilities in quantum computation.

The research   was published in Nature on Wednesday, Jan. 8.

The team's discovery centers around a phenomenon known as the fractional quantum Hall effect, which builds on the classical Hall effect, where a magnetic field is applied to a material with an electric current to create a sideways voltage.

The quantum Hall effect, occurring at extremely low temperatures and high magnetic fields, shows that this sideways voltage increases in clear, separate jumps. In the fractional quantum Hall effect, these steps become even more peculiar, increasing by only fractional amounts—carrying a fraction of an electron's charge.

In their experiments, the researchers built a structure with two thin layers of graphene, a two-dimensional nanomaterial, separated by an insulating crystal of hexagonal boron nitride. This setup allowed them to carefully control the movement of electrical charges. It also allowed them to generate particles known as excitons, which are formed by combining an electron and the absence of an electron known as a hole.

They then exposed the system to incredibly strong magnetic fields that are millions of times stronger than Earth's. This helped the team observe the novel fractional excitons, which showed an unusual set of behaviours.

Fundamental particles typically fall into two categories. Bosons are particles that can share the same quantum state, meaning many of them can exist together without restrictions. Fermions, on the other hand, follow what's known as the Pauli exclusion principle, which says no two fermions can occupy the same quantum state.

The fractional excitons observed in the experiment, however, didn't fit cleanly into either category. While they had the fractional charges expected in the experiment, their behavior showed tendencies of both bosons and fermions, acting almost like a hybrid of the two. That made them more like anyons, a particle type that sits between fermions and bosons—yet the fractional excitons had unique properties that set them apart from anyons, as well.

Part 1

This unexpected behavior suggests fractional excitons could represent an entirely new class of particles with unique quantum properties.

This shows that excitons can exist in the fractional quantum Hall regime and that some of these excitons arise from the pairing of fractionally charged particles, creating fractional excitons that don't behave like bosons.

The existence of a new class of particles could one day help improve the way information is stored and manipulated at the quantum level, leading to faster and more reliable quantum computers, the team noted.

Naiyuan J. Zhang et al, Excitons in the fractional quantum Hall effect, Nature (2025). DOI: 10.1038/s41586-024-08274-3. www.nature.com/articles/s41586-024-08274-3

Part 2

Human 'domainome' reveals root cause of heritable disease

Most mutations which cause disease by swapping one amino acid out for another do so by making the protein less stable, according to a massive study of human protein variants published in the journal Nature. Unstable proteins are more likely to misfold and degrade, causing them to stop working or accumulate in harmful amounts inside cells.

The work helps explain why minimal changes in the human genome, also known as missense mutations, cause disease at the molecular level. The researchers discovered that protein instability is one of the main drivers of heritable cataract formation, and also contributes to different types of neurological, developmental and muscle-wasting diseases.

Researchers  studied 621 well-known disease-causing missense mutations. Three in five (61%) of these mutations caused a detectable decrease in protein stability.

The study looked at some disease-causing mutations more closely. For example, beta-gamma crystallins are a family of proteins essential for maintaining lens clarity in the human eye. They found that 72% (13 out of 18) of mutations linked to cataract formation destabilize crystallin proteins, making the proteins more likely to clump together and form opaque regions in the lens.

The study also directly linked protein instability to the development of reducing body myopathy, a rare condition which causes muscle weakness and wasting, as well as ankyloblepharon-ectodermal defects-clefting (AEC) syndrome, a condition characterized by the development of a cleft palate and other developmental symptoms.

However, some disease-causing mutations did not destabilize proteins and shed light on alternative molecular mechanisms at play.

Part 1

Rett Syndrome is a neurological disorder which causes severe cognitive and physical impairments. It is caused by mutations in the MECP2 gene, which produces a protein responsible for regulating gene expression in the brain.
The study found that many mutations in MECP2 do not destabilize the protein but are instead found in regions which affect how MECP2 binds to DNA to regulate other genes. This loss of function could be disrupting brain development and function.
By distinguishing whether a mutation destabilizes a protein or alters its function without affecting stability, we can tailor more precise treatment strategies. This could mean the difference between developing drugs that stabilize a protein versus those that inhibit a harmful activity. It's a significant step toward personalized medicine.
The study also found that the way mutations cause disease often relates to whether the disease is recessive or dominant. Dominant genetic disorders occur when a single copy of a mutated gene is enough to cause the disease, even if the other copy is normal, while recessive conditions occur when an individual inherits two copies of a mutated gene, one from each parent.

Mutations causing recessive disorders were more likely to destabilize proteins, while mutations causing dominant disorders often affected other aspects of protein function, such as interactions with DNA or other proteins, rather than just stability.

For example, the study found that a recessive mutation in the CRX protein, which is important for eye function, destabilizes the protein significantly, which could be causing heritable retinal dystrophies because the lack of a stable, functional protein impairs normal vision.

However, two different types of dominant mutations meant the protein remained stable but functioned improperly anyway, causing retinal disease even though the protein's structure is intact.
Part 2

The discoveries were possible thanks to the creation of Human Domainome 1, an enormous library of protein variants. The catalog includes more than half a million mutations across 522 human protein domains, the bits of a protein which determine its function. It is the largest catalog of human protein domain variants to date.

Protein domains are specific regions which can fold into a stable structure and perform a job independently of the rest of the protein. Human Domainome 1 was created by systematically changing each amino acid in these domains to every other possible amino acid, creating a catalog of all possible mutations.

The impact of these mutations on protein stability was discovered by introducing mutated protein domains into yeast cells. The transformed yeast could only produce one type of mutated protein domain, and cultures were grown in test tubes under conditions which linked the stability of the protein to the growth of the yeast. If a mutated protein was stable, the yeast cell would grow well. If the protein was unstable, the yeast cell's growth would be poor.
Using a special technique, the researchers ensured only the yeast cells producing stable proteins could survive and multiply. By comparing the frequency of each mutation before and after the yeast growth, they determined which mutations led to stable proteins and which caused instability.

Though Human Domainome 1 is around 4.5 times bigger than previous libraries of protein variants, it still only covers 2.5% of known human proteins. As researchers increase the size of the catalog, the exact contribution of disease-causing mutations to protein instability will become increasingly clear.

In the meantime, researchers can use the information from the 522 protein domains to extrapolate to proteins that are similar. This is because mutations often have similar effects on proteins that are structurally or functionally related. By analyzing a diverse set of protein domains, the researchers discovered patterns in how mutations affect protein stability that are consistent across related proteins.

Essentially, this means that data from one protein domain can help predict how mutations will impact other proteins within the same family or with similar structures. The 'rules' from these 522 domains are enough to help us make educated predictions about many more proteins than there are in the catalog.
The study has limitations. The researchers examined protein domains in isolation rather than within full-length proteins. In living organisms, proteins interact with other parts of the protein and with other molecules in the cell.

The study might not fully capture how mutations affect proteins in their natural habitat inside human cells. The researchers plan on overcoming this by studying mutations in longer protein domains, and eventually, full-length proteins.

Ben Lehner, Site saturation mutagenesis of 500 human protein domains, Nature (2025). DOI: 10.1038/s41586-024-08370-4. www.nature.com/articles/s41586-024-08370-4

Part 3

Plant cells gain immune capabilities when it's time to fight disease, scientists discover

Human bodies defend themselves using a diverse population of immune cells that circulate from one organ to another, responding to everything from cuts to colds to cancer. But plants don't have this luxury.

Because plant cells are immobile, each individual cell is forced to manage its own immunity in addition to its many other responsibilities, like turning sunlight into energy or using that energy to grow. How these multitasking cells accomplish it all—detecting threats, communicating those threats, and responding effectively?

Research by  scientists reveals how plant cells switch roles to protect themselves against pathogens. When a threat is encountered, the cells enter a specialized immune state and temporarily become PRimary IMmunE Responder (PRIMER) cells—a new cell population that acts as a hub to initiate the immune response.

The researchers also discovered that PRIMER cells are surrounded by another population of cells they call bystander cells, which seem to be important for transmitting the immune response throughout the plant.

The findings, published in Nature on January 8, 2025, bring researchers closer to understanding the plant immune system—an increasingly important task amid the growing threats of antimicrobial resistance and climate change, which both escalate the spread of infectious disease.

Plants encounter a wide range of pathogens, like bacteria that sneak in through leaf surface pores or fungi that directly invade plant "skin" cells. Since plant cells are stationary, when they encounter any of these pathogens, they become singularly responsible for responding and alerting nearby cells.

Another interesting side effect of immobile cells is the fact that different pathogens may enter a plant at different locations and times, leading to varying immune response stages occurring simultaneously across the plant.

With factors like timing, location, response state, and more all at play, an infected plant is a complicated organism to understand.

To tackle this, the research team turned to two sophisticated cell profiling techniques called time-resolved single-cell multiomics and spatial transcriptomics. By pairing the two, the team was able to capture the plant immune response in each cell with unprecedented spatiotemporal resolution.

Discovering these rare PRIMER cells and their surrounding bystander cells is a huge insight into how plant cells communicate to survive the many external threats they face day-to-day.

Joseph Ecker, A rare PRIMER cell state in plant immunity, Nature (2025). DOI: 10.1038/s41586-024-08383-z. www.nature.com/articles/s41586-024-08383-z

Why do birds make so many different sounds?

Birds make sounds to communicate, whether to find a potential mate, ward off predators, or just sing for pleasure.

But the conditions that contribute to the immense diversity of the sounds they make are not well understood. Researchers have conducted the first-ever global study of the factors that influence bird sounds, using more than 100,000 audio recordings from around the world. The new study, recently published in the journal Proceedings of the Royal Society B, revealed insightful patterns for why birds make certain noises and at what frequency.

Researchers analyzed audio recordings of bird sounds taken by people around the world and submitted to a bird-watching repository called xeno-canto. The analyzed recordings represented 77% of known bird species.

The study's major takeaways included:

The habitats of bird species influence the frequency of the sounds they may make in unexpected ways. For example, in ecosystems with a lot of rushing water there is a constant level of white noise occurring at a lower frequency. In such cases, researchers found that birds tend to make sounds of higher frequency, likely so they wouldn't be drowned out by the water.

Bird species living at the same latitudes make similar sounds. Observing this pattern on a global scale is an important piece of the puzzle in the evolutionary story of bird sounds. It could inspire further research into the aspects of geographic location that influence bird sounds.

A bird's beak shape and body mass are important. Generally, smaller birds create higher frequency sounds while larger birds create lower frequency sounds. The global analysis not only proved this hypothesis correct, but it also added new information about the nature of the relationship between beak shape, body mass and sound.

Smaller bird species tend to have a wider range of frequencies at which they can make sound as a protection mechanism. Smaller, more vulnerable birds can benefit from being able to make a range of sounds. Higher frequencies can help them communicate with fellow birds of the same species, while lower frequencies can serve as camouflage, tricking potential threats into thinking they are larger and less vulnerable than they actually are.

The research also contributed to the broader understanding of soundscapes—all of the sounds heard in any particular landscape.

: H. S. Sathya Chandra Sagar et al, Global analysis of acoustic frequency characteristics in birds, Proceedings of the Royal Society B: Biological Sciences (2024). DOI: 10.1098/rspb.2024.1908

What we eat not only affects our health—but can also alter how our genes function

Fiber is well known to be an important part of a healthy diet, yet not many take it as 'food'.

 A study from  Medical field might finally convince us to fill our plates with beans, nuts, cruciferous veggies, avocados and other fiber-rich foods.

The research, published in Nature Metabolism on Jan. 9 identified the direct epigenetic effects of two common byproducts of fiber digestion and found that some of the alterations in gene expression had anti-cancer actions.

When we eat fiber, the gut microbiome produces short-chain fatty acids. These compounds are more than just an energy source for us: they have long been suspected to indirectly affect gene function. The researchers traced how the two most common short-chain fatty acids in our gut, propionate and butyrate, altered gene expression in healthy human cells, in treated and untreated human colon cancer cells, and in mouse intestines.

They found direct epigenetic changes at specific genes that regulate cell proliferation and differentiation, along with apoptosis, or pre-programmed cell death processes—all of which are important for disrupting or controlling the unchecked cell growth that underlies cancer.

A direct link between eating fiber and modulation of gene function that has anti-cancer effects is likely a global mechanism because the short-chain fatty acids that result from fiber digestion can travel all over the body. 

It is generally the case that people's diet is very fiber poor, and that means their microbiome is not being fed properly and cannot make as many short-chain fatty acids as it should. This is not doing our health any favours.

By identifying the gene targets of these important molecules, we can understand how fiber exerts its beneficial effects and what goes wrong during cancer.

Short-chain fatty acid metabolites propionate and butyrate are unique epigenetic regulatory elements linking diet, metabolism and gene expression, Nature Metabolism (2025). DOI: 10.1038/s42255-024-01191-9

Scientists drill nearly 2 miles down to pull 1.2 million-year-old ice core from Antarctic

An international team of scientists announced this week they've successfully drilled one of the oldest ice cores yet, penetrating nearly 2 miles (2.8 kilometers) to Antarctic bedrock to reach ice they say is at least 1.2 million years old.

Analysis of the ancient ice is expected to show how Earth's atmosphere and climate have evolved. That should provide insight into how Ice Age cycles have changed, and may help in understanding how atmospheric carbon  changed climate, they said.

The same team previously drilled a core about 800,000 years old. The latest drilling went 2.8 kilometers (about 1.7 miles) deep, with a team of 16 scientists and support personnel drilling each summer over four years in average temperatures of about minus-35 Celsius (minus-25.6 Fahrenheit).

Thanks to the analysis of the ice core of the previous Epica campaign they have assessed that concentrations of greenhouse gases, such as carbon dioxide and methane, even during the warmest periods of the last 800,000 years, have never exceeded the levels seen since the Industrial Revolution began.

Today we are seeing carbon dioxide levels that are 50% above the highest levels we've had over the last 800,000 years, the scientists say.

Source: News Agencies

Mining dust is suffocating nearby forests in India, study shows

Dust from open cast mining suffocates surrounding forests and inhibits trees' ability to capture carbon from the atmosphere more than previously thought, according to new research by scientists in India and the UK.

Researchers  have assessed the impact of mining dust on forests in Eastern India, which is home to some of the world's major open-pit coal mines. The work is published in the Journal of Geophysical Research: Biogeosciences.

Focusing on the coal mining region of Eastern India, the research team studied detailed satellite images to inform its findings. They also collected 300 leaf samples from 30 different sites in Jharsuguda, and found dust deposits containing aluminum, silica and iron on them.

"Pollution from open cast mines creates a layer of dust that settles on the leaves of trees, making them increasingly less productive and less healthy. We knew this was the case, but we have learned that it is unfortunately worse—and more far spread—than we thought", say the scientists.

The dust affects trees' complex physiological processes, hindering their ability to capture carbon dioxide and damaging their overall health.

Dust from mines that settles on leaves impacts their function, impeding photosynthesis, light interception, nutrient availability, gas-energy exchange, plant-pathogen interactions, and causing physical damage.

Dust particles obstruct the leaves' stomata, the tiny openings through which plants exchange gases with the atmosphere. This reduces the plant's ability to capture carbon and release oxygen.

Mining dust is also impacting trees in a wide geographical area, reaching far beyond the immediate vicinity of the mines—up to 30km away from the mines. The highest concentration of negative impact is along transportation routes to and from the mines.

 This research should provide a solid foundation to inform future environmental management, as well as demonstrate the need for ongoing research to fully understand and mitigate the negative impact of mining on the delicate surrounding ecosystems.

Avinash Kumar Ranjan et al, A New Approach for Prediction of Foliar Dust in a Coal Mining Region and Its Impacts on Vegetation Physiological Processes Using Multi‐Source Satellite Data Sets, Journal of Geophysical Research: Biogeosciences (2024). DOI: 10.1029/2024JG008298

Scientists create comprehensive map of protein locations within human cells

 Each of our cells is built from a collection of about 10,000 kinds of proteins. Researchers have long had the ability to track the positions of small numbers of these proteins under the lens of a microscope. However, capturing the full scope of their locations in the cell has remained more challenging, let alone following how they change locations as a cell adapts to different conditions.

Proteins in a cell must be in the right department to do their jobs. Scientists  are trying to fully map the cell's organization and  determine how these cellular proteins may be reassigned in a time of crisis or change. A hostile takeover by a virus, for example, can send a cell's proteins to new stations, from which they may either serve the pathogen's aims or help the cell as it attempts to resist the infection.

A new method, described Dec. 31 in Cell and devised by a multidisciplinary team captures spatial organization across the entire cell at an unprecedented level of detail. Their approach maps the majority of a human cell's roughly 10,000 kinds of proteins according to the organelles and other compartments containing them, providing a crucial reference to understand how our cells are built. The team also applied their method to characterize how a portion of these proteins relocate during viral infection.

The new work is an example of "spatial proteomics," a burgeoning field that was named the 2024 "Method of the Year" by the journal Nature Methods. Spatial proteomics aims to increase our understanding of how proteins function by building detailed maps of their locations in cells and tissues.

Researchers typically study cellular responses by looking for increases or decreases in the quantity of particular proteins or their precursor mRNA molecules, as the cell "hires" or "fires" proteins to adapt to changing circumstances. In the experiments reported in the article, however, changes in proteins' location occurred largely independently from changes in their abundance — suggesting this conventional approach captures only a portion of a cell's response.

If we want to get the full picture of what's going on in cells during disease, we need to think not only about measuring abundance, but also changes in spatial organization.

Part 1