To steer organizer cells and control stem cell development, the scientists uploaded genetic codes into the cells and engineered two key features in the cells.

First, they instructed the cells to stick to the stem cells in the form of a node or a shell clustering around the clump of stem cells. Second, the investigators engineered the organizer cells to produce specific biochemical signals crucial to inducing early embryonic development.

To effectively and precisely control the organizer cells, researchers developed a chemical switch within the cells, allowing scientists to turn the delivery of instructions to stem cells on or off. Additionally, they installed a "suicide" switch to eliminate the organizer cells when needed.

These synthetic organizers show that we can provide more refined developmental instructions to stem cells by engineering where and when specific morphogen signals are provided.

The organizer cells carry both spatial information and biochemical information, thus giving us an incredible amount of control that we have not had before.

The use of engineered synthetic organizer cells could ultimately allow the team to build real-world applications in the future. The remarkable science of programming instructions to coax stem cells could one day open the door to tackle complex diseases.

Toshimichi Yamada et al, Synthetic organizer cells guide development via spatial and biochemical instructions, Cell (2024). DOI: 10.1016/j.cell.2024.11.017

Part 2

Commercial tea bags release millions of microplastics, entering human intestinal cells

Do you know why I never use these tea bags? Because my instinct told me they don't have good vibes! And I am right!

Research has characterized in detail how polymer-based commercial tea bags release millions of nanoplastics and microplastics when infused. The study shows for the first time the capacity of these particles to be absorbed by human intestinal cells, and are thus able to reach the bloodstream and spread throughout the body.

Plastic waste pollution represents a critical environmental challenge with increasing implications for the well-being and health of future generations. Food packaging is a major source of micro and nanoplastic (MNPLs) contamination and inhalation and ingestion is the main route of human exposure.

A study by the Mutagenesis Group of the UAB Department of Genetics and Microbiology has successfully obtained and characterized micro and nanoplastics derived from several types of commercially available tea bags. The paper is published in the journal Chemosphere.

The researchers observed that when these tea bags are used to prepare an infusion, huge amounts of nano-sized particles and nanofilamentous structures are released, which is an important source of exposure to MNPLs.

The tea bags used for the research were made from the polymers nylon-6, polypropylene and cellulose. The study shows that, when brewing tea, polypropylene releases approximately 1.2 billion particles per milliliter, with an average size of 136.7 nanometers; cellulose releases about 135 million particles per milliliter, with an average size of 244 nanometers; while nylon-6 releases 8.18 million particles per milliliter, with an average size of 138.4 nanometers.

To characterize the different types of particles present in the infusion, a set of advanced analytical techniques such as scanning electron microscopy (SEM), transmission electron microscopy (TEM), infrared spectroscopy (ATR-FTIR), dynamic light scattering (DLS), laser Doppler velocimetry (LDV), and nanoparticle tracking analysis (NTA) were used.

Interactions with human cells observed for the first time.

The particles were stained and exposed for the first time to different types of human intestinal cells to assess their interaction and possible cellular internalization. The biological interaction experiments showed that mucus-producing intestinal cells had the highest uptake of micro and nanoplastics, with the particles even entering the cell nucleus that houses the genetic material.

The result suggests a key role for intestinal mucus in the uptake of these pollutant particles and underscores the need for further research into the effects that chronic exposure can have on human health.

As the use of plastic in food packaging continues to increase, it is vital to address MNPLs contamination to ensure food safety and protect public health, the researchers add.

Gooya Banaei et al, Teabag-derived micro/nanoplastics (true-to-life MNPLs) as a surrogate for real-life exposure scenarios, Chemosphere (2024). DOI: 10.1016/j.chemosphere.2024.143736

Having Your Tonsils removed as a Child May Have a Drastic Impact on Your Life

Thousands of children around the world   have their tonsils surgically removed each year to improve breathing while sleeping or reduce recurrent infection.

A study by an international team of researchers now suggests this relatively common procedure could increase a patient's risk of developing an anxiety-related disorder later in life.

Scientists analyzed data on over a million people held in a Swedish health registry, finding that a tonsillectomy was linked to a 43 percent increased risk of developing conditions such as post-traumatic stress disorder (PTSD), depression, or anxiety. 

Being an observational study, the research can't determine the cause of this outcome, however the increased risk was present even after accounting for the sex of the participants, the age at which they had their tonsils out, any family history of stress-related disorders, and the education level of the parents (an indicator of socioeconomic status).

These findings suggest a potential role of adenotonsillar diseases or associated health conditions in the development of stress-related disorders, the researchers write in their published paper.

Of the conditions identified, PTSD presented the greatest risk increase; a rise of some 55 percent was shown for those who had tonsillectomies earlier in life, compared with those who hadn't.

The researchers compared siblings in some families to control for certain genetic and environmental factors. Even among this sample there was a 34 percent greater risk of anxiety disorders for those family members who had their tonsils removed.

If our findings here are validated in future studies of independent study populations, mechanistic studies would be needed to disentangle the role of human tonsils and their diseases, via inflammation or other associated health conditions, in the development of psychiatric disorders in general and stress-related disorders specifically," write the researchers.

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2827613

Part 2

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Antarctica's tipping points threaten global climate stability

Antarctica is approaching a series of cascading tipping points that could reshape ecosystems and intensify global climate disruptions, according to a new study by an international team of scientists.

The study identifies eight potential tipping points spanning physical, biological, chemical, and governance systems. The research is published in the journal Ambio.

These include collapsing ice sheets, invasive species, ocean acidification, and pressures on the Antarctic Treaty System (ATS), which oversees human activity in the region.

The findings highlight the region's critical role in global climate stability.

Antarctica's ice sheets are vital to regulating the Earth's climate and oceans. If they collapse, we'll see significant sea-level rise, impacting millions of people living in coastal areas.

The study warns that these tipping points are interconnected, creating a risk of cascading effects. Melting ice sheets, for example, not only contribute to sea-level rise but also disrupt ocean circulation, which is crucial for transporting heat, carbon, and nutrients around the globe. Such disruptions threaten marine ecosystems, global fisheries, and food security.

The Antarctic Treaty System has been a cornerstone in preserving this fragile environment. But it's increasingly under pressure from geopolitical tensions and expanding human activity. Strengthening it is critical to mitigating these cascading impacts.

Ida Kubiszewski et al, Cascading tipping points of Antarctica and the Southern Ocean, Ambio (2024). DOI: 10.1007/s13280-024-02101-9

Scientists observe 'negative time' in quantum experiments

Scientists have long known that light can sometimes appear to exit a material before entering it—an effect dismissed as an illusion caused by how waves are distorted by matter.

Now, researchers through innovative quantum experiments, say they have demonstrated that "negative time" isn't just a theoretical idea—it exists in a tangible, physical sense, deserving closer scrutiny.

The findings, posted on the preprint server arXiv but not yet published in a peer-reviewed journal, have attracted both global attention and skepticism.

The researchers emphasize that these perplexing results highlight a peculiar quirk of quantum mechanics rather than a radical shift in our understanding of time.

While the term "negative time" might sound like a concept lifted from science fiction, some physicists defend its use, hoping it will spark deeper discussions about the mysteries of quantum physics.

Years ago, the research team began exploring interactions between light and matter.

When light particles, or photons, pass through atoms, some are absorbed by the atoms and later re-emitted. This interaction changes the atoms, temporarily putting them in a higher-energy or "excited" state before they return to normal.

The team now set out to measure how long these atoms stayed in their excited state. "That time turned out to be negative" —meaning a duration less than zero.

Part 1

The explanation lies in quantum mechanics, where particles like photons behave in fuzzy, probabilistic ways rather than following strict rules.

Instead of adhering to a fixed timeline for absorption and re-emission, these interactions occur across a spectrum of possible durations—some of which defy everyday intuition.

Critically, the researchers say, this doesn't violate Einstein's theory of special relativity, which dictates that nothing can travel faster than light. These photons carried no information, sidestepping any cosmic speed limits.
The concept of "negative time" has drawn both fascination and skepticism, particularly from prominent voices in the scientific community.

German theoretical physicist Sabine Hossenfelder, for one, criticized the work in a YouTube video viewed by over 250,000 people, noting, "The negative time in this experiment has nothing to do with the passage of time—it's just a way to describe how photons travel through a medium and how their phases shift."

Angulo and Steinberg, the researchers who did this work, pushed back, arguing that their research addresses crucial gaps in understanding why light doesn't always travel at a constant speed.

Steinberg acknowledged the controversy surrounding their paper's provocative headline but pointed out that no serious scientist has challenged the experimental results.

"We've made our choice about what we think is a fruitful way to describe the results," he said, adding that while practical applications remain elusive, the findings open new avenues for exploring quantum phenomena.

"I'll be honest, I don't currently have a path from what we've been looking at toward applications," he admitted. "We're going to keep thinking about it, but I don't want to get people's hopes up."

Daniela Angulo et al, Experimental evidence that a photon can spend a negative amount of time in an atom cloud, arXiv (2024). DOI: 10.48550/arxiv.2409.03680 , arxiv.org/abs/2409.03680

Part 2

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How does being born preterm affect long-term health?

Research has found that adults who were born preterm showed no statistically significant differences in diabetes, prediabetes, or dyslipidemia and had fewer cardiovascular events compared with adults born at term. A higher likelihood of developing high blood pressure by age 50 was seen among the preterm group.

Preterm birth occurs before 37 weeks gestation and affects an estimated one in 10 births worldwide. Outcomes in adulthood have previously been associated with elevated risk for cardiovascular disorders, including hypertension and stroke. These earlier investigations rarely included individuals who reached midlife in the modern era of improved neonatal care.

Long-term consequences for people born preterm are therefore lacking a contemporary research evaluation to identify potential age-related health risks.

In the study, "Health Outcomes 50 Years After Preterm Birth in Participants of a Trial of Antenatal Betamethasone," published in Pediatrics, researchers performed a follow-up of individuals originally enrolled in a double-blind, placebo-controlled trial of antenatal betamethasone at the National Women's Hospital in Auckland.
Participants completed a health questionnaire and provided consent for administrative health data review. Clinical endpoints measured included hypertension, diabetes mellitus, prediabetes, treated dyslipidemia, and major adverse cardiovascular events. Secondary outcomes covered respiratory, mental health, educational, and additional health metrics.

More than one-third of preterm-born adults showed higher reported rates of high blood pressure (34.7% vs. 19.8%), yet the overall risk of major adverse cardiovascular events was lower in this group than in term-born peers (2.8% vs. 6.9%).

Rates of diabetes, prediabetes, and treated dyslipidemia were not significantly different. Respiratory outcomes were generally comparable, and no significant differences were observed in chronic kidney disease prevalence.
Part 1

Mental health disorders were less common in preterm participants (38.2% vs. 52.9%). Self-reported depression was less common in the preterm group. Educational attainment and mortality after the first year of life did not vary significantly.

The results suggest that worsened cardiovascular outcomes are not universal for all individuals born preterm, particularly for those born at moderate gestation. These findings offer nuanced insights into the long-term impacts of preterm birth in the era of antenatal corticosteroid use.

Anthony G. B. Walters et al, Health Outcomes 50 Years After Preterm Birth in Participants of a Trial of Antenatal Betamethasone, Pediatrics (2024). DOI: 10.1542/peds.2024-066929

Part 2

Digest this: Ants prove superior to humans in group problem-solving maze experiment

Anyone who has dealt with ants in the kitchen knows that ants are highly social creatures; it's rare to see one alone. Humans are social creatures too, even if some of us enjoy solitude. Ants and humans are also the only creatures in nature that consistently cooperate while transporting large loads that greatly exceed their own dimensions.

Researchers have used this shared trait to conduct a fascinating evolutionary competition that asks the question: Who will be better at maneuvering a large load through a maze? The surprising results, published in the Proceedings of the National Academy of Sciences, shed new light on group decision making, as well as on the pros and cons of cooperation versus going it alone.

To enable a comparison between two such disparate species, the research team  created a real-life version of the "piano movers puzzle," a classical computational problem from the fields of motion planning and robotics that deals with possible ways of moving an unusually shaped object—say, a piano—from point A to point B in a complex environment.

Instead of a piano, the participants were given a large T-shaped object that they had to maneuver across a rectangular space divided into three chambers connected by two narrow slits.

The researchers created two sets of mazes that differed only in size, to match the dimensions of ants and humans, as well as groups of different sizes. Recruiting study participants was easier in the case of humans, who volunteered simply because they were asked to participate, and probably because they liked the idea of a competition. Ants, on the other hand, are far from competitive. They joined because they were misled into thinking that the heavy load was a juicy edible morsel that they were transporting into their nest.

The ants chosen to compete against Homo sapiens were Paratrechina longicornis. They are called this because of their long antennae, though they are sometimes referred to as "crazy ants" for their tendency to dash around. This familiar species of black ant, about 3 mm long, is common around the world.

Part 1

The ants tackled the maze challenge in three combinations: a single ant, a small group of about seven ants and a large group of about 80. Humans handled the task in three parallel combinations: a single person, a small group of six to nine individuals and a large group of 26.

To make the comparison as meaningful as possible, groups of humans were in some cases instructed to avoid communicating through speaking or gestures, even wearing surgical masks and sunglasses to conceal their mouths and eyes. In addition, human participants were told to hold the load only by the handles that simulated the way in which it is held by ants. The handles contained meters that measured the pulling force applied by each person throughout the attempt.

The researchers repeated the experiment numerous times for each combination, then meticulously analyzed the videos and all the advanced tracking data while using computer simulations and various physics models.

Unsurprisingly, the cognitive abilities of humans gave them an edge in the individual challenge, in which they resorted to calculated, strategic planning, easily outperforming the ants.
In the group challenge, however, the picture was completely different, especially for the larger groups. Not only did groups of ants perform better than individual ants, but in some cases they did better than humans. Groups of ants acted together in a calculated and strategic manner, exhibiting collective memory that helped them persist in a particular direction of motion and avoid repeated mistakes.

Humans, on the contrary, failed to significantly improve their performance when acting in groups. When communication between group members was restricted to resemble that of ants, their performance even dropped compared to that of individuals. They tended to opt for "greedy" solutions—which seemed attractive in the short term but were not beneficial in the long term, and—according to the researchers—opted for the lowest common denominator.
An ant colony is actually a family. All the ants in the nest are sisters, and they have common interests. It's a tightly knit society in which cooperation greatly outweighs competition. That's why an ant colony is sometimes referred to as a super-organism, sort of a living body composed of multiple 'cells' that cooperate with one another.

These new findings validate this vision. Researchers shown that ants acting as a group are smarter, that for them the whole is greater than the sum of its parts. In contrast, forming groups did not expand the cognitive abilities of humans. The famous 'wisdom of the crowd' that's become so popular in the age of social networks didn't come to the fore in these experiments.

Tabea Dreyer et al, Comparing cooperative geometric puzzle solving in ants versus humans, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2414274121

Part 2

 Preventing Christmas tree fires, with science

Perceptein, a protein-based artificial neural network in living cells

Researchers have designed a protein-based system inside living cells that can process multiple signals and make decisions based on them.

The researchers have also introduced a unique term, "perceptein," as a combination of protein and perceptron. Perceptron is a foundational artificial neural network concept, effectively solving binary classification problems by mapping input features to an output decision.

By merging concepts from neural network theory with protein engineering, "perceptein" represents a biological system capable of performing classification computations at the protein level, similar to a basic artificial neural network. This "perceptein" circuit can classify different signals and respond accordingly, such as deciding to stay alive or undergo programmed cell death.

In the study, "A synthetic protein-level neural network in mammalian cells," published in Science, researchers showed that perceptein circuits could distinguish signal inputs with tunable decision boundaries, offering the possibility of controlling complex cellular responses without transcriptional regulation.

 Zibo Chen et al, A synthetic protein-level neural network in mammalian cells, Science (2024). DOI: 10.1126/science.add8468

Salt-seeking behavior traced to specific brain neurons

Salt, or more precisely the sodium it contains, is very much a "Goldilocks" nutrient. Low sodium levels cause a drop in blood volume, which can have serious, sometimes deadly, health consequences. Conversely, too much salt can lead to high blood pressure and cardiovascular disease.

Given the critical importance of sodium for body and brain functions, evolution has developed a powerful drive to consume salt in situations where there is a deficiency.

Aldosterone triggers salt-appetite neurons.

Researchers made their discovery by teasing out the actions of aldosterone, a key hormone for controlling sodium levels.

Normally, aldosterone is produced when body fluid volume (including blood volume) is low, for example, after sweating without drinking enough fluid, or blood loss, or during an illness with vomiting or diarrhea. Aldosterone tells the kidney and other organs to retain sodium, which helps maintain the existing fluid in the body.

However, when aldosterone is inappropriately high, a condition called primary aldosteronism, blood pressure can rise to dangerous levels. Aldosteronism is the cause of hypertension in as many as 10-30% of all patients with high blood pressure, and the risk of stroke, heart failure, and abnormal heart rhythms is three times higher in these patients than in other patients with hypertension, although it is not clear why.

The research team focused on an unappreciated aspect of aldosteronism—a tendency to eat more salt. Almost a century ago, studies showed that aldosterone and related hormones cause salt appetite to go up in rats. More recent human studies have also found that patients with aldosteronism consume more salt than other patients with hypertension.

The team first confirmed that lack of sodium in the diet of mice increases aldosterone production and salt intake. It also increases the activity of a tiny group of neurons in the brainstem known as HSD2 neurons. The researchers had previously discovered these HSD2 neurons and had circumstantial evidence suggesting they were responsible for salt appetite.

Researchers used genetically targeted cell deletion to show that the HSD2 neurons were required for aldosterone-driven salt consumption. Moreover, they showed that humans also have a small population of HSD2 neurons in the same part of the brainstem, indicating that the same neural circuit may be relevant to people with elevated aldosterone.

Overall, the findings suggest that aldosterone acts on the tiny population of HSD2 neurons (there are roughly 200 HSD2 neurons in mice and 1,000 in humans) to induce the highly specific behavior of seeking and consuming sodium. The team's findings suggest that boosting sodium appetite may be the only central function of HSD2 neurons.

Silvia Gasparini et al, Aldosterone-induced salt appetite requires HSD2 neurons, JCI Insight (2024). DOI: 10.1172/jci.insight.175087

Unclogging the immune system: Scientists use immunotherapy to remove aging cell buildup

 As we age, our bodies are flooded by aging, or senescent cells, which have stopped dividing but, instead of dying, remain active and build up in body tissues. Recent studies have shown that getting rid of these cells might delay age-related diseases, reduce inflammation and extend lives. Despite the great potential, however, there is currently no drug that can target these cells directly and efficiently.

researchers suggest an alternative approach. In a new study published in Nature Cell Biology, they reveal that senescent cells  build up in the body by clogging up the immune system, thereby preventing their own removal.

The scientists demonstrated in mice how to unclog this blockage using immunotherapy, the new generation of treatments that is revolutionizing cancer therapy.  These findings could pave the way for innovative treatment of age-related diseases and other chronic disorders.

Julia Majewska et al, p16-dependent increase of PD-L1 stability regulates immunosurveillance of senescent cells, Nature Cell Biology (2024). DOI: 10.1038/s41556-024-01465-0

How gold reaches Earth's surface

A research team has discovered a new gold-sulfur complex that helps researchers understand how gold deposits are formed.

Gold in ore deposits associated with volcanoes around the Pacific Ring of Fire originates in Earth's mantle and is transported by magma to its surface. But how that gold is brought to the surface has been a subject of debate. Now, the research team has used numerical modeling to reveal the specific conditions that lead to the enrichment of gold in magmas that rise from the Earth's mantle to its surface.

Specifically, the model reveals the importance of a gold-trisulfur complex whose existence has been vigorously debated.

The presence of this gold-trisulfur complex under a very specific set of pressures and temperatures in the mantle 30 to 50 miles beneath active volcanoes causes gold to be transferred from the mantle into magmas that eventually move to the Earth's surface. The team's results are published in the Proceedings of the National Academy of Sciences.

This offers the most plausible explanation for the very high concentrations of gold in some mineral systems in subduction zone environments.

Gold deposits associated with volcanoes form in what are called subduction zones. Subduction zones are regions where a continental plate—the Pacific plate, which lies under the Pacific Ocean—is diving under the continental plates that surround it. In these seams where continental plates meet each other, magma from Earth's mantle has the opportunity to rise to the surface.

On all of the continents around the Pacific Ocean, from New Zealand to Indonesia, the Philippines, Japan, Russia, Alaska, the western United States and Canada, all the way down to Chile, we have lots of active volcanoes. All of those active volcanoes form over or in a subduction zone environment. The same types of processes that result in volcanic eruptions are processes that form gold deposits.

Part 1

Gold is present in Earth's mantle above the subducting ocean plate. But when the conditions are just right that a fluid containing the trisulfur ion is added from the subducting plate to the mantle, gold strongly prefers to bond with trisulfur to form a gold-trisulfur complex. This complex is highly mobile in magma.

Scientists have previously known that gold complexes with various sulfur ions, but this study is the first to present a robust thermodynamic model for the existence and importance of the gold-trisulfur complex.

To identify this new complex, the researchers developed a thermodynamic model based on lab experiments in which the researchers control pressure and temperature of the experiment, then measure the results of the experiment. Then, the researchers developed a thermodynamic model that predicts the results of the experiment. This thermodynamic model can then be applied to real-world conditions.

These results provide a really robust understanding of what causes certain subduction zones to produce very gold-rich ore deposits.

Deng-Yang He et al, Mantle oxidation by sulfur drives the formation of giant gold deposits in subduction zones, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2404731121

Part 2

From Earth to alien worlds: The fundamental limits to life

Extraterrestrial and artificial life have long captivated the human mind. Knowing only the building blocks of our own biosphere, can we predict how life may exist on other planets? What factors will rein in the Frankensteinian life forms we hope to build in laboratories here on Earth?

An open-access paper published in Interface Focus and co-authored by several SFI researchers takes these questions out of the realm of science fiction and into scientific laws.

Reviewing case studies from thermodynamics, computation, genetics, cellular development, brain science , ecology and evolution, the paper concludes that certain fundamental limits prevent some forms of life from ever existing.

Requirements include entropy reduction (which includes, for instance, the ability to heal and repair), closed-compartment cells as the inevitable units of life, and a system—such as brains—that integrates information and makes decisions using neuron-like units.

The authors point to historical examples where people predicted some complex feature of life that biologists later confirmed. Examples include the Schrodinger view of information molecules as "aperiodic crystals," or mid-century simulations predicting that parasites are inevitable when complex life evolves.

That such correct predictions were possible with almost no available evidence suggests all living systems follow an underlying universal logic.

 Ricard Solé et al, Fundamental constraints to the logic of living systems, Interface Focus (2024). DOI: 10.1098/rsfs.2024.0010

Scientists discover a 'Goldilocks' zone for DNA organization, opening new doors for drug development

In a discovery that could redefine how we understand cellular resilience and adaptability, scientists  have unlocked the secret interactions between a primordial inorganic polymer of phosphate known as polyphosphate (polyP), and two basic building blocks of life: DNA and the element magnesium. These components formed clusters of tiny liquid droplets–also known as condensates–with flexible and adaptable structures.

PolyP and magnesium are involved in many biological processes. Thus, the findings could lead to new methods for tuning cellular responses, which could have impactful applications in translational medicine.

The ensuing study, published in Nature Communications on October 26, 2024, reveals a delicate "Goldilocks" zone—a specific magnesium concentration range—where DNA wraps around polyP-magnesium ion condensates. Similar to a thin eggshell covering a liquid-like interior, this seemingly simple structure may help cells organize and protect their genetic material.

The microscopy images revealed that DNA wraps itself around a condensate, creating a thin eggshell-like barrier. This shell could affect molecule transportation and also slow down fusion: the process where two condensates merge into one. Without DNA shells, polyP-magnesium ion condensates readily fused—like how oil drops and vinegar fuse in a salad dressing bottle when shaken. However, careful examination showed that fusion overall slowed to varying extents, depending on DNA length. Longer DNA, the researchers suspected, caused greater entanglement on condensate surfaces—similar to how long hair tangles more than short hair.

Another crucial discovery: DNA shell formation only occurred within a specific magnesium concentration range—too much or too little, and the shell wouldn't materialize. This "Goldilocks" effect highlights how cells can regulate condensate structure, size and function simply by tuning control parameters.

 Ravi Chawla et al, Reentrant DNA shells tune polyphosphate condensate size, Nature Communications (2024). DOI: 10.1038/s41467-024-53469-x

The Risk of Cancer Fades as We Get Older

Aging brings two opposing trends in cancer risk: first, the risk climbs in our 60s and 70s, as decades of genetic mutations build up in our bodies. But then, past the age of around 80, the risk drops again – and a new study may explain a key reason why.

The international team of scientists behind the study analyzed lung cancer in mice, tracking the behavior of alveolar type 2 (AT2) stem cells. These cells are crucial for lung regeneration, and are also where many lung cancers get started.

What emerged was higher levels of a protein called NUPR1 in the older mice. This caused cells to act as if they were deficient in iron, which in turn limited their regeneration rates – putting restrictions on both healthy growth and cancerous tumors.

The aging cells actually have more iron, but for reasons we don't yet fully understand, they function like they don't have enough. Aging cells lose their capacity for renewal and therefore for the runaway growth that happens in cancer.

The same processes were found to be happening in human cells too: more NUPR1 leads to a drop in the amount of iron available to cells. When NUPR1 was artificially lowered or iron was artificially increased, cell growth capabilities were boosted again.

That potentially gives researchers a way of exploring treatments that target iron metabolism – especially in older people. 

These findings also have implications for cancer treatments based on a type of cell death called ferroptosis, which is triggered by iron. This cell death is less common in older cells, the researchers found, because of their functional iron deficiency.

This perhaps also makes them more resistant to cancer treatments based on ferroptosis that are in development– so the earlier a ferroptosis treatment can be tried, the better it's likely to work.

https://www.nature.com/articles/s41586-024-08285-0

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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

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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.
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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.
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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

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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