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Comment by Dr. Krishna Kumari Challa on December 26, 2024 at 1:34pm

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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Comment by Dr. Krishna Kumari Challa on December 26, 2024 at 10:26am

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

Comment by Dr. Krishna Kumari Challa on December 26, 2024 at 10:03am

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

Comment by Dr. Krishna Kumari Challa on December 26, 2024 at 9:56am

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

Comment by Dr. Krishna Kumari Challa on December 26, 2024 at 9:54am

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

Comment by Dr. Krishna Kumari Challa on December 24, 2024 at 11:22am

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

Comment by Dr. Krishna Kumari Challa on December 24, 2024 at 11:16am

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

Comment by Dr. Krishna Kumari Challa on December 24, 2024 at 10:59am

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

Comment by Dr. Krishna Kumari Challa on December 24, 2024 at 10:36am

 Preventing Christmas tree fires, with science

Comment by Dr. Krishna Kumari Challa on December 24, 2024 at 10:03am

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

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