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Comment by Dr. Krishna Kumari Challa on January 9, 2025 at 9:58am

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

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

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

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

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

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

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

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

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

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

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

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

Comment by Dr. Krishna Kumari Challa on January 9, 2025 at 9:21am

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

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

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

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

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

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

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

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

Part 3

Comment by Dr. Krishna Kumari Challa on January 9, 2025 at 9:19am

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

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

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

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

Comment by Dr. Krishna Kumari Challa on January 9, 2025 at 9:17am

Human 'domainome' reveals root cause of heritable disease

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

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

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

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

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

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

Part 1

Comment by Dr. Krishna Kumari Challa on January 9, 2025 at 9:13am

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

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

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

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

Part 2

Comment by Dr. Krishna Kumari Challa on January 9, 2025 at 9:12am

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

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

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

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

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

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

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

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

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

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

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

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

Part 1

Comment by Dr. Krishna Kumari Challa on January 9, 2025 at 8:55am

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

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

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

Part 2

Comment by Dr. Krishna Kumari Challa on January 9, 2025 at 8:52am

Mathematical methods point to possibility of particles long thought impossible

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

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

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

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

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

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

Part 1

Comment by Dr. Krishna Kumari Challa on January 8, 2025 at 11:11am

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

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

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

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

Part 2

Comment by Dr. Krishna Kumari Challa on January 8, 2025 at 11:09am

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

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

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

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

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

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

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

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

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

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

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

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