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Comment by Dr. Krishna Kumari Challa 10 hours ago

Normally, this would have been a huge surprise. EPO is well known as the primary instigator of red blood cell production, and it was named for this function (erythro meaning "red" and poiein meaning "to produce").

But earlier in 2025,  the researchers showed that cancer cells in immunologically tolerated, or "cold," tumors trick the immune system by making EPO and releasing it into the tumor environment where it binds to a type of immune cell called macrophages and causes these cells to become immunosuppressive. So, they knew that EPO has a second role as a master immune regulator.

When they genetically manipulated the mice to remove the ability of the dendritic cells to express the EPO receptor, the animals rejected transplants of unmatched tissue after total lymphoid irradiation, showing conclusively that the EPO signaling pathway is necessary for the development of immune tolerance. But there was another intriguing finding.

"What was quite a surprise  is that when you remove or block the EPO receptor on the dendritic cells, you don't just block the development of tolerance.

"Instead, you have now converted these dendritic cells into super stimulators, or powerful activators of immune response. There is a dual opportunity to not just induce tolerance to treat autoimmune diseases, but also to trigger a strong immune response to cancer cells or to life-threatening infections."

Essentially, dendritic cells continuously sample their environment by capturing and swallowing dead or dying cells (either self or non-self) as well as pathogens and displaying fragments of the cells on their surfaces to be recognized by many types of T cells, including killer T cells, helper T cells or Tregs.

When EPO interacts with its EPO receptors on the dendritic cells, it causes the dendritic cells to embark on a series of maturation steps that cause them to promote tolerance and selectively activate Tregs that tamp down any immune response to that antigen.

"This mechanism is not only required for physiological tolerance that prevents autoimmune disease, but it is often hijacked by cancers and probably some infectious pathogens, too, enabling their ability to evade immune attack.

Conversely, removing the EPO receptor from dendritic cells resulted in tumor regression in mice with immune-resistant melanoma or colon cancer tumors.

"It's fascinating that this fundamental mechanism took so long to discover. "It's even possible that this is the primary function of EPO, and that its effect on red blood cell formation is secondary. There is no doubt these findings will light many research fires."

Edgar Engleman, Erythropoietin receptor on cDC1s dictates immune tolerance, Nature (2025). DOI: 10.1038/s41586-025-09824-z. www.nature.com/articles/s41586-025-09824-z

Part 3

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Comment by Dr. Krishna Kumari Challa 10 hours ago

The immune system's response—threatening or welcoming—is governed by the Tregs, which tamp down inappropriate attack impulses of other immune cells called T and B cells.
The researchers used an experimental approach first identified in mice and subsequently in humans in which irradiating the thymus, spleen and lymph nodes—all places in the body where immune cells hang out—kills off many of the T cells and B cells while leaving antigen-presenting cells such as dendritic cells relatively unscathed.

The treatment, called total lymphoid irradiation, reprograms the recipient's immune system to permanently tolerate genetically mismatched transplanted cells or organs.

But dendritic cells don't act alone and instead recruit other immune cells, including T cells, to carry out their missions.

"All T cells, including Tregs, must first be 'presented' with a structure called an antigen that is recognized by their receptors for the cells to develop into mature T cells that either attack a target or suppress the immune response to that target," Engleman said. "Dr. Zhang and I reasoned that this process of tolerance or activation must be initiated by antigen-presenting cells."

The most powerful antigen-presenting cells in the body are called type 1 dendritic cells, which engulf dead or dying cells or pathogens and display bits of those cells like immunological fishing lures for T or B cells.

To learn how dendritic cells are involved in the development of immune tolerance, Zhang and Engleman decided to investigate whether and how the genes they express change in mice after total lymphoid irradiation.

They found that the gene for the EPO receptor is expressed at much higher levels in the dendritic cells of irradiated animals, and that the levels of EPO are elevated in the animals' blood circulation.
Part 2

Comment by Dr. Krishna Kumari Challa 10 hours ago

Immune system's 'on-off' switch may hold answers for cancer and autoimmunity

A single signaling pathway controls whether immune cells attack or befriend cells they encounter while patrolling our bodies, researchers have found. Manipulating this pathway could allow researchers to toggle the immune response to treat many types of diseases, including cancers, autoimmune disorders and those that require organ transplants.

The research, which was conducted in mice, illuminates the mechanism of an important immune function that prevents inappropriate attacks on healthy tissue. Called peripheral immune tolerance, the key cellular players, known as regulatory T cells (or Tregs), were first described in the late 1990s in a series of discoveries that were recently recognized with the 2025 Nobel Prize in physiology or medicine.

The work is published in the journal Nature.

The findings extend those of a related study published in Science by the same researchers that described a surprising new role for a molecule known for decades to promote red blood cell formation.

Now it is clear that this molecule, erythropoietin, or EPO, is the lynchpin controlling how our immune systems react to real or perceived threats—acting through immune cells called dendritic cells.

The critically important building of immune tolerance to "self" is a two-step process. The first, called central immune tolerance, occurs in the bone marrow and the thymus, where B cells and T cells undergo a first round of selection to eliminate or reprogram self-reactive cells before they are released into the bloodstream.
The second, peripheral immune tolerance, serves as a backup to screen circulating cells that escape the first culling.

The stakes are high. An overly enthusiastic immune system that attacks healthy tissues leads to autoimmune diseases like rheumatoid arthritis, multiple sclerosis, lupus and diabetes. Conversely, a too complacent, or tolerant, response allows cancer cells to escape immune destruction, instead of sending them on their way with a handshake and a pat on the back.

Part 1

Comment by Dr. Krishna Kumari Challa 10 hours ago

How the immune system stalls weight loss

Neutrophils, a type of immune cell, infiltrate fat tissue during physiological stress and release signals that suppress fat breakdown, helping to prevent excessive weight loss. This mechanism, observed in both mouse models and human data, involves specific inflammatory pathways and is more active in obese individuals. The findings highlight a key role for the immune system in regulating energy balance.

In a study published in Nature, a research team demonstrates that when the body is exposed to physiological stressors, such as low temperature, neutrophils—a type of white blood cell—infiltrate fat tissue and release signals that slow fat breakdown.

The researchers hypothesize that this mechanism helped our early human ancestors preserve vital energy stores when food was scarce or when exposed to prolonged periods of cold. Today, the findings could help yield new approaches to managing obesity and other metabolic disorders.

White adipose tissue (WAT)—commonly known as body fat—plays a vital role in maintaining energy balance by storing excess energy and releasing it as needed during periods of fasting, cold or other metabolic stress. These biochemical processes are carefully managed by the body in order to prevent excessive fat loss, which can be very dangerous.

Until now, the mechanisms that protect the body against runaway fat burning in times of stress have remained unclear.

To address this, the researchers studied a combination of mouse models and human genetic data.

Key findings include:
In mouse models, activating the sympathetic nervous system triggered a rapid influx of neutrophils into visceral fat, the fat surrounding vital organs. This neutrophil recruitment depended on both ongoing fat breakdown and activation of specific inflammatory pathways in fat cells.
Neutrophils arriving in the fat tissue produced signaling molecules that suppressed further fat loss in surrounding tissue.
When either these molecules or neutrophils themselves were depleted, mice experienced increased fat breakdown under metabolic stress.
In obese individuals, genes involved with this pathway were more active.
These findings reveal an unexpected physiological partnership between fat cells and immune cells, demonstrating that the immune system is crucial not only for fighting infection but also for maintaining energy balance.

The study also provides new insight into the underlying metabolism of obesity and other metabolic disorders. Targeting this newly discovered pathway may eventually offer new strategies for treating obesity, metabolic syndrome or conditions involving unintended weight loss.

Seunghwan Son et al, Neutrophils preserve energy storage in sympathetically activated adipocytes, Nature (2025). DOI: 10.1038/s41586-025-09839-6 , doi.org/10.1038/s41586-025-09839-6

Comment by Dr. Krishna Kumari Challa 11 hours ago

Ghostly solar neutrinos caught transforming carbon atoms deep underground

Solar neutrinos have been directly observed transforming carbon-13 nuclei into nitrogen-13 within the SNO+ underground detector. Using a delayed coincidence method, 5.6 events were detected over 231 days, matching the 4.7 events expected from neutrino interactions. This marks the first direct measurement of this low-energy neutrino-induced reaction, advancing the study of rare atomic processes.

SNO+ Collaboration et al, First Evidence of Solar Neutrino Interactions on ¹³C, Physical Review Letters (2025). DOI: 10.1103/1frl-95gj On arXiv: DOI: 10.48550/arxiv.2508.20844

Comment by Dr. Krishna Kumari Challa 11 hours ago

Genetic overlap of 14 psychiatric disorders explains why patients often have multiple diagnoses

An international collective of researchers is delivering new insights into why having multiple psychiatric disorders is the norm rather than the exception. In a study published recently in the journal Nature, the team provides the largest and most detailed analysis to date on the genetic roots shared among 14 conditions.

The majority of people diagnosed with a psychiatric disorder will ultimately be diagnosed with a second or third disorder in their lifetime, creating challenges for defining and treating these conditions. While a person's environment and lived experience influence their risk for developing multiple disorders, their genetic makeup can also play a significant role.

By analyzing data from over 6 million individuals, the working group mapped the genetic landscape of 14 psychiatric conditions and revealed five families of disorders with high levels of genetic overlap. The results mark an important step toward understanding the genetic connections among psychiatric disorders and could ultimately help clinicians better serve their patients.

Analysis of genetic data from over 6 million individuals reveals that 14 psychiatric disorders cluster into five groups with significant genetic overlap. Major depression, anxiety, and PTSD share about 90% of genetic risk, while schizophrenia and bipolar disorder share 66%. Shared genetic variants and expression patterns help explain frequent comorbidity among these conditions.

Through statistical modeling, the researchers found that the 14 disorders could be divided into these five groups based on genetic similarities:

• Compulsive disorders: obsessive-compulsive disorder, anorexia nervosa and, to a lesser extent, Tourette disorder and anxiety disorders.
• Internalizing disorders: major depression, anxiety disorders and post-traumatic stress disorder.
• Neurodevelopmental disorders: autism spectrum disorder, attention-deficit/hyperactivity disorder and, to a lesser extent, Tourette disorder.
• Schizophrenia and bipolar disorder
• Substance use disorders: opioid use disorder, cannabis use disorder, alcohol use disorder and nicotine dependence.

Andrew D. Grotzinger et al, Mapping the genetic landscape across 14 psychiatric disorders, Nature (2025). DOI: 10.1038/s41586-025-09820-3

Abdel Abdellaoui, Shared genetic risk in psychiatric disorders, Nature (2025). DOI: 10.1038/d41586-025-03728-8 , doi.org/10.1038/d41586-025-03728-8

Comment by Dr. Krishna Kumari Challa yesterday

Decoding the chemistry of life: Maximum entropy reveals how mutations alter enzymes and drive drug resistance
Maximum entropy, a statistical measure, enables accurate prediction of how mutations alter enzyme activity and drive drug resistance, particularly in viruses with constrained evolutionary pathways like hepatitis C. The approach outperforms traditional simulations in speed and accuracy, effectively forecasting disease-related mutations in proteins such as myosin, and aiding in enzyme design and disease prediction 

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Blinking less may mean brain is working harder, study shows
Blink rates decrease when individuals focus on understanding speech in noisy environments, indicating that reduced blinking reflects increased cognitive effort. This suppression of blinking occurs regardless of lighting conditions, suggesting cognitive demand, not visual input, drives the effect. Blink timing aligns with periods of salient information, supporting its use as a marker of mental workload. 

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How the 'hypnagogic state' of drowsiness could enhance your creativity
The hypnagogic state, the transitional phase between wakefulness and sleep, is linked to increased creativity, as it allows ideas from the subconscious to surface when conscious mental activity is reduced. This state enhances cognitive flexibility and openness, and practices like meditation or conscious napping can help harness its creative potential. Recording ideas immediately is crucial, as insights are easily forgotten 

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Harnessing the power of clay to protect communities from toxins
Clay-based materials act as effective sorbents, binding toxins such as aflatoxins, heavy metals, PFAS, and pesticides to prevent their absorption in humans, animals, and plants. These clays can be ingested or applied topically, and their use extends to environmental remediation, including soil and air purification, offering practical solutions for reducing exposure to hazardous chemicals. 

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Trust in science is low among minorities for a reason, research finds
Trust in science among underrepresented groups in the U.S., such as African Americans and women, remains low, partly due to a lack of diversity within scientific fields and historical abuses like the Tuskegee study. People are more likely to trust scientists who share their demographic background, but these groups are underrepresented in STEM. This trust gap can negatively impact health outcomes, as seen during the COVID-19 pandemic. Reducing social distance between scientists and society may improve trust 

Comment by Dr. Krishna Kumari Challa yesterday

Concrete with a human touch: Can we make infrastructure that repairs itself?
Self-healing concrete incorporates materials such as bacteria or chemical agents that can autonomously repair cracks, improving durability and reducing maintenance costs. Bacteria-based methods rely on microbiologically induced calcite precipitation but are slow and limited to small cracks, while chemical-based approaches can address larger cracks more rapidly. Encapsulation of healing agents is a promising strategy, though standardization and integration challenges remain 

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Helping crops survive in saltwater: Mangroves reveal key cellular traits
Mangroves possess unusually small cells and thicker cell walls compared to inland relatives, traits that enhance mechanical strength and prevent wilting under saltwater exposure. These cellular adaptations have evolved repeatedly in saline environments, suggesting that modifying cell size and wall properties could be a promising approach for developing salt-tolerant crops 

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Microbial molecule that disarms inflammation discovered, offering new diabetes treatment strategy
Trimethylamine (TMA), a metabolite produced by gut bacteria from dietary choline, directly inhibits the immune protein IRAK4, reducing inflammation and improving insulin sensitivity in models of type 2 diabetes. Blocking IRAK4, either genetically or pharmacologically, yields similar benefits, highlighting a potential therapeutic target for diabetes management 

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Immunotherapy works for sepsis thanks to precision approach
Tailoring immunotherapy to the specific immune status of sepsis patients—either overactive immunity or immune paralysis—improves clinical outcomes compared to standard care. Biomarker-guided selection enables targeted treatment, leading to faster organ function recovery and infection resolution in these subgroups, representing about 25% of sepsis cases 

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Pancreatic cancer cells 'speak the language' of organs they will later invade, study reveals
Pancreatic cancer cells at the primary tumor site exhibit gene expression patterns resembling those of the organs they will later invade, predisposing them to metastasize to specific locations. This organ-specific adaptation occurs without a single identifiable genetic mutation and may also be present in other cancer types. These findings could inform future strategies for predicting and preventing metastasis 

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How brain activity changes throughout the day: Findings offer clues to fatigue and mental health
Brain activity patterns shift throughout the day, with neuronal activity moving from subcortical regions upon waking to cortical areas as wakefulness continues. These dynamic changes are reversed during sleep. The findings provide a framework for identifying objective markers of fatigue and have potential implications for understanding mental health and developing new assessment tools 

Comment by Dr. Krishna Kumari Challa yesterday

Comment by Dr. Krishna Kumari Challa yesterday

Is The Y Chromosome Vanishing?

The Y chromosome has long been rumored to be vanishing. So what does that mean for the future of men?
Some evolutionary biologists  say what’s in store for the human species.

They think the Y chromosome is running out of time.
Already, it’s lost 97 percent of its ancestral genes in the last 300 million years.

At that rate, it could disappear in another 6 million years, and a new sex gene may take its place.

Still, not everyone agrees that the Y chromosome is doomed. A potent scientific debate is brewing.

https://www.sciencealert.com/is-the-y-chromosome-vanishing-a-new-se...

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