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Comment by Dr. Krishna Kumari Challa on March 29, 2024 at 9:00am

'Exhausted' immune cells in healthy women could be target for breast cancer prevention

Risk-reducing surgery, in which the breasts are removed, is offered to those at increased risk of breast cancer. This can be a difficult decision for young women to make and can have a significant effect on body image and conjugal relationships.

Late-stage breast cancer tends to be very unpredictable and hard to manage. As we make better and better drugs, the tumors just seem to find a way around it.

The best way to prevent breast cancer is to really understand how it develops in the first place. Then we can identify these early changes and intervene.

Researchers at the University of Cambridge have created the world's largest catalogue of human breast cells, which has revealed early cell changes in healthy carriers of BRCA1 and BRCA2 gene mutations.

Everyone has BRCA1 and BRCA2 genes, but mutations in these genes—which can be inherited—increase the risk of breast and ovarian cancer.

The study found that the immune cells in breast tissue of healthy women carrying BRCA1 or BRCA2 gene mutations show signs of malfunction known as exhaustion. This suggests that the immune cells can't clear out damaged breast cells, which can eventually develop into breast cancer.
This is the first time that exhausted immune cells have been reported in non-cancerous breast tissues at such scale—normally these cells are only found in late-stage tumors. The results raise the possibility of using existing immunotherapy drugs as early intervention to prevent breast cancer developing, in carriers of BRCA1 and BRCA2 gene mutations.

The researchers plan to trial this preventative approach in mice. Existing drugs have serious side effects, so testing in mice is necessary to find the right safe dosage. If effective, this will pave the way to a pilot clinical trial in women carrying BRCA gene mutations.

The research  results suggest that in carriers of BRCA mutations, the immune system is failing to kill off damaged breast cells—which in turn seem to be working to keep these immune cells at bay.

Scientists are very excited about this discovery, because it opens up potential for a preventative treatment other than surgery for carriers of BRCA breast cancer gene mutations. Drugs already exist that can overcome this block in immune cell function, but so far, they've only been approved for late-stage disease. No one has really considered using them in a preventative way before.

Using samples of healthy breast tissue collected from 55 women across a range of ages, the researchers catalogued over 800,000 cells—including all the different types of breast cell. The resulting Human Breast Cell Atlas is now available as a resource for other researchers to use and add to. It contains huge amounts of information on other risk factors for breast cancer including Body Mass Index (BMI), menopausal status, contraceptive use and alcohol consumption. Researchers found that there are multiple breast cell types that change with pregnancy, and with age, and it's the combination of these effects—and others—that drives the overall risk of breast cancer.

A single-cell atlas enables mapping of homeostatic cellular shifts in the adult human breast, Nature Genetics (2024). DOI: 10.1038/s41588-024-01688-9

Comment by Dr. Krishna Kumari Challa on March 28, 2024 at 8:20am

In fact, two of these seven genetic findings are located in this particular region containing the genes of the XG blood group, and that region is highly atypical because it is shared by both X and Y sex chromosomes. This is really quite intriguing as we do not know much about these parts of the genome; our work shows there is benefit in exploring further this genetic terra incognita.

It is with this kind of comprehensive, holistic approach—and once we had taken into account the effects of age and sex—that three emerged as the most harmful: diabetes, air pollution, and alcohol.

This research sheds light on some of the most critical risk factors for dementia, and provides novel information that can contribute to prevention and future strategies for targeted intervention.

The effects of genetic and modifiable risk factors on brain regions vulnerable to ageing and disease, Nature Communications (2024). DOI: 10.1038/s41467-024-46344-2

Part 2

Comment by Dr. Krishna Kumari Challa on March 28, 2024 at 8:19am

Risk factors for faster aging in the brain revealed in new study

In a new study published in Nature Communications, researchers investigated the genetic and modifiable influences on fragile brain regions by looking at the brain scans of 40,000 UK Biobank participants aged over 45.

Previously, the researchers had identified a 'weak spot' in the brain, which is a specific network of higher-order regions that not only develop later during adolescence, but also show earlier degeneration in old age. They showed that this brain network is also particularly vulnerable to schizophrenia and Alzheimer's disease.

In their latest study, the researchers examined 161 risk factors for dementia, and ranked their impact on this vulnerable brain network, over and above the natural effects of age.

They classified these so-called 'modifiable' risk factors—as they can potentially be changed throughout life to reduce the risk of dementia—into 15 broad categories: blood pressure, cholesterol, diabetes, weight, alcohol consumption, smoking, depressive mood, inflammation, pollution, hearing, sleep, socialization, diet, physical activity, and education.

We know that a constellation of brain regions degenerates earlier in aging, and in this new study researchers  have shown that these specific parts of the brain are most vulnerable to diabetes, traffic-related air pollution—increasingly a major player in dementia—and alcohol, of all the common risk factors for dementia.

They have found that several variations in the genome influence this brain network, and they are implicated in cardiovascular deaths, schizophrenia, Alzheimer's and Parkinson's diseases, as well as with the two antigens of a little-known blood group, the elusive XG antigen system, which was an entirely new and unexpected finding.

Part 1

Comment by Dr. Krishna Kumari Challa on March 28, 2024 at 8:12am

Scientists discover how caterpillars can stop their 'bleeding' in seconds

Fully grown tobacco hornworms, ready to pupate, are between 7.5cm and 10cm long. They only contain a minute amount of hemolymph, which typically clots within seconds

Blood is a remarkable material: it must remain fluid inside blood vessels, yet clot as quickly as possible outside them, to stop bleeding. The chemical cascade that makes this possible is well understood for vertebrate blood. But hemolymph, the equivalent of blood in insects, has a very different composition, being notably lacking in red blood cells, hemoglobin, and platelets, and having amoeba-like cells called hemocytes instead of white blood cells for immune defense.

Just like blood, hemolymph clots quickly outside the body. How it does so has long remained an enigma. Now, materials scientists have shown in Frontiers in Soft Matter how this feat is managed by caterpillars of the Carolina sphinx moth. This discovery has potential applications for human medicine, the authors said.

 These caterpillars, called tobacco hornworms, can seal the wounds within a minute. They do that in two steps: first, in a few seconds, their thin, water-like hemolymph becomes 'viscoelastic' or slimy, and the dripping hemolymph retracts back to the wound.

Next, hemocytes aggregate, starting from the wound surface and moving up to embrace the coating hemolymph film that eventually becomes a crust sealing the wound.

To seal a wound, caterpillars transform blood from a viscous to a viscoelastic fluid in a few seconds, Frontiers in Soft Matter (2024). DOI: 10.3389/frsfm.2024.1341129. www.frontiersin.org/articles/1 … fm.2024.1341129/full

Comment by Dr. Krishna Kumari Challa on March 28, 2024 at 7:28am

During the week required to complete the inflammatory process, the mouse memory-encoding neurons were found to have changed in various ways, including becoming more resistant to new or similar environmental stimuli.

This is noteworthy because we're constantly flooded by information, and the neurons that encode memories need to preserve the information they've already acquired and not be 'distracted' by new inputs.

Importantly, the researchers found that blocking the TLR9 inflammatory pathway in hippocampal neurons not only prevented mice from forming long-term memories but also caused profound genomic instability, i.e., a high frequency of DNA damage in these neurons.

Genomic instability is considered a hallmark of accelerated aging as well as cancer and psychiatric and neurodegenerative disorders such as Alzheimer's.

Drugs that inhibit the TLR9 pathway have been proposed for relieving the symptoms of long COVID. But caution needs to be shown because fully inhibiting the TLR9 pathway may pose significant health risks, say the researchers. 

 Jelena Radulovic, Formation of memory assemblies through the DNA-sensing TLR9 pathway, Nature (2024). DOI: 10.1038/s41586-024-07220-7. www.nature.com/articles/s41586-024-07220-7

Part 3

Comment by Dr. Krishna Kumari Challa on March 28, 2024 at 7:26am

Triggering inflammation to make memories

Further analysis showed that DNA fragments, along with other molecules resulting from the DNA damage, were released from the nucleus, after which the neurons' TLR9 inflammatory pathway was activated; this pathway in turn stimulated DNA repair complexes to form at an unusual location: the centrosomes.

These organelles are present in the cytoplasm of most animal cells and are essential for coordinating cell division. But in neurons—which don't divide—the stimulated centrosomes participated in cycles of DNA repair that appeared to organize individual neurons into memory assemblies.

Cell division and the immune response have been highly conserved in animal life over millions of years, enabling life to continue while providing protection from foreign pathogens.

It seems likely that over the course of evolution, hippocampal neurons have adopted this immune-based memory mechanism by combining the immune response's DNA-sensing TLR9 pathway with a DNA repair centrosome function to form memories without progressing to cell division.

Part 2

Comment by Dr. Krishna Kumari Challa on March 28, 2024 at 7:24am

Making long-term memories requires DNA damage, researchers discover

Just as you can't make an omelet without breaking eggs, scientists at Albert Einstein College of Medicine have found that you can't make long-term memories without DNA damage and brain inflammation. Their surprising findings were published in the journal Nature in a paper titled "Formation of memory assemblies through the DNA sensing TLR9 pathway."

Inflammation of brain neurons is usually considered to be a bad thing, since it can lead to neurological problems such as Alzheimer's and Parkinson's disease. But these new findings suggest that inflammation in certain neurons in the brain's hippocampal region is essential for making long-lasting memories.

The hippocampus has long been known as the brain's memory center.  Researchers found that a stimulus sets off a cycle of DNA damage and repair within certain hippocampal neurons that leads to stable memory assemblies—clusters of brain cells that represent our past experiences.

The researchers discovered this memory-forming mechanism by giving mice brief, mild shocks sufficient to form a memory of the shock event (episodic memory). They then analyzed neurons in the hippocampal region and found that genes participating in an important inflammatory signaling pathway had been activated.

Researchers observed strong activation of genes involved in the Toll-Like Receptor 9 (TLR9) pathway. This inflammatory pathway is best known for triggering immune responses by detecting small fragments of pathogen DNA. So at first scientists assumed the TLR9 pathway was activated because the mice had an infection. But looking more closely, they found, to their surprise, that TLR9 was activated only in clusters of hippocampal cells that showed DNA damage.

Brain activity routinely induces small breaks in DNA that are repaired within minutes. But in this population of hippocampal neurons, the DNA damage appeared to be more substantial and sustained.

Part 1

Comment by Dr. Krishna Kumari Challa on March 28, 2024 at 7:16am

Light is an oscillating or moving, electromagnetic wave that allows us to see objects. Sometimes, light oscillates in a preferred orientation, and we call it "polarized." Although polarized light surrounds us, to human eyes it is indistinguishable from "normal" light.

In the plasma around these black holes, particles whirling around magnetic field lines impart a polarization pattern perpendicular to the field. This allows astronomers to see in increasingly vivid detail what's happening in black hole regions and map their magnetic field lines.

By imaging polarized light from hot glowing gas near black holes, researchers are directly inferring the structure and strength of the magnetic fields that thread the flow of gas and matter that the black hole feeds on and ejects. Polarized light teaches us a lot more about the astrophysics, the properties of the gas, and mechanisms that take place as a black hole feeds.

Scientists are excited to have images of both supermassive black holes in polarized light because these images and the data that come with them provide new ways to compare and contrast black holes of different sizes and masses. As technology improves, the images are likely to reveal even more secrets of black holes and their similarities or differences.

 "M87* and Sgr A* are different in a few important ways: M87* is much bigger, and it's pulling in matter from its surroundings at a much faster rate. So, we might have expected that the magnetic fields also look very different. But in this case, they turned out to be quite similar, which may mean that this structure is common to all black holes.

A better understanding of the magnetic fields near black holes helps us answer several open questions—from how jets are formed and launched to what powers the bright flares we see in infrared and X-ray light. 

Issaoun, S. et al, First Sagittarius A* Event Horizon Telescope Results. VII. Polarization of the Ring, The Astrophysical Journal Letters (2024), DOI: 10.3847/2041-8213/ad2df0

Ricarte A. et al, "First Sagittarius A* Event Horizon Telescope Results. VIII. Physical Interpretation of the Polarized Ring," The Astrophysical Journal Letters (2024), DOI: 10.3847/2041-8213/ad2df1

Part 2

Comment by Dr. Krishna Kumari Challa on March 28, 2024 at 7:13am

Astronomers unveil strong magnetic fields spiraling at the edge of Milky Way's central black hole

A new image from the Event Horizon Telescope (EHT) collaboration—which includes scientists from the Center for Astrophysics | Harvard & Smithsonian (CfA)— has uncovered strong and organized magnetic fields spiraling from the edge of the supermassive black hole Sagittarius A* (Sgr A*).

Seen in polarized light for the first time, this new view of the monster lurking at the heart of the Milky Way galaxy has revealed a magnetic field structure strikingly similar to that of the black hole at the center of the M87 galaxy, suggesting that strong magnetic fields may be common to all black holes. This similarity also hints toward a hidden jet in Sgr A*.

The results were published in The Astrophysical Journal Letters.

Scientists unveiled the first image of Sgr A*—which is approximately 27,000 light-years away from Earth—in 2022, revealing that while the Milky Way's supermassive black hole is more than a thousand times smaller and less massive than M87's, it looks remarkably similar.

So scientists decided to check whether they are similar in all the  ways possible.

Part 1

Comment by Dr. Krishna Kumari Challa on March 27, 2024 at 10:49am

symbolic gesture in birds

Japanese tits (Parus minor) flutter their wings to invite their mate to enter the nest first. Scientists who observed eight breeding pairs of wild tits noticed that when one of the birds sat in front of the next box and fluttered its wings, the other would go in first. It’s the first documented evidence of birds using a symbolic gesture: one that has a specific meaning (like waving ‘goodbye’) but isn’t simply pointing at an object of interest. “It implies that birds have a level of understanding of symbolism that probably a lot of people wouldn’t have given them credit for before.

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