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Comment by Dr. Krishna Kumari Challa on March 30, 2024 at 6:58am

An infamous 'inflammasome'—a rogue protein complex—appears to underlie a rare and disabling autoimmune disorder

Autoimmune diseases are among the most puzzling because turncoat constituents of the body wage a constant state of war. Sometimes the underlying cause of an autoimmune condition is so obscure—hidden within chemical miscues of the body—that a long investigatory search must be mounted to sleuth out a cause.

And so it has been with in-depth research to understand an extremely rare autoimmune disorder. The condition is known as CAPS—cryopyrin-associated periodic syndrome. It afflicts patients with an array of disparate symptoms, ranging from skin rashes to permanent hearing loss.

To understand the disorder, scientists have had to explore the influences of cellular biomechanics and the roles of chemical miscues linked to an infamous inflammasome, a protein complex that triggers extreme inflammatory activity. CAPS, scientists now say, occurs because of an inflammasome that's gone rogue. Inflammasomes are multi-protein complexes found in the cytosol of cells that rapidly assemble and activate proinflammatory signaling in response to a diverse number of stimuli.

Normally, inflammasomes guard us against infection and cancer by triggering the domino effect of a powerful immune response. But inflammasome activity can also go awry and cause uncontrolled inflammation. Indeed, conditions known as autoinflammatory disorders, like CAPS, can occur when the body creates an immune response without an easily discernable cue, leading to a host of debilitating lifelong symptoms.

Like CAPS, there are other rare autoinflammatory conditions that cause a range of symptoms, from skin rashes to devastating inflammatory responses leading to fever, blindness, deafness, and cognitive decline.

CAPS, researchers say, is related to the overactivation of a notorious inflammasome—NLRP3—which can be influenced by miscues in mechanical signaling. Mechanical signaling occurs when cells in close contact with each other send errant signals that move through the cytoskeletons of affected cells.

The new research describes how mechanical signaling involving immune cells' membrane proteins can lead to autoimmunity affecting patients with CAPS. The rare disorder, which usually begins in infancy, is marked by waxing and waning lifelong symptoms. It's characterized by rashes, joint pain, red eyes and severe headaches with vomiting. Hearing loss usually occurs during the teen years and is often permanent.

Li Ran et al, KCNN4 links PIEZO-dependent mechanotransduction to NLRP3 inflammasome activation, Science Immunology (2023). DOI: 10.1126/sciimmunol.adf4699

Comment by Dr. Krishna Kumari Challa on March 30, 2024 at 6:49am

Researchers calculate that the r-process has provided 96% of the abundance of 127I on Earth, an isotope essential for human life, and most of the abundance of bromine and gadolinium in the Earth's crust, plus all of the Earth's thorium and uranium and a fraction of the molybdenum and cadmium.

Where does the r-process occur? One possibility is the material ejected during the rebound from a core-collapse supernova, the explosions of stars near the end of their thermonuclear lifetimes. But there is long-standing uncertainty in the detailed physics of this process.
One phenomenon where the r-process does occur is the merger of two neutron stars, called a kilonova. Such mergers are directly caused by gravitational waves.

As the binary pair spiral towards one another over hundreds of millions of years, they radiate an enormous amount of energy in the form of gravitational waves near the end. The amount of energy can be huge—trillions of trillions of watts in the last few milliseconds.
Kilonovae outbursts are important sites of the r-process, as neutron stars are made almost entirely of neutrons. Besides the gravitational wave observatories, other detectors detected GW170817 in the electromagnetic spectrum, and found spectroscopic evidence of the material created and tossed out from the merger.

The paper concludes that the iodine essential for human life was "probably produced by the r-process in the collisions of neutron stars that were induced by the emissions of gravitational waves, as well as other essential heavy elements." The group suggests searching for 129I in lunar regolith, which is uncontaminated by manmade sources.
Neutron star collisions occur because binary systems lose energy by emitting gravitational waves - so these fundamental physics phenomena may have made human life possible.

John Ellis et al, Do we owe our existence to gravitational waves?, arXiv (2024). DOI: 10.48550/arxiv.2402.03593

Part 2

Comment by Dr. Krishna Kumari Challa on March 30, 2024 at 6:47am

Gravitational waves may have made human life possible

Could it be that human existence depends on gravitational waves? Some key elements in our biological makeup may come from astrophysical events that occur because gravitational waves exist, a research team suggests.

In particular, iodine and bromine are found on Earth thanks to a particular nuclear process that happens when neutron stars collide. In turn, orbiting neutron star pairs inspiral and collide due to their emissions of energy in the form of gravitational waves. There may thus be a direct path from the existence of gravitational waves to the existence of mammals.

Humans are mostly made up of hydrogen, carbon and oxygen, with many additional trace elements. (There are 20 elements essential to human life.) Those with an atomic number less than 35 are produced in supernovae, implosions of stars that have exhausted their nuclear fuel and collapsed inward. The collapse results in an explosion that spews their atoms all over the universe.

But two elements are provided by other means—iodine, needed in key hormones produced by the thyroid, and bromine, used to create collagen scaffolds in tissue development and architecture.

Thorium and uranium have been indirectly important for human life, as their radioactive decays in Earth's interior heat the lithosphere and allow tectonic activity. The movement of tectonic plates removes and submerges carbon from the crust of the planet, which is itself removed from the atmosphere via water reacting with carbon dioxide and silicates, avoiding the possibility of a runaway greenhouse effect like has happened on Venus.

About half the heavy elemental atoms on Earth (heavier than iron) are produced by what's known as the "r-process"—the rapid neutron-capture process. The r-process occurs when a heavy atomic nucleus captures a succession of free neutrons before the nucleus has had a chance to decay (usually by beta decay). With a high enough density of free neutrons, calculated to be about 1024 per cubic centimeter, and at high temperatures, around a billion Kelvin, neutrons are absorbed and heavier isotopes of an element are synthesized.

Part 1

Comment by Dr. Krishna Kumari Challa on March 29, 2024 at 12:11pm

Old immune system becomes young again
Antibodies rejuvenate immune responses in old mice by targeting stem cells that replenish white and red blood cells. The balance of these stem cells changes as mice (and humans) age — this might be one reason why older animals mount less of an immune response against pathogens. Aged mice that received the antibody treatment had a stronger reaction to vaccination, and were better able to fend off viral infection, than untreated rodents.

Nature | 
Read an expert analysis by developmental biologist Yasar Arfat Kasu and stem-cell biologist Robert Signer in the Nature News & Views article 
Reference: Nature paper

Comment by Dr. Krishna Kumari Challa on March 29, 2024 at 12:10pm

Climate change is slowing Earth’s rotation
Melting ice caps are slowing the rotation of the Earth and could delay the next leap second by three years. Adding or removing seconds every few years keeps official atomic-clock time in line with the natural day, which varies slightly in line with the planet’s rotation rate. Since the early 1990s, the flow of water away from Earth’s axis of rotation and towards the Equator has worked to slightly slow down its spin. “It’s yet another way of impressing upon people just how big a deal [climate change] is,” says geophysicist and study author Duncan Agnew.

https://www.nature.com/articles/d41586-024-00932-w?utm_source=Live+...

Comment by Dr. Krishna Kumari Challa on March 29, 2024 at 9:18am

Google Street View reveals how built environment correlates with risk of cardiovascular disease

Researchers have used Google Street View to study hundreds of elements of the built environment, including buildings, green spaces, pavements and roads, and how these elements relate to each other and influence coronary artery disease in people living in these neighborhoods.

Their findings, published in the European Heart Journal recently, show that these factors can predict 63% of the variation in the risk of coronary heart disease from one area to another.

Coronary heart disease, where a build-up of fatty substances in the coronary arteries interrupts the blood supply to the heart, is one of the most common forms of cardiovascular disease.

Researchers say that using Google Street View can help provide an overview of physical environmental risk factors in the built and natural environments that could help not only in understanding risk factors in these environments, but ultimately help towards building or adapting towns and cities to make them healthier places to live.

The research revealed that features of the built environment visible on Google Street View images could predict 63% of the variation in coronary heart disease between these small regions.

The association of residential location with outcomes often supersedes that of known biological risk factors. This is often summarized with the expression that a person's postal code is a bigger determinant of their health than their genetic code. However, our ability to appropriately classify environmental risk factors has relied on population surveys that track wealth, pollution, and community resources.

Zhuo Chen et al, Artificial intelligence-based assessment of built environment from Google Street View and coronary artery disease prevalence, European Heart Journal (2024). DOI: 10.1093/eurheartj/ehae158

Rohan Khera, Artificial intelligence-enhanced exposomics: novel insights into cardiovascular health, European Heart Journal (2024). DOI: 10.1093/eurheartj/ehae159

Researchers have shown that  they can use computer vision approaches to help identify environmental factors influencing cardiovascular risk and this could play a role in guiding heart-healthy urban planning. The fact that they  can do this at scale is something that is absolutely unique and important for urban planning.

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

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