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Comment by Dr. Krishna Kumari Challa on March 30, 2024 at 8:43am

Keeping cells together—how our body resists mechanical stress

Our body consists of ~30 trillion cells. These cells need to tightly attach to each other to maintain the integrity of our body. However, we are constantly exposed to mechanical stress, which continuously challenges the integrity of our bodies. How are cells able to resist mechanical force to maintain the integrity of our body? Why doesn't our body fall apart when we fall down on the street or when the guts move to digest the food? The secret lies in the cell-to-cell adhesion apparatus that keeps our cells together.

Cells hold on to each other through junctions that serve to connect the neighboring cells. At least three types of junctions are known: tight junctions, adherens junctions, and desmosomes. Previous studies have shown that adherens junctions and desmosomes play critical roles in maintaining the integrity of our body. However, the roles of tight junctions in resisting mechanical stress have not been demonstrated till recently.
One reason that hindered the attempts to understand the roles of tight junctions was that it had been difficult to specifically and completely eliminate its activity due to the overlapping functions of its key constituents. A few years ago, a research group succeeded in generating an epithelial cell line that specifically and completely lacks tight junction membrane proteins claudins and JAM-A, and demonstrated that these cells completely lack tight junctions.

In carefully examining these cells, the researchers found something bizarre. While normal cells are always connected to each other by a continuous belt of cell-to-cell junctions, sporadic disruption and fragmentation of cell-to-cell junctions were observed in these cells. Scientists had never seen something like this before and became curious about this issue.
Part 1

Comment by Dr. Krishna Kumari Challa on March 30, 2024 at 8:25am

Study shows common water pollutants cause heart damage in fish

Recent findings highlight the persistence of dihalogenated nitrophenols (2,6-DHNPs) in drinking water, resisting standard treatments like sedimentation, filtration, and boiling. The research demonstrates the severe cardiotoxic effects of these contaminants on zebrafish embryos at concentrations as low as 19 μg/L, indicating potential health risks for humans.

2,6-DHNPs, a group of disinfection byproducts (DBPs), are raising alarm bells for public health. These bad actors in the water world are tougher and more toxic than many other pollutants, making it hard for typical water cleaning methods to get rid of them.

They pack a powerful punch, being significantly more harmful to marine life and cells than similar pollutants. Found in places like sewage, swimming pools, and our drinking taps, 2,6-DHNPs are everywhere, signaling a pressing need for better ways to clean our water and keep us safe.

A new study, published in Eco-Environment & Health has uncovered the severe cardiotoxic impacts 2,6-DHNPs have on zebrafish embryos, serving as a model for potential human health risks.

2,6-DHNPs, a group of DBPs resistant to traditional water purification methods like boiling and filtration. These DBPs pose a significant risk, showing a toxicity level 248 times higher than the known regulated DBPs, dichloroacetic acid, in zebrafish embryos. Using zebrafish as a biological model due to their genetic similarity to humans the study meticulously detailed how these emerging contaminants wreak havoc on cardiac health.

The zebrafish embryos exposed to 2,6-DHNPs suffered from severe heart damage characterized by increased production of harmful reactive oxygen species, cell death (apoptosis), and disrupted heart development.

This research underscores a critical environmental and public health issue: the contaminants that survive water treatment processes can lead to severe health outcomes in exposed organisms, hinting at the possible public health risks faced by these persistent waterborne chemicals.

The study revealed that 2,6-DCNP and 2,6-DBNP, two types of DBPs, exhibited significant resistance to removal in drinking water treatment plants. Boiling and filtration were found to be the most effective household water treatment methods, reducing 2,6-DCNP and 2,6-DBNP levels by 47% and 52%, respectively. Exposure to 2,6-DHNPs caused heart failure in zebrafish embryos through increased production of harmful reactive oxygen species (ROS) and delayed heart development. Notably, the antioxidant N-acetyl-L-cysteine was able to mitigate the cardiotoxic effects induced by 2,6-DHNPs.

Hongjie Sun et al, Dihalogenated nitrophenols in drinking water: Prevalence, resistance to household treatment, and cardiotoxic impact on zebrafish embryo, Eco-Environment & Health (2024). DOI: 10.1016/j.eehl.2024.02.004

Comment by Dr. Krishna Kumari Challa on March 30, 2024 at 7:54am

What causes a landslide? | Natural Disasters

Comment by Dr. Krishna Kumari Challa on March 30, 2024 at 7:10am

The study is based on electronic medical records and registry data for 15,760 women with obesity in Stockholm and Gotland (the so-called Stockholm Gotland Perinatal Cohort). Of the women in the study, 11,667 had obesity class 1; 3,160 had obesity class 2; and 933 had obesity class 3. The study included singleton pregnancies that delivered between 2008 and 2015. The women were followed for a median of eight years after delivery.

Ten known adverse outcomes associated with weight gain during pregnancy were studied: pre-eclampsia, gestational diabetes, excess postpartum weight retention, maternal cardiometabolic disease, unplanned cesarean delivery, preterm birth, large for gestational age and small for gestational age at birth, stillbirth and infant death. These adverse outcomes were assigned weights according to their severity and combined into an adverse composite outcome.

Overall, the study shows no increased risks of the adverse composite outcome with weight gain below current IOM guidelines in women with obesity classes 1 and 2. For women with obesity class 3, on the contrary, weight gain values below the guidelines or weight loss were associated with reduced risk of the adverse composite outcome. For example, an absence of weight gain (i.e., 0kg) was associated with a risk reduction of about 20%.

Based on this, researchers have concluded that weight gain below current recommendations is likely safe in pregnancies with obesity, and might even be beneficial for those with class 3 obesity.
The results also indicate that there is a need for specific recommendations for women with class 3 obesity. Unlike today, this group could receive separate recommendations.

Kari Johansson et al, Safety of low weight gain or weight loss in pregnancies with class 1, 2, and 3 obesity: a population-based cohort study, The Lancet (2024). DOI: 10.1016/S0140-6736(24)00255-1

Part 2

Comment by Dr. Krishna Kumari Challa on March 30, 2024 at 7:08am

Women with obesity do not need to gain weight during pregnancy, new study suggests

The guidelines for weight gain during pregnancy in obese women have long been questioned. New research  supports the idea of lowering or removing the current recommendation of a weight gain of at least 5 kg. The results are published in The Lancet.

International guidelines from the U.S. Institute of Medicine (IOM) state that women with obesity should gain a total of 5 to 9 kg during pregnancy, compared to 11.5 to 16 kg for normal-weight women. The guidelines have long been questioned, but there has been no evidence to warrant a re-examination.

A new study from Karolinska Institutet in Sweden now shows that there are no increased health risks for either the mother or the child with weight gain below current guidelines for women with obesity class 1 and 2 (BMI of 30–34.9 and 35–39.9 respectively). On the contrary, for women with obesity class 3 (BMI over 40), weight gain below current guidelines might even be beneficial for those with class 3 obesity.

The study supports previous calls to either lower or remove the current recommended lower limit of a weight gain of at least 5 kg.

Part 1

Comment by Dr. Krishna Kumari Challa on March 30, 2024 at 7:04am

Genetic causes of cerebral palsy uncovered through whole-genome sequencing

A new study by researchers  has identified genes which may be partially responsible for the development of cerebral palsy.

Cerebral palsy (CP), a condition that affects the development of motor skills in children, is the most common childhood-onset physical disability. CP can have different causes, such as infections, injuries, or lack of oxygen before or during birth, but the genetic contributors to CP have remained largely unknown till recently.

Novel research by scientists  provides a more detailed look into the genetic causes of the condition. Their findings suggest the existence of many genetic variants contributing to CP, which may inform future diagnosis and treatment.

Now that we have a better understanding into the complex relationship between cerebral palsy's genetic and environmental factors, we hope we can improve care for these children.

One in ten children with CP have a genetic variant associated with their condition Published in Nature Genetics, the scientists conducted whole-genome sequencing in 327 children with CP, including their biological parents, and compared it to three independent clinical cohorts as well as two pediatric control cohorts, to identify whether genetic variants may be involved in CP.

The seven-year study found that more than one in ten children (11.3 percent) had a genetic variant or likely genetic variant for their CP, and 17.7 percent of children had variants of uncertain significance that may be linked with CP after further research. Many of the variants also overlapped with other neurodevelopmental conditions, including autism spectrum disorder (ASD), which is highly prevalent in children with CP.

The findings suggest that CP and its causes may be much more diverse than previously thought and showcases the strength of combining precision medicine programs, a movement to deliver individualized care to each patient.

Comprehensive whole-genome sequence analyses provide insights into the genomic architecture of cerebral palsy, Nature Genetics (2024). DOI: 10.1038/s41588-024-01686-x. www.nature.com/articles/s41588-024-01686-x

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

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