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Comment by Dr. Krishna Kumari Challa on February 9, 2023 at 9:14am

Donor hearts can be reprogrammed with medication for longer storage, improved transplant outcomes

Although thousands of people are sick with heart failures around the world,  only around few heart transplants are performed annually.

One reason for this gap is the time window during which a heart can survive outside the donor body before transplant hovers around four hours. And the longer it takes for the donor heart to be transported to the recipient, the more likely that heart will not work well once it's implanted.

Using a drug previously used to treat seizures, researchers have found a way to reprogram donor hearts to boost the production of a beneficial enzyme that both increases the amount of time they can be stored and transported, as well as improves their function after they are transplanted, a study published in Science Translational Medicine suggests. This technology that coaxes donor hearts to mount adaptive responses to existence outside the body could lead to a paradigm shift not only for extending the time a heart can be outside of the donor during transport but for improving heart function after transplant.

Being able to extend the storage of hearts by figuring out the pathways that define and modulate preservation biology is the first step toward the ultimate goal of organ banking.

Current donor preservation techniques focus on cold storage and, more recently, technologies that keep the organs perfused during transport to minimize injury to the heart, but there are no targeted molecular therapies to improve heart preservation in a very precise fashion.

When an organ is in cold storage, succinate is free to build up in excess—more ammunition for stress against the soon-to-be-transplanted heart. To reprogram hearts to take on the heart-damaging succinate, researchers used valproic acid, a histone deacetylase inhibitor previously used as an anti-seizure medication. They found that it defused a significant amount of this cumulative stress in both human and pig hearts by instructing the donor heart to produce antioxidants and anti-inflammatory proteins while preserved on ice.

Using a metabolomic screen, researchers found that valproic acid can reprogram the donor heart to produce beneficial itaconate during preservation.

Ienglam Lei et al, Metabolic reprogramming by immune-responsive gene 1 upregulation improves donor heart preservation and function, Science Translational Medicine (2023). DOI: 10.1126/scitranslmed.ade3782. www.science.org/doi/10.1126/scitranslmed.ade3782

Comment by Dr. Krishna Kumari Challa on February 9, 2023 at 9:05am

Three hallmarks of aging work together to prevent cancer: 

telomeres, mitochondria, and inflammation

As we age, the end caps of our chromosomes, called telomeres, gradually shorten. Now,  scientists have discovered that when telomeres become very short, they communicate with mitochondria, the cell's powerhouses. This communication triggers a complex set of signaling pathways and initiates an inflammatory response that destroys cells that could otherwise become cancerous.

The findings, published in Nature on February 8, 2023, could lead to new ways of preventing and treating cancer as well as designing better interventions to offset the harmful consequences of aging.

It is surprising to note that telomeres talk to mitochondria. They clearly synergize in well-controlled biological processes to initiate cellular pathways that kill cells that could cause cancer.

When telomeres shorten to a point where they can no longer protect chromosomes from damage, a process called "crisis" occurs and cells die. This beneficial natural process removes cells with very short telomeres and unstable genomes and is known to be a powerful barrier against cancer formation. Cells in crisis are removed by a process called autophagy, in which the body rids itself of damaged cells.

 Jan Karlseder, Telomere-to-mitochondria signalling by ZBP1 mediates replicative crisis, Nature (2023). DOI: 10.1038/s41586-023-05710-8. www.nature.com/articles/s41586-023-05710-8

Comment by Dr. Krishna Kumari Challa on February 9, 2023 at 8:33am

A new ring system discovered in our solar system

Scientists have discovered a new ring system around a dwarf planet on the edge of the solar system. The ring system orbits much further out than is typical for other ring systems, calling into question current theories of how ring systems are formed.

The ring system is around a dwarf planet, named Quaoar, which is approximately half the size of Pluto and orbits the sun beyond Neptune.

The discovery, published in Nature, was made by an international team of astronomers using HiPERCAM—an extremely sensitive high speed camera developed by scientists at the University of Sheffield which is mounted on the world's largest optical telescope, the 10.4 meter diameter Gran Telescopio Canarias (GTC) on La Palma.

The rings are too small and faint to see directly in an image. Instead, the researchers made their discovery by observing an occultation, when the light from a background star was blocked by Quaoar as it orbits the sun. The event lasted less than a minute, but was unexpectedly preceded and followed by two dips in light, indicative of a ring system around Quaoar.

Ring systems are relatively rare in the solar system. In addition to the well-known rings around the giant planets Saturn, Jupiter, Uranus and Neptune, only two other minor planets possess rings—Chariklo and Haumea. All of the previously known ring systems are able to survive because they orbit close to the parent body, so that tidal forces prevent the ring material from accreting and forming moons.

What makes the ring system around Quaoar remarkable is that it lies at a distance of over seven planetary radii—twice as far out as what was previously thought to be the maximum radius according to the so-called "Roche limit," which is the outer limit of where ring systems were thought to be able to survive. For comparison, the main rings around Saturn lie within three planetary radii. This discovery has therefore forced a rethink on theories of ring formation.

Bruno Morgado, A dense ring of the trans-Neptunian object Quaoar outside its Roche limit, Nature (2023). DOI: 10.1038/s41586-022-05629-6. www.nature.com/articles/s41586-022-05629-6

Comment by Dr. Krishna Kumari Challa on February 8, 2023 at 10:54am

What generative AI means for science

Some scientists now frequently use generative artificial-intelligence (AI) systems, such as ChatGPT, to help them write and edit manuscripts, check their code and brainstorm ideas. But the excitement about the use of such tools is tempered with apprehe..., because of their propensity to make factual errors, reproduce biases in training data and provide fuel for fakery. They also rely on humans to tag reams of violent, abusive and other horrific content so that it can be filtered out, and require a huge amount of energy to train. Researchers are grappling with these issues, in part by urging more regulation and transparency.

https://www.nature.com/articles/d41586-023-00340-6?utm_source=Natur...

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If wormholes exist, they might magnify light by 100,000 times

A small team of astrophysicists affiliated with several institutions in China has found evidence that suggests if wormholes are real, they might magnify light by 100,000 times. In their paper published in the journal Physical Review Letters, the group describes the theories they have developed and possible uses for them.

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This exoplanet orbits around its star's poles

In 1992, humanity's effort to understand the universe took a significant step forward. That's when astronomers discovered the first exoplanets. They're named Poltergeist (Noisy Ghost) and Phobetor (Frightener), and they orbit a pulsar about 2300 light-years away.

Comment by Dr. Krishna Kumari Challa on February 8, 2023 at 10:22am

New way climate change is fueling itself

Healthy, undisturbed soil sinks carbon, storing what's generated when plants and other living things decompose so it doesn't get released as a planet-warming greenhouse gas.

But a new study  suggests nitrogen pollution from cars and trucks and power plants might make soil release that carbon in dry places—worsening, rather than helping to fight, climate change.

In places that get more regular rain and snow, other studies have shown that adding nitrogen to soil can increase carbon storage. Nitrogen fuels plant growth, which captures carbon and draws it down into the soil. It also helps slow decomposition of whatever is in the soil.

Dryland ecosystems cover roughly 45% of land on Earth. They also store 33% of the carbon found in the top layer of soil worldwide. So if nitrogen pollution is making the carbon stored in these soils vulnerable, that definitely rings some alarm bells.

The findings offer new motivation, then, to speed the transition away from fossil fuels and cut back on nitrogen-rich fertilizer if we want to slow global warming that's already creating climate refugees due to worsening heat waves, droughts, floods and wildfires.

https://phys.org/news/2023-02-dirty-truth-climate-fueling.html?utm_...

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Comment by Dr. Krishna Kumari Challa on February 7, 2023 at 12:38pm

Scientists Create Semi-Living 'Cyborg' Cells That Could Transform Medicine

Through a complex chemical process, scientists have been able to develop versatile, synthetic 'cyborg' cells in the lab. They share many characteristics of living cells while lacking the ability to divide and grow.

That non-replication part is important. For artificial cells to be useful, they need to be carefully controlled, and that can't happen as easily if they're propagating in the same way that actual cells do.

The researchers behind the new development think these cyborgs could have a huge variety of applications, from improving treatments for diseases like cancer to cleaning up pollution through targeted chemical processes.

The cyborg cells are programmable, do not divide, preserve essential cellular activities, and gain nonnative abilities.

Cell engineering is currently based on two key approaches: genetically remodeling existing cells to give them new functions (more flexible but also able to reproduce) and building synthetic cells from scratch (which can't replicate but have limited biological functions).

These cyborg cells are the result of a new, third strategy. The researchers took bacterial cells as their foundation and added elements from an artificial polymer. Once inside the cell, the polymer was exposed to ultraviolet light to build it into a hydrogel matrix by cross-linking, mimicking a natural extracellular matrix.

While able to maintain much of their normal biological functions, these cyborg cells proved to be more resistant to stressors like high pH and antibiotic exposure – stressors that would kill off normal cells. Much like actual cyborgs, they're tough.

Cyborg cells preserve essential functions, including cellular metabolism, motility, protein synthesis, and compatibility with genetic circuits.

Lab tests on tissue samples showed that the newly developed cells were able to invade cancer cells, highlighting the potential of these modified biological building blocks for health treatments further down the line – they could one day be used to deliver drugs to very specific parts of the body.

he researchers say they now want to experiment with the use of different materials to create these cells, as well as investigate how they could be used.

It's also not clear exactly what is stopping the cells from replicating, which needs to be determined. The authors think the hydrogel matrix may stop cell division by inhibiting cell growth or DNA replication, or both.

The blending of the natural and the artificial demonstrated here in some ways takes the best elements of both, opening up new possibilities – a state of "quasi vita" or "almost life", as the researchers put it.

https://onlinelibrary.wiley.com/doi/10.1002/advs.202204175

Comment by Dr. Krishna Kumari Challa on February 7, 2023 at 12:28pm

Harmful bacteria can elude predators when in mixed colonies

 Efforts to fight disease-causing bacteria by harnessing their natural predators could be undermined when multiple species occupy the same space, according to a new study.

When growing in mixed colonies, some harmful bacteria may be able to withstand attacks from the bacteria and viruses that target them by finding protection inside groups of rival species, according to a report published in the Proceedings of the National Academy of Sciences (PNAS).

The researchers found that the intestinal bacterium Escherichia coli became surrounded by tightly packed colonies of Vibrio cholerae—which causes the deadly disease cholera—when the species were grown together. These clusters protected E. coli from the bacteria Bdellovibrio bacteriovorus that preys on both species individually, but in the study could only kill the outer layer of V. cholerae. This left the unscathed cells of E. coli and V. cholerae insulated within the colonies free to multiply.

The findings add a new layer of complication to the development of biological antimicrobials, wherein bacteria-killing bacteria or viruses—known as bacteriophages—are deployed to fight infections.

For E. coli, if it grew with V. cholerae, it could do better than on its own, but V. cholerae did worse. It's fascinating that growing together had opposite effects on each species' chances of survival. This new research shows that the way prey populations can resist or not resist predators can be very different in multispecies conditions. The efficacy of bacteriophages and predatory bacteria to kill off harmful bacteria might depend on the other species their prey are living with, and on the biofilm structures they produce alone versus together.

These organisms can be more effective than antibiotics at penetrating bacterial colonies, or biofilms, and have emerged as a possible supplement or alternative to antibiotics. Bacteria worldwide have become more resistant to antibiotics due to the drugs' overuse.

Most of earlier research on predatory bacteria and phages, however, has focused on liquid cultures or single-species biofilms, not on mixed colonies like we see in human eco-systems. 

This work highlights the importance of studying other examples of multispecies biofilm structures. What the scientists  saw in this work will apply to other cases, but it's a question of when and to what extent.

Benjamin R. Wucher et al, Breakdown of clonal cooperative architecture in multispecies biofilms and the spatial ecology of predation, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2212650120

James B. Winans et al, Multispecies biofilm architecture determines bacterial exposure to phages, PLOS Biology (2022). DOI: 10.1371/journal.pbio.3001913

Comment by Dr. Krishna Kumari Challa on February 7, 2023 at 12:07pm

Scientists first in the world to regenerate diseased kidney cells

In a world first, scientists at Duke-NUS Medical School, the National Heart Center Singapore (NHCS) and colleagues in Germany have shown that regenerative therapy to restore impaired kidney function may soon be a possibility.

In a preclinical study reported in Nature Communications, the team found that blocking a damaging and scar-regulating protein called interleukin-11 (IL-11) enables damaged kidney cells to regenerate, restoring impaired kidney function due to disease and acute injuries.

Searching for ways to restore the kidney's ability to regenerate damaged cells, researchers investigated the role of IL-11, which is known to trigger scarring in other organs, including the liver, lungs and heart, in acute and chronic kidney disease.

Their findings implicate the protein in triggering a cascade of molecular processes in response to kidney injury that leads to inflammation, fibrosis (scarring) and loss of function. They also discovered that inhibiting IL-11 with a neutralizing antibody can prevent and even reverse kidney damage in this setting.

They found that IL-11 is detrimental to kidney function and triggers the development of chronic kidney disease. They also showed that anti-IL11 therapy can treat kidney failure, reverse established chronic kidney disease, and restore kidney function by promoting regeneration in mice, while being safe for long term use.

More specifically, the researchers showed that renal tubular cells, which line the tiny tubes inside kidneys, release IL-11 in response to kidney damage. This turns on a signaling cascade that ultimately leads to increased expression of a gene, called Snail Family Transcriptional Repressor 1 (SNAI1), which arrests cellular growth and promotes kidney dysfunction.

In a preclinical model of human diabetic kidney disease, turning off this process by administering an antibody that binds to IL-11 led to proliferation of the kidney tubule cells and reversal of fibrosis and inflammation, resulting in the regeneration of the injured kidney and the restoration of renal function.

While clinical trials of an antibody that binds to another pro-fibrotic molecule called transforming growth factor beta have been unsuccessful, this new approach brings hope of a new target.  This work has shown that scientists  can restore function to a damaged kidney.

This discovery could be a real game-changer in the treatment of chronic kidney disease—which is a major public health concern globally—bringing us one step closer to delivering the benefits promised by regenerative medicine.

Anissa A. Widjaja et al, Targeting endogenous kidney regeneration using anti-IL11 therapy in acute and chronic models of kidney disease, Nature Communications (2022). DOI: 10.1038/s41467-022-35306-1

Comment by Dr. Krishna Kumari Challa on February 7, 2023 at 11:52am

"Car brain" heard about it? It seems driving culture gives us a car brain, according to new research.

One of the conditions suffered by car-brained people is the belief in superiority of cars as a means of transport at the expense of bicycles, public transport and walking. 

I was surprised to read several of the conditions suffered by "car brained" people. Some of them even think drinking and driving is okay even if this causes accidents and kills people! 

Hmm! No wonder the accident rate is increasing day by day.

Comment by Dr. Krishna Kumari Challa on February 7, 2023 at 11:35am

Bacteria use dogma-defying DNA packaging

Some bacteria have a bizarre way of packaging chromosomes and regulating gene expression: they use proteins that weren’t thought to exist in bacteria at all. Researchers report that proteins called histones seem to coat regions of the bacterial chro... in two species. This is a marked difference from histones’ function in eukaryotes (which includes animals, plants and fungi), in which the proteins form a spool for DNA to wind around. The researchers surveyed thousands of bacterial genomes and found histone-like proteins in about 2%. For now, it’s unclear what the histones might be doing, and how their unusual mode of action might help the bacteria to survive.

https://www.biorxiv.org/content/10.1101/2023.01.26.525422v1?utm_sou...

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Driving culture gives us ‘car brain’

People seem to be more likely to excuse the negative effects of driving — such as pollution and accidents — than those in other areas of life. In a survey of 2,157 drivers and non-drivers in the United Kingdom, roughly half were asked to rate a statement about cars. The others were given an almost identical sentence about another issue. For example, 75% agreed that people shouldn’t smoke in highly populated areas where others have to breathe in the fumes — but only 17% agreed that people shouldn’t drive in highly populated areas. The researchers suggest that this ‘motonormativity’ inhibits our ability to think objectively about how we use cars.

https://psyarxiv.com/egnmj/

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