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Comment by Dr. Krishna Kumari Challa on August 25, 2024 at 11:54am

Researchers discover gene scissors that switch off with a built-in timer

CRISPR gene scissors, as new tools of molecular biology, have their origin in an ancient bacterial immune system. But once a virus attack has been successfully overcome, the cell has to recover.

Researchers  have discovered a timer integrated into the gene scissors that enables the gene scissors to switch themselves off. The results of the study have been published in the journal Nucleic Acids Research.

Sophie C Binder et al, The SAVED domain of the type III CRISPR protease CalpL is a ring nuclease, Nucleic Acids Research (2024). DOI: 10.1093/nar/gkae676

Some bacteria have developed CRISPR gene scissors in response to attacks by so-called phages. This bacterial immune system recognizes the phage genetic material, destroys it and thus protects against viral attacks.

When detecting phages, the type III variants of these immune systems produce messenger substances with cyclic oligoadenylates (cOAs), which the bacteria use to switch on a complex emergency plan. This ensures that a virus can be fought optimally and on a broad front.

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Comment by Dr. Krishna Kumari Challa on August 25, 2024 at 11:20am

Thyroid hormone fuels the drive to explore by rewiring brain circuits, new study suggests

Thyroid hormone plays a key role in regulating a range of physiologic functions, including metabolism, temperature, heart rate, and growth. It accomplishes this impressive array of activities by interacting with almost every organ system in the body. Yet despite a long history of research on how thyroid hormone influences different organs, its effects on arguably the most crucial organ—the brain—have remained shrouded in mystery.

Now, scientists have gained new insights into thyroid hormone's effects on the brain. The work, conducted in mice and published Aug. 22 in Cell, shows that thyroid hormone changes the wiring of brain circuits in a manner that drives animals to engage in exploratory behaviour. 

By simultaneously changing brain wiring and altering metabolic rate, the researchers concluded that thyroid hormone coordinates the brain and body to produce exploratory behavior when it is most needed—for example, during seasons when animals need to find mates or stockpile resources.

It's well known that thyroid hormone modulates metabolism, and now scientists have shown that it also modulates exploratory behaviours through direct action on the brain.

The findings also help elucidate how low levels of the hormone could lead to depressive states marked by a low desire to explore, while too much could precipitate manic states characterized by an extreme desire for exploration. Thus, the researchers see their work as an important step toward understanding how aberrant levels of thyroid hormone could contribute to certain psychiatric conditions.

Daniel Hochbaum et al, Thyroid hormone remodels cortex to coordinate body-wide metabolism and exploration, Cell (2024). DOI: 10.1016/j.cell.2024.07.041. www.cell.com/cell/fulltext/S0092-8674(24)00835-3

Comment by Dr. Krishna Kumari Challa on August 25, 2024 at 11:15am

What's more, the dendrocolloidal host material itself is relatively inexpensive and easy to fabricate.

 A Primordial DNA Store and Compute Engine, Nature Nanotechnology (2024). DOI: 10.1038/s41565-024-01771-6. www.nature.com/articles/s41565-024-01771-6

Part 2

Comment by Dr. Krishna Kumari Challa on August 25, 2024 at 11:14am

For first time, DNA tech offers both data storage and computing functions

Researchers have demonstrated a technology capable of a suite of data storage and computing functions—repeatedly storing, retrieving, computing, erasing or rewriting data—that uses DNA rather than conventional electronics. Previous DNA data storage and computing technologies could complete some but not all of these tasks.

The paper, titled "A Primordial DNA Store and Compute Engine," appears in the journal Nature Nanotechnology.

In conventional computing technologies, we take for granted that the ways data are stored and the way data are processed are compatible with each other.

But in reality, data storage and data processing are done in separate parts of the computer, and modern computers are a network of complex technologies.

DNA computing has been grappling with the challenge of how to store, retrieve and compute when the data is being stored in the form of nucleic acids.

For electronic computing, the fact that all of a device's components are compatible is one reason those technologies are attractive. But, to date, it's been thought that while DNA data storage may be useful for long-term data storage, it would be difficult or impossible to develop a DNA technology that encompassed the full range of operations found in traditional electronic devices: storing and moving data; the ability to read, erase, rewrite, reload or compute specific data files; and doing all of these things in programmable and repeatable ways.

Now researchers have  demonstrated that these DNA-based technologies are viable, because  they have made one.

The new technology is made possible by recent techniques that have enabled the creation of soft polymer materials that have unique morphologies.

Specifically, the tech developers have created polymer structures that they call dendricolloids—they start at the microscale, but branch off from each other in a hierarchical way to create a network of nanoscale fibers.

This morphology creates a structure with a high surface area, which allows the techies to deposit DNA among the nanofibrils without sacrificing the data density that makes DNA attractive for data storage in the first place.

You could put a thousand laptops' worth of data into DNA-based storage that's the same size as a pencil eraser.

The ability to distinguish DNA information from the nanofibers it's stored on allows us to perform many of the same functions you can do with electronic devices.

We can copy DNA information directly from the material's surface without harming the DNA. We can also erase targeted pieces of DNA and then rewrite to the same surface, like deleting and rewriting information stored on the hard drive. It essentially allows us to conduct the full range of DNA data storage and computing functions. In addition, they found that when we deposit DNA on the dendricolloid material, the material helps to preserve the DNA.

The researchers have demonstrated that the new data storage and computing technology—which they call a "primordial DNA store and compute engine"—is capable of solving simple sudoku and chess problems. Testing suggests that it could store data securely for thousands of years in commercially available spaces without degrading the information-storing DNA.

Part1

Comment by Dr. Krishna Kumari Challa on August 25, 2024 at 10:59am

When they tested the compound in rats that have a specific type of vasculitis, it decreased the disease severity, which was evident by reduced inflammation and damage in the blood vessels, especially in their kidneys and lungs.
Their findings suggest that CatC inhibition shows promise as a new treatment strategy to reduce neutrophil overactivation and improve conditions in diseases where overactive neutrophils and excessive NET formation play a critical role. This approach differs from current treatments that may have broader immunosuppressive effects.
Current treatments for inflammatory diseases often involve the use of glucocorticoids and immunosuppressive drugs which suppress the immune system's activity as a whole and can lead to secondary immunodeficiency, increasing the risk of opportunistic infections. By specifically targeting the activation of multiple NSPs through CatC inhibition without broadly suppressing the immune system, MOD06051 potentially offers a safer alternative that could reduce the risk of infections and other side effects.

These findings pave the way for further research and clinical trials to evaluate the safety and efficacy of MOD06051 in humans. The team is optimistic that this novel approach holds the promise of providing safer and more effective therapies for patients around the world suffering from a variety of inflammatory diseases, improving their quality of life.

Cathepsin C inhibition reduces neutrophil serine protease activity and improves activated neutrophil-mediated disorders, Nature Communications (2024). DOI: 10.1038/s41467-024-50747-6

Part 2

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Comment by Dr. Krishna Kumari Challa on August 25, 2024 at 10:57am

A new compound shows great potential for patients with neutrophil-associated inflammation

A newly developed compound that reduces harmful inflammation caused by overactive neutrophils in rats shows great potential as a safer treatment for various inflammatory diseases in humans.

Neutrophils are the most abundant type of white blood cells in the human body, and they play a crucial role in immune response. These immune cells help fight infections by engulfing pathogens and releasing enzymes that kill the invaders.

But although they're essential for fighting infections, neutrophils can also become overactive, leading to various inflammatory diseases. When they are activated by infection, neutrophils can release neutrophil extracellular traps (NETs), web-like structures consisting of DNA and proteins, which trap and kill pathogens as a part of the normal host defense mechanism. However, too much NET formation can significantly damage tissues, thus contributing to inflammation.

A team of researchers  has investigated a recently-developed drug candidate, MOD06051, which reduces harmful inflammation in rat models by targeting neutrophils. The results of their joint research appear in Nature Communications.

They found that MOD06051 works as a selective inhibitor for Cathepsin C (CatC), a key regulator that activates multiple enzymes inside of neutrophils known as neutrophil serine proteases (NSPs). One such NSP is neutrophil elastase, an enzyme involved in killing pathogens but also an essential factor for NET formation.

The scientists found that inhibiting CatC reduces the active form of neutrophil elastase and decreases the ability of neutrophils to form NETs. Excessive NET formation has been linked to several diseases, including vasculitis, lupus, rheumatoid arthritis, and diabetes.

Part 1

Comment by Dr. Krishna Kumari Challa on August 25, 2024 at 10:41am

The trick the sellers play:Why orange netting packaging makes oranges look more appealing

People who shop for groceries at their local supermarket may have noticed that some of the fruit they purchase may not look the same at home as it did in the store—or more specifically, after it is removed from its packaging. This is due to what has come to be known as the "confetti illusion"—in which pieces of coloured material partially obstructing the view of an image can change the way our brain processes its colouring.

Karl Gegenfurtner, a psychologist at Giessen University, in Germany, has found that the "confetti illusion" used by fruit sellers and others to push products is due to a perceptual illusion that involves the way our brains are programmed to interpret visual information. In his paper published in the journal i-Perception, he describes a brain phenomenon called color assimilation and how it contributes to optical illusions.

Food growers learned a long time ago that if they packed oranges in orange netting, the oranges inside look more orange, which the mind interprets as a more luscious ripe fruit. The same thing is true for yellow netting for lemons and green netting for limes. The color of the fruit as seen between the plastic netting is altered by what Gegenfurtner describes as colour assimilation.

This could be explained by prior research showing that sensory stimuli are always made up of partial information—the things we see are assembled into images only after the brain has knitted together input from several sources. When we look at an ordinary sidewalk, for example, we may perceive different images depending on ambient temperature, scents like recently mowed grass, or even the leftover residue in our mouths from our latest meal. 

By posting pictures of human faces with colored bars drawn across their faces in his paper, Gegenfurtner demonstrates that the change in fruit color is not due to the way light reflects off the netting. Because the images are 2D, there is no chance of colors from the bars reflecting off the imagery under them, yet the skin color and tone of the person behind them seems to change anyway.

Karl R. Gegenfurtner, Perceptual ripening of oranges, i-Perception (2024). DOI: 10.1177/20416695241258748

Comment by Dr. Krishna Kumari Challa on August 24, 2024 at 1:06pm

Mathematicians Prove Hawking Wrong About the Most Extreme Black Holes

For decades, extremal black holes were considered mathematically impossible. A new proof reveals otherwise.

Now two mathematicians have proved Hawking and his colleagues wrong. The new work — contained in a pair of recent papers by Christoph Kehle of the Massachusetts Institute of Technology and Ryan Unger of Stanford University and the University of California, Berkeley — demonstrates that there is nothing in our known laws of physics to prevent the formation of an extremal black hole.

https://arxiv.org/abs/2402.10190

https://arxiv.org/abs/2211.15742

https://www.quantamagazine.org/mathematicians-prove-hawking-wrong-a...

Comment by Dr. Krishna Kumari Challa on August 24, 2024 at 11:37am

Smallpox vaccination in childhood could offer protection against monkeypox clade II viruses, study finds

A study by co-authors from the ECDC, WHO and national public health institutes in four European countries, and published in Eurosurveillance, has found that prior smallpox vaccination in childhood could protect against infections caused by monkeypox virus (MPXV) clade II in men. However, the estimated degree of protection varied among countries, highlighting the need for further research to validate the study findings.

The study findings suggest that historical childhood smallpox vaccination in a European setting could protect two-thirds of men against mpox caused by MPXV clade II. However, there was significant uncertainty in the results and variation between countries. The results of this study are therefore not sufficient to support differential smallpox vaccination to protect against mpox based on historical smallpox vaccination status or age.

The authors recommend that individuals with a high risk of exposure be offered mpox vaccination, regardless of vaccination history.

 Effectiveness of historical smallpox vaccination against mpox clade II in Denmark, France, the Netherlands and Spain, 2022, Eurosurveillance (2024). DOI: 10.2807/1560-7917.ES.2024.29.34.2400139. www.eurosurveillance.org/conte … S.2024.29.34.2400139

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Comment by Dr. Krishna Kumari Challa on August 24, 2024 at 11:33am

Researchers identify piRNAs as a highly relevant genetic cause of male infertility

Many couples struggle with infertility. Contrary to popular belief, men are just as often the cause of an unfulfilled desire for children as women—and genetics play a significant role in this. Researchers from the Institute of Reproductive Genetics at the University of Münster have now provided new insights on this topic.

The study, published in Nature Communications, shows for the first time that disruptions in the so-called piRNA pathway are an underestimated cause of defective sperm production.

RNA, short for ribonucleic acid, is a single-stranded molecule composed of nucleotides present in every cell of an organism and acts as a carrier of genetic information. PiRNA refers to specialized, very small RNA fragments found in the testes that help suppress the activity of transposons, also known as jumping genes. 

The researchers analyzed the DNA of more than 2,000 infertile men, mostly from the Münster Center for Reproductive Medicine and Andrology, for variations in piRNA pathway genes.

They identified 39 men with variations in 14 piRNA genes, many of which are reported  for the first time.  Their findings reveal that faulty regulation of piRNAs is a far more common cause of male infertility than previously recognized.

The impact of these genetic variants on sperm production differed between humans and mouse models, suggesting that findings from mice are not universally applicable to humans. In some patients with piRNA variants, an increased number of transposons was detected.

A higher count of jumping genes in germ cells causes genomic instability, leading to various disruptions in sperm production, from abnormal shapes to complete absence of sperm.

While the newly discovered disruptions in the piRNA pathway cannot yet be treated, these insights will help provide more men with an accurate diagnosis in the future—offering relief to many who have faced years of uncertainty and allowing for more targeted treatments.

Birgit Stallmeyer et al, Inherited defects of piRNA biogenesis cause transposon de-repression, impaired spermatogenesis, and human male infertility, Nature Communications (2024). DOI: 10.1038/s41467-024-50930-9

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