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Comment by Dr. Krishna Kumari Challa on November 7, 2024 at 8:26am

Those featured circles, ecDNAs, are small and often contain a few genes on their circular DNA. Frequently, these genes are cancer-associated genes called oncogenes. When a cancer cell contains multiple oncogene-encoding ecDNAs, they can supercharge the cell's growth and allow it to evade internal checkpoints meant to regulate cell division.

The ecDNAs also sometimes encode genes for proteins that can tamp down the immune system's response to a developing cancer—further advantaging tumor growth.
Until recently, it was thought that only about 2% of tumors contained meaningful amounts of ecDNA. But in 2017, research showed that the small circles were widespread and likely to play a critical role in human cancers.

In 2023, researchers further showed that their presence jumpstarts a cancerous transformation in precancerous cells.

In the first of the three papers researchers built on 2017 finding by analyzing the prevalence of ecDNA in nearly 15,000 cancer patients and 39 tumor types.

They found that 17.1% of tumors contained ecDNA, that ecDNA was more prevalent after targeted therapy or cytotoxic treatments like chemotherapy, and that the presence of ecDNA was associated with metastasis and poorer overall survival.

The researchers also showed that the circles can contain not just cancer-driving oncogenes and genes that modulate the immune response, but also that others can contain only DNA sequences called enhancers that drive the expression of genes on other circles by linking two or more ecDNAs together.
The ecDNAs with enhancer elements don't confer any benefit to the cell on their own; they have to work with other ecDNAs to spur cancer cell growth. If looked at through a conventional lens, the presence of ecDNAs that solely encode enhancers wouldn't seem to be a problem. But the teamwork and physical connection between different types of circles is actually very important in cancer development."
Through these studies researchers learned critical lessons about which cancer patients are affected and what genes or DNA sequences are found in ecDNAs. They identified the genetic backgrounds and mutational signatures that give them clues as to how cancers originate and thrive.

Howard Chang, Coordinated inheritance of extrachromosomal DNAs in cancer cells, Nature (2024). DOI: 10.1038/s41586-024-07861-8. www.nature.com/articles/s41586-024-07861-8

Paul Mischel, Enhancing transcription–replication conflict targets ecDNA-positive cancers, Nature (2024). DOI: 10.1038/s41586-024-07802-5. www.nature.com/articles/s41586-024-07802-5

Charles Swanton, Origins and impact of extrachromosomal DNA, Nature (2024). DOI: 10.1038/s41586-024-08107-3. www.nature.com/articles/s41586-024-08107-3

Part2

Comment by Dr. Krishna Kumari Challa on November 7, 2024 at 8:19am

Cracking the code of DNA circles in cancer: Scientists uncover potential therapy

A trio of research papers from Stanford Medicine researchers and their international collaborators transforms scientists' understanding of how small DNA circles—until recently dismissed as inconsequential—are major drivers of many types of human cancers.

The papers, published simultaneously in Nature on Nov. 6, detail the prevalence and prognostic impact of the circles, called ecDNA for extrachromosomal DNA, in nearly 15,000 human cancers; highlight a novel mode of inheritance that overthrows a fundamental law of genetics; and describe an anti-cancer therapy targeting the circles that is already in clinical trials.

The team, jointly known as eDyNAmiC, are a group of international experts led by professor of pathology Paul Mischel, MD. In 2022, Mischel and the eDyNAmiC team were awarded a grant to learn more about the circles.

Cancer Grand Challenges, a research initiative co-founded by Cancer Research UK and the National Cancer Institute in the United States, supports a global community of interdisciplinary, world-class research teams to take on cancer's toughest challenges.

We're in the midst of a completely new understanding of a common and aggressive mechanism that drives cancer, say these scientists. 

Each paper alone is noteworthy, and taken together they represent a major inflection point in how we view cancer initiation and evolution.

Part 1

Comment by Dr. Krishna Kumari Challa on November 6, 2024 at 11:23am

Researchers suspected that hearing played a role in this behaviour, so they investigated the insect's auditory neurons. These lie at the base of the antennae in a structure called the Johnston's organ.

The antennae are magnificent multi-sensory apparatuses, chock-full of olfactory, mechanosensory and even thermal infrared sensilla, scientists recently discovered. In the current study, the team focused on a particular sensory channel called TRPVa—and the corresponding gene, trpVa—which is the mosquito analog of a channel required for hearing in fruit flies.
The team used CRISPR-Cas9 to knock out the gene that codes for TRPVa in Aedes aegypti mosquitoes. The resulting animals showed no reaction to sound. In fact, they found that sound elicited no electrical activity from neurons in the Johnston's organ. The insects were truly deaf.

And when the reearchers placed deaf males in chambers with females … nothing happened. If they can't hear the female wingbeat, they're not interested. Their hearing counterparts, on the other hand, wasted no time in getting busy: mating many times in the course of a few minutes.
Hearing is not only necessary for males to mate, it seems to be sufficient to rouse their desires. When the authors played the sound of female wingbeats to normal males, the males typically responded with abdominal thrusts. They were primed and ready for action. Deaf males barely twitched.
Females, however, were a different story. Deaf females still had some desire to mate left in them. The impact on the female is minimal, but the impact on the male is absolute.
In most organisms, mating behaviour is dependent on a combination of several sensory cues. In mosquitoes it depends on only one! A mosquito's physiology reveals just how important hearing is to these insects.

 Yijin Wang et al, Deafness due to loss of a TRPV channel eliminates mating behavior in Aedes aegypti males, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2404324121

Part 2

Comment by Dr. Krishna Kumari Challa on November 6, 2024 at 11:18am

Deaf male mosquitoes don't mate, researchers discover

Romance is a complex affair in humans. There's personality, appearance, seduction, all manner of physical and social cues. Mosquitoes are much more blunt. Mating occurs for a few seconds in midair. And all it takes to woo a male is the sound of a female's wingbeats. Imagine researchers' surprise when a single change completely killed the mosquitoes' libidos.

Now a study  reveals that this is really all there is to it. Researchers created deaf mosquitoes and found that the males had absolutely no interest in mating. You could leave them together with the females for days, and they will not mate.

The dramatic change was simple to produce. The absence of a single gene, trpVa, produced this profound effect on mosquito mating behaviour.

The results, published in the Proceedings of the National Academy of Sciences could have major implications for how we manage disease transmission by better controlling the populations of mosquito vectors, such as Aedes aegypti, that infect hundreds of millions of people every year with viruses that cause diseases.

Courtship for Aedes aegypti usually progresses like this: Females flap their wings at around 500 Hz. When males hear this, they take off, buzzing at about 800 Hz. The males also rapidly modulate this frequency when the ladies are around. Then there's a quick midair rendezvous, and the paramours go their separate ways. Males are always scouting out new potential partners, but a female that's successfully mated generally won't do so again.

Part 1

Comment by Dr. Krishna Kumari Challa on November 6, 2024 at 11:10am

The scientists found that only one protein controlled the color difference in the lories, a type of aldehyde dehydrogenase (or ALDH), essential "tools" for detoxification in complex organisms—for example, they contribute to elimination of alcohol in the liver of humans.
Parrot feathers found a way to 'borrow' this protein, using it to transform red to yellow psittacofulvins." According to the scientists, "This functions like a dial, in which higher activity of the protein translates to less intense red colour."
To understand the general role of this protein in controlling the plumage color in other parrot species, scientists studied another parrot, the rosy-faced lovebirds, a species that displays both green (i.e., yellow psittacofulvin-containing) and red plumage patches.

The rosy-faced lovebird is a familiar parrot that provides an excellent system to study the genes determining the color difference between red and yellow psittacofulvin-containing plumage patches.
They found that the same aldehyde dehydrogenase gene in the lovebirds is expressed at high levels in yellow psittacofulvin-containing feathers, but not in red feathers. When this gene expresses at a high level, the psittacofulvins turn from red to yellow.
To demonstrate this simple dial mechanism, scientists turned to an even more familiar parrot, the budgerigar and, in a world-first, explored how individual cells turn different genes on or off throughout feather growth, pinpointing a small number of cells that use this detox protein for controlling pigment conversion.

The final validation came when the scientists genetically engineered yeasts with the parrot color gene, Incredibly, their modified yeast produced parrot colours, demonstrating that this gene is sufficient to explain how parrots control the amount of yellow and red in their feathers.
This study showcases how cutting-edge developments in biotechnology are increasingly used to unravel nature's mysteries.
Scientists now understand how these stunning colours can evolve in wild animals through a simple dial-like "molecular switch" that "borrows" a detoxifying protein to serve a new function.

These findings help scientists paint a new colorful picture of evolution as a process in which complexity can be achieved through simple innovations.

 Roberto Arbore et al, A molecular mechanism for bright color variation in parrots, Science (2024). DOI: 10.1126/science.adp7710

Part 2

Comment by Dr. Krishna Kumari Challa on November 6, 2024 at 11:06am

Biologists reveal the genetic 'switch' behind parrot color diversity

Parrots are synonymous with colour for people across the world. In a study published in the journal Science, scientists  have uncovered for the first time a "switch" in the DNA of parrots that controls their wide gamut of colours.

Parrots are unique birds in many ways, including how they produce their vibrant colour diversity.

Although other birds also produce yellow and red feathers, parrots evolved unique pigments, called psittacofulvins. Parrots combine these with other pigments to create vibrant yellows, reds, and greens, making these animals among nature's most colourful.

To understand this unique colouration the scientists started by demonstrating that, across all major parrot lineages, yellow and red in feathers correspond to two specific pigments that do not occur in other birds.

The scientists focused on a species with naturally occurring red or yellow forms, a phenomenon that is extremely rare in nature.

Part 1

Comment by Dr. Krishna Kumari Challa on November 6, 2024 at 10:47am

Prodrug: Researchers discover localized pain relief using known chemical reaction

A team of international researchers have taken a well-known chemical reaction as the basis of a new generation of targeted pain relief medication.

The team has created a targeted prodrug (a compound which metabolizes inside the body into a pharmacologically active drug), and found it to be capable of relieving chronic pain during preclinical trials.

The mechanism of action for the targeted prodrug involves activation of the active drug by a chemical reaction with reactive oxygen species such as hydrogen peroxide, which are present in much higher amounts at sites of pain than the rest of the body.

This means that the prodrug is distributed around the body as an inactive chemical until it reaches a site of pain where it is then converted into the active drug.

The prodrug was tested in both chemical and preclinical models and found to provide localized relief of sciatic nerve injuries, as well as other models of chronic pain featuring oxidative stress like osteoarthritis, chemotherapy-induced peripheral neuropathy and diabetic neuropathy.

Testing found multi-day oral administration of the compound six months after the injury reversed hypersensitivity to touch and cold stimuli; while further tests demonstrated the effects of the drug were dose dependent, with maintained pain relief upon repeated dosing. This showed us that the compound did not induce a tolerance, which is a major limiting factor to powerful painkillers like morphine.

Chronic pain remains a large unmet medical need and nonaddictive treatments like this would revolutionize the field, which is currently dominated by addictive opioids.

The project will now undergo more pre-clinical trials to determine effectiveness and safety.

Thomas D. Avery et al, Site-specific drug release of monomethyl fumarate to treat oxidative stress disorders, Nature Biotechnology (2024). DOI: 10.1038/s41587-024-02460-4

Comment by Dr. Krishna Kumari Challa on November 6, 2024 at 9:49am

Study disproves idea that weather-dependent renewable energy systems are more prone to blackouts

Wind turbines and photovoltaics (PVs) are becoming increasingly widespread worldwide, which could contribute to reducing air pollution caused by fossil fuel emissions. To produce energy, however, these renewable energy solutions rely on specific weather conditions (e.g., the presence of wind and sufficient hours of sunlight).

As the use of these technologies grows, some energy system operators have expressed concerns about the weather-dependency of these systems, suggesting that an overreliance on these technologies could increase the risk of blackouts. In some instances, renewable energy systems were even blamed for blackouts experienced during adverse weather events.

Researchers at the University of Tennessee recently carried out a study exploring the vulnerability of renewable energy systems to adverse weather and the extent to which these systems could be responsible for severe blackouts. Their findings, published in Nature Energy, suggest that solar panels and wind turbines are less likely to cause severe blackouts than traditional power systems.

In this study, researchers find that although WD-RESs are non-dispatchable and weather sensitive, blackout intensities and extreme weather vulnerability are mitigated in high-penetration WD-RES grids.

Overall, the results of this recent study suggest that weather-dependent renewable energy systems, particularly solar panels and wind turbines, are not as prone to causing severe bulk power system blackouts during extreme weather as some people have assumed them to be. In fact, blackouts that occurred in regions with a high penetration of WD-RES power grids were often less severe than those occurring in places that only relied on the traditional power grid.

Jin Zhao et al, Impacts of renewable energy resources on the weather vulnerability of power systems, Nature Energy (2024). DOI: 10.1038/s41560-024-01652-1

Comment by Dr. Krishna Kumari Challa on November 6, 2024 at 9:17am

Spraying rice with zinc oxide nanoparticles protects yields during heat waves

A small team of horticulturists has found that spraying rice plants with a zinc oxide nanoparticle solution helps them better handle the stress of a heat wave. In their study, published in Proceedings of the National Academy of Sciences, the group conducted experiments involving spraying rice plants in a heated greenhouse.

Prior research has shown that heat waves can reduce rice yields or kill plants altogether, depending on the severity of the heat wave. Because of that, plant scientists have been looking for ways to help plants survive the likely increase in number and severity of heat waves expected due to global warming. The research team found that zinc oxide nanoparticles may be one such tool.

Prior research has also shown that zinc oxide is a natural part of plant metabolism—rice farmers have used it as a form of fertilizer for many years.

More recently, researchers have found that applying zinc nanoparticles is a much more efficient approach—it allows the particles to pass through the pores in leaves.

The team wondered if zinc oxide might also help rice plants maintain their yields during heat waves. To find out, the researchers planted rice in a climate-controlled greenhouse. Once the plants were grown, the team raised the temperature to 37°C for six consecutive days. During the induced heat wave, they sprayed some of the plants with a zinc oxide nanoparticle solution, while the other plants were only watered. Upon harvesting the rice, the research team found that those plants that had been sprayed with zinc oxide nanoparticles had yields that were 22.1% greater than the plants that had been sprayed with water alone.

In taking a closer look at the rice grains, the research team also found that they contained more nutrients, as well. In conducting another similar experiment, the researchers found that spraying rice plants with zinc oxide nanoparticles also led to increased yields compared to those not sprayed even when there was no heat wave.

Shuqing Guo et al, Zinc oxide nanoparticles cooperate with the phyllosphere to promote grain yield and nutritional quality of rice under heatwave stress, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2414822121

Comment by Dr. Krishna Kumari Challa on November 5, 2024 at 9:51am

Why do flowers wilt? 

Wilting flowers might not signal poor flower or plant health, but rather the effects of a sophisticated resource management strategy in plants, millions of years in the making.

A study in the journal Plant Biology by researchers from Macquarie University and international collaborators has shown for the first time that plants reuse resources from wilting flowers to support future reproduction.

It turns out the plants were playing a longer game than we anticipated, not using their reclaimed resources immediately, but saving them for the next flowering season.

Plants have evolved diverse strategies for managing their flowers after they've served their primary reproductive function, with wilting just one of several possible approaches.

Not all plants follow the flower wilt pattern; flowers will still bloom on some plants long after they can be fertilized and after they stop producing nectar.

Flowers make the whole plant more attractive to pollinators even when they are just there as part of the overall display.

Some plants will even drop their blooms well before they wilt. For example, jacaranda flowers that seem perfectly good will just drop to the ground; frangipani trees will also shed intact flowers rather than have them wilt.

The study tested resource reuse in different ways.

Results showed plants with wilting flowers were more likely to reflower the next season than those where wilting was prevented. The study also considered other factors that might influence seed production, such as flowering stem height, number of flowers per stem, and flower position. Taller flowering stems, for example, produced more seeds and heavier seeds, as did stems with more flowers. But flowers positioned lower down on the plant tended to have fewer seeds, and seeds that weighed less.

 G. H. Pyke et al, Why do flowers wilt?, Plant Biology (2024). DOI: 10.1111/plb.13720

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