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Comment by Dr. Krishna Kumari Challa on October 8, 2024 at 12:44pm

What is microRNA? 

The Nobel Prize in Medicine was awarded on Monday to two US scientists for discovering microRNA, a previously unknown type of genetic switch which is hoped can pave the way for new medical breakthroughs.

But while several treatments and tests are under development using microRNAs against cancer, heart disease, viruses and other illnesses, none have actually yet reached patients.

And the world paid little attention when the new Nobel laureates Victor Ambros and Gary Ruvkun revealed their discovery decades ago, thinking it was just "something weird about worms".

How exactly these tiny genetic switches work inside our bodies?

Each cell in the human body has the same set of instructions, called DNA. Some turn into brain cells, while others become muscles.

So how do the cells know what to become? The relevant part of the DNA's instructions is pointed to via a process called gene regulation.

Ribonucleic acid (RNA) normally serves as a messenger. It delivers the instructions from the DNA to proteins, which are the building blocks of life that turn cells into brains—or muscles.

A good example  is the messenger RNA vaccines rolled out against COVID-19 during the pandemic, which insert a message with new instructions to build proteins that block viruses.

But the two new Nobel winners Ambros and Ruvkun discovered a whole new type of gene regulator that had previously been overlooked by science.

Rather than being the messenger which relays information, microRNA instead acts as a switch to turn other genes off and on.

This was a whole new level of control that we had totally missed.

The discovery of microRNAs brought an additional level of complexity by revealing that regions that were thought to be non-coding play a role in gene regulation.

Part 1

Comment by Dr. Krishna Kumari Challa on October 8, 2024 at 12:35pm

More detailed observations showed that the fused comb jellies had spontaneous movements for the first hour. After that, the timing of contractions on each lobe started to synch up more. After just two hours, 95% of the fused animal's muscle contractions were completely synchronous, they report.

They also looked closely at the digestive tract to find that it also had fused. When one of the mouths ingested fluorescently labeled brine shrimp, the food particles worked their way through the fused canal. Eventually, the comb jelly expelled waste products from both anuses, although not at the same time.
The allorecognition mechanisms are related to the immune system, and the fusion of nervous systems is closely linked to research on regeneration.

Rapid Physiological Integration of Fused Ctenophores, Current Biology (2024). DOI: 10.1016/j.cub.2024.07.084. www.cell.com/current-biology/f … 0960-9822(24)01023-6

Part 2

Comment by Dr. Krishna Kumari Challa on October 8, 2024 at 12:34pm

After injury,  comb jellies can fuse to become one!

Researchers reporting in the journal Current Biology on October 7 have made the surprising discovery that one species of comb jelly (Mnemiopsis leidyi) can fuse, such that two individuals readily turn into one following an injury. Afterwards, they rapidly synchronize their muscle contractions and merge digestive tracts to share food.

These  findings suggest that ctenophores may lack a system for allorecognition, which is the ability to distinguish between self and others.

Additionally, the data imply that two separate individuals can rapidly merge their nervous systems and share action potentials.

Researchers made the observation after keeping a population of the comb jellies in a seawater tank in the lab. They noticed an unusually large individual that seemed to have two backends and two sensory structures known as apical organs instead of one. They wondered if this unusual individual arose from the fusion of two injured jellies.

To find out, they removed partial lobes from other individuals and placed them close together in pairs. It turned out that, nine out of 10 times, it worked. The injured individuals became one, surviving for at least three weeks.

Further study showed that after a single night, the two original individuals seamlessly became one with no apparent separation between them. When the researchers poked at one lobe, the whole fused body reacted with a prominent startle response, suggesting that their nervous systems were also fully fused.

Mechanical stimulation applied to one side of the fused ctenophore resulted in a synchronized muscle contraction on the other side

Part 1

Comment by Dr. Krishna Kumari Challa on October 8, 2024 at 12:25pm

They found that the δ1 tail interacts more extensively with the main part of the protein, leading to greater self-inhibition compared to δ2. This means that δ1 is more tightly regulated by its tail than δ2. When these sites are mutated or removed, δ1 becomes more active, which leads to changes in circadian rhythms. In contrast, δ2 does not have the same regulatory effect from its tail region.
This discovery highlights how a small part of CK1δ can greatly influence its overall activity. This self-regulation is vital for keeping CK1δ activity balanced, which, in turn, helps regulate our circadian rhythms.

The study also addressed the wider implications of these findings. CK1δ plays a role in several important processes beyond circadian rhythms, including cell division, cancer development, and certain neurodegenerative diseases. By better understanding how CK1δ's activity is regulated, scientists could open new avenues for treating not just circadian rhythm disorders but also a range of conditions.

Rachel L. Harold et al, Isoform-specific C-terminal phosphorylation drives autoinhibition of Casein kinase 1, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2415567121

Part 2

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Comment by Dr. Krishna Kumari Challa on October 8, 2024 at 12:24pm

End of Jetlag: Scientists discover secret to regulating our body clock

Scientists have discovered a revolutionary way to put an end to jet lag by uncovering the secret at the tail end of Casein Kinase 1 delta (CK1δ), a protein that regulates our body clock. This breakthrough, achieved by researchers  offers a new approach to adjusting our circadian rhythms, the natural 24-hour cycles that influence sleep-wake patterns and overall daily functions.

Published in the journal Proceedings of the National Academy of Sciences (PNAS), their findings could pave the way for new approaches to treating disorders related to the body clock.

CK1δ regulates circadian rhythms by tagging other proteins involved in our biological clock to fine-tune the timing of these rhythms. In addition to modifying other proteins, CK1δ itself can be tagged, thereby altering its own ability to regulate the proteins involved in running the body's internal clock.

Previous research identified two distinct versions of CK1δ, known as isoforms δ1 and δ2, which vary by just 16 building blocks or amino acids right at the end of the protein in a part called the C-terminal tail. Yet these small differences significantly impact CK1δ's function. While it was known that when these proteins are tagged, their ability to regulate the body clock decreases, no one knew exactly how this happened.

Using advanced spectroscopy and spectrometry techniques to zoom in on the tails, the researchers found that how the proteins are tagged is determined by their distinct tail sequences.

The findings pinpoint to three specific sites on CK1δ's tail where phosphate groups can attach, and these sites are crucial for controlling the protein's activity. When these spots get tagged with a phosphate group, CK1δ becomes less active, which means it doesn't influence our circadian rhythms as effectively. Using high-resolution analysis, we were able to pinpoint the exact sites involved .

Part 1

Comment by Dr. Krishna Kumari Challa on October 8, 2024 at 12:17pm

Such editing, the team notes, is particularly challenging due to issues with delocalization—prior attempts have involved applying high temperatures or radiation. Neither approach has been found to be suitable.

In this new approach, the team used light as a photocatalyst for activating a furan ring. The technique can be used to carry out single electron oxidation on a furan, resulting in radicalization.

The approach, they note, allows for a facile reaction that is susceptible to the addition of an amine. That leads to a cascade of electron and proton transfer between the product and the photocatalyst, resulting in the creation of a ring aldehyde intermediate.

Donghyeon Kim et al, Photocatalytic furan-to-pyrrole conversion, Science (2024). DOI: 10.1126/science.adq6245

Ellie F. Plachinski et al, Single-atom editing with light, Science (2024). DOI: 10.1126/science.ads2595

Comment by Dr. Krishna Kumari Challa on October 8, 2024 at 12:17pm

Chemists use light to replace an oxygen atom with a nitrogen atom in a molecule

A team of chemists  has succeeded in pulling an oxygen atom from a molecule and replacing it with a nitrogen atom. In their study, published in the journal Science, the group used photocatalysis to edit a furan in their lab.

Prior research has shown that some complex molecules can be edited using chemical reactions, but they are few and far between. So chemists must synthesize molecules from scratch when they want to change a small part of a molecule, or even just one atom, for testing.

Such work has shown that even minor changes can have a major impact - changing a single atom in a heterocycle can have a profound impact on the efficacy of a drug. Chemists have been looking for more efficient ways to edit molecules—or more specifically, to remove a single atom and replace it with another.

In this new study, the research team developed a technique they describe as a pencil-and-eraser technique in which one atom is erased and another penciled in.
The researchers were inspired by a paper written by chemists Axel Couture and Alain Lablache-Combier in 1971, in which they used ultraviolet light to convert a furan to a N-propylpyrrole as a way of improving yield. They used ultraviolet light to swap an oxygen atom in a furan with a nitrogen atom.
Part 1

Comment by Dr. Krishna Kumari Challa on October 7, 2024 at 9:45am

47 tigers dead in Vietnam zoos due to bird flu

Forty-seven tigers, three lions and a panther have died in zoos in south Vietnam due to the H5N1 bird flu virus, state media reported recently.

The deaths occurred in August and September at the private My Quynh safari park in Long An province and the Vuon Xoai zoo in Dong Nai, near Ho Chi Minh City, the official Vietnam News Agency (VNA) reported.

According to test results from the National Center for Animal Health Diagnosis, the animals died "because of H5N1 type A virus", VNA said.

No zoo staff members in close contact with the animals had experienced respiratory symptoms, the VNA report added.

Education for Nature Vietnam (ENV), an NGO that focuses on wildlife conservation, said there were a total of 385 tigers living in captivity in Vietnam at the end of 2023.

About 310 are kept at 16 privately owned farms and zoos, while the rest are in state-owned facilities.

The World Health Organization (WHO) says that since 2022, there have been increasing reports of deadly outbreaks among mammals caused by influenza viruses, including H5N1.

It also says H5N1 infections can range from mild to severe in humans, and in some cases can even be fatal.

Vietnam notified the WHO about a human fatality from the virus in March.

In 2004, dozens of tigers died from bird flu or were culled at the world's largest breeding farm in Thailand.

Source: News agencies

Comment by Dr. Krishna Kumari Challa on October 7, 2024 at 9:43am

How a bacterium becomes a permanent resident in a fungus

Comment by Dr. Krishna Kumari Challa on October 7, 2024 at 9:41am

When the researchers allowed the spores with the resident bacteria to germinate, they found that they germinated less frequently and that the young fungi grew more slowly than without them. The endosymbiosis initially lowered the general fitness of the affected fungi.
The researchers continued the experiment over several generations of fungi, deliberately selecting those fungi whose spores contained bacteria. This enabled the fungus to recover and produce more inhabited but viable spores. As the researchers were able to show with genetic analyses, the fungus changed during this experiment and adapted to its resident.
The researchers also found that the resident, together with its host, produced biologically active molecules that could help the host obtain nutrients and defend itself against predators such as nematodes or amoebae.

The initial disadvantage can thus become an advantage.

In their study, the researchers show how fragile early endosymbiotic systems are. The fact that the host's fitness initially declines could mean the early demise of such a system under natural conditions.
For new endosymbioses to arise and stabilize, there needs to be an advantage to living together.
The prerequisite for this is that the prospective resident brings with it properties that favor endosymbiosis. For the host, it is an opportunity to acquire new characteristics in one swoop by incorporating another organism, even if it requires adaptations.

In evolution, endosymbioses have shown how successful they ultimately can become.

Julia Vorholt, Inducing novel endosymbioses by implanting bacteria in fungi, Nature (2024). DOI: 10.1038/s41586-024-08010-x. www.nature.com/articles/s41586-024-08010-x

Part 2

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