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Comment by Dr. Krishna Kumari Challa on October 15, 2024 at 9:07am

As the mice gradually learned to complete the perceptual learning task, the researchers stimulated their vagus nerve using the electrode they developed. Concurrently, they also recorded activity in the animals' auditory cortex (involved in processing sounds), as well as in the locus coeruleus of the brainstem and the basal forebrain, two regions implicated in attention.

They found that indeed, VNS could augment training and improve perceptual discrimination beyond the limit achieved by training and effort alone. However, it takes a while, a few weeks of daily training and stimulation to see enduring gains at the most challenging difficulty levels. They also identified neural changes supporting this perceptual improvement..
The evidence gathered by the team at New York University suggests that in mice VNS activates the central cholinergic system, a neural network that utilizes the neurotransmitter acetylcholine to communicate with other neurons and supports various brain functions. The activation of this neural network was found to in turn enhance the performance of mice in the perceptual learning task they developed.

 Kathleen A. Martin et al, Vagus nerve stimulation recruits the central cholinergic system to enhance perceptual learning, Nature Neuroscience (2024). DOI: 10.1038/s41593-024-01767-4.

Part 2

Comment by Dr. Krishna Kumari Challa on October 15, 2024 at 9:06am

Vagus nerve stimulation enhances perceptual learning in mice, study suggests

Recent neuroscience studies have been investigating how the stimulation of some nerves, particularly the vagus nerve, using electrical pulses affects neural activity in the mammalian brain. The vagus nerve, the longest cranial nerve in the human body, is known to play a key role in the regulation of heart rate, digestion, stress and other physiological processes.

Some findings suggest that stimulating the vagus nerve can enhance the plasticity of the brain, which is its ability to reorganize itself following experiences. This could in turn facilitate perceptual learning, the process by which humans and other animals become better at distinguishing and interpreting different sensory inputs.

Researchers at New York University School of Medicine set out to further examine the effects of vagus nerve stimulation (VNS) on neural activity and perceptual learning in mice. Their findings, published in Nature Neuroscience, suggest that stimulating the vagus nerve enhances the performance of mice on a perceptual learning task by activating the central cholinergic system.

Part 1

Comment by Dr. Krishna Kumari Challa on October 15, 2024 at 8:43am

The finding could be correlating sleep patterns to microbiome outcomes or the inverse, where the microbiome influences sleep patterns. While the study focused on the first scenario, the children's sleep schedules were their own regular, habitual bedtimes without any intervention from the researchers.

These correlations have great potential to be followed up in multiple directions to determine the causal mechanisms behind the sleep-gut-cognitive connection.

 Chunmei Mao et al, Characteristics of gut flora in children who go to bed early versus late, Scientific Reports (2024). DOI: 10.1038/s41598-024-75006-y

Part 2

Comment by Dr. Krishna Kumari Challa on October 15, 2024 at 8:42am

Study links children's bedtimes to gut health, finds early sleepers have greater microbial diversity in gut flora

Researchers  have found significant differences in the gut microbiota of children who go to bed early compared to those who stay up late. The study revealed that children with earlier bedtimes had greater microbial diversity in their gut flora.

Beneficial bacteria like Akkermansia muciniphila were more abundant in the early sleepers. These bacteria are associated with maintaining gut health and have been linked to healthy cognitive functions.

Previous studies have shown that adequate sleep improves academic performance, physical growth and is associated with healthier BMI levels. The current study investigated the relationship between children's sleep patterns and their gut microbiota.

In a paper, "Characteristics of gut flora in children who go to bed early versus...," published in Scientific Reports, researchers analyzed the genomics of fecal samples from 88 healthy children aged 2 to 14 years.

The children were split into two groups based on their bedtimes: those who slept before 9:30 p.m. and those who slept after. Over two weeks, sleep diaries recorded factors such as time at falling asleep, night awakenings, sleep efficiency, and sleep quality.

Genomic analysis found that children who went to bed early had a higher abundance of certain beneficial gut bacteria. Specifically, Akkermansia muciniphila was significantly more prevalent in the early bedtime group.

Other elevated bacteria among early sleepers included Holdemania filiformis, Firmicutes bacterium CAG-95, Streptococcus sp. A12, Weissella confusa, Clostridium sp. CAG-253, Alistipes finegoldii, and Eubacterium siraeum. Additionally, levels of CAG-83 fungi were higher in the early bedtime group.

At the phylum and genus levels, Verrucomicrobia, Akkermansia, Holdemania and unclassified Firmicutes showed greater abundance in the early sleep group.

Correlation analysis between sleep metrics and microbial species revealed that Akkermansia muciniphila and Alistipes finegoldii were positively correlated with the time it took to fall asleep. Clostridium sp. CAG-253 was negatively correlated with sleep onset latency.

Alistipes finegoldii was positively correlated with total sleep duration but negatively correlated with dream frequency and sleep efficiency. Negative correlations were observed between Alistipes finegoldii, Akkermansia muciniphila and Holdemania filiformis in relation to sleep quality.
Metabolic analysis showed increased activity in amino acid metabolism and neurotransmitter regulation among early sleepers. These pathways are crucial for brain function and development, hinting at a possible relationship with gut health and cognition.

These differences in species diversity and metabolic pathways suggest that sleep patterns significantly influence gut microbiota," the research paper states. These findings may lead to new pharmacological interventions targeting sleep disorders in children."

Comment by Dr. Krishna Kumari Challa on October 15, 2024 at 8:33am

When a lightning bolt flashes in the sky on Earth, that burst of energy may also send radio waves spiraling deep into space. If those waves smack into electrons in the radiation belts, they can jostle them free—a bit like shaking your umbrella to knock the water off. In some cases, such "lightning-induced electron precipitation" can even influence the chemistry of Earth's atmosphere.
Here's what the team thinks is happening: Following a lightning strike, radio waves from Earth kick off a kind of manic pinball game in space. They knock into electrons in the inner belt, which then begin to bounce between Earth's northern and southern hemispheres—going back and forth in just 0.2 seconds.

And each time the electrons bounce, some of them fall out of the belt and into our atmosphere.

You have a big blob of electrons that bounces, and then returns and bounces again. You'll see this initial signal, and it will decay away.

Researchers aren't sure how often such events happen. They may occur mostly during periods of high solar activity when the sun spits out a lot of high-energy electrons, stocking the inner belt with these particles.

The researchers want to understand these events better so that they can predict when they may be likely to occur, potentially helping to keep people and electronics in orbit safe.

Max Feinland et al, Lightning-induced relativistic electron precipitation from the inner radiation belt, Nature Communications (2024). DOI: 10.1038/s41467-024-53036-4

Part 2

Comment by Dr. Krishna Kumari Challa on October 15, 2024 at 8:30am

'Killer electrons' of Lightning storms 

When lightning strikes, the electrons come pouring down. In a new study, researchers have discovered a novel connection between weather on Earth and space weather. The team utilized satellite data to reveal that lightning storms on our planet can dislodge particularly high-energy, or "extra-hot," electrons from the inner radiation belt—a region of space enveloped by charged particles that surround Earth like an inner tube.

The team's results could help satellites and even astronauts avoid dangerous radiation in space. This is one kind of downpour you don't want to get caught in.

These particles are the scary ones or what some people call 'killer electrons. They can penetrate metal on satellites, hit circuit boards and can be carcinogenic if they hit a person in space.

The findings cast an eye toward the radiation belts, which are generated by Earth's magnetic field.

 Two of these regions encircle our planet: While they move a lot over time, the inner belt tends to begin more than 600 miles above the surface. The outer belt starts roughly around 12,000 miles from Earth. These pool floaties in space trap charged particles streaming toward our planet from the sun, forming a sort of barrier between Earth's atmosphere and the rest of the solar system.

But they're not exactly airtight. Scientists, for example, have long known that high-energy electrons can fall toward Earth from the outer radiation belt.

Researchers also spotted a similar rain coming from the inner belt.

Earth and space, in other words, may not be as separate as they look. Space weather is really driven both from above and below.

Part 1

Comment by Dr. Krishna Kumari Challa on October 12, 2024 at 10:49am

Protein degrader molecules work in a way that is fundamentally different from the way conventional drugs work. However, until recently the exact details of how this process works at the molecular level had remained elusive.

Proteins are typically a few nanometers large, which is 1 billionth of a meter, or 1 millionth of the width of a hair. So being able to 'see' them in action has not been possible, up until now.
Scientists have now been able to build a moving image of how it all happens, which means they can more specifically control the process with an incredible level of detail.
Proteins are essential for our cells to function properly, but when these do not work correctly they can cause disease.

Targeted protein degradation involves redirecting protein recycling systems in our cells to destroy the disease-causing proteins. Protein degraders work by capturing the disease-causing protein and making it stick like a glue to the cellular protein-recycling machinery, which then tags the protein as expired in order to destroy it.

The tag is a small protein called ubiquitin, which effectively gets fired at the disease-causing protein like a bullet. In order for the process to work effectively, ubiquitin must hit the right spots on the target protein so that it gets tagged effectively. The new work by the researchers enables them to see how the bullet hits the proverbial bull's eye.
Working with a protein degrader molecule called MZ1, which was developed in the Ciulli laboratory at Dundee, and using high-end mass spectrometry, they were able to identify exactly where on the target protein the vital "tags" are added.

The work shows how degrader drugs hold onto and position disease-causing proteins, making them good targets for receiving ubiquitin molecules (i.e., "ubiquitin-atable") which then leads to their destruction inside the cell.

Protein degradation efficiency and productivity is dependent on the degrader molecule's ability to hold tight onto the disease-causing protein, and in a position where it can most effectively act. This latest research paints a bull's eye and holds it steady enough for the molecule to be accurately targeted.

Charlotte Crowe et al, Mechanism of degrader-targeted protein ubiquitinability, Science Advances (2024). DOI: 10.1126/sciadv.ado6492. www.science.org/doi/10.1126/sciadv.ado6492

Part 2

Comment by Dr. Krishna Kumari Challa on October 12, 2024 at 10:44am

Targeting 'undruggable' diseases: Researchers reveal new levels of detail in targeted protein degradation

Researchers  have revealed in the greatest detail yet the workings of molecules called protein degraders which can be deployed to combat what have previously been regarded as "undruggable" diseases, including cancers and neurodegenerative diseases.

Protein degrader molecules are heralding a revolution in drug discovery, with more than 50 drugs of this type currently being tested in clinical trials for patients with diseases for which no other options exist.

Now researchers have revealed previously invisible levels of detail and understanding of how the protein degraders work, which in turn is allowing for even more targeted use of them at the molecular level.

They used a technique called cryo-electron microscopy (cryo-EM), which enables scientists to see how biomolecules move and interact with each other.

This works by flash-freezing proteins and using a focused electron beam and a high-resolution camera to generate millions of 2D images of the protein. They then used sophisticated software and artificial intelligence (AI) models which allowed them to generate 3D snapshots of the degrader drugs working in action.

Their latest research is published in the journal Science Advances and is expected to constitute a landmark contribution to research in the field of TPD and ubiquitin mechanisms.

They  have reached a level of detail where they can see how these protein degraders work and can be deployed to recruit the disease-causing protein  and target the 'bull's eye,' in molecular terms.

Part 1

Comment by Dr. Krishna Kumari Challa on October 12, 2024 at 10:32am

Scientists discover how innate immunity envelops bacteria and destroy them

The protein GBP1 is a vital component of our body's natural defense against pathogens. This substance fights against bacteria and parasites by enveloping them in a protein coat, but how the substance manages to do this has remained unknown until now.

Researchers  have now unraveled how this protein operates. This new knowledge, published in Nature Structural & Molecular Biology, could aid in the development of medications and therapies for individuals with weakened immune systems.

Guanylate Binding Proteins (GBPs) play a crucial role in our innate immune system. GBPs form the first line of defense against various infectious diseases caused by bacteria and parasites. Examples of such diseases include dysentery, typhoid fever caused by Salmonella bacteria, and tuberculosis. The protein also plays a significant role in the sexually transmitted infection chlamydia as well as in toxoplasmosis, which is particularly dangerous during pregnancy and for unborn children. 

In their publication,  researchers describe for the first time how the innate immune system fights against bacteria using GBP1 proteins.

The protein surrounds bacteria by forming a sort of coat around them. By pulling this coat tighter, it breaks the membrane of the bacteria—the protective layer surrounding the intruder—after which immune cells can clear the infection.

To decode the defense strategy of GBPs, the researchers examined how GBP1 proteins bind to bacterial membranes using a cryogenic electron microscope. This allowed them to see the process in great detail down to the scale of molecules.

 Tanja Kuhm et al, Structural basis of antimicrobial membrane coat assembly by human GBP1, Nature Structural & Molecular Biology (2024). DOI: 10.1038/s41594-024-01400-9

Comment by Dr. Krishna Kumari Challa on October 12, 2024 at 9:45am

The level of contamination they studied is on par with a soil contaminated with microplastics. Contaminated soils have been found to have up to approximately 100,000 mg per kg of microplastics with most soils below 10,000 mg per kg.

In comparison to conventional glitter, there were no toxic effects on springtail reproduction at any concentration of the cellulose glitter.

So, although it's promising that neither type of glitter was directly harmful to the springtails, it's worrying that the conventional glitter affected their ability to reproduce.

Fewer springtails being born can weaken their population, which might lead to bigger problems for soil health like less organic matter breaking down and fewer nutrients being released for plants.

The researchers suggest you think twice before using conventional glitter in make-up, clothing or for arts and crafts, but are hopeful that peope will soon be able to buy a safer, more sustainable and just as sparkly alternative.

Po-Hao Chen et al, Assessing the ecotoxicological effects of novel cellulose nanocrystalline glitter compared to conventional polyethylene terephthalate glitter: Toxicity to springtails (Folsomia candida), Chemosphere (2024). DOI: 10.1016/j.chemosphere.2024.143315

Part 4

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