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Comment by Dr. Krishna Kumari Challa on June 15, 2022 at 10:29am

Shedding light on how bacteria communicate their way to causing infection

Scientists have identified proteins that prevent a bacterial cell from becoming misguided by its own messaging, allowing it to instead wait for collective communication from its group. The research is important because understanding this type of signaling, known as quorum sensing and integral to bacterial pathogens, opens the door to potential new drugs that can disrupt it and thwart infection. Findings were published in the Proceedings of the National Academy of Sciences. 

Sometimes  single-celled organisms need to work together with other cells.  Bacteria and other single-celled microbes can coordinate behaviors and act as a group via quorum sensing, in which cells produce and sense a small chemical signal that is shared within the population. As the signal is released from cells and reaches a high enough concentration in their environment, a quorum is achieved—certain genes are simultaneously activated and specific group behaviors are set in motion.

It's a strength-in-numbers approach that allows bacteria to join forces to do things they could not do by themselves, like causing infection in animals and plants, acquiring certain nutrients and competing against other microbes.

Bacterial infection often involves toxins that only harm the host at high levels, when produced by all bacterial cells at once. 

A major unresolved question about quorum sensing, the researchers said, has been why the signal that's produced inside an individual cell is not sensed by that same cell before it is released, spurring the cell into premature, solo action.
What prevents signal 'short-circuiting' from happening? A set of proteins called antiactivators are crucial for short-circuit prevention. The proteins work as a quorum sensing "tuner" by causing cells to be less sensitive to the quorum signal.

This research shows how bacteria put the brakes on quorum sensing to achieve true communication in a group.

In addition to helping the quest for new antibiotics that can inhibit quorum sensing in bacterial pathogens, the findings also provide background knowledge useful for the engineering of cells with new properties in a field called synthetic biology.

Antiactivators prevent self-sensing in quorum sensing, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2201242119.

Comment by Dr. Krishna Kumari Challa on June 15, 2022 at 9:57am

A few proteins form a little barrel, and as the protein is threaded through that little cylinder, it gets degraded. This inactivates and breaks down the protein. Many proteasomes are present in cells at any given time, he added, but what makes this particular proteasome (labeled 20S) special is that it can accept proteins that are already somewhat misfolded and would not fit in the other cellular trash cans.

The limiting cap present on many proteasomes is not there in the BAG2 condensates. These promising results could point to a way to interrupt the development of Alzheimer's disease, which is marked by an accumulation of misfolded tau.

Daniel C. Carrettiero et al, Stress routes clients to the proteasome via a BAG2 ubiquitin-independent degradation condensate, Nature Communications (2022). DOI: 10.1038/s41467-022-30751-4

Comment by Dr. Krishna Kumari Challa on June 15, 2022 at 9:56am

Scientists discover and characterize a novel membraneless organelle that could play a role in Alzheimer's treatment

Researchers  have discovered a novel organelle—a previously unknown cell structure whose function it is to help clean up faulty proteins in times of stress and keep cells functioning in top condition. Optimizing this membraneless organelle, which they call a BAG2 condensate, could lead to treatments for conditions that are the result of misfolded proteins, including Alzheimer's disease, Parkinson's disease and other neurodegenerative conditions. Their results are reported in a paper  and published in the journal Nature Communications.

People have known for quite a while that are a few objects floating around in cells that don't have membranes. And it's never been clear how they're held together, what they are and what they're doing until relatively recently.

Thanks to advanced imaging techniques, scientists have uncovered structures that were once invisible, revealing cells for the truly complex and sophisticated systems that they are.

Of particular interest are biomolecular condensates, which don't have the recognizable cell membrane enclosure, but instead, are separated from the surrounding cytoplasm by a difference in density that can be loosely compared to a drop of oil in water. This liquid-liquid phase separation creates a specialized, relatively concentrated environment for certain functions and reactions. For example, a stress granule is a membraneless organelle that appears when the cell is under stress—maybe there's too much glucose, maybe it's too hot or cold, maybe the cell is experiencing dehydration—and its job is to sweep up RNA floating around in the cytoplasm, storing those genetic instructions and pausing their translation into proteins. If your cell is under stress, you want to shut down making proteins so you can really conserve your energy and get past the stress.

But that's only part of the picture, according to the researchers.

When there's stress, what happens to the proteins that are already in the cell?. If they're under those stress conditions, some of those proteins could get damaged and they could misfold." Misfolds of the tau protein, for example, can become pathological and turn into the neurofibrillary tangles that characterize Alzheimer's disease.

This is where the researchers' newly discovered BAG2 condensate comes in. Named for the BAG2 protein that it contains, the organelle, they found, is capable of sweeping up these faulty proteins in the cytoplasm and stuffing them into a proteasome—the cell's version of a trash can—located in the organelle.

Part 1

Comment by Dr. Krishna Kumari Challa on June 14, 2022 at 12:39pm

Nanoparticle sensor can distinguish between viral and bacterial pne...

Many different types of bacteria and viruses can cause pneumonia, but there is no easy way to determine which microbe is causing a particular patient's illness. This uncertainty makes it harder for doctors to choose effective treatments because the antibiotics commonly used to treat bacterial pneumonia won't help patients with viral pneumonia. In addition, limiting the use of antibiotics is an important step toward curbing antibiotic resistance.

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Bacterial intimacy insights could help tackle antimicrobial resistance

One of the primary ways harmful bacteria acquire resistance to antibiotics is by receiving DNA from other bacteria that are already resistant. This DNA exchange is made via a process called conjugation, akin to bacterial sex, whereby two bacteria form an intimate attachment, and one transfers a packet of DNA to the other.

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Shedding light on how bacteria communicate their way to causing inf...

Oregon State University scientists have identified proteins that prevent a bacterial cell from becoming misguided by its own messaging, allowing it to instead wait for collective communication from its group.

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Polluted air cuts global life expectancy by two years

Microscopic air pollution caused mostly by burning fossil fuels shortens lives worldwide by more than two years, researchers reported Tuesday.

Comment by Dr. Krishna Kumari Challa on June 14, 2022 at 12:31pm

Study describes new way of generating insulin-producing cells

Researchers show how a molecule that they have identified stimulates the formation of new insulin-producing cells in zebrafish and mammalian tissue, through a newly described mechanism for regulating protein synthesis. The results are published in Nature Chemical Biology.

These findings indicate a new potential target for treating diabetes, in that researchers demonstrate a possible way of stimulating the formation of new insulin-producingcells.

Insulin injections and glucose-lowering drugs can control the disease, but not cure it.

One alternative could be a treatment that regulates blood glucose by increasing the number of insulin-producing pancreatic β cells.

The researchers has previously identified a small molecule able to stimulate the regeneration of insulin-producing β cells. This they did by analyzing a large quantity of substances in a zebra fish model.

In this present study, they examined the molecular mechanism of this stimulation.

By analyzing a large number of molecular interactions in yeast cells, the researchers show that their molecule binds to a protein called MNK2. Subsequent studies of zebrafish and cell cultures indicate that the molecule operates by regulating the translation of mRNA and boosting the synthesis of proteins, without which the formation of new β cells cannot be increased. Zebrafish given the molecule also showed lower levels of blood glucose than controls.

The study also shows that the molecule can induce the formation of new pancreatic β cells from pigs and stimulate the expression of insulin in human organoids (organ-like cell formations).

Scientists now will be studying the effect of this and similar molecules in human tissue and analyzing the molecule's target protein, MNK2, in tissue from healthy donors and donors with diabetes.

Olov Andersson, MNK2 deficiency potentiates β-cell regeneration via translational regulation, Nature Chemical Biology (2022). DOI: 10.1038/s41589-022-01047-x. www.nature.com/articles/s41589-022-01047-x

Comment by Dr. Krishna Kumari Challa on June 14, 2022 at 9:46am

The  results showed that differences in V1 surface area could predict measurements of people's contrast sensitivity. First, people with a large V1 had better overall contrast sensitivity than did those with a small V1 (the largest surface area being 1,776 square millimeters [mm2] and the smallest being 832 mm2). Second, people whose V1 had more cortical tissue processing visual information from a specific region in their field of view had higher contrast sensitivity at that region relative to those with less cortical tissue dedicated to the same region. Third, across participants, higher contrast sensitivity at a specific location (e.g., left) than at another location equidistant from fixation (e.g., above) corresponded to regions with more or less cortical tissue, respectively.

In sum, the more local V1 surface area dedicated to encoding a specific location, the better the vision at that location.

Linking individual differences in human primary visual cortex to contrast sensitivity around the visual field, Nature Communications (2022). DOI: 10.1038/s41467-022-31041-9

Part 2

Comment by Dr. Krishna Kumari Challa on June 14, 2022 at 9:45am

Neuroscientists find new factors behind better vision

The size of our primary visual cortex and the amount of brain tissue we have dedicated to processing visual information at certain locations of visual space can predict how well we can see, a team of neuroscientists has discovered. Its study, which appears in the journal Nature Communications, reveals a new link between brain structure and behavior.

Scientists can now predict how well someone can see based on the unique structure of their primary visual cortex. By showing that individual variation in the structure of the human visual brain is linked to variation in visual functioning, they can better understand what underlies differences in how people perceive and interact with their visual environment.

As with fingerprints, the bumps and grooves on each person's brain surface are unique. However, the significance of these differences is not fully understood, especially when it comes to their impact on behavior, such as distinctions in our ability to see.

Using functional magnetic resonance imaging (fMRI), the scientists mapped the primary visual cortex (or "V1") size of more than two dozen humans. The researchers also measured the quantity of V1 tissue these individuals have dedicated to processing visual information from different locations in their field of view—locations to the left, right, above, and below fixation.

Part 1

Comment by Dr. Krishna Kumari Challa on June 14, 2022 at 8:46am

Physicists Caught Sound Moving at Two Different Speeds in 3D Quantum Gas

After previously studying the phenomena of two sound waves in quantum liquids, scientists have now observed sound moving at two different speeds in a quantum gas.

If you were somehow immersed in the three-dimensional gas used for this study, you would hear every sound twice: each individual sound carried by two different sound waves moving at two different speeds.

This is an important development in the field of superfluidity – fluids with no viscosity that can flow without any loss of energy.

Remarkably, the behavior observed in the gas in terms of densities and velocities matched the parameters set down by Landau's two-fluid model, a theory developed for superfluid helium in the 1940s. To a large extent, it seems that when it comes to quantum gas setups, the same rules apply.

"These observations demonstrate all the key features of the two-fluid theory for a highly compressible gas.

https://journals.aps.org/prl/abstract/10.1103/PhysRevLett.128.223601

Comment by Dr. Krishna Kumari Challa on June 10, 2022 at 9:15am

Each patient treated in the study was infected with one or more strains of Mycobacterium, a group of bacteria that can cause deadly, treatment-resistant infections in those with compromised immune systems or with the lung disorder cystic fibrosis.

For clinicians, these are really a nightmare: They're not as common as some other types of infections, but they're amongst some of the most difficult to treat with antibiotics. And especially when you take these antibiotics over extended periods of time, they're toxic or not very well-tolerated.

Looking at measures of patient health and whether samples from the patient still showed signs of Mycobacterium infections, the team found that the therapy was successful in 11 out of 20 cases. No patients showed any adverse reactions to the treatment.

In another five patients the results of the therapy were inconclusive, and four patients showed no improvement.

Several unexpected patterns emerged from the case studies. In 11 cases, researchers were unable to find more than one kind of phage that could kill the patient's infection, even though standard practice would be to inject a cocktail of different viruses so the bacteria would be less likely to evolve resistance.

In addition, the team saw that some patients' immune systems attacked the viruses, but only in a few cases did their immune systems render the virus ineffective. And in some instances, the treatment was still successful despite such an immune reaction. The study paints an encouraging picture for the therapy.

 hage Therapy of Mycobacterium Infections: Compassionate-use of Phages in Twenty Patients with Drug-Resistant Mycobacterial Disease, Clinical Infectious Diseases (2022). DOI: 10.1093/cid/ciac453

Comment by Dr. Krishna Kumari Challa on June 10, 2022 at 9:11am

The largest ever series of phage therapy case studies shows a success rate of more than half

The number of reported cases using viruses to treat deadly Mycobacterium infections just went up by a factor of five.

In a new paper published recently in the journal Clinical Infectious Diseases, a team of researchers report 20 new case studies on the use of the experimental treatment, showing the therapy's success in more than half of the patients.

It's the largest ever set of published case studies for therapy using bacteria-killing viruses known as bacteriophages, providing unprecedented detail on their use to treat dire infections while laying the groundwork for a future clinical trial.

The phages are contributing to favorable outcomes—and in patients who have no other alternatives

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