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Comment by Dr. Krishna Kumari Challa on March 21, 2023 at 12:49pm

Bacteria-killing viruses deploy genetic code-switching to deceive hosts

Scientists have confirmed that bacteria-killing viruses called bacteriophages deploy a sneaky tactic when targeting their hosts: They use a standard genetic code when invading bacteria, then switch to an alternate code at later stages of infection.

Their study provides crucial information on the life cycle of phages. It could be a key step toward the development of new technologies such as therapeutics targeting human pathogens or of methods to control phage-bacterial interactions in applications ranging from plant production to carbon sequestration.

Scientists have predicted since the mid-1990s that some organisms may use an alternate genetic code, but the process had never been observed experimentally in phages.

Researchers now obtained the first experimental validation of this theory using uncultivated phages in human fecal samples and the lab's high-performance mass spectrometry to reveal the intricacies of how phage proteins are expressed in the host organism. The work is detailed in Nature Communications.

The scientists confirmed that the phages convert a genome-coding signal that usually halts protein production to instead express a different amino acid entirely, one that supports replication of the phage. That code switch allows the phage to take over the bacteria's biological processes.

These phages use a standard genetic code early on as they infect bacteria, one that's compatible with the bacterial host. Once the phages are integrated into the host, they hijack the machinery and begin pumping out phage proteins. By the late stage of infection, the host bacterium is unable to stop producing phages and dies.

Recognizing this change to an alternate genetic code helps ensure that scientists' assumptions about phage protein structure and function are correct.

Samantha L. Peters et al, Experimental validation that human microbiome phages use alternative genetic coding, Nature Communications (2022). DOI: 10.1038/s41467-022-32979-6

Comment by Dr. Krishna Kumari Challa on March 21, 2023 at 12:36pm

Researchers discover molecular basis for alkaline taste

Whether or not animals can taste basic or alkaline food and how they do it has remained a mystery until now. A research group recently addressed this question, as they similarly did for sour taste in 2021 on the lower end of the pH scale. Their work, published recently in Nature Metabolism, identified a previously unknown chloride ion channel, which they named alkaliphile (Alka), as a taste receptor for alkaline pH.

The level of pH, which is a scale of how acidic or basic a substance is, must be just right to instigate many biological processes, such as breaking down food and creating enzymatic reactions. While researchers are familiar with sour taste, which is associated with acids and allows people to sense the acidic end of the pH scale, little is known about how animals perceive bases on the opposite end of the pH spectrum. Detecting both acids and bases, which are commonly present in food sources, is important because they can significantly impact the nutritional properties of what animals consume.

Researchers now found that Alka is expressed in the fly's gustatory receptor neurons (GRNs), the counterpart of taste receptor cells of mammals. When facing neutral food versus alkaline food, wild-type flies normally choose neutral foods because of the toxicity of high pH. In contrast, flies lacking Alka lose the ability to discriminate against alkaline food when presented with it. If the pH of a food is too high, it can be harmful and cause health concerns in humans such as muscle spasms, nausea, and numbness. Likewise, after fruit flies eat food with high pH, their lifespan can be shortened.

This work demonstrates that Alka is critical for flies to stay away from harmful alkaline environments. Detecting the alkaline pH of food is an advantageous adaptation that helps animals avoid consuming toxic substances. 

To understand how Alka senses high pH, the researchers performed electrophysiological analyses and found that Alka forms a chloride ion (Cl-) channel that is directly activated by hydroxide ions (OH-). Like olfactory sensory neurons in mammals, the concentration of Cl- inside the fly's GRN is typically higher than outside this nerve cell. The researchers propose that when exposed to high-pH stimuli, the Alka channel opens, leading to negatively charged Cl- flowing from inside to outside the fly's GRN. This efflux of Cl- activates the GRN, ultimately signaling to the fly brain that the food is alkaline and should be avoided.

In addition, the scientists studied how flies detect the taste of alkaline substances using light-based optogenetic tools. They found that when they turned off alkaline GRNs, the flies were no longer bothered by the taste of alkaline food. Conversely, they activated these alkaline GRNs by shining red light on them. Interestingly, when these flies were given sweet food and exposed to red light at the same time, the flies did not want to eat the sweet food anymore. Alkaline taste can make a big impact on what flies choose to eat.

Overall, they have established that Alka is a new taste receptor dedicated to sensing the alkaline pH of food.

Yali Zhang, Alkaline taste sensation through the alkaliphile chloride channel in Drosophila, Nature Metabolism (2023). DOI: 10.1038/s42255-023-00765-3. www.nature.com/articles/s42255-023-00765-3

Comment by Dr. Krishna Kumari Challa on March 21, 2023 at 12:13pm

Scientists use tardigrade proteins for human health breakthrough

Researchers' study of how microscopic creatures called tardigrades survive extreme conditions has led to a major breakthrough that could eventually make life-saving treatments available to people where refrigeration isn't possible. They have shown that natural and engineered versions of tardigrade proteins can be used to stabilize an important pharmaceutical used to treat people with hemophilia and other conditions without the need for refrigeration—even amid high temperatures and other difficult conditions.

The pharmaceutical known as human blood clotting Factor VIII is an essential therapeutic used to treat genetic disease and instances of extreme bleeding. Despite being critical and effective in treating patients in these circumstances, Factor VIII has a serious shortcoming, in that it is inherently unstable. Without stabilization within a precise temperature range, Factor VIII will break down.

In underdeveloped regions, during natural disasters, during space flight or on the battlefield, access to refrigerators and freezers, as well as ample electricity to run this infrastructure, can be in short supply. This often means that people who need access to Factor VIII do not get it. 

This new work provides a proof of principle that we can stabilize Factor VIII, and likely many other pharmaceuticals, in a stable, dry state at room or even elevated temperatures using proteins from tardigrades—and, thus, provide critical lifesaving medicine to everyone everywhere. 

Measuring less than half a millimeter long,  tardigrades- also known as water bears—can survive being completely dried out; being frozen to just above absolute zero (about minus 458 degrees Fahrenheit, when all molecular motion stops); heated to more than 300 degrees Fahrenheit; irradiated several thousand times beyond what a human could withstand; and even survive the vacuum of outer space. They are able to do so, in part, by manufacturing a sugar called trehalose and a protein called CAHS D.

According to the research paper published, researchers fine-tuned the biophysical properties of both trehalose and CAHS D to stabilize Factor VIII, noting that CAHS D is most suitable for the treatment. The stabilization allows Factor VIII to be available in austere conditions without refrigeration, including repeated dehydration/rehydration, extreme heat and long-term dry storage.

The researchers think the same thing can be done with other biologics—pharmaceuticals containing or derived from living organisms—such as vaccines, antibodies, stem cells, blood and blood products.

Maxwell H. Packebush et al, Natural and engineered mediators of desiccation tolerance stabilize Human Blood Clotting Factor VIII in a dry state, Scientific Reports (2023). DOI: 10.1038/s41598-023-31586-9. www.nature.com/articles/s41598-023-31586-9

Comment by Dr. Krishna Kumari Challa on March 21, 2023 at 10:20am

Gut Bacterium Linked to Depression in Premenopause

The opportunistic pathogen Klebsiella aerogenes degrades estradiol and induces depressive-like behavior in mice, a study finds.

Klebsiella aerogenes, a bacterium associated with poor clinical outcomes in hospitals, is more prevalent in the gut of premenopausal women with depression than in premenopausal women without it, reports a study published today (March 17) in Cell Metabolism. The authors identified a key enzyme in the bacterium’s genome that degrades the ovarian hormone estradiol. Mice fed this bacterium or a different one engineered to carry the enzyme had lower estradiol levels and evidence of depressive-like behaviors compared to control mice.

Declining estradiol levels have been linked to female depression in humans.

While studies like this one certainly provide indications that [alterations of] gut bacteria can have quite striking phenotypic effects, for humans, there is at this time more smoke than fire. Yet, these data will encourage further studies of the [role of the] microbiome in affective disorders.

https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00053-0

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Comment by Dr. Krishna Kumari Challa on March 20, 2023 at 1:30pm

Dry Cleaning Chemical Could Be Major Cause of Parkinson's, Scientists Warn

The chemical trichloroethylene (TCE), once used widely in everything from producing decaf coffee to typewriter correction fluids, has been highlighted in a new study as potentially being a significant cause of many cases of Parkinson's disease.

Having already been associated with increased risks of cancer and miscarriages, TCE isn't used as widely as it once was, but the researchers behind the new report suggest that its role in Parkinson's disease has been largely overlooked.

They pull together evidence of the extent to which TCE has been used in industrial processes, review previous studies linking the chemical with Parkinson's, and investigate several cases where TCE and the disease could well be linked.

TCE is a simple, six-atom molecule that can decaffeinate coffee, degrease metal parts, and dry clean clothes. It was being used to do everything from clean engines to anesthetize patients. The colorless chemical was first linked to Parkinsonism in 1969.

While TCE use is now much more restricted in the EU and certain US states, globally it continues to be in demand, particularly from China. Even in areas where the chemical is banned, the researchers argue, we're still being exposed to it due to the ongoing contamination of water and soil.

The time between exposure and disease onset may be decades," write the researchers. Individuals, if they were aware of their exposure to the chemical, may have long since forgotten about it.

Those who worked with the solvent or who lived near a contaminated site may have changed jobs or moved, making retrospective evaluation of potential clusters challenging.

The team behind the new study now wants to see a complete ban on TCE and the closely related perchloroethylene (PCE), as well as the decontamination of sites where TCE exposure is known to have happened in the past.

https://content.iospress.com/articles/journal-of-parkinsons-disease...

Comment by Dr. Krishna Kumari Challa on March 20, 2023 at 1:12pm

How can you generate electricity from living plants?

In simple terms, electrons are a waste product of bacteria living around plant roots – plants excrete organic matter into the soil, which is broken down by bacteria. In the breakdown process electrons are released. It is possible to harvest them using inert electrodes and turn them into electricity, without affecting the plant’s growth in any way.

Comment by Dr. Krishna Kumari Challa on March 20, 2023 at 11:28am

Antibody fragment-nanoparticle therapeutic eradicates cancer
A novel cancer therapeutic, combining antibody fragments with molecularly engineered nanoparticles, permanently eradicated gastric cancer in treated mice, a multi-institutional team of researchers found.

The results of the “hit and run” drug delivery system, published in the March issue of Advanced Therapeutics, were the culmination of more than five years of collaboration between various research groups.
Targeted cancer treatments such as antibody and nanoparticle therapies have seen narrow clinical use because of each therapy’s limitations, but the new therapeutic – an evolution of what the researchers call Cornell prime dots, or C’ dots – combines the best attributes of both into an ultrasmall, powerfully effective system.

As silica nanoparticles just 6 nanometers in size, C’ dots are small enough to penetrate tumors and safely pass through organs once injected into the body. Scientists first developed them more than 15 years ago and published a 2018 study that found an antibody fragment-nanoparticle hybrid to be especially effective in finding tumors.

This collaborative work with AstraZeneca set off the search for a new, molecularly engineered therapeutic version of this immuno-conjugate.

AstraZeneca “site engineered” fragments of antibodies so they would effectively attach to the C’ dots and target HER2 proteins associated with gastric cancer. The researchers optimized fragment conjugation to the C’ dot surface, along with specialized inhibitor drugs developed by AstraZeneca. This enabled the nanoparticles to carry about five times more drugs than most antibodies.

The final product was a version of C’ dots, armed with cancer-targeting antibody fragments and a large drug payload, all packed into a sub-7-nanometer, drug-immune conjugate therapy – a first of its kind in that size class, according to the researchers.

https://onlinelibrary.wiley.com/doi/10.1002/adtp.202200209

Comment by Dr. Krishna Kumari Challa on March 20, 2023 at 10:54am

Why Are Electric Vehicle Fires So Hard To Put Out?

Comment by Dr. Krishna Kumari Challa on March 20, 2023 at 10:48am

Researchers create virus-resistant, safely restrained E. coli for medical, industrial applications

In a step forward for genetic engineering and synthetic biology, researchers have modified a strain of Escherichia coli bacteria to be immune to natural viral infections while also minimizing the potential for the bacteria or their modified genes to escape into the wild. The work promises to reduce the threats of viral contamination when harnessing bacteria to produce medicines such as insulin as well as other useful substances, such as biofuels.

Currently, viruses that infect vats of bacteria can halt production, compromise drug safety, and cost millions of dollars.

 So far, based on extensive laboratory experiments and computational analysis, Researchers haven't found a virus that can break the bacterium. 

The work also provides the first built-in safety measure that prevents modified genetic material  from being incorporated into natural cells.

Akos Nyerges et al, A swapped genetic code prevents viral infections and gene transfer, Nature (2023). DOI: 10.1038/s41586-023-05824-z. www.nature.com/articles/s41586-023-05824-z

Comment by Dr. Krishna Kumari Challa on March 20, 2023 at 10:41am

To manipulate the enzyme's role in microglia energy production, the  researchers developed a light-activated tool. Their tool involves shining blue light onto a genetically modified version of the hexokinase-2 enzyme to "switch off" one of its functions.

When this happens, it blocks the enzyme's ability to stick to the energy-generating parts of the microglia and forces the cells to stop relying on an inefficient method of energy production. Experimental results showed that this improves their ability to clear beta amyloid by nearly 20 percent.

However, if hexokinase-2's sticking ability is not blocked and its function is disrupted by simply inactivating the enzyme, it does not help the microglia to clear away waste. This insight provides a critical clue for future drug targets.

Lauren H. Fairley et al, Mitochondrial control of microglial phagocytosis by the translocator protein and hexokinase 2 in Alzheimer's disease, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2209177120

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