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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

Part 2

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

Study shows new way to spur brain immune cells to clear toxic waste linked to Alzheimer's disease

A newly discovered "energy switch" in the immune cells of the brain may lead to the development of drugs for Alzheimer's disease, the most common form of dementia.

Scientists discovered that after blocking and turning off this "switch," brain immune cells called microglia were able to remove toxic proteins that can build up and lead to Alzheimer's disease.

Microglia tend to be damaged in people with the disease, which makes them less capable of clearing cellular toxic waste. To restore the clean-up function, the scientists "switched off" their inefficient metabolism by preventing a key enzyme from attaching to energy-generating parts of the immune cells.

The findings from lab experiments set the stage for developing drugs that can specifically target metabolism in brain immune cells in order to treat Alzheimer's disease, which contributes to 60% to 70% of all dementia cases globally. Such drugs are of high interest in health care. 

Researchers had previously shown that drugs that activated the toxic protein led to less toxic waste build-up in the brain, which improved the condition of mice with Alzheimer's disease. But how this worked was not clear.

The researchers now cracked the puzzle with their latest experiments on cells from mice with Alzheimer's. Their work revealed that the translocator protein is critical for the microglia immune cells of the brain to generate their own energy.

Microglia perform the important function of "gobbling up" and removing beta amyloid, a toxic protein whose build-up in the brain causes damage and death to nerve cells, resulting in Alzheimer's disease. To do their job properly and remove the toxic waste, the immune cells need a lot of energy.

The researchers showed that without the translocator protein, microglia from mice with Alzheimer's had an energy problem and could not remove the beta amyloid, which resulted in the disease worsening in the mice.

 Microglia lacking the translocator protein resembled damaged microglia observed in aging and Alzheimer's disease. These damaged microglia inefficiently produced energy and could not clean up toxic waste in mice with Alzheimer's disease.

The experiments also demonstrated that when the translocator protein is absent, an enzyme called hexokinase-2, which metabolizes sugar, kicks into action in microglia to compensate. The enzyme promotes an inefficient way for cells to produce energy. What was surprising was that hexokinase-2 became activated when it stuck to the energy-generating parts of cells called mitochondria.

The researchers found that hexokinase-2 was also activated in microglia when exposed to more toxic forms of beta amyloid, just as happens in Alzheimer's disease. The scientists believe this finding helps to partly explain how microglia fail in patients with Alzheimer's disease and when people age.
Part1

Comment by Dr. Krishna Kumari Challa on March 18, 2023 at 1:36pm

How DNA-PK Facilitates Repair from Double-Stranded DNA Breaks

Comment by Dr. Krishna Kumari Challa on March 18, 2023 at 1:34pm

When someone sneezes on Everest, their germs can last for centuries

Almost five miles above sea level in the Himalayan mountains, the rocky dip between Mount Everest and its sister peak, Lhotse, lies windswept, free of snow. 

According to new research, mountaineers visiting this place are leaving behind a frozen legacy of hardy microbes, which can withstand harsh conditions at high elevations and lie dormant in the soil for decades or even centuries.

The research not only highlights an invisible impact of tourism on the world’s highest mountain, but could also lead to a better understanding of environmental limits to life on Earth, as well as where life may exist on other planets or cold moons.

The research not only highlights an invisible impact of tourism on the world’s highest mountain, but could also lead to a better understanding of environmental limits to life on Earth, as well as where life may exist on other planets or cold moons. The findings were published last month in Arctic, Antarctic, and Alpine Research.

There is a human signature frozen in the microbiome of Everest, even at that elevation.

In decades past, scientists have been unable to conclusively identify human-associated microbes in samples collected above 26,000 feet. This study marks the first time that next-generation gene sequencing technology has been used to analyze soil from such a high elevation on Mount Everest, enabling researchers to gain new insight into almost everything and anything that’s in them.

The researchers weren’t surprised to find microorganisms left by humans. Microbes are everywhere, even in the air, and can easily blow around and land some distance away from nearby camps or trails.

If somebody even blew their nose or coughed, that's the kind of thing that might show up. Certain microbes which have evolved to thrive in warm and wet environments like our noses and mouths were resilient enough to survive in a dormant state in such harsh conditions.

Most of the microbial DNA sequences they found were similar to hardy, or “extremophilic” organisms previously detected in other high-elevation sites in the Andes and Antarctica. The most abundant organism they found using both old and new methods was a fungus in the genus Naganishia that can withstand extreme levels of cold and UV radiation.

But researchers also found microbial DNA for some organisms heavily associated with humans, including Staphylococcus, one of the most common skin and nose bacteria, and Streptococcus, a dominant genus in the human mouth.

At high elevation, microbes are often killed by ultraviolet light, cold temperatures and low water availability. Only the hardiest critters survive. Most—like the microbes carried up great heights by humans—go dormant or die, but there is a chance that organisms like Naganishia may grow briefly when water and the perfect ray of sunlight provides enough heat to help it momentarily prosper. But even for the toughest of microbes, Mount Everest is a Hotel California: “You can check out any time you like/ But you can never leave.”

The researchers don’t expect this microscopic impact on Everest to significantly affect the broader environment. But this work does carry implications for the potential for life far beyond Earth, if one day humans step foot on Mars or beyond.

https://www.colorado.edu/today/2023/03/14/when-someone-sneezes-ever...

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