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Comment by Dr. Krishna Kumari Challa on May 25, 2023 at 11:13am

Unique molecular machinery of a woman who can't feel pain

The biology underpinning a rare genetic mutation that allows its carrier to live virtually pain-free, heal more rapidly and experience reduced anxiety and fear, has been uncovered by new research.

The study, published in Brain, follows up the team's discovery in 2019 of the FAAH-OUT gene and the rare mutations that cause a woman, Jo Cameron, to feel virtually no pain and never feel anxious or afraid. The new research describes how the mutation in FAAH-OUT "turns down" FAAH gene expression, as well as the knock-on effects on other molecular pathways linked to wound healing and mood. It is hoped the findings will lead to new drug targets and open up new avenues of research in these areas.

Jo, who lives in Scotland, was first referred to pain geneticists at UCL in 2013, after her doctor noticed that she experienced no pain after major surgeries on her hip and hand. After six years of searching, they identified a new gene that they named FAAH-OUT, which contained a rare genetic mutation. In combination with another, more common mutation in FAAH, it was found to be the cause of Jo's unique characteristics.

The area of the genome containing FAAH-OUT had previously been assumed to be "junk" DNA that had no function, but it was found to mediate the expression of FAAH, a gene that is part of the endocannabinoid system and that is well-known for its involvement in pain, mood and memory.

In this study, the team from UCL sought to understand how FAAH-OUT works at a molecular level, the first step towards being able to take advantage of this unique biology for applications like drug discovery.

The team observed that FAAH-OUT regulates the expression of FAAH. When it is significantly turned down as a result of the mutation carried by Jo Cameron, FAAH enzyme activity levels are significantly reduced.

Hajar Mikaeili et al, Molecular basis of FAAH-OUT-associated human pain insensitivity, Brain (2023). DOI: 10.1093/brain/awad098

Comment by Dr. Krishna Kumari Challa on May 25, 2023 at 10:53am

The researchers realized that they could design an electricity harvester based around this number. This harvester would be made from a thin layer of material filled with nanopores smaller than 100 nm that would let water molecules pass from the upper to the lower part of the material. But because each pore is so small, the water molecules would easily bump into the pore's edge as they pass through the thin layer. This means that the upper part of the layer would be bombarded with many more charge-carrying water molecules than the lower part, creating a charge imbalance, like that in a cloud, as the upper part increased its charge relative to the lower part. This would effectually create a battery—one that runs as long as there is any humidity in the air.

Xiaomeng Liu et al, Generic Air‐Gen Effect in Nanoporous Materials for Sustainable Energy Harvesting from Air Humidity, Advanced Materials (2023). DOI: 10.1002/adma.202300748. onlinelibrary.wiley.com/doi/10.1002/adma.202300748

Part 2

Comment by Dr. Krishna Kumari Challa on May 25, 2023 at 10:52am

Engineers harvest abundant clean energy from thin air, 24/7

A team of engineers  has recently shown that nearly any material can be turned into a device that continuously harvests electricity from humidity in the air. The secret lies in being able to pepper the material with nanopores less than 100 nanometers in diameter. The research appeared in the journal Advanced Materials.

The air contains an enormous amount of electricity. Think of a cloud, which is nothing more than a mass of water droplets. Each of those droplets contains a charge, and when conditions are right, the cloud can produce a lightning bolt—but we don't know how to reliably capture electricity from lightning. What  the engineers have done is to create a human-built, small-scale cloud that produces electricity for us predictably and continuously so that we can harvest it.

The heart of the man-made cloud depends on what the engineers call the "generic Air-gen effect".

It builds on an earlier work completed in 2020 showing that electricity could be continuously harvested from the air using a specialized material made of protein nanowires grown from the bacterium Geobacter sulfurreducens.

The ability to generate electricity from the air turns out to be generic: literally any kind of material can harvest electricity from air, as long as it has a certain property. That property: "It needs to have holes smaller than 100 nanometers (nm), or less than a thousandth of the width of a human hair."

This is because of a parameter known as the "mean free path," the distance a single molecule of a substance, in this case water in the air, travels before it bumps into another single molecule  of the same substance. When water molecules are suspended in the air, their mean free path is about 100 nm.

part1

Comment by Dr. Krishna Kumari Challa on May 24, 2023 at 12:07pm

The analysis showed that endotoxins reduced the body's ability to turn white fat cells into brown-like fat cells and reduce the amount of stored fat.

This browning process is crucial in maintaining a healthy weight, and if scientists can figure out more about how it works and how to control it, then it opens up more potential treatments and therapies for obesity.

"Endotoxin from the gut reduces fat cell metabolic activity and its ability to become brown-like fat cells that can be useful to help lose weight.

We know that the guts of obese people are less resilient than normal, so endotoxins have more of a chance to escape. What this study also shows is that those leaking substances are then making it even harder for fat cells to function normally.

The study authors also point out that bariatric surgery reduces the levels of endotoxins in the blood, which adds to its value as a weight control method. It should mean that fat cells are more able to function normally.

All kinds of factors play into how our weight is controlled on a biological level, and now there's another significant one to consider. With obesity and its associated health problems becoming more of a problem worldwide, we need all the insight we can get.

As such, this work suggests the need to limit endotoxin-induced fat cell damage is even more important when you have excess weight, as the endotoxin contributes to reduce healthy cellular metabolism.

https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-023-0...

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Comment by Dr. Krishna Kumari Challa on May 24, 2023 at 12:05pm

Toxic Fragments of Bacteria Leaking From The Gut May Drive Weight Gain

Toxic substances leaking out from the gut can interfere with the functioning of fat cells and drive obesity, according to a recent study by a team of international researchers. The results could inform how we treat excessive and dangerous weight gain in the future.

The substances, called endotoxins, are fragments of bacteria in our guts. While they're a normal part of the digestive tract's ecosystem, the microbial debris can cause significant damage to the body should they find their way into the bloodstream.

Here, the researchers wanted to look specifically at the impact of endotoxins on fat cells (adipocytes) in people. They discovered that key processes that usually help control the buildup of fat are affected by the material.

"Gut microbe fragments that enter the bloodstream reduce normal fat cell function and their metabolic activity, which is exacerbated with weight gain, contributing to increased diabetes risk.

It appears that as we gain weight, our fat stores are less able to limit the damage that gut microbe fragments may cause to fat cells.

The study involved 156 participants, 63 of whom were classed as obese, and 26 of whom had undergone bariatric surgery for obesity – a procedure where the size of the stomach is reduced to limit food intake.

Samples from these participants were processed in the lab as the team looked at two different types of fat cell, described as white and brown.

White fat cells, which make up most of our fat storage tissues, stores lipids in larger volumes. Brown fat cells take stores of fat and break them down using their numerous mitochondria, such as when the body is cold and needs warmth. Under the right conditions, the body can convert the lipid-storing white fat cells that behave like lipid-burning brown fat cells.

Part 1

Comment by Dr. Krishna Kumari Challa on May 24, 2023 at 10:58am

Why AI black boxes matter

In many cases, there is good reason to be wary of black box machine-learning algorithms and models. Suppose a machine-learning model has made a diagnosis about your health. Would you want the model to be black box or glass box? What about the physician prescribing your course of treatment? Perhaps she would like to know how the model arrived at its decision.

What if a machine-learning model that determines whether you qualify for a business loan from a bank turns you down? Wouldn't you like to know why? If you did, you could more effectively appeal the decision, or change your situation to increase your chances of getting a loan the next time.

Black boxes also have important implications for software system security. For years, many people in the computing field thought that keeping software in a black box would prevent hackers from examining it and therefore it would be secure. This assumption has largely been proved wrong because hackers can reverse-engineer software—that is, build a facsimile by closely observing how a piece of software works—and discover vulnerabilities to exploit.

If software is in a glass box, then software testers and well-intentioned hackers can examine it and inform the creators of weaknesses, thereby minimizing cyberattacks.

original article.

Comment by Dr. Krishna Kumari Challa on May 24, 2023 at 10:54am

What is a black box? What it means when the inner workings of AIs are hidden?

For some people, the term "black box" brings to mind the recording devices in airplanes that are valuable for postmortem analyzes if the unthinkable happens. For others it evokes small, minimally outfitted theaters. But black box is also an important term in the world of artificial intelligence.

AI black boxes refer to AI systems with internal workings that are invisible to the user. You can feed them input and get output, but you cannot examine the system's code or the logic that produced the output.

Machine learning is the dominant subset of artificial intelligence. It underlies generative AI systems like ChatGPT and DALL-E 2. There are three components to machine learning: an algorithm or a set of algorithms, training data and a model.

An algorithm is a set of procedures. In machine learning, an algorithm learns to identify patterns after being trained on a large set of examples—the training data. Once a machine-learning algorithm has been trained, the result is a machine-learning model. The model is what people use.

For example, a machine-learning algorithm could be designed to identify patterns in images, and training data could be images of dogs. The resulting machine-learning model would be a dog spotter. You would feed it an image as input and get as output whether and where in the image a set of pixels represents a dog.

Any of the three components of a machine-learning system can be hidden, or in a black box. As is often the case, the algorithm is publicly known, which makes putting it in a black box less effective. So to protect their intellectual property, AI developers often put the model in a black box. Another approach software developers take is to obscure the data used to train the model—in other words, put the training data in a black box.

That's because researchers don't fully understand how machine-learning algorithms, particularly deep-learning algorithms, operate. The field of explainable AI is working to develop algorithms that, while not necessarily glass box, can be better understood by humans.

Part 1

Comment by Dr. Krishna Kumari Challa on May 24, 2023 at 10:50am

MRI scans and AI technology really could read what we're thinking. ...

For the first time, researchers have managed to use GPT1, precursor to the AI chatbot ChatGPT, to translate MRI imagery into text in an effort to understand what someone is thinking.

Comment by Dr. Krishna Kumari Challa on May 24, 2023 at 9:46am

Oxygen restriction helps fast-aging lab mice live longer

For the first time, researchers have shown that reduced oxygen intake, or "oxygen restriction," is associated with longer lifespan in lab mice, highlighting its anti-aging potential.

Research efforts to extend healthy lifespan have identified a number of chemical compounds and other interventions that show promising effects in mammalian lab animals— for instance, the drug metformin or dietary restriction. Oxygen restriction has also been linked to longer lifespan in yeast, nematodes, and fruit flies. However, its effects in mammals have been unknown.

To explore the anti-aging potential of oxygen restriction in mammals, researchers conducted lab experiments with mice bred to age more quickly than other mice while showing classic signs of mammalian aging throughout their bodies. The researchers compared the lifespans of mice living at normal atmospheric oxygen levels (about 21%) to the lifespans of mice that, at 4 weeks of age, had been moved to a living environment with a lower proportion of oxygen (11%—similar to that experienced at an altitude of 5000 meters).

They found that the mice in the oxygen-restricted environment lived about 50% longer than the mice in normal oxygen levels, with a median lifespan of 23.6 weeks compared to 15.7 weeks. The oxygen-restricted mice also had delayed onset of aging-associated neurological deficits.

Prior research has shown that dietary restriction extends the lifespan of the same kind of fast-aging mice used in this new study. Therefore, the researchers wondered if oxygen restriction extended their lifespan simply by causing the mice to eat more. However, they found that oxygen restriction did not affect food intake, suggesting other mechanisms were at play.

These findings support the anti-aging potential of oxygen restriction in mammals, perhaps including humans. However, extensive additional research will be needed to clarify its potential benefits in humans and illuminate the molecular mechanisms by which it operates.

Rogers RS, Wang H, Durham TJ, Stefely JA, Owiti NA, Markhard AL, et al. Hypoxia extends lifespan and neurological function in a mouse model of aging, PLoS Biology (2023). DOI: 10.1371/journal.pbio.3002117

Comment by Dr. Krishna Kumari Challa on May 23, 2023 at 9:41am

Lab-grown meat's carbon footprint potentially worse than retail bee...

Lab-grown meat, which is cultured from animal cells, is often thought to be more environmentally friendly than beef because it's predicted to need less land, water and greenhouse gases than raising cattle. But in a preprint, not yet peer-reviewed, researchers at the University of California, Davis, have found that lab-grown or "cultivated" meat's environmental impact is likely to be "orders of magnitude" higher than retail beef based on current and near-term production methods.

Researchers conducted a life-cycle assessment of the energy needed and greenhouse gases emitted in all stages of production and compared that with beef. One of the current challenges with lab-grown meat is the use of highly refined or purified growth media, the ingredients needed to help animal cells multiply. Currently, this method is similar to the biotechnology used to make pharmaceuticals. This sets up a critical question for cultured meat production: Is it a pharmaceutical product or a food product?

"If companies are having to purify growth media to pharmaceutical levels, it uses more resources, which then increases global warming potential.

The scientists defined the global warming potential as the carbon dioxide equivalents emitted for each kilogram of meat produced. The study found that the global warming potential of lab-based meat using these purified media is four to 25 times greater than the average for retail beef.

Derrick Risner et al, Environmental impacts of cultured meat: A cradle-to-gate life cycle assessment, bioRxiv (2023). DOI: 10.1101/2023.04.21.537778

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