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Comment by Dr. Krishna Kumari Challa on January 25, 2024 at 10:03am

Difference between T cells and CAR T cells

CAR T cells are made by collecting T cells from the patient and re-engineering them in the laboratory to produce proteins on their surface called chimeric antigen receptors, or CARs. The CARs recognize and bind to specific proteins, or antigens, on the surface of cancer cells.

These receptors are synthetic molecules, they don't exist naturally.

After the revamped T cells are “expanded” into the millions in the laboratory, they’re then infused back into the patient. If all goes as planned, the CAR T cells will continue to multiply in the patient's body and, with guidance from their engineered receptor, recognize and kill any cancer cells that harbor the target antigen on their surfaces.

https://www.cancer.gov/about-cancer/treatment/research/car-t-cells#....

Comment by Dr. Krishna Kumari Challa on January 25, 2024 at 9:55am

With modification, CAR T cells can attack senescent cells, leading to slower aging in mice

Researchers have discovered that T cells can be reprogrammed to fight aging, so to speak. Given the right set of genetic modifications, these white blood cells can attack another group of cells known as senescent cells. These cells are thought to be responsible for many of the diseases we grapple with later in life.

Senescent cells are those that stop replicating. As we age, they build up in our bodies, resulting in harmful inflammation. While several drugs currently exist that can eliminate these cells, many must be taken repeatedly over time.
As an alternative, scientists turned to a "living" drug called CAR (chimeric antigen receptor) T cells. They discovered CAR T cells could be manipulated to eliminate senescent cells in mice. As a result, the mice ended up living healthier lives. They had lower body weight, improved metabolism and glucose tolerance, and increased physical activity. All benefits came without any tissue damage or toxicity.
If we give it to aged mice, they rejuvenate. If we give it to young mice, they age slower. No other therapy right now can do this.
Perhaps the greatest power of CAR T cells is their longevity. The team found that just one dose at a young age can have lifelong effects. That single treatment can protect against conditions that commonly occur later in life, like obesity and diabetes.
T cells have the ability to develop memory and persist in your body for really long periods, which is very different from a chemical drug. With CAR T cells, you have the potential of getting this one treatment, and then that's it. For chronic pathologies, that's a huge advantage. Think about patients who need treatment multiple times per day versus you get an infusion, and then you're good to go for multiple years.
CAR T cells have been used to treat a variety of blood cancers, receiving FDA approval for this purpose in 2017. But this team is one of the first scientists to show that CAR T cells' medical potential goes even further than cancer.

Nature Aging (2024). DOI: 10.1038/s43587-023-00560-5

Comment by Dr. Krishna Kumari Challa on January 25, 2024 at 9:50am

So they turned to the concept of high-entropy design to come up with a porous ceramic material that achieved a good balance between strength and heat resistance without the usual downsides.

High-entropy design focuses on the use of equal measures of multiple elements that can be used to create stronger, more heat-resistant and more stable components.

The researchers developed a material that achieved the demanding insulation and weight criteria for aerospace flight. Their new ceramic creation, which goes by the unassuming name 9PHEB—9-cation porous high-entropy diboride—provides "exceptional thermal stability" and "ultrahigh compressive strength," the researchers said.

"High-quality interfaces, characterized by strong bonding without defects or amorphous phases, can promote the rapid force transfer along the building block and to many other ones through connections upon loading, leading to a significant enhancement of mechanical strength," the report said.

 Zihao Wen et al, Ultrastrong and High Thermal Insulating Porous High‐Entropy Ceramics up to 2000 °C, Advanced Materials (2024). DOI: 10.1002/adma.202311870

Part 2

Comment by Dr. Krishna Kumari Challa on January 25, 2024 at 9:49am

Scientists announce breakthrough in hypersonic heat shield

In a giant leap for future hypersonic flight,  scientists have turned to multi-scale technology to develop a revolutionary new material that has achieved record high marks in tests for vital strength and thermal insulation properties.

The scientists say their porous ceramic creation opens the door to wider exploration in the fields of aerospace, chemical engineering and energy transfer and production.

For the first time, it is reported a multi-scale structure design and fast fabrication of … high-entropy ceramics via an ultrafast high-temperature synthesis technique that can lead to exceptional mechanical load-bearing capability and high thermal insulation performance," the researchers said in a paper published Jan. 2 in the journal Advanced Materials.

Scientists have long faced challenges in developing strong, lightweight materials boasting low-thermal conductivity that are critical, especially for hypersonic travel. Ceramic materials offer promise because they exhibit low thermal conductivity, high melting points and corrosion resistance, and they are also non-combustible.
But exploration projects at great depths below the Earth's surface as well as in outer space encounter extremely high temperatures and pressure. Traditional ceramic materials are insufficient in those instances.

Lightweight, porous materials offered low thermal transfer but that desirable property often came with a tradeoff—greater fragility.

In their report, "Ultrastrong and High Thermal Insulating Porous High-Entropy Ceramics up to 2000 °C," researchers stated, "It is imperative to find ways to simultaneously improve the mechanical strength and thermal insulation capacity of porous ceramics."
Part 1

Comment by Dr. Krishna Kumari Challa on January 24, 2024 at 6:44am

Membranes form boundaries in nearly all kinds of cells. Not only does a cell have an outer membrane that contains and protects the interior, but often there are other membranes inside, forming parts of organelles such as mitochondria and the Golgi apparatus. Understanding membranes is important to medical science, not least because proteins lodged in the cell membrane are frequent drug targets. Some membrane proteins are like gates that regulate what gets into and out of the cell.

The region near these membranes can be a busy place. Thousands of types of different molecules crowd each other and the cell membrane—and as anyone who has tried to push through a crowd knows, it can be tough going. Smaller molecules such as salts move with relative ease because they can fit into tighter spots, but larger molecules, such as proteins, are limited in their movements.

This sort of molecular crowding has become a very active scientific research topic, because it plays a real-world role in how the cell functions. How a cell behaves depends on the delicate interplay of the ingredients in this cellular "soup." Now, it appears that the cell membrane might have an effect too, sorting molecules near itself by size and charge.

How does crowding affect the cell and its behavior? How, for example, do molecules in this soup get sorted inside the cell, making some of them available for biological functions, but not others? The effect of the membrane could make a difference.

Marcel Aguilella-Arzo et al, Charged Biological Membranes Repel Large Neutral Molecules by Surface Dielectrophoresis and Counterion Pressure, Journal of the American Chemical Society (2024). DOI: 10.1021/jacs.3c12348. pubs.acs.org/doi/full/10.1021/jacs.3c12348

Comment by Dr. Krishna Kumari Challa on January 24, 2024 at 6:42am

Cells' electric fields keep nanoparticles at bay, scientists confirm

The humble membranes that enclose our cells have a surprising superpower: They can push away nano-sized molecules that happen to approach them. A team including scientists at the National Institute of Standards and Technology (NIST) has figured out why, by using artificial membranes that mimic the behavior of natural ones. Their discovery could make a difference in how we design the many drug treatments that target our cells.

The team's findings, which appear in the Journal of the American Chemical Society, confirm that the powerful electrical fields that cell membranes generate are largely responsible for repelling nanoscale particles from the surface of the cell.
This repulsion notably affects neutral, uncharged nanoparticles, in part because the smaller, charged molecules the electric field attracts crowd the membrane and push away the larger particles. Since many drug treatments are built around proteins and other nanoscale particles that target the membrane, the repulsion could play a role in the treatments' effectiveness.

The findings provide the first direct evidence that the electric fields are responsible for the repulsion.

This repulsion, along with the related crowding that the smaller molecules exert, is likely to play a significant role in how molecules with a weak charge interact with biological membranes and other charged surfaces.

This has implications for drug design and delivery, and for the behavior of particles in crowded environments at the nanometer scale.

Part 1

Comment by Dr. Krishna Kumari Challa on January 24, 2024 at 6:37am

Chemists tie a knot using only 54 atoms

A trio of chemists  has tied the smallest knot ever, using just 54 atoms. In their study, published in the journal Nature Communications, the researchers accidentally tied the knot while trying to create metal acetylides in their lab.

The researchers were attempting to create types of alkynes called metal acetylides as a means to conduct other types of organic reactions. More specifically, they were attempting to connect carbon structures to gold acetylides—typically, such work results in the creation of simple chains of gold known as caternames.
But, unexpectedly, the result of one reaction created a chain that knotted itself into a trefoil knot with no loose ends. Trefoil knots are used in making pretzels and play a major role in knot theory. The researchers noted that the knot had a backbone crossing ratio (BCR) of 23. Knot BCRs are a measure of the strength of the knot. Most organic knots, the team notes, have a BCR somewhere between 27 and 33.

The knot represents a record—its three-leaf clover shape beats out a previous record held by a different team in China that created a 69-atom knot back in 2020. The prior record holder was created on purpose by that team using techniques developed to entwine strands into knots. The new record holder self-assembled, and the team behind it still does not understand how it happened. It is not yet known if it is possible to make a knot any smaller.

The creation of such tiny knots, the research team points out, is not just an interesting lab trick—microscopic knots are formed in many natural settings, such as in RNA and DNA and several other proteins. By creating tiny knots, chemists are learning more about how and why they come about in nature. It also could help in the discovery of new types of polymers and/or plastics.

More information: Zhiwen Li et al, Self-assembly of the smallest and tightest molecular trefoil knot, Nature Communications (2024). DOI: 10.1038/s41467-023-44302-y

Comment by Dr. Krishna Kumari Challa on January 23, 2024 at 12:07pm

Developmental biologist Sarah Hadyniak, who co-authored the study while at Johns Hopkins University, says their findings have implications for figuring out exactly how retinoic acid is acting on genes.

To get a sense of how much this could be affecting human vision, the researchers studied the retinas of 738 male adults with no signs of color vision deficiency.

The researchers were astonished at the natural variation in red/green cone ratio across this group.

"Seeing how the green and red cone proportions changed in humans was one of the most surprising findings of the new research", Hadyniak says.

It's unclear how this much variation could occur without affecting changes in vision. As Johnston put it, "if these types of cells determined the length of a human arm, the different ratios would produce amazingly different arm lengths."

This research was published in PLOS Biology.
Part 3
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Comment by Dr. Krishna Kumari Challa on January 23, 2024 at 12:07pm

Now, new research offers some clarity as to what those key vision-defining ingredients – making up just a 4 percent difference between the genes that code for these proteins – actually are.
We previously thought cone determination was basically random, though more recent studies have pointed to thyroid levels playing a role.

But a team from Johns Hopkins University and the University of Washington has discovered that levels of a molecule derived from vitamin A called retinoic acid make or break red-green cone ratios, at least in the case of their lab-grown retinas.

"These retinal organoids allowed us for the first time to study this very human-specific trait," says developmental biologist Robert Johnston from Johns Hopkins University. "It's a huge question about what makes us human, what makes us different."

In the lab, retinas exposed to more retinoic acid during early development (the first 60 days) resulted in higher ratios of green cones across the organoid after 200 days, while immature cones exposed to low levels of the acid developed into red cones later on.

The timing matters, too. If the retinoic acid was introduced at 130 days onwards, the effect was the same as if none had been added at all. This suggests the acid determines cone type early, and can't cause red cones to 'switch' into green cones that have already matured.

All the lab-grown retinas had similar cone densities, which allowed the team to rule out cone cell death as affecting the ratio of red to green.
part 2

Comment by Dr. Krishna Kumari Challa on January 23, 2024 at 12:06pm

Just One Molecule Allows Us to See Millions More Colors Than Our Pets

It's pretty hard to imagine the world through someone else's eyes, especially different animals. But a new study using lab-grown human retinas reveals that even between different humans, our vision is extremely diverse. And it might be to do with how the red and green cones form in our retinas. Cones are light-sensing cells in vertebrates' eyes; their combined responses to different wavelengths enable color vision.

Humans and some closely related primates are some of the only mammals known that can see the color red, as well as green and blue.

Other animals can also see red, like many birds and some insects. The kind of vision an animal has is closely related to its evolution alongside plants that produce fruits and flowers. This ability has been pretty useful, for instance, for spotting a ripe red apple among a dense canopy of green.

Another mammal outlier with the ability to see red is the honey possum (Tarsipes rostratus). This Australian marsupial pollinator has a bird-like ability to probe the nectar from a blushing banksia, in a fascinating example of convergent evolution.

Our red and green cones are basically identical, with slightly different chemistry to determine which color they'll detect. A protein called opsin comes in two different 'flavors', red-sensitive or green-sensitive, and their genetic 'recipes' sit side-by-side on the X chromosome.

So it's very easy for them to get mixed up in recombination, resulting in variations of congenital red-green color blindness.
Part 1

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