Comment

Comment by Dr. Krishna Kumari Challa on January 27, 2022 at 8:57am

Animals naturally capable of regeneration live mostly in an aquatic environment. The first stage of growth after loss of a limb is the formation of a mass of stem cells at the end of the stump called a blastema, which is used to gradually reconstruct the lost body part. The wound is rapidly covered by skin cells within the first 24 hours after the injury, protecting the reconstructing tissue underneath.

"Mammals and other regenerating animals will usually have their injuries exposed to air or making contact with the ground, and they can take days to weeks to close up with scar tissue.

Using the BioDome cap in the first 24 hours helps mimic an amniotic-like environment which, along with the right drugs, allows the rebuilding process to proceed without the interference of scar tissue."

Nirosha J. Murugan et al, Acute multidrug delivery via a wearable bioreactor facilitates long-term limb regeneration and functional recovery in adult Xenopus laevis, Science Advances (2022). DOI: 10.1126/sciadv.abj2164. www.science.org/doi/10.1126/sciadv.abj2164

https://medicalxpress.com/news/2022-01-regrow-frog-lost-leg.html?ut...

Comment by Dr. Krishna Kumari Challa on January 27, 2022 at 8:56am

Researchers regrow frog's lost leg

For millions of patients who have lost limbs for reasons ranging from diabetes to trauma, the possibility of regaining function through natural regeneration remains out of reach. Regrowth of legs and arms remains the province of salamanders and superheroes.

But in a study published in the journal Science Advances, scientists at Tufts University and Harvard University's Wyss Institute have brought us a step closer to the goal of regenerative medicine.

On adult frogs, which are naturally unable to regenerate limbs, the researchers were able to trigger regrowth of a lost leg using a five-drug cocktail applied in a silicone wearable bioreactor dome that seals in the elixir over the stump for just 24 hours. That brief treatment sets in motion an 18-month period of regrowth that restores a functional leg.

Many creatures have the capability of full regeneration of at least some limbs, including salamanders, starfish, crabs, and lizards. Flatworms can even be cut up into pieces, with each piece reconstructing an entire organism. Humans are capable of closing wounds with new tissue growth, and our livers have a remarkable, almost flatworm-like capability of regenerating to full size after a 50% loss.

But loss of a large and structurally complex limb—an arm or leg—cannot be restored by any natural process of regeneration in humans or mammals. In fact, we tend to cover major injuries with an amorphous mass of scar tissue, protecting it from further blood loss and infection and preventing further growth.

researchers triggered the regenerative process in African clawed frogs by enclosing the wound in a silicone cap, which they call a BioDome, containing a silk protein gel loaded with the five-drug cocktail.

Each drug fulfilled a different purpose, including tamping down inflammation, inhibiting the production of collagen which would lead to scarring, and encouraging the new growth of nerve fibers, blood vessels, and muscle. The combination and the bioreactor provided a local environment and signals that tipped the scales away from the natural tendency to close off the stump, and toward the regenerative process.

The researchers observed dramatic growth of tissue in many of the treated frogs, re-creating an almost fully functional leg. The new limbs had bone structure extended with features similar to a natural limb's bone structure, a richer complement of internal tissues (including neurons), and several "toes" grew from the end of the limb, although without the support of underlying bone.

The regrown limb moved and responded to stimuli such as a touch from a stiff fiber, and the frogs were able to make use of it for swimming through water, moving much like a normal frog would.

Part 1

Comment by Dr. Krishna Kumari Challa on January 26, 2022 at 1:35pm

Researchers recruited a total of 104 people, all OHSU employees who were vaccinated by the Pfizer vaccine, and then carefully divided them into three groups: 42 who were vaccinated with no infection, 31 who were vaccinated after an infection, and 31 who had breakthrough infections following vaccination. Controlling for age, sex and time from vaccination and infection, the researchers drew blood samples from each participant and exposed the samples to three variants of the live SARS-CoV-2 virus in a Biosafety Level 3 lab . 

They found both of the groups with "hybrid immunity" generated greater levels of immunity compared with the group that was vaccinated with no infection.

1. Timothy A. Bates, Savannah K. McBride, Hans C. Leier, Gaelen Guzman, Zoe L. Lyski, Devin Schoen, Bradie Winders, Joon-Yong Lee, David Xthona Lee, William B. Messer, Marcel E. Curlin, Fikadu G. Tafesse. Vaccination before or after SARS-CoV-2 infection leads to robust humoral response and antibodies that effectively neutralize variants. Science Immunology, 2022; DOI: 10.1126/sciimmunol.abn8014
2. Timothy A. Bates, Savannah K. McBride, Bradie Winders, Devin Schoen, Lydie Trautmann, Marcel E. Curlin, Fikadu G. Tafesse. Antibody Response and Variant Cross-Neutralization After SARS-CoV-2 Breakthrough Infection. JAMA, 2022; 327 (2): 179 DOI: 10.1001/jama.2021.22898

https://researchnews.cc/news/11272/New-study-suggests-two-paths-tow...

Part 2

Comment by Dr. Krishna Kumari Challa on January 26, 2022 at 1:33pm

New study suggests two paths toward 'super immunity' to COVID-19

New laboratory research from Oregon Health & Science University reveals more than one path toward robust immunity from COVID-19.

A new study finds that two forms of immunity—breakthrough infections following vaccination or natural infection followed by vaccination—provide roughly equal levels of enhanced immune protection.

The new study was published in the journal Science Immunology.

It makes no difference whether you get infected-and-then-vaccinated, or if you get vaccinated-and-then-a-breakthrough infection. In either case, you will get a really, really robust immune response—amazingly high.

The research follows an OHSU study published in December that described extremely high levels of immune response following breakthrough infections—so-called "super immunity." That study was the first to use multiple live SARS-CoV-2 variants to measure cross-neutralization of blood serum from breakthrough cases.

The new study found that it doesn't matter whether someone gets a breakthrough infection or gets vaccinated after a natural infection. In both cases, the immune response measured in blood serum revealed antibodies that were equally more abundant and more potent—at least 10 times more potent—than immunity generated by vaccination alone.

The study was done before the emergence of the omicron variant, but researchers expect the hybrid immune responses would be similar with the new highly transmissible variant.

The likelihood of getting breakthrough infections is high because there is so much virus around us right now. But we position ourselves better by getting vaccinated. And if the virus comes, we'll get a milder case and end up with this super immunity.

Part 1

Comment by Dr. Krishna Kumari Challa on January 26, 2022 at 1:26pm

Ice Or Not To Ice A Muscle Injury

Applying ice to a severe muscle injury may prolong the recovery process, researchers from Japan have found.

A pack of ice is often regarded as one’s best weapon against a muscle injury. But new research from Japan suggests otherwise, revealing that applying ice might actually prolong the recovery time. The findings were published in the Journal of Applied Physiology.

Whether you are a professional athlete or a casual gym-goer, skeletal muscle injuries are quite common. To soothe the injuries, coaches and physiotherapists have long been advising the application of ice. The logic being that icing helps in reducing inflammation. However, little has been established about the long-term effects of this widely practiced intervention, especially for severe injuries.

Our bodies respond to the muscle injuries through inflammation, which is a critical process helping regeneration of the destroyed tissue. Given that icing suppresses the inflammation, it might be derailing the self-repair mechanisms for severe muscle damage even if the coolness may soothe the pain early on. There have been inconsistent scientific data on whether or not icing helps in tissue repair. The answer may lie in how severe is the injury.

To advance the debate, researchers led by Associate Professor Takamitsu Arakawa from Kobe University in Japan investigated post-injury icing on a cellular level. A mouse model was used to mimic common sports injuries, where the muscles lengthen due to overexertion of force beyond the body’s current capacity—effectively tearing the muscle tissue.

The team immediately applied ice on the mice leg muscles. Then it examined the extent of muscle recovery two weeks later. For comparison, the researchers injured another set of mice but didn’t apply any ice. The non-iced group showed a significantly greater number of medium to large muscle fibers, while the iced group had mostly regenerated small muscle fibers, suggesting that icing delayed recovery of severe injuries.

According to the researchers, immune cells called pro-inflammatory macrophages may be involved in the repair mechanisms. They infiltrate the injured muscle tissue and remove damaged cells, which results in inflammation. This, in turn, spurs anti-inflammatory macrophages to swarm the injury site, suppressing inflammation and jumpstarting the building of new muscle cells.

That means the inflammation itself is key to the recovery of damaged tissues. Applying ice, however, seems to dampen this inflammatory response. The team speculated that icing may have deterred the arrival of the pro-inflammatory macrophages and consequently delayed the formation of new muscle tissue.

While skipping the ice step could speed up recovery for severe injuries, mild muscle damage might still benefit from the chilly interventions. The next step is to work out where to draw the line between mild and severe injuries, the researchers noted.

https://journals.physiology.org/doi/abs/10.1152/japplphysiol.01069....

 Kawashima et al. (2021) Icing After Eccentric Contraction-induced M...

https://www.asianscientist.com/2022/01/in-the-lab/icing-muscle-inju...

Comment by Dr. Krishna Kumari Challa on January 26, 2022 at 11:15am

This work investigated the patterns of disturbed blood flow in two different model carotids, one with high risk geometrical factors and the other without.

 high-risk factors include high flare and low proximal curvature in the sinus. Flare is defined as the ratio of the maximum cross section in the sinus bulb to its minimal value, while proximal curvature measures how much the artery curves above the bifurcation point.

To model exercise, the authors digitized blood flow measurements from individuals in three different age groups: 32-34, 54-55, and 62-63. These digitized flowrates were used as input to their computational model.

"Overall, the effects of exercise are different for different people. Particularly, we show that exercising decreases the reversed flow volume for the 62-63 age group with the low-risk carotid, which is probably related to the decrease of systolic time interval.

This suggests that evaluating the effect of exercise on atherosclerosis requires consideration of patient-specific geometries and ages.

"Effects of exercise on flow characteristics in human carotids" Physics of Fluids (2022). aip.scitation.org/doi/full/10.1063/5.0078061

https://phys.org/news/2022-01-simulation-age-effects-plaque-formati...

Part 2

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Comment by Dr. Krishna Kumari Challa on January 26, 2022 at 11:14am

 Exercise, age effects on plaque formation in arteries

Plaque formation in the arteries carrying blood to the head and neck is a serious medical problem, potentially leading to strokes and heart attacks. In Physics of Fluids, engineers from China use fluid dynamics simulations to study the effect of exercise at various ages on plaque formation.

It has been known for years that exercise and age affect the formation of plaques through a process known as atherosclerosis. What has not been fully understood, however, is how the geometrical features of the arteries affect plaque formation, although a dilated region in the inner carotid branch, the sinus, appears to be a vulnerable site.

"It is commonly accepted that the disturbed flow induces atherosclerosis.

To study this, the authors considered two arterial geometries, one with a bulging outer artery and the other without, and modeled the effect of exercise and age on blood flow through the two model arteries.

Two main arteries carrying blood to the head and neck, known as the carotid arteries, branch off from a single large artery at a position near the thyroid gland. One branch, the internal carotid artery, or ICA, carries blood inside the cranium to the brain, while the external carotid artery remains outside the cranium and brings blood to the neck, face, and scalp.

Just above the bifurcation, the ICA bulges outward, forming a region known as a sinus that is sensitive to blood pressure changes and helps regulate blood flow and heart rate.

Part 1

Comment by Dr. Krishna Kumari Challa on January 26, 2022 at 11:10am

Next, the researchers combined a computer program called dTERMen with X-ray crystallography in order understand how and why PCARE binds to ENAH over ENAH's two nearly identical sister proteins (VASP and EVL). Researchers saw that the amino acids flanking PCARE's core SliM caused ENAH to change shape slightly when the two made contact, allowing the binding sites to latch onto one another. VASP and EVL, by contrast, could not undergo this structural change, so the PCARE SliM did not bind to either of them as tightly.

Inspired by this unique interaction, researchers designed their own protein that bound to ENAH with unprecedented affinity and specificity. "It was exciting that we were able to come up with such a specific binder," she says. "This work lays the foundation for designing synthetic molecules with the potential to disrupt protein-protein interactions that cause disease—or to help scientists learn more about ENAH and other SLiM-binding proteins.

Native proline-rich motifs exploit sequence context to target actin-remodeling Ena/VASP protein ENAH, eLife, DOI: 10.7554/eLife.70680 , elifesciences.org/articles/70680

A distributed residue network permits conformational binding specificity in a conserved family of actin remodelers, eLife, DOI: 10.7554/eLife.70601 , elifesciences.org/articles/70601

https://phys.org/news/2022-01-probing-proteins-pair-cells.html?utm_...

Part 3

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Comment by Dr. Krishna Kumari Challa on January 26, 2022 at 11:07am

The ability to test hundreds of thousands of potential SLiMs for binding provides a powerful tool to explore why proteins prefer specific SLiM partners over others.

As we gain an understanding of the tricks that a protein uses to select its partners, we can apply these in protein design to make our own binders to modulate protein function for research or therapeutic purposes.

The researchers also suspected that the amino acids on either side of the SLiM's core 4-6 amino acid sequence might play an underappreciated role in binding. To test their theory, they used MassTitr to screen the human proteome in longer chunks comprised of 36 amino acids, in order to see which "extended" SLiMs would associate with the protein ENAH.

ENAH, sometimes referred to as Mena, helps cells to move. This ability to migrate is critical for healthy cells, but cancer cells can coopt it to spread. Scientists have found that reducing the amount of ENAH decreases the cancer cells's ability to invade other tissues—suggesting that formulating drugs to disrupt this protein and its interactions could treat cancer.

Part 2

Comment by Dr. Krishna Kumari Challa on January 26, 2022 at 10:58am

How proteins pair up inside cells

A  single cell contains billions of molecules that bustle around and bind to one another, carrying out vital functions. The human genome encodes about 20,000 proteins, most of which interact with partner proteins to mediate upwards of 400,000 distinct interactions. These partners don't just latch onto one another haphazardly; they only bind to very specific companions that they must recognize inside the crowded cell. If they create the wrong pairings—or even the right pairings at the wrong place or wrong time—cancer or other diseases can ensue. Scientists are hard at work investigating these protein-protein relationships, in order to understand how they work, and potentially create drugs that disrupt or mimic them to treat disease.

The average human protein is composed of approximately 400 building blocks called amino acids, which are strung together and folded into a complex 3D structure. Within this long string of building blocks, some proteins contain stretches of 4-6 amino acids called short linear motifs (SLiMs), which mediate protein-protein interactions. Despite their simplicity and small size, SLiMs and their binding partners facilitate key cellular processes. However, it's been historically difficult to devise experiments to probe how SLiMs recognize their specific binding partners.

To address this problem, a group of researchers designed a screening method to understand how SLiMs selectively bind to certain proteins, and even distinguish between those with similar structures. Using the detailed information they gleaned from studying these interactions, the researchers created their own synthetic molecule capable of binding extremely tightly to a protein called ENAH, which is implicated in cancer metastasis. The team shared their findings in a pair of eLife studies, one published on January 25, 2022 and the other on December 2, 2021.

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