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Comment by Dr. Krishna Kumari Challa on January 5, 2023 at 8:25am

Scientists found the structure and function of newly discovered CRISPR immune system

 Biochemists in their new research papers  described the structure and function of a newly discovered CRISPR immune system that—unlike better-known CRISPR systems that deactivate foreign genes to protect cells—shuts down infected cells to thwart infection.

CRISPR, a manageable acronym for the mouthful "Clustered Regularly Interspaced Short Palindromic Repeats," has captured the imaginations of scientists and lay people alike, with its gene-editing potential. Study of CRISPR DNA sequences and CRISPR-associated (Cas) proteins, which are actually bacterial immune systems, is still a young field, although it's receiving widespread attention for its gene-editing applications.

Identified as a distinct immune system within the last five years, the Class 2, type V Cas12a2 is somewhat similar to the better-known CRISPR-Cas9, which binds to target DNA and cuts it—like molecular scissors—effectively shutting off a targeted gene. But CRISPR-Cas12a2 binds a different target than Cas9, and that binding has a very different effect.

The Cas12a2 protein undergoes major conformational changes upon binding to RNA that opens an indiscriminate active site for DNA destruction. "Cas12a2 destroys the DNA and RNA in target cells, causing them to go senescent."

Using cryo-electron microscopy or "cryo-EM," the researchers demonstrated this unique aspect of CRISPR-Cas12a2, including its RNA-triggered degradation of single-stranded RNA, single-stranded DNA and double-stranded DNA, resulting in a naturally occurring defensive strategy called abortive infection.

Abortive infection is a natural phage resistance strategy used by bacteria and archaea to limit the spread of viruses and other pathogen. For example, abortive infection prevents viral components that have infected a cell from replicating.

The team captured the structure of Cas12a2 in the act of cutting double-stranded DNA.

Incredibly, Cas12a2 nucleases bend the usually straight piece of double-helical DNA 90 degrees, to force the backbone of the helix into the enzymatic active site, where it is cut. It's a change in structure that's extraordinary to observe.

Dymtrenko, Oleg, et al. "Cas12a2 Elicits Abortive Infection via RNA-triggered Destruction of dsDNA," Nature, 04 January 2023. DOI: 10.1038/s41586-022-05559-3 , www.nature.com/articles/s41586-022-05559-3

Bravo, Jack and Hallmark, Thomson, et al. "RNA Targeting Unleashes Indiscriminate Nuclease Activity of CRISPR-Cas12a2," Nature, 04 January 2023. DOI: 10.1038/s41586-022-05560-w , www.nature.com/articles/s41586-022-05560-w

Comment by Dr. Krishna Kumari Challa on January 5, 2023 at 7:23am

New type of entanglement lets scientists 'see' inside nuclei

Nuclear physicists have found a new way to use the Relativistic Heavy Ion Collider (RHIC) to see the shape and details inside atomic nuclei. The method relies on particles of light that surround gold ions as they speed around the collider and a new type of quantum entanglement that's never been seen before.

Through a series of quantum fluctuations, the particles of light (a.k.a. photons) interact with gluons—gluelike particles that hold quarks together within the protons and neutrons of nuclei. Those interactions produce an intermediate particle that quickly decays into two differently charged "pions" (π). By measuring the velocity and angles at which these π⁺ and π^- particles strike RHIC's STAR detector, the scientists can backtrack to get crucial information about the photon—and use that to map out the arrangement of gluons within the nucleus with higher precision than ever before.
This technique is similar to the way doctors use positron emission tomography (PET scans) to see what's happening inside the brain and other body parts. But in this case, physicists are talking about mapping out features on the scale of femtometers—quadrillionths of a meter—the size of an individual proton.
Even more amazing, the STAR physicists say, is the observation of an entirely new kind of quantum interference that makes their measurements possible.
Physicists measure two outgoing particles and clearly their charges are different—they are different particles—but they see interference patterns that indicate these particles are entangled, or in sync with one another, even though they are distinguishable particles! This is the first-ever experimental observation of entanglement between dissimilar particles.
That discovery may have applications well beyond the lofty goal of mapping out the building blocks of matter.
James Brandenburg, Tomography of ultra-relativistic nuclei with polarized photon-gluon collisions, Science Advances (2023). DOI: 10.1126/sciadv.abq3903. www.science.org/doi/10.1126/sciadv.abq3903

Comment by Dr. Krishna Kumari Challa on January 4, 2023 at 12:50pm

Black Hole Tidal Disruption Event (Animation)

Comment by Dr. Krishna Kumari Challa on January 4, 2023 at 12:39pm

Normally when an antibody binds to a cell, it acts as a sort of tag, calling out for an immune cell to bind to the antibody and set off an efficient process of destroying the tagged cell. To stop this chain reaction, researchers devised a method to catch the antibodies before they bind to cells, preventing activation of the immune response.

The researchers genetically engineered three types of cells—insulin-producing pancreatic islet cells, thyroid cells, and CAR-T cells—so that each type made and displayed large numbers of a protein called CD64 on their surfaces.

On these engineered cells, CD64, which tightly binds the antibodies responsible for this type of immune rejection, acted as a kind of decoy, capturing the antibodies and binding them to the engineered cell, so they wouldn't activate immune cells.

Indeed this was the case when this approach was tested. This is clear proof-of-concept for this approach.

Tobias Deuse, Protection of cell therapeutics from antibody-mediated killing by CD64 overexpression, Nature Biotechnology (2023). DOI: 10.1038/s41587-022-01540-7. www.nature.com/articles/s41587-022-01540-7

Part2

Comment by Dr. Krishna Kumari Challa on January 4, 2023 at 12:37pm

Duping antibodies with a decoy, researchers aim to prevent rejection of transplanted cells

Researchers  have developed a novel, potentially life-saving approach that may prevent antibodies from triggering immune rejection of engineered therapeutic and transplant cells.

Rejection mediated by antibodies—as opposed to the chemical assault initiated by immune cells—has proven particularly tricky to resolve, a factor holding held back the development of some of these treatments. The new strategy, described in the Monday, Jan. 2, 2023 issue of Nature Biotechnology, involved using a "decoy" receptor to capture the antibodies and take them out of circulation before they could kill the therapeutic cells, that they treat as invading foreigners. The tactic may also be useful for organ transplants.

The most celebrated cellular therapies  are chimeric antigen receptor (CAR) T-cell therapies. These CAR-T therapies are often used to successfully treat specific forms of lymphomas, a type of often-deadly cancer. But deploying them against solid tumors has proved much more difficult. Until recently, most CAR-T therapies have been made using the patient's own cells, but the long-term commercial viability of cellular therapies of all types will rely on "allogeneic" cells—mass-produced therapeutic cells grown from a source outside the patient. As with transplanted organs, the recipient's immune system is likely to treat any outsider cells, or tissues developed from them, as foreign and to reject them. This issue is likely to be a severe obstacle in any type of allogeneic cell transplantation.

Part1

Comment by Dr. Krishna Kumari Challa on January 4, 2023 at 12:32pm

Good hydration linked to healthy aging

Adults who stay well-hydrated appear to be healthier, develop fewer chronic conditions, such as heart and lung disease, and live longer than those who may not get sufficient fluids, according to a National Institutes of Health study published in eBioMedicine.     Using health data gathered from 11,255 adults over a 30-year period, researchers analyzed links between serum sodium levels—which go up when fluid intake goes down—and various indicators of health. They found that adults with serum sodium levels at the higher end of a normal range were more likely to develop chronic conditions and show signs of advanced biological aging than those with serum sodium levels in the medium ranges. Adults with higher levels were also more likely to die at a younger age. 

The results suggest that proper hydration may slow down aging and prolong a disease-free life.

The study expands on research the scientists published in March 2022, which found links between higher ranges of normal serum sodium levels and increased risk for heart failure. Both findings came from the Atherosclerosis Risk in Communities (ARIC) study, which includes sub-studies involving thousands of  adults.

The researchers found that adults with higher levels of normal serum sodium—with normal ranges falling between 135-146 milliequivalents per liter (mEq/L)—were more likely to show signs of faster biological aging. This was based on indictors like metabolic and cardiovascular health, lung function, and inflammation. 

The conclusion therefore was people whose serum sodium is 142 mEq/L or higher would benefit from evaluation of their fluid intake. Doctors may also need to defer to a patient's current treatment plan, such as limiting fluid intake for heart failure. The authors also cited research that finds about half of people worldwide don't meet recommendations for daily total water intake, which often starts at 6 cups (1.5 liters).  

Decreased body water content is the most common factor that increases serum sodium, which is why the results suggest that staying well hydrated may slow down the aging process and prevent or delay chronic disease.

Natalia I. Dmitrieva et al, Middle-age high normal serum sodium as a risk factor for accelerated biological aging, chronic diseases, and premature mortality, eBioMedicine (2023). DOI: 10.1016/j.ebiom.2022.104404

Comment by Dr. Krishna Kumari Challa on January 4, 2023 at 12:01pm

COVID-19 vaccines, prior infection reduce transmission of omicron, finds study 

Vaccination and boosting, especially when recent, helped to limit the spread of COVID-19 in California prisons during the first omicron wave, according to an analysis by researchers.

 The study demonstrates the benefits of vaccination and boosting, even in settings where many people are still getting infected, in reducing transmission. And it shows the cumulative effects from boosting and the additional protection that vaccination gives to those who were previously infected. The likelihood of transmission fell by 11% for each additional dose.

A lot of the benefits of vaccines to reduce infectiousness were from people who had received boosters and people who had been recently vaccinated.

Vaccinated residents with breakthrough infections were significantly less likely to transmit them: 28% versus 36% for those who were unvaccinated. But the likelihood of transmission grew by 6% for every five weeks that passed since someone's last vaccine shot.

Natural immunity from a prior infection also had a protective effect, and the risk of transmitting the virus was 23% for someone with a reinfection compared to 33% for someone who had never been infected.

Those with hybrid immunity, from both infection and vaccination, were 40% less likely to transmit the virus. Half of that protection came from the immunity that one acquires from fighting an infection and the other half came from being vaccinated.

 Infectiousness of SARS-CoV-2 breakthrough infections and reinfections during the Omicron wave, Nature Medicine (2022). DOI: 10.1038/s41591-022-02138-x , www.nature.com/articles/s41591-022-02138-x

Comment by Dr. Krishna Kumari Challa on January 4, 2023 at 11:56am

Dry eye disease affects how the eye's cornea heals itself after injury

People with a condition known as dry eye disease are more likely than those with healthy eyes to suffer injuries to their corneas. Studying mice, researchers at Washington University School of Medicine in St. Louis have found that proteins made by stem cells that regenerate the cornea may be new targets for treating and preventing such injuries.

Dry eye disease occurs when the eye can't provide adequate lubrication with natural tears. People with the common disorder use various types of drops to replace missing natural tears and keep the eyes lubricated, but when eyes are dry, the cornea is more susceptible to injury.

We have drugs to treat this condition, but they only work well in about 10% to 15% of patients. In this new study involving genes that are key to eye health, researchers identified potential targets for treatment that appear different in dry eyes than in healthy eyes. 

The researchers analyzed genes expressed by the cornea in several mouse models—not only of dry eye disease, but also of diabetes and other conditions. They found that in mice with dry eye disease, the cornea activated expression of the gene SPARC. They also found that higher levels of SPARC protein were associated with better healing.

Lin, Joseph B. et al, Dry eye disease in mice activates adaptive corneal epithelial regeneration distinct from constitutive renewal in homeostasis, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2204134120. doi.org/10.1073/pnas.2204134120

Comment by Dr. Krishna Kumari Challa on January 4, 2023 at 9:06am

Self-assembling proteins can store cellular 'memories'

As cells perform their everyday functions, they turn on a variety of genes and cellular pathways. Researchers have now coaxed cells to inscribe the history of these events in a long protein chain that can be imaged using a light microscope.

Cells programmed to produce these chains continuously add building blocks that encode particular cellular events. Later, the ordered protein chains can be labeled with fluorescent molecules and read under a microscope, allowing researchers to reconstruct the timing of the events.

This technique could help shed light on the steps that underlie processes such as memory formation, response to drug treatment, and gene expression.

If the technique could be extended to work over longer time periods, it could also be used to study processes such as aging and disease progression, the researchers say.

Recording of cellular physiological histories along optically readable self-assembling protein chains, Nature Biotechnology (2022). DOI: 10.1038/s41587-022-01586-7

Comment by Dr. Krishna Kumari Challa on December 31, 2022 at 11:09am

Researchers identify 100,000 new types of viruses

A groundbreaking  study has discovered about 100,000 new types of previously unknown viruses , a ninefold increase in the amount of RNA viruses known to science until now. The viruses were discovered in global environmental data from soil samples, oceans, lakes, and a variety of other ecosystems. The researchers believe that the discovery may help in the development of anti-microbial drugs and in protecting against agriculturally harmful fungi and parasites. 

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