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Comment by Dr. Krishna Kumari Challa on January 6, 2023 at 9:57am

The study documents three types of discoveries from a genotype-first approach.

First, the researchers found that this approach helped discover new relationships between genomic variants and specific clinical traits. For example, one NIH study found that having more than two copies of the TPSAB1 gene was associated with symptoms related to the gastrointestinal tract, connective tissues, and the nervous system.

Second, this approach helped researchers find novel symptoms related to a disorder that clinicians previously missed because the patient did not have the typical symptoms. NHGRI researchers identified a person with a genomic variant associated with a known metabolic disorder. Further testing found that the individual had high levels of certain chemicals in their body associated with the disorder, despite having only minor symptoms.

Third, this approach allowed researchers to determine the function of specific genomic variants, which has the potential to help clinicians understand newly described disorders. For example, in one study, NHGRI researchers and their collaborators found that a genomic variant was associated with immune dysfunction at the molecular level in blood cells.

Leslie G. Biesecker, Genotype First: Clinical Genomics Research Through a Reverse Phenotyping Approach, The American Journal of Human Genetics (2023). DOI: 10.1016/j.ajhg.2022.12.004. www.cell.com/ajhg/fulltext/S0002-9297(22)00538-9

Part 2

Comment by Dr. Krishna Kumari Challa on January 6, 2023 at 9:56am

New approach successfully traces genomic variants back to genetic disorders

Researchers have published an assessment of 13 studies that took a genotype-first approach to patient care. This approach contrasts with the typical phenotype-first approach to clinical research, which starts with clinical findings. A genotype-first approach to patient care involves selecting patients with specific genomic variants and then studying their traits and symptoms; this finding uncovered new relationships between genes and clinical conditions, broadened the traits and symptoms associated with known disorders, and offered insights into newly described disorders. The study was published in the American Journal of Human Genetics.

Genotype-first research can work, especially for identifying people with rare disorders who otherwise might not have been brought to clinical attention.

Typically, to treat genetic conditions, researchers first identify patients who are experiencing symptoms, then they look for variants in the patients' genomes that might explain those findings. However, this can lead to bias because the researchers are studying clinical findings based on their understanding of the disorder. The phenotype-first approach limits researchers from understanding the full spectrum of symptoms of the disorders and the associated genomic variants.

Genomics has the potential to change reactive medicine into preventative medicine. Studying how taking a genotype-first approach to research can help us learn how to model predictive and precision medicine in the future.

Part 1

Comment by Dr. Krishna Kumari Challa on January 6, 2023 at 9:02am

The brain's ability to perceive space expands like the universe

Young children sometimes believe that the moon is following them, or that they can reach out and touch it. It appears to be much closer than is proportional to its true distance. As we move about our daily lives, we tend to think that we navigate space in a linear way. But  scientists have discovered that time spent exploring an environment causes neural representations to grow in surprising ways.

The findings, published in Nature Neuroscience on December 29, 2022, show that neurons in the hippocampus essential for spatial navigation, memory, and planning represent space in a manner that conforms to a nonlinear hyperbolic geometry—a three-dimensional expanse that grows outward exponentially. (In other words, it's shaped like the interior of an expanding hourglass.) The researchers also found that the size of that space grows with time spent in a place. And the size is increasing in a logarithmic fashion that matches the maximal possible increase in information being processed by the brain.

This discovery provides valuable methods for analyzing data on neurocognitive disorders involving learning and memory, such as Alzheimer's disease.

This new study demonstrates that the brain does not always act in a linear manner. Instead, neural networks function along an expanding curve, which can be analyzed and understood using hyperbolic geometry and information theory.It is exciting to see that neural responses in this area of the brain formed a map that expanded with experience based on the amount of time devoted in a given place. The effect even held for miniscule deviations in time when animal ran more slowly or faster through the environment.

In the current study, the scientists found that hyperbolic geometry guides neural responses as well. Hyperbolic maps of sensory molecules and events are perceived with hyperbolic neural maps. The space representations dynamically expanded in correlation with the amount of time the rat spent exploring each environment. And, when a rat moved more slowly through an environment, it gained more information about the space, which caused the neural representations to grow even more.

The findings provide a novel perspective on how neural representations can be altered with experience. The geometric principles identified in our study can also guide future endeavors in understanding neural activity in various brain systems.

You would think that hyperbolic geometry only applies on a cosmic scale, but that is not true. Our brains work much slower than the speed of light, which could be a reason that hyperbolic effects are observed on graspable spaces instead of astronomical ones.

Huanqiu Zhang et al, Hippocampal spatial representations exhibit a hyperbolic geometry that expands with experience, Nature Neuroscience (2022). DOI: 10.1038/s41593-022-01212-4

Comment by Dr. Krishna Kumari Challa on January 5, 2023 at 10:02am

An Organism That Can Dine Exclusively on Viruses Has Been Found in a World First

A type of freshwater plankton has become the first organism seen thriving on a diet of viruses, according to a new study by researchers.

Viruses are often consumed incidentally by a range wide of organisms, and may even season the diets of certain marine protists. But to qualify as a true step in the food chain – described as virovory – viruses ought to contribute a significant amount of energy or nutrients to their consumer.

The microbe Halteria is a common genus of protist known to flit about as its hair-like cilia propel it through the water. Not only did laboratory samples of the ciliate consume chloroviruses added to its environment, the giant virus fueled Halteria's growth and increased its population size.

The knock-on effects of widespread consumption of chloroviruses in the wild could have a profound impact on the carbon cycle. Known to infect microscopic green algae, chloroviruses cause their hosts to burst apart, releasing carbon and other nutrients into the environment – a process that serious amounts of virus-eating could be limiting.

There's some good stuff inside viruses if you're an organism looking to feed, including amino acids, nucleic acids, lipids, nitrogen, and phosphorus. Surely something would want to make a meal out of that.

While the Paramecium snacked on the viruses, its sizes and numbers barely budged. Halteria, on the other hand, dined on them, using the chlorovirus as a source of nutrients. The ciliate's population grew about 15 times larger in two days, while the virus population dropped a hundredfold.

Fluorescent green dye was used to tag chlorovirus DNA before it was introduced to the two types of plankton. This confirmed that the viruses were being eaten: the vacuoles – microbial equivalent of stomachs – were glowing green from the feeding.

Further analysis revealed that the growth of Halteria in comparison to the decline of the chlorovirus matched the ratios seen in other microscopic predator vs prey relationships in aquatic environments, giving the team more evidence of what was happening.

https://www.pnas.org/doi/10.1073/pnas.2215000120

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Comment by Dr. Krishna Kumari Challa on January 5, 2023 at 9:07am

Insulin has changed little throughout evolution

Do the results allow conclusions to be drawn about humans? Probably.

Although the release of insulin in fruit flies is mediated by different cells than in humans, the insulin molecule and its function have hardly changed in the course of evolution.

In the past 20 years, using Drosophila as a model organism, many fundamental questions have already been answered that could also contribute to a better understanding of metabolic defects in humans and associated diseases, such as diabetes or obesity.

Less insulin means longevity

One exciting point is that reduced insulin activity contributes to healthy aging and longevity. This has already been shown in flies, mice, humans and other species. The same applies to an active lifestyle. Our work shows a possible link explaining how physical activity could positively affect insulin regulation via neuronal signaling pathways.

Sander Liessem et al, Behavioral state-dependent modulation of insulin-producing cells in Drosophila, Current Biology (2022). DOI: 10.1016/j.cub.2022.12.005

Part 2

Comment by Dr. Krishna Kumari Challa on January 5, 2023 at 9:05am

Exercise curbs insulin production in fruit flies

Insulin is an essential hormone for humans and many other living creatures. Its best-known task is to regulate sugar metabolism. How it does this job is well understood. Much less is known about how the activity of insulin-producing cells and consequently the secretion of insulin is controlled.

Researchers  have now presented new information on this question in the scientific journal Current Biology. They used the fruit fly Drosophila melanogaster as their study object. Interestingly, this fly also secretes insulin after a meal. However, in the fly, the hormone does not come from the pancreas as in humans, but is instead released by nerve cells in the brain.

They  figured out that physical activity of the fly has a strong effect on its insulin-producing cells. For the first time, the researchers measured the activity of these cells electrophysiologically in walking and flying Drosophila.

The result: when Drosophila starts to walk or fly, its insulin-producing cells are immediately inhibited. When the fly stops moving, the activity of the cells rapidly increases again and shoots up above normal levels.

The scientists hypothesize that the low activity of insulin-producing cells during walking and flight contributes to the provision of sugars to meet the increased energy demand. They suspect that the increased activity after exercise helps to replenish the fly's energy stores, for example, in the muscles.

The team was also able to demonstrate that the fast, behaviour-dependent inhibition of insulin-producing cells is actively controlled by neural pathways. It is largely independent of changes in the sugar concentration in the fly's blood.

It makes a lot of sense for the organism to anticipate an increased energy demand in this way to prevent extreme fluctuations in blood sugar levels.

Part 1

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

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