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Comment by Dr. Krishna Kumari Challa 7 hours ago

Man's COVID Infection Lasted 2 Years, Setting a New Record

An immunocompromised man endured ongoing acute COVID-19 for more than 750 days. During this time, he experienced persistent respiratory symptoms and was hospitalized five times.
In spite of its duration, the man's condition differs from long COVID as it wasn't a case of symptoms lingering once the virus had cleared out, but the viral phase of SARS-CoV-2 that continued for over two years.

While this record may be easy to dismiss as something that occurs only to vulnerable people, persistent infections have implications for us all, researchers warn in their new study.

https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(25)00050-3/fulltext

Comment by Dr. Krishna Kumari Challa 7 hours ago

Researchers used two different and powerful methods—single cell RNA sequencing and advanced 3D imaging. They studied samples from both healthy and transplant rejection patients.

Single-cell sequencing allows scientists to study the activity of genes in individual cells, one at a time. The researchers did this on a very large scale to generate a huge amount of data. Then the team stained large chunks of kidney tissue while still intact and used a procedure to make it transparent. This 3D imaging helped validate the predictions from the single-cell genetic analysis.

The researchers found that during kidney transplant rejection, the lymphatic vessels within the transplant change their shape and organization. The vessels spread into deeper parts of the kidney known as the medulla, which normally has no lymphatic vessels within it. At the same time, the cell junctions, which are protein anchors that connect cells, go from looking like loose buttons to tightening up like zippers. This is a change that in other contexts is associated with immune cells getting trapped and unable to escape.

Additionally, the researchers found that the balance of T cells inside and around the vessels was disrupted. These T cells released signals that made the vessels switch on molecules acting like "brakes" for the immune system, in an attempt to calm inflammation. However, this protective response was not enough, as other immune cells and antibodies were seen to be directly attacking the kidney. Strikingly, the vessels themselves were also carrying signs that they too were being targeted by the same harmful antibodies.
These findings challenge the view that lymphatic vessels are simply good or bad in transplant rejection. This study suggests that the lymphatic system is normally protective but impaired in transplant rejection as the findings show the vessels change in ways that could encourage rejection by altering their structure and fueling immune responses. The results pave the way for research to focus on regenerating or protecting the lymphatic system in chronic kidney rejection.

Daniyal J. Jafree et al, Organ-specific features of human kidney lymphatics are disrupted in chronic transplant rejection, Journal of Clinical Investigation (2025). DOI: 10.1172/jci168962

Part 2

Comment by Dr. Krishna Kumari Challa 7 hours ago

Kidney transplant rejection associated with changes in lymphatic vessels, new research shows

Scientists have uncovered how lymphatic vessels—the kidney's "plumbing system"—undergo dramatic changes during chronic transplant rejection, becoming structurally disorganized and spreading to unusual parts of the kidney.

Researchers used single-cell sequencing combined with powerful 3D imaging to look at small lymphatic vessels in kidney tissue, comparing healthy kidneys with transplanted kidneys that had been rejected.

Published in the Journal of Clinical Investigation, the research sheds new light on a major unsolved challenge in kidney transplantation and could open the door to new treatments that help transplants last longer.
Kidney transplantation is the most common form of solid organ transplant worldwide. Although the short-term outcomes of kidney transplantation—within a year after surgery—are very good, the long-term outcomes are poorer. Within 10 years, and depending on what country patients are treated in, roughly 50% of kidney grafts will fail.

Researchers know that a big component of why kidney transplant failure occurs is that the patient's immune system attacks parts of the new kidney—such as the blood vessels within it. However, the role of the lymphatic vessels is far less understood. In healthy kidneys, lymphatic vessels act as the organ's plumbing system—playing a vital role in draining excess fluid and helping to regulate immune activity. Therefore, the researchers sought to gain a deeper understanding of the lymphatic system during transplant rejection.

Part 1

Comment by Dr. Krishna Kumari Challa 7 hours ago

Similarities in the structure of the T2Rs were also analyzed for this study. For these receptors, part of the protein remains inside the cell, known as the intracellular region, while another part stays outside the cell (extracellular region). The interaction with signal molecules happens in the extracellular region. The study demonstrated that there are more structural similarities and consistencies among the intracellular regions of the T2Rs. The extracellular region of the receptors shows significant structural variation.
"Clustering of proteins is based on their structural similarity and dissimilarity. Based on their findings, the researchers divided the T2Rs into three different clusters.
The structure of T2Rs probably allows them to recognize the thousands of different bitter substances via interaction with another taste receptor-specific G protein, α-gustducin.

"With the receptors' involvement in detecting bitter tastants and maintaining the gut-brain axis, this can play an important role in health and pharmaceutical-based research, specifically targeting lifestyle diseases like diabetes.

 Takafumi Shimizu et al, The three-dimensional structure prediction of human bitter taste receptor using the method of AlphaFold3, Current Research in Food Science (2025). DOI: 10.1016/j.crfs.2025.101146

Part 2

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Comment by Dr. Krishna Kumari Challa 7 hours ago

Scientists use AI to decode protein structures behind bitter taste detection

Receptor proteins, expressed on the cell surface or within the cell, bind to different signaling molecules, known as ligands, initiating cellular responses. Taste receptors, expressed in oral tissues, interact with tastants, the molecules responsible for the sensation of taste.

Bitter taste receptors (T2Rs) are responsible for the sensation of bitter taste. However, apart from oral tissue, these receptors are also expressed in the neuropod cells of the gastrointestinal tract, which are responsible for transmitting signals from the gut to the brain. Thus, T2Rs might play a crucial role in maintaining the gut-brain axis.

25 types of human T2Rs have been identified to date. However, due to certain complexities, the structure of most of these receptors is not yet elucidated. In recent times, AI-based prediction models have been used to understand protein structure accurately. Previously, a Nobel Prize-winning artificial intelligence (AI)-based model, AlphaFold2 (AF2), was utilized to decipher the structures of T2Rs. However, with the advancement in technology, the model has been updated to its latest version, AlphaFold3 (AF3). The latest model allows a more detailed structural prediction compared to the previous version.

In this study, a group of researchers decided to analyze the structure of T2Rs using the AF3 model and compare the accuracy with the results from the AF2-based prediction study and the available three-dimensional structures of the two T2Rs, T2R14 and T2R46.

The expression of bitter taste receptors in the gastrointestinal tract indicates that they are involved in maintaining the gut-brain axis, glucose tolerance, and appetite regulation. Hence, understanding the structure can provide a better insight into its function.

The researchers obtained the amino acid sequences of all human T2Rs from the UniProt database and used the AF3 model to predict their three-dimensional structures. For comparison, previously generated AF2 prediction data were retrieved from the AlphaFold database. The experimentally determined structures of T2R14 and T2R46 were sourced from the Protein Data Bank (PDB). Various software tools were employed for structure visualization, alignment, and accuracy assessment.

The analysis revealed that AF3 provided consistently more accurate structural predictions than AF2. For T2R14, predictions were benchmarked against 115 cryo-EM structures, and AF3 showed a higher agreement with experimental data. Similarly, for T2R46, comparisons with three experimentally resolved structures confirmed that AF3 achieved the closest match in all cases.

Part1

Comment by Dr. Krishna Kumari Challa 10 hours ago

Geologists discover where energy goes during an earthquake

The ground-shaking that an earthquake generates is only a fraction of the total energy that a quake releases. A quake can also generate a flash of heat, along with a domino-like fracturing of underground rocks. But exactly how much energy goes into each of these three processes is exceedingly difficult, if not impossible, to measure in the field.

Earthquakes are driven by energy that is stored up in rocks over millions of years. As tectonic plates slowly grind against each other, stress accumulates through the crust. When rocks are pushed past their material strength, they can suddenly slip along a narrow zone, creating a geologic fault. As rocks slip on either side of the fault, they produce seismic waves that ripple outward and upward.

We perceive an earthquake's energy mainly in the form of ground shaking, which can be measured using seismometers and other ground-based instruments. But the other two major forms of a quake's energy—heat and underground fracturing—are largely inaccessible with current technologies.

Now  geologists have traced the energy that is released by "lab quakes"—miniature analogs of natural earthquakes that are carefully triggered in a controlled laboratory setting. For the first time, they have quantified the complete energy budget of such quakes, in terms of the fraction of energy that goes into heat, shaking, and fracturing.

They found that only about 10% of a lab quake's energy causes physical shaking. An even smaller fraction—less than 1%—goes into breaking up rock and creating new surfaces. The overwhelming portion of a quake's energy—on average 80%—goes into heating up the immediate region around a quake's epicenter. In fact, the researchers observed that a lab quake can produce a temperature spike hot enough to melt surrounding material and turn it briefly into liquid melt.

The geologists also found that a quake's energy budget depends on a region's deformation history—the degree to which rocks have been shifted and disturbed by previous tectonic motions. The fractions of quake energy that produce heat, shaking, and rock fracturing can shift depending on what the region has experienced in the past.

The team's lab quakes are a simplified analog of what occurs during a natural earthquake. Down the road, their results could help seismologists predict the likelihood of earthquakes in regions that are prone to seismic events.

 Daniel Ortega‐Arroyo et al, "Lab‐Quakes": Quantifying the Complete Energy Budget of High‐Pressure Laboratory Failure, AGU Advances (2025). DOI: 10.1029/2025av001683

Comment by Dr. Krishna Kumari Challa yesterday

Comment by Dr. Krishna Kumari Challa yesterday

Scientists shoot lasers into brain cells to uncover how illusions work

An illusion is when we see and perceive an object that doesn't match the sensory input that reaches our eyes.

In a new study published in Nature Neuroscience, researchers identified the key neural circuit and cell type that plays a pivotal role in detecting these illusions—more specifically, their outer edges or "contours"—and how this circuit works.

They discovered a special group of cells called IC–encoder neurons that tell the brain to see things that aren't really there as part of a process called recurrent pattern completion.

Because IC–encoder neurons have this unique capacity to drive pattern completion, the researchers think that they might have specialized synaptic output connectivity that allows them to recreate this pattern in a very effective manner.

They also also know that they receive top-down inputs from higher visual areas. The representation of the illusion arises in higher visual areas first and then gets fed back to the primary visual cortex; and when that information is fed back, it's received by these IC–encoders in the primary visual cortex.

 In the context of the brain and vision—using the above shape diagram—higher levels of the brain interpret the image as a square and then tell the lower-level visual cortex to "see a square" even though the visual stimulus consists of four semi-complete black circles.

They made the discovery by observing the electrical brain activity patterns of mice when they were shown illusory images like the Kanizsa triangle. They then shot beams of light at the IC-encoder neurons, in a process called two-photon holographic optogenetics, when there was no illusory image present.

When this happened, they noticed that even in the absence of an illusion, IC-encoder neurons triggered the same brain activity patterns that exist when an illusory image was present. They successfully emulated the same brain activity by stimulating these specialized neurons.

The findings shed light on how the visual system and perception work in the brain and have implications for diseases where this system malfunctions. In certain diseases you have patterns of activity that emerge in your brain that are abnormal, and in schizophrenia these are related to object representations that pop up randomly.

If you don't understand how those objects are formed and a collective set of cells work together to make those representations emerge, you're not going to be able to treat it; so understanding which cells and in which layer this activity occurs is helpful.

Recurrent pattern completion drives the neocortical representation of sensory inference, Nature Neuroscience (2025). DOI: 10.1038/s41593-025-02055-5.

Comment by Dr. Krishna Kumari Challa yesterday

A second study published in Proceedings of the National Academy of Sciences examined the human P2X2 receptor, a protein in the same family as the P2X7 receptor, but is predominantly found in the cochlea, the hearing organ of the inner ear.

The P2X2 receptor is involved in hearing processes and in the ear's adaptation to loud noise. Certain genetic mutations of this receptor have been linked to hearing loss. Currently, there are no drugs that target this receptor effectively, and until now, scientists had limited insight into how it functions.

Researchers  used cryo-electron microscopy—a powerful imaging method—to capture 3D structures of the human P2X2 receptor in two states: in a resting state and in a state bound to ATP but desensitized, meaning it's not active anymore. The team discovered unique structural features and pinpointed areas where hearing-related mutations occur.

Together, the studies mark a leap forward in understanding how P2X receptors contribute to a wide range of diseases by triggering inflammation and sensory changes.

Adam C. Oken et al, A polycyclic scaffold identified by structure-based drug design effectively inhibits the human P2X7 receptor, Nature Communications (2025). DOI: 10.1038/s41467-025-62643-8

Franka G. Westermann et al, Subtype-specific structural features of the hearing loss–associated human P2X2 receptor, Proceedings of the National Academy of Sciences (2025). DOI: 10.1073/pnas.2417753122

Part2

 

Comment by Dr. Krishna Kumari Challa yesterday

Scientists uncover how cellular receptors trigger inflammation and sensory changes

In two new studies, scientists have uncovered detailed blueprints of how certain molecular "gates" in human cells work—findings that could open doors to new treatments for conditions ranging from certain cancers and brain diseases to hearing loss and atherosclerosis, or plaque build-up in the arteries.

They studied a group of proteins known as P2X receptors, which sit on the surface of cells and detect ATP—a molecule best known as the body's energy source inside of cells.

When ATP leaks outside of cells, often as a sign of stress or damage, P2X receptors act like alarm bells, triggering responses related to inflammation, pain and sensory processing.

Extracellular ATP is a universal danger signal. When it builds up outside cells, P2X receptors sense it and change how the cells respond. Understanding these receptors at the atomic level is key to designing drugs that can either calm them down or fine-tune their activity.

In a study published in Nature Communications, researchers examined the molecular structure of the human P2X7 receptor, a protein linked to inflammatory diseases such as cancer, Alzheimer's and atherosclerosis. Despite years of effort, no drugs targeting P2X7 have reached the clinical market, partly because drugs that have worked well in animal models have not had the same success in humans.

Building on a previous study, where they determined how to turn the rat P2X7 receptor off, the team has now mapped how drugs turn off the human P2X7 receptor for the first time. They now know what makes the human receptor different from the receptor that is present in animal models. This is important for understanding how to better customize drugs to fit the binding pockets within the human receptor.

Using that information, the researchers, in collaboration with groups from around the world, designed a new compound referred to as UB-MBX-46. The compound complements the binding pocket in the human receptor, translating to a molecule that blocks the human receptor with high precision and strength.

This is the first time scientists have visualized the human P2X7 receptor and really understood how it is different from others. With that knowledge, they can now create a drug candidate that perfectly fits binding pockets within the human receptor, much like how a key fits in a lock. It gives us hope for developing therapies that have better chances to reach the clinic.

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