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Comment by Dr. Krishna Kumari Challa on May 28, 2022 at 11:06am

How the brain links memories

Our brains rarely record single memories. Instead, they store memories in groups so that the recollection of one significant memory triggers the recall of others that are connected chronologically. As we age, however, our brains gradually lose this ability to link related memories.

Now researchers have discovered a key molecular mechanism behind this memory linking. They’ve also identified a way to restore this brain function genetically in aging mice — and an FDA-approved drug that achieves the same thing.

Published in the journal Nature, the findings suggest a new method for strengthening human memory in middle age and a possible early intervention for dementia.

Brain cells are studded with receptors. To enter a cell, a molecule must latch onto a specific receptor, which operates like a doorknob to provide access inside. The UCLA team focused on a gene that encodes a receptor for CCR5 molecules — the same receptor that HIV hitches a ride on to infect brain cells and cause memory loss in AIDS patients.

As people age, the amount of CCR5 expressed in the brain rises, and increased CCR5 gene expression reduces memory recall.

In the current study, researchers discovered a key mechanism underlying mice’s ability to link memories of their experiences in two different cages. A tiny microscope opened a window into the animals’ brains, enabling the scientists to observe neurons firing and creating new memories.

They found that boosting CCR5 gene expression in the brains of mice interfered with memory linking. The animals forgot the connection between the two cages. But when the scientists deleted the CCR5 gene in the animals, the mice were able to link memories that normal mice could not.

When the researchers gave maraviroc, a drug used for HIV patients, to older mice, the drug duplicated the effect of genetically deleting CCR5 from their DNA. The older animals were able to link memories again.

The finding suggests that beyond reversing the cognitive deficits caused by HIV infection, maraviroc can also be used to help restore middle-aged memory loss.

Yang Shen, Miou Zhou, Denise Cai, Daniel Almeida Filho, Giselle Fernandes, Ying Cai, André F. de Sousa, Min Tian, Nury Kim, Jinsu Lee, Deanna Necula, Chengbin Zhou, Shuoyi Li, Shelbi Salinas, Andy Liu, Xiaoman Kang, Masakazu Kamata, Ayal Lavi, Shan Huang, Tawnie Silva, Won Do Heo, Alcino J. Silva. CCR5 closes the temporal window for memory linking. Nature, 2022; DOI: 10.1038/s41586-022-04783-1

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Comment by Dr. Krishna Kumari Challa on May 28, 2022 at 10:44am

T cells found to require rest and maintenance

T cells are the soldiers of the immune system, constantly on the ready to respond to a variety of threats, from viruses to tumors. However, without rest and maintenance T cells can die and leave their hosts more susceptible to pathogens,  scientists report May 27 in the journal Science.

Until pathogens are detected, T cells remain in a quiescent state. However, the molecular mechanisms that keep T cells inactive were previously unknown.

In the new study,  researchers show that a protein known as CD8a—which is found in a subset of T cells called CD8 cells—is crucial to keeping the cells in this dormant state. When scientists deleted this protein in mice, the protective CD8 cells were unable to enter a quiescent state and died, leaving the host vulnerable to infections.

Further, they identified another protein, PILRa, that provides a biochemical signal to CD8a. By disrupting this protein pair, both "memory" CD8 cells—cells that previously had been exposed to pathogens—and naïve cells died because they lacked the ability to stay in a quiescent state.

The researchers hope that understanding why this resting state is crucial to maintenance and survival of T cells can lead to improved immune system function.

They noted that as people age they tend to lose both naïve and memory T cells, making older individuals more susceptible to infections. It is possible that the inability of T cells to remain in a quiescent state could lead to people becoming more susceptible to infections and cancer, the authors suggest.

Linghua Zheng et al, The CD8α–PILRα interaction maintains CD8 + T cell quiescence, Science (2022). DOI: 10.1126/science.aaz8658

Comment by Dr. Krishna Kumari Challa on May 28, 2022 at 10:18am

Mixing drugs into oil-based gels could help the medicine go down

For most children and even some adults, swallowing pills or tablets is difficult. To make it easier to give those medicines, researchers  have created a drug-delivering gel that is much easier to swallow and could be used to administer a variety of different kinds of drugs.

The gels, made from plant-based oils such as sesame oil, can be prepared with a variety of textures, from a thickened beverage to a yogurt-like substance. The gels are stable without refrigeration, which could make them easier to get to children in developing nations, but they could also be beneficial for children anywhere, the researchers say. They could also help adults who have difficulty swallowing pills, such as older people or people who have suffered a stroke.

This platform will change our capacity for what we can do for kids, and also for adults who have difficulty receiving medication. Given the simplicity of the system and its low cost, it could have a tremendous impact on making it easier for patients to take medications.

Ameya R. Kirtane et al, Development of Oil-Based Gels as Versatile Drug Delivery Systems for Pediatric Applications, Science Advances (2022). DOI: 10.1126/sciadv.abm8478. www.science.org/doi/10.1126/sciadv.abm8478

Comment by Dr. Krishna Kumari Challa on May 27, 2022 at 10:04am

Worms Live Longer with Mitochondria Powered by Light: Preprint

Increasing mitochondrial activity in worms by engineering a light-activated proton pump into the organelle’s membrane extends the animals’ lifespan without evidence of health decline, according to a preprint.

Mitochondrial dysfunction has long been associated with aging, making preventing or reversing the organelle’s decay a high priority for longevity researchers. One key target for such work is the decline in the organelle’s membrane potential: the difference in electrical charge between each side of the inner mitochondrial membrane that is essential for energy production. Now, research published May 12 as a bioRxiv preprint that has not yet been peer reviewed demonstrates that it’s possible to genetically engineer a light-activated proton pump into the mitochondria of Caenorhabditis elegans that maintains the voltage across the inner mitochondrial membrane as the worms age—and doing so, prolongs the animals’ lifespan.

The underlying technology was first described in 2020 research, in which University of Rochester Medical Center mitochondria researcher Andrew Wojtovich and his colleagues uncovered the proton pump’s impact on mitochondria. When they engineered the pump—naturally found in the cells of a fungus—into C. elegans, the animals’ mitochondrial membrane potential was increased, which ramped up the production of molecular fuel. The process, they showed, required neither metabolic substrates like glucose nor oxygen. Instead, the pump used light to fuel the movement of protons across the inner membrane, driving the synthesis of ATP. The team named this tool mitochondria-ON (mtON), which only works if the gene-edited animals are treated with light and supplemented with a vitamin A derivative called all-trans retinal, which acts as a cofactor for the pump. 

https://www.the-scientist.com/news-opinion/worms-live-longer-with-m...

Comment by Dr. Krishna Kumari Challa on May 27, 2022 at 9:48am

Why unprecedented bird flu outbreaks sweeping the world are concerning scientists

Mass infections in wild birds pose a significant risk to vulnerable species, are hard to contain and increase the opportunity for the virus to spill over into people.

A highly infectious and deadly strain of avian influenza virus has infected tens of millions of poultry birds across Europe, Asia, Africa and North America. But scientists are particularly concerned about the unprecedented spread in wild birds — outbreaks pose a significant risk to vulnerable species, are hard to contain and increase the opportunity for the virus to spill over into people.

Since October, the H5N1 strain has caused nearly 3,000 outbreaks in poultry in dozens of countries. More than 77 million birds have been culled to curb the spread of the virus, which almost always causes severe disease or death in chickens. Another 400,000 non-poultry birds, such as wild birds, have also died in 2,600 outbreaks — twice the number reported during the last major wave, in 2016–17.

Researchers say that the virus seems to be spreading in wild birds more easily than ever before, making outbreaks particularly hard to contain. Wild birds help to transport the virus around the world, with their migration patterns determining when and where it will spread next. Regions in Asia and Europe will probably continue to see large outbreaks, and infections could creep into currently unaffected continents such as South America and Australia.

Although people can catch the virus, infections are uncommon.  But scientists are concerned that the high levels of virus circulating in bird populations mean that there are more opportunities for spillover into people. Avian influenza viruses change slowly over time, but the right mutation could make them more transmissible in people and other species.

https://www.nature.com/articles/d41586-022-01338-2

Comment by Dr. Krishna Kumari Challa on May 27, 2022 at 8:29am

Autonomous vehicles can be tricked into dangerous driving behaviour

When a driverless car is in motion, one faulty decision by its collision-avoidance system can lead to disaster, but researchers  have identified another possible risk: Autonomous vehicles can be tricked into an abrupt halt or other undesired driving behavior by the placement of an ordinary object on the side of the road.

A box, bicycle or traffic cone may be all that is necessary to scare a driverless vehicle into coming to a dangerous stop in the middle of the street or on a freeway off-ramp, creating a hazard for other motorists and pedestrians. Vehicles can't distinguish between objects present on the road by pure accident or those left intentionally as part of a physical denial-of-service attack.

The vehicle's planning module is designed with an abundance of caution, logically, because you don't want driverless vehicles rolling around, out of control. But real testing has found that the software can err on the side of being overly conservative, and this can lead to a car becoming a traffic obstruction, or worse.

 Ziwen Wan et al, Too Afraid to Drive: Systematic Discovery of Seman..., (2022)

Comment by Dr. Krishna Kumari Challa on May 27, 2022 at 8:00am

Harnessing the immune system to treat traumatic brain injury in mice

A therapeutic method for harnessing the body's immune system to protect against brain damage is published recently by researchers. The collaboration between various researchers has produced a targeted delivery system for boosting the numbers of specialized anti-inflammatory immune cells specifically within the brain to restrict brain inflammation and damage. Their brain-specific delivery system protected against brain cell death following brain injury, stroke and in a model of multiple sclerosis. The research is published in the journal Nature Immunology.

Traumatic brain injury, like that caused during a car accident or a fall, is a significant cause of death worldwide and can cause long-lasting cognitive impairment and dementia in people who survive. A leading cause of this cognitive impairment is the inflammatory response to the injury, with swelling of the brain causing permanent damage. While inflammation in other parts of the body can be addressed therapeutically, but in the brain it is problematic due to the presence of the blood-brain barrier, which prevents common anti-inflammatory molecules from getting to the site of trauma.

The research team found that regulatory T cell numbers were low in the brain because of a limited supply of the crucial survival molecule interleukin 2, also known as IL2. Levels of IL2 are low in the brain compared to the rest of the body as it can't pass the blood-brain barrier.

Together the team devised a new therapeutic approach that allows more IL2 to be made by brain cells, thereby creating the conditions needed by regulatory T cells to survive. A 'gene delivery' system based on an engineered adeno-associated viral vector (AAV) was used: this system can actually cross an intact blood brain barrier and deliver the DNA needed for the brain to produce more IL2 production.

Matthew Holt, Astrocyte-targeted gene delivery of interleukin 2 specifically increases brain-resident regulatory T cell numbers and protects against pathological neuroinflammation, Nature Immunology (2022). DOI: 10.1038/s41590-022-01208-z. www.nature.com/articles/s41590-022-01208-z

Comment by Dr. Krishna Kumari Challa on May 27, 2022 at 7:52am

New type of extremely reactive substance discovered in the atmosphere

For the first time, an entirely new class of super-reactive chemical compounds has been discovered under atmospheric conditions. Researchers from the University of Copenhagen, in close collaboration with international colleagues, have documented the formation of so-called trioxides—an extremely oxidizing chemical compound that likely affects both human health and our global climate.

Hydrogen peroxide is a commonly known chemical compound. All peroxides have two oxygen atoms attached to each other, making them highly reactive and often flammable and explosive. They are used for everything from whitening teeth and hair to cleaning wounds, and even as rocket fuel. But peroxides are also found in the atmosphere. In recent years, there has been speculation as to whether trioxides—chemical compounds with three oxygen atoms attached to each other, and thereby even more reactive than the peroxides—are found in the atmosphere as well. But until now, it has never been unequivocally proven.

The type of compounds now discovered are unique in their structure. And, because they are extremely oxidizing, they most likely bring a host of effects that we have yet to uncover.

Hydrotrioxides (ROOOH), as they are known, are a completely new class of chemical compounds. Researchers at the University of Copenhagen (UCPH), together with colleagues at the Leibniz Institute for Tropospheric Research (TROPOS) and the California Institute of Technology (Caltech), have demonstrated that these compounds are formed under atmospheric conditions. 

The researchers have also shown that hydrotrioxides are formed during the atmospheric decomposition of several known and widely emitted substances, including isoprene and dimethyl sulfide.

Torsten Berndt et al, Hydrotrioxide (ROOOH) formation in the atmosphere, Science (2022). DOI: 10.1126/science.abn6012. www.science.org/doi/10.1126/science.abn6012

Comment by Dr. Krishna Kumari Challa on May 26, 2022 at 2:13pm

Scientists detect deadly arrhythmia trifecta: Salt, swelling, and leaky sodium channels

Less than 1 percent of the population has been diagnosed with Long QT syndrome – a rare heart condition that can cause chaotic, sometimes fatal, heart rhythms.

Now, researchers  have identified two core factors that may put patients with Long QT syndrome Type 3 at significantly higher risk of sudden cardiac death. Their findings were recently published in the American Journal of Physiology – Heart and Circulatory Physiology.

Some Long QT syndrome patients are born with the disease, while others develop it as a result of natural aging, certain medications, tissue swelling, or heart disease.

The syndrome remodels the heart’s sodium channels to become hyperactive and leaky, which disrupts the heart’s normal electrical pathways. Long QT is diagnosed when the length of time it takes for a heartbeat to drop from its peak to baseline, the QT interval, is extended on an electrocardiogram reading.

Some patients with Long QT live long, healthy, and event-free lives, while others suddenly die. Some Long QT syndrome patients are born with the disease, while others develop it as a result of natural aging, certain medications, tissue swelling, or heart disease.

The syndrome remodels the heart’s sodium channels to become hyperactive and leaky, which disrupts the heart’s normal electrical pathways. Long QT is diagnosed when the length of time it takes for a heartbeat to drop from its peak to baseline, the QT interval, is extended on an electrocardiogram reading.

Some patients with Long QT live long, healthy, and event-free lives, while others suddenly die. 

This research  data suggests that the combination of tissue edema, elevated blood sodium, and faulty sodium channels trigger deadly heart arrhythmias. While Long QT is a rare disorder, anyone could acquire similar sodium channel dysfunction with age, ischemia, or other heart disease.

https://pubmed.ncbi.nlm.nih.gov/34623182/

https://vtx.vt.edu/articles/2022/05/scientists-detect-deadly-arrhyt...

Comment by Dr. Krishna Kumari Challa on May 26, 2022 at 1:58pm

A similar process is at work all over the universe. However, in stars and galaxies and in the space between them, the electrically conducting fluid is not molten metal, but plasma—a state of matter that exists at extremely high temperatures where the electrons are ripped away from their atoms. On Earth, plasmas can be seen in lightning or neon lights. In such a medium, the dynamo effect can amplify an existing magnetic field, provided it starts at some minimal level.

Where does this seed field come from? Present studies developed the underlying theory and performed numerical simulations on powerful supercomputers that show how the seed field can be produced and what fundamental processes are at work. An important aspect of the plasma that exists between stars and galaxies is that it is extraordinarily diffuse—typically about one particle per cubic meter. That is a very different situation from the interior of stars, where the particle density is about 30 orders of magnitude higher. The low densities mean that the particles in cosmological plasmas never collide, which has important effects on their behavior that had to be included in the model that these researchers were developing.

Calculations performed by the MIT researchers followed the dynamics in these plasmas, which developed from well-ordered waves but became turbulent as the amplitude grew and the interactions became strongly nonlinear. By including detailed effects of the plasma dynamics at small scales on macroscopic astrophysical processes, they demonstrated that the first magnetic fields can be spontaneously produced through generic large-scale motions as simple as sheared flows. Just like the terrestrial examples, mechanical energy was converted into magnetic energy.

An important output of their computation was the amplitude of the expected spontaneously generated magnetic field. What this showed was that the field amplitude could rise from zero to a level where the plasma is "magnetized"—that is, where the plasma dynamics are strongly affected by the presence of the field. At this point, the traditional dynamo mechanism can take over and raise the fields to the levels that are observed. Thus, their work represents a self-consistent model for the generation of magnetic fields at cosmological scale.

Muni Zhou et al, Spontaneous magnetization of collisionless plasma, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2119831119

Part 3

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