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Comment by Dr. Krishna Kumari Challa on September 15, 2021 at 9:49am

Scientists pinpoint the uncertainty of our working memory

The human brain regions responsible for working memory content are also used to gauge the quality, or uncertainty, of memories, a team of scientists has found. Its study uncovers how these neural responses allow us to act and make decisions based on how sure we are about our memories.

Access to the uncertainty in our working memory enables us to determine how much to 'trust' our memory in making decisions.

This research is the first to reveal that the neural populations that encode the content of working memory also represent the uncertainty of memory.

Working memory, which enables us to maintain information in our minds, is an essential cognitive system that is involved in almost every aspect of human behavior—notably decision-making and learning.

For example, when reading, working memory allows us to store the content we just read a few seconds ago while our eyes keep scanning through the new sentences. Similarly, when shopping online, we may compare, "in our mind," the item in front of us on the screen with previous items already viewed and still remembered.

"It is not only crucial for the brain to remember things, but also to weigh how good the memory is: How certain are we that a specific memory is accurate?

 The study results yielded the first evidence that the human brain registers both the content and the uncertainty of working memory in the same cortical regions.

The knowledge of uncertainty of memory also guides people to seek more information when we are unsure of our own memory.

Joint representation of working memory and uncertainty in human cortex, Neuron (2021). DOI: 10.1016/j.neuron.2021.08.022

https://medicalxpress.com/news/2021-09-scientists-uncertainty-memor...

Comment by Dr. Krishna Kumari Challa on September 15, 2021 at 9:45am

Researchers find immune cells that guard frequent site of cancer spread

In the progressing field of immunotherapy, surprisingly little is known about immunity to metastatic tumors in locations such as lymph nodes, a frequent place where cancers first spread. Not only do lymph nodes act as a gateway for cancer cells to travel throughout the body, but they are also home to infection-fighting white blood cells called T cells. In some cases, T cells in lymph nodes activate to kill invading cancer cells. In other cases, that process clearly fails.

While T cells can freely travel from lymph nodes into the bloodstream and back to the lymph nodes, researchers in Turk's lab have discovered a novel population of tumor-fighting T cells that do not circulate, but rather stay in lymph nodes where they provide protection against melanoma. "These T cells, for whatever reason, have changed their program and stay in the lymph nodes where they persist and kill tumor cells for many months while never entering circulation," says Turk.

These long-lived T cells, called "lymph node resident memory T cells," were shown to counteract melanoma spreading in mice. Turk's team found that when melanoma cells were put back into mice that had been cured of cancer with immunotherapy a month earlier, the lymph nodes were still resistant to the cancer—the melanoma would not grow.

Researchers identified T cells with similar characteristics in melanoma-invaded patient lymph nodes, showing that similar populations exist in humans.

Computational analysis of melanoma specimen data from The Cancer Genome Atlas revealed that the presence of T cells with this gene signature predicted better outcomes and improved survival for human melanoma patients with lymph node metastases. "These studies reveal a new population of T cells that is vital for counteracting the earliest stages of cancer metastasis.

Resident memory T cells in regional lymph nodes mediate immunity to metastatic melanoma, Immunity, DOI: 10.1016/j.immuni.2021.08.019

https://medicalxpress.com/news/2021-09-immune-cells-frequent-site-c...

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Comment by Dr. Krishna Kumari Challa on September 15, 2021 at 9:10am

In some cases, the presence of those newly detected autoantibodies may reflect an increase, driven by the immune response, of antibodies that had been flying under the radar at low levels, Utz said. It could be that inflammatory shock to the systems of patients with severe COVID-19 caused a jump in previously undetectable, and perhaps harmless, levels of autoantibodies these individuals may have been carrying prior to infection.

In other cases, autoantibody generation could result from exposure to viral materials that resemble our own proteins.

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It's possible that, in the course of a poorly controlled SARS-CoV-2 infection—in which the virus hangs around for too long while an intensifying immune response continues to break viral particles into pieces—the immune system sees bits and pieces of the virus that it hadn't previously seen," he said. "If any of these viral pieces too closely resemble one of our own proteins, this could trigger autoantibody production."

The finding bolsters the argument for vaccination. Vaccines for COVID-19 contain only a single protein—SARS-CoV-2's so-called spike protein—or the genetic instructions for producing it. With vaccination, the immune system is never exposed to—and potentially confused by—the numerous other novel viral proteins generated during infection.

In addition, vaccination is less intensely inflammatory than an actual infection, so there's less likelihood that the immune system would be confused into generating antibodies to its own signaling proteins or to the body's own tissues.

Patients who, in response to vaccination, quickly mount appropriate antibody responses to the viral spike protein should be less likely to develop autoantibodies.

Indeed, a recent study in Nature showed that, unlike SARS-CoV-2 infection, the COVID-19 vaccine produced by Pfizer doesn't trigger any detectable generation of autoantibodies among recipients.

1. Sarah Esther Chang, Allan Feng, Wenzhao Meng, Sokratis A. Apostolidis, Elisabeth Mack, Maja Artandi, Linda Barman, Kate Bennett, Saborni Chakraborty, Iris Chang, Peggie Cheung, Sharon Chinthrajah, Shaurya Dhingra, Evan Do, Amanda Finck, Andrew Gaano, Reinhard Geßner, Heather M. Giannini, Joyce Gonzalez, Sarah Greib, Margrit Gündisch, Alex Ren Hsu, Alex Kuo, Monali Manohar, Rong Mao, Indira Neeli, Andreas Neubauer, Oluwatosin Oniyide, Abigail E. Powell, Rajan Puri, Harald Renz, Jeffrey Schapiro, Payton A. Weidenbacher, Richard Wittman, Neera Ahuja, Ho-Ryun Chung, Prasanna Jagannathan, Judith A. James, Peter S. Kim, Nuala J. Meyer, Kari C. Nadeau, Marko Radic, William H. Robinson, Upinder Singh, Taia T. Wang, E. John Wherry, Chrysanthi Skevaki, Eline T. Luning Prak, Paul J. Utz. New-onset IgG autoantibodies in hospitalized patients with COVID-19. Nature Communications, 2021; 12 (1) DOI: 10.1038/s41467-021-25509-3

https://medicalxpress.com/news/2021-09-links-severe-covid-self-atta...

part 2

Comment by Dr. Krishna Kumari Challa on September 15, 2021 at 9:08am

Study links severe COVID-19 to increase in self-attacking antibodies

Hospitalized COVID-19 patients are substantially more likely to harbor autoantibodies—antibodies directed at their own tissues or at substances their immune cells secrete into the blood—than people without COVID-19, according to a new study.

Autoantibodies can be early harbingers of full-blown autoimmune disease.

If you get sick enough from COVID-19 to end up in the hospital, you may not be out of the woods even after you recover.

The scientists looked for autoantibodies in blood samples drawn during March and April of 2020 from 147 COVID-19 patients at the three university-affiliated hospitals and from a cohort of 48 patients at Kaiser Permanente in California. Blood samples drawn from other donors prior to the COVID-19 pandemic were used as controls.

The researchers identified and measured levels of antibodies targeting the virus; autoantibodies; and antibodies directed against cytokines, proteins that immune cells secrete to communicate with one another and coordinate their overall strategy.

Upward of 60% of all hospitalized COVID-19 patients, compared with about 15% of healthy controls, carried anti-cytokine antibodies, the scientists found. This could be the result of immune-system overdrive triggered by a virulent, lingering infection. In the fog of war, the abundance of cytokines may trip off the erroneous production of antibodies targeting them.

If any of these antibodies block a cytokine's ability to bind to its appropriate receptor, the intended recipient immune cell may not get activated. That, in turn, might buy the virus more time to replicate and lead to a much worse outcome.

Part1

Comment by Dr. Krishna Kumari Challa on September 15, 2021 at 8:55am

People only pay attention to new information when they want to

A new paper in the Journal of the European Economic Association, published by Oxford University Press, indicates that we tend to listen to people who tell us things we'd like to believe and ignore people who tell us things we'd prefer not to be true. As a result, like-minded people tend to make one another more biased when they exchange beliefs with one another.

While it would reasonable to think that people form decisions based on evidence and experience alone, previous research has demonstrated that decision makers have "motivated beliefs;" They believe things in part because they would like such things to be true. Motivated beliefs (and the reasoning that leads to them) can generate serious biases. Motivated beliefs have been speculated to explain the proliferation of misinformation on online forums.

The experiment conducted supports a lot of popular suspicions about why biased beliefs might be getting worse in the age of the internet. We now get a lot of information from social media and we don't know much about the quality of the information we're getting. As a result, we're often forced to decide for ourselves how accurate various opinions and sources of information are and how much stock to put in them. Our results suggest that people resolve this quandary by assigning credibility to sources that are telling us what we'd like to hear and this can make biases due to motivated reasoning a lot worse over time.

Ryan Oprea et al, Social Exchange of Motivated Beliefs, Journal of the European Economic Association (2021). DOI: 10.1093/jeea/jvab035

https://phys.org/news/2021-09-people-attention.html?utm_source=nwle...

Comment by Dr. Krishna Kumari Challa on September 15, 2021 at 8:41am

Mechanical buckling of petals produces iridescent patterns visible to bees

Flowers are employing a materials science phenomenon typically associated with failures in structural engineering to produce exquisite three-dimensional petal patterns to lure pollinators.

In civil engineering "buckling" is a dirty word with the buckling of beams and columns leading to mechanical failure—and is something that engineers want to avoid.

But for some plants, buckling is being employed to advantage.

Flowers use several different strategies to lure pollinators. Chemical color from pigments is just one of these strategies and recent research is finding that iridescence could be just as important for attracting pollinators like bees.

This optical effect is produced by an intricate pattern of nano-scale ridges on the surface of petals that diffract light to cause iridescence, like that seen on the surface of CDs or soap bubbles, but how the plant develops these ridges was not known.

Research from the University of Cambridge has demonstrated that plants employ buckling to precisely alter the deformation of the surface of petals in hibiscus flowers. The findings are published in Cell Reports today.

Mechanical buckling can pattern the light-diffracting cuticle of Hibiscus trionum, Cell Reports (2021). DOI: 10.1016/j.celrep.2021.109715

https://phys.org/news/2021-09-mechanical-buckling-petals-iridescent...

Comment by Dr. Krishna Kumari Challa on September 14, 2021 at 11:39am

Our mobile phones are covered in bacteria and viruses… and we never wash them

Comment by Dr. Krishna Kumari Challa on September 14, 2021 at 11:31am

In this case, the siRNA is designed to specifically target the mRNA which carries instructions for the PCSK9 protein. It binds to its target mRNA and destroys the instructions, which significantly reduces the amount of these proteins that are produced.

Gene therapies are usually delivered using a viral vector – a virus-like vehicle that delivers genes to our cells in the same way a virus might infect them. So far, viral vector therapies have been used to treat rare genetic blood disorders, genetic blindness and spinal muscular atrophy.

Although viral vectors are very effective with one treatment, it may be impossible to deliver a second dose if needed due to adverse immune reactions. These drugs are also extremely costly.

Because of this, many of the gene silencing drugs currently being investigated are delivered using a different technique. Known as non-viral vector gene therapies, these deliver the drug using a nanoparticle which protects it from degradation in the blood so it can be delivered specifically to the target – such as the liver, which is the target of the cholesterol jab.

https://www.sciencealert.com/this-gene-silencing-injection-was-just...

Part 2

Comment by Dr. Krishna Kumari Challa on September 14, 2021 at 11:31am

A Clever 'Gene Silencing' Injection Has Been Approved For Treating High Cholesterol

cholesterol-busting jab to save thousands of lives in UK

The revolutionary new treatment, Inclisiran, is delivered as an injection twice a year and can be used alongside statins, adding to the options available to patients to help control their cholesterol levels.

It has been estimated that Inclisiran could prevent 55,000 heart attacks and strokes, saving 30,000 lives within the next decade.

It will mainly be prescribed to patients who suffer with a genetic condition that leads to high cholesterol, those who have already suffered a heart attack or stroke, or those who haven't responded well to other cholesterol-lowering drugs, such as statins.

This is an emerging therapeutic technique that works by targeting the underlying causes of a disease, rather than the symptoms it causes. It does this by targeting a particular gene, and preventing it from making the protein that it produces.

Until now, most treatments using gene silencing technology have been used to treat rare genetic diseases. This means the cholesterol jab will be one of the first gene silencing drugs used to treat people on a wider scale.

Researchers are also currently investigating whether gene silencing could be used to treat a wide variety of health conditions, including Alzheimer's disease and cancer.

Gene silencing drugs work by targeting a specific type of RNA (ribonucleic acid) in the body, called "messenger" RNA. RNAs are found in every cell of the body, and play an important role in the flow of genetic information.

But messenger RNA (mRNA) is one of the most important types of RNA our body has, as it copies and carries genetic instructions from our DNA and makes specific proteins depending on the instructions.

In the case of the cholesterol jab, gene silencing works by targeting a protein called PCSK9 and degrading it. This protein is involved in regulating cholesterol in our bodies, but occurs in excess in people with high levels of LDL cholesterol (the "bad" cholesterol). Preventing this protein from being produced in the first place will reduce cholesterol levels.

https://www.england.nhs.uk/2021/09/nhs-cholesterol-busting-jab-to-s...

Comment by Dr. Krishna Kumari Challa on September 14, 2021 at 10:56am

Gut flora composition may impact susceptibility to konzo, a neurological disease caused by world staple crop cassava

Konzo is a severe, irreversible neurologic disease that results in paralysis. It occurs after consuming poorly processed cassava -- a manioc root and essential crop for DRC and other low-income nations. Poorly processed cassava contains linamarin, a cyanogenic compound. While enzymes with glucosidase activity convert starch to simple sugars, they also break down linamarin, which then releases cyanide into the body.

 Differences between gut flora and genes from konzo-prone regions of the Democratic Republic of Congo (DRC) may affect the release of cyanide after poorly processed cassava is consumed, according to a study with 180 children. Cassava is a food security crop for over half a billion people in the developing world. Children living in high-risk konzo areas have high glucosidase (linamarase) microbes and low rhodanese microbes in their gut, which could mean more susceptibility and less protection against the disease, suggest  researchers who led the study published in Nature Communications.

Knowing who is more at risk could result in targeted interventions to process cassava better or try to diversify the diet. An alternative intervention is to modify the microbiome to increase the level of protection. This is, however, a difficult task which may have unintended consequences and other side effects.

While the gut microbiome is not the sole cause of disease given that environment and malnourishment play a role, it is a required modulator. "Simply stated, without gut microbes, linamarin and other cyanogenic glucosides would pose little to no risk to humans."

1. Matthew S. Bramble, Neerja Vashist, Arthur Ko, Sambhawa Priya, Céleste Musasa, Alban Mathieu, D’ Andre Spencer, Michel Lupamba Kasendue, Patrick Mamona Dilufwasayo, Kevin Karume, Joanna Nsibu, Hans Manya, Mary N. A. Uy, Brian Colwell, Michael Boivin, J. P. Banae Mayambu, Daniel Okitundu, Arnaud Droit, Dieudonné Mumba Ngoyi, Ran Blekhman, Desire Tshala-Katumbay, Eric Vilain. The gut microbiome in konzo. Nature Communications, 2021; 12 (1) DOI: 10.1038/s41467-021-25694-1

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