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Comment by Dr. Krishna Kumari Challa on March 9, 2024 at 9:52am

Water guides the assembly of collagen, the building block of all humans

Water determines life: humans are three-quarters water. An international research team  has now discovered how water also determines the structure of the material that holds us together: collagen.

In a paper published in PNAS, the researchers elucidate the role of water in the molecular self-assembly of collagen. They show that by replacing water with its 'twin molecule' heavy water (D₂O), one can 'tune' the interaction between collagen molecules, and thus influence the process of collagen self-assembly. The findings will help to better understand the tissue failures resulting from heritable collagen-related diseases, such as brittle bone disease (osteogenesis imperfecta).

Collagen is to a large extent 'the stuff we're made of'—around a third of all protein in our body is collagen which ensures the mechanical integrity of all human connective tissue.

For instance, our skin and arteries stretch without tearing and our bones can resist high stress without breaking. Collagen is produced by our cells as single proteins that assemble into larger structures called fibrils. These fibrils further assemble into networks that form the scaffolds for our tissues.

Since collagen is formed in the aqueous environment of human cells, water plays a crucial role in its assembly. The interaction of water molecules with proteins results in collagen that is best suited for its function. But what exactly is behind this collagen-optimizing role of water? How does water do it? And will understanding this mechanism offer insights into conditions where something is wrong with collagen, such as osteogenesis imperfecta? These were the central questions of the research published in PNAS.

Part 1

Comment by Dr. Krishna Kumari Challa on March 9, 2024 at 8:47am

Many immune checkpoints are receptors on the surface of T cells that act to translate docking information from the outside of the cell to the signaling portion of the receptor inside the cell. Connecting the outside-of-the-cell portion of PD-1 with the inside portion is the transmembrane segment. Many immune receptors function in pairs called dimers, but to date, PD-1 has been thought to function alone, not in the dimer form.

Study results showed that PD-1 forms a dimer through interactions of its transmembrane segment. Researchers say this finding is in sharp contrast to other immune receptors, which typically form dimers through the segment of the receptor that is outside the cell.

Further immune cell testing in mice showed that encouraging PD-1 to form dimers, specifically in the transmembrane domain but not in its outer or inner regions, increased its ability to suppress T cell activity, while decreasing transmembrane dimerization lowered PD-1's ability to inhibit immune cell activity.

The study reveals that the PD-1 receptor functions optimally as dimers driven by interactions within the transmembrane domain on the surface of T cells, contrary to the dogma that PD-1 is a monomer.

These findings offer new insights into the molecular workings of the PD-1 immune cell protein that have proven pivotal to the development of the current generation of anticancer immunotherapies, and which are proving essential in the design and developing of the next generation of immunotherapies for autoimmune diseases.

Among the study's other findings was that a single change in the amino acid structure of the transmembrane segment can act to either enhance or diminish the inhibitory function of PD-1 in immune responses.

The team plans further investigations of PD-1 inhibitors and agonists to see if they can tailor what they say are more effective, "rationally designed" therapies for both cancer and autoimmune disorders.

Elliot Philips et al, Transmembrane Domain Driven PD-1 Dimers Mediate T Cell Inhibition, Science Immunology (2024). DOI: 10.1126/sciimmunol.ade6256. www.science.org/doi/10.1126/sciimmunol.ade6256

Part 2

Comment by Dr. Krishna Kumari Challa on March 9, 2024 at 8:42am

'Double life' of key immune protein reveals new strategies for treating cancer and autoimmune diseases

Insights into the workings of an immune cell surface receptor, called PD-1, reveal how treatments that restrict its action can potentially be strengthened to improve their anticancer effect, a new study shows. The same findings also support experimental treatment strategies for autoimmune diseases, in which the immune system attacks the body, because stimulating the action of PD-1, as opposed to restricting it, can potentially block an overactive immune response.

The study is published  in the journal Science Immunology.

The study results revolve around the body's immune system, which is primed to attack virally infected and cancerous cells while leaving normal cells alone. To spare normal cells from immune attack, the system uses "checkpoints," sensors on the surface of immune cells, including T cells, which turn them off or dampen activation when they receive the right signal. The immune system recognizes tumors as abnormal, but cancer cells can hijack checkpoints to turn off immune responses.

Among the most important checkpoints is a protein called programmed cell death receptor 1 (PD-1), which is shut down by a relatively new drug class called checkpoint inhibitors to make tumors "visible" again to immune attack. Such drugs are at least somewhat effective in a third of patients with a variety of cancers, say the study authors, but the field is urgently seeking ways to improve their performance and scope.

At the same time, PD-1 signaling is slowed in autoimmune diseases like rheumatoid arthritis, lupus, and type 1 diabetes, such that the action of unchecked immune cells creates inflammation that can damage tissues. Agonists, drugs that stimulate PD-1, are now showing promise in clinical trials. Part 1

Comment by Dr. Krishna Kumari Challa on March 8, 2024 at 9:30am

Bull's-Eye Cancer Treatment
A promising new class of cancer drugs is gaining momentum. Antibody-drug conjugates, or ADCs, target specific hormone receptors on cancer cells and deliver growth-stopping drugs directly to tumors. Fourteen ADCs have been approved for breast, bladder, ovarian, blood, and other cancers, some difficult to treat with traditional tactics. About 100 other ADCs are in the preclinical pipeline.

How these drugs are different: Traditional chemotherapeutic drugs kill cancer cells, but also kill healthy cells in the process, leading to severe side effects in the patient. Because of the debilitating side effects, most patients cannot endure a maximum dose of chemotherapy. ADC technology could also be used to deliver radiation therapy directly to tumor cells, or deliver drugs that activate the patient’s immune system to eradicate the cancer.

What the experts say: Enhertu, a new ADC treatment for breast cancer that uses special molecules to link the antibody to the drug that targets cancer cells, has been shown to stop cancer growth for four times longer than a compound without the linker molecules. “It was a landslide in terms of how much better it was,” says oncologist Sara M. Tolaney of the Dana-Farber Cancer Institute in Boston. “It's a really nice example of how ADC technology leads to dramatic differences in outcomes.”

deliver growth-stopping drugs directly to tumors.

Comment by Dr. Krishna Kumari Challa on March 8, 2024 at 9:07am

Plastic pollution's effect on heart health

We breathe, eat and drink tiny particles of plastic. But are these minuscule specks in the body harmless, dangerous or somewhere in between?

A small study published recently in the New England Journal of Medicine raises more questions than it answers about how these bits—microplastics and the smaller nanoplastics—might affect the heart. The Italian study has weaknesses, but is likely to draw attention to the debate over the problem of plastic pollution. Most plastic waste is never recycled and breaks down into these particles.

It's a wake-up call that perhaps we need to take the problem of microplastics more seriously. As a cause for heart disease? Not proven. As a potential cause? Maybe!

The study involved 257 people who had surgery to clear blocked blood vessels in their necks. Italian researchers analyzed the fatty buildup that the surgeons removed from the carotid arteries, which supply blood and oxygen to the brain.

Using two methods, they found evidence of plastics—mostly invisible nanoplastics—in the artery plaque of 150 patients and no evidence of plastics in 107 patients.

They followed these people for three years. During that time, 30 or 20% of those with plastics had a heart attack, stroke or died from any cause, compared to eight or about 8% of those with no evidence of plastics.

The researchers also found more evidence of inflammation in the people with the plastic bits in their blood vessels. Inflammation is the body's response to injury and is thought to raise the risk of heart attacks and strokes.

It's very small and looked only at people with narrowed arteries, who were already at risk for heart attack and stroke. The patients with the plastics had more heart disease, diabetes and high cholesterol than the patients without plastics. They were more likely to be men and more likely to be smokers.

The researchers tried to adjust for these risk factors during their statistical analysis, but they may have missed important differences between the groups that could account for the results. This kind of study cannot prove that the plastics caused their problems.

The researchers had no information on what the people consumed or breathed that might account for the plastics.

The specimens could have been contaminated in the lab. The researchers acknowledge as much in their paper and suggest that future studies be done in clean rooms where air is filtered for pollutants.

The researchers suggest the risk of heart attack, stroke or death was four times greater in the people with the plastics. That seems high.

More research is needed as it does not prove cause and effect, but it suggests cause and effect. And it needs urgently to be either replicated or disproven by other studies done by other investigators in other populations.

This just makes us more alert to the problem.

Raffaele Marfella et al, Microplastics and Nanoplastics in Atheromas and Cardiovascular Events, New England Journal of Medicine (2024). DOI: 10.1056/NEJMoa2309822

Philip J. Landrigan, Plastics, Fossil Carbon, and the Heart, New England Journal of Medicine (2024). DOI: 10.1056/NEJMe2400683

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Comment by Dr. Krishna Kumari Challa on March 8, 2024 at 8:57am

For childhood cancer survivors, inherited genetic factors influence risk of cancers later in life

Common inherited genetic factors that predict cancer risk in the general population may also predict elevated risk of new cancers among childhood cancer survivors, according to a study  by researchers .

The findings, published in Nature Medicine, provide additional evidence that genetics may play an important role in the development of subsequent cancers in survivors of childhood cancer and suggest that common inherited variants could potentially inform screening and long-term follow-up of those at greatest risk. Childhood cancer survivors are known to have a higher risk of developing a new cancer later in life due to adverse effects of cancer treatment or rare inherited genetic factors.

In the new study, the researchers evaluated the combined effect of common variants with history of radiation treatment and found the resulting elevated cancer risk was greater than the sum of the individual associations for treatment and genetic factors alone.

Polygenic risk scores, radiation treatment exposures and subsequent cancer risk in childhood cancer survivors, Nature Medicine (2024).

Comment by Dr. Krishna Kumari Challa on March 8, 2024 at 8:18am

Bullying Could Lead To Psychosis In Teens

The study shows that bullying could alter the levels of neurotransmitter, Glutamate, which is linked with phychosis.
New research work show a link between teenagers who get bullied and the early stages of psychotic episodes they experience.
The study, published in Molecular Psychiatry, found that bullied teens not only face a higher risk of experiencing early psychotic symptoms but also exhibit lower levels of a critical neurotransmitter in the brain responsible for emotion regulation. The finding suggests that this neurotransmitter, called glutamate, may be a potential target for pharmaceutical interventions aimed at reducing the risk of psychotic disorders. Glutamate is involved in a wide range of functions, including learning, memory and mood regulation.
Psychosis has been linked to altered levels of glutamate, which is abundant in the brain’s anterior cingulate cortex (ACC). The ACC plays a crucial role in regulating emotions, decision-making and cognitive control, making it a key area for understanding mental health. Psychosis is a mental state characterized by loss of contact with reality, incoherent speech and behaviour and typically hallucinations and delusions.
Researchers have noticed reduced glutamate levels in people undergoing their initial episode of psychosis or those with treatable schizophrenia. Changes in glutamate levels are also linked to mental health conditions like depression and anxiety.
Researchers used magnetic resonance spectroscopy (MRS), a type of radiological imaging applied to depict brain structure and function, to measure glutamate levels in the ACC region of Japanese adolescents. They measured glutamate levels at a later stage, enabling them to evaluate changes over time. They then compared these changes with experiences of bullying, or lack thereof, and assessed whether individuals facing bullying had any intention to seek help.
By tracking bullying through questionnaires and psychiatric measurements, the researchers identified a significant association between bullying and higher levels of subclinical psychotic experiences in early adolescence. These subclinical experiences, resembling psychosis but not meeting full diagnostic criteria, include hallucinations, paranoia, or significant changes in thinking or behaviour, and can have a significant impact on well-being and functioning, even in the absence of a psychotic disorder diagnosis.
The study found that higher levels of these experiences were linked to lower levels of anterior cingulate glutamate in early adolescents.
Researchers say anti-bullying programs in schools that focus on promoting positive social interactions and reducing aggressive behaviours are essential for their own sake and to reduce the risk of psychosis and its subclinical precursors. These programs can help create a safe and supportive environment for all students, reducing the likelihood of bullying and its negative consequences.

https://www.nature.com/articles/s41380-023-02382-8

Comment by Dr. Krishna Kumari Challa on March 7, 2024 at 12:38pm

COVID protections wiped out a strain of flu
For the first time, an influenza virus has been eliminated from the human population through non-pharmaceutical interventions. The public-health protections brought in during the COVID-19 pandemic — such as wearing a mask, social distancing and better ventilation — seem to have eliminated the influenza B/Yamagata lineage; no cases have been confirmed since March 2020. In September, the World Health Organization recommended that countries no longer include Yamagata-lineage antigens in flu vaccines, and US Food and Drug Administration advisors have now voted to remove it from flu jabs in the United States.

https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(23)00697-7/fulltext?utm_source=Live+Audience&utm_campaign=c98e4d006c-briefing-dy-20240306&utm_medium=email&utm_term=0_b27a691814-c98e4d006c-50323416

https://edition.cnn.com/2024/03/05/health/flu-vaccine-yamagata-stra...

Comment by Dr. Krishna Kumari Challa on March 7, 2024 at 12:03pm

Researchers find exception to 200-year-old scientific law governing heat transfer

A team of researchers has recently found an exception to the 200-year-old law, known as Fourier's Law, that governs how heat diffuses through solid materials.

Though scientists have shown previously that there are exceptions to the law at the nanoscale, the research, published in the Proceedings of the National Academy of Sciences, is the first to show that the law doesn't always hold true at the macro scale, and that pure electromagnetic radiation is also at work in some common materials like plastics and glasses.

Radiant heat is the heat that we feel from the sun; its electromagnetic waves warm our skin when the sun shines. Diffusion, on the other hand, is how your tea mug will warm your hand after you've poured yourself a fresh cup. For 200 years, scientists have believed that diffusion explains how heat travels through solids. "But sometimes creativity requires that you put the textbook aside for a moment."

Researchers surmised that an exception to Fourier's Law might be found in translucent polymers and inorganic glasses. Heat diffuses through both materials, but the team hypothesized that their translucence might also allow energy to radiate through the materials as well.

To test the hypothesis, they situated samples of the materials in a vacuum chamber, which would eliminate the air that is responsible for convective distribution of heat. They then created a pulse of heat in one sample by using a laser to heat a small area, and, in the other sample, heated one side while keeping the other side cold.

They then used a special infrared camera to watch as the heat spread through their samples. In repeating the experiment many times, they kept finding anomalies that Fourier's Law could not entirely explain.

It turns out that the translucent materials allow energy to radiate internally, interacting with small structural imperfections, which then become secondary heat sources. These secondary heat sources themselves continue to radiate heat through the material.

It's not that Fourier's Law is wrong. It is just that it doesn't explain everything we see when it comes to heat transmission. Fundamental research like this gives us an expanded understanding of how heat works, which will offer engineers new strategies for designing heat circuits.

Granick, Steve et al, Exceptions to Fourier's Law at the Macroscale, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2320337121. doi.org/10.1073/pnas.2320337121

Comment by Dr. Krishna Kumari Challa on March 7, 2024 at 10:46am

The researchers' device represents the first hydrovoltaic application of a technique called nanosphere colloidal lithography, which allowed them to create a hexagonal network of precisely spaced silicon nanopillars. The spaces between the nanopillars created the perfect channels for evaporating fluid samples and could be finely tuned to better understand the effects of fluid confinement and the solid/liquid contact area.

In most fluidic systems containing saline solutions, you have an equal number of positive and negative ions. However, when you confine the liquid to a nanochannel, only ions with a polarity opposite to that of the surface charge will remain. This means that if you allow liquid to flow through the nanochannel, you will generate current and voltages.

As the fluid ion concentration increases, so does the surface charge of the nanodevice. As a result, we can use larger fluid channels while working with higher-concentration fluids. This makes it easier to fabricate devices for use with tap or seawater, as opposed to only purified water.

Because evaporation can occur continuously over a wide range of temperatures and humidities—and even at night—there are many exciting potential applications for more efficient HV devices.

Tarique Anwar et al, Salinity-dependent interfacial phenomena toward hydrovoltaic device optimization, Device (2024). DOI: 10.1016/j.device.2024.100287

Part 2

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