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Comment by Dr. Krishna Kumari Challa on October 4, 2023 at 11:54am

The goal before the scientists now is  to develop a highly focused method or methods for blocking STING within targeted immune cells, without disrupting its other important functions. If they  can achieve that, they may have a powerful new tool for controlling hyper-inflammation.

Hannah Meibers et al, Effector Memory T cells induce innate inflammation by triggering DNA damage and a non-canonical STING pathway in dendritic cells, Cell Reports (2023). DOI: 10.1016/j.celrep.2023.113180. www.cell.com/cell-reports/full … 2211-1247(23)01192-0

Part 3

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Comment by Dr. Krishna Kumari Challa on October 4, 2023 at 11:54am

The chain reaction appears to start when T_em cells interact with dendritic cells, which serve as the immune system's primary detector of viral and bacterial invasions. These starburst shaped cells carry a large collection of receptors to detect various types of invaders. Once they encounter a harmful visitor, dendritic cells latch on and sound an alarm that instructs the rest of the immune system's machinery to begin producing T cells that are custom designed to eliminate that type of invader.

When the immune system wins the battle, most of the custom T cells stand down. But a few guards linger in the blood and other body tissues to be ready to "effect" a rapid response should the same type on infection occur again. Hence the name effector memory T cells.

However, the research team discovered that ongoing encounters with T_em cells, such as those occurring when people have autoimmunity or live in a state of chronic inflammation, actually cause DNA strands within dendritic cells to break. This, in turn, prompts a DNA repair pathway that rapidly generates large numbers of inflammatory cytokines, including IL-1b, IL-6 and IL-12.

This flood, or storm, of cytokines causes the tissue damage that occurs in autoinflammatory diseases including type 1 diabetes, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel diseases like Crohn's disease. For some people with these conditions, ongoing inflammation also increases their risk of developing cancer.

Scientists worked for the last 10 years to examine the genetic activity and cell-to-cell communications occurring behind this process. 

The team found a surprising clue when examining the transcriptional profile of dendritic cells following their interaction with T_em cells. Specifically, they detected upregulation of expression of Tmem173, which encodes for stimulator of interferon genes (STING). The STING pathway has been described in previous research as being important to detect viral infections. But when T_em cells harm dendritic cells, the STING pathway does not follow the same route that it typically does when directly responding to viral infections.

In this situation, STING teams up with the gene TRAF6 and the transcription factor NFkB to form an "axis" of activity that drives runaway production of innate inflammatory cytokines.

The researchers further reasoned that if they could prevent STING and TRAF6 from working together, they could cut off the inflammation chain reaction at an early stage. In mice gene-edited to lack the STING pathway, that's exactly what they found. When treated with a drug known to induce an intense T cell-mediated inflammatory response, these mice did not produce a flood of innate cytokines.

The mouse study involved a whole-body elimination of STING. Attempting the same in humans would not be advisable because STING is used by a number of cell types outside the immune system in necessary ways.

Part 2

Comment by Dr. Krishna Kumari Challa on October 4, 2023 at 11:49am

Science trying to take the STING out of runaway inflammation

Cytokine storm: Everybody came to know about it during the covid-19 pandemic.  But once this dangerous form of infection-triggered runaway inflammation started claiming lives by the thousands, a legion of scientists jumped into the hunt for ways to calm these storms.

Now, a study led by immunobiology experts at Cincinnati Children's, offers important new details on how two elements of our body's immune system clash with each other to prompt a chain of reactions that can release deadly floods of cell-killing, organ-damaging cytokines. Details were published Oct. 3, 2023, in the journal Cell Reports.

These findings have implications for both autoimmunity as well as cancer. Researchers have discovered an independent cell signaling pathway that allows a type of immune cell called an effector memory T cell (T_em) to become a critical driver of innate cytokine storms.

With a pathway defined, next steps include confirming whether medications that target key points along the pathway can disrupt the inflammation cycle before it becomes uncontrollable.

Part 1

Comment by Dr. Krishna Kumari Challa on October 4, 2023 at 11:38am

Atmospheric microplastic transport predominantly derived from oceans, study finds

Microplastics in our natural environments are of increasing concern as these tiny particles (<5mm diameter) pollute ecosystems, posing issues to the well-being of animals and humans alike. There are two principal categories of microplastics: primary particles are manufactured for their size and originate from consumer products, such as the microbeads used in cosmetics, while secondary microplastics occur due to the breakdown of larger materials, such as plastic water bottles and matter from industrial waste.

This breakdown occurs due to ultraviolet radiation from the sun causing plastic to become brittle and thus susceptible to the erosive action of waves in particular to shear off flakes into the surrounding environment.

Their longevity during decomposition, taking upwards of 500 years to complete in a landfill, is a critical factor of their detrimental impact on habitats. Marine animals ingest microplastics suspended in the ocean, and microplastics mixed with the sand on our beaches is barely noticeable. Research has discovered microplastics in the smallest plankton all the way through to filter feeding giants of the sea—whales.

But it is not just the ocean that transports these tiny particles across the globe. Atmospheric wind regimes can carry microplastics vast distances, and their shape has a critical impact on airborne retention before deposition.

New research published in Nature Geoscience considers a theory-based model to determine the settling velocity (the point at which a particle stops being suspended in air and settles due to gravity) of microplastics of various sizes and shapes (up to 100μm long and down to 2μm wide), as compared to previous research that has assumed spherical microplastics. The effect of air turbulence on settling velocity was also factored to determine long distance transport.

 Shuolin Xiao et al, Long-distance atmospheric transport of microplastic fibres influenced by their shapes, Nature Geoscience (2023). DOI: 10.1038/s41561-023-01264-6

Comment by Dr. Krishna Kumari Challa on October 4, 2023 at 11:33am

Nobel Prize in physics for split-second glimpse of superfast spinning world of electrons

Three scientists won the Nobel Prize in physics on Tuesday for giving us the first split-second glimpse into the superfast world of spinning electrons, a field that could one day lead to better electronics or disease diagnoses.

The award went to French-Swedish physicist Anne L'Huillier, French scientist Pierre Agostini and Hungarian-born Ferenc Krausz for their work with the tiny part of each atom that races around the center and is fundamental to virtually everything: chemistry, physics, our bodies and our gadgets.

Electrons move so fast that they have been out of reach of human efforts to isolate them, but by looking at the tiniest fraction of a second possible, scientists now have a "blurry" glimpse of them and that opens up whole new sciences. 

The electrons are very fast, and the electrons are really the workforce in everywhere. Once you can control and understand electrons, you have taken a very big step forward.

The scientists, who worked separately, used ever-quicker laser pulses to catch the atomic action that happened at such dizzying speeds—one quintillionth of a second, known as an attosecond.

www.nobelprize.org/uploads/202 … physicsprize2023.pdf

Comment by Dr. Krishna Kumari Challa on October 3, 2023 at 11:35am

How muscles change during endurance training

Comment by Dr. Krishna Kumari Challa on October 3, 2023 at 10:45am

The very first beat: How a heart starts to pulse

Comment by Dr. Krishna Kumari Challa on October 3, 2023 at 10:07am

 Scientists find microplastics  in clouds too!

Researchers  have confirmed microplastics are present in clouds, where they are likely affecting the climate in ways that aren't yet fully understood.

In a study published in Environmental Chemistry Letters, scientists climbed Mount Fuji and Mount Oyama in order to collect water from the mists that shroud their peaks, then applied advanced imaging techniques to the samples to determine their physical and chemical properties.

The team identified nine different types of polymers and one type of rubber in the airborne microplastics—ranging in size from 7.1 to 94.6 micrometers.

Each liter of cloud water contained between 6.7 to 13.9 pieces of the plastics.

What's more, "hydrophilic" or water-loving polymers were abundant, suggesting the particles play a significant role in rapid cloud formation and thus climate systems.

"If the issue of 'plastic air pollution' is not addressed proactively, climate change and ecological risks may become a reality, causing irreversible and serious environmental damage in the future," the researchers warned.

When microplastics reach the upper atmosphere and are exposed to ultraviolet radiation from sunlight, they degrade, contributing to greenhouse gasses.

Microplastics—defined as plastic particles under 5 millimeters—come from industrial effluent, textiles, synthetic car tires,  personal care productsand much more.

Yize Wang et al, Airborne hydrophilic microplastics in cloud water at high altitudes and their role in cloud formation, Environmental Chemistry Letters (2023). DOI: 10.1007/s10311-023-01626-x

Comment by Dr. Krishna Kumari Challa on October 3, 2023 at 10:01am

Separating molecules requires a lot of energy. A nanoporous, heat-resistant membrane could change that

Industry has long relied upon energy-intensive processes, such as distillation and crystallization, to separate molecules that ultimately serve as ingredients in medicine, chemicals and other products.

In recent decades, there has been a push to supplant these processes with membranes, which are potentially a lower-cost and eco-friendly alternative. Unfortunately, most membranes are made from polymers that degrade during use, making them impractical.

To solve this problem, a  research team has created a new, sturdier membrane that can withstand harsh environments—high temperatures, high pressure and complex chemical solvents—associated with industrial separation processes.

Made from an inorganic material called carbon-doped metal oxide, it is described in a study published Sept. 7 in Science.

Researchers have developed is a technique to easily fabricate defect-free, strong membranes that have rigid nanopores that can be precisely controlled to allow different-sized molecules to pass through.

To create the membrane, the research team took inspiration from two common, but unrelated, manufacturing techniques.

The first is molecular layer deposition, which involves layering thin films of materials and is most often associated with semiconductor production. The second technique is interfacial polymerization, which is a method of combining chemicals that is commonly used to create fuel cells, chemical sensors and other electronics.

Bratin Sengupta et al, Carbon-doped metal oxide interfacial nanofilms for ultrafast and precise separation of molecules, Science (2023). DOI: 10.1126/science.adh2404

Comment by Dr. Krishna Kumari Challa on October 3, 2023 at 9:47am

Nobel in medicine goes to two scientists whose work enabled creation of mRNA vaccines against COVID-19

Two scientists won the Nobel prize in medicine on Monday for discoveries that enabled the creation of mRNA vaccines against COVID-19 that were critical in slowing the pandemic—technology that's also being studied to fight cancer and other diseases.

Katalin Karikó and Drew Weissman were cited for contributing "to the unprecedented rate of vaccine development during one of the greatest threats to human health," according to the panel that awarded the prize in Stockholm.

The panel said the pair's "groundbreaking findings ... fundamentally changed our understanding of how mRNA interacts with our immune system."

Traditionally, making vaccines required growing viruses or pieces of viruses and then purifying them before next steps. The messenger RNA approach starts with a snippet of genetic code carrying instructions for making proteins. Pick the right virus protein to target, and the body turns into a mini vaccine factory.

But in early experiments with animals, simply injecting lab-grown mRNA triggered a reaction that usually destroyed it. Karikó and Weissman figured out a tiny modification to the building blocks of RNA that made it stealthy enough to slip past immune defenses.

mRNA   vaccine is a "game changer" in shutting down the coronavirus pandemic, crediting the shots with saving millions of lives.

The duo's pivotal mRNA research was combined with two other earlier scientific discoveries to create the COVID-19 vaccines.

www.nobelprize.org/prizes/medi … dvanced-information/

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