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Comment by Dr. Krishna Kumari Challa on March 10, 2023 at 11:30am

Researchers discover how too much oxygen damages cells and tissues

Breathing air that contains higher levels of oxygen than the usual 21 percent found in Earth's atmosphere can cause organ damage, seizures, and even death in people and animals, particularly if it's in excess of the body's oxygen needs. Until now, however, scientists have mostly speculated about the mechanisms behind this phenomenon, known as oxygen toxicity, or hyperoxia.

Now, researchers at Gladstone Institutes have discovered how excess  oxygen changes a handful of proteins in our cells that contain iron and sulfur—a chemical process similar to the rusting of iron. In turn, those "rusty" proteins trigger a cascade of events that damage cells and tissues. The findings, published in the journal Molecular Cell, have implications for conditions such as heart attacks and sleep apnea.

At high levels, oxygen is toxic to every form of life, from bacteria and plants to animals and people. Of course, not enough oxygen is also fatal; there's an intermediate, "Goldilocks" amount under which most life on Earth thrives—not too much and not too little.

While clinicians have long studied the details of how oxygen shortage impacts cells and tissues (for example, in heart attacks and strokes), the effects of excess oxygen have been relatively understudied.

Studies have recently revealed, for instance, that breathing too much supplemental oxygen might be detrimental to heart attack  patients and premature infants. Similarly, in obstructive sleep apnea,  the sudden bursts of oxygen that follow pauses in breathing have been shown to be a key component of how the disorder increases patients' risks of chronic health problems.

Part 1

Comment by Dr. Krishna Kumari Challa on March 10, 2023 at 10:59am

Low-dose radiation linked to increased lifetime risk of heart disease

Exposure to low doses of ionizing radiation is associated with a modestly increased excess risk of heart disease, finds an analysis of the latest evidence published by The BMJ recently.

The researchers say these findings "have implications for patients who undergo radiation exposure as part of their medical care, as well as policy makers involved in managing radiation risks to radiation workers and the public." A linked editorial suggests that these risks "should now be carefully considered in protection against radiation in medicine and elsewhere."

It's well recognized that exposure to high dose radiation can damage the heart, but firm evidence linking low dose radiation to heart disease (e.g., scatter radiation dose from radiotherapy or working in the nuclear industry) is less clear.

To address this knowledge gap, an international team of researchers examined scientific databases for studies evaluating links between a range of cardiovascular diseases and exposure to radiation (mostly radiotherapy and occupational exposures).

They excluded uninformative datasets or those largely duplicating others, leaving 93 studies, published mainly during the past decade, suitable for analysis. These studies covered a broad range of doses, brief and prolonged exposures, and evaluated frequency (incidence) and mortality of various types of vascular diseases.

After taking account of other important factors, such as age at exposure, the researchers found consistent evidence for a dose dependent increase in cardiovascular risks across a broad range of radiation doses.

For example, the relative risk per gray (Gy) increased for all cardiovascular disease and for specific types of cardiovascular disease, and there was a higher relative risk per dose unit at lower dose ranges (less than 0.1 Gy), and also for lower dose rates (multiple exposures over hours to years).

At a population level, excess absolute risks ranged from 2.33% per Gy for a current England and Wales population to 3.66% per Gy for Germany, largely reflecting the underlying rates of cardiovascular disease mortality in these populations.

This equates to a modest but significantly increased excess lifetime risk of 2.3-3.9 cardiovascular deaths per 100 persons exposed to one Gy of radiation, explain the authors.

Ionising radiation and cardiovascular disease: systematic review and meta-analysis, The BMJ (2023). DOI: 10.1136/bmj-2022-072924

Comment by Dr. Krishna Kumari Challa on March 9, 2023 at 1:19pm

Heavy alcohol consumption increases brain inflammation and influences decision making

For people with alcohol use disorder (AUD), there is a constant, vicious cycle between changes to the brain and changes to behavior. AUD can alter signaling pathways in the brain; in turn, those changes can exacerbate drinking.

Now, scientists  have uncovered new details about the immune system's role in this cycle. They reported in the journal Brain, Behavior and Immunity on Feb. 28, 2023, that the immune signaling molecule interleukin 1β (IL-1β) is present at higher levels in the brains of mice with alcohol dependence. In addition, the IL-1β pathway takes on a different role in these animals, causing inflammation in critical areas of the brain known to be involved in decision-making.

These inflammatory changes to the brain could explain some of the risky decision-making and impulsivity we see in people with alcohol use disorder.

In addition, these findings are incredibly exciting because they suggest a potential way to treat alcohol use disorder with existing anti-inflammatory drugs targeting the IL-1β pathway.

AUD is characterized by uncontrolled and compulsive drinking, and it encompasses a range of conditions including alcohol abuse, dependence and binge drinking. Researchers have previously discovered numerous links between the immune system and AUD—many of them centered around IL-1β. People with certain mutations in the gene that codes for the IL-1β molecule, for instance, are more prone to developing AUD. In addition, autopsies of people who had AUD have found higher levels of IL-1β in the brain.

In the new study, researchers compared alcohol-dependent mice with animals drinking moderate or no alcohol at all. They discovered that the alcohol-dependent group had about twice as much IL-1β in the medial prefrontal cortex (mPFC), a part of the brain that plays a role in regulating emotions and behaviors.

The research team then went on to show that IL-1β signaling in the alcohol-dependent group was not only increased, but also fundamentally different. In mice that had not been exposed to alcohol, as well as in mice that had drunk moderate amounts of alcohol, IL-1β activated an anti-inflammatory signaling pathway. In turn, this lowered levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), a signaling molecule known to regulate neural activity in the brain.

However, in alcohol-dependent mice, IL-1β instead activated pro-inflammatory signaling and boosted levels of GABA, likely contributing to some of the changes in brain activity associated with AUD. Notably, these changes in IL-1β signaling in the alcohol-dependent mice persisted even during alcohol withdrawal.

F.P. Varodayan, A.R. Pahng, T.D. Davis, P. Gandhi, M. Bajo, M.Q. Steinman, W.B. Kiosses, Y.A. Blednov, M.D. Burkart, S. Edwards, A.J. Roberts, M. Roberto. Chronic ethanol induces a pro-inflammatory switch in interleukin-1β regulation of GABAergic signaling in the medial prefrontal cortex of male mice. Brain, Behavior, and Immunity, 2023; 110: 125 DOI: 10.1016/j.bbi.2023.02.020

Comment by Dr. Krishna Kumari Challa on March 9, 2023 at 9:44am

A spontaneous gravity prior: newborn chicks prefer stimuli that move against gravity

Comment by Dr. Krishna Kumari Challa on March 9, 2023 at 9:34am

Enzyme that turns air into electricity discovered, providing a new clean source of energy

Scientists have discovered an enzyme that converts air into energy. The finding, published recently in the journal Nature, reveals that this enzyme uses the low amounts of the hydrogen in the atmosphere to create an electrical current. This finding opens the way to create devices that literally make energy from thin air.

The researchers produced and analyzed a hydrogen-consuming enzyme from a common soil bacterium. Recent work by the team has shown that many bacteria use hydrogen from the atmosphere as an energy source in nutrient-poor environments. Bacteria can use the trace hydrogen in the air as a source of energy to help them grow and survive, including in Antarctic soils, volcanic craters, and the deep ocean. But this new discovery made it clear that this enzyme used by the bacteria can produce electricity from air.

The researchers extracted the enzyme responsible for using atmospheric hydrogen from a bacterium called Mycobacterium smegmatis. They showed that this enzyme, called Huc, turns hydrogen gas into an electric current. Huc is extraordinarily efficient. Unlike all other known enzymes and chemical catalysts, it even consumes hydrogen below atmospheric levels—as little as 0.00005% of the air we breathe.

The researchers used several cutting-edge methods to reveal the molecular blueprint of atmospheric hydrogen oxidation. They used advanced microscopy (cryo-EM) to determine its atomic structure and electrical pathways, pushing boundaries to produce the most resolved enzyme structure reported by this method to date. They also used a technique called electrochemistry to demonstrate the purified enzyme creates electricity at minute hydrogen concentrations.

Laboratory work performed by researchers shows that it is possible to store purified Huc for long periods. It is astonishingly stable. It is possible to freeze the enzyme or heat it to 80 degrees celsius, and it retains its power to generate energy. This reflects that this enzyme helps bacteria to survive in the most extreme environments. 

Huc is a "natural battery" that produces a sustained electrical current from air or added hydrogen. While this research is at an early stage, the discovery of Huc has considerable potential to develop small air-powered devices, for example as an alternative to solar-powered devices.

The bacteria that produce enzymes like Huc are common and can be grown in large quantities, meaning we have access to a sustainable source of the enzyme.

 Chris Greening, Structural basis for bacterial energy extraction from atmospheric hydrogen, Nature (2023). DOI: 10.1038/s41586-023-05781-7. www.nature.com/articles/s41586-023-05781-7

Comment by Dr. Krishna Kumari Challa on March 9, 2023 at 7:39am

UN forges historic deal to protect ocean life: what researchers think

High Seas Treaty aims to preserve marine biodiversity while encouraging research-capacity building among nations.

Nations forge a historic High Seas Treaty

After two decades of talks and a marathon 38-hour final session of negotiations, United Nations member countries have agreed on a framework to protect marine biodiversity and provide oversight of international waters. The High Seas Treaty will cover waters outside countries’ national .... The treaty establishes a mechanism to designate marine protected areas and creates several groups — including a scientific and technical body — to oversee regulations covering issues including marine genetic resources. “We’re ecstatic,” says Kristina Gjerde, who researches marine environmental law. “This long-awaited treaty contains many of the vital things we need to safeguard our oceans.”

Comment by Dr. Krishna Kumari Challa on March 8, 2023 at 11:33am

International Women's Day 2023 - "DigitALL: Innovation & Technology for Gender Equality"

Comment by Dr. Krishna Kumari Challa on March 7, 2023 at 11:28am

Trapping and killing superbugs with novel peptide 'nanonets'

Scientists have developed synthetic peptide nanonets for treating infections by bacteria strains resistant to last-resort antibiotics.

In nature, trap-and-kill is a common immune defense mechanism employed by various species, including humans. In response to the presence of pathogens, peptides are released from host cells and they promptly self-assemble in solution to form cross-linked nanonets, which then entrap the bacteria and render them more vulnerable to antimicrobial components.

Several research groups have explored synthetic biomimetics of nanonets as an avenue for addressing the global healthcare challenge of widespread antibiotic resistance. However, most prominent studies in the field only yielded disjointed short nanofibrils restricted to the bacterial surfaces and are incapable of physically immobilizing the bacteria. Additionally, these designs were lacking in control over the initiation of the self-assembly process.

A research team has now designed short β-hairpin peptides of 15 to 16 residues that are capable of self-assembling into nanonets selectively in response to lipopolysaccharide or lipoteichoic acid, which are integral membrane components unique to bacteria.
This specificity towards bacteria is an appealing attribute not yet achieved in the field. The peptide nanonets displayed both trapping and antimicrobial killing functionalities, thus offering a direct upgrade from the trap-only nanonets in nature as well as synthetic designs reported in the field. This opens up opportunities for modulating the activity spectrum of the material.
Nhan Dai Thien Tram et al, Bacteria‐Responsive Self‐Assembly of Antimicrobial Peptide Nanonets for Trap‐and‐Kill of Antibiotic‐Resistant Strains, Advanced Functional Materials (2022). DOI: 10.1002/adfm.202210858

Comment by Dr. Krishna Kumari Challa on March 7, 2023 at 10:32am

New treatment of autoimmune diseases revealed in new study

Scientists  have revealed a chemical compound that could be used for the treatment of various autoimmune diseases like multiple sclerosis and rheumatoid arthritis. These diseases occur when the body's immune response goes awry. The immune system, which normally attacks pathogens and infections, instead attacks healthy cells and tissues. For the millions of people who suffer from autoimmune diseases worldwide, the result can be debilitating—rheumatoid arthritis causes excessive joint pain, while multiple sclerosis can disable one's brain and spinal cord function.

The research focused on T helper 17 cells, or Th17 cells. Th17 cells are a type of T cell—a group of cells, which form major parts of the immune system. These cells, which exist in high numbers in our guts, evolved to help us fight invasive pathogens but, sometimes, they're overactivated and mistake normal, healthy tissue as pathogens, resulting in autoimmunity. The generation of Th17 cells requires glycolysis, a metabolic process in which glucose is broken down and converted to energy to support the metabolic needs of cells. Glycolysis is essential for the growth of not only Th17 cells but also a variety of cells in our body.

 Excessive glycolysis seems to suppress Th17 cell activity. So scientists hypothesized that molecules produced during glycolysis may inhibit the cells.

Enter phosphoenolpyruvate, or PEP for short. This chemical compound  is a metabolite produced when glucose is converted to energy. Since it is part of such an important process, PEP is generated every day in our bodies. The researchers found that treatment with PEP can inhibit the maturation of TH17 cells, leading to resolution of inflammatory response.

The research led to a protein called JunB, which is essential for the maturation of Th17 cells. JunB promotes Th17 maturation by binding to a set of specific genes. The researchers found that PEP treatment inhibits the generation of Th17 cells by blocking JunB activity.

Armed with this knowledge, the researchers went on to treat mice that had neuroinflammation caused by autoimmunity with PEP. This disease is very similar to multiple sclerosis and these mice showed positive signs of recovery. The scientists have now filed a patent to continue with this research.

Tsung-Yen Huang et al, Phosphoenolpyruvate regulates the Th17 transcriptional program and inhibits autoimmunity, Cell Reports (2023). DOI: 10.1016/j.celrep.2023.112205

In the past, researchers who were interested in developing a treatment for autoimmune diseases, often looked at inhibiting glycolysis and thus Th17 cells. But glycolysis is essential to various types of cells in the body and inhibiting it could have significant side-effects. PEP has the potential to be used as a treatment without resulting in such side-effects.

Comment by Dr. Krishna Kumari Challa on March 6, 2023 at 3:53pm

Plasticosis may be the first wildlife disease connected to plastics, but it may not be the last.

https://www.sciencedirect.com/science/article/pii/S0304389423003722...

Part 3

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