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Comment by Dr. Krishna Kumari Challa on December 17, 2022 at 11:37am

Immune surprise: Recently evolved alarm molecule drives inflammation

Scientists  have made an important breakthrough in understanding how inflammation is regulated. They have just discovered that a key immune alarm protein previously believed to calm down the immune response actually does the opposite.

Their work has numerous potential impacts, especially in the context of understanding and responding to autoimmune disorders and inflammation.

While our immune system serves a very important function protecting us from infection and injury, when immune responses become too aggressive this can lead to damaging inflammation, which occurs in conditions such as rheumatoid arthritis and psoriasis. Inflammation is triggered when our bodies produce "alarm proteins" (interleukins), which ramp up our defenses against infection and injury by switching on different components of our immune system.

Understanding how and when such alarm proteins are produced and how they activate our immune system has led to major breakthroughs in the treatment of many immune conditions.

Now, scientists  have found that Interleukin-37 has an unexpected function as an immune-activating molecule, as previous studies suggested that this interleukin instead served as an "off switch" for the immune system.

Prior to the new study, Interleukin-37 was thought to have immune-suppressive functions but how exactly it switched off inflammation was hotly debated. However, the scientists now report that, when activated in the correct way, Interleukin-37 displays potent pro-inflammatory activity.

Part 1

Comment by Dr. Krishna Kumari Challa on December 17, 2022 at 10:52am

Study finds higher levels of common diet-associated microbe elevates heart failure risk

New research  expands the link between what we eat and how the gut microbiome impacts our susceptibility to develop different diseases—in this case, how a specific gut microbe-generated byproduct is linked to heart failure risk.

Elevated levels of phenylacetylglutamine (PAG)—a byproduct created when microbes in the gut breakdown dietary protein—can be directly linked to both increased heart failure risk and severity, according to findings published in Circulation: Heart Failure.

The new findings improve researchers' understanding of how the gut microbiome, through PAG levels, are linked to cardiac disease risks, and suggest potential approaches to modify PAG-associated risks through interventions such as diet and beta blocker use.

Elevated PAG levels also were shown to correspond with types of heart failure. For example, elevated blood PAG was observed in subjects with heart failure with preserved ejection fraction, a condition where the heart muscle doesn't relax enough between beats and becomes too stiff, making it less able to fill and consequently pump blood.

Kymberleigh A. Romano et al, Gut Microbiota-Generated Phenylacetylglutamine and Heart Failure, Circulation: Heart Failure (2022). DOI: 10.1161/CIRCHEARTFAILURE.122.009972

Ina Nemet et al, A Cardiovascular Disease-Linked Gut Microbial Metabolite Acts via Adrenergic Receptors, Cell (2020). DOI: 10.1016/j.cell.2020.02.016

Comment by Dr. Krishna Kumari Challa on December 16, 2022 at 11:19am

Physics-Based Planning for Generalizable Assembly by Disassembly

Comment by Dr. Krishna Kumari Challa on December 15, 2022 at 12:09pm

Discovery could explain why women are more likely to get Alzheimer's

Scientists  have found a clue to the molecular cause of Alzheimer's—a clue that may also explain why women are at greater risk for the disease.

In the study, reported on December 14, 2022, in Science Advances, the researchers found that a particularly harmful, chemically modified form of an inflammatory immune protein called complement C3 was present at much higher levels in the brains of women who had died with the disease, compared to men who had died with the disease. They also showed that estrogen—which drops in production during menopause—normally protects against the creation of this form of complement C3.

These new findings suggest that chemical modification of a component of the complement system helps drive Alzheimer's, and may explain, at least in part, why the disease predominantly affects women.

Hongmei Yang et al, Mechanistic insight into female predominance in Alzheimer's disease based on aberrant protein S-nitrosylation of C3, Science Advances (2022). DOI: 10.1126/sciadv.ade0764. www.science.org/doi/10.1126/sciadv.ade0764

Comment by Dr. Krishna Kumari Challa on December 15, 2022 at 11:57am

Pollination loss removes healthy foods from global diets, increases chronic diseases causing excess deaths

Inadequate pollination has led to a 3-5% loss of fruit, vegetable, and nut production and an estimated 427,000 excess deaths annually from lost healthy food consumption and associated diseases, including heart disease, stroke, diabetes, and certain cancers, according to research. It is the first study to quantify the human health toll of insufficient wild (animal) pollinators on human health.

A critical missing piece in the biodiversity discussion has been a lack of direct linkages to human health. This research establishes that loss of pollinators is already impacting health on a scale with other global health risk factors, such as prostate cancer or substance use disorders.

Increasing human pressure on natural systems is causing alarming losses in biodiversity, the topic of the COP 15 UN Biodiversity Conference currently taking place in Montreal. This includes 1-2% annual declines of insect populations, leading some to warn of an impending "insect apocalypse" in the coming decades. Key among insect species are pollinators, which increase yields of three-fourths of crop varieties and are critical to growing healthy foods like fruits, vegetables, and nuts. Changes in land-use, use of harmful pesticides, and advancing climate change threaten wild pollinators, imperiling human supply of healthy foods. The researchers used a model framework, which included empirical evidence from a network of hundreds of experimental farms across Asia, Africa, Europe and Latin America, that looked at "pollinator yield gaps" for the most important pollinator-dependent crops, to show how much crop loss was due to insufficient pollination. They then used a global risk-disease model to estimate the health impacts the changes in pollination could have on dietary risks and mortality by country. Additionally, they calculated the loss of economic value from lost pollination in three case study countries. The results showed that lost food production was concentrated in lower-income countries but that the health burden was greater in middle- and higher-income countries, where rates of non-communicable diseases are higher. The geographic distribution was somewhat unusual in that generally the health effects from global environmental change are centered among the poorest populations in regions such as South Asia and Sub-Saharan Africa. Here, middle-income countries with large populations—China, India, Indonesia, and Russia—suffered the greatest burden. The analysis also showed that lower-income countries lost significant agricultural income due to insufficient pollination and lower yields, potentially 10-30% of total agricultural value.

Strategies to protect wild pollinators are not just an environmental issue, but a health and economic one as well. This study shows that doing too little to help pollinators does not just harm nature, but human health as well.

Pollinator deficits, food consumption, and consequences for human health: a modeling study, Environmental Health Perspectives (2022). DOI: 10.1289/EHP10947

Comment by Dr. Krishna Kumari Challa on December 15, 2022 at 9:39am

World-First Trial Transfusing Lab-Grown Red Blood Cells Begins

A trial testing how long a teaspoon-sized transfusion of lab-grown red blood cells lasts in the body could revolutionize clinical care for people with blood disorders who require regular blood transfusions.

The world-first trial, underway in the UK, is studying whether red blood cells made in the laboratory last longer than blood cells made in the body. Although the trial is only small, it represents a "huge stepping stone for manufacturing blood from stem cells.

To generate the transfusions, the team of researchers isolated stem cells from donated blood and coaxed them into making more red blood cells, a process that takes around three weeks.

In the past, researchers showed they could transfuse lab-grown blood cells back into the same donor they were derived from. This time, they have infused the manufactured cells into another compatible person – a process known as allogeneic transfusion.

Only two people have so far received the lab-made red cells under close monitoring and "no untoward side effects" have been reported by the clinical team, according to a statement released last month. At least another eight participants will receive two transfusions of 5 to 10 milliliters of blood, spaced at least four months apart. One transfusion will contain red blood cells provided by a donor; the other will have lab-grown red cells derived from stem cells from the same donor. Once transfused into the bodies of healthy volunteers, the manufactured cells – which are labeled with a tracer dye – will be tracked as they whiz through the body's circulatory system, until they are worn out, gobbled up, and recycled. The lab-grown blood cells are all freshly made from donated stem cells, whereas a typical blood donation contains a swirling mix of new and months-old blood cells, so the researchers are hopeful the manufactured cells will go the distance and last longer.

https://www.cam.ac.uk/research/news/first-ever-clinical-trial-under...

Comment by Dr. Krishna Kumari Challa on December 14, 2022 at 9:30am

Mighty proteins keep DNA regions close for longer

New work by researchers shows that key proteins help to stabilize the interaction between otherwise highly dynamic DNA structures. The findings shed light onto how the complex folds that help to fit nearly two meters of DNA into the cell’s nucleus influence important biological processes.

Comment by Dr. Krishna Kumari Challa on December 14, 2022 at 9:22am

Producing 'green' energy from living plant 'bio-solar cells'

Though plants can serve as a source of food, oxygen and décor, they're not often considered to be a good source of electricity. But by collecting electrons naturally transported within plant cells, scientists can generate electricity as part of a "green," biological solar cell.

Now, researchers reporting in ACS Applied Materials & Interfaces have, for the first time, used a succulent plant to create a living "bio-solar cell" that runs on photosynthesis.

In all living cells, from bacteria and fungi to plants and animals, electrons are shuttled around as part of natural, biochemical processes. But if electrodes are present, the cells can actually generate electricity that can be used externally. Previous researchers have created fuel cells in this way with bacteria, but the microbes had to be constantly fed. Instead, scientists have turned to photosynthesis to generate current.

During this process, light drives a flow of electrons from water that ultimately results in the generation of oxygen and sugar. This means that living photosynthetic cells are constantly producing a flow of electrons that can be pulled away as a "photocurrent" and used to power an external circuit, just like a solar cell.

The researchers created a living solar cell using the succulent Corpuscularia lehmannii, also called the "ice plant." They inserted an iron anode and platinum cathode into one of the plant's leaves and found that its voltage was 0.28V. When connected into a circuit, it produced up to 20 µA/cm2 of photocurrent density, when exposed to light and could continue producing current for over a day. Though these numbers are less than that of a traditional alkaline battery, they are representative of just a single leaf. Previous studies on similar organic devices suggest that connecting multiple leaves in series could increase the voltage.

The team specifically designed the living solar cell so that protons within the internal leaf solution could be combined to form hydrogen gas at the cathode, and this hydrogen could be collected and used in other applications. The researchers say that their method could enable the development of future sustainable, multifunctional green energy technologies.

Yaniv Shlosberg et al, Self-Enclosed Bio-Photoelectrochemical Cell in Succulent Plants, ACS Applied Materials & Interfaces (2022). DOI: 10.1021/acsami.2c15123

Comment by Dr. Krishna Kumari Challa on December 14, 2022 at 9:11am

Fusion energy breakthrough

Nuclear fusion: harnessing the power of the stars US researchers have finally surpassed an important milestone for nuclear fusion technology: getting more energy out than was put in.

Researchers at the Lawrence Livermore National Laboratory in California for the first time produced more energy in a fusion reaction than was used to ignite it, something called net energy gain, according to one government official and one scientist familiar with the research.

Proponents of fusion hope that it could one day produce nearly limitless, carbon-free energy, displacing fossil fuels and other traditional energy sources. Producing energy that powers homes and businesses from fusion is still decades away. But researchers said it was a significant step nonetheless.

Net energy gain has been an elusive goal because fusion happens at such high temperatures and pressures that it is incredibly difficult to control.

Fusion works by pressing hydrogen atoms into each other with such force that they combine into helium, releasing enormous amounts of energy and heat. Unlike other nuclear reactions, it doesn't create radioactive waste.

The net energy gain achievement applied to the fusion reaction itself, not the total amount of power it took to operate the lasers and run the project. For fusion to be viable, it will need to produce significantly more power and for longer.

It is incredibly difficult to control the physics of stars. It has been challenging to reach this point because the fuel has to be hotter than the center of the sun. The fuel does not want to stay hot—it wants to leak out and get cold. Containing it is an incredible challenge.

It takes enormous resources and effort to advance fusion research. One approach turns hydrogen into plasma, an electrically charged gas, which is then controlled by humongous magnets. This method is being explored in France in a collaboration among 35 countries called the International Thermonuclear Experimental Reactor as well as by researchers at the Massachusetts Institute of Technology and a private company.

Last year the teams working on those projects in two continents announced significant advancements in the vital magnets needed for their work.

Source: The Associated Press

'Breakthrough' as fusion energy generates excess energy for first time

Scientists have hailed a "true breakthrough" as a fusion reaction has successfully generated more energy than was used to create it.

Comment by Dr. Krishna Kumari Challa on December 14, 2022 at 9:02am

Subcutaneous fat emerges as a protector of females' brains

Females' propensity to deposit more fat in places like their hips, buttocks and the backs of their arms, so-called subcutaneous fat, is protective against brain inflammation, which can result in problems like dementia and stroke, at least until menopause, scientists report.

Males of essentially any age have a greater propensity to deposit fat around the major organs in their abdominal cavity, called visceral adiposity, which is known to be far more inflammatory. And, before females reach menopause, males are considered at much higher risk for inflammation-related problems from heart-attack to stroke.

When people think about protection in women, their first thought is estrogen. But sceintists need to get beyond the kind of simplistic idea that every sex difference involves hormone differences and hormone exposure. We need to really think more deeply about the underlying mechanisms for sex differences so that we can treat them and acknowledge the role that sex plays in different clinical outcomes. Diet and genetics are other likely factors that explain the differences broadly assigned to estrogen.

To learn more about how the brain becomes inflamed, they looked at increases in the amount and location of fat tissue as well as levels of sex hormones and brain inflammation in male and female mice at different time intervals as they grew fatter on a high-fat diet. Since, much like with people, obese female mice tend to have more subcutaneous fat and less visceral fat than male mice, they reasoned that the distinctive fat patterns might be a key reason for the protection from inflammation the females enjoy before menopause.

They found again the distinctive patterns of fat distribution in males and females in response to a high-fat diet. They found no indicators of brain inflammation or insulin resistance, which also increase inflammation and can lead to diabetes, until after the female mice reached menopause. At about 48 weeks, menstruation stops and fat positioning on the females starts to shift somewhat, to become more like males.

They then compared the impact of the high-fat diet, which is known to increase inflammation body wide, in mice of both sexes following surgery, similar to liposuction, to remove subcutaneous fat. They did nothing to directly interfere with normal estrogen levels, like removing the ovaries.

The subcutaneous fat loss increased brain inflammation in females without moving the dial on levels of their estrogen and other sex hormones.

Bottom line: The females' brain inflammation looked much more like the males', including increased levels of classic inflammation promoters like the signaling proteins IL-1β and TNF alpha in the brain, researchers report.

We can't just say obesity. We have to start talking about where the fat is. That is the critical element here.

Alexis M. Stranahan et al, Sex Differences in Adipose Tissue Distribution Determine Susceptibility to Neuroinflammation in Mice With Dietary Obesity, Diabetes (2022). DOI: 10.2337/db22-0192

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