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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

Comment by Dr. Krishna Kumari Challa on December 13, 2022 at 11:05am

Experimental cancer therapy shows success in more than 70% of patients in global clinical trials

A new therapy that makes the immune system kill bone marrow cancer cells was successful in as many as 73% of patients in two clinical trials, according to researchers . 

The therapy, known as a bispecific antibody, binds to both T cells and multiple myeloma cells and directs the T cells—white blood cells that can be enlisted to fight off diseases—to kill multiple myeloma cells. The researchers described this strategy as "bringing your army right to the enemy." The success of the off-the-shelf immunotherapy, called talquetamab, was even seen in patients whose cancer was resistant to all approved multiple myeloma therapies. It uses a different target than other approved therapies: a receptor expressed on the surface of cancer cells known as GPRC5D. Talquetamab was tested in phase 1 and phase 2 trials. The phase 1 trial, which was reported in the New England Journal of Medicine, established two recommended doses that were tested in the Phase 2 trial. The results of the Phase 2 trial were reported at the American Society of Hematology annual meeting on Saturday, December 10. The study participants had all been previously treated with at least three different therapies without achieving lasting remission, suggesting talquetamab could offer new hope for patients with hard-to-treat multiple myeloma. This means that almost three-quarters of these patients are looking at a new lease on life.

The efficacy and safety findings in the phase 1 study were validated in the phase 2 trial presented at ASH. The overall response rate in these two groups was about 73%.

Ajai Chari et al, New England Journal of Medicine (2022).

Conference: www.hematology.org/meetings/annual-meeting

Comment by Dr. Krishna Kumari Challa on December 12, 2022 at 12:14pm

Antibodies to common antibiotic possible new risk factor for type 1 diabetes

Antibodies produced against the commonly used antibiotic, gentamicin, appear to increase the risk of type 1 diabetes in children already genetically at risk, scientists say.

When  scientists compared the blood of nearly 300 individuals with type 1 diabetes to healthy controls, they found that a higher level of antibodies against gentamicin was associated with increased risk of progression to type 1 diabetes. G418 and sisomicin, analogs of gentamicin, also showed a similar association.

Their study analyzed samples from the Diabetes Autoimmunity Study in the Young (DAISY) and Phenome and Genome of Diabetic Autoantibody (PAGODA). The databases studied did not state whether study participants had been given gentamicin. However, anywhere between 5-10% of newborns receive the broad-spectrum antibiotic to treat potentially lethal sepsis.

They report in the journal Nature Communications that a similar percentage, 5.3% of the participants, had high levels of these antibodies and a high percentage of this group later developed type 1 diabetes.

To compound the scenario, it's known that premature babies are considered at higher risk for both sepsis and type 1 diabetes. The current standard of care for newborns with sepsis is giving gentamicin, per World Health Organization guidelines.

These infections are common, and the babies need the antibiotic because their own immune systems are not well developed at that juncture, and the drug may be a lifesaving therapy.

It's not uncommon for antibiotics to prompt production of antibodies because the body views them as foreign. In this study, scientists looked at antibodies to glycans, which are found on the surface our cells as well as the cells of microorganisms like bacteria and are known to be a ready target for this immune response.

Gentamicin and other similar antibiotics are a class of compounds called aminoglycosides, which are commonly used to treat serious infections, and are also broadly classified as glycans because of their sugar content.

When the  scientists did "profiling" of all the antibodies, they clustered the glycans two ways. The first was by glycans with similar function and secondly, by antibody levels in patients. They also found an association between the multitasking FUT2 gene and the antibodies against both gentamicin and the islet cells of the pancreas. The  data reveals that they are compounding the risks.

Paul M. H. Tran, Fran Dong, Eileen Kim, Katherine P. Richardson, Lynn K. H. Tran, Kathleen Waugh, Diane Hopkins, Richard D. Cummings, Peng George Wang, Marian J. Rewers, Jin-Xiong She, Sharad Purohit. Use of a glycomics array to establish the anti-carbohydrate antibody repertoire in type 1 diabetes. Nature Communications, 2022; 13 (1) DOI: 10.1038/s41467-022-34341-2

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