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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

Comment by Dr. Krishna Kumari Challa on December 12, 2022 at 10:57am

Researchers reveal how trauma changes the brain

Exposure to trauma can be life-changing—and researchers are learning more about how traumatic events may physically change our brains. But these changes are not happening because of physical injury; rather, the brain appears to rewire itself after these experiences.

Understanding the mechanisms involved in these changes and how the brain learns about an environment and predicts threats and safety is a focus of neuro-scientists. 

Scientists  are learning more about how people exposed to trauma learn to distinguish between what is safe and what is not. Their brain is giving them insight into what might be going awry in specific mechanisms that are impacted by trauma exposure, especially when emotion is involved.

Their research, recently published in Communications Biology, identified changes in the salience network—a mechanism in the brain used for learning and survival—in people exposed to trauma (with and without psychopathologies, including PTSD, depression, and anxiety).

Using fMRI, the researchers recorded activity in the brains of participants as they looked at different-sized circles—only one size was associated with a small shock (or threat). Along with the changes in the salience network, researchers found another difference—this one within the trauma-exposed resilient group. They found the brains of people exposed to trauma without psychopathologies were compensating for changes in their brain processes by engaging the executive control network—one of the dominant networks of the brain.

The possibility of threat can change how someone exposed to trauma reacts. Researchers found this to be the case in people with post-traumatic stress disorder (PTSD). Patients with PTSD can complete the same task as someone without exposure to trauma when no emotion is involved. However, when emotion invoked by a threat was added to a similar task, those with PTSD had more difficulty distinguishing between the differences.

 researchers observed that people with PTSD had less signaling between the hippocampus (an area of the brain responsible for emotion and memory) and the salience network (a mechanism used for learning and survival).

They also detected less signaling between the amygdala (another area linked to emotion) and the default mode network (an area of the brain that activates when someone is not focused on the outside world). These findings reflect the inability of a person with PTSD to effectively distinguish differences between the circles.

Xi Zhu et al, Sequential fear generalization and network connectivity in trauma exposed humans with and without psychopathology, Communications Biology (2022). DOI: 10.1038/s42003-022-04228-5

Comment by Dr. Krishna Kumari Challa on December 11, 2022 at 6:52am

The toughest material on Earth

Scientists have measured the highest toughness ever recorded, of any material, while investigating a metallic alloy made of chromium, cobalt, and nickel (CrCoNi). Not only is the metal extremely ductile—which, in materials science, means highly malleable—and impressively strong (meaning it resists permanent deformation), its strength and ductility improve as it gets colder. This runs counter to most other materials in existence.

Dong Liu et al, Exceptional fracture toughness of CrCoNi-based medium- and high-entropy alloys at 20 kelvin, Science (2022). DOI: 10.1126/science.abp8070

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Did physicists make a wormhole in the lab? Not quite, but a new exp...

Scientists made headlines last week for supposedly generating a wormhole. The research, reported in Nature, involves the use of a quantum computer to simulate a wormhole in a simplified model of physics.

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Forget net-zero: Aim for net-negative to halt global warming, argue...

In the fight against climate change, the lever every policymaker has been focusing on has been the reduction in (net) emissions. Curbing the rate at which greenhouse gases are pumped into the atmosphere clearly remains a priority. Yet every serious scientific analysis—in particular the latest IPCC report—agrees that a substantial amount of CO2 must be removed from the atmosphere via negative-emission technologies if we want to have a reasonable chance of limiting the temperature increase by the end of the century to 1.5 to 2C above pre-industrial levels.

Comment by Dr. Krishna Kumari Challa on December 11, 2022 at 6:49am

Another defining property is the level of gene expression in stem cells, which must have hundreds of genes expressed. To determine if 3a/3b fit this property, they took the progeny with 3a/3b glowing in red and all other cells glowing in green and used a sorting machine that separated the red and green cells. they then applied single-cell sequencing technology to ask, which genes are being expressed in the red cells and in the green cells. That data confirmed that at the molecular level only the progeny of the 3a/3b cells matched stem cells and not the progeny of any other cell.

That was definitive confirmation of the fact that we found the cellular source of the stem cell population in our system. But, importantly, knowing the cellular source of stem cells now gives them a way to capture the cells as they mature and define what genes are involved in making them.

They generated a huge dataset of embryonic development at the single-cell level detailing which genes were being expressed in all of the cells in embryos from the beginning to the end of development. They allowed the converted 3a/3b cells to develop a little bit further, but not all the way to hatchling stage. They then captured these cells using the sorting technology. By doing this they could clearly define which genes were specifically being expressed in the lineage of cells that make the stem cells.

This study reveals a set of genes that could be very important controllers for the formation of stem cells. Homologues of these genes have important roles in human stem cells and this is relevant across species.

The researchers plan to continue digging deeper into the mechanism of how these genes are working in the stem cells of Hofstenia miamia, which will help to tell how nature evolved a way to make and maintain pluripotent stem cells. Knowing the molecular regulators of aPSCs will allow researchers to compare these mechanisms across species, revealing how pluripotent stem cells have evolved across animals.

Mansi Srivastava, Embryonic origins of adult pluripotent stem cells, Cell (2022). DOI: 10.1016/j.cell.2022.11.008. www.cell.com/cell/fulltext/S0092-8674(22)01420-9

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