Toxic Fragments of Bacteria Leaking From The Gut May Drive Weight Gain

Toxic substances leaking out from the gut can interfere with the functioning of fat cells and drive obesity, according to a recent study by a team of international researchers. The results could inform how we treat excessive and dangerous weight gain in the future.

The substances, called endotoxins, are fragments of bacteria in our guts. While they're a normal part of the digestive tract's ecosystem, the microbial debris can cause significant damage to the body should they find their way into the bloodstream.

Here, the researchers wanted to look specifically at the impact of endotoxins on fat cells (adipocytes) in people. They discovered that key processes that usually help control the buildup of fat are affected by the material.

"Gut microbe fragments that enter the bloodstream reduce normal fat cell function and their metabolic activity, which is exacerbated with weight gain, contributing to increased diabetes risk.

It appears that as we gain weight, our fat stores are less able to limit the damage that gut microbe fragments may cause to fat cells.

The study involved 156 participants, 63 of whom were classed as obese, and 26 of whom had undergone bariatric surgery for obesity – a procedure where the size of the stomach is reduced to limit food intake.

Samples from these participants were processed in the lab as the team looked at two different types of fat cell, described as white and brown.

White fat cells, which make up most of our fat storage tissues, stores lipids in larger volumes. Brown fat cells take stores of fat and break them down using their numerous mitochondria, such as when the body is cold and needs warmth. Under the right conditions, the body can convert the lipid-storing white fat cells that behave like lipid-burning brown fat cells.

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The analysis showed that endotoxins reduced the body's ability to turn white fat cells into brown-like fat cells and reduce the amount of stored fat.

Engineers harvest abundant clean energy from thin air, 24/7

A team of engineers  has recently shown that nearly any material can be turned into a device that continuously harvests electricity from humidity in the air. The secret lies in being able to pepper the material with nanopores less than 100 nanometers in diameter. The research appeared in the journal Advanced Materials.

The air contains an enormous amount of electricity. Think of a cloud, which is nothing more than a mass of water droplets. Each of those droplets contains a charge, and when conditions are right, the cloud can produce a lightning bolt—but we don't know how to reliably capture electricity from lightning. What  the engineers have done is to create a human-built, small-scale cloud that produces electricity for us predictably and continuously so that we can harvest it.

The heart of the man-made cloud depends on what the engineers call the "generic Air-gen effect".

It builds on an earlier work completed in 2020 showing that electricity could be continuously harvested from the air using a specialized material made of protein nanowires grown from the bacterium Geobacter sulfurreducens.

The ability to generate electricity from the air turns out to be generic: literally any kind of material can harvest electricity from air, as long as it has a certain property. That property: "It needs to have holes smaller than 100 nanometers (nm), or less than a thousandth of the width of a human hair."

This is because of a parameter known as the "mean free path," the distance a single molecule of a substance, in this case water in the air, travels before it bumps into another single molecule  of the same substance. When water molecules are suspended in the air, their mean free path is about 100 nm.

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The researchers realized that they could design an electricity harvester based around this number. This harvester would be made from a thin layer of material filled with nanopores smaller than 100 nm that would let water molecules pass from the upper to the lower part of the material. But because each pore is so small, the water molecules would easily bump into the pore's edge as they pass through the thin layer. This means that the upper part of the layer would be bombarded with many more charge-carrying water molecules than the lower part, creating a charge imbalance, like that in a cloud, as the upper part increased its charge relative to the lower part. This would effectually create a battery—one that runs as long as there is any humidity in the air.

Xiaomeng Liu et al, Generic Air‐Gen Effect in Nanoporous Materials for Sustainable Energy Harvesting from Air Humidity, Advanced Materials (2023). DOI: 10.1002/adma.202300748. onlinelibrary.wiley.com/doi/10.1002/adma.202300748

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Unique molecular machinery of a woman who can't feel pain

The biology underpinning a rare genetic mutation that allows its carrier to live virtually pain-free, heal more rapidly and experience reduced anxiety and fear, has been uncovered by new research.

The study, published in Brain, follows up the team's discovery in 2019 of the FAAH-OUT gene and the rare mutations that cause a woman, Jo Cameron, to feel virtually no pain and never feel anxious or afraid. The new research describes how the mutation in FAAH-OUT "turns down" FAAH gene expression, as well as the knock-on effects on other molecular pathways linked to wound healing and mood. It is hoped the findings will lead to new drug targets and open up new avenues of research in these areas.

Jo, who lives in Scotland, was first referred to pain geneticists at UCL in 2013, after her doctor noticed that she experienced no pain after major surgeries on her hip and hand. After six years of searching, they identified a new gene that they named FAAH-OUT, which contained a rare genetic mutation. In combination with another, more common mutation in FAAH, it was found to be the cause of Jo's unique characteristics.

The area of the genome containing FAAH-OUT had previously been assumed to be "junk" DNA that had no function, but it was found to mediate the expression of FAAH, a gene that is part of the endocannabinoid system and that is well-known for its involvement in pain, mood and memory.

In this study, the team from UCL sought to understand how FAAH-OUT works at a molecular level, the first step towards being able to take advantage of this unique biology for applications like drug discovery.

The team observed that FAAH-OUT regulates the expression of FAAH. When it is significantly turned down as a result of the mutation carried by Jo Cameron, FAAH enzyme activity levels are significantly reduced.

Hajar Mikaeili et al, Molecular basis of FAAH-OUT-associated human pain insensitivity, Brain (2023). DOI: 10.1093/brain/awad098

Mind-Blowing Dream-To-Video Could Be Coming With Stable Diffusion Video Rebuild From Brain Activity

The most effective ways of foraging can attract predators, scientists find

Animals using the most of efficient methods of searching for resources may well pay with their lives, scientists  have discovered.

The findings, published today in Behavioral Ecology, reveal why animals may not always use a searching strategy that maximizes results.

How animals move through their habitat, particularly in search for food, is a major question in biology, and has application in how animals will respond to environmental change.

Numerous studies have demonstrated that a special kind of movement, known as Lévy motion, increases the ability to find resources because it includes long-distance moves between areas being searched, as well as periods of concentrated searching in one area. It has also been shown that a range of animals use this kind of movement.

This study is the first to demonstrate a potential cost of Lévy motion in an experiment, showing prey using Lévy motion are targeted twice as often as prey using Brownian motion—the movement observed in molecules in a gas, and thus a baseline expectation.

This is because the predators prefer to target prey that are moving with straighter paths of motion, possibly because this makes the future position of the prey more predictable.

This study demonstrates that prey animals might not always use a searching strategy that maximizes finding a resource because there might be costs that were, previous to the study, unknown. This might explain why some studies have found animals use different kinds of searches other than Lévy motion.

This study shows, for the first time, that animals using a common and very effective way of searching for resources may actually pay a cost of being more susceptible to predators.

Christos C Ioannou et al, Virtual prey with Lévy motion are preferentially attacked by predatory fish, Behavioral Ecology (2023). DOI: 10.1093/beheco/arad039

Sudden infant death syndrome may have biologic cause

Sudden infant death syndrome (SIDS) is a case where the death of an apparently healthy infant before their first birthday remains unexplained even after thorough investigation. Death generally seems to occur when infants are sleeping.

Whether causing the common cold or COVID-19, coronaviruses deploy key enzymes to elude human immune response

The entire family of coronaviruses is equipped with multiple methods of evading the human immune system, and two new studies have taken a deep dive into how these viruses, including SARS-CoV-2, leverage highly specialized enzymes that keep human immune forces at bay.

The studies train a bright spotlight on the stealthy strategies that coronaviruses deploy to antagonize and destabilize human cells, steps scripted in their genetic code that ultimately help these viruses evade immune system assault.

Some members of the broad coronavirus family are more adept at these strategies than others. Indeed, one of the constants throughout the COVID pandemic has been the worrying discovery of a growing suite of molecular methods that SARS-CoV-2 uses to elude the human immune system. New research has opened a window into an evasion strategy in which coronaviruses destabilizes human cells and damages leap forward by comparing the evasion capabilities of milder coronaviruses to the trio of coronaviruses known to cause serious, even lethal respiratory infections.

Regardless of whether the coronavirus causes a bout with the common cold or serious infections, such as COVID-19 or MERS, most set the stage for immune evasion by damaging critical human proteins that prompt the immune response. Coronaviruses launch their attack by deploying the same type of protein-cleaving enzyme.

The researchers  zeroed in on the viral enzymes known as papain-like proteases, protein-cleaving enzymes that evolved to help coronaviruses ensure their survival by damaging critical signaling proteins that regulate human cells. Once attacked by these enzymes, human cells become destabilized and lose their capacity to marshal innate immune system responses.

While these enzymes have been elucidated in the trio of dangerous coronaviruses, researchers have identified protein-like proteases—PLPs—in HCoV-229E, HCoV-HKU1, and HCoV-OC43, three coronaviruses that cause the common cold. Their enzymatic properties correlated with their ability to suppress innate immune responses.

The researchers  describe how coronaviruses use their PLPs to damage the protein ubiqutin and a related ubiquitin-like protein called ISG15. Human cells use ubiquitin and ISG15 as cell regulators. By damaging these regulating proteins, the innate immune response is impaired and the viruses are free to proliferate unchecked.

 Yuxian Xiong et al, The substrate selectivity of papain-like proteases from human-infecting coronaviruses correlates with innate immune suppression, Science Signaling (2023). DOI: 10.1126/scisignal.ade1985

Dan Cao et al, The SARS-CoV-2 papain-like protease suppresses type I interferon responses by deubiquitinating STING, Science Signaling (2023). DOI: 10.1126/scisignal.add0082

Termite mounds reveal secret to creating 'living and breathing' bui...

Among the approximately 2,000 known species of termites, some are ecosystem engineers. The mounds built by some genera—for example Amitermes, Macrotermes, Nasutitermes, and Odontotermes—reach up to eight meters high, making them some of the world's largest biological structures. Natural selection has been at work improving the 'design' of their mounds over tens of millions of years. What might human architects and engineers learn if they go to the termites and consider their ways?

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Researchers discover Chinmo, 'the youth gene'

A new study published on eLife has revealed that the Chinmo gene is responsible for establishing the juvenile stage in insects. It also confirms that the Br-C and E93 genes play a regulatory role in insect maturity. These genes, which are also present in humans, act as a promoter and as a suppressor, respectively, of cancerous processes.

The results of the research, which was carried out with the fruit fly Drosophila melanogaster and the cockroach Blatella germanica, reveal that these genes have been conserved throughout the evolution of insects. Therefore, it is thought that they could play a key role in the evolution of metamorphosis.

Insects that undergo complete metamorphosis, such as flies, go through the following three stages of development: the embryo, which is formed inside the egg; the larva (juvenile stage), which grows in several phases; and the pupa, which is the stage that encompasses metamorphosis and the formation of the adult organism.

Previous studies had discovered that the Br-C gene determines pupal formation in insects. In 2019, the same IBE team that has led this study described the essential function of E93 to complete metamorphosis in insects and initiate the maturation of the tissues that go on to form the adult. However, the gene responsible for determining the juvenile stage was unknown until now. This study has now identified the Chimno gene as the main precursor of this stage in insects.

By deleting the Chinmo gene in Drosophila specimens, the scientists observed that these insects progressed to the pupal stage without completing the juvenile stage, moving to the adult stage early. These findings thus confirm that Chinmo is essential for juvenile development.

Researchers have discovered that Chinmo promotes tissue growth during the juvenile stage of Drosophila by keeping the cells undifferentiated. Thus, while Chinmo is expressed, cells cannot differentiate as the gene suppresses the action of those genes responsible for forming adult tissues.

Thus, the study concludes that the Chinmo gene has to be inactivated for Drosophila to progress from the juvenile to the pupal stage and to carry out metamorphosis successfully. Likewise, it confirms that the sequential action of the three genes, namely Chinmo, Br-C, and E93, during the larval, pupal, and adult stages, respectively, coordinate the formation of the different organs that form the adult organism.

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Chinmo and Br-C belong to the large family of BTB-ZF transcription factors—proteins involved in cancer and that are also found in humans. Although previous studies had shown that Chinmo is a precursor of cancer, the role of Br-C and E93 in this disease was unknown until now.

Understanding the molecular functioning of cell growth can help to better comprehend cancer processes. Healthy cells grow, differentiate, and mature. In contrast, cancer cells grow uncontrollably, do not differentiate, and fail to mature. So determining the role of Chinmo, Br-C, and E93 may be key to future clinical research.

The study shows that while Chinmo is an oncogenic precursor because it promotes tissue growth and prevents differentiation, C-Br and E93 serve as tumor suppressors by activating tissue maturation.

The complete metamorphosis of insects such as butterflies and flies is an evolutionary innovation that has emerged gradually during the evolution from insects that undergo a much simpler metamorphosis, such as cockroaches. To understand how this gradual process has taken place, the researchers analyzed the function of Chinmo, Br-C, and E93 in cockroaches.

"Analyzing the function of these genes in different species of insects allows us to observe how evolution works. The observation that Chinmo function is conserved in insects as evolutionarily separated as flies and cockroaches gives us clues as to how metamorphoses originated.

The results of the study indicate that the regulatory action of Chinmo and E93 in more basal insects such as the cockroach are sufficient to determine the transition from the juvenile to the adult form.

Sílvia Chafino et al, Antagonistic role of the BTB-zinc finger transcription factors chinmo and broad-complex in the juvenile/pupal transition and in growth control, eLife (2023). DOI: 10.7554/eLife.84648

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Microorganisms are key to storing carbon in soils, shows new study

According to a study recently published in Nature, microorganisms play a key role in soil carbon storage. The study, conducted by an international team of scientists  reveals that microbial carbon use efficiency is at least four times more influential than other biological or environmental factors when it comes to global soil carbon storage and distribution. The study's result has implications for improving soil health and mitigating climate change.

Soils serve as crucial carbon sinks in the battle against climate change, storing more carbon than any other terrestrial ecosystem and three times more than the atmosphere. However, the processes involved in soil carbon storage have not been well understood. While microorganisms have long been recognized as important contributors to the accumulation and loss of soil organic carbon (SOC), the specific contributions of different biological and environmental processes have remained largely unknown.

The study, titled "Microbial Carbon Use Efficiency Promotes Global Soil Carbon Storage," and published on May 24 in Nature, employed a novel approach to quantifying the processes that determine soil carbon dynamics. The international research team comprehensively explored the relationship between carbon use efficiency, SOC preservation, and various factors such as climate, vegetation, and soil properties. The study represents the first successful integration of global-scale datasets, a microbial-process explicit model, data assimilation, deep learning, and meta-analysis to examine this relationship.

Microbial carbon use efficiency (CUE) measures the proportion of carbon used by microbes for growth versus metabolism. When carbon is used for microbial growth, it becomes incorporated into microbial cells, which supports its storage in the soil. Conversely, when carbon is used for metabolism, it is released into the air as carbon dioxide,  acting as a greenhouse gas. The study emphasizes that microbial growth is more crucial than metabolism in determining the amount of carbon stored in the soil.

Feng Tao et al, Microbial carbon use efficiency promotes global soil carbon storage, Nature (2023). DOI: 10.1038/s41586-023-06042-3

Connection between immune system and brain in mice may explain why stress can worsen gut inflammation

A team of medical researchers affiliated with multiple institutions has found a connection between the immune system and the brain in mice that could explain why psychological stress can lead to worsening gut inflammation problems in people with gut ailments. In their study, reported in the journal Cell, the group tested stressed lab mice.

Prior research has shown that people with colitis or Crohn's disease, the two main types of inflammatory bowel disease (IBD), tend to experience flareups under stressors such as job loss or divorce. In this new effort, the research team sought to find the biological processes involved when such events occur. To that end, they conducted tests with lab mice.

To induce stress conditions, the mice were confined inside small tubes. They then were given chemical irritants to bring on IBD-like symptoms. Then, the mice were given drugs to block the production of inflammation-inducing glucocorticoids, which the brains of mice and humans produce during times of stress. Following that, the team conducted colonoscopies to rate intestinal damage.

They found that the mice with blocked glucocorticoid production had less damage to their intestines, suggesting that stress played a role in inflammation damage in the intestines. The research team then collected tissue samples from the colons of the mice to study their genetic makeup. They found that the mice with higher levels of glucocorticoids also had differences in glia nerve cells—such cells, the team notes perform maintenance and communication functions and tend to respond to stress hormones.

Further study of the mice cells showed that higher stress levels resulted in preventing the maturing of some nerve cells. The researchers note that this is relevant because prior research has shown that mature nerve cells are needed to drive movement of fecal material in the bowels. The research team then compared what they found in the test mice with tissue samples collected from 63 people with IBD and found similar results.

They also asked the IBD patients to fill out a questionnaire and found that those patients who experienced more stressful events, reported stronger symptoms and had more intestinal damage.

Kai Markus Schneider et al, The enteric nervous system relays psychological stress to intestinal inflammation, Cell (2023). DOI: 10.1016/j.cell.2023.05.001

Low-flavanol diet drives age-related memory loss, study finds

A large-scale study by researchers  is the first to establish that a diet low in flavanols—nutrients found in certain fruits and vegetables—drives age-related memory loss.

The study found that flavanol intake among older adults tracks with scores on tests designed to detect memory loss due to normal aging and that replenishing these bioactive dietary components in mildly flavanol-deficient adults over age 60 improves performance on these tests.

The improvement among study participants with low-flavanol diets was substantial and raises the possibility of using flavanol-rich diets or supplements to improve cognitive function in older adults.

The finding also supports the emerging idea that the aging brain requires specific nutrients for optimal health, just as the developing brain requires specific nutrients for proper development.

The current study builds on over 15 years of research  linking age-related memory loss to changes in the dentate gyrus, a specific area within the brain's hippocampus—a region that is vital for learning new memories - and showing that flavanols improved function in this brain region.

Additional research, in mice, found that flavanols—particularly a bioactive substance in flavanols called epicatechin—improved memory by enhancing the growth of neurons and blood vessels and in the hippocampus.

The research  team tested flavanol supplements in people. One small study confirmed that the dentate gyrus is linked to cognitive aging. A second, larger trial showed that flavanols improved memory by acting selectively on this brain region and had the most impact on those starting out with a poor-quality diet.

 Brickman, Adam M. et al, Dietary flavanols restore hippocampal-dependent memory in older adults with lower diet quality and lower habitual flavanol consumption, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2216932120

Glowing Tumor Surgery 

Humans evolved to walk with an extra spring in our step, shows foot arch study

A new study has shown that humans may have evolved a spring-like arch to help us walk on two feet. Researchers studying the evolution of bipedal walking have long assumed that the raised arch of the foot helps us walk by acting as a lever which propels the body forward.

But a global team of scientists have now found that the recoil of the flexible arch repositions the ankle upright for more effective walking. The spring-like arch recoils to help the ankle lift the body. The effects in running are greater, which suggests that the ability to run efficiently could have been a selective pressure for a flexible arch that made walking more efficient too. This discovery could even help doctors improve treatments for present-day patients' foot problems.

The evolution of our feet, including the raised medial arch which sets us apart from great apes, is crucial to bipedal walking.

Michael Rainbow et al, Mobility of the human foot's medial arch enables upright bipedal locomotion, Frontiers in Bioengineering and Biotechnology (2023). DOI: 10.3389/fbioe.2023.1155439

Small fusion experiment hits temperatures hotter than the sun's core

To produce commercial energy, future fusion power plants will need to achieve temperatures of 100 million degrees C. To do so requires careful control of the plasma. In a study published in the journal Nuclear Fusion, researchers refined operating conditions to achieve the necessary temperatures in a compact spherical tokamak device called ST40.

This device is unique; it is much smaller and has a more spherical plasma than other fusion devices. To achieve these results, the researchers used an approach similar to past "supershots" that produced more than 10 million watts of fusion power in the TFTR tokamak in the 1990s.

This effort demonstrated fusion-relevant ion temperatures in a compact, high magnetic field, spherical tokamak for the first time. This confirms that the spherical tokamak can achieve one of the conditions necessary for commercial fusion energy production. These results also show that similar fusion pilot plants may lead to more compact, and potentially more economical, fusion power sources than other configurations.

In the research, ST40 plasmas operated at toroidal magnetic field values of just over 2 Tesla and were heated by 1.8 million watts of high energy neutral particles. While the ST40 plasma discharges lasted for only 150 milliseconds, the plasma showed ion temperatures of more than 100 million degrees Celsius.

S.A.M. McNamara et al, Achievement of ion temperatures in excess of 100 million degrees Kelvin in the compact high-field spherical tokamak ST40, Nuclear Fusion (2023). DOI: 10.1088/1741-4326/acbec8

New high resolution X-ray imaging technique can image biological specimens without causing damage

A pollen grain showing the nanofoam within or a diatom with the individual geometric structures inside clearly visible: Using high-energy X-rays from the PETRA III synchrotron light source at DESY, a team of scientists has managed to image these structures without damaging them.

Their new technique generates high resolution X-ray images of dried biological material that has not been frozen, coated, or otherwise altered beforehand—all with little to no damage to the sample. This method, which is also used for airport baggage scanning, can generate images of the material at nanometre resolution.

Using high energy X-rays that are intensely focused through a set of novel diffractive lenses, the special technique allows imaging to be performed at less than 1% of the X-ray damage threshold of the specimen. The results, which reveal this method as a promising tool for brighter next-generation light sources such as the planned upgrade project PETRA IV, have been published in the journal Light: Science & Applications.

X-ray light interacts with biological material in a variety of ways, mostly depending on the energy and intensity of the light. At the same time, radiation damage, such as small structural changes up to complete degradation of the sample, is the limiting factor during X-ray imaging of biological samples.

At low energies, the X-rays are primarily absorbed by the atoms in the sample, whose electrons take on the energy, causing them to spring out of the atoms and cause damage to the sample. Images using these low-energy X-rays thus map out the sample's absorption of the radiation. At higher energies, absorption is less likely, and a process called elastic scattering occurs, where the X-ray photons "bounce" off of the matter like billiard balls without depositing their energy.

Techniques such as crystallography or ptychography use this interaction. Nevertheless, absorption can still occur, meaning damage to the sample happens anyway. But there is a third interaction: Compton scattering, where the X-rays leave only a tiny amount of their energy in the target material. Compton scattering had been largely ignored as a viable method of X-ray microscopy, since it requires even higher X-ray energies where until now no suitable high-resolution lenses existed.

Tang Li et al, Dose-efficient scanning Compton X-ray microscopy, Light: Science & Applications (2023). DOI: 10.1038/s41377-023-01176-5

How the humble neutron can help solve some of the universe's deepest mysteries

Scientists are unleashing the power of neutrons to improve understanding of everyday materials and tackle fundamental questions in physics.

 The humble neutron, found in the nucleus of every atom but hydrogen, can—if manipulated in just the right way—shed light on everything from the climate crisis and energy, to health and quantum computing.

One such way is a rather spectacular process known as spallation, high energy particles destabilize an atom's nucleus, which in turn releases some of the neutrons found there.

When harnessed, these newly freed neutrons can be used like X-rays to map the inner structure of materials.

Currently under construction in Lund, Sweden, the European Spallation Source (ESS) is expected to come online in 2027. Once it achieves its full specifications, its unprecedented flux and spectral range is set to make it the most powerful and versatile neutron source for science in the world.

The purpose of the facility "is to create neutrons, a neutron beam, to be used for scientific purposes."

Once the facility is up and running, scientists from across Europe and the rest of the world will be able to use its 15 different beamlines to conduct fundamental research. 

a neutron beam "is not the same as an X-ray, but it is complementary and uses some of the same physical laws."

Like X-rays, neutrons can be used to probe materials and biological systems. But they interact with materials in different ways to the photons in high-energy X-ray beams, and therefore provide different types of information about their targets.

For example, neutron beams can say something about the interior dynamics of lithium-ion batteries, reveal obscured details from ancient artifacts or clarify the mechanisms of antibiotic resistance in bacteria. They can also be used to explore fundamental physics. It almost seems like a case of "what can't they do?"

https://cordis.europa.eu/project/id/823867

https://cordis.europa.eu/project/id/951782

https://research-and-innovation.ec.europa.eu/funding/funding-opport...

https://phys.org/news/2023-05-humble-neutron-universe-deepest-myste...

The olfactory responses of patients in a coma or vegetative state can display different signs of consciousness

Severe brain injuries or head traumas in humans can lead to various stages of so-called disorders of consciousness (DoC). These are states in which consciousness is either partly or entirely absent, such as a coma; unresponsive wakefulness syndrome, also known as a vegetative state; and minimally conscious state.

Accurately evaluating patients who have lost consciousness is of crucial importance, as it allows doctors to determine what treatments to administer and how to facilitate the re-emergence of consciousness. Typically, to clinically evaluate consciousness, doctors observe the behavior of patients in response to sensory stimuli, such as sounds or images.

For instance, while patients in a vegetative state are awake but continue to be unresponsive to external stimuli, patients with MCS exhibit some behaviors that indicate that they are conscious. So far, most methods to assess the consciousness level of patients rely on sounds or visual stimuli, yet olfactory stimuli could potentially prove useful too.

Researchers recently carried out a study investigating the responses of patients in a coma or vegetative state to smells, to understand whether they could be used to evaluate consciousness. Their findings, published in Frontiers in Neuroscience, appear to highlight the potential of olfactory stimuli for assessing consciousness in clinical settings.

This study aimed to explore whether olfactory response can be a sign of consciousness and represent higher cognitive processing in patients with disorders of consciousness (DoC) using clinical and electroencephalogram data.

As part of their study, the researchers evaluated the responses of 28 patients at different stages of DoC to olfactory stimuli. Out of these patients, 13 were in a vegetative state (UMS) and 15 in MCS. The study participants were divided into two groups based on whether they responded to olfactory stimuli or not. After three months, the outcomes of DoC patients were followed up using the coma recovery scale-revised (CRS-R)" [i.e., a standard assessment used to measure DoC in clinical settings].
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When researchers analyzed the data they collected, they found that there was a relationship between the patients' olfactory responses and their levels of consciousness. They also found that patients in the no-olfactory responses group showed higher theta functional connectivity than patients in the olfactory response group after they were presented with the vanillin scent, and lower alpha and beta relative powers than healthy participants with no DoC.

The follow-up data collected three months later showed that 10 out of 16 of the patients who responded to olfactory stimuli during the study had recovered consciousness, while only 2 out of the 12 participants who did not respond to olfactory stimuli did. This suggests that a brain response to olfactory stimuli is typically a sign that patients with DoC are gradually recovering and regaining consciousness.
Olfactory responses should be considered signs of consciousness," teh researchers explained in their paper. "The differences in olfactory processing between DoC patients with and without olfactory responses may be a way to explore the neural correlates of olfactory consciousness in these patients. The olfactory response may help in the assessment of consciousness and may contribute to therapeutic orientation."

Wanchun Wu et al, Olfactory response is a potential sign of consciousness: electroencephalogram findings, Frontiers in Neuroscience (2023). DOI: 10.3389/fnins.2023.1187471.

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Sleep deprivation is a risk factor for Alzheimer's, say scientists

Scientists have long explored the link between disturbances in sleep patterns and neurodegenerative diseases. Powerful evidence has emerged in recent years linking disrupted sleep to Parkinson's, and a massive body of research has explored the serious sleep disturbances associated with chronic traumatic encephalopathy—CTE—a condition linked with repeated head injuries, such as the trauma sustained in boxing, football and other aggressive sports.

Scientists' report world's first X-ray of a single atom

A team of scientists has taken the world's first X-ray SIGNAL (or SIGNATURE) of just one atom. This groundbreaking achievement could revolutionize the way scientists detect the materials.

An important usage of X-rays in science is to identify the type of materials in a sample. Over the years, the quantity of materials in a sample required for X-ray detection has been greatly reduced thanks to the development of synchrotron X-rays sources and new instruments. To date, the smallest amount one can X-ray a sample is in attogram, that is about 10,000 atoms or more. This is due to the X-ray signal produced by an atom being extremely weak so that the conventional X-ray detectors cannot be used to detect it. It is a long-standing dream of scientists to X-ray just one atom, which is now being realized by the research team .

Atoms can be routinely imaged with scanning probe microscopes, but without X-rays one cannot tell what they are made of. Scientists can now detect exactly the type of a particular atom, one atom-at-a-time, and can simultaneously measure its chemical state.

Once they are able to do that, they can trace the materials down to ultimate limit of just one atom. This will have a great impact on environmental and medical sciences and maybe even find a cure that can have a huge impact for humankind. This discovery will transform the world.

Saw-Wai Hla, Characterization of just one atom using synchrotron X-rays, Nature (2023). DOI: 10.1038/s41586-023-06011-w. www.nature.com/articles/s41586-023-06011-w

Biological cleanup discovered for certain 'forever chemicals'

Chemical and environmental engineering scientists have identified two species of bacteria found in soil that break down a class of stubborn "forever chemicals," giving hope for low-cost biological cleanup of industrial pollutants.

These bacteria destroy a subgroup of per- and poly-fluoroalkyl substances, or PFAS, that have one or more chlorine atoms within their chemical structure.

Unhealthful forever chemicals persist in the environment for decades or much longer because of their unusually strong carbon-to-fluorine bonds. Remarkably, the researchers found that the bacteria cleave the pollutant's chlorine-carbon bonds, which starts a chain of reactions that destroy the forever chemical structures, rendering them harmless.

What they discovered is that bacteria can do carbon-chlorine bond cleavage first, generating unstable intermediates. And then those unstable intermediates undergo spontaneous defluorination, which is the cleavage of the carbon-fluorine bond.

Bosen Jin et al, Substantial defluorination of polychlorofluorocarboxylic acids triggered by anaerobic microbial hydrolytic dechlorination, Nature Water (2023). DOI: 10.1038/s44221-023-00077-6

Darker skies are disappearing:

From genes to gestation, researchers probe predictive markers for pregnancy complications

A new study has identified genetic markers associated with preeclampsia and gestational hypertension in a large cohort study. In the paper, "Polygenic prediction of preeclampsia and gestational hypertension," published in Nature Medicine, the researchers detail how these genetic markers could be used as a predictive risk assessment and offers mechanistic insights into pregnancy disorders.

Preeclampsia and gestational hypertension are common pregnancy complications associated with adverse outcomes, including substantial morbidity and mortality for both mother and child. Current tools for prediction, prevention and treatment are limited.

The team examined the associations of maternal DNA variants in 20,064 preeclampsia cases compared to 703,117 control individuals and gestational hypertension in 11,027 cases compared with 412,788 controls. Polygenic risk scores were tuned to a UK Biobank and then tested against other data sets for validation.

The analysis identified 18 independent loci associated with preeclampsia and gestational hypertension, 12 of which were previously unknown, and an additional two genes were implicated in a follow-up meta-analysis. The genes associated highlight potential roles of natriuretic peptide signaling, angiogenesis, renal glomerular function, trophoblast development and immune dysregulation.

Interestingly, almost none of the associated genes reside on the same chromosome, making them less likely to be inherited together.

Low-dose aspirin starting after week 12 gestation is an evidence-based but underused strategy to reduce risk of preeclampsia. To probe the potential clinical impact of incorporating PRS to guide aspirin allocation, researchers examined aspirin eligibility according to current US Preventive Service Task Force major criteria. Those with polygenic risk scores in the top 10% were shown to increase identification as low-dose aspirin-eligible by 30.4%, offering a potential preemptive intervention.

Part 1

The lead risk variant at the MTHFR–CLCN6 locus has been previously associated with reduced levels of circulating N-terminal pro-BNP43. A recent analysis found that first-trimester levels of N-terminal pro-BNP were unexpectedly lower among female individuals who subsequently developed hypertensive disorders of pregnancy later in pregnancy. These findings suggest that genetic network-driven deficiency in endogenous natriuretic peptide signaling may predispose individuals to hypertensive disorders of pregnancy.

Synthetic natriuretic peptides have been developed, and the authors suggest that natriuretic peptides may represent a future therapeutic target for direct or indirect modulation toward hypertensive disorders of pregnancy prevention and treatment.

Study examines how DNA damage is repaired by antioxidant enzymes

A typical human cell is metabolically active, roaring with chemical reactions that convert nutrients into energy and useful products that sustain life. These reactions also create reactive oxygen species, dangerous by-products like hydrogen peroxide which damage the building blocks of DNA in the same way oxygen and water corrode metal and form rust. Similar to how buildings collapse from the cumulative effect of rust, reactive oxygen species threaten a genome's integrity.

Cells are thought to delicately balance their energy needs and avoid damaging DNA by containing metabolic activity outside the nucleus and within the cytoplasm and mitochondria. Antioxidant enzymes are deployed to mop up reactive oxygen species at their source before they reach DNA, a defensive strategy that protects the roughly 3 billion nucleotides from suffering potentially catastrophic mutations. If DNA damage occurs anyway, cells pause momentarily and carry out repairs, synthesizing new building blocks and filling in the gaps.

Despite the central role of cellular metabolism in maintaining genome integrity, there has been no systematic, unbiased study on how metabolic perturbations affect the DNA damage and repair process. This is particularly important for diseases like cancer, characterized by their ability to hijack metabolic processes for unfettered growth.

A research team has now addressed this challenge by carrying out various experiments to identify which metabolic enzymes and processes are essential for a cell's DNA damage response. The findings are published today in the journal Molecular Systems Biology.

Part 1

The researchers experimentally induced DNA damage in human cell lines using a common chemotherapy medication known as etoposide. Etoposide works by breaking DNA strands and blocking an enzyme that helps repair the damage. Surprisingly, inducing DNA damage resulted in reactive oxygen species being generated and accumulating inside the nucleus. The researchers observed that cellular respiratory enzymes, a major source of reactive oxygen species, relocated from the mitochondria to the nucleus in response to DNA damage.

The findings represent a paradigm shift in cellular biology because it suggests the nucleus is metabolically active. Where there's smoke there's fire, and where there's reactive oxygen species there are metabolic enzymes at work. Historically, scientists have thought of the nucleus as a metabolically inert organelle that imports all its needs from the cytoplasm, but this study demonstrates that another type of metabolism exists in cells and is found in the nucleus.

The researchers also used CRISPR-Cas9 to identify all the metabolic genes that were important for cell survival in this scenario. These experiments revealed that cells order the enzyme PRDX1, an antioxidant enzyme also normally found in mitochondria, to travel to the nucleus and scavenge reactive oxygen species present to prevent further damage. PRDX1 was also found to repair the damage by regulating the cellular availability of aspartate, a raw material that is critical for synthesizing nucleotides, the building blocks of DNA.

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The findings can guide future lines of cancer research. Some anti-cancer drugs, such as the etoposide used in this study, kill tumor cells by damaging their DNA and inhibiting the repair process. If enough damage accumulates, the cancer cell initiates a process where it autodestructs.

During their experiments, the researchers found that knocking out metabolic genes critical for cellular respiration—the process that generates energy from oxygen and nutrients—made normal healthy cells become resistant to etoposide. The finding is important because many cancer cells are glycolytic, meaning that even in the presence of oxygen they generate energy without doing cellular respiration. This means etoposide, and other chemotherapies with a similar mechanism, is likely to have a limited effect in treating glycolytic tumors.

The authors of the study call for the exploration of new strategies such as dual treatment combining etoposide with drugs that also boost the generation of reactive oxygen species to overcome drug resistance and kill cancer cells faster. They also hypothesize that combining etoposide with inhibitors of nucleotide synthesis processes could potentiate the effect of the drug by preventing the repair of DNA damage and ensuring cancer cells self-destruct correctly.

"A metabolic map of the DNA damage response identifies PRDX1 in the control of nuclear ROS scavenging and aspartate availability", Molecular Systems Biology (2023). DOI: 10.15252/msb.202211267

Part 2

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Brain’s wrinkles help to drive how it works

Our brains’ walnut-like wrinkles have a large effect on brain activity, in much the same way that the shape of a bell determines how it sounds. The discovery challenges the paradigm that brain function emerges from the intricate web of connections between specialized brain-cell populations, called the connectome. Researchers used mathematical models that predict how waves travel across surfaces, and found that the shape of the brain’s outer surface was a better predictor of brainwave data than was the model of the connectome.

We are exceeding most of Earth’s limits

In 2009, a seminal paper in Nature showed that humanity had crossed three of nine ‘Earth-system boundaries’: the limits of what the planet can support before human activities make it uninhabitable. Now, there’s a reboot of the extraordinarily influential concept that takes into account how changes to climate, ecosystems and other factors disproportionately affect vulnerable communities. We have crossed seven of the eight safe and just boundaries. Only air pollution was inside dangerous limits globally, despite it causing an estimated 4.2 million deaths annually. If our planet got a check-up, “our doctor would say that the Earth is really quite sick right now, and it is sick in terms of many different areas or systems, and this sickness is also affecting the people living on Earth”, says climate-policy researcher and co-author Joyeeta Gupta.

https://apnews.com/article/earth-environment-climate-change-nature-...

DNA: a novel, green, natural flame retardant and suppressant for cotton

DNA could be considered an intrinsically intumescent flame retardant as it contains the three main components that are usually present in an intumescent formulation, namely: the phosphate groups, able to produce phosphoric acid, the deoxyribose units acting as a carbon source and blowing agents (upon heating a (poly)saccharide dehydrates forming char and releasing water) and the nitrogen-containing bases (guanine, adenine, thymine, and cytosine) that may release ammonia. The flammability tests in horizontal configuration have clearly shown that after two applications of a methane flame for 3 s, the DNA-treated cotton fabrics do not burn at all. Furthermore, when exposed to an irradiative heat flux of 35 kW m⁻², no ignition has been observed. Finally, an LOI value of 28% has been achieved for the treated fabrics as opposed to 18% of the untreated fabric.

https://pubs.rsc.org/en/content/articlelanding/2013/ta/c3ta00107e#:...(upon%20heating%20a

Researchers find DNA can work as a flame retardant 

https://phys.org/news/2013-03-dna-flame-retardant-video.html

Scientists reveal new details of cellular process that prevents spread of cancer

Researchers have for the first time characterized a unique molecular mechanism of the early stages of programmed cell death or apoptosis, a process which plays a crucial role in prevention of cancer.

 It is the most recent in a series of research collaborations by this team, investigating the cellular proteins responsible for apoptosis.

Apoptosis is essential for human life, and its disruption can cause cancerous cells to grow and not respond to cancer treatment. In healthy cells, it is regulated by two proteins with opposing roles known as Bax and Bcl-2.

The soluble Bax protein is responsible for the clearance of old or diseased cells, and when activated, it perforates the cell mitochondrial membrane to form pores that trigger programmed cell death. This can be offset by Bcl-2, which is embedded within the mitochondrial membrane, where it acts to prevent untimely cell death by capturing and sequestering Bax proteins.

In cancerous cells, the survival protein Bcl-2 is overproduced, leading to uninhibited cell proliferation.

Using neutron reflectometry on SURF and OFFSPEC, they were able to study in real time the way that the protein interacts with lipids present in the mitochondrial membrane, during the initial stages of apoptosis. By employing deuterium-isotope labeling, they determined for the first time that when Bax creates pores, it extracts lipids from the mitochondrial membrane to form lipid-Bax clusters on the mitochondrial surface.

By using time-resolved neutron reflectometry in combination with surface infrared spectroscopy in the ISIS biolab, they were able to see that this pore creation occurred in two stages. Initial fast adsorption of Bax onto the mitochondrial membrane surface was followed by a slower formation of membrane-destroying pores and Bax-lipid clusters, which occurred simultaneously. This slower perforation process occurred on timescales of several hours, comparable to cell death in vivo.

This is the first time that scientists have found direct evidence of the involvement of mitochondrial lipids during membrane perturbing in cell death initiated by Bax proteins.

This mechanism by which Bax initiates cell death is previously unseen. Once we know more about the interplay between Bax and Bcl-2 and how it relates to this mechanism, we'll have a more complete picture of a process that is fundamental to human life.

Luke Clifton et al, Creation of distinctive Bax-lipid complexes at mitochondrial membrane surfaces drives pore formation to initiate apoptosis, Science Advances (2023). DOI: 10.1126/sciadv.adg7940. www.science.org/doi/10.1126/sciadv.adg7940

Reducing noise by ionizing air

Scientists show that a thin layer of plasma, created by ionizing air, could be promising as an active sound absorber, with applications in noise control and room acoustics.

Did you know that wires can be used to ionize air to make a loudspeaker? Simply put, it’s possible to generate sound by creating an electric field in a set of parallel wires, aka a plasma transducer, strong enough to ionize the air particles. The charged ions are then accelerated along the magnetic field lines, pushing the residual non-ionized air in a way to produce sound.

If a loudspeaker can generate sound, it can also absorb it.

While this plasma loudspeaker concept is not new,  scientists went ahead and built a demonstration of the plasma transducer, with the aim to study noise reduction. They came up with a new concept, what they call the active “plasmacoustic metalayer” that can be controlled to cancel out noise. Their results are published in Nature Communications.

Not only is the plasma efficient at high frequencies, but it is also versatile since it can be tuned to work at low frequencies as well. Indeed, the scientists show that the dynamics of thin layers of air plasma can be controlled to interact with sound over deep-subwavelength distances, to actively respond to noise and cancel it out over a broad bandwidth. The fact that their device is active is key, since passive noise reduction technologies are limited in the band of frequencies that can be controlled.

The plasma absorber is also more compact that most conventional solutions. Exploiting the unique physics of plasmacoustic metalayers, the scientists experimentally demonstrate perfect sound absorption: 100% of the incoming sound intensity is absorbed by the metalayer and nothing is reflected back.

Stanislav Sergeev, Romain Fleury, Hervé Lissek. Ultrabroadband sound control with deep-subwavelength plasmacoustic metalayers. Nature Communications, 2023; 14 (1) DOI: 10.1038/s41467-023-38522-5

First experimental confirmation that some microbes are powered by electricity

 In microbial electrosynthesis, microorganisms use CO2 and electricity to produce alcohol, for example. How this process works biologically, however, has only been speculated about, until now. Researchers have now been able to confirm experimentally for the first time that the bacteria use electrons from hydrogen and can produce more chemical substances than previously known. Their research has been published in the journal Green Chemistry.

Microbial electrosynthesis is a promising technology against the backdrop of climate change and the energy transition: it can bind carbon dioxide, produce ethanol and other organic compounds that can be used as fuel, and thus store excess electricity. Nevertheless, the technology, which has been known for more than a decade, has so far failed to achieve any significant breakthrough towards commercialization

 The researchers were able to show that bacteria do not directly absorb the electrons supplied by electric current, but instead use hydrogen to transfer the electrons. This had long been suspected as a possibility, but until now no one had provided experimental proof. They also found that the method could produce even more useful chemicals than previously thought and optimized the process for the highest possible yields.

In this way, the research team was able to optimize voltage and bacterial concentration for the highest possible acetate yields.

Santiago T. Boto et al, Microbial electrosynthesis with Clostridium ljungdahlii benefits from hydrogen electron mediation and permits a greater variety of products, Green Chemistry (2023). DOI: 10.1039/D3GC00471F

Space solar power demonstrator wirelessly transmits power in space

A space solar power prototype that was launched into orbit in January is operational and has demonstrated its ability to wirelessly transmit power in space and to beam detectable power to Earth for the first time.

MAPLE, short for Microwave Array for Power-transfer Low-orbit Experiment and one of the three key experiments within SSPD-1, consists of an array of flexible lightweight microwave power transmitters driven by custom electronic chips that were built using low-cost silicon technologies. It uses the array of transmitters to beam the energy to desired locations. For SSPP to be feasible, energy transmission arrays will need to be lightweight to minimize the amount of fuel needed to send them to space, flexible so they can fold up into a package that can be transported in a rocket, and a low-cost technology overall.

Using constructive and destructive interference between individual transmitters, a bank of power transmitters is able to shift the focus and direction of the energy it beams out—without any moving parts. The transmitter array uses precise timing-control elements to dynamically focus the power selectively on the desired location using the coherent addition of electromagnetic waves. This enables the majority of the energy to be transmitted to the desired location and nowhere else.

MAPLE features two separate receiver arrays located about a foot away from the transmitter to receive the energy, convert it to direct current (DC) electricity, and use it to light up a pair of LEDs to demonstrate the full sequence of wireless energy transmission at a distance in space. MAPLE tested this in space by lighting up each LED individually and shifting back and forth between them. The experiment is not sealed, so it is subject to the harsh environment of space, including the wide temperature swings and solar radiation that will be faced one day by large-scale SSPP units.

MAPLE also includes a small window through which the array can beam the energy. This transmitted energy was detected by a receiver on the roof of the Gordon and Betty Moore Laboratory of Engineering on Caltech's campus in Pasadena. The received signal appeared at the expected time and frequency, and had the right frequency shift as predicted based on its travel from orbit.

Space solar power provides a way to tap into the practically unlimited supply of solar energy in outer space, where the energy is constantly available without being subjected to the cycles of day and night, seasons, and cloud cover—potentially yielding eight times more power than solar panels at any location on Earth's surface. When fully realized, SSPP will deploy a constellation of modular spacecraft that collect sunlight, transform it into electricity, then convert it to microwaves that will be transmitted wirelessly over long distances to wherever it is needed—including locations that currently have no access to reliable power.

https://www.spacesolar.caltech.edu/

https://researchnews.cc/news/19753/In-a-first--Caltech-s-space-sola...

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Scientists Hacked Human Cells to Make Insulin, And It Reversed Diabetes in Mice

Chemical found in common sweetener damages DNA

A new study finds a chemical formed when we digest a widely used sweetener is "genotoxic," meaning it breaks up DNA. The chemical is also found in trace amounts in the sweetener itself, and the finding raises questions about how the sweetener may contribute to health problems.

At issue is sucralose, a widely used artificial sweetener sold under the trade name Splenda. Previous work by researchers established that several fat-soluble compounds are produced in the gut after sucralose ingestion. One of these compounds is sucralose-6-acetate.

This new work established that sucralose-6-acetate is genotoxic. Researchers also found that  trace amounts of sucralose-6-acetate can be found in off-the-shelf sucralose, even before it is consumed and metabolized.

To put this in context, the European Food Safety Authority has a threshold of toxicological concern for all genotoxic substances of 0.15 micrograms per person per day. This work suggests that the trace amounts of sucralose-6-acetate in a single, daily sucralose-sweetened drink exceed that threshold. And that's not even accounting for the amount of sucralose-6-acetate produced as metabolites after people consume sucralose.

For the study, researchers conducted a series of in vitro experiments exposing human blood cells to sucralose-6-acetate and monitoring for markers of genotoxicity. They found that sucralose-6-acetate is genotoxic, and that it effectively broke up DNA in cells that were exposed to the chemical.

The researchers also conducted in vitro tests that exposed human gut tissues to sucralose-6-acetate. When they exposed sucralose and sucralose-6-acetate to gut epithelial tissues—the tissue that lines your gut wall—they found that both chemicals caused 'leaky gut.' Basically, they make the wall of the gut more permeable. The chemicals damage the 'tight junctions,' or interfaces, where cells in the gut wall connect to each other.

A leaky gut is problematic, because it means that things that would normally be flushed out of the body in feces are instead leaking out of the gut and being absorbed into the bloodstream. 

The researchers also looked at the genetic activity of the gut cells to see how they responded to the presence of sucralose-6-acetate. They found that gut cells exposed to sucralose-6-acetate had increased activity in genes related to oxidative stress, inflammation and carcinogenicity.

This work raises a host of concerns about the potential health effects associated with sucralose and its metabolites. It's time to revisit the safety and regulatory status of sucralose, because the evidence is mounting that it carries significant risks.

Susan S. Schiffman et al, Toxicological and pharmacokinetic properties of sucralose-6-acetate and its parent sucralose: in vitro screening assays, Journal of Toxicology and Environmental Health, Part B (2023). DOI: 10.1080/10937404.2023.2213903

Genetic variants may affect treatment response to commonly prescribed type 2 diabetes medication

Various medications can be prescribed to lower blood sugar levels in individuals at high risk for developing type 2 diabetes, but it's often unclear which patients will benefit most from which drugs.

How chocolate could counter climate change

At a red-brick factory in the German port city of Hamburg, cocoa bean shells go in one end, and out the other comes an amazing black powder with the potential to counter climate change.

The plant, one of the largest in Europe, takes delivery of the used cocoa shells via a network of gray pipes from a neighboring chocolate factory.

The substance, dubbed biochar, is produced by heating the cocoa husks in an oxygen-free room to 600 degrees Celsius (1,112 Fahrenheit). The process locks in greenhouse gases and the final product can be used as a fertilizer, or as an ingredient in the production of "green" concrete.

While the biochar industry is still in its infancy, the technology offers a novel way to remove carbon from the Earth's atmosphere, experts say.

The biochar traps the CO₂ contained in the husks—in a process that could be used for any other plant.

If the cocoa shells were disposed of as normal, the carbon inside the unused byproduct would be released into the atmosphere as it decomposed.

Instead, the carbon is sequestered in the biochar "for centuries". One metric ton of biochar—or bio coal—can stock "the equivalent of 2.5 to three tons of CO₂".

Biochar was already used by indigenous populations in the Americas as a fertilizer before being rediscovered in the 20th century by scientists researching extremely fecund soils in the Amazon basin.

The surprising substance's sponge-like structure boosts crops by increasing the absorption of water and nutrients by the soil.

The production process, called pyrolysis, also produces a certain volume of biogas, which is resold .

https://phys.org/news/2023-06-chocolate-counter-climate.html?utm_so...

Source: AFP

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Breakthrough treatments for accelerated wound healing

Patients who undergo skin injuries endure hospital stays, infection and/or succumb to death; therefore, advances in wound healing aim to improve clinical practices underlying macroscale healing to effectively intervene in microscale pathophysiology. As a result, strategies that optimize wound healing have motivated the design of new therapeutic products.

In a new report in Science Advances, researchers summarized advances in the development of new drugs, biomaterial therapies and biological products suited for wound healing. They classified the products as marketed therapies and agents for clinical trials to explore their successful and accelerated translation for wound healing.

The dynamics of chronic wound healing mechanisms The timeframe of wound healing can vary and affect the process of patient recovery. Most wounds are classified as acute or chronic situations according to their clinical presentations. Untreated wounds can undergo cell death and necrosis, and represent ischemia relative to inadequate circulation due to microvascular damage and vasoconstriction. The nutritional status, fibroblast cell and progenitor health, as well as infectious bioburden, can contribute to disease progression.

Normal healing is associated with a series of events, including inflammation, remodeling and repair. Wounds that do not proceed through normal phases remain in a dysregulated inflammatory state with several delineating nuances.

For example, pressure ulcers result from an increasing depth of tissue necrosis and pain from microvascular injury causing ulceration and skin degradation to reach underlying fat or deeper structures. The resulting wounds require specialty care. Bioengineers and materials scientists in medical research have formed extensive libraries of wound care technologies to facilitate progressive healing.

Researchers observed the economic challenges of wound care on health care systems that showed an increasing risk in patients with age and obesity alongside those who presented with high-risk comorbidities. Surgical wounds are the largest wound subset, accounting for careful surgical techniques and optimal suture materials in hospitals. Existing standards for interventional healing rely on the preparation of a viable wound bed for assisted healing to remove foreign materials and ischemic tissue. More complex wounds require secondary healing or a bridge for closure. Pressure injuries represent a more serious problem in bedridden patients.

Part 1

The researchers listed the principles of open wound management as follows:

Moisture balance
Infection prevention
Medical optimization of comorbidities including vascular disease and blood glucose control
They discussed the possibilities of minimizing inflammation, and progression towards active proliferation as a healing response. Several methods in the market aim to detect elevated protease activity for impaired wounds, and apply topical oxygen therapy and ultrasound therapy.
The study outcomes highlighted the need for additional strategies, including healing the chronic wounds at complex and intricate levels. Most advances in intervention target coordinated cellular processes to optimize wound care, however, such methods remain incompletely understood, requiring ongoing research innovations. Researchers described the primary aim of existing commercially available interventional biomaterials to impart fluid exudation, moisture balance, and pressure relief to prevent infection.

The advanced biomaterials in development for interventional healing can mimic extracellular matrix-inspired biophysical cues to regulate immune responses to treat and resolve inflammation. Such advances can be delivered to treat patients at the cellular level, where hydrogel influenced delivery systems can allow the sustained release of stimuli-responsive drug molecules to assist patients in adhering to new therapies. The outcomes can facilitate clinical trials of new drugs and biological products to therapeutically interfere in acute and chronic wounds.
Acute wounds arising from surgical and traumatic events can be treated with bandages to inhibit bleeding and effectively promote healing. Researchers have recently combined adhesive hydrogels with surgical meshes to demonstrate their strong adhesion and flexibility under mechanical stress. The present study described existing advanced wound therapies in the clinical pipeline for wound management, anti-infection and biological intervention. These include advanced anti-scarring and healing-promoting therapies. For example, a cell-penetrating asymmetric interfering RNA delivered as an intradermal injection can target connective tissue growth factor to combat scarring.

New peptide formulas engineered to treat venous leg ulcers and diabetic foot ulcers are currently in phase 1 and 2 clinical trials. Next-generation therapies to treat burns are also in clinical trials. For instance, commercially available NexoBrid is a topical agent made of enzymes isolated from a pineapple plant containing a few proteinases to provide selective and quick removal of damaged/dead tissues within hours of application. Phase 3 clinical trial outcomes have shown the impact of the topical agent on healing tissue areas of interest without adverse serious effects. Several cell-based therapies are also similarly under study for adequate intervention.
Part 2

In this way, the researchers in the present analysis summarized multiple methods of interventional wound care and detailed their mechanisms-of-action in preclinical and clinical environments to treat acute and chronic wounds. These methods focus on highly diverse phases of wound healing, including tight closure of the wound to establish homeostasis and modulate the immune system during inflammation, and cell proliferation alongside remodeling in the area of intervention. The bioengineers and materials scientists hope that future wound dressings may sense the unique environment of an inflicted region to deliver personalized strategies to autonomously regulate drug doses for every patient.

As a strategic plan-of-work for bioengineers, the researchers suggest developing an evidence-based target profile and patenting strategy to effectively translate new wound care products from the bench to the bedside in health care. The industrial translation of standard care requires strong clinical data for emerging methods to survive beyond the bench and positively influence the quality of life of patients.

 Benjamin R. Freedman et al, Breakthrough treatments for accelerated wound healing, Science Advances (2023). DOI: 10.1126/sciadv.ade7007

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Part 3

Ants inflict pain with neurotoxins

Researchers have shown for the first time that some of the world's most painful ant stings target nerves, like snake and scorpion venom. This research is published in Nature Communications.

Investigators discovered the ant neurotoxins while studying the Australian green ant and South American bullet ant which have stings that cause long-lasting pain.

These ant venoms target our nerve cells that send pain signals. Normally, the sodium channels in these sensory neurons open only briefly in response to a stimulus. However,  the ant toxins bind to the sodium channels and cause them to open more easily and stay open and active, which translates to a long-lasting pain signal.

Bullet ant stings can be painful for up to 12 hours and it's a deep drilling pain you feel in your bones with sweating and goosebumps, quite unlike the 10-minute impact of a typical bee sting.

The bullet ant was rated as having the most painful insect sting in the world by the late Dr. Justin Schmidt, an American entomologist who created a pain index of stinging insects.

These neurotoxins which target sodium channels are unique to ants. Ants developed their defensive neurotoxins to fend off predators during the time of the dinosaurs and have since become one of the most successful animal groups on Earth..

Samuel D. Robinson et al, Ant venoms contain vertebrate-selective pain-causing sodium channel toxins, Nature Communications (2023). DOI: 10.1038/s41467-023-38839-1

Data show no evidence that chronic disease treatment efficacies depend on number of comorbidities

Treatment efficacy for a broad range of chronic diseases does not differ depending on patients' comorbidities, according to a new study publishing June 6 in the open access journal PLOS Medicine.

There is often uncertainty about how treatments for single conditions should be applied to people who have multiple chronic conditions (multimorbidity). This confusion stems, in part, from the fact that people with multimorbidity are under-represented in randomized controlled trials, and trials rarely report whether the efficacy of treatment differs by the number of comorbidities or the presence of specific comorbidities.

In the new study, the researchers used existing data from 120 industry-sponsored randomized controlled phase 3 and 4 clinical trials carried out between 1990 and 2017. The dataset included a total of 128,331 participants and spanned 23 common long-term conditions, including asthma, diabetes, hypertension, osteoporosis, and migraine. For each trial as well as each treatment type spanning multiple trials, the team modeled whether there were any interactions between treatment efficacy and comorbidities.

Across trials, the percentage of participants with three or more comorbidities ranged from 2.3% (in allergic rhinitis trials) to 57% (in trials for systemic lupus erythematosus). Overall, the new study found no evidence of comorbidities modifying treatment efficacy across any of the 23 conditions studied. However, the authors noted that the trials were not designed to assess variation in treatment efficacy by comorbidity.

These findings suggest that for modest levels of comorbidities, this assumption is reasonable.

Hanlon P, Butterly EW, Shah AS, Hannigan LJ, Lewsey J, Mair FS, et al. Treatment effect modification due to comorbidity: Individual participant data meta-analyses of 120 randomised controlled trials, PLoS Medicine (2023). DOI: 10.1371/journal.pmed.1004176

Synthetic species created without biochemistry operate according to Darwinian evolutionary principles

Imagine the possibility of life forms on other planets that don't resemble any on Earth. What might they look like, and why would they be so different?

This may be possible and the answer may be that they developed from a different type of chemistry.

Some researchers have studied how to produce synthetic living systems—without relying on biochemistry, or the chemistry that has enabled life on Earth. They have been have been trying to build a non-biochemical system, which unaided is capable of executing the essential properties common to all natural living systems. 

  One latest study, published last month in Cell Reports Physical Science, even finds such a system engaged in what Charles Darwin called "the struggle for life.

Researchers   created two synthetic models (or "species") and observed the ensuing competition between them. They figured out how to create non-biochemical but carbon-chemistry-based systems called protocells. These are made up of self-assembling polymer vesicles that emerge from a homogenous blend of smaller synthetic chemicals with no relation to living organisms. "These systems act like biochemical cells. They are born, metabolize what they need, grow, move, reproduce, and perhaps even evolve.

Now the researchers wanted to see whether these systems would operate according to the evolutionary principle of competitive exclusion. As we know from Darwin's work, this involves the struggle for survival—with the species with the greatest competitive advantage edging out the other when vying for resources.

They created two new species of protocells for this particular study—one with the advantage of light sensitivity, the other without. When the researchers watched how these systems behaved as they shared food in an illuminated environment, they saw that the light-sensitive "species" endured while the other did not. "It's the struggle for existence where the best-suited structure survived in its environment.

With these results, these researchers are  willing to go as far as to suggest that biochemicals are not essential to the struggle for life. This shows that non-biochemical carbon chemistry can lead to the extinction of the less 'fit' protocell species. 

Could there be chemistries beyond Earth capable of implementing the fundamental properties of life?

It's possible there are materials, which once on a planetary surface somewhere with appropriate conditions, could react chemically, self-organize, and perhaps do the things that this experiment shows.

Under the right circumstances, these materials may evolve from very simple chemistry into more complicated structures.

So these scientists think we should be very open about other forms of life elsewhere in the universe, and that they may not resemble life as we recognize it now.

Sai Krishna Katla et al, Competitive exclusion principle among synthetic non-biochemical protocells, Cell Reports Physical Science (2023). DOI: 10.1016/j.xcrp.2023.101359

A documented case of a crocodile virgin birth

A team of entomologists and reptile specialists from Virginia Polytechnic Institute and State University, the Chiricahua Desert Museum, the Illinois Natural History Survey, Reptilandia Reptile Lagoon and Parque Reptilandia has documented a case of a virgin crocodile laying viable eggs. In their paper published in the journal Biology Letters, the group describes their surprise at the discovery of a clutch of eggs laid by an American crocodile who had been kept alone in an enclosure at Parque Reptilandia park in Costa Rica for 16 years prior to laying the eggs.

Prior research has found instances of "virgin birth"—a type of asexual reproduction in a species that normally reproduces sexually—in snakes, lizards, sharks and birds, but never in Crocodilia, an order that includes gharials, caimans, alligators and crocodiles. So the handlers at Parque Reptilandia were surprised to see a clutch of eggs in an enclosure hosting a single American crocodile.

Alligators are well known in North America, but crocodiles live there, too, in parts of Florida. They also live in Central and South America. They normally mate to reproduce, like most other reptiles, and lay eggs that later hatch. But now, it appears that they can reproduce asexually if need be.

The clutch of 14 eggs was discovered back in 2016. After handlers noted their arrival, they notified local specialists. The eggs were collected and taken to a lab for study, where researchers found that half of them were viable. The viable eggs were placed in an incubator with the hope of producing hatchlings.

None of the eggs produced any, unfortunately, leading the researchers to crack them open after three months to see what was going on. All of the eggs had progressed toward hatching, but only one actually resembled a fetus. A genetic study of the most advanced specimen revealed that it was nearly identical to its mother.

The research team notes that it was not surprising that none of the eggs were hatchable; eggs laid in such fashion rarely are. Now that virgin births have been documented in both birds and Crocodilia, it raises the question of whether pterosaurs and/or dinosaurs were able to do so, as well.

Remains of an extinct world of organisms discovered

Newly discovered biomarker signatures point to a whole range of previously unknown organisms that dominated complex life on Earth about a billion years ago. They differed from complex eukaryotic life as we know it, such as animals, plants and algae in their cell structure and likely metabolism, which was adapted to a world that had far less oxygen in the atmosphere than today.

An international team of  researchers now reports on this breakthrough for the field of evolutionary geobiology in the journal Nature.

The previously unknown "protosteroids" were shown to be surprisingly abundant throughout Earth's Middle Ages. The primordial molecules were produced at an earlier stage of eukaryotic complexity—extending the current record of fossil steroids beyond 800 and up to 1,600 million years ago. Eukaryotes is the term for a kingdom of life including all animals, plants and algae and set apart from bacteria by having a complex cell structure that includes a nucleus, as well as a more complex molecular machinery.

This "stem" represents the common ancestral lineage that was a precursor to all still living branches of eukaryotes. Its representatives are long extinct, yet details of their nature may shed more light on the conditions surrounding the evolution of complex life.

Although more research is needed to evaluate what percentage of protosteroids may have had a rare bacterial source, the discovery of these new molecules not only reconciles the geological record of traditional fossils with that of fossil lipid molecules, but yields a rare and unprecedented glimpse of a lost world of ancient life.

The competitive demise of stem group eukaryotes, marked by the first appearance of modern fossil steroids some 800 Million years ago, may reflect one of the most incisive events in the evolution of increasingly complex life.

How an earthquake becomes a tsunami

The movement between continental and oceanic plates at the bottom of the sea, so-called megathrust earthquakes, generates the strongest tremors and the most dangerous tsunamis. How and when they occur, however, has been poorly understood so far, since the ocean floor is difficult to access for measurements.

Thanks to new technologies, an international research team was able to take measurements to the nearest centimeter for the first time in an underwater-earthquake zone off Alaska. The researchers reported on their findings in the specialist journal Science Advances.

The Chignik earthquake on July 28, 2021, occurred 32 km below the seafloor off the coast of Alaska and, with a magnitude of 8.2, was the seventh strongest earthquake in US history. It occurred because the oceanic Pacific Plate is sliding past the continental North American Plate, thereby causing an enormous thrust.

In the sparsely populated region, the damage caused by the quake was limited. In general, however, such megathrust earthquakes have enormous destructive potential in the so-called subduction zone, i.e. the zone where oceanic and continental tectonic plates meet. In particular, tsunami waves can be generated. These are not very high at their place of origin, but hours later and many 100 or 1000 kilometers away, they can hit the coasts as a catastrophic tsunami and endanger many lives.

Researchers examined the seafloor off Alaska shortly before and about 2.5 months after the Chignik quake, using a global navigation satellite system (GNSS), an acoustic positioning system, and a robotic ship.

In the project, a key role was played by autonomous vessels , called wave gliders, that operate on the water surface.

The modern technology allowed measurements of the movements in the subduction zones to the nearest centimeter and thus a precise picture of the complicated slip processes and faults. Particular attention was paid to the shallow portions of the slip zones, as these are critical to whether or not a tsunami will occur. The measurements were taken at a water depth of 1,000 to 2,000 meters.

Benjamin A. Brooks et al, Rapid shallow megathrust afterslip from the 2021 M8.2 Chignik, Alaska earthquake revealed by seafloor geodesy, Science Advances (2023). DOI: 10.1126/sciadv.adf9299

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