New treatment of autoimmune diseases revealed in new study

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

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

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

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

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

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

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

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

Trapping and killing superbugs with novel peptide 'nanonets'

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

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

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

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

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

Nations forge a historic High Seas Treaty

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

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

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

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

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

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

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

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

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

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

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

Heavy alcohol consumption increases brain inflammation and influences decision making

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Researchers discover how too much oxygen damages cells and tissues

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

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

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

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

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

Part 1

So researchers now turned to the genome editing technology CRISPR to test the roles of a variety of genes in hyperoxia.

Using CRISPR, the researchers removed, one at a time, more than 20,000 different genes from human cells grown in the lab and then compared the growth of each group of cells at 21 percent oxygen and 50 percent oxygen.

This kind of unbiased screen let researchers probe the contributions of thousands of different pathways in hyperoxia rather than just focusing on those we already suspected might be involved.

Four molecular pathways stood out in the screen as being involved in the effects of hyperoxia. They related to diverse cellular functions including the repair of damaged DNA, the production of new DNA building blocks, and the generation of cellular energy.

It took some molecular sleuthing to discover that each pathway had a critical protein that contained iron atoms connected to sulfur atoms—so-called "iron-sulfur clusters"—in its molecular structure.

The researchers went on to show that in as little as 30 percent oxygen, the iron-sulfur clusters in the four proteins become oxidized—they chemically react with oxygen atoms—and that change causes the proteins to degrade. As a result, cells stop functioning correctly and consume even less oxygen, causing a further increase in oxygen levels in the surrounding tissues.

One important thing found in this work is that hyperoxia is not impacting cells and tissues solely through reactive oxygen species, as many had assumed. That means the use of antioxidants—which can combat reactive oxygen species to some degree—is unlikely to be sufficient to prevent oxygen toxicity.

 Alan H. Baik et al, Oxygen toxicity causes cyclic damage by destabilizing specific Fe-S cluster-containing protein complexes, Molecular Cell (2023). DOI: 10.1016/j.molcel.2023.02.013

Part 2

Bacterial enzyme traps and breaks down PFAS molecules

Highly nondegradable chemicals such as PFAS and pesticides can have useful properties in some situations, but are extremely difficult for nature to remove afterwards. Now researchers have found that certain bacteria use an enzyme that acts as a molecular nutcracker to crush the harmful substances.

All cells contain a large number of enzymes, each of which functions as a small machine that carries out a specific task. Inside E. coli bacteria, researchers have found an enzyme, C-P lyase, that enables the microbe to degrade highly stable chemicals. By rapidly freezing purified samples of the enzyme, the researchers have succeeded in capturing the molecular nutcracker in two different states that represent an open and closed form, respectively. The results show that the bacterium uses the energy from ATP, the cellular energy source, to both open and close the nutcracker.

Two similar, ATP-consuming modules, which are mostly known from transport proteins, have been put together to be able to open and close the enzyme.

The results, which have recently been published in the journal, Nature Communications, are expected to be useful in developing dedicated strains of bacteria that survive by breaking down the difficult substances and therefore potentially can be of great importance for the future use of pesticides in agriculture.

Søren K. Amstrup et al, Structural remodelling of the carbon–phosphorus lyase machinery by a dual ABC ATPase, Nature Communications (2023). DOI: 10.1038/s41467-023-36604-y

**

Scientists harness power, precision of RNA to make mutations invisible

Scientists have discovered a new way to suppress mutations that lead to a wide range of genetic disorders.

A study recently published in the journal Molecular Cell describes a strategy that co-opts a normal RNA modification process within cells to transform disease genes into normal genes that produce healthy proteins. The findings are significant because they may ultimately help researchers alter the course of devastating disorders such as cystic fibrosis, muscular dystrophy and many forms of cancer.

About 15% of mutations that lead to genetic diseases are called nonsense mutations. Aptly named, nonsense mutations occur when an mRNA molecule contains an early "stop" signal. When the mRNA takes genetic instructions from DNA to create a protein, this early stop sign orders the cell to stop reading the instructions partway through the process. This results in the creation of an incomplete protein that can lead to disease.

A team of researchers  designed an artificial guide RNA—a piece of RNA that can modify other types of RNA—to target mRNA molecules that contain early stop signals (also called premature termination codons). Guide RNAs are a natural mechanism that cells use all the time; This  team altered this already existing process.

Like DNA, RNA is made up of molecular building blocks that are represented by the letters A (adenine), G (guanine), U (uracil), and C (cytosine). Premature termination codons always have the building block U in the first position (for example, UAG, UAA or UGA). The team's artificial guide RNA was designed to modify the U in the first position, changing the molecular makeup of the targeted mRNA so that the stop signal is no longer—or less well—recognized by the cell.

Researchers tested the artificial guide RNA in yeast cells and in human disease cells (derived from cystic fibrosis and neurofibromatosis patients). In both cases, they found the action of the artificial guide RNA rendered the premature termination codon (stop sign) invisible, allowing cells to read the genetic instructions all the way through and create full-length, functional proteins.

They also discovered that the guide RNA suppressed another mechanism in the cell known as nonsense-mediated mRNA decay or NMD. One of the major surveillance systems in the body, NMD targets and eliminates mRNAs with premature termination codons, so no protein is produced. Curbing NMD is another way the artificial guide RNA ensured that a significant amount of mRNA was present in the cell, and that the genetic instructions carried by the targeted mRNAs were read all the way through and translated into complete proteins.

Hironori Adachi et al, Targeted pseudouridylation: An approach for suppressing nonsense mutations in disease genes, Molecular Cell (2023). DOI: 10.1016/j.molcel.2023.01.009

In the world's smallest ball game, scientists throw and catch singl...

In many baseball-obsessed countries like Korea, Japan and the United States, with spring months comes the start of the season and quite a few balls flying through the air. But it's not just balls that can be thrown. On the tiniest field imaginable, scientists have now shown they can also throw and catch individual atoms using light.

This amazing feat was achieved with optical traps, which use a highly focused laser beam to hold and move tiny objects. Although optical traps have been used to move individual atoms before, this is the first time an atom has been released from a trap—or thrown—and then caught by another trap.

 Jaewook Ahn et al, Optical tweezers throw and catch single atoms, Optica (2023). DOI: 10.1364/OPTICA.480535

The mice with two dads: scientists create eggs from male cells

How wildfires shred the ozone layer

Huge wildfires that raged across Australia in 2019–20 unleashed chemicals that chewed through the ozone layer. The wildfire smoke combined with harmless remnants of now-banned chlorinated compounds, reactivating their ozone-eating form — a reaction that doesn’t usually happen in the warm air away from the poles. More-frequent wildfires resulting from climate change could expand ..., which protects Earth from harmful ultraviolet rays.

https://www.nature.com/articles/d41586-023-00687-w?utm_source=Natur...

https://www.nature.com/articles/s41586-022-05683-0.epdf?sharing_tok...

Ancient dormant viruses found in permafrost, once revived, can infect 

A team of climate scientists has found that ancient viruses dormant for tens of thousands of years in permafrost can infect modern amoeba when they are revived. For their study, reported on the open-access site Viruses, the group collected several giant virus specimens from permafrost in Siberia and tested them to see if they could still infect modern creatures.

Prior research has shown that permafrost—frozen soil—is an excellent preservative. Many carcasses of frozen extinct animals have been extracted from permafrost in the Northern Hemisphere. Prior research has also shown that plant seeds lying dormant in permafrost can be coaxed to grow once revived. And there is evidence suggesting that viruses and bacteria trapped in permafrost could infect hosts if revived. In this new effort, the researchers tested this theory.

The effort by the research team followed up on prior work in 2014 that showed a 30,000-year-old virus could be revived—and that it could be infectious. The team followed up on that effort by reviving a different virus in 2015 and allowing it to infect an amoeba. In this new effort, the team collected several virus specimens from multiple permafrost sites across Siberia for lab testing. For safety reasons, the research team collects only so-called giant viruses and only those that can infect amoeba, not humans or any other creature. In reviving the virus samples, the team found that they were still capable of infecting amoeba. They also found, via radiocarbon dating of the permafrost in which they were found, that the viruses had been in a dormant state for between 27,000 and 48,500 years.

The researchers suggest their findings hint at a much bigger problem—as the planet warms and the permafrost melts, there is a chance of viruses emerging that are capable of infecting humans. Such a threat is not science fiction, they note—prior researchers found influenza viruses in a lung sample of a woman who had died in Alaska during the flu pandemic of 1918. And another team found a virus related to smallpox in a mummified woman found in Siberia—she had been there for 300 years.

Jean-Marie Alempic et al, An Update on Eukaryotic Viruses Revived from Ancient Permafrost, Viruses (2023). DOI: 10.3390/v15020564

You're stuck with your same old genome, but corals aren't

Some corals live to be hundreds, and even thousands, of years old. They were born with genes that were successful back in their parent's generation, so how can these old corals still be successful now? Especially in a changing climate? It's possible that the generation and the filtering of mutations that occur in different parts of a big coral act as a proving ground for adaptive genetics for the future. A new study shows a novel way that some very ancient animals might be surviving.

You got your entire set of genes—good or bad—from your parents, and those are the only genes you will have for your entire life. Those genes are also the only ones you will pass along to your children. Of course, there are a few exceptions—like mutations that happen in sperm or egg cells that you might pass along to the next generation. And a growing chorus of technologies is poised to alter harmful mutations in human genes that make life difficult, such as recent success in altering the genes in lung cells that cause cystic fibrosis.

Nearly every animal must make a living with a set of genes that remains virtually unchanged during their lifetime, but a recent study of tropical reef building corals shows something different. These very long-lived animals are constantly changing and testing their genes—and some of these changes make it into the next generation. In this way a centuries-old coral might be a cauldron of genetic innovation, and it might help prepare them for climate change.

Elora H. López-Nandam et al, Mutations in coral soma and sperm imply lifelong stem cell renewal and cell lineage selection, Proceedings of the Royal Society B: Biological Sciences (2023). DOI: 10.1098/rspb.2022.1766

**

Microbes can create a more peaceful world: Scientists issue call to action

Microorganisms should be 'weaponized' to stave off conflicts across the globe, according to a team of eminent microbiologists.

The paper 'Weaponising microbes for peace'  outlines the ways in which microbes and microbial technologies can be used to tackle global and local challenges that could otherwise lead to conflict, but warns that these resources have been severely underexploited to date.

Worldwide deficits and asymmetries in basic resources and services considered to be human rights, such as drinking water, sanitation, healthy nutrition, access to basic healthcare and a clean environment, can lead to competition between peoples for limited resources, tensions, and in some cases conflicts. "There is an urgent need to reduce such deficits, to level up, and to assure provision of basic resources for all peoples. This will also remove some of the causes of conflicts. There is a wide range of powerful microbial technologies that can provide or contribute to this provision of such resources and services, but deployment of such technologies is seriously underexploited.

The paper then lists a series of ways in which microbial technologies can contribute to challenges such as food supply and security, sanitation and hygiene, healthcare, pollution, energy and heating, and mass migrations and overcrowding. For example, microbes are at the core of efforts to tackle pollution by bioremediation, replacing chemical methods of treating drinking water with metalloid conversion systems, and producing biofuels from wastes. "There is now a desperate need for a determined effort by all relevant actors to widely deploy appropriate microbial technologies to reduce key deficits and asymmetries, particularly among the most vulnerable populations.

There is now a desperate need for a determined effort by all relevant actors to widely deploy appropriate microbial technologies to reduce key deficits and asymmetries, particularly among the most vulnerable populations.

Not only will this contribute to the improvement of humanitarian conditions and leveling up, and thereby to a reduction in tensions that may lead to conflicts, but also advance progress towards attainment of Sustainable Development Goals.

"We must weaponise microbes for peace."

The editorial is published in Microbial Biotechnology.

Shailly Anand et al, Weaponising microbes for peace, Microbial Biotechnology (2023). DOI: 10.1111/1751-7915.14224

Your Heartbeat Shapes Your Perception of Time, Study Finds

Right now, your brain is keeping track of the passage of time without your awareness, letting you focus on better things.

This happens automatically, but not consistently. The brain's perception of time can fluctuate, with some moments seeming to stretch or shrink relative to each objective second.

While these wrinkles in time may be distortions of reality, technically they aren't all in your head. According to a new study, some originate in your heart.

Heartbeats set the pace for time perception.Time is a dimension of the Universe and a core basis for our experience of self. This new research shows that the moment-to-moment experience of time is synchronized with, and changes with, the length of a heartbeat.

These variations in time perception – or "temporal wrinkles" – are normal, researchers say, and may be adaptive. Previous research has also explored their origins, suggesting thoughts and emotions can distort our sense of time, making some moments seem to expand or contract.

part1

In a study last year it was found that virtual-reality train rides seemed to last longer for passengers when the simulated trains were more crowded.

But many prior studies have focused on perception of relatively long time intervals,  and therefore tend to reveal more about how people estimate time than how they experience it directly in the moment.

To shed more light on the latter, the new study looked for links between time perception and bodily rhythms, with a focus on natural fluctuations in heart rate. While the overall cadence of a heart sounds steady, each individual beat can be slightly shorter or longer than the one before.

Research has shown that heartbeats can influence our perception of external stimuli, and the heart has long been suspected of helping the brain keep time.

The heartbeat is a rhythm that our brain is using to give us our sense of time passing.  "And that is not linear – it is constantly contracting and expanding.

While the heart may wield heavy influence on the brain's perception of time, it's a two-way street, the researchers note. Hearing a tone led subjects to focus their attention on the sound, an "orienting response" that in turn changed their heart rate and readjusted their experience of time.

Incorrectly perceiving the passage of time might sound like a bad thing, and sometimes it is. But while losing track of time can lead to trouble, there may also be adaptive benefits to the kind of temporal wrinkles identified in this study.

The heart seems to help the brain work more efficiently with limited resources, the researchers add, influencing how it experiences the passage of time on the smallest scales, and operating at time periods too brief for conscious thoughts or feelings.

"Even at these moment-to-moment intervals, our sense of time is fluctuating" . "A pure influence of the heart, from beat to beat, helps create a sense of time."

https://onlinelibrary.wiley.com/doi/epdf/10.1111/psyp.14270

**

part2

Estrogen receptor in the heart found to regulate obesity in postmenopausal women

Estrogen is known to play an important role in the protection of women's hearts, but once women are postmenopausal and estrogen levels drop, they are at an increased risk of a number of diseases and conditions, including heart disease, obesity and diabetes.

Published in Nature Cardiovascular Research, the study found that reduced ERα in the cells responsible for heart contraction (cardiomyocytes) led to moderate heart dysfunction and increased rates of obesity in female mice, but not in male mice.

Researchers  identified a sex hormone receptor in the heart that can regulate adiposity (obesity) in females. They were interested in trying to understand the role of this estrogen receptor in the heart for some time, to see how it provides protection to the heart.

When they blocked this estrogen receptor, they were expecting to see changes and damage largely to the heart. But rather than seeing a dramatic heart phenotype, what they saw was an adiposity phenotype. So, they observed that the female mice were heavier and had more fat mass, which they  weren't expecting at all.

Genes that are important for contractility of the heart and metabolic function of the heart were also lower in the female heart when ERα was reduced, explaining why the female study hearts did not pump as well.

Extracellular vesicles, that were released from the female hearts with reduced ERα also contained proteins that differed from both the control group and male hearts.

Researchers found that reducing ERα in heart muscle cells (cardiomyocytes) of female mice leads to transcriptional, lipidomic and metabolic dysregulation in the heart, together with metabolic dysregulation in skeletal muscle and adipose tissue. 

Furthermore, the extracellular vesicles that are released from heart cells with reduced ERα had the capacity to reprogram skeletal muscle cells in cell culture. These changes to tissues, the extracellular vesicles proteome and reprogrammed skeletal muscle cells altered the cells' molecular landscape and function. So rather than energy being expended, energy is instead stored, which explains the increased adiposity in female mice in the absence of Erα.

This important work has implications for preventing and treating heart and metabolic disease in post menopausal women, but also cardiotoxicity in premenopausal women receiving therapies that may inhibit or reduce ERα in the heart.

David Greening, Estrogen receptor alpha deficiency in cardiomyocytes reprograms the heart-derived extracellular vesicle proteome and induces obesity in female mice, Nature Cardiovascular Research (2023). DOI: 10.1038/s44161-023-00223-z. www.nature.com/articles/s44161-023-00223-z

Scientists identify substance that may have sparked life on Earth

A team of scientists dedicated to pinpointing the primordial origins of metabolism—a set of core chemical reactions that first powered life on Earth—has identified part of a protein that could provide scientists clues to detecting planets on the verge of producing life.

The research, published in Science Advances, has important implications in the search for extraterrestrial life because it gives researchers a new clue to look for.

Based on laboratory studies,  scientists say one of the most likely chemical candidates that kickstarted life was a simple peptide with two nickel atoms they are calling "Nickelback" not because it has anything to do with the Canadian rock band, but because its backbone nitrogen atoms bond two critical nickel atoms. A peptide is a constituent of a protein made up of a few elemental building blocks known as amino acids.

Scientists think that sometime between 3.5 and 3.8 billion years ago there was a tipping point, something that kickstarted the change from prebiotic chemistry—molecules before life—to living, biological systems. They think the change was sparked by a few small precursor proteins that performed key steps in an ancient metabolic reaction. And they think they've now found one of these 'pioneer peptides.

When scouring the universe with telescopes and probes for signs of past, present or emerging life, NASA scientists look for specific "biosignatures" known to be harbingers of life. Peptides like nickelback could become the latest biosignature employed by NASA to detect planets on the verge of producing life.

An original instigating chemical, the researchers reasoned, would need to be simple enough to be able to assemble spontaneously in a prebiotic soup. But it would have to be sufficiently chemically active to possess the potential to take energy from the environment to drive a biochemical process.

To do so, the researchers adopted a "reductionist" approach: They started by examining existing contemporary proteins known to be associated with metabolic processes. Knowing the proteins were too complex to have emerged early on, they pared them down to their basic structure.

After sequences of experiments, researchers concluded the best candidate was Nickelback. The peptide is made of 13 amino acids and binds two nickel ions.

Nickel, they reasoned, was an abundant metal in early oceans. When bound to the peptide, the nickel atoms become potent catalysts, attracting additional protons and electrons and producing hydrogen gas. Hydrogen, the researchers reasoned, was also more abundant on early Earth and would have been a critical source of energy to power metabolism.

This work shows that, not only are simple protein metabolic enzymes possible, but that they are very stable and very active—making them a plausible starting point for life.

Jennifer Timm et al, Design of a Minimal di-Nickel Hydrogenase Peptide, Science Advances (2023). DOI: 10.1126/sciadv.abq1990. www.science.org/doi/10.1126/sciadv.abq1990

What is Plasma?

'Counterportation': Quantum breakthrough paves way for world-first experimental wormhole

One of the first practical applications of the much-hyped but little-used quantum computing technology is now within reach, thanks to a unique approach that sidesteps the major problem of scaling up such prototypes.

The invention, by a  physicist, who gave it the name "counterportation," provides the first-ever practical blueprint for creating in the lab a wormhole that verifiably bridges space, as a probe into the inner workings of the universe.

By deploying a novel computing scheme, revealed in the journal Quantum Science and Technology, which harnesses the basic laws of physics, a small object can be reconstituted across space without any particles crossing. Among other things, it provides a "smoking gun" for the existence of a physical reality underpinning our most accurate description of the world. It provides a theoretical as well as practical framework for exploring afresh enduring puzzles about the universe, such as the true nature of spacetime.

The need for detectable information carriers traveling through when we communicate has been a deeply ingrained assumption among scientists, for instance a stream of photons crossing an optical fiber, or through the air, allowing people to read this text. Or, indeed, the myriad neural signals bouncing around the brain when doing so. This holds true even for quantum teleportation, which, "Star Trek" aside, transfers complete information about a small object, allowing it to be reconstituted elsewhere, so it is indistinguishable in any meaningful way from the original, which disintegrates. The latter ensures a fundamental limit preventing perfect copying. Notably, the recent simulation of a wormhole on Google's Sycamore processor is essentially a teleportation experiment.

Here's the sharp distinction. While counterportation achieves the end goal of teleportation, namely disembodied transport, it remarkably does so without any detectable information carriers traveling across.

The defining task of a traversable wormhole, however, can be neatly abstracted as making space traversable disjunctly; in other words, in the absence of any journey across observable space outside the wormhole.

The pioneering research, fittingly completed to the spine-tingling "Interstellar" score, sets out a way to carry this task out.

If counterportation is to be realized, an entirely new type of quantum computer has to be built: an exchange-free one, where communicating parties exchange no particles.

By contrast to large-scale quantum computers that promise remarkable speed-ups, which no one yet knows how to build, the promise of exchange-free quantum computers of even the smallest scale is to make seemingly impossible tasks—such as counterportation—possible, by incorporating space in a fundamental way alongside time.

The goal in the near future is to physically build such a wormwhole in the lab, which can then be used as a testbed for rival physical theories, even ones of quantum gravity.

Hatim Salih, From counterportation to local wormholes, Quantum Science and Technology (2022). DOI: 10.1088/2058-9565/ac8ecd

Extreme nighttime pollution in New Delhi air explained by new study

In a major joint project with top Indian scientists, PSI researchers have determined why smog forms at night in the Indian capital New Delhi, contrary to all the rules of atmospheric chemistry. Their results have now been published in the journal Nature Geoscience.

For the past three years, New Delhi has been ranked the world's most polluted capital. Its high levels of air pollution are responsible for a large number of premature deaths. In winter, the particulate matter levels exceed 500 micrograms per cubic meter of air. To get some idea of this magnitude, compare this value with the Chinese capital Beijing. In that smog-plagued metropolis, one cubic meter of air contains "only" 70 micrograms of particulates; whereas in Zurich the figure is just 10 micrograms per cubic meter.

Where do these extremely high particulate levels come from in nighttime New Delhi in winter? A team of researchers from the Laboratory for Atmospheric Chemistry at PSI has been investigating this question together with local scientists, including members of the Indian Institute of Technology Kanpur.

They found an extraordinary explanation. "The chemical processes that take place in the air at night are unique to the Indian capital and have not been observed anywhere else in the world.

 In their study, the team found that the trigger for the high levels of particulate matter is the fumes emitted when wood is burnt.

Wood burning is common practice for around 400 million people living in the Indo-Gangetic Plain, who use wood for cooking and heating. In the absence of strict regulations, materials other than wood are also burnt, sometimes including plastic and other waste materials.

Such fires produce a mixture of gases containing countless chemical compounds, such as cresol, which our noses associate with the typical smell of fire, as well as sugar-like molecules from the burnt cellulose in the wood. These molecules cannot be seen in the air with the naked eye, even in high concentrations. However, as night falls the temperature in New Delhi drops so rapidly that some of the gas molecules condense and within a few hours clump together to form particles up to 200 nanometers across, which can be seen as a gray haze.

"Condensation from gas to particulate phase resembles the way in which water droplets form on kitchen surfaces when one is cooking. Particles in the atmosphere act as large surfaces on which gases can condense.

Part 1

This process is very different from that in other places. Beijing, for example, is probably the best-studied megacity in the world in terms of its air pollution. However, in the atmosphere of the Chinese capital, particle formation follow different chemical pathways. In China, the gases from emissions such as traffic and wood burning react in the atmosphere during the day when they are exposed to light resulting in the formation of less volatile fumes capable of forming particles during the haze.

Such a pathway was also expected in New Delhi, however the opposite happens. Haze formation from the condensation of directly emitted fumes occurs at night, without photooxidation, driven by increased emissions together with a sharp decrease in temperatures. This work has shown for the first time that semi-volatile gases can form such particles at night, contributing to the haze.

The measurements were carried out in January and February 2019. For this purpose, the researchers from India, Sweden and Switzerland set up a station in the center of New Delhi with measuring equipment that included instruments to determine the number and size of the particles, as well as their chemical composition.

The mass spectrometers deployed are very sensitive and can detect thousands of different molecules in the air of New Delhi, whereby the particle concentrations sometimes reached hundreds of thousands of particles within the volume of air corresponding to a sugar cube. Some of the instruments came from PSI, others from partners such as the Indian Institute of Technology Kanpur and the University of Stockholm.

A second measuring station was also set up in the city with scaled-down equipment to verify that the formation of particulates is indeed a regional phenomenon. Switzerland's contribution was financed by the Swiss Agency for Development and Cooperation.

It took four years of data analysis and peer review before the results were ready to be published in Nature Geoscience.

Suneeti Mishra et al, Rapid night-time nanoparticle growth in Delhi driven by biomass-burning emissions, Nature Geoscience (2023). DOI: 10.1038/s41561-023-01138-x

Part 2

Why do people pull their faces when applying make-up?

This is called 'Mascara Mouth' or 'Mascara face'. Intense focus, raised eyebrows, and a slightly open mouth, combine to create a familiar 'look' when trying to achieve the perfect lash.

‘Mascara face’, as it’s sometimes called, is thought to be a result of nerves in our brains cross-firing. The two nerves controlling our eyeball and eyelid movements are rooted in a very similar part of the brain to another nerve that controls the opening and closing of our jaw. So, it’s possible that when the two nerves in charge of eye movements are activated, they trigger off the nearby mouth-opening nerve.

This is only a theory, though. A simpler explanation is that we’ve learnt that opening our mouths stretches our skin, which helps with applying make-up, so people keep doing it.

The FDA Just Approved The First Fast-Acting Nasal Spray For Migraines

The US Food and Drug Administration has approved a fast-acting nasal spray from Pfizer designed to treat migraines, the US pharmaceutical giant said Friday.

​Pfizer said it expected the drug, marketed under the name Zavzpret, to be available in pharmacies in July 2023.

​The FDA approval of Zavzpret marks a significant breakthrough for people with migraine who need freedom from pain and prefer alternative options to oral medications.

​A Phase 3 study of the drug found that it delivered pain relief to some migraine sufferers in as little as 15 minutes.

​As a nasal spray with rapid drug absorption, Zavzpret offers an alternative treatment option for people who need pain relief or cannot take oral medications due to nausea or vomiting.

​The treatment for a condition generally tackled with orally taken medicines was double-blind tested on a sample of 1,405 people, with half taking a single spray dose and the remainder receiving a placebo.

​The spray was found to reduce pain significantly when assessed two hours after the onset of a migraine, which as well as causing often severe headaches can include nausea and sensitivity to light or noise.

​Pfizer acquired Zavzpret, also known as Zavegepant, last year for some $10 billion from Biohaven, along with other migraine treatments from the firm.

​source: News agencies

**

Air travel: Turbulence increases as climate change becomes worse

Atmospheric turbulence accounts for 71% of in-flight weather-related injuries, and according to scientists turbulence is only worsening with global warming. While winter is typically the most turbulent season, modeling suggests that by the year 2050, summers will be as turbulent as winters were back in the 1950s.

The paper, "Clear‑air turbulence trends over the North Atlantic in high‑resolution climate models," has been published in the international journal Climate Dynamics.

Clear-air turbulence (CAT) is one of the more dangerous weather-related hazards. It usually develops in cloud-free environments of the upper-level atmosphere; offering no visual clues to pilots and undetectable by onboard radar, these events seemingly come out of nowhere. Prolonged exposure to turbulence will shorten the fatigue life, which is the time the aircraft can be in service. Aircraft fittings can be damaged and severe structural damage can result from more intense clear-air turbulence. In extremely rare cases, this could even lead to the break-up of the aircraft. During moderate turbulence, unrestrained items of cargo, passenger luggage or passengers themselves can collide, causing damage or injury.

The intensity of a jet stream depends on latitudinal horizontal temperature gradients. Due to the steepening of the pole-to-equator temperature gradient in the upper troposphere and lower stratosphere, jet streams are expected to intensify in wind shear with anthropogenic climate change.

The study used three global climate  modeling simulators covering the period 1950–2050 in the formation analysis.

Based on the assessment, for every 1 °C of global near-surface warming, moderate CAT events will increase by 14% in summer and autumn and by 9% for winter and spring. Moderate turbulence is described as inflicting vertical accelerations of up to 0.5g.

With increased turbulence in all seasons, more fights will encounter CAT events on current flight paths. One option for airlines will be to attempt to avoid areas where CAT forms. This might cause longer transatlantic flight times and thousands of additional hours of accumulated flight and fuel costs—a good reminder that the seatbelt sign is there for a reason, and keeping yours on even when the light is off might be the safest plan in the future.

Isabel H. Smith et al, Clear-air turbulence trends over the North Atlantic in high-resolution climate models, Climate Dynamics (2023). DOI: 10.1007/s00382-023-06694-x

Where did Earth's water come from? Not melted meteorites, according to scientists

Water makes up 71% of Earth's surface, but no one knows how or when such massive quantities of water arrived on Earth.

A new study published in the journal Nature brings scientists one step closer to answering that question.

Researchers analyzed melted meteorites that had been floating around in space since the solar system's formation 4 1/2 billion years ago. They found that these meteorites had extremely low water content—in fact, they were among the driest extraterrestrial materials ever measured. These results, which let researchers rule them out as the primary source of Earth's water, could have important implications for the search for water—and life—on other planets. It also helps researchers understand the unlikely conditions that aligned to make Earth a habitable planet.

After analyzing the achondrite meteorite samples, researchers discovered that water comprised less than two millionths of their mass. For comparison, the wettest meteorites—a group called carbonaceous chondrites—contain up to about 20% of water by weight, or 100,000 times more than the meteorite samples.

This means that the heating and melting of planetesimals leads to near-total water loss, regardless of where these planetesimals originated in the solar system and how much water they started out with. Researchers discovered that, contrary to popular belief, not all outer solar system objects are rich in water. This led them to conclude that water was likely delivered to Earth via unmelted, or chondritic, meteorites.

Megan Newcombe, Degassing of early-formed planetesimals restricted water delivery to Earth, Nature (2023). DOI: 10.1038/s41586-023-05721-5. www.nature.com/articles/s41586-023-05721-5

**

Study: Experimental COVID shot made via egg-based technology elicits higher antibody proportion than mRNA vax

An experimental COVID-19 vaccine produced with technology based on a decades-old method, elicited virus-neutralizing antibodies in higher proportion than the amount induced by mRNA immunizations, a Phase 1 clinical trial has found.

The investigational vaccine was developed in New York City and tested in Thailand where the shots were produced using a form of egg-based technology. The fact that researchers are still racing to develop new COVID-19 vaccines highlights an ongoing need, especially in low- and middle-income countries—and for good reason.

There is a need for SARS-CoV-2 vaccines that can be produced at low cost locally in low- and middle-income countries and this is one such experiment.

The study analyzed antibody responses elicited by the investigational vaccine known as NDV-HXP-S, which is produced in hens' eggs.

The research found that the investigational vaccine prompted a higher proportion of neutralizing antibodies against SARS-CoV-2 in volunteers compared with the proportion of neutralizing antibodies produced by a separate group of people who were vaccinated with Pfizer's mRNA vaccine.

A neutralizing antibody is one that defends healthy cells from a virus by neutralizing the pathogen's efforts to get inside. For instance, a neutralizing antibody can stop a virus from making a conformational change—swapping its structure for a new shape. Viral shape-shifting is a way to infect a cell.

Neutralizing antibodies differ from binding antibodies, which latch onto the pathogen and alert warrior cells of the immune system that a viral invasion is underway. While people who were vaccinated with NDV-HXP-S had a higher proportion of neutralizing antibodies, their binding to neutralizing antibody ratios were lower than those who were vaccinated with Pfizer's mRNA vaccine. When all variables were taken into account, the team concluded that the antibody responses between the two vaccines were comparable.

Findings from the research suggest that even in regions with previously limited vaccine-production infrastructure, it's possible to manufacture robust COVID shots at low cost. Western countries averse to technology sharing early in the pandemic, a factor that left scores of people in low- and middle-income countries with few opportunities for vaccination. Now, the tide is turning, albeit three years after the global SARS-CoV-2 pandemic was declared.

"Locally produced vaccines can increase vaccine access and vaccine independence, especially for low- and middle-income countries. The NDV-HXP-S vaccine is designed to help close this gap because it can be economically produced in influenza vaccine manufacturing plants that are located in [these countries]. Moreover, it can be stored and distributed without the need for freezers.

Part1

Although mRNA vaccines have dominated the U.S. response to the pandemic, the technology underlying those shots is expensive. The finicky, temperature-sensitive ingredients required for mRNA vaccines may be difficult to store in far-flung regions of the globe. To address the global need for a low-cost vaccine that can be produced locally, scientists have been developing alternatives, such as NDV-HXP-S.

The vaccine's initials, NDV-HXP-S, stand for Newcastle disease virus, HexaPro, and spike protein. Producing the vaccine involves a vector, which in this case is the Newcastle disease virus, an agent that infects birds. The vaccine is manufactured by way of egg-based technology, which has been used for decades to produce annual flu shots. The Newcastle viral vector is not used in the production of influenza vaccines.

The vector works exquisitely well in the NDV-HXP-S production process, ferrying vaccine components into embryonated chicken eggs. The result, in the case of the vaccine used in Thailand, is an inactivated vaccine, which is a viral particle displaying SARS-C0V-2's spike protein on its surface.

"NDV-HXP-S can be used as a live vaccine or as an inactivated vaccine

The team analyzed antibody responses after Thai volunteers were vaccinated in the phase 1 clinical study. Researchers studied serum samples from 210 Thai volunteers who received either a placebo or the inactivated NDV-HXP-S vaccine.

They compared antibodies from the Thai volunteers to those from 20 people who received the Pfizer mRNA vaccine in New York City. Antibodies elicited by NDV-HXP-S tended to target the receptor binding domain of the virus rather than the spike protein's S2 subunit, the researchers found.

"Neutralizing activity of sera from NDV-HXP-S vaccinees was comparable to that of [Pfizer] vaccinees, whereas spike protein binding activity of the NDV-HXP-S vaccinee samples was lower than that of sera obtained from mRNA vaccines," the researchers say. This led them to calculate ratios between binding and neutralizing antibody titers.

This work show that a vaccine candidate that can be produced locally in [low- and middle-income countries] at low-cost induces neutralizing antibody titers to SARS-CoV-2 comparable to those observed in cohorts having received mRNA-based COVID-19 vaccines.

Juan Manuel Carreño et al, An inactivated NDV-HXP-S COVID-19 vaccine elicits a higher proportion of neutralizing antibodies in humans than mRNA vaccination, Science Translational Medicine (2023). DOI: 10.1126/scitranslmed.abo2847

Part 2

**

Deactivating mosquito sperm: A human bite back!

New  research makes it likely that proteins responsible for activating mosquito sperm can be shut down, preventing them from swimming to or fertilizing eggs.

The study could help control populations of Culex, the common house mosquito that transmits brain-swelling encephalitis and West Nile Virus.

During mating, mosquitoes couple tail to tail, and the males transfer sperm into the female reproductive tract. It can be stored there awhile, but it still has to get from point A to point B to complete fertilization. 

Key to completing that journey are the specialized proteins secreted during ejaculation that activate the sperm flagella, or 'tails,' that power their movement.

Without these proteins, the sperm cannot penetrate the eggs. They'll remain immotile, and will eventually just degrade.

The study, detailed in the journal PLOS ONE, details a full portrait of all the proteins in the insect's sperm, allowing researchers to find the specific ones that maintain the quality of the sperm while they're inactive, and that also activate them to swim.

To get this detailed information the researchers  worked with a team of graduate and undergraduate students who isolated as many as 200 male mosquitoes from a larger population. They then extracted enough sperm from the tiny reproductive tracts for mass spectrometry equipment to detect and identify the proteins.

Previously, the team determined that sperm need calcium upon entering a reproductive tract to power forward motion. They can now look in the completed protein profile they've created, find the calcium channel proteins, and design experiments to target these channels.

This kind of protein profiling offers a path toward controlling mosquitoes that is more environmentally friendly than other methods that can have unintended, toxic effects. 

This  work sets the foundation for a form of biological control, which most would agree is preferable.

The operative word is control, rather than eradicate. Even though immobilizing the sperm would be 100% effective for the treated mosquitoes, it is not possible or desirable to kill all mosquitoes. This technology would change the proportion of fertile to infertile males in a given mosquito population, rather than wiping them all out.

The team is hoping that information about sperm motility regulators in Culex will also apply to other species of mosquitoes. And other pests too! What we learn in one system, such as mosquitoes, can translate to others.

Catherine D. Thaler et al, Using the Culex pipiens sperm proteome to identify elements essential for mosquito reproduction, PLOS ONE (2023). DOI: 10.1371/journal.pone.0280013

A new way to remove waste from the brain after hemorrhage

Intracerebral hemorrhage, and bleeding into the brain tissue, is a devastating neurological condition affecting millions of people annually. It has a high mortality rate, while survivors are affected by long-term neurological deficits. No medication has been found to support brain recovery following hemorrhage.

In an international collaboration, researchers investigated whether a protein called cerebral dopamine neurotrophic factor (CDNF) has potential as a treatment for brain hemorrhage.

Researchers suggest that cerebral dopamine neurotrophic factor, a protein being currently tested for Parkinson's disease treatment, also has therapeutic effects and enhances immune cell's response after brain hemorrhage.

The authors found that the administration of cerebral dopamine neurotrophic factor accelerates hemorrhagic lesion resolution, reduces brain swelling, and improves functional outcomes in an animal model of brain hemorrhage.

They found that found that cerebral dopamine neurotrophic factor acts on immune cells in the bleeding brain, by increasing anti-inflammatory mediators and suppressing the production of the pro-inflammatory cytokines that are responsible for cell signaling. This is a significant step towards the treatment of injuries caused by brain hemorrhage, for which we currently have no cure.

The administration of cerebral dopamine neurotrophic factor also resulted in the alleviation of cell stress in the area that surrounds the hematoma.

Finally, the researchers demonstrated that systemic administration of cerebral dopamine neurotrophic factor promotes scavenging by the brain's immune cells after brain hemorrhage and has beneficial effects in an animal model of brain hemorrhage. 

Kuan-Yin Tseng et al, Augmenting hematoma-scavenging capacity of innate immune cells by CDNF reduces brain injury and promotes functional recovery after intracerebral hemorrhage, Cell Death & Disease (2023). DOI: 10.1038/s41419-022-05520-2

Casting light on counterfeit products through nano-optical technology

Each year, an estimated two trillion dollars is lost globally due to counterfeit products ranging from jewelry to medicine. As current security labels and product authentication methods are rapidly becoming obsolete or easy to hack, there is a rising urgency for more secure anti-counterfeiting labels.

A research team fabricated a 3D printed nano optical security label that provides 33100 possible combinations for heightened security in optical anti-counterfeiting. 

The research team achieved such a feat by exploiting higher dimensional structured light, i.e., colored Orbital Angular Momentum (OAM) beams, through the fabrication of 3D printed spiral phase plates. Importantly, these plates were miniaturized down to a diameter smaller than that of a strand of human hair and further integrated with structural color filters—spiky looking structures that allow specific colors of light through.

In their study, they included color, spatial position, and OAM of light (one degree of freedom of light) onto a small colored vortex beam (CVB) generator (25 μm). With only 10-by-10 CVB unit array to demonstrate, the optical security label they designed could open pathways for the next generation of optical anti-counterfeiting.
We see things clearly when we hold them up to the light. What this team has done is to learn how to use the natural light that surrounds us and extract tiny beams from it that carry information encoded in not just color, but also by how much we 'twist' its wavefront. This optical version of the combination lock that utilizes high-dimensional structured light provides us with a powerful platform for advanced anti-counterfeiting and information security.

Casting light on counterfeit products through nano-optical technology (2023, March 14)
retrieved 18 March 2023 from https://phys.org/news/2023-03-counterfeit-products-nano-opticaltech...

The video shows the optical security label or photonic tally, consisting of colored vortex beam array. The photonic tally turns into colorful dots when overlapped with each other. During this process, the color and OAM (orbital angular momentum) information is decoded. Credit: Singapore University of Technology and Design

New tool for organ repair: curvature of the environment

A ball, a saddle, or a flat plate. The curvature of biomaterials inhibits or stimulates bone cells to make new tissue. This is what TU Delft engineers show in research published in Nature Communications. This study of geometries could be an important step in research into repairing damaged tissues. In this video, Amir Zadspoor (professor of Biomaterials and Tissue Biomechanics) and Lidy Fratila-Apachitei (assistant professor of Biomaterials) explain exactly how this new tool for organ repair works.

Elite soccer players are more likely to develop dementia, suggests new study

Elite male soccer players were 1.5 times more likely to develop neurodegenerative disease than population controls, according to an observational study published in The Lancet Public Health journal.

Among male soccer players playing in the Swedish top division, 9% (537 out of 6,007) were diagnosed with neurodegenerative disease, compared to 6% (3,485 out of 56,168) population controls.

The soccer players were both amateur and professional. Sweden was a prominent soccer nation during the 20th century and many of the players from the top division were competing at the highest international level. However, due to ideals of sportsmanship and amateurism, soccer clubs in Sweden were not allowed to pay salaries to their soccer players until the late 1960s.

In recent years, there have been growing concerns about exposure to head trauma in soccer (soccer) and whether it can lead to increased risk of neurodegenerative disease later in life. A previous study from Scotland suggested that soccer players were 3.5 times more likely to develop neurodegenerative disease. Following this evidence, certain footballing associations implemented measures to reduce heading in younger age groups and training settings.

While the risk increase in this study is slightly smaller than in the previous study from Scotland, it confirms that elite [soccer players] have a greater risk of neurogenerative disease later in life. As there are growing calls from within the sport for greater measures to protect brain health, this new study adds to the limited evidence base and can be used to guide decisions on how to manage these risks.

The authors caution that although 9% of soccer players and 6% of controls were diagnosed with neurodegenerative disease during their study, most participants were still alive at the end of data collection, so the lifetime risks of developing neurodegenerative disease for both groups are likely to be higher.

The risk of neurodegenerative disease was 1.5 times higher for outfield players than controls but was not significantly higher for goalkeepers compared to controls. Accordingly, in a direct comparison, outfield players had a risk of neurodegenerative disease 1.4 times higher than that of goalkeepers.

Soccer players had a risk of Alzheimer's disease and other dementias 1.6 times that of controls—with 8% (491 out of 6,007) of soccer players being diagnosed with the condition compared to 5% (2889 out of 56,168) of controls.

Part 1

The authors discuss some limitations of their study. The findings' generalizability to soccer players playing today is uncertain. As neurodegenerative disease usually occurs later in life, most players in the study who were old enough to have developed one of these conditions played elite soccer during the mid-20th century. Since then, soccer has changed in many ways that may impact the risk of neurodegenerative disease. It may be that switching from leather to synthetic balls (that do not soak up water and become heavier), having more rigorous training and better equipment, or switching towards a playstyle associated with less head trauma may have reduced the risk. On the other hand, the risk might be higher among soccer players who nowadays train and play more intensely from a young age. The study also looked at male elite soccer players only, so the study's generalizability to female elite players and to male and female amateur and youth players is uncertain.

Neurodegenerative disease among male elite football (soccer) players in Sweden: a cohort study, The Lancet Public Health (2023). DOI: 10.1016/S2468-2667(23)00027-0 , www.thelancet.com/journals/lan … (23)00027-0/fulltext

Part 2

**

An extra X chromosome-linked gene may explain decreased viral infection severity in females

It has long been known that viral infections can be more severe in males than females, but the question as to why has remained a mystery—until possibly now. The key may lie in an epigenetic regulator that boosts the activity of specialized anti-viral immune cells known as natural killer (NK) cells.

In a study published March 16 in the peer-reviewed journal Nature Immunology, a collaborative team of  researchers have found that female mouse and human NK cells have an extra copy of an X chromosome-linked gene called UTX. UTX acts as an epigenetic regulator to boost NK cell anti-viral function, while repressing NK cell numbers.

While it is well-known that males have more NK cells compared to females, researchers did not understand why the increased number of NK cells was not more protective during viral infections. It turns out that females have more UTX in their NK cells than do males, which allows them to fight viral infections more efficiently.

The researchers noted that this held true whether or not the mice had gonads (ovaries in females; testes in males), indicating that the observed trait was not linked to hormones. Furthermore, female mice with lower UTX expression had more NK cells which were not as capable of controlling viral infection.

This implicates UTX as a critical molecular determinant of sex differences in NK cells.

The findings suggest that therapies involving immune responses need to move beyond a "one-size-fits-all" approach and toward a precision medicine model, also known as personalized medicine, that tailors treatments that take into account people's individual differences, such as genetics, environment and other factors that influence health and disease risk, the researchers write.

Mandy I. Cheng et al, The X-linked epigenetic regulator UTX controls NK cell-intrinsic sex differences, Nature Immunology (2023). DOI: 10.1038/s41590-023-01463-8

How tumors transform blood vessels

Increasingly dense cell clusters in growing tumors convert blood vessels into fiber-filled channels. This makes immune cells less effective, as findings by researchers suggest.

It was almost ten years ago that researchers first observed that tumours occurring in different cancers—including colorectal cancer, breast cancer and melanoma—exhibit channels leading from the surface to the inside of the cell cluster. But how these channels form, and what functions they perform, long remained a mystery.

Through a series of elaborate and detailed experiments, scientists  have found possible answers to these questions. There is a great deal of evidence to suggest that these channels, which the researchers have dubbed tumour tracks, were once blood vessels.

These blood vessels start out by supplying the fast-growing cell clusters with glucose and oxygen. But then the vessels undergo a process that strips them of their original function of transporting blood: the vessel walls change and the vessel cavity gradually fills up.

This filler material consists mainly of cells and newly formed protein fibers, which make up what is known as the extracellular matrix. Collagen fibers are found here, as are fibronectin fibers. The latter play a role in growth processes that take place mainly during embryonic development or wound healing. In their article, the researchers show that the fibers within the tumor tracks are capable of trapping immune cells.

While this happens, the immune cells stretch out along the channels and stick to the loose fibronectin fibers. In this elongated form, the immune cells switch from fighting diseases to supporting healing processes. Instead of attacking the tumour cells, they excrete molecules that stimulate growth, thus helping the cancer cells to multiply.

It becomes clear that the tension of extracellular matrix fibers plays a key and previously unknown role in tumor development: in healthy tissue, the fibronectin fibers are stretched extremely taut; only in tumor tissue are they slack. In this looser, more relaxed form, surrounded by transformed blood vessel walls, the fibronectin fibers evidently create a recess in which cancer cells can grow undisturbed.

Charlotte M. Fonta et al, Infiltrating CD8+ T cells and M2 macrophages are retained in tumor matrix tracks enriched in low tension fibronectin fibers, Matrix Biology (2023). DOI: 10.1016/j.matbio.2023.01.002

Devadarssen Murdamoothoo et al, Tenascin‐C immobilizes infiltrating T lymphocytes through CXCL12 promoting breast cancer progression, EMBO Molecular Medicine (2021). DOI: 10.15252/emmm.202013270

Sweetener reduces mouse immune response

In high doses, the calorie-free sugar substitute sucralose suppresses the immune system in mice. The sweetener impairs the rodents’ T cells, immune cells that fight.... Once the mice stopped being fed sucralose, their T-cell responses recovered. The researchers say that it is unlikely that eating sucralose in normal amounts is harmful to humans. There might even be a bright side for autoimmune conditions: mice predisposed to type 1 diabetes were less likely to develop the condition after consuming the sweetener.

https://www.nature.com/articles/s41586-023-05801-6.epdf?sharing_tok...

https://www.nature.com/articles/d41586-023-00784-w?utm_source=Natur...

When someone sneezes on Everest, their germs can last for centuries

Almost five miles above sea level in the Himalayan mountains, the rocky dip between Mount Everest and its sister peak, Lhotse, lies windswept, free of snow. 

According to new research, mountaineers visiting this place are leaving behind a frozen legacy of hardy microbes, which can withstand harsh conditions at high elevations and lie dormant in the soil for decades or even centuries.

The research not only highlights an invisible impact of tourism on the world’s highest mountain, but could also lead to a better understanding of environmental limits to life on Earth, as well as where life may exist on other planets or cold moons.

The research not only highlights an invisible impact of tourism on the world’s highest mountain, but could also lead to a better understanding of environmental limits to life on Earth, as well as where life may exist on other planets or cold moons. The findings were published last month in Arctic, Antarctic, and Alpine Research.

There is a human signature frozen in the microbiome of Everest, even at that elevation.

In decades past, scientists have been unable to conclusively identify human-associated microbes in samples collected above 26,000 feet. This study marks the first time that next-generation gene sequencing technology has been used to analyze soil from such a high elevation on Mount Everest, enabling researchers to gain new insight into almost everything and anything that’s in them.

The researchers weren’t surprised to find microorganisms left by humans. Microbes are everywhere, even in the air, and can easily blow around and land some distance away from nearby camps or trails.

If somebody even blew their nose or coughed, that's the kind of thing that might show up. Certain microbes which have evolved to thrive in warm and wet environments like our noses and mouths were resilient enough to survive in a dormant state in such harsh conditions.

Most of the microbial DNA sequences they found were similar to hardy, or “extremophilic” organisms previously detected in other high-elevation sites in the Andes and Antarctica. The most abundant organism they found using both old and new methods was a fungus in the genus Naganishia that can withstand extreme levels of cold and UV radiation.

But researchers also found microbial DNA for some organisms heavily associated with humans, including Staphylococcus, one of the most common skin and nose bacteria, and Streptococcus, a dominant genus in the human mouth.

At high elevation, microbes are often killed by ultraviolet light, cold temperatures and low water availability. Only the hardiest critters survive. Most—like the microbes carried up great heights by humans—go dormant or die, but there is a chance that organisms like Naganishia may grow briefly when water and the perfect ray of sunlight provides enough heat to help it momentarily prosper. But even for the toughest of microbes, Mount Everest is a Hotel California: “You can check out any time you like/ But you can never leave.”

The researchers don’t expect this microscopic impact on Everest to significantly affect the broader environment. But this work does carry implications for the potential for life far beyond Earth, if one day humans step foot on Mars or beyond.

https://www.colorado.edu/today/2023/03/14/when-someone-sneezes-ever...

How DNA-PK Facilitates Repair from Double-Stranded DNA Breaks

Study shows new way to spur brain immune cells to clear toxic waste linked to Alzheimer's disease

A newly discovered "energy switch" in the immune cells of the brain may lead to the development of drugs for Alzheimer's disease, the most common form of dementia.

Scientists discovered that after blocking and turning off this "switch," brain immune cells called microglia were able to remove toxic proteins that can build up and lead to Alzheimer's disease.

Microglia tend to be damaged in people with the disease, which makes them less capable of clearing cellular toxic waste. To restore the clean-up function, the scientists "switched off" their inefficient metabolism by preventing a key enzyme from attaching to energy-generating parts of the immune cells.

The findings from lab experiments set the stage for developing drugs that can specifically target metabolism in brain immune cells in order to treat Alzheimer's disease, which contributes to 60% to 70% of all dementia cases globally. Such drugs are of high interest in health care. 

Researchers had previously shown that drugs that activated the toxic protein led to less toxic waste build-up in the brain, which improved the condition of mice with Alzheimer's disease. But how this worked was not clear.

The researchers now cracked the puzzle with their latest experiments on cells from mice with Alzheimer's. Their work revealed that the translocator protein is critical for the microglia immune cells of the brain to generate their own energy.

Microglia perform the important function of "gobbling up" and removing beta amyloid, a toxic protein whose build-up in the brain causes damage and death to nerve cells, resulting in Alzheimer's disease. To do their job properly and remove the toxic waste, the immune cells need a lot of energy.

The researchers showed that without the translocator protein, microglia from mice with Alzheimer's had an energy problem and could not remove the beta amyloid, which resulted in the disease worsening in the mice.

 Microglia lacking the translocator protein resembled damaged microglia observed in aging and Alzheimer's disease. These damaged microglia inefficiently produced energy and could not clean up toxic waste in mice with Alzheimer's disease.

The experiments also demonstrated that when the translocator protein is absent, an enzyme called hexokinase-2, which metabolizes sugar, kicks into action in microglia to compensate. The enzyme promotes an inefficient way for cells to produce energy. What was surprising was that hexokinase-2 became activated when it stuck to the energy-generating parts of cells called mitochondria.

The researchers found that hexokinase-2 was also activated in microglia when exposed to more toxic forms of beta amyloid, just as happens in Alzheimer's disease. The scientists believe this finding helps to partly explain how microglia fail in patients with Alzheimer's disease and when people age.
Part1

To manipulate the enzyme's role in microglia energy production, the  researchers developed a light-activated tool. Their tool involves shining blue light onto a genetically modified version of the hexokinase-2 enzyme to "switch off" one of its functions.

When this happens, it blocks the enzyme's ability to stick to the energy-generating parts of the microglia and forces the cells to stop relying on an inefficient method of energy production. Experimental results showed that this improves their ability to clear beta amyloid by nearly 20 percent.

However, if hexokinase-2's sticking ability is not blocked and its function is disrupted by simply inactivating the enzyme, it does not help the microglia to clear away waste. This insight provides a critical clue for future drug targets.

Lauren H. Fairley et al, Mitochondrial control of microglial phagocytosis by the translocator protein and hexokinase 2 in Alzheimer's disease, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2209177120

Part 2

Researchers create virus-resistant, safely restrained E. coli for medical, industrial applications

In a step forward for genetic engineering and synthetic biology, researchers have modified a strain of Escherichia coli bacteria to be immune to natural viral infections while also minimizing the potential for the bacteria or their modified genes to escape into the wild. The work promises to reduce the threats of viral contamination when harnessing bacteria to produce medicines such as insulin as well as other useful substances, such as biofuels.

Currently, viruses that infect vats of bacteria can halt production, compromise drug safety, and cost millions of dollars.

 So far, based on extensive laboratory experiments and computational analysis, Researchers haven't found a virus that can break the bacterium. 

The work also provides the first built-in safety measure that prevents modified genetic material  from being incorporated into natural cells.

Akos Nyerges et al, A swapped genetic code prevents viral infections and gene transfer, Nature (2023). DOI: 10.1038/s41586-023-05824-z. www.nature.com/articles/s41586-023-05824-z

Why Are Electric Vehicle Fires So Hard To Put Out?

Antibody fragment-nanoparticle therapeutic eradicates cancer
A novel cancer therapeutic, combining antibody fragments with molecularly engineered nanoparticles, permanently eradicated gastric cancer in treated mice, a multi-institutional team of researchers found.

The results of the “hit and run” drug delivery system, published in the March issue of Advanced Therapeutics, were the culmination of more than five years of collaboration between various research groups.
Targeted cancer treatments such as antibody and nanoparticle therapies have seen narrow clinical use because of each therapy’s limitations, but the new therapeutic – an evolution of what the researchers call Cornell prime dots, or C’ dots – combines the best attributes of both into an ultrasmall, powerfully effective system.

As silica nanoparticles just 6 nanometers in size, C’ dots are small enough to penetrate tumors and safely pass through organs once injected into the body. Scientists first developed them more than 15 years ago and published a 2018 study that found an antibody fragment-nanoparticle hybrid to be especially effective in finding tumors.

This collaborative work with AstraZeneca set off the search for a new, molecularly engineered therapeutic version of this immuno-conjugate.

AstraZeneca “site engineered” fragments of antibodies so they would effectively attach to the C’ dots and target HER2 proteins associated with gastric cancer. The researchers optimized fragment conjugation to the C’ dot surface, along with specialized inhibitor drugs developed by AstraZeneca. This enabled the nanoparticles to carry about five times more drugs than most antibodies.

The final product was a version of C’ dots, armed with cancer-targeting antibody fragments and a large drug payload, all packed into a sub-7-nanometer, drug-immune conjugate therapy – a first of its kind in that size class, according to the researchers.

https://onlinelibrary.wiley.com/doi/10.1002/adtp.202200209