How a biological pathway leads stem cells to die or regenerate

A new study has determined that altering a cellular process can lead stem cells—cells from which other cells in the body develop—to die or regenerate.

The findings, published in the journal Cell Stem Cell, may assist in the development of new drugs that can manipulate this process to slow or stop cancer from growing and spreading, and enable regeneration in the context of other diseases.

If you have too much cell division, you end up with tumors. If you have too little, you have poor replacement of old cells.

The body's cells are regulated by various biological pathways. Each pathway involves a series of molecular actions inside a cell that produce a change in the cell, like creating a new molecule, such as a protein.

For this study, investigators  observed the effects of a gene called Discs large 1 (Dlg1) on the Wnt signaling pathway. This pathway involves a series of molecular interactions that regulate the growth or death of stem cells.

The Wnt pathway, which begins on the surface of a cell and ends inside of it, is critical for stem cell renewal and tissue regeneration. Although the pathway has been studied extensively, much is still unknown about how small increases and decreases in the frequency of communication signals through the pathway may affect the creation of new cells.

The signals or instructions can vary over time and under different conditions of health and disease.

Investigators studied intestinal tissue samples from laboratory mice to learn how mutations in Dlg1 affect the interaction between Wnt signaling and stem cells in the highly regenerative gastrointestinal tract. By performing gene expression analysis on the samples, the team looked for changes in genes that typically send signals along the Wnt pathway.

Through this process, investigators were able to see how changes in signaling frequency affected the creation of stem cells. The investigators found that when they inhibited the expression of Dlg1 and then increased signaling along the Wnt pathway by the addition of a specific molecule, such as a virus or drug, the stem cells died rather than generate new daughter cells.

 Ophir D. Klein, A DLG1-ARHGAP31-CDC42 axis is essential for the intestinal stem cell response to fluctuating niche Wnt signaling, Cell Stem Cell (2023). DOI: 10.1016/j.stem.2022.12.008. www.cell.com/cell-stem-cell/fu … 1934-5909(22)00492-1

Raman spectroscopy method for rapid identification of beer spoilage bacteria

In a study published in Analytical Methods, a research group proposed the rapid detection of beer spoilage bacteria based on label-free surface-enhanced Raman spectroscopy (SERS) technology.

Lactic acid bacteria are common spoilage bacteria in beer and need to be monitored and controlled at all stages of beer production. Traditional spoilage bacteria detection methods are time-consuming and cannot meet the demand for real-time, in-situ, rapid detection during the production process.

Raman spectroscopy has been widely used for microbial detection due to its fast, non-destructive and accurate properties, but conventional Raman spectroscopy has the disadvantage of poor signal-to-noise ratio, which affects the accuracy of microbial identification.

Compared with conventional Raman spectroscopy, the SERS technique has a stronger and more sensitive signal and is well suited to the detection of beer spoilage bacteria. Furthermore, the label-free SERS technique is ideal for commercialization due to its low cost and good results.

In this study, the researchers improved the existing process for the preparation of label-free SERS silver nanoparticles (AgNPs). The effect of the AgNPs@KCl agglomeration effect on SERS enhancement was investigated. Eight species of beer spoilage bacteria produced during the beer brewing process were identified by SERS.

The researchers further investigated the effect of the method on the final identification rate by combining the t-distributed stochastic neighbor embedding (t-SNE) dimensionality reduction analysis algorithm, Support Vector Machine (SVM), k-NearestNeighbor (KNN) and Linear Discriminant Analysis (LDA) machine learning algorithms. All three machine learning algorithms achieved an accuracy of around 90% and performed well in identifying beer spoilage bacteria.

In the stability analysis and mixing tests, two known spoilage bacteria were mixed with pure beer and incubated at constant temperature for a period of time to identify the bacteria in the beer. The two spoilage bacteria were successfully detected in the samples and had good spectral stability.

According to the final validation study, the technique can indeed identify the target spoilage bacteria from the simulated samples, which is of great significance to the rapid identification of spoilage bacteria in the beer brewing process.

Lindong Shang et al, Rapid detection of beer spoilage bacteria based on label-free SERS technology, Analytical Methods (2022). DOI: 10.1039/D2AY01221A

Migrating birds: Disturbances in magnetic field suspected when bird...

It seems logical enough that bad weather can sometimes cause birds to become disoriented during their annual fall migrations—causing them to wind up in territory they're unaccustomed to. But why, even when weather is not a major factor, do birds travel far away from their usual routes?

Novel lipstick formula could offer protection against a variety of disease-causing microorganisms.

Lipstick can be a confidence booster, enhance a costume and keep lips from chapping. But sharing a tube with a friend or family member can also spread infections. To develop a version with antimicrobial properties, researchers reporting in ACS Applied Materials & Interfaces have added cranberry extract to the formulation. Their deep red cream quickly inactivates disease-causing viruses, bacteria and a fungus that come in contact with it.

According to historians, people in ancient Egypt were the first to use make-up, applying pastes made from minerals and other substances in their environment. The formulations have evolved over the centuries, but now researchers have come full circle, looking again toward natural ingredients. For example, recent studies have reported that lipstick formulas incorporating natural colorants, such as red dragon fruit, can result in products with both vibrant colors and antimicrobial activity. And previously, cranberry extract has been shown to inactivate viruses, bacteria and fungi. So, researchers wanted to use cranberry extract to create a deep red lip tint with antimicrobial properties.

They mixed cranberry extract into a lipstick cream base, which contained shea butter, vitamin E, provitamin B5, babassu oil and avocado oil. In experiments, the reddened cream was added to cultures containing different viruses, bacteria and one fungal species. Both enveloped and non-enveloped virus types were completely inactivated within a minute of contact with the cranberry-containing cream. And the multidrug-resistant bacteria, mycobacteria and fungus were substantially inactivated within five hours of applying the cream. The researchers suggest that their novel lipstick formula could offer protection against a variety of disease-causing microorganisms.

https://www.acs.org/pressroom/presspacs/2022/acs-presspac-december-...

https://pubs.acs.org/doi/abs/10.1021/acsami.2c19460

Blue light might be bad for humans - but good for mangoes

 We’re often told to limit our “screen time,” thanks in part to the harsh blue light that screens can emit. Plants can detect blue light too, but instead of causing sleepless nights for our green friends, it could help make their fruits taste better. Researchers now report in ACS’ Journal of Agricultural and Food Chemistry that mangoes can become redder, sweeter and more ripe when exposed to blue light over several days.

Plants rely on sunlight to carry out photosynthesis and ripen their fruits. Studies have shown that exposure to light can affect the appearance of some fruits’ peels and can increase the amount of sugar and pigments in fruits such as tomatoes, which contain chlorophyll throughout their flesh. However, other fruits such as mangoes only contain this pigment in their thick peels, which could change how light affects the flesh. Plus, sunlight contains many colors, so different wavelengths could have different effects. So, researchers wanted to investigate how blue light impacts the quality and ripeness of mangoes.

To understand this phenomenon, the researchers placed a group of mangoes in blue light and another group in darkness for nine days. They found that mangoes in blue light contained far more anthocyanins in their peels, making them redder than those left in the dark. The flesh of these mangoes was also softer, sweeter and more yellow, and had more sucrose and carotenoids than the other group. In further tests, the team found that light-responsive genes involved in the photosynthesis pathway, as well as key genes involved in producing sucrose, anthocyanin and carotenoids, were upregulated under blue light. This meant that the mangoes could directly perceive this light and trigger an internal genetic signaling pathway, say the researchers. The effect was more pronounced in the peel than in the flesh, indicating that the blue light did not penetrate much past the skin. The researchers say that this work could help shed light on the complex relationship behind colored light and the internal quality of fruit.

https://www.acs.org/pressroom/presspacs/2022/acs-presspac-december-....

https://pubs.acs.org/doi/abs/10.1021/acs.jafc.2c07137

How Rocky Planets Form

Humans Are Still Evolving Thanks to Microgenes

A study sheds light on the tiny genes that have evolved in human genomes since we split from our mammalian ancestors.

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Humans are still evolving new genes, according to a study published in Cell Reports on December 20. As our lineage evolved, at least 155 human genes sprung up from DNA regions previously thought of as “junk,” including two human-specific genes that emerged since humans branched off from chimpanzees around 4 to 6 million years ago, the researchers report.

The genes described in the new study went undiscovered for so long because they’re teeny: They top out at about 300 nucleotides in length, while a typical human gene is 10 to 15,000 base pairs on average. Even though they possess start and stop codons that allow them to be read by cells’ transcriptional machinery just like traditional genes, these so-called microgenes—sometimes called short open reading frames (sORFs)—have long been assumed to be nonfunctional.

But recent studies found that knocking out sORFs stunts cell growth, indicating they’re important after all. One 2020 study, for example, found hundreds of functional sORFs in human cells, both in the coding and noncoding regions of the genome. The number was intriguing to evolutionary biologists and they were compelled to investigate these genetic oddities further, launching what became the newly published research. “We find species-specific genes everywhere,” the researchers say. “So there has to be an evolutionary route for them to originate.”

Using data from the 2020 study, the team scanned human and vertebrate genomes for functional sORFs that produced proteins. Then, using known human and vertebrate phylogenetic information, they predicted the evolutionary relationships among the sORFs estimated when in evolutionary history new microgenes had come about.

Through this process, the team identified 155 microgenes that all vertebrates share. Forty-four of these are critical for cell growth, according to data from the previous study. Three have disease markers associated with ailments such as muscular dystrophy, retinitis pigmentosa, and Alazami syndrome. The team also found one microgene—associated with human heart tissue—that cropped up after chimps and humans split off from gorillas about 7 to 9 million years ago.

The researchers found that these new genes had emerged from the noncoding regions of DNA, rather than by mutation or duplication of existing genes. While gene duplication is thought to be the main source of new genes in all species, the appearance of microgenes might explain how humans developed some uniquely human characteristics, as well as how other animals gained uniquely species-specific phenotypes.

https://www.cell.com/cell-reports/fulltext/S2211-1247(22)01696-5?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124722016965%3Fshowall%3Dtrue

Mucus-Eating Gut Bacteria May Promote Fever After Cancer Treatment

The expansion of mucus-degraders in the mouse gut—possibly due to poor nutrition—thins the colon’s mucus layer and may weaken defenses against blood-infecting microbes.

One of the most common consequences of cytotoxic cancer treatments, such as chemotherapy and radiation, is the loss of a type of white blood cell called neutrophils—a phenomenon known as neutropenia. In some severe cases of neutropenia, patients develop a fever. Research published November 16 in Science Translational Medicine links this fever to mucus-degrading bacteria in the gut, specifically the commensal Akkermansia muciniphila. The study authors show that these microbes thin the mucus layer in mice, potentially exposing hosts to further bacterial infections—a finding that hints at possible ways to stave off treatment-related fevers in humans.

https://www.science.org/doi/10.1126/scitranslmed.abo3445

Building blocks of life found in meteorite that crash landed on Earth

New research has been published on the organic analysis of the Winchcombe meteorite that crash landed onto a driveway in Winchcombe, Gloucestershire in 2021. The research found organic compounds from space that hold the secrets to the origin of life.

In the study, the analysis found a range of organic matter, which reveals that the meteorite was once from part of an asteroid where liquid water occurred, and if it that asteroid had been given access to the water, a chemical reaction could have occurred leading to more molecules turning into amino acids and protein—the building blocks of life. The Winchcombe meteorite is a rare carbon rich chondritic meteorite (approximately 4% of all recovered meteorites, containing up to 3.5 weight percent of carbon) and is the first ever meteorite of this type to be found in the U.K. with an observed meteorite fall event, with more than 1,000 eyewitnesses and numerous footages of the fireball. The amino acid abundance of Winchcombe is ten times lower than other types of carbonaceous chondritic meteorites and was a challenge to study due to the limited detection of amino acids, but with the meteorite so promptly recovered and curated, the team were able to study the organic content of the meteorite prior to its interaction with the Earth's environment. The organic matter suggests the meteorite could represent a class of unique, weak meteorite not previously studied.

Winchcombe belongs to a rare type of carbonaceous meteorite which typically contains a rich inventory of organic compounds and water. The first Winchcombe meteorite stone was recovered within 12 hours of the fireball observation event and properly curated to restrict any terrestrial contamination. This allowed the researchers to study the organic signature truly essential to the meteorite itself.

Studying the organic inventory of the Winchcombe meteorite provided scientists with a window into the past, how simple chemistry kick started the origin of life at the birth of our solar system. Discovering these life's precursor organic molecules allowed them to comprehend the fall of similar material to the surface of the Earth, prior to the emergence of life on our own planet.

Queenie H. S. Chan et al, The amino acid and polycyclic aromatic hydrocarbon compositions of the promptly recovered CM2 Winchcombe carbonaceous chondrite, Meteoritics & Planetary Science (2023). DOI: 10.1111/maps.13936

Does Light Experience Time?

Mathematics at the speed of light

Researchers created a nanostructured surface capable of solving equations using light. This discovery opens exciting new opportunities in the field of analog processing based on optical metasurfaces.

The world's ever-growing needs for efficient computing have been driving researchers from diverse research fields to explore alternatives to the current digital computing paradigm. The processing speed and energy efficiency of standard electronics have become limiting factors for novel disruptive applications entering our everyday life, such as artificial intelligence, machine learning, computer vision, and many more. In this context, analog computing has resurfaced and regained significant attention as a complementary route to traditional architectures.

Optical analog processing refers to the use of light to perform analog computations, as opposed to traditional electronic methods which use electricity. One major benefit of using light to perform specific computing tasks is that it can operate at much higher speeds than electronic methods, as the computation is performed at the speed of light traveling through very thin nanostructured surfaces called metasurfaces. In addition, optical analog processing can be more energy efficient than electronic methods, since it does not generate heat in the same way that electronic circuits do. This makes it well-suited for use in high-performance computing applications where speed and energy efficiency are important.

The  researchers developed a thin dielectric nanostructure, called a metagrating, and incorporated a semi-transparent mirror into the sample to continuously send back the signal to the nanostructures, each time multiplied by the metagrating scattering matrix.

They used  a special optimization technique to design the unit cell of the nanostructured array, or metagrating, that can perform the desired matrix multiplication. Each mathematical problem requires a specific design for the metagrating, but in theory one could engineer a surface with multiple parallel gratings to solve several integral equations in parallel.

These results demonstrate the possibility of solving complex mathematical problems and a generic matrix inversion at speeds that are far beyond those of the typical digital computing methods. Indeed, the solution converges in about 349 fs (i.e., less than one thousand-millionth of a second), orders of magnitude faster than the clock speed of a conventional processor.

Andrea Cordaro et al, Solving integral equations in free space with inverse-designed ultrathin optical metagratings, Nature Nanotechnology (2023). DOI: 10.1038/s41565-022-01297-9

Highly accurate test for common respiratory viruses uses DNA as 'bait'

Researchers have developed a new test that "fishes" for multiple respiratory viruses at once using single strands of DNA as bait and gives highly accurate results in under an hour.

The test uses DNA "nanobait" to detect the most common respiratory viruses—including influenza, rhinovirus, RSV and COVID-19—at the same time. In comparison, PCR (polymerase chain reaction) tests, while highly specific and highly accurate, can only test for a single virus at a time and take several hours to return a result.

While many common respiratory viruses have similar symptoms, they require different treatments. By testing for multiple viruses at once, the researchers say their test will ensure patients get the right treatment quickly and could also reduce the unwarranted use of antibiotics.

In addition, the tests can be used in any setting, and can be easily modified to detect different bacteria and viruses, including potential new variants of SARS-CoV-2, the virus which causes COVID-19. 

The researchers based their test on structures built from double strands of DNA with overhanging single strands. These single strands are the "bait": they are programmed to "fish" for specific regions in the RNA of target viruses. The nanobaits are then passed through very tiny holes called nanopores. Nanopore sensing is like a ticker tape reader that transforms molecular structures into digital information in milliseconds. The structure of each nanobait reveals the target virus or its variant.

The researchers showed that the test can easily be reprogrammed to discriminate between viral variants, including variants of the virus that causes COVID-19. The approach enables near 100% specificity due to the precision of the programmable nanobait structures.

Ulrich Keyser, Simultaneous identification of viruses and viral variants with programmable DNA nanobait, Nature Nanotechnology (2023). DOI: 10.1038/s41565-022-01287-x. www.nature.com/articles/s41565-022-01287-x

Blood vessel protein found to reduce mortality in infectious disease

The vascular system plays an essential role in carrying oxygen and nutrients throughout the body, but too much vascular permeability, or space between the cells lining the blood vessels, can have devastating results. Recently, researchers  have shed new light on a key protein involved in vascular permeability and its impact on mortality in infectious disease.

In a new study published in PNAS, researchers  have demonstrated the potential of endothelial cell-specific protein Roundabout4 (Robo4) as a therapeutic target to reduce mortality resulting from severe infection. Robo4 is expressed by endothelial cells that line the blood vessels. These cells regulate vascular permeability and allow for the exchange of substances from the blood vessels into the surrounding tissue and vice versa.

During the body's immune response, vascular permeability facilitates the movement of important immune cells and the elimination of dangerous pathogens. However, in severe immune responses, such as may occur in infectious diseases like COVID-19, an excessive increase in vascular permeability, known as vascular hyperpermeability, may lead to organ damage and death.

Currently, no drugs directly suppress vascular hyperpermeability. Because Robo4 has been previously shown to play a role in vascular permeability, the researchers  set out to explore Robo4 as a potential target to reduce vascular permeability in severe infection.

To investigate the effects of Robo4 on vascular hyperpermeability, researchers generated an endothelial cell-specific mouse model of conditional Robo4 overexpression. Upon exposing these mice to lipopolysaccharide (LPS), which induces a severe immune response, the mice exhibited decreased vascular permeability and increased rates of survival.

 Researchers found  that treatment with ALK1 inhibitor increases Robo4 expression and reduces mortality in mice under sepsis and SARS-CoV-2 conditions. Increasing Robo4 expression may represent a strategy to reduce vascular permeability and alleviate severe infections.

The researchers screened a library of drugs using a mouse endothelial cell line to identify pathways that are involved in the regulation of Robo4 and found that two competitive SMAD signaling pathways appear to regulate Robo4 expression. When the researchers treated LPS-injected mice with a drug that inhibits ALK1-SMAD signaling, they observed increased Robo4 expression, decreased vascular permeability, and reduced mortality. A reduction in mortality was also observed in mice exposed to SARS-CoV-2, the virus that causes COVID-19.

Maaya Morita et al, Upregulation of Robo4 expression by SMAD signaling suppresses vascular permeability and mortality in endotoxemia and COVID-19 models, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2213317120

How the last 12,000 years have shaped what humans are today

How the last 12,000 years have shaped what humans are today

While humans have been evolving for millions of years, the past 12,000 years have been among the most dynamic and impactful for the way we live today, according to an anthropologist who organized a special journal feature on the topic in the Proceedings of the National Academy of Sciences.

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Our toilets can yield excellent alternatives for widespread polluti...

To tackle the climate crisis, biodiversity loss, and pollution, humanity will need to move to a circular economy, where all resources are recycled. Why not recycle our own body waste too as fertilizer, provided there is no risk that harmful microbes or traces from pharmaceuticals end up in the consumed crops? Most nutrients needed for plant growth occur in human urine and feces. Urine is especially rich in nitrogen and potassium, and also contains trace amounts of metals such as boron, zinc, and iron. Feces could in theory supply other nutrients such as phosphorus, calcium, and magnesium or valuable organic carbon to soils.

Study finds that UV-emitting nail polish dryers damage DNA and cause mutations in cells

The ultraviolet nail polish drying devices used to cure gel manicures may pose more of a public health concern than previously thought. Researchers at the University of California San Diego have studied these ultraviolet (UV) light emitting devices, and found that their use leads to cell death and cancer-causing mutations in human cells.

Eating one wild fish same as month of drinking tainted water: study

Eating one freshwater fish caught in a river or lake in the United States is the equivalent of drinking a month's worth of water contaminated with toxic "forever chemicals", new research said recently.

The invisible chemicals called PFAS were first developed in the 1940s to resist water and heat, and are now used in items such as non-stick pans, textiles, fire suppression foams and food packaging.

But the indestructibility of PFAS, per- and polyfluoroalkyl substances, means the pollutants have built up over time in the air, soil, lakes, rivers, food, drinking water and even our bodies.

There have been growing calls for stricter regulation for PFAS, which have been linked to a range of serious health issues including liver damage, high cholesterol, reduced immune responses and several kinds of cancer.

To find out PFAS contamination in locally caught fish, a team of researchers analyzed more than 500 samples from rivers and lakes across the United States between 2013 and 2015.

The median level of PFAS in the fish was 9,500 nanogrammes per kilogram, according to a new study published in the journal Environmental Research.

Eating just one freshwater fish equalled drinking water with PFOS at 48 parts per trillion for a month, the researchers calculated.

Nadia Barbo et al, Locally caught freshwater fish across the United States are likely a significant source of exposure to PFOS and other perfluorinated compounds, Environmental Research (2022). DOI: 10.1016/j.envres.2022.115165

Unusual compound found in Rembrandt's The Night Watch

An international team of scientists from the Rijksmuseum, the CNRS, the ESRF the European Synchrotron, the University of Amsterdam and the University of Antwerp, have discovered a rare lead compound (named lead formate) in Rembrandt's masterpiece The Night Watch. This discovery, which is a first in the history of the scientific study of paintings, provides new insight into 17th-century painting technique and the conservation history of the painting. The study is published in Angewandte Chemie International Edition.

 How iron dysregulation might contribute to neurodegenerative diseases

Past neuroscience research consistently found a link between deviations from the "normal" iron metabolism, also known as iron dysregulation, and different neurodegenerative diseases, including Parkinson's disease (PD) and Multiple Sclerosis (MS). Specifically, brain regions associated with these diseases have been found to be often populated by microglia (i.e., resident immune cells) packed with Iron.

While the association between iron dysregulation and neurodegenerative diseases is well documented, the ways in which iron accumulation affects the physiology of microglia and neurodegeneration are yet to be fully grasped. Researchers  have recently carried out a study aimed at filling this gap in the literature, by better understanding how microglia respond to iron.

For years it has been known that iron accumulates in affected brain regions in PD, MS and other neurodegenerative diseases.

The key objective of the recent work  was to better understand how iron accumulation in microglia affects these cells' functioning and health. Their work builds on their previous studies, and on the 2012 discovery of an iron-dependent form of cell death, known as ferroptosis.

Ferroptosis is a form of cell death that is mediated by iron-dependent lipid peroxidation, a process that damages lipids by oxidizing them. In their paper, the researchers' hypothesized that iron-laden microglia are susceptible to ferroptosis and that this might play a role in neurodegenerative diseases.

To conduct their experiments, the researchers grew microglia in a tri-culture system. Using a series of genetic and experimental techniques, they then showed that these microglia are highly responsive to iron and also susceptible to ferroptosis.

In addition, the team showed that an overload of iron causes a shift in the microglial transcriptional state, which overlaps with a transcriptomic signature observed in microglia in brain tissue from deceased patients with PD. When they removed microglia from their tri-culture system, the researchers observed that iron-induced neurotoxicity in the system significantly slowed down. This suggests that microglia responses to iron overload play a crucial role in neurodegeneration.

Sean K. Ryan et al, Microglia ferroptosis is regulated by SEC24B and contributes to neurodegeneration, Nature Neuroscience (2022). DOI: 10.1038/s41593-022-01221-3

Jonathan D. Proto et al, Disrupted microglial iron homeostasis in progressive multiple sclerosis, bioRxiv (2021). DOI: 10.1101/2021.05.09.443127

A molecular zoo of epigenetics

Our genes are encoded in the DNA sequence of the genome, which is highly similar across the diverse cell types of our body. Yet, each cell can only access those genes that are in an epigenetically permissive state. The epigenome thus provides a form of molecular access control to the genes—epigenetic "software" that protects our genetic "hardware" from activation in the wrong cells.

This layer of regulatory control has been essential for the development of complex organisms comprising of many hundred different cell types. Moreover, epigenetic regulation helps reduce our risk of cancer by protecting critical areas of the genome from accidental activation.

DNA methylation is the best known and arguably the most important epigenetic mechanism. Methyl groups (CH₃) mark those parts of the DNA that are to be tightly packaged and protected from faulty activation. DNA methylation has many roles throughout our lives—ranging from the fertilized egg to the adult organism, in diseases such as cancer and in the biological aging of our bodies.

DNA methylation provides the cells with epigenetic memory, ensuring that a liver cell always remains a liver cell and a heart cell always remains a heart cell—even though all cells in our body are equipped with the same genes.

DNA methylation is well-studied only in mammals, most notably in mice and humans. In a decade-long effort to fill critical gaps in our understanding of epigenetics, scientists from Bock's research group at CeMM have now mapped and analyzed DNA methylation profiles across 580 different animal species.

The data of the study data show that DNA methylation in animals followed very similar principles 500 million years ago as it does today.

Researchers looked at the relationship between DNA methylation and the underlying genetic DNA sequence in mammals, birds, reptiles, amphibians, fish and invertebrates. The patterns are very similar. For example, they were able to predict the distribution of DNA methylation in elephants genome using a model they  had created for the octopus. These epigenetic patterns therefore very likely existed in the last common ancestor of these animals, a very long time ago.

Part 1

The fundamental principles of DNA methylation thus appear highly conserved, enabling a deep look at the evolutionary history of vertebrates. However, this does not mean that DNA methylation remained unchanged over millions of years. The genetic code of epigenetics looks clearer and more prescriptive in vertebrates than in invertebrates, even though the underlying patterns are similar. And with the emergence of reptiles, birds, and mammals, the genetic determinants of DNA methylation become even more pronounced. It seems that complex animals including humans particularly depend on epigenetic protection of the genome through DNA methylation.

Large animals with a long lifespan should in theory have a higher risk of cancer, because their bodies consist of many more cells, and these cells have more time to develop into cancer cells. Yet elephants are no more likely to develop cancer than mice or trout. Scientists refer to this as Peto's paradox. The most plausible explanation is that large animals with a long lifespan have evolved special mechanisms that substantially reduce their cancer risk.

Results from the current study indicate that DNA methylation constitutes such a cancer-protective mechanism. Higher theoretical risk of cancer was generally associated with higher DNA methylation levels. This correlation was particularly evident in birds. Most birds have a low risk of cancer, even big birds with long lifespans such as eagles and penguins. The higher DNA methylation levels in large and long-lived birds may thus help protect them against cancer.

Overall, this study provides the most comprehensive analysis of epigenetics in its evolutionary context to date. It also establishes new methods for studying DNA methylation in diverse animal species. For many species, no high-quality genomes are yet available, which is why the team developed and optimized a method the analyze DNA methylation independently of any reference genomes.

This new method allows us to explore the interplay of genetics and epigenetics in all those animal species that were hardly accessible for epigenetic analyses. Hopefully, such evolutionary and comparative analyses will lead to a better understanding of epigenetics in humans, in diseases such as cancer, and in healthy aging.

Johanna Klughammer et al, Comparative analysis of genome-scale, base-resolution DNA methylation profiles across 580 animal species, Nature Communications (2023). DOI: 10.1038/s41467-022-34828-y

Part 2

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New study shows 'self-cleaning' of marine atmosphere

Scientists have shed new light on the "self-cleaning" capacity of the atmosphere.

This process of self-cleaning is essential to remove gaseous pollutants and regulate green house gasses such as methane from the atmosphere.

Researchers were already aware that the atmosphere had this "self-cleaning" ability, but in a new study, experts have now shown a new process that increases the ability of the marine atmosphere to self-cleanse.

Using a combination of aircraft and ground-based observations, scientists were able to confirm the widespread presence of nitrous oxide (HONO) in the remote Atlantic troposphere formed by so-called "renoxification", whereby photolysis of aerosol nitrate returns nitrogen oxides (NOx) and HONO to the marine atmosphere. Historically, aerosol nitrate had been considered a permanent sink for NOx. This new process could increase the ability of the atmosphere to self-cleanse on a global scale. Scientists say the findings, published in Science Advances, could be highly significant for atmospheric chemistry and largely reconcile widespread uncertainty on the importance of renoxification.

Importantly, the observations showed that the efficiency of renoxification increased with relative humidity and decreased with the concentration of nitrate." "This observation reconciled the very large discrepancies in the rates of renoxification found across multiple laboratory and field studies." "It was also consistent with renoxification occurring on the surface of aerosols, rather than within their bulk, a new and exciting finding with implications for how this fundamental process is controlled and parameterized in models." Recycling of nitrogen oxides on nitrate aerosol could have important, increasing, and as yet unexplored implications for the trends and distributions of atmospheric oxidants such as tropospheric ozone, an important greenhouse gas.

Simone Andersen et al, Extensive field evidence for the release of HONO from the photolysis of nitrate aerosols, Science Advances (2023). DOI: 10.1126/sciadv.add6266. www.science.org/doi/10.1126/sciadv.add6266

Scientists demonstrate quantum recoil for the first time

For the first time since it was proposed more than 80 years ago, scientists have demonstrated the phenomenon of "quantum recoil," which describes how the particle nature of light has a major impact on electrons moving through materials. The research is published online recently (January 19) in the journal Nature Photonics.

Making quantum recoil a practical reality should eventually allow businesses to more accurately produce X-rays of specific energy levels, leading to superior accuracy in healthcare and manufacturing applications such as medical imaging and flaw detection in semiconductor chips.

Quantum recoil was theorized by Russian physicist and Nobel laureate Vitaly Ginzburg in 1940 to accurately account for radiation emitted when charged particles like electrons move through a medium, such as water, or materials with repeated patterns on the surface, including those on butterfly wings and graphite.

This radiation is created when the moving electrons disturb atoms in the medium or the material. As the atoms return to an undisturbed state, they emit radiation, such as X-rays.

Although the electrons are supposed to lose energy and slow down when this happens, classical theory predicts that its impact on the emitted radiation is negligible.

However, Ginzburg posited that this assumption breaks down when considering the quantum electrodynamics theory that deals with how charged particles interact with an electromagnetic field, as well as how light interacts with matter.

According to the theory, when moving electrons decelerate after disturbing nearby atoms, the energy and momentum these electrons lose should be transferred to the radiation emitted. This happens because light exists as particles that have energy and momentum, and which move in a wave as radiation.

The transfer causes the energies of the radiation released to shift from classical predictions and also affects the slowing electrons by causing them to deviate from their path of travel.

This phenomenon is known as quantum recoil. However, no one has been able to experimentally prove it—until now.

Physicists now demonstrated the phenomenon through separate experiments that bombarded electrons from a scanning electron microscope onto two very thin materials, about 1,000 times thinner than a strand of hair.

The two materials were boron nitride in a hexagonal form often used as a lubricant in paints, and graphite which is used to make rechargeable battery terminals and also found in pencil lead.

Using an energy dispersive X-ray spectrometer detector, the researchers measured the X-rays emitted from this bombardment and found that they had energies that were different from those predicted by classical theory but could instead be explained by quantum recoil.

Sunchao Huang et al, Quantum recoil in free-electron interactions with atomic lattices, Nature Photonics (2023). DOI: 10.1038/s41566-022-01132-6. www.nature.com/articles/s41566-022-01132-6

'Living medicine' created to tackle drug-resistant lung infections

Researchers have designed the first "living medicine" to treat lung infections. The treatment targets Pseudomonas aeruginosa, a type of bacteria that is naturally resistant to many types of antibiotics and is a common source of infections in hospitals.

The treatment involves using a modified version of the bacterium Mycoplasma pneumoniae, removing its ability to cause disease and repurposing it to attack P. aeruginosa instead. The modified bacterium is used in combination with low doses of antibiotics that would otherwise not work on their own.

Researchers tested the efficacy of the treatment in mice, finding that it significantly reduced lung infections. The "living medicine" doubled mouse survival rate compared to not using any treatment. Administering a single, high dose of the treatment showed no signs of toxicity in the lungs. Once the treatment had finished its course, the innate immune system cleared the modified bacteria in a period of four days.

Luis Serrano, Engineered live bacteria suppress Pseudomonas aeruginosa infection in mouse lung and dissolve endotracheal-tube biofilms, Nature Biotechnology (2023). DOI: 10.1038/s41587-022-01584-9. www.nature.com/articles/s41587-022-01584-9

Ariadna Montero‐Blay et al, Bacterial expression of a designed single‐chain IL ‐10 prevents severe lung inflammation, Molecular Systems Biology (2023). DOI: 10.15252/msb.202211037

Stopping a childhood cancer in its tracks

Ewing sarcoma causes tumors to grow in bones or the soft tissues surrounding them. Once a tumor begins to spread to other parts of the body, it can be very difficult to halt the disease's progression. Even for patients with positive outcomes, treating Ewing sarcoma often causes toxic side effects.

Scientists  have discovered a new drug target for Ewing sarcoma, a rare kind of cancer usually diagnosed in children and young adults. Their experiments show that the cells causing this cancer can essentially be reprogrammed with the flick of a genetic switch.

Shutting down a single protein forces the cancer cells to take on a new identity and behave like normal connective tissue cells, a dramatic change that reins in their growth. This discovery suggests researchers may be able to stop Ewing sarcoma by developing a drug that blocks the protein known as ETV6.

Christopher Vakoc, ETV6 dependency in Ewing sarcoma by antagonism of EWS-FLI1-mediated enhancer activation, Nature Cell Biology (2023). DOI: 10.1038/s41556-022-01060-1. www.nature.com/articles/s41556-022-01060-1

Why gas stoves matter to the climate, and the gas industry: Keeping...

Gas stoves are a leading source of hazardous indoor air pollution, but they emit only a tiny share of the greenhouse gases that warm the climate. Why, then, have they assumed such a heated role in climate politics?

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Quantum computer solves protein puzzle

Physicist and code specialist Dr. Sandipan Mohanty has been working on molecular biology simulations for the world's fastest supercomputers for 20 years. Such simulations help to unravel the building blocks of life and provide new insights into cellular machinery.

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Harvesting energy from moving trains

The Virginia Tech Center for Vehicle Systems and Safety (CVeSS) and the Railway Technologies Laboratory want to harness the energy created by moving trains and transform that energy into usable electricity.

New Swelling Technique Makes Cells Visible to the Naked Eye

A new technique, called Unclearing Microscopy, physically inflates and then stains cells to circumvent the need for expensive microscopes.

ABOVE:A sample of cells enlarged via Unclearing MicroscopyONS M’SAAD; CC-BY-NC-NC 4.0

Microscopes have been fine-tuned to image cells in granular detail, with the most sophisticated instruments capable of resolving individual atoms within a protein. The expense of microscopes creates an economic divide, however, hindering research at organizations with less funding.

In 2015, scientists developed a technique called expansion microscopy that physically enlarges cells, making some small features large enough to view with simple microscopes. In a preprint uploaded to bioRxiv on December 2, Bewersdorf and his colleague Ons M’Saad further developed the technique, enabling cells to be seen with the naked eye and increasing detail with a simple microscope.

The team developed a two-step strategy that involves both expanding and staining cells, and tested their technique on human cells and mouse brain tissue. First, they submerged the samples in a hydrogel solution containing small compounds that behave as liquid until they link up into polymer chains that absorb water and congeal into a gel. These included sodium polyacrylate, a super-absorbent powder found in diapers. After the cells take in the solution, water absorption swells the gel, physically expanding cells to about the same size as sesame seeds.

Cells remain invisible by this point because their contents have been diluted 8,000 times with water,” M’Saad tells The Scientist. “We needed to come up with an augmented stain to ‘unclear’ the cells so that they appear vivid.”

The new technique, which the team patented and named “Unclearing Microscopy,” involves two staining methods. The first uses large stainable polymers to augment the signal, making the cell more visible. The research team achieved this by targeting all the proteins in the cell with small molecules that subsequently link up with other compounds under light to produce large polymers that can be stained blue. The other technique involved depositing silver on the sample in increasing concentrations until the researchers determined the optimal dose that, in concert with the other technique, amplified the signal more than 100,000 times. This enhanced the contrast enough to view cells with the naked eye.

https://www.biorxiv.org/content/10.1101/2022.11.29.518361v1

Ripples in fabric of universe may reveal start of time

Scientists have advanced in discovering how to use ripples in space-time known as gravitational waves to peer back to the beginning of everything we know. The researchers say they can better understand the state of the cosmos shortly after the Big Bang by learning how these ripples in the fabric of the universe flow through planets and the gas between the galaxies.

We can't see the early universe directly, but maybe we can see it indirectly if we look at how gravitational waves from that time have affected matter and radiation that we can observe today.

adapted this technique from their research into fusion energy, the process powering the sun and stars that scientists are developing to create electricity on Earth without emitting greenhouse gases or producing long-lived radioactive waste. Fusion scientists calculate how electromagnetic waves move through plasma, the soup of electrons and atomic nuclei that fuels fusion facilities known as tokamaks and stellarators.

It turns out that this process resembles the movement of gravitational waves through matter. Researchers basically put plasma wave machinery to work on a gravitational wave problem.

Gravitational waves, first predicted by Albert Einstein in 1916 as a consequence of his theory of relativity, are disturbances in space-time caused by the movement of very dense objects. They travel at the speed of light and were first detected in 2015 by the Laser Interferometer Gravitational Wave Observatory (LIGO) through detectors in Washington State and Louisiana.

Researchers 

created formulas that could theoretically lead gravitational waves to reveal hidden properties about celestial bodies, like stars that are many light years away. As the waves flow through matter, they create light whose characteristics depend on the matter's density.

A physicist could analyze that light and discover properties about a star millions of light years away. This technique could also lead to discoveries about the smashing together of neutron stars and black holes, ultra-dense remnants of star deaths. They could even potentially reveal information about what was happening during the Big Bang and the early moments of our universe.

Deepen Garg et al, Gravitational wave modes in matter, Journal of Cosmology and Astroparticle Physics (2022). DOI: 10.1088/1475-7516/2022/08/017

74,963 Kinds of Ice

There are somewhere between 20 and 74,963 kinds of ice. Water can do all kinds of weird stuff when it freezes. So far scientists have experimentally shown crystal structures for 19 kinds of ice. Or maybe 20, depending on who you ask. We’re going to charge through as many as we can in ten minutes or so.

Using origami DNA to trap large viruses and prevent infections

A team of researchers has found that it is possible to build origami DNA structures that can be used to trap large viruses. In their paper published in the journal Cell Reports Physical Science, the group describes how they built their structures and how well they worked when tested.

As the global pandemic continues, albeit in a less deadly phase, the medical science community continues to look for ways to prevent people from becoming infected with not just the SARS-CoV-2 virus, but all viruses. One such approach involves the use of structures designed to attract viruses and when they come close enough, to trap them. In this new effort, the researchers have tested the idea of using origami DNA. DNA origami involves strands of DNA manipulated to create two or three-dimensional shapes, all at the nanoscale. In this new work, the researchers expanded on prior work done by some of the team members who together had developed a process for using DNA origami to trap very small viral particles. To create larger traps for larger viruses, the team used both long and short strands of DNA that had been designed to stick together in useful ways. They then used them to create triangular 2D building blocks that when placed near each other would snap together like puzzle pieces. They then set to work creating structures that they believed could serve as virus traps. After confirming that the structures they had in mind had the desired shapes, they coated the insides of them with chemicals or antibodies that are known to bind with viruses. They then tested the traps by placing them in the vicinity of live viruses. They found that the traps worked as hoped, capturing viruses as large as 100nm in diameter. When trapped, viruses were unable to bond with other cells, thus preventing infections. The researchers tested their traps with several types of viruses—from Zika, to influenza to SARS-CoV-2—and found that they worked equally well on all of them. They also found that they could make them more durable by shining a UV light on them and by covering them with an oligosine polymer. They next plan to test their traps in live lab animals.

Alba Monferrer et al, DNA origami traps for large viruses, Cell Reports Physical Science (2023). DOI: 10.1016/j.xcrp.2022.101237

How antioxidants produced by mitochondria reach the cell surface to protect against death

Antioxidants are often advertised as a cure-all in nutrition and offered as dietary supplements. However, our body also produces such radical scavengers itself, one of which is coenzyme Q. Now researchers have discovered how the substance, which is produced in our mitochondria, reaches the cell surface and protects our cells from dying.

Coenzyme Q is an antioxidant that is essential for our body. A deficiency of coenzyme Q leads to serious diseases such as Leigh syndrome—a hereditary disease in which certain brain regions become affected and, among other things, muscle weakness  can occur. A deficiency of coenzyme Q is also one of the first signs of aging and can occur as early as the early 20s. But why can't we simply take this substance in with our food?

Because Coenzyme Q is a highly hydrophobic molecule that our bodies absorb very little from food.  But it is also a problem in our cells that coenzyme Q is not water soluble. The antioxidant is formed in mitochondria and must pass through the watery cell interior called cytoplasm to the surface of the cells in order to neutralize oxidized lipid species.

With this new research work, scientists have now been able to identify the proteins involved in coenzyme Q transport from the mitochondria to the cell surface.

The researchers found that an enzyme called STARD7 helps transport the coenzyme. This protein is not only localized in the mitochondria, but also inside the cytoplasm. The mitochondria actively transport coenzyme Q to the cell surface to protect cells from cell death. It is as if the mitochondria deliver band-aids to the surface to protect the cell. This again shows that mitochondria are not only important as an energy supplier for our cells, but also play crucial regulatory roles.

A precise understanding of this transport process will enable Coenzyme Q to be delivered into the cells of affected patients and thus provide a new therapeutic approach for diseases such as Leigh syndrome.

Soni Deshwal et al, Mitochondria regulate intracellular coenzyme Q transport and ferroptotic resistance via STARD7, Nature Cell Biology (2023). DOI: 10.1038/s41556-022-01071-y

Harnessing the healing power within our cells

Researchers have identified a pathway in cells that could be used to reprogram the body’s immune system to fight back against both chronic inflammatory and infectious diseases. Molecular bio-scientists have discovered that a molecule derived from glucose in immune cells can both stop bacteria growing and dampen inflammatory responses.

The effects of this molecule called ribulose-5-phosphate on bacteria are striking – it can cooperate with other immune factors to stop disease-causing strains of the E. coli bacteria from growing.  It also reprograms the immune system to switch off destructive inflammation, which contributes to both life-threatening infectious diseases such as sepsis as well as chronic inflammatory diseases like respiratory diseases, chronic liver disease, inflammatory bowel disease, rheumatoid arthritis, heart disease, stroke, diabetes and dementia.

The research was carried out on a strain of E. coli bacteria that causes approximately 80 per cent of urinary tract infections and is a common cause of sepsis. Pre-clinical trials were used to confirm the role of this pathway in controlling bacterial infections.

 Human cells were also used to demonstrate that ribulose-5-phosphate reduces the production of molecules that drive chronic inflammatory diseases.

Host-directed therapies which train our immune systems to fight infections, will become increasingly important as more types of bacteria become resistant to known antibiotics.

A bonus is that this strategy also switches off destructive inflammation, which gives it the potential to combat chronic disease.

By boosting the immune pathway that generates ribulose-5-phosphate, scientists may be able to give the body the power to fight back against inflammatory and infectious diseases – not one, but two of the major global challenges for human health.

Many current anti-inflammatory therapies target proteins on the outside of cells but because this pathway occurs inside cells, the researchers devised a new approach to target the pathway using mRNA technology.

Kaustav Das Gupta et al, HDAC7 is an immunometabolic switch triaging danger signals for engagement of antimicrobial versus inflammatory responses in macrophages, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2212813120

Microalgae abundance and proportions affect nutrient exchange in a coral symbiotic relationship

Milky Way found to be too big for its 'cosmological wall'

Is the Milky Way special, or, at least, is it in a special place in the universe? An international team of astronomers has found that the answer to that question is yes, in a way not previously appreciated. A new study shows that the Milky Way is too big for its "cosmological wall," something yet to be seen in other galaxies.

A cosmological wall is a flattened arrangement of galaxies found surrounding other galaxies, characterized by particularly empty regions called "voids" on either side of it. These voids seem to squash the galaxies together into a pancake-like shape to make the flattened arrangement. This wall environment, in this case called the Local Sheet, influences how the Milky Way and nearby galaxies rotate around their axes, in a more organized way than if we were in a random place in the universe, without a wall.

Typically, galaxies tend to be significantly smaller than this so-called wall. The Milky Way is found to be surprisingly massive in comparison to its cosmological wall, a rare cosmic occurrence.

The new findings are based on a state-of-the-art computer simulation, part of the IllustrisTNG project. The team simulated a volume of the universe nearly a billion light-years across that contains millions of galaxies. Only a handful—about a millionth of all the galaxies in the simulation—were as "special" as the Milky Way, i.e., both embedded in a cosmological wall like the Local Sheet, and as massive as our home galaxy.

M A Aragon-Calvo et al, The unusual Milky Way-local sheet system: implications for spin strength and alignment, Monthly Notices of the Royal Astronomical Society: Letters (2022). DOI: 10.1093/mnrasl/slac161

Head injury is associated with doubled mortality rate long-term

Adults who suffered any head injury during a 30-year study period had two times the rate of mortality than those who did not have any head injury, and mortality rates among those with moderate or severe head injuries were nearly three times higher, according to new research.

Head injury can be attributed to a number of causes, from motor vehicle crashes, unintentional falls, or sports injuries. What's more, head injury has been linked with a number of long-term health conditions, including disability, late-onset epilepsy, dementia, and stroke.

Studies have previously shown increased short-term mortality associated with head injuries primarily among hospitalized patients. This longitudinal study evaluated 30 years of data from over 13,000 community-dwelling participants (those not hospitalized or living in nursing home facilities) to determine if head injury has an impact on mortality rates in adults over the long term. Investigators found that 18.4 percent of the participants reported one or more head injuries during the study period, and of those who suffered a head injury, 12.4 percent were recorded as moderate or severe. The median period of time between a head injury and death was 4.7 years.

Death from all causes was recorded in 64.6 percent of those individuals who suffered a head injury, and in 54.6 percent of those without any head injury. Accounting for participant characteristics, investigators found that the mortality rate from all-causes among participants with a head injury was 2.21 times the mortality rate among those with no head injury. Further, the mortality rate among those with more severe head injuries was 2.87 times the mortality rate among those with no head injury.

Investigators also evaluated the data for specific causes of death among all participants. Overall, the most common causes of death were cancers, cardiovascular disease, and neurologic disorders (which include dementia, epilepsy, and stroke). Among individuals with head injuries, deaths caused by neurologic disorders and unintentional injury or trauma (like falls) occurred more frequently.

When investigators evaluated specific neurologic causes of death among participants with head injury, they found that nearly two-thirds of neurologic causes of death were attributed to neurodegenerative diseases, like Alzheimer's and Parkinson's disease. These diseases composed a greater proportion of overall deaths among individuals with head injury (14.2 percent) versus those without (6.6 percent).

This highlights the importance of safety measures, like wearing helmets and seatbelts, to prevent head injuries.

 Holly Elser et al, Head Injury and Long-term Mortality Risk in Community-Dwelling Adults, JAMA Neurology (2023). DOI: 10.1001/jamaneurol.2022.5024

Study reveals new genetic disorder that causes susceptibility to opportunistic infections

Researchers have discovered a new genetic disorder that causes immunodeficiency and profound susceptibility to opportunistic infections including a life-threatening fungal pneumonia.

The discovery, reported Jan. 20 in the journal Science Immunology, will help identify people who carry this in-born error of immunity (IEI).

IEIs, also known as primary immunodeficiencies, are genetic defects characterized by increased susceptibility to infectious diseases, autoimmunity, anti-inflammatory disorders, allergy, and in some cases, cancer.

To date, 485 different IEIs have been identified. It is now thought that they occur in one of every 1,000 to 5,000 births, making them as prevalent as other genetic disorders, including cystic fibrosis and Duchene's muscular dystrophy.

Despite recent medical advances, about half of patients with IEIs still lack a genetic diagnosis that could help them avoid debilitating illness and death. This new work helps with that. 

The error in this case is a mutation in the gene for the protein IRF4, a transcription factor that is pivotal for the development and function of B and T white blood cells, as well as other immune cells.

The researchers sequenced the protein-encoding regions of a boy's - who was suffering from severe and recurrent fungal, viral, mycobacterial, and other infections -  genome  and discovered a de novo IRF4 mutation, which originated in the patient and was not inherited from his parents.

In the current study, the researchers identified seven patients from six unrelated families across four continents with profound combination immunodeficiency who experienced recurrent and serious infections, including pneumonia caused by the fungus Pneumocystis jirovecii. Each patient had the same mutation in the DNA-binding domain of IRF4.

Extensive phenotyping of patients' blood cells revealed immune cell abnormalities associated with the disease, including impaired maturation of antibody-producing B cells, and reduced T-cell production of infection-fighting cytokines.

Two knock-in mouse models, in which the mutation was inserted into the mouse genome, exhibited a severe defect in antibody production consistent with the combined immune deficiency observed in the patients.

The researchers also discovered the mutation had a "multimorphic" effect detrimental to the activation and differentiation of immune cells.

While the mutant IRF4 binds to DNA with a higher affinity than the native form of the protein (in a hypermorphic way), its transcriptional activity in common, canonical genes is reduced (hypomorphic), and it binds to other DNA sites (in a neomorphic way), altering the protein's normal gene expression profile.

This multimorphic activity is a new mechanism for human disease. "We anticipate that variants with multimorphic activity may be more widespread in health and disease," the researchers concluded.

A multimorphic mutation in IRF4 causes human autosomal dominant combined immunodeficiency, Science Immunology (2023). DOI: 10.1126/sciimmunol.ade7953

Novel method helps recover obscured images

A novel method that produces a clear image by using a simple cost-effective random scattering medium in real time could help overcome problems of obscured images.

When light passes through a light-scattering material, it is diffused rather than absorbed, which means a clear image of the source object is lost. Scattering media include clouds, which poses problems for Earth-based astronomy, and body tissue, which affects medical imaging.

Previous methods for reconstructing scattered light have required some initial knowledge of the object and the ability to control the wavefront of light illuminating it. This has involved complicated optical elements and high vulnerability to motion and mechanical instability. Computational algorithms are then able to post-process the detected light to generate an image.

To get more efficient ways of reconstruction, speckle-correlation imaging was proposed. This extracts information about the source from fluctuations in the intensity, or speckles, in the transmitted light.

However, many of the technologies based on speckle-correlation need time-consuming and intricately calibrated computational reconstruction. Also, still missing is some information such as the image orientation and location.

Now researchers have developed a way to directly obtain a clear image from a single shot of the speckle image.

They passed light from a small standardized test object through a thin diffusing material. By moving a camera in a direction away from the diffuser, they were able to build a three-dimensional image, taking slices through the speckles.

By looking at enlarged sections of these images, the researchers, to their surprise, could directly see reproductions of the test object; they could see through the random diffuser with the naked eye and real-time video imaging. It required no complex equipment for the active control of light nor prior knowledge of the source or diffusion medium. They could also find the lost orientation information and location of the test object.

Jietao Liu et al, Directly and instantly seeing through random diffusers by self-imaging in scattering speckles, PhotoniX (2023). DOI: 10.1186/s43074-022-00080-2

A sugar cane pathogen is gearing up a new era of antibiotic discovery

A potent plant toxin with a unique way of killing harmful bacteria has emerged as one of the strongest new antibiotic candidates in decades.

The antibiotic, called albicidin, is produced by the bacterial plant pathogen Xanthomonas albilineans, which causes the devastating leaf scald disease in sugar cane. Albicidin is thought to be used by the pathogen to attack the plant, enabling its spread. It has been known for some time that albicidin is highly effective at killing bacteria including E. coli and S. aureus. These superbugs, notorious for their growing resistance to existing antibiotics, have prompted a vital need for effective new drugs.

Despite its antibiotic potential and low toxicity in pre-clinical experiments, pharmaceutical development of albicidin has been hampered because scientists did not know precisely how it interacted with its target, the bacterial enzyme DNA gyrase (gyrase). This enzyme binds to DNA and, through a series of elegant movements, twists it up, a process known as supercoiling which is vital for cells to function properly.

Now researchers  have exploited advances in cryo-electron microscopy to obtain a first snapshot of albicidin bound to gyrase. It showed that albicidin forms an L-shape, enabling it to interact with both the gyrase and the DNA in a unique way.

In order for gyrase to do its job, it must momentarily cut the DNA double helix. This is dangerous, as broken DNA is lethal to the cell. Normally, gyrase quickly joints the two pieces of DNA back together again as it works, but albicidin prevents it from happening, resulting in broken DNA and bacterial death. The effect of albicidin is akin to a spanner thrown between two gears.

The way albicidin interacts with gyrase is sufficiently different from existing antibiotics that the molecule and its derivatives are likely to be effective against many of the current antibiotic resistant bacteria.

 By the nature of the interaction, albicidin targets a really essential part of the enzyme and it's hard for bacteria to evolve resistance to that. Trials have already started to use this knowledge to produce new era antibiotics.

Jonathan Heddle, Molecular mechanism of topoisomerase poisoning by the peptide antibiotic albicidin, Nature Catalysis (2023). DOI: 10.1038/s41929-022-00904-1. www.nature.com/articles/s41929-022-00904-1

Researchers use bacterial communication as a target for new drugs

The pathogen Pseudomonas aeruginosa is the cause of a large number of serious infections and places a particular burden on immunocompromised patients. The increasing spread of antimicrobial resistance makes it even more difficult to combat the dreaded hospital pathogen.

A research team  has now discovered a new class of active compounds that disrupt the bacterium's chemical communication pathways. This not only reduces the pathogen's disease-causing properties, but also simultaneously enhances the effectiveness of antibiotics. 

Although bacteria are among the simplest life forms on our planet, in the course of evolution they have developed ways to communicate efficiently with one another. Unlike humans, their communication is not mediated with words but with chemical signals. This interaction also plays a fundamental role in infection processes of pathogenic bacteria in humans. For example, bacteria communicate to their swarm when it is time to produce substances that counteract the human immune system. Interfering with these communication pathways is a promising starting point for the development of new therapies.

The researchers  did not focus now on the communication messengers themselves, but on their receptors—i.e., the parts of the bacterium that are responsible for signal processing. In this specific case, the researchers targeted the receptor PqsR.

When this receptor is activated, inflammation-promoting substances and biofilms are formed, in which P. aeruginosa is largely protected from antibiotics. The drug class now described was chemically designed and optimized by the researchers so that it can attack its target PqsR as efficiently as possible. This was based on structural data obtained by X-ray crystallography. 

In further laboratory experiments, the scientists were able to show that the optimized substances reliably prevent the formation of the pro-inflammatory molecule pyocyanin in a large number of clinical isolates of P. aeruginosa. Furthermore, they were able to show that the new active ingredient is capable of impairing biofilm formation and can even further enhance the effect of the antibiotic tobramycin. Finally, the researchers were able to transfer the promising properties of their active substance to a mouse model. Here, the combined administration of tobramycin and the new PqsR inhibitor was able to combat the P. aeruginosa infection significantly better than either substance alone.

The authors see great potential in the new compound class for future application in humans. 

Mostafa M. Hamed et al, Towards Translation of PqsR Inverse Agonists: From In Vitro Efficacy Optimization to In Vivo Proof‐of‐Principle, Advanced Science (2023). DOI: 10.1002/advs.202204443

How cancer cells die: Scientists explore new pathways of pyroptosis, killer kin of apoptosis

You can't understand the life cycle of a cell without learning how they die. That is why the concept of apoptosis—programmed cell death—is taught in schools.

What's usually not taught is another way that cells die, a process called pyroptosis, an inflammatory and necrotic form of cell death that primarily involves cancer cells. During chemotherapy, apoptosis can morph into pyroptosis. For patients receiving chemo, apoptosis not only turns into pyroptosis, the process can help activate the immune system. Both the initiation of pyroptosis and activation of the immune system are mediated through specific protein pathways.

To date, most studies have connected chemotherapy-induced pyroptosis to a mediator protein called gasdermin E, which is typically thought of as the sole executioner in this process. Yet, an intriguing round of research has taken a deep dive into the process of pyroptosis, uncovering new molecular pathways that trigger this form of programmed cell death.

New discoveries have emerged from a novel series of investigations that challenge prevailing scientific wisdom about the way cells die under the influence of chemotherapy. The research sheds new light on pyroptosis in chemo-based cancer treatment by expanding the possible number of protein pathways involved in this form of cell death, and hinting that still other pathways may be found in the future.

In response to chemotherapy, the induction of apoptotic cell death can be converted to a form of lytic cell death called pyroptosis.

The term "lytic cell death," or "cell lysis," refers to the breakdown of a cell caused by irrevocable damage to its outermost membrane. A cell can't survive when its contents are spilling out through holes, and that's what pyroptosis is all about. It's bruising and violent—and aimed at cell death. During pyroptosis, a cascade of molecular reactions punch large pores in cell membranes, irrevocably destabilizing, and ultimately, destroying the cells.

For chemo to have an impact, it must trigger biological pathways that lead to cell death. The scientists' elegant recent research, which includes analyses of blood and bone marrow biopsies from patients with acute myeloid leukemia, open a new window of understanding into the multiple pathways that pyroptosis can be triggered under the influence of chemo.

Pyroptosis is a mechanism of programmed, necrotic cell death mediated by the gasdermins, a family of pore-forming proteins. The new research, published in the journal Science Signaling, highlights several pore-forming pathways that can lead to cell death under the influence of widely used chemotherapeutic agents.

Part 1

In addition to their role in cancer-cell death via pyroptosis, pore-forming gasdermins are a family of proteins also implicated in the immune response. One of these proteins, gasdermin D, has held sway in cancer-cell death when induced by the formation of caspase-1–activating inflammasomes. But the story of pyroptosis apparently doesn't begin and end with gasdermin D or or its close cousin, gasdermin E. It is a molecular saga that is far more complex than other studies have reported, scientists say.

Caspase-1 activates gasdermin D under inflammatory conditions, whereas caspase-3 activates gasdermin E under apoptotic conditions, such as those induced by chemotherapy, scientists asserted. These pathways are thought to be separate.

However, researchers found that they are part of an integrated network of gatekeepers that enables pyroptotic cell death. They observed that gasdermin D was the primary pyroptotic mediator in cultured blood cells in response to doxorubicin and etoposide, two common chemotherapies for hematopoietic malignancies.

 just to illustrate how complex gasdermins are in health and disease, another gasdermin protein, gasdermin A, along with gasdermin D, additionally have been implicated in autoimmune diseases and certain cancers. Yet, as reported in intricate detail in the Case Western study, gasdermin proteins are noteworthy for their pore-forming capabilities, particularly under the influence of chemotherapy.

 offers fresh insight into pyroptotic pathways by uncovering multiple routes to cancer-cell death—a contrarian stance to prevailing scientific wisdom. Even though a high abundance of gasdermin E had a dominant effect, the conversion to pyroptosis in human myeloid cells could be independently mediated via the transmembrane protein pannexin-1, a channel also known as PANX1. This occurred either through the induction of an alternate pyroptotic pathway dependent on gasdermin D or independent entirely of gasdermins.

In blood and bone marrow biopsies from 15 leukemia patients, the relative abundance of gasdermin E, gasdermin D, and PANX1 predicted which pathway would mediate pyroptotic cell death in response to chemotherapy exposure.

The take home message from the study is multifocal: Cancer cells don't simply die just because they've been exposed to chemo. They die through a programmed mechanism that can proceed through any one of several signaling pathways. 

They also have soundly demonstrated that pyroptosis during chemotherapy doesn't rely solely on gasdermin E. Studying human myeloid cells exposed to chemo, the scientists found that pyroptosis can also proceed through PANX1. And even in the face of dogma-challenging research, there may be other pore-forming pathways that have yet to be found.

 Bowen Zhou et al, Gasdermins and pannexin-1 mediate pathways of chemotherapy-induced cell lysis in hematopoietic malignancies, Science Signaling (2022). DOI: 10.1126/scisignal.abl6781

Part 2

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Study shows that the lateral orbitofrontal cortex 'writes' cognitive maps in the brain

The orbitofrontal cortex (OFC) is a region in the frontal lobe of the brain known to be involved in decision-making and information processing. The lateral part of this brain region, known as the lOFC, has been identified as a particularly salient region for the creation of so-called "cognitive maps."

Cognitive maps are mental representations of the world that are thought to guide human behaviour. While past studies have linked the lOFC to the brain's use of these maps, it is still unclear whether it creates these maps or merely deploys them when necessary.

Researchers have recently carried out a study exploring these two hypotheses, with the hope of better understanding the functions of the lOFC. Their findings, published in Nature Neuroscience, suggest that the lateral OFC is directly involved in the writing of cognitive maps.

Scientists reasoned that if the lOFC is needed for updating maps, then it would also be critical for the creation of new maps during the initial learning of a new association, i.e., the creation of a new cognitive map.

They conducted experiments using rats and the findings gathered by them provide additional evidence for the cartographer hypothesis, suggesting that the lOFC plays a key role in writing cognitive maps. However, they also show that blocking activity in the lOFC does not fully disrupt model-based behavior, but rather prevents the rats from incorporating all aspects of the task they are learning to complete into cognitive maps.

Overall, it now seems that the lOFC is most important for incorporating, or updating, information that is related to the specific identity of predicted outcomes. This represents a new and more nuanced hypothesis for lOFC function, and really of how the brain parses information when learning about the structure of reality.

Kauê Machado Costa et al, The role of the lateral orbitofrontal cortex in creating cognitive maps, Nature Neuroscience (2022). DOI: 10.1038/s41593-022-01216-0

Earth's inner core may have started spinning other way: Study

Earth's inner core, a hot iron ball the size of Pluto, has stopped spinning in the same direction as the rest of the planet and might even be rotating the other way, recent research suggested.

Roughly 5,000 kilometers (3,100 miles) below the surface we live on, this "planet within the planet" can spin independently because it floats in the liquid metal outer core.

Exactly how the inner core rotates has been a matter of debate between scientists—and the latest research is expected to prove controversial.

What little is known about the inner core comes from measuring the tiny differences in seismic waves—created by earthquakes or sometimes nuclear explosions—as they pass through the middle of the Earth.

Seeking to track the inner core's movements, new research published in the journal Nature Geoscience analyzed seismic waves from repeating earthquakes over the last six decades.

The study's authors said they found that the inner core's rotation "came to near halt around 2009 and then turned in an opposite direction".

Researchers think the inner core rotates, relative to the Earth's surface, back and forth, like a swing.

One cycle of the swing is about seven decades", meaning it changes direction roughly every 35 years, they added.

They said it previously changed direction in the early 1970s, and predicted the next about-face would be in the mid-2040s.

The researchers said this rotation roughly lines up with changes in what is called the "length of day"—small variations in the exact time it takes Earth to rotate on its axis.

So far there is little to indicate that what the inner core does has much effect on surface dwellers.

But the researchers said they think there were physical links between all Earth's layers, from the inner core to the surface.

However, experts not involved in the study expressed caution about its findings, pointing to several other theories and warning that many mysteries remain about the center of the Earth. None of the models made so far explain all the data very well, according to them.

Other researchers published research last year suggesting that the inner core oscillates far more quickly, changing direction every six years or so. Their work was based on seismic waves from two nuclear explosions in the late 1960s and early 1970s.

Another theory has some good evidence supporting it—is that the inner core only moved significantly between 2001 to 2013 and has stayed put since.

These mathematical models are most likely all incorrect because they explain the observed data but are not required by the data.

So scientists keep guessing and make more efforts to gather more data till evidence becomes more convincing.

Yi Yang et al, Multidecadal variation of the Earth's inner-core rotation, Nature Geoscience (2023). DOI: 10.1038/s41561-022-01112-z

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Study shows how cells prevent harmful extra copies of DNA

A protein that prepares DNA for replication also prevents the replication process from running out of control, according to a new study.

 The cells of humans and all other higher organisms use a complex system of checkpoints and "licensing" proteins to ensure that they replicate their genomes precisely once before dividing. In preparation for cell division, the licensing proteins attach to specific regions in the DNA, designating them as replication origins. When the DNA synthesis phase of the cell cycle begins, replication begins only at those licensed sites, and only initiates, or "fires" once, according to the current model.

That model was missing a crucial point, though. The same factor that is allowing for this licensing to happen is only degraded after these replication origins have fired. In principle, the cell could load these licensing machines onto DNA that's already replicated, so, instead of two copies, you're getting three or four copies of that segment of the DNA, and these cells would be expected to lose genome integrity and die or become cancerous.

Figuring out how cells avoid that fate has been tricky.  Scientists needed to be studying events in the first minutes of the DNA synthesis phase of the cell cycle, so it's a very transient period. 

 To solve this difficult experimental problem, researchers used computer-aided microscopy to monitor thousands of growing cells simultaneously, catching the replicating cells in the act and analyzing the activities of their licensing and replication factors.

The work revealed that a well-known licensing factor, CDT1, not only licenses a segment of DNA to become a replication origin, but also acts as a brake for DNA replication, preventing an essential replication enzyme called CMG helicase from functioning. To start synthesizing DNA, the cell's enzymes must first break down CDT1.

Nalin Ratnayeke et al, CDT1 inhibits CMG helicase in early S phase to separate origin licensing from DNA synthesis, Molecular Cell (2023). DOI: 10.1016/j.molcel.2022.12.004

Expert analysis refutes claims that humans are colonized by bacteria before birth

Scientific claims that babies harbor live bacteria while still in the womb are inaccurate, and may have impeded research progress, according to University College Cork (UCC) researchers at APC Microbiome Ireland, a world-leading Science Foundation Ireland (SFI) Research Center, which led a perspective published today in the journal Nature.

Prior claims that the human placenta and amniotic fluid are normally colonized by bacteria would, if true, have serious implications for clinical medicine and pediatrics and would undermine established principles in immunology and reproductive biology.

To examine these claims, UCC & APC Principal Investigator Prof. Jens Walter assembled a trans-disciplinary team of 46 leading experts in reproductive biology, microbiome science, and immunology from around the world to evaluate the evidence for microbes in human fetuses.

A healthy human fetus is sterile

The team unanimously refuted the concept of a fetal microbiome and concluded that the detection of microbiomes in fetal tissues was due to contamination of samples drawn from the womb. Contamination occurred during vaginal delivery, clinical procedures or during laboratory analysis.

In the report in Nature, the international experts encourage researchers to focus their studies on the microbiomes of mothers and their newborn infnats and on the microbial metabolites crossing the placenta that prepare the fetus for post-natal life in a microbial world.

The expert international authors also provide guidance on how scientists in the future can avoid pitfalls of contamination in the analysis of other samples where microbes are expected to be absent or present at low levels, such as internal organs and tissues within the human body.

Using running to escape everyday stresses may lead to exercise dependence instead of mental well-being

Recreational running offers a lot of physical and mental health benefits—but some people can develop exercise dependence, a form of addiction to physical activity which can cause health issues. Shockingly, signs of exercise dependence are common even in recreational runners. A study published in Frontiers in Psychology investigated whether the concept of escapism can help us understand the relationship between running, well-being, and exercise dependence.

Escapism is an everyday phenomenon among humans, but little is known regarding its motivational underpinnings, how it affects experiences, and the  psychological outcomes from it.

Escapism is often defined as 'an activity, a form of entertainment, etc. that helps you avoid or forget unpleasant or boring things. In other words, many of our everyday activities may be interpreted as escapism. The psychological reward from escapism is reduced self-awareness, less rumination, and a relief from one's most pressing, or stressing, thoughts and emotions.

Escapism can restore perspective, or it can act as a distraction from problems that need to be tackled. Escapism which is adaptive, seeking out positive experiences, is referred to as self-expansion. Meanwhile maladaptive escapism, avoiding negative experiences, is called self-suppression. Effectively, running as exploration or as evasion.

These two forms of escapism are stemming from two different mindsets, to promote a positive mood, or prevent a negative mood.

Escapist activities used for self-expansion have more positive effects but also more long-term benefits. Self-suppression, by contrast, tends to suppress positive feelings as well as negative ones and lead to avoidance.

Part 1