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.

Aww - wonderful insights Dr Krishna.

Dear Doctor Krishna - the years pass - I encountered your kkartlab in 2016 - thought I'd let you know that my son also completed his P Hd from Stanford in 2017 and set up his own Robotics Company soon after. https://www dexterity.ai
You never post your poetry here ... please do so - 'twill be nice
Cheers
Deepak Menon (Author on Amazon)

 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

Very very interesting research on the DNA trap. Will these trap specific viruses and how will they recognise them?

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

Self-suppression associated with exercise dependence
The team recruited 227 recreational runners, half men and half women, with widely varying running practices. They were asked to fill out questionnaires which investigated three different aspects of escapism and exercise dependence: an escapism scale which measured preference for self-expansion or self-suppression, an exercise dependence scale, and a satisfaction with life scale designed to measure the participants' subjective well-being.

The scientists found that there was very little overlap between runners who favored self-expansion and runners who preferred self-suppression modes of escapism. Self-expansion was positively related with well-being, while self-suppression was negatively related to well-being. Self-suppression and self-expansion were both linked to exercise dependence, but self-suppression was much more strongly linked to it. Neither escapism mode was linked to age, gender, or amount of time a person spent running, but both affected the relationship between well-being and exercise dependence. Whether or not a person fulfilled criteria for exercise dependence, a preference for self-expansion would still be linked to a more positive sense of their own well-being.

Although exercise dependence corrodes the potential well-being gains from exercise, it seems that perceiving lower well-being may be both a cause and an outcome of exercise dependency: the dependency might be driven by lower well-being as well as promoting it.

Similarly, experiencing positive self-expansion might be a psychological motive that promotes exercise dependence.

These findings may enlighten people in understanding their own motivation, and be used for therapeutical reasons for individuals striving with a maladaptive engagement in their activity.

 Frode Stenseng et al, Running to Get "Lost"? Two Types of Escapism in Recreational Running and Their Relations to Exercise Dependence and Subjective Well-Being, Frontiers in Psychology (2023). DOI: 10.3389/fpsyg.2022.1035196

Part 2

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Cancer cells may shrink or super-size to survive

Cancer cells can shrink or super-size themselves to survive drug treatment or other challenges within their environment, researchers have discovered.

Scientists combined biochemical profiling technologies with mathematical analyses to reveal how genetic changes lead to differences in the size of cancer cells—and how these changes could be exploited by new treatments.

The researchers think smaller cells could be more vulnerable to DNA-damaging agents like chemotherapy combined with targeted drugs, while larger cancer cells might respond better to immunotherapy. The study combines innovative high-powered image analysis with examination of DNA and proteins to study size control in millions of skin cancer cells.

The skin cancer melanoma is driven by two different genetic mutations—60% of cases are caused by a BRAF gene mutation, while 20% to 30% of cases are caused by an NRAS mutation. The researchers set out to investigate the differences in size and shape of skin cancer cells harboring the two mutations, by using mathematical algorithms to analyze huge amounts of data on DNA and proteins. The major difference was cell size.

BRAF-mutant cancer cells were very small whereas NRAS-mutant cancer cells were much bigger. Drug resistant NRAS cells were even bigger. Smaller cells appear to be able to tolerate higher levels of DNA damage, as they are very concentrated with proteins that repair DNA—like PARP, BRCA1, or ATM1 proteins. The researchers think that this could make them more vulnerable to drugs like PARP inhibitors—drugs blocking proteins responsible for repairing DNA damage—especially when combined with DNA-damaging agents such as chemotherapy.

In contrast, the larger NRAS-mutant cancer cells contained damage to their DNA instead of repairing it, accumulating mutations and enlarging. These larger cells were not as reliant on DNA repair machinery, so using chemotherapy and PARP inhibitors against them might not be as effective. Scientists think larger cells could be more responsive to immunotherapy—because their larger number of mutations could make them look more alien to the body.

They are already exploring this theory with further studies. The researchers think BRAF and NRAS mutations may be driving the differences in cell size by regulating levels of a protein known as CCND1—which is involved in cell division, growth and maintaining the cytoskeleton—and its interactions with other proteins.

While the study focused on skin cancer cells, researchers suspect that this size-shifting ability and its impact on treatment response is common to multiple cancer types. They have already identified similar mechanisms in breast cancer and are now investigating whether the findings could apply to head and neck cancers.

The discovery provides new insight into how the size of cancer cells affects the overall disease, allowing for better predictions of how people with cancer will respond to different treatments simply by analyzing cell size.

Existing drugs could even be used to force cancer cells into a desired size prior to treatments like immunotherapy or radiotherapy, which could improve their effectiveness.

Ian Jones et al, Characterization of proteome-size scaling by integrative omics reveals mechanisms of proliferation control in cancer, Science Advances (2023). DOI: 10.1126/sciadv.add0636. www.science.org/doi/10.1126/sciadv.add0636

Scientists discover evolutionary secret behind different animal life cycles

Why do some animals become larvae before growing into adults while some embryos directly  develop into miniature version of the adult?

In a new paper, scientists prove that the timing of activation of essential genes involved in embryogenesis—the transformation of a fertilized egg into an organism—correlates with the presence or absence of a larval stage and with whether the larva feeds from their surroundings or relies on nourishment the mother deposited in the egg.

It's impressive to see how evolution shaped the way animal embryos 'tell the time' to activate important groups of genes earlier or later in development. Suppose a larval stage is no longer essential for your survival. In that case, it might be evolutionarily advantageous to, for example, activate the genes to form the trunk earlier and develop straight into an adult instead.

This new study used state-of-the-art approaches to decode the genetic information, activity, and regulation in three species of marine invertebrate worms called annelids. They combined these with public datasets from other species in a large-scale study involving more than 600 datasets of more than 60 species separated by more than 500 million years of evolution.

Only by combining experimental datasets generated in the lab and systematic computational analyses were we able to unravel this new undiscovered biology.

José Martín-Durán, Annelid functional genomics reveal the origins of bilaterian life cycles, Nature (2023). DOI: 10.1038/s41586-022-05636-7. www.nature.com/articles/s41586-022-05636-7

Drug pollution: What happens to drugs after they leave your body?

Swallowing a pill only seems to make it disappear. In reality, the drug eventually leaves your body and flows into waterways, where it can undergo further chemical transformations. And these downstream products aren't dead in thewater.

Many pharmaceuticals, for example, are designated as contaminants of emerging concern, or CECs, because they alter hormone levels or otherwise harm wildlife. Some downstream products formed during drug breakdown are even more harmful than their parent molecule. It's critical, then, to chart out the chemical course of drugs to assess risk, but this is a daunting task because it depends on myriad hard-to-predict reaction patterns that are difficult to observe.

In a new study published in Water Resources Research, researchers devise a new method to chart these reaction possibilities. The newly proposed method is based on a multimodel global sensitivity analysis. This balances model fit and mathematical complexity: It generates a well-fitting model by simplifying it.

The researchers estimated how the arthritis drug diclofenac breaks down upon entering groundwater. First, using existing chemical transformation data, they built a comprehensive model of breakdown that included the gamut of possible chemical reactions. However, the estimates from this model were highly uncertain.

To adjust the model to better fit their data, the researchers quantified the relative importance of each possible chemical process and removed the least relevant ones.

This led to three simplified yet plausible models of drug breakdown. They ranked these models on the basis of their fit with the data and showed that a simplified model outperformed the most complex one.

The method yielded a flexible and accurate model. The team says their new method is especially useful when data are limited. Applying it to other drugs, they say, could reveal the full toll that pharmaceutical pollution takes on the planet.

Experimental vaccine for deadly Marbug virus guards against infection with just a single dose

An experimental vaccine for Marburg virus—a deadly cousin of the infectious agent that causes Ebola—can protect large animals from severe infections for up to a year with a single shot, scientists have found in a new study.

Developed by the National Institute of Allergy and Infectious Diseases, along with collaborators at other institutions, the vaccine produces durable protection, a factor that underlines its promise for clinical translation and pandemic preparedness. So far its safety profile suggests that investigators may be on the brink of a vaccine that, in the not-too-distant future, may help control a Marburg virus outbreak.

The pathogen is extraordinarily virulent, one of the most lethal in the world—an infectious agent so dangerous that it's on lists of viruses with potential to be exploited in devastating acts of bioterrorism. It causes a severe infection that once was known as Marburg hemorrhagic fever, but now is widely referred to as Marburg virus disease. The pathogen belongs to the Filovirdae family, the same viral family as Ebolavirus.

As with Ebolavirus, it's posited that the Marburg infectious agent jumped the species barrier from bats to people and nonhuman primates. While bats live without harm from the pathogen, scientists at the World Health Organization estimate human mortality at 90%.

The authors of the research paper report that in nonhuman primates
 a single shot of the vaccine generated protective immunity within seven days of vaccination. Additionally—and perhaps more important—the investigational vaccine protected nonhuman primates when they were challenged with exposure to the lethal Marburg virus.

 Ruth Hunegnaw et al, A single-shot ChAd3-MARV vaccine confers rapid and durable protection against Marburg virus in nonhuman primates, Science Translational Medicine (2022). DOI: 10.1126/scitranslmed.abq6364

New spray fights infections and antibiotic resistance

Antibiotic resistance as one of the top ten threats to global health. There is therefore a great need for new solutions to tackle resistant bacteria and reduce the use of antibiotics. A group of researchers at Chalmers University of Technology in Sweden are now presenting a new spray that can kill even antibiotic-resistant bacteria, and that can be used for wound care and directly on implants and other medical devices.

This innovation  can have a dual impact in the fight against antibiotic resistance. The material has been shown to be effective against many different types of bacteria, including those that are resistant to antibiotics, such as Methicillin-resistant Staphylococcus aureus (MRSA), while also having the potential to prevent infections and thus reduce the need for antibiotics.

The material consists of small hydrogel particles equipped with a type of peptide that effectively kills and binds bacteria. Attaching the peptides to the particles provides a protective environment and increases the stability of the peptides. This allows them to work together with body fluids such as blood, which otherwise inactivates the peptides, making them difficult to use in health care. In previous studies, the researchers showed how the peptides can be used for  wound care materials such as wound dressings.

They have now published two new studies in which the bactericidal material is used in the form of a wound spray and as a coating on medical devices that are introduced into our bodies. This new step in the research means that the innovation can be used in more ways and be of even greater benefit in health care.

Edvin Blomstrand et al, Cross-linked lyotropic liquid crystal particles functionalized with antimicrobial peptides, International Journal of Pharmaceutics (2022). DOI: 10.1016/j.ijpharm.2022.122215

Annija Stepulane et al, Multifunctional Surface Modification of PDMS for Antibacterial Contact Killing and Drug-Delivery of Polar, Nonpolar, and Amphiphilic Drugs, ACS Applied Bio Materials (2022). DOI: 10.1021/acsabm.2c00705

E. coli: Lab discovers evidence of multicellularity in single cell organism

Researchers have uncovered something new in one of the most studied organisms on Earth, and their discoveries could impact the treatment and prevention of devastating bacterial diseases.

Escherichia coli, or E. coli, gets a bad rap, and for good reason. This diverse group of bacteria that live in our intestines are mostly harmless and play an important role in sustaining a healthy digestive system. But some E. coli are among the most virulent disease-causing micro-organisms.

Pathogenic E. coli takes a deadly, costly toll on humanity, costing billions of dollars to treat and killing millions of people worldwide each year. It's responsible for diarrheal diseases, peritonitis, colitis, respiratory illness and pneumonia, and other illnesses, and is the main cause in 80% of urinary tract infections, which are the most common bacterial infection.

Consequently, researchers have been keen to learn everything they can about E. coli for the past century or so. They have probed it from every angle, synthesized it, scrutinized it to the extent that, many people believe, there isn't much else to learn.

But some researchers have taken a closer look at E. coli and their research is yielding novel insights, and raising new questions, about this prevalent unicellular organism. For one thing, it appears that E. coli may not always be unicellular. The research team explained it all in their study, "Evidence of a possible multicellular life cycle in Escherichia coli," published in the journal iScience.

In nature, bacteria live in communities called biofilms, which are clusters of microbes encased in a self-made, self-sustaining slime matrix, and attached to many kinds of wet surfaces. They're everywhere around us and inside of us. Common, everyday examples of biofilms include dental plaque and pond scum. They can grow on plant and animal tissue, like the inside of our digestive tract, and cause serious infections. On top of that, the bacteria living inside a biofilm's protective matrix are less likely to be affected by antibiotics. Biofilms are clinically important, particularly in relation to infection.

Approximately 80% of all bacterial infections have a biofilm component. "And almost any bacteria that's ever been studied can make them."

Researchers now 

discovered something new—a multicellular self-assembly process in E. coli. Researchers observed unattached, single-celled organisms combining into four-cell rosettes, a natural multicellular formation thought to be uncommon in bacteria.

Rosettes are rather significant in higher organisms, like mammals, because they initiate developmental processes like embryogenesis.

They observed E. coli rosettes grow into constant-width chains, which continue growing for 10 generations before attaching to a surface and creating a biofilm. They saw and recorded the bacterial processes that had never been seen or recorded before.

Devina Puri et al, Evidence of a possible multicellular life cycle in Escherichia coli, iScience (2022). DOI: 10.1016/j.isci.2022.105795

Liquid-metal robots can melt and re-form

Researchers have created a material that can move, soften and re-harden under the influence of magnetic fields. To demonstrate the material’s promise, researchers showed how it could be manipulated to pass through barriers, extract an object from an artificial stomach, and move a tiny light bulb into place and then melt into the solder required to make it work.

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How much greenhouse gas do tropical soils emit?

Nitrogen changes form as it cycles between air, soil, and life. Soils, for example, emit nitrogen either as inert dinitrogen (N2), which dominates our atmosphere, or as nitric oxide (NO) or nitrous oxide (N2O), the greenhouse gases that warm it.

One of the causes of aggressive liver cancer discovered: A 'molecular staple' that helps repair broken DNA

Error-correcting mechanisms are very important for cells, because with all the cellular activity constantly going on, malfunctions arise all the time. But when it comes to killing cancer cells, it is in the cells' best interest to induce errors. Radiotherapy and chemotherapy can cause cellular defects by breaking the DNA of the cells. However, some tumor cells have an exceptionally efficient DNA repair machinery that allows them to evade cancer treatment. Researchers have now revealed the workings of one of these extraordinary repair systems: a molecular staple that has been shown in action for the first time using a new nanotechnology technique.

A few years ago, scientists discovered that about half of patients with hepatocellular carcinoma (the most common type of liver cancer) produce an RNA molecule called NIHCOLE, which is found mainly in the most aggressive tumors and is associated with a poor prognosis.

NIHCOLE is not a protein synthesized by a gene, but an RNA molecule. It is part of what biologists dubbed junk DNA two decades ago when the human genome was being sequenced. At the time, they mistakenly believed that this DNA was useless.

Cancer researchers concluded that NIHCOLE is very effective at helping repair broken DNA, which is why radiotherapy is less effective in tumors where it is present. By eliminating NIHCOLE, cancer cells treated with radiotherapy die more easily. However, the molecular mechanism by which NIHCOLE facilitates the repair of DNA breaks was not known. The paper just published in Cell Reports explains this: NIHCOLE forms a bridge that binds the broken DNA fragments together. It interacts simultaneously with proteins that recognize the two ends of a fragmented DNA, as if stapling them together. Only a small piece of NIHCOLE is required for it to act as a molecular staple.

Understanding this mechanism may help in the development of strategies to combat liver cancers with the worst prognosis. 

Sara De Bragança et al, APLF and long non-coding RNA NIHCOLE promote stable DNA synapsis in non-homologous end joining, Cell Reports (2022). DOI: 10.1016/j.celrep.2022.111917

Harvesting energy from moving trains

Researchers  want to harness the energy created by moving trains and transform that energy into usable electricity. And they are conducting various experiments to do the same. 

After several years of design review,  researchers created a new kind of tie that replaces the conventional wooden variety and is equipped to generate power. Their high-tech tie, placed underneath the rail, is topped with a heavy metal bar mounted on a spring. As the wheels of the train pass over the rail, the train’s weight pushes down on that bar, triggering a series of gears. Those gears rotate a generator, creating electricity, which can then be stored in a battery.

As trains passed over the rail, researchers got a clearer picture of how much power it might produce and how that power might be put into use. For every wheel of the train that goes by, they are harvesting 15 to 20 watts of power.

 A long train with maybe 200 railcars, that’s 800 wheels, makes 1.6 kilowatts. Once that energy is stored,  they are able to use it to make the tracks more intelligent by embedding sensors in them.

Deploying their energy harvesting system could mean greater expansion of the vital sensor systems that keep railways safe.

Yu Pan et al, A half-wave electromagnetic energy-harvesting tie towards safe and intelligent rail transportation, Applied Energy (2022). DOI: 10.1016/j.apenergy.2022.118844

Robot clears foreign body from stomach

Study of 500,000 Medical Records Links Viruses to Alzheimer's Again And Again

A study of around 500,000 medical records has suggested that severe viral infections like encephalitis and pneumonia increase the risk of neurodegenerative diseases like Parkinson's and Alzheimer's.

Researchers found 22 connections between viral infections and neurodegenerative conditions in the study of around 450,000 people.

People treated for a type of inflammation of the brain called viral encephalitis were 31 times more likely to develop Alzheimer's disease. (For every 406 viral encephalitis cases, 24 went on to develop Alzheimer's disease – around 6 percent.)

Those who were hospitalized with pneumonia after catching the flu seemed to be more susceptible to Alzheimer's disease, dementia, Parkinson's disease, and amyotrophic lateral sclerosis (ALS).

Intestinal infections and meningitis (both often caused by a virus), as well as the varicella-zoster virus, which causes shingles, were also implicated in the development of several neurodegenerative diseases.

The impact of viral infections on the brain persisted for up to 15 years in some cases. And there were no instances where exposure to viruses was protective.

Around 80 percent of the viruses implicated in brain diseases were considered 'neurotrophic', which means they could cross the blood-brain barrier.

"Strikingly, vaccines are currently available for some of these viruses, including influenza, shingles (varicella-zoster), and pneumonia," the researchers write.

"Although vaccines do not prevent all cases of illness, they are known to dramatically reduce hospitalization rates. This evidence suggests that vaccination may mitigate some risk of developing neurodegenerative disease.

https://www.cell.com/neuron/fulltext/S0896-6273(22)01147-3?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0896627322011473%3Fshowall%3Dtrue

A fairy-like robot flies by the power of wind and light

The development of stimuli-responsive polymers has brought about a wealth of material-related opportunities for next-generation small-scale, wirelessly controlled soft-bodied robots. For some time now, engineers have known how to use these materials to make small robots that can walk, swim and jump. 

Researchers are now trying how to make smart material fly. They have come up with a new design for their project called FAIRY—Flying Aero-robots based on Light Responsive Materials Assembly. They have developed a polymer-assembly robot that flies by wind and is controlled by light.

The artificial fairy developed by them has several biomimetic features. Because of its high porosity (0.95) and lightweight (1.2 mg) structure, it can easily float in the air directed by the wind. What is more, a stable separated vortex ring generation enables long-distance wind-assisted traveling. The fairy can be powered and controlled by a light source, such as a laser bean or LED.

This means that light can be used to change the shape of the tiny dandelion seed-like structure. The fairy can adapt manually to wind direction and force by changing its shape. A light beam can also be used to control the take-off and landing actions of the polymer assembly.

Jianfeng Yang et al, Dandelion‐Inspired, Wind‐Dispersed Polymer‐Assembly Controlled by Light, Advanced Science (2022). DOI: 10.1002/advs.202206752

 Muscle-kidney cross talk might be an essential piece in the puzzle of potassium regulation.

Having levels of potassium that are too high or too low can be fatal. A new mathematical model sheds light on the often mysterious ways the body regulates this important electrolyte. Potassium, a common mineral abundant in food like bananas and leafy greens, is essential to normal cellular function. It helps the cardiac muscle work correctly and aids in the transmission of electrical signals within cells.

Using existing biological data, researchers built a mathematical model that simulates how an average person's body regulates potassium, both in times of potassium depletion and during potassium intake. Because so many foods contain abundant potassium, our bodies constantly store, deploy, and dispose of potassium to maintain healthy levels—a process known as maintaining potassium homeostasis. Understanding potassium homeostasis is essential in helping diagnose the source of the problem when something goes wrong—for example, when kidney disease or medication leads to dysregulation.
Too much potassium in the body, or hyperkalemia, can be just as dangerous as hypokalemia, or too little. Dysregulation of potassium can lead to dangerous and potentially fatal consequences.
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The model could be used for a virtual patient trial, allowing researchers to generate dozens of patients and then predict which ones would have hyper- or hypokalemia based on different controls.

"A lot of our models are pieces of a bigger picture," said Anita Layton, professor of applied mathematics and Canada 150 Research Chair in mathematical biology and medicine. "This model is one new and exciting piece in helping us understand how our incredibly complex internal systems work."

The model is especially exciting because it allows scientists to test something called the muscle-kidney cross-talk signal hypothesis. Scientists have hypothesized that skeletal muscles, which are responsible for most of the potassium storage in the body, can directly signal to the kidneys that it's time to excrete excess when too much potassium is stored, and vice versa. When the math researchers tested the hypothesis in their model, it more accurately reflected existing biological data regarding potassium homeostasis, suggesting that muscle-kidney cross talk might be an essential piece in the puzzle of potassium regulation.

The study was published in PLOS Computational Biology.

The cognitive effects of air pollution- Even chess experts perform worse when air quality is lower, suggesting a negative effect on cognition

Here's something else chess players need to keep in check: air pollution.

That's the bottom line of a newly published study co-authored by an MIT researcher, showing that chess players perform objectively worse and make more suboptimal moves, as measured by a computerized analysis of their games, when there is more fine particulate matter in the air.

Fine particulate matter refers to tiny particles 2.5 microns or less in diameter, notated as PM_2.5. They are often associated with burning matter—whether through internal combustion engines in autos, coal-fired power plants, forest fires, indoor cooking through open fires, and more. The World Health Organization estimates that air pollution leads to over 4 million premature deaths worldwide every year, due to cancer, cardiovascular problems, and other illnesses.

More specifically, given a modest increase in fine particulate matter, the probability that chess players will make an error increases by 2.1 percentage points, and the magnitude of those errors increases by 10.8%. In this setting, at least, cleaner air leads to clearer heads and sharper thinking.

When individuals are exposed to higher levels of air pollution, they make more more mistakes, and they make larger mistakes, this study finds. Moreover, air pollution may affect people in settings where they might not think it makes a difference. It's not like you have to live next to a power plant. You can live miles away and be affected.

And while the focus of this particular study is tightly focused on chess players, the authors write in the paper that the findings have "strong implications for high-skilled office workers," who might also be faced with tricky cognitive tasks in conditions of variable air pollution. 

Steffen Künn et al, Indoor Air Quality and Strategic Decision Making, Management Science (2023). DOI: 10.1287/mnsc.2022.4643

Why do the cores of stars spin more slowly than expected?

Under certain conditions, the cores of stars contract. When this happens, they start to spin faster than the external layers of the star. However, the study of oscillations in stars, asteroseismology, has uncovered an astonishing phenomenon: The cores of such stars actually rotate more slowly than calculations predict. Why is this so?

Three  scientists from CNRS, INRIA and ENS-PSL have studied this question and report their findings in an article published in Science on January 19, 2023. Their numerical stimulations, which model plasma flow in the deep layers of a star, have shown that the slowing down of the core can be produced by an internal magnetic field. More specifically, plasma flow can amplify a magnetic field to the point where it generates strong turbulent motions. Such turbulence may further amplify the magnetic field until it causes the star's core to spin down.

The results obtained with the research team's simulations are also in agreement with asteroseismological observations of many stars. In addition, the simulations show that the magnetic field would be hidden by the outer layers of the star, which explains why no magnetic field of this kind has yet been measured with current techniques.