Disarming the immune system's lethal lung response

Neutrophils, the most abundant type of white blood cell, are the body's first line of defense against infection. Foreign pathogens can stress the body and activate neutrophils. When activated, neutrophils employ various weapons to protect the body. But if overactivated, these weapons can damage the body's own tissues. Lung tissue is saturated with blood vessels, making them very susceptible to neutrophil attacks. If severe enough, acute lung injuries can lead to acute respiratory distress syndrome (ARDS), the leading cause of death due to COVID-19.

Researchers have found a drug candidate that can prevent lethal lung inflammation in mice by inhibiting a protein called PTP1B. Their discovery may help develop better treatments for severe inflammatory conditions like sepsis and COVID-19.

They investigated whether using a PTP1B inhibitor drug candidate could dampen the lethal consequences of overactive neutrophils in mice. They found that pretreating mice with the PTP1B inhibitor reduced lung tissue damage. When untreated, less than half of the mice survived acute lung injuries and ARDS. But when pretreated, they all survived.

The researchers exploited a natural process, called neutrophil aging, that the body uses to control the immune cell's lifespan. As they age, neutrophils become less dangerous. They discovered PTP1B inhibition speeds up neutrophil aging. An aged neutrophil is like a soldier without a weapon. So regardless of how many neutrophils flood an area, they won't be able to do serious damage.

Dongyan Song et al, PTP1B inhibitors protect against acute lung injury and regulate CXCR4 signaling in neutrophils, JCI Insight (2022). DOI: 10.1172/jci.insight.158199

New study shows transmission of epigenetic memory across multiple generations

Without altering the genetic code in the DNA, epigenetic modifications can change how genes are expressed, affecting an organism's health and development. The once radical idea that such changes in gene expression can be inherited now has a growing body of evidence behind it, but the mechanisms involved remain poorly understood.

A new study by researchers  shows how a common type of epigenetic modification can be transmitted via sperm not only from parents to offspring, but to the next generation ("grandoffspring") as well. This is called "transgenerational epigenetic inheritance," and it may explain how a person's health and development could be influenced by the experiences of his or her parents and grandparents.

The study, published the week of September 26 in the Proceedings of the National Academy of Sciences (PNAS), focused on a particular modification of a histone protein that changes the way DNA is packaged in the chromosomes. This widely studied epigenetic mark (called H3K27me3) is known to turn off or "repress" the affected genes and is found in all multicellular animals—from humans to the nematode worm C. elegans used in this study.

These results establish a cause-and-effect relationship between sperm-transmitted histone marks and gene expression and development in offspring and grandoffspring.

Sperm-inherited H3K27me3 epialleles are transmitted transgenerationally in cis, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2209471119

Researchers reconstruct the genome of the common ancestor of all mammals

Every modern mammal, from a platypus to a blue whale, is descended from a common ancestor that lived about 180 million years ago. We don't know a great deal about this animal, but the organization of its genome has now been computationally reconstructed by an international team of researchers. The work is published Sept. 30 in Proceedings of the National Academy of Sciences.

The researchers drew on high-quality genome sequences from 32 living species representing 23 of the 26 known orders of mammals. They included humans and chimps, wombats and rabbits, manatees, domestic cattle, rhinos, bats and pangolins. The analysis also included the chicken and Chinese alligator genomes as comparison groups. Some of these genomes are being produced as part of the Earth BioGenome Project and other large-scale biodiversity genome sequencing efforts. 

The reconstruction shows that the mammal ancestor had 19 autosomal chromosomes, which control the inheritance of an organism's characteristics outside of those controlled by sex-linked chromosomes (these are paired in most cells, making 38 in total), plus two sex chromosomes.

Scientists  identified 1,215 blocks of genes that consistently occur on the same chromosome in the same order across all 32 genomes. These building blocks of all mammal genomes contain genes that are critical to developing a normal embryo.

The researchers found nine whole chromosomes or chromosome fragments in the mammal ancestor, whose order of genes is the same in modern birds' chromosomes.

This remarkable finding shows the evolutionary stability of the order and orientation of genes on chromosomes over an extended evolutionary timeframe of more than 320 million years.

In contrast, regions between these conserved blocks contained more repetitive sequences and were more prone to breakages, rearrangements and sequence duplications, which are major drivers of genome evolution.

The researchers were able to follow the ancestral chromosomes forward in time from the common ancestor. They found that the rate of chromosome rearrangement differed between mammal lineages.

Joana Damas et al, Evolution of the ancestral mammalian karyotype and syntenic regions, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2209139119

Scientists develop novel technique to grow meat in the lab using magnetic field

Scientist  have found a novel way of growing cell-based meat by zapping animal cells with a magnet. This new technique simplifies the production process of cell-based meat by reducing reliance on animal products, and it is also greener, cleaner, safer and more cost-effective.

Cultured meat is an alternative to animal farming with advantages such as reducing carbon footprint and the risk of transmitting diseases in animals. However, the current method of producing cultured meat involves using other animal products, which largely defeats the purpose, or drugs to stimulate the growth of the meat.

To cultivate cell-based meat, animal cells are fed animal serum—usually fetal bovine serum (FBS), which is a mixture harvested from the blood of fetuses excised from pregnant cows slaughtered in the dairy or meat industries—to help them grow and proliferate. This is a critical, yet cruel and expensive, step in the current cell-based meat production process. Ironically, many of these molecules come from the muscles within the slaughtered animal, but scientists did not know how to stimulate their release in production scale bioreactors. Other methods to promote cell growth are using drugs or relying on genetic engineering.

The complex production process for cell-based meat increases cost, limits the manufacturing scale and undermines the commercial viability of cell-based meat.

To help address this challenge, a multidisciplinary research team  came up with an unconventional method of using magnetic pulses to stimulate the growth of cell-based meat.

Growing cell-based meat with the help of a magnet
The new technique uses a delicately tuned pulsed magnetic field developed by the team to culture myogenic stem cells, which are found in skeletal muscle and bone marrow tissue.

In response to a short 10-minute exposure to the magnetic fields, the cells release a myriad of molecules that have regenerative, metabolic, anti-inflammatory and immunity-boosting properties. These substances are part of what is known as the muscle 'secretome' (for secreted factors) and are necessary for the growth, survival and development of cells into tissues. We are very excited about the possibility that magnetically-stimulated secretome release may one day replace the need for FBS in the production of cultured meat.

The growth-inducing secretomes can be harvested in the lab safely and conveniently, and also at low cost. This way, the myogenic stem cells will act as a sustainable and green bioreactor to produce the nutrients-rich secretomes for growing cell-based meat at scale for consumption. The muscle knows how to produce what it needs to grow and develop—it simply needs a little bit of encouragement when it is outside its owner. This is what the magnetic fields can provide.

Applications in regenerative medicine
The harvested secretomes can also be used for regenerative medicine. The  team used the secreted proteins to treat unhealthy cells and found that they help to accelerate the recovery and growth of the unhealthy cells. Therefore, this method can potentially help to cure injured cells and speed up a patient's recovery.

Craig Jun Kit Wong et al, Brief exposure to directionally-specific pulsed electromagnetic fields stimulates extracellular vesicle release and is antagonized by streptomycin: A potential regenerative medicine and food industry paradigm, Biomaterials (2022). DOI: 10.1016/j.biomaterials.2022.121658

Tiny Robots Have Successfully Cleared Pneumonia From The Lungs of Mice

Scientists have been able to direct a swarm of microscopic swimming robots to clear out pneumonia microbes in the lungs of mice, raising hopes that a similar treatment could be developed to treat deadly bacterial pneumonia in humans.

The microbots are made from algae cells and covered with a layer of antibiotic nanoparticles. The algae provide movement through the lungs, which is key to the treatment being targeted and effective.

In experiments, the infections in the mice treated with the algae bots all cleared up, whereas the mice that weren't treated all died within three days.

The technology is still at a proof-of-concept stage, but the early signs are very promising. Based on this mouse data, researchers see that the microrobots could potentially improve antibiotic penetration to kill bacterial pathogens and save more patients' lives.

The nanoparticles on the algae cells are made of tiny polymer spheres coated with the membranes of neutrophils, a type of white blood cell. These membranes neutralize inflammatory molecules produced by bacteria and the body's own immune system, and both the nanoparticles and the algae degrade naturally.

Harmful inflammation is reduced, improving the fight against infection, and the swimming microbots are able to deliver their treatment right where it's needed – it's the precision that makes this approach work so well.

The researchers also established that the microbot treatment was more effective than an intravenous injection of antibiotics – in fact, the injection dose had to be 3,000 times higher than the one loaded on to the algae cells to achieve the same effect in the mice.

These results show how targeted drug delivery combined with active movement from the microalgae improves therapeutic efficacy.

https://www.nature.com/articles/s41563-022-01360-9

Scientists create 'non-psychedelic' compound with same anti-depressant effect

While illegal for recreational use, psychedelic drugs are showing great promise as treatments for severe depression and anxiety, as well as alcohol addiction and other conditions. Some  scientists think the actual psychedelic trip—hallucinations and profound emotional experiences—is what leads to long-lasting therapeutic effects. Other scientists speculate that if the "trip" could be eliminated from such drugs, then only the therapeutic effects might remain. Researchers have taken a major step toward answering that question.

Research in animal models show it's possible to create a compound that hits the same exact target as psychedelic drugs  hit—the 5-HT2A serotonin receptors on the surface of specific neurons—but does not cause the same psychedelic effects when given to mice. The new compound triggers the same anti-depressant action that researchers have long observed in mice treated with SSRI drugs over the past two decades, with just two differences: the anti-depressant action of the new compound was immediate and long-lasting after just one dose.

Brian Shoichet, Bespoke library docking for 5-HT2A receptor agonists with anti-depressant activity, Nature (2022). DOI: 10.1038/s41586-022-05258-z

Nanoparticles can improve stroke recovery by enhancing brain stimulation, study shows

In a recent study, researchers have reported that brain stimulation combined with a nose spray containing nanoparticles can improve recovery after ischemic stroke in an animal model.

The nasal spray is a non-invasive method for delivering magnetic nanoparticles into the brain that the study finds can increase the benefits of transcranial magnetic stimulation (TMS). TMS is a method of non-invasive brain stimulation already used clinically or in clinical trials to treat neurological conditions like stroke, Parkinson's disease, Alzheimer's disease, depression, and addiction.

Rats that were given combined nanoparticle and TMS treatment every 24 hours for 14 days after an ischemic stroke had better overall health, put on weight more quickly and had improved cognitive and motor functions compared to those treated with TMS alone. During TMS treatment, an electrical current runs through an electric coil placed outside the skull, producing a magnetic field that stimulates brain cells by inducing a further electrical current inside the brain. However, the stimulation is often not intense enough to penetrate far enough into the brain to reach the areas needing treatment. In this new study, published in Materials Today Chemistry, the researchers show that magnetic nanoparticles, administered intranasally, can make neurons more responsive and amplify the magnetic signal from TMS to reach deeper brain tissue, aiding recovery. The finding offers new opportunities for treating neurological disorders.

Researchers overcame the blood brain barrier by guiding the magnetic nanoparticles closer to the correct area with a large magnet near the head.

 Y. Hong et al, Enhancing non-invasive brain stimulation with non-invasively delivered nanoparticles for improving stroke recovery, Materials Today Chemistry (2022). DOI: 10.1016/j.mtchem.2022.101104

A robotic pill that clears mucus from the gut to deliver meds

RoboCap administers medicine to the intestines and makes its way out of the body

The multivitamin-sized device houses a motor and a cargo hold for drugs, including ones that are typically given via injections or intravenously, such as insulin and some antibiotics. If people could take such drugs orally, they could potentially avoid daily shots or a hospital stay, which would be “a huge game changer". 

Drugs that enter the body via the mouth face a tough journey. They encounter churning stomach acid, raging digestive enzymes and sticky slicks of mucus in the gut. Intestinal mucus “sort of acts like Jell-O". The goo can trap drug particles, preventing them from entering the bloodstream.

The new device, dubbed RoboCap, whisks away this problem. The pill uses surface grooves, studs and torpedo-inspired fins to scrub away intestinal mucus like a miniature brush whirling inside a bottle. In experiments in pigs, RoboCap tunneled through mucus lining the walls of the small intestine, depositing insulin or the IV antibiotic vancomycin along the way,  researchers report September 28 in Science Robotics. After churning for about 35 minutes, the pill continued its trip through the gut and eventually out of the body.

RoboCap is the latest pill-like gadget made to be swallowed.

S. Srinivasan et al. RoboCap: Robotic mucus-clearing capsule for enhanced drug delivery .... Science Robotics. Published online September 28, 2022. doi: 10.1126/scirobotics.abp9066.

Next-generation liquid biopsy detects nano-sized signs of breast cancer in early-stage patients

A team of scientists has found indications that a special blood test called a liquid biopsy could determine whether a patient has breast cancer at its early stage and if that cancer is unlikely to return.

These high-definition comprehensive liquid biopsies are conducted using a standard blood draw from the arm of a patient in a doctor's office. Once in the laboratory, the sample is examined for signs of cancer. The results raise hopes that one day doctors could detect breast cancer in patients with a simple blood draw.

Researchers tested a theory that the high-definition liquid biopsy could detect multiple cancer biomarkers, including the so-called "oncosomes"—nano-sized, membraned cargo carriers that enrich the body's environment for cancer growth. These oncosomes are secreted by cancer cells as the group has shown previously.

They  found the vast majority of early-stage breast cancer patients have these oncosomes at very robust levels. They're about 5-10 microns in diameter. About the size of a cell. They first identified these large vesicles in prostate cancer about a year-and-a-half ago and showed that they are related to the cancer. They are hiding in plain sight.

If further studies produce similar results, this could mean that the next generation high-definition liquid biopsy may become a diagnostic tool for early breast cancer detection and other cancers. The test also could inform patients who have been treated for cancer that they will most likely remain cancer-free.

Sonia Maryam Setayesh et al, Multianalyte liquid biopsy to aid the diagnostic workup of breast cancer, npj Breast Cancer (2022). DOI: 10.1038/s41523-022-00480-4

Make cooking safe for all, including those in developing countries, say indoor air pollution experts

Developing countries should focus on keeping unnecessary occupants, such as children, out of kitchens during cooking to help reduce their exposure to dangerous levels of air pollution, recommends a study.

Researchers also highlighted the benefits of using cleaner fuels and electric appliances that help reduce carbon dioxide levels within a kitchen by more than 32 percent, compared to the use of polluting fuels.

The GCARE researchers and their partners found that kitchens that regularly had more than two people present during cooking sessions exhibited higher carbon dioxide levels.

The researchers found that cooking resulted in an average increase of 22 percent in carbon dioxide levels across the 60 homes.

Kitchens with their doors and windows open, that also used extractor fans during cooking were found to be the environments with optimal thermal comfort conditions. Having both kitchen doors and windows open during cooking was shown to reduce carbon dioxide levels by 14 percent when compared with environments that only kept their doors open.

Prashant Kumar et al, CO₂ exposure, ventilation, thermal comfort and health risks in low-income home kitchens of twelve global cities, Journal of Building Engineering (2022). DOI: 10.1016/j.jobe.2022.105254

Genetics of longevity are influenced by both gender and age

A team of researchers reports evidence that the genetics of longevity are influenced by both gender and age. In their paper published in the journal Science, the group describes their study of aging in mice and humans. A relevant  perspective piece  has also been published  in the same journal issue outlining the technical challenges to understanding how aging works and the work done by the team on this new effort.

Scientists have been studying the aging process for many years but still do not have a good explanation for why organisms age and why some live longer than others. In this new effort, the researchers wondered if something in the genome plays a role in how long a species lives on average.

Noting that another team had created a very large dataset of information regarding aging in nearly 3,000 mice, the researchers found that it also contained genetic information. After obtaining access to the database, they analyzed that genetic information—more specifically, they conducted quantitative trait locus mapping. They found multiple loci that they could associate with longevity, some that were specific to one or the other gender. They also found that mice who weighed more during their early years or who had small litter sizes tended to die younger. They suggest the same genes that were associated with aging may have also played a role in the other two traits. The researchers also found that the aging-related genes they isolated appeared to remain dormant until the latter stages of a given individual's life.

The researchers then studied data available in public biobanks and found human genes that appeared to play the same role as the age-associated genes in mice. Next, they looked for and found similar genes in a type of worm—disabling those genes influenced their longevity.

Maroun Bou Sleiman et al, Sex- and age-dependent genetics of longevity in a heterogeneous mouse population, Science (2022). DOI: 10.1126/science.abo3191

João Pedro de Magalhães, The genetics of a long life, Science (2022). DOI: 10.1126/science.ade3119

Researchers reveal new strategy to prevent blood clots without increasing the risk of bleeding

A nanoparticle therapy developed by investigators  targets overactive neutrophils, a specific kind of white blood cell, to prevent almost all types of blood clots while causing no increased risk for bleeding. The preclinical findings, published in Science Translational Medicine, may lead to safer ways to care for patients impacted by blood clots. 

According to the researchers, neutrophils are key drivers of both arterial and venous thrombosis. And when you target a neutrophil, you do not increase bleeding risk, you only decrease clotting risk. 

Earlier arterial and venous thrombosis have been thought of as distinct molecular events that require separate treatment paradigms. Arterial thrombosis (an artery clot), which can cause heart attack or stroke, is commonly treated with antiplatelet agents like aspirin, while anticoagulants are used to treat venous thrombosis (a vein clot), a cause of pain or swelling in the legs or clots in the lungs.

More recently, however, experts have begun to suspect commonalities between the two events that could be leveraged as novel therapeutic targets.

In the new study, researchers used animal models to show that overactive neutrophils participate in both arterial and venous thrombosis through an increased capacity to migrate and adhere to sites of injury. They also showed that overactive neutrophils increase the production of key factors used as building blocks for clots. In seeking to halt the process, the researchers identified a cluster of receptors unique to activated neutrophils and developed antibody-coated nanoparticles that specifically target those clusters.

Lalitha Nayak et al, A targetable pathway in neutrophils mitigates both arterial and venous thrombosis, Science Translational Medicine (2022). DOI: 10.1126/scitranslmed.abj7465

First-ever mycobiome Atlas describes associations between cancers and fungi

An international team of scientists has created the first pan-cancer mycobiome atlas — a survey of 35 types of cancer and their associated fungi.
Cancer cells and microbes have a long and enduring association. Both have coevolved within the ecosystems of the human body, often relying on the same resources. Competition for these resources often affects the replication and survival of cancer cells, microbes and the human host.

The association between cancer and individual microbes has long been studied case-by-case, but much recent attention focuses on the whole human microbiome, particularly in the gut, which houses more — and more diverse — communities of bacteria, viruses and fungi than anywhere else in or on the human body.
However, the roles and influence of cancer-associated fungi remain largely unstudied. Fungi are more complicated organisms than viruses and bacteria. They are eukaryotes — organisms with cells containing nuclei. Their cells are much more similar to animal cells than to bacteria or viruses.

The existence of fungi in most human cancers is both a surprise and to be expected. It is surprising because we don’t know how fungi could get into tumors throughout the body. But it is also expected because it fits the pattern of healthy microbiomes throughout the body, including the gut, mouth and skin, where bacteria and fungi interact as part of a complex community.

Fungi found on the human body come in two main types: environmental fungi, such as yeasts and mold that generally pose no harm to most healthy people, and commensal fungi, which live on or inside the human body and may be harmless, provide a benefit such as improving gut health or contribute to disease, such as yeast infections or liver disease. Fungi also play a role in shaping host immunity, for better or worse, which looms large in immunocompromised persons, including cancer patients.

The new study characterizes the cancer mycobiome — fungi linked to cancers — in 17,401 samples of patient tissues, blood and plasma across 35 types of cancer in four independent cohorts. The researchers found fungal DNA and cells in low abundances across many major human cancers, with differences in community compositions that differed among cancer types.

The finding that fungi are commonly present in human tumors should drive us to better explore their potential effects and re-examine almost everything we know about cancer through a ‘microbiome lens.

Analyses that compared fungal communities with matched bacteriomes (the bacterial component of the microbiome) and immunomes (genes and proteins constituting the immune system) revealed that the associations between them were often “permissive,” rather than competitive.

For example, one species of fungi was found to be enriched in breast cancer tumors of patients older than 50 years while another species was notably abundant in lung cancer samples.

The researchers said there were significant correlations between specific fungi and age, tumor subtypes, smoking status, response to immunotherapy and survival measures. Whether the fungi are simply correlated or causally associated remains to be determined.

These findings validate the view that the microbiome in its entirety is a key piece of cancer biology.

Ravid Straussman, Pan-cancer analyses reveal cancer type-specific fungal ecologies and bacteriome interactions, Cell (2022). DOI: 10.1016/j.cell.2022.09.005. www.cell.com/cell/fulltext/S0092-8674(22)01127-8

Nobel win for  unlocking secrets of Neanderthal DNA 

Scientist Svante Paabo won the Nobel Prize in medicine this year for his discoveries on human evolution that provided key insights into our immune system and what makes us unique compared with our extinct cousins.

Paabo spearheaded the development of new techniques that allowed researchers to compare the genome of modern humans and that of other hominins—the Neanderthals and Denisovans. He and his team also surprisingly found that gene flow had occurred from Neanderthals to Homo sapiens, demonstrating that they had children together during periods of co-existence.

This transfer of genes between hominin species affects how the immune system of modern humans reacts to infections, such as the coronavirus. People outside Africa have 1-2% of Neanderthal genes.

Paabo and his team also managed to extract DNA from a tiny finger bone found in a cave in Siberia, leading to the recognition of a new species of ancient humans they called Denisovans.

Water droplets hold the secret ingredient for building life

Chemists have uncovered a mechanism for peptide-forming reactions to occur in water—something that has puzzled scientists for decades.

This is essentially the chemistry behind the origin of life. This is the first demonstration that primordial molecules, simple amino acids, spontaneously form peptides, the building blocks of life, in droplets of pure water. This water-based chemistry, which leads to proteins and so to life on Earth, could also lead to the faster development of drugs to treat humanity's most debilitating diseases.

Water isn't wet everywhere. On the margins, where the water droplet meets the atmosphere, incredibly rapid reactions can take place, transforming abiotic amino acids into the building blocks of life. Places where sea spray flies into the air and waves pound the land, or where fresh water burbles down a slope, were fertile landscapes for life's potential evolution.

The chemists have spent more than 10 years using mass spectrometers to study chemical reactions in droplets containing water.

The rates of reactions in droplets are anywhere from a hundred to a million times faster than the same chemicals reacting in bulk solution. The rates of these reactions make catalysts unnecessary, speeding up the reactions and, in the case of early Earth chemistry, making the evolution of life possible.

 Holden, Dylan T. et al, Aqueous microdroplets enable abiotic synthesis and chain extension of unique peptide isomers from free amino acids, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2212642119. doi.org/10.1073/pnas.2212642119

Scientists discover dual-function messenger RNA

For the very first time, a study has discovered an unprecedented pathway producing telomerase RNA from a protein-coding messenger RNA (mRNA).

The central dogma of molecular biology specifies the order in which genetic information is transferred from DNA to make proteins. Messenger RNA molecules carry the genetic information from the DNA in the nucleus of the cell to the cytoplasm where the proteins are made. Messenger RNA acts as the messenger to build proteins.

Actually, there are many RNAs (ribonucleic acids) that are not used to make proteins. 

About 70 percent of the human genome is used to make noncoding RNAs that don't code for protein sequences but have other uses."

Telomerase RNA is one of the noncoding RNAs that assembles along with telomerase proteins to form the enzyme telomerase. Telomerase is crucial for cellular immortality in cancer and stem cells. In this study, scientists show that a fungal telomerase RNA is processed from a protein-coding mRNA, instead of being synthesized independently.

Most RNA molecules are synthesized independently and here scientists uncovered a dual function mRNA that can be used to produce a protein or to make a noncoding telomerase RNA, which is really unique.

 Logeswaran, Dhenugen et al, Biogenesis of telomerase RNA from a protein-coding mRNA precursor, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2204636119. doi.org/10.1073/pnas.2204636119

Nobel prize: physicists share prize for insights into the spooky world of quantum mechanics

The 2022 Nobel prize for physics has been awarded to a trio of scientists for pioneering experiments in quantum mechanics, the theory covering the micro-world of atoms and particles.

Alain Aspect from Université Paris-Saclay in France, John Clauser from J.F. Clauser & Associates in the US, and Anton Zeilinger from University of Vienna in Austria, will share the prize sum of 10 million Swedish kronor (US$915,000) “for experiments with entangled photons, establishing the violation of Bell inequalities and pioneering quantum information science”.

https://www.nobelprize.org/

Study finds the mechanism used by metastatic cancer cells to infiltrate the liver

Metastasis—when cancer spreads to form new tumors—causes approximately 90% of cancer-related deaths. Because metastatic cancer cells circulate in the blood, the liver—which filters the blood—is considered the most vulnerable organ, so treatments that prevent liver metastasis are urgently needed. A team of  researchers discovered a mechanism that allows metastatic cancer cells to infiltrate the liver, and how that infiltration can be blocked by inhibiting a related protein.

Approximately 90% of cancer-related deaths are due to metastasis when cancer spreads and forms new tumors. The liver is considered the most vulnerable organ to metastatic cancer: the 5-year survival rate after surgery to remove liver metastases is as low as 30–50%, so developing treatments to prevent liver metastasis is urgently needed.

A group of researchers has identified an alternative pathway for liver metastasis, showing that cancer cells invade via intracellular gap formation in endothelial cells, and clarified the molecular mechanism involved. The results of their research are expected to lead to the development of drugs to prevent and treat metastatic liver cancer.

Truong Huu Hoang et al, Cancer cells produce liver metastasis via gap formation in sinusoidal endothelial cells through proinflammatory paracrine mechanisms, Science Advances (2022). DOI: 10.1126/sciadv.abo5525

Far-ultraviolet LED can kill bacteria and viruses efficiently without harming humans

Ultraviolet germicidal lamps are extremely effective at exterminating bacteria and viruses, and they are routinely used in hospitals to sterilize surfaces and medical instruments.

Such lamps can be made with LEDs, making them energy efficient. But these LEDs use ultraviolet light in a range that damages DNA and thus cannot be used around people. The hunt is on to develop efficient LEDs that shine light within a narrow band of far-ultraviolet light that appears to be both good at disinfecting and safe for people.

A highly efficient LED that is deadly to microbes and viruses but safe for people has been engineered by  physicists. It could one day help countries emerge from the shadows of pandemics by killing pathogens in rooms full of people.

Germicidal LED lamps that operate in the absence of humans are often made from aluminum, gallium and nitrogen. By increasing the amount of aluminum they contain, these LEDs can be modified to work in a wavelength region that is safe for humans. But traditionally this has dramatically reduced their power.

To get around this, Masafumi Jo, Yuri Itokazu and Hideki Hirayama, all at the RIKEN Quantum Optodevice Laboratory, created an LED with a more complex design. They sandwiched together multiple layers, each containing slightly different proportions of aluminum, while in some layers they also added tiny amounts of silicon or magnesium.

This effectively created an obstacle course for electrons, hampering their movement across the material and trapping them for longer in certain areas. This, in turn, increased the amount of light emitted by the device and reduced the amount it absorbed.

To help pin down the best design, the team used  computer simulations to model all possible effects and came up with the best. They will still strive to improve their LED's performance even further, according to their research paper.

 Masafumi Jo et al, Milliwatt-power far-UVC AlGaN LEDs on sapphire substrates, Applied Physics Letters (2022). DOI: 10.1063/5.0088454

Pain relief without side effects and addiction

New substances that activate adrenalin receptors instead of opioid receptors have a similar pain relieving effect to opiates, but without the negative aspects such as respiratory depression and addiction.

This is the result of research carried out by an international team of researchers. 

Opiates cause addiction, new substances do not

They are a blessing for patients suffering from severe pain, but they also have serious side effects: Opioids, and above all morphine, can cause nausea, dizziness and constipation and can also often cause slowed breathing that can even result in respiratory failure. In addition, opiates are addictive—a high percentage of the drug problem  is caused by pain medication, for example.

In order to tackle the unwanted medical and social effects of opioids, researchers all over the world are searching for alternative analgesics.

They are focusing particularly on the molecular structures of the receptors that dock onto the pharmaceutical substances. It is only when researchers understand these on the atomic level that they can develop effective and safe active substances. They have now turned their attention to a new receptor that is responsible for binding adrenaline—the alpha 2A adrenergic receptor. There are already some analgesics that target this receptor such as brimonidine, clonidine and dexmedetomidine.

Part 1

The aim of the research consortium is to find a chemical compound that activates the receptor in the central nervous system without a sedative effect. In a virtual library of more than 300 million different and easily accessible molecules, the researchers looked for compounds that physically match the receptor but are not chemically related to known medication. After a series of complex virtual docking simulations, around 50 molecules were selected for synthesis and testing and two of these fulfilled the desired criteria. They had good bonding characteristics, activated only certain protein sub-types and thus a very selective set of cellular signal pathways, whereas dexmedetomidine responds to a significantly wider range of proteins.

By further optimizing the identified molecules, for which extremely high-resolution cryo-electron microscopic imaging was used, the researchers were able to synthesize agonists that produced high concentrations in the brain and reduced the sensation of pain effectively in investigations with animal models.

The successful separation of analgesic properties and sedation is a milestone in the development of non-opioid pain medication , especially as the newly-identified agonists are comparatively easy to manufacture and administer orally to patients.

Elissa A. Fink et al, Structure-based discovery of nonopioid analgesics acting through the α 2A -adrenergic receptor, Science (2022). DOI: 10.1126/science.abn7065

**

Part 2

Aftermath of DART Impact

Nobel prize for three chemists who made molecules 'click'

Three scientists were jointly awarded this year's Nobel Prize in chemistry  this year for developing a way of "snapping molecules together" that can be used to explore cells, map DNA and design drugs that can target diseases such as cancer more precisely.

Americans Carolyn R. Bertozzi and K. Barry Sharpless, and Danish scientist Morten Meldal were cited for their work on click chemistry and bioorthogonal reactions. It's all about snapping molecules together.

Some everyday materials have memories, and now they can be erased

Some solid materials have a memory of how they have previously been stretched out, which impacts how they respond to these kinds of deformations in the future. A new study lends insight into memory formation in the foams and emulsions common in food products and pharmaceuticals and provides a new method to erase this memory, which could guide how materials are prepared for future use.

A crease in a piece of paper serves as a memory of being folded or crumpled. A lot of other materials form memories when they are deformed, heated up, or cooled down, and you might not know it unless you ask the right questions. Improving our understanding of how to write, read, and erase memories provides new opportunities for diagnostics and programming of materials. We can find out the history of a material by doing some tests or erase a material's memory and program a new one to prepare it for consumer or industrial use.

The researchers studied memory in a type of material called disordered solids, which have particles that are often erratically arranged. For example, ice cream is a disordered solid made up of a combination of ice crystals, fat droplets, and air pockets mixed together in a random way. This is in stark contrast to materials with "crystalline structures," with particles arranged in highly ordered rows and columns. Disordered solids are common in food sciences, consumer products, and pharmaceuticals and include foams like ice cream and emulsions like mayonnaise.

"Preparation of materials often includes manipulating them in ways that change the arrangement of their molecules, bubbles, or drops, taking them from a higher energy state to a lower energy, more stable state.

part1

For some materials like glass, this involves carefully heating the material so its molecules are unstuck and can arrange themselves in a more organized way. But for some materials, like mayonnaise, heating has destructive or unappetizing side effects. So for materials where heating is not an option, we use a process called mechanical annealing to physically deform the material and bring it to a lower energy state.

Researchers previously investigated how mechanical annealing of disordered solids can allow a material to a form a memory of that deformation, impacting how it responds to future deformation. In a new paper appearing Oct. 5 in the journal Science Advances, the researchers provide a more refined understanding of how memories form in disordered solids and how existing memories can be "read" and even erased.

Nathan C. Keim et al, Mechanical annealing and memories in a disordered solid, Science Advances (2022). DOI: 10.1126/sciadv.abo1614

part2 

**

How the secrets of the tardigrade could improve lifesaving drugs like insulin

Tardigrade: This stocky microscopic animal, also known as a water bear, can survive in environments where survival seems impossible. Tardigrades have been shown to endure extremes of heat, cold and pressure—and even the vacuum of space—by entering a state of suspended animation and revitalizing, sometimes decades later, under more hospitable conditions.

If scientists  could understand the mechanism behind this extraordinary preservation they might be able to use the knowledge to improve medicines so that they remain potent longer and are less vulnerable to typical environmental challenges, ultimately broadening access and benefiting human health.

It turns out that one of the processes protecting tardigrades is spurred by a sugar molecule called trehalose, commonly found in living things from plants to microbes to insects, some of which use it as blood sugar. For a few select organisms, such as the water bear and the spiky resurrection plant, that can revive after years of near-zero metabolism and complete dehydration, trehalose's stabilizing power is the secret to their unearthly fortitude.

Armed with this insight, researchers invented a polymer based on the sugar. This polymer, called poly(trehalose methacrylate), or pTrMA, actually seems to improve upon nature in its ability to render drugs more robust to the ravages of time and temperature. They opted to investigate pTrMA's effects on insulin, a World Health Organization "essential medicine" that many people with diabetes inject daily to manage the disease.

Part 1

A series of studies  over the last three years has demonstrated pTrMA's potential. A recent study published in ACS Applied Materials & Interfaces found that the polymer preserved insulin at temperatures of nearly 200 degrees Fahrenheit—close to water's boiling point—and through almost a year of refrigerated storage, with 87% of the medication remaining intact, compared with less than 8% of insulin alone. Laboratory experiments into pTrMA's safety showed that it did not trigger an immune response in mice.

A 2021 study showed that insulin plus pTrMA has a low enough viscosity to be safely injected, and 2020 research demonstrated that a version of pTrMA designed to degrade inside the body retained the ability to stabilize insulin.

An early finding, from 2014, that pTrMA actually works better than trehalose as a preserving agent hasn't been the only pleasant surprise along the way.

Madeline B. Gelb et al, Poly(trehalose methacrylate) as an Excipient for Insulin Stabilization: Mechanism and Safety, ACS Applied Materials & Interfaces (2022). DOI: 10.1021/acsami.2c09301

Madeline B. Gelb et al, Effect of Poly(trehalose methacrylate) Molecular Weight and Concentration on the Stability and Viscosity of Insulin, Macromolecular Materials and Engineering (2021). DOI: 10.1002/mame.202100197

Emma M. Pelegri-O'Day et al, Synthesis of Zwitterionic and Trehalose Polymers with Variable Degradation Rates and Stabilization of Insulin, Biomacromolecules (2020). DOI: 10.1021/acs.biomac.0c00133

Juneyoung Lee et al, Trehalose Glycopolymers as Excipients for Protein Stabilization, Biomacromolecules (2013). DOI: 10.1021/bm4003046

Parental age could be key factor in helping thoroughbred horses be first past the post

In a sport where the finest of margins can determine the winner, a new study has shown that parental age can be a determining factor in who comes out on top in horse races.

Experts  have shown that the speed of thoroughbred horses declines as parental age at conception increases. The research team analyzed more than 900,000 race performances from more than 100,000 racehorses from races across Great Britain.

They found that the age of both the mothers and fathers of the horses played a significant role in the overall speed of the racehorses.

The researchers believe the study can play a pivotal part not only in optimizing racehorse breeding, but crucially offers further evidence that parental age can affect offspring characteristics.

Evidence of maternal and paternal age effects on speed in thoroughbred racehorses. Royal Society Open Science. doi.org/10.5061/dryad.qbzkh18m0

 How dormant bacteria calculate their return to life

While facing starvation and stress conditions, some bacteria enter a dormant state in which life processes stop. Shutting down into a deep dormancy allows these cells, called spores, to withstand punishing extremes of heat, pressure and even the harsh conditions of outer space.

Eventually, when conditions become favorable, spores that may have been dormant for years can wake up in minutes and spring back to life.

Spores wake up by re-hydrating and restarting their metabolism and physiology. But until now scientists did not know whether spores can monitor their environment "in their sleep" without waking up. In particular it was not known how spores deal with vague environmental signals that do not indicate clearly favorable conditions. Would spores just ignore such mixed conditions or take note?

Now biologists have solved this mystery in a new study published in the journal Science. Researchers  discovered that spores have an extraordinary ability to evaluate their surrounding environment while remaining in a physiologically dead state. They found that spores use stored electrochemical energy, acting like a capacitor, to determine whether conditions are suitable for a return to normal functioning life.

They show that cells in a deeply dormant state have the ability to process information. They discovered that spores can release their stored electrochemical potential energy to perform a computation about their environment without the need for metabolic activity.

A composite movie showing the phase contrast of a single spore (top left) to visualize the dormant state. A movie (top right) shows the color-coded electrochemical potential of the same spore. The plot (bottom left) shows the corresponding time trace of the electrochemical potential values changing over time. Finally, a corresponding bar plot (bottom right) visualizes the jumps toward the threshold for returning to life. Credit: Süel Lab

Kaito Kikuchi et al, Electrochemical potential enables dormant spores to integrate environmental signals, Science (2022). DOI: 10.1126/science.abl7484. www.science.org/doi/10.1126/science.abl7484

Why Does Salt Change the Taste of Everything?

If your coffee is too bitter, add a pinch of salt. If your salad isn’t sour enough, add a pinch of salt. If your beer is too bitter, add a pinch of salt. Salt has a seemingly magical ability to enhance good flavors and dampen bad ones.

What your breath could reveal about your health

Light-based therapy weakens antibiotic-resistant bacteria

Antibiotics are standard treatments for fighting dangerous bacterial infections. Yet the number of bacteria developing a resistance to antibiotics is increasing. Researchers  are overcoming this resistance with light.

The researchers tailored antimicrobial photodynamic therapy (aPDT)—a chemical reaction triggered by visible light—for use on antibiotic-resistant bacteria strains. Results showed the treatment weakened bacteria to where low doses of current antibiotics could effectively eliminate them.

The researchers began their work by choosing the bacteria and the three main parts of aPDT needed to combat it: molecular oxygen, light, and a photosensitizer—something that creates a reaction between oxygen and light. An already FDA-approved dye called methylene blue served as the photosensitizer. The light sources were specially constructed panels of 25 LEDs in reflective cones built by the Technical Support Laboratory of the São Carlos Institute of Physics. Methicillin-resistant Staphylococcus aureus served as the bacteria, and the researchers grew cultures with the blue dye in them to ensure the photosensitizer alone would not affect the bacteria.

At first, the team used aPDT by itself at various light strengths, durations, and in a specific series of follow-up treatments to log the bacteria's response. The idea was to find the lowest dose and shortest series that could weaken the bacterial membranes and other resistance mechanisms. Cell recoveries and reproductions revealed how many generations it took before antibiotic resistance returned. Next, the researchers added measured levels and combinations of antibiotics at different time intervals after aPDT treatments to note the weakened bacteria's responses.

Jace A. Willis et al, Breaking down antibiotic resistance in methicillin-resistant Staphylococcus aureus : Combining antimicrobial photodynamic and antibiotic treatments, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2208378119

How To Make Yourself FLOAT!

Magic? Not really!

TAZ protein protects from age-related loss of function of blood stem cells

A well-functioning immune system is essential for protection against infections. However, with increasing age, the functioning of the immune system diminishes, which is also due to age-related damage in hematopoietic (blood) stem cells. Researchers have now discovered how the co-activator of the Hippo signaling pathway, the TAZ protein, can protect hematopoietic stem cells from aging and thus prevent them from loss of function. Moreover, hematopoietic stem cells age very heterogeneously. In addition to old cells, one can also find "youthful" cells when the protective mechanism has worked effectively.

Our blood is constantly being regenerated from hematopoietic stem cells (HSCs). With increasing age, however, these blood stem cells experience a loss of function and their regenerative potential diminishes. In older people, there is another problem with blood formation (hematopoiesis): they form fewer lymphocytes (cells of the immune system), so they are often no longer able to cope as well with infections and usually do not show a highly effective immune response after a vaccination.

There are already numerous indications that these deficiencies associated with old age result primarily from age-related damage in the blood stem cells. How this damage occurs, and whether there are protective mechanisms that could possibly protect the blood stem cells from it, is not yet known. In a study recently published in Nature Communications, researchers have now used novel analytical mehtods at the single cell level to investigate in more detail what happens during the aging process in hematopoietic stem cells and what role the TAZ protein plays in this process.

The adult body replaces billions of cells every day; in this process, existing cells are continuously replaced by "new" cells. "Maintaining the balance between cell division, cell differentiation and cell death is tremendously important, because even the smallest imbalances disturb this equilibrium and sooner or later contribute to the development of cancer or can lead to premature aging.

Part 1

The researchers  found that blood stem cells do not age uniformly. Rather, they are very heterogeneous and exhibit mixed populations. Thus, it was possible to isolate subpopulations from old mice in which the cells were predominantly old, but also populations in which the cells were in a "youth-like" state. The gene expression pattern of these cells also tended to resemble those of young hematopoietic stem cells. This is an indication that TAZ can to some extent counteract the gradual loss of stem cell function and protect blood stem cells by rejuvenating them. Consequently, genetic downregulation of TAZ in old HSCs resulted in a drastic failure to restore the blood system upon transplantation of these HSCs.

Kyung Mok Kim et al, Taz protects hematopoietic stem cells from an aging-dependent decrease in PU.1 activity, Nature Communications (2022). DOI: 10.1038/s41467-022-32970-1

Part 2

**

How genetics influences our body weight beyond genes

Heredity plays a role in how strongly we are predisposed to put on excess weight. In recent years, researchers have extensively examined which genes and gene variants play a role in this, and have identified roughly one hundred obesity susceptibility genes. However, genome-wide association studies have shown that less than half of all cases of hereditary obesity can be explained by these genes. The other half are the result of factors that, although part of our DNA, are not genes in the classical sense. Epigenetic information would be one example of such a factor.

A group of researchers  have now identified a further non-classic genetic risk factor for hereditary obesity: an endogenous microRNA molecule known as microRNA-7. Like genes, the blueprints for microRNA molecules are part of our chromosomes. But while genes act as the building instructions for proteins, the information contained in microRNA is not translated into protein form. Instead, the microRNA molecules act in our cells in the form of RNA.

MicroRNA-7 is the first microRNA for which they have been able to demonstrate an association with obesity.

Mary P. LaPierre et al, MicroRNA-7 regulates melanocortin circuits involved in mammalian energy homeostasis, Nature Communications (2022). DOI: 10.1038/s41467-022-33367-w

NASA spaceship deflected asteroid in test to save Earth

NASA on Tuesday said it had succeeded in deflecting an asteroid in a historic test of humanity's ability to stop an incoming cosmic object from devastating life on Earth.

The fridge-sized Double Asteroid Redirection Test (DART) impactor deliberately smashed into the moonlet asteroid Dimorphos on September 26, pushing it into a smaller, faster orbit around its big brother Didymos, said NASA.

 DART shortened the 11 hour 55 minute orbit to 11 hours and 23 minutes. Speeding up Dimorphos' orbital period by 32 minutes exceeded NASA's own expectation of 10 minutes.

DART's success as a proof-of-concept has made a reality of science fiction—notably in films such as "Armageddon" and "Don't Look Up."

Kinetic impact with a spaceship is just one way to defend the planet, albeit the only method possible with current technology.

Should an approaching object be detected early, a spaceship could be sent to fly alongside it for long enough to divert its path via using the ship's gravitational pull, creating a so-called gravity tractor.

Another option would be launching nuclear explosives to redirect or destroy an asteroid.

Source: NASA

Algorithms predict sports teams’ moves with 80% accuracy.

Researchers have found a way to restore sight in adult mice

 Researchers have found a way to restore sight in adult mice with a form of congenital blindness, in spite of the rodents' relative maturity.

The mice were modeling a rare human disorder of the eye's retina, called leber congenital amaurosis (LCA), which often causes blindness or severe visual impairment at birth.

This inherited condition seems to be caused by a mutation in any one of dozens of genes associated with the retina and its light-sensing abilities.

Researchers have been working on treatments that could restore damaged or dysfunctional photoreceptors in this part of the eye for several decades. Some strategies include retinal implants, gene editing interventions, and drug treatments.

These emerging therapies all boost vision with varying levels of success, but synthetic compounds that target the retina look particularly promising for those with mutations that involve rod photoreceptors.

Rods are the photoreceptors at the back of the eye that sense dim light. These specialized neurons utilize a series of biochemical reactions to convert sensory light into electrical signals for the rest of the brain to 'read'.

As light-sensitive pigments in retinal rods absorb low levels of light, they convert the molecule 11-cis retinal into all-trans-retinal, which in turn generates an impulse that travels down the optic nerve to the brain.

Previous studies on children with LCA have shown that synthetic retinoid treatments can help compensate for some vision loss when injected straight into the eye. But how these treatments impact adults with the condition is not as well understood.

"Although some progress has been made, it still remains unclear the extent to which adult visual circuits can be restored to a fully functional state at the level of the visual cortex upon correction of the retinal defect. Traditionally, it's been thought that the brain's visual system is formed and strengthened during certain developmental windows in early life. If the eye isn't being exercised during these critical periods, then visual networks in the brain may never be wired properly for sight, leading to lifelong deficits in vision.

But a mammal's potential for vision may not be so rigidly wired; it could be far more plastic than assumed.

To explore this idea, researchers administered a synthetic retinoid for seven days to adult rodents born with retinal degeneration.

The treatment was ultimately successful at partially restoring the animals' light sensitivity and their typical light-orienting behaviors for 27 days.

Nine days after treatment, far more neurons in the visual cortex were being activated by the optic nerve.

This suggests the central visual pathway that carries information from the eye to the visual cortex can be significantly restored by retinoid treatment, even in adult mice.Immediately after the treatment, the signals coming from the opposite-side eye, which is the dominant pathway in the mouse, activated two times more neurons in the brain. What was even more mind-blowing was that the signals coming from the same-side eye pathway activated five-fold more neurons in the brain after the treatment and this impressive effect was long-lasting.

https://www.sciencedirect.com/science/article/pii/S096098222201449X...

Brain cells in a dish learn to play Pong in real time

A research team has for the first time shown that 800,000 brain cells living in a dish can perform goal-directed tasks—in this case the simple tennis-like computer game, Pong. They have shown they can interact with living biological neurons in such a way that compels them to modify their activity, leading to something that resembles intelligence.

DishBrain offers a simpler approach to test how the brain works and gain insights into debilitating conditions such as epilepsy and dementia,.

By building a living model brain from basic structures in this way, scientists will be able to experiment using real brain function rather than flawed analogous models like a computer.

Brett J. Kagan, In vitro neurons learn and exhibit sentience when embodied in a simulated game-world, Neuron (2022). DOI: 10.1016/j.neuron.2022.09.001. www.cell.com/neuron/fulltext/S0896-6273(22)00806-6

Scientists demonstrate that electricity may be obtainable from water with a high salt concentration

In an exciting new development, scientists  have demonstrated that electricity may be obtainable from water with a high salt concentration, such as seawater.

Some people think about "osmosis" as just a science term they were forced to learn in elementary school biology class. However, the spontaneous motion of dissolved ions or molecules through a semi-permeable membrane when there is a concentration difference between the two sides can be harnessed to generate electricity. And luckily for us, the oceans are filled with salty water, which may be used to help alleviate humanity's ever-growing demand for energy. However, in order to be practical, this membrane needs to be very thin and highly selective to allow ions—but not water molecules—to pass through.

Now, a research team led by Osaka University has used conventional semiconductor processing technology to precisely control the structure and arrangement of nanopores in an ultrathin silicon membrane. Because these fabrication methods have been around for decades, the costs and design complexities were minimized. Moreover, the size and location of the pores could be precisely controlled.

Whenever there is a non-equilibrium situation, such as two water tanks with different salt concentrations, there is often an opportunity to covert this thermodynamic energy into electricity.

Scientists are trying to use this opportunity.

Makusu Tsutsui et al, Sparse multi-nanopore osmotic power generators, Cell Reports Physical Science (2022). DOI: 10.1016/j.xcrp.2022.101065

New abiotic pathway for the formation of oxygen

Oxygen plays a crucial role for all living organisms on Earth. Researchers have now found evidence that double ionized sulfur dioxide contribute to the formation of oxygen molecules. This could, in particular, explain the presence of oxygen in sulfur dioxide-rich atmospheres of several of Jupiter's moons.

How does oxygen form? On earth, the main explanation involves the biological process of photosynthesis, which was developed by cyanobacteria and kicked off the Great Oxidation Event about two billion years ago. Researchers have long realized that non-biological or abiotic processes also contribute to the formation of oxygen—especially out in space. On other celestial bodies where such bacteria are not present, the presence of oxygen can be explained by abiotic processes.

Researchers have now found a possible new abiotic pathway: the formation of oxygen from sulfur dioxide. The sulfur dioxide molecule is found in the atmosphere of many celestial bodies and large quantities can be ejected into the atmosphere during volcanic eruptions.

When the sulfur dioxide molecule is exposed to radiation of a sufficiently high energy, as provided by radiation from the sun for example, this molecule can be ionized into a double positively charged system. It can then assume a linear form with the two oxygen atoms being adjacent and the sulfur atom at one of the terminal ends. Before ionization, sulfur dioxide has a shape similar to the "Mickey Mouse" shape of the water molecule.

Upon double ionization, two of the bound electrons in the molecule get ejected and can lead to changes in the angle between the atoms in the molecule. Alternatively, as crucial in the present case, roaming can occur, that is, the atoms switch places, and the molecule takes on a whole new shape.

Once roaming has occurred, the sulfur atom may break up, leaving behind a simple positively charged oxygen molecule O₂⁺, which can then be neutralized by receiving an electron from another molecule. This sequence of events can explain how oxygen  formed in the atmospheres of several of Jupiter's moons such as Io, Europa and Ganymede, despite the lack of biological life there. Researchers think this happens naturally on Earth too.

 Måns Wallner et al, Abiotic molecular oxygen production—Ionic pathway from sulfur dioxide, Science Advances (2022). DOI: 10.1126/sciadv.abq5411

Experimental antibiotic torpedoes the protective slime that makes resistant bacteria tougher to fight

An experimental antibiotic is under development that is capable of neutralizing a wide range of drug-resistant, Gram-positive bacteria—pathogens that protect themselves in a slimy shield, called a biofilm, designed by nature to keep threats out.

Bacterial infections are extraordinarily difficult to treat when pathogens are protected by a biofilm. The film forms as a consequence of bacterial colonies growing together in a tough and protective matrix. Infections caused by bacteria protected by biofilms are often chronic and extend across a complex range: Dental infections that lead to tooth loss can be worsened by biofilms. Deadly drug-resistant lung infections, bacterial infiltration of the sac surrounding the heart, wound infections, and even infections of the blood can all be complicated by the presence of biofilms. Antibiotic treatment of biofilm-shielded bacteria are challenging, doctors say, because many conventional antibiotics can't penetrate the slime to kill the active bacteria.

Researchers have  been working to address resistant infections that involve biofilms. Some call their experimental medication MCC5194, and describe it as a modified version of vancomycin, the potent antibiotic backed by decades of use.

The difference between MCC194 and unmodified vancomycin is that the experimental drug acts as a torpedo when encountering biofilms. In preclinical tests, MCC5194 killed major Gram-positive bacterial threats such as methicillin-resistant Staphylococcus aureus—MRSA—and destroyed the bacterial biofilm. The drug was also effective in tests against other Gram-positive bacteria, and eradicated their biofilms, too.

 Mark A. T. Blaskovich et al, A lipoglycopeptide antibiotic for Gram-positive biofilm-related infections, Science Translational Medicine (2022). DOI: 10.1126/scitranslmed.abj2381

Wildlife populations plunge 69% since 1970: WWF

Wild populations of monitored animal species have plummeted nearly 70 percent in the last 50 years, according to a landmark assessment released Thursday that highlights "devastating" losses to nature due to human activity.

Featuring data from 32,000 populations of more than 5,000 species of mammals, birds, amphibians, reptiles and fish, the WWF Living Planet Index shows accelerating falls across the globe.

In biodiversity-rich regions such as Latin America and the Caribbean, the figure for animal population loss is as high as 94 percent.

Globally, the report found that monitored animal populations had fallen 69 percent since 1970.

The Living Planet Report argues that increasing conservation and restoration efforts, producing and consuming food more sustainably, and rapidly and deeply decarbonising all sectors can alleviate the twin crises of climate change and biodiversity loss.

It also calls for governments to properly factor into policymaking the value of services rendered by nature, such as food, medicine and water supply.

Nature loss is not just a moral issue of our duty to protect the rest of the world. It is actually an issue of material value, an issue of security for humanity as well.

source: WWF

Researchers discovered driver of high blood pressure

Researchers have identified a key contributor to high blood pressure that could lead to new treatments. The discovery  breaks new ground in our understanding of how the body regulates blood pressure. It also shows how problems with this critical biological process drive high blood pressure, also known as hypertension.

This work  identifies a “new paradigm in hypertension,” according to an accompanying editorial in the journal where this work was published. The editorial says UVA’s “innovative” discoveries fill “major gaps” in our understanding of the fundamental molecular causes of high blood pressure. The discovery of a new mechanism for elevation of blood pressure could provide therapeutic targets for treating hypertension.

Blood pressure is controlled, in part, by calcium levels in smooth muscle cells that line blood vessel walls. Smooth muscle cells transport calcium in and use it to regulate the contraction of blood vessels as needed.

High blood pressure is commonly treated with “calcium blockers” that reduce the movement of calcium, but these medications have many side effects because they block a mechanism that is used by multiple organs in the body for carrying out normal functions. So a treatment option that targets the harmful effects of calcium, but not its beneficial effects, could be very helpful for patients with high blood pressure.

Researchers now discovered two critical – and previously unknown – signaling centers in smooth muscle cells that bring in calcium and regulate blood pressure. These “nanodomains,” the researchers found, act like symphony conductors for blood vessels, directing them to contract or relax as needed. These signaling centers, the researchers determined, are a key regulator of healthy blood pressure.

Further, these  scientists found that disruptions in this process contribute to high blood pressure. In both mouse models of the disease and hypertensive patients, the fine balance between constrictor and dilator signaling centers is lost. This caused the blood vessels to become too constricted, driving up blood pressure.

Understanding these components will help us target them to lower or raise the blood pressure in disease conditions that show high or low blood pressure, respectively.

https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.058607

https://newsroom.uvahealth.com/2022/10/11/uva-discovers-key-driver-...

The new findings help us better understand how our bodies maintain proper blood pressure and provide enticing targets for scientists seeking to develop treatments targeting underlying causes of high blood pressure. Developing treatments that do not affect the beneficial effects of calcium will require additional research and a deeper understanding of the calcium-use process

Plastics causing multi-organ damage in seabirds

New research shows that the presence of plastics in seabirds can induce multiple organ and tissue damage affecting the entire body in a multitude of ways, not just limited to the stomach as previously assumed.

Shearwaters are known to ingest large quantities of plastics. Upon examining the proventriculus (main stomach component), kidney and spleen of the birds the team found all organs to have microplastic particles embedded within them. Severe physiological and medical issues were reported in each bird including tissue damage, a significant reduction in tubular glands, and folds within the proventriculus as well as evidence of inflammation, fibrosis and loss of organ structures in the kidney and spleen.

This damage correlated to the birds exposure to macroplastics and indicates that once ingested, macroplastics can release microplastics through a form of shedding or digestive fragmentation. As a result, there is potential for macroplastic exposure to further induce both direct and indirect medical issues and disease through microplastics meaning that the health impacts of plastic pollution on seabirds could previously have been grossly underestimated.

Jack Rivers-Auty et al, The one-two punch of plastic exposure: Macro- and micro-plastics induce multi-organ damage in seabirds, Journal of Hazardous Materials (2022). DOI: 10.1016/j.jhazmat.2022.130117

Study finds unexpected protective properties of pain

Pain has been long recognized as one of evolution's most reliable tools to detect the presence of harm and signal that something is wrong—an alert system that tells us to pause and pay attention to our bodies.

But what if pain is more than just a mere alarm bell? What if pain is in itself a form of protection? A new study led by researchers suggests that may well be the case in mice. The research, published Oct. 14 in Cell, shows that pain neurons in the mouse gut regulate the presence of protective mucus under normal conditions and stimulate intestinal cells to release more mucus during states of inflammation.

The work details the steps of a complex signaling cascade, showing that pain neurons engage in direct crosstalk with mucus-containing gut cells, known as goblet cells. It turns out that pain may protect us in more direct ways than its classic job to detect potential harm and dispatch signals to the brain. This work shows how pain-mediating nerves in the gut talk to nearby epithelial cells that line the intestines. This means that the nervous system has a major role in the gut beyond just giving us an unpleasant sensation and that it's a key player in gut barrier maintenance and a protective mechanism during inflammation.

Our intestines and airways are studded with goblet cells. Named for their cup-like appearance, goblet cells contain gel-like mucus made of proteins and sugars that acts as protective coating that shields the surface of organs from abrasion and damage. The new research found that intestinal goblet cells release protective mucus when triggered by direct interaction with pain-sensing neurons in the gut.

In a set of experiments, the researchers observed that mice lacking pain neurons produced less protective mucus and experienced changes in their intestinal microbial composition—an imbalance in beneficial and harmful microbes known as dysbiosis. To clarify just how this protective crosstalk occurs, the researchers analyzed the behavior of goblet cells in the presence and in the absence of pain neurons.

They found that the surfaces of goblet cells contain a type of receptor, called RAMP1, that ensures the cells can respond to adjacent pain neurons, which are activated by dietary and microbial signals, as well as mechanical pressure, chemical irritation or drastic changes in temperature. The experiments further showed that these receptors connect with a chemical called CGRP, released by nearby pain neurons, when the neurons are stimulated. These RAMP1 receptors, the researchers found, are also present in both human and mouse goblet cells, thus rendering them responsive to pain signals.

Experiments further showed that the presence of certain gut microbes activated the release of CGRP to maintain gut homeostasis.

Isaac M. Chiu, Nociceptor neurons direct goblet cells via a CGRP-RAMP1 axis to drive mucus production and gut barrier protection, Cell (2022). DOI: 10.1016/j.cell.2022.09.024. www.cell.com/cell/fulltext/S0092-8674(22)01196-5

Human brain cells implanted in rats

Miniature human-brain-like structures transplanted into rats can send signals and respond to environmental cues. Researchers grew the structures from human stem cells and then injected them into the brains of newborn rat pups. After six months, the organoids became fully integrated into the rat brains. The approach could lead to a way to test therapies for human brain disorders. But some researchers have ethical concerns about such experiments: creating rodent–human hybrids could harm the animals or produce animals with human-like brains.

--

Would you like a QR code embedded in that cookie? Unobtrusive edibl...

There is currently a race to develop edible tags for food so that, for example, you can see where the food comes from or its ingredients, and the information disappears once you've eaten it. Now, researchers from Japan have developed a way to include an unobtrusive edible tag embedded inside the food—in their original experiments, cookies—that can be read without having to first destroy the food. Another major advantage of their method, known as "interiqr," is that the tag doesn't change the outer appearance or taste of the food at all.

Unobtrusive Edible Tags using Food 3D Printing

Inner structure of the body during physical rehab