Strange planets

A Chance Event 1 Million Years Ago Changed Human Brains Forever

Like treasured recipes passed down from generation to generation, there are just some regions of DNA that evolution doesn't dare tweak. Mammals far and wide share a variety of such encoded sequences, for example, which have remained untouched for millions of years.

Humans are a strange exception to this club. For some reason, recipes long preserved by our ancient ancestors were suddenly 'spiced up' within a short evolutionary period of time.

Because we're the only species in which these regions have been rewritten so rapidly, they are called 'human accelerated regions' (or HARs). What's more, scientists think at least some HARs could be behind many of the qualities that set humans apart from their close relatives, like chimpanzees and bonobos.

In a new study, researchers found the 3D folding of human DNA in the nucleus is a key factor in this pivotal moment for our species.

A big difference between human and chimpanzee DNA is structural: large chunks of the DNA's building blocks have been inserted, deleted, or rearranged in the human genome. So human DNA folds differently in the nucleus compared with the DNA of other primates.

In a study published earlier this year, researchers created a model suggesting the rapid variations appearing in HARs in early humans often opposed each other, turning the activity of an enhancer up and down in a kind of genetic fine-tuning – a model supported by their new research.

Part 1

For their most recent study, the team compared the genomes of 241 mammal species using machine learning to cope with a large amount of data.

They identified 312 HARs and examined where they are located within the 3D 'neighborhoods' of folded DNA. Almost 30 percent of HARs were in the regions of DNA where structural variations had caused the genome to fold differently in humans compared to other primates.

The team also discovered neighborhoods containing HARs were rich with the genes that differentiate humans from our closest relatives, chimpanzees.

In an experiment that compared DNA within growing human and chimpanzee stem cells, one-third of identified HARs were transcribed specifically during the development of the human neocortex.

Many HARs play a role in embryo development, especially in forming neural pathways associated with intelligence, reading, social skills, memory, attention and focus – traits we know are distinctly different in humans than other animals.

In HARs, these enhancer genes, unchanged for millions of years, may have had to adapt to their different target genes and regulatory domains.

Something big happens like this massive change in genome folding, and our cells have to quickly fix it to avoid an evolutionary disadvantage."

We don't yet understand exactly how these changes have impacted specific aspects of our brain development, and how they became an integral part of our species' DNA. 

https://www.science.org/doi/10.1126/science.abm1696

Part 2

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Replaying outcomes in the brain could predict whether we approach or avoid situations

Past neuroscience studies suggest that when deciding their next actions, mice and other rodents tend to replay past outcomes of similar situations in their brain, which is reflected in a rapid activation of certain brain regions in a sequence. Recently, some studies recorded similar replay-associated brain activity in the human brain using imaging techniques.

Researchers  have carried out a study exploring the possibility that this rapid "replay" of past positive and negative outcomes could predict the choices that humans make in a situation where they could either lose or gain money. Their findings, published in Nature Neuroscience, unveil a possible link between replay in the brain and the planned behaviour of humans, suggesting that while choosing to approach or avoid a situation, humans mentally represent the worst case scenario that could result from their choice.

Researchers wanted to examine how different paths are replayed in the human brain in situations where the outcome is not easy to deduce. Specifically, they examined scenarios in which humans might be conflicted about whether to approach or avoid a given path, a dilemma known as the approach-avoidance conflict.

Choosing whether to stay (avoid) or go (approach) is hard when we're uncertain, and it's possible that replay in the brain could explain how we eventually make up our mind. To test this hypothesis, researchers used a brain imaging technique called magnetoencephalography, which entails the use of a machine that sits on the scalp to pick up the tiny electric currents that pass through human neurons.

Magnetoencephalography allows researchers to precisely measure bursts of activity in different areas of the brain and when they occur. They specifically used it to measure the very fast bursts of brain activity that happen in the brain during replay, which are only about 40 milliseconds apart.

After they collected their brain recordings, the researchers used machine learning to analyze them and determine which of the images they were previously presented with were replayed in the brain while participants made a new decision. In other words, the models they used detected the re-activation of sequences of brain activity that were first recorded while the participants were initially presented with a given image.

By analyzing these results in combination with the decisions that participants took (i.e., whether they approached or avoided a given situation), researchers were then able to determine what sequences were being replayed before participants decided to approach or avoid a given path.

Their biggest finding was that humans play out paths of the worst-case scenario. If participants eventually decided to avoid altogether, they tended to replay (or rather 'simulate') paths leading to the desired but forgone reward. On the other hand, if participants eventually decided to approach and take the risk, they tended to replay paths leading to the feared negative outcome. This sort of counterfactual thinking could be a way for the brain to make sure we don't forget alternative outcomes.

Part 1

The findings gathered by this team of researchers offer some interesting new insight about what past experiences humans tend to replay in their brain before deciding whether to approach or avoid a certain situation.

Jessica McFadyen et al, Differential replay of reward and punishment paths predicts approach and avoidance, Nature Neuroscience (2023). DOI: 10.1038/s41593-023-01287-7

Part 2

Early signals of Parkinson's found in gut microbiota of REM sleep behaviour disorder patients

Scientists have found that the gut microbiome holds Parkinson's disease markers and may indicate a method of early diagnosis.

In the study, "Gut microbiome dysbiosis across early Parkinson's disease, REM sleep behavior disorder and their first-degree relatives" published in Nature Communications, the research team looked for correlations in the gut microbiota between comorbid pathologies to see if they could find a causal link.

REM sleep behavior disorder (RBD) causes people to physically act out their dreams while sleeping. RBD affects around 40% of patients with Parkinson's disease (PD), which is also a condition of unintended movements. Patients with RBD are even more likely to acquire PD at some point. The partial overlap in conditions raises interesting questions, and researchers looked to the gut for answers.

In recent years growing knowledge around the gut-brain connection and the relationship between neurological pathologies and microbiota populations has inspired researchers to focus more attention on the role the gut plays in overall human health. While causal relationships are not always clear, correlations between pathologies and microbiota profiles can be strikingly similar across patients with shared diagnoses.

Parkinson's is characterized by the abnormal aggregation of a presynaptic neuronal protein in the central nervous system (spine and brain), alpha-synuclein (α-syn). While this had been considered causal to the pathology, the authors cite studies offering increasing evidence that α-syn pathology has already occurred in the enteric nervous system (neurons embedded into the walls of the gastrointestinal system).

Following the related symptom progression backward, RBD is considered the most specific precursor signal of Parkinson's. Patients with RBD report having an increased prevalence of constipation and increased phosphorylated α-syn immunostaining in their enteric nervous system. Parkinson's patients with RBD features also exhibit these increased constipation and enteric α-syn histopathology effects compared to those without RBD, suggesting a distinct subtype of Parkinson's disease that reflects a gut-brain link of α-synucleinopathy.

The researchers performed a cross-sectional microbiome study across prediagnoses and early stages of the diseases along with controls and RBD relative to disentangle the associations of gut microbiota with the progression of α-synucleinopathy.

The study found gut microbiota compositions significantly altered in early PD and RBD compared with controls and the relative cohort. In RBD patients, the overall microbiota composition shifted closer to those with early Parkinson's.

Random forest modeling identified 12 microbial markers, including depletion of butyrate-producing bacteria and an overabundance of Collinsella, Desulfovibrio, and Oscillospiraceae UCG-005. The profile produced a signal distinct enough to distinguish RBD from controls reliably with machine learning assistance. These findings suggest that Parkinson's-like microbiota profile changes occur at the early stages of RBD-related Parkinson's when RBD first develops.

Another interesting find was the depletion of butyrate-producing bacteria and enrichment of pro-inflammatory Collinsella in RBD relatives, a group that had not yet shared any of the other tell-tale signatures in the microbiota, hinting at a pre-precursor signal that needs further investigation.

Part 1

The study finds markers for pathology pre-symptom progression of Parkinson's disease and REM sleep behavior disorder, highlighting the potential role of gut microbiota in the pathogenesis of α-synucleinopathy. The observations open the door for future research to go beyond the correlations and seek the early causative path of both diseases in hopes of discovering what could be a pre-clinical diagnostic intervention to prevent Parkinson's from developing in the first place.

Bei Huang et al, Gut microbiome dysbiosis across early Parkinson's disease, REM sleep behavior disorder and their first-degree relatives, Nature Communications (2023). DOI: 10.1038/s41467-023-38248-4

Part 2

Study finds that experts support DNA sequencing in newborns

New born babies  undergoing routine newborn screening, a laboratory test to identify the risk of up to 60 treatable conditions is beneficial. Because hundreds of genetic disorders, including a growing number of devastating childhood diseases, now have targeted treatments, including gene and cell therapies, that can offer permanent cures. Despite these advances, the addition of genomic sequencing to newborn screening programs has remained controversial.

Findings from a new study led by researchers  suggest that rare disease experts are now in favour of more expansive newborn testing. In a study published recently in JAMA Network Open, 88% of rare disease experts agreed that DNA sequencing to screen for treatable childhood disorders should be made available to all newborns.

The study further identified 432 gene-disease pairs that are not currently screened for, but that were recommended for newborn screening by more than 50% of the experts. Among the genes that most experts recommended for newborn screening were those associated with a lethal liver and brain disorder, the severe bleeding disorders known as hemophilia A and B, and an increased risk for retinoblastoma, a rare and fatal eye tumour in young children.

Early identification of infants who are at risk for genetic disorders can be lifesaving and screening has the potential to improve health care disparities for affected children.

In many cases in which DNA sequencing identifies a child at risk, a blood test or imaging study can then determine whether the disease condition is already underway, enabling early treatment. In other cases, the child will be entirely healthy despite the positive DNA screen and can be followed for the appearance of symptoms and signs in the future. The researchers note that future studies will be needed to determine whether newborn sequencing is cost-effective and positively contributes to short- and long-term outcomes.

Perspectives of Rare Disease Experts on Newborn Genome Sequencing, JAMA Network Open (2023). DOI: 10.1001/jamanetworkopen.2023.12231

Smallest species shifting the fastest: Bird body size predicts rate of change in a warming world

Birds across the Americas are getting smaller and longer-winged as the world warms, and the smallest-bodied species are changing the fastest.

That's the main finding of a new study of online publication  in the journal Proceedings of the National Academy of Sciences.

The study combines data from two previously published papers that measured body-size and wing-length changes in a total of more than 86,000 bird specimens over four decades in North and South America. One study examined migrating birds killed after colliding with buildings in Chicago; the other looked at nonmigrating birds netted in the Amazon.

Though the two datasets are nonoverlapping in both species composition and geography, and the data were collected independently using different methods, the birds in both studies displayed similarly widespread declines in body size with concurrent increases in wing length.

Now, a new analysis of the combined data has revealed an even more striking pattern: In both studies, smaller bird species declined proportionately faster in body size and increased proportionately faster in wing length.

Both the Chicago and Amazonian studies attributed the reductions in species body size to increasing temperatures over the past 40 years, suggesting that body size may be an important determinant of species responses to climat4e change.

Even so, exactly why smaller-bodied species are changing faster remains an open question, according to the researchers.

 Zimova, Marketa et al, Body size predicts the rate of contemporary morphological change in birds, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2206971120

Recycling plastics might be making things worse

A team of environmental engineers  has found that techniques for recycling plastics may inadvertently lead to increased environmental microplastics. In their study, reported in the Journal of Hazardous Materials Advances, the group tested water used to clean plastic at a recycling plant.

By most accounts, plastic recycling efforts have been a resounding failure. Prior research has shown that only 9% of plastic worldwide is recycled.

This is despite millions of people around the world dutifully separating out their plastic bottles; most of them wind up in landfills anyway. And now, it appears that the recycling process itself might be making things worse. In this new effort, the research team received permission to test a plastic recycling plant to see if it was emitting plastic pollution.

The problem, the researchers note, is that for plastic to be recycled, it must first be cleaned. This is done by washing it in water several times. The rest of the process involves shredding and melting to create pellets. Prior research has suggested washing may result in the release of microplastics into the water. In this new effort, the group found that the plastic was being washed four times. Each water source was tested to find out how much plastic (in the form of micron-sized particles) remained in the water. The research team found microplastics in all four sources. They also noted that most of the water is routed to sewage systems or directly into the environment at most recycling plants. After adding up all the particles they observed, the team estimated that the facility could be emitting approximately 6.5 million pounds of microplastics into the environment each year.

But there was more to the story. The researchers revealed that the facility under study had installed a filtration system, which reduced the number of particles by approximately 50%. However, there was a caveat—the researchers only tested for plastics down to 1.6 microns. Plastic particles can be much smaller than that. Prior research has shown that some can be small enough to make their way into individual cells in an animal's body.

Erina Brown et al, The potential for a plastic recycling facility to release microplastic pollution and possible filtration remediation effectiveness, Journal of Hazardous Materials Advances (2023). DOI: 10.1016/j.hazadv.2023.100309

Nutrition, cognition, and brain health

Rising temperatures are drying up Asia's water tower

Climate models predict that melting glaciers and snowpacks in High Mountain Asia will make one of the largest freshwater reserves unsustainable, threatening water security for Asia’s rapidly growing population.

One of the world’s largest freshwater reserves outside the polar regions, High Mountain Asia is a vast expanse of mountain ranges that encircle the Tibetan Plateau. This area has been recognized as Asia’s water tower for delivering a continuous supply of freshwater into the continent’s major river basins, supplying water to over 2 billion people.

But, as global temperatures continue to rise, evidence shows that water supply in this region is increasingly in danger. In two separate climate models, researchers found that 84% and 97% of the Tibetan Plateau could experience extensive water deficits by the end of the 21st century.

Now, scientists are leveraging this data to help build on immediate policy changes that would protect the future of affected communities in Asia.

A team of researchers from the United States has warned that this critical water resource is on an alarming path of becoming unsustainable due to rising temperatures and climate change, putting downstream communities and biodiversity at serious risk. Their findings were published in Nature.

https://www.nature.com/articles/s41586-022-05643-8

Scientists raise concerns about popular COVID disinfectants

The COVID-19 pandemic has boosted the unnecessary use of antimicrobial chemicals linked to health problems, antimicrobial resistance, and environmental harm, warn more than two dozen scientists in Environmental Science & Technology.

Their critical review details how quaternary ammonium compounds (QACs) are increasingly marketed and used in home, health care, education, and workplace settings despite the availability of safer alternatives and in some cases limited evidence of reduced disease transmission.

Disinfectant wipes containing QACs are often used on children's school desks, hospital exam tables, and in homes where they remain on these surfaces and in the air.  And disinfecting with these chemicals in many cases is unhelpful or even harmful. So experts recommend regular cleaning with soap and water and disinfecting only as needed with safer products.

Human studies have found associations between QACs and asthma, dermatitis, and inflammation. Laboratory animal studies also raise concerns about potential links to infertility, birth defects, and more. Further, there has been evidence dating back to the 1950s that QACs contribute to antimicrobial resistance, making certain bacteria species resistant both to QACs themselves and to critical antibiotics.

It's ironic that the chemicals we're deploying in vain for one health crisis are actually fueling another.

Erica Hartmann et al, Quaternary Ammonium Compounds: A Chemical Class of Emerging Concern, Environmental Science & Technology (2023). DOI: 10.1021/acs.est.2c08244

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Supercomputers have revealed the giant 'pillars of heat' funneling diamonds upward from deep within Earth

Most diamonds are formed deep inside Earth and brought close to the surface in small yet powerful volcanic eruptions of a kind of rock called "kimberlite."

A supercomputer modeling, published in Nature Geoscience, shows these eruptions are fueled by giant "pillars of heat" rooted 2,900 kilometers below ground, just above our planet's core.

Understanding Earth's internal history can be used to target mineral reserves—not only diamonds, but also crucial minerals such as nickel and rare earth elements.

Part 1

Kimberlite eruptions leave behind a characteristic deep, carrot-shaped "pipe" of kimberlite rock, which often contains diamonds. Hundreds of these eruptions that occurred over the past 200 million years have been discovered around the world. Most of them were found in Canada (178 eruptions), South Africa (158), Angola (71) and Brazil (70).

Between Earth's solid crust and molten core is the mantle, a thick layer of slightly goopy hot rock. For decades, geophysicists have used computers to study how the mantle slowly flows over long periods of time.

In the 1980s, one study showed that kimberlite eruptions might be linked to small thermal plumes in the mantle—feather-like upward jets of hot mantle rising due to their higher buoyancy—beneath slowly moving continents.

It had already been argued, in the 1970s, that these plumes might originate from the boundary between the mantle and the core, at a depth of 2,900km.

Then, in 2010, geologists proposed that kimberlite eruptions could be explained by thermal plumes arising from the edges of two deep, hot blobs anchored under Africa and the Pacific Ocean.

And last year, scientists reported that these anchored blobs are more mobile than they thought.

Geologists assumed that mantle plumes could be responsible for igniting kimberlite eruptions. However, there was still a big question remaining: how was heat being transported from the deep Earth up to the kimberlites?

Researchers used supercomputers  to create three-dimensional geodynamic models of Earth's mantle. Their models account for the movement of continents on the surface and into the mantle over the past one billion years.

They calculated the movements of heat upward from the core and discovered that broad mantle upwellings, or "pillars of heat," connect the very deep Earth to the surface. Their modeling shows these pillars supply heat underneath kimberlites, and they explain most kimberlite eruptions over the past 200 million years.

Part 2

The model successfully captured kimberlite eruptions in Africa, Brazil, Russia and partly in the United States and Canada. 

Towards the center of the pillars, mantle plumes rise much faster and carry dense material across the mantle, which may explain chemical differences between kimberlites in different continents.

Lifesaving solution dramatically reduces severe bleeding after childbirth

A new solution, known as E-MOTIVE, could provide a major breakthrough in reducing deaths from childbirth-related bleeding, according to a landmark study published recently (May 9) in the New England Journal of Medicine by researchers from the World Health Organization (WHO).

Postpartum hemorrhage (PPH)—defined as the loss of more than 500 mL of blood within 24 hours after birth—is the leading cause of maternal mortality worldwide. It affects an estimated 14 million women each year and results in around 70,000 deaths, mostly in low and middle-income countries, equivalent to one death every six minutes.

Postpartum hemorrhage is scary, not always predictable, but absolutely treatable. Nonetheless, its impacts around the world are tragic.

The study, which involved more than 200,000 women in four countries, found that objectively measuring blood loss using a simple, low-cost collection device called a "drape" and bundling together WHO-recommended treatments—rather than offering them sequentially—resulted in dramatic improvements in outcomes for women. Severe bleeding—when a woman loses more than a liter of blood after birth—was reduced by 60%, and they were less likely to die.

There was also a substantial reduction in the rate of blood transfusions for bleeding, which is of particular importance in low-income countries where blood is a scarce and expensive resource.

This new approach to treating postpartum hemorrhage could radically improve women's chances of surviving childbirth globally, helping them get the treatment they need when they need it.

The recommended E-MOTIVE package includes early and accurate detection of PPH using a blood-collection drape. This is complemented by an immediate treatment bundle where indicated, including uterine massage, medicines to contract the womb and stop the bleeding, intravenous fluid administration, an examination and, when needed, escalation to advanced care. In the trial, the E-MOTIVE intervention was supported with an implementation strategy consisting of specific training, PPH trolleys or carry cases, engagement of local champions, audits and feedback. All components of the E-MOTIVE intervention can be performed by midwives.

Ioannis Gallos et al, Randomized Trial of Early Detection and Treatment of Postpartum Hemorrhage, New England Journal of Medicine (2023). DOI: 10.1056/NEJMoa2303966

Researchers overcome stem cell delivery barrier, paving the way for regenerative medicine

A recent study published in Nano Letters has introduced a new method for delivering particles into stem cells, which are notoriously difficult to penetrate. The discovery will make it easier to direct and enhance the processes involved in regenerative medicine.

Regenerative medicine takes advantage of the fact that our body's stem cells can change into many other cell types that are vital for the regeneration of tissue and organs, such as heart or nerve cells.

Each type of cell has specialized properties and functions, so harnessing the potential of stem cell development means that regenerative medicine offers some of the most promising treatments for many diseases. To control the type of cell the stem cells change into, scientists need to reprogram the cells' genes by inserting genetic information into the stem cell's nucleus.

However, stem cells have robust protection to stop anything from getting in, similar to our skin, so manipulating the differentiation of stem cells has been problematic.

The researchers have been working to overcome this using rat stem cells and have created a way to bypass the cells' protective barrier.

As we age, the number of stem cells in our body decreases dramatically. So, to harness their potential to regenerate damaged cell tissue and organs, we need to implant them into the body.

But the introduced stem cells usually die within about a week once they are in the body, yet can take around four weeks to differentiate into other cell types.

So scientists  grew stem cells outside the body. Then using a new method, they can insert specific genetic information into the cells using nanoparticles to cause them to change into a particular type of cell.

Once the cells have differentiated into the target cell type, they put them into the area of the body where there is damaged tissue so that they can help to restore it.

Part 1

In a previous study, the research team identified the bottleneck in the process of delivery of nanoparticles to stem cells. They showed that the nanoparticles got trapped in bubble-like vesicles that prevented them from getting into the stem cell, but it wasn't clear why.

To understand how to overcome the difficulties posed by the stem cell barrier, the team of researchers studied ways to improve the movement of nanoparticles across the cell membranes, which could carry genetic information that would direct the transformation of a stem cell to its new cell type.

Eventually, they found that coating the nanoparticles in a type of polymer helped them to get into the stem cells.

The coated nanoparticles avoided getting trapped in vesicles, unlike the uncoated ones. In fact, they seemed to circumvent the vesicles altogether and enter the cell more directly.

It's not yet clear why the coating works, but the discovery will help to make the delivery of genetic information to stem cells more efficient so that it is easier to control which cells they become.

However, the team recognizes there is a long way to go before this method can be used clinically.

Wanchuan Ding et al, Mechanism-Driven Technology Development for Solving the Intracellular Delivery Problem of Hard-To-Transfect Cells, Nano Letters (2023). DOI: 10.1021/acs.nanolett.2c04834

Part 2

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A New Way to Activate Dormant Cells in The Retina Could Restore Vision

Degenerative retinal disease is a problem for millions of people worldwide, as light-sensitive cells called photoreceptors at the back of the eye die without being replaced. Thanks to new research, a solution to the problem might not be far off.

Scientists  have come up with a way to transform dormant support neurons called Müller glial cells into tissues that work like cone photoreceptors, which are required for color perception and visual acuity. While the process has only been tested on mice cells, it could eventually be developed into a therapy that can restore vision in people.

Part of the reason the Müller glial cells were chosen for investigation is their ability to be reprogrammed in some animals. Unfortunately it's not a trick that these cells can do in humans.

What's interesting is that these Müller cells are known to reactivate and regenerate retina in fish. But in mammals, including humans, they don't normally do so, not after injury or disease. And we don't yet fully understand why.

Key to the study were the genes Ikzf1 and Ikzf4, and the proteins they produced. These proteins are known as temporal identity factors, already known to play important roles in the development of cells into various types.

The Müller glial cells were isolated and cultured before being reprogrammed using a variety of temporal identity factors, including Ikzf1 and Ikzf4. These factors didn't fully transform the glial cells into cone cells, but they did take on some of the necessary characteristics to function like the photoreceptors.

While glial cells help nourish, regulate, and organize other cells in the eye, the researchers say there's enough of a surplus to safely convert a number of the support cells into the photoreceptor-like cells – crucial for seeing light and identifying colors.

It's early days, but the process could eventually be adapted to work in humans, without the need to transplant any new cells. Further down the line, these findings could also be useful in treating diseases in the brain – being able to replace certain neurons that have been damaged by reprogramming other types of cells.

https://www.pnas.org/doi/10.1073/pnas.2122168120

Breakthrough research could bring stem cell therapy to the masses

Researchers  have made a significant breakthrough in realizing the promise of stem cell therapy: stem cells that do not trigger an immune response from an immunologically incompatible donor.

In the paper "Hypoimmune induced pluripotent stem cells survive long term in fully immunocompetent, allogeneic rhesus macaques," published in Nature Biotechnology, the researchers detail how they cloaked a line of hypoimmune pluripotent (HIP) stem cells to evade the normal rejection and destruction obstacles to therapeutic use.

In an experimental setting, hypoimmune pluripotent cells did not trigger an immune cell response. They were also impervious to cytotoxicity incited by wild-type stem cells transplanted along with them, successfully evading direct detection and effects from the enrichment of untargeted threats.

The HIP cells survived unrestricted for 16 weeks (the entire test duration) in fully immunocompetent allogeneic recipients and differentiated into several lineages, whereas wild-type cells were vigorously rejected.

In a humanized diabetic mouse model, pancreatic differentiated human HIP cells lasted four weeks and showed evidence of improving the condition. The mice were not immunosuppressed and were not a type match for the cell types used.

An additional long-term test of HIP cells found cell islets 40 weeks after implantation in rhesus macaque recipients without immunosuppression, compared to an unedited wild-type version that was destroyed within a week.

Stem cells have the potential to revolutionize medicine as they can be manipulated to differentiate into various cell types, making them a promising source of new cells for transplantation or regenerative medicine. By introducing stem cells to damaged tissue or organs, it may be possible to regenerate healthy tissue and restore proper function. This has implications for developing new therapies for various diseases, including cancer, heart disease, and neurological disorders.

Xiaomeng Hu et al, Hypoimmune induced pluripotent stem cells survive long term in fully immunocompetent, allogeneic rhesus macaques, Nature Biotechnology (2023). DOI: 10.1038/s41587-023-01784-x

Scientists discover microbes in the Alps and Arctic that can digest plastic at low temperatures

Finding, cultivating, and bioengineering organisms that can digest plastic not only aids in the removal of pollution, but is now also big business. Several microorganisms that can do this have already been found, but when their enzymes that make this possible are applied at an industrial scale, they typically only work at temperatures above 30°C.

The heating required means that industrial applications remain costly to date, and aren't carbon-neutral. But there is a possible solution to this problem: finding specialist cold-adapted microbes whose enzymes work at lower temperatures.

Scientists  knew where to look for such microorganisms: at high altitudes in the Alps, or in the polar regions. When they did that, novel microbial taxa obtained from the 'plastisphere' of alpine and arctic soils were able to break down biodegradable plastics at 15°C. Their findings are published in Frontiers in Microbiology.

How did the ability to digest plastic evolve? Since plastics have only been around since the 1950s, the ability to degrade plastic almost certainly wasn't a trait originally targeted by natural selection.

Microbes have been shown to produce a wide variety of polymer-degrading enzymes involved in the break-down of plant cell walls. In particular, plant-pathogenic fungi are often reported to biodegrade polyesters, because of their ability to produce cutinases which target plastic polymers due their resemblance to the plant polymer cutin.

Discovery of plastic-degrading microbial strains isolated from the alpine and Arctic terrestrial plastisphere, Frontiers in Microbiology (2023). DOI: 10.3389/fmicb.2023.1178474 , www.frontiersin.org/articles/1 … cb.2023.1178474/full

New method for delivering an antioxidant directly to mitochondria in the liver, mitigating oxidative stress

Mitochondria are microscopic organelles found within cells, and are by far the largest producer of the molecule adenosine triphosphate (ATP), which provides energy to many processes in living cells. The process by which mitochondria synthesize ATP generates a large amount of reactive oxygen species (ROS), chemical groups that are highly reactive.

In a healthy cell, the ROS are controlled by the mitochondria; however, when this balance is lost, the excess ROS damages the mitochondria and subsequently cells and tissues. This phenomenon, known as oxidative stress, can cause premature aging and disease. The ROS that cause oxidative stress can be controlled by antioxidants.

A research team has developed a system to deliver antioxidants to mitochondria to mitigate the effects of excess ROS. Their findings have been published in Scientific Reports.

They  developed a drug delivery system which they named CoQ₁₀-MITO-Porter. This system consists of the antioxidant molecule Coenzyme Q₁₀ (CoQ₁₀)—which is also required by mitochondria for ATP production—encapsulated by a lipid nanoparticle that would target mitochondria. 

Variations of the formula for the synthesis of CoQ₁₀-MITO-Porter were tested, and their structures were examined with electron microscopy. CoQ₁₀-MITO-Porter was administered to mice models with acetaminophen-induced liver damage. Acetaminophen overdoses cause excess ROS in mitochondria, which in turn damages cells in the liver. CoQ₁₀-MITO-Porter was transported primarily to the liver and measurably reduced the damage caused by ROS. A further discovery was that downsized CoQ₁₀-MITO-Porter particles with more efficient packaging of CoQ₁₀ were more effective at treating liver damage than the original formulation.

Mitsue Hibino et al, A System that Delivers an Antioxidant to Mitochondria for the treatment of Drug-Induced Liver Injury, Scientific Reports (2023). DOI: 10.1038/s41598-023-33893-7. www.nature.com/articles/s41598-023-33893-7

A New Urine Test Could Be a Simple Way to Check For Cancer

Diagnosing cancer early makes a significant difference to the chances of a patient's successful recovery, which is why cheap, non-invasive screening tests are so important.

A new diagnostic tool development by researchers 

needs little more than a sample of urine, making it possible for some types of cancer to be screened at home much like a pregnancy test. No need for a trip to the doctor or to hospital, and no need for expensive scanning procedures or bothersome blood tests.

While the test might be simple, the technology behind it is rather sophisticated, relying on the presence of enzymes that are specific to the emergence of different cancers.

Researchers developed a new type of nanoparticle with a coating of proteins tagged with an array of DNA sequences. When cancer-related enzymes encounter a nanoparticle in the blood, they snip off a protein specific to that enzyme. Excreted out of the body through the urine, the sequences connected to the protein can then be read like a barcode, identifying the presence of cancer.

Tested on mice via an injection, the same nanoparticles could eventually be developed to be taken orally, through an inhaler, or as a local treatment such as a cream, according to the researchers.

Not only do the nanoparticle's various DNA barcodes have the potential to identify whether or not a tumor is present, they could also be able to distinguish between types of tumors, and spot if a tumor has metastasized (spread to other parts of the body). All of this is vital information for developing and targeting treatments.

The nanoparticle sensors were shown to detect five different enzymes produced by tumors. Up to 46 different DNA barcodes can potentially be expressed in a single sample, once the technology has been scaled up further.

https://www.nature.com/articles/s41565-023-01372-9

Cold Water Therapy Might Do More Harm Than Good. 

Immersion in cold water is definitely an activity that divides people – some love it, others hate it. But many now practice it weekly or even daily in the belief that it's good for their mental and physical health.

Cold water therapy, as it has come to be known, can take the form of outdoor swimming – in lakes, rivers or the ocean – cold showers, or even ice baths. It has been used for a while by sportspeople as a way to reduce muscle soreness and speed up recovery time – with people typically spending about ten minutes after exercise in cold water that's about 10 to 15 °C (50 to 59 °F).

Cold water has also been used to help treat symptoms of depression, pain, and migraine. Indeed, there are many accounts of how cold water therapy has changed lives, cured broken hearts, and helped people during difficult times.

While many studies have shown benefits linked to ice baths and post-exercise recovery, research from 2014 found there could be a placebo effect going on here.

Part 1

New Synthetic Blood Clotting System Could Help Stop Internal Bleeding

Blood clots are one of the body's most important natural defense systems, a mechanism for plugging internal and external gaps to keep us alive. However, in cases where the body is losing a lot of blood, the clotting process can't keep up. This is where a new synthetic replacement could come in.

Researchers have developed a two-component system that targets internal injuries without causing any unwanted damage of its own. The two components match the body's platelets (cell fragments that trigger clotting) and fibrinogen (a protein that helps clots to form). So far, the synthetic process has only been tested on mice, but it effectively triggered the blood clotting part of the natural hemostasis reaction to wounds and proved significantly better at stopping bleeding than previous approaches.

The idea of using two components allows selective gelation of the hemostatic system as the concentration is enhanced in the wound, mimicking the end effect of the natural clotting cascade.

The first part of the system is a biocompatible polymer nanoparticle called PEG-PLGA that is engineered to bind to whatever platelets the body can provide while injured. Platelets are drawn to the site of an injury, which in turn carries in these bound nanoparticles.

The second part of the system is a polymer that takes the place of fibrinogen and starts creating clumps through a reaction with the nanoparticles. The team describes this second component as a crosslinker, essentially getting the particles that have formed around a wound to join together.

Crucially, the researchers designed the particles in a form where they wouldn't accumulate in places where they shouldn't (in the wrong spots, blood clots can also be dangerous to our health) by having them only crosslink at a high enough concentration.

In a tiny initial mouse trial, not only did the synthetic system prove highly effective, but also it lasted longer than normal blood clots would. Moreover, the system didn't trigger any unwanted immune system reactions in the animals.

https://onlinelibrary.wiley.com/doi/full/10.1002/adhm.202202756

Growing crops under solar panels provide food and energy at the same time

 Imagine growing greens in your back yard under a solar panel, and then juicing them in a blender powered by the same energy. A new  project is working to make that a reality. By growing spinach under different solar panels,  researchers are measuring how the process affects both plant growth and the electrical output of the panels. Known as agrivoltaics, the fairly new sustainable practice integrates solar panels with crops, making simultaneous use of land for both food and energy production. Agrivoltaics has the potential to address several pressing issues around sustainability.

https://www.ualberta.ca/folio/2023/05/could-growing-crops-under-sol....

Using reflections to see the world from new points of view

As a car travels along a narrow city street, reflections off the glossy paint or side mirrors of parked vehicles can help the driver glimpse things that would otherwise be hidden from view, like a child playing on the sidewalk behind the parked cars.

Drawing on this idea, researchers have created a computer vision technique that leverages reflections to image the world. Their method uses reflections to turn glossy objects into “cameras,” enabling a user to see the world as if they were looking through the “lenses” of everyday objects like a ceramic coffee mug or a metallic paper weight.

Using images of an object taken from different angles, the technique converts the surface of that object into a virtual sensor which captures reflections. The AI system maps these reflections in a way that enables it to estimate depth in the scene and capture novel views that would only be visible from the object’s perspective. One could use this technique to see around corners or beyond objects that block the observer’s view.

This method could be especially useful in autonomous vehicles. For instance, it could enable a self-driving car to use reflections from objects it passes, like lamp posts or buildings, to see around a parked truck.

The researchers  have shown that any surface can be converted into a sensor with this formulation that converts objects into virtual pixels and virtual sensors. This can be applied in many different areas.

In real life, exploiting these reflections is not as easy as just pushing an enhance button. Getting useful information out of these reflections is pretty hard because reflections give us a distorted view of the world.

Part 1

This distortion depends on the shape of the object and the world that object is reflecting, both of which researchers may have incomplete information about. In addition, the glossy object may have its own color and texture that mixes with reflections. Plus, reflections are two-dimensional projections of a three-dimensional world, which makes it hard to judge depth in reflected scenes.

The researchers found a way to overcome these challenges. Their technique, known as ORCa (which stands for Objects as Radiance-Field Cameras), works in three steps. First, they take pictures of an object from many vantage points, capturing multiple reflections on the glossy object.

Then, for each image from the real camera, ORCa uses machine learning to convert the surface of the object into a virtual sensor that captures light and reflections that strike each virtual pixel on the object’s surface. Finally, the system uses virtual pixels on the object’s surface to model the 3D environment from the point of view of the object.

Imaging the object from many angles enables ORCa to capture multiview reflections, which the system uses to estimate depth between the glossy object and other objects in the scene, in addition to estimating the shape of the glossy object. ORCa models the scene as a 5D radiance field, which captures additional information about the intensity and direction of light rays that emanate from and strike each point in the scene.

The additional information contained in this 5D radiance field also helps ORCa accurately estimate depth. And because the scene is represented as a 5D radiance field, rather than a 2D image, the user can see hidden features that would otherwise be blocked by corners or obstructions.

In fact, once ORCa has captured this 5D radiance field, the user can put a virtual camera anywhere in the scene and synthesize what that camera would see, Dave explains. The user could also insert virtual objects into the environment or change the appearance of an object, such as from ceramic to metallic.

It 's especially challenging to go from a 2D image to a 5D environment. You have to make sure that mapping works and is physically accurate, so it is based on how light travels in space and how light interacts with the environment. 

The researchers evaluated their technique by comparing it with other methods that model reflections, which is a slightly different task than ORCa performs. Their method performed well at separating out the true color of an object from the reflections, and it outperformed the baselines by extracting more accurate object geometry and textures.

They compared the system’s depth estimations with simulated ground truth data on the actual distance between objects in the scene and found ORCa’s predictions to be reliable.

Consistently, with ORCa, it not only estimates the environment accurately as a 5D image, but to achieve that, in the intermediate steps, it also does a good job estimating the shape of the object and separating the reflections from the object texture.

https://news.mit.edu/2023/using-reflections-shiny-objects-camera-0510

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What happens when fish encounter their robotic counterparts?

Study observes the interactions between live fish and fish-like robots

In recent decades, engineers have created a wide range of robotic systems inspired by animals, including four legged robots, as well as systems inspired by snakes, insects, squid and fish. Studies exploring the interactions between these robots and their biological counterparts, however, as still relatively rare.

So recently researchers set out to explore what happens when live fish are placed in the same environment as a robotic fish. Their findings, published in Bioinspiration & Biomimetics, could both inform the development of fish-inspired robots and shed some new light on the behavior of real fish.

During their field experiments, the researchers observed an exciting phenomenon where live fish were observed following the swimming robotic fish. They  are eager to further explore the underlying principles behind this phenomenon and gain a deeper understanding of this 'fish following' behaviour.

 The robotic fish used in their experiments was carefully designed to replicate the appearance, body shape, and movements of koi fish, large and colorful freshwater fish originating from Eastern Asia.

In their experiments, the researchers placed one or two prototypes of their koi fish-like robot in the same tank with one or more live fishes. They then observed how the fish behaved in the presence of this robot and assessed whether their behavior varied based on how many other live fish were present in the tank with them.

Through extensive experimentation, they discovered that live fish exhibit significantly lower proactivity when alone, and the most proactive case is one where a robotic fish is interacting with two real fish. In addition, their experiments on parameter variation indicated that live fish may respond more proactively to robotic fish that swim with high frequency and low amplitude, but they may also move together with the robotic fish at high frequency and high amplitude.

The researchers' observations shed an interesting new light on the collective behavior of fish, which could potentially guide the design of additional fish-like robots. 

Ziye Zhou et al, Proactivity of fish and leadership of self-propelled robotic fish during interaction, Bioinspiration & Biomimetics (2023). DOI: 10.1088/1748-3190/acce87

This video is not related to this research work. I just posted it here to get an idea of robotic fish swimming along with real fish in the ocean

Fearful memories of pain stored in the prefrontal cortex could shape the experience of pain later in life

While pain and fear are very different experiences, past studies showed that they can sometimes be closely related to one another. For instance, when many animals and humans are in dangerous or life-threatening situations, acute fear can suppress their perception of pain, allowing them to fully focus their attention on what is happening to them.

Conversely, research showed that when humans experience high levels of pain, they can create long-term and associative fear memories that make them fearful of situations that they associate with the pain they felt. These memories can in turn increase their sensitivity to pain or lead to the development of unhelpful behavioral patterns aimed at avoiding pain.

The increase in the intensity with which animals or humans perceive pain after very painful past experiences could be liked to their fearful anticipation of pain. The exact neural underpinnings of this process, however, are still poorly understood.

Researchers have recently carried out a study aimed at better understanding which regions of the mice brain stores very painful experiences and how these stored memories can affect future experiences of pain. Their findings, published in Nature Neuroscience, suggest that these memories are stored in the prefrontal cortex, the area covering the front part of the mammalian brain.

The researchers conducted a series of experiments on adult mice using a neural tagging method and optogenetic techniques. During these experiments, the mice received small electric shocks on their feet and were conditioned to become fearful of receiving these shocks again. The team also used optogenetic techniques to either activate or suppress different neural circuits in the mice's brain, to determine how this would affect their sensitivity to pain.

They found that in mice that long-term associative fear memory stored in neuronal engrams in the prefrontal cortex determines whether a painful episode shapes pain experience later in life.

Furthermore, under conditions of inflammatory and neuropathic pain, prefrontal fear engrams expand to encompass neurons representing nociception and tactile sensation, leading to pronounced changes in prefrontal connectivity to fear-relevant brain areas. Conversely, silencing prefrontal fear engrams reverses chronically established hyperalgesia and allodynia.

These results reveal that a discrete subset of prefrontal cortex neurons can account for the debilitating comorbidity of fear and chronic pain and show that attenuating the fear memory of pain can alleviate chronic pain itself.

Alina Stegemann et al, Prefrontal engrams of long-term fear memory perpetuate pain perception, Nature Neuroscience (2023). DOI: 10.1038/s41593-023-01291-x

New study puts a definitive age on Saturn's rings

A new study has delivered the strongest evidence yet that Saturn's rings are remarkably young—potentially answering a question that has boggled scientists for well over a century.

The research, published May 12 in the journal Science Advances, pegs the age of Saturn's rings at no more than 400 million years old. That makes the rings much younger than Saturn itself, which is about 4.5 billion years old.

The researchers arrived at that closure by studying what might seem like an unusual subject: dust.

Tiny grains of rocky material wash through Earth's solar system on an almost constant basis. In some cases, this flux can leave behind a thin layer of dust on planetary bodies, including on the ice that makes up Saturn's rings.

In the new study, researchers set out to put a date on Saturn's rings by studying how rapidly this layer of dust builds up.

Think about the rings like the carpet in your house. If you have a clean carpet laid out, you just have to wait. Dust will settle on your carpet. The same is true for the rings.

It was an arduous process: From 2004 to 2017, the research team used an instrument called the Cosmic Dust Analyzer aboard NASA's late Cassini spacecraft to analyze specks of dust flying around Saturn. Over those 13 years, the researchers collected just 163 grains that had originated from beyond the planet's close neighborhood. But it was enough. Based on their calculations, Saturn's rings have likely been gathering dust for only a few hundred million years.

The planet's rings, in other words, are new phenomena, arising (and potentially even disappearing) in what amounts to a blink of an eye in cosmic terms.

Sascha Kempf, Micrometeoroid infall onto Saturn's rings constrains their age to no more than a few hundred million years, Science Advances (2023). DOI: 10.1126/sciadv.adf8537. www.science.org/doi/10.1126/sciadv.adf8537

Scientists identify mutated gene behind mirror movement disorder

Mirror movement disorder is an inherited neurological condition first manifested by involuntary movements, primarily in the arms and hands, at an early age. In those affected, the right hand involuntarily reproduces the movements of the left hand and vice versa, hence the term "mirror movement."

The disorder can cause pain in the arms during prolonged activities as well as difficulties in performing tasks requiring left-right coordination.

Mirror movement disorder has a daily impact on the life of those affected.

In fact, the simple act of buttoning one's shirt or tying one's shoelaces can be challenging, as well as practicing certain sports or music instruments such as the piano.

Over the last 30 years, scientists have identified a group of genes called the Netrin signaling pathway that work together to attract neurons connecting the left and right sides of the brain to each other and to the spinal cord. This mechanism of neuronal guidance during embryonic development is essential for motor development.

A 

new study sheds light on a new genetic mutation that causes mirror movement disorder and incites its mechanism of action at the molecular level. Using a preclinical model, the researchers found that the mutation in a gene newly involved in the Netrin pathway results in abnormal movements, similar to those observed in the disorder.

The Canadian study is based on studying the genetics of a family whose members have carried the disease for more than four generations. The advance is good news for people with the condition who, until now, did not know which mutated gene was the cause, the scientists say.

Identifying the genes involved is an important first step towards rapid and effective diagnosis; understanding the mechanisms causing mirror movements is also essential in the search for innovative treatments, and could also help target other conditions caused by developmental defects of the nervous system.

 Sabrina Schlienger et al, Genetics of mirror movements identifies a multifunctional complex required for Netrin-1 guidance and lateralization of motor control, Science Advances (2023). DOI: 10.1126/sciadv.add5501

Accretion disk around black holes recreated in the lab

Researchers have created a spinning disk of plasma in a lab, mimicking disks found around black holes and forming stars.

The experiment more accurately models what happens in these plasma disks, which could help researchers discover how black holes grow and how collapsing matter forms stars. As matter approaches black holes it heats up, becoming plasma—a fourth state of matter consisting of charged ions and free electrons. It also begins to rotate, in a structure called an accretion disk. The rotation causes a centrifugal force pushing the plasma outwards, which is balanced by the gravity of the black hole pulling it in.

These glowing rings of orbiting plasma pose a problem—how does a black hole grow if the material is stuck in orbit rather than falling into the hole? The leading theory is that instabilities in magnetic fields in the plasma cause friction, causing it to lose energy and fall into the black hole.

The primary way of testing this has been using liquid metals that can be spun, and seeing what happens when magnetic fields are applied. However, as the metals must be contained within pipes, they are not a true representation of free-flowing plasma.

Now, researchers have used their Mega Ampere Generator for Plasma Implosion Experiments machine (MAGPIE) to spin plasma in a more accurate representation of accretion disks. Details of the experiment are published May 12 in the journal Physical Review Letters.

V. Valenzuela-Villaseca et al, Characterization of Quasi-Keplerian, Differentially Rotating, Free-Boundary Laboratory Plasmas, Physical Review Letters (2023). DOI: 10.1103/PhysRevLett.130.195101

Black holes might be defects in spacetime

A team of theoretical physicists have discovered a strange structure in space-time that to an outside observer would look exactly like a black hole, but upon closer inspection would be anything but: they would be defects in the very fabric of the universe.

Einstein's general theory of relativity predicts the existence of black holes, formed when giant stars collapse. But that same theory predicts that their centers are singularities, which are points of infinite density. Since we know that infinite densities cannot actually happen in the universe, we take this as a sign that Einstein's theory is incomplete. But after nearly a century of searching for extensions, we have not yet confirmed a better theory of gravity.

But we do have candidates, including string theory. In string theory all the particles of the universe are actually microscopic vibrating loops of string. In order to support the wide variety of particles and forces that we observe in the universe, these strings can't just vibrate in our three spatial dimensions. Instead, there have to be extra spatial dimensions that are curled up on themselves into manifolds so small that they escape everyday notice and experimentation. That exotic structure in spacetime gave a team of researchers the tools they needed to identify a new class of object, something that they call a topological soliton. In their analysis they found that these topological solitons are stable defects in space-time itself. They require no matter or other forces to exist—they are as natural to the fabric of space-time as cracks in ice. The research is published in the journal Physical Review D.

Part 1

The researchers studied these solitons by examining the behavior of light that would pass near them. Because they are objects of extreme space-time, they bend space and time around them, which affects the path of light. To a distant observer, these solitons would appear exactly as we predict black holes to appear. They would have shadows, rings of light, the works. Images derived from the Event Horizon Telescope and detected gravitational wave signatures would all behave the same.

It's only once you got close would you realize that you are not looking at a black hole. One of the key features of a black hole is its event horizon , an imaginary surface that if you were to cross it you would find yourself unable to escape. Topological solitons, since they are not singularities, do not feature event horizons.

These topological solitons are incredibly hypothetical objects, based on our understanding of string theory, which has not yet been proven to be a viable update to our understanding of physics. However, these exotic objects serve as important test studies. If the researchers can discover an important observational difference between topological solitons and traditional black holes, this might pave the way to finding a way to test string theory itself.

Pierre Heidmann et al, Imaging topological solitons: The microstructure behind the shadow, Physical Review D (2023). DOI: 10.1103/PhysRevD.107.084042

Part 2

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Study reveals 'developmental window' for thinking styles

While people change and learn throughout life, experts recognize that certain formative periods, known as developmental windows, are crucial for acquiring particular skills. For example, using vocalizations and words to interact with people in the first few years of life is critical for children's language learning.

The researchers found that following the collapse of Romania's authoritarian communist regime in 1989, the rapid increase in education and technology use and the transition from a single, government-controlled source of information to diverse sources had a strong effect on the way people, particularly younger generations, thought about and determined truthfulness, a process known as "epistemic thinking."

Epistemic thinking runs the gamut from absolutist thinking, the belief that only one claim can be right, to multiplist thinking, the belief that more than one claim could be right—it's just a matter of opinion. Finally, evaluativist thinking posits that assertions can be evaluated in terms of both logic and evidence.

Amalia Ionescu et al, The effects of sociocultural changes on epistemic thinking across three generations in Romania, PLOS ONE (2023). DOI: 10.1371/journal.pone.0281785

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Mouse Study Reveals Unlikely Connection Between Menthol And Alzheimer's

A new study reports something strange: When mice with Alzheimer's disease inhale menthol, their cognitive abilities improve. It seems the chemical compound can stop some of the damage done to the brain that's usually associated with the disease.

In particular, researchers noticed a reduction in the interleukin-1-beta (IL-1β) protein, which helps to regulate the body's inflammatory response – a response that can offer natural protection but one that leads to harm when it's not controlled properly.

The team behind the study says it shows the potential for particular smells to be used as therapies for Alzheimer's. If we can figure out which odors cause which brain and immune system responses, we can harness them to improve health.

Researchers  have focussed on the olfactory system's role in the immune and central nervous systems, and they have confirmed that menthol is an immunostimulatory odour in animal models.

They observed that short exposures to this substance for six months prevented cognitive decline in the mice with Alzheimer's and, what is most interesting, also improved the cognitive ability of healthy young mice.

https://www.frontiersin.org/articles/10.3389/fimmu.2023.1130044/full

Unique insights into differences between primary and metastatic cancer by large-scale DNA data analyses

Cancer is caused by DNA changes that cause a cell to gradually change from benign to malignant. This can lead to metastases in other parts of the body. By analyzing the DNA data of more than 7,000 patients, the researchers show that there are major differences between primary and metastatic cancer and that there are also tumor types in which the primary tumor and the metastasis hardly differ from one another. By studying the types of DNA changes and the consequences of the changes, important insights into the underlying biological processes were obtained.

Researchers have mapped the DNA changes of the 23 most common tumor types. They have studied the differences in genetic characteristics between the source of the cancer, the primary tumor, and metastatic tumors.

Unique collections of whole genome sequencing data from tumors were used. This enabled the researchers to study in great detail which changes in the tumor had occurred during and after the tumor had developed. The researchers have harmonized and systematically compared the world's largest publicly available data sets of primary tumors (from the international PCAWG consortium with information from ~2,800 patients) and metastatic tumors (Hartwig Medical Database, ~4,400 patients). The results of this research were published May 10 in the journals Nature and Nature Genetics.

Part 1

The paper published in Nature describes the overall genomic differences found when comparing primary and metastatic tumors and highlights the fact that the differences are highly dependent on the type of cancer studied, as well as the tumor's exposure to previous anti-tumor treatments.

One could state that this work confirms many observations that were previously done in cancer type-specific studies. However, the pan-cancer nature of the current study demonstrates which processes and mechanisms are shared between tumor types and also quantifies their prevalence per tumor type. Such a systematic analysis and comparison from a genome-wide perspective has never been performed before.

The second study, published in parallel in the journal Nature Genetics, presents an analysis of the genomic alterations that allow tumors to escape the immune system, as well as a comparison of their prevalence in primary and metastatic tumors.

The researchers found that the prevalence of genetic immune escape is highly variable between tumor types and that in certain tumor types only a single mechanism is present, while in others various processes were affected. Furthermore, they showed that there are not many differences between primary and metastatic tumors, indicating that immune evasion is a characteristic that is acquired relatively early in tumor development.

This is the first time a complete tumor genome-wide sequencing dataset has been generated for primary and metastatic tumors of this magnitude. These data are public and available for research, providing a new global resource for further research into the biology and evolution of cancer, as well as the development of new therapies to combat the disease.

Part 2

Metastatic spread involves the detachment of tumor cells from a primary tumor, colonization of secondary tissue and growth in a hostile environment. Advanced metastatic tumors are often able to withstand aggressive treatment regimens and represent the leading cause of cancer-associated death.

 The researchers found that the differences are highly dependent on the type of tumor. In some types of tumors, such as pancreatic cancer, the genomic differences between primary and metastatic tumors are subtle. While in others, such as prostate, thyroid and some subtypes of breast cancer, there are very important genomic differences.

In addition, the exhaustive analysis has allowed the researchers to identify recurrent genomic patterns in metastatic tumors such as the presence of high genomic instability, greater enrichment of structural genomic alterations versus point mutations, and the presence of genomic alterations associated with the acquisition of resistance to treatment. However, hardly any driver alterations exclusively associated with the metastatic process could be identified.

Francisco Martínez-Jiménez et al, Pan-cancer whole-genome comparison of primary and metastatic solid tumours, Nature (2023). DOI: 10.1038/s41586-023-06054-z

Francisco Martínez-Jiménez et al, Genetic immune escape landscape in primary and metastatic cancer, Nature Genetics (2023). DOI: 10.1038/s41588-023-01367-1

Part 3

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Viruses in the guts of centenarians may help them resist pathogens

New research suggests that centenarians—people who live to be at least 100—have a diverse collection of viruses in their gut that could help protect them from infectious diseases. The findings, published May 15 in Nature Microbiology, shed light on some of the biological pathways that may help centenarians live long, healthy lives.

In the study, researchers analyzed the viromes—or viral genomes—from 195 individuals from Japan and Sardinia. They found that centenarians  had a greater diversity of bacteria and viruses in their guts.

They also found that viruses found in centenarians increased the ability of the healthy gut bacteria to break down sulfate, which could help preserve the gut's ability to fight bacterial infections.

The study adds to a growing body of evidence showing that the interactions between bacteria, viruses, and fungi in the gut play an important role in preventing age-related conditions.

This snapshot of how the virome interacts with gut microbiomes could tell us about how microbial and viral ecology evolves over the lifetime of a person. This offers an important starting point for uncovering the mechanisms behind how the gut ecosystem maintains health.

Part 1

Earlier  it was found that intestinal bacteria in centenarians produced unique bile acids that could help keep infections at bay. Other researchers have found that bacteriophages—or viruses that infect bacteria—had an effect on cognition and memory in mice.

 Now the researchers compared the viromes of young adults over 18, older adults over 60, and centenarians aged 100 and over. 

 In centenarians, the team found not only more diverse bacteria and viruses, but also more viruses in the lytic life cycle, during which viruses are active and burst and kill the bacteria they infect—a phase that is more common in infants than adults. At least a quarter of the viruses found in centenarians encoded genes that support key stages of sulfate metabolism. The researchers think this could help sustain the integrity of the mucosal barrier, a highly selective collection of tightly-bound cells that allows the body to absorb nutrients in the gut while keeping bacteria and toxins at bay.

Joachim Johansen et al, Centenarians have a diverse gut virome with the potential to modulate metabolism and promote healthy lifespan, Nature Microbiology (2023). DOI: 10.1038/s41564-023-01370-6

Part 2

This is made of plants. Why do we call it “meat”?

Deficiency causes rare tropical plant to develop appetite for meat

Under certain circumstances, a rare tropical plant develops into a carnivore. A research team  has now deciphered the mechanism responsible for this.

Triphyophyllum peltatum is a unique plant. Native to the tropics of West Africa, the liana species is of great interest for medical and pharmaceutical research due to its constituents: In the laboratory, these show promising medically useful activities against pancreatic cancer and leukemia cells, among others, as well as against the pathogens that cause malaria and other diseases.

However, the plant species is also interesting from a botanical perspective: Triphyophyllum peltatum is the only known plant in the world that can become a carnivore under certain circumstances. Its menu then includes small insects, which it captures with the help of adhesive traps in the form of secretion drops and digests with lytic enzymes synthesized.

A high flexibility can be observed in the leaves of the plant, which develop three different types depending on the stage of development. While in the juvenile phase simple leaves are initially formed, later so-called "trap leaves" can be formed, which carry a large number of adhesive traps. When these trap leaves have served their purpose, the plant either forms normal leaves again or—if the plant has entered the liana stage—leaves with two hooks at the tip as a climbing support.

As far as the expression of leaf identity is concerned, Triphyophyllum peltatum shows a high degree of flexibility: the developmental stages can vary in length, and the carnivorous stage can be omitted completely or made up for at a later stage. Thus, the plant seems to adapt to the prevailing conditions of its habitat.

The trigger that turns the plant into a carnivore was previously unknown. One reason for this was the fact that Triphyophyllum peltatum was considered very difficult to cultivate and therefore the formation of trap leaves was difficult to study experimentally. This problem has now been solved by scientists now.

But what is even more significant is that with the help of these plants, the research team was able to identify the factor that triggers the transformation to the carnivore lifestyle. The team has now published the results of this research in the current issue of the journal New Phytologist.

Researchers exposed the plant to different stress factors, including deficiencies of various nutrients, and studied how it responded to each. Only in one case were we able to observe the formation of traps: in the case of a lack of phosphorus. In fact, a greatly reduced supply of phosphorus is already sufficient to trigger the development into a carnivorous plant, according to the scientists.

Part 1

In its original habitat in African tropical forests on nutrient-poor soils, Triphyophyllum peltatum can thus avoid the threat of malnutrition by forming traps and accessing the important nutritional element through digestion of its insect prey. "These new findings are a breakthrough because they allow future molecular analyses that will help understand the origins of carnivory," the scientists say.

Traud Winkelmann et al, Carnivory on demand: phosphorus deficiency induces glandular leaves in the African liana Triphyophyllum peltatum, New Phytologist (2023). DOI: 10.1111/nph.18960

How superbug A. baumannii survives metal stress and resists antibiotics

The deadly hospital pathogen Acinetobacter baumannii can live for a year on a hospital wall without food and water. Then, when it infects a vulnerable patient, it resists antibiotics as well as the body's built-in infection-fighting response. The World Health Organization (WHO) recognizes it as one of the three top pathogens in critical need of new antibiotic therapies.

Now a team of international researchers have discovered how the superbug can survive harsh environments and then rebound, causing deadly infections. They have found a single protein that acts as a master regulator. When the protein is damaged, the bug loses its superpowers allowing it to be controlled, in a lab setting. The research is published in Nucleic Acids Research.

During infection our cells fight back by either flooding or starving bacteria of essential metals such as copper and zinc. A. baumannii has strong drug pumps that push antibiotics, metals and other threats out of the cell.

By studying how this bug deals with infection stresses,  researchers have found an important uncharacterized regulatory protein (DksA). When scientists disrupted this protein, it lead to changes in about 20 percent of the bug's genome and breaks its pumping system.

Ram P Maharjan et al, DksA is a conserved master regulator of stress response in Acinetobacter baumannii, Nucleic Acids Research (2023). DOI: 10.1093/nar/gkad341

Why wavy wounds heal faster than straight wounds

Wavy wounds heal faster than straight wounds because shapes influence cell movements, a team of researchers has found.

Scientists observed the motion of cells and found that those near wavy shaped wounds moved in a swirling manner while cells near straight wounds moved in straight lines, traveling parallel to the edges.

The team concluded that the swirling or vortex-like movement is crucial to gap bridging, in which cells build bridges to heal damaged tissues, and which accelerates the wound healing process in wavy wounds.

This is the first time that the relationship between gap bridging, and the speed of wound healing has been determined. The scientists said their findings open the door to the development of more effective strategies to speed up wound healing, for better wound management, tissue repair, and plastic surgery.

An essential component of wound healing is re-epithelialization, a process in which the epithelial cell—a type of cell found on the skin—moves to form a bridge between the wound and the skin, closing its gap.

While previous studies have found that zig zag wounds healed faster than straight wounds, little is known about how different wound curvatures (shape) and wound sizes influence healing efficiency, nor about the mechanism of re-epithelialization.

To investigate, the NTU scientists prepared synthetic wounds with a range of widths (30 micrometers to 100 micrometers) and curvatures (radius of curvature: 30 micrometers, 75 micrometers, 150 micrometers and straight line) to learn how cells moved to close wound gaps in different circumstances.

Using particle image velocimetry—an optical measurement technique for fluid flow—researchers found that wavy wounds induced more complex collective cell movements, such as a swirly, vortex-like motion. By contrast in a straight wound, cells moved parallel to the wound front, moving in straight lines like a marching band.

Wavy wounds heal nearly five times faster

The  team also observed the healing progress of the synthetic wounds over a period of 64 hours and found that the healing efficiency of wavy gaps—measured by the percentage area covered by the cells over time—is nearly five times faster than straight gaps.

 Hongmei Xu et al, Geometry-mediated bridging drives nonadhesive stripe wound healing, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2221040120

How bending implantable medical devices can lead to bacterial growth

A study by researchers  shows that mechanical deformation of medically implantable materials—such as bending or twisting—can have a big impact on the formation of potentially harmful biofilms.

The study, described in a paper published in Scientific Reports, shows that even slight bending of elastomeric materials such as polydimethylsiloxane (PDMS)—also known as silicone—opens up microscopic cracks that are perfect environments for colonizing bacteria.

These kinds of materials are used in all kinds of biomedical applications, from catheters to tracheal tubes and prosthetic breast implants.

The formation of microbial biofilms on these materials is common, but scientists were surprised by the degree to which bending silicone, and other rubber materials, causes these cracks to reversibly open and close—and how big a difference they make in terms of biofilm formation.

Biofilms are complex communities of organisms that grow on surfaces. While individual microbial cells are susceptible both to antibiotics and the body's natural defensive systems, the biofilm environment can shield them from these interventions, which can lead to persistent infections.

Infections associated with medical-device biofilms, which sometimes develop after surgery, can be serious health risks—lengthening hospital stays or causing patients who have been discharged to be readmitted.

They have combined not only   microbiology and materials science, but also mechanical engineering, because they're talking about mechanical stress, strain and deformation. This bending effect is something that had not been noticed before.

Part 1