Male pheromones improve health of females' eggs

Male pheromones just might be the fountain of youth for aging female animals’ eggs, according to a new study.

In the new study, researchers used the tiny transparent roundworm C. elegans, a well-established model organism commonly used in biology research. Exposure of female roundworms to male pheromones slowed down the aging of the females’ egg cells, resulting in healthier offspring.

Not only did the exposure decrease embryonic death by more than twofold, it also decreased chromosomal abnormalities in surviving offspring by more than twofold. Under the microscope, egg cells also looked younger and healthier, rather than tiny and misshapen, which is common with aging.

To conduct the study, the team aged female roundworms in the presence of a pheromone that is normally produced by male roundworms. The researchers saw that egg quality in females exposed to the pheromone was higher than in control roundworms that did not encounter the pheromone.

Although continuous exposure to male pheromones worked best, even shorter exposure improved overall egg quality. Researchers think this result can be explained by the animals’ “shifting energy budgets.”

Acting outside the body, pheromones are chemicals that animals produce and release to elicit social responses from other members of their species. Pheromones also inform animals about how to budget their finite energy.

When conditions are not conducive to reproduction, female animals will spend resources and energy maintaining their overall body health, including muscles, neurons, intestines and other nonreproductive organs. Sensing male pheromones triggers downstream signaling from the nervous system to the rest of the body, causing the female animals to shift their energy and resources to increasing reproductive health instead. The result? Better eggs but faster decay of the body.

The pheromone tricks the female into sending help to her eggs and shortchanging the rest of her body. It’s not all or nothing, but it’s shifting the balance.

The researchers think this finding potentially could lead to pharmacological interventions that combat infertility issues in humans by improving egg cell quality and delaying the onset of reproductive aging.

Reproductive aging affects everyone. One of the first signs of biological aging is the decreased quality of reproductive cells, which causes reduced fertility, increased incidence of fetal defects including miscarriages, and eventually loss of fertility. By all criteria scientists could think of, male pheromones made the eggs better.

Of course, there are unfortunate trade-offs. When female roundworms neglected the rest of their body to focus their energy on reproductive health, they were more likely to experience early death.

Erin Z. Aprison, Svetlana Dzitoyeva, David Angeles-Albores, Ilya Ruvinsky. A male pheromone that improves the quality of the oogenic germline. Proceedings of the National Academy of Sciences, 2022; 119 (21) DOI: 10.1073/pnas.2015576119

https://news.northwestern.edu/stories/2022/05/male-pheromones-impro....

Drug treatment for cataracts moves a step closer

A revolutionary new treatment for cataracts has shown extremely positive results in laboratory tests, giving hope that the condition, which currently can only be cured with surgery, could soon be treated with drugs.

Cataract is a clouding of the eye lens that develops over time and affects the quality of vision. It is caused by a disorganization of the proteins in the lens that leads to clumps of protein forming, which scatter light and severely reduce transmission to the retina. Cataracts cause vision loss  and blindness for millions of people worldwide.

Scientists have  been carrying out advanced optical tests on an oxysterol compound that had been proposed as an anti-cataract drug.  In laboratory trials, treatment with the oxysterol compound VP1-001 showed an improvement in refractive index profiles—a key optical parameter that is needed to maintain high focusing capacity—in 61% of lenses. This means that the protein organization of the lens is being restored, resulting in the lens being better able to focus. This was supported by a reduction in lens opacity in 46% of cases.

It has shown that there is a remarkable difference and improvement in optics between eyes with the same type of cataract that were treated with the compound compared to those that were not.

"Improvements occurred in some types of cataract but not in all, indicating that this may be a treatment for specific cataracts. This suggests distinctions may need to be made between cataract types when developing anti-cataract medications. It is a significant step forward towards treating this extremely common condition with drugs rather than surgery.

Oxysterol compounds in mouse mutant αA- and αB-crystallin lenses 2 can improve the optical properties of the lens, Investigative Ophthalmology & Visual Science (2022).

'Next generation wonder material' created for first time

For over a decade, scientists have attempted to synthesize a new form of carbon called graphyne with limited success. That endeavor is now at an end.

Graphyne has long been of interest to scientists because of its similarities to the "wonder material" graphene—another form of carbon that is highly valued by industry . 

However, despite decades of work and theorizing, only a few fragments have ever been created before now.

This research, announced last week in Nature Synthesis, fills a longstanding gap in carbon material science, potentially opening brand-new possibilities for electronics, optics and semiconducting material research.

Scientists have long been interested in the construction of new or novel carbon allotropes, or forms of carbon, because of carbon's usefulness to industry, as well as its versatility.

There are different ways carbon allotropes can be constructed depending on how sp2, sp3 and sp hybridized carbon (or the different ways carbon atoms can bind to other elements), and their corresponding bonds, are utilized. The most well-known carbon allotropes are graphite (used in tools like pencils and batteries) and diamonds, which are created out of sp2 carbon and sp3 carbon, respectively.

Using traditional chemistry methods, scientists have successfully created various allotropes over the years, including fullerene and graphene.

However, these methods don't allow for the different types of carbon to be synthesized together in any sort of large capacity, like what's required for graphyne, which has left the theorized material—speculated to have unique electron conducting, mechanical and optical properties—to remain that: a theory.

Part 1

Some researchers are now  studying reversible chemistry, which is chemistry that allows bonds to self-correct, allowing for the creation of novel ordered structures, or lattices, such as synthetic DNA-like polymers.

Using a process called alkyne metathesis—which is an organic reaction that entails the redistribution, or cutting and reforming, of alkyne chemical bonds (a type of hydrocarbon with at least one carbon-carbon triple covalent bond)—as well as thermodynamics and kinetic control, the researchers were able to successfully create what had never been created before: A material that could rival the conductivity of graphene but with control.

This could be the next generation wonder material. 

While the material has been successfully created, the scientists still want to look into the particular details of it, including how to create the material on a large scale and how it can be manipulated.

Yiming Hu et al, Synthesis of γ-graphyne using dynamic covalent chemistry, Nature Synthesis (2022). DOI: 10.1038/s44160-022-00068-7

Part 2

Low-cost gel film can pluck drinking water from desert air

More than a third of the world's population lives in drylands, areas that experience significant water shortages. Scientists and engineers have developed a solution that could help people in these areas access clean drinking water.

Researchers now developed a low-cost gel film made of abundant materials that can pull water from the air in even the driest climates. The materials that facilitate this reaction cost a mere $2 per kilogram, and a single kilogram can produce more than 6 liters of water per day in areas with less than 15% relative humidity and 13 liters in areas with up to 30% relative humidity.

The research builds on previous breakthroughs from the team, including the ability to pull water out of the atmosphere and the application of that technology to create self-watering soil. However, these technologies were designed for relatively high-humidity environments.

This new work is about practical solutions that people can use to get water in the hottest, driest places on Earth. This could allow millions of people without consistent access to drinking water to have simple, water generating devices at home that they can easily operate.

The researchers used renewable cellulose and a common kitchen ingredient, konjac gum, as a main hydrophilic (attracted to water) skeleton. The open-pore structure of gum speeds the moisture-capturing process. Another designed component, thermo-responsive cellulose with hydrophobic (resistant to water) interaction when heated, helps release the collected water immediately so that overall energy input to produce water is minimized.

The film is flexible and can be molded into a variety of shapes and sizes, depending on the need of the user. Making the film requires only the gel precursor, which includes all the relevant ingredients poured into a mold.

The gel takes 2 minutes to set simply. Then, it just needs to be freeze-dried, and it can be peeled off the mold and used immediately after that.

Youhong Guo et al, Scalable super hygroscopic polymer films for sustainable moisture harvesting in arid environments, Nature Communications (2022). DOI: 10.1038/s41467-022-30505-2

Study reveals evidence that bacteria can live in snake and spider venoms

Newly published research  shows that, contrary to what is commonly believed, the venom of snakes and spiders is actually populated with microbes, including bacteria that could cause infection in people who have suffered a bite.

For decades scientists have thought that animal venom is an entirely sterile environment due to it being full of antimicrobial substances—materials that can kill bacteria.

However, new scientific evidence from research has shown that this is not the case. 

The work, published today in scientific journal Microbiology Spectrum demonstrates how adaptable microorganisms are. The study provides strong genetic and culture evidence that bacteria can not only survive in the venom glands of several species of snakes and spiders, but can also mutate to resist the notoriously toxic liquid that is venom.

The findings also suggest that victims of venomous animal bites may therefore also need to be treated for infections, not just antivenom to tackle the toxins deposited through the bite.

Common diagnostic tools failed to identify these bacteria correctly—if you were infected with these, a doctor would end up giving you the wrong antibiotics, potentially making matters worse.

When researchers sequenced their DNA recently they clearly identified the bacteria and discovered they had mutated to resist the venom. This is extraordinary because venom is like a cocktail of antibiotics, and it is so thick with them, you would have thought the bacteria would not stand a chance. Not only did they stand a chance, they had done it twice, using the same mechanisms.

They also directly tested the resistance of Enterococcus faecalis, one of the species of bacteria they found in the venom of black-necked spitting cobras, to venom itself and compared it to a classic hospital isolate: the hospital isolate did not tolerate the venom at all, but the two isolates from venom  happily grew in the highest concentrations of venom researchers could throw at them.

The researchers say that their study shows the need for clinicians to consider treating snakebite victims not just for tissue destruction, but for infection too, as quickly as possible.

 Elham Esmaeilishirazifard et al, Bacterial Adaptation to Venom in Snakes and Arachnida, Microbiology Spectrum (2022). DOI: 10.1128/spectrum.02408-21. journals.asm.org/doi/10.1128/spectrum.02408-21

Nuclear pasta, the hardest known substance in the universe

A team of scientists has calculated the strength of the material deep inside the crust of neutron stars and found it to be the strongest known material in the universe.

Neutron stars are born after supernovas, an implosion that compresses an object the size of the sun to about the size of Montreal, making them "a hundred trillion times denser than anything on earth." Their immense gravity makes their outer layers freeze solid, making them similar to earth with a thin crust enveloping a liquid core.

This high density causes the material that makes up a neutron star, known as nuclear pasta, to have a unique structure. Below the crust, competing forces between the protons and neutrons cause them to assemble into shapes such as long cylinders or flat planes, which are known in the literature as 'lasagna' and 'spaghetti,' hence the name 'nuclear pasta.' Together, the enormous densities and strange shapes make nuclear pasta incredibly stiff.

Thanks to their computer simulations, which required 2 million hours worth of processor time or the equivalent of 250 years on a laptop with a single good GPU, Caplan and his colleagues were able to stretch and deform the material deep in the crust of neutron stars.

M. E. Caplan, A. S. Schneider, C. J. Horowitz. The Elasticity of Nuclear Pasta. Physical Review Letters, 2018 [abstract]

https://www.sciencedaily.com/releases/2018/09/180918110836.htm#:~:t....

First Patient Injected With Experimental Cancer-Killing Virus in New Clinical Trial

An experimental cancer-killing virus has been administered to a human patient for the first time, with hopes the testing will ultimately reveal evidence of a new means of successfully fighting cancer tumors in people's bodies.

The drug candidate, called CF33-hNIS (aka Vaxinia), is what's called an oncolytic virus, a genetically modified virus designed to selectively infect and kill cancer cells while sparing healthy ones. In the case of CF33-hNIS, the modified pox virus works by entering cells and duplicating itself. Eventually, the infected cell bursts, releasing thousands of new virus particles that act as antigens, stimulating the immune system to attack nearby cancer cells. Previous research in animal models has shown the drug can harness the immune system in this way to hunt and destroy cancer cells, but up until now no testing has been done in humans. That's just changed, with co-developers of the drug – the City of Hope cancer care and research center in Los Angeles, and Australia-based biotech company Imugene – now announcing that the first clinical trial in human patients is underway.

https://clinicaltrials.gov/ct2/show/NCT05346484

https://www.sciencealert.com/first-patient-injected-with-experiment...

A candlelight-like glow from a flexible organic LED

Giving off a comfortable glow, candles set the ambiance for a special dinner or just a quiet evening at home. However, some lighting alternatives, such as electronic candles, give off unwanted blue wavelengths that interfere with the body's circadian rhythm. Now, researchers reporting in ACS Applied Electronic Materials have fabricated an improved bendable organic LED that releases candlelight-like light for flexible lighting and smart displays that people can comfortably use at night.

researchers developed organic LEDs that released warm-white light, similar to that produced by candles. However, the devices still emitted some blue wavelength light, which can interfere with sleep because it dampens the body's production of melatonin. These devices were made of solid materials and weren't flexible.

One option for making them bendable is to use a plastic backing, as has been done for other organic LEDs. But plastics don't stand up well to repeated bending. Another option for the backing is mica—a natural mineral with extreme temperature tolerance that can be split into bendable, transparent sheets. So, Jou, Ying-Hao Chu and colleagues wanted to develop an even better organic LED and apply it to a mica backing, creating a bendable candle-like light with a long lifespan.

The researchers deposited a clear indium tin oxide film onto a transparent mica sheet as the LED's anode, which could bend 50,000 times without breaking. Next, the team mixed the luminescent substance N,N'-dicarbazole-1,1'-biphenyl with red and yellow phosphorescent dyes to produce a light-emitting layer. This layer was then placed between electrically conductive solutions with the anode on one side and an aluminum layer on the other side, creating a flexible organic LED.

When a constant current was applied to the device, it produced a bright, warm light with even less blue wavelength emissions than natural candlelight. Calculations showed that exposure to the LED for 1.5 hours would suppress a person's melatonin production by about 1.6%, whereas light from a cold-white compact fluorescent lamp would suppress melatonin production by 29%. The researchers say that the flexibility of their candlelight-like organic LED opens up the design opportunities for blue-light-free nighttime devices.

Tun-Hao Chen et al, Flexible Candlelight Organic LED on Mica, ACS Applied Electronic Materials (2022). DOI: 10.1021/acsaelm.2c00123

Scientists discover new tools to fight potentially deadly protozoa

Investigating whether epigenetic aging is the manifestation of one or more aging hallmarks

A team of researchers affiliated with a host of institutions in the U.K. and the U.S. has conducted an investigation into whether epigenetic aging is the manifestation of one or more aging hallmarks. In their paper published in the journal Nature Aging, the group describes subjecting human cells to three kinds of abuse and then testing them to see if the cells aged epigenetically.

Over the past several years, some researchers focusing on the science of aging have become proponents of what is described as epigenetic aging, whereby certain attributes of our bodies age at a rate that may not be consistent with our biological age. That has led to studies aimed at measuring the epigenetic age of people (and other animals) using DNA methylation clocks, ostensibly as a means to circumvent them and allow people to live longer. In this new effort, the researchers studied hallmarks of aging such as exposure to radiation, reproduced them and tested the effects on the pace of epigenetic aging.

The work involved collecting tissue samples from 14 healthy people and dividing them into four groups. One group was subjected to a small dose of radiation, another had some of their cell properties altered to become cancerous, and yet another set was subjected to induced senescence. The fourth group was left undisturbed. Each of the groups represented a hallmark of aging. Exposure to radiation can, for example, make changes to the genome that results in accelerated aging.

Part 1

None of the tissue samples exhibited changes in epigenetic aging. But the researchers did find changes to the way the cells handled energy—their ability to sense nutrients was impacted. This ability plays a major role in cell growth, reproduction and death. The researchers also found changes in mitochondrial activity and in the number of stem cells in their samples. They suggest that epigenetic aging does not predict changes in senescence, nor does it match with age-related changes to telomeres, one of the major indicators of aging in general.

How the universe got its magnetic field

When we look out into space, all of the astrophysical objects that we see are embedded in magnetic fields. This is true not only in the neighborhood of stars and planets, but also in the deep space between galaxies and galactic clusters. These fields are weak—typically much weaker than those of a refrigerator magnet—but they are dynamically significant in the sense that they have profound effects on the dynamics of the universe. Despite decades of intense interest and research, the origin of these cosmic magnetic fields remains one of the most profound mysteries in cosmology.

In previous research, scientists came to understand how turbulence, the churning motion common to fluids of all types, could amplify preexisting magnetic fields through the so-called dynamo process. But this remarkable discovery just pushed the mystery one step deeper. If a turbulent dynamo could only amplify an existing field, where did the "seed" magnetic field come from in the first place?

We wouldn't have a complete and self-consistent answer to the origin of astrophysical magnetic fields until we understood how the seed fields arose. New work carried out recently provides an answer that shows the basic processes that generate a field from a completely unmagnetized state to the point where it is strong enough for the dynamo mechanism to take over and amplify the field to the magnitudes that we observe.

Naturally occurring magnetic fields are seen everywhere in the universe. They were first observed on Earth thousands of years ago, through their interaction with magnetized minerals like lodestone, and used for navigation long before people had any understanding of their nature or origin. Magnetism on the sun was discovered at the beginning of the 20th century by its effects on the spectrum of light that the sun emitted. Since then, more powerful telescopes looking deep into space found that the fields were ubiquitous.

And while scientists had long learned how to make and use permanent magnets and electromagnets, which had all sorts of practical applications, the natural origins of magnetic fields in the universe remained a mystery. Recent work has provided part of the answer, but many aspects of this question are still under debate.

Part 1

Scientists started thinking about this problem by considering the way that electric and magnetic fields were produced in the laboratory. When conductors, like copper wire, move in magnetic fields, electric fields are created. These fields, or voltages, can then drive electrical currents. This is how the electricity that we use every day is produced. Through this process of induction, large generators or "dynamos" convert mechanical energy into the electromagnetic energy that powers our homes and offices. A key feature of dynamos is that they need magnetic fields in order to work.

But out in the universe, there are no obvious wires or big steel structures, so how do the fields arise? Progress on this problem began about a century ago as scientists pondered the source of the Earth's magnetic field. By then, studies of the propagation of seismic waves showed that much of the Earth, below the cooler surface layers of the mantle, was liquid, and that there was a core composed of molten nickel and iron. Researchers theorized that the convective motion of this hot, electrically conductive liquid and the rotation of the Earth combined in some way to generate the Earth's field.

Eventually, models emerged that showed how the convective motion could amplify an existing field. This is an example of "self-organization"—a feature often seen in complex dynamical systems—where large-scale structures grow spontaneously from small-scale dynamics. But just like in a power station, you needed a magnetic field to make a magnetic field.

part 2

A similar process is at work all over the universe. However, in stars and galaxies and in the space between them, the electrically conducting fluid is not molten metal, but plasma—a state of matter that exists at extremely high temperatures where the electrons are ripped away from their atoms. On Earth, plasmas can be seen in lightning or neon lights. In such a medium, the dynamo effect can amplify an existing magnetic field, provided it starts at some minimal level.

Where does this seed field come from? Present studies developed the underlying theory and performed numerical simulations on powerful supercomputers that show how the seed field can be produced and what fundamental processes are at work. An important aspect of the plasma that exists between stars and galaxies is that it is extraordinarily diffuse—typically about one particle per cubic meter. That is a very different situation from the interior of stars, where the particle density is about 30 orders of magnitude higher. The low densities mean that the particles in cosmological plasmas never collide, which has important effects on their behavior that had to be included in the model that these researchers were developing.

Calculations performed by the MIT researchers followed the dynamics in these plasmas, which developed from well-ordered waves but became turbulent as the amplitude grew and the interactions became strongly nonlinear. By including detailed effects of the plasma dynamics at small scales on macroscopic astrophysical processes, they demonstrated that the first magnetic fields can be spontaneously produced through generic large-scale motions as simple as sheared flows. Just like the terrestrial examples, mechanical energy was converted into magnetic energy.

An important output of their computation was the amplitude of the expected spontaneously generated magnetic field. What this showed was that the field amplitude could rise from zero to a level where the plasma is "magnetized"—that is, where the plasma dynamics are strongly affected by the presence of the field. At this point, the traditional dynamo mechanism can take over and raise the fields to the levels that are observed. Thus, their work represents a self-consistent model for the generation of magnetic fields at cosmological scale.

Muni Zhou et al, Spontaneous magnetization of collisionless plasma, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2119831119

Part 3

**

Scientists detect deadly arrhythmia trifecta: Salt, swelling, and leaky sodium channels

Less than 1 percent of the population has been diagnosed with Long QT syndrome – a rare heart condition that can cause chaotic, sometimes fatal, heart rhythms.

Now, researchers  have identified two core factors that may put patients with Long QT syndrome Type 3 at significantly higher risk of sudden cardiac death. Their findings were recently published in the American Journal of Physiology – Heart and Circulatory Physiology.

Some Long QT syndrome patients are born with the disease, while others develop it as a result of natural aging, certain medications, tissue swelling, or heart disease.

The syndrome remodels the heart’s sodium channels to become hyperactive and leaky, which disrupts the heart’s normal electrical pathways. Long QT is diagnosed when the length of time it takes for a heartbeat to drop from its peak to baseline, the QT interval, is extended on an electrocardiogram reading.

Some patients with Long QT live long, healthy, and event-free lives, while others suddenly die. Some Long QT syndrome patients are born with the disease, while others develop it as a result of natural aging, certain medications, tissue swelling, or heart disease.

The syndrome remodels the heart’s sodium channels to become hyperactive and leaky, which disrupts the heart’s normal electrical pathways. Long QT is diagnosed when the length of time it takes for a heartbeat to drop from its peak to baseline, the QT interval, is extended on an electrocardiogram reading.

Some patients with Long QT live long, healthy, and event-free lives, while others suddenly die. 

This research  data suggests that the combination of tissue edema, elevated blood sodium, and faulty sodium channels trigger deadly heart arrhythmias. While Long QT is a rare disorder, anyone could acquire similar sodium channel dysfunction with age, ischemia, or other heart disease.

https://pubmed.ncbi.nlm.nih.gov/34623182/

https://vtx.vt.edu/articles/2022/05/scientists-detect-deadly-arrhyt...

New type of extremely reactive substance discovered in the atmosphere

For the first time, an entirely new class of super-reactive chemical compounds has been discovered under atmospheric conditions. Researchers from the University of Copenhagen, in close collaboration with international colleagues, have documented the formation of so-called trioxides—an extremely oxidizing chemical compound that likely affects both human health and our global climate.

Hydrogen peroxide is a commonly known chemical compound. All peroxides have two oxygen atoms attached to each other, making them highly reactive and often flammable and explosive. They are used for everything from whitening teeth and hair to cleaning wounds, and even as rocket fuel. But peroxides are also found in the atmosphere. In recent years, there has been speculation as to whether trioxides—chemical compounds with three oxygen atoms attached to each other, and thereby even more reactive than the peroxides—are found in the atmosphere as well. But until now, it has never been unequivocally proven.

The type of compounds now discovered are unique in their structure. And, because they are extremely oxidizing, they most likely bring a host of effects that we have yet to uncover.

Hydrotrioxides (ROOOH), as they are known, are a completely new class of chemical compounds. Researchers at the University of Copenhagen (UCPH), together with colleagues at the Leibniz Institute for Tropospheric Research (TROPOS) and the California Institute of Technology (Caltech), have demonstrated that these compounds are formed under atmospheric conditions. 

The researchers have also shown that hydrotrioxides are formed during the atmospheric decomposition of several known and widely emitted substances, including isoprene and dimethyl sulfide.

Torsten Berndt et al, Hydrotrioxide (ROOOH) formation in the atmosphere, Science (2022). DOI: 10.1126/science.abn6012. www.science.org/doi/10.1126/science.abn6012

Harnessing the immune system to treat traumatic brain injury in mice

A therapeutic method for harnessing the body's immune system to protect against brain damage is published recently by researchers. The collaboration between various researchers has produced a targeted delivery system for boosting the numbers of specialized anti-inflammatory immune cells specifically within the brain to restrict brain inflammation and damage. Their brain-specific delivery system protected against brain cell death following brain injury, stroke and in a model of multiple sclerosis. The research is published in the journal Nature Immunology.

Traumatic brain injury, like that caused during a car accident or a fall, is a significant cause of death worldwide and can cause long-lasting cognitive impairment and dementia in people who survive. A leading cause of this cognitive impairment is the inflammatory response to the injury, with swelling of the brain causing permanent damage. While inflammation in other parts of the body can be addressed therapeutically, but in the brain it is problematic due to the presence of the blood-brain barrier, which prevents common anti-inflammatory molecules from getting to the site of trauma.

The research team found that regulatory T cell numbers were low in the brain because of a limited supply of the crucial survival molecule interleukin 2, also known as IL2. Levels of IL2 are low in the brain compared to the rest of the body as it can't pass the blood-brain barrier.

Together the team devised a new therapeutic approach that allows more IL2 to be made by brain cells, thereby creating the conditions needed by regulatory T cells to survive. A 'gene delivery' system based on an engineered adeno-associated viral vector (AAV) was used: this system can actually cross an intact blood brain barrier and deliver the DNA needed for the brain to produce more IL2 production.

Matthew Holt, Astrocyte-targeted gene delivery of interleukin 2 specifically increases brain-resident regulatory T cell numbers and protects against pathological neuroinflammation, Nature Immunology (2022). DOI: 10.1038/s41590-022-01208-z. www.nature.com/articles/s41590-022-01208-z

Autonomous vehicles can be tricked into dangerous driving behaviour

When a driverless car is in motion, one faulty decision by its collision-avoidance system can lead to disaster, but researchers  have identified another possible risk: Autonomous vehicles can be tricked into an abrupt halt or other undesired driving behavior by the placement of an ordinary object on the side of the road.

A box, bicycle or traffic cone may be all that is necessary to scare a driverless vehicle into coming to a dangerous stop in the middle of the street or on a freeway off-ramp, creating a hazard for other motorists and pedestrians. Vehicles can't distinguish between objects present on the road by pure accident or those left intentionally as part of a physical denial-of-service attack.

The vehicle's planning module is designed with an abundance of caution, logically, because you don't want driverless vehicles rolling around, out of control. But real testing has found that the software can err on the side of being overly conservative, and this can lead to a car becoming a traffic obstruction, or worse.

 Ziwen Wan et al, Too Afraid to Drive: Systematic Discovery of Seman..., (2022)

Why unprecedented bird flu outbreaks sweeping the world are concerning scientists

Worms Live Longer with Mitochondria Powered by Light: Preprint

Increasing mitochondrial activity in worms by engineering a light-activated proton pump into the organelle’s membrane extends the animals’ lifespan without evidence of health decline, according to a preprint.

Mitochondrial dysfunction has long been associated with aging, making preventing or reversing the organelle’s decay a high priority for longevity researchers. One key target for such work is the decline in the organelle’s membrane potential: the difference in electrical charge between each side of the inner mitochondrial membrane that is essential for energy production. Now, research published May 12 as a bioRxiv preprint that has not yet been peer reviewed demonstrates that it’s possible to genetically engineer a light-activated proton pump into the mitochondria of Caenorhabditis elegans that maintains the voltage across the inner mitochondrial membrane as the worms age—and doing so, prolongs the animals’ lifespan.

The underlying technology was first described in 2020 research, in which University of Rochester Medical Center mitochondria researcher Andrew Wojtovich and his colleagues uncovered the proton pump’s impact on mitochondria. When they engineered the pump—naturally found in the cells of a fungus—into C. elegans, the animals’ mitochondrial membrane potential was increased, which ramped up the production of molecular fuel. The process, they showed, required neither metabolic substrates like glucose nor oxygen. Instead, the pump used light to fuel the movement of protons across the inner membrane, driving the synthesis of ATP. The team named this tool mitochondria-ON (mtON), which only works if the gene-edited animals are treated with light and supplemented with a vitamin A derivative called all-trans retinal, which acts as a cofactor for the pump. 

https://www.the-scientist.com/news-opinion/worms-live-longer-with-m...

Mixing drugs into oil-based gels could help the medicine go down

For most children and even some adults, swallowing pills or tablets is difficult. To make it easier to give those medicines, researchers  have created a drug-delivering gel that is much easier to swallow and could be used to administer a variety of different kinds of drugs.

The gels, made from plant-based oils such as sesame oil, can be prepared with a variety of textures, from a thickened beverage to a yogurt-like substance. The gels are stable without refrigeration, which could make them easier to get to children in developing nations, but they could also be beneficial for children anywhere, the researchers say. They could also help adults who have difficulty swallowing pills, such as older people or people who have suffered a stroke.

This platform will change our capacity for what we can do for kids, and also for adults who have difficulty receiving medication. Given the simplicity of the system and its low cost, it could have a tremendous impact on making it easier for patients to take medications.

Ameya R. Kirtane et al, Development of Oil-Based Gels as Versatile Drug Delivery Systems for Pediatric Applications, Science Advances (2022). DOI: 10.1126/sciadv.abm8478. www.science.org/doi/10.1126/sciadv.abm8478

T cells found to require rest and maintenance

T cells are the soldiers of the immune system, constantly on the ready to respond to a variety of threats, from viruses to tumors. However, without rest and maintenance T cells can die and leave their hosts more susceptible to pathogens,  scientists report May 27 in the journal Science.

Until pathogens are detected, T cells remain in a quiescent state. However, the molecular mechanisms that keep T cells inactive were previously unknown.

In the new study,  researchers show that a protein known as CD8a—which is found in a subset of T cells called CD8 cells—is crucial to keeping the cells in this dormant state. When scientists deleted this protein in mice, the protective CD8 cells were unable to enter a quiescent state and died, leaving the host vulnerable to infections.

Further, they identified another protein, PILRa, that provides a biochemical signal to CD8a. By disrupting this protein pair, both "memory" CD8 cells—cells that previously had been exposed to pathogens—and naïve cells died because they lacked the ability to stay in a quiescent state.

The researchers hope that understanding why this resting state is crucial to maintenance and survival of T cells can lead to improved immune system function.

They noted that as people age they tend to lose both naïve and memory T cells, making older individuals more susceptible to infections. It is possible that the inability of T cells to remain in a quiescent state could lead to people becoming more susceptible to infections and cancer, the authors suggest.

Linghua Zheng et al, The CD8α–PILRα interaction maintains CD8 + T cell quiescence, Science (2022). DOI: 10.1126/science.aaz8658

How the brain links memories

Our brains rarely record single memories. Instead, they store memories in groups so that the recollection of one significant memory triggers the recall of others that are connected chronologically. As we age, however, our brains gradually lose this ability to link related memories.

Now researchers have discovered a key molecular mechanism behind this memory linking. They’ve also identified a way to restore this brain function genetically in aging mice — and an FDA-approved drug that achieves the same thing.

Published in the journal Nature, the findings suggest a new method for strengthening human memory in middle age and a possible early intervention for dementia.

Brain cells are studded with receptors. To enter a cell, a molecule must latch onto a specific receptor, which operates like a doorknob to provide access inside. The UCLA team focused on a gene that encodes a receptor for CCR5 molecules — the same receptor that HIV hitches a ride on to infect brain cells and cause memory loss in AIDS patients.

As people age, the amount of CCR5 expressed in the brain rises, and increased CCR5 gene expression reduces memory recall.

In the current study, researchers discovered a key mechanism underlying mice’s ability to link memories of their experiences in two different cages. A tiny microscope opened a window into the animals’ brains, enabling the scientists to observe neurons firing and creating new memories.

They found that boosting CCR5 gene expression in the brains of mice interfered with memory linking. The animals forgot the connection between the two cages. But when the scientists deleted the CCR5 gene in the animals, the mice were able to link memories that normal mice could not.

When the researchers gave maraviroc, a drug used for HIV patients, to older mice, the drug duplicated the effect of genetically deleting CCR5 from their DNA. The older animals were able to link memories again.

The finding suggests that beyond reversing the cognitive deficits caused by HIV infection, maraviroc can also be used to help restore middle-aged memory loss.

Yang Shen, Miou Zhou, Denise Cai, Daniel Almeida Filho, Giselle Fernandes, Ying Cai, André F. de Sousa, Min Tian, Nury Kim, Jinsu Lee, Deanna Necula, Chengbin Zhou, Shuoyi Li, Shelbi Salinas, Andy Liu, Xiaoman Kang, Masakazu Kamata, Ayal Lavi, Shan Huang, Tawnie Silva, Won Do Heo, Alcino J. Silva. CCR5 closes the temporal window for memory linking. Nature, 2022; DOI: 10.1038/s41586-022-04783-1

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Why the memory of fear is seared into our brains

Experiencing a frightening event is likely something you’ll never forget. But why does it stay with you when other kinds of occurrences become increasingly difficult to recall with the passage of time?

A team of neuroscientists have been studying the formation of fear memories in the emotional hub of the brain – the amygdala — and think they have a mechanism.

In a nutshell, the researchers found that the stress neurotransmitter norepinephrine, also known as noradrenaline, facilitates fear processing in the brain by stimulating a certain population of inhibitory neurons in the amygdala to generate a repetitive bursting pattern of electrical discharges. This bursting pattern of electrical activity changes the frequency of brain wave oscillation in the amygdala from a resting state to an aroused state that promotes the formation of fear memories.

If you are held up at gunpoint, your brain secretes a bunch of the stress neurotransmitter norepinephrine, akin to an adrenaline rush.

This changes the electrical discharge pattern in specific circuits in your emotional brain, centered in the amygdala, which in turn transitions the brain to a state of heightened arousal that facilitates memory formation, fear memory, since it’s scary. This is the same process, we think, that goes awry in PTSD and makes it so you cannot forget traumatic experiences.

https://www.nature.com/articles/s41467-022-28928-y

https://news.tulane.edu/pr/study-examines-why-memory-fear-seared-ou...

Threat to 6G: Eavesdroppers can hack 6G frequency with DIY metasurface

Driver mutations vs passenger mutations

A world first: Human liver was treated in a machine and then successfully transplanted

The Liver4Life research has developed a perfusion machine that makes it possible to implant a human organ into a patient after a storage period of three days outside a body. The machine mimics the human body as accurately as possible, in order to provide ideal conditions for human livers. A pump serves as a replacement heart, an oxygenator replaces the lungs and a dialysis unit performs the functions of the kidneys. In addition, numerous hormone and nutrient infusions perform the functions of the intestine and pancreas.

Like the diaphragm in the human body, the machine also moves the liver to the rhythm of human breathing. In January 2020, the multidisciplinary Zurich research team—involving the collaboration of University Hospital Zurich (USZ), ETH Zurich and the University of Zurich (UZH)—demonstrated for the first time that perfusion technology makes it possible to store a liver outside the body for several days.

The team prepared the liver in the machine with various drugs. In this way, it was possible to transform the liver into a good human organ, even though it was originally not approved for transplantation due to its poor quality. The multi-day perfusion—the mechanical circulation of the organ—enables antibiotic or hormonal therapies or the optimization of liver metabolism, for example. In addition, lengthy laboratory or tissue tests can be carried out without time pressure. Under normal circumstances, this is not possible because organs can only be stored for 12 hours if they are stored conventionally on ice and in commercially available perfusion machines.

As part of an approved individual treatment attempt, the doctors gave a cancer patient on the Swiss transplant waiting list the choice of using the treated human liver. Following his consent, the organ was transplanted in May 2021. The patient was able to leave hospital a few days after the transplantation and is now doing well.

Pierre-Alain Clavien, Transplantation of a human liver following 3 days of ex situ normothermic preservation, Nature Biotechnology (2022). DOI: 10.1038/s41587-022-01354-7. www.nature.com/articles/s41587-022-01354-7

Science academies publish statements on primary concerns for international action ahead of the G7 summit

The science academies of the G7 states are calling for urgent international action to protect the ocean and polar regions and to accelerate decarbonization. In the healthcare sector, scientists demand increased global pandemic preparedness and the implementation of a One Health approach, which considers the health of humans, animals, plants and the wider environment as closely linked and interdependent. Their recommendations are set out in four statements which were submitted to the German federal government today at the Science7 Dialogue Forum 2022 in Berlin/Germany.

https://www.leopoldina.org/en/events/event/event/2962/

Alzheimer's disease causes cells to overheat and 'fry like eggs'

Researchers have shown that aggregation of amyloid-beta, one of two key proteins implicated in Alzheimer's disease, causes cells to overheat and "fry like eggs."

The researchers  used sensors small and sensitive enough to detect temperature changes inside individual cells , and found that as amyloid-beta  misfolds and clumps together, it causes cells to overheat.

In an experiment using human cell lines, the researchers found the heat released by amyloid-beta aggregation could potentially cause other, healthy amyloid-beta to aggregate, causing more and more aggregates to form.

The researchers used tiny temperature sensors called fluorescent polymeric thermometers (FTPs) to study the link between aggregation and temperature. They added amyloid-beta to human cell lines to kickstart the aggregation process and used a chemical called FCCP as a control, since it is known to induce an increase in temperature.

They found that as amyloid-beta started to form thread-like aggregates called fibrils, the average temperature of the cells started to rise. The increase in cellular temperature was significant compared to cells that did not have any amyloid-beta added.

As the fibrils start elongating, they release energy in the form of heat. Amyloid-beta aggregation requires quite a lot of energy to get going, but once the aggregation process starts, it speeds up and releases more heat, allowing more aggregates to form.

Once the aggregates have formed, they can exit the cell and be taken up by neighboring cells, infecting healthy amyloid-beta in those cells.

In the same series of experiments, the researchers also showed that amyloid-beta aggregation can be stopped, and the cell temperature lowered, with the addition of a drug compound. The experiments also suggest that the compound has potential as a therapeutic for Alzheimer's disease, although extensive tests and clinical trials would first be required.

Using a drug that inhibits amyloid-beta aggregation, the researchers were able to pinpoint the fibrils as the cause of thermogenesis. It had previously been unknown whether protein aggregation or potential damage to mitochondria—the "batteries" that power cells—was responsible for this phenomenon.

The researchers say their assay could be used as a diagnostic tool for Alzheimer's disease, or to screen potential drug candidates.

Chyi Wei Chung et al, Intracellular Aβ42 Aggregation Leads to Cellular Thermogenesis, Journal of the American Chemical Society (2022). DOI: 10.1021/jacs.2c03599

How moonlight fine-tunes animal reproduction

Animals possess circadian clocks, or 24-hour oscillators, to regulate daily behaviour. These typically take their cues from the periodic change of sunlight and darkness. However, many animals are also exposed to moonlight, which reoccurs with ~25h periodicity.

Researchers have now discovered that moonlight adjusts the daily clock of marine bristle worms, which helps them to fine-tune their reproductive cycle to certain hours during the night. The study, published in the Proceedings of the National Academy of Sciences, provides an explanation for the phenomenon that daily clocks from flies to humans can exhibit plastic run-times.

In order to produce the next generation, the marine bristle worm Platynereis dumerilii releases its eggs and sperm freely into the open seawater. The correct timing of their reproductive cycles is therefore essential for the survival of the species. It was already known that bristle worms schedule their reproduction to few days of the month. Now, the researchers uncovered that they also synchronize to very specific hours during each night.

Moonlight determines when, precisely, during the night the worms start their reproductive behavior, which is always during the darkest portion of the night.

Rather than acting as the direct stimulus for swarming, moonlight changes the circadian clock period length. In nature, the time of moonlight changes every day by about 50 minutes. The plasticity of the clock allows the worms to factor in these changes. 

 Humans show such circadian plasticity, too. For instance, patients with bipolar disorder exhibit enigmatic circalunidian (i.e. 24.8h) periods correlated with their mood switches. The scientists hope that their work will help to understand the origin and consequences of biological timer plasticity, as well as its interplay with natural timing cues.

Martin Zurl et al, Two light sensors decode moonlight versus sunlight to adjust a plastic circadian/circalunidian clock to moon phase, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2115725119

How wingless salamanders fly

World’s largest organism found in Australia

Single hybrid seagrass plant now stretches across 180 kilometers

Two closely related species hybridize and create a superorganism whose growth and expansion seems unstoppable. That’s what’s happened in Western Australia’s Shark Bay, researchers say, where a seagrass meadow (see above) stemming from a single hybrid plant has extended its reach across more than 180 kilometers—an area the size of Washington, D.C. Two years ago, scientists discovered some of the seagrass there was a clone of a Poseidon’s ribbon weed (Posidonia australis) that had 40 chromosomes instead of the typical 20. They think half those chromosomes may come from the ribbon weed and half from an unknown species. That second half appears to have provided a big survival advantage, as this hybrid has taken over all but one of the 10 seagrass meadows surveyed, the scientists report today in the Proceedings of the Royal Society B. The clone is about 1.5 orders of magnitude larger than the largest fungi and the longest sea animal. The team suspects the clone arose 4500 years ago and has been spreading ever since. That would make it among the oldest organisms on Earth, although not quite as old as the oldest tree. Shark Bay is at the northern edge of where this seagrass can survive, and global warming is making it harder for the plants to hang on there. Low rainfall and high evaporation rates have also caused the water to become much saltier. The clone’s extra genes may be providing a way for it to adapt to these stresses, the authors note.

https://www.science.org/content/article/world-s-largest-organism-fo...

How the brain responds to surprising events

When your brain needs you to pay attention to something important, one way it can do that is to send out a burst of noradrenaline, according to a new  study.

This neuromodulator, produced by a structure deep in the brain called the locus coeruleus, can have widespread effects throughout the brain. In a study of mice, the MIT team found that one key role of noradrenaline, also known as norepinephrine, is to help the brain learn from surprising outcomes.

Noradrenaline is one of several neuromodulators that influence the brain, along with dopamine, serotonin, and acetylcholine. Unlike neurotransmitters, which enable cell-to-cell communication, neuromodulators are released over large swathes of the brain, allowing them to exert more general effects.

Neuromodulatory substances are thought to perfuse large areas of the brain and thereby alter the excitatory or inhibitory drive that neurons are receiving in a more point-to-point fashion. This suggests they must have very crucial brain-wide functions that are important for survival and for brain state regulation.

The researchers also found that the neurons that generate this noradrenaline signal appear to send most of their output to the motor cortex, which offers more evidence that this signal stimulates the animals to take action.

 Noradrenaline has been linked to arousal and boosting alertness, but too much noradrenaline can lead to anxiety.

This work shows that the locus coeruleus encodes unexpected events, and paying attention to those surprising events is crucial for the brain to take stock of its environment. 

In addition to its role in signaling surprise, the researchers also discovered that noradrenaline helps to stimulate behavior that leads to a reward, particularly in situations where there is uncertainty over whether a reward will be offered.

Mriganka Sur, Spatiotemporal dynamics of noradrenaline during learned behaviour, Nature (2022). DOI: 10.1038/s41586-022-04782-2. www.nature.com/articles/s41586-022-04782-2

Bacteria-killing nano-drills : Visible light triggers molecular machines to treat infections

Molecular machines that kill infectious bacteria have been taught to see their mission in a new light.

The latest iteration of nanoscale drills developed by researchers are activated by visible light rather than ultraviolet (UV), as in earlier versions. These have also proven effective at killing bacteria through tests on real infections.

Six variants of molecular machines were successfully tested by  chemists. All of them punched holes in the membranes of gram-negative and gram positive bacteria in as little as two minutes. Resistance was futile for bacteria that have no natural defenses against mechanical invaders. That means they are unlikely to develop resistance, potentially offering a strategy to defeat bacteria that have become immune to standard antibacterial treatments over time.

The new version gets its energy from still-blueish light at 405 nanometers, spinning the molecules' rotors at 2 to 3 million times per second.

It's been suggested by other researchers that light at that wavelength has mild antibacterial properties of its own, but the addition of molecular machines supercharges it. Bacterial infections like those suffered by burn victims and people with gangrene will be early targets.

The researchers also found the machines effectively break up biofilms and persister cells, which become dormant to avoid antibacterial drugs.

The new machines also promise to revive antibacterial drugs considered ineffective. Drilling through the microorganisms' membranes allows otherwise ineffective drugs to enter cells and overcome the bug's intrinsic or acquired resistance to antibiotics. 

Ana L. Santos et al, Light-activated molecular machines are fast-acting broad-spectrum antibacterials that target the membrane, Science Advances (2022). DOI: 10.1126/sciadv.abm2055. www.science.org/doi/10.1126/sciadv.abm2055

How electric fish were able to evolve electric organs

Electric organs help electric fish, such as the electric eel, do all sorts of amazing things: They send and receive signals that are akin to bird songs, helping them to recognize other electric fish by species, sex and even individual. A new study in Science Advances explains how small genetic changes enabled electric fish to evolve electric organs. The finding might also help scientists pinpoint the genetic mutations behind some human diseases.

Evolution took advantage of a quirk of fish genetics to develop electric organs. All fish have duplicate versions of the same gene that produces tiny muscle motors, called sodium channels. To evolve electric organs, electric fish turned off one duplicate of the sodium channel gene in muscles and turned it on in other cells. The tiny motors that typically make muscles contract were repurposed to generate electric signals, and voila! A new organ with some astonishing capabilities was born.

In the new paper, researchers  describe discovering a short section of this sodium channel gene—about 20 letters long—that controls whether the gene is expressed in any given cell. They confirmed that in electric fish, this control region is either altered or entirely missing. And that's why one of the two sodium channel genes is turned off in the muscles of electric fish. But the implications go far beyond the evolution of electric fish.

This control region is in most vertebrates, including humans. So, the next step in terms of human health would be to examine this region in databases of human genes to see how much variation there is in normal people and whether some deletions or mutations in this region could lead to a lowered expression of sodium channels, which might result in disease. 

Sarah LaPotin et al, Divergent cis-regulatory evolution underlies the convergent loss of sodium channel expression in electric fish, Science Advances (2022). DOI: 10.1126/sciadv.abm2970. www.science.org/doi/10.1126/sciadv.abm2970

Capturing carbon with crops, trees and bioenergy

An integrated approach to land management practices in the U.S. can reduce carbon dioxide in the atmosphere far more than earlier estimates based on separate approaches, Michigan State University researchers say. Their research was published May 31 in the journal Global Change Biology.

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Automated drones could scare birds off agricultural fields

In the future, cameras could spot blackbirds feeding on grapes in a vineyard and launch drones to drive off the avian irritants, then return to watch for the next invading flock. All without a human nearby.

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Physicists demonstrate novel mechanism that can prevent light waves...

In collaboration with the group of Professor Mordechai Segev (Technion, Israel Institute of Technology), physicists from the group of Professor Alexander Szameit (University of Rostock) have demonstrated a novel type of mechanism that can prevent light waves from spreading freely. So far, the underlying physical effect had been considered far too weak to fully arrest wave expansion. In their recent experiments, the physicists observed that such light localization is nevertheless possible, demonstrating the uncanny sensitivity of wave propagation across a wide range of spatial length scales. Their discovery was recently published in the journal Science Advances.

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Less air pollution leads to higher crop yields, study shows

Usually, increasing agricultural productivity depends on adding something, such as fertilizer or water. A new Stanford University-led study reveals that removing one thing in particular—a common air pollutant—could lead to dramatic gains in crop yields. The analysis, published June 1 in Science Advances, uses satellite images to reveal for the first time how nitrogen oxides—gases found in car exhaust and industrial emissions—affect crop productivity. Its findings have important implications for increasing agricultural output and analyzing climate change mitigation costs and benefits around the world.

The brain’s immunological wonderland

Researchers once thought that the brain was walled off from the rest of the body’s immune system, but an exciting picture is emerging of the brain as a unique immunologi.... The brain’s border control actually does allow immune cells from the body into the fluid-filled membranes that surround the organ, which are an “immunological wonderland”, says neuroimmunologist Kiavash Movahedi. Special immune cells produced in the skull’s bone marrow could be gentler than normal immune cells. Researchers are exploring how these and other kinds of immune cells in the brain play a role in fighting diseases and could be harnessed in treatments.

Time crystals 'impossible' but obey quantum physics

Time crystals: First theorized in 2012 by Nobel Laureate Frank Wilczek and identified in 2016, time crystals exhibit the bizarre property of being in constant, repeating motion in time despite no external input. Their atoms are constantly oscillating, spinning, or moving first in one direction, and then the other.

Time crystals are different from a standard crystal—like metals or rocks—which is composed of atoms arranged in a regularly repeating pattern in space.

Scientists have created the first "time-crystal" two-body system in an experiment that seems to bend the laws of physics. It comes after the same team recently witnessed the first interaction of the new phase of matter.

Time crystals were long believed to be impossible because they are made from atoms  in never-ending motion. The discovery, published in Nature Communications, shows that not only can time crystals be created, but they have potential to be turned into useful devices.

Everybody knows that perpetual motion  machines are impossible. However, in quantum physics perpetual motion is okay as long as we keep our eyes closed. By sneaking through this crack we can make time crystals. It turns out putting two of them together works beautifully, even if time crystals should not exist in the first place. And we already know they also exist at room temperature.

A "two-level system" is a basic building block of a quantum computer. Time crystals could be used to build quantum devices that work at room temperature. 

An international team of researchers observed time crystals by using Helium-3 which is a rare isotope of helium with one missing neutron. The experiment was carried out in Aalto University.

They cooled superfluid helium-3 to about one ten thousandth of a degree from absolute zero (0.0001 K or -273.15 C). The researchers created two time crystals inside the superfluid, and brought them to touch. The scientists then watched the two time crystals interacting as described by quantum physics.

Nonlinear two-level dynamics of quantum time crystals, Nature Communications (2022). DOI: 10.1038/s41467-022-30783-w

Researchers develop nanoparticles that cross the blood-brain barrier

There are currently few good treatment options for glioblastoma, an aggressive type of brain cancer with a high fatality rate. One reason that the disease is so difficult to treat is that most chemotherapy drugs can't penetrate the blood vessels that surround the brain.

A team of  researchers is now developing drug-carrying nanoparticles that appear to get into the brain more efficiently than drugs given on their own. Using a human tissue model they designed, which accurately replicates the blood-brain barrier, the researchers showed that the particles could get into tumors and kill glioblastoma cells.

The researchers grew patient-derived glioblastoma cells in a microfluidic device. Then, they used human endothelial cells to grow blood vessels in tiny tubes surrounding the sphere of tumor cells. The model also includes pericytes and astrocytes, two cell types that are involved in transporting molecules across the blood-brain barrier.

Joelle P. Straehla et al, A predictive microfluidic model of human glioblastoma to assess trafficking of blood–brain barrier-penetrant nanoparticles, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2118697119

Cynthia Hajal et al, Engineered human blood–brain barrier microfluidic model for vascular permeability analyses, Nature Protocols (2022). DOI: 10.1038/s41596-021-00635-w

Scientists May Have Found a Way to Inject Oxygen Into The Bloodstream Intravenously

There are many illnesses and injuries, including COVID-19, where the body struggles to get the amount of oxygen into the lungs necessary for survival.

In severe cases, patients are put on a ventilator, but these machines are often scarce and can cause problems of their own, including infection and injury to the lungs.

Scientists may have now found a breakthrough, and it's one that that could significantly impact how ventilators are used. 

In addition to traditional mechanical ventilation, there's another technique called Extracorporeal Membrane Oxygenation (ECMO), where blood is carried outside the body so that oxygen can be added and carbon dioxide can be removed.

Thanks to a new discovery, oxygen may now be able to be added directly, and the patient's blood can stay where it is. With a condition like refractory hypoxemia, which can be brought on by being on a ventilator, having this approach available could save lives.

If successful, the described technology may help to avoid or decrease the incidence of ventilator-related lung injury from refractory hypoxemia.

The new technique works by channeling an oxygen-laden liquid through a series of nozzles that get smaller and smaller. By the time the process is finished, the bubbles are smaller than red blood cells – and that means they can be directly injected into the bloodstream without blocking blood vessels.

A lipid membrane is used to coat the bubbles before they're added to the blood, which prevents toxicity and stops the bubbles from clumping together. After the solution is injected, the membrane dissolves and the oxygen is released.

In experiments on donated human blood, blood oxygen saturation levels could be lifted from 15 percent to over 95 percent within just a few minutes. In live rats, the process was shown to increase saturation from 20 percent to 50 percent.

"Importantly, these devices allow us to control the dosage of oxygen delivered and the volume of fluid administered, both of which are critical parameters in the management of critically ill patients.

https://www.pnas.org/doi/full/10.1073/pnas.2115276119

Move Over Apoptosis: Another Form of Cell Death May Occur in the Gut

Though scientists don’t yet know much about it, a newly described process called erebosis might have profound implications for how the gut maintains itself.

Every day, billions of our cells die and new, healthy ones take their place. In a healthy gut lining, as in most tissues, a type of cell death called apoptosis is thought to mediate this process almost entirely on its own. But researchers from RIKEN in Kobe, Japan, suspect they have discovered a new kind of cell death in the gut of a fruit fly. The new process, which they call erebosis or “deep darkness,” may be present in other tissues, the team reports April 25 in PLOS Biology —and if found in humans, it could affect how we understand diseases of the gastrointestinal tract. 

https://www.the-scientist.com/news-opinion/move-over-apoptosis-anot...

Part 1

l cells have a limited lifespan, and their death can come about in several ways. As they age and accumulate mutations, internal or external signals trigger apoptosis, which can be thought of as an organized auto-destruct. The cell shrinks and dissolves into discrete packages called apoptotic bodies, which are later consumed by cell-eating immune cells called phagocytes. Less commonly, damaged, oxygen-starved, or cancerous cells can undergo necrosis, swelling and eventually bursting open to spill their contents into the body. Cells can also die via autophagy, a process akin to consuming themselves, which is thought to be brought about by a lack of food. In autophagy, cells dissolve their internal contents through autophagosomes, large vesicles that break down the cell’s contents. 

At that point, these researchers were still trying to explain Ance cell activity within the context other forms of cell death, especially apoptosis, as it is thought to be the most common driver of the gut’s quick (once every four-day to three-week) tissue turnover. They began searching for evidence that Ance cells were producing markers of necrosis and autophagy, the other, less-common forms of cell death. But they failed to find evidence that any of the three were taking place. Furthermore, inactivating caspases (which are molecules typically found in cells undergoing apoptosis that signal cells to start breaking down) with microRNAs failed to stop the cells from losing organelles, proteins, or ATP. 

To figure out what was going on, the researchers used a general cell death marker called TUNEL, which labels fragmented DNA. TUNEL labeled some Ance cells but not others. The cells that were labeled had lower GFP signals and squatter nuclei, which strongly indicated that these cells were indeed approaching the end of their lives. 

The researchers also looked at whether this newly-described, Ance-related pathway to death still occurred in Drosophila mutants that lacked important apoptosis, necrosis, and autophagy-related proteins. In all cases, erebosis persisted. In all, their findings pointed to one conclusion: Ance was a marker for a cell’s eventual fate—a kind of cell death no one had described before, which they decided to call erebosis.

 Technically, the team didn’t prove that cells are dying through erebosis, nor have they worked out a lot of the details. Though they’ve documented that these cells are undergoing a process that seems difficult to bounce back from, they haven’t shown them disappearing in real-time. They could still be alive.

Part 2

The researchers suppose, existing indefinitely in a new, low-metabolic state. Also, exactly how erebotic cells begin to lose organelles or break down cytoplasmic proteins is still unknown. “It’s really hard to prove that a cell is dying” . It’s almost . . . a philosophical question. But without organelles or a nucleus, say teh scientists, it only makes sense that death is on the horizon for these cells. 

It’s still unclear how [erebosis] fits into homeostasis . . . and they want to know more about where else erebosis is happening. If erebosis is a death pathway, it could help explain confusing results from other studies.

The findings could also have clinical implications. Defective cell turnover, Yoo says, is related to several gastrointestinal diseases, including ulcerative colitis and gastroenteritis. If erebosis occurs in the human gut, it could go wrong and play a role in certain diseases.

And in a strange twist, the researchers have already found that Ance isn’t actually required. The process of molecule- and organelle-dumping and nuclei flattening continued unabated when Ance was knocked out using miRNAs. So, although gut cells tend to take up Ance during erebosis, the researchers don’t yet know why. 

The story continues as researchers try to learn what really is happening. 

https://journals.plos.org/plosbiology/article?id=10.1371/journal.pb...

https://www.the-scientist.com/news-opinion/move-over-apoptosis-anot...

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Part 3

A soft wearable stethoscope designed for automated remote disease diagnosis

Digital stethoscopes provide better results compared to conventional methods to record and visualize modern auscultation(the action of listening to sounds from the heart, lungs, or other organs, typically with a stethoscope, as a part of medical diagnosis). Current stethoscopes are bulky, non-conformal, and not suited for remote use, while motion artifacts can lead to inaccurate diagnosis. In a new report now published in Science Advances,  a research team in engineering, nanotechnology, and medicine described a class of methods to offer real-time, wireless, continuous auscultation. The devices are part of a soft wearable system for quantitative disease diagnosis across various pathologies. Using the soft device, researchers  detected continuous cardiopulmonary sounds with minimal noise to characterize signal abnormalities in real-time. The team conducted a clinical study with multiple patients and control subjects to understand the unique advantage of the wearable auscultation method, with integrated machine learning, to automate diagnoses of four types of disease in the lung, ranging from a crackle, to a wheeze, stridor and rhonchi, with 95% accuracy. The soft system is applicable for a sleep study to detect disordered breathing and to detect sleep apnea.

Sung Hoon Lee et al, Fully portable continuous real-time auscultation with a soft wearable stethoscope designed for automated disease diagnosis, Science Advances (2022). DOI: 10.1126/sciadv.abo5867

Pranav Gupta et al, Precision wearable accelerometer contact microphones for longitudinal monitoring of mechano-acoustic cardiopulmonary signals, npj Digital Medicine (2020). DOI: 10.1038/s41746-020-0225-7

Scientists announce a breakthrough in determining life's origin on Earth

Scientists  announced recently that ribonucleic acid (RNA), an analog of DNA that was likely the first genetic material for life, spontaneously forms on basalt lava glass. Such glass was abundant on Earth 4.35 billion years ago. Similar basalts of this antiquity survive on Mars today.

The study shows that long RNA molecules, 100-200 nucleotides in length, form when nucleoside triphosphates do nothing more than percolate through basaltic glass.

Basaltic glass was everywhere on Earth at the time. For several hundred million years after the Moon formed, frequent impacts coupled with abundant volcanism on the young planet formed molten basaltic lava, the source of the basalt glass. Impacts also evaporated water to give dry land, providing aquifers where RNA could have formed.

The same impacts also delivered nickel, which the team showed gives nucleoside triphosphates from nucleosides and activated phosphate, also found in lava glass. Borate (as in borax), also from the basalt, controls the formation of those triphosphates.

The same impactors that formed the glass also transiently reduced the atmosphere with their metal iron-nickel cores. RNA bases, whose sequences store genetic information, are formed in such atmospheres. The research team had previously showed that nucleosides are formed by a simple reaction between ribose phosphate and RNA bases

The beauty of this model is its simplicity. It can be tested by anybody. Mix the ingredients, wait for a few days and detect the RNA. The same rocks resolve the other paradoxes in making RNA in a path that moves all of the way from simple organic molecules to the first RNA.

Craig A. Jerome et al, Catalytic Synthesis of Polyribonucleic Acid on Prebiotic Rock Glasses, Astrobiology (2022). DOI: 10.1089/ast.2022.0027

Hyo-Joong Kim et al, Prebiotic stereoselective synthesis of purine and noncanonical pyrimidine nucleotide from nucleobases and phosphorylated carbohydrates, Proceedings of the National Academy of Sciences (2017). DOI: 10.1073/pnas.1710778114

Hyo-Joong Kim et al, A Prebiotic Synthesis of Canonical Pyrimidine and Purine Ribonucleotides, Astrobiology (2019). DOI: 10.1089/ast.2018.1935

New nanoparticles aid sepsis treatment in mice

Sepsis, the body's overreaction to an infection, affects more than 1.5 million people and kills at least 270,000 every year in the U.S. alone. The standard treatment of antibiotics and fluids is not effective for many patients, and those who survive face a higher risk of death.

In new research published in the journal Nature Nanotechnology recently,  reported a new nanoparticle-based treatment that delivers anti-inflammatory molecules and antibiotics.

The new system saved the lives of mice with an induced version of sepsis meant to serve as a model for human infections, and is a promising proof-of-concept for a potential new therapy, pending additional research.

The new nanoparticles delivered the chemical NAD⁺ or its reduced form NAD(H), a molecule that has an essential role in the biological processes that generate energy, preserve genetic material and help cells adapt to and overcome stress. While NAD(H) is well known for its anti-inflammatory function, clinical application has been hindered because NAD(H) cannot be taken up by cells directly.

These nanoparticles can directly transport and release NAD(H) into the cell, while preventing premature drug release and degradation in the bloodstream.

Sepsis can be deadly in two phases. First, an infection begins in the body. The immune system responds by creating drastic inflammation that impairs blood flow and forms blood clots, which can cause tissue death and trigger a chain reaction leading to organ failure. Afterward, the body overcorrects itself by suppressing the immune system, which in turn increases infection susceptibility. Controlling complications caused by inflammation is vital in sepsis therapy.

The lipid-coated calcium phosphate or metal-organic framework nanoparticles designed by the researchers can be used to co-deliver NAD(H) and antibiotics.

Shaoqin Gong, NAD(H)-loaded nanoparticles for efficient sepsis therapy via modulating immune and vascular homeostasis, Nature Nanotechnology (2022). DOI: 10.1038/s41565-022-01137-w. www.nature.com/articles/s41565-022-01137-w

Sharp X-ray images despite imperfect lenses

X-rays make it possible to explore inside human bodies or peer inside objects. The technology used to illuminate the detail in microscopically small structures is the same as that used in familiar situations—such as medical imaging at a clinic or luggage control at the airport. X-ray microscopy enables scientists to study the three-dimensional structure of materials, organisms or tissues without cutting and damaging the sample. Unfortunately, the performance of X-ray microscopy is limited by the difficulties in producing the perfect lens. A team from the Institute for X-ray Physics at the University of Göttingen has now shown that, despite the manufacturing limitations of lenses, a much higher image quality and sharpness than ever before can be achieved using a special experimental arrangement and numerical image reconstruction downstream: an algorithm compensates for the deficits of the lenses. The results were published in the journal Physical Review Letters.

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