Catalyst makes drugs inside the body to minimize side effects

A highly active catalyst capable of synthesizing drug molecules within the body has been developed by  chemists. In mice, an anticancer drug assembled near tumors using the injected catalyst suppressed tumour growth.

In conventional medicines delivered by injection or pill, the active drug molecule circulates throughout the body, flooding not only the target site but also healthy tissues. The resulting side effects can be so serious that they can cause permanent damage and force treatment to be stopped. Assembling drug molecules at target sites within the body could make them more effective while minimizing their side effects.

The direct synthesis of drugs in the body would enable drugs to treat diseases without causing side effects in healthy tissues. That's why we need a biocompatible biocatalysis system to perform drug synthesis near target sites in the body.

The team targeted drug assembly in the body using a catalytic chemical reaction called olefin metathesis. Olefin metathesis is one of the most efficient methods for constructing carbon–carbon double bonds for synthesizing drugs. If it could be worked out in the body, it should enable us to synthesize many different types of drugs.

Most chemical catalysts are rapidly deactivated by biomolecules in the bloodstream. To overcome this problem, the team wrapped a ruthenium-based olefin metathesis catalyst inside a protective protein called human serum albumin.

Tanaka's team had previously shown that a ruthenium chloride complex embedded inside human serum albumin—forming a catalytic assembly called an artificial metalloenzyme—was somewhat active in blood. Now, they have shown that switching to a ruthenium iodide complex produces a far superior artificial metalloenzyme.

At low catalyst concentrations, the new albumin-based ruthenium iodide (AlbRuI) catalyst catalyzed three types of olefin metathesis reactions in blood at high yield.

AlbRuI also showed robust stability for 24 hours in blood.This expands the biocompatibility of artificial metalloenzymes and opens the door for developing general, metal-based artificial metalloenzymes for catalytic reactions in blood.

The team also showed that a low dose of cancer-targeting AlbRuI significantly inhibited tumour growth in mice through localized synthesis of an antitumour drug.

 Igor Nasibullin et al, Catalytic olefin metathesis in blood, Chemical Science (2023). DOI: 10.1039/D3SC03785A

‘Tweezers’ hold quantum molecule
Physicists have used lasers as ‘optical tweezers’ to position molecules so precisely that the molecules can be used as qubits to process quantum information. Pairs of calcium monofluoride molecules were gingerly manoeuvred so that they became entangled and behaved as a single collective quantum system. The molecules were cooled to close to absolute zero, making them almost completely still. When their rotation was completely stopped, they represented the ‘0’ state of the qubit. Meanwhile, molecules allowed to rotate with just one quantum of rotational momentum represented the ‘1’ state. Molecules have some advantages over other qubit candidates, such as atoms. For example, molecules could be pushed into service as ‘qutrits’, which have three possible states: −1, 0 and +1.

https://www.science.org/doi/10.1126/science.adf8999

https://www.science.org/doi/10.1126/science.adf4272

The Climate Change We've Already Created Will Last 50,000 Years, Scientists Warn

The idea of an entirely new and human-created geological epoch is a sobering scenario as context for the current UN climate summit, COP28. The impact of decisions made at these and other similar conferences will be felt not just beyond our own lives and those of our children, but perhaps beyond the life of human society as we know it.

Enormous deforestation, the mushrooming of dams across the world's large rivers, overfishing, a planet's nitrogen cycle overwhelmed by fertiliser use, the rapid rise in greenhouse gases.....

As for climate change itself, well, the warning bells were ringing, certainly. Global mean surface temperatures had risen by about half a degree since the mid-20th century. But, they were still within the norm for an interglacial phase of the ice ages. Among many emerging problems, climate seemed one for the future.

A little more than two decades on, the future has arrived. By 2022, global temperature had climbed another half a degree, the past nine years being the hottest since records began. And 2023 has seen climate records being not just broken, but smashed.

With this leap in temperatures came record-breaking heatwaves, wildfires and floods, exacerbated by other local human actions. Climate has moved centre stage on an Anthropocene Earth.

To see how this might play out on a geological timescale, we need to look through the lens of the Anthropocene. A delicately balanced planetary machinery of regular, multi-millennial variations in the Earth's spin and orbit has tightly controlled patterns of warm and cold for millions of years.

Now, suddenly, this control machinery has been overridden by a trillion tons of carbon dioxide injected into the atmosphere in little more than a century.

Part 1

Modelling the effects of this pulse through the Earth System shows that this new, suddenly disrupted, climate pattern is here for at least 50,000 years and probably far longer. It's a large part of the way our planet has changed fundamentally and irreversibly, to become comparable to some of the great climate change events in deep Earth history.

So will this particular COP meeting, with fossil fuel interests so strongly represented, make a difference? The bottom line is that attaining, and stabilising carbon emissions at "net zero" is only a crucial first step.

This latest warming step has already taken the Earth into levels of climate warmth not experienced for some 120,000 years, into those of the last interglacial phase, a little warmer than the current one. There is yet more warming in the pipeline over coming centuries, as various feedbacks take effect. A recent study on the effects of this warming on Antarctica's ice suggests that "policymakers should be prepared for several metres of sea-level rise over the coming centuries" as the pulse of warmth spreads through the oceans to undermine the great polar ice-sheets.

https://theconversation.com/the-climate-change-we-caused-is-here-fo...

Part 2

Biocrusts on Great Wall of China found to be protecting it from erosion

A small international team of soil and water ecosystem conservation specialists has found that biocrusts clinging to parts of the Great Wall of China have been serving to protect the famous structure from erosion. In their paper published in the journal Science Advances (1), the group describes their study and analysis of material growing on the wall.

The Great Wall of China was built over several centuries starting approximately 221 BC—its function was to protect the people living behind it from enemies attempting to invade from the other side. Prior research has shown that different parts of the wall were made with different materials—mostly rammed earth or stone.

Rammed earth is made by mixing organic materials with inorganic materials. Because of their nature, such materials are more susceptible to erosion. That has led to questions regarding how sections of the wall made with the material have survived for so many years. In this new effort, the researchers wondered if perhaps biocrusts may have played a role.

For many years, scientists have assumed that such biocrusts, which are generally made of cyanobacteria, lichen and mosses, speed up the erosion process. To find out if that is the case, the research team collected samples of the biocrusts from several points along the wall and brought them back to a lab for study.

The researchers measured the mechanical strength and soil stability of the samples. They also tested parts of the wall directly comparing those covered in biocrusts and those that were directly exposed to the elements.

They found that the biocrusts were stronger than the rammed earth material upon which they were growing—in some cases, three times as strong. The researchers also found the strength in the biocrusts was due to secretion of tightly bound polymers.

The research team concluded that rather than speeding up erosion, the biocrusts have been slowing the process, helping to preserve the famed structure. Somewhat analogous to their findings were those by a team from the University of Granada working in Honduras that found that organic plant materials added to plasters by early Mayan people have served to reduce weathering of the stone structures they built(2). 

Footnotes:

1.Yousong Cao et al, Biocrusts protect the Great Wall of China from erosion, Science Advances (2023). DOI: 10.1126/sciadv.adk5892

2. Carlos Rodriguez-Navarro et al, Unveiling the secret of ancient Maya masons: Biomimetic lime plasters with plant extracts, Science Advances (2023). DOI: 10.1126/sciadv.adf6138

Phenomena called 'Steve' and 'picket fence' are masquerading as auroras

The shimmering green, red and purple curtains of the northern and southern lights—the auroras—may be the best-known phenomena lighting up the nighttime sky, but the most mysterious are the mauve and white streaks called Steve and their frequent companion, a glowing green "picket fence."

First recognized in 2018 as distinct from the common auroras, Steve and its associated picket fence were nevertheless thought to be caused by the same physical processes. But scientists were left scratching their heads about how these glowing emissions were produced.

Vibrant auroras and glowing phenomena such as Steve and the picket fence are becoming more common as the sun enters the active period of its 11-year cycle.

Because all these transient luminous phenomena are triggered by solar storms and coronal mass ejections from the sun, the approaching solar maximum is an ideal time to study rare events like Steve and the picket fence.

In a region of the upper atmosphere farther south than that in which auroras form, electric fields parallel to Earth's magnetic field could produce the color spectrum of the picket fence. If correct, this unusual process has implications for how physicists understand energy flow between Earth's magnetosphere, which surrounds and protects Earth from the solar wind, and the ionosphere at the edge of space.

A new  paper  showed that parallel electric fields are capable of explaining this exotic spectrum.

Part 1

The common auroras are produced when the solar wind energizes particles in Earth's magnetosphere, often at altitudes higher than 1,000 kilometers above the surface. These energized particles spiral around Earth's magnetic field lines toward the poles, where they crash into and excite oxygen and nitrogen molecules in the upper atmosphere. When those molecules relax, oxygen emits specific frequencies of green and red light, while nitrogen generates a bit of red, but primarily a blue, emission line.

The colorful, shimmering curtains that result can extend for thousands of kilometers across the northern or southern latitudes.

Steve, however, displays not individual emission lines, but a broad range of frequencies centered around purple or mauve. And unlike auroras, neither Steve nor the picket fence emit blue light, which is generated when the most energetic particles hit and ionize nitrogen. Steve and the picket fence also occur at lower latitudes than the aurora, potentially even as far south as the equator.

Some researchers proposed that Steve is caused by ion flows in the upper atmosphere, referred to as subauroral ion drift, or SAID, though there's no well accepted physical explanation for how SAID could generate the colorful emissions.

There are also other suggestions that the picket fence's emissions could be generated by low-altitude electric fields parallel to Earth's magnetic field, a situation thought to be impossible because any electric field aligned with the magnetic field should quickly short out and disappear.

One model showed that a moderate parallel electric field—around 100 millivolts per meter—at a height of about 110 km could accelerate electrons to an energy that would excite oxygen and nitrogen and generate the spectrum of light observed from the picket fence. Unusual conditions in that area, such as a lower density of charged plasma and more neutral atoms of oxygen and nitrogen, could potentially act as insulation to keep the electric field from shorting out.

If you look at the spectrum of the picket fence, it's much more green than you would expect. And there's none of the blue that's coming from the ionization of nitrogen. What that's telling us is that there's only a specific energy range of electrons that can create those colors, and they can't be coming from way out in space down into the atmosphere, because those particles have too much energy.

Instead the light from the picket fence is being created by particles that have to be energized right there in space by a parallel electric field, which is a completely different mechanism than any of the aurora that researchers have studied or known before.

They also suspect that Steve itself may be produced by related processes. Their calculations also predict the type of ultraviolet emissions that this process would produce, which can be checked to verify the new hypothesis about the picket fence.

Though some calculations don't directly address the on-off glow that makes the phenomenon look like a picket fence, it's likely due to wavelike variations in the electric field. And while the particles that are accelerated by the electric field are probably not from the sun, the scrambling of the atmosphere by solar storms  probably triggers Steve and the picket fence, as it does the common aurora.

Part 2

Scientists are trying to test this now . They are trying to   launch a rocket from Alaska through these phenomena and measure the strength and direction of the electric and magnetic fields. SSL scientists specialize in designing and building instruments that do just that. Many of these instruments are on spacecraft now orbiting Earth and the sun.

Initially, the target would be what's known as an enhanced aurora, which is a normal aurora with picket fence-like emissions embedded in it.

The enhanced aurora is basically this bright layer that's embedded in the normal aurora. The colors are similar to the picket fence in that there's not as much blue in them, and there's more green from oxygen and red from nitrogen. The hypothesis is that these are also created by parallel electric fields, but they are a lot more common than the picket fence.

The plan is not only to fly a rocket through that enhanced layer to actually measure those parallel electric fields for the first time but also to distinguish the conditions from those that cause the auroras. Eventually, researchers hope  for a rocket that will fly directly through Steve and the picket fence.

 L. Claire Gasque et al, It's Not Easy Being Green: Kinetic Modeling of the Emission Spectrum Observed in STEVE's Picket Fence, Geophysical Research Letters (2023). DOI: 10.1029/2023GL106073

Part 3

**

Corrosion at atomic level

The cost of repairing corrosion worldwide is estimated at $2.5 trillion a year, which is more than 3% of the global GDP—so developing better ways to manage oxidation would be an economic boon.

When water vapor meets metal, the resulting corrosion can lead to mechanical problems that harm a machine's performance. Through a process called passivation, it also can form a thin inert layer that acts as a barrier against further deterioration.

A technique called environmental transmission electron microscopy (TEM),  allows researchers to directly view molecules interacting on the tiniest possible scale.

Researchers  introduced water vapour to clean aluminum samples and observed the surface reactions. They discovered something that had never been observed before: In addition to the aluminum hydroxide layer that formed on the surface, a second amorphous layer developed underneath it, which indicates there is a transport mechanism that diffuses oxygen into the substrate.

Understanding how a water molecule's hydrogen and oxygen atoms break apart to interact with metals could lead to clean-energy solutions.

Xiaobo Chen et al, Atomistic mechanisms of water vapor–induced surface passivation, Science Advances (2023). DOI: 10.1126/sciadv.adh5565

Frostquakes: A new earthquake risk

A new study has identified a potentially growing natural hazard in the north: frostquakes. With climate change contributing to many observed changes in weather extremes, such as heavy precipitation and cold waves, these seismic events could become more common. Researchers were surprised by the role of wetlands and drainage channels in irrigated wetlands in origin of frostquakes.

Frostquakes are seismic events caused by the rapid freezing of water in the ground. They are most common during extreme winter conditions, when wet, snow-free ground freezes rapidly. They have been reported in northern Finland in 2016, 2019 and 2022, as well as in Chicago in 2019 and Ottawa in 2022, among others.

Roads and other areas cleared of snow in winter are particularly vulnerable to frostquakes. "It was previously thought that roads were the main areas, from which frostquakes originate. Unpredicted in a new study was the importance of wetlands and drainage channels. 

When water in the ground, accumulated during heavy rainfalls in autumn or melting of snow during warm winter weather, freezes and expands rapidly, it causes cracks in the ground, accompanied by tremors and booms. When occurred in populated areas, frostquakes, or cryoseisms, are felt by people and they can be accompanied by specific noises. Ground motions during frostquakes are comparable to those of other seismic events, such as more distant earthquakes, mining explosions and vibrations produced by freight trains. Frostquakes are also known phenomenon in permafrost regions.

The new study, currently available as a preprint and set to be published in the journal EGUsphere, is the first applied study of seismic events from marsh and wetland areas.

Fracturing in the uppermost frozen ground can be initiated if the thickness of frozen layer is about 5 cm and larger. Ruptures can propagate deeper and damage infrastructure such as buildings, basements, pipelines and roads.

With climate change, rapid changes in weather patterns have brought frostquakes to the attention of the wider audience, and they may become more common. Although their intensity is usually low, a series of relatively strong frostquakes rupture roads.

 Nikita Afonin et al, Frost quakes in wetlands in northern Finland during extreme winter weather conditions and related hazard to urban infrastructure (2023). DOI: 10.5194/egusphere-2023-1853

New genes found that can arise 'from nothing'

The complexity of living organisms is encoded within their genes, but where do these genes come from? Researchers  resolved outstanding questions around the origin of small regulatory genes, and described a mechanism that creates their DNA palindromes. Under suitable circumstances, these palindromes evolve into microRNA genes.

The human genome contains ca. 20,000 genes that are used for the construction of proteins. Actions of these classical genes are coordinated by thousands of regulatory genes, the smallest of which encode microRNA molecules that are 22 base pairs in length. While the number of genes remains relatively constant, occasionally, new genes emerge during evolution. Similar to the genesis of biological life, the origin of new genes has continued to fascinate scientists.

All RNA molecules require palindromic runs of bases that lock the molecule into its functional conformation. Importantly, the chances of random base mutations gradually forming such palindromic runs are extremely small, even for the simple microRNA genes.

Hence, the origin of these palindromic sequences has puzzled researchers till now. Experts  now resolved this mystery, describing a mechanism that can instantaneously generate complete DNA palindromes and thus create new microRNA genes from previously noncoding DNA sequences.

In their project, the researchers studied errors in DNA replication. DNA replication can be compared to typing of text. DNA is copied one base at a time, and typically mutations are erroneous single bases, like mis-punches on a laptop keyboard. So researchers studied a mechanism creating larger errors.

Researchers recognized that DNA replication errors could sometimes be beneficial. Some researchers saw the connection to the structure of RNA molecules.

In an RNA molecule, the bases of adjacent palindromes can pair and form structures resembling a hairpin. Such structures are crucial for the function of the RNA molecules.

Part 1

Researchers decided to focus on microRNA genes due to their simple structure: the genes are very short—just a few tens of bases—and they have to fold into a hairpin structure to function correctly.

A central insight was to model the gene history using a custom computer algorithm. This enables the closest inspection of the origin of genes thus far.

The whole genome of tens of primates and mammals is known. A comparison of their genomes reveals which species have the microRNA palindrome pair and which lack it. With a detailed modeling of the history, they could see that whole palindromes are created by single mutation events.

By focusing on humans and other primates, researchers  demonstrated that the newly found mechanism can explain at least a quarter of the novel microRNA genes. As similar cases were found in other evolutionary lineages, the origin mechanism appears universal.

In principle, the rise of microRNA genes is so easy that novel genes could affect human health. 

The emergence of new genes from nothing has fascinated researchers. Although the results are based on small regulatory genes, researchers think that the findings can be generalized to other RNA genes and molecules.

 Heli A. M. Mönttinen et al, Generation of de novo miRNAs from template switching during DNA replication, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2310752120

Part 2

People Living in Green Areas Seem to Age Slower at The Cellular Level

Surrounding ourselves with nature does wonders for our bodies, from better mental health to healthier hearts and stronger developing immune systems. So much so that some doctors are literally prescribing nature as a treatment.

New research may have found a potential explanation for some of these benefits: People living in areas surrounded by nature tend to have younger biological ages.

Green spaces are well known to mitigate stresses in many ways. Plants help protect and insulate us from the environment, keeping our surrounds up to several degrees cooler during heat waves. They decrease air and noise pollution.

Green spaces encourage physical activity and social interactions and are associated with lower risk of crime.

Yet at the same time we've been learning just how intrinsically reliant our minds and bodies are on the natural world.

https://www.sciencedirect.com/science/article/pii/S0048969723060795...

Part 2

Brain tissue on a chip achieves voice recognition

Clusters of lab-raised brain cells connected to a computer are capable of elementary speech recognition and math problems.

his study by Bio-engineers  is a major step in demonstrating how brain-inspired computer neural networks can advance artificial intelligence capabilities.

Researchers grew bundles of specialized stem  cells that developed into neurons, the main component of the brain. A typical brain consists of 86 billion neurons, each neuron connected to as many as 10,000 other neurons.

The ball of neurons, known as an organoid, created in their lab is less than a nanometer wide. It was connected by an array of electrodes to a circuit board, where machine-learning algorithms decoded responses from the organoid.

The researchers dubbed their creation Brainoware.

After a brief training period, Brainoware was able to distinguish between the voices of eight subjects based on their varying pronunciation of vowels. The system achieved an accuracy rate of 78%.

Brainoware was also able to successfully predict a Henon map, a mathematical construct in the field of chaotic dynamics, with greater accuracy than an artificial network.

This is a first demonstration of using brain organoids [for computing]. It's exciting to see the possibilities of organoids for biocomputing in the future, say the researchers. 

A key advantage of biocomputing is its energy efficiency. Currently, artificial neural networks consume several million watts of energy a day. The human brain, on the other hand, requires only about 20 watts to function for a day. Brainoware is a bridge between AI and organoids.

Challenges remain. Among them will be the task of keeping organoids healthy and well-nourished, a 24/7 task.

And there are other concerns as well.

As the sophistication of these organoid  systems increases, it is critical for the community to examine the myriad of neuroethical issues that surround biocomputing systems incorporating human neural tissue.

Hongwei Cai et al, Brain organoid reservoir computing for artificial intelligence, Nature Electronics (2023). DOI: 10.1038/s41928-023-01069-w

Lena Smirnova et al, Reservoir computing with brain organoids, Nature Electronics (2023). DOI: 10.1038/s41928-023-01096-7

Patients told to get pregnant to treat endometriosis by doctors despite lack of evidence: Research 

Research shows patients with endometriosis are being told to plan a pregnancy to help manage or treat the condition, despite a lack of evidence to show it reduces symptoms. The controversial advice has prompted calls to improve medical education about endometriosis.

More than 3,000 medically diagnosed patients were surveyed across the globe as part of the collaborative study involving researchers and a not-for-profit charity focusing on awareness, information, and advocacy.

The research, which focused on patient experiences, revealed more than half (1,892 of 3,347 total) were advised to fall pregnant or have a baby to manage or treat endometriosis, which can include severe pelvic pain and infertility. Almost 90% (1,691 of 1,892) of endometriosis patients were given this recommendation by health care professionals, including gynecologists and GPs, with 36% told it would cure their condition.

Pregnancy or having a baby isn't a treatment for endometriosis and this advice from health professionals can have negative impacts on those who receive it, according to scientists.

While a third of the respondents felt the advice was appropriate given their situation at the time, many other women in this survey reported feeling too young to have a baby and felt stressed and pressured after being given this inappropriate albeit well-intentioned advice.

Some of the patient responses from the research paper, which has been published in BMC Women's Health , include: "I was 21, single and at uni so it simply wasn't an option" and "I was 13. It wasn't appropriate."

The research also revealed the life-altering impact this advice had on the mental health of patients, their relationships, major life decisions and their trust in the health care system.

"It ended up ruining my relationship as I felt a huge pressure to have kids young and my partner couldn't understand this intense conversation at a young age," said one respondent.

The European Society for Human Reproduction Embryology (ESHRE) Guidelines for Management of Endometriosis state that patients should not be advised to become pregnant with the sole purpose of treating endometriosis, as pregnancy does not always lead to improvement of symptoms or reduction of disease progression.

 Diksha Sirohi et al, Patient experiences of being advised by a healthcare professional to get pregnant to manage or treat endometriosis: a cross-sectional study, BMC Women's Health (2023). DOI: 10.1186/s12905-023-02794-2

Study shows how hurricane acted as a highway to transport microplas...

When a hurricane approaches and crosses land, severe damage can occur—often leaving an obvious trail of physical destruction. What's less obvious to the naked eye is how these storms can carry harmful microplastics across the world.

Wildfires can unlock toxic metal particles from soils, study finds

Wildfires can transform a benign metal in soils and plants into toxic particles that easily become airborne, according to a new study from Stanford University.

Scientists develop environment-friendly and cost-effective approach...

A group of scientists have discovered a new application to generate and store chilled water to reduce the impact of air conditioning on the environment, reduce energy consumption, and lower dependence on fossil fuels.

Climate change research: If warming approaches 2°C, a trickle of extinctions will become a flood

As delegates discuss the climate crisis in Dubai for COP28, the dazzling variety of life found on Earth hangs in the balance.

Our world has warmed by roughly 1.2°C since the pre-industrial period. Many species are already exposed to increasingly intolerable conditions, driving some populations to die off or contract at the hottest edges of their geographic ranges. Biodiversity is feeling the heat in all ecosystems and regions, from mountain tops to ocean depths.

If all national plans to cut emissions are fulfilled, the world would still be on track for 2.5 to 2,9 C of global warming by the end of the century. If species are stressed now, imagine how they will fare over the coming decades.

Are there thresholds of warming beyond which the risks to wildlife accelerate? And if so, where and when might we cross them? In short, what does the future hold for Earth's biodiversity?

Answering these questions has been tricky. Computer simulations that attempt to model how biodiversity will behave in a  warming world have only compared the current status of species to how it may look at a particular point in the future, such as 2050 or 2100.

In a recent paper, researchers studied how the area over which species are exposed to potentially dangerous temperatures will expand from one year to the next, from now until the end of the century.

They overlaid the projections of climate models with data on the geographic distributions of more than 35,000 species on land and in the ocean. We found that the area over which each species will be exposed to intolerable temperatures is likely to increase abruptly during the coming decades.

Most populations may initially appear safe. But then, suddenly, a threshold of global warming is crossed beyond which multiple populations across widespread areas face intolerable conditions in rapid succession.

Of the populations within a species projected to be at risk this century, researchers found that, on average, more than half will switch from being relatively safe to facing dangerous heat in as little as a single decade. A good example is Coral Reefs. Just a few decades ago, coral bleaching events driven by extreme sea surface temperatures were rare and localized. Today, these events degrade reefs globally on an almost annual basis.

The sudden increase in risk to species that scientists' models project is in part due to the rapid pace of global warming itself. When combined with natural variability in the climate (El Niño events are one example), warming tends to raise regional temperatures in sudden jumps rather than smooth inclines.

However, they also found that these thermal thresholds are sharpened by the shape of the planet. For instance, across the Amazon basin in South America, temperatures are similarly hot from one place to another. If one population of a species exceeds its thermal limit, it will also be exceeded across many other populations simultaneously.

https://www.nature.com/articles/s41559-023-02070-4.epdf?sharing_tok...

 

Read the original article.

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Newly created ultra-hard material rivals diamond

Scientists have solved a decades-long puzzle and unveiled a near unbreakable substance that could rival diamond as the hardest material on Earth. The research is published in the journal Advanced Materials. Researchers found that when carbon and nitrogen precursors were subjected to extreme heat and pressure, the resulting materials—known as carbon nitrides—were tougher than cubic boron nitride, the second hardest material after diamond.

The breakthrough opens doors for multifunctional materials to be used for industrial purposes including protective coatings for cars and spaceships, high-endurance cutting tools, solar panels and photodetectors, experts say.

Materials researchers have attempted to unlock the potential of carbon nitrides since the 1980s, when scientists first noticed their exceptional properties, including high resistance to heat.

Researchers subjected various forms of carbon nitrogen precursors to pressures of between 70 and 135 gigapascals—around 1 million times our atmospheric pressure—while heating it to temperatures of more than 1,500°C.

To identify the atomic arrangement of the compounds under these conditions, the samples were illuminated by an intense X-ray beam at three particle accelerators—the European Synchrotron Research Facility in France, the Deutsches Elektronen-Synchrotron in Germany and the Advanced Photon Source based in the United States.

Researchers discovered that three carbon nitride compounds were found to have the necessary building blocks for super-hardness.

Remarkably, all three compounds retained their diamond-like qualities when they returned to ambient pressure and temperature conditions.

Further calculations and experiments suggest the new materials contain additional properties including photoluminescence and high energy density, where a large amount of energy can be stored in a small amount of mass.

Researchers say the potential applications of these ultra-incompressible carbon nitrides is vast, potentially positioning them as ultimate engineering materials to rival diamonds.

Dominique Laniel et al, Synthesis of Ultra‐Incompressible and Recoverable Carbon Nitrides Featuring CN4 Tetrahedra, Advanced Materials (2023). DOI: 10.1002/adma.202308030

Natural gas is actually migrating under permafrost, and could see methane emissions skyrocket if it escapes
Beneath Svalbard's permafrost, millions of cubic meters of methane are trapped—and scientists have now learned that it can migrate beneath the cold seal of the permafrost and escape. A large-scale escape could create a cycle of warming that would send methane emissions skyrocketing: warming thaws the permafrost, causing more gas to escape, allowing more permafrost to thaw and more gas to be released.
Because Svalbard's geological and glacial history is very similar to the rest of the Arctic region, these migrating deposits of methane are likely to be present elsewhere in the Arctic.
Methane is a potent greenhouse gas. At present, the leakage from below permafrost is very low, but factors such as glacial retreat and permafrost thawing may 'lift the lid' on this in the future.

Thomas Birchall et al, Permafrost Trapped Natural Gas in Svalbard, Norway, Frontiers in Earth Science (2023). DOI: 10.3389/feart.2023.1277027

Carbon footprints of wars

War is bad for the environment, with toxic chemicals left polluting the soil and water for decades after fighting ceases. Much less obvious are the carbon emissions from armed conflicts and their long-term impacts on the climate.

Some military emissions are not necessarily specific to wartime, but dramatically increase during combat. Among the largest sources are jet fuel for planes and diesel for tanks and naval ships.

Other sources include weapons and ammunition manufacturing, troop deployment, housing, and feeding armies. Then there is the havoc that militaries cause by dropping bombs, including fires, smoke and rubble from damage to homes and infrastructure—all amounting to a massive "carbon war bootprint".

In order to account for all of this carbon, researchers must begin with basic data surrounding direct "tailpipe" emissions, known as Scope 1 emissions. This is the carbon emitted directly from burning fuel in the engine of a plane, for instance. If we know how much fuel is consumed per kilometre by a certain type of jet plane, we can begin to estimate how much carbon is emitted by a whole fleet of those planes over a certain amount of missions.

Then we have emissions from heating or electricity that are an indirect result of a particular activity—emissions from burning gas to produce electricity to light up an army barracks, for instance. These are Scope 2 emissions.

From there, we can try to account for the complex "long tail" of indirect or embodied emissions, known as Scope 3. These are found in extensive military supply chains and involve carbon emitted by anything from weapons manufacturing to IT and other logistics.

To understand combat emissions better, my colleagues have even proposed a new category, Scope 3 Plus, which includes everything from damage caused by war to post-conflict reconstruction. For example, the emissions involved in rebuilding Gaza or Mariupol in Ukraine will be enormous.

Then there is use of concrete to build walls,  Ammunition and explosives 

https://theconversation.com/how-to-assess-the-carbon-footprint-of-a...

Landmark Study Shows Antibody Therapy Controls 92% of Severe Asthma Cases

Safer relief for people suffering from severe asthma is a step closer with a large clinical trial finding a monocolonal antibody treatment called benralizumab can radically reduce the need for more dangerous high-dose steroid treatments. Asthma impacts almost 300 million people worldwide, around 5 percent of whom have a severe version of this respiratory disease. They face a horrifying struggle to get enough air on a daily basis, with all the associated chest tightness, coughing, panic, and frequent hospital visits.

Patients with severe asthma rely on inhaling high doses of steroids to keep it under control. They work by reducing the body's inflammation in general, decreasing the production of mucus in the lungs as a consequence.

Yet high levels of steroids come with all sorts of risks, including increased diabetes, fractures, cataracts, and suppression of the adrenal system which helps regulate everything from metabolism to stress through hormones.
What's more, the value of such high doses of steroids in treating severe asthma remains debated. Lower doses have a proportionally larger impact, but patients have little other option than to resort to the riskier amounts when these fail.
The treatment investigated in a phase four clinical trial funded by its producer AstraZeneca, works in a far more targeted way. Benralizumab is a protein antibody that reduces the number of inflammation-causing immune cells called eosinophils, which are produced in abnormal amounts in severe asthma cases.

Benralizumab has been so effective that in the trial of over 200 patients across Europe an incredible 92 percent of them safely reduced the use of inhaled steroids, with more than 60 percent no longer needing them at all.

Almost 90 percent of patients in the steroid reduction group remained exacerbation-free by the end of the trial.
Part 1

However, these promising results only apply to a very specific type of asthma, the researchers caution. They only tested people who responded well to benralizumab, patients who have severe eosinophilic asthma and don't respond as well to benralizumab likely still require the intensive steroid treatments.

Due to the risks from high steroid doses the Global Initiative for Asthma recommends lowering doses in patients who are responding positively to immune therapies. This research supports that recommendation, however the results may not be the same across all similar treatments.

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)02284-5/fulltext

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New way to charge batteries harnesses the power of 'indefinite causal order'

Batteries that exploit quantum phenomena to gain, distribute and store power promise to surpass the abilities and usefulness of conventional chemical batteries in certain low-power applications. For the first time, researchers take advantage of an unintuitive quantum process that disregards the conventional notion of causality to improve the performance of so-called quantum batteries, bringing this future technology a little closer to reality.

There are several upcoming quantum technologies worth paying attention to. One such item is the quantum battery which, though initially puzzling in name, holds unexplored potential for sustainable energy solutions and possible integration into future electric vehicles. Nevertheless, these new devices are poised to find use in various portable and low-power applications, especially when opportunities to recharge are scarce.

At present, quantum batteries only exist as laboratory experiments, and researchers around the world are working on the different aspects that are hoped to one day combine into a fully functioning and practical application. 

Researchers are investigating the best way to charge a quantum battery, and this is where time comes into play. One of the advantages of quantum batteries is that they should be incredibly efficient, but that hinges on the way they are charged.

Current batteries for low-power devices, such as smartphones or sensors, typically use chemicals such as lithium to store charge, whereas a quantum battery uses microscopic particles like arrays of atoms. While chemical batteries are governed by classical laws of physics, microscopic particles are quantum in nature, so we have a chance to explore ways of using them that bend or even break our intuitive notions of what takes place at small scales.

Part 1

Researchers experimented with ways to charge a quantum battery using optical apparatuses such as lasers, lenses and mirrors, but the way they achieved it necessitated a quantum effect where events are not causally connected the way everyday things are.

Earlier methods to charge a quantum battery involved a series of charging stages one after the other. However, here, the team instead used a novel quantum effect they call indefinite causal order, or ICO. In the classical realm, causality follows a clear path, meaning that if event A leads to event B, then the possibility of B causing A is excluded. However, at the quantum scale, ICO allows both directions of causality to exist in what's known as a quantum superposition, where both can be simultaneously true.

With ICO, researchers demonstrated that the way you charge a battery made up of quantum particles could drastically impact its performance. They saw huge gains in both the energy stored in the system and the thermal efficiency. And somewhat counterintuitively, we discovered the surprising effect of an interaction that's the inverse of what you might expect: A lower-power charger could provide higher energies with greater efficiency than a comparably higher-power charger using the same apparatus.

The phenomenon of ICO the team explored could find uses beyond charging a new generation of low-power devices. The underlying principles, including the inverse interaction effect uncovered here, could improve the performance of other tasks involving thermodynamics or processes that involve the transfer of heat. One promising example is solar panels, where heat effects can reduce their efficiency, but ICO could be used to mitigate those and lead to gains in efficiency instead.

Charging Quantum Batteries via Indefinite Causal Order: Theory and Experiment, Physical Review Letters (2023). journals.aps.org/prl/accepted/ … 109d959f76f487564a34

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Nanoparticles amplify potential cancer vaccine power

Researchers have identified minuscule particles that supercharge therapeutic cancer vaccines, which train the immune system to attack tumors. These new lipid nanoparticles—tiny structures made of fat—not only stimulate a two-pronged immune system response that enhances the body's ability to fight cancer but also make vaccines more effective in targeting tumours.

This research marks a pivotal turning point in our understanding of how lipid nanoparticles can be harnessed to optimize anticancer immunity. These findings  unlock new avenues for enhancing the efficacy of RNA-based treatments for cancer and infectious diseases.

Lipid nanoparticles, made famous for their use in delivering messenger RNA in COVID-19 vaccines, have gained attention as carriers in cancer immunotherapy. Previous research focused on optimizing lipid nanoparticles to trigger a strong response by T helper 1 cells, cells that enable the immune system to identify and attack cancerous cells.

Using a new screening method, researchers fine-tuned the composition of lipid nanoparticles to customize and maximize immune-response activation. They identified lipid nanoparticles that generated responses simultaneously using two parallel pathways to present tumor antigens to both Th1 and Th2 cells, another type of helper cell.

The team also combined lipid nanoparticles with "checkpoint inhibitor treatment," a type of cancer immunotherapy drug that helps the immune system recognize and attack cancer cells. These inhibitors block "checkpoints:" molecules on immune cells that either stimulate or inhibit an immune response. Cancer cells sometimes evade these checkpoints and thus go undetected by the immune system. The team's LNPs enhance the therapeutics' ability to reduce tumor size and extend patient survival time.

The researchers say that their study is unique because it demonstrates that lipid nanoparticles can boost both Th1 and Th2 responses, producing coordinated attacks on cancer by multiple immune cell types.

Yining Zhu et al, Screening for lipid nanoparticles that modulate the immune activity of helper T cells towards enhanced antitumour activity, Nature Biomedical Engineering (2023). DOI: 10.1038/s41551-023-01131-0

Extremely rare half female, half male bird captured on film

 A striking and extremely rare half female, half male bird has been spotted by a  zoologist.

Sesquicentennial Distinguished Professor Hamish Spencer was holidaying in Colombia when an amateur ornithologist John Murillo pointed out a wild Green Honeycreeper with distinct half green, or female, and half blue, male, plumage.
Many birdwatchers could go their whole lives and not see a bilateral gynandromorph in any species of bird. The phenomenon is extremely rare in birds.

Photographs of the bird make the discovery even more significant as they are "arguably the best of a wild bilateral gynandromorphic bird of any species ever."

A report on the find, only the second recorded example of gynandromorphism in the species in more than 100 years, has been published in the Journal of Field Ornithology.

Professor Spencer says gynandromorphs—animals with both male and female characteristics in a species that usually have separate sexes—are important for our understanding of sex determination and sexual behavior in birds.

The main groups in which the phenomenon has been recorded include animal species that feature strong sexual dimorphism; most often insects, especially butterflies, crustaceans, spiders, and even lizards and rodents.

"This particular example of bilateral gynandromorphy—male one side and female the other—shows that, as in several other species, either side of the bird can be male or female.

The phenomenon arises from an error during female cell division to produce an egg, followed by double-fertilization by two sperm.

Part 1

Bilaterally gynandromorphic Green Honeycreeper near Manizales, Colombia, 20 May 2022. Image courtesy: John Murillo.

John Murillo et al, Report of bilateral gynandromorphy in a Green Honeycreeper ( Chlorophanes spiza ) from Colombia, Journal of Field Ornithology (2023). DOI: 10.5751/JFO-00392-940412

Rubber that doesn't grow cracks when stretched many times

Researchers  have increased the fatigue threshold of particle-reinforced rubber, developing a new, multiscale approach that allows the material to bear high loads and resist crack growth over repeated use. This approach could not only increase the longevity of rubber products such as tires but also reduce the amount of pollution from rubber particles shed during use.

Naturally-occurring rubber latex is soft and stretchy. For a range of applications, including tires, hoses, and dampeners, rubbers are reinforced by rigid particles, such as carbon black and silica. Since their introduction, these particles greatly improve the stiffness of rubbers but not their resistance to crack growth when the material is cyclically stretched, a measurement known as the fatigue threshold.

In fact, the fatigue threshold of particle-reinforced rubbers hasn't improved much since it was first measured in the 1950s. This means that even with the improvements to tires that increase wear resistance and reduce fuel consumption, small cracks can shed large amounts of rubber particles into the environment, which cause air pollution for humans and accumulate into streams and rivers.

Previous research markedly increased the fatigue threshold of rubbers by lengthening polymer chains and densifying entanglements. But how about particle-reinforced rubbers?

The present research team added silica particles to their highly entangled rubber, thinking the particles would increase stiffness but not affect fatigue threshold, as commonly reported in the literature. They were wrong. Adding particles would increase the fatigue threshold and they discovered that it increased by a factor of 10.

This material deconcentrates stress around a crack over two length scales: the scale of polymer chains, and the scale of particles. This combination stops the growth of a crack in the material. The team demonstrated their approach by cutting a crack in a piece of their material and then stretching it tens of thousands of times. In their experiments, the crack never grew.

 Jason Steck et al, Multiscale stress deconcentration amplifies fatigue resistance of rubber, Nature (2023). DOI: 10.1038/s41586-023-06782-2

Captive Goffin's cockatoos found to dunk hard bread to improve its texture

A pair of veterinary medicine researchers has found that some captive Goffin's cockatoos prefer to dunk their hard bread before eating it, seemingly as a means to improve its texture. In their paper published in the journal Biology Letters, they describe their observations of the birds and their theories on why the birds dunk the bread.

Many animals have been observed dunking food in water before consumption—raccoons are a prime example. Prior research has shown that at least 25 species of birds dunk food in water before consumption, though why they do so has remained unclear. In this new effort, the researchers discovered by happenstance that some of the birds in the lab carried pieces of rusk to a nearby water bowl and dunked it for several seconds before consuming their treat. Rusk is a type of twice-baked, dry and brittle bread that is commonly given to teething babies. In this instance, it is given to captive Goffin's cockatoos as part of their daily rations at the lab.

The researchers report that they happened to note that one of the birds, a male named Pippin, picked up a piece of rusk and headed to a nearby water bowl, normally used for bathing. Once there, he pushed the bread piece underwater and held it there for several seconds. He then pulled the snack from the water and ate it.

Intrigued by their observation, the researchers began to watch more closely as the birds were given their food—the rusk was served along with seeds, bird pellets, dried fruit and cornflakes. As they watched, the researchers noted that several of the birds mimicked the actions of Pippin, though they varied in both dedication and the amount of time they dunked the bread.

After watching the birds eat over a 12-day period, the researchers noted that 7 of the 18 birds in the lab dunked their food—and it was almost always rusk. The birds left the bread in the water for an average of 23 seconds, more than enough time to soften its texture. They also found that some of the birds were willing to go to great lengths to soak their bread before eating it, such as climbing ladders and moving things out of the way.

J. S. Zewald et al, Dunking rusk: innovative food soaking behaviour in Goffin's cockatoos (Cacatua goffiniana), Biology Letters (2023). DOI: 10.1098/rsbl.2023.0411

Enzymes can't tell artificial DNA from the real thing

The genetic alphabet contains just four letters, referring to the four nucleotides, the biochemical building blocks that comprise all DNA. Scientists have long wondered whether it’s possible to add more letters to this alphabet by creating brand-new nucleotides in the lab, but the utility of this innovation depends on whether or not cells can actually recognize and use artificial nucleotides to make proteins.

Now, researchers  have come one step closer to unlocking the potential of artificial DNA. They found that RNA polymerase, one of the most important enzymes involved in protein synthesis, was able to recognize and transcribe an artificial base pair in exactly the same manner as it does with natural base pairs.

The findings, published December 12, 2023 in Nature Communications, could help scientists create new medicines by designing custom proteins.
Considering how diverse life on Earth is with just four nucleotides, the possibilities of what could happen if we can add more are enticing. Expanding the genetic code could greatly diversify the range of molecules we can synthesize in the lab and revolutionize how we approach designer proteins as therapeutics.

The four nucleotides that comprise DNA are called adenine (A), thymine (T), guanine (G) and cytosine (C). In a molecule of DNA, nucleotides form base pairs with a unique molecular geometry called Watson and Crick geometry, named for the scientists who discovered the double-helix structure of DNA in 1953. These Watson and Crick pairs always form in the same configurations: A-T and C-G. The double-helix structure of DNA is formed when many Watson and Crick base pairs come together.

This is a remarkably effective system for encoding biological information, which is why serious mistakes in transcription and translation are relatively rare. As scientists have also learned, they may be able to exploit this system by using synthetic base pairs that exhibit the same geometry.

The study uses a new version of the standard genetic alphabet, called the Artificially Expanded Genetic Information System (AEGIS), that incorporates two new base pairs. Originally developed by Benner, AEGIS began as a NASA-supported initiative to try to understand how extraterrestrial life could have developed.

By isolating RNA polymerase enzymes from bacteria and testing their interactions with synthetic base pairs, they found that the synthetic base pairs from AEGIS form a geometric structure that resembles the Watson and Crick geometry of natural base pairs. The result: the enzymes that transcribe DNA can’t tell the difference between these synthetic base pairs and those found in nature.

In biology, structure determines function. By conforming to a similar structure as standard base pairs, our synthetic base pairs can slip in under the radar and be incorporated in the usual transcription process.

Part1

In addition to expanding the possibilities for synthetic biology, the findings also support a hypothesis that dates back to Watson and Crick’s original discovery. This hypothesis, called the tautomer hypothesis, says the standard four nucleotides can form mismatched pairs due to tautomerization, or the tendency of nucleotides to oscillate between several structural variants with the same composition. This phenomenon is thought to be one source of point mutations, or genetic mutations that only impact one base pair in a DNA sequence.

Tautomerization allows nucleotides to come together in pairs when they aren’t usually supposed to. Tautomerization of mispairs has been observed in replication and translation processes, but here we provide the first direct structural evidence that tautomerization also happens during transcription.

Juntaek Oh, Zelin Shan, Shuichi Hoshika, Jun Xu, Jenny Chong, Steven A. Benner, Dmitry Lyumkis, Dong Wang. A unified Watson-Crick geometry drives transcription of six-letter expanded DNA alphabets by E. coli RNA polymerase. Nature Communications, 2023; 14 (1) DOI: 10.1038/s41467-023-43735-9

The researchers are next interested in testing whether the effect they observed here is consistent in other combinations of synthetic base pairs and cellular enzymes.

Part 2

A global biodiversity tipping point as first marine fish extinction declared

A species of ray, so rare it has only ever been recorded once back in the late 1800s, has been declared extinct after an assessment by an international team led by Charles Darwin University (CDU). The loss of the Java Stingaree, a small relative of stingrays, is the first marine fish extinction as a result of human activity.

This news comes as the International Union for Conservation of Nature (IUCN) released its updated Red List of Threatened Species.

The Java Stingaree (Urolophus javanicus) was known only from a single specimen collected in 1862 from a fish market in Jakarta, Indonesia.

The team conducted new modeling encompassing all available information on the species which has revealed the Java Stingaree as extinct.

Intensive and generally unregulated fishing is likely the major threat resulting in the depletion of the Java Stingaree population, with coastal fish catches in the Java Sea already declining by the 1870s.

The northern coast of Java, particularly Jakarta Bay where the species was known to occur, is also heavily industrialized, with extensive, long-term habitat loss and degradation.

These impacts were severe enough to unfortunately cause the extinction of this species.

 www.iucnredlist.org/species/60 … sessment-information

People, not the climate, found to have caused the decline of the giant mammals

For years, scientists have debated whether humans or the climate have caused the population of large mammals to decline dramatically over the past several thousand years. A new study confirms that climate cannot be the explanation.

About 100,000 years ago, the first modern humans migrated out of Africa in large numbers. They were eminent at adapting to new habitats, and they settled in virtually every kind of landscape—from deserts to jungles to the icy taiga in the far north.

Part of the success was human's ability to hunt large animals. With clever hunting techniques and specially built weapons, they perfected the art of killing even the most dangerous mammals.

But unfortunately, the great success of our ancestors came at the expense of the other large mammals.

It is well-known that numerous large species went extinct during the time of worldwide colonization by modern humans. Now, new research reveals that those large mammals that survived also experienced a dramatic decline.

By studying the DNA of 139 living species of large mammals, scientists have been able to show that the abundances of almost all species fell dramatically about 50,000 years ago.

For the past 800,000 years, the globe has fluctuated between ice ages and interglacial periods about every 100,000 years. If the climate was the cause, we should see greater fluctuations when the climate changed prior to 50.000 years ago. But we don't. Humans are, therefore, the most likely explanation.

So far, some of the most important evidence in the debate has been fossils from the past 50,000 years. They show that the strong, selective extinction of large animals in... Therefore, the extinction of animals can hardly be linked to climate.

Juraj Bergman et al, Worldwide Late Pleistocene and Early Holocene population declines in extant megafauna are associated with Homo sapiens expansion rather than climate change, Nature Communications (2023). DOI: 10.1038/s41467-023-43426-5

Kids with cats have more than double the risk of developing schizophrenia, researchers find

Researchers  have added to the growing body of evidence that cat ownership is a major risk factor for schizophrenia and quantified the risk at more than double.

In a paper, "Cat Ownership and Schizophrenia-Related Disorders and Psychotic-Like Experiences: A Systematic Review and Meta-Analysis," published in Schizophrenia Bulletin, the team details the connections between youth cat ownership and later-in-life schizophrenia-related diagnosis.

The researchers conducted an extensive study search across various databases and gray literature from January 1, 1980, to May 30, 2023, without geographical or language limitations. They included studies reporting original data on cat ownership and schizophrenia-related outcomes. Out of 1,915 identified studies, 17 were used from 11 different countries.

Cat ownership was associated with an increased risk of schizophrenia-related disorders. The unadjusted pooled odds ratio (OR) was 2.35, and the adjusted estimate was 2.24, indicating an over twofold increase in the odds of developing schizophrenia-related disorders among all individuals exposed to cats.

While some studies suggest childhood exposure to cats might be associated with an increased risk of developing schizophrenia-related disorders, the exact age or specific time frame of exposure is not clearly defined across all studies.

One included study from Finland initially reported higher scores on perceptual aberration, schizoid, and social anhedonia scales for those exposed to cats under age seven, though they limited their conclusion to perceptual aberration. Another study from the UK found associations between cat exposure during childhood (at 4 and 10 years) and higher psychotic-like experiences at age 13.

The research suggests that the critical window of exposure needs to be better defined and might be influenced by various factors. More robust investigations are needed to precisely identify the specific period of exposure that might pose the highest risk for schizophrenia-related disorders associated with youth cat exposure.

The overall risk trend focuses on the interaction between the developing brain and feline exposure. But of course, it is not just hanging out with cat personalities that is to blame for the higher risk. There is a causal agent operating unseen in the cat environment that is likely the true culprit—Toxoplasma gondii.

Part1

Toxoplasma gondii (T. gondii) is an intracellular protozoan parasite that causes toxoplasmosis, an infection that around 25% of the world population has gotten at some point.

It is the reason kitty litter bags have a warning label for pregnant women to avoid contact with cat feces, as toxoplasmosis infection is the leading cause of newborn blindness globally, as well as later vision loss, mental disability, and seizures.

Toxoplasmosis can be a significant cause of death among people with severely weakened immune systems. A daily drug is taken by patients with AIDS, undergoing organ transplant, or with intense chemotherapy treatments just to counter the effects of this one parasite.

T. gondii has previously been linked with all sorts of neurological impairments and behavioural changes, from guilt issues to novelty seeking and increased car accidents. Some presentations of schizophrenia can be reversed by antiprotozoal drugs, suggesting that a T. gondii infection may have been the root cause of those case symptoms.

A 2012 meta-analysis of 38 studies, "Toxoplasma gondii and Other Risk Factors for Schizophrenia," also published in Schizophrenia Bulletin, found that patients with schizophrenia were nearly three times more likely to have toxoplasma antibodies in their blood, suggesting past infections were far more prevalent with the pathology.

A striking find in that study, while comparing risk factors for schizophrenia, was the discrepancy between the risk associated with having a first-degree relative with schizophrenia (RR 6.99–9.31) and the risk associated with specific genetic polymorphisms (OR 1.09–1.24). While a family disease pattern can suggest the involvement of shared genes, it can also point to nongenetic factors like environmental exposure to an infectious agent, like a chemical superfund site, or cats.

Toxoplasmosis has also been linked to various wildlife illnesses, as behavioral changes in wild animals often result in poor survival strategies. Rats, for example, become unafraid of cats while infected. It is a common comorbidity for most California sea lions found distressed or dead to have a toxoplasma infection. If anyone is wondering how a sea lion has contact with a cat, try to see a sandy beach from a cat's perspective. That and the human habit of flushing cat litter have created a massive problem for marine mammals.

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The connection to cats has to do with T. gondii's affinity for reproducing only in domestic cats. This affinity may be related to the lack of a single enzyme in feline guts, delta-6-desaturase.

While any mammal can become infected by the parasite, the digestive enzyme delta-6-desaturase prevents the parasite from getting high enough levels of linoleic acid the parasite requires to fuel reproduction.

Unlike all other mammals, cats are full of linoleic acid due to not producing the data-6-desaturase enzyme that would convert linoleic acid to oleic acid. So, the parasite only reproduces in cat intestines.

Cats then shed oocytes (protozoan parasite eggs) by the millions when they defecate, trapping them on fur and paw used to dutifully cover up their deposit, tracking them wherever a cat's paw may wander.

With the parasite completing its lifecycle, it may not affect the rest of cat biology. In humans and other animals, the failure to turn into the larger reproductive form allows the tiny parasite to migrate past the blood-brain barrier, where the disruption occurs.

The missing enzyme and the independent social lives of outdoor cats, mingling in shared sandboxes and loose garden soils around the world, make cat contact the primary vector for the infection. The secondary vector would be anything that has been in contact with a cat, such as a kitchen counter or any surface a cat has walked on or rubbed against.

While social media has clearly made the case that society would crumble without cats, it is important for all cat owners never to allow their cats outdoors to prevent the continued spread of the T. gondii parasite.

It is even more important that parents, with or without cats, understand the danger cat-borne parasites can pose to the long-term mental health of their children.

A framework to train multi-skilled robots for domestic use

Roboticists have been trying to develop robots that can tackle various everyday house chores, such as washing dishes or tidying up, for several years. However, so far none of the robots created has been commercialized adopted on a large scale.

Researchers  recently introduced Dobb-E, a new framework specifically designed to effectively train mobile robots on domestic tasks, ultimately contributing to their future widespread use. This framework, outlined in a paper pre-published on the server arXiv, could be applied to various robots designed to assist humans in their homes.

We already have specialist 'robots' in our homes, such as a dishwasher or a laundry machines, but a generalist robot that can learn how to complete each home-work and how it can help best in that situation has been a distant goal for all too long now.

So researchers developed an ergonomic demonstration collection tool, enabling us to gather task-specific demonstrations in unfamiliar homes without direct robot operation.

The Dobb-E framework has four key components, namely a data collection tool, a pre-trained model, a diverse data set and a deployment scheme. 

Remarkably, the robot was taught to complete 109 different household tasks. For each of these tasks, the researchers fine-tuned their model with five minutes of new video data on average.

The most exciting result of this paper is the confirmation that with our current level of technology we can build learned robotic agents that can address a wide range of tasks in a similarly large range of homes.

Now I want to buy one!

Nur Muhammad Mahi Shafiullah et al, On Bringing Robots Home, arXiv (2023). DOI: 10.48550/arxiv.2311.16098

Common Forever Chemicals May Trigger Cancer Cells to Spread

When colorectal cancer cells are exposed to two different types of 'forever chemicals' in the lab, the chemicals can potentially accelerate cancer progression, new research suggests.

A new study conducted an analysis of exposure levels comparable to those found in firefighters and other people who come into regular contact with per- and poly-fluoroalkyl substances (PFAS). Firefighters' blood levels of PFAS tend to be higher than the general population's because of their frequent exposure to firefighting foam, which contains PFAS chemicals for its flame retardant properties. Firefighters are more likely than the general population to develop and die from a variety of cancers that include colorectal cancer. Environmental factors are believed to be related to about 80 percent of CRC cases. In the new research, PFAS exposure in the lab induced CRC cells to migrate to new positions, implying a potential role in cancer spreading (metastasis) in living organisms. It doesn't prove it's metastasis, but they have increased motility, which is a feature of metastasis, according to researchers.

PFAS are human-made chemicals based on carbon-fluorine bonds, and as the nickname 'forever chemicals' suggests, these bonds are very strong and resistant to degradation, which makes PFAS popular for use in many kinds of products. Unfortunately, it also allows them to survive in the environment for years in ever-increasing concentrations.

They have been frequently detected in the environment, such as in drinking water, indoor dust, cleaning products, and coatings.

Many of these 'forever chemicals' are still present in everyday items, though the hazards of PFAS are largely unclear – partially because of the many different compounds involved. Research has shown that these long-lasting chemicals spread throughout the environment, and exposure to high levels has been linked to harmful health effects in people and animals. Perfluorooctanoic acid (PFOA), a widely used PFAS, was classified as carcinogenic to humans by the International Agency for Research on Cancer in November 2023, and perfluorooctanesulfonic acid (PFOS), another common PFAS, was classified as possibly carcinogenic to humans.

Part 1

When exposed to PFOS and PFOA, the cells showed increased movement and a higher tendency of spreading. In a different test with CRC cells grown in a flat layer, a line was scratched down the middle to split them. When the chemicals were introduced, the cells grew and moved toward each other again.

To dig deeper, the researchers examined the chemicals' effects on the cell's metabolism. PFAS exposure altered various metabolites crucial for cell function, like amino acids and fatty acids, as well as signaling proteins associated with metastasis.

Substances that are usually anti-inflammatory and protective against cancer were reduced in the CRC cells after exposure, too. Some differences were more noticeable in the mutated cells, which could mean that cancers with this mutation may be more likely to spread with exposure to PFAS.

These results in the lab indicate that exposure to high levels of PFOS and PFOA could potentially increase the risk of CRC spreading in real-life conditions. This is crucial information for those in jobs with potential high exposure, the team says, and monitoring these chemicals is key to safeguarding their health, as are future clinical studies.

"Many in vitro studies can't be translated into humans but  understanding first the mechanisms of how they can actually affect cancer cell growth is important."

https://pubs.acs.org/doi/10.1021/acs.est.3c04844

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Part 2

Massive drug search uncovers infinitesimal molecule that kills cancers while sparing immune cells

Scientists have found an experimental small molecule that induces a form of cell death to kill a variety of cancers while enhancing the power of the immune system and leaving healthy cells totally unscathed.

The molecule triggers ferroptosis, a unique form of cell death that is increasingly being tested as an anti-cancer strategy. The international team of scientists reported their findings in the journal Science Translational Medicine.

All biologists know that the three major forms of cell death are  apoptosis, or type 1 cell death; autophagy, type 2 cell death; and cell necrosis, or type 3. Ferroptosis, by contrast, is a distinct form of cell death that relies on a buildup of iron and the generation of reactive oxygen species, which ultimately cause a doomed cell to self-destruct.

Turning to a different form of cell death is vital because most forms of cancer treatment today trigger cell death by enzyme-dependent apoptosis. Unfortunately, a key hallmark of human cancers is their capacity to develop resistance to treatment, and many tumor types have shockingly developed resistance to apoptosis, hence the hunt for a different way to kill tumour cells.

Even though ferroptosis is being actively pursued as a potential cancer treatment, other researchers are studying the process for its pathological role in a variety of disparate diseases that range from Alzheimer's, cardiovascular disease to even various forms of cancer. Ferroptosis is intimately involved in the disease processes of these conditions, studies have shown.

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In terms of harnessing this form of cell death as a therapeutic, teams worldwide are racing to overcome a number of conundrums, especially what's known as the "non-selective" activities of ferroptotic cell death. It doesn't just kill cancer cells, it kills a multitude of cells in the immediate micro-environment, particularly the Big Three: dendritic cells, T cells and neutrophils, which seemingly defeats the promise that ferroptosis holds as a cancer fighter.

That means most compounds capable of inducing ferroptosis in cancer cells may also inflict the same fate on various immune cells, weakening the immune system's ability to swoop in and wage war on deadly tumours.

Part 1

Now researchers have pinpointed a promising small molecule called N6F11, which not only triggers ferroptotic cell death, it also selectively causes the degradation of glutathione peroxidase-4, also known as GPX4, a notorious blocker of ferroptosis.

With N6F11 in the mix, ferroptosis can be triggered and GPX4 is no longer in the way to prevent this specialized form of cell death from annihilating tumors. Even more eye-opening, N6F11 degraded GPX4 in human pancreatic, bladder, breast, and cervical cancer cells without affecting GPX4 in that vital trio of the immune system: dendritic cells, T cells and neutrophils. They also also found that N6F11 slowed the growth of active tumors in mouse models inoculated with pancreatic cancer cells. The animals endured the treatment without severe side effects—an effect the authors tied to N6F11's ability to stimulate T cells.

In summary, researchers now identified a small molecule, N6F11, that induces the selective degradation of GPX4 in malignant, but not immune cells in small tumours, N6F11-induced ferroptosis and initiates a powerful antitumour immune system.

Jingbo Li et al, Tumor-specific GPX4 degradation enhances ferroptosis-initiated antitumor immune response in mouse models of pancreatic cancer, Science Translational Medicine (2023). DOI: 10.1126/scitranslmed.adg3049

Part 2

Scientists construct a synthetic yeast genome

Chromosomes are long DNA molecules that collectively form a genome, containing all the genetic material of an organism. Advances in technology have allowed scientists to redesign and construct different chromosomal sequences, facilitating the study of the link between gene variations and traits.

Notably, yeast is an important model organism for the understanding of basic cellular processes, owing to its similarity to plants and animals at the cellular level while being considerably simpler to manipulate and study. Therefore, redesigning and synthesizing a yeast genome can help scientists to understand the impact of genetic variations on individual traits, potentially elucidating the mechanisms of genetic diseases.

With this goal in mind, scientists 

have synthesized a redesigned yeast—chromosome XV, that comprises 1.05 million base pairs—the largest synthesized chromosome in Asia.

The work is published in Cell Genomics. It is seen as a major milestone in the field of synthetic biology. 

In creating the synthetic Chromosome XV (synXV), the Medicine team extensively redesigned the original DNA to incorporate various changes that resulted in a sequence which is distinctively unique and different from the natural one.

In order to streamline the assembly process of synXV, the team developed a groundbreaking technology, called CRISPR/Cas9-mediated mitotic recombination with endoreduplication (CRIMiRE). This innovative technology significantly speeds up the exchange of large chromosomal DNA segments at specific sites, hence enabling multiple synthetic chromosome segments to be assembled concurrently and stitched together into a complete synthetic Chromosome XV.

Upon generating the synthetic yeast chromosome, CRIMiRE further allows for the intentional mixing and matching of synXV with another yeast chromosome. This generates different genetic combinations for studies, which illuminates the association between genetic variations and individual traits.

Given the challenges of working with extremely long DNA sequences, the traditional approaches are unable to change the sequences efficiently. However, the use of CRIMiRE has simplified the process, shortening it tenfold, potentially revolutionizing the way larger synthetic chromosomes are built for more complex organisms. This achievement opens the door to understanding basic questions about biological processes.

 Jee Loon Foo et al, Establishing chromosomal design-build-test-learn through a synthetic chromosome and its combinatorial reconfiguration, Cell Genomics (2023). DOI: 10.1016/j.xgen.2023.100435

Research suggests women lose more muscle than men in spaceflight

New research published ahead of print in the Journal of Applied Physiology suggests women lose more muscle than men in a microgravity environment such as spaceflight. The study "represent[s] the longest bed rest study on a large cohort of women" and underscores the need for more sex-specific studies on physiological responses to microgravity, the research team wrote.

Historically, only about 2 out of every 10 astronauts sent into space have been women. With NASA's decision to diversify crewmembers in future spaceflight missions, including the agency's intention to send the first woman to the moon in 2024, scientists are more interested than ever in discovering how biological sex plays a role in the physiological response to microgravity. However, existing literature on the female response to low-gravity environments is sparse.

The current study explored muscle loss (atrophy) in men and women during two extended bed rest trials. The men spent 90 days, and the women spent 60 days in a 6-degree head-down tilt position, where their head was below their feet. This simulated a weightless condition similar to what crewmembers experience during spaceflight. Both volunteer groups ate, slept, performed personal hygiene, and all other activities in either the head-down tilt or a horizontal position.

The research team conducted magnetic resonance imaging tests on the volunteers' thigh and calf muscles before and after the trial as well as at the one-month mark of bed rest. These muscles were chosen "because they are critical for ambulation and extravehicular activities that likely will be required of space crews visiting the moon or Mars," the researchers said.

The researchers found that all participants lost a significant amount of muscle mass in both areas of the leg throughout their bed rest period compared to before bed rest. The women lost more muscle from the quadriceps at one month compared to the men, and the women lost more muscle mass at two months than the men lost at three months. This trend is concerning not only because of the impact on typical muscle function but also because "it is now established that muscle serves as an endocrine organ, communicating with numerous other organs," the research team explained.

The current findings from two spaceflight simulation studies suggest that women are more susceptible to weightlessness-induced muscle atrophy," the researchers wrote. "Therefore, a more appropriate path to understand sex-specific responses to microgravity (including the muscle atrophy issue) and to obtain data to better protect the health of future crewmembers may be through well-controlled long-duration bed rest studies with only exercise countermeasure groups."

The research team explained that they suggest this path because other studies have shown women to be very responsive to exercise countermeasures during (simulated) weightlessness. In addition, future space missions are likely to be much longer than the current study and information in this area is needed for longer durations of weightlessness.

Weaponized mosquitoes

The World Mosquito Program will start producing disease-fighting mosquitoes at a factory in Brazil next year. The mosquitos are infected by a bacterial strain that prevents them from transmitting pathogenic viruses, and could protect up to 70 million people from diseases such as dengue and zika. The non-profit organization will produce up to five billion bacteria-infected mosquitoes per year over the next decade.

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Illuminating dark matter

Results of an experiment to detect dark-matter particles known as axions will see light in 2024. Axions are thought to be emitted by the Sun and converted into light, but the tiny particles have not yet been observed experimentally because they require sensitive detection tools and an extremely strong magnetic field. The experiment BabyIAXO at the German Electron Synchrotron in Hamburg is using a solar telescope made of a 10-metre-long magnet and ultra-sensitive noise-free X-ray detectors to track the centre of the Sun for 12 hours per day, to capture the conversion of axions into photons.

And 2024 could be the year that scientists nail down the mass of the neutrino — the most mysterious particle in the standard model of particle physics. Results of the Karlsruhe Tritium Neutrino experiment in 2022 showed that neutrinos had a maximum mass of 0.8 electron volts. Researchers will finish collecting data in 2024 and are expected to make a definite measurement of the tiny particles.

What we can expect in the year 2024 in the field of science

The consciousness debate: round two

Next year could bring new insights into the neural basis of consciousness. A large project that is testing two theories of consciousness through a series of adversarial experiments is expected to release the results of its second experiment by the end of 2024. In the first round, both theories failed to completely align with observed brain-imaging data, settling a 25-year bet in favour of philosophy over neuroscience. The second round could put neuroscience closer to deciphering the mysteries of the subjective experience.

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Saving the planet

In the second half of 2024, the International Court of Justice in the Hague could give an opinion on nations’ legal obligations to combat climate change, and rule on legal consequences for those deemed to be damaging the climate. Although the ruling will not be legally binding, the court’s clout can push countries to strengthen their climate goals and can be cited in domestic legal cases.

Negotiations for the UN plastics treaty, which seeks to establish a binding international agreement to eliminate plastic pollution, will wrap up next year. Since the 1950s, the world has produced 10 billion tonnes of plastic, of which more than 7 billion tonnes is now waste — much of which is polluting oceans and harming wildlife. But there is growing concern among researchers that the UN negotiations, which started last year, are advancing too slowly and will not accomplish the intended goals.

https://www.nature.com/articles/d41586-023-04044-9?utm_source=Live+...

Flu has long-term illness risk — like COVID

People who have been very ill with flu could develop a long-haul illness similar to long COVID. The medical records of more than 81,000 people who were hospitalized with COVID-19 and almost 11,000 with flu show that both infections carried a risk of health problems in the following .... ‘Long flu’ symptoms were more likely to be respiratory — shortness of breath or cough. We need to “stop trivialising viral infections and understand that they are major drivers of chronic diseases”, says clinical epidemiologist and study co-author Ziyad Al-Aly.

Reference: The Lancet Infectious Diseases paper

Using AI, researchers identify a new class of antibiotic candidates that can kill a drug-resistant bacterium

Using a type of artificial intelligence known as deep learning, researchers have discovered a class of compounds that can kill a drug-resistant bacterium that causes thousands of deaths around the world every year.

In a  study  appearing in Nature, the researchers showed that these compounds could kill methicillin-resistant Staphylococcus aureus (MRSA) grown in a lab dish and in two mouse models of MRSA infection. The compounds also show very low toxicity against human cells, making them particularly good drug candidates. A key innovation of the new study is that the researchers were also able to figure out what kinds of information the deep-learning model was using to make its antibiotic potency predictions. This knowledge could help researchers to design additional drugs that might work even better than the ones identified by the model.

James Collins, Discovery of a structural class of antibiotics with explainable deep learning, Nature (2023). DOI: 10.1038/s41586-023-06887-8. www.nature.com/articles/s41586-023-06887-8